Equine Respiratory Medicine and Surgery

For Elsevier:
Commissioning Editor: Joyce Rodenhuis

Development Editor: Rita Demetriou-Swanwick
Editorial Assistant: Louisa Welch
Project Manager: Anne Dickie
Design Direction: Andy Chapman
Illustrations Buyer: Gillian Murray
Illustrator: Samantha J Elmhurst & Hardlines
Equine
Respiratory
Medicine and
Surgery
Edited by
Bruce C McGorum BSc, BVM&S, PhD, CertEM, DipECEIM, MRCVS

Division of Veterinary Clinical Sciences
Easter Bush Veterinary Centre
University of Edinburgh, UK
Padraic M Dixon MVB, PhD, MRCVS

Division of Veterinary Clinical Sciences
Easter Bush Veterinary Centre
University of Edinburgh, UK
N Edward Robinson BVetMed, PhD, MRCVS

Department of Large Animal Clinical Sciences
Michigan State University, USA
Jim Schumacher DVM, MS, Diplomate ACVS

Department of Large Animal Clinical Studies
University of Tennessee, USA
Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2007
An imprint of Elsevier Limited
© 2007 Elsevier Limited. All rights reserved.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form
or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior
permission of the Publishers. Permissions may be sought directly from Elsevier’s Health Sciences Rights
Department, 1600 John F. Kennedy Boulevard, Suite 1800, Philadelphia, PA 19103-2899, USA: phone:
(+1) 215 239 3804; fax: (+1) 215 239 3805; or, e-mail: [email protected]. You may also
complete your request on-line via the Elsevier homepage (http://www.elsevier.com), by selecting ‘Support
and contact’ and then ‘Copyright and Permission’.
First published 2007
ISBN 10: 0 7020 2759 6

ISBN 13: 978 0 7020 2759 8
British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library
Library of Congress Cataloging in Publication Data

A catalog record for this book is available from the Library of Congress
Notice
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or
appropriate. Readers are advised to check the most current information provided (i) on procedures
featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose
or formula, the method and duration of administration, and contraindications. It is the responsibility of
the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to
determine dosages and the best treatment for each individual patient, and to take all appropriate safety
precautions.
To the fullest extent of the law, neither the publisher nor the author assumes any liability for any injury
and/or damage.
The Publisher
Printed in China
Contributors
Dr Christine M Adreani VMD Dr Frederik J Derksen DVM, PhD

School of Veterinary Medicine, New Bolton Center Department of Large Animal Clinical Sciences
University of Pennsylvania, USA College of Veterinary Medicine, Michigan State University, USA
Dr Brian H Anderson BVSc, MVSc, MS, Dip ACVS Professor Padraic M Dixon MVB, PhD, MRCVS
Ballarat Veterinary Practice, Ballarat, Australia Division of Veterinary Clinical Studies
Easter Bush Veterinary Centre, University of Edinburgh
Miss Safia Barakzai BVSc, MSc, Cert ES (Soft tissue), Roslin, UK
Dip ECVS, MRCVS
Royal (Dick) School of Veterinary Studies Professor Norm G Ducharme DVM, MSc, Dip ACVS
Easter Bush Veterinary Centre, University of Edinburgh Department of Clinical Sciences, College of Veterinary Medicine
Roslin, UK Cornell University, USA
Dr Cormac Breathnach BS, PhD Professor G Barrie Edwards BVSc, DVM, FRCVS
Department of Veterinary Science Department of Veterinary Clinical Science
Gluck Equine Research Center, USA University of Liverpool, UK
Dr T Douglas Byars DVM, Dip ACVIM, Dip ACVECC Dr Kira L Epstein DVM
Byars Equine Advisory, Georgetown, USA School of Veterinary Medicine, New Bolton Center
University of Pennsylvania, USA
Dr Elizabeth A Carr DVM, PhD, Dip ACVIM
Department of Large Animal Clinical Sciences Professor David E Freeman MVB, PhD, Dip ACVS
College of Veterinary Medicine, Michigan State University, USA Department of Large Animal Clinical Sciences
College of Veterinary Medicine, University of Florida, USA
Dr Robert Christley BVSc, MVCS, Dip VCS, MACVSc, PhD,
Dip ECVPH(PM), MRCVS Dr Ian C Fulton BVSc, MSc, MACVS
Department of Veterinary Clinical Science Ballarat Veterinary Practice, Ballarat, Australia
Faculty of Veterinary Science, University of Liverpool, UK
Mr Paul W Furlow BS
Dr R Eddie Clutton BVSc, MRCVS, DVA, Dip ECVA, MRCA Department of Physiology, College of Veterinary Medicine
Royal (Dick) School of Veterinary Studies Michigan State University, USA
Roslin, UK Dr Vincent Gerber DVM, PhD, Dip ACVIM
Equine Clinic, Department of Clinical Veterinary Medicine
Professor Noah D Cohen VMD, MPH, PhD, DACVIM University of Berne, Switzerland
Department of Large Animal Medicine & Surgery
College of Veterinary Medicine, Texas A&M University, USA Professor Tim Greet BVMS, MVM, Cert EO, DESTS,
Dip ECVS, FRCVS
Miss Niamh Collins MVB, MRCVS Rossdales Equine Hospital, Newmarket, UK
Royal (Dick) School of Veterinary Studies
Easter Bush Veterinary Centre, University of Edinburgh Dr Caroline Hahn BS, DVM, MSc, PhD, MRCVS
Roslin, UK Royal (Dick) School of Veterinary Studies
Dr Janet M Daly BSc PhD Roslin, UK
Centre for Preventative Medicine, Animal Health Trust
Newmarket, UK Professor Kenneth W Hinchcliff BVSc, MS, PhD, Dip ACVIM
Equine Medicine, The Ohio State University, USA
Dr Elizabeth G Davis DVM, PhD, DACVIM
Equine Medicine, Kansas State University, USA Professor David R Hodgson BVSc, PhD, Dip ACVIM,
FACSM, MACVSc
Dr Christopher M Deaton BSc (Hons), PhD Faculty of Veterinary Science, University of Sydney
Centre for Equine Studies, Animal Health Trust, Newmarket, UK Australia
ix
x Contributors
Professor Jennifer L Hodgson BVSc, PhD, Dip Vet Path, Dr J Richard Newton BVSc, MSc, PhD, DLSHTM, Dip ECVPH,
Dip ACVM, MAS, Grad Cert ED FRCVS
Faculty of Veterinary Science, University of Sydney Animal Health Trust, Newmarket, UK
Australia
Dr Eric J Parente DVM, Dip ACVM
Dr Susan J Holcombe VMD, MS, PhD, Dip ACVS, ACVECC School of Veterinary Medicine, New Bolton Center
Department of Large Animal Clinical Sciences University of Pennsylvania, USA
College of Veterinary Medicine
Michigan State University, USA Professor John F Peroni DVM, MS
College of Veterinary Medicine, University of Georgia, USA
Mr J Geoffrey Lane BVetMed, DESTS, FRCVS
Department of Clinical Veterinary Science Dr Martin J Philipp Dip ECVDI
University of Bristol, UK Murten, Switzerland
Professor Jean-Pierre Lavoie DMV, Dip ACVIM Professor N Edward Robinson BVetMed, PhD, MRCVS
Department of Clinical Sciences, Faculty of Veterinary Medicine Department of Large Animal Clinical Sciences
University of Montreal, Canada College of Veterinary Medicine, Michigan State University, USA
Professor Pierre Lekeux DVM, PhD, Dip ECVPT Professor Diana S Rosenstein DVM, MS, Dip ACVR
Faculty of Veterinary Medicine, University of Liege, Belgium College of Veterinary Medicine, Michigan State University, USA
Professor Joel Lugo DVM, MS, Dip ACVS Professor Bonnie R Rush DVM, MS, DACVIM
JT Vaughan Teaching Hospital, College of Veterinary Medicine College of Veterinary Medicine, Kansas State University, USA
Auburn University, Auburn, USA
Professor Jim Schumacher DVM, MS, Diplomate ACVS
Professor D Paul Lunn BVSc, MS, PhD, Dip ACVIM Department of Large Animal Clinical Studies
Department of Clinical Sciences University of Tennessee, USA
James L Voss Veterinary Teaching Hospital
Colorado State University, USA Dr Josh Slater BVM&S, PhD, MRCVS
Royal Veterinary College, Hatfield, UK
Dr Tim Mair BVSc, PhD, DEIM, DESTS, Dip ECEIM, MRCVS
Bell Equine Veterinary Clinic, Maidstone, UK Dr Kenneth C Smith BVM&S, PhD, MRCPath, MRCVS
Centre for Equine Studies, Animal Health Trust, Newmarket, UK
Dr David J Marlin BSc (Hons), PhD
Equine Centre, Faculty of Medical and Veterinary Sciences Dr Gisela Soboll DVM, MS, PhD
University of Bristol, Langford, UK Dartmouth Medical School Department of Physiology
Lebanon, USA
Professor Ronald J Martens DVM
Department of Large Animal Medicine & Surgery Mr Henry Tremaine BVetMed, MPhil, Cert ES, Dip ECVS
College of Veterinary Medicine, Texas A&M University, USA Department of Clinical Veterinary Sciences
University of Bristol, UK
Professor Joe Mayhew BVSc, PhD, DACVIM, DECVS, FRCVS
Royal (Dick) School of Veterinary Studies Mrs Thea L Vincent BSc (Hons)
Easter Bush Veterinary Centre, University of Edinburgh Hartpury College, Gloucester, UK
Roslin, UK
Dr Dominique-Marie Votion DVM, PhD
Ms Hester McAllister MVB, DVR, Dip ECVDI, MRCVS Faculty of Veterinary Medicine, University of Liege, Belgium
Faculty of Veterinary Medicine, University College Dublin
Ireland Professor Matilda R Wilson
Department of Large Animal Clinical Sciences
Professor Bruce C McGorum BSc, BVM&S, PhD, CertEM, Michigan State University, USA
DECEIM, MRCVS
Division of Veterinary Clinical Sciences Dr James Wood BSc, BVetMed, MSc, PhD, MRCVS, DLSHTM,
Easter Bush Veterinary Centre, University of Edinburgh Dip ECVPH
Roslin, UK Department of Veterinary Medicine, University of Cambridge, UK
Preface
The horse has an impressive capacity for strenuous exer- considerably from the era of Vegetius Renatus (4th century
cise, being capable of running at speeds up to 20 meters Roman author), who advocated the following treatment for
per second for long distances, even while carrying a rider. “horses with a grievous cough:”
Not unexpectedly, the equine respiratory system is extremely
well adapted to provide the gas exchange requirements The shank of a fat boar is boiled till the flesh be loosened.
of such exercise that can include an oxygen demand of Add 3 ounces of deer marrow, suet of a he goat, half ounce
50–80 liters per minute, which is approximately twice that of bull glue, 3 sextari of raisin wine, a sextarius of
of an elite human athlete on a weight-for-weight basis. To psafin, half a hemina of sharpest vinegar, and 3 ounces
meet this oxygen demand, the racing horse must inhale of gumdragant, linseed and fenugreek
and exhale in the region of 15 liters of air, twice per second, Vegetius Renatus
which equates to an impressive minute volume of 1,800 Of the Distempers of Horses and
liters. Clearly, any one of the numerous disorders that impair of the Art of Curing Them.
English Translation. Printed for A. Millar,
the horse’s ability to ventilate its lungs and exchange oxygen London, MDCCXLVII
compromises exercise performance, prompting veterinary
attention. We hope that future readers of our book will not use it
Equine Respiratory Medicine and Surgery provides clinicians, as a source of entertainment when they write editorials
undergraduate and postgraduate students, and research 2000 years from now, but will recognize that progress in
scientists with a fully comprehensive, state-of-the-art refer- the diagnosis and treatment of equine respiratory diseases
ence source, written by world leaders in the field of equine has been a consequence of modern technology. Improve-
respiratory tract disease. The book begins with a review ments in equipment for endoscopy, improved diagnostic
of the relevant applied basic science. This is followed by imaging techniques, use of immunohistochemistry and
sections that cover current diagnostic techniques, infec- polymerase chain reaction for diagnoses, and the advent
tious diseases, disorders of the upper and lower respiratory of safe techniques for lung biopsy have all advanced the
tract, neonatal respiratory tract disorders, and, finally, practice of equine respiratory medicine. We know that
disorders of the chest wall, diaphragm, and pleurae. the next 10 years will be just as exciting as the previous
The book highlights the remarkable progress that has decade, and we look forward with excitement to future
been made in our understanding of diseases of the equine advances.
respiratory tract over the last 10–15 years, and the result-
ant improvements in diagnosis of these diseases and Bruce McGorum, Paddy Dixon,
management of affected horses. We have clearly moved on Ed Robinson, and Jim Schumacher
xi
Acknowledgments
We are gratefully indebted to the many authors for their Louisa Welch, and Zoë Youd, and from Tim Stratton of
excellent and timely contributions and revisions. We Prepress Projects. Last, but certainly not least, we extend
acknowledge the invaluable support from Elsevier, espe- our gratitude to our four families for their great patience
cially from Rita Demetriou-Swanwick, Joyce Rodenhuis, and understanding throughout the duration of this project.
xii
Anatomy of the Respiratory System
1 N Edward Robinson and Paul W Furlow
The major function of the respiratory system is to deliver hair-lined cavity known as the false nostril. It is approxi-
oxygen to and remove carbon dioxide from the blood. Air is mately 10 cm in depth and its function is unknown. The
delivered into the lungs through a series of conducting sebaceous glands in the walls of the false nostril can give
airways that connect the ambient air to the alveoli where rise to epidermal cysts.
gas exchange with blood takes place. These conducting
airways include the nares, nasal cavity, pharynx, larynx, The nasal cavity
trachea, bronchi, and bronchioles. Gas exchange occurs in
the alveolar ducts and alveoli, both of which are lined by Extending a finger up the medial and ventral aspect of the
an extensive pulmonary capillary network so that there is a external nares, one enters the nasal cavity through its
huge vascular surface area for oxygen and carbon dioxide narrowest part known as the nasal valve. On the medial
diffusion. Blood reaches the pulmonary capillaries from the side of the nasal valve is the nasal septum while on the
right ventricle through the pulmonary arteries and returns lateral side is the alar fold, which is a mucosal extension of
to the left atrium via the pulmonary veins. In addition, the the ventral turbinate. The nasal septum separates the two
bronchial circulation, which is a branch of the systemic sides of the nasal cavity. In its caudal portion it is bony but
circulation, provides nutrients to the bronchi, large vessels, rostrally it is cartilaginous. It is covered with a highly vascu-
and pleura. This chapter describes the gross and micro- lar mucosa. The rostral end of the mucosa to the level of
scopic structure of the respiratory system and forms a basis the second or third cheek tooth is covered by a non-ciliated
for future chapters. The structures are described in the stratified cuboidal epithelium with a low density of mucous
sequence that they might be approached during a clinical cells. Caudally, the epithelium becomes ciliated pseudostrati-
examination. fied columnar and mucous cell density increases progressively.
Nasal turbinates
The Nose Each side of the horse’s nasal cavity has two turbinates
The external nares and false nostril that divide the cavity into three air passages, the ventral,
middle and dorsal meatuses. The ventral meatus, which
The respiratory system begins at the external nares, which has the largest cross-sectional area, provides the direct
provide very mobile valves that can be closed to prevent pathway for airflow between the external nares and the
water entry during swimming or can be opened maximally nasopharynx and is the primary path for an endoscope or
during exercise to facilitate high airflow rates. The alar stomach tube. The dorsal meatus extends into the ethmoid
cartilages provide rigidity to the external wall of the nostril. region. The turbinates enlarge the mucosal surface of the
Movements of the external nares are a result of the action nasal cavity, which facilitates its air-conditioning and
of the muscles (levator nasolabialis, dilator naris lateralis, defense functions.
and transversus nasi) that attach to these cartilages. The It is easiest to understand the gross structure of the
lateralis nasi inserts into the cartilaginous extension of the turbinates if one imagines them initially as a mucosa-
ventral turbinate so that it draws the lateral wall of the covered bony plate extending into each nasal cavity from
nasal vestibule outwards and compresses the false nostril, its lateral wall. To be accommodated within the nasal
thereby enlarging the nasal opening. cavity, each of these structures must scroll. The ventral
The junction between the skin and the nasal mucosa is turbinate scrolls upwards while the dorsal turbinate scrolls
visible just within the external nares. On the ventral aspect downwards (Fig. 1.1). This scrolling results in the shell-like
of this mucocutaneous junction is the opening of the structures known as the nasal conchae. The conchae of
nasolacrimal duct. This is one source of the small amount both the dorsal and ventral turbinates form dorsal and
of moisture frequently seen on the horse’s external nares. ventral conchal sinuses. The dorsal conchal sinus is
If one extends an index finger into the nose and up the contiguous with the frontal sinus and the ventral conchal
lateral surface of the external nares, one enters the blind, sinus with the maxillary sinus (Fig. 1.2).
3
SECTION 1 : Basic Sciences
4 1 Anatomy of the Respiratory System
D
DCS
m n
VCS
V C
RMS
Fig. 1.2. Cross-sectional image of the nose at the level of the junction
of the fourth and fifth cheek teeth. The dorsal (d), middle (m), ventral
Fig. 1.1. Cross-sectional image of the nose at the level of the first (v), and common (c) meatuses are visible. The ventral conchal sinus
cheek tooth. The scrolling of the dorsal (D) and ventral (V) turbinates is (VCS) communicates with the rostral maxillary sinus (RMS) over the
clearly visible. nasolacrimal canal (n). The dorsal conchal sinus (DCS) communicates
with the frontal sinus (F).
The ventral turbinate is the shorter of the two the parasympathetic nerves in the nose chiefly regulate
turbinates extending between the first and sixth cheek glandular blood flow and secretion.
teeth. Rostrally, the ventral turbinate continues to the
external nares as the alar fold. The longer dorsal turbinate The ethmoids
terminates rostrally at the first cheek tooth and caudally The ethmoid region of the nasal cavity is clearly visible
extends to the ethmoid region. The epithelial lining of when an endoscope is directed dorsally from within the
the rostral portion of the alar fold is stratified squamous ventral meatus of nasal cavity (Fig. 1.4). One sees the
epithelium with numerous duct openings from the large rostral surface of the ethmoturbinates, a mass of highly
number of submucosal glands. Caudally, there is a pro- vascularized, scroll-like plates of bone that ramify toward
gressive transition of epithelium through stratified non- the olfactory region of the brain (Fig. 1.5). The ethmoid
ciliated cuboidal, and ciliated pseudostratified columnar, to region receives most of its blood supply from intracranial
typical respiratory epithelium with numerous mucus cells sources (Bell et al 1995). The olfactory epithelium that
(Kumar et al 2000) (Fig. 1.3). lines the ethmoturbinates contains three types of cells:
The submucosa of the nasal cavity is highly vascular sensory neurons, exhibiting odor receptors that transmit
allowing it to warm inspired air and regulate mucus electrical signals to the brain; sustentacular cells, which
production. Postganglionic sympathetic nerves (supplied provide protection to the neurons and secrete mucus; and
via cervical sympathetic preganglionic fibers synapsing in basal cells, which differentiate to replace dead sensory
the superior cervical ganglion) innervate the nasal blood neurons. The axons of nerves in the olfactory epithelium
vessels. Upon release of norepinephrine these nerves cause converge to form the olfactory nerve (CN I) giving rise to
vasoconstriction. Congestion of the nasal mucosa is a the sense of smell. Progressive ethmoid hematoma is a
feature of Horner syndrome and is a consequence of loss of slowly growing, uncommon, hemangiomatous mass that
the sympathetic nerve supply. Parasympathetic innervation originates in the ethmoidal region and can cause chronic
of the nose is from the facial nerve (CN VII) and has little epistaxis.
effect on the diameter of blood vessels, suggesting that The maxillary sinus drains into the caudal part of the
vasodilatation is a largely passive process. When activated, middle meatus of the nasal cavity via the nasomaxillary
1 Anatomy of the Respiratory System 5
Fig. 1.3A–D. Types of epithelium found in

the equine nose. (A) Stratified squamous
epithelium typical of the most rostral part
of the ventral turbinate. (B) Non-ciliated
stratified cuboidal epithelium with low
mucus cell count found on the rostral third
of the nasal septum and the alar fold.
(C) Transitional epithelium that occurs on
the rostral third of the turbinate bones
and the middle third of the nasal septum.
(D) Ciliated pseudostratified respiratory
A B epithelium with many mucus cells (MC)
typical of caudal parts of the turbinates and
nasal septum.
MC
C D
Fig. 1.4. Lateral radiograph of the caudal

nasal cavity and pharynx (P) showing the
cranium (Cr), ethmoturbinates (E), guttural
pouch (gp), stylohyoid bone (sh) and soft
palate (sp).
Cr
sh
gp
P
sp
Fig. 1.5. Endoscopic view of the caudal

nasal cavity showing the ethmoid turbinates
(E), caudal end of the dorsal turbinate (D),
nasal septum (ns), and the pathway that
leads to the maxillary sinus opening (m). The
D nasopharynx (P) is at the bottom of the
picture.
E n
s
opening. Although this opening cannot be seen directly comprise the ethmoidal sinus that drains laterally into the
with an endoscope, purulent drainage from the sinus CMS by way of the sphenopalatine sinus that lies adja-
appears lateral to the caudal part of the dorsal turbinate cent to CN II–VI and blood vessels (Bell et al 1995, McCann
where it joins the ethmoid region (Fig. 1.5). et al 2004).
Drainage of the paranasal sinuses does not strictly rely
The paranasal sinuses on gravity alone but also on ciliary transport directed
toward the middle meatus of the nasal cavity (Barakzai
There are seven pairs of paranasal sinuses in the horse 2004). The RMS and VCS drain into the middle meatus via
(Fig. 1.6). These are the rostral and caudal maxillary, the slit-like nasomaxillary aperture (NMA), which is
ventral and dorsal conchal, frontal, sphenopalatine, and located at the highest point in the VCS. The remaining
ethmoid sinuses. The rostral maxillary sinus (RMS) is paranasal sinuses drain into the CMS and thence into the
located dorsal to the third and fourth maxillary cheek posterior part of the nasal cavity via the NMA of the CMS.
teeth. The lateral portion of the RMS communicates with The drainage from these two separate NMAs merges. When
the medial portion, known as the ventral conchal sinus the drainage from the sinuses is purulent it can be observed
(VCS), over the infraorbital canal. The RMS is separated entering the nose lateral to the caudal limit of the dorsal
from the caudal maxillary sinus (CMS) by a bony septum turbinate (Fig. 1.5). The narrow drainage pathways are
usually positioned between the fourth and fifth cheek teeth. easily obstructed as a result of mild inflammation.
The CMS is located dorsal to the fifth and sixth cheek teeth.
The frontal sinus is triangular and located dorsal to the
ethmoturbinates and rostral to the cranium. The frontal
The Pharynx
sinus and the dorsal conchal sinus functionally form a The pharynx delivers air from the posterior nasal cavity to
single compartment known as the conchofrontal sinus. the larynx and is also the pathway that delivers food from
Within the ethmoturbinates lie many small sinuses that the oral cavity to the esophagus. In horses, the oral cavity
lingual tonsil has been described at the base of the tongue

A
FS (Kumar & Timoney 2005).
DCS CR Unlike the nasal cavity, larynx and trachea, the pharynx
E
lacks rigid support from bone or cartilage. The patency of
RMS CMS SP the pharynx depends on the activity of muscles associated
6 7 8 9 10 11 with the hyoid bone, soft palate and tongue (Holcombe et al
1997, Holcombe et al 1998, Tessier et al 2004). These are
discussed extensively in Chapter 29. Dysfunction of these
muscles or their nerves has been associated with pharyn-
B geal collapse or dorsal displacement of the soft palate,
FS
conditions that are exaggerated during exercise.
When the pharynx is viewed endoscopically from the
posterior nares, the following structures are generally
SP
visible: the soft palate forms the ventral floor, the slit-like
guttural pouch openings are visible on the lateral wall, and
DCS
the larynx and glottis are visible ventrally (Fig. 1.7). If the
11 soft palate is located in its normal position, the pointed
epiglottis is visible. The epiglottis is held down against the
soft palate by the action of the hyoepiglotticus muscle
CMS 10 (Holcombe et al 2002). If the soft palate is displaced
dorsally, the epiglottis is hidden.
Lateral VCS
When the endoscope tip is directed dorsally within the
09 pharynx, the dorsal pharyngeal recess becomes visible. In
cases of follicular lymphoid hyperplasia, the dorsal pharyn-
RMS
geal recess can become severely affected and edematous.
08 In mules, a muscular sphincter surrounds the entrance
Rostral into the dorsal pharyngeal recess.
The anatomy of the guttural pouches is described in
07 Chapter 28. They are lined by ciliated epithelium with
mucus-secreting cells and have a close association with the
vagus (CN X), glossopharyngeal (CN IX) and hypoglossal
06 (CN XII) nerves (Manglai et al 2000a,b). The internal
carotid artery runs in the wall of the guttural pouch and it
is thought that this association allows for cooling of
Fig. 1.6. The paranasal sinuses of the horse. (A) Lateral view.
arterial blood on its way to the brain (Baptiste et al 2000).
(B) Diagrammatic representation to show the relationship to the
cheek teeth and the intercommunications. CMS = caudal maxillary The 5-cm long slit-like openings into the guttural pouches
sinus, CR = cranium, DCS = dorsal conchal sinus, E = ethmoidal sinuses, extend downward and backward in the lateral wall of the
FS = frontal sinus, RMS = rostral maxillary sinus, SP = sphenopalatine pharynx, beginning just caudal to the level of the posterior
sinus, VCS = ventral conchal sinus. Arrow shows communication nares. A fold of mucus membrane that needs to be lifted
between RMS and VCS over the infraorbital canal. Teeth are labeled in
to pass an endoscope into the guttural pouch covers
the Triadian system: 06–08 = premolars, 09–11 = molars.
the medial wall of the guttural pouch opening. During
swallowing, the guttural pouch openings dilate widely and
the mucus membrane folds almost make contact with
and pharynx are normally separated by the soft palate each other in the pharyngeal midline (Fig. 1.7B).
except during swallowing. For this reason, horses are
obligate nasal breathers.
The nasopharynx is lined with pseudostratified
The Larynx
columnar ciliated epithelium containing goblet cells and The main function of the larynx is to prevent inhalation of
the oropharynx is lined by stratified squamous epithelium. food into the lower airway during swallowing. The larynx
Lymphoid tissue that is organized into follicles is visible in also has evolved a second function, which is phonation.
rows along the dorsal wall and represents part of the The cartilaginous support of the larynx is provided by the
equine tonsil (Kumar & Timoney 2001). In young horses, ring-shaped cricoid cartilage adjacent to the first tracheal
these follicles can become large and edematous. This ring, the large thyroid cartilage, a pair of arytenoid
condition, known as follicular lymphoid hyperplasia, is cartilages that support the vocal folds and the epiglottis
generally self-limiting as the horse matures. In addition, a that provides a protective flap to cover the glottis during
thyroid cartilage. The thyroid cartilage has a narrow

2 ventral body from which arise two plate-like laminae that
form the lateral walls of the larynx and articulate with
the cricoid in diarthrodial joints at their caudal cornua.
The ventral borders of the laminae unite rostrally at the
1
body of the thyroid and thereby form a ventral triangular
space – the thyroid notch – that is bounded caudally by the
ventral part of the cricoid cartilage. The cricothyroid
membrane fills the thyroid notch, and is easily palpable.
The rostral border of each thyroid lamina is attached to the
hyoid bone by the thyrohyoid membrane. The paired
arytenoids are mobile and under the control of the
intrinsic laryngeal muscles. They lie medial to the thyroid
laminae and rostral to the cricoid cartilage. At the caudal
edge of the medial surface of each arytenoid is the
3
diarthrodial cricoarytenoid articulation. On the lateral
surface dorsal to the articulation is the muscular process
for the insertion of the cricoarytenoideus dorsalis muscle.
A notch in the arytenoid cartilage separates the caudal
muscular process from the rostral corniculate cartilages
that are attached to the arytenoids by cartilaginous joints.
A
The bilateral corniculate cartilages are visible endo-
scopically dorsal and lateral to the glottis. In the normal
horse, these abduct almost symmetrically during inhala-
tion but, in the horse with recurrent laryngeal neuropathy,
the left corniculate fails to abduct or lags considerably. The
most ventral point of the arytenoid cartilage is the vocal
process. This forms the attachment for the vocal ligament,
a band of elastic fibers that originates on the caudal
border of the thyroid body and underlies the membranous
vocal fold. Movements of the arytenoids and corniculate
cartilages abduct and adduct the vocal folds. The single
almost triangular epiglottic cartilage is pointed rostrally
and normally visible endoscopically above the soft palate.
Attached to either side of its base are the bar-like
cuneiform cartilages that project caudodorsally.
Three extrinsic muscles regulate the position of the
larynx in relation to the head and neck. A small muscle,
the hyoepiglotticus, connects the ventral surface of the
epiglottis to the basihyoid bone and thereby pulls the
B epiglottis ventrally to enlarge the entrance to the glottis.
Fig. 1.7. (A) Endoscopic view of the pharynx showing 1, the tissue
Dysfunction of this muscle results in inspiratory epiglottic
flaps that cover the openings to the Eustachian tubes and gut- retroversion during exercise. The thyrohyoideus connects
tural pouches; 2, the dorsal pharyngeal recess; and 3, the larynx. the lateral surface of the thyroid laminae to the caudal
(B) The guttural pouch openings during swallowing. Note how the border of the stylohyoid bone. Contraction of the thyro-
tissue mucosal flaps over the openings converge in the midline of hyoideus pulls the larynx rostrad. The sternothyrohyoideus
the pharynx.
originates at the manubrium of the sternum and inserts
onto both the caudal border of the thyroid laminae and the
basihyoid bone and the lingual process of the hyoid bone.
deglutition (Fig. 1.8A). Corniculate and cuneiform carti- Contraction pulls the larynx backward and downward.
lages are attached to the arytenoid and epiglottic cartilages Intrinsic muscles of the larynx (Fig. 1.8B) regulate the
respectively. The cricoid cartilage, which is the most caudal, position of the vocal folds and the size of the glottic open-
has a broad dorsal surface that provides the origin of the ing (rima glottidis). Contraction of the cricoarytenoideus
cricoarytenoideus dorsalis muscle. It also has articular dorsalis abducts the vocal folds and enlarges the rima
surfaces for the arytenoids and for the caudal cornu of the glottidis. Paresis of this muscle results in left laryngeal
4
3
1 2
4 5
Fig. 1.8. (A) The cartilages of the larynx. 1 = cuneiform cartilage, 2 = muscular processes of the arytenoid
cartilages, 3 = cricoid cartilage, 4 = lamina of thyroid cartilage, 5 = epiglottic cartilage. (B) The intrinsic
muscles of the larynx. 1 = arytenoideus transversus, 2 = cricoarytenoideus dorsalis, 3 = cricoarytenoideus
lateralis, 4 = ventricularis, 5 = vocalis, 6 = cricothyroideus. After Budras, Sack & Röck: The Anatomy of the
Horse (page 44). Schlütersche GmbH & Co. KG, Hannover, Germany, 2003.
hemiplegia. Contraction of the arytenoideus transversus There are numerous mucus glands beneath the laryngeal
also abducts the vocal folds. The adductor muscles of the mucosa, especially in the epiglottis.
vocal folds are cricoarytenoideus lateralis, arytenoideus The laryngeal saccules are bilaterally paired, 2.5–5.0 cm
transversus, vocalis and ventralis. Contraction of the latter deep, mucosa-lined cavities that extend upwards and back-
muscles during swallowing forms a sphincter that closes wards on the medial surface of the thyroid cartilage. The
the glottis and prevents food inhalation. Innervation of entrance to the saccules is from the lateral ventricle of the
the intrinsic muscles of the larynx is via the recurrent larynx, a pocket-like depression lateral to the vocal folds.
laryngeal nerves except for the cricothyroideus, which The function of the laryngeal saccules is unknown but they
receives innervation via the cranial laryngeal nerves. are thought to participate in generation of the noise charac-
The laryngeal mucosa is contiguous with that of the teristic of horses with recurrent laryngeal neuropathy.
pharynx and trachea. It is tightly adherent to the dorsal
surface of the epiglottis, over the vocal ligaments and to the
cricoid cartilage. Between the lateral border of the epiglottis
The Trachea
and the cuneiform/arytenoid cartilages, the mucosa forms The trachea provides a flexible connection between the
the aryepiglottic fold that can sometimes cause an larynx and bronchial bifurcation (carina). The trachea can
inspiratory obstruction during exercise. The loose mucosal be palpated immediately beneath the skin on the ventral
folds on the ventral side of the epiglottis can sometimes midline of the neck. Its lowest point is where it enters the
displace dorsally to entrap the epiglottis. Most of the larynx thoracic inlet immediately above the manubrium of the
is lined by respiratory, pseudostratified, columnar, ciliated sternum and it is here that mucoid secretions tend to accu-
epithelium with goblet cells but the epiglottis and vocal mulate. The trachea then ascends and terminates at the
folds are covered by a stratified squamous epithelium. bronchial bifurcation, which is just dorsal to the left atrium.
dorsally. When this muscle relaxes, the ends of the

cartilage do not meet. Contraction of the trachealis pulls
the cartilage tips together so that the trachea becomes
more rigid. During endoscopic examination, one can see
the outline of the cartilages ventrally and laterally and
often appreciate the flatter dorsal surface that overlies
1 the trachealis muscle (Fig. 1.9). In older horses, it is not
uncommon to see “spikes” of epithelium-covered cartilage
protruding into the tracheal lumen on its ventral floor
(Fig. 1.9B). In some horses, these can be extensive and
form ridges. Their cause is unknown and they appear to
be benign.
In older Shetland ponies and in Miniature Horses, the
trachea often becomes flattened dorsoventrally and the
region between the tips of the tracheal cartilages that
includes the trachealis muscle becomes wider. In these
same animals, the trachea sometimes rotates in the middle
third of the neck so that the trachealis is on the right side
A
of the neck rather than dorsal. This can cause problems if
it is necessary to perform a tracheotomy. A midline incision
in the neck of these animals enters the trachea near the
margin of the cartilage leaving no rigid support on the
right side of the tracheotomy.
The pseudostratified columnar tracheal epithelium
consists primarily of mucus-producing goblet cells and
ciliated cells above a layer of basal cells. The horse has few
submucosal bronchial glands. The lamina propria contains
many branches of the bronchial circulation that serve to
warm and humidify the air and participate in the
inflammatory response of the trachea. The larger of these
vessels are visible endoscopically beneath the mucosa.
The lamina propria is richly supplied with both sensory
2
and autonomic nerves. Non-myelinated sensory nerves
containing neuropeptides ramify into the epithelium.
Parasympathetic nerves reach the cranial and caudal
trachea via the cranial laryngeal nerve and vagus,
respectively. Parasympathetic ganglia located along the
dorsal wall of the trachea send postganglionic fibers to
a submucosal and a muscular plexus. Postganglionic
sympathetic fibers enter the wall of the trachea in
association with the vagus nerve and terminate in the
lamina propria around the bronchial blood vessels.
B Sympathetic nerves innervate the trachealis muscle only in
its cranial third (Yu et al 1994).
Fig. 1.9. Endoscopic views of the trachea. (A) A ventral stream of
mucus in a horse with recurrent airway obstruction. The larger
bronchial vessels are clearly visible as is the junction of the ends of the
tracheal cartilages in the dorsal wall (1). (B) Cartilage spike on the The Bronchi
ventral floor of the trachea (2).
As an endoscope is advanced towards the carina, the
openings of the main bronchi become visible. The right
The trachea is supported throughout its length by main-stem bronchus forms an almost straight line with the
C-shaped sections of cartilage that are tightly apposed to trachea, while the left bronchus deviates slightly. On each
one another so as to give rigidity to the airway (Art & side, the first bronchus arising from the lateral wall of the
Lekeux 1991a,b). A band of smooth muscle, known as the main-stem bronchus is to the cranial part of the lung.
trachealis muscle, connects the free ends of the cartilages There is also a large ventral branch to the region of lung
corresponding to a middle lobe. The bronchus to the

accessory or intermediate lobe of the lung arises medio-
ventrally from the right bronchus (Fig. 1.10). After giving
off these large branches, the main bronchi then run
parallel to the dorsal border of each lung toward its caudal
extremity (Fig. 1.11). Branches are given off both dorsally
and ventrally to various parts of the lung. The branching
pattern is consistent and has been mapped and labeled
4
(Smith et al 1994).
3
The bronchial branching pattern is monopodial. Each
1 2
main bronchus continues almost directly toward the
lung periphery and gives off a series of smaller branches
(Fig. 1.11B). The exact number of branches of the horse’s
tracheobronchial tree has not been determined but varies
with lung region. There are more branches between the
A
carina and caudal extremity of the lung (we have counted
more than 40) than between the carina and the tip of the
cranial lobe. Bronchi are identified by the presence of
cartilage in their walls and include all airways greater than
approximately 2-mm diameter.
The trachea and bronchi are lined by a pseudostratified
columnar epithelium that overlies the basement membrane
and consists of ciliated and non-ciliated cells that differ-
entiate from basal cells (Fig. 1.12). The non-ciliated cells 4
are primarily mucus-secreting cells (also known as goblet
cells). The mucus-secreting goblet cells produce the 1
mucins, which form a large percentage of the mucoid layer
that lines the airways. The horse has very few submucosal
glands in its tracheobronchial tree (Widdicombe & Pecson
2002). The mucoid layer is propelled craniad by the ciliary
cells (see Chapter 5). The lamina propria is immediately 2
B
beneath the basement membrane and contains a rich
supply of bronchial blood vessels and nerves. The former Fig. 1.10. Main branches of (A) the right and (B) the left bronchi.
are involved in warming and humidifying the air. The 1: branch to cranial region of lung; 2: branch to cardiac region of lung;
3: branch to accessory lobe; 4: branch to caudal lobe.
nerves include non-myelinated neuropeptide-containing
sensory nerves and branches of the sympathetic nervous
system that supply the bronchial blood vessels (Sonea et al
1993a,b, 1994a,b, 1999). Smooth muscle encircles the diaphragm. The surface of the horse lung shows the
bronchi and bronchioles and receives parasympathetic and fibrous connective tissue septa that divide the lung into
inhibitory non-adrenergic non-cholinergic innervation lobules. However, these are less distinct than in the pig or
(Broadstone et al 1991, Yu et al 1992, 1994). cow. The separation of the lung into lobules limits the
collateral movement of air between different lung regions
(Robinson & Sorenson 1978, Robinson 1982). The greatest
bulk of the horse lung is in its caudodorsal region. This
The Lungs means that in the standing animal, much of the lung is
Apart from their first few centimeters, the bronchi are almost dorsal to the diaphragm (Figs 1.11 and 1.13).
totally surrounded by the lung parenchyma (Fig. 1.11).
Unlike the lungs of most other mammals, the horse lung is The bronchovascular bundle
not divided into distinct lobes. Viewed from the costal
surface, both the right and left lung have a similar shape Anyone who views a radiograph of the lung notices
with a ventral notch that accommodates the heart that the bronchi and large blood vessels run together
separating the smaller cranial portion from the larger (Fig. 1.11B). The distribution of bronchi and arteries is
caudal portion. The right lung is larger than the left in part almost identical down to the most peripheral airways.
because it includes the intermediate or accessory lobe, While most veins follow the larger bronchi, some also track
which fills the space caudal to the heart and cranial to the through the lung away from the airways and arteries.
T
B
Cr
Cup
Fig. 1.11. (A) Lateral view of the thorax of a foal with pneumonia. The
radiograph was taken with the foal standing. Note that much of the
lung is dorsal to the diaphragm, which slopes steeply forward to the
cupola (Cup) that is at the level of the sixth to seventh rib. The trachea
reaches a low point at the thoracic inlet (T) and bifurcates into the
bronchi (B) above the heart. The white arrow marks the shadow
created by the caudal margin of the shoulder muscles. In older horses,
the mass of these muscles obscures much of the cranial lung (Cr).
(B) Enlargement of the caudal region of the lung to show the branch-
ing of the airways and vasculature in this abnormal lung.
The associated bronchi and blood vessels are contained in are not useful for the identification of bronchiolar inflam-
the bronchovascular bundle, which is a loose connective- mation such as occurs in inflammatory airway disease. In
tissue sheath that also contains lymphatics and nerves. some mammals, there are respiratory bronchioles, the
The loose connective tissue is a sink in which edema latter being identified by alveoli that open directly from the
accumulates whenever fluid filtration rate in the lung is bronchiolar wall. Horses lack these respiratory bronchioles
increased, for example in pulmonary edema. When this and the terminal non-respiratory bronchiole connects
occurs, the fluid increases the radiographic density in the directly to the alveolar duct (McLaughlin et al 1961, Tyler
peribronchial region. et al 1971). In the bronchioles, the epithelium is a single
layer of cuboidal cells (Fig. 1.14). The primary secretory
Bronchioles cell is the Clara cell that has an extensive network of
smooth endoplasmic reticulum (Plopper et al 1980).
Several generations of bronchioles, which can be differen- Ciliated epithelial cells are also present in the bronchioles
tiated from bronchi by the absence of cartilage in their but are less dense in number than in the larger airways.
walls, connect the small bronchi to the alveolar ducts and Mucus-secreting goblet cells do not occur in the
alveoli. Because of their small size and the absence of carti- bronchioles of young healthy horses but are found in horses
lage, bronchioles cannot be distinguished radiographically that have airway inflammation (Kaup et al 1990). As in the
from the surrounding alveoli. For this reason, radiographs bronchi, a layer of smooth muscle encircles the bronchioles.
m m
gc gc
gc gc
n n
V
L
A
Fig. 1.12. Bronchial epithelium of a horse with recurrent airway Fig. 1.13. Ventrodorsal radiograph of the lung of a foal with pneu-
obstruction (heaves). Note the thick layer of mucus (m) containing monia. The shadow of the diaphragm is outlined. Note that the lung
many neutrophils, the multiple layers of epithelial nuclei (n) in the (L) extends far caudally and dorsally on either side of the abdomen.
pseudostratified columnar epithelium, and the mucus-producing The bronchi and vessels (V) in the caudal part of the lung are difficult
goblet cells (gc) interspersed among the ciliated epithelium. (Giemsa to see because the abdomen overlies that part of the lung. Without
stain.) careful scrutiny, it would be easy to miss the abscess (A) because it is
obscured by the abdominal contents.
Alveolar ducts and alveoli

Gas exchange occurs in the alveolar ducts and alveoli. The endoplasmic reticulum and the Golgi apparatus is large.
former are extensions of the bronchioles and can form The characteristic feature of the type II cell is the presence
several generations, each of which has numerous alveoli in of large vesicles that contain the precursors of pulmonary
its walls. The alveolar structure of the lung results in a surfactant, the phospholipid that is essential for lung
large surface area for gas exchange. In a 510-kg horse, stability. Surfactant is released from the type II cells in the
the total alveolar surface area is reported to be 2,456 m2 form of myelin coils that unfurl when they reach the
(Gehr & Erni 1980) (one-quarter of a hectare) of which alveolar surface. Type II cells also re-uptake components of
about 1,500 m2 is in contact with pulmonary capillaries surfactant to be resynthesized. In addition to production
and available for gas exchange (Gehr & Erni 1980, Stone of surfactant, type II cells also reabsorb edema fluid from
et al 1992). Two types of epithelial cells line the alveoli. the alveoli, and, when the alveolar surface is injured and
The terminally differentiated squamous type I cell covers type I cells are lost, the type II cells differentiate into type I
most of the surface but the cuboidal type II cell is more cells to recover the surface.
numerous (Stone et al 1992). The type I cell is charac-
terized by very thin cytoplasmic extensions that extend The alveolar septum
away from the nucleus over the alveolar surface in the
same way that egg white extends away from the egg yolk Neighboring alveoli are separated by the alveolar septum
in a frying pan. Its cytoplasm has few organelles other that contains the pulmonary capillaries (Fig. 1.15). The
than pinocytotic vesicles and a few mitochondria. By air is separated from the capillary blood by the type I
contrast with the type I cell, the type II cell shows evidence epithelial cell, a basement membrane, a variable amount
of being metabolically very active. Its cytoplasm is rich in of interstitium and the endothelial cell. The quantitative
(Fig. 1.16). The capillary network in the septum is so

extensive that it has been compared to a sheet of blood.
Because there are no lymphatics in the alveolar septum,
fluid that filters from the pulmonary capillaries must
track through the interstitium to the lymphatics in the
peribronchial tissue.
e
Lymphatic networks
The lung possesses two networks of lymphatics. One
L surrounds the bronchi while the other is subpleural. Both
these networks connect to the hilar and mediastinal lymph
nodes and drain into the thoracic duct.
The Pulmonary Circulation

m The pulmonary circulation receives the whole output of
the right ventricle and delivers it through the pulmonary
capillaries and back to the left atrium. It is the branch of
the circulation involved in the uptake of oxygen and
removal of carbon dioxide. Its anatomy and function are
Fig. 1.14. Bronchiole from a healthy horse. The epithelial layer (e) described in Chapter 3.
consists of a single layer of cuboidal cells that encircles the lumen (L).
The epithelium is folded because the lung was collapsed when the
section was taken. In life the perimeter of the airway would form a The Bronchial Circulation
circle. A layer of smooth muscle (m) encircles the airway. There are no
The bronchial circulation is a branch of the systemic
mucus-producing goblet cells in this healthy bronchiole. (Hematoxylin
and eosin) circulation from which it receives about 2% of the cardiac
output (Magno 1990). It provides the nutritional blood
flow to the walls of the bronchi and large blood vessels
characteristics of this barrier have been described in the and to the pleura. In the bronchi, the submucosal plexus
horse and other species (Stone et al 1992). On one side of of bronchial vessels is important for warming and
the septum, the separation of air and blood is less than humidifying air and in the immune response. As the
0.1 μm because there is no interstitium and few organelles intensity of exercise increases, so does the magnitude of
in the epithelial or endothelial cells. On the opposite side, bronchial circulatory blood flow (Manohar et al 1992). The
the membrane is somewhat thicker because an inter- venous drainage of the bronchial circulation is complex.
stitial space separates the two cell types and they contain Some returns to the azygos vein but some also enters
more organelles. It is thought that gas exchange occurs on the pulmonary veins thereby adding venous blood to the
the thin side of the septum and fluid exchange between oxygenated blood that is leaving the capillaries. If the blood
the capillary and interstitium occurs on the thicker side supplied by the pulmonary circulation becomes reduced in
BR
BR
AD
A
AD
A B C
Fig. 1.15. Scanning electron micrographs of the alveoli of a horse. (A) An artery (A) adjacent to several
bronchioles (BR). An alveolar duct (AD) and alveoli are also visible. (B) A bronchiole (BR) terminating in an
alveolar duct (AD) and surrounded by alveoli. (C) Several alveoli that have been overdried during
preparation so that the outlines of the numerous erythrocytes in the alveolar capillaries are visible.
Reproduced with the permission of W.S. Tyler, University of California, Davis, CA.
Endo, BM, Epi
Alveolus
Capillary
Interstitium
Alveolus Epithelium
Fig. 1.16. Transmission electron micrograph of a pulmonary capillary in the alveolar septum. The septum
separates two alveoli. On the lower side of this capillary, the endothelium and epithelium are separated
by a thick layer of interstitium that allows movement of interstitial fluid within the alveolar septum. On
the upper side, the endothelium (Endo) and epithelium (Epi) are separated only by a thin common
basement membrane (BM). This thin side, which is less than 1 μm in thickness, is probably where most
gas exchange occurs.
a region of lung, the connections between the pulmonary sists of the skin, subcutaneous tissues, intercostal muscles,
and bronchial circulations allow blood to enter that region ribs, parietal pleura, sternum and thoracic vertebrae.
from the bronchial circulation thereby tending to reduce The diaphragm is attached to the thoracic wall along the
the chance of ischemia. eighth to tenth costal cartilages, then to the costochondral
The bronchial circulation is involved in inflammation, junctions of ribs 10 to 13 and then to the ribs at increasing
healing and remodeling of the lung. In horses with lesions distances from their costochondral junctions until it
of exercise-induced pulmonary hemorrhage, the bronchial reaches the last intercostal space. In the median plane,
circulation proliferates in the walls of the inflamed airways each hemidiaphragm extends cranially to the level of the
(O’Callaghan et al 1987). In humans, this neovasculariza- fifth or sixth rib, which approximates to the level of the
tion can be a cause of hemoptysis. olecranon in the standing horse. Because the cupola of the
diaphragm extends so far cranially and its attachments are
to each rib, much of the thoracic cavity is lateral to or
The Thorax above the abdomen (Figs 1.11 and 1.13). For this reason,
The horse’s thorax has 18 ribs that form a fairly rigid borborygmi originating in the intestines are frequently
protection for the intrathoracic organs. Each rib articulates heard during auscultation of the lung. The diaphragm
dorsally with the vertebral column and is extended consists of a tendinous center through which passes
ventrally by a costal cartilage. The costochondral junctions the vena cava. The striated muscle is arranged around the
can be palpated beneath the skin in a line that follows diaphragm’s periphery. It consists of the pars costalis,
roughly a line drawn between the tuber sacrale and which originates from the ribs and inserts into the central
the elbow. The first eight ribs articulate directly with the tendinous portion, and the left and right crura, which are
sternum. The costal cartilages of ribs 9 to 17 are attached connected to the vertebrae by tendons and insert in the
to each other by elastic tissue to form the costal arch. The tendinous center of the diaphragm. The left crus is pierced
last rib is a floating rib. The thorax is long and laterally by the aorta, esophagus and vagus nerve. The phrenic
compressed at its anterior end. Because of the downward nerve innervates the muscles of the diaphragm.
curvature of the vertebra in the anterior thorax, the
thoracic inlet is only 18–20 cm high and it is about 10 cm The pleurae
wide. The proximal forelimb covers the cranial part of the
thoracic wall to the level of the fifth or sixth rib (Fig 1.11), The pleurae cover all of the surfaces of the thoracic cavity
while the thinner serratus ventralis thoracis muscle covers without interruption. The visceral pleura covers the lungs
much of the first eight or nine ribs. The thoracic wall con- and joins the mediastinal pleura at the hilar region. The
parietal pleura is described as costal, diaphragmatic and Holcombe SJ, Derksen FJ, Stick JA et al 1998 Effect of bilateral
mediastinal where it covers the ribs, diaphragm and medi- blockade of the pharyngeal branch of the vagus nerve
astinal structures, respectively. In some horses the two on soft palate function in horses. American Journal of
Veterinary Research 59: 504–508
pleural sacs communicate via small fenestrations where the Holcombe SJ, Cornelisse CJ, Berney C et al 2002 Electro-
two thin layers of mediastinal pleura are apposed in the myographic activity of the hyoepiglotticus muscle and
caudal mediastinum. The pleural and peritoneal cavities control of epiglottis position in horses. American Journal
communicate via diaphragmatic pores and lymphatics. of Veterinary Research 63: 1617–1621
The parietal pleura has numerous stomata connected Kaup F-J, Drommer W, Damsch S et al 1990 Ultrastructural
findings in horses with chronic obstructive pulmonary
to subpleural lymphatics that serve to remove excessive disease (COPD) II: pathomorphological changes of the
pleural fluid, protein, and cells. The pleural cavity is a terminal airways and the alveolar region. Equine
potential space that normally contains only a small volume Veterinary Journal 22: 349–355
of clear to slightly turbid yellowish, non-clotting pleural Kumar P, Timoney JF 2001 Light and electron microscope
fluid. The chest wall and parietal pleura, but not the studies on the nasopharynx and nasopharyngeal ton-
sil of the horse. Anatomy Histology and Embryology
visceral pleura, are well endowed with sensory nerve fibers 30: 77–84
from the intercostal nerves, and consequently pleural Kumar P, Timoney JF 2005 Histology and ultrastructure of
inflammation can cause overt pleurodynia (thoracic pain). the equine lingual tonsil. I. Crypt epithelium and asso-
The parietal pleura receives its blood supply from the inter- ciated structures. Anatomy Histology and Embryology
costal vessels, with the principal vessels running imme- 34: 27–33
Kumar P, Timoney JF, Southgate HH et al 2000 Light and
diately caudal to each rib. Blood supply to the visceral pleura scanning electron microscopic studies of the nasal tur-
is from the pulmonary and bronchial vasculature with binates of the horse. Anatomy Histology and Embryology
capillary loops occupying the deep aspect of the pleura. 29: 103–109
The pleurae comprise a single layer of mesothelial cells Magno M 1990 Comparative anatomy of the tracheo-
and underlying connective tissue. Mesothelial cells not bronchial circulation. European Respiratory Journal
12: 557s–562s; discussion 562s–563s
only act as an envelope lining the pleural cavities but also Manglai D, Wada R, Endo H et al 2000a Macroscopic anatomy
have an active role in trans-serosal transport of fluid and of the auditory tube diverticulum (guttural pouch) in
electrolytes, aided by apical microvilli that increase their the thoroughbred equine – a silicon mold approach.
surface area for absorption. Mesothelial cells also synthe- Okajimas Folia Anatomica Japonica 76: 335–346
size components of the underlying connective tissue, Manglai D, Wada R, Kurohmaru M et al 2000b Histological
and morphometrical studies on the mucosa of the equine
cytokines, growth peptides and chemotaxins. Inflammatory guttural pouch (auditory tube diverticulum). Okajimas
stimuli activate mesothelial cells leading to increased Folia Anatomica Japonica 77: 69–76
production of biologically active compounds, fibrinolysis Manohar M, Duren SE, Sikkes BP et al 1992 Bronchial
and possibly phagocytic function. circulation during prolonged exercise in ponies. American
Journal of Veterinary Research 53: 925–929
McCann JL, Dixon PM, Mayhew IG 2004 Clinical anatomy of
REFERENCES the equine sphenopalatine sinus. Equine Veterinary
Journal 36: 466–472
Art T, Lekeux P 1991a The effect of shape, age and exten- McLaughlin RF, Tyler WS, Canada RO 1961 A study of the
sion on the compliance of equine tracheal segments. subgross pulmonary anatomy in various mammals.
Veterinary Research Communications 15: 135–146 American Journal of Anatomy 108: 149
Art T, Lekeux P 1991b Mechanical properties of the isolated O’Callaghan MW, Pascoe JR, Tyler WS et al 1987 Exercise-
equine trachea. Research in Veterinary Science 51: 55–60 induced pulmonary haemorrhage in the horse: results of
Baptiste KE, Naylor JM, Bailey J et al 2000 A function for a detailed clinical, post mortem and imaging study. III.
guttural pouches in the horse. Nature 403: 382–383 Subgross findings in lungs subjected to latex perfusions of
Barakzai S 2004 The equine paranasal sinuses. Part 1: the bronchial and pulmonary arteries. Equine Veterinary
Anatomy. UK Vet 9: 1–3 Journal 19: 394–404
Bell BT, Baker GJ, Abbott LC et al 1995 The macroscopic Plopper CG, Mariassy AT, Hill LH 1980 Ultrastructure of the
vascular anatomy of the equine ethmoidal area. Anatomy nonciliated bronchiolar epithelial (Clara) cell of mam-
Histology and Embryology 24: 39–45 malian lung: II. A comparison of horse, steer, sheep, dog,
Broadstone RV, Scott JS, Derksen FJ et al 1991 In vitro response and cat. Experimental Lung Research 1: 155–169
of airway smooth muscle from horses with recurrent air- Robinson NE 1982 Some functional consequences of species
way obstruction. Pulmonary Pharmacology 4: 191–202 differences in lung anatomy. Advances in Veterinary
Gehr P, Erni H 1980 Morphometric estimation of pulmonary Science and Comparative Medicine 26: 1–33
diffusion capacity in two horse lungs. Respiration Robinson NE, Sorenson PR 1978 Collateral flow resistance and
Physiology 41: 199–210 time constants in dog and horse lungs. Journal of
Holcombe SJ, Derksen FJ, Stick JA et al 1997 Effect of bilateral Applied Physiology 44: 63–68
tenectomy of the tensor veli palatini muscle on soft palate Smith BL, Aguilera-Tejero E, Tyler WS et al 1994 Endoscopic
function in horses. American Journal of Veterinary anatomy and map of the equine bronchial tree. Equine
Research 58: 317–321 Veterinary Journal 26: 283–290
Sonea IM, Bowker RM, Broadstone RV et al 1993a Adrenergic Stone KC, Mercer RR, Gehr P et al 1992 Allometric relation-
and peptidergic innervation of the trachealis muscle in ships of cell numbers and size in the mammalian lung.
the normal horse: a preliminary report. Research in American Journal of Respiratory Cell and Molecular
Veterinary Science 54: 335–339 Biology 6: 235–243
Sonea IM, Bowker RM, Robinson NE et al 1993b Distribution Tessier C, Holcombe SJ, Derksen FJ et al 2004 Effects of stylo-
of dopamine β-hydroxylase and neuropeptide Y immuno- pharyngeus muscle dysfunction on the nasopharynx in
reactive nerves in healthy equine lungs. American exercising horses. Equine Veterinary Journal 36: 318–323
Journal of Veterinary Research 54: 507–513 Tyler WS, Gillespie JR, Nowell JA 1971 Modern functional
Sonea IM, Bowker RM, Robinson NE et al 1994a Substance P morphology of the equine lung. Equine Veterinary Journal
and calcitonin gene-related peptide-like immunoreactive 3: 84–94
nerve fibers in lungs from adult equids. American Journal Widdicombe JH, Pecson IS 2002 Distribution and numbers of
of Veterinary Research 55: 1066–1074 mucous glands in the horse trachea. Equine Veterinary
Sonea IM, Bowker RM, Robinson NE et al 1994b Distribution Journal 34: 630–633
of SP- and CGRP-like immunoreactive nerve fibers in the Yu M, Robinson NE, Wang Z et al 1992 Muscarinic receptor
lower respiratory tract of neonatal foals: evidence for loss subtypes in equine tracheal smooth muscle. Veterinary
during development. Anatomy and Embryology (Berlin) Research Communications 16: 301–310
190: 469–477 Yu M, Wang Z, Robinson NE et al 1994 Inhibitory nerve
Sonea IM, Bowker RM, Robinson NE 1999 Distribution of distribution and mediation of NANC relaxation by nitric
substance P binding sites in equine airways. Equine oxide in horse airways. Journal of Applied Physiology
Veterinary Journal 31: 238–242 76: 339–344
How Horses Breathe: the Respiratory Muscles
and the Airways
2 N Edward Robinson
A maximally exercising thoroughbred horse consumes chial tree until it reaches the alveoli. Here, by diffusion,
75 liters or 19 gallons of oxygen per minute. This oxygen oxygen passes into the pulmonary capillary blood where it
consumption of 150 ml·kg–1·min–1, which is one of the combines with hemoglobin to be transported to the tissues,
highest among mammals, is the result of densely packed for example, exercising muscle. Because the exercising
mitochondria in the skeletal muscles (Kayar et al 1989). muscle is continually consuming oxygen, the local tissue
The delivery of oxygen from the air to the mitochondria PO2 is lower than that of arterial blood. This allows
begins with ventilation, which is the process that moves air diffusion of oxygen from hemoglobin through plasma into
into and out of the lung. To supply its oxygen demand, the the tissues. At the same time, carbon dioxide is leaving the
galloping thoroughbred inhales a tidal volume of 13 liters tissues and entering the blood to be returned to the lungs
about 120 times per minute, which results in a minute and eliminated by ventilation. This whole process is care-
ventilation of approximately 1400 liters/min. Moving fully regulated so that ventilation, blood flow through the
13 liters of air into and out of the lung within half a lungs to the tissues, and gas transport in the blood are
second requires peak airflows of up to 90 liters/second. adjusted to meet the needs of exercise and other metabolic
demands. This chapter describes the processes involved in
ventilation. Pulmonary blood flow and gas exchange are
The Pathway for Oxygen described in Chapters 3 and 4, respectively.
Oxygen reaches the mitochondria from, and carbon dioxide
is eliminated to, the atmosphere by processes of bulk flow,
diffusion and transport in the blood. At all stages of
What are Airways?
delivery, oxygen is moving down a concentration gradient The airways begin at the external nares and terminate at
that is measured as the oxygen partial pressure (PO2) the alveoli. Between these points is a series of branching
(Fig. 2.1). Atmospheric air enters the nares and is dis- tubes of decreasing diameter (see Chapter 1), the main
tributed among the various branches of the tracheobron- purpose of which is to conduct air into and out of the
alveoli. Secondary, but also vital, functions of the airways
include defense of the lungs against airborne irritants,
infectious agents, and toxins, and warming and humidi-
175 Airflow fication of air. These functions occur to varying degrees at
150 different levels of the airways (Table 2.1).
125 Diffusion
Blood flow Diffusion
Po2 (torr)
100 Replenishing the Air in the Lungs

75
Once the newborn foal takes its first breath, the lungs
50
never empty completely. At all times, the lungs contain a
25 large volume of air that allows gas exchange to continue as
0 some of the used air is eliminated during exhalation and
y
y
r
us
ell
ry
lus
Ai
ter
lar
some new air is brought in during inhalation.

illa
c
ch
pil
Ar
le
ve
on
ap
sc
ca
Al
Br
Mu
le
v.
Al
sc
Mu
Volume expansion in the lung occurs in the

alveolar ducts and alveoli
Fig. 2.1. Oxygen is delivered from the atmosphere to the muscle cells
down a partial pressure (PO2) gradient that is steeper during exercise
During inhalation, the increased capacity of the lung is
(white bars) than at rest (blue bars). Oxygen is transported by airflow
from the atmosphere into the smaller airways, by diffusion within the brought about by expansion of the alveoli and alveolar
alveoli and into the blood, by vascular transport to the capillaries, and ducts. A network of elastic fibers ramifying throughout the
then by diffusion into the tissues. alveolar septa and walls of the terminal airways and
19
20 2 How Horses Breathe: the Respiratory Muscles and the Airways
have been reported after transportation (Hobo et al 1997).

Table 2.1. Major functions of the
divisions of the airways The functional significance of these changes awaits further
investigation.
Airway Functions The presence of adequate amounts of surfactant is
Nasal cavity High-velocity airflow essential for lung stability after birth. While the use of
Warming and humidification of air naturally derived and synthetic surfactants is routine
Thermoregulation by evaporative heat loss procedure in the treatment of premature humans, their
Removal of large particulates use is only beginning to be explored in neonatal and
Removal of soluble pollutants
premature foals.
Pharynx High-velocity airflow
Separation of air and food
Lung volumes
Larynx High-velocity airflow
Regulation of airflow The volume of air inhaled in each breath is known as a
Separation of air and food tidal volume. In a resting 500-kg horse, tidal volume
Phonation averages 4–5 liters. At the end of a tidal exhalation, the
Trachea High-velocity airflow lung still contains about 20 liters of air (approximately
Warming and humidification 40 ml/kg) (Aguilera-Tejero et al 1993), about 45% of its
Removal of moderate-sized particulates total lung capacity. This volume of air, known as the
Removal of soluble pollutants functional residual capacity, provides a reservoir so that
Initiation of cough
gas exchange continues unabated between each breath.
Bronchi Moderate-velocity airflow Maintaining a functional residual capacity also ensures
Distribution of air within the lung that the airways and alveoli stay open, which decreases
Removal of moderate-sized particulates the work required to inhale. In many mammals, includ-
Initiation of cough
ing humans, functional residual capacity represents the
Bronchioles Low-velocity airflow mechanical equilibrium of the respiratory system where
Distribution of air to gas exchange units the inward pull of the lungs is balanced by the outward
Removal of small particulates recoil of the rib cage. By contrast, in horses, the mechan-
Alveoli Air moves by diffusion ical equilibrium of the respiratory system occurs in the
Gas exchange with pulmonary capillary blood midst of the tidal volume. This has important consequences
Phagocytosis of small particulates for the strategy that horses use to breathe (see below).
Total lung capacity is the maximal volume of air that
can be held by the respiratory system and residual volume
connected to the pleura and larger bronchi provides this is the air remaining after a maximal exhalation. These two
part of the respiratory tract with elasticity. In addition, the volumes are determined by the mechanical limits of the
air–liquid interface in the alveoli generates a surface lung and chest wall. Vital capacity is the difference between
tension that is also responsible for lung elasticity. the two and is the maximal possible tidal volume. In
horses, vital capacity measured by forcefully inflating and
Pulmonary surfactant greatly reduces the then deflating the lungs is about 42 liters (Couetil et al
surface tension of the alveolar lining 2000). It is unlikely that a horse ever takes a breath equal
Type II alveolar epithelial cells produce pulmonary to the vital capacity.
surfactant without which the surface tension of the lung
lining fluid would be so high that the lung would col-
lapse. Surfactant is a mixture of phospholipids, primarily
Breathing in the Resting Horse
dipalmitoyl phosphatidylcholine, and proteins. It seeks the Because the mechanical equilibrium of the respiratory
surface of the alveolar lining fluid and by displacing water system of the horse lies at the midpoint of a normal tidal
molecules it reduces the surface tension. As the lung volume, the resting horse uses a biphasic pattern of
decreases in volume during exhalation, the surfactant breathing with passive and active components to both
molecules became more concentrated on the surface and inhalation and exhalation (Fig. 2.2) (Koterba et al 1988).
further reduce surface tension, which makes the alveoli This pattern of breathing can be easily observed by watch-
very stable at low lung volumes. The proteins in surfactant ing a horse’s flanks. The lung volume at end exhalation is
have a variety of functions concerned with recruitment of below the equilibrium position of the respiratory system so
surfactant to the lung surface, recycling of surfactant into that inhalation begins by allowing the respiratory system
type II cells, and antibacterial defense. In horses, changes to passively expand back to the equilibrium position. This
in surfactant activity have been described after exercise can be seen as a rapid outward movement of the lower
(Morrison et al 1999) and changes in surfactant content abdomen. The second part of inhalation involves active
2 How Horses Breathe: the Respiratory Muscles and the Airways 21
I
300 A B
14 1600 0.2
Flow 0
(l/min) 12 1400
300 1200 0.4
E 10
Ventilation (l/min)
1000
Volume (l)
8
Edi 800
6
600
4 400
Eint
2 200 0.6
0 0
Eabd 0 10 14 0 10 14
Speed (m/s)
Time 2s
Fig. 2.3. Tidal volume and ventilation in exercising horses. (A) Tidal
volume (height of total bar), physiological dead space volume (height
Fig. 2.2. Airflow and respiratory muscle EMG activity in a resting
of gray bar), and alveolar volume (height of blue bar). (B) Minute
horse. The upper trace shows airflow with inhalation upwards and
ventilation (height of total bar), dead space ventilation (height of gray
exhalation downwards. Note that inhalation and to a lesser extent
bar), and alveolar ventilation (height of blue bar). As exercise intensity
exhalation are biphasic. Electrical activity in the diaphragm (Edi) is
increases, tidal volume and minute ventilation increase but the physio-
greatest during the second peak of inhalation. Intercostals (Eint) are
logical dead space remains constant so that more of each breath
active during inhalation and the early exhalation. Abdominal muscle
participates in gas exchange (alveolar ventilation). The dead space to
activity (Eabd) peaks in the latter half of exhalation but persists
tidal volume ratio is indicated above each bar. Drawn from data in
somewhat into early inhalation. Redrawn from Koterba et al, 1988,
Pelletier & Leith, 1995, with permission.
Fig. 5, with permission.
contraction of the diaphragm and other inspiratory 2000

Minute
muscles that is visible as an expansion of the caudal part of
the rib cage. Exhalation begins with passive recoil of the 1600
Ventilation (l/min)
respiratory system down to its equilibrium position (inward

movement of the caudal ribs) and ends with contraction 1200
of the abdominal muscles that is visible as an upward Alveolar
800
movement of the abdomen. The latter forces the respiratory
system below its equilibrium so that the next inhalation
400
begins with relaxation of the abdomen. The combination of
both passive and active components to inhalation and 0
exhalation results in a biphasic pattern of airflow in the –10 0 10 20 30 40
resting horse. Rest Minutes of exercise
Fig. 2.4. Effect of prolonged heavy exercise on minute and alveolar

Not all the air entering the lungs participates ventilation. As exercise at a constant workload progresses, alveolar
in gas exchange ventilation remains virtually constant but minute ventilation increases
because the horse requires more dead space ventilation for thermo-
In the resting horse, only one-third of each breath regulation. Redrawn from Hopkins et al, 1998, Fig. 1, with permission.
participates in gas exchange by reaching the alveoli
(Pelletier & Leith 1995, Hopkins et al 1998). The rest of
the breath occupies the dead space, that is the conduct- horse, most of the minute ventilation participates in gas
ing airways and some unperfused or poorly perfused exchange as alveolar ventilation increases and the dead
alveoli. Thus out of the total minute ventilation of space to tidal volume ratio decreases during exercise
60–100 liters/min, one-third is alveolar ventilation and (Fig. 2.3). As the horse exercises for longer periods, however,
two-thirds is dead space ventilation (Fig. 2.3). its dead space ventilation increases to meet the demands of
thermoregulation (Fig. 2.4) (Hopkins et al 1998).
Ventilation Increases During Exercise
Breathing pattern during exercise
As the gas exchange demands increase during exercise,
there is a need for more minute ventilation; this increase is At the walk and trot, there is no clear relationship between
accomplished by an increase in both tidal volume and the frequency of breathing and footfall (Hornicke et al
respiratory frequency. Unlike the situation in the resting 1982). However, at the canter and the gallop, breathing is
140 0
120 –10
100
Ppl (cmH2O)
–20
Per min
80
–30
60
–40
40
20 –50
0 120
Rest Walk Slow trot Canter Gallop
100
EMG (% maximum)
Fig. 2.5. Relationship between respiratory and step frequencies. At 80
slow gaits, step frequency (black line) is unrelated to breathing fre-
quency (blue line). At the canter and gallop, the two frequencies are 60
identical. Drawn from data in Hornicke et al, 1982, with permission.
40
20
0
synchronized with gait (Fig. 2.5), so that inhalation occurs Rest Walk Canter Gallop
when the forelimbs extend and exhalation occurs when the
Fig. 2.6. Effect of exercise on pleural pressure change during breath-
forelimbs are on the ground and hind limbs are moving
ing (Ppl) and on diaphragmatic EMG activity. As exercise intensity
forwards. The horse usually takes one breath per stride but increases, the diaphragm becomes increasingly active and this leads to
when it sighs, it takes two strides to inhale the larger tidal a greater decrease in pleural pressure. Redrawn from Ainsworth et al,
volume. The coordination between gait and breathing is 1996, with permission.
also altered if the horse is having difficulty breathing, for
example, as the result of an airway obstruction. In the
latter situation, the horse may need more time to inhale
and may therefore take two strides to inhale. 350
Blood flow (ml•min-1•100g-1)
Rest
300 Exercise
The coordination of gait and breathing can help 250
in the diagnosis of airway obstructions 200
Certain types of upper airway obstructions, for example
150
recurrent laryngeal neuropathy, cause dynamic collapse of
100
the airway during inhalation while others, for example
dorsal displacement of the soft palate, cause obstruction 50
during exhalation. Temporally relating the occurrence of 0
Diaphragm Intercostal Gluteus
the abnormal sounds to the phase of the stride can help to medius
determine if the obstruction is occurring during inhalation
or exhalation. For example, if the abnormal sound occurs Fig. 2.7. Effect of exercise on blood flow in respiratory and locomotor
while the forelimbs are being extended, the obstruction muscles. Diaphragmatic and gluteal (locomotor) blood flow increase
is occurring during inhalation. If it occurs when the to similar degrees and more than intercostal blood flow. Drawn from
data in Manohar, 1986, with permission.
forelimbs are weight bearing, the obstruction is occurring
during exhalation.
so that contraction pulls the tendinous center of the

The Respiratory Muscles diaphragm backwards, thus making it flatter and thereby
The diaphragm is the principal enlarging the thorax and compressing the abdominal
inspiratory muscle contents. Diaphragmatic activity increases as exercise
intensity increases and concurrently the magnitude of the
Contraction of the respiratory muscles provides the energy decrease in pleural pressure also increases (Fig. 2.6)
necessary to move air between the atmosphere and the (Ainsworth et al 1996). The increase in diaphragmatic
lungs. The diaphragm, which is the principal inspiratory blood flow during exercise is dramatic and similar to that in
muscle, is dome-shaped with a tendinous center that the muscles of locomotion (Fig. 2.7) (Manohar 1986).
reaches forward to contact the heart. The muscles of the Diaphragmatic activity also increases during the hyperpnea
diaphragm are at its margin and muscle fibers are aligned associated with hypoxia or hypercapnia and when the
horse breathes against an airway obstruction such as that Exhalation involves contraction
provided by laryngeal hemiplegia. The diaphragm has a of abdominal muscles
large functional reserve of oxidative capacity so that even
during heavy work it seems able to generate its energy As noted above, exhalation results in part from the elastic
by aerobic metabolism (Manohar et al 1988, 1992, Poole recoil of the respiratory system towards its equilibrium
et al 2002). The hypoventilation that occurs in cases of position but also from activity of expiratory muscles,
diaphragmatic paralysis indicates the importance of the primarily the abdominal muscles (Koterba et al 1988).
diaphragm as a respiratory muscle (Amory et al 1994). Measurements of blood flow during exercise suggest that
the internal abdominal oblique muscle is more active
Intercostals are active during inhalation than the transversus abdominis, rectus abdominis, or exter-
In most mammals, the external intercostal muscles are nal abdominal oblique muscles (Manohar et al 1992).
active during inhalation and serve to move the ribs When the abdominal muscles contract, abdominal pressure
forwards and outwards, so enlarging the thorax. In the increases and the diaphragm is pushed forwards, thus
horse, there is very little change in chest circumference reducing the volume of the thorax. The internal intercostal
during quiet breathing and therefore the contribution of muscles are active during exhalation. Because there is little
the external intercostal muscles to thoracic enlargement is change in chest circumference, these muscles probably
probably quite small. Under certain circumstances, for stiffen the ribs to resist the increase in intrathoracic
example in post-exercise hyperpnea, chest circumference pressure caused by cranial movement of the diaphragm.
increases during inhalation. Surprisingly, during exercise, Muscular activity is not required to keep the upper airway
the chest circumference decreases slightly rather than open during exhalation because pressure within the airway
increasing during inhalation and therefore contributes is greater than atmospheric pressure and therefore passive
nothing to the large tidal volume (Marlin et al 2002). This airway dilatation occurs.
decrease in circumference is probably a result of the large
negative pressures being generated in the thorax by
contraction of the diaphragm. Even though the chest
During Breathing there are Cyclic Changes
circumference does not increase, the increase in intercostal
in Pleural Pressure
muscle blood flow during exercise (Manohar 1986) During inhalation, contraction of the respiratory muscles
indicates that these muscles are active and probably enlarges the thorax and this causes a decrease in pleural
stiffening the rib cage to resist the deformation caused by pressure (Ainsworth et al 1996) (Fig. 2.6) that is used to
the change in pleural pressure. Not only does the chest stretch the lung, to generate airflow against the fric-
circumference not change much during exercise, neither tional resistance provided by the tracheobronchial tree,
does the abdominal circumference. This leads to the and to accelerate and decelerate the inspired air. During
conclusion that most of the large tidal volume taken in exhalation, the energy stored in the stretched lung
during exercise is accommodated by the elongation of the plus that generated by the expiratory muscles increases
thoracoabdominal segment (Young et al 1992, Marlin et al the pleural pressure and generates airflow against the
2002) that is occurring in synchrony with gait and with airway resistance.
diaphragmatic contraction. At the end of exhalation in the resting horse, pleural
pressure is between –3 and –5 cmH2O, that is, 3 to
Other muscles that are active during inhalation 5 cmH2O below atmospheric pressure. This subatmospheric
Other muscles that are active during inhalation include the pressure occurs because the lung is stretched and therefore
abductor muscles of the larynx, pharynx, and external trying to collapse away from the rib cage. If the rib cage is
nares. Activity in the latter group of abductor muscles opened, the subatmospheric pressure causes air to rush
begins late in exhalation and peaks early in inhalation so into the pleural cavity and the lung collapses (Fig. 2.8).
that the upper airway is dilated and stiffened before it is When the inspiratory muscles contract and the thorax
exposed to the subatmospheric pressures that are generated enlarges, pressure in the pleural cavity decreases, that is, it
during inhalation. Failure of the abductor muscles to becomes more subatmospheric. The lung is expanded by
activate during inhalation can give rise to dynamic collapse this decrease in pleural pressure and expansion decreases
of the upper airway. Laryngeal hemiplegia, which results the pressure within the alveoli so that air flows into the
from recurrent laryngeal neuropathy, is a prime example lung. In the resting horse, pleural pressure decreases to
of dynamic collapse that is a result of the failure of abduc- about –10 cmH2O but, during intense exercise, pleural
tor muscle function, in this case the cricoarytenoideus pressure decreases to –30 cmH2O or less (Fig. 2.6). During
dorsalis. In other species, the muscles that connect the exhalation, pleural pressure increases (becomes less nega-
sternum to the head, for example the sternocephalicus, tive) and, even in the resting horse, transiently may
become active during intense exercise and serve to pull the become slightly positive with respect to atmospheric pres-
sternum forward. sure. As exercise intensity increases and expiratory muscles
Normal Pneumothorax
Trachea
Palv = 0 cmH2O Terminal
Palv = 0 cmH2O bronchioles
Bronchi
Air To nares To alveoli

Turbulent
Ppl = –5 cmH2O
Velocity
Ppl = 0 cmH2O of Laminar
airflow
Distance
Fig. 2.9. Schematic representation of the tracheobronchial tree
showing the increase in total cross-sectional area between the trachea
and bronchioles. The velocity of airflow is represented by the triangle
Mediastinum
that shows the highest velocity in the trachea and decreasing velocity
Fig. 2.8. Mechanisms of pneumothorax. On the left is the normal toward the peripheral airways.
hemithorax in which the lung is inflated. The outward recoil of the
thoracic cage (blue outward arrows) balances the inward recoil of the
lung (blue inward arrows). As a result of these opposing forces, there
is a slightly subatmospheric (–5 cmH2O) pleural pressure (Ppl). The breathing is provided by the nasal cavity, one-quarter by
alveolar pressure (Palv) is atmospheric (zero) because the alveoli are
the trachea and the remainder by the bronchi and
connected to the atmosphere by the tracheobronchial tree. On the
right side, the injury to the thorax allows air to rush into the thorax bronchioles (Art et al 1988). Within the nose, the greatest
until the pleural pressure equals atmospheric pressure. The loss of the point of resistance is just inside the nares at the nasal valve
negative pleural pressure allows the lung to collapse until it has no and this is the part of the respiratory tract that is dilated by
more elastic recoil. application of the commercially available strip (Holcombe
et al 2002).
The magnitude of the resistance of a tube is determined
are recruited, pleural pressure becomes increasingly primarily by the tube’s diameter and to a much lesser
positive during exhalation, reaching a value of about extent by the tube’s length. This can be seen in the
+30 cmH2O at the gallop (Slocombe et al 1991). following equation:
What is ⌬Pplmax? R = 8 u l /r 4
The ΔPplmax is the maximal change in pleural pressure where R is the resistance, u is the viscosity of air, l is the
during tidal breathing and is the difference between peak length of the airway and r is the radius of the airway.
inspiratory and peak expiratory pleural pressure. In the Using this formula, it is possible to compare the
resting healthy horse ΔPplmax averages less than 10 cmH2O; resistance of an individual bronchiole with that of the
with exercise it increases to 60 cmH2O or more (Slocombe trachea. A bronchiole with a length of 1 cm and a radius of
et al 1991) to cause greater enlargement of the lung and 1 mm has a resistance that is almost 400 times greater
generate the higher airflow that occurs during exercise. than the trachea with a length of 1 m and a radius of
Measurement of the ΔPplmax can be used as a simple 2.5 cm. When trying to understand the distribution of
indicator of lung function (Robinson et al 1999). An resistance within the tracheobronchial tree, it is important
increase in ΔPplmax is simply an indicator that the to realize that the number of airways doubles at each
respiratory muscles are working harder. Such an increase bifurcation so that while there is only one trachea, there
in ΔPplmax can simply be a result of a large tidal volume or are 1,024 tenth-generation bronchi. Although the exact
high airflow rates but it can also indicate that the lung is number of generations of bronchi and bronchioles has not
more difficult to inflate because the airways are obstructed been determined in horses, it approaches 50. This means
or the lung parenchyma is stiffer than normal, that is the that there are many thousands of bronchioles running in
lung has a low compliance. parallel in the periphery of the lung. The sum total of the
cross-sectional area of all these bronchioles is much
greater than the cross-sectional area of the trachea and
Frictional Resistance of the Air Passages for this reason the resistance contributed by the bron-
Opposes Airflow chioles is much less than that contributed by the larger
Frictional resistance opposes movement of any fluid such airways (Fig. 2.9). The type of airflow occurring within a
as air when it moves through a series of tubes. In the tube also determines resistance and is least when flow is
resting horse, about half of the frictional resistance to laminar and greatest when flow is turbulent. In the
respiratory system flow is turbulent in the larger airways, The pharynx dilates during exercise as a result of the
that is, in the upper airway, trachea and larger bronchi. coordinated contraction of pharyngeal dilator muscles.
Flow becomes laminar in the more peripheral airways, These include the stylopharyngeus that lifts the roof of the
including the bronchioles. This further accentuates the pharynx, tensor veli palatini that prevents dorsal bulging of
contribution of the larger airways to airway resistance. the soft palate, and hyoepiglotticus that pulls the epiglottis
ventrally. Overall, the pharynx takes on an almost
Flow patterns are responsible for the rectangular cross-section during intense exercise. In
generation of respiratory sounds addition, contraction of the abductor muscle of the larynx,
specifically the dorsal cricoarytenoid muscle, opens the
Turbulent airflow generates the breath sounds audible glottis and reduces the resistance provided by the larynx.
through a stethoscope. In the normal horse, breath sounds
are loudest over the trachea and large bronchi because Head position affects upper airway resistance
turbulence is greatest in these airways (Fig. 2.9). Breath
sounds are least in the lung periphery because flow is When a horse exercises unrestrained, it extends its head so
laminar. Exercising a horse before auscultation of the lungs that there are fewer bends in the airways between the
accentuates breath sounds because airflow velocity is external nares and the lung. During many of the sports
increased at all levels of the airways. activities in which horses are used, the horse is restrained
In disease, any narrowing of the airways tends to so that its head cannot be extended. Flexion of the head
increase airflow velocity at the site of obstruction. These and neck impedes the normal dilatation of the naso-
increases in velocity, which can be quite local, promote pharynx that occurs during exercise and may tend to
turbulence and lead to the abnormal breath sounds. accentuate some of the dynamic problems of the upper
airway that are described below (Petsche et al 1995).
Clinical consequences of the distribution
of resistance Some diseases increase upper
airway resistance
Because the upper airway and trachea provide most of the
frictional resistance, obstruction of these airways can result Several disease processes can increase the resistance of the
in dramatic clinical signs and even cause hypoventilation. upper airway by decreasing its diameter. Foreign bodies,
For example in a foal with guttural pouch tympany, the neoplasms, abscesses, or distended guttural pouches that
obstruction of the pharynx causes severe respiratory impinge on the upper airway can cause severe obstruc-
distress even in the resting animal. By contrast, a horse tion. In the nasal cavity, engorgement of the submucosal
with bronchiolitis and mucus accumulation in these vascular sinuses can narrow the nasal cavity and obstruct
small airways may show few clinical signs of obstruction airflow. This can occur in association with Horner
at rest. It may only be when the horse is required to syndrome, when loss of sympathetic innervation leads to
exercise that bronchiolar obstruction becomes evident vascular engorgement in the nasal cavity. These types of
as reduced exercise tolerance. However, extensive and problems provide a fixed obstruction that is present during
diffuse obstruction of the bronchioles, such as occurs in both inhalation and exhalation.
severe heaves, causes clinical respiratory distress in the
resting horse. Upper airway obstructions are usually dynamic
Failure of the abductor muscles of the pharynx and larynx
to contract during inhalation can also increase the
Upper Airway Resistance frictional resistance to breathing but, in these cases,
is Actively Regulated the obstruction is dynamic and is present only during
During exercise, many mammals reduce their upper airway inhalation. Dynamic obstructions are a result of pressure
resistance by breathing through their mouths, which changes within the airway acting on poorly supported
bypasses the resistance provided by the nasal cavity. tissue. They occur primarily during inhalation and during
Because the horse is an obligate nose breather and does not exercise because at this time pressure within the lumen of
have the option of breathing through its mouth, it uses the airway is subatmospheric and therefore most likely
other methods to decrease the resistance provided by to displace the unsupported tissue into the airway lumen.
its nasal cavity. Dilatation of the external nares by The displaced tissue reduces the diameter of the airway,
abduction of the nasal cartilages, and opening of the nasal which causes airflow velocity to increase at the point of
valve by contraction of the lateralis nasi muscle both obstruction, just as a river flows most rapidly through a
reduce the resistance of the nasal opening. In addition, narrow gorge. As a result of the Bernouilli principle, the
catecholamines released during exercise cause contraction high-velocity airflow further decreases pressure within the
of the vasculature within the nasal mucosa, which shrinks airway lumen and accentuates the obstruction. Recurrent
the mucosa and dilates the nasal cavity. laryngeal neuropathy provides the best example of this
2.5 secretions, exudates and mucosal thickening, which are a
Impedance (cmH2O•l–•1s–1)
Rest consequence of inflammation, can narrow the lumen.
2.0 Exercise
1.5 Clinical consequences of changes in airway

diameter during breathing
1.0
The expansion of the lung during inhalation causes
0.5 dilatation of the intrapulmonary airways. Conversely,
during exhalation, the decrease in lung volume reduces the
0
Inhalation Exhalation diameter of the airways. These changes in diameter have
some important clinical consequences. Wheezes tend to
Fig. 2.10. Effect of exercise on upper airway impedance in horses occur at the end of exhalation because, at this point in
with laryngeal hemiplegia. During exercise impedance to inhalation the respiratory cycle, the airways are narrowed so that
increases as a consequence of the dynamic collapse of the vocal fold.
Impedance during exhalation is unaffected. Drawn from data in
obstructions by mucus or bronchospasm are accentuated.
Lumsden et al, 1993, with permission. Turbulent airflow across the obstruction gives rise to
wheezes. Horses with heaves have the highest airflow rate
at the end of inhalation and the start of exhalation
type of problem (Lumsden et al 1993). The paralyzed because this is when the airways have the widest diameter.
dorsal cricoarytenoid muscle cannot abduct the arytenoid The typical heave occurs at end exhalation as the horse
cartilage and so the unsupported vocal fold is sucked into tries to push air out through very narrowed airways.
the airway lumen during inhalation, thereby increasing the
impedance to airflow (Fig. 2.10). Horses with recurrent Intrathoracic airways can undergo dynamic
laryngeal neuropathy have no problem exhaling. Other collapse
dynamic inspiratory obstructions include pharyngeal Dynamic collapse of intrapulmonary airways normally
collapse, and collapse of the aryepiglottic folds. occurs during coughing when the intrapleural pressure
becomes greatly positive and thereby compresses the larger
Control of the upper airway muscles bronchi and trachea. This narrows the lumen of the
airway so that air must flow with a high velocity through
Because failure of the abductor muscles of the upper the narrowed portion and thereby displace any accumu-
airway is such an important cause of upper airway lated mucus. Dynamic collapse also occurs during the
obstruction in the horse, it is useful to know how these forced exhalation that is typical of horses with heaves.
airways become activated during exercise. The motor nerve Under these conditions, the horse activates its expiratory
supply to the muscles of the pharynx and larynx is muscles to speed exhalation but by so doing increases the
provided through cranial nerves IX (glossopharyngeal) and pleural pressure, compresses the airways, increases airway
X (vagus). During exercise, neural activity to these muscles resistance and reduces airflow at the end of exhalation.
increases along with neural activity to other respiratory
muscles such as the diaphragm and intercostals. In Smooth muscle contraction regulates the
addition, further activity can be generated when receptors diameter of the tracheobronchial tree
in the pharynx are activated (Sant’Ambrogio et al 1995).
These receptors respond to changes in pressure and flow The most important factor actively regulating tracheo-
and to cooling. If for example the nose is obstructed, there bronchial resistance is airway smooth muscle. Airway
is less flow of air through the pharynx and/or pressure smooth muscle occurs in the walls of airways from the
decreases more than normal within the pharynx. Both of trachea to the alveolar ducts. In the trachea, the smooth
these actions can initiate a reflex increase in the activity of muscle occurs only between the tips of the tracheal
the abductor muscles of the upper airway. Abductor muscle cartilages. In the bronchi and bronchioles, a layer of
failure could therefore be a result of a lesion within the smooth muscle encircles the airways beneath the mucosa.
muscle itself, its motor nerve supply, the sensory receptor, In the alveolar ducts, smooth muscle encircles the mouths
or the sensory nerve (Holcombe et al 2001). of the alveoli. When airway smooth muscle contracts the
main result is narrowing of the diameter of the airways.
The purpose of airway smooth muscle is still unknown.
Tracheobronchial Tree Diameter is It has been suggested that it regulates the amount of
Affected by Passive and Active Factors anatomic dead space, performs a defensive function to
The diameter of the trachea, bronchi, and bronchioles prevent entry of foreign materials into the lung, or that it
changes passively during breathing and is actively regu- undergoes peristalsis that helps move mucus. Recently, it
lated by contraction of smooth muscle. In addition, mucoid was suggested that smooth muscle may have no normal
Parasympathetic Parasympathetic
nerve nerve Sympathetic nerves
Norepinephrine
M2 α2
Adrenal medulla
Negative Epinephrine
feedback
ACh ↓ ACh
NO β2
M3 M2 ↓ M3
↓ ↓
cGMP cAMP
↓ cAMP
↓
Cai++
Relaxation
Contraction
Smooth muscle Smooth muscle
A B
Fig. 2.11. Autonomic regulation of smooth muscle contraction in the airways. (A) Postganglionic
parasympathetic fibers release acetylcholine (Ach) that activates the M3 muscarinic receptor on the
smooth muscle membrane, which releases intracellular calcium and causes contraction. In addition, Ach
activates M2 receptors on the smooth muscle cell. This inhibits the production of cAMP, which facilitates
contraction. On the nerve fiber, activation of this receptor inhibits Ach release. (B) Inhibition of smooth
muscle contraction can occur by activation of β2-adrenoceptors or by release of nitric oxide (NO) from
nerve fibers in the parasympathetic system. Activation of β2-adrenoceptors, which is primarily by
epinephrine that is released from the adrenal medulla, leads to an increase in cAMP. Release of nitric oxide
increases cGMP. Both cAMP and cGMP cause smooth muscle relaxation.
physiological function and may simply be in the airways Activation of ␤-adrenoceptors relaxes airway
because the lung originates as an outpouching of the smooth muscle
foregut (Mitzner 2004). In horses with heaves and in Activation of the numerous β2-adrenergic receptors
people with asthma, severe contraction (bronchospasm) of on equine airway smooth muscle increases the produc-
airway smooth muscle occurs when the airways become tion of cAMP, which causes muscle relaxation (Torneke
inflamed. For this reason, there has been extensive investi- et al 1997). There are few sympathetic nerves in equine
gation of the neural regulation of airway smooth muscle. airway smooth muscle (Sonea et al 1993) and the norepi-
nephrine that they release is not a strong agonist for the
Activation of parasympathetic nerves contracts β2-adrenoceptor. The principal agonist for this receptor
airway smooth muscle is circulating epinephrine, which is released from the
The principal excitatory innervation of equine airway adrenal gland at times of stress and excitement. Many
smooth muscle is the parasympathetic nervous system, of the drugs used to treat bronchospasm, including
which reaches the lung in the vagus nerve. Autonomic clenbuterol (Erichsen et al 1994), albuterol (Derksen et al
ganglia of the parasympathetic system are located in the 1999), and salmeterol (Henrikson and Rush 2001), are
walls of the larger airways and postganglionic fibers extend β2-adrenergic agonists. However, it is important to realize
to smooth muscle where they release acetylcholine, which that in the normal horse, airway smooth muscle is usually
binds to muscarinic receptors to cause contraction. Airway relaxed and almost certainly the airways are maximally
smooth muscle possesses both M2 and M3 muscarinic dilated during exercise. For this reason administration
receptors. Activation of the M3 receptors releases calcium of bronchodilators is unlikely to increase airflow during
from intracellular stores to cause contraction of smooth exercise in the normal horse.
muscle (Fig. 2.11). Activation of the M2 receptors decreases
the production of the muscle-relaxing cAMP and thereby Several other types of nerves also have effects
facilitates contraction. Blockade of the muscarinic on smooth muscle
receptors by the non-specific antagonist atropine prevents There are two other components to the nerve supply of
or treats bronchospasm (Broadstone et al 1988). There the tracheobronchial tree. These are the non-adrenergic
are also M2 receptors on postganglionic parasympathetic non-cholinergic inhibitory and excitatory nervous systems
nerve fibers and activation of these receptors inhibits (iNANC and eNANC, respectively). The iNANC system
the release of acetylcholine (Wang et al 1995). There is supplies the airway smooth muscle in the larger bronchi of
evidence that inflammatory airway diseases cause dysfunc- horses (Yu et al 1994a). When activated, it releases nitric
tion of these prejunctional receptors, which facilitates oxide that relaxes airway smooth muscle (Sweeney et al
the release of acetylcholine and leads to bronchospasm 1999). This system seems to be dysfunctional in horses
(Coulson & Fryer 2003). with heaves (Broadstone et al 1991, Yu et al 1994b), and
interestingly, drugs that provide a source of nitric oxide In horses with influenza, airway hyperresponsiveness
were used to treat heaves in the 19th century. persists for several weeks after the clinical signs abate. For
The eNANC system is composed of small non- this reason, such horses should be allowed adequate time
myelinated sensory nerves that contain neuropeptides such for healing and should be kept in an environment that is
as substance P (Sonea et al 1994). This system is activated free of irritants such as dusts and ammonia. In heaves-
by inhalation of irritating materials, for example ammonia. susceptible horses, exposure to allergens and dusts for just
When this occurs, sensory information is sent to the a few hours can cause hyperresponsiveness that persists for
central nervous system but in addition, neuropeptides are days (Fairbairn et al 1993). This makes the horse prone to
released locally in the walls of the airways where they bronchospasm and is one reason that owners tend to fail
can initiate inflammation, edema formation, and mucus when using environmental control to treat heaves. They
secretion. The physiological importance of the system in bring their horses into pro-inflammatory environments for
the horse is unknown. grooming or overnight stabling and this is sufficient to keep
the airways hyperresponsive.
In horses with heaves, there is increasing evidence
Inflammatory mediators can also cause smooth that airway hyperresponsiveness can persist even with
muscle contraction environmental treatments that greatly reduce overt clinical
Many inflammatory mediators, such as histamine, sero- signs of disease. When heaves-affected horses are fed silage
tonin, and leukotriene D4, can also cause smooth muscle (Vandenput et al 1998), their lung function improves but
contraction while others, such as prostaglandin E2, cause they remain hyperresponsive. Similarly, with pelleted feed
relaxation. The individual roles of such agonists in the (Jackson et al 2000) or when fed soaked hay, low-level
bronchospasm of heaves are unclear. Present evidence airway inflammation can persist and can be associated
suggests that these inflammatory mediators may act with airway hyperresponsiveness. Under these conditions,
indirectly by facilitating the release of acetylcholine, which exposure to inhaled irritants may precipitate overt signs of
then binds to the muscarinic receptors to cause broncho- airway obstruction.
spasm (Olszewski et al 1999a,b). That is why atropine
(Broadstone et al 1988) and other anticholinergic agents
(Robinson et al 1993, Duvivier et al 1999) are such potent
bronchodilators in horses with heaves.
Distribution of Ventilation
within the Lung
For optimal gas exchange in the lung, the air and blood
must be delivered to the alveoli in approximately equal
Airway Hyperresponsiveness amounts. In healthy horses, the average ventilation to
• •
Exaggerated airway narrowing in response to a variety blood flow (V /Q ) ratio of 1.0 and the narrow spread of
of endogenous and exogenous stimuli is described as such ratios indicates that this is so (Hedenstierna et al
non-specific airway hyperresponsiveness. Such stimuli 1987). In humans, there are gravitational effects on both
would not cause respiratory distress in a normal horse but ventilation and blood flow so that the lower parts of
result in extreme airway narrowing and difficult breathing the lung receive more ventilation and blood flow per unit
in a hyperresponsive horse. Hyperresponsiveness is asso- of lung volume than does the top part of the lung.
ciated with inflammation and occurs in horses with heaves Recent studies suggest that gravity plays only a small
(Derksen et al 1985a,b, Klein & Deegen 1986) and also is part in the distribution of blood flow in horse lungs
• •
associated with viral respiratory infections, especially (Hlastala et al 1996) and so, if V /Q ratios average 1.0,
influenza. Airway inflammation leads to hyperrespon- gravity also should play only a small part in the distri-
siveness by a variety of mechanisms. Hypertrophy of the bution of ventilation. This would be in conflict with
epithelium and mucus-producing cells causes thickening of earlier observations that the lower parts of the horse lung
the airway wall internal to the smooth muscle layer so that receive more ventilation than the upper portions (Amis
a small contraction of the smooth muscle causes greater et al 1984) because of regional differences in pleural
narrowing of the airway lumen than normal (Moreno et al pressure (Derksen & Robinson 1980). Clearly there is a
1986). Other causes of hyperresponsiveness include need for further investigation.
facilitation of acetylcholine release by inflammatory In diseased lungs, uneven distribution of ventilation is
mediators (Olszewski et al 1999a,b), reduced inhibition caused by airway obstruction and by restriction of lung
of smooth muscle contraction as a result of decreased inflation in regions with low compliance. This abnormal
production of prostaglandin E2 (Gray et al 1989, Yu et al distribution of ventilation, which has been demonstrated in
1994b), lack of iNANC function (Yu et al 1994a), and horses with chronic airway disease (Rush et al 1999,
decreased activity of β-adrenoceptors. Votion et al 1999), can be partially reversed by use of a
45
body or mucus, or can be a change in osmolarity or release
Day 1
40
of inflammatory mediators. Cough begins with a full
inhalation followed by exhalation against a closed glottis.
30
Coughs/15 min
This action increases intrathoracic pressure so that when

25
the glottis opens there is a high driving pressure that
20
causes high-velocity airflow. In addition, the elevated
15
intrathoracic pressure dynamically compresses the larger
10
intrathoracic airways so that the high airflow passes
5
through narrowed airways. The resultant high-velocity air
0
11:00
11:15
11:30
11:45
09:30
09:45
10:00
10:15
10:30
10:45
12:00
12:15
12:30
12:45
13:00
13:15
movement dislodges mucus and other foreign materials.
Coughing is a sign of inflammation

20 Day 2 Healthy horses rarely, if ever, cough. Coughing frequency
increases whenever the airways become inflamed but the
15
magnitude of the increase in frequency varies greatly
Coughs/15 min
(Xiang et al 1998). In horses with heaves for example,

10
some horses may cough 40 times per hour while others
with similar severity of inflammation may cough less than
5 10 times per hour (Robinson et al 2003). Coughing is
usually paroxysmal. A horse may not cough for several
0 hours and then may cough 40 times in the next 15 min-
11:00
11:15
11:30
11:45
09:30
09:45
10:00
10:15
10:30
10:45
12:00
12:15
12:30
12:45
13:00
13:15
utes (Fig. 2.12). For this reason, horse owners may not
notice that their horse is coughing if they only go to the
stable to feed their horse twice a day.
30 Day 3 The mechanisms whereby inflammation increases
25 cough sensitivity are not well understood. It is clear that
prostanoids, such as prostaglandin E2 and thromboxane,
Coughs/15 min
20
increase cough sensitivity and that neuropeptides may also
15 be involved. This is leading to a search for more effective
10 methods to treat cough (Belvisi & Geppetti 2004).
5
REFERENCES
0
09:30
09:45
11:00
11:15
11:30
11:45
10:00
10:15
10:30
10:45
12:00
12:15
12:30
12:45
13:00
13:15
Aguilera-Tejero E, Pascoe JR, Amis TC et al 1993 Measure-

Time ment of pulmonary diffusing capacity for carbon
monoxide and functional residual capacity during
rebreathing in conscious thoroughbreds. American
Fig. 2.12. Coughs per 15 min in a horse with heaves during the first,
second and third days of stabling. Cough frequency increases from
Ainsworth DM, Eicker SW, Nalevanko ME et al 1996 The effect
day 1 to 3 but the number of coughs per 15 min is very variable.
of exercise on diaphragmatic activation in horses.
Redrawn from Robinson et al, 2003, with permission.
Respiration Physiology 106: 35–46
Amis TC, Pascoe JR, Hornof W 1984 Topographic distri-
bution of pulmonary ventilation and perfusion in
the horse. American Journal of Veterinary Research
bronchodilator (Rush et al 1999). Horses with such air- 45: 1597–1601
• •
way disease have an abnormal distribution of V/Q ratios Amory H, Lomba F, Lekeux PM et al 1994 Bilateral diaphrag-
(Nyman et al 1991). matic paralysis in a pony. Journal of the American
Veterinary Medical Association 205: 587–591
Art T, Serteyn D, Lekeux P 1988 Effect of exercise on the
Cough partitioning of equine respiratory resistance. Equine
Veterinary Journal 20: 268–273
Cough is a forced exhalation that clears mucus and foreign Belvisi MG, Geppetti P 2004 Cough. 7: Current and future
material from the larger bronchi. Cough is initiated by drugs for the treatment of chronic cough. Thorax
59: 438–440
activation of irritant receptors that are located in the Broadstone RV, Scott JS, Derksen FJ et al 1988 Effects of
mucosa of the bronchi (Widdicombe 1996). The stimulus atropine in ponies with recurrent airway obstruction.
for these receptors can be mechanical, such as a foreign Journal of Applied Physiology 65: 2720–2725
Broadstone RV, Scott JS, Derksen FJ et al 1991 In vitro Hopkins SR, Bayly WM, Slocombe RF et al 1998 Effect of
response of airway smooth muscle from horses with prolonged heavy exercise on pulmonary gas exchange in
recurrent airway obstruction. Pulmonary Pharmacology horses. Journal of Applied Physiology 84: 1723–1730
4: 191–202 Hornicke H, Meixner R, Pollmann U 1982 Respiration in
Couetil LL, Rosenthal FS, Simpson CM 2000 Forced expiration: exercising horses. In Snow DH, Persson SGB, Rose RJ
a test for airflow obstruction in horses. Journal of Applied (editors) Equine Exercise Physiology: Proceedings of the
Physiology 88: 1870–1809 first international conference, Oxford, Granta Editions,
Coulson FR, Fryer AD 2003 Muscarinic acetylcholine recep- pp.7–16.
tors and airway diseases. Pharmacology and Therapeutics Jackson CA, Berney C, Jefcoat AM et al 2000 Environment and
98: 59–69 prednisone interactions in the treatment of recurrent
Derksen FJ, Robinson NE 1980 Esophageal and intrapleural airway obstruction (heaves). Equine Veterinary Journal
pressures in the healthy conscious pony. American 32: 432–438
Journal of Veterinary Research 41: 1756–1761 Kayar SR, Hoppeler H, Lindstedt SL et al 1989 Total muscle
Derksen FJ, Robinson NE, Armstrong PJ et al 1985a Airway mitochondrial volume in relation to aerobic capacity of
reactivity in ponies with recurrent airway obstruction horses and steers. Pflügers Archiv European Journal of
(heaves). Journal of Applied Physiology 58: 598–604 Physiology 413: 343–347
Derksen FJ, Scott JS, Miller DC et al 1985b Bronchoalveolar Klein H-J, Deegen E 1986 Histamine inhalation provocation
lavage in ponies with recurrent airway obstruction test: Method to identify nonspecific airway reactivity
(heaves). American Review of Respiratory Disease in equine. American Journal of Veterinary Research
132: 1066–1070 47: 1796–1800
Derksen FJ, Olszewski MA, Robinson NE et al 1999 Aerosolized Koterba AM, Kosch PC, Beech J et al 1988 Breathing strategy
albuterol sulfate used as a bronchodilator in horses with of the adult horse (Equus caballus) at rest. Journal of
recurrent airway obstruction. American Journal of Applied Physiology 64: 337–346
Veterinary Research 60: 689–693 Lumsden JM, Derksen FJ, Stick JA et al 1993 Use of flow-
Duvivier DH, Bayly WM, Votion D et al 1999 Effects of inhaled volume loops to evaluate upper airway obstruction in
dry powder ipratropium bromide on recovery from exercise exercising standardbreds. American Journal of Veterinary
of horses with COPD. Equine Veterinary Journal 31: 20–24 Research 54: 766–775
Erichsen DF, Aviad AD, Schultz RH et al 1994 Clinical efficacy Manohar M 1986 Vasodilator reserve in respiratory muscles
and safety of clenbuterol HCl when administered to during maximal exertion in ponies. Journal of Applied
effect in horses with chronic obstructive pulmonary Physiology 60: 1571–1577
disease. Equine Veterinary Journal 26: 331–336 Manohar M, Goetz TE, Nganwa D 1988 Costal diaphrag-
Fairbairn SM, Lees P, Page CP et al 1993 Duration of antigen- matic O2 and lactate extraction in laryngeal hemiplegic
induced hyperresponsiveness in horses with allergic ponies during exercise. Journal of Applied Physiology
respiratory disease and possible links with early airway 65: 1723–1728
obstruction. Journal of Veterinary Pharmacology and Manohar M, Duren S E, Sikkes B et al 1992 Respiratory
Therapeutics 16: 469–476 muscle perfusion in ponies during prolonged submaximal
Gray PR, Derksen FJ, Robinson NE et al 1989 Decreased exercise in thermoneutral environment. American Journal
airway mucosal prostaglandin E2 production during of Veterinary Research 53: 558–562
airway obstruction in an animal model of asthma. Marlin DJ, Schroter RC, Cashmann PMM et al 2002 Move-
American Review of Respiratory Disease 146: 586–691 ments of thoracic and abdominal compartments during
Hedenstierna G, Nyman G, Kvart C et al 1987 Ventilation- ventilation at rest and during exercise. Equine Veterinary
perfusion relationships in the standing horse: an inert Journal Supplement 34: 384–390
elimination study. American Journal of Veterinary Mitzner W 2004 Airway smooth muscle: the appendix of the
Research 47: 277–282 lung. American Journal of Respiratory and Critical Care
Henrikson SL, Rush BR 2001 Efficacy of salmeterol xinafoate Medicine 169: 787–790
in horses with recurrent airway obstruction. Journal Moreno RH, Hogg JC, Pare PD 1986 Mechanics of airway
of the American Veterinary Medical Association narrowing. American Review of Respiratory Disease
218: 1961–1965 133: 1171–1180
Hlastala MP, Bernard SL, Erickson HH et al 1996 Pulmonary Morrison KE, Slocombe RF, McKane SA et al 1999 Functional
blood flow distribution in standing horses is not and compositional changes in pulmonary surfactant in
dominated by gravity. Journal of Applied Physiology response to exercise. Equine Veterinary Journal Supplement
81: 1051–1061 30: 62–66
Hobo S, Oikawa M, Kuwano A et al 1997 Effect of trans- Nyman G, Lindberg R, Weckner D et al 1991 Pulmonary gas
portation on the composition of bronchoalveolar lavage exchange correlated to clinical signs and lung pathology
fluid obtained from horses. American Journal of in horses with chronic bronchiolitis. Equine Veterinary
Veterinary Research 58: 531–534 Journal 23: 253–260
Holcombe SJ, Derksen FJ, Berney C et al 2001 Effect of topical Olszewski MA, Robinson NE, Zhou FX et al 1999a Mediators of
anesthesia of the laryngeal mucosa on upper airway anaphylaxis but not activated neutrophils augment
mechanics in exercising horses. American Journal of cholinergic responses of equine small airways. American
Veterinary Research 62: 1706–1710 Journal of Physiology 276: L522–L529
Holcombe SJ, Berney C, Cornelisse CJ et al 2002 Effect of Olszewski MA, Zhang XY, Robinson NE 1999b Pre- and
commercially available nasal strips on airway resistance post-junctional effects of inflammatory mediators
in exercising horses. American Journal of Veterinary in horse airways. American Journal of Physiology
Research 63: 1101–1105 277: L327–L333
Pelletier N, Leith DE 1995 Ventilation and carbon dioxide Sonea IM, Bowker RM, Robinson NE et al 1994 Substance P
exchange in exercising horses: effect of inspired oxygen and calcitonin gene-related peptide-like immunoreactive
fraction. Journal of Applied Physiology 78: 654–662 nerve fibers in lungs from adult equids. American Journal
Petsche VM, Derksen FJ, Berney CE et al 1995 Effect of head of Veterinary Research 55: 1066–1074
position on upper airway function in exercising horses. Sweeney CR, Tomasic M, Russell GE 1999 A preliminary
Equine Veterinary Journal Supplement 18: 18–22 study of the effect of inhaled nitric oxide on lung
Poole DC, Petrisko RN, Anderson L et al 2002 Structural and mechanics in the standing horse with histamine-
oxidative enzyme characteristics of the diaphragm. induced bronchoconstriction. Equine Veterinary Journal
Equine Veterinary Journal Supplement 34: 459–463 Supplement 30: 67–70
Robinson NE, Derksen FJ, Berney C et al 1993 The airway Torneke K, Larsson CI, Appelgren LE 1997 Relaxation of
response of horses with recurrent airway obstruc- equine tracheal muscle in vitro by different adreno-
tion (heaves) to aerosol administration of ipratropium ceptor drugs. Journal of Veterinary Pharmacology and
bromide. Equine Veterinary Journal 25: 299–303 Therapeutics 20: 216–219
Robinson NE, Berney C, Olszewski M et al 1999 Determinants Vandenput S, Votion D, Duvivier D et al 1998 Effect of a set
of maximal changes in pleural pressure in horses during stabled environmental control on pulmonary function
tidal breathing in COPD-affected horses. Veterinary and airway reactivity of COPD affected horses. Veterinary
Journal 157: 160–165 Journal 155: 189–195
Robinson NE, Berney C, DeFeijter-Rupp H et al 2003 Cough, Votion D, Ghafir Y, Vandenput S et al 1999 Analysis of
mucus, airway obstruction, and inflammation in heaves- scintigraphical lung images before and after treatment
affected and control horses. American Journal of of horses suffering from chronic pulmonary disease.
Veterinary Research 64:550–557 Veterinary Record 144: 232–236
Rush BR, Hoskinson JJ, Davis EG et al 1999 Pulmonary distri- Wang Z-W, Yu M-F, Robinson NE 1995 Prejunctional mus-
bution of aerosolized technetium Tc 99m pentetate after carinic autoreceptors on horse airway cholinergic nerves.
administration of a single dose of aerosolized albuterol Life Sciences 56: 2255–2262
sulfate in horses with recurrent airway obstruction. Widdicombe JG 1996 Sensory neurophysiology of the cough
American Journal of Veterinary Research 60: 764–769 reflex. Journal of Allergy and Clinical Immunology 98:
Sant’Ambrogio G, Tsubone H, Sant’Ambrogio FB 1995 S84-89; discussion S89–S90
Sensory information from the upper airway: role in the Xiang A, Uchida Y, Nomura A et al 1998 Effects of airway
control of breathing. Respiration Physiology 102: 1–16 inflammation on cough response in the guinea pig.
Slocombe RF, Brock K, Covelli G et al 1991 Effect of tread- Journal of Applied Physiology 85: 1847–1854
mill exercise on intrapleural, transdiaphragmatic and Young IS, Alexander R, Woakes AJ et al 1992 The synchro-
intra-abdominal pressures in standardbred horses. In: nization of ventilation and locomotion in horses (Equus
Persson SGB, Lindholm A, Jeffcott LB (editors) Equine caballus). Journal of Experimental Biology 166: 19–31
Exercise Physiology 3: Proceedings of the Third Interna- Yu M, Wang Z, Robinson NE et al 1994a Inhibitory nerve
tional Conference on Equine Exercise Physiology, Uppsala, distribution and mediation of NANC relaxation by nitric
ICEEP Publications, pp.83–91 oxide in horse airways. Journal of Applied Physiology
Sonea IM, Bowker RM, Broadstone RV et al 1993 Adrenergic 76: 339–344
and peptidergic innervation of the trachealis muscle in Yu M, Wang ZW, Robinson NE et al 1994b Modulation of
the normal horse: a preliminary report. Research in bronchial smooth muscle function in horses with heaves.
Veterinary Science 54: 335–339 Journal of Applied Physiology 77: 2149–2154
Pulmonary Blood Flow
3 David J Marlin and Thea L Vincent
The lungs receive blood from two sources: the pulmonary healthy resting horse, the mean pressure of large pul-
and bronchial circulations. Whilst the primary function of monary arteries is 20–30 mmHg. During intense exercise,
the pulmonary circulation is gas exchange, it acts as a mean pressures may easily exceed 100 mmHg, thereby
reservoir for blood between the right and left sides of placing high stress on the vessel walls. Simultaneous
the heart and also serves to filter thrombi and emboli. A measurements of pulmonary artery, aortic and esophageal
wide range of chemically active substances, including pressures in horses during moderately strenuous exercise
hormones, are also either produced or removed by the indicate transmural pressures (an index of stress on the
pulmonary vasculature. In contrast, the role of the bron- vessel wall) of 150 mmHg for the pulmonary artery and
chial circulation is primarily to ensure nutrition of the 175 mmHg for the aorta (Erickson et al 1990). Taking into
airways, vessels, parenchyma, and visceral pleura. However, account the considerably thinner wall of the pulmonary
another important function of the bronchial circulation artery, rupture of the main pulmonary arteries is perhaps
is its contribution, via airway mucosal perfusion, to the surprisingly rare.
conditioning of inspired air and in thermoregulation as a Within the lung, the pressure gradient between the
route for heat dissipation. pulmonary arteries and capillaries is similar to that
The pulmonary circulation is in series with the systemic between capillaries and pulmonary veins, which is in
circulation and therefore receives the total cardiac output marked contrast to the gradients in the systemic circula-
from the right side of the heart, despite the fact that it only tion in which most of the pressure decrease occurs between
has approximately one-tenth the capacity of the systemic arteries and capillaries. As a result, approximately half of
circulation. The pulmonary circulation is a highly com- the total pulmonary vascular resistance is precapil-
pliant, highly conductive, low-pressure system, relative to lary and flow is pulsatile rather than constant. At rest
the systemic circulation. The fact that the pulmonary the pulmonary circulation contains around one-fifth of the
circulation is a low-pressure system compared with total blood volume. The volume of blood within the pul-
the systemic arterial circulation is also reflected in the monary capillaries is relatively small compared to that
characteristics of the ventricles and the pressures within the larger vessels. However, disturbances such as
developed within them. Thus, the left ventricle has exercise or disease will increase the number of pulmonary
significantly more muscular walls than the right ventricle capillaries that are recruited (perfused).
and pressures within the right heart are also considerably
lower than those on the left. The right ventricle is
commonly referred to as a volume pump, whilst the left
Anatomy
ventricle is referred to as a pressure pump. The muscularity Pulmonary circulation
of the ventricular walls is primarily a function of the
pressure they must pump against, or the after-load. In the The branches of the pulmonary artery carry venous blood
case of the right ventricle the pressure in the pulmonary to the lung, accompany the bronchi (as in man and sheep),
artery is low whilst for the left ventricle the aortic pressure and form rich capillary plexuses on the walls of the alveoli.
is considerably higher. Although the absolute pressure This allows gas exchange to take place. The blood is
within the pulmonary arterial circulation is considerably returned through the pulmonary veins, which run
lower than in the systemic arterial circulation, the pressure intersegmentally and amass blood from adjacent broncho-
waves, flow patterns, and cardiac valve movements of both pulmonary segments, to the left side of the heart. The
circulations are similar. equine pulmonary arteries adjacent to the bronchioles and
The greater compliance of the pulmonary circulation is the alveolar ducts have a thick medial smooth muscle layer.
primarily because the arteries and arterioles are generally The main pulmonary trunk, the truncus pulmonalis, arises
shorter and have less smooth muscle than those of the from the conus arteriosus of the right ventricle. From its
systemic circulation. Thus, pulmonary arteries are closer in origin, the pulmonary artery extends dorsally to the left
structure to systemic veins as opposed to arteries. In the and cranial to the aorta, exiting the pericardium at a point
33
34 3 Pulmonary Blood Flow
above the left atrium. Here the pulmonary trunk is joined role of which is most likely to facilitate heat dissipation.
to the aorta by the ligamentum arteriosum, a remnant of There is also a system of branches of the bronchial
the ductus arteriosus. A short distance further on from this circulation that follow the pulmonary arteries and provide
point the first division of the truncus pulmonalis occurs to nutrition for the alveolar capillary network. In most
form the a.pulmonalis sinistra and the a.pulmonalis dextra, species, the bronchial veins drain the blood in the walls of
which supply the left and right lung, respectively. These the large bronchi; however, bronchial veins are not present
vessels then divide to form numerous thinner walled in horses. The bronchial circulation of the horse is,
branches over a relatively short distance. The transition therefore, drained by either the azygos vein (which
from pulmonary arteries to pulmonary arterioles is usually terminates in the superior vena cava) or the pulmonary
considered to occur at an internal diameter of around veins. At the level of the terminal bronchioles, the pul-
100 μm. At this level the vessels are almost devoid of monary and bronchial circulations anastomose. Most of
smooth muscle. these anastomoses occur at the level of the capillaries and
Pulmonary capillaries form a dense network over the veins rather than the arteries (McLaughlin 1983). These
walls of alveoli and a single capillary network is spread anastomoses have been reported to be frequent in horse
over multiple alveoli. The radius of the pulmonary capil- lungs and provide a potential route for shunting blood flow
laries in horses has been reported to be ~3 μm and is to attenuate increases in capillary pressure that may result
therefore similar to that in rabbits and dogs. However, from increases in pulmonary arterial (e.g. during exercise)
compared with the rabbit and dog, the horse has a thicker or venous (e.g. in cases of left-sided heart failure) pres-
blood–gas barrier. These characteristics are reflected in the sure. The amount of flow through these anastomoses is
pressures required to cause rupture, which are in the determined by the pressure gradient between the bronchial
region of 50, 90 and 130 cmH2O in rabbit, dog and horse, and pulmonary circulations, which is also modulated
respectively (Birks et al 1994). Flow within the pulmonary by the alveolar pressure. In circumstances where the
capillaries is pulsatile, in contrast to the flow in the pulmonary circulation is damaged, for example in exercise-
systemic circulation, which is essentially constant. It is induced pulmonary hemorrhage (EIPH), the bronchial
estimated that each red blood cell spends less than 1 second vasculature can act as an alternative supply.
in the pulmonary capillary network, but the fact that this
allows sufficient time for gas exchange illustrates the Innervation of the circulation
efficiency of the process.
The veins of the pulmonary circulation, in contrast to Whilst a considerable amount is known about the
those in the systemic circulation, are devoid of valves and innervation of the equine airways, relatively little is known
carry blood from the pulmonary capillaries to the left about the innervation of the pulmonary vasculature. The
atrium. From the capillary bed, blood collects into venules, lung is innervated by branches of the vagus and
which are effectively identical to arterioles in structure. sympathetic nerves that form plexuses within the lungs
Pulmonary veins do not run adjacent to pulmonary and then subdivide into smaller branches to supply the
arteries but rather lie close to the septa, which separate the blood vessels. The extent to which these nerves regulate
different segments of the lung. perfusion in the horse has not been determined; however,
in most species innervation appears to play only a minor
Bronchial circulation role in the control of blood flow.
The bronchial arterial circulation, a branch of the systemic

circulation, carries arterial blood for the nutrition of
Pulmonary Hemodynamics
the airways and other lung structures and receives In an artificial system, the non-pulsatile flow of a homo-
around 1–2% of the total cardiac output of the left geneous liquid through a rigid tube is a function of driving
ventricle. It originates from the broncho-esophageal artery pressure, tube diameter and length, and the viscosity of
(a.broncho-esophagea) giving rise to the right, middle and the liquid; this relationship is described by Poiseuille’s law
left bronchial arteries (r.bronchalis, m.bronchalis and (Fig. 3.1). Poiseuille’s law can reasonably be applied to
l.bronchalis). The right and left bronchial arteries supply describe blood flow within the body, despite the fact that
the cranial lobes, whilst the middle bronchial artery blood is a complex and non-homogeneous fluid, that the
supplies the caudal lobes, branching at the level of the blood vessels vary in stiffness (dependent on both their
tracheal bifurcation. In the horse the bronchial branches location and the smooth muscle tone), that these vessels
supply both the interlobular septa and the subpleural exhibit complex and intricate branching patterns, and that
connective tissue (McLaughlin et al 1961). Bronchial the flow of blood is pulsatile. The Poiseuille equation
arteries form a circulatory plexus in the connective tissues describes the factors contributing to resistance to flow.
along the airways. Branches from this plexus penetrate the Ignoring the constants in the equation (π and 8), and
bronchial walls to form a subepithelial vascular plexus the recognizing that the only energy for flow comes from the
3 Pulmonary Blood Flow 35
ΔP ΔP . r 4 . π
Q=
ηL . 8
Q r
Driving pressure = ΔP
r4
Resistance to flow (R) =
ηL
L ∴Flow = Driving pressure/Resistance to flow
ΔP . r 4 . π Q = ΔP . 1/R
Q=
ηL . 8
= ΔP / R
Fig. 3.1. The relationship between pressure, tube caliber and length OR R = ΔP / Q
according to Poiseuille’s law. Poiseuille’s law applies to the flow of a
homogeneous fluid through a rigid, cylindrical tube. The flow (Q) in
Fig. 3.2. Extension of Poiseuille’s law to describe the relationship
this system is proportional to the driving pressure along the tube (ΔP)
between flow, pressure, and resistance. The force driving flow is
and the fourth power of the radius (r) and inversely proportional to
simply the driving pressure (ΔP), whilst the forces opposing flow can
the length of the tube (L) and the viscosity of the liquid (η).
be considered the tube caliber (r), the fluid viscosity (η) and the tube
length ( L). These can be grouped to describe the resistance to flow (R).
As flow is a function of driving pressure divided by resistance to flow,
this can be arranged to solve for resistance.
driving pressure (ΔP), then the remaining factors, vessel
length, caliber and fluid (blood) viscosity comprise the
resistance to flow (Fig. 3.2). Thus, in the pulmonary
circulation the pulmonary driving pressure divided by the increase in proportion to driving pressure if the diameter
pulmonary blood flow gives an index of pulmonary and length of the tube and the fluid viscosity are kept
vascular resistance (PVR). This term is correct when mean constant. However, blood vessels are not rigid and have
pressure and flow values are used to calculate resistance some capacity to distend. Thus the pressure–flow relation-
in a “steady-state” or continuous flow system. However, ships in blood vessels are not linear and the relationship
where flow is more markedly pulsatile, for example in the varies according to their distensibility or compliance
aorta, the term “vascular impedance” is more appropriate. (Fig. 3.4). This phenomenon is extremely important in
There are two other important principles that should be terms of the lung’s ability to accommodate the large
appreciated concerning flow and resistance. Firstly, laminar increases in pulmonary blood flow that occur with exercise,
flow (sometimes referred to as Poiseuille or streamline flow) as discussed later. The shape of the curve is related to the
requires less driving pressure than turbulent flow, at the fact that as the blood vessel distends under increasing
same flow rate (Fig. 3.3). The Reynolds ratio or number perfusion pressure, the resulting flow will increase not in a
(Re ), a non-dimensional index of the ratio of inertial forces linear fashion, but to the fourth power of the radius.
to viscous forces within the fluid, predicts the type of flow The pressures within the pulmonary circulation depend
at a defined velocity. Thus, in a vessel where flow is on a range of factors, including the pressures of the right
turbulent, a greater driving pressure is required to generate
that flow than in a vessel in which the flow is laminar:
Reynolds number (Re ) = ( ρ.ν. d ) /μ
where ρ is density, ν is the velocity of the fluid, d is <2000 2000-4000 >4000

the vessel diameter and μ is the fluid viscosity. At a Laminar Transitional Turbulent
Reynolds number < 2000, flows of fluid other than blood
are considered to be laminar. Between 2000 and 4000 flow
is described as transitional, whilst when Re > 4000 flows
are considered to be turbulent. For blood the threshold
for the change between laminar and transitional flow is
Flow
much lower, at around 1000. Blood flow is more likely to

become turbulent in large blood vessels where flow is high,
such as the larger pulmonary arteries, than in smaller
vessels. An important point to note is that laminar flow
produces virtually no sound, whilst sound intensity Driving pressure (ΔP)
increases with turbulence.
The nature of the tube in which a liquid is flowing has Fig. 3.3. Relationship between pressure and flow. The Reynolds
an important impact on the relationship between pressure number (in boxes) predicts the type of flow that is likely to
and flow. Referring again to Poiseuille’s law, flow will predominate in rigid tubes.
Distensible tube
(e.g. blood vessel)
TLC
Pulmonary vascular resistance

Flow
RV
Rigid tube
FRC
Driving pressure (ΔP)
Fig. 3.4. The relationship between driving pressure and the resulting
flow in rigid and distensible tubes. In a rigid tube, the flow rate Lung volume
increases in direct proportion to driving pressure. In a distensible
tube, flow rate increases in a non-linear manner because of the
increase in radius resulting from distension, according to Poiseuille’s Fig. 3.5. The effect of lung volume on blood vessel caliber and
law (see Fig. 3.2). pulmonary vascular resistance (PVR). At functional residual capacity
(FRC), tethering of vessels by parenchyma maintains vessel patency.
At lower lung volumes up to residual volume (RV), the degree of
tethering is reduced and vessels receive minimal additional support.
This may be exacerbated in dependent lung regions. At high lung
and left heart, size of animal, proportion of the vascular volumes, up to total lung capacity (TLC) and at the top of the
bed perfused, age, disease and activity. Right ventricular lung gravitationally, tethering may lead to stretching and elongation
pressures in the healthy resting horse range from around of vessels. This increases PVR both by increasing the vessel length
15 mmHg during diastole to approximately 50 mmHg and decreasing caliber.
during systole. These pressures are higher than those in
humans and smaller mammals and are thought to be
related to the physical size of the lungs, with longer dis-
tances for blood to travel, and the volume of the circulation a low-resistance system (Robinson 1985). This is primarily
containing blood that is above the height of the heart itself because the pulmonary arteries are relatively short but
(i.e. an effect of hydrostatic pressure). large in diameter.
PVR in the horse is low. The PVR is calculated from the The pressure, and hence flow, within the pulmonary
difference between pulmonary arterial and left atrial arterial system is not only influenced by pulmonary
pressure divided by cardiac output. It has been estimated arterial smooth muscle tone, but also by circulatory
that the majority (~72%) of PVR at rest is the result of volume, relative (tidal volume) and absolute lung volume,
precapillary resistance (Sinha et al 1996). For calcula- and the changes in intrathoracic pressure that occur with
tion of PVR, direct measurements of pulmonary artery ventilation; thus, PVR changes during each respiratory
pressure can readily be obtained by passing a catheter cycle. When the lung inflates during inspiration, the
inserted into the right or left jugular vein, through the attachments between the parenchyma and the vasculature
right atrium and right ventricle and into the main result in radial expansion of the blood vessels, thereby
pulmonary trunk. However, left atrial pressure is tech- decreasing PVR, whilst on expiration the vessel diameter is
nically difficult to measure. Whilst a pressure catheter can reduced and flow may even be prevented if vessels are
be inserted into the carotid artery and passed down into compressed sufficiently. PVR therefore changes more
the aortic arch and into the left ventricle, it cannot be during breathing as tidal volume becomes greater. In
readily or reliably advanced into the left atrium. For this addition, absolute lung volume contributes to PVR. At very
reason, pulmonary artery wedge pressure is used as an low lung volumes, the support of parenchyma may become
index of left atrial pressure. negligible such that the caliber of the vessel is determined
In the resting horse, mean pulmonary arterial pressure by its wall stiffness as opposed to by its tethering by lung
is in the region of 20–30 mmHg (Manohar & Goetz 1998) tissue. In this situation PVR is maximal. At high lung
compared to around 120 mmHg in a systemic artery, such volumes and up to total lung capacity, PVR also becomes
as the aorta or carotid artery (around one-fifth to one-sixth elevated because of longitudinal stretching of smaller
that in the systemic arterial circulation). Pulmonary blood vessels in the alveolar septa. This stretching increases
arterial wedge pressure (considered to be equivalent to left the vessel’s length and concurrently decreases its caliber.
atrial pressure) is around 24 mmHg (Manohar & Goetz The PVR is generally least in healthy animals when their
1998), and thus the pressure to drive the blood through breathing is close to the functional residual capacity (FRC;
the pulmonary circulation is only a few mmHg, implying Fig. 3.5). Large increases in pulmonary arterial pressure
A B
Fig. 3.6. Distribution of perfusion in the equine lung at rest according to (A) gravity-dominated and
(B) gravity-independent models.
Regulation of the Pulmonary Circulation

and hence PVR can also be observed during coughing
because the markedly elevated intrathoracic pressure Pulmonary blood flow is actively regulated by changes in
compresses some of the pulmonary vasculature. smooth muscle tone. The equine pulmonary vasculature
receives sympathetic innervation (Sonea et al 1993).
Distribution of blood flow in the lung Whilst it has been demonstrated that cholinergic nerves
supply equine airways, little is known concerning the
In humans, blood flow distribution is mainly influenced by innervation of the pulmonary vasculature. Despite this,
gravity and consequently there is a vertical gradient of and in contrast to the airways, many studies suggest that
pulmonary perfusion with the ventral regions receiving these autonomic nerves play a relatively minor func-
more perfusion per unit lung volume than the dorsal tional role.
regions. This phenomenon is thought to be related to the A wide range of mediators released both locally and
balance between pulmonary arterial, pulmonary venous, remotely can modulate smooth muscle tone leading to
and alveolar pressures (West et al 1964) whereby, in the an increase or decrease in pulmonary blood flow, or
upper regions of the lungs, pulmonary artery pressure may complete closure of capillary beds and shunting. Many
be less than the alveolar pressure. For many years, the different drugs and mediators act on pulmonary vessel
perfusion of the equine lung was also thought to be smooth muscle. Norepinephrine, epinephrine, dopamine,
strongly influenced by gravity. Work by Amis et al (1984) phenylephrine, arachidonic acid, thromboxane, leuko-
using krypton perfusion and scintigraphy confirmed the trienes, serotonin, histamine (via H1 receptors), angio-
presence of a vertical gradient of pulmonary perfusion tensin II, endothelin and some prostaglandins (e.g. PGF2α )
increasing from dorsal to ventral in the standing conscious can produce vasoconstriction, whilst epinephrine, iso-
horse. Puzzlingly, however, the ventilation to perfusion ratio proterenol, bradykinin, prostaglandin E1, prostacyclin,
approximated 1.0 at all heights in the lung. The results of a arachidonic acid, histamine (via H2 receptors), nitric oxide
more recent study using microspheres (Bernard et al 1996) (NO), aminophylline, and acetylcholine can produce vaso-
suggested that blood may be preferentially distributed dilatation. These effects may be mediated through α1, α2,
to the dorsal regions of the lung. Furthermore, within the β or H1/H2 receptors. In some instances the effects may be
same vertical plane, blood flow can vary significantly. on specific vessels or sizes of vessels. Some mediators may
Taken together, this implies that gravitational forces are also have different effects depending on other factors;
not a major determinant of equine pulmonary perfusion epinephrine can produce vasoconstriction or vasodilatation
(Fig. 3.6). However, it should be noted that these studies depending on the level of smooth muscle tone.
were only undertaken on four horses and this phenomenon Nitric oxide regulates vascular tone in both the pul-
could be demonstrated in only three. monary and systemic circulations. It is one of the major
vasodilators released by vascular endothelial cells and plays pigs but greater than that in sheep and dogs. Animals with
an important role in regulating pulmonary vascular the strongest HPV response to hypoxia appear to have more
resistance. Nitric oxide is released by the vascular endo- smooth muscle surrounding the pulmonary arterial
thelium in response to, amongst other stimuli, increased vessels, show well-developed interlobular connective tissue
blood flow. Following its synthesis by endothelial nitric septae and have high collateral resistance to airflow.
oxide synthase (eNOS), NO diffuses into the vessel smooth Endothelial cells as well as other cell types release
muscle cells and lumen (Lancaster 1997, Butler et al endothelin, the most potent endogenous vasoconstrictor
1998). The interaction of NO with the enzyme guanylate yet identified. Its potency is around 100 times that of
cyclase results in increased production of cGMP, which norepinephrine, it has a long-lasting action and has been
relaxes smooth muscle cells leading to vasodilatation. In implicated in many vascular disorders including those of
the vascular lumen, NO is either oxidized to form nitrite the lung. Vascular smooth muscle cells also release
(Rhodes et al 1995) or is taken up by red blood cells (Liao endothelin but at a much lower level than endothelial cells.
et al 1999); the interactions of NO with hemoglobin are A wide range of stimuli can initiate endothelin release,
thought to play a regulatory role in the uptake and delivery including angiotensin II, catecholamines, vasopressin,
of oxygen. In primary pulmonary hypertension and in bradykinin, thrombin, insulin, interleukin-1, tumor necro-
high-altitude pulmonary edema, reduced NO availability sis factor-α, transforming growth factor-β, endotoxin,
has been highlighted as a potential cause of the excessive low mechanical shear stress and thermal stress. However,
rise in pulmonary arterial pressure. it is the release of endothelin from endothelial cells
Evidence that NO plays a major role in modulating in response to hypoxia that has led to a proposed role in
pulmonary vascular resistance in the horse comes from the control of regional blood flow. Equine pulmonary
several sources. L-NAME (Nω-nitro-L-arginine methyl ester) arteries (2–4 mm diameter) constrict in response to
a competitive inhibitor of eNOS, significantly increases endothelin in vitro and a vasoconstrictive response can
right atrial and pulmonary arterial, capillary, and venous also be observed following administration in vivo. In
pressures in horses at rest (Manohar & Goetz 1998); it also addition, there is evidence for the involvement of endo-
increases both pulmonary and systemic vascular resistance thelin in the HPV response of the horse to hypoxia (~11%
during moderate and intense exercise (Kindig et al 2000). inspired oxygen). However, although both pulmonary
Furthermore, inhalation of NO during exercise produces a arterial pressure and levels of endothelin in plasma and
small, but significant, decrease in pulmonary arterial bronchoalveolar lavage fluid were elevated in horses with
pressure (Kindig et al 2001). symptomatic recurrent airway obstruction (RAO), they
were not correlated.
Hypoxic pulmonary vasoconstriction
Non-respiratory Functions of the
One of the most potent vascular smooth muscle responses
of the lung is constriction in response to hypoxia, referred
Pulmonary Circulation
to as hypoxic pulmonary vasoconstriction (HPV). This is Because all the output from the right ventricle passes
the opposite of the response of the systemic circulation, in through the pulmonary circulation (except in the case of
which hypoxia produces vasodilatation. HPV is a pro- subjects with a right-to-left shunt), it is ideally suited
gressive response, i.e. as the severity of alveolar hypoxia to perform other “processing” roles, including protection
increases so does the magnitude of vasoconstriction. HPV of the systemic circulation by filtration of particulates
produces a regional reduction in blood flow in the hypoxic such as clots and air bubbles. In addition, a wide range of
area. By so doing, it diverts blood flow from unventilated or chemically active substances are produced or removed by
poorly ventilated regions of lung to those areas that are the pulmonary circulation.
well ventilated, thereby improving overall gas exchange. Thrombi can be eliminated faster in the lung than in
This is often referred to as ventilation/perfusion matching. any other organ because the pulmonary endothelium is
The mechanism of HPV is not entirely understood. rich in plasmin activator that converts plasminogen
Hypoxic vasoconstriction can occur as a consequence of into plasmin, which in turn degrades fibrin. Paradoxically,
pulmonary disease, during exercise or at altitude. Long- the pulmonary vasculature is also rich in heparin and
term HPV as may occur with chronic pulmonary disease, thromboplastin, which catalyze the conversion of pro-
such as chronic obstructive pulmonary disease in humans, thrombin to thrombin. The pulmonary circulation there-
can result in the development of pulmonary hypertension fore has a tremendous ability to control blood coagulation
and lead in turn to right heart failure (cor pulmonale), both locally and possibly also systemically.
although this is relatively rare in horses. The lung has the capacity to remove and process
The magnitude of the HPV differs among species. The selective vasoactive compounds, including hormones. This
response of horses to hypoxia is less than that in cattle and role is primarily undertaken by the pulmonary vascular
endothelium in vessels of all sizes, although the smaller Kindig et al 2003). The reductions in PVR despite the
vessels are thought to be most active. Norepinephrine, increased cardiac output are the result of a combination
5-hydroxytryptamine, bradykinin, ATP, ADP, AMP, prosta- of factors: recruitment of vessels previously unperfused;
glandins E2, E1, and F2α, and leukotrienes are essentially further active vasodilatation in vessels already perfused;
removed from the circulation whilst epinephrine, angio- and distension of vessels already maximally relaxed. As
tensin II, vasopressin, isoprenaline, dopamine, histamine, a result of the significant pressure increase in both the
and prostaglandins I2 and A2 all pass through the pul- pulmonary artery and left atrium during exercise, capillary
monary vasculature largely unaffected. The lung is also pressure is also greatly increased (Fig. 3.8).
a major site for the synthesis, metabolism and uptake Perfusion studies using microspheres (Bernard et al
and secretion of eicosanoids. Drugs that are taken up by 1996) and macroaggregates of human albumin labeled
the endothelium of the pulmonary circulation include with technetium-99m (Harmegnies et al 2002) have both
propranolol, lignocaine, chlorpromazine, imipramine, and shown an increase in pulmonary blood flow in the dorsal
nortriptyline. The lung also has some ability to process and dorsocaudal regions of the equine lung during intense
anesthetic agents. exercise. The mechanism for preferential redistribution of
blood flow to dorsal regions during exercise and the fact
that, even at rest, blood flow is not dominated by gravity as
The Effect of Exercise in the conventional perfusion model (Fig. 3.6) may relate
At the transition from rest to intense exercise, cardiac to regional variations in pulmonary arterial endothelial
output, and therefore pulmonary blood flow, increases by function. Thus, mediators that may produce vasocon-
around 10–12-fold. Pulmonary vascular pressures also striction in pulmonary vessels from the ventral lung
increase both as a result of the increased blood flow regions may paradoxically induce vasodilatation in vessels
and the increases in blood viscosity caused by splenic of the dorsal lung (Pelletier et al 1998). It appears that the
contraction. However, pulmonary vascular pressures do regional differences in pulmonary perfusion, at least under
not increase to the same extent as blood flow, with the resting conditions and in isolated vessels, may be largely
overall effect that PVR initially falls during the transition determined by differences in NO release (Pelletier et al
from rest to light exercise and is then unchanged with 1998). Further evidence that NO may play a role in the
increasing exercise intensity, despite further increases in control of pulmonary smooth muscle tone and pulmonary
cardiac output (Butler et al 1993, Manohar & Goetz 1999) perfusion during exercise comes from studies using NO
(Fig. 3.7). Inclined running reduces PVR even further administration and antagonism. Thus, there is evidence
compared with running on the flat (McDonough et al 2002, that inhaled administration of NO reduces mean pul-
monary artery pressure (Mills et al 1996a, Kindig et al
2001) whilst antagonism with L-NAME increases pressure
(Mills et al 1996b).
250
The redistribution of pulmonary blood flow to the dorsal
regions of the lung during exercise almost certainly has
(b.p.m., l/min, mmHg)
200 implications when considering EIPH. However, increased

HR, Q, PAP
150
100
50
Heart rate 80
Rest
0 Cardiac output
PA pressure HRmax
1.0 60
Pressure (mmHg)
(mHg•l–1•min–1)
PVR
PVR
0.5 40
0.0 20
0 2 4 6 8 10 12
Speed (m/s)
0
Pulmonary Pulmonary Pulmonary
artery capillary wedge
Fig. 3.7. Pulmonary hemodynamic variables in the horse at rest and
during exercise. Despite increases in heart rate (HR), flow (cardiac
output, Q), and pulmonary arterial pressure (PAP), pulmonary vascular Fig. 3.8. The relationship between pulmonary arterial, capillary, and
resistance (PVR) falls in the transition from rest to exercise. Drawn from wedge pressures in horses at rest and during intense exercise (HRmax
data in Butler et al, 1993 with permission. – maximal heart rate). Redrawn from Sinha et al, 1996.
Conventional model: 160

Pulmonary vascular bed is fully dilated during exercise Ambient oxygen pressure (760 mmHg)
(I.e. no pulmonary arterial smooth muscle tone)
140
120 Alveolar O2 light exercise

Blood flow Alveolar O2 rest
PO2 (mmHg)
100 Alveolar O2 intense exercise
100 mmHg 50 mmHg 80
60
60 mmHg
40 Mixed venous PO2
Pre-capillary Pulmonary Pulmonary Arterial PO2
arterioles capillaries venous 20
circulation
0
Proposed model: 0.0 0.25 0.50 0.75
Pulmonary vascular bed is not normally fully dilated during exercise Capillary transit time (seconds)
Blood flow Fig. 3.10. The relationship between alveolar and blood oxygen tension
and capillary transit time in horses at rest and during light and intense
exercise. Drawn from data in Butler et al, 1993.
100 mmHg 50 mmHg
60 mmHg
• •
Pre-capillary Pulmonary Pulmonary V /Q mismatch), which is only of the order of 1% of the
arterioles capillaries venous total cardiac output at rest, is reduced to around a half
circulation
(Wagner et al 1989). Even in standardbreds with mild
Proposed model: bronchiolitis, shunt was not increased during moderate
Dilate arterioles (e.g. NO), pressure drop now occurs across
exercise compared with healthy controls (Nyman et al
→
→
pulmonary capillaries, capillary pressure = EIPH

1991b). In addition, despite the increases in total blood
Blood flow flow and redistribution during exercise and evidence for
NO NO heterogeneity of intrapleural pressures (which may
• •
influence regional ventilation), V /Q relationships during
exercise appear to be similar to those at rest (Wagner et al
80 mmHg 70 mmHg 50 mmHg
1989, Seaman et al 1995).
The very high pulmonary vascular pressures in the
NO NO equine lung during exercise, and in particular, the pul-
Pre-capillary Pulmonary Pulmonary monary capillary pressures, might be reasonably con-
arterioles capillaries venous sidered to lead to an increase in extravasation of plasma
circulation
into the interstitial space and airways. However, attempts
Fig. 3.9. Conventional and proposed models relating to smooth muscle to measure extravascular lung water with a dilution
tone during exercise in the pulmonary vascular bed. method failed to demonstrate a significant increase in
extravascular lung fluid in horses during intense exercise
(Wilkins et al 2001). In addition, although diffusion limi-
flow does not necessarily imply increased pressure! A tation has been identified as the main component of
simple analogy is with a garden hose. If the tap is turned exercise-induced arterial hypoxemia in the exercising horse
on and the outflow is obstructed by the thumb, then the (Wagner et al 1989), this appears to be primarily the result
pressure is high but the flow is low. When the thumb is of a function of short pulmonary capillary transit times
removed the flow increases but the pressure falls. The fact rather than of thickening of the diffusion pathway by edema
that NO can attenuate pulmonary vascular pressures fluid (Fig. 3.10). However, in EIPH there is clearly evidence
during exercise, possibly by pulmonary endothelium- of disruption to the integrity of the alveolar capillary
dependent vasodilatation, also goes against the conven- membrane leading to red blood cells being found in the
tional view of the pulmonary vascular bed being fully interstitium. It is not inconceivable that some extravasation
dilated during exercise. An explanation of why inhaled NO would occur prior to frank hemorrhage. In fact, the total
may increase EIPH is that it may transfer the site of protein concentration in bronchoalveolar lavage fluid col-
pressure drop (resistance) into the capillary bed (Fig. 3.9). lected from horses soon after exercise is often increased,
As a result of exercise, the pulmonary right-to-left shunt even without significant evidence of EIPH (Marlin, Schroter,
(as a result of the coronary and bronchial circulations and Brown-Feltner and Deaton, unpublished observation).
The Impact of Disease 20
Exercise-induced pulmonary hemorrhage

15
Normal
Endoscopic studies have highlighted the high prevalence of
RAO
visible blood in the airways of horses following exercise. % 10
The increase in capillary pressure with strenuous and near
maximal exercise is sufficient to lead to stress failure of the
capillaries (Birks et al 1994, 1997) and the leakage of 5
blood from the circulation into the lungs (Fig. 3.9).
The most widely accepted theory to explain EIPH 0
is pulmonary capillary stress failure because of high 0.0 1.0 2.0 3.0
• •
V/Q ratio
transmural pressures (pressures or stresses acting on the
pulmonary capillaries). Pulmonary capillary transmural • • • •
Fig. 3.11. Distribution of ventilation (V ) perfusion (Q ) ratios (V /Q )
pressure is determined by the difference between in horses affected by recurrent airway obstruction (RAO) when in
pulmonary capillary pressure and airway pressure. When a high degree of clinical remission and in healthy,
•
normal horses
the high pressures (exceeding 100 mmHg during intense determined using inhaled krypton gas in air (V• ) and technetium-99m
exercise) distending the capillaries are opposed by highly macroaggregates of human albumin (MAA) (Q ).
positive airway pressures, such as occur during expiration,
the transmural pressure (and by implication, wall stress) is
low. However, when the distending internal vascular mechanism caused by arteriolar vasoconstriction to safe-
pressure is associated with a large negative airway pressure guard the capillary bed from the extremely high pressures
(as occurs during inspiration), the transmural pressure and induced by maximal exercise (Fig. 3.9).
wall stress will be high.
Lesions indicative of EIPH are predominantly present in Recurrent airway obstruction
the dorsal caudal region of the lung and it is possible that
this is the result of the reported greater perfusion (Bernard In human patients with pulmonary diseases such as
et al 1996, Harmegnies et al 2002) leading to increased asthma and chronic obstructive pulmonary disease, pul-
distension of the thin-walled capillaries in this region. monary hypertension may be observed. Human patients
Studies in isolated, perfused horse lungs have demon- may also develop pulmonary hypertension secondary
strated that significant disruption of the pulmonary to hypoventilation via the HPV mechanism. Pulmonary
capillaries occurs at pressures of approximately 80 mmHg. hypertension has been identified in RAO-affected horses
It has also been shown in vivo that there is probably a (Dixon 1978, Littlejohn & Bowles 1980, Nyman et al
threshold mean pulmonary artery pressure of around 1991a, Benamou et al 1998). However, in contrast
80–95 mmHg, above which significant hemorrhage is more to human patients with chronic pulmonary disease,
likely to occur (Meyer et al 1998, Langsetmo et al 2000). RAO-affected horses do not generally develop right heart
Consequently, any factor that serves to increase pulmonary failure secondary to primary pulmonary disease (i.e. cor
vascular pressures (e.g. hypervolemia) or to increase the pulmonale). Right ventricular hypertrophy may, however,
magnitude of the negative pressures in the lung during occur in severe and chronic cases of RAO. Although
inspiration (e.g. dynamic upper airway obstruction) would pulmonary artery pressure can be elevated in RAO-affected
be expected to increase the severity of EIPH. Indeed, horses, cardiac output is not, indicating that PVR is
hypervolemia is known to be associated with EIPH in increased (Nyman et al 1991a). Hypoxic pulmonary vaso-
racing standardbreds and the severity of EIPH is reduced constriction likely plays some role in the development of
following phlebotomy (Funkquist et al 2001). Interestingly, pulmonary hypertension in the horse as increased inspired
upper airway obstructions (neither experimentally induced oxygen fraction has been shown to reduce hypertension
laryngeal hemiplegia nor dorsal displacement of the soft (Dixon 1978). As might be reasonably expected, RAO-
• •
palate) have been found to increase pulmonary capillary affected horses show poor V /Q matching that improves
transmural pressure (Jackson et al 1997). after treatment (Votion et al 1999). Asymptomatic RAO-
Although NO administration reduces pulmonary affected horses in a high degree of clinical remission (less
arterial pressure during maximal exercise, the severity of than 10% bronchoalveolar lavage neutrophils) and main-
• •
EIPH is significantly greater following inhaled NO treat- tained at pasture have V/Q ratio distributions that are not
ment (Kindig et al 2001). This finding lends weight to the discernible from those of healthy controls (Fig. 3.11).
theory that the high pulmonary arterial pressures observed During intense exercise, RAO-affected horses have
during exercise of high intensity are in fact a protective higher mean pulmonary artery pressures (of the order
of ~10 mmHg higher) both in clinical remission and Kindig CA, Ramsel C, McDonough P et al 2003 Inclined run-
during an exacerbation compared to non-RAO controls ning increases pulmonary haemorrhage in the Thorough-
(Harmegnies et al 2002). Furthermore, RAO-affected bred horse. Equine Veterinary Journal 35: 581–585
Lancaster JR 1997 A tutorial on the diffusibility and reactivity
horses also have a greater redistribution of pulmonary of free nitric oxide. Nitric Oxide 1: 18–30
perfusion to the dorsal lung than non-RAO controls. Langsetmo I, Meyer MR, Erickson HH 2000 Relationship
of pulmonary arterial pressure to pulmonary haemor-
rhage in exercising horses. Equine Veterinary Journal
32: 379–384
REFERENCES Liao JC, Hein TW, Vaughn MW et al 1999 Intravascular flow
decreases erythrocyte consumption of nitric oxide.
Amis TC, Pascoe JR, Hornof W 1984 Topographic distri- Proceedings of the National Academy of Sciences USA
bution of pulmonary ventilation and perfusion in 96: 8757–8761
the horse. American Journal of Veterinary Research Littlejohn A, Bowles F 1980 Studies on the physiopathology of
45: 1597–1601 chronic obstructive pulmonary disease in the horse. II.
Benamou AE, Art T, Marlin DJ et al 1998 Variations in Right heart haemodynamics. Onderstepoort Journal of
systemic and pulmonary endothelin-1 in horses with Veterinary Research 47: 187–192
recurrent airway obstruction (heaves). Pulmonary Manohar M, Goetz TE 1998 L-NAME does not affect exercise-
Pharmacology and Therapeutics 11: 231–235 induced pulmonary hypertension in thoroughbred
Bernard SL, Glenny RW, Erickson HH et al 1996 Minimal horses. Journal of Applied Physiology 84: 1902–1908
redistribution of pulmonary blood flow with exercise in Manohar M, Goetz TE 1999 Pulmonary vascular resist-
racehorses. Journal of Applied Physiology 81: 1062–1070 ance of horses decreases with moderate exercise and
Birks EK, Mathieu-Costello O, Fu Z et al 1994 Comparative remains unchanged as workload is increased to maximal
aspects of the strength of pulmonary capillaries in rabbit, exercise. Equine Veterinary Journal Supplement
dog, and horse. Respiration Physiology 97: 235–246 30: 117–121
Birks EK, Mathieu-Costello O, Fu Z et al 1997 Very high McDonough P, Kindig CA, Hildreth TS et al 2002 Effect of
pressures are required to cause stress failure of pul- body incline on cardiac performance. Equine Veterinary
monary capillaries in thoroughbred racehorses. Journal Journal Supplement 34: 506–509
of Applied Physiology 82: 1584–1592 McLaughlin RF 1983 Bronchial artery distribution in
Butler AR, Megson IL, Wright PG 1998 Diffusion of nitric various mammals and in humans. American Review
oxide and scavenging by blood in the vasculature. of Respiratory Diseases 128: S57–S58
Biochimica et Biophysica Acta 1425: 168–176 McLaughlin RF, Tyler WS, Canada RO 1961 A study of the
Butler PJ, Woakes AJ, Smale K et al 1993 Respiratory subgross pulmonary anatomy in various mammals.
and cardiovascular adjustments during exercise of American Journal of Anatomy 108: 149–165
increasing intensity and during recovery in thorough- Meyer TS, Fedde MR, Gaughan EM et al 1998 Quantifica-
bred racehorses. Journal of Experimental Biology tion of exercise-induced pulmonary haemorrhage with
179: 159–180 bronchoalveolar lavage. Equine Veterinary Journal
Dixon PM 1978 Pulmonary artery pressures in normal 30: 284–288
horses and in horses affected with chronic obstruc- Mills PC, Marlin DJ, Demoncheaux E et al 1996a Nitric
tive pulmonary disease. Equine Veterinary Journal oxide and exercise in the horse. Journal of Physiology
10: 195–198 495: 863–874
Erickson BK, Erickson HH, Coffman JR 1990 Pulmonary Mills PC, Marlin DJ, Scott CM 1996b Pulmonary artery
artery, aortic and oesophageal pressure changes during pressure during exercise in the horse after inhibition
high intensity treadmill exercise in the horse: a possible of nitric oxide synthase. British Veterinary Journal
relation to exercise-induced pulmonary haemorrhage. 152: 119–122
Equine Veterinary Journal Supplement 9: 47–52 Nyman G, Lindberg R, Weckner D et al 1991a Pulmonary gas
Funkquist P, Sandhagen B, Persson SG et al 2001 Effects exchange correlated to clinical signs and lung pathology
of phlebotomy on haemodynamic characteristics during in horses with chronic bronchiolitis. Equine Veterinary
exercise in standardbred trotters with red cell hyper- Journal 23: 253–260
volaemia. Equine Veterinary Journal 33: 417–424 Nyman N, Bjork M, Funkquist P 1991b Gas exchange during
Harmegnies NF, Duvivier DH, Vandenput SN et al 2002 exercise in Standardbred trotters with mild bronchiolitis.
Exercise-induced pulmonary perfusion redistribution Equine Exercise Physiology 30: 96–101
in heaves. Equine Veterinary Journal Supplement Pelletier N, Robinson NE, Kaiser L et al 1998 Regional
34: 478–484. differences in endothelial function in horse lungs:
Jackson JA, Ducharme NG, Hackett RP et al 1997 Effects of possible role in blood flow distribution? Journal of
airway obstruction on transmural pulmonary artery Applied Physiology 85: 537–542
pressure in exercising horses. American Journal of Rhodes P, Leone AM, Francis PL et al 1995 The
Veterinary Research 58: 897–903 L-arginine:nitric oxide pathway is the major source
Kindig CA, Gallatin LL, Erickson HH et al 2000 Cardio- of plasma nitrite in fasted humans. Biochemical and
respiratory impact of the nitric oxide synthase inhibitor Biophysical Research Communications 209: 590–596
L-NAME in the exercising horse. Respiration Physiology Robinson NE 1985 Respiratory adaptations to exercise.
120: 151–166 Veterinary Clinics of North America: Equine Practice
Kindig CA, McDonough P, Finley MR et al 2001 NO inhalation 1: 497–512
reduces pulmonary arterial pressure but not hemorrhage Seaman J, Erickson BK, Kubo K et al 1995 Exercise induced
in maximally exercising horses. Journal of Applied ventilation/perfusion inequality in the horse. Equine
Physiology 91: 2674–2678 Veterinary Journal 27: 104–109
Sinha AK, Gleed RD, Hakim TS et al 1996 Pulmonary Wagner PD, Gillespie JR, Landgren GL et al 1989 Mechanism
capillary pressure during exercise in horses. Journal of of exercise-induced hypoxemia in horses. Journal of
Applied Physiology 80: 1792–1798 Applied Physiology 66: 1227–1233
Sonea IM, Bowker RM, Robinson NE et al 1993 Distribu- West JB, Dollery CT, Naimark A 1964 Distribution of blood
tion of dopamine beta-hydroxylase and neuropeptide flow in isolated lung: relation to vascular and alveolar
Y-immunoreactive nerves in healthy equine lungs. pressures. Journal of Applied Physiology 19: 713–724
American Journal of Veterinary Research 54: 507–513 Wilkins PA, Gleed RD, Krivitski NM et al 2001 Extravascular
Votion D, Ghafir Y, Vandenput S et al 1999 Analysis of lung water in the exercising horse. Journal of Applied
scintigraphical lung images before and after treatment of Physiology 91: 2442–2450
horses suffering from chronic pulmonary disease.
Veterinary Record 144: 232–236
Gas Exchange in Horses
4 R Eddie Clutton
Oxygen (O2) is required in aerobic organisms to oxidize the energy substrate being oxidized. The RQ is 1.0 for
energy-dense compounds like glucose to produce adenosine carbohydrate metabolism, 0.8 for protein metabolism and
triphosphate (ATP), the most common energy source 0.7 for fat oxidation.
for biochemical reactions. Glucose oxidation involves
glycolysis, in which 1 mole of glucose is converted into
2 moles of pyruvic acid and some ATP, and the Krebs cycle,
Units and Definitions
in which each mole of pyruvate yields an additional Gas diffusion involves random molecular movement from
15 moles of ATP. Therefore, the complete oxidation of areas of high partial pressure to areas of low partial
1 mole of glucose to carbon dioxide (CO2) and water (H2O) pressure. The rate of diffusion depends on the partial
yields either 36 or 38 moles of ATP. pressure (or tension) difference between each area. The
partial pressure (P) of a gas in a mixture is the pressure
Reaction 1. 6 O2 + C6H12O6 → 6 CO2 + 6 H2O + 36 ATP
that a given gas would exert if it alone occupied the
The pyruvate produced by glycolysis only enters the space. Partial pressures are not the same as “contents” or
Krebs cycle if O2 is available. Under anaerobic conditions, “concentrations” but are important because they deter-
pyruvate is converted to lactic acid in a reaction that is mine the rate and direction of gas diffusion. The concen-
relatively inefficient in terms of ATP production and tration or content of gases in liquids (usually expressed as
which lowers tissue pH. These reactions occur within ml of gas per dl of blood) are important because in the final
• •
mitochondria, which represent the final destination of analysis, O2 consumption (VO2) and CO2 production (VCO2)
inspired O2 in the “oxygen cascade” (Table 4.1). occur on a ml/kg basis. The link between tension and
The simultaneous production of CO2 creates a diffusion content of a gas in a liquid is given by Henry’s law, which
gradient that initiates CO2 movement in the opposite states that the volume (V) of gas dissolving in a liquid is
direction. The prompt removal of CO2 from metabolically proportional to the partial pressure (P) of the gas:
active tissue is important because its accumulation results
Equation 1. V = kP
in a rapid lowering of tissue pH through carbonic acid
formation. where k is the solubility coefficient of a specified gas in a
liquid. For CO2 in water, k = 0.07 ml·mmHg–1·dl–1. For O2 in
Reaction 2. H2O + CO2 ↔ H2CO3 ↔ HCO3– +
+H
water, k = 0.0225 ml·kPa–1·dl–1 (0.003 ml·mmHg–1·dl–1).
In excess, protons (H+) denature enzymes, affect ion Two measurement systems are used for partial pressure.
complex dissociation, alter biological membrane behavior, These are mmHg (also known as Torr) and the SI unit
and disrupt membrane transport systems. kPa where 1 kPa = 7.52 mmHg. Blood gas values from
The ratio of CO2 production to O2 consumption is horses and foals are listed in Table 14.5 in Chapter 14.
known as the respiratory quotient (RQ) and indicates
Oxygen Movement from Atmosphere
to Alveolus
Table 4.1. The oxygen cascade The partial pressure (P) of O2 in inspired (i) air (PI O2) is
Site Notation kPa mmHg given by FI O2 × PB, where FI O2 is the fractional con-
centration (F) of inspired O2 and PB is the barometric
Inspired PIO2 21.21 159
pressure. When breathing air (21% O2), FI O2 is 0.21 given a
Alveolar PAO2 13.7 103
Arterial PAO2 13.3 100 normal barometric pressure of 101 kPa (760 mmHg),
Capillary PcO2 6.8 51 although this value changes with meteorological con-
Mitochondrial PMITOO2 0.13–1.3 1–10 ditions and falls with increasing altitude. Thus, the inspired
O2 tension is 0.21 × 101 = 21.21 kPa (or 159 mmHg) and
45
46 4 Gas Exchange in Horses
the overall maximum tension gradient of the O2 cascade is probably an important means of heat dissipation in
21.21 – 0.13 = 21.08 kPa (or 158 mmHg). However, the exercising horses (Pelletier 1987). The proportion of
alveolar (A) O2 tension (PAO2) is less than this, because inspired gas that inflates non-perfused alveoli also fails to
inspired air is humidified as it traverses the airways, contribute to gas exchange and is known as alveolar dead
becoming saturated with water vapor before it reaches the space (VDALV). The combination of VDANAT and VDALV is
alveolar space. The saturated vapor pressure of water called physiological dead space (VDPHYS).
(PH2O) is 6.26 kPa (47 mmHg) at body temperature (37°C)
Equation 3. V DPHYS = V DANAT + V DALV
and reduces the partial pressures of other inspired gases.
Alveolar O2 is also diluted by CO2 evolving into the alveolar The volume of gas reaching alveoli per minute and
space from pulmonary capillaries. The dilution of inspired potentially able to participate in gas exchange is known as
•
O2 is described by the alveolar gas equation: the alveolar minute ventilation (VA) and is given by:
•
Equation 2. PAO2 = FIO2 ( PB – P H2O ) – ( PaCO2 /RQ) Equation 4. VA = (V T – V DPHYS) fR
•
where PaCO2 is the arterial tension of CO2 and RQ is the where f R is the respiratory rate. Alveolar ventilation (VA ) is
respiratory quotient (see above). an important physiological variable, being the principal
Ventilation, which is the bulk movement of O2-rich determinant of CO2 tension in blood (see equations 1 and
and CO2-free gas into the alveolar space has two purposes: 2 in Chapter 14). The relationship between dead space
(1) to ensure that the alveolar O2 tension is sufficiently volume and tidal volume is given by Bohr’s equation:
greater than that in pulmonary capillary blood to main-
Equation 5. VD /V T = ( PACO2 – P E៮ CO2 ) / PACO2
tain constant O2 diffusion across the alveolar–capillary
membrane; and (2) to maintain a sufficiently low alveolar where PaCO2 is used to indicate PACO2 and PE៮ CO2, the mixed
CO2 tension (PACO2) to maintain constant CO2 diffusion in expired CO2 tension, is measured by capnometry during
the reverse direction. However, not all inspired gas reaches expiration. Ventilation ensures the bulk flow of fresh gas
the alveolar space to fulfil these functions (see Fig. 4.1). into the terminal bronchioles while gas movement into the
In horses, approximately 50% of the tidal volume (VT) alveoli occurs because of rapid diffusion.
remains within the upper airway and is exhaled unchanged
with the next breath (Gallivan et al 1989). These regions
of the tracheobronchial tree do not participate in gas
Gas Diffusion Across the Alveolar
exchange and gas contained within them constitutes
Capillary Membrane
anatomic dead space (VDANAT ). Dead space ventilation is Alveolar gases (CO2 and O2) diffuse passively across the
alveolar–capillary membrane in accordance with Fick’s law
(equation 6). The rate of gas transfer (Vgas ) is directly
proportional to the alveolar–capillary surface area avail-
able for exchange (A), the difference in gas partial pres-
sures between the alveolus and capillary (PA – PV), and the
solubility of each gas in water (s). Diffusion rate is inversely
proportional to the thickness of the alveolar–capillary
membrane (d) and the square root of each gas’s molecular
mass (RMM).
Equation 6. Vgas = [A ( PA – PV ) s] / d (RMM)1⁄ 2
On the basis of its relative molecular mass, O2 diffuses

more rapidly than CO2. The diameter of the human
alveolus is only 0.1 mm and differences between gas
tensions at the center and periphery of the alveolus are
A. End-expiration B. Inspiration C. End-inspiration D.Expiration theoretically eliminated in about a millisecond. However, in
human emphysema, alveoli coalesce to form air sacs,
which may themselves form bullae with diameters of
Alveolar gas Fresh inspired gas
10 mm or more. In these, diffusion from the center to the
Fig. 4.1. Dead space ventilation in the resting horse. Approximately periphery may be slow enough to limit Vgas. While this in
50% of the tidal volume resides in the anatomic dead space at the theory may lead to CO2 retention, hypercapnia does not
end of expiration (A). Therefore, when a 500-kg horse inspires 6 litres •
occur for this reason because compensatory increases in VA
of air (each block represents 3 litres of gas) only 3 litres participates
in gas exchange (B and C). The anatomic dead space is augmented occur. Values for A in horses are high compared to other
by inspired gas distributed to underperfused alveoli, or alveolar species, which satisfies their high VO2 during exercise (Gehr
dead-space. & Erni 1980, Gehr et al 1981, Taylor et al 1981).
4 Gas Exchange in Horses 47
Oxygen and CO2 passage across the alveolar membrane During this period, the O2 tension in flowing alveolar blood
involves solution in the alveolar fluid layer and so aqueous rises from 5.33 towards 13.3 kPa (40–100 mmHg), with
solubility is important. CO2 is 25 times more soluble than equilibration (when capillary tension (Pc′ O2) equals PAO2)
O2 in the alveolar fluid layer. The relative rates of diffusion occurring within approximately 250 ms (curve A, Fig. 4.2).
for O2 and CO2 between alveoli and capillaries is found by This leaves an additional 500 ms for equilibration should
combining diffusibility and water solubility; this reveals any diffusion impediment arise. However, when diffusion is
CO2 to be about 20 times more diffusible than O2. For this severely curtailed, e.g. at altitude, equilibration may not
reason, outward diffusion of CO2 from the blood into the occur in the 750 ms available (curve B), in which case the
alveolus is rarely, if ever, a clinical problem. end-capillary O2 tension (Pc′O2) will be lower than PAO2 and
The difference between alveolar and mixed venous O2 will increase venous admixture (see below). During
tensions in pulmonary capillaries, i.e. the P(A–V)O2 , is strenuous exercise, pulmonary transit time may be reduced
the generator for O2 passage across the alveolar–capillary to 150 ms, which may be insufficient time for equilibration
membrane and is increased when high O2 concentrations if diffusion is also retarded (curve C). The passage of large
are inspired. Its value can be calculated using the alveolar blood volumes at high rates through the lungs when there
gas equation (equation 2). In the following example is insufficient time for P(A–a)O2 equilibration contributes to
(equation 7) PaCO2 is taken as 5.33 kPa (40 mmHg), RQ hypoxemia in exercising horses (Wagner et al 1989). Curve
is taken as 1.0, and the O2 tension in blood returning D illustrates the benefits of inspiring enriched O2 mixtures
to the lungs (PVO2) is 5.33 kPa (40 mmHg). Under nor- (50% O2 in this example). This accelerates O2 diffusion
mal conditions and when breathing room air, FI O2 has a
value of 0.21:
Equation 7. PAO2 = [0.2 (101 – 6.26)] – 5.33
= 13.62 kPa (102.6 mmHg)
PVo2 Pc’o2
and P(A–V)O2 = (13.62 – 5.33)
5.3 kPa 13.3 kPa
= 8.29 kPa (62 mmHg)
(40 mmHg) (100 mmHg)
When breathing 100% O2 (FI O2 = 1): PAO2
Equation 8. PAO2 = [1.0 (101 – 6.26)] – 5.33

= 89.41 kPa (673 mmHg)
and P(A–V)O2 = (89.41 – 5.33)
= 84.1 kPa (633 mmHg)
42 D 316
Consequently, providing 100% O2 to breathe increases
Pc’O2 end-capillary oxygen tension (mmHg)

the P(A–V)O2 tension gradient 10-fold and greatly accelerates
Pvo2 mixed venous oxygen tension (kPa)
O2 movement into pulmonary capillaries. This contrasts

with the small increase produced by controlled or
voluntary hyperventilation, which increases PAO2 by
reducing PaCO2. High altitude may have an incapacitating
effect on alveolar O2 diffusion, which may be important in PA O 2 A
13.3 100
international competition horses. At an altitude of 3048 m B
(10,000 feet), the barometric pressure is only 69.6 kPa
C
(522 mmHg). According to the alveolar gas equation, at
this altitude: 5.3 Pvo2 40
Equation 9. PAO2 = [0.2(69.6 – 6.26)] – 5.33

= 7.34 kPa (55 mmHg) 0 250 500 750
and P(A–V)O2 = (7.34 – 5.33) Capillary transit time (ms)
= 2.01 kPa (15 mmHg),
Fig. 4.2. The effects of alveolar oxygen tension and pulmonary
which is inadequate for O2 transfer into pulmonary capil- capillary transit time on end-capillary oxygen tensions. Curve A,
laries (Greene et al 1999). alveolar (PAO2) and end-capillary (Pc′O2) oxygen tensions normally
Oxygen uptake also depends on pulmonary capillary equilibrate within 250 ms. Curve B, diffusion impairment may
transit time because there is a finite time available for prevent equilibration in which case Pc′O2 is less than PAO2 and con-
tributes to venous admixture. Curve C, short capillary transit times
alveolar gases to equilibrate with pulmonary capillary
(250 ms) and diffusion impairment prevent alveolar and end-capillary
blood (Fig. 4.2). Estimates in resting human beings indicate oxygen tension equilibration. Curve D, breathing oxygen-enriched gas
that pulmonary capillary blood remains in contact with increases PAO2 and greatly accelerates alveolar and end-capillary
the alveolar capillary membrane for 750 milliseconds (ms). oxygen tension equilibration.
into pulmonary capillary blood by greatly increasing the • •

A) V/Q = 1.0 •
alveolar–capillary O2 tension difference. VA
PVo2 Pc’o2 Pulmonary vein
In diffusing from the alveolus to the erythrocyte, an O2
5.3 kPa 13.3 kPa
molecule must cross several layers before combining with
40 mmHg C A O2 100 mmHg
hemoglobin (Hb). These include the alveolar gas, the
surfactant/fluid layer, the alveolar epithelial membrane,
the capillary endothelial membrane, the plasma, the
•
erythrocyte membrane, and the intra-erythrocytic fluid. QT
The diffusion path length thus outlined may be increased • •
B) V/Q > 1.0 •
pathologically in several ways, e.g. by edema, fibrosis, VA
and in theory may impair diffusion. The area of perfused
5.3 kPa >13.3 kPa
alveoli available for gas exchange is reduced in human
emphysema when alveolar walls are broken down, and O2 40 mmHg C A O2 100 mmHg Venous
admixture
diffusion may be limited by a decrease in the area available
•
for gas exchange. QT
Ventilation/Perfusion Ratios • •
C) V/Q < 1.0 •
VA
• •
The link between ventilation (V ) and lung perfusion (Q )
affects the efficiency of gas exchange. Breathing expends 5.3 kPa <13.3 kPa
metabolic energy because work is performed in ventilating 40 mmHg C A O2 100 mmHg
alveoli. Biological efficiency is best served when the
gas volume inspired is only just sufficient to arterialize
•
pulmonary capillary blood. In normal lungs most alveoli QT
are adequately perfused although the best-ventilated units
are not necessarily the best perfused. Alveolar O2 con- D) “shunt”
•
centration (CAO2) is a function of VA (input) and the rate of
O2 removal by perfusion. Therefore, CAO2 and ultimately 5.3 kPa 5.3 kPa
• •
pulmonary capillary O2 tension depends on the V/Q ratio 40 mmHg 40 mmHg
• •
(Fig. 4.3A). Optimally, the VA and Q T are almost the same
• •
and so the normal ratio of VA to Q T is approximately
• • •
1.0. Disparity between ventilation and perfusion (V /Q QT
discrepancy, scatter or mismatch) is important because • •
• • Fig. 4.3. Ventilation/perfusion (V /Q ) relationships in the lung.
it represents inefficient gas exchange. V /Q matching is • • • •
(A) normal, (B) high V /Q , (C) low V /Q and (D) “shunt” flow units and
profoundly altered during general anesthesia in horses their effects on pulmonary venous oxygen levels. The content of
when the effects of reduced cardiac output are aggravated oxygen in alveolar gas (CAO2) determines blood oxygenation, and
•
by changes in position. It was previously believed that depends on input by minute alveolar ventilation (VA ) and uptake
•
by
dorsal lung regions received less ventilation and perfusion pulmonary perfusion, which is the same as cardiac output (Q T).
than ventral areas in conscious standing horses (Amis et al
1984). However, more recent studies have challenged this
by demonstrating that pulmonary blood flow distribution is ventilation is more uniform when animals are in sternal,
largely independent of gravity in healthy, standing horses compared to lateral or dorsal, recumbency. This suggests
(Hlastala et al 1996) and that there is good ventilation/ that the sloping diaphragm protects the lungs from
• •
perfusion matching with VA and Q T being directed to units compression by abdominal contents in standing animals
• •
in which the V/Q ratio is 1.0 (Hedenstierna et al 1987). (Sorensen & Robinson 1980). The heterogeneous distribu-
• •
Despite this, V/Q mismatching is probably the commonest tion of inspired gas arises because the suspended lung
cause of low PAO2 in Equids and arises when pulmonary has mass that stretches dorsal alveoli and increases
ventilation and perfusion are not distributed evenly their volume more than those at the base. Also, intra-
throughout the lungs. pleural pressure becomes less subatmospheric towards
Dependent lung regions are better ventilated than upper the sternum. Both effects place dorsal alveoli at the upper
zones during spontaneous breathing at normal lung end of their volume–pressure curve where compliance is
volumes, irrespective of body position (see Fig. 4.4). How- low. By contrast, ventral alveoli operate on the steeper
ever, when lung volume is low, as may be found in portion of their curve and therefore have higher com-
pregnant mares at term, dependent parts of the lung are pliance. As a consequence of the differences in regional
poorly ventilated or not ventilated at all. The distribution of lung compliance, decrements in intrapleural pressure
Dorsal alveoli
(normal volumes)
B
FRC
Lung volumes
A Ventral alveoli (normal volumes)
Residual volume C Dorsal alveoli (low volumes)
Ventral alveoli (low volumes)

D
+ 0 –
Pleural pressure
Fig. 4.4. Volume–pressure relationships for the equine lung at low and normal volumes. Ventral alveoli
receive greater ventilation (curve A) than dorsal alveoli (curve B) when breathing from the resting
expiratory level of functional residual capacity (FRC). This pattern is reversed at low lung volumes when
ventral alveoli (curve D) may be collapsed.
during inspiration cause relatively larger increases in ventricle. In addition, the thin alveolar–capillary mem-
ventral (Fig. 4.4A) compared with dorsal alveoli (Fig. 4.4B). brane that separates air and blood in the pulmonary
This is not the case when the lung is operating at low circulation means that hydrostatic pressures exert a major
volumes, for example during anesthesia or in advanced effect on small blood vessel caliber, while alveolar pressures
pregnancy. Under these conditions, the pleural pressure at also exert an appreciable effect on local blood flow. West
the lung’s base can exceed atmospheric pressure so that (1977) summarized the effects of different pulmonary
ventral lung is under compressive rather than expansive arterial, alveolar, and venous pressures on pulmonary
pressures. This corresponds to the flat, left-hand portion blood flow by describing four lung zones; however, this
of the volume–pressure curve. Thus, small decreases in model may be less applicable to the horse.
• •
pleural pressure cause dorsal (Fig. 4.4C), rather than Two intrinsic mechanisms operate to optimize V/Q ratios
ventral (Fig. 4.4D) ventilation. Only when ventral pleural in the normal mammalian lung. The more important is
pressure falls below atmospheric pressure will alveoli here known as hypoxic pulmonary vasoconstriction (HPV), which
•
begin to expand. Regional differences in alveolar size also diverts blood from underventilated lung to areas where VA
confer different patterns of radial traction on conducting is higher (Bisgard et al 1975, Marshall & Marshall 1985).
airways. Expanded alveoli at the lung’s apex increase the Hypoxic vasoconstriction is strong in ponies compared to
airway diameter in this region rendering it a low-resistance some other species but is incapacitated by some anesthetics
pathway for inspired gas. The paucity of collateral venti- and possibly by inflammatory lung disease (Robinson 1982).
lation in the equine lung aggravates the effects of uneven Hypercapnic bronchodilatation is a complementary though
ventilation distribution (Robinson & Sorenson 1978). relatively impotent reaction compared with HPV. In hyper-
Regional inequalities in perfusion occur in human capnic bronchodilatation, high CO2 concentrations from
• •
beings in whom blood flow is greatest in dependent regions, low V/Q units induce bronchodilatation and this increases
• •
and least in non-dependent regions. However, this pattern local ventilation, returning V/Q ratios towards normal.
is less typical of horses (Hlastala et al 1996), in which
perfusion is position-independent and tends to be greatest
in dorsocaudal regions (Dobson et al 1985, Jarvis et al
Ventilation/Perfusion Mismatching
1992). Exercise affects pulmonary blood distribution with Scanning studies performed in standing horses were unable
• • •
Q T increasing five- or six-fold and pulmonary arterial to demonstrate a gradient of V /Q ratios between dorsal
pressures reaching 100 mmHg in exercising horses (Sinha and ventral regions of the lung (Amis et al 1984). More
et al 1996). Both dorsal and ventral blood flows increase recently performed multiple inert gas studies showed that
• • •
accordingly but the proportion of total flow reaching the up to 10% of Q T is directed towards high V/Q units in the
dorsocaudal regions is disproportionately greater. Lung upper portions of the lung (Hedenstierna 1987). The latter
• •
volumes also affect perfusion because pulmonary vascular indicates that V /Q ratio scatter in conscious horses is
resistance is high when the lung is deflated to a low similar to that seen in human beings (Hedenstierna et al
• •
volume. In human beings, uneven blood flow distribution 1987). This variation in V/Q ratios makes regional differ-
throughout the lung results from the combined effects of ences in gas exchange inevitable and reduces gas exchange
• •
gravity and the low pressures generated by the right efficiency. Gas exchange in lungs in which V/Q ratios are
widely dispersed is less efficient than that occurring in chitis, alveolitis, and neoplasia) or intracardiac (e.g. ven-
• •
lungs in which V/Q variation is low. tricular septal defects that cause blood to flow from the
• •
The effect of V /Q mismatching in normal lungs is of right to left side of the heart). The response to breathing
little significance. PAO2 may be reduced by perhaps 1–2 kPa, 100% O2 can differentiate hypoxemia caused by shunts
• •
while PaCO2 increases are even less. Regardless, both from that caused by low V/Q ratios. The hypoxemia caused
discrepancies are readily corrected by increased ventilation, by shunts is unresponsive to increased inspired O2 concen-
• • • •
which increases the overall V /Q ratio. Any lung abnor- tration. In contrast in low V/Q alveoli, increasing the per-
mality such as recurrent airway obstruction (Nyman et al centage of inspired O2 causes some improvement in PAO2.
• •
1991) can cause V/Q inequalities and severely affect gas With regard to O2 exchange, blood from lung regions
• • •
transfer. It is important to realize that no amount of VA can with high V/Q ratios is rarely able to compensate for the
• • • •
resolve V /Q discrepancies causing more than a 6.6 kPa venous admixture from low V/Q regions. This is because
(50 mmHg) depression of PAO2. In contrast, increasing total the volume of blood is small even though its Hb is almost
ventilation can reduce PaCO2 but this can lead to an saturated. In the case of CO2 exchange, this does not apply
unsustainable increase in the work of breathing, in which because the relationship between blood content and
• •
case chronic hypercapnia ensues. alveolar tension is more linear. Blood leaving high V /Q
• •
Alveoli with high V/Q ratios are ventilated but under- units contains proportionately less CO2. Increasing total
• •
perfused and are found in West’s Zone 1 and periodically, in lung ventilation in the presence of V /Q abnormalities
parts of Zone 2 (Fig. 4.3B). Oxygenation is usually not a increases CO2 excretion and thereby compensates for
problem in these units because O2 added by ventilation reduced CO2 losses from underventilated lung. However,
• •
exceeds that removed by blood flow. However, high V /Q increased ventilation does not compensate for reduced O2
units contribute relatively little to O2 uptake because PAO2 is uptake in poorly ventilated lung. Impaired pulmonary
likely to be at levels producing near-complete Hb satura- O2 exchange may be quantified while the animal breathes
tion and total blood flow is low. However, this situation air by use of the alveolar gas equation to calculate P(A–a)O2
changes on exercise when blood flow to the dorsal lung (see Equation 2 and Chapter 14).
• •
regions increases. Areas with high V/Q ratios effectively,
though inefficiently, remove excessive CO2. The alveolar
gas equation indicates that alveolar dead space may
Hemoglobin Binding of Oxygen
cause hypoxemia because of alveolar CO2 accumulation. Plasma carries only small volumes of O2 in solution
•
Increasing VA and/or increasing the inspired O2 concen- because the solubility coefficient of O2 is low (see equa-
tration may ameliorate this effect. tion 1). At a normal PAO2 of 13.3 kPa (100 mmHg) each
• •
Lung units with low V/Q ratios impair the oxygenation deciliter of plasma contains only 0.3 ml O2. Hemoglobin
of blood (Fig. 4.3C). This poorly oxygenated blood dilutes increases the O2 carrying capacity of blood 65-fold
oxygenated blood returning to the left heart from because each gram Hb combines with 1.34 ml of O2. When
appropriately ventilated and perfused alveoli. This diluting the plasma Hb concentration is normal (15 g/dl) the
action, known as venous admixture, always lowers PAO2. volume of Hb-bound O2 is 15 × 1.34 × SO2 ml (where SO2
In the West model of gas exchange in human lungs is the percentage saturation of Hb). Reference to the oxy-
(Fig. 4.3B), venous admixture comes predominantly from hemoglobin (HbO2) dissociation curve (Fig. 4.5) illustrates
• •
low V /Q units in ventral alveoli. These units strongly that SO2 has a value of 0.97 (Hb is 97% saturated) when
influence arterial blood composition because they receive a arterial O2 tensions are normal [13.3 kPa (100 mmHg)].
large percentage of the pulmonary blood flow, have a low Thus, the volume of Hb-bound O2 under these conditions
PAO2 and an increased PACO2. It is important to point out, is 15 × 1.34 × 0.97 = 19.5 ml/dl and the total arterial O2
however, that recent studies in horses indicate that gravity content (CaO2) is given by:
is not an important determinant of blood flow distribution
Equation 10. CaO2 = [(Hb) × 1.34 × 0.97] + (13.3 × 0.0225)
(Hlastala et al 1996), which questions the relevance of the
= 19.8 ml/dl
West model for equine lungs.
Anatomic and pathological shunt contributes to venous Breathing 100% O2 increases PAO2 to 89.5 kPa
admixture. “Shunt” describes the passage of blood from (673 mmHg) and the amount of O2 in solution in plasma
right (pulmonary) to left (systemic) circulations without to 1.8 ml/dl. However, because the Hb is almost fully
exposure to alveolar gas (see Fig. 4.3D). Anatomic shunt saturated when breathing air, breathing pure O2 increases
refers to the small volume of Thebesian (coronary) and CaO2 by only 10%.
bronchial venous blood that normally drains into the The reaction of Hb with O2 has three important
systemic circulation. In some conditions, e.g. pleuritis, properties. First, it is rapid and reversible. Second, the
this normal fraction increases during the hyperemic molecular structure, which involves four globin chains,
response to inflammation. Pathological shunts can be causes the reaction of each chain with O2 to facilitate
either intrapulmonary (e.g. pneumonia, atelectasis, bron- subsequent binding. This accounts for the sigmoid shape of
100 Cardiac Output and Oxygen Flux

90
Oxygen flux (DO2) describes the total volume of O2 delivered
Hemoglobin saturation (%)
80
70 to peripheral tissue. It is equal to the product of the O2
60 content of arterial blood and cardiac output:
50 •
40
Equation 11. DO2 = Q T ([Hb] × 1.34 × SaO2) + (PAO2 × 0.0225)
30 where PAO2 is in kPa. Substituting figures for a horse with
20 a resting cardiac output of 0.6 dl·kg–1·min–1 gives a value
10 P50
for DO2 of 12.2 ml·kg–1·min–1, which considerably exceeds
0 •
0 2.5 6.6 8.0 13.3 kPa the resting animal’s requirements (VO2) of 4 ml·kg–1·min–1
0 10 20 30 40 50 60 70 80 90 100 mmHg and ensures that a state of aerobic metabolism prevails.
Po2 This can be expressed in terms of the “coefficient for O2
•
utilization” which is given as VO2/DO2, and in the above
Fig. 4.5. The dissociation curve for equine hemoglobin. The oxygen example is 32.7%
tension corresponding to 50% hemoglobin saturation (P50) value in A consequence of the factorial nature of equation 11 is
horses is less than the corresponding value for human hemoglobin, that relatively minor reductions in each factor produce a
indicating a “left-shifted” curve. The “shoulder” of the dissociation
curve lies at a correspondingly lower value of PO2 (40 mmHg). Drawn
disproportionately great effect on DO2. For example, when
from data in Clerbaux et al, 1986 and Fenger et al, 2000, with values for plasma Hb concentration, cardiac output and
permission. SO2 are halved, DO2 is reduced to 12.5% of normal. Such
changes culminate in critical DO2 reductions and are com-
monly encountered in equine anesthesia, where low PAO2
•
values are inevitable and Q T is often severely depressed by
the HbO2 dissociation curve (ODC), which is required for inhaled anesthetics. Under these conditions, mildly anemic
optimal pulmonary uptake and tissue O2 release. Third, the horses may experience critical reductions in O2 flux.
rate of reaction of Hb with O2 is affected by pH.
The ODC (Fig. 4.5) depicts the relationship between
The Movement of Gas from Blood
plasma O2 tension and Hb saturation (SO2). The latter is the
to Tissues
amount of O2 combined with Hb (O2 content) divided by
the total Hb O2 capacity. The equine ODC lies to the left of The tension gradient causing O2 diffusion from plasma
the normal human curve. The sigmoid relationship across capillary walls into interstitial fluid and finally
means the slope is steep at low, and flat at high PO2 values. into cells depends on the metabolic activity of the
The upper flat (associative) part of the curve corresponds latter, because arteriolar PO2 is normally constant at
to PO2 values normally encountered in the lung, while the 13.3 kPa (100 mmHg). Metabolically active cells lower
lower steep (dissociative) part covers tissue PO2 values. local O2 tensions below those in the capillary, which in
The important features of the association segment are turn lowers plasma PO2 and causes HbO2 dissociation.
that (1) Hb is almost 100% saturated at relatively low Tissue O2 tensions normally range from 1.33 to 5.33 kPa
PO2 values; (2) increasing PO2 much above physiological (10–40 mmHg).
values (5.33 kPa or 100 mmHg) does not produce cor- The dissociation portion of the ODC is adapted to release
respondingly larger increases in the SO2; and (3) Hb O2 at tissue level. The steep part corresponds to PO2 values
saturation does not change appreciably over the PO2 range from 1.33 to 5.33 kPa and so small decrements in tissue O2
6.56–13.3 kPa (50–100 mmHg). cause disproportionately large reductions in SO2 and
The steep dissociative part of the ODC occurs over the O2 release. This is facilitated by the right shift in the
range of PO2 encountered in metabolically active tissues. In ODC caused by the low pH and elevated temperatures
these tissues there are factors that reduce the affinity of found in active tissue (see previous section).
Hb for O2 and cause a “right-shift” in the ODC. Increased Tissue O2 delivery depends on the rate and pattern of
temperature, increased H+ (decreased pH), increased PCO2, tissue blood flow and, while most gas exchange occurs at
increased ADP and increased 2,3-diphosphoglycerate all capillary level, considerable diffusion is possible wherever
facilitate the unloading of O2 at the tissue level. In the lung vessel walls are gas permeable and adequate transmural O2
and pulmonary capillaries the opposite conditions prevail. tension gradients exist. Tissue perfusion depends on the
Carbon dioxide is evolved, blood pH rises and blood is arteriovenous pressure gradient and vascular resistance.
cooled. Even though all three factors increase the affinity Arterial and venous pressures are generally maintained
of Hb for O2 and augment pulmonary uptake, the effect within a small range so the principal determinant of local
is small over the associative part of the ODC, which is perfusion is vascular resistance. Gas diffusion into the
operative in the lung. tissues is facilitated when the distance between cells
and capillaries is small. During the high oxygen demands syndromes contribute to the two main causes of alveolar
of exercise, diffusion distance is effectively reduced by hypoxemia: (1) venous admixture, arising from “shunt”
• •
recruitment of previously unperfused capillaries and and/or a predominance of diseased lung with low V /Q
by local vasodilatation. These changes are initiated by ratios and (2) low PVO2 in the presence of shunt. A third
the same factors that promote HbO2 dissociation, i.e. local factor, diffusion limitation, is not thought to cause arterial
hypoxia, acidosis, hypercapnia and temperature elevation. hypoxia in human beings or Equids (Derksen 1991) although
Hemoglobin itself may contribute to blood flow control. A the evidence is elusive.
major portion of the vasodilator nitric oxide in the blood is In hemoglobinemic hypoxia, the O2 carrying capacity of
bound to Hb, forming S-nitroso-Hb. On deoxygenation of blood is reduced because of inadequate concentrations of
Hb, the bound nitric oxide is released into the micro- functional Hb. Stagnant hypoxia reflects the inadequate
circulation, causing vasodilatation. delivery of oxygenated blood to meet tissue demands and
•
When tissue metabolic requirements are met, O2 extrac- can occur because of low cardiac output (Q T), increased
tion is fairly constant, irrespective of DO2. When DO2 blood viscosity or severe vasoconstriction. Histotoxic
becomes limited by inadequate flow, a linear relationship hypoxia is seldom encountered in practice, but occurs
develops between O2 delivery and O2 extraction. This flow- when metabolic poisons like cyanide block the enzymes
limited or critical O2 delivery system is altered by shock, involved in oxidative phosphorylation. Finally, demand
when critically low DO2 causes anaerobic metabolism. hypoxia arises when O2 delivery falls short of total
body requirements. It is encountered during exercise at
•
workloads approximating 90% VO2MAX, when horses
Tissue Hypoxia become both hypoxemic and hypercapnic. It has been
The steps of the O2 cascade (Table 4.1) provide a sequential proposed that the metabolic demand of horses surpasses
basis for describing the development of tissue hypoxia, their ventilatory capacity to meet the O2 demand. Ponies
•
which occurs when tissue O2 requirements (VO2) fall below are less athletic and so their ventilatory responses can meet
the rate of supply (DO2). The earlier in the cascade when metabolic requirements (Katz et al 1999).
hypoxia develops, the greater the consequence at the
mitochondrial level. Conversely, breathing O2 greatly
improves O2 delivery to the tissues.
Carbon Dioxide Elimination
Atmospheric hypoxemia results when the O2 tension of Generally O2 consumption is matched by CO2 production,
inspired gas (PI O2) is inadequate. This can occur at very though this depends on the metabolic substrate (carbo-
high altitudes where barometric pressure is low, or in hydrate, fat or protein). The processes involved in CO2
any situation where the fraction of inspired O2 (FI O2) is elimination are the reverse of those involved in O2 uptake.
reduced. Examples of the latter are rare, except during The same principles of partial pressure gradients and gas
nitrous oxide anesthesia. exchange apply although CO2 is more soluble than O2 in
•
Tidal hypoxemia results from inadequate VA and is water and undergoes more rapid diffusion.
therefore readily identified by a concurrent elevation
in PaCO2. The decrease in PAO2 is approximately equal to the
increase in PaCO2: increases in PaCO2 from 5.33 to
Carbon Dioxide Transport in Blood
10.66 kPa (40 to 80 mmHg) are accompanied by falls in Metabolically generated CO2 diffuses from active cells into
PAO2 from 13.3 to 7.99 kPa (100 to 60 mmHg). It follows interstitial fluid and thence across capillary walls into
that hypoventilation must be severe for O2 tensions to plasma. A proportion of CO2 diffusing into plasma enters
fall critically. In any case, tidal hypoxemia responds readily the erythrocyte. In plasma, CO2 undergoes one of three
to both ventilation and to increased O2 administration. reactions. First, some CO2 forms carbonic acid upon
Tidal hypoxemia is caused by (1) suppressing neural hydration (see reaction 2) although the absence of car-
control of breathing, e.g. heavy sedation or depression; bonic anhydrase in plasma and the accumulation of H+
(2) reducing respiratory muscle function, e.g. diaphrag- and HCO3– ensures that this reaction proceeds slowly.
matic hernia, tympany, pleuritis; or (3) obstructing the The second reaction involves physical solution and is
upper airway, e.g. pharyngeal collapse, laryngeal paresis, or proportional to the solubility coefficient. This process is
tracheal obstruction. relatively unimportant and accounts for about 6% of total
Low PAO2 despite adequate levels of inspired O2 (PI O2) CO2 transfer. Third, some CO2 forms carbamino compounds
•
and VA indicates hypoxemia arising from the alveoli. It by combining reversibly with the terminal amino groups
occurs because of venous admixture, low O2 tension in of plasma proteins. The total CO2 content carried in this
blood returning to the lung (PVO2) and in theory, diffu- way is negligible, and the most important carbamino for-
sion impairment. This alveolar hypoxemia is commonly mation occurs with Hb.
encountered in anesthetized horses and in pulmonary Carbon dioxide entering erythrocytes dissolves, and forms
disease. Foal pneumonias and neonatal maladjustment both HCO3– and carbamino compounds. The formation of
HCO3– (reaction 2) proceeds approximately 13,000 times

REFERENCES
faster than in plasma because of carbonic anhydrase, and
because the H+ and HCO3– produced do not accumulate. Amis TC, Pascoe JR, Hornof W 1984 Topographic distri-
Instead, Hb buffers the H+ and the HCO3– diffuses out bution of pulmonary ventilation and perfusion in
the horse. American Journal of Veterinary Research
of the red cell. Electrochemical neutrality is maintained 45: 1597–1601
by ingress of chloride ions (the chloride or Hamburger Bisgard GE, Orr JA, Will JA 1975 Hypoxic pulmonary
shift). The majority of HCO3– formed in the erythrocyte hypertension in the pony. American Journal of
enters the plasma. The formation of carbamino com- Veterinary Research 36: 49–52
pounds does not rely on enzymatic catalysis but is Clerbaux T, Serteyn D, Willems E, et al 1986 Determination of
the standard oxyhemoglobin dissociation curve in horses.
nevertheless rapid. At the normal pH of the erythrocyte, Effects of temperature, pH and diphosphoglycerate.
the reaction proceeds promptly to the right yielding H+ Canadian Journal of Veterinary Research 50: 188–192
that is readily buffered by Hb. Derksen FJ 1991 Applied respiratory physiology. In: Beech J.
(editor) Equine Respiratory Disorders. Lea & Febiger,
Reaction 3. Philadelphia, p.10
Dobson A, Gleed RD, Meyer RE et al 1985 Changes in blood
Hb NH2 + CO2 ←→ Hb NH COOH ←→ Hb NH COO– + H+ flow distribution in equine lungs induced by anes-
thesia. Quarterly Journal of Experimental Physiology
The formation of both HCO3– and carbamino compounds is 70: 283–297
facilitated by the combination of H+ with Hb. Because Fenger CK, McKeever KH, Hinchcliff KW et al 2000
reduced hemoglobin is less acidic than HbO2, it readily Determinants of oxygen delivery and haemoglobin satu-
ration during incremental exercise in horses. American
accepts H+ when HbO2 dissociates at the tissue level. This Journal of Veterinary Research 10: 1325–1332
increases the production of HCO3– and carbamino Gallivan GI, McDonell WN, Forrest JB 1989 Comparative
compounds from CO2, which in turn facilitates CO2 uptake ventilations and gas exchange in the horse and cow.
from the tissues. As a consequence of its large buffering Research in Veterinary Science 46: 331–336
capacity for H+, reduced Hb is at least three times more Gehr P, Erni H 1980 Morphometric estimation of pulmonary
diffusion capacity in two horse lungs. Respiratory
capable of binding CO2 than is HbO2. Physiology 41: 199–210
Gehr P, Mwangi DK, Ammann A et al 1981 Design of the
mammalian respiratory system. V. Scaling morphometric
Carbon Dioxide Release at the Lungs diffusing capacity to body mass: wild and domestic
animals. Respiratory Physiology 144: 61–86
In the lung, the alveolar CO2 tension (PACO2) of 5.33 kPa Greene HM, Wickler SJ, Anderson TP et al 1999 High-altitude
(40 mmHg) is less than that of mixed venous blood effects on respiratory gases, acid–base balance and
perfusing pulmonary capillaries. This, and its high solu- pulmonary artery pressures in equids. Equine Veterinary
Journal Supplement 30: 71–76
bility, ensure rapid CO2 diffusion into the alveolar space. Hedenstierna G, Nyman G, Kvart C et al 1987 Ventilation/
The reactions involved are the same as those described perfusion relationships in the standing horse: an inert
previously, but occur in the opposite direction. The binding gas elimination study. Equine Veterinary Journal
of O2 and Hb drives CO2 from the erythrocyte. This occurs 19: 514–519
because the carbamino groups of HbO2 can hold less CO2 Hlastala MP, Bernard SL, Erickson HH et al 1996 Pulmo-
nary blood flow distribution in standing horses is not
than can Hb. Also HbO2 is a stronger acid than Hb and dominated by gravity. Journal of Applied Physiology
releases H+ that combines with HCO3–, which diffuses into 81: 1051–1061
the erythrocyte to form H2CO3. Catalyzed by carbonic Jarvis KA, Steffey EP, Tyler WS et al 1992 Pulmonary blood
anhydrase, this dissociates into H2O and CO2. The latter flow distribution in anesthetized ponies. Journal of
diffuses across the erythrocyte membrane into plasma Applied Physiology 72: 1173–1178
Katz LM, Bayly WM, Hines MT et al 1999 Differences in
and finally into the alveolus, from which it is expired. This the ventilatory responses of horses and ponies to exercise
continues until the capillary CO2 tension is equal to of varying intensities. Equine Veterinary Journal
that in the alveolus. The rapid transit of CO2 across Supplement 30: 49–51
the alveolar–capillary membrane makes CO2 diffusion Marshall BE, Marshall C 1985 Anesthesia and pulmonary
impairment extremely unlikely. Oxygenated blood then circulation. In: Covino BC, Fozzard HA, Rehder K et al
(editors) Effects of Anesthesia. American Physiological
flows back to the left heart with a normal PCO2 of 5.33 kPa Society, Bethesda, pp.121–136
(40 mmHg). Nyman G, Lindberg R, Weckner D et al 1991 Pulmonary gas
exchange correlated to clinical signs and lung pathology
in horses with chronic bronchiolitis. Equine Veterinary
Impaired Carbon Dioxide Elimination Journal 23: 253–260
Pelletier N 1987 Effect of submaximal exercise and training on
Impaired CO2 elimination (hypercapnia) can result from dead space ventilation in the horse. In: Gillespie JR,
•
reduced VA , increased metabolic production or re-breathing Robinson NE (editors) Equine Exercise Physiology 2.
ICEEP Publications, Davis, pp.225–234.
expired air, and is detailed in Chapter 14.
Robinson NE 1982 Some functional consequences of species Taylor CR, Maloiy GM, Weibel ER 1981 Design of the
differences in lung anatomy. Advances in Veterinary mammalian respiratory system. III. Scaling aerobic
Science and Comparative Medicine 26: 1–33 capacity to body mass: wild and domestic animals.
Robinson NE, Sorenson PR 1978 Collateral flow resistance and Respiratory Physiology 44: 25–37
time constants in dog and horse lungs. Journal of Wagner PD, Gillespie JR, Landgren GL 1989 Mechanism of
Applied Physiology 44: 63–68 exercise-induced hypoxemia in horses. Journal of Applied
Sinha AK, Gleed RD, Hakim TS 1996 Pulmonary capillary Physiology 66: 1227–1233
pressure during exercise in horses. Journal of Applied West JB 1977 Ventilation perfusion relationships. American
Physiology 80: 1792–1798 Review of Respiratory Disease 116: 919–943
Sorensen PR, Robinson NE 1980 Postural effects on lung
volumes and synchronous ventilation in anesthetized
horses. Journal of Applied Physiology 48: 97–103
Airway Secretions and Mucociliary Function
5 Vincent Gerber and N Edward Robinson
This chapter focuses on the airway mucociliary apparatus (1%), and proteins (2–3%), in particular, high molecular
that includes mucus secretions, secretory and ciliated weight O-linked glycoproteins referred to as mucins, as well
cells; other components of the innate airway defense as variable amounts of epithelial and inflammatory cells
system, such as cough, bronchospasm, and macrophages (Matthews et al 1963).
are discussed in Chapter 6. In this chapter, the terms
“mucus (accumulation)” and “(airway) secretions” are Mucus-producing cells
used interchangeably to describe the entity of gel-like
secretions with all their components. Respiratory mucus Goblet cells and submucosal glands synthesize, store and
has important physiological roles: trapping, inhibition, release mucins. In the horse, unlike all other investigated
destruction, and removal by mucociliary clearance of species, submucosal glands are very sparse even in the
inhaled materials as well as humidification of air and large airways (Widdicombe & Pecson 2002). Goblet cells, in
prevention of fluid loss. Increased mucus can be a normal contrast, are found in normal equine airways down to
defense reaction enhancing some of these physiological 0.5 mm diameter but not including the terminal airways
functions. There can also be “too much of a good thing”, (Viel 1980).
however. When mucus production and secretion exceed Alcian blue–periodic acid Schiff (AB-PAS) is the
clearance capacity, excessive accumulation is observed in standard histological stain for mucus-storing cells but
the airways. Giemsa–PAS will also stain mucus-storing cells and pro-
The clinician evaluating the lower respiratory tract of vides better overall morphological detail (Fig. 5.2B). For
horses is frequently confronted with airway mucus accu- ultrastructural studies, transmission electron microscopic
mulation and is then faced with the following questions. fixation and osmium-staining methods have been used to
identify mucus-producing cells based on their morphologi-
● What degree of mucus accumulation is clinically
cally characteristic storage granules and the osmiophilic
relevant?
surfactant film at the air–mucus interface (Fig. 5.1).
● What are the causes and mechanisms of excess mucus
Semi-quantitative scoring systems allow grading of
accumulation?
mucus cell hyperplasia and metaplasia. Quantitative
● How can excess mucus accumulation be treated and
morphometric methods (Harkema et al 1987) can be used
prevented?
to (1) count the number of goblet cells, (2) measure the
Mucus accumulation is a major pathophysiological volume of stored mucus product, and (3) measure sub-
component of equine lower airway disease. Compared with mucosal gland size (the Reid index). Except for investigation
airway inflammation and bronchospasm/airway hyper- of very small airways where a biopsy will suffice, post-
reactivity, however, it has received much less investiga- mortem or large biopsy samples requiring thoracoscopy
tive attention and is therefore less well understood. In (see Chapter 20) are necessary.
the following, we examine the available information on the
mucociliary apparatus in the horse with a focus on Mucins
recurrent airway obstruction (RAO) and inflammatory
airway disease (IAD). Comparative aspects are included Mucins, also called mucus glycoproteins, are high
when relevant to the above questions. molecular weight glycoconjugates (Fig. 5.3). Numerous
oligosaccharide side chains are O-glycosidically linked to
threonine and serine tandem repeat sequences of the
Components of the Mucociliary Apparatus peptide core or apomucin, which represents the primary
The mucus blanket overlying the airway epithelium gene product. Gel-forming mucins contain non-repetitive
(Figs 5.1 and 5.2) is composed of a liquid sol layer that cysteine-rich regions, believed to allow intra- and inter-
bathes the cilia, overlain by a more viscous mucus gel layer. molecular cross-linking through disulfide bond formation.
Mucus is a mix of water (~95%), electrolytes (1%), lipids Three gel-forming mucin apoproteins are known in
55
56 5 Airway Secretions and Mucociliary Function
A B
Fig. 5.1. (A,B) Transmission electron microscopic photographs of mucus storage granules. On top of the cilia an osmiophilic surfactant
respiratory epithelium and mucus. The healthy respiratory epithelium film (arrows) is present at the air–liquid interface. (A) Bar = 1 μm;
(A) shows the sol layer that bathes the cilia and a practically absent (B) bar = 2 μm. Photomicrographs by Gerber, Kupferschmied & Gehr,
mucus gel layer. The inflamed respiratory epithelium (B) has a promi- Equine Clinic and Department of Anatomy, University of Berne,
nent gel layer with inflammatory cell debris. The left lower corner of Switzerland.
B shows the apex of a goblet cell (arrowhead) with characteristic
A B
Fig. 5.2. (A,B) Staining for stored mucosubstance (arrows) in goblet crographs by deFeijter-Rupp & Gerber, Pulmonary Laboratory, College
cells with AB-PAS (A) and Giemsa-PAS (B) on ultrathin sections of Veterinary Medicine, Michigan State University, East Lansing, MI,
from methacrylate-embedded equine airway sections. Photomi- USA.
human and rodent airways: MUC2, MUC5AC and MUC5B the human mucins, MUC5B has also been described
(Jeffery & Li 1997). (Walley et al 2001). In healthy horses, eqMUC5AC mRNA
Two equine homologs of mucin genes MUC5AC and can be detected in all airway generations and in the
MUC2 have been genetically identified and, based on stomach (Fig. 5.4). In contrast, eqMUC2 is expressed in the
reactivity with polyclonal antibodies raised against colon but not in the airways (Gerber et al 2003b).
5 Airway Secretions and Mucociliary Function 57
S S which because of their size readily form entanglements

among each other. Oligosaccharide side chains form
S hydrogen bonds with complementary sugar units on
S neighboring mucins and ionic interactions between
negatively charged sugar units and positively charged
Central tandem-repetitive domain amino acids extend the macromolecular conformation.
• Core protein – apomucin Furthermore, inflammation can add an extra network of
• Abundant O-glycosylation sites (Ser and Thr)
• Sequence varies widely from mucin to mucin high molecular weight DNA and actin filaments released
from dying leukocytes. Interactions with water, elec-
trolytes, hydrogen ions, lipids, enzymes, and proteins
Flanking regions Flanking regions
• Naked protein – few oligosaccharides influence these mucin gel-bonds, resulting in the physical
• Unique and non-repetitive sequence (Cys-rich) properties of mucus.
• Mucin oligomer formation by disulfide linkages
The viscosity of normal horse mucus measured by
Fig. 5.3. Basic molecular structure of gel-forming mucins. Redrawn microrheometry is in the range observed in healthy
from J. Hotchkiss, Laboratory for Experimental and Toxicologic humans and dogs (Gerber et al 2000). Rheological meas-
Pathology, College of Veterinary Medicine, Michigan State University,
urements are difficult to perform, so clinical researchers
East Lansing, MI, USA, with permission.
have tried to grade endoscopically the viscosity, or rather
the apparent stiffness and stickiness of tracheal mucus
accumulations. However, apparent viscosity scores do not
The oligosaccharide side chains that make up 90% of correlate with measured mucus viscoelasticity. Only the
the molecular weight of equine mucins are composed localization of mucus in the trachea can give an indication
of fucose, N-acetyl-galactosamine, sialic acid (N-acetyl- of its viscoelasticity (Gerber et al 2004b), because dorsally
neuraminic acid) and galactose (Jefcoat et al 2001). located mucus is more viscous.
The composition of these carbohydrate side chains
imparts specific binding activity to certain bacterial Clearance of mucus by ciliary cells
adhesion molecules and can influence the viscoelasticity
of the mucus layer. The rate of mucociliary clearance is determined by ciliary
amplitude and beat frequency and by the physical prop-
The physical properties of mucus – erties of mucus, with the latter being most important
rheological measurements (Gerber et al 1997). The bronchiolar cilia are less densely
packed than those in the bronchi so mucociliary transport
The mucus physical properties of viscoelasticity, spin- is slower in the bronchioles than in the bronchi and
nability and adhesivity determine its clearability (see trachea. Because gravity affects clearance (Gerber et al
below). Viscosity and viscoelasticity are the only mucus 1996), mucociliary transport is faster when the horse’s
physical properties that have been investigated in the horse. head is down than when it is up. Defects occur in 5%
Mucus viscoelasticity is a result of its three-dimensional, of equine airway epithelial cilia (Galati et al 1991), a
cross-linked mucin network structure. Disulfide bonds join frequency comparable to other species but well below the
mucin subunits into extended macromolecular chains, 50% ciliary loss necessary to reduce clearance.
MUC 5AC MUC 2
250 bp
190 bp
Control RAO Stomach Colon 100 bp Control RAO Stomach Colon

G1 G1 ladder G1 G1
Fig. 5.4. Tissue specificity of MUC5AC and MUC2 mRNA detected by RT-PCR. Samples from airway
generation 1 (G1) from control and RAO-affected horses, as well as from stomach and colon tissue.
Ethidium bromide-stained PCR products on 3% agarose gel. Reproduced from Gerber et al, 2003, with
permission.
Table 5.1. Summary of methods for assessing mucus with their advantages and limitations
Techniques and methods Practicality; advantages and limitations
Endoscopic scoring of mucus accumulation Reliable, clinically applicable technique when using standardized
(see Fig. 5.5; Gerber et al 2004b) grading scale and repeated observations.
Do not use compounded scores that include cytological criteria.
Scoring of mucus viscosity, color and location Extremes of localization (dorsal versus ventral) give indication of
(Dieckmann 1987, Gerber et al 2004b) viscoelasticity and apparent viscosity is associated with severity of
disease, but inter- and even intra-observer repeatability is unreliable.
Rheology; microrheometry, bulk viscosimetry and other Research methods; technically demanding, available only in specialized
specialized techniques (see Figs 5.8 and 5.9; Gerber et al laboratories.
2000)
RT-PCR; ELISA/ELLA for measurement of mucin Research methods; can be established with moderate effort.
production (see Fig. 5.4; Jefcoat et al 2001, Problems with specificity of ELISAs and ELLAs, especially when
Gerber et al 2003b) carbohydrates are characterized.
Mucus cell histology and morphometry Laborious techniques, reliable results. Invasive; thoracoscopy necessary
(see Figs 5.1 and 5.2; some in Viel 1980) for large biopsy samples
Measurements of mucus clearance rate with endoscopy Mostly for research, but basically clinically applicable techniques;
(Sweeney 1989, Turgut & Sasse 1989, Im Hof et al 1996) standardization not trivial, repeat measurements necessary
or radioactive markers (Willoughby et al 1991)
Ciliated cells: ex vivo ciliary beat frequency Research method; technically demanding
(Gerber et al 1996)
RT-PCR, reverse transcription polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; ELLA, enzyme-linked lectin assay.
Mucociliary clearance is under autonomic control: (1987) was recently proven to be a reliable clinical and
β-adrenergic agonists are potent stimulants of clearance, research tool (Fig. 5.5A–C) (Gerber et al 2004b): it showed
and cholinergic antagonists are potent depressants, excellent intra- and inter-observer agreement, moderate
while the effect of cholinergic agonist drugs is variable horse-related variance and a good correlation with
(Houtmeyers et al 1999). In the standing horse, muco- measured volumes of “artificial mucus”.
ciliary clearance can be determined by use of a radioactive Of all the techniques that have been used in the horse
marker that is followed up the airway by scintigraphy and that are outlined here (Table 5.1), only endoscopic
(Willoughby et al 1991) and by simpler endoscopic scoring of gross mucus accumulation can presently be
methods using surface markers (Sweeney 1989, Turgut & regarded as a readily available and reliable clinical tool. It is
Sasse 1989, Im Hof et al 1996). In healthy horses, the also the method that has provided the most data on the
mean tracheal mucus velocity is about 2 cm/min but there clinical significance of mucus accumulation.
are considerable differences between individual horses
(Sweeney 1989) as in humans where genetic determina-
tion of mucociliary clearance rate has been suggested by
Epidemiology and Clinical Significance
twin studies.
of Mucus Accumulation
Mucus accumulation is a non-specific sign
Quantifying mucus accumulation of respiratory disease
Subjective scoring of mucus accumulation by endoscopy is Mucus accumulation is generally regarded as a hallmark of
often employed to quantify mucus accumulation. Various both RAO (Robinson et al 1996, Anon 2001) and IAD
systems with scores from 0 to 3 (Dixon et al 1995a) and (Burrell 1985, MacNamara et al 1990, Anon 2002) and
0 to 5 (Dieckmann 1987, Holcombe et al 2001) have been is often attributed a causative role in airway obstruc-
used. In some studies, however, a mucus score can be tion. However, mucus increases not only in RAO, but
compounded into a general airway inflammation score by also in “undifferentiated pulmonary disease”, “infectious
inclusion of cell parameters (Chapman et al 2000), so that pulmonary disease”, “Streptococcus zooepidemicus pulmo-
it is impossible to extract mucus-specific information. A nary infection”, “lungworm infestation”, “exercise-induced
standardized illustrated grading scale based on Dieckmann pulmonary hemorrhage” and “miscellaneous pulmonary
60 A
50
40
Frequency (%)
30
20
10
0 1 2 3 4 5
None Little Moderate Marked Large Extreme
Mucus accumulation score
5 10000
B C
4
1000
BALF neutrophil numbers /μL
100
10
1
r2 = 0.86 r2 = 0.88
0 0
0 1 2 3 4 5 0 1 2 3 4 5
Mucus accumulation score Mucus accumulation score
Fig. 5.5. Illustrated scoring scale for mucus accumulation (A) showing correlation (B) of scoring endoscopic videos once and then again
the frequency distribution between unselected horses from 16 stables 3 weeks later; (C) illustrates correlation of mucus accumulation scores
in six geographic regions in Michigan, USA (gray bars, n = 260 with neutrophil numbers in bronchoalveolar lavage fluid (BALF).
observations), clinically healthy research control horses (white bars, Redrawn in part from Gerber et al, 2003, 2004, from data in Robinson
n = 44) and RAO-affected animals (blue bars, n = 48). Intra-observer et al, 2004, with permission.
disease” (Dixon et al 1995b). Horses with RAO show the amount is consistent with the estimate of about
highest score (median score of 3), but this is not signifi- 10–15 ml/day in adult healthy humans. In RAO-affected
cantly different from all the other groups. Throughout animals, the volumes can be extrapolated to 6–14 ml/h at
all studies, the large variation between individuals of all pasture and 15–30 ml/h or 540 ml/day when stabled,
disease categories is obvious. which is proportionally less than the estimated
200–300 ml/day in humans with exacerbations of chronic
Mucus accumulation in RAO is a function bronchitis. It is important to note, however, that these
of disease status and/or environment estimates only account for mucus volumes cleared by
mucociliary action, but not by coughing.
When RAO-affected horses have been at pasture for several
weeks, bronchospasm and inflammation wane, but mucus Clinical significance of increased
accumulation scores are still increased in comparison to mucus accumulations
clinically healthy horses (Gerber et al 2004a) (Fig. 5.6).
During exacerbations of RAO, endoscopic mucus accumu- Increased mucus accumulation can directly cause
lations further increase in RAO-affected horses. This is in bronchial obstruction as well as effectively increase resting
accordance with the results of carbohydrate-specific airway wall thickness. This latter effect amplifies to the
enzyme-linked lectin assays (ELLAs): RAO-affected horses fourth power the lumen-narrowing effect of broncho-
in remission show increased levels of α-1,2-fucose, which constriction (Moreno et al 1986). That is, the same
may be associated with MUC5AC (Jefcoat AM, personal amount of mucus will for simple geometrical reasons
communication) and which further increases during acute obstruct the lumen increasingly as the inner diameter of
exacerbations (Jefcoat et al 2001). the airway is decreased by contraction of the surrounding
In clinically healthy horses, in contrast, short-term airway smooth muscle. The logic of this argument is simple
exposure to the environment in the stable does not increase and convincing, and the obstructive effect of excessive
mucus accumulation despite a moderate increase in airway secretions seems intuitively clear. However, in human
neutrophils. As a result of the overall large variation in airway diseases, the magnitude of any direct causative
mucus scores in clinically healthy horses, however, inter- effect of excessive airway mucus on morbidity and
mediate grades (Grade 2–3) completely overlap between mortality by causing the patient discomfort and airflow
RAO-affected and control animals. Only high mucus grades obstruction is controversial and, at best, difficult to assess
(Grade >3) separate RAO-affected horses from clinically (Kim 1997). The same is true for horse airway diseases.
healthy animals (Gerber et al 2003a, 2004,a,b) (Fig. 5.5). Increased mucus accumulation scores are associated
The combination of our studies on endoscopic mucus with decreased lung function (Luft 1987) and following
grades and reports on mucociliary clearance rates from administration of bronchodilators to RAO-affected horses
ours and other groups allow for an estimate to be made of in clinical exacerbation, airway resistance rapidly decreases
the mucus transport and thus its production. In clinically but still remains greater than in control horses (Broadstone
healthy horses, 2–8 ml/h or 120 ml/day of endoscopically et al 1988, Derksen et al 1992). It has been suggested but
visible mucus is transported along the trachea. This not proven that these remaining lung function deficits and
the inconsistent effect of bronchodilators on dynamic
compliance are the result of mucus accumulation and
airway wall thickening (Robinson et al 1996).
5 When the amount of mucus exceeds the mucociliary
clearance capacity, secretions progressively accumulate,
4 * * and must then be cleared by coughing (King & Rubin

* # # #
1994). The association of excess mucus accumulation and
3 +
cough in horses has been shown in several studies (Dixon
2 et al 1995c, Christley et al 2001, Robinson et al 2003).
Clinically healthy racehorses (Holcombe et al 2004)
1 and pleasure horses (Robinson et al 2004) in the USA
frequently have several small non-coalescent drops of
0
0 6 24 48 mucus (Grade 1) in their trachea. This amount is not
Hours
associated with altered racing performance but larger
amounts (Grade 2 or greater: coalescent drops or a stream
Fig. 5.6. Mucus grades in RAO-affected (blue bars) and control (grey of mucus) are associated with poorer race placement in
bars) horses before and at 6, 24, and 48 h after stabling. *Significantly
different (P < 0.05) from 0 h; # significantly different from control
standardbreds (MacNamara et al 1990) and thoroughbreds
at same time point; + trend toward a difference compared to control at (Holcombe et al 2004). Many asymptomatic pleasure
that time point (P = 0.054). horses (Robinson et al 2004) and well-performing sport
horses (Gerber et al 2003a) of various ages have mucus airway contribute to the volume of airway secretions. In
scores >2 (Fig. 5.5), so it appears that mild to moderate addition, neutrophilic inflammation unfavorably alters
degrees of mucus accumulation (and also airway inflam- mucus physical properties and decreases the clearability of
mation) are tolerated as long as horses are not asked to the secretions. However, the major link between mucus
perform intense exercise like racing. accumulation and inflammation is through increased
Finally, increased mucus accumulations are also asso- production and secretion of mucins.
ciated with bacterial colonization of the airways. When
horses are prevented from lowering their head for a Mucin production and secretion
prolonged period of time, mucus pooling with excessive
bacterial growth occurs in the distal trachea (Raidal et al Many particulate and gaseous irritants can directly
1995). This may increase the risk of bacterial pleuro- increase airway mucus. Inhaled endotoxin may be of
pneumonia in immunocompromised animals. Further- particular importance in horses that are stabled and fed
more, inflammation scores, which include mucus accumu- hay (Pirie et al 2001). Furthermore, mucus stasis may
lation, are highly correlated with positive bacterial cultures encourage bacterial growth in the airways, which in turn
from tracheobronchial secretions in IAD of young race- may also directly stimulate the production and secretion of
horses (Chapman et al 2000). Molecular interactions mucins. However, most effects of inhaled irritants and
between bacteria and mucin glycoproteins may play a role allergens are likely mediated by inflammation. Figure 5.7
here. However, even in healthy horses Streptococcus illustrates some immunological and pathophysiological
zooepidemicus and other upper airway commensals mechanisms that may be involved in mucin hypersecretion
are frequently isolated from tracheal secretions (Sweeney of equine lower airway disease (see also next section).
et al 1985), and exacerbations associated with bacterial “Too much of a good thing” aptly describes the situation
infections are not a clinical problem recognized in where the airway mucosa produces and releases so much
RAO-affected horses (Anon 2001). mucin glycoprotein as to overwhelm the capacity of the
In summary, increased mucus accumulation is a mucociliary transport system. Such a hypersecretory state
characteristic, but not a specific feature, of IAD and RAO, is found in human chronic bronchitis, asthma exacerba-
and it is associated with: tion, and cystic fibrosis. Relative amounts, gene expression,
and glycosylation variants of the gel-forming mucins,
● lung function deficits
MUC2, MUC5AC, and MUC5B, can be altered signifi-
● poor performance in racehorses (mucus accumulation
score >1)
● exacerbations in RAO-affected horses (mucus accumu-
lation score >3)
● coughing (mucus accumulation score >1) and bacterial Molds, mites and HAY + DUST Endotoxin, particles
colonization of large airways. other allergens and irritant gases
The foregoing discussion clearly shows that these are

mere associations, however, and no causative relationships Th2 M TNF-α
between mucus accumulation and any of these negative Th1
IL-4, -13 IFN-γ IL-1β
effects have been firmly established. The clinician must
therefore judge the clinical relevance of an observed B ROS, Elastase
excessive mucus accumulation in the light of the overall
assessment and situation of the patient. Before discussing CACC1 EGFR
therapeutic options, however, it is necessary to shed light EGF
on the causes and mechanisms that may lead to mucus Bronchospasm
accumulation.
Hyperreactivity MUC5AC and mucosubstance
Causes and Mechanisms of Airway Fig. 5.7. Illustrated view of some immunological and pathophysio-
Mucus Accumulation logical mechanisms that may be involved in equine lower airway
disease. Th = T-helper cell; M = macrophage; B = B cell; MC = mast
In horses with IAD or RAO, mucus accumulation cell; IL = interleukin; IFN = interferon; TNF = tumor necrosis factor;
scores correlate well with tracheobronchial secretion CACC = calcium-activated chloride channel (also, CLCA); ROS =
reactive oxygen species; EGF(R) = epidermal growth factor (receptor);
neutrophil percentages and bronchoalveolar lavage
MUC = mucin. Conceptual model and figure by V. Gerber; some
fluid neutrophil numbers in horses (Gerber et al 2004b) graphic elements from J.A. Hotchkiss, Laboratory for Experimental and
(Fig. 5.5C). Inflammatory cells in large numbers and the Toxicologic Pathology, Department of Pathobiology and Diagnostic
inflammation-associated transudation of fluid into the Investigation, Michigan State University, USA, with permission.
cantly, both in rodent models and in human airway stored mucosubstance is not increased in RAO airways:
diseases. Most studies, however, have shown predominant the higher numbers of goblet cells can be in a “high-
MUC5AC up-regulation in response to various stimuli and throughput state” with increased production and secretion
mediators. Presently, MUC5AC is regarded as the main but decreased storage of mucin products.
“signature” mucin in experimental and natural models of
airway disease. Immunological context of mucin production
In the horse, present evidence indicates:
In this section, based mainly on comparative data and not
● MUC2 probably does not play a role, because no detect-
on direct evidence from studies in horses, we present a
able mRNA levels of this mucin were observed in the
possible model (Fig. 5.7) of the inflammatory and immu-
airways of healthy and or RAO-affected horses (Fig. 5.4)
nological background of mucin gene induction and
(Gerber et al 2001).
secretion in equine lower airway disease.
● MUC5B, which has not yet been studied in equine lower
Many different T helper type 1 and 2 (Th1, Th2)
airway disease, is probably not a key mucin, because
pathways, as well as innate immunity pathways, converge
submucosal glands are sparse in equine airways and no
on up-regulation of MUC5AC with subsequent mucus cell
enlargement has been found in RAO-affected animals
metaplasia and hypersecretion. Epidermal growth factor
(Viel 1980, Kaup et al 1990a,b).
receptor (EGFR) and a chloride channel (calcium-activated,
● MUC5AC may be the key inducible mucin in equine
family member 1; CLCA1) as well as the B-cell leukemia-2
RAO (Gerber et al 2003b).
(Bcl-2) protein are key signaling molecules involved in
These findings are supported by our findings of these pathways but are only beginning to be investigated
increased α-1,2-fucose levels – a mucin sugar associated in equine lung disease.
with MUC5AC (Jefcoat AM, personal communication) – in Neutrophils, the predominant inflammatory cell type in
the bronchoalveolar lavage fluid of RAO-affected horses RAO, produce potent secretagogues that are increased
both in exacerbation and during remission (Jefcoat et al in equine RAO: reactive oxygen species (Art et al 1999),
2001). MUC5AC is produced predominantly by goblet proteases, in particular elastase (Jefcoat AM, personal
cells. Several histopathological and ultrastructural studies communication), and leukotriene B4 (Lindberg et al 2002).
describe goblet cell hyperplasia, metaplasia, and hyper- Neutrophils can up-regulate EGFR expression through
trophy in the pulmonary airways of RAO-affected horses tumor necrosis factor-α and subsequently activate EGFR
(reviewed in Dixon 1992). in a ligand-independent fashion through the release of
Only a few studies are based on quantitative morpho- oxidative radicals (Takeyama et al 2000, Shim et al 2001).
metric techniques, however: Viel (1980) found increased CLCA1 has been identified as an important downstream
goblet cell counts in RAO- and IAD-affected horses, but effector element of interleukin-13 (IL-13), mediating
only in the small airways of <2-mm diameter. The increase airway hyperresponsiveness and overproduction of mucus
correlated with the severity of clinical disease and was in animal models and, possibly, in asthmatic subjects
most marked in preterminal airways, which contain almost (Nakanishi et al 2001, Zhou et al 2001, Toda et al 2002).
no goblet cells in normal horses. Recent investigations of IL-13 as well as Th1-type and innate immunity cytokines
heaves-affected and control animals exposed to the same can also up-regulate and activate EGFR.
environment have found no differences in the amount of Furthermore, irritants and toxins, in particular endo-
stored mucosubstances in bronchi or bronchioles (Bartner toxin that is abundant in the stable environment (Pirie
et al 2006, Lugo et al 2006). In the bronchioles, mucous 1998), can both directly and indirectly increase and
cell metaplasia was associated with the severity of potentiate airway mucin expression and mucous cell hyper-
inflammation regardless of whether the animal had heaves and metaplasia (Gordon et al 1996, Fanucchi et al 1998,
or not (Lugo et al 2006). In the bronchi, severe Harkema & Wagner 2002).
inflammation in the heaves-affected animals was associated Less well studied, but just as important as the induction
with emptying of mucous cells; that is, a reduction in the of mucin hypersecretion, is what happens afterwards.
amount of stored mucosubstances, presumably because the There is evidence that the Th2 cytokine IL-13 and up-
mucus had been secreted into the airway lumen. regulated Bcl-2 can delay apoptosis of goblet cells, leading
Such measurements reflect a “moment in time” within to persistence of mucus cell metaplasia (Tesfaigzi et al
the dynamic process of mucin production, storage, 2000, Shi et al 2002). The persistence of mucus accumu-
and secretion. Current understanding of inflammatory lation in RAO may thus be, at least in part, mediated by
airway pathogenesis indicates that after injury, imme- Bcl-2, but other mechanisms, such as increased nuclear
diate release of stored mucosubstance is followed by factor-κB, which is involved in mucin gene up-regulation
up-regulation of mucin production within hours, and an in vitro (Basbaum et al 1999), may also play a role. Finally,
increase in goblet cell numbers within days (Haschek although neural control of mucus secretions is likely
1998). These dynamics may explain why at times, total less important in the horse than in species with many
submucosal glands, mediators of “neurogenic inflam- 3.5 A Principal group

mation” such as substance P may induce mucus hyper- Control group
# *
secretion in horses (Sonea et al 1999).
Log G* (dyn/cm2)
3.0
In the horse the first few pieces of this complex puzzle
are starting to fall into place: 2.5
● Equine CLCA1 and EGFR mRNA levels as well as
neutrophil percentages are associated with eqMUC5AC 2.0
mRNA levels in the airways of horses suffering from
0.0
RAO as well as of horses with milder degrees of airway 0 6 24 48
inflammation (Gerber V, unpublished results). 1.0 B
● Horses with RAO show an increased percentage of
Bcl-2-positive mucus cells compared to their normal
counterparts (Bartner et al 2006). 0.8
MCI
● When RAO horses are removed from conventional stable
environments, residual lung function deficits, airway #
neutrophils and mucus persist and are associated with 0.6
increased nuclear factor-κB activity of epithelial cells
0.0
(Bureau et al 2000). 0 6 24 48
1.6 C
Mucus biophysical properties and their
1.2
alterations in disease
CCI
The available data suggest that alterations in mucus 0.8

rheology in horses are a function of the intensity and
duration of exposure to irritants and allergens as well as 0.4 #
the severity of airway disease in the individual (Gerber et al
2000; Figs 5.8 and 5.9). 0.0
0 6 24 48
● When RAO-affected horses are in remission, viscoelas- Hours
ticity and clearability of mucus are similar to that in
clinically healthy horses. Fig. 5.8. Viscoelasticity and derived clearability of mucus in RAO-
● In clinical crisis as a result of stabling and hay-feeding, affected horses (blue dots) compared with control horses (white
dots): (A) viscoelasticity at 10 radian/s on a logarithmic scale (log G*;
the viscoelasticity of mucus in RAO-affected horses dyn/cm2), (B) mucociliary clearability index (MCI), and (C) cough
increases three-fold into the range observed in human clearability index (CCI) before (0; pasture) and after environmental
patients suffering from cystic fibrosis. challenge (6, 24 and 48 h; stabling, feeding hay). # Significant
difference between groups; * significant difference between time
These results are in accordance with an older point and baseline in the same group. Redrawn from Gerber et al,
report indicating increased viscosity of tracheal mucus 2000, with permission.
in RAO-affected horses in crisis, but normal viscosity in
horses with RAO after hay was eliminated from the diet
(Hajer 1979, PhD thesis, cited in Turgut & Sasse 1989). A strated in equine mucus with unfavorably altered mucus
recent study found significantly higher values of mucus rheological properties.
viscosity in horses with RAO than in horses affected with Changes in the mucin carbohydrate side chains – fucose
IAD (Pietra et al 2000). We have also observed that horses (α-1,2 linkage), N-acetyl-glucosamine, and N-acetyl-
with mild to moderate clinical signs of RAO even showed galactosamine – that we detected in RAO-affected horses in
remarkably lower average viscoelasticity than clinically acute disease (Jefcoat et al 2001), may also contribute to
healthy horses (Fig. 5.9) (Gerber et al 1998). the degree of viscoelasticity of the mucus layer.
Although rheological values overall do not significantly Rheological factors other than viscoelasticity may
correlate with bronchoalveolar lavage fluid cytology, the negatively influence clearability in RAO-affected horses
increase of mucus viscoelasticity in RAO coincides with as well. Adhesivity and wettability, which contribute to
the dramatic influx of neutrophils in the airways of the optimal interface properties of mucus, are primarily
RAO-affected horses. Neutrophils released into the airways influenced by its phospholipid content and composi-
degenerate and release breakdown products. Specifically, tion. Exogenous surfactant increases equine tracheal
high molecular weight DNA (Pietra et al 2000) and mucus transport velocity ex vivo (Gerber 1995) and in vivo
filamentous (F)-actin (Gerber 2003) have been demon- (Im Hof et al 1996). Surfactant can be observed at the
4 ance, but unfavorable for mucociliary transport (King &

Rubin 1994). Alternatively, clearance can be decreased by
changes in the ciliary apparatus or unfavorable physical
properties of the mucus gel.
Log G* (dyn/cm2)
3
Ultrastructural studies revealed a loss of ciliated cells
and abnormal ciliary structure in the large conducting
airways of RAO-affected horses (Kaup et al 1990b), with
2
large differences in severity and extent between indi-
viduals. Considering the high reserve capacity of the ciliary
apparatus (Houtmeyers et al 1999), the clinical signifi-
1 cance of these changes is unclear and it seems more likely
Healthy controls IAD RAO
pasture/stabled stabled stabled that a combination of excessive mucus production and
rheological changes play the major roles in mucus clear-
Fig. 5.9. Mucus rheological differences between disease groups: ance. In ex vivo experiments we have also shown that
Viscoelasticity at 10 radian/s on a logarithmic scale (log G*; dyn/cm2) ciliary beat frequency is less important for clearance rate
in healthy control horses both at pasture and when stabled, compared
than mucus quality (Gerber et al 1997). Changes in visco-
to stabled IAD- and RAO-affected horses. All measurements by
microrheometry. Figure based on data from Gerber et al, 2000, with elasticity that are dependent on environment and on
permission, and from Gerber, unpublished results. disease-status (Gerber et al 2000) may thus explain the
contradictory findings reported in studies of mucociliary
clearance in RAO-affected horses (Coombs & Webbon
air–mucus interface (Fig. 5.1) and is present in amounts 1987, Turgut & Sasse 1989, Willoughby et al 1991).
sufficient to significantly reduce surface tension in the The importance of ciliary damage is thus inconclusive in
trachea of healthy horses (Im Hof et al 1997), but clinical RAO, and fatal ciliary diseases – such as the human
observation (reduced foam of bronchoalveolar lavage) and syndromes of immotile cilia and ciliary dyskinesia – have
biochemical analysis of airway secretions suggest that not been described in horses. Notwithstanding, ciliary
a deficit and altered composition of surfactant are present defects are important sequelae of certain equine viral
in RAO-affected horses (Dorwald et al 1991), and after infections. Mucociliary clearance is severely depressed
horses have been subjected to long periods of transport in all horses after influenza infection and takes 4 weeks
(Hobo et al 2001). to return to normal. Herpes virus reduces clearance in half
of the infected horses. In contrast, infection with rhino-
Mucociliary clearance virus has no detectable effect on mucociliary clearance
(Willoughby et al 1992).
A variety of airborne pollutants may have deleterious
effects on mucociliary clearance in horses, and, similar to
smoking cessation in humans (Houtmeyers et al 1999), it
Prevention and Therapy
may take months to return to normal (Schlesinger 1985).
of Mucus Accumulation
A single allergen challenge reduces mucociliary clearance Some of the therapeutic options presented here specifically
rate by 28% in asthmatics (Houtmeyers et al 1999, target certain components of the mucociliary system, but
Del Donno et al 2000). Airway inflammation appears to others act much more broadly. Common to most of them,
play a significant part in compromising mucociliary clear- however, is the lack of good evidence for their effectiveness
ance, and may similarly contribute to the accumulation of in decreasing mucus accumulation in equine lower airway
airway secretions in horses with allergic lower airway diseases. This is mainly because of the absence of studies
disease (Dixon 1992). in the horse, but even in human medicine the value of
Investigations of the effectiveness of mucociliary clear- mucoactive drugs is mostly controversial. Similar to the
ance in RAO-affected horses have yielded conflicting situation in the horse, the main consensus in human
results, however. Clearance rate was found in one study to medicine is that mucus accumulation is difficult to treat.
be decreased by between 24 and 90% and markers were The following section outlines the sparse data on
less likely to move as a discrete bolus (Coombs & Webbon mucoactive treatment in the horse. All of these therapeutic
1987). Other studies, in contrast, found no difference options presently appear to have their risks (e.g. side effects
between RAO-affected and healthy horses (Willoughby et al of long-term corticosteroid treatment, botulism with feed-
1991). No studies have investigated mucociliary clearance ing bad haylage), questionable efficacy and benefit (e.g.
rate in IAD. classical mucolytics) or economic drawbacks (e.g. peptide
Excessive mucus loads may simply overwhelm muco- mucolytics).
ciliary clearance. Mucus that is deep, i.e. more than the Before choosing one of these treatments, the clinician
physiological 5–10 μm depth, is well suited for cough clear- must therefore carefully judge the clinical relevance of the
observed mucus accumulation. In particular, the use of the was slower and less consistent than the response of clinical
horse, its stable environment, cough, respiratory distress and signs and bronchospasm (Robinson et al 2003). Even more
the severity of other clinical signs must be taken into account remarkably, in a double-blind placebo-controlled study
to decide if and what kind of therapy should be instituted. (0.1 mg dexamethasone/kg body weight orally for 3 weeks)
in clinical patients with IAD and RAO, we observed
Prevention of mucus accumulation significant effects on coughing, arterial oxygenation,
even on nasal discharge, abnormal lung sounds and
An environment as free of respirable irritants and allergens performance but no decrease of mucus accumulation
as possible is the mainstay of both prevention and therapy scores (Gerber et al 2003c).
of RAO and likely also of most forms of IAD. Also, frequent
and targeted influenza vaccination should prevent the Influencing mucociliary clearance
decreased mucociliary function that is a sequel of clinical
infection. The severe and prolonged depression of mucocil- While atropine (0.02 mg/kg intravenous) significantly
iary clearance after influenza infection (Willoughby et al decreases tracheal clearance rate (Maxson et al 1995), a
1992) underlines the importance of adequate rest periods β2-agonist (clenbuterol 0.8 μg/kg intravenous) significantly
and good air hygiene after clinically apparent respiratory increases tracheal mucus velocity in vivo (Turgut & Sasse
viral infections. 1989). In contrast, water vapor-saturated air therapy,
However, neither the benefit of environmental control exercise and mild dehydration by furosemide have no effect
nor of vaccinations against influenza for prevention of on mucociliary clearance in healthy horses (Sweeney et al
mucus accumulation has been specifically studied. In 1989). Gravitational force can decrease or accelerate
contrast, allowing horses to lower their heads during long tracheal mucus velocity in vivo (Raidal 1996) and in vitro
transport has been shown to decrease tracheal mucus (Gerber et al 1996), which has important implications
pooling, thereby decreasing bacterial colonization and the for horses during longer periods of transportation, when
risk of ensuing pneumonia. they should be allowed to lower their heads and be fed
on the ground.
Environment
Secretolytics
RAO-affected horses at pasture have lower mucus scores
than when they are exposed to hay, but still more mucus The chemically closely related molecules bromhexine,
in the airways than clinically healthy horses (Gerber ambroxol and dembrexine, alone or in combination with
et al 2004a). Thus, the therapeutic effect is useful but bronchodilators, are extensively used in parts of Europe to
incomplete, as mucus accumulation persists for weeks treat horses with lower airway disease. None of their
(Jefcoat et al 2001), and, as in ex-smokers, it may return to purported mechanisms of action, such as increasing the sol
normal levels only after months or possibly not at all. Thus, layer through alteration in epithelial ion transport,
it appears that we can only expect a reliable effect of favorably altering mucin glycosylation to decrease viscosity,
environmental control in RAO exacerbation with mucus or increasing surfactant, have been investigated in the
scores >3. Even then the effect is mostly limited to a horse. Most of the studies reporting clinical benefits like
decrease towards mucus scores of 2–3. The effect is even improved endoscopic mucus scores, decreased coughing
more inconsistent with only moderately increased mucus and improved lung function in IAD and RAO (Pearce et al
scores (Holcombe et al 2001). 1978, Sasse & Deegen 1984, Matthews et al 1988) can be
criticized on methodological grounds, e.g. unblinded
Corticosteroids observers and lack of placebo control groups. However,
because we have little to offer as valid therapeutic alter-
Dexamethasone decreases mucin gene expression and natives, these molecules remain interesting.
mucous cell hyperplasia in vitro and in some rodent models
of asthma (Jungsuwadee et al 2004) but not in others Classical mucolytics
(Kibe et al 2003). Based on our present results, which are
comparable to those in human asthma patients (Fahy & The agent N-acetyl cysteine (NAC), which breaks down
Boushey 1998), we cannot expect a comparably good effect mucin disulfide bonds and has antioxidant effects, is also
of corticosteroids on mucus accumulation as on other widely used in Europe to decrease mucus accumulation in
components of equine lower airway disease such as horses. Relatively high doses (5–10 mg/kg body weight
coughing and bronchospasm. Dexamethasone (0.1 mg/kg, orally, twice a day for 20 days) decreased mucus apparent
intravenously once daily for 7 days) decreased mucus viscosity and accumulation scores in RAO-affected patients
accumulation by an average of about 1.7 scores in a cross- in a double-blind, placebo-controlled study (Keller et al
over study with RAO-affected horses. The effect, however, 2001). However, these decreases were small (about 1–2
scores) and there was no improvement of blood gas values. State University, June 2000. Equine Veterinary Journal
Furthermore, we have shown that such apparent viscosity 33: 5–19
scores are unreliable (Gerber et al 2004b). Anon 2002 International Workshop on Inflammatory Airway
Disease: Defining the Syndrome. Proceedings of Work-
We have been unable to demonstrate an effect of oral shop in Boston, October 2002. Equine Veterinary
NAC (5 mg/kg body weight) on mucus viscoelasticity Education 15: 61–63
(Gerber & King, unpublished data). This could be the result Art T, Kirschvink N, Smith N et al 1999 Indices of oxidative
of poor uptake of the orally administered drug because stress in blood and pulmonary epithelium lining fluid in
there was no measurable increase in blood levels (Gerber & horses suffering from recurrent airway obstruction.
Equine Veterinary Journal 31: 397–401
Marlin, unpublished results). These latter findings call into Bartner LR, Tesfaigzi Y, Robinson NE 2006 Persistent mucus
question the validity of using oral NAC in horses. accumulation: A consequence of delayed mucous cell
Inhalation instead of the oral route would improve the death in heaves-affected horses? American Journal
availability of NAC in the airways by circumventing the of Physiology. Lung Cell Molecular Physiology: 171:
liver first-pass and would avoid the potential side effects in press
Basbaum C, Lemjabbar H, Longphre M et al 1999 Control of
induced by damage to the protective gastric mucus. mucin transcription by diverse injury-induced signaling
Unfortunately, NAC can induce bronchoconstriction pathways. American Journal of Respiratory and Critical
because of its acidity and osmolar effects. Nacystelyn, a Care Medicine 160: S44–S48
novel lysine salt of NAC, is better suited for inhalation and Broadstone RV, Scott JS, Derksen FJ et al 1988 Effects of
has been successful in human clinical trials, but for equine atropine in ponies with recurrent airway obstruction.
Journal of Applied Physiology 65: 2720–2725
veterinary use its cost is likely to be prohibitive. Finally, Bureau F, Bonizzi G, Kirschvink N et al 2000 Correlation
because NAC and similar mucolytics indiscriminately break between nuclear factor-kappaB activity in bronchial
down mucin disulfide bonds, they may not be beneficial in brushing samples and lung dysfunction in an animal
horses with mild to moderate lower airway disease, whose model of asthma. American Journal of Respiratory and
mucus viscoelasticity can already be abnormally low Critical Care Medicine 161: 1314–1321
Burrell MH 1985 Endoscopic and virological observations
(Gerber et al 1998) (Fig. 5.9). on respiratory disease in a group of young thorough-
bred horses in training. Equine Veterinary Journal
Peptide mucolytics 17: 99–103
Chapman PS, Green C, Main JP et al 2000 Retrospective study
There is good evidence that leukocyte breakdown products, of the relationships between age, inflammation and the
isolation of bacteria from the lower respiratory tract of
specifically DNA and filamentous (F-)actin released from thoroughbred horses. Veterinary Record 146: 91–95
dying neutrophils, have an unfavorable effect on mucus Christley RM, Hodgson DR, Rose RJ et al 2001 Coughing in
rheology of RAO horses in exacerbation. DNase (Pietra thoroughbred racehorses: risk factors and tracheal
et al 2000) and Gelsolin (Gerber 2003) decrease mucus endoscopic and cytological findings. Veterinary Record
viscoelasticity of this abnormal mucus in RAO-affected 148: 99–104
Coombs SL, Webbon PM 1987 Observations on tracheal
horses. Unfortunately, these peptide mucolytics, used mucociliary clearance in horses. Tierärztliche Praxis
mainly in human cystic fibrosis, are prohibitively expensive Supplement 2: 5–9
for use in horses. Del Donno M, Bittesnich D, Chetta A et al 2000 The effect of
inflammation on mucociliary clearance in asthma: an
overview. Chest 118: 1142–1149
Conclusions Derksen FJ, Robinson NE, Berney CE 1992 Aerosol pirbuterol:
bronchodilator activity and side effects in ponies with
Clearly, the options for prevention and therapy to avoid and recurrent airway obstruction (heaves). Equine Veterinary
reduce mucus accumulation in the horse are unsatisfac- Journal 24: 107–112
tory at present. Economical treatments such as the secreto- Dieckmann MP 1987 Zur Wirksamkeit von Ambroxol-
lytics, NAC, hypertonic saline inhalation, and possibly the hydrochlorid (Mukovent) bei lungenkranken Pferden-
mucoactive effect of macrolide antibiotics should be further klinische, funktionelle und zytologische Untersuchungen,
Inaugural Dissertation (Dr. med. vet.), Tierärztliche
evaluated not only for their effect on the mucociliary Hochschule Hannover, Germany
apparatus, but specifically for any potential lung function Dixon PM 1992 Respiratory mucociliary clearance in the
improvement and clinical benefit. Meanwhile, it is crucial horse in health and disease, and its pharmaceutical
to carefully evaluate whether any given mucus accumula- modification. Veterinary Record 131: 229–235
tion should be treated in the individual horse and to always Dixon PM, Railton DI, McGorum BC 1995a Equine pulmo-
nary disease: a case control study of 300 referred cases.
address the underlying causes. Part 1: Examination techniques, diagnostic criteria and
diagnoses. Equine Veterinary Journal 27: 416–421
REFERENCES Dixon PM, Railton DI, McGorum BC 1995b Equine pulmonary
disease: a case control study of 300 referred cases. Part
Anon 2001 International Workshop on Equine Chronic 2: details of animals and historical and clinical findings.
Airway Disease. Proceedings of Workshop at Michigan Equine Veterinary Journal 27: 422–427
Dixon PM, Railton DI, McGorum BC 1995c Equine pulmo- Gerber V, Straub R, Marti E et al 2004b Endoscopic scoring of
nary disease: a case control study of 300 referred cases. mucus: Reproducibility, and relation to mucus viscosity
Part 3: Ancillary diagnostic findings. Equine Veterinary and airway inflammation. Equine Veterinary Journal
Journal 27: 428–435 36: 576–582
Dorwald M, Vanden Bosche G, Gerull A 1991 Zura Surfactant- Gordon T, Nadziejko C, Plant M et al 1996 One-month expo-
phospholipidzusammensetzung im Tracheobronchialsekret sure to inhaled endotoxin produces a dose-dependent
des Pferdes und ihrer klinischen relevanz fuer die increase in stored mucosubstances in rat intrapulmonary
Beurteilung des Lungenstatus bei chronisch lungen- airways. Experimental Lung Research 22: 509–523
kranken Pferden. Wiener Tierärztliche Wochenschrift Harkema JR, Wagner JG 2002 Non-allergic models of mucous
78: 118–126 cell metaplasia and mucus hypersecretion in rat nasal
Fahy JV, Boushey HA 1998 Effect of low-dose beclomethasone and pulmonary airways. Novartis Foundation Symposium
dipropionate on asthma control and airway inflam- 248: 181–197; discussion 197–200, 277–182
mation. European Respiratory Journal 11: 1240–1247 Harkema JR, Plopper CG, Hyde DM et al 1987 Regional
Fanucchi MV, Hotchkiss JA, Harkema JR 1998 Endotoxin differences in quantities of histochemically detectable
potentiates ozone-induced mucous cell metaplasia in rat mucosubstances in nasal, paranasal, and nasopharyn-
nasal epithelium. Toxicology and Applied Pharmacology geal epithelium of the bonnet monkey. Journal of
152: 1–9 Histochemistry and Cytochemistry 35: 279–286
Galati P, Roperto F, De Vico G et al 1991 Atypical cilia in Haschek WM 1998 Respiratory system. In: Haschek WM,
the tracheal epithelium of healthy horses. Journal of Rousseaux CG (editors) Fundamentals of Toxicologic
Comparative Pathology 105: 185–190 Pathology. Academic Press, San Diego, pp.108–122
Gerber V 1995 Untersuchungen über die mukoziliäre Clear- Hobo S, Yoshihara T, Oikawa M et al 2001 Surfactant proteins
ance in der Luftröhre des Pferdes [Investigation of muco- in bronchoalveolar lavage fluid of horses: assay tech-
ciliary clearance in equine trachea]. Inaugural Dissertation nique and changes following road transport. Veterinary
(Dr. med. vet.), University of Berne, Switzerland Record 148: 74–80
Gerber V 2003 Nature and causes of mucus accumulation in Holcombe SJ, Jackson C, Gerber V et al 2001 Stabling is
equine lower airway disease. PhD thesis, Michigan State associated with airway inflammation in young Arabian
University, USA horses. Equine Veterinary Journal 33: 244–249
Gerber V, Gehr P, Straub R et al 1996 Influence of gravity on Holcombe SJ, Robinson NE, Derksen FJ et al 2004 Tracheal
tracheal mucus velocity in excised horse tracheas. mucus is associated with poor racing performance
American Journal of Respiratory and Critical Care in thoroughbred horses. Proceedings of the 50th Annual
Medicine 153: A483 Convention of the American Association of Equine
Gerber V, Gehr P, Straub R et al 1997 Mucus quality on horse Practitioners, AAEP, Lexington, USA, pp. 272–273
tracheal epithelium: microscopic grading based on Houtmeyers E, Gosselink R, Gayan-Ramirez G et al 1999
transparency. Respiration Physiology 107: 67–74 Regulation of mucociliary clearance in health and
Gerber V, King M, Lee M et al 1998 Rheology of mucus in disease. European Respiratory Journal 13: 1177–1188
horses with moderate COPD. World Equine Airways Im Hof V, Gerber V, Gehr P et al 1996 Exogenous surfactant
Symposium CD-ROM, Lifelearn, Guelph, Canada accelerates tracheal mucus velocity in spontaneously
Gerber V, King M, Schneider DA et al 2000 Tracheobronchial breathing non-anaesthetized horses. American Journal of
mucus viscoelasticity during environmental challenge in Respiratory and Critical Care Medicine 153: A109
horses with recurrent airway obstruction. Equine Im Hof V, Gehr P, Gerber V et al 1997 In vivo determination of
Veterinary Journal 32: 411–417 surface tension in the horse trachea and in vitro model
Gerber V, Robinson NE, Rawson J et al 2001 Equine mucin studies. Respiration Physiology 109: 81–93
genes: MUC5AC but not MUC2 is expressed in equine Jefcoat AM, Hotchkiss JA, Gerber V et al 2001 Persistent
airways. Proceedings of the Annual Veterinary Medical mucin glycoprotein alterations in equine recurrent
Forum. American College of Veterinary Internal Medicine. airway obstruction. American Journal of Physiology.
CD-ROM, Omnipress, Chicago. Lung Cell Molecular Physiology 281: L704–L712
Gerber V, Robinson NE, Luethi S et al 2003a Airway inflam- Jeffery PK, Li D 1997 Airway mucosa: secretory cells, mucus,
mation and mucus in two age groups of asymptomatic and mucin genes. European Respiratory Journal 10:
well-performing sport horses. Equine Veterinary Journal 1655–1662
35: 491–495 Jungsuwadee P, Dekan G, Stingl G et al 2004 Inhaled
Gerber V, Robinson NE, Venta RJ et al 2003b Mucin genes dexamethasone differentially attenuates disease relapse
in horse airways: MUC5AC, but not MUC2, may play a and established allergic asthma in mice. Clinical
role in recurrent airway obstruction. Equine Veterinary Immunology 110: 13–21
Journal 35: 252–257 Kaup FJ, Drommer W, Damsch S et al 1990a Ultrastructural
Gerber V, Schott HC, Carr E et al 2003c Oral dexamethasone findings in horses with chronic obstructive pulmonary
resolves owner complaints but inconsistently improves disease (COPD). II: Pathomorphological changes of the
clinical parameters of equine lower airway disease in a terminal airways and the alveolar region. Equine
randomized, double-blind placebo-controlled study. Veterinary Journal 22: 349–355
Proceedings of the Annual Veterinary Medical Forum. Kaup FJ, Drommer W, Deegen E 1990b Ultrastructural findings
American College of Veterinary Internal Medicine. CD- in horses with chronic obstructive pulmonary disease
ROM, Omnipress, Chicago. (COPD). I: Alterations of the larger conducting airways.
Gerber V, Lindberg A, Berney C et al 2004a Airway mucus in Equine Veterinary Journal 22: 343–348
recurrent airway obstruction—short-term response to Keller H, Faulstich M, Elker M et al 2001 Klinische Studie zur
environmental challenge. Journal of Veterinary Internal Wirksamkeit und Verträglichkeit von N-Acetylcystein bei
Medicine 18: 92–97 der Behandlung der COB/COPD des Pferdes [efficacy and
tolerance study of acetylcysteine in the COB/COPD Pirie RS, Dixon PM, Collie DD et al 2001 Pulmonary and
therapy in horses]. Praktischer Tierarzt 82: 108–117 systemic effects of inhaled endotoxin in control and
Kibe A, Inoue H, Fukuyama S et al 2003 Differential heaves horses. Equine Veterinary Journal 33: 311–318
regulation by glucocorticoid of interleukin-13-induced Raidal SL 1996 The incidence and consequences of failure of
eosinophilia, hyperresponsiveness, and goblet cell passive transfer of immunity on a thoroughbred breeding
hyperplasia in mouse airways. American Journal of farm. Australian Veterinary Journal 73: 201–206
Respiratory and Critical Care Medicine 167: 50–56 Raidal SL, Love DN, Bailey GD 1995 Inflammation and
Kim WD 1997 Lung mucus: a clinician’s view. European increased numbers of bacteria in the lower respira-
Respiratory Journal 10: 1914–1917 tory tract of horses within 6 to 12 hours of confinement
King M, Rubin BK 1994 Rheology of airway mucus: with the head elevated. Australian Veterinary Journal
relationship with clearance function. Takashima T, 72: 45–50
Shimura S (editors) Airway Secretion: Physiological Bases Robinson NE, Derksen FJ, Olszewski MA et al 1996 The
for the Control of Mucous Hypersecretion. Marcel Dekker, pathogenesis of chronic obstructive pulmonary disease of
Inc., New York, pp.283–314 horses. British Veterinary Journal 152: 283–306
Lindberg A, Nasman-Glaser B, Lindgren JA et al 2002 Robinson NE, Berney C, Eberhart S et al 2003 Cough, mucus,
Evaluation of leukotriene biosynthetic capacity in airway obstruction, and inflammation in heaves-affected
lung tissues from horses with recurrent airway obstruc- and control horses. American Journal of Veterinary
tion. American Journal of Veterinary Research 63: Research 64: 550–557
794–798 Robinson NE, Kamaus W, Holcombe SJ et al 2006 Airway
Luft J 1987 Der Einfluss koerperlicher Belastung auf die inflammation in Michigan pleasure horses: prevalence
Zytologie des Tracheobronchialsekretes beim Pferd and risk factors. Equine Veterinary Journal (in press)
[The effect of exercise of the composition of tracheo- Sasse W, Deegen E 1984 Zur Wirksamkeit von Sputolysin
bronchial secretions in the horse]. Inaugural Disserta- bei Pferden mit chronischen Bronchialerkrankungen
tion (Dr. med. vet.), Tierärztliche Hochschule Hannover, [On the efficacy of sputolysin in horses with chronic
Germany bronchial diseases]. Tierärztliche Umschau 39: 941–949
Lugo J, Harkema J, Defeijter-Rupp H et al 2006 Airway Schlesinger RB 1985 Clearance from the respiratory tract.
inflammation is associated with mucous cell metaplasia Fundamental and Applied Toxicology 5: 435–450
and increased epithelial stored mucosubstances in horses. Shi ZO, Fischer MJ, De Sanctis GT et al 2002 IFN-gamma, but
The Veterinary Journal (in press) not Fas, mediates reduction of allergen-induced mucous
MacNamara B, Bauer S, Iafe J 1990 Endoscopic evalua- cell metaplasia by inducing apoptosis. Journal of
tion of exercise-induced pulmonary hemorrhage and Immunology 168: 4764–4771
chronic obstructive pulmonary disease in associa- Shim JJ, Dabbagh K, Ueki IF et al 2001 IL-13 induces mucin
tion with poor performance in racing Standardbreds. production by stimulating epidermal growth factor
Journal of the American Veterinary Medical Association receptors and by activating neutrophils. American
196: 443–445 Journal of Physiology. Lung Cellular and Molecular
Matthews AG, Hackett IJ, Lawton WA 1988 The mucolytic Physiology 280: L134–L140
effect of Sputolosin in horses with respiratory disease. Sonea IM, Bowker RM, Robinson NE 1999 Distribution of
Veterinary Record 122: 106–108 substance P binding sites in equine airways. Equine
Matthews LM, Spector S, Lemm J et al 1963 Studies on Veterinary Journal 31: 238–242
pulmonary secretions. American Review of Respiratory Sweeney CR 1989 Tracheal mucus transport rate in healthy
Disease 88: 199–204 horses. American Journal of Veterinary Research
Maxson AD, Soma LR, May LL et al 1995 Effects of 50: 2135–2137
furosemide, exercise, and atropine on tracheal mucus Sweeney CR, Beech J, Roby KA 1985 Bacterial isolates from
transport rate in horses. American Journal of Veterinary tracheobronchial aspirates of healthy horses. American
Research 56: 908–912 Journal of Veterinary Research 46: 2562–2565
Moreno RH, Hogg JC, Pare PD 1986 Mechanics of airway Sweeney CR, Leary HJ 3rd, Ziemer EL et al 1989 Effect of
narrowing. American Review of Respiratory Disease water vapor-saturated air therapy on bronchoalveolar
133: 1171–1180 lavage and tracheal mucus transport rate in clinically
Nakanishi A, Morita S, Iwashita H et al 2001 Role of gob-5 in normal horses. American Journal of Veterinary Research
mucus overproduction and airway hyperresponsiveness 50: 276–279
in asthma. Proceedings of the National Academy of Takeyama K, Dabbagh K, Jeong Shim J et al 2000 Oxidative
Sciences, USA 98: 5175–5180 stress causes mucin synthesis via transactivation of
Pearce HG, Wyburn RS, Goulden BE 1978 A clinical epidermal growth factor receptor: role of neutrophils.
evaluation of Bisolvon® for the treatment of some Journal of Immunology 164: 1546–1552
equine respiratory diseases. New Zealand Veterinary Tesfaigzi Y, Fischer MJ, Martin AJ et al 2000 Bcl-2 in LPS- and
Journal 26: 28–30 allergen-induced hyperplastic mucous cells in airway
Pietra M, Guglielmini C, Forni M et al 2000 In vitro epithelia of Brown Norway rats. American Journal of
mucolytic activity of recombinant human deoxyribo- Physiology: Lung Cellular and Molecular Physiology
nuclease on equine tracheobronchial mucus. Veterinary 279: L1210–L1217
Record 147: 627–629 Toda M, Tulic MK, Levitt RC et al 2002 A calcium-activated
Pirie RS 1998 In: Role of inhaled endotoxin in the chloride channel (HCLCA1) is strongly related to
pathogenesis of equine COPD. Dixon PM, Schmallenbach IL-9 expression and mucus production in bronchial
K, Maisi P, et al (editors) Proceedings of Workshop on epithelium of patients with asthma. Journal of Allergy
Allergic Diseases of the Horse. Lipica, Slovenia, p.10 and Clinical Immunology 109: 246–250
Turgut K, Sasse HH 1989 Influence of clenbuterol on Willoughby R, Ecker G, McKee S et al 1992 The effects of
mucociliary transport in healthy horses and horses with equine rhinovirus, influenza virus and herpesvirus
chronic obstructive pulmonary disease. Veterinary infection on tracheal clearance rate in horses. Canadian
Record 125: 526–530 Journal of Veterinary Research 56: 115–121
Viel L 1980 Structural-functional correlations of the lung Willoughby RA, Ecker GL, McKee SL et al 1991 Use of scin-
in the normal light horse. MSc thesis, University of tigraphy for the determination of mucociliary clearance
Guelph, Canada rates in normal, sedated, diseased and exercised horses.
Walley EA, Thornton DJ, Corfield AP et al 2001 Characteriza- Canadian Journal of Veterinary Research 55: 315–320
tion of equine respiratory tract mucins. World Equine Zhou Y, Dong Q, Louahed J et al 2001 Characterization of a
Airway Symposium, CD-ROM, Lifelearn, Guelph, Canada calcium-activated chloride channel as a shared target of
Widdicombe JH, Pecson IS 2002 Distribution and numbers of Th2 cytokine pathways and its potential involvement
mucous glands in the horse trachea. Equine Veterinary in asthma. American Journal of Respiratory Cell and
Journal 34: 630–633 Molecular Biology 25: 486–491
Immunology and Immunopathology
6 D Paul Lunn, Cormac Breathnach and Gisela Soboll
The immune defenses of the equine respiratory tract published (Lunn & Horohov 2003), and this chapter will
protect an area of over 2,000 m2 from the myriad micro- focus on the specific specialization of the equine respiratory
organisms, particulates, and noxious agents inhaled in an tract, and mucosal immune responses in particular.
estimated 100,000 liters of air on a daily basis (Dixon &
McGorum 1997). All this while maintaining surfaces that
can allow the free diffusion of respiratory gases to the blood
Innate and Adaptive Immunity
across barriers no more than two cells thick. Although a Respiratory defense mechanisms are complex, integrating
robust immune response must be mounted against many responses that include mechanical barriers, the chemical
serious pathogens, the same system must establish and poisons, neutrophils and macrophages of the innate
maintain tolerance to many non-threatening but antigenic immune system, and the development of highly specific
inhaled materials. antibody and lymphocyte responses by the adaptive
The respiratory immune system shares all the compo- immune system. The upper and lower airways, and the
nents of the immunological response found throughout the alveolar space each have different defense mechanisms
rest of the body, but also has several unique features that (Table 6.1) (Pilette et al 2001). Mechanical defenses,
are characteristic of the mucosal immune system. An capable of removing inhaled particulate matter, pre-
extensive review of equine immune responses was recently dominate in the airways and are reviewed in the previous
Table 6.1. Defence mechanisms of the respiratory tract

Mechanical Innate immunity Adaptive immunity
Upper respiratory tract (nasopharynx and larynx)
● Nasal, oropharyngeal and ● Complement ● Secretory IgA and IgM in mucus layer (major Ig classes), in lamina
sinus ciliated epithelium ● Proteases propria, and in transit through endosomal compartment of
and sneezing ● Lactoferrin repiratory epithelial cells
● Vocal cords ● IgG subclasses (IgGa and IgGb) in mucus layer, and in lamina propria
● Mucus ● Full complement of lymphocyte subsets, including inflammatory CD4
cells and cytotoxic lymphocytes in organized (tonsils) and dispersed
lymphoid tissues in mucosa
Lower respiratory tract (tracheobronchial tree)
● Mucociliary clearance ● Recruited neutrophils ● Secretory IgA and IgM as in upper respiratory tract, plus increasing
● Impaction on bronchial ● (Alveolar?) amounts of IgG
branching and coughing Macrophages ● Full complement of lymphocyte subsets as in upper respiratory tract,
organized as bronchial-associated lymphoid tissue
Lung parenchyma (alveoli and lung interstitium)
● None ● Surfactant products ● Parenchymal lymphocytes and recruited lymphocytes in case of

● Phagocytic cells inflammatory response
including resident
alveolar macrophages
and recruited
neutrophils and their
products
Adapted from Pilette et al, 2001
71
72 6 Immunology and Immunopathology
Box 6.1. T-helper cells and cytokines
The CD4+ T-helper lymphocytes “help” other effector cells to two types of T-helper subsets and the cytokines they pro-
fight off pathogens or respond to antigens. At least two duce, tend to suppress each other. As a result, in an immune
different subsets of T-helper cells, characterized by their response to a particular pathogen, either the Th1 or Th2 subset
cytokine production profile, are responsible for regulating will predominate and give rise to either an inflammatory/
the immune response to infectious agents or to inhaled cytotoxic immune response or different antibody-mediated
antigens. The subsets are the T-helper 1 (Th1) subset which immune responses. Several factors have been identified which
stimulates cytotoxic and inflammatory functions and pro- may influence whether a Th1 or Th2 response will predomi-
duction of the equine IgG subclasses IgGa and IgGb, and the nate and these include the type of antigen-presenting cell,
T-helper 2 (Th2) subset which stimulates equine IgG subclasses the dose of antigen, and the cytokines present during antigen
IgG(T), IgA, and allergic responses mediated by IgE. These presentation.
Cytokines associated with different T-helper responses
Cytokine Function Th1 Th2
IL-2 Provides proliferative signal for T cells. Also affects B cells, macrophages and NK cells. X
High concentrations of IL-2 stimulate cytolytic activity in NK cells and T cells.
IL-12 NK-cell differentiation factor. Augments NK-cell function and stimulates generation of Th-1 cells. X
Produced by macrophages.
IFN-γ Produced by NK cells in response to IL-12, and by Th-1 cells. Leads to increased MHC I and II X
expression, activation of macrophages and cytotoxic lymphocytes, and IgGa and IgGb production.
IL-4 Stimulates growth, maturation and differentiation of B cells. X
IL-5 Stimulates B-cell proliferation and immunoglobulin synthesis. Also stimulates T-cell proliferation X
and differentiation as well as eosinophil formation in the bone marrow.
IL-6 Promotes maturation and immunoglobulin production by B cells. Stimulates T-cell growth and X
IL-2 synthesis. Induces the production of acute-phase proteins by hepatocytes. Produced by
macrophages, T cells, stromal cells, fibroblasts, and a variety of other cell lines.
IL-10 Cytokine synthesis inhibitory factor. Inhibits the production of IL-2 and IFN-γ by Th-1 cells. X
IL-13 Down-regulates cytokine production by macrophages/monocytes while activating B cells. X
IL = interleukin; NK = natural killer; IFN-γ = interferon-γ; MHC = major histocompatibility complex
chapter (Chapter 5). In contrast, the alveolar epithelium lymphocyte responses is present or readily recruited from
lacks mucociliary properties and removes particles and the systemic lymphocyte pool, together with the unique
microorganisms by use of resident alveolar macrophages. adaptations of the mucosal immune system that play a
The innate immune response provides a constant defense critical response in all aspects of respiratory immunology.
against everyday encounters with potential invaders, One important concept in understanding the adaptive
and in the face of greater threats can rapidly recruit poly- immune system is the importance of the regulatory role of
morphonuclear neutrophils to the airways and support- T-helper cell subsets, which modulate immune responses
ing tissues. Danger signals leading to this response can through the secretion of cytokines. A detailed review is
come from several sources, but it is interesting to note that available elsewhere (Lunn & Horohov 2003), but Box 6.1
even respiratory epithelial cells can initiate inflamma- highlights the essential elements of this process.
tory reactions by release of cytokines, this recruiting
phagocytic myeloid cells and lymphocytes, and can serve
as effective antigen-presenting cells to initiate adaptive
Mucosal Immunity
immune responses by lymphoid cells. The adaptations that maximize absorption and exchange at
The adaptive immune response depends on lymphocytes, mucosal surfaces render these tissues especially vulnerable
which are relatively scarce in the normal airway and alveo- to invasion by pathogens. This challenge is confronted by
lar lumen, although they are common in the submucosa the mucosal immune system, consisting of organized and
throughout the respiratory tract. The full complement of dispersed lymphoid tissues that are closely associated with
6 Immunology and Immunopathology 73
mucosal epithelial surfaces (Mestecky et al 2003). The Inductive site

mucosal immune system maintains immune surveillance
High endothelial c.
across the largest external surface area of the body, and venule a.
mucosal immune responses generated in one location are b. Efferent
transferred throughout the mucosal immune system by lymphatic
lymphocytes that are programmed to home to regional
effector sites. The principal immunoglobulin produced
by the mucosal immune system is secretory immuno- Lymphoid
Submucosa
globulin A (sIgA), which, in humans, is the most abundant follicle
immunoglobulin class in the body. Secretory IgA has
unique adaptations that promote transport out onto Epithelial
mucosal surfaces, where it protects the body from bacteria cells
and viruses principally by immune exclusion, i.e. by Microbes M cell
in airway
physically preventing attachment to mucosal surfaces.
The importance of mucosal IgA has already been Effector site
demonstrated in immunity to equine influenza virus
(Hannant et al 1989b, 1999, Nelson et al 1998), equine High endothelial
venule
herpesvirus-1 (EHV-1) infection (Breathnach & Allen
2001), and Streptococcus equi (Sheoran et al 1997). For Lamina
many equine diseases, and especially viral respiratory propria
infections, a mucosal immune response may be the
most effective type of immune protection. In addition to
regulating this mammoth defense strategy, the mucosal
system must distinguish food and other antigens against
which an immune response would be disastrous. Airway
lumen
Distribution of lymphoid tissues in the Fig. 6.1. Initiation of mucosal immune responses. Respiratory mucosal
immune responses typically originate after antigenic encounter
respiratory tract at inductive sites, which are the tonsils of the nasopharynx and
oropharynx in the horse. Naive lymphocytes enter the inductive sites
Coordination of the mucosal immune response depends on
from high endothelial venules via the specialized cuboidal endo-
organized mucosa-associated lymphoid tissue (MALT), thelium of those vessels in response to specific molecular signals.
principal examples of which are the pharyngeal tonsils Antigens, such as microbes, are taken up by microfold or M cells
and the intestinal Peyer’s patches. In the gastrointestinal which are part of the highly specialized follicle-associated epithelium
tract MALT is distributed throughout the gut, but in present at these sites. Antigenic material is transported across the M
cell, and antigen presentation to B and T lymphocytes is accomplished
the respiratory tract these tissues are only found in the
by dendritic cells in the underlying tissues. The underlying lymphoid
nasopharynx and oropharynx. MALT consists of lymphoid follicle is composed primarily of B lymphocytes, surrounded by
follicles containing IgA-committed B cells, surrounded by T-lymphocyte areas. Antigen-specific B lymphocytes become com-
interfollicular T-cell areas with antigen-presenting cells mitted primarily to IgA production at these sites, although some IgG B
and high endothelial venules, with an overlying follicle- lymphocytes are also generated. Subsequently the primed lymphocyte
populations exit the inductive site via efferent lymphatics, eventually
associated epithelium. Naive lymphocytes enter the MALT
reaching the blood circulation through the thoracic duct. Subsequently
by extravasation from the high endothelial venules (there these cells traffic to high endothelial venules of effector sites throug-
are no afferent lymphatics in MALT), and after antigen hout the respiratory epithelium, and extravasate to make up the intra-
encounter in the MALT they leave through efferent epithelial lymphocyte and lamina propria lymphocyte population, and to
lymphatics. The follicle-associated epithelium is specialized give rise to lymphoid aggregates. Subsequent antigen encounter results
in terminal differentiation to plasma cells, primarily IgA-producing
for antigen sampling, by having reduced secretion of
although some IgG plasma cells are also formed. IgG is largely
mucus, and by the presence of specialized antigen uptake restricted to tissues, but secretory IgA is transported to the respiratory
cells termed microfold or M cells. These M cells are typically epithelial surface where it can aggregate infectious organisms.
closely associated with underlying aggregates of lympho-
cytes, often within large basolateral membrane pockets,
and play a critical role in mucosal immune surveillance. activation of antigen-specific B cells (Fig. 6.1). Subsequent
Adherent macromolecules or particles bound to the apical trafficking and recirculation of memory IgA-positive B cells
M-cell membrane undergo endocytosis or phagocytosis and to the other components of the mucosal immune system
are released at the pocket membrane, where antigen (respiratory tract, intestinal tract, etc.) is responsible
presentation is initiated by dendritic cells resulting in the for the dissemination of local mucosal IgA responses
Nasopharyngeal
tonsil
Guttural pouch Retropharyngeal

opening surrounded lymph nodes
by tubal tonsil
Soft palate Lingual tonsil

tonsil
Palatine
tonsil
Submandibular
lymph nodes
Fig. 6.2. Lymphoid tissues of the equine upper respiratory tract. The nasopharyngeal tonsils are bilateral
structures in the dorsolateral nasopharyngeal roof, and are the largest mass of lymphoid tissue in the
respiratory tract of horses of all ages. Lymphoid aggregates are common in the adjacent mucosa. Tubal
tonsils surround the operculum (opening to the guttural pouch). Palatine tonsils extend longitudinally
along each side of the oropharynx at the base of the tongue. Embedded within the base of the tongue lies
the lingual tonsil. The tonsil of the soft palate consists of strings of lymphoid nodules extending
longitudinally along the center of the soft palate. Regional lymphatic drainage is via the retropharyngeal
lymph nodes and to the submandibular lymph nodes.
throughout what is termed the “common mucosal immune ● Isolated lamina propria lymphocytes are present through-
system”. After the homing of these B cells to effector sites out the subepithelial connective tissue, primarily in
such as the lamina propria of the gut and respiratory tract, areas surrounding lymphoid nodules.
and extravasation into the lamina propria from high ● Densely packed aggregated lymphocytes are present close
endothelial venules, further antigen encounter and second to serous gland ducts in the nasal mucosa, and make up
signals from antigen-presenting cells and from T-helper subepithelial lymphoid nodules throughout the bronchi.
cells result in further differentiation into IgA-producing ● Nodular lymphoid tissue, which in the nasopharynx and
plasma cells. The short half-life of IgA-secreting plasma oropharynx can have an overlying lymphoepithelium
cells requires a constant generation of precursors in specialized for antigen uptake and processing as in the
induction sites and flow to effector sites. Antigen sampling case of tonsillar tissues. Additional nodular lymphoid
and presentation are not restricted to organized MALT, tissue is typically present at sites where antigen-laden
and throughout the mucosal surfaces, including areas mucus and air currents converge throughout the
such as pseudostratified airway epithelium, dendritic cells trachea and bronchi and is called bronchus-associated
play a key role in antigen uptake and presentation, subse- lymphoid tissue or BALT. Mucosal lymphoid nodules
quently migrating to local lymph nodes or MALT to initiate are apparent in foals as early as 9 months of gestational
immune responses. age and develop at specific locations, suggesting that
In the horse, understanding of the architecture and the ontogeny of mucosal lymphoid tissue is genetically
functions of respiratory lymphoid tissues largely comes regulated (Mair et al 1988a). The number of mucosal
from work conducted by Mair et al (1987, 1988a,b). This lymphoid nodules peaks in young adult horses (≤5 years
group described five levels of respiratory tract-associated of age), and wanes in older animals (Mair et al 1988a).
lymphoid tissue in the horse: Tonsils represent the most complex mucosal nodular
lymphoid tissues. Horses possess all of the various
● Free luminal lymphocytes exist primarily in the respira- tonsillar tissues that are recognized in other species
tory mucus overlying subepithelial lymphoid aggregates. (depicted in Fig. 6.2). Tubal tonsils surround the
● Intraepithelial lymphocytes are scattered throughout the operculum (opening to the guttural pouch). Palatine
respiratory epithelium, but cluster at the base of the tonsils extend longitudinally along each side of the
epithelia overlying mucosal lymphoid nodules. oropharynx at the base of the tongue. Embedded within
Table 6.2. Immunophenotype of respiratory mucosal and lymph node lymphocytes

Source of lymphocytes CD3 CD4 CD8 MHCII CD8/CD4
PBMC 71.1 42.9 3.9 63.8 0.09

Retropharyngeal lymph node 40.6 30.8 5.5 73.2 0.18
Hilar lymph node 52.7 36.6 6.1 76.9 0.17
Inguinal lymph node 43.0 28.8 7.1 71.4 0.25
Pharyngeal follicular tissue 35.8 22.9 7.2 62.0 0.31
Nasal mucosa 36.8 30.4 6.1 74.4 0.20
Tissues were dissected and dissociated with hyaluronidase and collagenase prior to purification of mononuclear cells by density-gradient centrifuga-
tion and flow cytometric analysis using previously described monoclonal antibodies (Lunn et al 1998). Results of lymphocyte antigen expression by
peripheral blood mononuclear cells (PBMCs), regional lymph node lymphocytes, and pharyngeal wall (nasopharyngeal tonsil) and nasal mucosa are
shown. All results are means of percentage positive staining; n = 6 horses. These results demonstrate that in comparison to PBMCs, lymph nodes and
mucosal tissue T-cell numbers (CD3-positive) are reduced, but the proportion of CD8 cells is increased.
the base of the tongue lies the lingual tonsil. The tonsil intranasal challenge of yearling and 2-year-old horses with
of the soft palate consists of strings of lymphoid nodules EHV-1, virus-specific cytotoxic activity is detectable in
extending longitudinally along the center of the soft several mucosal lymphoid tissues of the upper respiratory
palate. Finally, the best studied tonsillar tissue in the tract, as well as the local draining lymph nodes, and
horse is the nasopharyngeal tonsil, deemed to represent is particularly evident in the nasopharyngeal lining
the largest mass of lymphoid tissue in the respiratory (Breathnach et al 2006). This cellular immune response is
tract of horses of all ages (Mair et al 1988a). Kumar et presumably mediated by CD8+ T lymphocytes found in
al (2001) have characterized this tissue and identified a the nasopharyngeal epithelium and underlying lamina
classical follicle-associated epithelium overlying it. This propria, and may provide an important contribution to
epithelium is heavily folded to form crypts, and also the clearance of infectious virus from the upper res-
contains M cells. The nasopharyngeal tonsil exists in the piratory tract.
dorsal recess of the nasopharynx, and extends ventrally
towards the opercula on either side of the nasopharynx.
Therefore, it is ideally placed for the sampling of
Immunoglobulins of the Respiratory Tract
antigens prior to entry to the airways or alimentary Immunoglobulin G (IgG) is composed of two identical light
tract and may serve as an important target for chains and two identical heavy chains that form a
intranasal vaccines. This tissue appears to be most disulfide-linked Y-shaped molecule (Fig. 6.3). The multi-
abundant in young foals, and atrophies with age, meric immunoglobulins are IgM (five IgG-like units) and
though many lymphoid follicles remain throughout the IgA (a dimeric structure: Fig. 6.3). The association of the
nasopharynx. It is not known whether the other
tonsils of the horse have a classical follicle-associated
epithelium, and this could significantly affect their role IgG molecule
in initiating respiratory immune responses as they may Heavy chain
not necessarily all be components of the mucosal Variable region
(antigen recognition)
immune system. Light
chain
The nasopharynx is a dynamic immunological site. Constant region Hinge
(effector functions) region
Within the nasopharyngeal epithelium lie numerous
lymphocytes. Immmunohistochemical studies indicate that
the majority of these lymphocytes are CD8+ T lymphocytes IgA molecule
although B lymphocytes are also present (Kumar et al Secretory
2001). However, when these tissues are dissociated and component
studied by flow cytometry, B lymphocytes predominate,
although the numbers of CD8+ T lymphocytes is con-
siderably greater than in blood or respiratory tract lymph
nodes (Table 6.2). The contribution of these lympho-
J chain
cytes to mucosal cellular immune defense of the upper
respiratory tract is poorly studied. However, following Fig. 6.3. Immunoglobulin molecules; see text for details.
amino ends of a light and a heavy chain forms the antigen- Submucosa Airway
binding region of all antibody molecules, while the lumen
carboxyl end of the heavy chain determines the isotype of plgR synthesized and
the molecule (the Fc region). Five different classes or traffics to basolateral
membrane
isotypes of antibody molecules have been identified in most
species: IgD, IgM, IgG, IgA, and IgE. Additionally, antibody
classes can be subdivided into subclasses, each with distinct
pIgR binds dimeric
properties. Analysis of equine genomic DNA has indicated IgA and is endocytosed
the existence of one IgM, IgD, IgE, and IgA genes, and
seven IgG heavy-chain genes (Wagner et al 1998, Wagner Dimeric IgA released
to submucosa by
2006). This means that only one subclass or subisotype of plasma cells
each equine IgM, IgD, IgE, and IgA is formed. For equine
IgG the situation is more complex. At least four IgG
subclasses have been previously identified by monoclonal pIgR–dimeric IgA complex
antibodies and functional studies, and these are called transcytosed and released
to airway as secretory IgA
IgGa, IgGb, IgGc, and IgG(T) (Lunn et al 1998). Currently
IgGa is known to be endocoded by heavy-chain gene G1, Fig. 6.4. Transcellular transport of IgA. Epithelial cells synthesize the
IgGb by G4, IgGc by G6, and IgG(T) by G3 and G5. The polymeric immunoglobulin receptor (pIgR), which traffics to the
product of heavy-chain gene G2 is currently unknown basolateral membrane, where it associates with dimeric IgA. During
transcytosis the pIgR forms covalent bonds with IgA, and is sub-
(Wagner 2006). The products of heavy-chain genes G2 sequently cleaved to release secretory component (a fragment of pIgR)
and G7 are presently unknown. It is possible that IgG(T), as combined with the dimeric IgA as secretory IgA onto the respiratory
defined by monoclonal antibodies, each represent two epithelial surface.
subclasses, as genetic studies suggest each IgG(T) heavy-
chain gene is expressed. However, these may represent
gene replications with limited implications for immuno-
logical function. In the future, equine immunoglobulins (Fig. 6.4). Subsequently the sIgA is transported across the
are likely to be named by their genetic derivation, but for epithelial cell and released at the luminal surface together
the present the older names (IgGa etc.) are more useful with the secretory component formed by cleavage of part
for interpretation of the literature and explanation of of the polymeric immunoglobulin receptor. Secretory
biological effects. What is known about equine immuno- component can also be found in a free form in mucosal
globulins is that IgGa and IgGb have Fc receptors capable of secretions. Secretory component confers resistance to
reacting with components of the innate immune system the proteolytic enzymes found in the respiratory and
including complement, neutrophils, and macrophages to gastroenteric environment, some of which are secreted by
facilitate antimicrobial immunity, while IgGc and IgG(T) pathogens, and prolongs the longevity of sIgA. During its
are better adapted to immunity to toxins and parasites transit through the epithelial cell, sIgA can neutralize
(Lunn & Horohov 2003). intracellular infections encountered in the endosomal
The principal immunoglobulin produced by the mucosal compartments of cells (Mazanec et al 1993). In addition,
immune system is sIgA. Secretory IgA is formed by dimeri- sIgA can bind antigens in the submucosa and literally
zation of two IgA monomers, which are attached by means transport or excrete them to the mucosa by this mech-
of disulfide bonds to a J-chain, also produced by the same anism. The majority of the IgA in the mucosa is dimeric
plasma cell that secretes the IgA. This confers the advan- sIgA, while the bone-marrow-derived IgA in the circulation
tage of increased valency to sIgA, which can bind up to is predominantly monomeric.
four of its targets so increasing its agglutinating ability. Studies by Mair (1987, 1988a) indicated that IgA-
Secretory IgA protects the body from bacteria and viruses producing plasma cells predominate in the upper airways
principally by immune exclusion, i.e. by physically prevent- but IgG-producing cells are more common in the lower
ing attachment to mucosal surfaces. Immunoglobulin A is respiratory tract (Mair et al 1988b). However, a recent
relatively “non-inflammatory” (i.e. does not fix complement study of the pulmonary humoral immune system found
as effectively as IgGa or IgGb), which is consistent with a that IgA-producing plasma cells predominated in this
role in defense by immune exclusion (Mestecky et al 2003). location also (Blunden & Gower 1999). Antigen-specific
Similarly, although myeloid cells possess Fc receptors for IgA has been demonstrated in nasal mucus directed against
IgA it is not clear that it functions as an efficient opsonin or a number of pathogens including influenza virus, EHV-1,
promotes phagocytosis. and S. equi (Sheoran et al 1997, Nelson et al 1998,
After release of sIgA by plasma cells into the Breathnach et al 2001). These same studies also identified
interstitium, it is bound by the polymeric immunoglobulin antigen-specific IgG subclasses, in particular IgGa and
receptor on the abluminal surface of epithelial cells IgGb, in these locations, although at much lower titers
than were detected in serum. It is likely that some of this 1992). In a murine model, IgA in respiratory secretions
IgG represents a transudate from the lamina propria and specific for the viral hemagglutinin glycoprotein protects
from serum. However, when tissue samples from the nasal against influenza virus infection (Renegar & Small 1991).
respiratory mucosa are processed to harvest lymphocytes, Intravenously administered IgA is transported physio-
these mucosal cells will secrete antigen-specific IgGa and logically to the respiratory tract and appears in secretions.
IgGb, demonstrating that local immune responses are not This transport occurs by diffusion into the lamina propria
restricted to IgA (Soboll et al 2003a,b). and by receptor-mediated transport across respiratory
epithelial cells as described above. Such transport is a basic
characteristic of IgA and is the reason for its predomi-
Respiratory Immunity nant role in local immunity as described above. It has
to Infectious Disease subsequently been shown that IgA not only neutralizes
The importance of respiratory mucosal immunity in virus in respiratory secretions, but can also neutralize
defense against infectious disease cannot be overempha- intracellular virus, a role previously ascribed only to
sized. Our understanding of specific equine respiratory cellular immunity (Mazanec et al 1992). A critical differ-
defense against fungal infections is limited, although ence between natural equine influenza virus infection and
examples of these relatively infrequent infections are most vaccination is that infection induces high levels of IgA in
common in immunocompromised or very young horses. nasal mucosal secretions whereas killed vaccines induce no
Similarly there is relatively little information available IgA antibodies (Hannant et al 1989a, Nelson et al 1998).
about immunity to parasites of the lung (Klei 2000). While the importance of IgA is clear, other components of
However, we have a growing understanding of respiratory the immune response are also important for respiratory
tract immunity to both viral and bacterial pathogens. immunity. Both influenza-specific IgGa and IgGb can be
found in respiratory secretions after infection, the source of
Respiratory immunity to viruses which includes serum transudates and local production
(Soboll et al 2003a).
Equine antiviral immunity has been extensively reviewed While viral pathogens that typically produce short-lived
(Slater & Hannant 2000). Both the innate and adaptive infections of the respiratory epithelium, such as influenza
immune responses are important in resistance to respiratory virus, are highly susceptible to antibody-mediated protec-
viral infection. The earliest immune response is the innate tion, more invasive pathogens such as EHV-1 require
response, which aims to limit viral spread until an effective additional immune responses for their control (Slater &
adaptive immune response can be mounted. Key compo- Hannant 2000). Once EHV-1 has invaded the lamina propria
nents of the innate response include complement, mono- of the respiratory tract, it rapidly becomes cell-associated,
nuclear phagocytic cells, and cytokines. In the respiratory and is then protected from antibody-mediated immunity
tract the cytokines with direct antiviral action are the (Allen et al 1999). It is known that cytotoxic lymphocytes
type 1 interferons (IFN-α and IFN-β) and tumor necrosis measured at the systemic level play a critical role in EHV-1
factor-α (TNF-α). The type 1 interferons are rapidly immunity (O’Neill et al 1999). Recent research indicates
induced by viral invasion and induce cellular enzymes that that these effector cytotoxic lymphocytes can also be found
interfere with viral replication and up-regulate antigen in the respiratory epithelium (Breathnach et al 2006), and
presentation. IFN-α is produced by macrophages and virus- it remains possible that these cytotoxic lymphocytes are
infected cells produce IFN-γ. In contrast, TNF-α is produced amongst the most important defense mechanisms for
by a variety of cells, and can directly kill virus-infected cells invasive viral pathogens such as EHV-1.
by cytolysis or by inducing apoptosis.
The best understood example of the role of the adaptive Respiratory immunity to bacteria
immune response to respiratory viral pathogens in the
horse is equine influenza virus. Natural equine influenza For a comprehensive review of equine immunity to
virus infection confers complete clinical immunity for over bacterial infections, the reader is referred to an excellent
6 months and partial immunity for over 1 year (Hannant review (Giguere & Prescott 2000). Much of what has been
et al 1988). Serum antibody to influenza virus is frequently said about immunity to viral infection also applies to
undetectable by 12 months post infection. This indicates bacterial infection. Mucosal antibody responses are a
that factors other than circulating IgG are responsible for critical defense against bacterial invaders such as S. equi
protection after natural infection, such as local respiratory (Sheoran et al 1997), although results can be more
tract antibody production (IgA) or cellular immunity. variable in the case of intracellular bacteria such as
Studies of host defenses in other species have demon- Rhodococcus equi (Prescott et al 1997). The importance of
strated the importance of both local antibody responses in T-helper cells in modulating inflammatory responses to
preventing infection and cell-mediated immunity for viral pathogens such as R. equi is critical to the outcome of
clearance and recovery from infection (Bender & Small these infections, and one specific defense strategy of these
agents is to down-regulate the production of macrophage- tolerance if disease is to be avoided. The mechanisms by
activating IFN-γ by T-helper 1 lymphocytes (Giguere et al which tolerance is induced are complex (Weiner 1997), but
1999). While foals appear susceptible to this strategy, adult the consequences of failure may be most clearly illustrated
horses normally immune to R. equi can generate potent in pharyngeal lymphoid hyperplasia and recurrent airway
IFN-γ responses to infection (Hines et al 2003). obstruction (RAO).
Pharyngeal lymphoid hyperplasia

Vaccine-induced Respiratory Immunity Pharyngitis in horses, also called lymphoid follicular
There are several vaccines that can provide partial or hyperplasia, has been extensively reviewed (Pascoe 1996)
complete protection from viral infection of the respiratory and is discussed elsewhere in this text. The condition
tract, although protection against bacterial infections such involves both the nasopharyngeal tonsil, and the extensive
as S. equi is frequently less effective (Lunn & Townsend lymphoid tissue in the roof and walls of the pharynx. The
2000). However, the principal immunological responses condition occurs from 2 to 3 months of age, reaching
generated and measured consequent to vaccination its highest prevalence in 2-year-old horses in training
are systemic, and there are very few examples of respira- and then declining considerably by 5 years of age. The
tory immune responses generated by equine vaccines. pathology and epidemiology of equine pharyngeal lym-
Manipulation of the equine mucosal immune response to phoid hyperplasia is very similar to that of tonsillitis and
generate specific IgA responses remains extremely difficult, adenoiditis in humans (Richardson 1999). In both species
despite some experimental successes (Hannant et al 1999, both the etiology and the appropriate treatments are
Soboll et al 2003b). Generating mucosal IgA responses uncertain. Inflammation of the respiratory tract in young
with killed vaccines is challenging, and the most effective horses is common, and the role of nasopharyngeal lym-
mucosal adjuvants are the bacterial exotoxins of enteric phoid tissue in the etiopathogenesis is unknown. Although
bacterial pathogens such as cholera toxin or the labile toxin pharyngeal lymphoid hyperplasia and inflammatory
of Escherichia coli (Foss & Murtaugh 1999). An obvious and airway disease (IAD) are associated with stabling and
major disadvantage of using cholera toxin is that it can exposure to organic dust, no direct link has been demon-
produce cholera diarrhea in humans. An alternative strated between the two (Holcombe 2000). Inflammation
approach to mucosal vaccination involves the use of of the equine tonsil may have additional ramifications
microspheres, which are preferentially taken up by the in that it is likely involved in lymphadenopathy of the
M cells of the tonsils. This approach has been used with retropharyngeal lymph nodes, a condition that may
success in the case of experimental S. equi intranasal play a role in dorsal displacement of the soft palate
vaccination (Nally et al 2000). (Holcombe et al 1999, Holcombe 2000). The identifica-
Modified live vaccines have enjoyed the greatest success tion of M cells in the equine nasopharyngeal tonsil may
as mucosal vaccines. An intranasal cold-adapted equine help explain the common involvement of pharyngeal
influenza vaccine is amongst the most effective equine lymphoid tissue in infectious inflammatory disease.
vaccine available (Townsend et al 2001). Surprisingly it is The antigen sampling adaptations of the M cell also
very difficult to detect measurable antibody responses to make it an attractive site for pathogen involvement, and
this vaccine (Lunn et al 2001), and nasal IgA responses bacteria and viruses that exploit M-cell transport can
cannot be detected even after repeated vaccination (Lunn, rapidly infect the mucosa and spread systemically (Neutra
unpublished data). Nevertheless, it is very probable that the et al 1996). The exuberant inflammatory response that
success of this vaccine depends on the establishment of characterizes pharyngeal lymphoid hyperplasia has at least
immunological responses at the respiratory mucosal level, a partial infectious etiology. The age-related improve-
although currently these are difficult to measure. Live ment in this condition probably reflects a combination of
vector vaccines can also be used for mucosal vaccination, maturation of immune responses and age-related changes
and an attenuated salmonella strain has been used in the in management of the horse.
horse to generate immune responses to S. equi proteins
(Sheoran et al 2001). Recurrent airway obstruction
The horse is commonly affected by two forms of chronic
respiratory disease, RAO in middle-aged horses and IAD in
Immunopathology of the young performance horses (Robinson 2001), that are very
Respiratory Tract probably caused at least in part by immunopathological
Hypersensitivity and inflammatory disorders or hypersensitivity responses. Because moldy hay can
exacerbate RAO, it has been described as a hypersensitivity
While much of the foreign material that the equine tonsil reaction to molds such as Aspergillus fumigatus and Faenia
meets requires a vigorous immunological response, there is rectivirgula. In RAO-susceptible horses, exposure to hay
an equal or greater number of antigens that require dust leads to invasion of the lungs and airways by
neutrophils within 4–6 hours and concurrent airway monia between 2 and 4 months of age, when maternally
obstruction as a result of bronchospasm, inflammation, derived antibody is waning and cellular immunity has
and increased mucus viscosity, which principally affects the yet to become fully developed, also supports this theory.
bronchioles. In contrast, IAD commonly affects young Possible explanations for increased susceptibility to
horses in training, and has been associated with bacterial infection in foals in the first year of life could also include
and viral infections, although in many horses no infectious low concentrations of IgA or other immunoglobulin classes
etiology is identified and allergic and environmental factors (Holznagel et al 2003). While lack of development of adult
are implicated. The condition is typically associated with immunocompetence may be an important factor in
neutrophilic airway inflammation, although in some cases juvenile respiratory infection, it is critical to remember that
eosinophils or mast cell numbers are increased. the foal is also antigenically naive, and development of a
Both RAO and IAD have been extensively studied, and full complement of immune responses requires exposure
are discussed in detail in Chapters 41 and 42 respectively. through infection or vaccination.
The immunological basis of RAO remains poorly elucidated In humans, IgA deficiency is the most common immune
(Marti et al 2003). While IgE levels are increased in defect after AIDS, affecting as many as 1 in 400 people
bronchoalveolar lavage fluid of RAO-affected horses, con- in some societies (Mestecky et al 2003). However, this
sistent with a type-1 hypersensitivity, the immediate condition is not reported in the horse. Certainly IgA
onset of airway obstruction typical of a type-1 reaction deficiency occurs in horses but to date it has only been
to allergen exposure is not observed. In addition, intra- reported in combination with other immunoglobulin class
dermal tests with various allergen extracts correlate poorly and cellular deficits (Freestone et al 1987, Boy et al 1992,
with the clinical diagnosis (Jose-Cunilleras et al 2001). MacLeay et al 1997, Flaminio et al 2000). Acquired equine
Results of initial studies on the type of immune response mucosal immunodeficiency, which may result from
associated with RAO have been inconsistent. A number of immunosuppression caused by leukoproliferative diseases,
studies have found cytokine profiles consistent with can result in bacterial or fungal respiratory tract disease
T-helper 2 responses (Lavoie et al 2001, Beadle et al 2002, (McClure 2000). Exercise may also cause changes in
Cordeau et al 2004), while another study found T-helper 1 equine immune responses, and may result in an increased
responses were more characteristic of at least chronic susceptibility to influenza virus infection (Folsom et al
RAO (Ainsworth et al 2003). A full understanding of 2001). In elite human athletes, both transient and chronic
the immunological basis of equine chronic airway dis- respiratory mucosal immunodeficiency is described after
eases requires more investigation, and our lack of under- exercise (Gleeson & Pyne 2000).
standing of this critically important disease complicates The impact of cellular immunodeficiency on respiratory
therapeutic decisions. tract immunity is best understood by considering foals
affected by severe combined immunodeficiency (SCID;
Immunodeficiency McClure et al 1993). Passive transfer of antibodies can
protect these foals from common bacterial infections, but
Foals are born essentially with no IgA, although IgA is does not prevent the development of bronchopneumonia,
passively transferred in colostrum (Wilson et al 2001), and which is often caused by adenovirus which affects two-
antigen-specific IgA can subsequently be found in nasal thirds of all SCID foals (Perryman et al 1978). Other
secretions (Galan et al 1986). Onset of endogenous common pulmonary pathogens are Pneumocystis carinii
production of foal IgA appears to occur in the first weeks and R. equi. This respiratory adenoviral infection fre-
of life, and IgA is one of the earliest immunoglobulins to quently extends to the gastrointestinal and urogenital
be synthesized by foals, although adult levels are not systems, and causes pancreatic disease leading to loss of
achieved for several months (Holznagel et al 2003). In endocrine and exocrine tissue and possibly contributing
terms of cellular responses, there is evidence that alveolar to the impaired growth and weight loss observed in
macrophages recovered from bronchoalveolar lavages may SCID foals (Perryman 2000).
be low in number up to 2 weeks of age and have impaired
chemotactic function (Liu et al 1987). However, other
components of the foal immune system are in place at
Concluding Remarks
birth, even if these responses remain immature and The respiratory tract of the horse is superbly adapted
antigen-naive. to athletic function, and is specialized for stressful
It has been postulated that foals are susceptible to an physiological conditions and for the maximal possible
age-related immunodeficiency that leads to common exchange of respiratory gases. The performance extremes
respiratory infections (Prescott 1993). Several studies have of which the horse is capable also maximize the challenges
reported an increased susceptibility to bacterial respira- to the respiratory immune system, and any perturbation
tory tract infection during the first 2–5 months of life of respiratory function is immediately manifest as
(Hoffman et al 1993), and the occurrence of R. equi pneu- decreased performance. It is perhaps remarkable that
the equine immune system performs so well under Freestone JF, Hietala S, Moulton J et al 1987 Acquired immu-
these exacting challenges. Nevertheless, in the case of nodeficiency in a seven-year-old horse. Journal of the
many disease conditions, such as RAO, or viral infections American Veterinary Medical Association 190: 689–691
Galan JE, Timoney JF, Lengeman FW 1986 Passive transfer of
such as EHV-1, our understanding of respiratory immunity mucosal antibody to Streptococcus equi in the foal.
remains rudimentary, and the potential for further Infection and Immunity 54: 202–206
refinements of our therapeutic and prophylactic treatments Giguere S, Prescott JF 2000 Equine immunity to bacteria.
is considerable. Veterinary Clinics of North America; Equine Practice
16: 29–47
Giguere S, Wilkie BN, Prescott JF 1999 Modulation of cytokine
REFERENCES response of pneumonic foals by virulent Rhodococcus equi.
Infection and Immunity 67: 5041–5047
Ainsworth DM, Grunig G, Matychak MB et al 2003 Recurrent Gleeson M, Pyne DB 2000 Special feature for the Olympics:
airway obstruction (RAO) in horses is characterized effects of exercise on the immune system: exercise effects
by IFN-gamma and IL-8 production in bronchoalveolar on mucosal immunity. Immunology and Cell Biology
lavage cells. Veterinary Immunology and Immuno- 78: 536–544
pathology 96: 83–91 Hannant D, Mumford JA, Jessett DM 1988 Duration of
Allen GP, Kydd JH, Slater JD et al 1999 Advances in circulating antibody and immunity following infec-
understanding of the pathogenesis, epidemiology, tion with equine influenza virus. Veterinary Record
and immunological control of equid herpesvirus 122: 125–128
abortion. In: Wernery U, Wade JF, Mumford JA, Kaaden Hannant D, Jessett DM, O’Neill T et al 1989 Antibody isotype
O-R (editors) Equine Infectious Diseases VIII. Proceed- responses in the serum and respiratory tract to primary
ings of the Eighth International Conference, Dubai and secondary infections with equine influenza virus
23–26 March 1998. R & W Publications, Newmarket, (H3N8). Veterinary Microbiology 19: 293–303
pp.129–146 Hannant D, Easeman R, Mumford JA 1999 Equine mucosal
Beadle RE, Horohov DW, Gaunt SD 2002 Interleukin-4 and immune system: intranasal vaccination with inacti-
interferon-gamma gene expression in summer pasture- vated equine influenza virus protects from infection, In:
associated obstructive pulmonary disease affected horses. Wernery U, Wade JF, Mumford JA, Kaaden O-R. (editors)
Equine Veterinary Journal 34: 389–394 Equine Infectious Diseases VIII. Proceedings of the Eighth
Bender BS, Small PAJ 1992 Influenza: pathogenesis and host International Conference, Dubai 23–26 March 1998.
defense. Seminars in Respiratory Infection 7: 38–45 R & W Publications, Newmarket, pp.50–56
Blunden AS, Gower SM 1999 A histological and immuno- Hines SA, Stone DM, Hines MT et al 2003 Clearance of
histochemical study of the humoral immune system of virulent but not avirulent Rhodococcus equi from the
the lungs in young Thoroughbred horses. Journal of lungs of adult horses is associated with intracytoplasmic
Comparative Pathology 120: 347–356 gamma interferon production by CD4+ and CD8+
Boy MG, Zhang C, Antczak DF et al 1992 Unusual selective T lymphocytes. Clinical and Diagnostic Laboratory
immunoglobulin deficiency in an arabian foal. Journal of Immunology 10: 208–215
Veterinary Internal Medicine 6: 201–205 Hoffman AM, Viel L, Prescott JF 1993 Microbiologic changes
Breathnach CC, Yeargan MR, Sheoran AS et al 2001 The during antimicrobial treatment and rate of relapse of
mucosal humoral immune response of the horse to infec- distal respiratory tract infections in foals. American
tive challenge and vaccination with equine herpesvirus-1 Journal of Veterinary Research 54: 1608–1614
antigens. Equine Veterinary Journal 33: 651–657 Holcombe SJ 2000 Stabling, airway inflammation, and
Breathnach CC, Yeargan MR, Timoney JF et al 2006 Detection dorsal displacement of the soft palate in young horses.
of equine herpesvirus-specific effector and memory In: Proceedings of the 46th annual convention of
cytotoxic immunity in the equine upper respiratory the American Association of Equine Practitioners,
tract. Veterinary Immunology and Immunopathology San Antonio, TX, pp.254–255
(in press) Holcombe SJ, Derksen FJ, Stick JA et al 1999 Pathophysiology
Cordeau ME, Joubert P, Dewachi O et al 2004 IL-4, IL-5 of dorsal displacement of the soft palate in horses. Equine
and IFN-g mRNA expression in pulmonary lymphocytes Veterinary Journal Supplement 30: 45–48
in equine heaves. Veterinary Immunology and Immuno- Holznagel DL, Hussey S, Mihalyi J et al 2003 Onset of
pathology 97: 87–96 immunoglobulin production in foals. Equine Veterinary
Dixon PM, McGorum BC 1997 Clinical immunology of the Journal 35: 620–622
equine respiratory tract. In: Rantanen NW, Hauser ML Jose-Cunilleras E, Kohn CW, Hillier A et al 2001 Intradermal
(editors) Dubai International Equine Symposium: The testing in healthy horses and horses with chronic
Diagnosis and Treatment of Respiratory Disease. obstructive pulmonary disease, recurrent urticaria, or
Matthew R. Rantanen Design, San Diego, pp.69–87 allergic dermatitis. Journal of the American Veterinary
Flaminio MJ, LaCombe V, Kohn CW et al 2000 Common variable Medical Association 219: 1115–1121
immunodeficiency in a horse. Journal of the American Klei TR 2000 Equine immunity to parasites. Veterinary Clinics
Veterinary Medical Association 221: 1296–1302 of North America; Equine Practice 16: 69–78
Folsom RW, Littlefield-Chabaud MA, French DD et al 2001 Kumar P, Timoney JF, Sheoran AS 2001 M cells and associated
Exercise alters the immune response to equine influenza lymphoid tissue of the equine nasopharyngeal tonsil.
virus and increases susceptibility to infection. Equine Equine Veterinary Journal 33: 224–230
Veterinary Journal 33: 664–669 Lavoie JP, Maghni K, Desnoyers M et al 2001 Neutrophilic air-
Foss DL, Murtaugh MP 1999 Role of macrophage cytokines in way inflammation in horses with heaves is characterized
mucosal adjuvanticity. Advances in Veterinary Medicine: by a Th2-type cytokine profile. American Journal of
Veterinary Vaccines and Diagnostics 41: 83–104 Respiratory and Critical Care Medicine 164: 1410–1413
Liu IKM, Walsh EM, Bernoco M et al 1987 Bronchoalveolar precursor frequencies in ponies. Veterinary Immunology
lavage in the newborn foal. Journal of Reproduction and and Immunopathology 70: 43–54
Fertility Supplement 35: 587–592 Pascoe JR 1996 Pharyngitis. In: Smith BP (editor) Large
Lunn DP, Townsend HGG 2000 Equine vaccination. Veterinary Animal Internal Medicine. Mosby, St. Louis, pp.607–609
Clinics of North America; Equine Practice 16: 199–226 Perryman LE 2000 Primary immunodeficiencies of horses.
Lunn DP, Horohov DW 2003 Immunology. In: Reed S, Veterinary Clinics of North America; Equine Practice
Bayly W, Sellon DC (editors) Equine Internal Medicine. 16: 105–116
WB Saunders, Philadelphia, pp.1–58 Perryman LE, McGuire TC, Crawford TB 1978 Maintenance of
Lunn DP, Holmes MA, Antczak DF et al 1998 Report of the foals with combined immunodeficiency: causes and
Second Equine Leucocyte Antigen Workshop, Squaw control of secondary infections. American Journal of
Valley, CA, July 1995. Veterinary Immunology and Veterinary Research 39: 1043–1047
Immunopathology 62: 101–143 Pilette C, Ouadrhiri Y, Godding V et al 2001 Lung mucosal
Lunn DP, Hussey S, Sebring R et al 2001 Safety, efficacy, and immunity: immunoglobulin-A revisited. European
immunogenicity of a modified-live equine influenza virus Respiratory Journal 18: 571–588
vaccine in horses after induction of exercise-induced Prescott JF 1993 Immunodeficiency and serious pneumonia
immunosuppression. Journal of American Veterinary in foals: the plot thickens. Equine Veterinary Journal
Medical Association 218: 900–906 25: 88–89
MacLeay JM, Ames TR, Hayden DW et al 1997 Acquired Prescott JF, Nicholson VM, Patterson MC et al 1997 Use
B lymphocyte deficiency and chronic enterocolitis in a of Rhodococcus equi virulence-associated protein for
3-year-old quarter horse. Veterinary Immunology and immunization of foals against R. equi pneumonia.
Immunopathology 57: 49–57 American Journal of Veterinary Research 58: 356–359
Mair TS, Batten EH, Stokes CR et al 1987 The histological Renegar KB, Small PAJ 1991 Immunoglobulin A mediation of
features of the immune system of the equine respiratory murine nasal anti-influenza virus immunity. Journal of
tract. Journal of Comparative Pathology 97: 575–586 Virology 65: 2146–2148
Mair TS, Batten EH, Stokes CR et al 1988a The distribution of Richardson MA 1999 Sore throat, tonsillitis, and adenoiditis.
mucosal lymphoid nodules in the equine respiratory Medical Clinics of North America 83: 75–83
tract. Journal of Comparative Pathology 99: 159–168 Robinson NE 2001 International Workshop on Equine
Mair TS, Stokes CR, Bourne FJ 1988b Immunohistochemical Chronic Airway Disease. Michigan State University
study of the local humoral immune system of the equine 16–18 June 2000. Equine Veterinary Journal 33: 5–19
respiratory mucosa. Research in Veterinary Science Sheoran AS, Sponseller BT, Holmes MA et al 1997 Serum
45: 160–165 and mucosal antibody isotype responses to M-like
Marti E, Horohov DW, Antczak DF et al 2003 Advances in protein (SeM) of Streptococcus equi in convalescent
equine immunology: Havemeyer workshop reports from and vaccinated horses. Veterinary Immunology and
Santa Fe, New Mexico, and Hortobagy, Hungary. Veteri- Immunopathology 59: 239–251
nary Immunology and Immunopathology 91: 233–243 Sheoran AS, Timoney JF, Tinge SA et al 2001 Intranasal
Mazanec MB, Kaetzel CS, Lamm ME et al 1992 Intracellular immunogenicity of a Delta cya Delta crp-pabA mutant of
neutralization of virus by immunoglobulin A antibodies. Salmonella enterica serotype typhimurium for the horse.
Proceedings of the National Academy of Sciences, USA Vaccine 19: 3787–3795
89: 6901–6905 Slater J, Hannant D 2000 Equine immunity to viruses. Veterinary
Mazanec MB, Nedrud JG, Kaetzel CS et al 1993 A three-tiered Clinics of North America; Equine Practice 16: 49–68
view of the role of IgA in mucosal defense. Immunology Soboll G, Horohov DW, Aldridge BM et al 2003a Regional
Today 14: 430–435 antibody and cellular immune responses to equine
McClure JT 2000 Leukoproliferative disorders in horses. influenza virus infection, and particle mediated DNA
Veterinary Clinics of North America; Equine Practice vaccination. Veterinary Immunology and Immuno-
16: 165–182 pathology 94: 47–62
McClure JT, Lunn DP, McGuirk SM 1993 Combined immu- Soboll G, Nelson KM, Leuthner ES et al 2003b Mucosal
nodeficiency in 3 foals. Equine Veterinary Education co-administration of cholera toxin and influenza virus
5: 14–18 hemagglutinin DNA in ponies generates a local IgA
Mestecky J, Blumberg RS, Kiyona H et al 2003 The mucosal response. Vaccine 21: 3081–3092
immune system. In: Paul WE (editor) Fundamental Townsend HG, Penner SJ, Watts TC et al 2001 Efficacy of a
Immunology. Lippincott-Raven, Philadelphia, pp.965–1020 cold-adapted, intranasal, equine influenza vaccine: chal-
Nally JE, Artiushin S, Sheoran AS et al 2000 Induction of lenge trials. Equine Veterinary Journal 33: 637–643
mucosal and systemic antibody specific for SeMF3 of Wagner B 2006 Immunoglobulins and immunoglobulin genes
Streptococcus equi by intranasal vaccination using a of the horse. Developmental and Comparative Immunology
sucrose acetate isobutyrate based delivery system. 30: 155–164
Vaccine 19: 492–497 Wagner B, Overesch G, Sheoran AS et al 1998 Organization of
Nelson KM, Schram BR, McGregor MW et al 1998 Local and the equine immunoglobulin heavy chain constant region
systemic isotype-specific antibody responses to equine genes. III. Alignment of c mu, c gamma, c epsilon and
influenza virus infection versus conventional vaccination. c alpha genes. Immunobiology 199: 105–118
Vaccine 16: 1306–1313 Weiner HL 1997 Oral tolerance: immune mechanisms and
Neutra MR, Pringault E, Kraehenbuhl JP 1996 Antigen treatment of autoimmune diseases. Immunology Today
sampling across epithelial barriers and induction 18: 335–343
of mucosal immune responses. Annual Review of Wilson WD, Mihalyi JE, Hussey S et al 2001 Passive transfer
Immunology 14: 275–300 of maternal immunoglobulin isotype antibodies against
O’Neill T, Kydd JH, Allen GP et al 1999 Determination of equid tetanus and influenza and their effect on the response of
herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte foals to vaccination. Equine Veterinary Journal 33: 644–650
Pharmacology and Therapeutics
of Pulmonary Medications
7 Bonnie R Rush and Elizabeth G Davis
A wide range of therapeutic preparations is routinely used added to augment penicillin’s predominantly Gram-positive
successfully in clinical practice for treatment of pulmonary spectrum. Gentamicin and enrofloxacin are rarely indicated
diseases in horses. This is because the lower respiratory as the only antibiotic therapy given the limited Gram-
tract is readily accessible for diagnostic testing and positive spectrum, and the regularity of Gram-positive
relatively easy to manipulate pharmacologically. In addi- bacterial isolates obtained from horses with pneumonia.
tion, most veterinary clinicians have a good understanding Trimethoprim–sulfonamide (15 mg/kg, PO, q 12 h) has
of the pathophysiology of equine pulmonary diseases, and the advantages of ease of administration, Gram-positive
are able to make an accurate diagnosis in cases of clinical and Gram-negative spectrum for common opportunistic
respiratory disease. This chapter discusses the pharma- pathogens, and inexpensive cost. Ceftiofur [5 mg/kg,
cological agents most commonly used in horses including intramuscularly (IM), q 12 h] has an appropriate anti-
antimicrobials, immunostimulants, anti-inflammatory microbial spectrum for common opportunistic pathogens,
agents, and bronchodilators. and is often successful as the only therapy for uncom-
plicated pneumonia. Antimicrobial therapy for mixed
infections or extensive pulmonary compromise may require
Antimicrobial Therapy more sophisticated antimicrobial therapy, as directed by
The most common organisms associated with pneumonia in vitro sensitivity testing.
in horses are opportunistic bacteria originating from the Polymicrobial and mixed anaerobic–aerobic infections
resident microflora of the upper respiratory tract. These are common in horses with pleuropneumonia (Chaffin &
bacteria are not capable of primary invasion and require Carter 1993, Racklyeft & Love 2000). Of horses with
diminished pulmonary defense mechanisms to establish pleuropneumonia, 50–90% have more than one organism
infection. Streptococcus equi var. zooepidemicus is the most isolated from transtracheal aspirates (Sweeney et al 1991).
common opportunistic pathogen of the equine lung, Aerobic bacteria are isolated from more than 90% of
although Actinobacillus equuli, Bordetella bronchiseptica, the cases of pleuropneumonia, and the most common
Escherichia coli, Pasteurella spp., and Pseudomonas aeruginosa organisms are Strep. zooepidemicus, E. coli, Actinobacillus
are frequently isolated. Strep. equi var. equi, the causative spp., Klebsiella spp., Enterobacter spp., Staphylococcus aureus,
agent of strangles, is a primary bacterial pathogen of the and Pasteurella spp. Anaerobic bacteria are isolated
upper respiratory tract, and is capable of mucosal invasion from 40–70% of horses with pleuropneumonia, and
without predisposing factors. Rhodococcus equi is a primary Bacteroides spp., Clostridium spp., Peptostreptococcus spp.,
pathogen of the lower respiratory tract of foals less than and Fusobacterium spp., are the most commonly isolated
5 months of age, which produces pulmonary consolidation anaerobic bacteria. Although fetid breath and malodorous
and abscessation. Rhodococcus equi pneumonia is not found pleural fluid are reliable indicators of the presence of an
in adult horses with a functional immune system. anaerobic infection, the absence of odor does not preclude
Bacterial culture and sensitivity of transtracheal an anaerobic pulmonary infection. The etiology of pleural
aspirate samples directs appropriate antimicrobial therapy infection in horses is usually bacterial, although fungal,
in bacterial pneumonia. However, pending results of in Mycoplasma felis, and nocardial agents have been isolated
vitro testing, antimicrobial therapy is based on severity of from pleural effusion (Chaffin & Carter 1993).
clinical signs, knowledge of common pathogens, and Medical therapy for bacterial pneumonia and pleuro-
results of Gram stain of tracheal secretions (Chaffin & pneumonia requires broad-spectrum antimicrobial therapy,
Carter 1993). Because streptococci are the most common anti-inflammatory drugs, and supportive care (Chaffin et al
isolates, penicillin (22,000 IU/kg) is often a component 1994). The combination of penicillin, gentamicin, and
of treatment for uncomplicated, Gram-positive bacterial metronidazole is often used for initial therapy in horses
pneumonia. If a polymicrobial infection is suspected, with pleuropneumonia. Streptococcus zooepidemicus isolates
gentamicin sulfate (6.6 mg/kg, q 24 h) or enrofloxacin are usually sensitive to β-lactam drugs such as penicillin or
[7.5 mg/kg, intravenous (IV) or orally (PO), q 24 h] can be sodium ampicillin, and an aminoglycoside drug such as
83
84 7 Pharmacology and Therapeutics of Pulmonary Medications
gentamicin sulfate provides Gram-negative spectrum human patients. Azithromycin is administered orally
for organisms such as E. coli, Actinobacillus spp., and (10 mg/kg) once daily until clinical signs stabilize, followed
Pasteurella spp.. Although penicillin is effective against by every other day administration until resolution of
many anaerobic bacterial infections, Bacteroides spp. are disease. The principal advantage of azithromycin–rifampin
penicillin resistant as a result of β-lactamase production. over erythromycin–rifampin is the convenience of once-
Therefore, metronidazole (15 mg/kg, PO, q 8 h) is adminis- per-day dosing.
tered initially to provide more complete anaerobic bacterial Clarithromycin is an alternative macrolide with the most
coverage until the results of anaerobic culture are negative favorable minimum inhibitory concentration against
and clinical signs of anaerobic infection (gas echoes, putrid R. equi isolates obtained from pneumonic foals (90% of
breath) have resolved. The antimicrobial regimen may isolates are inhibited at 0.12, 0.25, and 1.0 μg/ml;
require adjustment based on the results of bacterial culture clarithromycin, erythromycin, and azithromycin respec-
and sensitivity. Alternative antimicrobial agents for tively) (Jacks et al 2003). In foals with R. equi pneumonia,
successful treatment of pleuropneumonia include enro- the combination of clarithromycin (7.5 mg/kg, PO,
floxacin, ceftiofur, amikacin, trimethoprim–sulfadiazine, q 12 h) and rifampin is superior to erythromycin–rifampin
doxycycline, chloramphenicol, and rifampin. Intravenous and azithromycin–rifampin, particularly in foals with
antibiotics are preferable in the initial stages of treat- severe disease (Giguere et al 2004). Foals treated
ment (14–28 days) to ensure adequate drug concen- with clarithromycin–rifampin have improved short-term
trations. Oral antimicrobial therapy can be instituted as and long-term survival rates and fewer febrile days
the horse becomes more stable and production of pleural than foals treated with erythromycin–rifampin and
fluid subsides. azithromycin–rifampin. Reported adverse effects of
clarithromycin–rifampin have been limited to diarrhea in a
Rhodococcus equi small number of treated foals.
The survival rate of R. equi pneumonia is approximately
Rhodococcus equi is a Gram-positive, facultative intracellular 70–90% with appropriate therapy. The case fatality rate
pathogen that is one of the most important causes of without therapy (or with inappropriate antimicrobial
pneumonia in foals between 5 weeks and 4 months of age. therapy) is approximately 80%. Cases with dyspnea and
Routine evaluation of R. equi isolates to identify suscepti- severe pulmonary lesions visible on thoracic radiographs
bility to antimicrobial agents is misleading. In vitro, R. equi carry a poor prognosis; treatment success with this group
appears sensitive to a wide variety of antimicrobial agents. of foals has improved with the use of clarithromycin.
However, the organism exists intracellularly and within Parameters for successful cessation of therapy include reso-
granulomatous masses in the patient; therefore, most lution of clinical signs, normalization of fibrinogen concen-
antimicrobial agents are ineffective in vivo. The combina- tration, and radiographic or ultrasonographic evidence of
tion of erythromycin (25 mg/kg, q 6 h, PO; esters or salts) resolution of pulmonary consolidation and abscessation.
and rifampin (5–10 mg/kg, PO, q 12 h) has historically Life-threatening, antibiotic-induced enterocolitis, as a
been the treatment of choice for R. equi infections in foals. result of Clostridium difficile, has been reported in the dams
These antimicrobials may be bacteriostatic but their of nursing foals treated with erythromycin (Baverud
activity is synergistic, and the combination has markedly 1998). The authors have observed peracute colitis in
improved survival of foals with R. equi pneumonia. The hospital-housed mares with foals receiving azithromycin
duration of antimicrobial therapy using this combina- and clarithromycin. This is likely the result of the mare’s
tion of medications typically ranges from 4 to 9 weeks. coprophagic behavior that leads to ingestion of sufficient
Rifampin is lipid soluble (able to penetrate abscess active macrolide to perturb the intestinal flora. The dams of
material) and is concentrated in phagocytic cells. foals being treated for R. equi should be closely observed for
Erythromycin is concentrated in granulocytes and alveolar signs of fever, toxemia, anorexia, depression, and diarrhea
macrophages; however, its antimicrobial activity is some- during the treatment period.
what inhibited by intracellular pH. Adverse reactions are
relatively common in foals treated with the erythromycin/ Bordetella bronchoseptica
rifampin combination (Stratton-Phelps et al 2000). Diar-
rhea, idiosyncratic hyperthermia, tachypnea, anorexia, Bordetella bronchoseptica pneumonia in foals represents a
bruxism, and salivation can occur as a consequence of unique treatment challenge. The organism appears to be
erythromycin administration, and antimicrobial resistance overlooked as a significant respiratory pathogen in foals,
of R. equi to erythromycin/rifampin has been reported. but is frequently isolated and may be associated with herd
Azithromycin is a newer generation macrolide with outbreaks of pneumonia. B. bronchoseptica is a potent
greater bioavailability than erythromycin, and achieves β-lactamase producer that may result in bacterial
higher drug concentrations in phagocytic cells and tissues. overgrowth as a result of the death of competing,
Azithromycin produces fewer gastrointestinal side effects in penicillin-susceptible organisms. Foals with Bordetella spp.
7 Pharmacology and Therapeutics of Pulmonary Medications 85
pneumonia may show an initially favorable response cost prohibitive for many horses. Recommended dosage
to administration of a β-lactam antibiotic, followed by regimens include the following schedule: 0.3, 0.45, and
deterioration in clinical status because of B. bronchoseptica 0.6 mg/kg on days 1, 2, and 3 respectively, followed by
overgrowth. In addition, because the organism lives every other day administration of 0.6 mg/kg until a
anchored to the epithelial surface of the airway, many foals cumulative dose of 6.75 mg/kg amphotericin B has
with B. bronchoseptica pneumonia require prolonged been administered. Amphotericin B is mixed in 1 liter of
antimicrobial administration for complete resolution of 5% dextrose and administered over 1 h via an intra-
disease as a result of extensive epithelial injury by venous catheter. Side effects include polyuria/polydipsia
bacterial toxins and inaccessibility of the respiratory (fourth week of treatment), intermittent fever (first
epithelium by antimicrobial agents. Aminoglycosides 2 weeks), and lethargy (after every treatment). Urinalysis
(gentamicin and amikacin) are the antibiotics of choice and serum biochemical profile should be obtained weekly
for treatment of B. bronchoseptica; however, erythromycin to detect evidence of renal or hepatic dysfunction.
and tetracycline may also be effective. Administration of Ketoconazole (30 mg/kg, intragastric, q 12 h) and oral
gentamicin via nebulization provides direct delivery of iodides (20 g/450 kg, q 24 h) are less expensive, but in
antibiotic to the respiratory epithelial surface, improving general, are less likely to resolve fungal pneumonia.
accessibility of the drug to the organism (McKenzie & Successful treatment has been described with ketoconazole
Murray 2000, 2004). initially, followed by aerosolized enilconazole (1.2 mg/kg in
saline via ultrasonic nebulization, q 12 h) for long-term
treatment in a horse with Scopulariopsis spp. pneumonia.
Pneumocystis carinii The horse responded favorably to ketoconazole therapy,
and the follow-up treatment with aerosolized enilconazole
Pneumocystis carinii is a ubiquitous, unicellular eukaryote
was an effective, economic, and safe alternative therapy
that causes opportunistic pneumonia in foals between
(Nappert et al 1996). Itraconazole may be an appropriate
6 and 12 weeks of age. Pneumocystis pneumonia is a
antifungal therapy for horses, based on the sensitivity
rarely recognized respiratory disorder, and has been
pattern of pulmonary isolates. However, bioavailability
associated with combined immunodeficiency syndrome,
appears to be poor in the tablet form; the liquid formula-
corticosteroid administration, CD4+ lymphopenia, and
tion may be sufficient to provide therapeutic efficacy.
R. equi infection. Treatment of pneumocystis pneu-
Alternatively, the oral bioavailability of fluconazole (load-
monia with trimethoprim–sulfamethoxazole (25 mg/kg,
ing dose 14 mg/kg PO, followed by 5 mg/kg PO) is sufficient
PO, q 12 h) has had variable success in foals. In some
to maintain the plasma concentrations above the mean
instances of treatment failure, the disease may have
inhibitory concentration reported for fungal pathogens in
been too advanced to respond to appropriate antimicro-
horses (Latimer et al 2001). Although fluconazole is well
bial therapy or death may have resulted from a concur-
absorbed in horses, it is ineffective against many classes of
rent infection (i.e. R. equi). Human patients are treated
fungal agents, including aspergillosis, that may result in
with potentiated sulfa antimicrobials or pentamidine
fungal pulmonary disease. A second-generation triazole
isethionate, an antiparasitic drug. Pentamidine is admin-
agent, voriconazole, is superior to amphotericin B for treat-
istered intravenously for active cases and via inhalation
ing invasive aspergillosis in humans. Recent data have
as prophylaxis for at-risk HIV patients (CD4+ cells
demonstrated that voriconazole is well absorbed in horses
<200 cells/μl). Dapsone (3 mg/kg, PO, q 24 h), a sulfone
and should be considered as a therapeutic agent for the
antimicrobial, also provides effective prophylaxis for
effective management of equine patients suffering from
at-risk patients, and may be useful as an adjunctive
fungal pulmonary disease (Clode et al 2006).
treatment to traditional administration of trimethoprim–
sulfamethoxazole (Clark-Price et al 2004).
Immunostimulant Preparations
Fungal pneumonia In weanlings and yearlings with opportunistic pulmonary
infections, clinical signs may fail to resolve completely
Fungal pneumonia is relatively uncommon in horses and is despite appropriate antimicrobial therapy; alternatively
typically associated with large colon disease with mucosal clinical signs may consistently recur upon withdrawal
disruption and profound neutropenia (colitis, colon torsion) of antimicrobial therapy. Such horses with chronic,
(Sweeney & Habecker 1999). Successful treatment is rarely unresponsive pulmonary infections may have secondary
documented, which may reflect rare ante-mortem diag- immunosuppression or may be immunotolerant to the
nosis and/or poor response to therapy. Specific antifungal pathogen, and may benefit from immunomodulatory
therapy for the treatment of mycotic pneumonia is therapy. The indications for immunomodulatory therapy
dependent on the isolate. Amphotericin B is an appro- in horses are relatively specific, and these compounds are
priate therapeutic choice for aspergillosis, but may be not intended to treat a broad spectrum of conditions.
Immunostimulant therapy is not recommended for horses and provides prophylactic protection against lethal
with acute infection and/or clinical signs of depression, bacterial and viral challenge (Cox 1988). Stimulation
anorexia, and fever. of systemic immunity can be documented in labora-
The mechanism of action of non-specific immuno- tory animals for several days after parenteral adminis-
stimulation is induction of macrophages to produce tration; however, prolonged immunostimulant activity is
pro-inflammatory cytokines that drive a T helper type 1 not demonstrated.
(Th1)-based immune response. Immunostimulant therapy In equine medicine, P. acnes (EqStim®, Neogen Inc.) is
may not be effective in patients with acute, fulminating labeled for treatment of chronic respiratory disease and
infections because the immune response is maximally is recommended for cases that are unresponsive or
stimulated by the pathogen. Horses with primary immuno- transiently responsive to conventional antibiotic treatment
deficiency syndromes, such as severe combined immuno- (Klimczak 1988). In addition, it is recommended for
deficiency syndrome of Arabian foals, are incapable of prophylactic administration before stressful events that
responding to immunostimulant therapy. Immuno- may impair pulmonary defense mechanisms, including
stimulant therapy is indicated in horses with chronic weaning and long-distance transport. Propionibacterium
bacterial or viral respiratory infections because of acnes is labeled for intravenous administration every
immunosuppression or immunotolerance to the organism. 2–3 days for three treatments, and is recommended to be
In addition, prophylactic administration of immuno- used as an adjunct to antibiotic therapy. Clinical signs of
stimulant preparations prior to stressful events such as naturally occurring, infectious respiratory disease (cough,
weaning or long-distance transportation may decrease fever, nasal discharge) improve within 14 days of treatment
morbidity and mortality associated with acute infection. in 96% of horses treated with P. acnes compared to 35% of
The benchmark of non-specific immunomodulation is horses treated with conventional therapy (Vail et al 1990).
protection against a 50% lethal bacterial challenge in Administration of P. acnes prior to long distance transport
laboratory animals. reduces the incidence of infectious respiratory disease
Most veterinary immunostimulants are derived from during the 7-day period after shipment (Nestved 1996).
bacterial, viral or plant sources. Bacterial DNA appears Administration of P. acnes to healthy, yearling horses
to be responsible for the immunostimulatory effects of using the recommended dosage regimen increases the
bacterial extracts (Klinman et al 1996). DNA sequences number of CD4+ lymphocytes, and enhances lymphokine-
consisting of alternating unmethylated cytosine and activated killing activity and non-opsonized phagocytic
guanine (connected by phosphate) in a repetitive pattern activity (Flaminio et al 1998). Total white blood cell count,
occur in non-coding sequences of bacterial DNA and are neutrophil count and serum fibrinogen concentrations are
termed CpG oligodeoxynucleotides or CpG motifs. These not affected by P. acnes administration but lymphocyte
CpG sequences (motifs) are highly expressed in the numbers in bronchoalveolar lavage fluid decrease,
bacterial genome and are detected by the innate immune probably as a result of the migration of pulmonary
system via defense pattern recognition receptors, which lymphocytes into adjacent lymphoid tissues or the
trigger a “danger signal”, stimulating non-specific immune resolution of subclinical infection. In addition, circulating
responses. Repetitive CpG sequences induce a strong mononuclear cell gene expression of IFN-γ and natural
Th1-biased innate and acquired immune response in killer-lysin (antimicrobial peptide) is increased in healthy,
murine, bovine, and human immune cells. Purified CpG adult horses 1 week after initiation of therapy, consistent
oligodeoxynucleotides demonstrate promise as vaccine with induction of a Th1 response (Davis et al 2003).
adjuvant (Sato et al 1996), and may eventually be an The duration of increased cytokine/peptide expression is
important component of antineoplastic and atopic (hypo- 7 days or less. Fever, anorexia, and lethargy may occur
sensitization) therapies (Whitmore et al 2001). 12–24 h after administration of the first or second
injection, presumably as a result of increased interleukin-1
Propionibacterium acnes production. Therefore, administration is not recommended
immediately before an athletic event. Subsequent injections
The immunostimulant activity of non-viable Propioni- usually elicit milder reactions.
bacterium acnes (formerly known as Corynebacterium
parvum) has been recognized for more than 30 years, and Mycobacterial preparations
the first report of its use in horses was published more than
a decade ago (Evans et al 1988). The DNA sequence of Mycobacterial preparations are potent stimulators of non-
P. acnes contains repetitive CpG sequences, which may specific immunity and act as adjuvants when administered
be responsible for its immunostimulatory activity. In with antigen. The bacillus Calmette–Guérin (BCG) vaccine
laboratory animals, administration of P. acnes stimulates was developed from a strain of Mycobacterium bovis that
macrophage function, natural killer cytotoxicity, and had been attenuated through serial passage in culture. Live
cytokine production [interleukin-1, interferon-γ (IFN-γ)], BCG, whole-inactivated BCG, and mycobacterial cell wall
fractions have been used as non-specific immunostimulant viral and bacterial infections. Poxvirus-mediated immuno-
agents and vaccine adjuvants for decades. The mechanism stimulation is independent of viral replication and the
of action is macrophage activation and subsequent release immunostimulating components are located within
of interleukin-1, tumor necrosis factor, and colony- the viral envelope. In mice, intraperitoneal administra-
stimulating factors. Whole, inactivated BCG preparations tion of inactivated parapoxvirus ovis increases natural
induce tuberculin sensitivity; therefore, deproteinized killer cytotoxicity 10–16 h after treatment. In addition,
mycobacterial cell wall products (muramyl dipeptide and parapoxvirus administration stimulates macrophage
lipoarabinomannan) have been developed to prevent induc- activation and interferon production, and protects mice
tion of tuberculin positivity in treated animals. Purified against experimental lethal viral infection (Buttner et al
muramyl dipeptides are the smallest subunits of the myco- 1991, Mayr et al 1997). The commercial product has
bacterial cell wall that retain immunostimulant activity. demonstrated efficacy against viral and bacterial diseases
Mycobacterial cell wall products are used in horses in livestock and companion animal species (Buttner et al
to treat infectious respiratory disease (Equimune®) and 1991, Ziebell et al 1997).
sarcoid skin tumors (Regressin®). Purified mycobacterial In horses, inactivated parapoxvirus ovis has predomi-
cell wall extract is labeled for single-dose, intravenous nately been used for prophylaxis and treatment of viral
treatment of equine herpesvirus infection. Administration respiratory disease. The recommended dosage schedule is
of purified mycobacterial cell wall extract improves the two to four doses at 48-h intervals, and the immuno-
clinical recovery of horses with respiratory disease result- stimulant activity is suspected to occur within hours of
ing from stress, transportation, or bacterial and/or viral administration. The maximum duration of immunostimu-
infections (Cormack et al 1991). Eighty-three per cent of latory activity after parapoxvirus ovis administration
horses treated with mycobacterial cell wall extract are is 8 days. Intramuscular administration of inactivated
clinically normal within 7 days after administration of a parapoxvirus ovis reduces the severity of respiratory
single, intravenous (1.5 ml) dose, whereas only 36% of horses disease caused by equine herpesvirus-1 and -4.
receiving a placebo injection are without clinical signs. Prophylactic administration of inactivated parapoxvirus
Adverse pulmonary reactions that are suspected to ovis 4 and 6 days before weaning reduces the incidence of
be the result of multiple intravenous administrations of respiratory disease in foals (7.9%) compared to placebo-
purified mycobacterial cell wall extract include multifocal treated foals (24%) (Bottcher 1994). Administration of the
granulomatous pneumonitis, bronchiolitis, and progressive product after weaning (three doses) reduces the clinical
pulmonary fibrosis (De Diego et al 1997) accompanied by signs of viral respiratory disease in foals subjected to long
cough, fever, tachypnea, lethargy, and leukocytosis. Diffuse distance transport and commingling (natural viral
interstitial infiltration is visible radiographically and exposure) (Ziebell et al 1997). The incidence of disease in
cytological examination of bronchoalveolar lavage fluid newborn foals is reduced by administration of parapox-
reveals increased total cell counts and marked lymphocytic virus ovis immediately after birth and at 24 or 48 h of
inflammation. A marked local reaction (20–40 cm in life (Bottcher 1994). Unlike its efficacy with equine
diameter) is elicited by intradermal injection of myco- respiratory disease, intralesional administration of inacti-
bacterial cell wall extract to affected horses. A similar vated parapoxvirus ovis is no more effective for treat-
adverse pulmonary reaction (interstitial pneumonitis with ment of sarcoid skin tumors than intralesional placebo
disseminated pulmonary granulomas) occurs in approxi- (Studer et al 1997).
mately 1% of human patients after intravesical BCG Recently, Lunn et al evaluated Baypamune N™ for
therapy (Viel & Kenney 1993). prophylactic administration in horses subjected to a
transport stress, followed by natural challenge with
Parapoxvirus ovis influenza virus (Lunn 2004). Immunostimulant adminis-
tration did not notably reduce clinical or virological signs
Inactivated, purified parapoxvirus ovis (BaypamuneN™) of infection in this study; however, antibody responses
is a virus-based immunostimulant recommended for were significantly higher in treated horses. While clinical
prophylaxis, metaphylaxis, and treatment of infectious disease was not affected in this model, the results
diseases and prevention of stress-induced diseases in dogs, indicate the potential value of this immunostimulant
cats, cattle, pigs, and horses. Metaphylaxis is defined therapy for improving immune responses in immuno-
as administration at the time of pathogen exposure. suppressed horses.
Parapoxvirus ovis is the etiologic agent of contagious
ecthyma or “orf ” in sheep. The immunostimulant Interferon-␣
properties of poxvirus were first noted after routine
smallpox vaccination (Buttner et al 1991, Mayr et al Interferon-α is an endogenous immunostimulant with
1997). Some human vaccine recipients experienced antiviral, immunomodulatory, and antiproliferative activity.
spontaneous tumor regression and resolution of chronic Endogenous interferon production is induced by viral
infection, and is an early, non-specific antiviral defense antibodies to recombinant IFN-α correlates with treatment
mechanism. Interferon-α induces an antiviral state in failure in human cancer patients (Antonelli et al 1991),
target host cells by stimulating production of more than 20 and anti-IFN-α antibody has been identified in calves
enzyme systems that inhibit viral protein synthesis and following treatment with the recombinant product
degrade viral RNA. In mice, administration of IFN-α (Roney et al 1985).
stimulates peripheral T lymphocytes to produce IFN-γ
and activate the Th1 cell response, promoting natural
killer cell cytotoxicity, macrophage activation, and cyto-
Miscellaneous Immunomodulatory
kine production.
Preparations
Oral administration of IFN-α reduces pulmonary Acemannan is a water-soluble, polydispersed beta-linked
inflammation in racehorses with chronic inflammatory mannan polymer extracted from the pulp of the Aloe vera
airway disease (IAD) (Rush Moore et al 1996). Low-dose plant. It is predominantly used for antineoplastic activity,
(50–150 IU, PO, q 24 h for 5 days) natural, human IFN-α and is labeled for treatment of fibrosarcomas in dogs and
(Interferon Sciences, NJ) reduces exudate in the respi- cats. The product is administered intralesionally and intra-
ratory tract, lowers total cell counts in bronchoalveolar peritoneally, and a combination of these routes of adminis-
lavage fluid, and converts the differential cell count to a tration is recommended for treatment of fibrosarcoma.
non-inflammatory cytologic profile. Interferon-α does not Acemannan stimulates macrophage activation and
improve the clinical signs of disease or bronchoalveolar release of interferon, interleukin-1, tumor necrosis factor,
lavage cytology in horses with IAD characterized by and prostaglandin E2 (MacEwen & Helfand 1993). In addi-
eosinophilic or mast cell inflammation. The etiology of IAD tion, acemannan enhances macrophage phagocytosis,
is unknown and the mechanism of therapeutic benefit of T-lymphocyte activity, and non-specific cytotoxicity (Kahlon
IFN-α is undetermined. Low-dose, oral interferon is capable et al 1991). It is an effective adjuvant, directly inhibits
of modulating the immune system in humans; however, in vitro viral replication, and has synergistic antiviral
little to no antiviral or antiproliferative activity is observed activity in vivo with azidothymidine and aciclovir.
at this dose. Acemannan has been recommended for extralabel use
The effects of orally administered IFN-α do not require in the treatment of equine respiratory disease and sarcoid
small intestinal absorption or peripheral circulation of skin tumor (Van Kampen 1997). The combination of direct
IFN-α. Oral administration appears to activate unique antiviral activity and immunostimulant activity may be
natural defense systems originating in oropharynx- particularly beneficial in horses with respiratory disease.
associated lymphoid tissue that involves cellular commu- Serious adverse effects have been reported after intravenous
nication and amplification of the biologic response administration including hypotension, tachycardia, and
(Bocci 1991). Lymphocytes exposed to IFN-α can transfer syncope (Van Kampen 1997). Adverse effects associated
enhanced biologic effects to naive lymphocytes by a process with intravenous administration are attributed to the
that requires direct cell-to-cell contact, does not involve a large molecular weight of acemannan, because marked
soluble mediator, and does not require the continued hypotension has been observed after rapid intravenous
presence of IFN-α. Cellular transfer of the antiviral state to administration of other large molecular weight com-
naive cells permits low to undetectable concentrations of pounds. Approximately 30% of horses develop a transient
IFN-α to produce potent activity, and possibly represents a reaction after intralesional administration including
major mechanism for amplification and dissemination of tachypnea, coughing, and sweating (Van Kampen 1997).
endogenous IFN-α activity. Levamisole phosphate is a synthetic anthelmintic
Interferon administration is not beneficial in the labeled for treatment of nematode infection in cattle. In
treatment of acute, fulminant viral respiratory infection in addition to its anthelmintic effects, it is reported to restore
horses (Seahorn et al 1990). Oral administration of low- or stimulate host defenses impaired by aging, stress or
dose (0.22–2.2 IU/kg, q 24 h) recombinant IFN-α2a does immaturity of the immune system. It appears to have little
not diminish the severity of clinical disease or the duration or no effect on humoral or cell-mediated immunity
of virus shedding in horses with experimental equine in healthy animals. The effects of levamisole are more
herpesvirus-1 infection. Treatment failure in this model is apparent in immunocompromised individuals, because
attributed to the lack of antiviral activity at this dose and it stimulates depressed cell-mediated immunity and
the overwhelming nature of the viral infection. neutrophil mobility, phosphodiesterase activity, adherence,
Treatment failure in human patients can occur after and chemotaxis (Saperstein et al 1983).
prolonged administration because of the production of In humans, levamisole enhances lymphoproliferative
anti-IFN-α antibody or down-regulation of IFN-α recep- responses in postoperative patients and reduces viremia
tors. The conformational structure of recombinant IFN-α in patients with chronic hepatitis B infection (Abdalla
is more likely to induce neutralizing antibody produc- et al 1995, Krastev et al 1999). Levamisole improves cell-
tion than natural IFN. The appearance of neutralizing mediated immune responses and lymphocyte cytotoxicity
in children suffering from severe protein-calorie mal- Triamcinolone is one of the most potent systemic
nutrition and chronic respiratory infection, and is reported corticosteroid preparations. Triamcinolone acetonide
to be an effective adjunct treatment for chronic bron- (0.09 mg/kg, IM, single dose) relieves airway obstruction
chitis (Prakash et al 1998). Controlled investigation of for up to 4 weeks, however, adrenal suppression is also
the immunostimulatory effects of levamisole in healthy evident for 4 weeks following administration (LaPointe
or immunocompromised horses has not been reported. et al 1993). Repeated administration of triamcinolone
However, a favorable clinical response has been reported in has produced iatrogenic Cushingoid syndrome, adrenal
horses with heaves. insufficiency, and laminitis. Because of the risk of adverse
Extract of Echinacea angustifolia is marketed over the side effects, administration of triamcinolone for the
counter as an immunostimulant nutriceutical for humans. treatment of heaves is limited to salvage efforts.
There is some evidence that Echinacea extract is a hema- Dexamethasone improves lung function within hours of
tinic and immunostimulant in the horse after 42 days of administration and the maximal response is obtained by
oral administration (O’Neill et al 2002). day 7 (Rush et al 1998a, Robinson et al 2003, Cornelisse et
al 2004). Intravenous administration (0.1 mg/kg body
weight) produces measurable therapeutic benefit within
Anti-inflammatory Therapy for 2 h, whereas oral administration (0.164 mg/kg body
Non-infectious Pulmonary Disease weight) improves pulmonary function within 6 h.
Indications for anti-inflammatory therapy for pulmonary Following cessation of 1 week of treatment, some thera-
disease in horses include recurrent airway obstruction peutic benefit can be detected 7 days later. Administration
(RAO, heaves) and some forms of IAD. Corticosteroid of dexamethasone produces marked suppression of endog-
preparations improve pulmonary function and reduce enous cortisol production (but not adrenal responsive-
pulmonary inflammation in horses with heaves. Because ness), which persists for a few days after discontinuation
aerosolized (surface-active) corticosteroids are poorly of drug (Rush et al 1998b). A long-acting intramuscular
distributed in the lungs of horses with diffuse severe airway form of dexamethasone (dexamethasone 21-isonicotinate;
obstruction, systemic corticosteroids are indicated in horses Voren®, Boehringer-Ingelheim; 0.04 mg/kg, q 3 days)
with marked respiratory difficulty. In heaves-affected reduces airway obstruction by day 3 and maximal effect is
horses in remission or with moderate to mild clinical achieved by day 7 (Robinson et al 2002). The dosage and
signs, aerosolized corticosteroids are indicated for main- frequency of administration of potent corticosteroid prepa-
tenance therapy or as a first-line treatment. Aerosolized rations should be reduced gradually to doses sufficient to
corticosteroids are no more effective than systemic maintain disease remission.
corticosteroids but they do reduce the total therapeutic Prednisolone (0.5–1 mg/kg q 24 h PO) is widely used
dose and limit drug exposure to other tissues, which in Europe as an anti-inflammatory agent in horses affected
provides a higher level of safety. Systemic corticosteroids by heaves, summer pasture-associated obstructive pul-
have the advantages of ease of administration and monary disease (SPAOPD), IAD and eosinophilic pulmonary
inexpensive cost. In horses with IAD, corticosteroid diseases (Mair 1996, Durham 2001). It is used primarily to
administration is indicated in cases with eosinophilic and aid resolution of pulmonary inflammation, in conjunction
mast cell inflammation, identified via cytologic evaluation with managemental changes. At a dose rate of 1 mg/kg
of bronchoalveolar lavage. q 24 h it may only partially attenuate signs of airway
obstruction in horses with heaves, but adverse effects such
Systemic corticosteroids as laminitis appear to be uncommon.
Oral prednisone (1.0–2.2 mg/kg, PO, q 24 h) is fre-
The therapeutic benefit of systemic corticosteroids quently used as an anti-inflammatory agent in horses
begins within hours of administration but may not be because of its ease of administration, minimal cost, and
detected clinically for 24–72 h in heaves-affected horses perceived safety relative to laminitis. Despite widespread
(Cornelisse et al 2004). Increasing the dose of cortico- use, there are no supportive pharmacokinetic or clinical
steroid during the response period does not provide response data to support its use (Traub-Dargatz et al 1992,
additional improvement in therapeutic efficacy in human Jackson et al 2000, Peroni et al 2002, Robinson et al
asthmatics or heaves-affected horses. Rather, the addition 2002). Clinical improvement in heaves-affected horses
of a bronchodilator optimizes control of clinical signs treated with oral prednisone has not been documented
during that critical stage of treatment. The therapeutic using objective parameters (Traub-Dargatz et al 1992,
effects of steroids are not dose-dependent beyond the Robinson et al 2002). Pretreatment of heaves-susceptible
recommended dosage range; however, the magnitude horses with prednisone fails to prevent the onset of airway
of adrenal suppression and adverse effects are dose- obstruction when horses are stabled in an allergen-
dependent. For these reasons, conservative dosing regimens challenged environment, and coupling prednisone with
are recommended. environmental management provides no additional benefit
A B C
Fig. 7.1. A series of ventilation scans of the caudodorsal lung fields of central airways. After a 7-day treatment period (B), the maximal
a heaves-affected horse obtained during an episode of airway change in pleural pressure is nearly normal (12 cmH2O) and the horse
obstruction before treatment (A), after a 7-day treatment period with appears clinically normal; however, the ventilation scan demonstrates
beclomethasone 500 μg, q 12 h (B), and after a 14-day treatment persistent areas of poor ventilation. After 14 days of treatment with
period with beclomethasone 500 μg, q 12 h (C). Prior to treatment (A) beclomethasone (C), the maximal change in pleural pressure is normal
the maximal change in pleural pressure was 35 cmH2O (normal (8 cmH2O) and the ventilation scan demonstrates uniform distribution
<10 cmH2O) and the ventilation scan revealed a patchy distribution of of radionuclide.
radioaerosol in the peripheral lung with excessive deposition in the
in pulmonary function over environmental management propionate has the most favorable therapeutic index.
alone (Jackson et al 2000). The lack of efficacy of The terminal half-life of fluticasone propionate after
prednisone likely results from its poor oral bioavailability; inhalation therapy is approximately 6 h.
serum prednisolone (active metabolite) concentrations are Fluticasone (2000 μg, q 12 h, administered by means of
minimum to undetectable after administration of oral the Equine AeroMask™) is very effective in the treatment
prednisone (Peroni et al 2002). of heaves. Administration of fluticasone to horses during
an episode of airway obstruction resolves clinical signs,
Aerosolized corticosteroids reduces pulmonary neutrophilia, normalizes pulmonary
function, reduces interleukin-4 expression, and reduces
Inhaled corticosteroids are effective in horses with mild to responsiveness to histamine challenge (Viel 1999, Giguere
moderate airway obstruction with clinical signs ranging et al 2002). In normal horses, (inhaled) fluticasone propi-
from exercise intolerance to horses with moderate res- onate reduces serum cortisol concentrations by 40% after
piratory difficulty. Aerosolized drugs reduce the total 1 day of therapy and 65% after 7 days. Serum cortisol con-
therapeutic dose and allow direct delivery of the drug centrations return to pretreatment values within 1–2 days
to the lower respiratory tract, but are generally more after discontinuation of drug.
expensive. There are three aerosolized corticosteroid Beclomethasone dipropionate is the most widely dis-
preparations available in metered-dose inhaler formula- pensed aerosolized corticosteroid for treatment of non-
tion for administration to horses using aerosol delivery infectious respiratory disease in humans. In heaves-affected
devices (see below): beclomethasone dipropionate, fluti- horses, beclomethasone reduces pulmonary inflamma-
casone propionate, and flunisolide. The relative potency of tion, improves parameters of pulmonary function, and
these surface-active corticosteroids is triamcinolone = improves pulmonary ventilation imaging (Rush et al
flunisolide < beclomethasone < fluticasone. Using the 1998a; Fig. 7.1). There is no immediate therapeutic
affinity of dexamethasone as the standard (equal to 1), effect; clinical signs do not begin to improve until 24 h
the relative glucocorticoid receptor affinity of common after administration (Rush et al 2000). Horses may
corticosteroids is flunisolide 1.9, triamcinolone 2.0, appear clinically normal at rest after a 7-day treat-
beclomethasone 13.5, and fluticasone propionate 18.0 ment period with beclomethasone; however, ventila-
(Barnes et al 1998). tion scanning reveals that regions of poor pulmonary
Fluticasone propionate is an androstane, carbothioate ventilation persist beyond the resolution of clinical signs
corticosteroid, and is the most potent, most lipophilic, and and may require a 14-day treatment period (Fig. 7.1).
most expensive aerosolized corticosteroid preparation. Administration of beclomethasone (3750 μg, q 12 h) using
Fluticasone also has the longest pulmonary residence the Equine AeroMask™, improves parameters of pul-
time (lipophilicity), and is not metabolized by the lung. monary function and arterial oxygen tension for a
It is absorbed into systemic circulation and undergoes 2-week treatment period (Ammann et al 1998). Clinical
extensive first-pass hepatic metabolism (99%) to inactive signs of airway obstruction and decreased pulmonary
metabolites. As a result of this extensive first-pass metabo- function return within days after discontinuation of
lism and its low oral bioavailability (<2%), fluticasone beclomethasone. Short-term administration of inhaled
beclomethasone without minimizing environmental aller- term aerosolized corticosteroids have not been objectively
gen exposure is not expected to provide prolonged anti- investigated in horses with heaves or IAD; however, clinical
inflammatory benefit for horses with RAO. use of these drugs in this manner is widespread.
Endogenous cortisol production is suppressed by approx-
imately 35–50% of baseline values within 24 h of admin- Mast cell stabilizers (cromones)
istration of high-dose inhaled beclomethasone (>1000 μg,
q 12 h), and further reduces by 80–90% after a 7-day The mast cell-stabilizing drugs, sodium cromoglycate and
treatment period. Serum cortisol concentrations recover nedocromil sodium, have a delayed onset of action and are
within days after discontinuation of beclomethasone, indicated for the prophylaxis of airway obstruction. Their
and adrenocorticotropic hormone responsiveness is not structures are dissimilar and their mechanism of action is
affected by a 7-day treatment period (Rush et al 1998b). unclear. These drugs are not recommended for the
The threshold for adrenal suppression in normal and stabilization of clinical signs during an episode of heaves.
heaves-affected horses is approximately 500 μg of inhaled In human asthmatics, aerosolized corticosteroids pro-
beclomethasone administered twice daily (Ammann et al vide superior asthma control compared to aerosolized
1998). The clinical response to this minimally adreno- cromones, and in fact, mast cell stabilizers do not reduce
suppressive dose of beclomethasone is equivalent to the pulmonary inflammation in patients with asthma.
efficacy of doses in excess of 1000 μg twice daily (Rush Nonetheless, the addition of nedocromil sodium to high-
et al 2000). dose corticosteroid therapy improves asthma control in
Flunisolide is the least potent of the synthetic, topically selected patients (Barnes et al 1998).
active corticosteroids. The primary advantage of flunisolide Mast-cell-stabilizing agents provide some benefit as
is cost. It is the least lipophilic (shortest pulmonary residence maintenance therapy for heaves-affected horses during
time), has relatively high oral bioavailability (21%), and is periods of remission. The administration of disodium
extensively absorbed from the respiratory tract (Barnes et al cromoglycate (80 mg via nebulization) 20–30 min prior
1998). Flunisolide is similar to triamcinolone in terms of to allergen challenge delays the induction of the clinical
potency, lipophilicity, and clinical efficacy. Much higher signs of airway obstruction (Thomson & McPherson
dosages are required to achieve therapeutic effects similar 1981). Administration of 80 mg for 4 consecutive days
to fluticasone or beclomethasone, and adverse effects (adrenal (once daily) delayed the induction of airway obstruction for
suppression) occur more frequently in human patients with approximately 3 weeks. Another study demonstrated a
flunisolide. Despite its limitations, the therapeutic index minimal benefit with doses up to 500 mg daily for 2 days
of flunisolide is superior to systemically administered cor- prior to allergen exposure (Soma et al 1987). It is impor-
ticosteroids. In human patients with steroid-dependent tant to recognize that the role of mast cells in the patho-
asthma initiation of flunisolide therapy as a replacement of physiology of RAO in horses is presently unclear and, for
oral prednisone allows adrenal recovery and superior asthma that reason, cromones should not be considered an alter-
control. The safety and efficacy of aerosolized flunisolide native to corticosteroid therapy in horses with heaves.
has not been evaluated in heaves-affected horses. Mast cell stabilizers may be indicated for the treatment
Horses in apparent remission from heaves may improve of a subset of horses with IAD demonstrating evidence of
exercise tolerance and performance by being maintained metachromatic (mast cells are 2–5% of total cell count)
on low-dose, long-term, aerosolized corticosteroids. The or eosinophilic (>10% of total cell count) inflammation
systemic effects of injectable corticosteroids preclude their in bronchoalveolar lavage fluid. This form of chronic
use for long-term, daily administration for maintenance IAD may represent a local pulmonary hypersensitivity
therapy. In human asthmatics, the dose timing of low-dose reaction, and arguably may represent an early form of
maintenance therapy has a pivotal effect on the safety RAO. Nebulization of sodium cromoglycate (80–200 μg)
profile and consequently the risk/benefit ratio of inhaled will improve the clinical signs of respiratory disease
corticosteroids (Barnes et al 1998). Maximum adrenal and will stabilize mast cell histamine release in young
suppression occurs with administration of aerosolized racehorses with mast cell pulmonary inflammation
corticosteroids in the early morning hours, whereas (Hare et al 1994).
endogenous cortisol production is least disrupted by
afternoon administration. The longer the terminal elimina- Leukotriene receptor antagonists
tion half-life of the drug, the earlier in the afternoon it
should be administered. The adrenosuppressive effects Leukotriene receptor antagonists (montelukast, zafirlukast)
of flunisolide (t 1 ⁄ 2 = 1.5 h) are minimized when a single were designed to provide oral, once daily, anti-inflammatory
daily dose is administered at 19.00 (7 P.M.), whereas the therapy for the treatment of asthma. These prepara-
optimum time for administration of fluticasone (t 1 ⁄ 2 = 6 h) tions are effective for approximately 70% of human
is 16.00 (4 P.M.). The safety and efficacy of once daily, long- asthmatics, and are effective for most cats with asthma.
Montelukast (0.11 mg/kg body weight, PO, q 24 h), blockade of the M3 receptor with a muscarinic antagonist
a cysteinyl leukotriene receptor antagonist, is ineffective has the greatest effect in large, central airways.
for the treatment of heaves in horses. The lack of efficacy Atropine is the prototypic, non-selective (M1, M2, M3)
may be the result of its poor bioavailability, as the active muscarinic antagonist, derived from the Atropa belladonna
metabolite is nearly undetectable (1/28th of therapeutic plant. By blocking the M3 receptor it decreases the release
drug concentrations) after oral administration (Kolm et al of intracellular calcium from the sarcoplasmic reticulum
2003). In contrast, the leukotriene D4 receptor antagonist, and thereby causes smooth muscle relaxation. Atropine
L-708,738 (2.5 mg/kg PO, q 12 h), is bioavailable after (5–7 mg/450-kg horse, IV) provides rapid and powerful
oral dosing and sustains plasma drug concentrations bronchodilation in horses with heaves; however, the
that exceed in vitro efficacy values. However, airway abbreviated duration of action (0.5–2.0 h) and adverse
function does not improve after 14 days of administration, effects of systemic administration (ileus, central nervous
suggesting that cysteinyl leukotrienes may not be pivotal system toxicity, tachycardia, increased viscosity of mucus
mediators of airway inflammation in heaves (Lavoie secretion, impaired mucociliary clearance) limit its use to
et al 2002). a single rescue dose for horses with severe airway obstruc-
tion. Atropine is not suitable for routine administration in
horses with RAO.
Bronchodilator Therapy Ipratropium bromide is a synthetic, anticholinergic
compound that produces bronchodilation, inhibits cough
Medical treatment for horses with heaves should consist of
and protects against stimuli that cause bronchoconstric-
a combination of bronchodilators and corticosteroids.
tion. Like atropine, ipratropium bromide is a non-selective
Corticosteroids reduce pulmonary inflammation and
muscarinic antagonist. As a result of its quaternary
bronchodilators provide symptomatic relief of airway
ammonium structure, absorption of ipratropium from
obstruction. Corticosteroid therapy does not relieve clinical
the respiratory and gastrointestinal tract is negligible.
signs of airway obstruction for several hours; therefore,
Consequently, ipratropium produces minimal systemic
bronchodilator therapy is indicated to provide immediate
effects, and does not inhibit gastrointestinal motility, dry
relief of airway obstruction until clinical signs of disease
respiratory secretions, or affect mucociliary clearance.
abate. Unlike aerosolized corticosteroids, aerosolized
Ipratropium bromide can be administered to horses
bronchodilators typically remain effective regardless of the
via an ultrasonic nebulizer (2–3 μg/kg), dry powder
severity of disease. Aerosolized bronchodilator therapy is
inhaler (200 μg/100 kg or 2.4 mg/horse), or metered dose
more rapid and powerful than oral administration of
inhaler coupled to the Equine AeroMask or Equinehaler
bronchodilators, and is the preferred route of adminis-
(180–360 μg/500 kg horse) (Robinson et al 1993, Hoffman
tration for horses during crises. It is inappropriate to treat
1997, Duvivier et al 1999). The onset of bronchodilation
heaves with bronchodilators as the sole therapy; broncho-
in heaves-affected horses is approximately 15–30 min and
dilators do not reduce the underlying inflammatory process
the effect lasts approximately 4–6 h. Administration of
and tolerance develops rapidly to β2-adrenergic agents
ipratropium (and atropine) produces a more significant
(12 days) when administered as sole therapy to horses with
improvement in pulmonary resistance than in dynamic
heaves. Corticosteroid therapy prevents and/or reverts
compliance. This finding is consistent with the broncho-
tolerance to β2-adrenergic drugs by preventing down-
dilatory effect of ipratropium on larger, more central
regulation of β2 receptors and inducing formation of new
airways. Administration of ipratropium before exercise in
β2 receptors on pulmonary cells (Abraham et al 2002).
horses with RAO does not improve exercise performance,
which may reflect the bronchodilation normally associated
Anticholinergic bronchodilators with the sympathetic drive of exercise.
Oxitropium bromide and tiotropium bromide are
The parasympathetic division is the dominant portion of quaternary scopolamine-derivative anticholinergic agents
the pulmonary autonomic nervous system in all mammals. with a prolonged duration of effect (>12 h) in human
Muscarinic receptors are abundant in airway smooth patients. Oxitropium is ten times more potent than atropine
muscle and stimulation of M3 receptors results in and has minimal absorption from the respiratory and
smooth muscle contraction and bronchoconstriction. gastrointestinal tract. Tiotropium is a non-selective mus-
Vagally mediated cholinergic stimulation (M3) is the carinic antagonist; however, it dissociates slowly from M3
primary mechanism of bronchospasm in horses with receptors, which is the mechanism for the prolonged
RAO. Parasympathetic innervation can be demonstrated (12–24 h) duration of activity. Tiotropium is approximately
throughout the tracheobronchial tree of the horse, but ten-fold more potent than ipratropium. These newer
smooth muscle contraction evoked by stimulation of generation anticholinergic agents may prove attractive for
cholinergic nerves is more pronounced in the trachea than treatment of heaves if the duration of action proves similar
in the smaller bronchi; as expected, parasympathetic to that in humans.
A B
Fig. 7.2. Ventilation scan of the caudodorsal lung fields of a heaves- horse with normal (improved) distribution after administration of
affected horse. (A) The restricted distribution of aerosolized 360 μg albuterol via an Equine Aerosol Delivery Device. Reproduced
radionuclide during a crisis and (B) the same pulmonary region of this from Rush et al 1999 with permission.
␤2-Adrenergic agonists
(Derksen et al 1992, 1996, 1999, Tesarowski et al 1994,
Sympathetic innervation of the respiratory tract is sparse; Rush et al 1999). The duration of effective bronchodilation
however, non-innervated β2-adrenergic receptors are is approximately 1–3 h. Albuterol and pirbuterol improve
distributed throughout the equine pulmonary system parameters of pulmonary function by approximately 70%
associated with respiratory smooth muscle, epithelium in horses with airway obstruction. Aerosolized short-acting
and submucosal glands. The β-adrenergic agonists stimu- β2-adrenergic bronchodilators produce minimal systemic
late non-innervated β2-adrenergic receptors that are effects and are safe for use in horses. Albuterol can be
coupled to Gs proteins, activation of which increases repeatedly dosed, every 15 min for up to 2 h, to relieve
intracellular cyclic adenosine monophosphate (cAMP), severe bronchoconstriction in horses with heaves through
resulting in relaxation of bronchial smooth muscle by a sequential bronchodilation. Systemic administration of
variety of mechanisms. Non-selective β-agonists are β2-adrenergic agents requires ten times the dose to achieve
not used for bronchodilation in clinical practice because the same level of bronchodilation and is associated with
of adverse effects of β1 stimulation (tachycardia, sweating sweating, trembling, muscle tremors, and excitement.
and excitement). Most albuterol sulfate preparations contain an
equimolar, racemic mixture of (R)- and (S)-stereoisomers.
Short-acting ␤2-agonists (R)-Albuterol has both bronchodilating and broncho-
There are three basic indications for administration of protective activities (Derksen et al 1992). (S)-Albuterol does
short-acting β2-adrenergic bronchodilators for horses: not activate β2 receptors and does not modify the activation
(1) emergency therapy in horses with marked airway of β2 receptors by (R)-albuterol. (S)-Albuterol is metab-
obstruction, (2) before exercise to relieve mild to moderate olized more slowly than (R)-albuterol and is retained
airway obstruction, (3) before administration of aerosol preferentially in the airways. Until recently, (S)-albuterol
corticosteroid preparations to improve pulmonary dis- was considered biologically inert; however, it has now
tribution of these surface-active agents. Figure 7.2 is been demonstrated to intensify allergic bronchospasm
a ventilation scan of the caudodorsal lung fields of a and appears to have the potential to induce paradoxical
heaves-affected horse, demonstrating the distribution of reactions in some asthmatic patients. We have observed
aerosolized radionuclide before and after administration two heaves-affected horses that appear to bronchoconstrict
of albuterol. after administration of albuterol. In horses, (S)-albuterol
Albuterol sulfate (360–900 μg) and pirbuterol acetate does not have bronchodilatory activity but does stimulate
(600 μg) are potent, short-acting β2-adrenergic agents acetylcholine release via activation of a prejunctional
that rapidly produce bronchodilation (5 min) in horses β2 receptor (Zhang et al 1998). Levalbuterol (homochiral
(R)-albuterol) has been marketed recently and reportedly provide rapid relief from bronchoconstriction whereas the
dramatically reduces the incidence of the side effects response to ipratropium is delayed. Conversely, the relief
associated with racemic albuterol in some patients. provided by ipratropium will last longer (4–6 h) than the
short-acting bronchodilator activity of albuterol.
Long-acting ␤2-agonists Clenbuterol hydrochloride (0.8–3.2 μg/kg, PO, q 12 h;
Salmeterol xinafoate is a long-acting β2-adrenergic agent Ventipulmin®, Boehringer Ingelheim Vetmedica) is the
that is a chemical analog of albuterol. The receptor-binding systemic alternative to the aerosolized, long-acting
site of salmeterol is structurally similar to that of albuterol, β2-agonist bronchodilators for management of horses with
although salmeterol has an elongated (aliphatic) side chain mild to moderate disease. The β2 : β1 selectivity of
thought to bind to an exosite proximal to the region of the clenbuterol is similar to that of albuterol, and the oral
β2-adrenoceptor protein. Exosite binding allows salmeterol bioavailability is approximately 80–90% in humans.
to contact the β2 receptor repeatedly while the drug In addition to bronchodilator activity, clenbuterol is a
remains anchored adjacent to the receptor site, allowing for mucokinetic agent which acts through increased ciliary
an extended duration of action. In addition, salmeterol beat frequency to speed mucociliary clearance. Controlled
has higher lipophilicity, β2 affinity, β2 selectivity and investigations to document the bronchodilator response
potency (ten-fold) than albuterol. Lipophilicity may be the to clenbuterol in horses with heaves have produced
most important determinant of duration of action by inconsistent results (Traub-Dargatz et al 1992, Erichsen et
influencing the amount of drug entering the cell al 1994, Sasse 1984). The disparity in results is likely
membrane in the vicinity of the β2 receptor. The β2/β1 related to differing dosage schedules, routes of adminis-
activity ratio of salmeterol is 50,000 : 1 compared with tration, and disease severity. In general, clenbuterol
650 : 1 for albuterol; isoproterenol is the standard (1 : 1) administration produces moderate improvement in objec-
for the β receptor activity ratio. Enhanced β2 selectivity tive parameters of pulmonary function, which may be
provides a greater margin of safety by reducing the fre- difficult to appreciate or detect by clinical observation. The
quency of β1 effects (anxiety, tachycardia, and sweating) at label recommendations outline an incremental dosage
therapeutic doses. In humans, twice daily administration of schedule based on the response to therapy. In a large
salmeterol provides superior control of bronchoconstriction clinical trial using incremental dosing and subjective
compared to regular (four times daily) administration or evaluation of airway obstruction, 25% of horses responded
as-needed administration of albuterol. In addition to bron- favorably to the lowest recommended dose (0.8 μg/kg, PO,
chodilator activity, salmeterol appears to have some anti- q 24 h) (Erichsen et al 1994), whereas the remaining 75%
inflammatory properties, such as inhibition of leukotriene of horses required higher doses to obtain observable thera-
and histamine release from mast cells and the reduction of peutic benefit. Recent in vivo and in vitro studies (Laan et al
eosinophil activity. Salmeterol (210 μg via Equine AeroMask) 2004, 2005) indicate that clenbuterol was effective at
provides relief of the clinical signs of airway obstruction inhibiting pro-inflammatory cytokine production by equine
for 8–12 h in heaves-affected horses (Henrikson & Rush alveolar macrophages following exposure to lipopoly-
2001). Salmeterol has been recommended for maintenance saccharide, hay dust suspension and Aspergillus fumigatus
therapy and pre-exercise administration to horses with extract. While this anti-inflammatory effect may be of
mild to moderate airway obstruction (Hoffman 1997). clinical use when treating horses with airway diseases such
Unfortunately, production of salmeterol in a metered dose as heaves, SPAOPD and IAD, clenbuterol should only be
inhaler formulation has been discontinued; the most used in conjunction with improvements in air hygiene.
popular current formulation for salmeterol is a dry-powder The equine industry has been concerned about the
inhalant device for human asthmatics (paired with abuse potential of clenbuterol among performance horse
fluticasone), which has been difficult to adapt for inhalant populations because of the repartitioning properties (it
delivery for horses. favors formation of muscle over deposition of fat) of this
The combination of albuterol sulfate and ipratropium β2-agonist in some species. Depending on discipline and
bromide is available commercially in a metered-dose jurisdiction, identification of clenbuterol in post-event
inhaler device for humans. In human patients with chronic samples can lead to sanctions. Consequently, there has
obstructive pulmonary disease this anticholinergic/ been a great deal of interest in the pharmacokinetics,
β2-agonist combination provides more complete broncho- pharmacodynamics, and limits of detection of clenbuterol
dilation than either drug alone. Albuterol predominantly in horses. Chronic administration of clenbuterol at
relaxes small (peripheral) airway smooth muscle whereas the higher doses (2.4 μg/kg, PO, q 12 h) does demonstrate
the ipratropium has a greater effect on the relaxa- repartitioning effects in horses (Kearns et al 2001) but does
tion of larger (more central) airways. Combination anti- not enhance exercise performance. In fact, clenbuterol
cholinergic/β2-agonist therapy provides broad-spectrum administration diminishes (rather than enhances) aerobic
relief of bronchoconstriction. Short-acting β2-agonists capacity (Beekley et al 2003) and performance (Kearns &
McKeever 2002), and negatively alters cardiac function in administration of albuterol as monotherapy. Down-
horses (Sleeper et al 2002). Regardless of these negative regulation of β2 receptors has been documented in horses
findings relative to performance, detection of clenbuterol after 12 days of administration of clenbuterol (0.8 μg/kg,
remains a priority in most drug testing situations. IV, q 12 h) (Abraham et al 2002). Administration of cor-
Clenbuterol accumulates in liver, lung, heart, and kidney ticosteroids (dexamethasone 0.1 mg/kg IV) accelerates
relative to plasma concentrations, which contributes to recovery from down-regulation in horses treated with
prolonged and inconsistent elimination (Soma et al 2004). clenbuterol alone and prevents clenbuterol-induced desen-
Nonetheless, current technology is able to quantify sitization when administered concurrently. Given that
clenbuterol in plasma and urine for a prolonged period β2-agonists have little anti-inflammatory activity, it is
of time (up to 30 days) after discontinuation of drug difficult to justify their use as monotherapy for a disease
administration. Serum samples are more consistent characterized by airway inflammation.
and reliable for detection compared to urine samples.
Surprisingly, it is possible to detect clenbuterol in mane and
tail hairs for 360 days after a 10-day administration period
Aerosol Delivery Devices
(Schlupp et al 2004). Several devices have been designed for convenient
Although higher doses of clenbuterol may be required to administration of aerosolized drugs in a metered-dose
produce notable clinical effects in heaves-affected horses, inhaler (MDI) preparation to horses. The advantages of an
adverse effects may also be observed. The most common MDI system include rapid administration, consistent
adverse effects reflect β1 stimulation and include sweat- ex-valve dose delivery, minimal risk of pulmonary con-
ing, trembling, tachycardia, and excitement. Clenbuterol tamination with environmental microorganisms, ease of
should not be administered to near-term gestational mares cleaning/maintaining equipment, and no requirement
because β2 stimulation relaxes uterine smooth muscle, for electricity.
which may delay the onset of labor. In fact, intravenous The Equine AeroMask™ (Canadian Monaghan, Ontario,
clenbuterol has been used to delay parturition (primarily in Canada) is used for administration of aerosolized drugs via
cattle) and facilitate uterine repair. hand-held MDI devices or nebulization solution. This
Terbutaline was previously considered to be an accept- system allows the clinician to administer any medica-
able systemic bronchodilator in horses; however, its tion available for human asthma therapy to horses with
bioavailability is negligible in horses, and clinical efficacy heaves. The MDI is actuated into a spacer device with
has not been demonstrated (Torneke et al 2000). Amino- a one-way inspiratory valve. The mask must fit snugly
phylline and theophylline (phosphodiesterase inhibitors) around the muzzle to ensure adequate negative inspira-
are alternative systemic bronchodilators for horses with tory pressure to facilitate drug delivery. Drug delivery to
airway obstruction, although the therapeutic index is rela- the lower respiratory tract using the Equine AeroMask™
tively narrow and the magnitude of bronchodilation is with an MDI is approximately 14% of actuated drug when
less than that of the β2-agonists. The phosphodiesterase using an hydrofluoroalkane (HFA) propellant. Inhalant
inhibitors delay fatigue of the muscles of respiration, and medication is uniformly distributed throughout all pul-
may be valuable in horses with severe airway obstruction monary fields.
with impending respiratory failure due to fatigue. The Equine Haler™ (Equine Healthcare APS, Hillerod,
There is growing concern in human medicine that the Denmark) is a spacer device that fits over the entire left
overuse of the β2-agonists for asthma is associated with nare of the horse, and is designed for administration of
increased morbidity and even mortality. Regular use of aerosolized drug using any hand-held MDI device. The
β2-agonists as monotherapy is associated with deterioration mean particle size generated using the Equine Haler™ is
in asthma control, increased non-specific and allergen- 2.1 μm with a range of 1.1–4.7 μm [fluticasone/chloro-
induced airway responsiveness, increased eosinophilic fluorocarbon (CFC)-free propellant]. Drug deposition in the
pulmonary infiltration and progressive deterioration in lower respiratory tract is approximately 8% of the actuated
lung function. Poor control of asthma symptoms triggers a dose with diffuse pulmonary drug delivery that is
cycle of intensifying need for symptomatic relief and more adequately distributed to the periphery of the lung. Unlike
frequent administration of β2-agonists. The mechanism the AeroMask™, the Equine Haler™ can accommodate any
of β2 tolerance (loss of bronchodilator response) and size of horse without concerns for ensuring an airtight seal
deterioration in pulmonary function appears to be down- with the mask. Poor pulmonary drug delivery can occur if
regulation or desensitization of β2 receptors. Down- the administrator does not pay particular attention to
regulation of β2-agonists occurs via receptor phosphory- aligning the MDI with the spacer and the spacer apparatus
lation, internalization, and destruction. Failure to respond with the nasal passages of the horse during actuation.
to β2 stimulation has been documented in asthmatic Pulmonary drug delivery can be improved by closing the
human patients after 3 weeks of regular (four times daily) opposite nostril during administration.
tory stimulant activity of this plant-derived alkaloid

Miscellaneous Pulmonary
(from Lobelia inflate) has been recognized for more than
Therapeutic Agents
200 years, and has been used in Europe for more than
Expectorant therapy 100 years to aid in auscultation and assessment of upper
airway obstruction. The mechanism of hyperpnea is
Expectorant therapy is intended to increase the volume and stimulation of peripheral chemoreceptors located in the
decrease the viscosity of bronchial secretions so that they carotid and aortic bodies. The duration of respiratory
can be more easily cleared by the mucociliary system and stimulation after rapid intravenous bolus administration
by coughing. It is discussed in Chapter 5. is approximately 90–160 seconds (Marlin et al 2000).
The response is dose-dependent, highly reproducible, and
Antitussive agents without apparent adverse effects. Respiratory alkalosis
(pH 7.77) and hypocapnia (PaCO2 20 mmHg) occur tran-
Cough is an important pulmonary defense mechanism siently, followed by a period of apnea (40–55 seconds) after
assisting the clearance of secretions and debris from the hyperpnea subsides.
lower respiratory tract. Cough suppressants are indicated
for patients with persistent, fatiguing, non-productive
cough. Opiate agonists (dextromethorphan, hydroco- REFERENCES
done, butorphanol) are potent antitussive agents. The Abdalla EE, Adam IJ, Blair GE et al 1995 The immuno-
mechanism of action is direct suppression of the cough modulatory effect of levamisole is influenced the post-
reflex at the cough center of the medulla. Antitussive operative changes and type of lymphocyte stimulant.
agents are generally used for inflammatory, non-infectious Cancer Immunology Immunotherapy 41: 193–198
tracheal and pulmonary diseases and during invasive Abraham G, Brodde OE, Ungemach FR 2002 Regulation of
equine lymphocyte beta-adrenoceptors under the
diagnostic techniques such as endoscopic examination and influence of clenbuterol and dexamethasone. Equine
bronchoalveolar lavage. Opiate agonists may increase the Veterinary Journal 34: 587–593
viscosity of respiratory secretions, and produce sedation Aguilera-Tejero E, Pascoe JR, Smith BL et al 1997 The effect
and constipation. of doxapram-induced hyperventilation on respiratory
mechanics in horses. Research in Veterinary Science
62: 143–146
Respiratory stimulants Ammann V, Vrins A, Lavoie J 1998 Effects of inhaled beclo-
methasone dipropionate on respiratory function in horses
Doxapram hydrochloride (Dopram®; 0.3 mg/kg, rapid with chronic obstructive pulmonary disease (COPD).
IV bolus) is a respiratory stimulant that is indicated Equine Veterinary Journal 30: 152–157
to promote ventilation in horses with reduced central Antonelli G, Currenti M, Turriziani O et al 1991 Neutralizing
antibodies to interferon-alpha: relative frequency in
respiratory drive, such as hypoxic–ischemic encephalopathy, patients treated with different interferon preparations.
sedation, general anesthesia, and head trauma. In the Journal of Infectious Disease 163: 882–885
neonatal foal with a poor ventilatory drive (and limited Barnes P, Pedersen S, Busse W 1998 Efficacy and safety of
venous access), doxapram can be administered topically inhaled corticosteroids. American Journal of Respiratory
under the tongue. Doxapram stimulates both central and Critical Care Medicine 157: 1–53
Baverud V, Franklin A, Gunnarsson A et al 1998 Clostridium
respiratory centers and peripheral carotid chemorecep- difficile associated with acute colitis in mares when their
tors (Aguilera-Tejero et al 1997). The net response is foals are treated with erythromycin and rifampin for
chemically induced hyperventilation, characterized by an Rhodococcus equi pneumonia. Equine Veterinary Journal
increase in tidal volume and respiratory frequency within 30: 482–488
1 min of administration (Wernette et al 1986). The Beekley MD, Ideus JM, Brechue WF et al 2003 Chronic
clenbuterol administration alters myosin heavy chain
duration of hyperpnea is less than 5 min. In addition to the composition in standardbred mares. Equine Veterinary
respiratory stimulant effects, doxapram increases cardiac Journal 165: 234–239
output and blood pressure and these effects are more Bocci V 1991 Absorption of cytokines via oropharyngeal-
prolonged (120 min) (Wernette et al 1986, Sams et al associated lymphoid tissues. Clinical Pharmacokinetics
1992). Continuous or repeated dosing may allow steady- 21: 411–417
Bottcher E 1994 Clinical trials and field experience with
state conditions, prolonging the duration of clinical effects parapoxvirus-based immunostimulants in companion
(Sams et al 1992). animals. In: Immunomodulator Symposium of the
The respiratory stimulant lobeline (0.20 mg/kg, rapid World Association of Veterinary Microbiologists,
IV bolus) is used in clinical practice in Europe to markedly Immunologists and Specialists in Infectious Disease.
increase inspiratory and expiratory airflow rates as an aid Perugia, Italy 28–33
Buttner M, Czerny CP, Mayr A 1991 A role of poxvirus
during auscultation (Marlin et al 2000). In addition, structural proteins in the induction of peritoneal NK cell
lobeline is used as a research tool to facilitate investiga- activity. Natural Immunity and Cell Growth Regulation
tion of upper and lower airway function. The respira- 10: 161–166
Chaffin MK, Carter GK 1993 Equine bacterial pleuro- Giguere S, Viel L, Lee E, MacKay RJ et al 2002 Cytokine induction
pneumonia Part 1 Epidemiology, pathophysiology, and in pulmonary airways of horses with heaves and effect of
bacterial isolates. Compendium on Continuing Education therapy with inhaled fluticasone propionate. Veterinary
for the Practicing Veterinarian 15: 1642–1650 Immunology and Immunopathology 85: 147–158
Chaffin MK, Carter GK, Byars TD 1994 Equine bacterial Giguere S, Jacks S, Roberts G D et al 2004 Retrospective
pleuropneumonia Part III Treatment, sequelae, and comparison of azithromycin, clarithromycin, and erythro-
prognosis. Compendium on Continuing Education for the mycin for the treatment of foals with Rhodococcus equi
Practicing Veterinarian 16: 1585–1595 pneumonia. Journal of Veterinary Internal Medicine
Clark-Price SC, Cox JH, Bartoe JT et al 2004 Use of dapsone 18: 568–573
in the treatment of Pneumocystis carinii pneumonia in Hare J, Viel L, O’Byrne P 1994 Effect of sodium cromoglycate
a foal. Journal of the American Veterinary Medical on light racehorses with elevated metachromatic cell
Association 224: 407–410 numbers on bronchoalveolar lavage. Journal of Veterinary
Clode AB, Davis JL, Salmon J et al 2006 Evaluation of Pharmacology and Therapeutics 17: 237–242
concentration of voriconazole in aqueous humor after Henrikson SL, Rush BR 2001 Efficacy of salmeterol xinafoate
topical and oral administration in horses. Journal of the in horses with recurrent airway obstruction. American
American Journal of Veterinary Research 67: 296–301 Journal of Veterinary Research 218: 1961–1965
Cormack SS, Alkemade AJ, Rogan D 1991 Clinical study Hoffman A 1997 Inhaled medications and bronchodilator use
evaluating a purified mycobacterial cell wall extract for in the horse. Veterinary Clinics of North America; Equine
the treatment of equine respiratory disease. Equine Practice 13: 519–530
Practice 13: 18–22 Jacks S, Giguere S, Nguyen A 2003 In vitro susceptibilities of
Cornelisse CJ, Robinson NE, Berney CE et al 2004 Efficacy of Rhodococcus equi and other common equine pathogens
oral and intravenous dexamethasone in horses with to azithromycin, clarithromycin and 20 other anti-
recurrent airway obstruction. Equine Veterinary Journal microbials. Antimicrobial Agents and Chemotherapy
36: 426–430 47: 1742–1745
Cox WI 1988 Examining the immunologic and hematopoietic Jackson CA, Berney C, Jefcoat AM et al 2000 Environment and
properties of an immunostimulant. Veterinary Medicine prednisone interactions in the treatment of recurrent
6: 424–428 airway obstruction (heaves). Equine Veterinary Journal
Davis EG, Rush BR, Blecha F 2003 Increases in cytokine 32: 432–438
and antimicrobial peptide gene expression in horses Kahlon JB, Kemp MC, Yawei N 1991 In vitro evaluation of the
by immunomodulation with Propionibacterium acnes. synergistic antiviral effects of acemannan in combination
Veterinary Therapy 4: 5–11 with azidothymidine and acyclovir. Molecular Biotherapy
De Diego A, Rogado MC, Prieto M et al 1997 Disseminated 3: 314–223
pulmonary granulomas after intravesical Bacillus Kearns CF, McKeever KH, Malinowski K 2001 Chronic
Calmette–Guérin immunotherapy. Respiration 64: administration of therapeutic levels of clenbuterol acts as
304–306 a repartitioning agent. Journal of Applied Physiology
Derksen F, Olszewski M, Robinson N 1999 Aerosolized 91: 2064–2070
albuterol sulfate used as a bronchodilator in horses with Kearns CF, McKeever KH 2002 Clenbuterol diminishes aerobic
recurrent airway obstruction. American Journal of performance in horses. Medicine and Science in Sports
Veterinary Research 60: 689–693 and Exercise 34: 1976–1985
Derksen F, Olszewski M, Robinson N 1996 Use of a hand-held, Klimczak C 1988 Immunostimulant quickly aids weanling
metered-dose aerosol delivery device to administer ERDC cases. Equine Veterinary Science 12: 68–69
pirbuterol acetate to horses with heaves. Equine Klinman DM, Yi A-K, Beaucag SL et al 1996 CpG motifs
Veterinary Journal 28: 306–310 present in bacterial DNA rapidly induce lymphocytes to
Derksen F, Robinson N, Berney C 1992 Aerosol pirbuterol: secrete interleukin 6, interleukin 12, and interferon
bronchodilator activity and side effects in ponies with gamma. Immunology 93: 2879–2883
recurrent airway obstruction (heaves). Equine Veterinary Kolm G, Zappe H, Schmid R et al 2003 Efficacy of montelukast
Journal 24: 107–112 in the treatment of chronic obstructive pulmonary
Durham A 2001 Update on therapeutics for obstructive disease in five horses. Veterinary Record 152: 804–806
pulmonary diseases in horses. In Practice 23: 474–481 Krastev Z, Jelev D, Antonov K 1999 Chronic HBV infection.
Duvivier D, Bayly W, Votion D et al 1999 Effects of inhaled Immunomodulation with levamisole in viremic HBeAg
dry powder ipratropium bromide on recovery from exer- positive or anti-HBe positive patients. Hepatogastro-
cise of horses with COPD. Equine Veterinary Journal enterology 46: 3184–3188
31: 20–24 Laan TTJM, Bull S, Fink-Gemmels J 2004 Cytokine modulation
Erichsen DF, Aviad AD, Schultz RH et al 1994 Clinical by beta-2-receptor agonists. American College of Veterinary
efficacy and safety of clenbuterol HCl when admin- Internal Medicine. 22nd Annual Forum, Minneapolis,
istered to effect in horses with chronic obstructive USA June 9–12, 2004
pulmonary disease (COPD). Equine Veterinary Journal Laan TTJM, Bull S, Pirie S et al 2005 Evaluation of cytokine
26: 331–336 production by equine alveolar macrophages exposed to
Evans DJ, Rollins JB, Huff GK et al 1988 Inactivated lipopolysaccharide, Aspergillus fumigatus, and a suspension
Propionibacterium acnes as adjunct to conventional of hay dust. American Journal of Veterinary Research
therapy in the treatment of equine respiratory diseases. 66: 1584–1589
Equine Practice 10: 17–21 LaPointe JM, Lavoie JP, Vrins AA 1993 Effects of triamcinolone
Flaminio MJBF, Rush BR, Shuman W 1998 Immunologic acetonide on pulmonary function and bronchoalveolar
function in horses after non-specific immunostimulant lavage cytologic features in horses with chronic obstruc-
administration. Veterinary Immunology and Immuno- tive pulmonary disease. American Journal of Veterinary
pathology 63: 303–315 Research 54: 1310–1316
Latimer FG, Colitz CM, Campbell NB et al 2001 Pharmaco- Robinson NE, Berney C, Eberhart S et al 2003 Coughing,
kinetics of fluconazole following intravenous and oral mucus accumulation, airway obstruction, and airway
administration and body fluid concentrations of flucona- inflammation in control horses and horses affected with
zole following repeated oral dosing in horses. American recurrent airway obstruction. American Journal of
Journal of Veterinary Research 62: 1606–1611 Veterinary Research 64: 550–557
Lavoie JP, Leguillette R, Pasloske K et al 2002 Comparison of Roney CS, Rossi CR, Smith PC 1985 Effect of human leukocyte
effects of dexamethasone and the leukotriene D4 receptor A interferon on prevention of infectious bovine
antagonist L-708,738 on lung function and airway rhinotracheitis infection of cattle. American Journal of
cytologic findings in horses with recurrent airway Veterinary Research 46: 1251–1255
obstruction. American Journal of Veterinary Research Rush BR, Raub ES, Rhoads WS et al 1998a Pulmonary
63: 579–585 function in horses with recurrent airway obstruc-
Lunn DP, Rush BR 2004 Immunomodulation: Principles tion after aerosol and parenteral administration of
and Mechanisms. Proceedings of the 50th Annual Con- beclomethasone dipropionate and dexamethasone,
vention of American Association of Equine Practitioners respectively. American Journal of Veterinary Research
447–453 59: 1039–1043
MacEwen EG, Helfand SC 1993 Recent advances in the Rush BR, Worster AA, Flaminio MJ et al 1998b Alteration in
biologic therapy of cancer. Compendium on Continuing adrenocortical function in horses with recurrent airway
Education for the Practicing Veterinarian 15: 909–916 obstruction after aerosol and parenteral administration of
Mair TS 1996 Obstructive pulmonary disease in 18 horses at beclomethasone dipropionate and dexamethasone,
summer pasture. Veterinary Record 138: 89–91 respectively. American Journal of Veterinary Research
Marlin DJ, Roberts CA, Schroter RC et al 2000 Respiratory 59: 1044–1047
responses of mature horses to intravenous lobeline bolus. Rush B, Hoskinson J, Davis E et al 1999 Pulmonary dis-
Equine Veterinary Journal 32: 200–207 tribution of radioaerosol in horses with heaves after
Mayr A, Ahne W, Vilsmeier B 1997 Evaluation of in vitro and inhalation of single-dose albuterol sulfate. American
ex vivo–in vitro experiments on the efficacy of inducers Journal of Veterinary Research 60: 764–769
of nonspecific immunity prepared from poxviruses. Rush BR, Raub ES, Thomsen MM et al 2000 Pulmonary
Tierarztlich Umschau 52: 3–11 function and adrenal gland suppression with incre-
McKenzie HC 3rd, Murray MJ 2000 Concentrations of mental doses of aerosolized beclomethasone dipropio-
gentamicin in serum and bronchial lavage fluid after nate in horses with recurrent airway obstruction.
intravenous and aerosol administration of gentamicin Journal of the American Veterinary Medical Association
to horses. American Journal of Veterinary Research 217: 359–364
61: 1185–1190 Rush Moore BR, Krakowka S, Cummins JJ et al 1996
McKenzie HC 3rd, Murray MJ 2004 Concentrations of Changes in airway inflammatory cell populations in
gentamicin in serum and bronchial lavage fluid Standardbred racehorses after interferon-alpha adminis-
after once-daily aerosol administration to horses for tration. Veterinary Immunology and Immunopathology
seven days. American Journal of Veterinary Research 49: 347–358
65: 173–178 Sams RA, Detra RL, Muir WW 3rd 1992 Pharmacokinetics
Nappert G, VanDyck T, Papich M et al 1996 Successful and metabolism of intravenous doxapram in horses.
treatment of a fever associated with consistent Equine Veterinary Journal Supplement 11: 45–51
pulmonary isolation of Scopulariopsis sp. in a mare. Saperstein G, Mohanty SB, Rockemann DD et al 1983
Equine Veterinary Journal 28: 421–424 Effect of levamisole on induced bovine viral diarrhea.
Nestved A 1996 Evaluation of an immunostimulant in Journal of the American Veterinary Medical Association
preventing shipping related respiratory disease. Journal of 183: 425–426
Equine Veterinary Science 16: 78–82 Sasse HHL 1984 Ein Vergleich des Effektes nach einmaliger
O’Neill W, McKee S, Clarke AF 2002 Immunological and parenteraler Gabe von Ventipulmin oder Euphyllin auf
haematinic consequences of feeding a standardised die Lungerfunktionsprugung bei an C.O.P.D. erkrankten
Echinacea (Echinacea angustifolia) extract to healthy Pferden. Sasse Tierarztl Umshau 39: 656–662
horses. Equine Veterinary Journal 34: 222–227 Sato Y, Roman M, Tighe H et al 1996 Immunostimulatory
Peroni DL, Stanley S, Kollias-Baker C et al 2002 Prednisone DNA sequences necessary for effective intradermal gene
per os is likely to have limited efficacy in horses. Equine immunization. Science 273: 352–354
Veterinary Journal 34: 283–287 Schlupp A, Anielski P, Thieme D et al 2004 The beta-agonist
Prakash MS, Rao VM, Reddy V 1998 Effect of levamisole on clenbuterol in mane and tail hair of horses. Equine
the immune status of malnourished children. Journal of Veterinary Journal 36: 102–103
Tropical Pediatrics 44: 165–166 Seahorn TL, Carter GK, Marens JG 1990 Effects of human-
Racklyeft DJ, Love DN 2000 Bacterial infection of the lower alpha interferon on experimentally induced equine
respiratory tract in 34 horses. Australian Veterinary herpesvirus-1 infection in horses. American Journal of
Journal 78: 549–559 Veterinary Research 51: 2006–2010
Robinson N, Derksen F, Berney C et al 1993 The airway Sleeper MM, Kearns CF, McKeever KH 2002 Chronic
response of horses with recurrent airway obstruction clenbuterol administration negatively alters cardiac
(heaves) to aerosol administration of ipratropium function. Medicine and Science in Sports and Exercise
bromide. Equine Veterinary Journal 25: 299–303 34: 634–650
Robinson NE, Jackson C, Jefcoat A et al 2002 Efficacy of three Soma L, Beech J, Gerber N 1987 Effects of cromolyn in horses
corticosteroids for the treatment of heaves. Equine with chronic obstructive pulmonary disease. Veterinary
Veterinary Journal 34: 17–22 Research Communications 11: 339–344
Soma LR, Uboh CE, Guan F et al 2004 Tissue distribution and clenbuterol hydrochloride. American Journal of
of clenbuterol in the horse. Journal of Veterinary Veterinary Research 53: 1908–1916
Pharmacology and Therapeutics 27: 91–98 Vail CD, Nestved AJ, Martins JB et al 1990 Adjunct treatment
Stratton-Phelps M, Wilson WD, Gardner IA 2000 Risk of of equine respiratory disease complex (ERDC) with the
adverse effects in pneumonic foals treated with erythro- Propionibacterium acnes, immunostimulant, EqStim.
mycin versus other antibiotics: 143 cases (1986–1996). Journal of Equine Veterinary Science 10: 399–403
Journal of the American Veterinary Medical Association Van Kampen KR 1997 Immunotherapy and cytokines.
217: 68–73 Seminars in Veterinary Medicine and Surgery (Small
Studer U, Marti E, Stornetta D et al 1997 [The therapy of Animal) 12: 186–192
equine sarcoid with a non-specific immunostimulator: Viel L, Kenney D 1993 Suspected adverse pulmonary reac-
the epidemiology and spontaneous regression of sarcoids]. tions to Equimune I.V. in four horses presented to the
Schweizer Archiv fur Tierheilkunde 139: 385–391 Ontario Veterinary College. 12th Veterinary Respiratory
Sweeney CR, Habecker PL 1999 Pulmonary aspergillosis in Symposium Kennett Square, PA, USA
horses: 29 cases (1974–1997). Journal of the American Viel L 1999 Therapeutic efficacy of inhaled fluticasone
Veterinary Medical Association 214: 808–811 propionate in horses with chronic obstructive pulmonary
Sweeney CR, Holcombe SJ, Barningham SC et al 1991 Aerobic disease. Proceedings of the 45th Annual Convention
and anaerobic bacterial isolates from horses with pneu- of the American Association of Equine Practitioners
monia or pleuropneumonia and antimicrobial suscep- 306–307
tibility patterns of the aerobes. Journal of the American Wernette KM, Hubbell JA, Muir WW 3rd et al 1986 Doxa-
Veterinary Medical Association 198: 839–842 pram: cardiopulmonary effects in the horse. American
Tesarowski D, Viel L, McDonell W 1994 The rapid and effective Journal of Veterinary Research 47: 1360–1362
administration of a beta2-agonist to horses with heaves Whitmore MM, Li S, Falo L Jr et al 2001 Systemic adminis-
using a compact inhalation device and metered-dose tration of LPD prepared with CpG oligonucleotides
inhalers. Canadian Veterinary Journal 35: 170–173 inhibits the growth of established pulmonary metas-
Thomson J, McPherson E 1981 Prophylactic effects of sodium tases by stimulating innate and acquired antitumor
cromoglycate on chronic obstructive pulmonary disease immune responses. Cancer Immunology Immunotherapy
in the horse. Equine Veterinary Journal 13: 243–251 50: 503–514
Torneke MK, Ingvast-Larsson JC, Johansson JM et al 2000 Zhang X, Zhu F, Olszewski M, Robinson N 1998 Effects of
Pharmacokinetics and pharmacodynamics of terbutaline enantiomers of beta 2-agonists on ACh release and
in healthy horses. American Journal of Veterinary smooth muscle contraction in the trachea. American
Research 61: 761–765 Journal of Physiology 274: 32–38
Traub-Dargatz JL, McKinnon AO, Thrall MA et al 1992 Ziebell KL, Kretzdorn D, Auer S et al 1997 The use of
Evaluation of clinical signs of disease, bronchoalveolar Baypamun N in crowding associated with infectious
and tracheal wash analysis, and arterial blood gas ten- respiratory disease: efficacy of Baypamun N (freeze dried
sions in 13 horses with chronic obstructive pulmonary product) in 4 to 10 month old horses. Journal of
disease treated with prednisone, methyl sulfonmethane, Veterinary Medicine B 44: 529–534
Clinical Examination of the Respiratory Tract
8 Bruce C McGorum and Padraic M Dixon
The widespread availability of ancillary diagnostic aids cation of nostril paralysis should prompt a thorough
such as endoscopy and ultrasonography has undoubtedly neurological examination.
greatly improved our ability to detect and diagnose The alar fold, which attaches to the nostril and ventral
disorders of the equine respiratory tract. However, it may concha, projects laterally into the dorsal part of the nostril
have inadvertently led to an over-reliance on these tech- and divides the nostril into a dorsal and ventral passage.
niques, with many clinicians performing only a cursory The dorsal passage leads into the nasal diverticulum (false
clinical examination of the equine respiratory tract. The nostril), whilst the ventral passage leads into the nasal
aim of this chapter is to review the considerable body cavity. During dilatation of the true nostril, the lumen of
of valuable diagnostic information that can be obtained the false nostril is reduced in size. The false nostrils are
simply by performing a detailed clinical examination. about 6–8 cm deep and are lined with epithelium, most
of which contains dark, hair-covered pigmented skin.
Particles of black sebaceous secretions normally lie on their
Signalment and History surface. Epidermal cysts are readily palpated as soft, oval-
Signalment and a thorough case history provide essential shaped fluctuant swellings on the lateral aspect of the
diagnostic information, because factors such as age, environ- nasal diverticulum.
ment, diet, exercise activity, vaccination history, previous Because of the mobility of the horse’s nostrils it is
and current medications, and transportation history can be possible, unlike in other domesticated species, to readily
important risk factors for particular respiratory diseases. examine a reasonable area of nasal mucosa and septum,
the alar folds and the rostral aspect of the nasal conchae.
The nasolacrimal orifice is readily identifiable in the ventro-
Clinical Examination of the Upper lateral aspect of the nostril, at the boundary between the
Respiratory Tract pink nasal mucosa and the pigmented nostril epithelium.
Nostrils and nasal cavity The more caudal aspects of the nasal cavities can only be
visualized by endoscopy. The nasal mucosa is normally
The equine muzzle is covered with hair and is very mobile pink in color and moist. With the aid of a light source it is
and tactile. The nasal area is normally dry, except for a possible to view 5–8 cm of the rostral nasal mucosa in the
few drops of serous fluid, which consists mainly of tears. mature horse, and proportionately less in foals. Inflam-
The nares should be assessed for symmetry; asymmetry mation of the nasal mucosa will lead to mucosal edema,
indicates the presence of disorders such as wry nose, facial erythema, and variable volumes of purulent to mucopu-
paralysis, or injuries. The equine nostrils are semilunar in rulent exudate. Some lesions of the nasal mucosa are
outline during normal breathing but during deep breathing readily visible and characteristic, for example rhinitis sicca
they dilate and become circular. Horses with dyspnea will in horses with chronic grass sickness (Fig. 8.1). Marked
fully dilate their nostrils during inspiration, and in horses ulceration of the nasal mucosa is characteristic of diseases
with severe dyspnea, the nostrils may remain permanently such as epizootic lymphadenitis in horses.
dilated at rest. In contrast, horses with nostril paralysis The volume of air exhaled from the nostrils can be
may have unilateral or bilateral inability to dilate the assessed by holding the back of the hand or some teased
nostrils and consequently may have asymmetry of the cotton wool in front of the nostrils. Manually occluding
muzzle. The ability of the nostrils to dilate can be assessed both nostrils for about 30 seconds will temporarily increase
by observing the nostril movements during the breath cycle the rate and depth of breathing, making it easier to assess
and following temporary occlusion of the nares, which airflow. In the normal horse the flow of air from each
normally induces transient bilateral symmetrical nostril nostril is approximately equal. A unilateral obstruction in a
dilatation. Nostril paralysis is of major significance to the nasal cavity, such as that caused by a large sinus cyst, will
equine athlete because the horse is an obligate nasal reduce or stop the airflow from the ipsilateral nostril.
breather and also because of the great mobility of its Variations in the volume of expired air can be further
nostrils compared to most other domestic species. Identifi- assessed by occluding each nostril individually.
103
SECTION 2 : Diagnostic Techniques
104 8 Clinical Examination of the Respiratory Tract
of discharge from the guttural pouch will cause a

predominantly unilateral nasal discharge, large volume
hemorrhage from the guttural pouch of a horse with
unilateral guttural pouch mycosis will cause bilateral
epistaxis. A small proportion of horses with pulmonary
disease inexplicably have unilateral or predominantly
unilateral nasal discharge (Dixon et al 1995). Most horses
with a unilateral purulent nasal discharge have an
underlying disorder, such as sinusitis caused by dental
apical infection, compromised sinus drainage or the
presence of inspissated pus within a sinus, with secondary
bacterial infection. Consequently, antibiotic therapy based
on culture and sensitivity testing of nasal swabs is rarely
curative, and often simply delays the establishment of a
Fig. 8.1. Rhinitis sicca in a horse with grass sickness (dysautonomia). specific diagnosis and institution of appropriate treatment,
The serum exudation and crusting evident on the nasal mucosa are
which usually involves surgery.
likely the result of desiccation of the mucosa because of dysfunction of
the autonomic control of nasal gland secretion. This often painful Lesions of the respiratory tract caudal to the nasal
complication is considered to be pathognomonic for grass sickness. septum typically result in bilateral nasal discharge.
Bilateral nasal discharge is usually indicative of pulmonary
disease, with the respiratory secretions being transported
Malodorous breath can occur in horses with sinusitis up to the nasopharynx by the mucociliary escalator, or by
(especially, but not exclusively, dental sinusitis), nasal gravity when the head is lowered below the level of the
mycosis, guttural pouch mycosis, and gangrenous pneu- thoracic trachea, and also by coughing. Once transported
monia. Attempts should be made to determine the source to the nasopharynx these secretions are usually swallowed,
of the odor. Malodorous breath is exhaled only from one but if large volumes flow into the nasopharynx (e.g. after
nostril in horses with lesions rostral to the nasopharynx, lowering of the head) the discharge may exit both nostrils.
while horses with dental, periodontal, or other oral diseases In horses with concurrent upper and lower respiratory
may have malodor originating from the mouth, and not tract inflammation, such as those with viral respiratory
from the nostrils. infections, nasal discharge may originate from both the
Nasal discharges can be characterized as being upper and lower respiratory tract.
unilateral or bilateral, continuous or intermittent, scant or Pharyngeal or esophageal dysphagia may lead to nasal
profuse or malodorous. The nature of any discharge can discharge that contains food. This food and saliva will flow
further be categorized as serous; mucoid; mucopurulent; down both nasal cavities, especially when the head is
serosanguineous; hemorrhagic; and containing food or lowered, usually within a minute or so after the ingestion
gastrointestinal contents. Inflammation of upper or lower of food or liquids.
respiratory tract mucosa characteristically increases
mucus production, leading to a mucoid nasal discharge. Epistaxis
However, with most equine inflammatory respiratory Epistaxis denotes hemorrhage from the nose, but does not
disorders the increased mucus production is accompanied indicate the origin of the hemorrhage. Hemoptysis
by transmucosal migration of large numbers of leuko- (coughing up blood of pulmonary origin through the oral
cytes, primarily neutrophils. Consequently, the respiratory or nasal cavity) is usually associated with disease of the
secretions, whether of upper or lower respiratory tract lower respiratory tract in other species but is a rare finding
origin, are commonly mucopurulent. Purulent secretions in horses. With exercise-induced pulmonary hemorrhage,
occur in disorders such as sinusitis and strangles, when epistaxis of pulmonary origin usually occurs without
respiratory secretions contain so many degenerating coughing. Unilateral epistaxis suggests a lesion rostral to
leukocytes (predominantly neutrophils) that they are the nasopharynx, while bilateral epistaxis indicates a lesion
highly viscous. Whilst purulent discharge is traditionally caudal to the nasal cavities.
associated with bacterial infection of the respiratory tract, In some cases of epistaxis, the origin of the blood
it may also be a feature of other disorders including may be obvious, but often other diagnostic procedures are
viral respiratory infections and recurrent airway obstruc- required to detect the cause. Endoscopy of the nasal
tion (RAO). Purulent secretions can be white, yellow, or cavities, nasopharynx, larynx, trachea, and large bronchi
green, with the color sometimes being dependent on is often necessary and usually diagnostic. Radiography of
bacterial pigments and metalloenzymes. the head may be necessary in some cases to detect lesions
Unilateral nasal discharge occurs in disorders of the of the sinuses (fractures and progressive ethmoidal
nasal cavity and paranasal sinuses. While small volumes hematoma), which may be the source of hemorrhage.
8 Clinical Examination of the Respiratory Tract 105
Submandibular lymph node make loud but normal breath sounds. Prolonged post-
exercise dyspnea is indicative of respiratory dysfunction.
The submandibular lymph node groups (which in the When assessing horses with suspected upper airway
horse comprises 70–150 small nodes) are usually not obstruction, it is important to determine whether abnormal
palpable or are barely palpable in healthy horses. Even noises made during fast exercise occur during inspiration
when these lymph nodes are enlarged, they are often not or expiration. This is readily achieved by assessing when
readily detected unless the dorsomedial aspect of the more the noises occur in relation to the horse’s gait, because at
caudal aspects of the mandible is specifically examined for the canter and gallop, locomotion and breathing are
their presence. Occasionally these lymph nodes are swollen synchronized. Expiration occurs when the forefeet hit the
with neoplasia of the head, mainly as a result of local ground, while inspiration occurs when the forefeet are
inflammation rather than by metastases. The presence of being elevated.
ipsilateral submandibular lymphadenopathy along with
unilateral nasal discharge is confirmatory evidence of a Examination of the paranasal sinuses
unilateral upper respiratory tract disorder. Bilateral sub-
mandibular lymphadenopathy is occasionally the result of Diseases of the paranasal sinuses often cause unilateral
bilateral upper respiratory disorders, such as bilateral nasal discharge, submandibular lymph node enlargement,
sinusitis or guttural pouch disorders, but is most commonly and epiphora. The thick lateral maxillary wall is not
a response to generalized respiratory infections, such as usually distorted in primary and dental sinusitis, unless
equine influenza, herpesviruses 1 and 4, or strangles. gross sinus distension and bone softening occur. In
contrast, the thin medial walls are readily distorted towards
Respiratory sounds the nasal septum, leading to unilateral nasal obstruction.
Percussion of a sinus may be of value in assessing its
In a normal resting horse, breathing is virtually inaudible. contents. An exudate-filled sinus may lose the resonance
However, during fast exercise, the increased (>60-fold) of a normal air-filled sinus. However, a diseased sinus
airflow causes the respiratory sounds to become audible at is not necessarily filled with exudate and, additionally,
a considerable distance from the horse. Normally, exercise- affected horses usually resent percussion of an inflamed
related expiratory sounds are almost twice as loud as and presumably painful sinus. In general, percussion is
inspiratory sounds. A common, loud expiratory sound in unreliable unless advanced sinus disease is present. It is
horses is caused by a snorting-like vibration of the nasal more useful to place a hand over the maxillary sinuses on
structures, including the true nostrils, and is termed “false both sides and assess the maxillary bones for pain, swelling,
nostril flutter” or “high blowing”. These normal sounds increased heat and softening of the bones. With low-grade
often occur at the beginning of exercise, and can also occur sinusitis all clinical examinations are unreliable. Therefore,
in aggressive horses at rest. Very unfit horses may have if sinusitis is suspected the diagnosis should be confirmed
increased levels of normal breath sounds, or coarse low- by radiography, endoscopy, or sinoscopy (Chapters 10, 18
pitched noises, during fast work, and horses making such and 26).
noises are referred to as being “thick winded”. These noises
normally disappear when the animal becomes fitter. Nasopharynx
Horses with dynamic upper airflow obstructions, such
as laryngeal paralysis or dorsal displacement of the soft The oropharynx is the part of the pharynx between the soft
palate, have normal breath sounds at rest when airflow palate, the tongue, and the epiglottis. The nasopharynx lies
is low, but make loud abnormal respiratory sounds medial to the vertical ramus of the mandible and the
during strenuous exercise, because of airflow turbulence at parotid salivary gland, while the laryngopharynx is rostral
sites of dynamic airway obstruction. These exercise- to the larynx. The omohyoid muscles, the cricothyroid
induced sounds may be audible at more than 50 m from ligament, and the hyoid apparatus fully cover the ventral
the exercising horse. aspect of the oropharynx. Because of the presence of these
It is not always possible to exercise a horse to listen for overlying structures, little information can be gained from
exercise-induced abnormal noises, because of the lack of external palpation of the pharynx. Swelling of the parotid
an exercise area or treadmill, inclement weather, or inter- region may indicate distension of the underlying guttural
current lameness. In such circumstances the importance of pouch, inflammation of the overlying parotid salivary
obtaining an accurate history cannot be overemphasized. gland, lymphadenitis of the retropharyngeal lymph nodes
Alternatively, the owner can make a video or audio (e.g. strangles infection), or evidence of neoplasia (usually
recording of the horse making the noise at exercise. After melanoma) of this region.
prolonged and fast exercise, such as racing, even normal, fit With use of sedation and a full mouth speculum,
horses will exhibit post-exercise dyspnea for 5–15 min, pharyngeal palpation may be performed per os in larger
when they will continue to breathe rapidly and deeply and horses, depending on the relative sizes of the horse’s oral
cavity and pharynx and the examiner’s hand and arm. The technique of choice for examining the guttural pouches.
base of the tongue, the large midline glossoepiglottic Guttural pouch distension may be evident in foals with
fold, the oropharyngeal walls and floor, the caudoventral guttural pouch tympany, and occasionally in horses with
aspect of the soft palate and the base of the epiglottis are empyema or chondroids. A very distended guttural pouch
palpable when the soft palate and epiglottis are in the may protrude caudolaterally between the angle of the
normal breathing position. This examination will often mandible and the larynx, with the floor of the guttural
cause the soft palate to become dorsally displaced, allow- pouch lying subcutaneously, lateral to the larynx.
ing palpation of the epiglottis and the rostral aspect of
the larynx. Larynx
Pharyngeal dysphagia in the horse is manifested by
food and saliva flowing down the nasal cavity, during Recurrent laryngeal neuropathy (RLN) causes abnormal
or immediately after eating; coughing caused by food breathing noises and reduced exercise performance. Abnor-
inhalation; and evidence of froth and masticated food in malities of phonation, as in the presence of an abnormal
the horse’s water bucket. Pharyngeal dysphagia can be the whinny, may also occur in some severely affected cases.
result of neuromuscular dysfunction, caused by lesions To assess for cricoarytenoideus dorsalis muscle atrophy,
affecting its sensory or motor nerves (cranial nerves IX, X, palpation of the dorsorostral aspects of the larynx will
and XI) or the pharyngeal muscles. Neuromuscular dys- demonstrate increased prominence of the muscular pro-
function may be part of a generalized neurological disorder, cess of the arytenoids. The degree of laryngeal muscling
such as botulism, rabies, or lead poisoning (when general- on each side should be compared. The fingers of both
ized weakness will be present), or may be a local disorder hands are advanced beneath the rostral aspect of each
such as guttural pouch mycosis, with damage to cranial sternocephalicus tendon and are moved rostromedially
nerves IX, X, or XI. The pharyngeal (gag) reflex is absent or along the dorsum of the larynx to the muscular processes
weak when there is paralysis of the pharynx. This reflex of the arytenoid on each side.
can be assessed by touching the nasopharyngeal wall or Some degree of laryngeal muscle atrophy is present in
soft palate with a nasogastric tube or endoscope and most large horses as a result of subclinical RLN, but
observing if a swallow reflex is induced. clinical signs may not appear until it is very marked. The
Acute pharyngitis, as occurs with strangles, occasion- thoracolaryngeal (“slap”) test can also be used to assess
ally causes transient pharyngeal dysphagia because the function of the recurrent laryngeal nerve and laryn-
of marked retropharyngeal lymphadenitis. The other geal adductor muscles. In this test, the dorsal laryngeal
clinical signs of strangles, such as bilateral purulent area on one side is palpated while the saddle area on the
nasal discharge, bilateral submandibular lymphadenitis contralateral thorax is slapped. Alternatively, the larynx
and fever, will aid diagnosis. Swelling of the parotid and is examined endoscopically during this maneuver. In
retropharyngeal lymph nodes frequently occurs with normal horses this maneuver induces transient adduc-
strangles but may not be readily detectable because of the tion of the opposite side of the larynx. The absence of
presence of the large overlying parotid salivary gland. this reflex can indicate laryngeal paresis or paralysis.
However, deep palpation of the parotid area may reveal A further technique to assess laryngeal function is the
focal areas of increased heat and pain resulting from “arytenoid depression maneuver”, which consists of sta-
inflammation of the parotid lymph nodes. bilizing the right side of the larynx with three to four
fingers while pressing the left arytenoid muscular process
Soft palate in a rostromedial direction with the right index finger.
This maneuver readily induces inspiratory stridor in horses
Only the rostral few centimeters of the oral aspect of the with severe RLN.
soft palate are visible on oral examination. Digital exami- In horses with cricopharyngeal–laryngeal dysplasia
nation of the entire ventral aspect of the soft palate (fourth branchial arch defect), laryngeal palpation may
is possible in well-sedated horses. Consequently, the soft reveal a short, possibly vertically oriented, larynx and an
palate is usually examined by nasopharyngeal endoscopy. abnormal space may be palpable between the caudal
aspect of the short thyroid cartilage and the cricoid
Guttural pouches (eustachian cartilage (the thyroid cartilage normally overlaps the
tube diverticulae) cricoid). Examination of affected horses when they eat may
reveal belching, caused by ingress and egress of large
The guttural pouches are positioned dorsal to the volumes of air into the esophagus, because of the absence
nasopharynx and medial to the mandible and parotid of the cricopharyngeal muscles.
salivary glands. Consequently, they cannot be visualized The most common and effective clinical technique
or palpated in the normal horse. Because of the limitations to assess laryngeal function is to listen for abnormal
of clinical examination of this area, endoscopy is the inspiratory noises at fast exercise. Initially during exercise,
horses with RLN make an abnormal “whistling-type” however this procedure should be performed with care to
inspiratory noise. With further or faster exercise these avoid inducing asphyxia.
whistling sounds change to coarse inspiratory noises External trauma may cause tracheal rupture with
resembling “wood sawing” (termed “roaring” by owners) ingress of air into tissues from external wounds, via tears
and in cases with severe RLN these sounds become very in the tracheal mucosa; or from infections by gas-
loud and will become biphasic (occur during inspiration producing bacteria. This may lead to localized painful
and expiration). Palpation of the larynx immediately after swellings on the ventral aspect of the neck and sub-
exercising a horse with severe laryngeal paralysis may cutaneous emphysema (manifested by crepitus on palpa-
transiently reveal fremitus as a result of turbulent airflow. tion). As a traumatic esophageal rupture can cause
Horses should be examined for the presence of a identical signs, clinical examination should be sup-
laryngotomy scar, beneath the thyroid notch on the ventral ported by endoscopic examinations of both the trachea
aspect of the larynx, and the rostral sternothyrohyoideus and esophagus.
area should be assessed for the presence of myectomy scars
and the absence of muscle.
Clinical Examination of the Lower
Respiratory Tract
Trachea
Audiovisual inspection of breathing
The space between the caudal aspect of the cricoid
cartilage and the first tracheal ring (the cricotracheal The clinician should determine the rate, depth, and pattern
ligament) can be readily identified by palpation, both by the of breathing, and listen for abnormal sounds associated
greater width of the cricoid cartilage as compared to a with breathing. This is best performed by distant
tracheal ring, and because the cricotracheal ligament observation, with the horse in a quiet location and
is wider than the spaces between the tracheal rings undisturbed, because anxiety can profoundly alter the
(interannular ligaments). In some horses, even with their breathing pattern and rate. Horses that are examined
heads in the normal flexed position the cricotracheal space outwith their normal environment, such as in an out-
can be very large and the ligament may appear to be slack, patient clinic, are often anxious and have alterations in
and with digital pressure it can be readily pushed into the the rate, depth, and pattern of breathing. Under such
airway lumen. This anatomical feature has been considered circumstances, the clinician must endeavor to differentiate
by some authors to cause inspiratory airflow obstruction these physiological changes from those resulting from
during fast work. respiratory disease.
The cervical portion of the trachea is examined by
inspection of the overlying skin to identify changes in Breathing rate
shape or position, deformities, and scars. Palpation may
detect pain, local swellings, deformities from a previous The breathing rate is most easily determined by observing
tracheostomy, and developmental defects such as dorso- the movement of the costal arch while standing caudo-
ventral or lateral collapse, and misalignment of the free laterally to the horse. Most of the changes in thoracic
borders of some tracheal rings. Mild digital pressure on volume that accompany resting breathing are the result
the trachea may elicit coughing in horses with tracheitis. of cranial and caudal movement of the diaphragm.
In many horses, particularly thoroughbreds, the first Consequently there is very little change in chest circum-
few tracheal rings have a slight, clinically insignificant ference during quiet breathing, and determination of the
degree of flattening, particularly of the ventral aspect. A breathing rate for normal resting horses is often difficult. To
prominent protrusion on the ventral aspect of these overcome this problem, the breathing rate may be
tracheal rings may be palpable in the cranial neck, determined by feeling the expiratory airflow with a hand
where they are covered by the relatively thin sterno- placed near the external nares. Alternatively, in cold
thyrohyoideus muscles. In small ponies, especially environments, the breathing rate is readily determined by
Shetlands and miniatures, a common congenital defect is observing the exhalation of condensed water vapor. The
dorsoventral flattening of the tracheal cartilages of the normal resting breathing rate is 8–12 breaths/min for
caudal cervical and intrathoracic trachea. Palpation of the horses and 15–20 breaths/min for ponies. Inspiration and
caudal cervical trachea may be very difficult because of expiration are normally of similar duration.
the thick skin, greater muscle covering over the distal
cervical trachea and frequently excessive body condition Depth of breathing
of these ponies. However, deep lateral palpation in the
jugular groove may reveal an abnormal sharp lateral edge During quiet breathing, resting horses have relatively
to the trachea. Deep midline pressure over the caudal subtle movements of the nostrils, costal arch, and inter-
cervical trachea may induce stridor in affected ponies; costal and abdominal muscles. These movements are
exaggerated in horses with dyspnea. As horses with

Table 8.1. Abnormalities in the rate,
pulmonary disease often have a nocturnal deterioration in depth, and pattern of breathing
pulmonary function (Deegen & Klein 1985), clinical
examinations performed during the day may underestimate Rapid deep breathing
● Physiological causes including exercise and anxiety
the severity of the nocturnal pulmonary dysfunction.
● Pathological causes including lung disease, anemia,
Clinicians should take into account this potential metabolic acidosis, pain
deterioration when considering case management.
Rapid shallow breathing
● Anxiety
Pattern of breathing ● Pleurodynia associated with chest wall injury or
pleuropneumonia. As deep breathing increases the intensity
The horse has a unique breathing strategy that is evident of pleurodynia, horses with pleurodynia adopt a rapid,
upon close inspection of breathing. Most other mammals shallow breathing strategy
● Disorders that reduce the compliance of the lungs or chest
inhale actively by contraction of the external intercostal
wall, including;
muscles and diaphragm but exhale passively because of
(a) space-occupying lesions of the thorax, such as pleural
passive lung recoil. In contrast, the normal horse has effusion and pneumothorax, that limit lung compliance
biphasic expiratory and inspiratory phases, with the first by reducing the intrathoracic volume available for lung
parts of inspiration and expiration being passive and the expansion
second parts being active (Koterba et al 1988). Thus the (b) restrictive lung diseases, such as interstitial pneumonia
and pulmonary fibrosis that reduce lung compliance
horse inhales initially by passive relaxation and recoil
directly. These disorders make it difficult for the horse
of the abdominal muscles to the resting equilibrium to inspire deeply. Consequently, affected horses adopt a
position, and then by active contraction of the diaphragm more energy efficient, fast and shallow breathing
and external intercostal muscles. Exhalation comprises pattern
initial passive recoil towards the resting equilibrium Slow deep breathing
position, followed by active contraction of the abdom- ● This is occasionally evident in horses with severe airway
inal muscles and internal intercostal muscles. The obstruction, when inspiratory or expiratory airflow is
end-expiratory abdominal lift or heave is often visible restricted to such an extent that the duration of inspiration
in normal resting horses. The biphasic breathing pattern, and/or expiration is markedly prolonged and as a result the
breathing rate cannot be increased
and in particular the end-expiratory abdominal heave, is
markedly exaggerated in horses with expiratory dyspnea Slow shallow breathing
(such as occurs in RAO). ● This is indicative of central nervous system depression, or a
compensatory response to metabolic alkalosis
Normally each hemithorax moves equally and sym-
metrically during breathing. Asymmetric reduction in Cheyne–Stokes breathing
movement of one hemithorax may occur with ipsilateral ● This is characterized by a cyclical waxing and waning of the
space-occupying lesions, such as pleural effusion or pneu- rate and depth of breathing.
mothorax, or with ipsilateral pleurodynia (pleural pain).
Paradoxical breathing may occur in dyspneic neonatal
foals; during inspiration the highly compliant thoracic wall
collapses inwards while the abdomen expands.
the breath cycle, or it may occur predominantly during
Abnormalities in the rate, depth, and pattern inspiration or expiration. Horses with fixed airway obstruc-
of breathing tions, such as those with a solid mass within the nasal
cavity, may have a relatively constant degree of dyspnea
Abnormalities in the rate, depth, and pattern of breathing throughout the breath cycle, because the degree of obstruc-
may be subdivided into five broad categories, as indi- tion remains constant throughout the breath cycle. The
cated in Table 8.1. Recognition of these abnormalities majority of horses with airway obstructions, however, have
may enable the clinician to determine the cause of the dyspnea that is significantly worse during inspiration (for
underlying problem. most upper airway obstructions) or expiration (for most
lower airway obstructions). This is because of dynamic
Differentiation of expiratory versus airway collapse, whereby the degree of obstruction varies
inspiratory dyspnea throughout the breath cycle as a consequence of changes
in the transmural pressure gradient. Knowledge of the
Dyspnea is defined as a difficulty in breathing. Horses with pathogenesis of expiratory and inspiratory dyspnea may
dyspnea have an obvious increase in breathing effort enable the clinician to determine the likely anatomical site
and may appear distressed. Dyspnea may occur throughout and nature of the underlying disease process (Table 8.2).
Inspiratory dyspnea
Table 8.2. Differentiating inspiratory
versus expiratory dyspnea Inspiratory dyspnea results in a prolonged and labored
inspiratory phase, and exaggerated activity of the
Expiratory dyspnea diaphragm and external intercostal muscles during inspi-
Signs ration. Inspiratory dyspnea is most commonly caused
● Prolonged and labored expiratory phase by obstruction of the extrathoracic airways, such as
● Exaggerated expiratory contraction or “heave” of the bilateral laryngeal paralysis or cervical tracheal col-
abdominal muscles lapse. This is because the subatmospheric pressures
● Heave line in chronically affected horses
● Pumping of anus
that develop within the extrathoracic airways during
● Dilatation of external nares throughout the breath cycle inspiration cause dynamic collapse of airways that have
● Extension of the head and neck lost their structural integrity. Disorders that reduce lung or
Causes
chest wall compliance, such as restrictive lung disorders
● Obstruction of the intrathoracic airways and space-occupying lesions of the thorax, may also lead
to inspiratory dyspnea because these conditions compro-
Inspiratory dyspnea
mise lung inflation.
Signs
● Prolonged and labored inspiratory phase
● Increased inspiratory effort
Abnormal Respiratory Sounds
● Exaggerated diaphragm and external intercostal muscle
activity The clinician should listen for respiratory sounds which are
● Dilatation of external nares throughout the breath cycle
audible without the aid of a stethoscope. Their presence
● Extension of the head and neck
usually indicates respiratory tract disease.
Causes
● Obstruction of the extrathoracic airways
● Restrictive lung disorders
● Space-occupying lesions of the thorax
Coughing
Mixed inspiratory and expiratory dyspnea Coughing is probably the most reliable clinical sign of
pulmonary disease, although it is inexplicably absent in
Cause some horses that have pulmonary disease and excessive
● Fixed obstructions of the airways
respiratory secretions. Coughing rarely results in expec-
toration of respiratory secretions from the oral cavity,
most of the respiratory secretions being swallowed.
Consequently differentiation of productive and non-
productive coughing has limited diagnostic value in equine
Expiratory dyspnea medicine, and in any case endoscopy will invariably
Horses with expiratory dyspnea have a prolonged and show excessive respiratory secretions in the trachea of
labored expiratory phase, and an exaggerated expira- horses with any type of pulmonary disease (Dixon et al
tory abdominal effort that is termed a “heave”. The marked 1995). Horses with pleurodynia may have a characteristic,
intra-abdominal pressure swings which result from severe soft cough.
expiratory abdominal efforts can cause rhythmic pumping
of the anus. Horses with longstanding severe expiratory
dyspnea may develop a heave line; a linear depression Wheezes and crackles
which develops ventral to the external abdominal oblique
Wheezes and crackles may be heard at the nostrils of
muscles, when these muscles hypertrophy (Fig. 8.2). Heave
horses with severe respiratory tract disease. Stridor is a
lines were previously common in horses with chronic severe
term used to describe a particularly loud monophonic
RAO but are rare today as a consequence of improvements
inspiratory wheeze that may be heard considerable
in the diagnosis and management of this disease. A heave
distances from the horse. It is indicative of an extrathoracic
line should be differentiated from the external abdominal
airway obstruction.
oblique muscle hypertrophy that is present in performance
horses as a result of athletic training.
Expiratory dyspnea is caused by obstruction of the Grunts or groans
intrathoracic airways (such as occurs in RAO), because the
transmural pressure gradients cause the inflamed and These loud expiratory sounds, produced by sudden
narrowed intrathoracic airways to undergo progressive laryngeal opening after a period of breath-holding against
dynamic airway collapse during expiration (Fig. 8.3). a closed glottis, are usually an indication of pain.
Fig. 8.2. A horse with a “heave line” (arrows). This is a linear depression which develops ventral to the
external abdominal oblique muscles, when these muscles hypertrophy in horses with longstanding severe
expiratory dyspnea.
A Inspiration recent simplification of the terminology of lung sounds

–3 has led to more accurate interpretation of auscultatory
–2 findings. The terms bronchial sounds, vesicular sounds,
–1 –1 0 alveolar sounds, sonorous sounds, rhonchi, moist rales, dry
0
rales, squeaks, whistles, and crepitation are now considered
obsolete. The mechanisms of breath sound production and
Transmural pressure gradient on inspiration tends to
• collapse extrathoracic airways transmission in domestic animals have been well reviewed
• dilate intrathoracic airways (Kotlikoff & Gillespie 1983, 1984).
Auscultation should be performed in quiet surround-
ings, and with the horse minimally restrained. The
B Expiration Extrathoracic
airways diagnostic sensitivity of the examination may be enhanced
Chest wall
by the use of an electronic stethoscope, which increases the
Pleural cavity +2 amplitude of breath sounds. A systematic pattern of
+1 +1 0
Lung 0
auscultation is essential. The clinician should auscultate
the distal cervical trachea and both lung fields, with each
site being examined for a minimum of one complete breath
Transmural pressure gradient on expiration tends to
• collapse intrathoracic airways cycle. During auscultation, the clinician should observe the
• dilate extrathoracic airways costal arch to (1) determine the stage of the breath cycle at
which breath sounds occur, and (2) assess the relative
Fig. 8.3. Schematic diagram showing the pathogenesis of dynamic
airway collapse. During inspiration (A), the pressure outside the audibility of inspiratory and expiratory sounds.
extrathoracic airways exceeds that within the airways. If this trans- Auscultation should also be performed while the horse is
mural pressure gradient overcomes the rigidity of the airways, dynamic hyperventilating because hyperventilation considerably
airway collapse will result. Conditions that compromise the rigidity of improves the audibility of breath sounds and hence
the extrathoracic airways, including nasal paralysis, laryngeal paralysis,
increases the sensitivity of the examination. Clearly, forced
and cervical tracheal collapse, may induce airway collapse and cause
inspiratory dyspnea. Conversely, during expiration (B) the transmural hyperventilation is contraindicated in horses with severe
pressure gradient favors dynamic collapse of the intrathoracic airways. dyspnea or pleurodynia. Hyperventilation is readily achieved
Conditions that lead to narrowing of these airways, such as RAO, using a rebreathing bag, which is tolerated by most horses
exacerbate airway closure and cause expiratory dyspnea. Redrawn (Fig. 8.4), but other clinicians induce hyperventilation by
from McGorum et al 2000, with permission.
occluding the horse’s external nares for 30–60 seconds.
This method is less useful than the rebreathing bag because
it induces only transient hyperventilation. Furthermore,
it often induces swallowing and chewing, resulting in
referred noise, which can mask breath sounds. The
Auscultation of the Lower
clinician should suspect respiratory tract disease if forced
Respiratory Tract
hyperventilation induces adventitious breath sounds,
Auscultation is the most frequently used technique for coughing, or pleurodynia, or if the time for the breathing
examining the respiratory tract. When performed by rate to return to normal is prolonged.
an astute clinician it can provide useful diagnostic During auscultation, the clinician should attempt to
information. However, as with all clinical techniques, address the following points:
auscultation has limitations. While it is important to
● Is the audibility of breath sounds heard on auscultation
understand these limitations, the clinician must avoid
of the distal cervical trachea and thorax normal?
dismissing thoracic auscultation as a technique to be
● Are there regional differences in the audibility of the
performed only as a diagnostic ritual, in deference to
breath sounds heard over the thorax?
tradition, rather than as a truly valuable technique. The
● Are adventitious breath sounds audible?
major limitation of auscultation is the inaudibility of
● If so, which adventitious sounds are audible, what is
breath sounds detectable over the equine thorax, especially
their location, and at what stage of the breath cycle do
when examining obese horses under noisy field condi-
they occur?
tions. A further limitation is the considerable confusion
that exists in the nomenclature and interpretation of
lung sounds. This has resulted from over-interpretation or Normal breath sounds
over-simplification of Laënnec’s original description of
breath sounds (Robertson 1957), and as a result of poor Certain sounds, termed normal breath sounds, always
understanding of the mechanisms of sound production accompany the movement of air within airways. These
and transmission within the respiratory tract. Thankfully, sounds are generated predominantly by turbulent airflow
High
Normal Pneumothorax
Low
Consolidation
Pleural effusion
Fig. 8.5. Schematic diagram showing the effects of pulmonary

consolidation, pneumothorax, and pleural effusion on the trans-
mission of high and low frequency breath sounds from their source in
the large airways to the stethoscope. Redrawn from McGorum et al
2000, with permission.
pharynx, larynx, trachea, and larger intrathoracic airways.

In contrast, small airways (<2 mm) transmit sound waves
poorly and probably do not contribute to the generation or
transmission of breath sounds.
Normal breath sounds audible at the distal

cervical trachea
The normal breath sounds produced in the large airways
are clearly audible on auscultation of the distal cervical
trachea because they are transmitted efficiently through
the thin peritracheal tissues to the stethoscope. In the
normal horse they are soft blowing sounds which should be
neither harsh nor accompanied by adventitious sounds.
They are heard predominantly during early inspiration and
early expiration. The inspiratory and expiratory noises
normally have similar amplitude.
Normal breath sounds audible over the

Fig. 8.4. The audibility of breath sounds detected by auscultation may lung fields
be increased by using a rebreathing bag. This induces prolonged Only a small fraction of the breath sounds produced in the
hyperventilation and considerably improves the sensitivity of thoracic large airways reaches a stethoscope placed against the
auscultation.
thorax. The remainder is lost by attenuation and reflection
as sound is transmitted from the large airways, through the
parenchyma and the relatively thick equine thoracic wall,
to the stethoscope (Fig. 8.5). Consequently, breath sounds
in the large (>2 mm) airways. Breath sounds are trans- audible over the thorax are considerably quieter than those
mitted efficiently up and down the lumina of the larger audible over the distal cervical trachea. Indeed, the breath
airways as airborne pressure waves, with relatively little sounds detected over the thorax during normal resting
sound attenuation. Consequently, breath sounds audible breathing are often barely audible and consequently are
over the trachea or over the thorax represent a mix of difficult to interpret. The acoustic transmission properties
sounds originating from many different sites throughout of the lung and thoracic wall are such that this loss of
the respiratory tract, including the nares, nasal cavity, sound is normally greater for high-frequency sounds than
for low-frequency sounds. Normally, breath sounds are factors such as the presence of pleural effusion. While
louder during inspiration than expiration, and are slightly physiological factors influence the audibility of the lung
louder over the right thorax than the left thorax. sounds over the entire thorax, pathological processes
usually result in regional differences in the audibility of
Increased audibility of normal breath sounds breath sounds and are accompanied by adventitious breath
sounds. The latter findings should alert the clinician to the
The audibility of breath sounds is determined largely by presence of disease.
two factors, namely:
● the amplitude of breath sounds produced within the Adventitious breath sounds
large airways
Adventitious breath sounds are abnormal sounds that are
● the proportion of sound which is lost during sound
superimposed on normal breath sounds (Table 8.3). As
transmission.
they are audible only in horses with respiratory tract
Increased audibility of normal breath sounds over the disease, they are a useful indicator of respiratory tract
entire lung field most commonly reflects hyperventilation, disease, but provide limited information regarding its
which increases the amplitude of breath sounds by etiology. Consequently, the clinician should be cautious
increasing the velocity of airflow in the large airways.
There are numerous causes of hyperventilation including
respiratory tract disease, anxiety, exercise, metabolic
Table 8.3. Adventitious respiratory sounds
acidosis, fever, severe anemia, and cardiac failure.
A focal increase in the audibility of normal breath Wheezes
sounds may be detected over pulmonary masses and areas
Prolonged (> 250 ms) musical sounds produced by air flowing
of pulmonary consolidation. The acoustic properties of through narrowed airways, causing the walls to vibrate
these lesions favor efficient transmission of high-frequency between the closed and barely open positions
breath sounds from the surrounding healthy airways to the ● Expiratory wheezes – indicate obstruction of the
overlying chest wall (Fig. 8.5). Breath sounds heard over intrathoracic airways such as occurs in RAO
● Inspiratory wheezes – audible in horses with atelectasis,
consolidated lung are thus similar to those audible over the
pulmonary consolidation or restrictive pulmonary diseases
distal cervical trachea. ● Stridor – a loud monophonic inspiratory wheeze indicating
obstruction of the extrathoracic airways, such as occurs in
Decreased audibility of normal breath sounds extrathoracic tracheal collapse
Crackles
Decreased audibility of breath sounds usually results from
increased attenuation of sound as it is transmitted from the Short duration, interrupted, non-musical sounds
● Coarse crackles – loud, short duration (typically 10–30 ms),
large airways to the stethoscope. Reduction in the
non-musical, “bubbling or crackling” sounds audible over
audibility of breath sounds over the entire thorax is
the distal cervical trachea. Probably caused by air bubbling
common in obese horses, because the thicker chest wall through, and causing vibrations within, respiratory
considerably reduces breath sound transmission. In secretions within the large airways
contrast, breath sounds of thin horses and foals are much ● Fine crackles – compared with coarse crackles, these are
more audible. The clinician must therefore interpret the shorter duration (typically 1–10 ms), lower amplitude and
higher pitch. Probably caused by sudden explosive opening
audibility of the lung sounds with reference to the body
of a series of airways which had become abnormally closed
condition of the animal. Rarely, a generalized reduction in during expiration
breath sounds may reflect reduced airflow velocity, as 1. Late inspiratory fine crackles: occur in restrictive
occurs in horses with hypoventilation. pulmonary diseases
Regional loss of breath sounds occurs when the pleural 2. Early inspiratory fine crackles: occur in obstructive
pulmonary diseases
cavity contains air, fluid, or displaced abdominal organs
(Fig. 8.5). In such circumstances, breath sounds are lost Pleural friction rubs
largely by reflection at the tissue/air or tissue/fluid inter-
Variable sounds produced as inflamed visceral and parietal
faces, because these interfaces act as near-complete acoustic pleurae rub together
barriers. Some intestinal sounds are auscultated in the
normal thorax but increased intestinal sounds may be Expiratory grunts
auscultated in horses with a diaphragmatic hernia. Loud expiratory sounds produced by sudden laryngeal
From the above discussion it will be evident that opening after a period of expiration against a closed larynx.
the audibility of breath sounds is influenced by physio- They indicate pain.
logical factors such as body condition and by pathological
when attributing a particular adventitious sound to a spasm, mucus accumulation, foreign bodies). Airway
specific disease process or etiology. Conversely, as significant narrowing is further exacerbated by the Bernouilli effect,
respiratory disease may occur in the absence of adventi- whereby acceleration of the air column as it flows through
tious sounds, the absence of adventitious sounds does not the narrowed airway causes a reduction in the intra-
preclude respiratory tract disease. The nature, anatomical luminal pressure. The airway narrowing, in turn, causes
location, and audibility of adventitious breath sounds may deceleration of the airflow, reducing the Bernouilli effect,
all vary considerably with time as a result of alterations in and opening up the airway. This rapid cyclical opening and
the underlying airway dysfunction, breathing pattern, or closing of the airway generates the wheeze. Many healthy
clearance of airway secretions. humans and most human asthmatics can generate
Adventitious noises tend to occur consistently at the expiratory wheezes simply by performing a violent forced
same stage of the breath cycle, over many consecutive expiration, which induces dynamic collapse of the central
breaths. The clinician should determine the stage of the airways at low lung volumes.
breath cycle at which they occur, because this may yield Two types of wheeze are recognized.
information regarding the nature and location of the under-
● Monophonic wheeze – this is a single note of constant
lying lesions. The anatomical location of the point of max-
pitch, location of origin and timing within the breath
imal intensity of adventitious sounds should also be deter-
cycle. As it usually indicates partial obstruction of a
mined because this usually indicates the site of the lesion.
single airway by a solitary space-occupying lesion such
Wheezes as a neoplasm, it is an uncommon finding in horses.
● Polyphonic wheezes – these comprise several differ-
These are prolonged (>250 ms) musical sounds that
ent notes of different pitch and timing. They indicate
occur when air flows through narrowed airways, causing
obstruction of multiple airways and are commonly
the airway walls to vibrate between the closed and barely
detected in horses with RAO.
open positions (Fig. 8.6). Airway narrowing may be caused
by extraluminal compressive lesions (e.g. neoplasms), Wheezes are frequently audible at the thoracic wall,
thickening of the airway walls (e.g. mucosal inflammation cervical trachea, and external nares, because they are
or edema), or intraluminal obstructions (e.g. broncho- transmitted efficiently up and down the large airways, and
through the thoracic wall, with relatively little sound
attenuation.
A Wheezes arising from fixed airway obstructions may be
audible throughout the breath cycle. However much more
commonly, wheezes are confined to either expiration or
inhalation because of exacerbation of airway obstruction
as a result of dynamic airway collapse (Fig. 8.3). Expiratory
Wheeze
wheezes indicate partial obstruction of the intrathoracic
airways, as occurs in RAO. In contrast, late inspiratory
B wheezes indicate atelectasis, pulmonary consolidation or
restrictive lung diseases. In these latter disorders, wheezes
are produced by air entering previously collapsed airways
as the lung expands and the airways open during late
Increasing traction inspiration. As noted, stridor is a term used to describe a
from surrounding particularly loud monophonic inspiratory wheeze that
parenchyma
may be heard considerable distances from the horse with-
out the use of a stethoscope. It is indicative of extrathoracic
Crackle airway obstruction.
Crackles
These are short duration, interrupted, non-musical sounds.
Two types can be recognized:
Fig. 8.6. Schematic representation of mechanisms underlying the ● Coarse crackles – these are loud, explosive, short
production of crackles and wheezes. (A) Wheezes are produced by duration (typically 10–30 ms), non-musical, “rattling or
air flowing through narrowed airways causing their walls to vibrate bubbling” sounds. They are probably the most common
between the closed and barely open positions. (B) Crackles are caused
by a series of collapsed airways suddenly opening as a result of
adventitious breath sound heard in the horse. They are
increasing traction from surrounding parenchyma. Redrawn from most readily detected over the distal cervical trachea,
McGorum et al 2000, with permission. especially during induced hyperventilation, and may
be heard during inspiration and expiration. They are Extraneous noises not associated
possibly caused by air bubbling through, and causing with the breath cycle
vibrations within, respiratory secretions in the larger
intrathoracic airways, including those that are pooling If the stethoscope is not held firmly against the horse’s
within the dependent part of the rostral thoracic body during auscultation, it can rub on the hair and
trachea (“tracheal sump”). produce sounds resembling crackles.
● Fine crackles – compared with coarse crackles, Gastrointestinal and cardiac sounds are frequently
fine crackles are of shorter duration (typically 1–10 ms), audible over the lung fields of normal horses. Consequently
lower amplitude and have a higher pitch. Fine crackles their presence should not arouse suspicion of diaphrag-
can be simulated by rolling a lock of hair between matic herniation. Gastrointestinal sounds may be differen-
the fingers, close to the ear, or by “rustling” cellophane. tiated from breath sounds because they are sporadic,
Most fine crackles are probably caused by sudden variable in intensity and duration, and bear no temporal
explosive popping open of a series of airways that have association with the breath cycle. The clinician may
become abnormally closed during expiration (Fig. 8.6). differentiate cardiac and breath sounds by determining
Thus fine crackles tend to occur consistently at a par- whether the sounds coincide consistently with the cardiac
ticular transpulmonary pressure. The audible sounds or breath cycle. To determine the source of the unidentified
are the result of sudden equalization of the downstream sounds, it is occasionally useful to transiently stop the
and upstream airway pressures, or the sudden altera- horse breathing, by occlusion of the external nares. If the
tion in the tensions of the airway walls. In some horses, unidentified sound persists despite the cessation of breath-
air bubbling through secretions in the large airways ing, it is clearly not associated with the breath cycle.
can cause fine crackles. Fine crackles are detectable Muscular tremors, such as occur in horses that are
mainly in peripheral and dependent lung areas. Fine anxious or cold (blanket taken off for thoracic auscultation
crackles may be detected in early or late inspiration. in cold environments), may preclude satisfactory thoracic
Late inspiratory crackles occur in restrictive lung auscultation.
diseases, which reduce the lung compliance and cause “Thumps” produced by contraction of the diaphragm
airway closure at low lung volumes. Crackles are may be heard over the thorax and flanks in horses with
produced by the sudden opening of these collapsed synchronous diaphragmatic flutter. It is probable that
airways during late inspiration. In contrast, early acid–base and electrolyte disturbances make the phrenic
inspiratory crackles occur in horses with obstructive nerve sensitive to the depolarizing electrical activity of the
pulmonary diseases that lead to expiratory airway adjacent myocardium. The diaphragmatic contraction
collapse. The crackles are produced by the airways as and resultant “thump” are thus synchronous with the
they pop open explosively during early inspiration. heartbeat and not with the breath cycle.
Pleural friction rubs

The gliding movement of the visceral and parietal pleurae
Acoustic Percussion of the Thorax
is normally silent because of the lubricant properties of the Acoustic percussion is a useful non-invasive technique for
pleural fluid. However, when inflamed visceral and parietal detecting pleural and superficial parenchymal lesions.
pleurae rub together, frictional resistance may produce Whilst it should be performed as part of the routine clinical
pleural friction rubs. These sounds vary considerably, from examination, it is especially indicated when auscultation
sounds resembling fine crackles to classical harsh pleural has revealed regional variations in the audibility of lung
friction sounds that can be simulated by rubbing two sheets sounds or there is other evidence of pleural disease. While
of sandpaper together. This variability makes it difficult percussion is a useful clinical technique, it is considerably
to recognize pleural friction sounds definitively, and to less sensitive than ultrasonography for detecting pleural
differentiate them from crackles originating from pulmo- and superficial parenchymal lesions and only relatively
nary disease. Pleural friction rubs are usually heard during large lesions can be detected. Furthermore, as the per-
both inspiration and expiration, and tend to recur cussive sound wave penetrates only to a depth of several
consistently at similar stages in the breath cycle, features centimeters, percussion will only detect pleural and
which are diagnostically useful. Most pleural friction rubs superficial parenchymal lesions. As with most clinical
are transient phenomena, disappearing when the pleurae techniques, considerable practice using normal and
are separated by pleural effusion. Thus the absence of abnormal animals is required to attain diagnostic pro-
pleural friction rubs does not preclude the presence of ficiency with percussion.
pleuritis. The clinician can differentiate between pleural Percussion may be performed by the direct technique
friction rubs and cardiac murmurs by determining whether using a plexor and a pleximeter, but as these are not always
the sounds are synchronous with the breath or with available, the indirect technique is described. The right-
cardiac cycles. handed clinician should hyperextend the middle finger
Table 8.4. Abnormal findings on acoustic percussion

Percussion of the thorax
field Pleural
reflection Costal
arch ● Dull area ventrally – pleural effusion (most common),
diaphragmatic hernia, marked cardiomegaly, marked
pericardial effusion
● Dull area at any focal site – large pleural or pulmonary
abscess or neoplasm
● Increased resonance dorsally – pneumothorax
Point of shoulder
● Increased resonance at any site – emphysematous bullae,
although these are unlikely to be of sufficient magnitude
to be detectable by percussion
Cardiac notch ● Coughing – percussion induces coughing only if there is
11th rib disease of the underlying lung parenchyma
● Pleurodynia – percussion is painful in horses with diseases of
the underlying thoracic wall, pleurae or lung parenchyma
From McGorum et al 2000, with permission.
Fig. 8.7. Schematic diagram showing the line of costodiaphragmatic

pleural reflection (black dotted line), the cardiac notch and the outline higher pitched tone that is described as dull. Pneumo-
of the equine lung field as determined by percussion (black and white
thorax causes increased resonance over the dorsal thorax.
dotted line). On percussion, the ventral limit of the lung field at the
11th rib is level with the point of the shoulder. The anatomical outline While many texts describe the use of percussion to detect
of the lung, however, varies during the breath cycle. Redrawn from enlargement of the lung fields in horses with RAO, this
McGorum et al 2000, with permission. feature is rarely detectable in the author’s experience.
Palpation of the Thorax

of the left hand and should press the distal phalanx Thoracic wall palpation may detect chest wall injuries,
firmly against the thoracic wall. To avoid dampening the fractured ribs, subcutaneous emphysema, or pleurodynia.
percussive wave, other parts of the left hand should not The clinician must be cautious when interpreting the
contact the thorax. This phalanx is then struck sharply response to thoracic palpation, as many normal horses
with the tips of the middle three fingers of the right hand, resent this procedure. Horses with pleurodynia may
while keeping these three fingers together in a rigid, semi- also have an anxious facial expression, are reluctant to
flexed position. The right hand is immediately withdrawn move, especially in a tight circle, or to lie down and may
to avoid damping the resultant sound wave. persistently point one forelimb or arch their back. They
Percussion is best performed at peak inspiration, when often have rapid shallow breathing, a soft and suppressed
the contrast between normal and abnormal sounds is cough, and an expiratory groan.
most easily detected. Percussion should be performed in a
systematic pattern, usually commencing at the cranio-
dorsal aspect of the thorax and working in a dorsal to
Additional Clinical Features of
ventral direction down each intercostal space, before
Respiratory Tract Disease
repeating the examination over the caudally adjacent As respiratory tract disease may result in additional clinical
intercostal space. It is essential to percuss and compare signs, a full clinical examination should be performed.
both sides of the thorax, as abnormalities may be confined Other signs include:
to one hemithorax.
Percussion over the lung fields in a normal horse ● Nasal discharge – usually bilateral but may be unilateral
(Fig. 8.7) results in a low-pitched hollow sound that is if scant and serous, mucoid, mucopurulent, purulent,
termed resonant, while percussion outwith this area pro- hemorrhagic, or food-containing in nature.
duces a dampened, higher pitched tone that is described ● Pyrexia – this is common in viral, bacterial, and
as dull. Percussion yields a more resonant tone in individ- neoplastic conditions of the respiratory tract.
uals with thin thoracic walls, such as foals and thin adults. ● Weight loss – this is common in chronic bacterial lung
Abnormal percussion findings are summarized in Table infections, respiratory tract neoplasia, and in horses
8.4. The presence of fluid or solid tissue masses within the with chronic severe dyspnea.
superficial lung parenchyma, pleural cavity or thoracic ● Cyanosis – an increase in the quantity of circulating
wall attenuate the sound wave, resulting in a flat or soft, reduced hemoglobin imparts a bluish coloration to the
mucous membranes. Cyanosis usually indicates profound Unilateral enlargement occurs with ipsilateral neoplasia,
arterial hypoxemia (PAO2 < 40 mmHg, assuming that the sinusitis and guttural pouch empyema. Generalized
hemoglobin concentration is within normal limits). It is peripheral lymphomegaly may occur in horses with
best appreciated when viewed under daylight, and may multicentric lymphosarcoma.
be unrecognizable under fluorescent lighting. ● Hypertrophic osteopathy (Marie’s disease) – affected
● Peripheral subcutaneous edema – an accumulation of horses have symmetrical, firm swelling of all four limbs
fluid within the subcutaneous tissues of the ventral and shifting leg lameness.
thorax is common in horses with pleuropneumonia.
Edema of the head may occur in horses with cranial
thoracic masses as a result of impaired venous and REFERENCES
lymphatic drainage from the head, and with purpura
Deegen E, Klein HJ 1985 On the variability of lung function
hemorrhagica following strangles. measurements in the horse – a preliminary report.
● Subcutaneous emphysema – air may track into the In: Deegen E, Beadle RE (editors) Lung Function
subcutaneous tissues following traumatic or surgical and Respiratory Diseases in the Horse. International
penetration of the upper airway or chest. Alternatively, Symposium in Hannover, Germany. Hippiatrika Verlags-
it may occur in horses with very severe pulmonary gesellshaft, Calw, pp.72–73
Dixon PM, Railton DI, McGorum BC 1995 Equine pulmonary
disorders that lead to air trapping or emphysema, disease: a case control study of 300 referred cases.
when air tracks from the ruptured alveoli through Part 3: Ancillary diagnostic findings. Equine Veterinary
the bronchovascular sheaths to the lung hilus and Journal 27: 428–435
mediastinum and thereafter into the subcutaneous Koterba AM, Kosch PC, Beech J et al 1988 Breathing strategy
tissues. Light palpation of the affected skin reveals a of the adult horse (Equus caballus) at rest. Journal of
Applied Physiology 64: 337–346
characteristic crepitation. Kotlikoff MI, Gillespie JR 1983 Lung sounds in veterinary
● Jugular vein distension –when the horse’s head is in the medicine. Part I: Terminology and mechanisms of sound
normal standing position, only that part of the jugular production. Compendium on Continuing Education for
vein in the lower third of the neck should be distended. the Practicing Veterinarian 5: 634–639
Distension above this point indicates increased central Kotlikoff MI, Gillespie JR 1984 Lung sounds in veterinary
medicine. Part II: Deriving clinical information from lung
venous pressure or obstruction of venous return such as sounds. Compendium on Continuing Education for the
occurs in horses with cranial thoracic masses. Practicing Veterinarian 6: 462–467
● Anemia – this may be detected in horses with internal McGorum BC, Dixon PM, Radostitis OM, Abbott JA 2000
carotid or pulmonary hemorrhage or with chronic Clinical examination of the respiratory tract. In:
bacterial or neoplastic diseases. Radostits OM, Mayhew IG, Houston DM (editors)
Veterinary Clinical Examination and Diagnosis. WB
● Peripheral lymphomegaly – palpable bilateral enlarge- Saunders, London, pp.213–244
ment of the intermandibular lymph nodes is common Robertson AJ 1957 Rales, rhonchi and Laënnec. Lancet
in horses with bacterial or viral respiratory diseases. ii: 417
Collection and Analysis of Respiratory
Tract Samples
9 Jennifer L Hodgson and David R Hodgson
(performance versus pleasure) may influence selection of

Introduction the laboratory technique.
There have been significant advances in our understanding
of equine pulmonary diseases over the past two decades, Indications for sampling the nasal cavity,
with much progress as a result of advances in ancillary nasopharynx, and guttural pouches
diagnostic testing. However, these techniques should not
replace the procurement of an accurate history and per- Diseases of the nasal cavity may result in nasal discharge,
forming a thorough clinical examination. The latter will epistaxis, dyspnea, inspiratory stridor, and malodorous
frequently dictate appropriate diagnostic tests to be performed. breath. Chronic unilateral nasal discharge usually results
Alternatively, a lack of specific clinical signs associated from a unilateral lesion of the URT and is seldom the
with respiratory tract disease, yet evidence of poor per- result of a primary bacterial infection. If a profuse bilateral
formance, may be indicative of subclinical or low-grade nasal discharge is present, particularly associated with
pulmonary pathology. In this situation ancillary diagnostic coughing, it is commonly indicative of pulmonary disease.
testing may detect subtle changes in the respiratory tract However, a small percentage of horses with pulmonary
that are not discernible by routine clinical evaluation. disease have unilateral nasal discharge (Dixon 1997).
Recent research has focused on the development of Diseases of the nasopharynx can be associated with
“in-field” diagnostic tests for equine practitioners. This abnormal respiratory noise, exercise intolerance, dyspnea,
chapter outlines the availability of, and requirements for, and dysphagia.
“field” techniques for collection of samples from the respi- When these signs are present, important steps in the
ratory tract of horses. Naturally the quality and diagnostic diagnostic pathway will be collection of a relevant history
value of any sample collected is directly related to the care followed by a thorough physical examination. In many
and skill used by the clinician in its gathering. Thus, tech- cases ancillary diagnostic aids, including endoscopy,
nical prowess and a solid understanding of the potential ultrasonography and radiography of the affected areas, are
errors in the processing, evaluation, and interpreta- indicated to further evaluate lesions of the URT (see
tion of these tests will improve the outcomes achieved Chapters 10, 11 and 18 respectively, for further details).
(Hoffman & Viel 1997). Based on this examination, specific sampling from rele-
A variety of samples may be collected in the field from vant sites may be undertaken as outlined in Table 9.1.
horses with respiratory disease. These include swabs,
washings, aspirates or biopsies from sites in the upper Indications for sampling the lower airways
respiratory tract (URT), as well as tracheobronchial wash- and pleural cavity
ings and aspirates (TA), bronchoalveolar lavage (BAL)
and pleural fluid (PF) collection. These samples may be Indications for TA and BAL include coughing, poor
evaluated by various methods including, but not limited to, performance, the presence of mucopus in the trachea,
cytological and biochemical analysis, bacterial culture, epistaxis post-exercise, fever of unknown origin and
viral immunology and virus isolation, and histopathology. possibly dyspnea (see Table 9.1). When choosing one or
The indications, collection techniques, handling, evaluation, both of these procedures the clinician needs to be
and interpretation of these samples will be discussed. cognizant of the differences between them. Tracheal
aspirates obtain secretions from the larger airways,
including the trachea and bronchi, and also from more
Indications distal airways, moved to the trachea by mucociliary
The indications for collection of samples from different sites clearance. Bronchoalveolar lavage harvests secretions from
within the respiratory tract will depend on the history, the smaller, more distal airways and specifically from the
clinical signs, and likely differential diagnoses. In addition, region lavaged. In certain instances, where a particular
the ease of performing the technique and the type of horse diagnosis has a high degree of certainty based on history
119
120 9 Collection and Analysis of Respiratory Tract Samples
Table 9.1. Possible sites of origin and approach to diagnosis for differing
clinical manifestations of disease relating to the respiratory tract
Site
Sinonasal Naso- Guttural Lungs Pleural

Clinical sign cavity pharynx pouch cavity Examination techniques
Nasal discharge +++ ++ +++ + – Physical exam, endoscopy, radiography likely to be most
(unilateral) diagnostically rewarding. Swab, wash or fine-needle
aspirate/biopsy of lesion(s) in nasal cavity or nasopharynx.
Wash from GP
Nasal discharge ++ ++ + ++ + Physical exam, endoscopy, radiography likely to be most

(bilateral) diagnostically rewarding. If evidence of LRT involvement
include TA, BAL. Culture of samples from nasal cavity,
nasopharynx and GP washings for diagnosis of strangles
Epistaxis +++ ++ +++ + – Physical exam, endoscopy (esp. of GPs), radiography likely
(unilateral) to be most diagnostically rewarding. If evidence of LRT
involvement include TA, BAL
Epistaxis + ++ +++ +++ + As for unilateral epistaxis

(bilateral)
Dysphagia – +++ +++ – – Endoscopy and radiography of nasopharynx, GPs and neck
Swelling of + ++ ++ – – Physical exam, ultrasound, endoscopy and radiography

sinonasal or likely to be most diagnostically rewarding. Possible
parotid area aspirate or biopsy of lesion in nose. Culture of swabs
from nose ± washings from GP for strangles
Horner – – +++ – + Physical exam including neurological exam, endoscopy

syndrome and radiology. Specific examination of GPs
Inspiratory +++ +++ ++ – – Physical exam, endoscopy and radiography. Fine-needle

stridor aspirate or biopsy of mass if observed in nares, naso-
pharynx or parotid area. Nasal and GP washing and
culture for strangles
Dyspnea + + + +++ +++ Physical exam, endoscopy and radiography. Possible

ultrasound of thorax. If evidence of LRT involvement
may include TA, BAL ± thoracocentesis
Cough – – – +++ + As for dyspnea
Poor exercise + +++ + +++ +++ As for dyspnea

performance
Fever of + + ++ +++ +++ As for dyspnea

unknown origin
Pleurodynia – – – + +++ As for dyspnea with particular attention to ultrasound

of thorax ± thoracocentesis
GP = guttural pouch; TA = transtracheal aspirate; BAL = bronchoalveolar lavage; LRT = lower respiratory tract.
and clinical signs, one or other of these techniques may et al 2003); therefore the cell population sampled by one
be indicated, e.g. BAL in cases of suspected “heaves” or technique is not representative of that obtained by the
exercise-induced pulmonary hemorrhage (EIPH); TA in other. Additionally, recent studies have shown that inflam-
suspected bacterial pneumonia, pleuropneumonia, or mation of the airways may be regionally localized; there-
fever of unknown origin. In other situations, where the fore a combination of TA and BAL is more likely to detect
diagnosis is unresolved, such as cases of poor performance airway inflammation.
or coughing during exercise, collection of samples using When there is an indication to perform both procedures,
both techniques is recommended to broaden assessment the TA should be performed first, particularly if bacterial
of the health of the lower airways. It is important to note culture is to be attempted. This is an important considera-
that no significant correlation between TA and BAL tion because BAL will result in transient bacterial contami-
cytology has been found (Derksen et al 1989, Malikides nation of the distal trachea with oropharyngeal flora.
9 Collection and Analysis of Respiratory Tract Samples 121
Contraindications for TA and BAL include horses or foals usually be collected from the nasopharynx or pharynx
with severe respiratory distress, cyanosis, marked hypo- without sedation. Nasal washes are more effective than
volemia or presence of significant dysrhythmias. In these swabs for the detection of small numbers of organisms
situations the combination of the restraint required for, because a greater surface area of the internal nares is
and stress-induced by, the procedure may have untoward sampled. The technique involves instilling about 50 ml of
effects. Similarly, horses with known defects in hemostasis warm normal saline via a 15-cm piece of sterile soft rubber
should be assessed carefully before being subjected to tubing (5–6-mm diameter) about 12 cm into the internal
these procedures. nares and collecting the washings. These are decanted into
Pleural effusion is the most common indication for sterile containers and centrifuged; the pellet obtained is
thoracocentesis (see Table 9.1). Pleural effusion may be then cultured. An alternative technique for collection of
suspected based on history, clinical signs, thoracic auscul- microbiological samples is the use of swabs. It is preferable
tation, and percussion. Confirmation of pleural effusion is to use a guarded swab to sample these sites to collect from
made with ultrasound. the specific site intended and to bypass, as much as possi-
ble, the normal flora of the nasal cavity. The latter will
contaminate samples and rapidly overgrow any pathogens
Collection Techniques during culture.
Nasal, nasopharyngeal, and guttural Samples from the URT may also be collected to confirm
pouch samples viral respiratory tract infections. Successful detection of
respiratory viruses is influenced by the time of sampling,
Lesions within the nasal passages and nasopharynx and techniques used for collection, transport, and process-
usually require endoscopic examination for adequate ing of samples. In general, success is greatest when naso-
visualization before sampling (Traub-Dargatz 1997). It pharyngeal mucus samples are collected within 48 h of the
should be remembered that sedation may distort the onset of illness, when the horse is febrile, and the nasal
nasopharynx as a result of relaxation of the surrounding discharge is serous and not mucoid. Rapid transport to, and
soft tissues. Therefore, the initial endoscopic examination of immediate processing by, the laboratory are critical to
this area should be conducted without sedation if possible. optimize chances of virus isolation.
Radiography may also help define the extent of a lesion Nasopharyngeal mucus samples can be obtained using a
prior to sample collection. Samples from lesions in the sterile 5 cm by 5 cm Dacron or cotton gauze swab inserted
nasal cavity, nasopharynx, and pharynx may be evaluated through a loop in a twisted stainless steel wire (60 cm
by cytological and histopathological examinations and long). Ideally the wire/swab combination is housed in a
culture (bacterial or fungal) (Clinkenbeard et al 2002). 40 cm length of soft rubber tubing for protection during
Lesions of the mucosal surfaces of the nasal cavity and insertion. Alternatively a guarded mare uterine swab may
nasopharynx are more frequently sampled than deeper be used. The swabs are passed via the ventral nasal meatus,
structures. For lesions close to the external nares, collection inserting the swab as far back as possible in the horse’s
of direct imprints, fine-needle aspirates and/or biopsies nasopharynx (~30 cm in 500-kg horse). Once in the naso-
is possible. Alternatively, superficial lesions such as pharynx, the swab is advanced out of the soft rubber
atheromas may be accessible via percutaneous aspiration. tubing, rubbed against the nasopharyngeal mucosa, and
Local secretions may be collected using swabs inserted then retracted into the tubing. After collection, the Dacron
through the external nares, or using a flexible endoscope. or cotton gauze swab should be placed immediately in virus
Exudates within these sites may be collected via a transport media and transported to the laboratory on ice.
transendoscopic catheter. Masses and fungal plaques can Viruses are unlikely to survive if swabs are allowed to dry
be sampled with the endoscopic biopsy instrument. out. Also, there is increased chance of sample contamina-
The varied structures (cartilage, bone, adipose tissue, tion if bacterial transport medium is used.
salivary glands, lymphoid tissue) that underlie the mucosal Some respiratory viruses (e.g. equine herpesviruses) may
surfaces may, on occasions, be sampled in the field. Core also be isolated from citrated or heparinized whole blood. If
biopsies, surgical biopsies, or fine-needle aspirates can be blood is collected for attempted virus isolation, at least
used to obtain cells from these structures if pathological 20 ml of venous blood should be obtained and transported
processes are suspected. chilled, but not frozen. Greatest success in virus isolation
from blood is usually within 4–10 days after onset of respi-
Microbiological samples ratory signs.
Complete bacteriological examination of nasal or naso- Serological tests may be used to detect antibodies to
pharyngeal samples is rarely warranted because of the respiratory viruses and therefore confirm infection. In
presence of a normal bacterial flora. In certain well-defined contrast, these tests are rarely useful for diagnosis of
circumstances isolation of specific pathogens may be bacterial diseases. Acute (taken as soon as possible after the
indicated; e.g. isolation of Streptococcus equi ss. equi from onset of clinical signs) and convalescent (taken at least
suspected cases of strangles. Microbiological samples can 10 days later) serum samples should be collected and
submitted to appropriate diagnostic laboratories. Antibody evaluation can be collected. These can be obtained by
induced by vaccination can confound interpretation of directly aspirating exudate present on the floor of the
serological results; thus vaccination history must be taken guttural pouch. If exudate is not present, 20–30 ml of
into account to ensure that detected rises in antibody titer sterile physiological saline should be infused through the
reflect the presence of infection rather than vaccination. tubing and onto the area of interest, with subsequent
Recent advances in the rapid diagnosis of viral respira- aspiration of fluid pooling on the floor of the pouch. In
tory infections have resulted from development of tests situations where concretions (chondroids) are present,
that detect the presence of viral antigens, viral nucleic acid, these may be sampled using a trans-endoscopic biopsy
or virus-infected cells in respiratory secretions. Some of forceps or basket forceps and subjected to microbial and
these tests are commercially available for field use (e.g. histopathological examinations.
Directigen FLU-A assay) and others can be performed in In horses where guttural pouch mycosis is suspected,
specialized diagnostic laboratories (e.g. polymerase chain lesions (mycotic plaques) are frequently visualized on the
reaction, PCR). Most of these tests require nasopharyngeal dorsal aspect of the pouch, often involving the internal
swabs or whole blood collected into ethylenediamine- carotid artery and adjacent neural structures. Biopsy of
tetraacetic acid (EDTA), but specialized diagnostic lab- these lesions, although tempting, may place the patient
oratories should be contacted for specific requirements at risk of severe hemorrhage. As a result, diagnosis of
if doubt exists. In addition, even when rapid “horse-side” guttural pouch mycosis is based usually on history, clinical
tests are used to diagnose equine influenza, a nasopharyn- signs, and the endoscopic appearance of the lesion.
geal swab should be taken and sent to an appropriate
laboratory for virus isolation. This will allow characteriza- Sampling the lower respiratory tract
tion of virus isolates and assist in determination of strains
for vaccines. Samples from the lower respiratory tract (LRT) are primarily
collected for cytological and microbiological evaluation.
Sampling from the guttural pouch The three most commonly used techniques for “in-field”
sampling of the LRT are TA, BAL, and thoracocentesis. The
Samples may be collected from the guttural pouches for choice of technique and method of sampling can signi-
cytological evaluation and/or microbial culture and ficantly affect bacterial numbers, cell numbers, and even
sensitivity testing. Several important structures are types of cells obtained. For this reason, standardization of
contained within the guttural pouches (Freeman 1991). technique with regard to type of technique used, time of
These structures and their anatomical associations must be sampling (e.g. at rest or after exercise), volume and type
kept in mind when sampling this site. of fluid instilled, sample handling and processing is
Samples from the guttural pouch may be collected by recommended.
blind catheterization, but with the ready availability of The timing of sample collection may influence results.
flexible endoscopes, endoscope-guided catheterization has Large increases in numbers of bacteria and inflammatory
become the preferred technique. Most clinicians find cells in the LRT can occur within 6 h of restricted head
catheterization easier if the endoscope is placed in the movement (cross tying, head elevation, transportation)
nasal passage opposite to the side of the pouch to be (Raidal et al 1995). This accumulation is generally cleared
sampled. This allows superior visualization of the pouch within 12 h of horses being released from confinement,
opening and therefore easier insertion of the catheter into although clearance may be prolonged if horses are
the pharyngeal orifice under view. Two different methods concomitantly dehydrated. This change in numbers of cells
have been described. One method involves inserting a and bacteria must be considered when interpreting the
biopsy instrument or cleaning brush in the biopsy channel results of samples collected from horses transported long
of the endoscope as a guide. This guide is extended 2–3 cm distances before collection of samples. Similarly, collection
beyond the end of the endoscope. The guide is inserted of samples after exercise can influence results. Samples
into the guttural pouch opening and the endoscope is collected 30–60 min after moderately intense exercise
rotated to open the guttural pouch flap, allowing the may yield specimens of greater diagnostic value than rest-
endoscope to be advanced into the guttural pouch. ing samples (Martin et al 1999, Malikides 2004). Samples
The guide is then removed. The second technique involves obtained at this time are more likely to contain extra
the use of a Chamber’s mare catheter, which is placed secretions, more likely to adequately represent different
into the guttural pouch and rotated to open the flap. The areas of the respiratory tract, and are therefore more likely
flexible endoscope is then passed dorsally or ventrally to to reveal the presence of airway disease if present.
the catheter and into the pouch with the Chamber’s
catheter then being withdrawn. Tracheal aspirates
Once access to the guttural pouch has been achieved, Several methods for obtaining cytological and micro-
samples for cytological, microbiological, or molecular (PCR) biological samples from the tracheobronchial tree have
been developed; each having advantages and disadvan- invasively and has fewer side effects (Mair 1987). The
tages. The most important consideration when choosing a method is well tolerated by horses and endoscopy allows
technique is whether microbiological culture of the visualization of the LRT at the time of sampling. Evalua-
tracheobronchial secretions is indicated, such as in cases of tion of the tracheal mucosa (degree of hyperemia) and its
suspected pneumonia. Aspirates obtained endoscopically luminal contents (quantity and quality of mucus, mucopus,
invariably become contaminated by upper airway flora and blood) may assist in interpretation of cytological and
and therefore are unsuitable for microbial culture unless microbiological results. Furthermore, if the length of the
specific precautions are taken. Use of a double- or triple- endoscope permits, the large bronchi may be visualized and
guarded catheter passed through the biopsy port of the purulent debris draining from a specific bronchus sugges-
endoscope may circumvent this problem. Alternatively, tive of pulmonary abscess may on occasions be recognized
the transtracheal (percutaneous) aspiration technique and sampled. However, it should be re-emphasized that
may be used. samples collected using unguarded catheters will inevitably
A variety of needle/catheter combinations may be be contaminated with bacteria from the nasopharynx
used to perform transtracheal aspiration, but maintaining and biopsy channel, making them unsuitable for micro-
asepsis is critical. The catheter/needle combinations may bial culture.
be purchased individually or pre-packaged. The latter To perform TA via an endoscope, the lowest point of the
usually include a catheter-over-needle (± stylet) and trachea, anterior to the carina and level with the thoracic
flushing/aspiration catheter. An alternative, but con- inlet (“tracheal puddle or sump”), should be visualized.
venient, combination comprises a 12-gauge needle, 7.5-cm
over-the-needle cannula and no. 5 French canine urinary
catheter with the tip cut off obliquely. Sedation is gener-
ally indicated when performing a transtracheal aspiration,
with α2-agonists being commonly used. An area measur-
ing approximately 6 × 6 cm over the middle third of the
cervical trachea should be prepared for aseptic surgery. A
bleb of local anesthetic (~0.5 ml 2% lidocaine) is injected
subcutaneously over the midline and a stab incision is
made through the skin and subcutaneous tissue with
a No. 15 scalpel blade. The trachea is stabilized with one
hand and the needle/cannula combination is introduced
into the tracheal lumen between two cartilage rings.
The needle (± stylet) is removed and the urinary catheter
is passed down into the tracheal lumen to the level of
the thoracic inlet where the washing and aspiration is
performed. A cough response may be elicited upon stimu-
lation of the tracheal mucosa. This may cause the catheter
to retroflex into the proximal trachea and result in con- A
tamination or inadvertent sampling from the URT.
Usually 20 ml of sterile isotonic saline is instilled to
obtain a satisfactory sample. However, larger volumes may
be required in some cases to ensure sufficient sample
recovery. In the adult horse, flushing and re-aspiration can
be repeated three or four times if necessary to obtain a
suitable sample. Other methods to facilitate retrieval of
infused fluid include slow retraction of the catheter while
applying gentle suction, or encouraging the horse to lower
its head slightly to facilitate more proximal pooling of fluid.
Once an adequate sample has been collected, the catheter
should be withdrawn, maintaining the cannula in situ
during this retraction to minimize contamination of
peritracheal tissues. B
An increasingly popular alternative for collection of
Fig. 9.1. (A) Tracheal aspirate being performed using a guarded
TAs is via a fiberoptic endoscope or videoendoscope (see catheter inserted via the biopsy port of a fiberoptic endoscope.
Fig. 9.1A,B). This technique has largely replaced the (B) Tracheal aspirate being performed using a videoendoscope.
percutaneous technique because it can be performed less Continued
D E
Fig. 9.1, cont’d. (C) Tracheal aspirate showing the tip of the aspiration catheter immersed in the “tracheal
puddle.” (D) Normal tracheal aspirate demonstrating a clear fluid with few mucous strands. (E) Tracheal
aspirate from a horse with severe pneumonia showing turbid, reddish-brown fluid.
A small polyethylene catheter is passed through the biopsy Another guarded catheter system involves a 5-gauge
channel and 10–15 ml of sterile isotonic saline is instilled. French inner catheter within an 8-gauge French guiding
Fluid will accumulate in the “tracheal puddle” from where catheter. Again, these guarded catheters are passed
it can be aspirated (see Fig. 9.1C). The principal use of through the biopsy channel and samples are aspirated
samples collected using this technique is for cytological whilst directly visualizing the collection site. Thorough
evaluation. disinfection of the endoscope, including the biopsy chan-
More recently, a number of guarded catheter systems nel, is essential before each collection. The risk of sample
have been developed for collection of uncontaminated contamination with organisms such as Pseudomonas spp.
samples from the LRT via endoscopy. One example is a increases substantially if disinfection is not performed. For
multi-lumen, telescoping catheter that contains a glycol this purpose, 2% chlorhexidine in 70% alcohol is an effec-
plug in the outer catheter to maintain sterility as the tive disinfectant provided that the endoscope, including the
catheter is advanced through the endoscope and into the biopsy channel, has 10–15 min contact time prior to use.
trachea. Once in place, the plug is ejected and the inner The endoscope and biopsy channel should then be flushed
catheter is advanced for aseptic retrieval of the specimen. thoroughly with sterile saline before sampling.
Although the advantages of guarded catheters are blood within the trachea should be recorded and described
many, there remains some controversy regarding the as to the location, quantity, and character/color. If a
adequacy of these samples for microbiological culture. pulmonary abscess is suspected, the bronchial segment of
Technical prowess definitely influences the quality of the the lung from which the mucopus is emanating should be
sample obtained and factors that help prevent contami- identified for later sampling.
nation include: The bronchoscope should optimally have a working
length of at least 160–180 cm to allow lavage of the distal
● rapid sample collection
lung segments of adult horses. The depth of lung
● small volume of instilled sterile isotonic saline
ultimately lavaged is dependent on the outer diameter of
(10–15 ml)
the endoscope. Bronchoscopes with a larger outer diameter
● advancement of only the inner (sterile) catheter into the
(10–13 mm) will generally wedge within a fourth- to sixth-
“tracheal puddle.”
generation bronchus and allow recruitment of cells from a
In addition, if the horse coughs frequently during larger number of airways and alveoli (Hewson & Viel
collection, the TA has an increased risk of contamination 2002). In contrast, a bronchoscope with a small outer
with oropharyngeal organisms and is rarely appropriate diameter, or use of a catheter passed through the biopsy
for bacteriological culture. Finally, isolation of upper channel, results in lavage of only a limited number of small
airway contaminants or transient bacteria, which are not airways and alveoli because wedging occurs in a more
causing inflammation, is possible with any method of peripheral bronchus or bronchiole.
aspiration and correlation of bacteriological, cytological Coughing may occur during passage of the endoscope
and clinical findings should always be performed. near the carina because of the stimulation of cough
Identification of the presence of squamous epithelial cells receptors. In most normal horses this response abates
and inflammatory cells, quantification of the numbers of within 5–10 seconds. In contrast, horses with airway
bacteria and differentiation of bacterial species is essential inflammation and hypersensitivity (particularly heaves)
when attempting to determine the significance of the may have a more prolonged period of coughing which
cultured isolates. may be alleviated by instillation of local anesthetic.
Pre-warmed, 0.4% lidocaine (12 ml 2% solution diluted
Bronchoalveolar lavage with sterile water to 60 ml) can be instilled onto the
Bronchoalveolar lavage collects samples from the distal carina when the endoscope is advanced to this point.
airways and alveoli and is most frequently used for This decreases the cough reflex and after approximately
diagnosis of diffuse and/or chronic disease processes. 30 seconds the endoscope can be further advanced into
In these cases, samples collected from either side of the the lower airways until a wedge is obtained in a seg-
lung are considered representative of the entire lung mental bronchus. This is detected as resistance to gentle
(McGorum et al 1993a). This constitutes the basis for attempts at further endoscope advancement. Once the
the use of a “blind” field technique using a flexible, cuffed bronchoscope is wedged, BAL can be performed using pre-
nasobronchial tube (see Fig. 9.2A). Alternatively, BAL warmed sterile normal saline. The fluid is instilled in two or
may be collected using an endoscope, which allows more three aliquots via the biopsy channel of the bronchoscope
specific selection of the site for lavage, especially when and retrieved using either gentle suction with 60-ml
there is suspicion of localized lung pathology. Samples syringes or using a suction apparatus set at a pressure of
obtained by BAL are most commonly evaluated cytologi- –5 to –15 cmH2O. Excessive negative pressure should be
cally, although culture of samples, on rare occasions, may avoided because it can cause collapse of the airway and
also be indicated. trauma to the respiratory epithelium resulting in decreased
BAL is usually performed in the standing animal fluid recovery and hemorrhage into the sample. The
following mild sedation with an α2-agonist. Concurrent volume of infused fluid impacts on the total and differential
administration of butorphanol tartrate (0.01–0.02 mg/kg cell counts of the resulting BAL sample (Sweeney et al
body weight) may be used in horses with severe clinical 1992). Smaller volumes typically yield a bronchial wash
signs of heaves and marked airway hypersensitivity to without retrieving cells from the alveolar space and
ameliorate the cough response. Application of a twitch is therefore have a higher percentage of neutrophils. Larger
recommended and cleaning the external nares with volumes yield samples more representative of the
moistened gauze before the procedure helps to reduce respiratory epithelial lining fluid within the alveoli. A
contamination. standard volume of 250–500 ml is currently recommended
The “blind” field and endoscopic techniques for BAL are (Robinson 2001). In general, 50–80% of the instilled fluid
technically similar except that endoscopy permits visual can be retrieved, although smaller proportions may be
inspection of the airways prior to BAL, guidance of the obtained from obstructed airways because airway edema
endoscope during collection, and the use of biopsy tools and bronchospasm result in lumen obstruction during
(Hoffman & Viel 1997). Any accumulation of secretions or suctioning. It is important to observe the presence of white
A B
Fig. 9.2. (A) Bivona® cuffed BAL tube. (B) BAL

tube being passed via the ventral nasal meatus.
(C) Schematic demonstrating BAL tube in situ sam-
pling the caudodorsal lung segment. (D) Normal
BAL sample demonstrating surface foam indica-
tive of the presence of surfactant. (E) Blood-tinged
BAL sample collected from a horse with severe,
D E
acute EIPH.
foam (surfactant) on the surface of the sample as this

indicates that alveoli have been sampled (see Fig. 9.2D).
Use of the “blind” BAL catheter technique is an alter-
native to bronchoscopy in the field if a suitable endoscope
is not available. The non-endoscopic collection of BAL uses
a flexible, cuffed nasobronchial tube with an outer
diameter of 11 mm. With the horse’s head extended the
nasobronchial tube is passed through the nasopharynx
into the trachea until a cough response is elicited (see
Fig. 9.2B). As with the endoscopic technique, use of a
topical anesthetic agent at this time may alleviate prolonged
coughing. The tube is then pushed into the lungs “blindly”
until an adequate wedge is detected as resistance to gentle
attempts for further advancement. In most cases the tube
will naturally travel to the right caudodorsal lung field Fig. 9.3. Right-sided thoracocentesis using a 14-gauge Teflon catheter
because of the anatomy of the main-stem bronchus (see and 20-ml syringe in a horse with bacterial pleuropneumonia. Note
Fig. 9.2C). The cuff is then gently inflated using 5–10 ml of reddish-brown, turbid fluid.
air, thus forming a complete wedge to prevent the backflow
of infused fluid. Again, 250 ml (and up to 500 ml) of pre-
warmed sterile saline (5 × 50 ml) is infused using 60-ml prepared. If the “blind” technique is used, the major
syringes, with 100 ml first infused and withdrawn, followed objective is to insert the needle at a site sufficiently caudad
by each additional 50–100 ml being infused and withdrawn. to the heart, yet obtain access to the more cranioventral
The samples are pooled at the end of collection where regions of the thorax. On the right hand side this site is
aspiration should yield 60–80% of the instilled fluid. located over the sixth or seventh intercostal spaces up to
Complications of BAL are minimal. A neutrophilic 10 cm dorsal to the level of the olecranon. On the left side,
inflammatory response occurs within the lavaged lung, and the sixth to ninth intercostal spaces may be selected,
can be detected if subsequent lavages are performed within 4–6 cm dorsal to the olecranon. The needle or catheter
48 h (Sweeney et al 1994). This response is usually limited should be inserted just anterior to the cranial margin of the
to the bronchus and lung segment lavaged, but occa- rib as this reduces the risk of laceration of the intercostal
sionally may be noted also in the contralateral lung. On vessels and nerves. Infiltration of local anesthetic
occasion a mild increase of rectal temperature has been (10–20 ml 2% lidocaine or prilocaine) into the subdermis,
reported in horses for less than 24 h after BAL, with no intercostal muscles, and, most importantly, the parietal
apparent adverse clinical effects. However, any persistent or pleura is regarded as essential to decrease the pain asso-
exaggerated pyrexia accompanied by signs of depression ciated with this procedure. The parietal pleura have a high
should prompt further evaluation. density of pain receptors that are irritated with pleural
inflammation. Local anesthesia reduces pain and patient
Thoracocentesis movement thereby increasing the likelihood of obtaining a
Thoracocentesis can be performed in the standing horse diagnostically useful sample.
with minimal restraint. Horses often have a fenestrated Although a variety of needles and cannulas are suitable
mediastinum, so PF collected from either side of the thoracic for thoracocentesis, a 14-gauge, 13.3-cm Teflon catheter is
cavity should be similar. However, in pathological condi- ideal (see Fig. 9.3). Alternatively, a sterile teat cannula
tions mediastinal fenestrations may become obstructed can be used, although a stab incision of the skin and
with fibrin resulting in the two sides of the thorax being muscle should be made to facilitate its insertion. Prior to
affected to different degrees. This will be reflected in insertion, a 10 or 20-ml syringe should be connected
differing physiochemical properties of PF from each hemi- to the catheter/cannula. Entry of the catheter/cannula
thorax. Thus, in cases where pleural pathology is sus- through the parietal pleura may be recognized by a
pected, samples should be collected from both sides of the palpable ‘popping’ and subsequent decrease in resistance
chest. The location of PF for sampling is best determined to insertion. If using a Teflon catheter the needle stylet
by ultrasound examination of the pleural spaces. If ultra- should be removed at this stage, then gentle aspiration
sound equipment is not available, thoracocentesis can performed (see Fig. 9.3). Alterations in the depth to which
be performed using a “blind” technique based on anatom- the catheter is inserted may be required to obtain fluid.
ical landmarks. In general multiple punctures of the parietal pleura
Thoracocentesis should always be undertaken using should be avoided as this may result in leakage of PF
aseptic technique regardless of the requirements of the within muscle planes and subcutaneous tissues causing
sample. A 4 × 4-cm area of the thorax should be surgically localized cellulitis.
Using standard techniques, 2–8 ml of PF may be can be extended to 24 h if samples are stored at 4°C. In
obtained from many normal horses, although no fluid is addition, bacterial overgrowth of samples rarely occurs
also common. If pleural effusion is present a sample can over 24 h in samples stored at 4°C. In contrast, samples
often be readily obtained on the first attempt. Only 1–2 ml that are not refrigerated are at risk of rapid bacterial
of fluid is usually required for a total nucleated cell count, overgrowth with pathogenic or contaminant organ-
cytological examination, total protein measurements, and isms, potentially confusing interpretation. Finally, strictly
bacteriological testing (if required). However, if no fluid is anaerobic bacteria, often isolated from horses with pneu-
collected another site may be selected or a sterile 30-cm monia, rarely survive any storage regimen, particularly if
bitch catheter or longer thoracic catheter can be used. at cooler temperatures.
Difficulty in collecting a sample usually indicates that If longer delays are anticipated or refrigeration of the
the volume of PF is not increased, an incorrect site has sample is not possible, samples for cytological evaluation
been sampled, or that the effusion is loculated rather may be of diagnostic use if a subsample is diluted in
than diffuse. In these cases use of ultrasonography is an equal volume of fixative solution. In these cases the
encouraged to guide thoracocentesis. Changes to PF, laboratory where the sample is to be processed should be
especially red discoloration, occurring during collection contacted to determine which fixative is preferred, as the
indicate peripheral blood contamination and should be subsequent staining technique will influence the choice of
taken into account during interpretation. fixative. In addition, a portion of the sample should be left
Pleural fluid should be collected into an EDTA tube undiluted in an EDTA tube for total red blood cell (RBC)
for cell counts, cytological analysis, and total protein and nucleated cell counts.
measurements (refractometric) (DeHeer et al 2002). A Samples for microbial culture should always be pro-
subsample should also be deposited into plain (serum) cessed as soon as possible. Realistically, the time between
tubes for biochemical analysis and bacterial culture. sample collection and processing may range from minutes
Alternatively, an appropriate liquid culture medium (e.g. to hours, but delays of longer than 24 h are likely to
blood culture media) may be inoculated directly after preclude valid microbiological results. Therefore culture
collection because this will facilitate isolation of causative after this period is not recommended. Sample drying
bacteria, especially strict anaerobes. If this culture (all microorganisms), exposure to a noxious atmosphere
system is not available to the practitioner, at least one plain (oxygen for obligate anaerobes), and bacterial overgrowth
tube should be filled completely with PF to remove all are the major concerns if samples are not analyzed
air from the tube for subsequent anaerobic culture of the promptly. Moistness may be maintained in swabs by placing
fluid. Ideally, the reference laboratory should be contacted them in transport medium composed of a balanced salt
for recommendations on handling and transportation of solution, usually in a gelled matrix. Because this medium
these samples. does not contain any nutrients, microorganisms in the
Complications of thoracocentesis are not common. sample multiply poorly and therefore relative numbers and
Improper technique may result in pneumothorax, lung ratios are preserved. Some organisms will remain viable for
laceration, hemothorax, cardiac dysrhythmias, or puncture up to a day, but the exact duration of survival will depend
of bowel, liver and heart. Mild pneumothorax resulting on the microorganism involved. For example, β-hemolytic
from aspiration of air through the catheter/cannula rarely streptococci do not survive as long as Escherichia coli.
causes clinical signs with small volumes of free air (up to This must be taken into consideration when interpreting
200 ml) in the thoracic cavity being resorbed rapidly. culture results. Samples placed in fluid culture media may
Occasionally, localized cellulitis surrounding the thoraco- support bacteria for longer periods but the original relative
centesis site may occur. proportions of bacteria will be lost because of the differen-
tial growth rates of bacterial species. Those samples sus-
pected of containing strictly anaerobic bacteria (e.g. pleural
Sample Handling, Transportation, effusions, lung abscesses) should be cultured immediately if
and Processing these bacteria are to be recovered. Swabs are an inferior
Sample handling method of transport for anaerobes compared to fluid
media. However, if swabs are used for collection of samples,
As samples from the respiratory tract are often collected one swab should be placed in an anaerobic transport
in the field, there is a necessary delay whilst samples medium and maintained at room temperature. Do not
are transported to the laboratory. Every effort should be refrigerate swabs suspected of containing strict anaerobes
made to transport these samples in a timely manner to because some species do not tolerate reduced temperatures.
prevent deterioration of cellular morphology and bacterial Specimens submitted for viral isolation should be placed
proliferation. Minimal cellular deterioration will occur if in virus transport media in sealed containers for safety
processing occurs within 8 h of collection when samples during transport. Submitted tissues should be stored
are stored at room temperature (Pickles et al 2001). This on ice (4°C), or alternatively may be frozen (–20°C) if
histopathology is not required because freezing destroys to prevent alterations in cell morphology; a small desk-top
tissue morphology. Tight plastic wrapping of the specimens fan will assist rapid drying.
should be avoided because it enhances autolysis and A variety of routine hematological stains may be used if
necrosis, which decrease the concentration of infectious cytological preparations are to be examined within the
viral particles. All samples submitted to a diagnostic labora- practice setting. In general, the use of a simple stain such
tory should be clearly identified. as Diff Quik is sufficient for routine analysis of samples
from the respiratory tract, although Wright–Giemsa,
Slide preparation and staining May–Grünwald or Leishmann’s stains also may be used. In
more complex cases, the use of special stains may be
In all situations it is optimal if smears are made as soon as indicated. Special stains can assist with further identi-
possible after sample collection. This is recommended fication of cytological elements. Examples include Gram
because the smears will serve as a reference point for stain for bacteria, non-specific esterase (α-naphthyl acetate
cellular morphology and microbial populations at the time esterase) to differentiate immature macrophages from
of sampling. Smears should be submitted to the laboratory large lymphocytes, and Perl’s Prussian blue for hemo-
with all other samples. siderin. In addition, the metachromatic granules of equine
Smears are made from swabs by gently rolling the swab mast cell are refractory to modified Wright–Giemsa stains
across a clean glass microscope slide and allowing it to air (Diff Quik) and require specific staining (e.g. Leishmann’s
dry. Rolling the swab reduces the risk of rupturing cells, or Toluidine Blue).
which often occurs if the swab is rubbed or dragged across Finally, when utilizing outside laboratories, it is best to
the slide. Samples collected by brushing of mucosal determine in advance of specimen collection any special
surfaces can be gently impressed on the slide. Similarly, requirements for sample storage, shipment, and submission
rubbing or dragging the brush across the slide surface favored by the particular laboratory. These requirements
should be avoided. A variety of techniques can be used to will be influenced by the analyses requested. In most
make smears from fine-needle aspirates and biopsies. These instances, air-dried, direct or concentrated line smears of
techniques are beyond the scope of this chapter and fluid, together with aliquots in EDTA and plain tubes, and
readers are referred to the extensive coverage provided in samples in culture transport media are appropriate.
texts on diagnostic cytology (Cowell & Tyler 2002).
Samples collected using washes (e.g. nasal or guttural
pouch washes, TA or BAL) should first be assessed grossly
Evaluation
to determine the amount of mucus, mucopus or blood Gross examination
present before making smears. If the sample is clear, or
contains only few strands of mucus, centrifugation is The gross appearance of fluid samples (TA, BAL or PF)
required before smear preparation because of its low should be assessed initially for turbidity, presence of
cellularity. Cells can be harvested by centrifugation of flocculent debris, odor, clot formation, and color. In
approximately 1–5 ml of sample for 5 min at 350 g. The addition, BAL fluid (BALF) should be examined for a
supernatant fluid is poured off, the pelleted material is surface layer of foamy surfactant indicating that the
gently resuspended, and a drop of suspension is applied to sampling process was adequate (see Fig. 9.2D).
a clean glass slide with an applicator or pipette. The Normal TAs, BALF and PF should appear clear or mildly
sediment can then be spread using a “blood (line) smear turbid (see Figs 9.1D, 9.2D). Turbidity of TAs and BALF
technique”. Alternatively, cells may be concentrated using from horses with clinical respiratory disease ranges from
a cytocentrifuge or using the perspex block and cell clear to opaque (see Figs 9.1D and E, 9.2D and E). Increased
sedimentation technique (Nicholls & Pirie 2001). The latter turbidity and the presence of flocculent material reflects
technique yields slightly greater lymphocyte numbers increased mucus, cells and cellular debris. Occasionally,
than cytocentrifugation, produces excellent quality slides pieces of plant material or debris may be observed in TAs
for interpretation of cell morphology and is reported to be and BALF if the horse had undertaken strenuous exercise
more suitable for use in the field. before sampling. Increased turbidity of PF reflects increased
If the sample is turbid, contains many mucus strands, or cellularity and protein content. Flocculent material visible
is dark red, a direct smear may be prepared from either the within PF usually comprises strands of fibrin. Rarely
freshly collected sample or the fixed diluted sample after ingesta may be observed in PF secondary to either
thorough mixing. Dilutions of a turbid TA may also be accidental enterocentesis or gastrointestinal rupture.
performed using sterile isotonic saline, and the diluted All fluids should be odorless normally. A putrid smell
sample can be processed by cytocentrifugation. Addition may be associated with anaerobic infections or necrosis of
of saline to thick tenacious samples helps to dilute the lung tissue and is consistent with a guarded prognosis.
cellular and mucous elements, making interpretation However, the absence of a foul odor does not rule out
easier. All smears should be air-dried as rapidly as possible disease processes.
Pleural fluid from healthy horses contains a negligible though mostly only in reference laboratories. The total
quantity of fibrinogen and will not clot. Blood contami- protein concentration of normal PF is < 25 g/l (2.5 g/dl)
nation of, or protein exudation into, PF will increase fluid (DeHeer et al 2002). With small sample volumes (i.e.
fibrinogen content resulting in clot formation when the EDTA tubes are less than a quarter full), erroneous
sample is exposed to air. results for fluid protein concentrations and cell counts
Tracheal aspirates and BALF are normally clear or may be obtained. Protein concentrations as determined
colorless, whereas PF is pale yellow. Color of the fluid by refractive index may be artificially increased (solute
samples in clinical cases will vary with numbers and effect of the EDTA), whereas protein concentrations as
relative proportions of erythrocytes and nucleated cells and determined chemically (e.g. biuret technique) may be
presence of biochemical constituents such as hemoglobin artificially decreased (dilutional effect).
or lipid. Thus, color is a useful gauge because it may ● Glucose and lactate concentrations and pH may
indicate the type of underlying pathology. For example, be measured to assist in differentiating septic from
shades of pink to red will occur with the presence of red non-septic pleural exudates. If these analytes are to
cells or free hemoglobin in the specimen. Tracheal aspirates be assayed, samples should be collected into tubes
or BALF from horses with recent EIPH may appear pink or containing fluoride–oxalate to prevent cellular metab-
red (see Fig. 9.2E), whereas more long-standing hemor- olism of glucose. Water-soluble molecules of low molec-
rhage may result in brown-tinged fluid because of the ular weight, such as glucose and lactate, readily
presence of hemosiderin. Reddish brown, port wine, or diffuse from the circulation into PF, resulting in similar
muddy-colored PF may be associated with ischemic tissue concentrations in blood and PF in normal horses.
injury, necrosis, or neoplasia. Milky or opalescent dis- Increased anaerobic glycolysis by metabolically active
coloration of PF is the result of increased nucleated cells cells (leukocytes or neoplastic cells) or bacterial organ-
or elevated lipid content, as occurs in chylous and pseudo- isms may decrease glucose concentrations, increase
chylous pleural effusions. Exudative pleural effusions are lactate concentrations, and decrease pH. Consequently,
more likely to be discolored and turbid, attributable to their decreased PF glucose (< 0.4 g/l or 40 mg/dl), increased
increased cellularity and protein content. In these circum- lactate (greater than a paired blood sample) and
stances, it is diagnostically useful to examine the sample’s decreased pH (< 7.0) are considered by some to be useful
sediment and supernatant fluid. In the field this can be in predicting sepsis, even in horses where PF microbial
done by allowing the fluid to sediment by gravity, whilst in cultures demonstrate no growth. Pleural fluid glucose
the laboratory microhematocrit or routine centrifugation concentrations > 0.6 g/l (> 60 mg/dl) may be inter-
can be used. The height of the sediment in the tube is preted to suggest an uncomplicated (non-septic) pleural
usually proportional to the cellularity of the fluid, while the effusion (DeHeer et al 2002).
color varies according to the relative numbers of RBCs and ● Pleural fluid triglyceride and cholesterol concen-
nucleated cells present. The sediment may be red when trations are useful in distinguishing chylous from
RBCs predominate or brown to off-white or gray when pseudochylous effusions. Chylous effusions are charac-
nucleated cells dominate. Red, reddish-brown, amber or terized by triglyceride concentrations greater than, and
brown discoloration of the supernatant fluid usually reflects cholesterol concentrations less than, paired serum values.
damage to RBCs that occurred before collection. Conversely, elevated PF cholesterol and low triglyceride
When PF grossly resembles whole blood, comparison values are expected in pseudochylous effusions.
of packed cell volume (PCV) of the fluid with venous blood
should be performed. In addition, determination of clot- Mucus
ting times and cytological appearance may be useful to
determine the source of the blood (venous versus tho- Evaluation of the quantity of mucus within a TA or BAL is
racic cavity). best performed in conjunction with endoscopy of the lower
airways. This will facilitate accurate estimation of the
Biochemical evaluation amount of mucus present in the airways, as opposed to just
the quantity of mucus collected. Endoscopic evaluation of
Biochemical evaluation is routinely performed only on PF, the quantity and quality of mucus in the lower airways is
and not on TAs or BALF. Generally, protein content is described elsewhere in this book (see Chapter 5).
measured, though a variety of additional biochemical The mucociliary clearance mechanism in normal horses
variables may be determined when specific pathological is efficient, such that mucus elimination keeps pace with
conditions are suspected. production (Whitwell & Greet 1984). Consequently, the
healthy LRT contains little or no mucocellular material and
● Total protein content of PF is routinely measured low numbers of free cells. Tracheal aspirates and BALF
using a refractometer on samples collected into EDTA. from normal horses are translucent and light gray, with a
Chemical methods (e.g. biuret technique) may be used, few fine strands of clear mucus, which may appear as
flocculent material. Cytologically, scant amounts of mucus mucus strands and other debris before analysis. However,
should be observed, which appears as fine strands of filtering of TAs or BALF can cause a significant reduction
pink to light blue amorphous or fibrillar material on in TNCC as well as selective loss of specific cell types
Diff-Quik-stained preparations. including epithelial cells, macrophages and mast cells
In cases where increased amounts of mucus are (Hewson & Viel 2002). In addition, results from automated
observed endoscopically, cytological evaluation is essential cell counters should be interpreted with caution as the
for accurate interpretation. For example, horses with a broad range of cell sizes and clumps of epithelial cells
history of chronic coughing may have TAs that appear within the sample may be outside the calibration range of
grossly mucoid and gray-white, giving the impression of the instrument. Total nucleated cell and erythrocyte counts
septic bronchitis. However, cytology frequently demon- of PF are performed as for a blood sample.
strates large numbers of active macrophages in a copious The TNCC varies appreciably in TAs and BALF based on
amount of mucus, with insignificant numbers of bacteria the collection technique and the method used to estimate
cultured (Beech 1991). cell counts. In addition, laboratories may have variable
The quantity of mucus in the lower airways increases ranges for TNCC depending on the horse population they
with pulmonary irritation. In these cases the TAs or BALF test. In general, a TA from a clinically normal horse usually
will contain variable amounts of thicker, more tenacious, contains <109 cells/liter, with few to no RBCs present. The
gray to cream mucus. Cytologically, the mucus may be reference range for BAL fluid is usually <109 cells/liter,
thick and inspissated (deeply basophilic staining) or form though an upper limit of 4 × 108 cells/liter is used in some
airway casts (Curschmann’s spirals). These may be found laboratories (Hewson & Viel 2002). The TNCC for normal
in increased numbers in chronic conditions and in severe PF should be less than 8 × 109 cells/liter and is frequently
suppurative inflammatory disease, although low numbers much lower (DeHeer et al 2002).
may be observed in normal horses. Additionally, trapped,
degenerating leukocytes may be observed within thick Cytology
mucus strands.
Cytological evaluation of samples obtained from the res-
Cell counts piratory tract is reliant on an appropriate knowledge of the
cells routinely present in various sites and their normal
Quantification of the total number of cells/ml of sample morphological appearance. In addition, determining
retrieved may help indicate overall cellularity as well as the relative proportions of these cells aids the interpre-
assisting interpretation of relative numbers of individual tation of pathological changes. Relative proportions are
types of inflammatory cells. However, a number of factors determined by performing a differential cell count on at
will influence the accuracy of these counts. Total nucleated least 200–300 consecutive cells. Additionally for PF, the
cell counts (TNCC) are accurate when samples are obtained percentage values should be related to the TNCC, total
without prior infusion of fluid, such as for PF. In contrast, protein concentration, and volume of fluid present to
only an estimate of the cell count within the lung optimize an accurate interpretation.
secretions can be deduced from TA and BALF cell counts as Before undertaking a differential cell count, the entire
the infused saline dilutes cell concentrations. Furthermore, slide should be examined under low (10× objective) and
the saline dilution factor varies depending on the amounts high (40× objective) power to identify regional discrep-
of saline infused and retrieved. A number of techniques ancies. These commonly occur in association with cells
have been developed to estimate the effect of saline dilution trapped in mucus strands and between the base and the tip
including the urea dilution technique (McGorum et al of a slide. If discrepancies are detected, all regions of the
1993b). However, urea concentration can increase slide should be included in the differential cell count. When
markedly in alveolar fluid with pulmonary inflammation assessed by an experienced cytologist, evaluation of a slide
affecting the accuracy of results. Alternatively, a crude under the 40× objective is usually sufficient to be able to
method to control for saline dilution is through routine use evaluate individual cells for their cytological features
of standard techniques and repeatable sites for performing including nuclear chromatin pattern and presence of
lavages/aspirates, combined with attempts to ensure nucleoli. Practitioners may find performing the final
40–80% of the instilled fluid is retrieved (Hewson & Viel differential cell count under oil immersion (100× objective)
2002). Finally, large amounts of mucus will also influence easier to more accurately identify the specific morpho-
the TNCC because of the trapping of cells. logical characteristics of each cell and to detect any intra-
Despite these shortcomings, TNCC and RBC counts or extra-cellular microorganisms.
should be performed as precisely as possible using either Tracheal respiratory secretions are an accumulation of
a Neubauer hemocytometer counting chamber or an discharges from all areas of the lung, with variable delay in
automated cell counter. If an automated cell counter is their transit to the trachea. These delays may be marked
used, flocculent samples may be filtered to remove excess when pulmonary disease is present because of decreased
10.0 μm
10.0 μm
Fig. 9.4. A small cluster of ciliated columnar epithelial cells. Note hair-
like cilia extending from apical ends of cells (arrows). Diff Quik (×400). Fig. 9.5. Goblet cell. Note the numerous, purplish-staining, cyto-
plasmic mucin granules in the apical end of the cell (arrow). Diff Quik
(×1000).
mucociliary clearance rates. Consequently, cells collected

by TAs are frequently degenerate and more difficult to squamous epithelium to pseudostratified ciliated and non-
differentiate. Cytological examination is also hampered by ciliated columnar epithelium containing numerous goblet
the presence of dark-staining mucus strands in the cells. Columnar epithelial cells appear as medium-sized,
background (Dixon 1997, Hodgson & Hodgson 2002b). elongated cells with basophilic cytoplasm and central to
In contrast, cells observed in cytological preparations of basal nuclei. Ciliated cells have pink-staining, hair-like cilia
BAL and PFs are better preserved and usually easier to extending as a fringe from the apical end of the cell (see
identify (McGorum & Dixon 1994). Fig. 9.4). Goblet cells are non-ciliated, mucus-producing
cells found interspersed between ciliated columnar
Red blood cells epithelial cells (see Figs 9.1B and 9.15). Goblet cells vary in
Although low numbers of RBC are frequently observed size and shape, depending on the number of secretory
in TAs, BALF and PF collected from clinically normal granules in their cytoplasm. The nucleus is generally
horses, they are usually considered to reflect minor located at one end of the cell (basal), with red to purplish-
iatrogenic hemorrhage during collection. Accordingly, staining secretory granules at the other (apical) end. Free
erythrophagocytosis by macrophages is not a feature of secretory granules may be observed in some preparations.
fluid samples from healthy horses. The supernatant fluid The pharynx is lined primarily by pseudostratified
should also be clear, with no evidence of hemolysis in ciliated columnar epithelium, but also has areas of
normal specimens. stratified squamous epithelium. The mucosa of the guttural
pouches and paranasal sinuses consists of transitional
Epithelial cells epithelium and simple ciliated columnar or cuboidal
The epithelial cells detected will differ depending on the site epithelium containing goblet cells (Chiesa et al 1999).
of collection (Clinkenbeard et al 2002). Thus, the types of Cytologically, cuboidal epithelial cells of transitional
epithelial cells observed can help confirm the actual site of epithelium appear as medium-sized cuboidal cells with
collection, or potential contamination from other areas rounded borders, basophilic cytoplasm, and large central
during collection. nuclei composed of finely stippled chromatin with areas of
Samples from the normal URT consist of exfoliated condensed chromatin.
epithelial cells characteristic of the area sampled together Samples collected from the LRT similarly reflect the
with low numbers of inflammatory cells. The nasal normal respiratory epithelium of this region, together with
epithelium caudal to the vestibule progresses from stratified inflammatory cells present as the first line of respiratory
Identification of the presence of these cells is important

to be able to interpret the results of microbial culture
accurately. They are large flat cells that usually stain
lightly basophilic. Their cytoplasmic borders are often
straight with distinct corners (see Fig. 9.6).
Epithelial cells may also be identified in BALF but are
less common than in TA. In this fluid, ciliated columnar
epithelial cells, cuboidal non-ciliated cells, and squamous
epithelial cells are most commonly observed. The latter
cells occur as a result of oropharyngeal contamination at
the time of sample collection.
Inflammatory cells
SEC
M Occasional inflammatory cells (macrophages, lymphocytes,
neutrophils, eosinophils) may be observed in samples from
the URT of normal horses. In the LRT, these cells are
present in higher numbers, and in BALF and PF samples
they are the predominant cell types. In TAs, moderate
20.0 μm
numbers of inflammatory cells, in particular pulmonary
alveolar macrophages, should be observed.
Fig. 9.6. Squamous epithelial cell (SEC) with surface bacteria (cocci).
Large variations in the proportion of inflammatory cells
A macrophage ingesting a pollen granule is also present (M). Diff Quik in TA and BALF from normal horses are reported. This may
(×1000). reflect differences in sampling technique and sample
processing, but also is influenced by the geographical
location of the horse at the time of collection. In general,
defense mechanisms. Tracheal aspirates collect cells from stabled horses will have a higher proportion of inflamma-
the entire LRT and should thus contain cells from all tory cells, most likely a response to low-level irritation by
levels of the pulmonary tree. This should include columnar inhaled agents. These mild elevations in the proportions of
and cuboidal epithelial cells and pulmonary alveolar inflammatory cells, often accompanied by a mild increase
macrophages. Limited interpretation is possible if cells in the amount of mucus, probably represent a normal
from all levels are not represented and TAs should be response to these noxious stimuli and in all probability do
regarded as diagnostically inadequate if there is scant not contribute to decreased respiratory function. However,
cellularity, or if epithelial cells predominate in the absence if prolonged, this irritation may act as a risk factor for the
of macrophages. development of more permanent respiratory tract
Tracheal aspirates from normal horses contain low pathology (Malikides 2004). Clear-cut reference values for
numbers of epithelial cells, although increased numbers normal horses under different environmental conditions
may be observed in samples obtained endoscopically. The need to be established for BALF and particularly TAs to
epithelial cells are predominantly ciliated, with their size better define abnormalities in these samples.
reflecting the site of origin. Columnar cells originate from Defining cut-off values for normal percentages of
the larger airways (trachea and bronchi) and cuboidal cells inflammatory cells is difficult because of the considerable
from the smaller airways (distal bronchi and bronchioles). variation between studies. In general, however, it is
Ciliated columnar epithelial cells are present commonly in considered that BALF should have <5% neutrophils,
small clumps or clusters and a thin, cone-shaped pedicle <2% mast cells and <0.5% eosinophils (Hoffman 1999,
may be observed on the basilar border, particularly if cells Robinson 2003). Wider ranges in the proportions of
are harvested by mechanical trauma. Goblet cells may lymphocytes (30–60%) and macrophages (40–70%) are
be observed interspersed among the tracheobronchial reported; therefore ascribing cut-off values for these cell
epithelial cells. They are rarely observed in TAs from types is more complicated. Tracheal aspirates should have
normal horses, though their numbers may be increased in <20% neutrophils, <1% eosinophils, <10% lymphocytes
samples collected by endoscopic methods. and very few mast cells (Hodgson & Hodgson 2002a).
Squamous epithelial cells should not be present in TAs Finally, wide variation in the proportions of inflamma-
from normal horses. When present they represent tory cells in PF may occur in normal horses, making
oropharyngeal contamination at the time of sampling or interpretation of any changes in the proportion of these
result from aspiration of oropharyngeal secretions. These cells difficult. Reported proportions include neutrophils
cells are frequently covered by bacteria, and therefore 32–91%, lymphocytes 0–22%, large mononuclear cells
provide a significant source of microbial contamination. 5–66%, and eosinophils 0–9% (DeHeer et al 2002).
20.0 μm 20.0 μm
A B
Fig. 9.7. (A) Two non-active macrophages in BALF (arrows). Diff Quik (×1000). (B) Activated macrophage
with increased vacuolation (arrow). The adjacent cell is a binucleate macrophage. Diff Quik (×1000).
Continued
Macrophages and hemosiderophages intracellular fungal spores or hyphae may be observed (see
Pulmonary alveolar macrophages are the most abundant Fig. 9.13), but should not be interpreted as evidence of
inflammatory cell in TAs and BALF from normal horses. fungal pneumonia. More commonly, fungal elements are
Typically non-reactive macrophages have an indented oval simply phagocytosed inhaled airborne fungal elements.
nucleus, with a relatively homogeneous chromatin pattern In the case of fungal pneumonia, other cytological or
and moderate amounts of gray cytoplasm (nucleus to clinical evidence of disease must be evident to confirm
cytoplasm ratio is typically <1 : 3) (see Fig. 9.7A). Their this rare diagnosis.
nucleus can be quite pleomorphic, varying from elongated, Multinucleated macrophages (giant cells) are com-
round, convoluted, to lobulated. These cells may contain monly observed in low numbers in TAs and BALF from
phagocytosed debris such as erythrocytes, apoptotic cells, horses with no evidence of inflammation (see Fig. 9.7D).
fungal spores, hemosiderin, and pollens (see Fig. 9.7C). In Increased numbers of these cells may occur in chronic
low amounts, such debris is considered normal because inflammation, but this is an inconsistent finding.
pulmonary alveolar macrophages constitute one of the first Following respiratory tract hemorrhage, RBCs within
pulmonary defense mechanisms. the airways are rapidly phagocytosed by pulmonary
The activity of macrophages present in fluid samples alveolar macrophages (erythrophages; see Fig. 9.7E). The
may vary considerably. Reactive macrophages tend to RBCs are subsequently degraded and their heme pigment is
have abundant, more basophilic cytoplasm with ruffled reduced to hemosiderin, giving rise to hemosiderophages
cytoplasmic margins. In addition, they often have promi- (see Fig. 9.7F). This pigment is easily recognized in prepa-
nent cytoplasmic vacuoles and inclusions (see Fig. 9.7B). rations using routine hematological stains, but may be
Macrophages with finely vacuolated cytoplasm are not confirmed with special stains such as Perl’s Prussian Blue,
considered abnormal, but marked increases in cytoplasmic which positively stains ferric iron. In Diff-Quik-stained
vacuolation, or large vacuoles that distort the cell and smears the color of the heme pigment is dependent on its
displace the nucleus, are usually present only when there is age, olive green pigment indicating more recent hemor-
pulmonary disease. This increase in cytoplasmic reactivity rhage, with the pigment becoming more golden brown as it
occurs in response to infective, irritant, and small airway ages. The amount of pigment within hemosiderophages
allergic disease or airway obstruction. The cytoplasmic varies and some cells may contain a few granules, whilst
inclusions reflect the amount and type of endogenous and others contain substantial pigment deposits.
exogenous materials present in the lower airways. In these
cases, the presence of many macrophages with ingested Large mononuclear cells
cellular debris or whole cells is common and reflects Macrophages in PF are frequently difficult to differentiate
increased cellular turnover. However, care must be taken in from other large mononuclear cells and therefore are cate-
the interpretation of ingested elements. For example, gorized in one group. This category incorporates non-reactive
20.0 μm
C
10.0 μm
20.0 μm Fig. 9.7, cont’d. (C) Macrophage containing pollen granules (arrow)
within strands of pink mucus. Diff Quik (×1000). (D) Multinucleated
giant cell. Diff Quik (×1000). (E) Macrophage ingesting numerous red
blood cells (erythrophagocytosis). Diff Quik (×1000). (F) Several
hemosiderophages containing numerous dark green/black hemo-
D
siderin granules. Diff Quik (×1000).
(tissue) macrophages of blood monocyte origin, reactive sheets or rafts, with a uniform cellular appearance that
(tissue) macrophages, and mesothelial cells. They may also is polygonal to rhomboid shape (see Fig. 9.8A). In exuda-
be referred to collectively as mononuclear phagocytes, tive effusions, mesothelial cells may become reactive or
because all have phagocytic potential. All of these cells are transformed and may exhibit hyperplastic and eventually
large, with a moderate nuclear to cytoplasmic ratio and dysplastic features indicative of increased proliferation,
abundant, somewhat basophilic cytoplasm. Their nucleus including increased cytoplasmic basophilia, multinu-
is usually oval with a finely reticular chromatin pattern. cleation, prominent nucleoli, and mitotic activity (see Fig.
Mesothelial cells may occasionally exhibit distinctive 9.8B) (DeHeer et al 2002). Care must be taken when
features. For example, a fine eosinophilic “corona” or halo interpreting these cellular changes because hyperplastic/
of glycocalyx may be evident along the cell margin. In dysplastic features can begin to mimic neoplasia in severe
transudative effusions, mesothelial cells may occur in inflammatory conditions.
chromatin pattern. In TAs, they may be difficult to

differentiate from some small macrophages, “stripped”
epithelial cell nuclei, and “end-on” epithelial cells. As a
result this group may be referred to as small mononuclear
cells. Plasma cells (or reactive lymphocytes) are anti-
genically stimulated lymphocytes. They are larger than
neutrophils and are recognized readily by their royal-blue
cytoplasm, which may contain a pale-staining Golgi
apparatus. The nuclear chromatin pattern is moderately
granular and nucleolar rings (a slight clearing of the
chromatin where the nucleolus is located) are seen
occasionally.
Neutrophils
These cells usually have a lobulated nucleus with a coarse
chromatin pattern and relatively colorless cytoplasm.
Although a population of well-preserved neutrophils
resides in horses’ airways, the relative proportion of these
cells is considered to be normally low. However, neutrophils
respond to a variety of stimuli, and their numbers may
100 μm fluctuate rapidly. In addition, neutrophils generally are
A found in higher proportions in TA than in BALF from
normal horses. This possibly reflects the greater exposure
to noxious influences occurring in the larger airways. The
proportion of neutrophils normally present in PF is highly
variable (30–90%) and the total number of neutrophils per
unit volume is a more reliable indicator of pathological
influences on this cell line in PF.
Neutrophils entering the airways and thoracic cavity do
not return to the bloodstream. Consequently, in situ cell
aging and death are normal events for this cell. Low
numbers of aged neutrophils are often observed with
moderately hypersegmented to pyknotic nuclei. In addition,
leukophagocytosis of senescent neutrophils by macro-
phages may be observed. Neutrophils in normal fluid
samples from the LRT exhibit little to no phagocytic
activity per se.
20.0 μm
Neutrophils may appear normal, with few degenerate or
toxic changes, in some disease conditions such as heaves.
In contrast, other pulmonary diseases may cause large
increases in the proportions of degenerative or toxic neu-
B trophils. The most common degenerative change of neutro-
phils is karyolysis which involves:
Fig. 9.8. (A) Large raft of mesothelial cells in thoracic fluid (arrow).
Diff Quik (×400). (B) Large activated mesothelial cell with intensely ● cell swelling
basophilic cytoplasm, multiple nuclei (arrows) and prominent nucleoli. ● nuclear swelling with loss of nuclear segmentation
Diff Quik (×1000). ● indistinct nuclear margins
● decrease in nuclear staining intensity from purple to
pink
Lymphocytes ● eventual lysis of the cell.
Lymphocytes are present in low numbers in normal The degree of nuclear disruption is roughly proportional
TAs and PF, but occur in higher proportions in BALF. to the degree of degeneration (see Fig. 9.9A,B). Degenerate
They appear as small to medium-sized spherical cells neutrophils are observed most commonly in samples from
with a scant rim of basophilic cytoplasm. Their nucleus is horses with infectious diseases, but care must be taken in
relatively large and may be slightly indented with a coarse their interpretation because samples collected by TA will
20.0 μm
20.0 μm
Fig. 9.10. Tracheal aspirate containing many eosinophils (arrow).
A Diff Quik (×1000).
B
cytic cells may be interpreted to suggest acute inflamma-
tion and mobilization of the neutrophil storage and
maturation pools. These are observed more commonly in
PF, but may also occur in TAs and BALF.
Eosinophils and basophils

The morphology of eosinophils and basophils is the same
in TA, BALF, and PF as in peripheral blood smears.
Eosinophils are slightly larger than neutrophils with a
B K lobulated nucleus and uniformly large, round, bright-red
cytoplasmic granules (see Fig. 9.10). Basophils also are
Fig. 9.9. (A) Mild karyolysis of neutrophils (arrows). Diff Quik (×1000). slightly larger than neutrophils with a lobulated nucleus
(B) Neutrophils demonstrating moderate to marked karyolysis (K).
and numerous, fine, dark-purple granules that may
Some neutrophils contain intracellular bacteria (B). Diff Quik (×1000).
K = karyolysis, B = bacteria. obscure nuclear detail.
Mast cells
Mast cells may be identified by their characteristic
contain more degenerate neutrophils than BALF even in staining granules, which are more prominent when
normal horses. metachromatic stains (e.g. Leishmann’s) are used (see
Another morphological change that may be observed in Fig. 9.11). In normal horses, mast cells in TAs are rare
neutrophils is apoptosis, which is characterized by a (Hughes et al 2003). This is in contrast to BALF where
condensed nucleus and minimal cytoplasm. Apoptotic higher numbers of mast cells may be observed. This
neutrophils may be observed in increased numbers in difference may be explained by the predominant distri-
horses with heaves or non-infectious inflammatory airway bution of equine mast cells within the smaller airways
disease (IAD). and alveoli.
The more “classical” toxic changes observed in
circulating neutrophils (such as increased cytoplasmic Cytological changes associated with
basophilia, vacuolation, or Döhle bodies) may be present delayed processing
in PF samples in horses with septicemia or endotoxemia. A number of changes to cellular morphology may be
Such toxic changes are considered to be “pre-existing”, observed in smears prepared after a delay of several hours,
occurring during production (myelopoiesis), rather than even in samples from normal horses. Macrophages can
subsequent to migration into the pleural cavity. If these become vacuolated in vitro and perform erythrophagia,
changes are accompanied by visualization of phagocytosed thus complicating the distinction between true hemor-
bacteria they are compatible with septic pleuritis. The rhagic effusions and specimens contaminated with
presence of band neutrophils or more immature granulo- peripheral blood. Nucleated cells may exhibit aging
10.0 μm
20.0 μm
Fig. 9.11. Mast cell (arrow) in BALF. Leishmann’s stain (×1000). Fig. 9.12. Several rows of Simonsiella spp. (arrow) on the surface of a
squamous epithelial cell. Diff Quik (×1000).
changes such as hypersegmentation and pyknosis, which

can resemble the changes associated with chronic
inflammatory processes. Neutrophil nuclear hyposeg-
mentation artifact may also be observed following
delayed processing of EDTA-preserved specimens. A similar
phenomenon occurs in normal TA fluid samples. The
potential for these changes must be kept in mind when
evaluating and interpreting these samples.
Incidental findings
A variety of non-significant objects and artifacts may be
observed in samples from the LRT. Bacteria normally
inhabit the URT and oral cavity and may occur transitorily
in the lower airways, especially after exercise or trans-
portation or if contamination occurs during sampling.
Consequently these bacteria, together with squamous
epithelial cells, may be observed in TAs and BALF collected
20.0 μm
subsequent to these events. Perhaps the most conspicuous
members of the normal flora of the oral cavity are
Simonsiella spp., which appear as giant rod-like structures Fig. 9.13. Fungal spore within a macrophage which is distorting the
cell (arrow). Diff Quik (×1000).
(see Fig. 9.12). These are composites of multiple Simonsiella
rods apposed side-to-side. This bacterial species, and other
normal flora of the URT, do not elicit a significant
inflammatory response in these sampling sites unless example of a fungal contaminant is the saprophytic fungus
clearance is impaired or if aspiration-induced pneumonia Alternaria. This fungus has large macroconidia (> 1–2 RBC
has occurred. diameters in size) seen as green to turquoise, round to
Various other microorganisms and airborne debris elliptical structures. It is important to note that the
may be observed in TAs, BALF, and URT samples from presence of these fungal elements does not indicate fungal
normal horses. These reflect the horse’s environment and infection. Other extraneous materials are frequently
mucociliary function at the time of sampling. Fungal observed including pollen and plant material, hairs
spores, macroconidia, fruiting bodies, and occasional and pigmented debris. Rarely, mites, small larvae (not
hyphae of saprophytic (“barn mold”) fungi are the most lungworm) or egg-like structures may be seen. Grass, dirt,
common elements observed and may be seen extra- and and artificial racetrack surface material may occur in
intra-cellularly in macrophages (see Fig. 9.13). A common samples collected post-exercise.
Glove powder (corn starch) may occasionally con- tissue clearance of previously administered antimicrobial
taminate PF samples. This appears as variably sized, round agents (at least 24 and preferably up to 72 h).
to hexagonal particles with a central fissure or cross. Aerobic and anaerobic culture should be performed on
Particles are usually clear (non-staining) but on occasion TAs and PF that have cytological evidence of airway
may have a bluish hue. inflammation. Quantitative cultures, which determine the
number of colony-forming units (cfu) for each bacterial
Evaluation of samples for bacterial species, provide additional information when culturing
and fungal infections TAs. Tracheal aspirates collected in an appropriate fashion
from normal horses, or from horses with airway inflamma-
Upper respiratory tract tion without a bacterial etiology, usually yield <103 cfu/ml
As a result of the presence of normal flora in the URT, and frequently no bacteria at all. If >103 cfu/ml are cul-
culture of samples from the nasopharynx is rarely helpful tured, it is likely that these bacteria are contributing to the
unless a specific pathogen is being investigated (e.g. S. equi disease process, and identification of each species present
ss. equi or viral pathogens). In addition, these samples do in high numbers will assist in interpretation of their
not reflect the bacterial population of the LRT, only those of significance. Furthermore, the greater the cfu/ml isolated,
the URT. Thus, they offer minimal diagnostic usefulness in the more likely the significance of the bacteria isolated.
the evaluation of LRT infections. Quantitative cultures are not performed on PF samples
Culture of samples from the nasal cavity, nasopharynx, because the thoracic cavity is normally a sterile site and
and guttural pouches should be directed at specific sample collection using appropriate techniques rarely
pathogens that are not part of the normal flora. As involves contamination. In addition, culture of PF samples
identification of individual bacterial pathogens based usually involves liquid culture media, allowing bacterial
on their cytological appearance is not reliable, culture proliferation, which precludes quantification of the numbers
should be used to identify the organism involved. When of bacteria that were present at the time of sampling.
attempting to isolate S. equi ss. equi, samples should be Identification of isolated bacteria allows differentiation
cultured on Columbia CNA (colistin, nalidixic acid) agar of possible pathogens from probable contaminants. The
with 5% sheep or horse blood to enhance isolation. bacteria isolated commonly from cases of pneumonia and
Alternatively, where available, PCR based on primer pleuropneumonia are listed in Table 9.2. The significance
sequences from the SeM should be used because this of isolation of various bacteria is discussed in the section
technique is three times more sensitive than culture for Interpretation.
detection of S. equi ss. equi (Timoney 2004). Isolation of fungal pathogens from the LRT, like the
Isolation of fungal pathogens from the URT should also URT, should be directed at specific pathogens. In addition,
be directed at specific pathogens. Specialized culture media characteristic cytological findings will assist in interpre-
(e.g. Sabouraud dextrose agar) is required for their tation of these isolates.
isolation. In addition, care should be taken as some
cultured fungal pathogens may be infective for humans Diagnosis of parasitic infections
(e.g. Coccidioides immitis) and if suspected, culture of these
organisms should be performed at reference laboratories. Parasitic bronchitis and pneumonitis has decreased in
prevalence as a result of improved anthelmintics. The most
Lower respiratory tract likely parasite involved in pulmonary disease of foals
Bacterial cultures of TAs and PF samples are helpful in and young horses is the roundworm Parascaris equorum.
diagnosing LRT infections and ideally should be performed In contrast, the lungworm Dictyocaulus arnfieldi occurs
in all suspected cases of pneumonia or pleuropneumonia. predominantly in adult horses pastured with donkeys.
Samples collected by BAL may occasionally be cultured, Parasitic pneumonitis may be difficult to diagnose
particularly when collected from a suspected lung abscess definitively, but a history of a poor anthelmintic regimen or
and when the endoscope is guided into an airway where close association with donkeys may provide clues. In
mucopus is draining. In foals, this technique may also be addition, large numbers of eosinophils and activated
used to diagnose Pneumocystis carinii infection, which is alveolar macrophages may be observed on cytological
interstitial in nature (Leguillette et al 2002). BAL samples preparations of TAs and BALF (see Fig. 9.10), but are
collected “blindly” are rarely of use for microbial culture not specific for parasitic infections as they may also be
because they are contaminated with oropharyngeal observed in other forms of eosinophilic pneumonia.
flora. This BAL technique also harvests cells from the Lungworm larvae may occasionally be observed in TAs
caudodorsal lung fields, which are rarely involved in or found in feces using the Baermann technique
bacterial infections. Ideally, any sample submitted for (Zinkl 2002). Fecal flotation may also be used to diagnose
microbial culture should be obtained before antimicrobial roundworm infection, but a negative result does not
administration or after a sufficient period is allowed for rule out their involvement as the pre-patent period for
Table 9.2. Bacterial and fungal isolates from Interpretation of samples from the URT
lower airway samples of horses
A number of characteristic cytological findings may be
Common pathogens Streptococcus equi associated with pathological processes of the URT.
ss. zooepidemicus
Actinobacillus spp.
Pasteurella spp.
Airway irritation
Rhodococcus equi (foals) Goblet cells are rarely observed in washes of the normal
nasopharynx. Conditions that irritate the mucosal lining of
Less common pathogens Escherichia coli
the URT can result in goblet cell hyperplasia and increased
Klebsiella pneumoniae
Enterobacter spp. production of mucus, which appears cytologically as mats
Bordetella bronchiseptica of homogeneous, pink-to-red staining material or as a
Streptococcus pneumoniae finely mottled pink background. Free mucin granules may
Streptococcus dysgalactiae also be seen in smears from irritated mucosa.
ss. equisimilis
Streptococcus equi ss. equi
Bacteroides spp.
Airway inflammation
Fusobacterium spp. The cytological hallmark of inflammation is increased
Peptostreptococcus spp. numbers of inflammatory cells (neutrophils and macro-
Mycoplasma spp. phages in particular). Normally, only small numbers of
Aspergillus spp.
Coccidioides immitis
inflammatory cells (<5%) are associated with the mucosa,
Histoplasma capsulatum submucosa, and associated structures of the URT
Cryptococcus neoformans (Chiesa et al 1999). Noxious stimuli, such as foreign
Blastomyces dermatitidis bodies, trauma causing tissue necrosis, or infectious
Likely contaminants Pseudomonas aeruginosa
organisms provoke an inflammatory response and will
Staphylococcus aureus result in increased proportions of inflammatory cells. If
Proteus spp. >25% of cells present in cytological preparations are
inflammatory cells, a source of irritation should be
Definite contaminants Staphylococcus epidermidis
(and other coagulase negative considered and investigated.
staphylococci)
Bacillus spp. Bacterial infections
Alternaria spp. Bacterial infections are typically associated with intense
infiltration of neutrophils into infected tissues and these
cells commonly constitute >85% of cells in smears (see
Fig. 9.14A). Thus, increased proportions of neutrophils in
this parasite is 71–110 days, while pulmonary migra- cytological preparations should prompt suspicion of
tion occurs 7–14 days after ingestion of infective larvae possible bacterial infection, even if bacteria are not
(Darien 1994). observed. As many bacteria produce toxins, neutrophils
may have degenerative or toxic changes. However, not all
Diagnosis of viral infections bacteria produce toxins (e.g. Actinomycetes, Actinobacillus
spp.), and absence of degenerative changes does not pre-
A presumptive diagnosis of viral respiratory tract infections clude bacterial infection. Bacteria appear as a collection of
may be based on history and clinical signs. However, uniform rods or coccoid structures that stain blue (Gram
confirmation requires viral isolation or detection by positive) or red (Gram negative) on grain stain (see Fig.
serological or molecular techniques. These procedures are 9.14B). Free mucin granules, free cilia, stain precipitate or
routinely performed in diagnostic laboratories and will necrotic debris can be mistaken for bacteria in smears.
vary between regions and countries. Advice should Bacteria can be located extra- or intra-cellularly (see Figs
therefore be sought regarding the most appropriate pro- 9.14B,C). If bacteria are located only extracellularly
cedures available. and only small numbers of neutrophils are seen, this is
more likely to reflect the presence of normal bacterial
flora or bacterial contamination of the sample rather than
Interpretation true bacterial infection. In contrast, the presence of phago-
Collection of appropriate samples from the respiratory tract cytosed bacteria, especially in combination with a neu-
is a key step in the investigative pathway. However, accurate trophilic infiltration and degenerative changes of the
interpretation of findings from these samples is critical if neutrophils, indicates either a primary or secondary bac-
an appropriate diagnosis, strategy for management and terial infection. The significance of bacteria isolated from
prognosis are to be ascribed to the affected horse. the URT is discussed later in this section.
Fig. 9.14. (A) Smear demonstrating predominance of neutrophils

(> 85%). Many of these cells are trapped within mucus (pink,
amorphous strands). Diff Quik (×400). (B) Gram stain demonstrating
multiple intra- and extra-cellular bacteria in a smear of a tracheal
aspirate obtained from a horse with mixed bacterial pneumonia.
Gram-positive cocci (long arrow) and Gram-negative rods (short
arrow) are present. Gram stain (×1000). (C) Multiple neutrophils
with intracellular bacteria staining dark purple (arrows). Diff Quik
(×1000).
20.0 μm
B C
Hypersensitivity reactions normal appearance of lymphoid tissue. In these cases, fine-

Inflammatory processes involving hypersensitivity (allergic) needle aspirate or biopsy samples reveal a cell population
reactions can result in increased numbers of eosinophils, that has > 80% small lymphocytes.
basophils, or mast cells in cytological smears. These
may occasionally be observed in samples obtained from the Cysts and hematomas
URT. Often the cause of the hypersensitivity reaction is Cytological examination of samples from fluid-filled
not identified. structures within the dermis, mucosa, salivary glands, or
associated ducts present in the URT often helps to identify
Lymphoid hyperplasia the process involved. Atheromas, which are epidermoid or
Antigenic stimulation, in the absence of an inflammatory sebaceous cysts of the nasal diverticulum, are distin-
stimulus, is associated with increased numbers of small guished by large numbers of squamous epithelial cells (see
lymphocytes and plasma cells. Pharyngeal lymphoid hyper- Fig. 9.6), cholesterol crystals, and a variable amount of
plasia, like other forms of benign lymphoid hyperplasia, sebum. Cysts involving the mucosa of the URT contain cells
has no cytological features distinguishing it from the characteristic of their mucosal linings and may also
contain mucin. Mild to chronic inflammatory processes are increased cellularity. Maximum increases in TNCC usually
often associated with cystic structures, therefore increased occur in cases of bacterial pneumonia or pleuropneu-
numbers of neutrophils are common. Hematomas will con- monia, heaves or lungworm infections.
tain RBC, leukocytes and platelets. The RBC will be fresh or
in various stages of catabolism with erythrophagocytosis Red blood cells
and hemosiderin, bilirubin or biliverdin crystals present. Free RBCs and hemosiderophages may be identified in
TAs or BALF after pulmonary hemorrhage. Free cells and
Polyps and neoplasia hemosiderophages usually result from EIPH whereas
Nasal polyps are usually secondary to chronic inflam- iatrogenic hemorrhage, occurring at the time of collection,
mation and not of neoplastic origin. They consist of fibrous yields just free cells in the sample.
tissue surrounded by a mucosal lining. Neoplasms involv-
ing the URT are usually carcinomas, arising from the Epithelial cells
mucosa and its associated glands, or tumors of structures An increase in the number of epithelial cells in samples is
underling the mucosa such as osteosarcomas or lympho- relatively rare. Increased numbers of epithelial cells, in the
sarcomas. Specific cytological diagnosis of neoplasms of absence of increased numbers of inflammatory cells, have
the URT is best performed by a trained cytologist. been reported in cases of unusual pulmonary lesions such
as chronic fibrosing alveolitis. In addition, an increase in
the epithelial cell population, together with an increase in
Interpretation of TAs and BALF the inflammatory cell population, is reported in association
with respiratory viral infection.
Evaluation of samples collected by TA and BAL may be Changes to the morphology of epithelial cells are more
used to assess pulmonary pathology in horses with clinical common and help indicate pulmonary pathology. Mild
signs consistent with pulmonary disease or to assist in the changes can occur in normal horses and include nuclear
evaluation of horses with poor performance. However, this changes and the loss of some cilia. These probably
evaluation should not be performed in isolation, but should represent normal “wear and tear” or turnover of cells, and
be interpreted in association with history, clinical signs, care must be taken in their interpretation. Pathological
and the results of other diagnostic tests. In addition, care changes to epithelial cells (epithelial atypia) result from
must be taken when assessing results as controversy inflammation. In addition, in cases of infectious respiratory
remains as to their significance. This is highlighted by tract disease, there may be direct damage to the epithelium
differing definitions of normal and abnormal cytological by viruses or bacterial toxins. Alterations to epithelial cells
findings between investigators/laboratories, unknown are best detected with polychrome stains (e.g. Pollack’s
significance of mild increases in numbers of inflammatory trichrome) as these provide superior staining of nuclear
cells and mucus (particularly in performance horses), morphology. Finally, it must be remembered that there
and variable interpretation of significance of results of are many causes of airway inflammation, and therefore
bacterial culture. the presence of epithelial atypia is not diagnostic for a
specific etiology.
Mucus A range of atypical features has been described in
The amount of mucus present in the lower airways epithelial cells in TAs and BALF from horses with
increases with pulmonary irritation. Specific causes of respiratory disease. These include cytoplasmic swelling,
increased mucus or mucopus include bacterial, fungal, or vacuolation (or ragged appearance of the cytoplasm),
parasitic pneumonia, chronic bronchitis, heaves, and IAD. nuclear degeneration and hypochromasia, and pyknotic
The significance of mild increases in the amounts of mucus nuclei. Early squamous metaplasia, dysplasia or hyper-
in the airways remains unresolved. This is particularly the plasia of bronchial or bronchoalveolar cells may be
case in horses with increased amounts of mucus, but no observed in chronic inflammatory processes. A variety of
change or mild increases in the number of neutrophils and “irritation forms” of bronchial epithelial cells have been
many activated macrophages. Furthermore, these findings described and include enlarged prominent nuclei, and
may be present in horses not exhibiting overt signs of rounded clusters of ciliated epithelial cells (see Fig. 9.15),
respiratory disease. In contrast, recent studies suggest which may represent fragments of hyperplastic bronchial
that mucus scores ⭓2 affect racing performance due to mucosa. Cytoplasmic and intranuclear inclusions have
impaired lung function (Holcombe et al 2006). been reported in suspected viral respiratory tract infections,
but are an inconsistent finding and therefore not of value
Total nucleated cell counts in the specific diagnosis of these infections.
Samples from horses with airway inflammation can have A specific epithelial change associated with respiratory
mild, moderate, or marked elevations in TNCC. These fluids viral infection in humans is ciliocytophthoria. This involves
may be white, gray, yellow, or brown because of this loss of the terminal plate of ciliated epithelial cells resulting
and amount of hemosiderin within individual pulmonary

A alveolar macrophages, should be interpreted with caution
and in conjunction with other diagnostic tests (e.g.
endoscopy, history).
B
Lymphocytes
The interpretation of increased lymphocyte ratios is
complicated by the wide range of proportions observed in
BALF from normal horses. Although increased proportions
have been reported in racehorses with exercise intoler-
ance and in other horses with chronic coughing, their
significance remains unclear (McGorum & Dixon 1994).
A narrower range of lymphocytes occurs in TAs, but no
consistent correlation has been made between an increased
50.0 μm
proportion and a specific disease processes.
Fig. 9.15. Numerous rounded clusters of bronchial epithelial cells
Neutrophils
representing irritation forms (A). Note increased numbers of goblet
cells (B). Diff Quik (×1000). The dilemma associated with interpretation of neutrophil
percentages is to determine what value (if any) represents a
significant change, particularly for TAs where numbers
in the presence of a spherical cell with pyknotic fragmented may fluctuate rapidly. Large variations in the proportion of
nuclear material and pink inclusions together with a small, neutrophils in TAs from normal horses are reported.
anucleate, rounded cytoplasmic fragment (or tuft) bearing However, recent studies have shown a strong association
the cilia. Both major cell changes are required for applica- between the presence of increased proportions of neu-
tion of the term “ciliocytophthoria.” This phenomenon is trophils, signs of respiratory disease (coughing), and an
reported to occur in horses with suspected viral respiratory increased likelihood of isolation of significant numbers
tract infections, though it is not a consistent feature. In of bacteria (Chapman et al 2000, Christley et al 2001).
addition, isolated ciliated tufts and epithelial cells with In addition, if evidence of lower airway inflammation
cytoplasmic damage may be seen in samples from horses (increased mucus, increased cell count) is taken into
with acute inflammation (e.g. acute bronchitis, heaves, and account in an inflammation score, horses with high scores
IAD) as a result of fragmentation of ciliated cells. have high relative proportions of neutrophils (>20–30%).
Finally, the TNCC should be taken into account when
Macrophages/hemosiderophages interpreting the significance of neutrophils in TAs. High
Macrophages constitute the predominant inflammatory proportions of neutrophils in samples with a low TNCC are
cell population in TAs and BALF. Therefore, increased pro- usually less significant than when the TNCC is elevated and
portions of these cells are difficult to detect. Occasionally the majority of these cells are neutrophils. In contrast,
increased amounts of mucus, increased TNCC and increased proportions of neutrophils in BALF from normal horses are
numbers of activated macrophages may be observed, but less variable and good agreement exists between the
the significance of these changes is currently not clear. presence of increased proportions of neutrophils in BALF
All causes of respiratory tract hemorrhage caudal to the and histological evidence of airway inflammation.
larynx will result in hemosiderophages, but the most Neutrophils are usually the most common cell present
common cause is EIPH. Whilst good correlation has been in TA samples where there is an increase in TNCC. For
reported between the presence of hemosiderophages in example, they are the predominant cell observed in horses
BALF and the presence of pulmonary hemorrhage in the with bacterial pneumonia or pleuropneumonia and the
caudodorsal lung lobes at necropsy, these cells are observed percentage of neutrophils is usually > 40%, and often
in a large proportion of horses in training, including those exceeds 90% in acute cases. Elevated total and relative
that are clinically normal (McKane et al 1993). The numbers of neutrophils also may be observed in cases of
“acceptable” number of hemosiderophages in TAs and heaves, IAD, EIPH, acute viral infections, chronic bron-
BALF is controversial because their number may not chitis, and summer-pasture-associated obstructive pulmonary
reflect the total amount of blood that has entered the disease. However the increase in percentage is variable.
airways. One reason is that much of the blood is likely to be Cases of interstitial pneumonia usually have low neu-
cleared by mucociliary clearance and swallowed. In trophil numbers in TAs, but these may be elevated in BALF.
addition, hemosiderophages are cleared slowly, and may Horses with clinical heaves will demonstrate elevated
be present many months after pulmonary hemorrhage has total numbers and proportions of neutrophils in BALF, but
occurred. Therefore, the numbers of hemosiderophages, horses in remission will have normal BALF cytology.
Such horses may be differentiated from normal horses Adjuncts to interpretation of cytological
after being housed for at least 5 h in an inadequately changes in TA and BAL
ventilated stable containing poorly saved straw or hay,
which induces a marked increase in neutrophils and other A number of alternative approaches to cytological evalua-
signs of heaves. tion of LRT samples have been described that may assist
The presence or absence of degenerative changes to interpretation.
neutrophils may assist in the interpretation of increased
proportions of this cell line, particularly when overall cell Patterns of respiratory cytological changes
numbers are low. In some disease conditions (e.g. heaves, Evaluation of cellular patterns may help analysis of
EIPH, and some cases of IAD) neutrophils are mostly samples from the LRT. This approach takes into account
mature with no degenerate or toxic changes. In contrast, subjective and quantitative, as well as morphological,
degenerate neutrophils are commonly observed in samples features of all material in a specimen, and as such
from horses with bacterial or fungal pneumonia or may be more useful than differential counts alone
pleuropneumonia because of the production of cytolysins (Freeman & Roszel 1997a,b). Pathological processes such
by the infective agent. In these cases, careful examina- as bronchitis and bronchiolitis (which may be neutrophilic
tion of neutrophils for intracellular organisms is often or eosinophilic, acute or chronic), alveolar edema, and
diagnostically rewarding. pulmonary hemorrhage may be identified in this way.
Alternatively, some patterns are suggestive of a specific
Eosinophils disease process such as bacterial or fungal broncho-
Low numbers of eosinophils are present in TAs and BALF pneumonia, lungworm infection, EIPH, heaves, or inter-
of normal horses. Increased proportions of eosinophils stitial pneumonia. However, care must be taken in the
may be observed in lungworm infection or during ascarid interpretation of cytological patterns because significant
migration. In these cases the relative percentage of overlap exists between different diagnoses. Therefore, the
eosinophils may be up to 85% of cells. Smaller elevations in conclusion derived from the cytological patterns observed
the proportions of eosinophils occur in the absence of must be consistent with other diagnostic tests as well as the
parasitic infections, and are often interpreted as evidence of clinical presentation of the horse.
a type I hypersensitivity response to inhaled allergens. In
these horses concurrent increases in the proportions of Compound inflammation and
mast cells may be observed. Frequently these elevations, hemorrhage scores
particularly of eosinophils, are transitory and may not Compound inflammation scores have been applied to TAs
be observed in samples collected 24 h later. A number of in the assessment of airway inflammation. This system
both acute and chronic pulmonary disorders associated provides a semi-quantitative evaluation of the amount of
with elevated eosinophil ratios in TA and BALF have been mucus present within the airways (assessed endoscopi-
described in horses and termed eosinophilic pulmonary cally), the TNCC and the relative proportion of neutrophils.
disease (see Chapter 43). Elevated eosinophil counts in Each variable is assigned a score between 0 and 3 and a
BALF of horses with heaves are an inconsistent finding, total score > 6 is determined to be indicative of significant
although heaves is proposed to have an underlying allergic airway inflammation. Good correlation between a high
etiopathogenesis. In young racehorses with poor perform- airway inflammation score (> 6) and the probability of
ance, increased airway hyperresponsiveness at rest has growing significant numbers of bacteria has been shown
been correlated with elevations in eosinophils in BALF (Chapman et al 2000).
(Hare & Viel 1998). Similarly, a compound EIPH score has been used to
determine the likelihood of significance of pulmonary
Mast cells hemorrhage (Chapman et al 2000). This score takes into
Mast cells are seldom seen in TAs, so alterations are account the amount of blood in the airways, bloodstain-
better detected in BALF. An increased percentage of mast ing of the sample, and the numbers of hemosiderophages
cells in BALF has been correlated with increased hyper- present. However, similar limitations to interpretation of
reactivity to histamine bronchoprovocation in horses with this score exist as those discussed for the presence of
decreased exercise tolerance (Hoffman et al 1998). The hemosiderophages.
increase in airway hyperreactivity is the result of the
release of pro-inflammatory mediators such as histamine, Interpretation of microbial culture of samples
leukotrienes and platelet-activating factor from mast cells.
However, care must be taken in interpretation of elevated Determination of the significance of bacteria isolated from
proportions of this cell population because high propor- the respiratory tract can be challenging. There are several
tions of mast cells (>20%) also have been reported in factors that will assist evaluation and interpretation of
clinically normal horses. these samples.
First, as a result of the presence of normal flora in the carrier horses. However, cultures may be negative if
URT, culture of bacteria from this site is not significant per collected during the incubation period or early clinical
se. This is the case regardless of the numbers cultured. phase of disease as S. equi ss. equi is normally not present
Only isolation of bacteria not routinely present in this site, on the mucosa until 24–48 h after the onset of fever. In
and which are capable of causing the clinical signs addition, the culture of nasal swabs or washes may fail to
observed, can be considered significant (e.g. S. equi ss. equi). detect organisms sequestered in the guttural pouches of
In contrast, isolation of bacteria that are part of the carrier horses as nasal shedding is sporadic (Newton et al
normal flora, even if they are potential pathogens of this 1997). In these cases, carriers may be identified by
site (e.g., S. equi ss. zooepidemicus, Pasteurella spp.) cannot be endoscopic examination of the guttural pouches to confirm
interpreted as significant. the presence of inflammation, mucopus, chondroids, or
Second, the normal bacterial flora of the URT ceases retropharyngeal lymph node abscessation. If present,
at the larynx and the LRT is considered a sterile site. mucopus or chondroids should be cultured. Alternatively,
However, bacteria may occur transitorily in the LRT, where available, PCR based on primer sequences from the
especially post-exercise or after transportation, or may SeM can be used and this technique, combined with
be introduced at the time of sampling. Thus, isolation culture of guttural pouch samples, greatly increases the
of bacteria from TAs or BALF may represent infection, detection rate of carriers. However, care must be taken
a transient lower airway population or contamination with interpretation of PCR “positive” samples from the
at the time of sampling. It is essential for appropriate guttural pouch because long-term carriers may remain
management of these cases to differentiate between these PCR “positive” for months after the last culture of viable
scenarios. Differentiation can be assisted by: organisms is achieved. This indicates that bacterial DNA
persists for a considerable period after death of the
● presence of clinical signs consistent with pneumonia or
organism (Timoney 2004). In contrast, in convalescing
pleuropneumonia
horses, nasal swabs and washes become PCR negative
● identification of isolates as known pathogens of the
shortly after viable organisms cease to be detectable. This
LRT in sufficient numbers (i.e. >103 cfu/ml)
can be explained by rapid mucociliary clearance of dead
● cytological evidence of inflammation.
bacteria from the nasopharynx. PCR may also be used to
Clinical signs consistent with pneumonia include fever, detect S. equi ss. equi from nasal swabs in suspected cases of
signs of depression, tachypnea, abnormal respiratory strangles, or it can be used as a method for rapid detection
sounds, coughing, and nasal (often purulent) discharge. of S. equi ss. equi in animals about to be exported or
However, absence of these signs does not preclude bacterial introduced to strangles-free premises (Timoney 2004).
infection, especially in milder cases of IAD caused by Pathogenic fungi (e.g., Aspergillus spp., Pseudoallescheria
bacteria. The major bacteria and fungi capable of causing boydii) may be cultured from the URT, but care must be
LRT infections in horses are included in Table 9.2. taken in interpretation of their isolation to ensure that they
Quantification of these isolates was discussed earlier. are not contaminants. Samples from horses with mycotic
Neutrophilic exudates are consistently observed in samples rhinitis, sinusitis, or guttural pouch mycosis typically
from horses with bacterial infections of the URT and LRT. contain large numbers of neutrophils and activated
These exudates are not present if non-pathogenic species or (epithelioid) macrophages. Multinucleated inflammatory
commensals are present, either transitorily (LRT) or as part giant cells, lymphocytes, plasma cells, and reactive stromal
of the normal flora (URT). Tracheal aspirates from horses cells may also be seen. Occasionally these samples will
with bacterial LRT infections will have increased mucus, contain increased numbers of eosinophils. If fungal
increased TNCC, and increased relative and absolute elements are identified in smears in the absence of
neutrophil counts with possibly degenerative neutrophils inflammation, no significance can be ascribed to their
and intracellular bacteria. No significance can be ascribed subsequent culture. Mycelium-producing fungi are readily
to bacteria isolated without this cytological evidence of recognized as filamentous structures having a width
inflammation. In addition, it is preferable not to culture greater than 1 ⁄ 2 RBC diameter (wider than filamentous
samples with large numbers of squamous epithelial cells, bacteria) and some may have septal divisions (see
even when there are many neutrophils present because Fig. 9.16). However, determining the species of mycelium-
this is evidence of oropharyngeal contamination. If such producing fungi using cytological features is not reliable
samples are cultivated, and large numbers of bacteria are and the organisms must be cultured if specific identification
isolated, it is not possible to assign any significance to these is desired. Mycotic rhinitis may occasionally be associated
isolates. Re-collection of the sample is recommended. with infection by Rhinosporidium seeberi or Cryptococcus
neoformans and a presumptive diagnosis of these infections
Upper respiratory tract can be made by identification of characteristic fungal
Isolation of S. equi ss. equi from nasopharyngeal swabs or elements in nasopharyngeal swabs in association with an
washes can confirm a diagnosis of strangles or identify intense inflammatory reaction.
part of a mixed culture, indicates contamination at the

time of sampling.
Occasionally, pathogenic fungi may be cultured from
TAs or BALF (Table 9.2). The most frequently identified
pathogenic fungus from the LRT of horses is Aspergillus spp.
(Zinkl 2002), although the primary pathogens Blastomyces
dermatitidis, Coccidioides immitis, Histoplasma capsulatum
and Cryptococcus neoformans are also occasionally iso-
lated in certain countries. Contaminating fungi, especially
Alternaria spp., must be distinguished from true pathogens.
The presence of an appropriate inflammatory reaction
(see discussion of URT), together with free and ingested
fungal elements, will help with this distinction. The fungal
parasite Pneumocystis carinii can also cause acute inter-
stitial pneumonia in immunosuppressed foals or secondary
20.0 μm to R. equi infections (Leguillette et al 2002). Mixed inflam-
matory reactions (neutrophils and macrophages) together
with the distinctive intact cysts can be identified in TAs or
BALF. Finally, the majority of respiratory fungal infec-
Fig. 9.16. Multiple branching septate fungal hyphae (arrow) trapped tions in horses are secondary to immunosuppression, other
within strands of mucus. Diff Quik (×1000). severe diseases of the lung, or severe systemic diseases such
as enterocolitis, peritonitis, endotoxemia or septicemia.
Therefore, investigation of potential underlying disorders
Lower respiratory tract should be conducted to appropriately assess and treat these
A variety of bacteria can cause LRT infections and secondary infections.
frequently these infections are mixed (Table 9.2). Bacteria
that are most commonly isolated from uncomplicated lower Interpretation of virus isolation and serology
airway infections in adult horses include streptococci
(both α- and β hemolytic), Pasteurella spp., Actinobacillus Virus isolation or detection of viral antigens or nucleic acid
spp. and occasionally Bordetella bronchiseptica. Bacteria will confirm the presence of specific viruses in clinical
in the Enterobacteriaceae family (e.g. E. coli, Klebsiella samples. However, positive results should be discussed with
pneumoniae) are more commonly secondary invaders and the laboratory to apportion appropriate significance to this
may be isolated following induction of antimicrobial finding. A number of serological tests for respiratory
therapy or when pneumonia is severe. Anaerobic bacteria viruses have been developed and include assay for equine
(e.g. Bacteroides spp., Fusobacterium spp., Peptostreptococcus herpesviruses 1, 2 and 4, equine influenza, equine rhino-
spp.) may be isolated from cases where sufficient necrosis viruses A and B, equine arteritis virus and adenovirus. The
of lung tissue has occurred such as within lung abscesses specific type of test, availability of tests, and the
or when pleuropneumonia is present. Mycoplasma interpretation of results will vary between laboratories.
equirhinis and M. felis have been implicated in some However, in most cases, a four-fold or greater increase in
outbreaks of equine respiratory infection. While it is titer between acute and convalescent serum samples is
difficult to culture these agents, some laboratories now considered significant and may be used to indicate retro-
perform serological evaluation to assist diagnosis of these spectively that a viral infection has occurred. Alternatively,
infections. Pneumonia in foals may be caused by all the a lack of an increasing titer does not rule out a viral
isolates causing disease in adults, as well as Rhodococcus infection as titers rise rapidly during infection and may be
equi. The diagnosis of R. equi infection is discussed in increased at the time of onset of clinical signs. Therefore
Chapter 24. the expected increase in a convalescent sample may not
Pathogenic bacteria that rarely cause LRT disease but be demonstrable. Although serological diagnosis of viral
are common contaminants during sampling include infections may not be of immediate value in the clinical
coagulase-positive Staphylococcus spp., Pseudomonas spp., management of cases, it may yield valuable information on
and Proteus spp. In particular, Ps. aeruginosa is a major the etiology of infections, particularly if virus isolation has
contaminant commonly residing in inadequately sterilized proven unsuccessful. Such epidemiological information has
endoscopes. This organism is rarely involved in LRT infec- apparent advantages in monitoring and designing effective
tions. Isolation of non-pathogenic bacteria (e.g. Bacillus vaccination programs, particularly for large susceptible
spp., coagulase-negative Staphylococcus spp.), especially if groups of horses, such as those kept in training yards.
Interpretation of pathological changes ● Transudates are characterized by low (normal) cellu-

in pleural fluid larity and protein concentration.
● Modified transudates are rare forms of pleural effusions
The purpose of thoracocentesis is to evaluate the and are modified predominantly by an increase in
physicochemical, bacteriological, and cytological compo- protein concentration.
nents of fluid accumulating within the pleural space. ● Exudates are the most common type of pleural effusion
Subjective assessment of the color, turbidity, odor and and arise when there is an increased pleural capillary
volume of PF often provides sufficient evidence for a permeability and compromised lymphatic drainage. This
provisional diagnosis. This may allow initiation of therapy, results in fluid with increased TNCC and protein
before complete laboratory results are obtained. For concentration.
example, if PF appears grossly turbid, discolored and has a
foul odor, pleuropneumonia with involvement of anaerobic Pleuropnemonia/pleuritis
bacteria should be strongly suspected. Conversely, if PF Exudative thoracic effusions in horses are most commonly
appears grossly normal and of low volume, it is probably caused by bacterial infections, with fungal pathogens (e.g.
normal, because most pleural effusions in horses are Coccidioides spp., Blastomyces dermatitidis) involved only
exudative and will be visibly abnormal. However, when rarely. The bacterial organisms isolated most commonly are
fluid volume is substantially increased, or if samples are similar to those causing pneumonia (Table 9.2). Delayed
moderately contaminated by peripheral blood, such diag- or inappropriate treatment is likely to result in a chronic
nostic inference is more difficult. To further evaluate PF in disease process characterized by involvement of strict
such cases, total protein concentration, TNCC, and cyto- anaerobes and poor response to therapy (Raidal 1995).
logical examination are required. In cases of pleuropneumonia, PF volume, TNCC, and
Evaluation of PF is first directed at determining the protein concentration will all be increased, but the degree
type of fluid as this will help establish the underlying of rise is not a good guide to prognosis. Neutrophils are the
pathogenesis. Pleural fluids may be characterized as predominant leukocyte in most septic pleural effusions, but
transudates or exudates (Table 9.3). some anaerobic infections may contain numerous bacteria
Table 9.3. Physical, biochemical, and cytological features of pleural effusions in horses
Transudate Modified transudate Exudate
Color Pale straw Usually pale straw, but may be Varies from reddish brown to
whitish pink if chylous off-white according to number and
relative proportion of RBCs and
nucleated cells
Turbidity Clear to slightly turbid Clear to slightly turbid Turbid
Protein (g / liter) < 25 (usually < 15) 20–50 > 30

9
TNCC (× 10 / liter) <5 5–15 > 15
Pathogenesis ↓ colloid osmotic pressure ↑ capillary hydrostatic pressure ↑ capillary permeability

↑ capillary hydrostatic pressure ↑ lymphatic hydrostatic pressure ↓ lymphatic drainage
Frequency < 10% Rare > 90%
Causes Hypoalbuminemia Congestive heart failure Bacterial or fungal pleuropneumonia

Congestive heart failure Neoplasia or pleuritis
Hepatic disease Lung lobe torsion Penetrating chest wound
Acute esophageal Neoplasia
perforation Thoracic esophageal perforation
Hepatic disease Inhaled foreign body
Chylothorax Vasculitis
Cytological Unremarkable. Normal proportions Unremarkable except in chylous May be classified as suppurative
findings and morphology of cells except effusions where small lympho- (neutrophilic), chronic suppurative
reactive mesothelial cells may be cytes predominate (pyogranulomatous) or chronic
present (granulomatous)
with few identifiable cells. This is most likely the result of depending on the relative numbers of RBCs and inflam-
the presence of potent bacterial cytotoxins. Degenerative matory cells, but is often reddish brown, port wine or
changes of neutrophils are observed commonly and may muddy colored. The supernatant fluid may appear dis-
be subjectively classified as mild, moderate, or marked colored as a result of hemolysis. Cytologically, erthryo-
depending on the degree of karyolysis (see earlier under phagocytosis may be observed.
Evaluation: Neutrophils). The more marked the degree Hemothorax is rare in horses, but the various potential
of karyolysis, the more likely an effusion is the result of causes are described in Chapter 46. The cytological
bacterial infection. Conversely, normal neutrophil mor- features associated with hemothorax will differ depend-
phology does not exclude a bacterial etiology. Neutrophil ing on the time at which samples are collected post
morphology may remain normal despite a marked inflam- hemorrhage and the degree of hemorrhage. If samples
matory response if the infected tissue is walled off from are collected shortly after intrathoracic hemorrhage, the
the section of the pleural cavity sampled, if the bacteria PCV and total protein concentration of PF is usually less
produce few cytotoxins, or if antimicrobial therapy is than that in peripheral blood, but may be similar if the
initiated. Careful examination of Gram-stained prepara- hemorrhage is severe. The supernatant fluid is usually
tions for bacteria should always be undertaken if an clear and cytologically the relative numbers of inflam-
exudate is detected. These fluids should always be cultured, matory cells will be similar to those in peripheral blood
even if no bacteria are observed. smears except for a decrease in the numbers of platelets. In
Large mononuclear cells may be plentiful and reactive in contrast, the supernatant of PF collected subsequent to
septic thoracic effusions, particularly when the effusion is hemorrhage of longer standing is often reddish brown as a
more chronic. Mesothelial cell hyperplasia and reactivity result of hemolysis. In these samples a common cytological
may mimic neoplastic changes and care must be taken finding is evidence of erythrophagocytosis and there
in their interpretation. Low numbers of lymphocytes are may be increased numbers of neutrophils because of an
usually present in exudative effusions, although numbers inflammatory reaction induced by the hemorrhage.
may increase with chronicity. Increased numbers of
plasma cells and large atypical lymphocytes may be
observed when there is chronic antigenic stimulation. Chylous and pseudochylous effusions
However, these atypical lymphocytes are present in Milky, pinkish or opalescent discoloration of PF is asso-
relatively low numbers as compared to effusions associated ciated with chylous and pseudochylous effusions. The tur-
with lymphoma where they are the predominant cell type. bidity and color change in chylous effusions are the result
of increased triglyceride content, with or without a con-
current increase in leukocytes. Pseudochylous effusions
Hemorrhagic effusions have a similar gross appearance because of high cellularity
Although RBCs are frequently seen in PF collected and cholesterol content. The cytological profile in both
from clinically normal horses, they are considered to be effusions is typified by increased proportions of small
the result of contamination at the time of sampling. lymphocytes together with a mixed inflammatory profile.
Accordingly, erythrophagocytosis is not a feature of normal Chylothorax is rare in horses, with most reports of this
PF. The supernatant fluid is also clear and non-hemolysed condition occurring in foals (DeHeer et al 2002). The
in normal samples. The presence of RBCs and their break- underlying disorders associated with chylothorax include
down products in PF may be the result of iatrogenic congenital diaphragmatic hernia, meconium impaction,
contamination, hemorrhagic diapedesis or intrapleural and idiopathic causes. Pseudochylous effusions result from
hemorrhage. Distinction between these different causes is severe chronic inflammatory processes. Differentiation
clinically important so that appropriate management of of chylous and pseudochylous effusions is best performed
cases of hemorrhagic effusions can be implemented. by determination of PF fluid triglyceride and cholesterol
Changes in the degree of red discoloration of PF during concentrations. Chylous effusions are characterized by
sample collection indicate peripheral blood contamination triglyceride concentrations greater than, and cholesterol
at the time of sampling. When PF resembles whole blood, concentrations less than, paired serum values, whereas the
comparison of PCV and clotting times with venous blood, converse is true for pseudochylous effusions.
and the cytological appearance of the PF may be useful to
determine the source of RBCs. Failure of the sample to clot
or presence of significant erythrophagia is indicative of Neoplasia
true hemothorax. Contaminated specimens often have a Thoracic neoplasia is a relatively common cause of pleural
PCV significantly less than peripheral blood, and platelet effusion in the horse, with more than one-third of effu-
clumps may be visualizd microscopically. sions reportedly being neoplastic (DeHeer et al 2002).
Hemorrhagic diapedesis may be associated with pleuritis The most common neoplasm causing thoracic effusion
or neoplasia. The gross appearance of the fluid will vary is lymphoma, although mesothelioma, squamous cell
carcinomas, adenocarcinomas, and hemangiosarcomas Dixon PM 1997 Ancillary diagnostic techniques for the inves-
also have been reported. Pleural fluids associated with tigation of equine pulmonary disease. Equine Veterinary
thoracic neoplasms are usually classified as modified Education 9: 72–80
Freeman DE 1991 Guttural pouches. In: Beech J (editor)
transudates (when lymphatic drainage is obstructed) or Equine Respiratory Disorders. Lea & Febiger, Philadelphia,
hemorrhagic exudates (when serosal surfaces and their pp.305–330
blood vessels are involved, or when there is tissue necrosis). Freeman KP, Roszel JF 1997a Equine cytology patterns in
Pleural fluid cytology may assist in diagnosis of thoracic respiratory conditions of noninfectious or unknown
neoplasia, although not all neoplasms exfoliate cells into origin. Compendium on Continuing Education for the
Practicing Veterinarian 19: 755–763
the PF and therefore a lack of neoplastic cells does not Freeman KP, Roszel JF 1997b Equine cytology patterns in
preclude this diagnosis. In addition, necrosis or infection of respiratory conditions of probable or known infectious
a tumor may result in pleuritis and this inflammatory origin. Compendium on Continuing Education for the
reaction may complicate the cytological diagnosis. Reactive Practicing Veterinarian 19: 378–383
mesothelial cells, which can be present in any type of Hare JE, Viel L 1998 Pulmonary eosinophilia associated with
increased airway responsiveness in young racing horses.
pleural effusion, may be mistaken for neoplastic cells. The Journal of Veterinary Internal Medicine 12: 163–170
distinction between reactive and neoplastic mesothelial Hewson J, Viel L 2002 Sampling, microbiology and cytology
cells may not be easy to determine, particularly in the of the respiratory tract. In: Lekeux P (editor) Equine
presence of concurrent inflammation. Therefore, a cyto- Respiratory Diseases. International Veterinary Informa-
logical diagnosis of mesothelioma, as with most other tion Service, Ithaca. Online. Available: http://www.ivis.org
Hodgson JL, Hodgson DR 2002a Inflammatory airway disease.
intrathoracic tumors, is best performed by a trained In: Lekeux P (editor) Equine Respiratory Diseases.
cytologist. There are a number of excellent texts which International Veterinary Information Service, Ithaca.
contain more detailed descriptions of thoracic neoplasms in Online. Available: http://www.ivis.org
the horse and which are recommended to the reader Hodgson JL, Hodgson DR 2002b Tracheal aspirates: indica-
(Cowell & Tyler 2002). tions, technique and interpretation. In: Robinson NE
(editor) Current Therapy in Equine Medicine V. WB
Saunders, Philadelphia, pp.401–406
Hoffman AM 1999 Bronchoalveolar lavage technique and
cytological diagnosis of small airway inflammatory
REFERENCES disease. Equine Veterinary Education 11: 208–214
Hoffman AM, Viel L 1997 Techniques for sampling the
Beech J 1991 Tracheobronchial aspirates. In: Beech J (editor) respiratory tract of horses. Veterinary Clinics of North
Equine Respiratory Disorders. Lea & Febiger, Philadelphia, America; Equine Practice 13: 463–475
pp.41–53 Hoffman AM, Mazan MR, Ellenberg S 1998 Association
Chapman PS, Green C, Main JPM et al 2000 Retrospective between bronchoalveolar lavage cytologic features and
study of the relationships between age, inflammation and airway reactivity in horses with a history of exercise
the isolation of bacteria from the lower respiratory tract intolerance. American Journal of Veterinary Research
of thoroughbred horses. Veterinary Record 146: 91–95 59: 176–181
Chiesa OA, Garcia F, Domingo M et al 1999 Cytological and Holcombe SJ, Robinson NE, Derksen FJ et al 2006 Tracheal
microbiological results from equine guttural pouch mucus is associated with poor racing performance
lavages obtained percutaneously; correlation with histo- in thoroughbred horses. Equine Veterinary Journal
pathological findings. Veterinary Record 144: 618–621 (in press)
Christley RM, Hodgson DR, Rose RJ et al 2001 A case-control Hughes KJ, Malikides N, Hodgson DR et al 2003 Comparison
study of respiratory disease in Thoroughbred race- of tracheal aspirates and bronchoalveolar lavage in
horses in Sydney, Australia. Equine Veterinary Journal racehorses. 1. Evaluation of cytological stains and
33: 256–264 the relative percentage of mast cells and eosinophils.
Clinkenbeard KD, MacAllister CG, Cowell RL et al 2002 Oral Australian Veterinary Journal 81: 681–684
and nasal cavities, pharynx, guttural pouches, and Leguillette R, Roy MF, Lavoie J-P 2002 Foal pneumonia.
paranasal sinuses. In: Cowell RL, Tyler RD (editors) In: Lekeux P (editor) Equine Respiratory Diseases.
Diagnostic Cytology and Haematology of the Horse, 2nd International Veterinary Information Service, Ithaca.
edn. Mosby, St Louis, pp.65–72 Online. Available: http://www.ivis.org
Cowell RL, Tyler RD 2002 Diagnostic Cytology and Haema- Mair TS 1987 Value of tracheal aspirates in the diagnosis of
tology of the Horse, 2nd edn. Mosby, St Louis chronic pulmonary diseases in the horse. Equine
Darien BJ 1994 Eosinophilic pneumonitis in foals and horses. Veterinary Journal 19: 463–465
Compendium on Continuing Education for the Practicing Malikides N 2004 A longitudinal cohort study of inflam-
Veterinarian 16: 1210–1212 matory airway disease in racing thoroughbreds in Sydney,
DeHeer HL, Parry BW, Grindem CB 2002 Pleural fluid. In: Australia. PhD thesis, University of Sydney, Australia
Cowell RL, Tyler RD (editors) Diagnostic Cytology and Malikides N, Hughes KJ, Hodgson DR et al 2003 Comparison
Haematology of the Horse, 2nd edn. Mosby, St Louis, of tracheal aspirates and bronchoalveolar lavage in
pp.107–126 racehorses. 2. Evaluation of the diagnostic significance of
Derksen FJ, Brown CM, Sonea IM et al 1989 Comparison of neutrophil percentages. Australian Veterinary Journal
transtracheal aspirate and bronchoalveolar lavage 81: 685–687
cytology in 50 horses with chronic lung disease. Equine Martin BB, Beech J, Parente EJ 1999 Cytologic examination
Veterinary Journal 21: 23–26 of specimens obtained by means of tracheal washes
performed before and after high-speed treadmill exer- Raidal SL 1995 Equine pleuropneumonia. British Veterinary
cise in horses with a history of poor performance. Journal 151: 233–261
Journal of the American Veterinary Medical Association Raidal SL, Love DN, Bailey GD 1995 Inflammation and
214: 673–677 increased numbers of bacteria in the lower respiratory
McGorum BC, Dixon PM 1994 The analysis and interpretation tract of horses within 6 to 12 hours of confinement
of equine bronchoalveolar lavage fluid (BALF) cytology. with the head elevated. Australian Veterinary Journal
Equine Veterinary Education 6: 203–209 72: 45–50
McGorum BC, Dixon PM, Halliwell REW et al 1993a Robinson NE 2001 International workshop on Equine Chronic
Comparison of cellular and molecular components of Airway Disease. Equine Veterinary Journal 33: 5–19
bronchoalveolar lavage fluid harvested from different Robinson NE 2003 Inflammatory airway disease: defining the
segments of the equine lung. Research in Veterinary syndrome. Conclusions of the Havemeyer Workshop.
Science 55: 57–59 Equine Veterinary Education 15: 61–63
McGorum BC, Dixon PM, Halliwell REW et al 1993b Sweeney CR, Rossier Y, Ziemer EL et al 1992 Effects of lung
Evaluation of urea and albumin as endogenous markers site and fluid volume on results of bronchoalveolar
of dilution of equine bronchoalveolar lavage fluid. lavage fluid analysis in horses. American Journal of
Research in Veterinary Science 55: 52–56 Veterinary Research 53:1376–1379
McKane SA, Canfield PJ, Rose RJ 1993 Equine bronchoalveolar Sweeney CR, Rossier Y, Ziemer EL et al 1994 Effect of
lavage cytology: survey of thoroughbred racehorses in prior lavage on bronchoalveolar lavage fluid cell
training. Australian Veterinary Journal 70: 401–404 population of lavaged and unlavaged lung segments
Newton JR, Wood JLN, Dunn KA et al 1997 Naturally in horses. American Journal of Veterinary Research
occurring persistent and asymptomatic infection of the 55: 1501–1504
guttural pouches of horses with Streptococcus equi. Timoney JF 2004 The pathogenic equine streptococci.
Veterinary Record 140: 84–90 Veterinary Research 35: 397–409
Nicholls R, Pirie RS 2001 Preparation of bronchoalveolar Traub-Dargatz JL 1997 Field examination of the equine
lavage fluid cytology slices by cellular gravitation – patient with nasal discharge. Veterinary Clinics of North
method of preparation and comparison with cytospin America; Equine Practice 13: 561–588
preparations. Proceedings of the Word Equine Airway Whitwell KE, Greet TRC 1984 Collection and evaluation of
Symposium, Edinburgh, p.75 tracheobronchial washes in the horse. Equine Veterinary
Pickles KJ, Pirie RS, Rhind S et al 2001 The effect of time, Journal 16: 499–508
temperature and fixatives on cytological assessment of Zinkl JG 2002 Lower respiratory tract. In: Cowell RL, Tyler RD
equine bronchoalveolar lavage fluid. Proceedings of the (editors) Diagnostic Cytology and Haematology of the
Word Equine Airway Symposium, Edinburgh, p.78 Horse, 2nd edn. Mosby, St Louis, pp.73–86
Radiography and Radiology of the
Respiratory Tract
10 Safia Barakzai and Hester McAllister
Upper Respiratory Tract Lateral radiographs (Fig. 10.1)

Radiography is an extremely useful diagnostic tool for the These views are obtained with the cassette positioned in a
evaluation of many parts of the equine upper respiratory vertical plane, as close as possible to the affected side of the
tract (URT), in particular for those parts of the URT head. The horizontal X-ray beam should be centered at the
that cannot easily be evaluated endoscopically such as area of interest (Table 10.1). The principal disadvantage of
the paranasal sinuses. The techniques described in this the lateral view is that the structures on the left and right
chapter are applicable to all equine practices because sides of the skull are superimposed, and therefore cannot
portable radiography machines are adequate for obtain- be evaluated individually.
ing diagnostic radiographs of the equine URT. Excellent
quality radiographs can be obtained in the standing,
heavily sedated horse, and consequently there is no
requirement for general anesthesia.
Radiographic Techniques
The X-ray machine used must be capable of allowing both
vertical and horizontal movements of the X-ray beam.
Exposure requirements are not high for equine URT
radiography, especially if cassettes with rare-earth inten-
sifying screens are used. The use of large (35 × 43 cm)
cassettes is often helpful when evaluating a complex
structure such as the equine head because the position of
any observed abnormality can be assessed in relation to
obvious anatomical landmarks. The use of grids is
discouraged for standing radiography because they are not
required to obtain high-quality radiographs and their use
causes increased risk of radiation exposure to personnel.
Radiation safety should be strictly adhered to when
taking radiographs of the equine URT, as personnel holding
the horse and the cassette are potentially close to the
primary beam. The primary beam should be collimated
to include only the areas of interest. All assisting person-
nel should wear lead aprons, lead gloves, and radiation
exposure badges (dosimeters) and should maintain a
distance of at least 2 m from the primary beam. Heavy
sedation (such as with xylazine/detomidine/romifidine plus
butorphanol) reduces head movement and thereby reduces
the need for repeat exposures because of movement
artifacts. Resting the nose of the horse on a stool may also
help to minimize the swaying movements caused by heavy
sedation. A fabric head collar without metal components Fig. 10.1. Diagram showing direction of X-ray beam (arrow) and
should be used during radiography of the equine skull. cassette position for lateral radiographs of the head.
151
152 10 Radiography and Radiology of the Respiratory Tract
Table 10.1. Center point of the X-ray beam

for lateral radiographs of various structures
in the equine upper respiratory tract
Structure(s) being radiographed X-ray beam center point
Maxillary sinuses and maxillary Dorsal to the rostral

cheek teeth apices aspect of the facial crest
Guttural pouches Caudal aspect of the

vertical ramus of the
mandible
Nasopharynx, larynx and proximal Caudoventral angle of

trachea/esophagus the mandible
30º
Fig. 10.2. Diagram showing direction of X-ray beam (arrow) and

cassette position for 30° dorsolateral–lateral radiographs of the head Fig. 10.3. Diagram showing center point (×) and cassette position for
to view the maxillary cheek teeth apices and sinuses. dorsoventral radiograph of the head in the standing horse.
30° dorsolateral–lateral oblique

radiographs (Fig. 10.2) (the horse’s head can be rested on the cassette). The X-ray
beam is directed perpendicular to the plate, centered on
This oblique radiographic view separates the left and right the midline, at the level of the rostral aspect of the facial
sides of the maxillary and frontal sinuses and the maxillary crests. Positioning is very important when taking this
cheek teeth rows, allowing evaluation of individual apices radiographic view, because any lateral deviation from a true
and the surrounding structures. The cassette is again dorsoventral will cause superimposition of the mandibular
positioned in a vertical plane, as close as possible to the and maxillary cheek teeth rows on one side, and also
affected side of the head. The X-ray tube is positioned at a obscure the ventral conchal sinus and nasal cavity on one
higher level on the opposite side, with the beam directed side. This view is most useful for evaluating the areas of
30° down from the horizontal and centered at the rostral the ventral conchal sinus (medial compartment of the
aspect of the facial crest and collimated to include all six rostral maxillary sinus), nasal cavities, and nasal septum.
cheek teeth, or alternatively at the suspected tooth root Abnormalities of the cheek teeth such as laterally or medially
apex. A higher exposure is required to optimally image the displaced teeth, sagittal fractures, advanced caries and
equine cheek teeth apices as compared to the paranasal alveolar changes associated with advanced apical infections
sinuses. The presence of rostrocaudal angulation is a com- can also be observed using this radiographic view.
mon technical fault associated with this projection and
should be avoided because it can complicate radiographic Additional radiographic techniques
interpretation.
The use of a small metal marker such as a paper clip,
Dorsoventral radiographs (Fig. 10.3) placed over an area of facial swelling can be useful when
evaluating radiographic changes and assessing their likely
This radiographic view is obtained by positioning the significance, particularly if there is suspicion of an apical
cassette underneath and parallel to the hemi-mandibles infection. If an external sinus tract is present, a blunt
10 Radiography and Radiology of the Respiratory Tract 153
Fig. 10.4. Lateral small radiograph outlining

the maxillary cheek teeth and paranasal
sinuses of a normal horse. Note that the
FS left and right rows of maxillary cheek teeth
DCS are superimposed, making it impossible to
evaluate the apex of any individual cheek
ET tooth. The apices and reserve crowns of
the upper 08s and 09s (third and fourth
maxillary cheek teeth) are within the rostral
CMS maxillary sinus (RMS), and the apices and
RMS reserve crowns of the upper 10s and 11s
(fifth and sixth maxillary cheek teeth) are
within the caudal maxillary sinus (CMS). The
positions of the ethmoturbinates (ET), dorsal
conchal sinus (DCS) and frontal sinus (FS)
are also shown.
06 07 08 09 10 11
malleable metallic probe should be inserted into the tract

and the appropriate lateral oblique radiograph should be
taken. This technique can provide irrefutable evidence of
dental disease, identify the affected apical area of the tooth,
and provide a landmark for surgical procedures. The
injection of contrast material such as Iohexol into a
draining tract can similarly provide valuable diagnostic and NS
CMS
spatial information.
The use of contrast paranasal sinusography has been
described by Behrens et al (1991). The injection of contrast VC VC
medium directly into the sinuses outlines solid masses that
may be difficult to distinguish in survey radiographs
because they closely conform to the contour of the sinuses,
RMS
and also allows detection of interruption of normal
gravitational flow of fluid through the sinuses. However,
direct sinoscopy, or three-dimensional imaging modalities MX
such as computed tomography or magnetic resonance
imaging, are likely to be of greater diagnostic value for
MD
such abnormalities.
Radiography of the guttural pouches, temporomandibu-
NC NC
lar joints and stylohyoid bones is occasionally necessary.
To separate and thereby differentiate the left and right
sides, these areas can be radiographed with the affected
side next to the cassette, and the X-ray beam directed
horizontally, angled at 10–15° in a rostrocaudal direction.
Nasal Cavity and Paranasal Sinuses Fig. 10.5. Dorsoventral radiograph of the skull of a normal horse. The
maxillary (MX) and mandibular (MD) cheek teeth rows are clearly
Normal anatomy and radiographic evident. The nasal cavities (NC), nasal septum (NS) and ventral conchal
appearance (Figs 10.4 and 10.5) sinuses (VC) can also be assessed on this view. The rostral (RMS) and
caudal (CMS) maxillary sinuses, located lateral to the upper 08s–11s,
The rostral maxillary sinus of the horse is usually may also be evaluated.
positioned dorsal to the apices of the upper 08s and 09s
(Triadan system, equivalent to the third and fourth radio-opaque line in lateral radiographs. In horses less than
maxillary cheek teeth) (Perkins 2002), and is separated 7 years of age, the reserve crowns of the upper 08s and
from the caudal maxillary sinus by a complete bony 09s can almost completely fill the rostral maxillary sinus,
septum. This septum is usually angled from rostrolateral to and even in the older horse, with shorter cheek teeth
caudomedial, and therefore is not usually seen as a single reserve crowns, the rostral maxillary sinus often remains a
Fig. 10.6. Lateral radiograph of the sinuses

of a horse with primary sinusitis. There are
fluid lines present (arrows) in the rostral and
caudal maxillary sinuses, and also in the
conchofrontal sinus, which appear as hori-
zontal lines with soft tissue opacities ventral
to them.
small structure. The medial compartment of the rostral sinus, plus the dorsal conchal sinus together make up the
maxillary sinus is also known as the ventral conchal sinus, conchofrontal sinus.
and communicates with the rostral maxillary sinus over The nasal cavities are positioned medial and rostral to
the infra-orbital canal. The ventral conchal sinus often the ventral conchal sinus, and the left and right cavities are
extends caudally (as the ventral conchal “bulla”) to the separated by the nasal septum, which runs in the midline.
level of 111/211 (sixth maxillary cheek teeth), and is best The septum, which can be seen on dorsoventral radio-
evaluated radiographically using a dorsoventral projection graphs, should be evaluated for lateral deviation, most
(see Figs 10.5 and 10.10). commonly as a result of expansive space-occupying lesions
The caudal maxillary sinus is usually positioned within the ventral conchal sinus or nasal cavity.
immediately dorsal to the apices of the upper 10s and 11s
(fifth and sixth cheek teeth), and communicates with Primary sinusitis
the dorsal conchal sinus via the large frontomaxillary
aperture. The frontal sinus is the dorsocaudal extension Horses with primary sinusitis often have free fluid within
of the dorsal conchal sinus, and appears as a triangular the sinuses, which can be seen as one or more horizontal
structure on lateral radiographs, positioned dorsal to the fluid lines (with increased opacity below the line) on lateral
ethmoturbinates and rostral to the cranium. The frontal radiographs (Fig. 10.6). Other changes associated with
108
Fig. 10.8. A 30° dorsolateral–lateral oblique radiograph of the

Fig. 10.7. A 30° dorsolateral oblique radiograph of a horse with maxillary cheek teeth and maxillary sinuses of a horse with chronic
periapical infection and dental sinusitis. The infected tooth (209) apical infection of 108. Note the marked remodeling of the apex
shows a soft tissue density (granuloma) around its rostral roots of this tooth, with loss of the normal pointed root outlines and
(black arrows), surrounded by a radiolucent halo (white arrows). The deposition of radiodense material (cementoma formation) around all
apex and reserve crown of this tooth lie within the rostral maxillary three roots.
sinus.
primary sinusitis are localized, diffuse or delineated These changes manifest as periapical radiolucent “haloes,”
intrasinus radio-opacity, nasal septum deviation and and rounded or “clubbed” appearance of the tooth roots as
mineralization of sinus walls in more chronic cases. In a result of gross lysis/destruction of the root structures
many cases of sinusitis, the increased soft tissue opacity (Fig. 10.7). In more chronic periapical infections, a zone of
within the sinuses may simply be the result of inflamed radiodense sclerosis usually surrounds the periapical “halo”,
and hypertrophied sinus mucosa, which occurs with because of new bone deposition around the lytic infected
any chronic sinus infection (Gibbs & Lane 1987, Tremaine area. More marked sclerosis develops around the apices
& Dixon 2001). It should be remembered that fluid or of the first two maxillary cheek teeth than the caudal
soft tissue opacities within the sinuses can also be seen maxillary cheek teeth. This is because the apices of the first
secondary to other disorders that cause sinusitis (as two maxillary cheek teeth are usually located in denser
detailed below). Trephination and lavage of the sinuses bone than those of the caudal four maxillary cheek teeth,
may decrease the amount of fluid accumulating within which are situated in thin alveolar bone within the
the sinuses and allow for more accurate radiographic maxillary sinuses. Longstanding periapical infection may
evaluation of intrasinus structures such as the cheek teeth result in abnormal depositions of radio-opaque cementum
apices and ethmoturbinates. at the tooth apex (Fig. 10.8). Dystrophic mineralization of
the nasal conchae (coral formation) may also occur with
Dental sinusitis chronic maxillary cheek tooth periapical infections (Gibbs
& Lane 1987, Tremaine & Dixon 2001).
Periapical dental infections are a common cause of sinusitis Soft tissue opacities may also be apparent in the sinuses
in horses (Boulton 1985, Gibbs & Lane 1987, Tremaine & if periapical infection of the caudal maxillary cheek teeth
Dixon 2001). The apices of the upper 08s, 09s, 10s, and has occurred. These opacities may be caused by a rounded,
11s (and variably the 07s) lie within the rostral and caudal soft tissue granuloma (Fig. 10.7) or later, an encapsulated
maxillary sinuses, and abscesses which form around abscess developing over the infected apex. Fluid lines may
the dental apices can erode the thin alveolar bone, with be apparent in straight lateral views of the sinuses, because
resultant infection of the sinuses. of accumulation of liquid purulent material. In cases of
Radiographic changes consistent with early periapical dental sinusitis, as in other chronic sinusitis cases, inflamed
infection include widening of the periodontal space and and hypertrophied sinus mucosa may cause generalized
thinning of the lamina dura denta (the dense rim of increased soft tissue opacity within the sinuses (Gibbs &
cortical bone which lines the alveolus). When periapical Lane 1987, Tremaine & Dixon 2001).
infection has been present for many weeks, the affected Although radiography has a good (95%) specificity for
apices develop lytic changes, especially in mature teeth the diagnosis of periapical infections, it is not very sensitive
where the true roots (non-enamel areas) are well formed. (50%), particularly in early cases (Weller et al 2001).
ET
VCS
Fig. 10.9. Lateral radiograph of a horse wtih an ethmoidal hematoma

(arrows) attached to the rostro-ventral aspects of the ethmotubinates
(ET). The mass appears as a rounded soft tissue density.
Fig. 10.11. Dorsoventral radiograph of the same horse as Fig. 10.10.

Note the soft tissue opacity mass causing enlargement of the left
ventral conchal sinus, slight deviation of the nasal septum to the right
and increased radio-opacity of the left rostral and caudal maxillary
sinuses, lateral to the 09s–11s (fourth to sixth cheek teeth) and
extending caudally.
Fig. 10.10. Lateral radiograph of a horse with a large sinus cyst in its
rostral and caudal maxillary sinuses. Note the calcified nature of the
cyst wall (arrows). interpretation of the ethmoidal area is complicated by the
superimposition of PEH lesions over the globes, orbits, and
ethmoidal labyrinths. A well-circumscribed, round mass
Studies have shown that in cases of dental sinusitis, of soft tissue radio-opacity in the area of the ethmoid
infected teeth can be recognized with confidence in only labyrinth or sphenopalatine sinus has been reported in
50–57% of cases (Gibbs & Lane 1987, Tremaine & Dixon 57% of horses with PEH (Tremaine & Dixon 2001).
2001). In part, this may be because the superimposition
of opaque sinus contents and maxillary osteitis on under- Sinus cysts (Figs 10.10 and 10.11)
lying dental structures prevents recognition of subtle
abnormalities. In such cases, scintigraphy is a useful As with other causes of secondary sinusitis, sinus cysts are
adjunctive diagnostic technique that may provide evidence commonly associated with increased radio-opacity and
to allow differentiation between cases of primary and fluid lines within the sinuses. Radiographic changes that
dental sinusitis (Weller et al 2001, Barakzai et al 2006). are strongly suggestive of sinus cysts include soft tissue
opacities, with a partially mineralized capsule containing
Progressive ethmoidal hematoma (PEH) irregular bony spicules; such changes are present in 35%
(Fig. 10.9) of horses with sinus cysts (Tremaine & Dixon 2001).
Distortion of the overlying facial bones, nasal septum
PEH lesions may be evident as discrete soft tissue opacity deviation and secondary dental deformities are also com-
lesions on lateral skull radiographs; however, small PEH monly associated with sinus cysts (Lane et al 1987a,b,
lesions can sometimes be missed because radiographic Tremaine & Dixon 2001).
Maxillary fractures
Maxillary fractures are commonly the result of kicks to gp
the skull, and affected horses often present with epistaxis
as a result of traumatic damage to the mucosa lining
the maxillary or frontal sinuses. If skull fractures are st
suspected, oblique views taken at varying angles may a
be necessary to highlight the fracture lines. However, aef
np
because of the complexity of bones within the skull, and Iv
e
particularly the sinus areas, non-displaced fractures are
often difficult to detect radiographically. Superimposition of sp
soft tissue opacities or fluid lines within the sinuses as a
result of intrasinus hemorrhage and mucosal inflam-
mation may further obscure fracture lines. Nasofrontal
suture periostitis is a common delayed sequel to maxillary
Fig. 10.12. Lateral radiograph of the nasopharynx (np), larynx and
fracture, and is seen radiographically as proliferative new
guttural pouches (gp). The borders of the guttural pouches are
bone formation, most commonly at the nasofrontal suture indicated with arrows. Note the stylohyoid bones (st), epiglottic
lines (Tremaine & Dixon 2001). cartilage (e), arytenoid cartilages (a), ary-epiglottic folds (aef),
laryngeal ventricles (lv) and soft palate (sp).
Neoplasia
The most frequently occurring tumor of the equine extended, may allow easy differentiation of unilateral from
sino-nasal area is squamous cell carcinoma (Priester & bilateral disease, as would a slightly (10–15°) rostro-
Mackay 1980, Head & Dixon 1999). Other reported tumor caudally angulated lateral view. Chronic empyema may
types include adenocarcinoma, fibrosarcoma, spindle lead to stagnation of pus within the pouch with its subse-
cell sarcoma, myxoma, lymphosarcoma, hemangiosar- quent inspissation and chondroid formation. Chondroids
coma, and osteoma/osteosarcoma (Head & Dixon 1999). may be seen as smooth, irregularly sized, discrete soft tissue
Neoplastic lesions within the sinus may appear radio- opacities within the lumen of the guttural pouch.
graphically as soft tissue opacities of variable size, and are Enlarged or abscessed retropharyngeal lymph nodes are
often radiographically indistinguishable from other space- often seen in the floor of the medial compartment of the
occupying masses. However, if gross destruction of bone is guttural pouches in horses with strangles. These will be
evident radiographically, this is strongly suggestive of evident radiographically as an irregular outline of the
neoplasia (Tremaine & Dixon 2001). ventral border of the pouch.
Guttural Pouch Guttural pouch mycosis

The guttural pouches appear radiographically as large Mycotic lesions of the guttural pouches are not usually
radiolucent structures located ventral to the base of the distinguishable on radiographs, unless they are very large
skull and atlas, dorsal to the nasopharynx, and mainly and proliferative. However, horses that have had a recent
caudal to the vertical ramus of the mandible (Fig. 10.12). episode of epistaxis as a result of guttural pouch mycosis
The guttural pouches are incompletely divided into medial may have a fluid line (blood) within the affected guttural
and lateral compartments by the stylohoid bones, which pouch (Fig. 10.13). Radiographs may be useful in some
articulate dorsally with the temporal bone at the cases to distinguish between guttural pouch mycosis and
temporohyoid joint. rupture of the rectus capitus ventralis muscles. This
traumatic muscle rupture may occur in horses that have
Guttural pouch empyema reared over backwards and sustained trauma to the base
of the skull. In both disorders, endoscopic examination
This disorder is most commonly associated with infection may reveal blood emerging from the ostia of one or both
with Streptococcus equi var. equi (strangles), following guttural pouches, and the guttural pouch may be blood-
abscessation and drainage of the retropharyngeal lymph filled, obscuring the endoscopist’s view, and preventing
nodes into the guttural pouches. Radiographically, fluid direct inspection of the structures within the guttural
accumulation may be evident in one or both guttural pouch. Radiography may reveal small avulsion fracture
pouches as an increased area of radio-opacity ventral to a fragments of the ventral aspect of the occipital and
horizontal fluid line. A dorsoventral radiograph of the basisphenoid bones if epistaxis is the result of rupture of
caudal skull and cranial neck, taken with the head fully the rectus capitus ventralis muscles.
Stylohyoid abnormalities
The temporohyoid articulation is most commonly affected
as a result of temporohyoid osteopathy. In some cases
extension of disease affecting the middle ear may result
in osseous proliferation of the dorsocaudal aspect of the
stylohyoid bone within the guttural pouch. Ossification of
the normally cartilaginous temporohyoid articulation may
occur, and normal tongue movements may then result in
fracture of the mid-portion of the affected stylohyoid bone,
or, more commonly, the petrous temporal bone (Blythe
1997). Fractures of the stylohyoid may also result from
chronic guttural pouch mycosis if the fungal plaque is
located over the stylohyoid bone.
Enlarged or fractured stylohyoid bones may be seen on
Fig. 10.13. Lateral view of the guttural pouch of a horse that has had lateral radiographs of the guttural pouch area, and slightly
a recent episode of epistaxis from the internal carotid artery as a result (10–15°) rostrocaudally angulated projections will allow
of guttural pouch mycosis. Note the fluid line (arrows) within the more accurate evaluation by preventing superimposition of
guttural pouch, and mottled soft tissue densities visible dorsal to this the left and right sides.
which may represent large proliferative fungal fibrinous plaques.
Nasopharynx/Larynx
More chronic cases of guttural pouch mycosis may have Normal anatomy and radiographic
bony remodeling of the ventral aspect of the petrous appearance (Fig. 10.12)
temporal bone, and possibly also of the dorsal aspect of the
stylohyoid bone. Pathological fractures of the stylohyoid The epiglottis is the most easily identifiable structure in
bone as a result of chronic fungal osteitis are uncommon. radiographs of this area. It is positioned just rostral to the
caudoventral angle of the mandible, and appears as a
Guttural pouch tympany curved, dorsally convex soft tissue opacity, with the free tip
pointing rostrally into the nasopharynx. It lies dorsal to the
This congenital condition is seen predominantly in filly soft palate, and the caudal border of the soft palate should
foals and yearlings, and occurs when the ostium of the form a seal around the epiglottic base. The dorsal aspect of
guttural pouch acts as a one-way valve, allowing air into the soft palate can be followed rostrally, lying on the base
but not out of one or both guttural pouches. The air- of the tongue, until superimposition of the caudal cheek
distended pouch is seen radiographically as a very large teeth obscures it from view. A small amount of air may be
radiolucent structure extending much further caudally detected between the soft palate and the base of the tongue.
than normal. In severely affected animals, compression of Dorsal and rostral to the epiglottis is the radiolucent
the nasopharynx by the distended pouch may result in (air-filled) nasopharynx. The caudodorsal border of the
stridor and dysphagia. The condition is usually unilateral, nasopharynx is demarcated by the soft tissue opacities of
and therefore the normal contour of the contralateral the arytenoid cartilages. Depending on the radiographic
pouch may also be seen radiographically. Some degree of exposure, the aryepiglottic folds may also be visible on
secondary empyema, caused by lack of drainage from the lateral radiographs. The laryngeal ventricles are apparent
affected pouch, is common. as small rounded or elliptical radiolucent areas caudal to
the base of the epiglottis. A degree of mineralization of the
Masses within the guttural pouches laryngeal cartilages may be considered normal even for
some younger horses.
Tumors of the guttural pouch are uncommon. Melanoma
is the most frequent (Fintl & Dixon 2000), but lympho- Arytenoid chondritis
sarcoma, hemangiosarcoma, fibroma, and squamous cell
carcinoma have also been reported. An abnormal outline of Young male thoroughbreds are particularly predisposed to
the pouch may be evident radiographically, with tumors this condition which involves infection and inflamma-
occurring most commonly in the area of the retropharyn- tion of one or both arytenoid cartilages. Radiography of
geal lymph nodes in the floor of the pouch. Large tumors the affected area in chronic cases may reveal abnormal
or secondary abscessation of the lymph nodes may cause mineralization of affected cartilages, and this is associated
nasopharyngeal compression and dyspnea or dysphagia. with a poor prognosis for return to athletic function.
Fig. 10.14. Lateral view of the pharynx and larynx of a 3-month-old

colt with fourth branchial arch defect showing an abnormal air
column in the proximal esophagus (red arrows), and rostrally displaced
palato-pharyngeal arch (white arrow). The normal radiolucent air Fig. 10.15. Lateral radiograph of the pharynx and larynx of a horse
column within the trachea is outlined with white arrowheads. with persistent DDSP. The soft palate (red outline) can be seen lying
dorsal to the ventrally curved epiglottic cartilage (yellow outline). Note
the artifacts caused by metal components of the headcollar.
Fourth branchial arch defect syndrome
(cricopharyngeal–laryngeal dysplasia)
to less than 6.5 cm (Linford et al 1983). When measuring
In 78% of animals affected by this condition, a continuous epiglottic length using a lateral radiograph, the effect of
column of air extending from the nasopharynx into the magnification must be taken into account and the length
lumen of the proximal esophagus (as a result of aplasia of corrected accordingly. Epiglottic hypoplasia may predis-
the cricopharyngeus muscles) will be evident on lateral pose affected animals to epiglottal entrapment. Although
radiographs (Lane 2001) (Fig. 10.14). In contrast, normal epiglottic hypoplasia was previously thought to predispose
horses may have only a small lucent linear air shadow, horses to intermittent dorsal displacement of the soft
often less than 5 cm in length in the proximal esophagus. palate, this association is now in doubt.
In some affected horses, rostral displacement of the palato-
pharyngeal arch may be evident on radiographs as a soft Subepiglottic cysts
tissue opacity “dew drop,” intruding from the dorsal wall of
the pharynx into the radiolucent nasopharynx. It is, Subepiglottic cysts are sometimes not visible using an
however, imperative that these radiographs are taken with endoscope passed per nasum because the cyst is positioned
the horse unsedated, as rostral displacement of the palato- ventral to the soft palate. Radiography is a particularly
pharyngeal arch and air in the proximal esophagus may be useful diagnostic aid for such cases to confirm the presence
observed in normal horses following sedation. and size of these lesions. Lateral radiographs of horses with
subepiglottic cysts show a well-demarcated, rounded soft
Epiglottic entrapment tissue mass ventral to the epiglottis, which may appear
to displace the epiglottic tip dorsally and caudally. The
The rostral free tip of the epiglottis can become trapped introduction of oropharyngeal contrast material may also
in a pouch of mucosa that develops from the mobile, sub- be of value for delineating the cyst.
epiglottic mucosal folds. Epiglottal hypoplasia will predis-
pose to this condition. Radiographically, the epiglottis appears Persistent dorsal displacement
shortened and less well defined than usual, and there may of the soft palate (Fig. 10.15)
be concurrent dorsal displacement of the soft palate.
Radiography of horses affected with persistent dorsal
Epiglottic hypoplasia displacement of the soft palate will reveal the soft palate
lying dorsal to the epiglottic cartilage, and an unusually
In a horse with a truly hypoplastic epiglottis, lateral large amount of air between the base of the tongue and
radiographs of the pharynx confirm that the epiglottal the soft palate. The epiglottis and subepiglottic area should
length is reduced from the normal length of 8.3–9.2 cm be carefully checked for abnormalities such as subepiglottic
from tip to hyoid articulation in a thoroughbred-type horse, cysts as these will not be visible endoscopically.
Fig. 10.16. Tracheal collapse. This 22-year-

old pony had poor exercise tolerance, inspira-
tory difficulty, and coughing over the previous
12 months. This radiograph of the caudal
cervical region (from the level of the fifth to
seventh cervical vertebrae) shows the tracheal
lumen is undulating and markedly narrowed.
The black arrowheads outline the position of
the normal tracheal lumen. A mucus plug
(black arrow) is visible within the tracheal
lumen.
Trachea Tracheal collapse
Normal anatomy and radiographic appearance Lateral radiographs of the trachea of ponies with this
disorder may appear normal if the radiograph is taken
The cartilaginous tracheal rings are distinguishable on the during expiration, but inspiratory radiographs may show
dorsal and ventral aspect of the radiolucent air column marked narrowing of the air column within the cervical
in the tracheal lumen. This radiolucent column may be trachea at the site of obstruction (Fig. 10.16) because the
slightly wider at the most rostral aspect of the trachea, but trachea collapses as a result of the subatmospheric
narrows to a uniform width within three or four tracheal pressures within the trachea at this stage in the respiratory
rings. The cartilage rings may become mineralized with cycle. Developmental rotation of a section of a collapsed
age. The intrathoracic trachea runs in a horizontal trachea can also be radiographically misleading. Similar
direction and then dips ventrally at the heart base. The radiographic features may be obtained after removal of a
trachea divides at the heart base into left and right main- tracheotomy tube, if the tracheal rings were completely
stem bronchi at the level of the fifth or sixth intercostal transected to allow placement of the tube, because the
space. The terminal trachea may be displaced dorsally remaining part of the ring may become unstable and tend
as a result of hilar lymphadenopathy or cardiomegaly to collapse inwards during inspiration.
particularly involving the left atrium.
Intra/extraluminal tracheal masses
Tracheal trauma/perforation
Primary neoplastic conditions of the trachea are rare
Horses that have sustained traumatic injury to the ventral but include lymphoma and squamous cell carcinoma.
neck may have tracheal perforations that are evident Excessive granulation tissue or chondroma-type masses
radiographically as radiolucent lines of air tracking up and affecting the adjacent cartilages may develop following
down the soft tissues of the neck. Rupture of the trachea removal of a temporary or permanent tracheostomy tube.
causes diffuse subcutaneous emphysema, which may track Intraluminal masses may be seen radiographically as soft
into the thoracic cavity and cause pneumomediastinum tissue opacities impinging on the radiolucent air column
and pneumothorax (Fubini et al 1985). within the trachea.
Fig. 10.17. (A) Diagram indicating the centering

points for a complete radiographic examination
of the adult equine thorax. The radiographic
images related to each centering point are
indicated in pictures 1–4. Redrawn from Farrow
1981b, with permission.
Continued
Extraluminal tracheal masses, such as abscesses of thorax and increase the tissue depth in this area. In adult
the caudal cervical lymph nodes as a result of strangles, horses, thoracic radiographs are taken in the standing
or tumors, may cause tracheal compression, thereby position with the cassette located on the side of interest.
narrowing the intraluminal air column, which may be seen The horse should stand level, with its weight evenly
radiographically. distributed on all four limbs. The largest cassette size
(35 × 43 cm) should be used. For thoracic radiography in
adult horses, the thorax is divided into at least three, and
Thoracic Radiography often four, overlapping radiographic areas (Fig. 10.17A),
Radiographic technique namely craniodorsal, caudodorsal, cranioventral and
caudoventral (Farrow 1981a). If the horse stands with the
Radiography of the thorax in adult horses presents a forelimbs extended forwards, the cranioventral thorax can
particular challenge because of the size of the chest. In be more clearly seen on the radiograph. Chemical restraint
addition, the muscles of the forelimb overly the cranial ensures a cooperative patient and provides maximum
Fig. 10.17, cont’d. (B) Lateral radiograph of the normal caudodorsal

lung field of an adult horse. The vessels are clearly seen tapering
towards the periphery. The thin, linear, radio-opaque bronchial walls
are visible in the hilar region. The background lung opacity is the
normal interstitial component of the lung field. (C) End-on blood
vessels (white arrows) are relatively radio-opaque, particularly when
superimposed on rib shadows. They reduce in size towards the lung
periphery, which helps to differentiate them from nodular infiltrates.
Bronchi are seen in cross-section (arrowheads). (D) The esophagus,
containing a small volume of fluid, is seen in the caudodorsal thorax
(arrows) running horizontally towards the diaphragm.
C D
radiation safety for the personnel but may not be required is placed 15–30 cm (depending on the animal’s size) away
if the animal is ill and depressed. Assisting personnel from the chest wall (King et al 1981). This technique
should be kept to the minimum and they should not stand has the disadvantage of increasing magnification of the
close to the X-ray tube or cassette. thoracic structures.
Breathing movement artifact is one of the main limiting Exposure factors vary depending on the area of interest,
factors in the production of diagnostic radiographs using size of animal and the nature of the pathological changes
low and medium output X-ray machines. Fast, rare-earth present. If the exposure is made in the expiratory phase,
intensifying screens, in combination with fast film, enable which is generally longer than the inspiratory phase, there
exposure times to be kept to a minimum and reduce is less likelihood of movement blur. However, expiratory
movement blur. The use of a grid improves the quality of studies reduce the air/tissue contrast and the resultant
the final image but the requirement for increased exposure increased lung opacity may be misconstrued as being
factors increases the risk of motion artifact. The cassette abnormal. Inspiratory images provide more tissue con-
and grid must be properly aligned with the X-ray tube to trast, but the incidence of movement blur is increased.
avoid grid artifacts. Accurate centering is optimal if there is Overexposure results in the lung fields appearing exces-
a gantry system to link the cassette, grid and X-ray tube, sively radiolucent, resulting in failure to identify subtle
although use of a drip stand and a large shoulder bag pulmonary changes. Conversely, underexposure empha-
to hold the cassette and grid may suffice. If a grid is not sizes soft tissues and simulates a generalized pulmonary
used, scattered radiation from the animal can be reduced infiltration and pulmonary overcirculation (Koblik &
by employing the “air gap” technique, whereby the cassette Hornof 1985). Gross pathological abnormalities that are
restricted to one hemithorax will be evident on either right system may be visible in this region. The poorly defined
or left lateral radiographs. However, subtle changes interlobar divisions are not evident on radiographs of
affecting only one hemithorax may be missed unless both normal horses. The interstitium, which surrounds the
left and right lateral radiographs are obtained. Thus, airways and pulmonary vessels, forms the normal back-
in larger horses, both sides of the thorax should be ground opacity of the lung field. It appears as a network or
radiographed. Lesions in the hemithorax that is closer to honeycomb of ill-defined, non-linear radio-opaque strands
the cassette will be more sharply defined. (Fig. 10.17B). Aerated radiolucent lung is imaged cranial,
Foals may be radiographed standing or in lateral dorsal, and caudal to the cardiac silhouette. The lung fields
recumbency; high output machines and grids are usually of newborn foals are more opaque than those of older foals
unnecessary (Lamb & O’Callaghan 1989, Mair & Gibbs and adults; this is exacerbated when foals are radiographed
1989). A ventrodorsal view may be obtained in very young in lateral recumbency as a result of postural atelectasis.
foals (Jean et al 1999). However, the potential benefit of
obtaining such a view must be weighed against the Bronchi
positional stress inflicted on the foal. On the lateral view, bronchi are seen as a series of
diverging air-filled tubes with gradually narrowing lumina
Indications for thoracic radiography as they course from the tracheal bifurcation towards the
lung periphery. The bronchial walls are clearly defined as
Indications for thoracic radiography in horses include thin, radio-opaque, linear shadows in the central and
abnormal findings on thoracic auscultation, chronic respi- middle lung-fields. In cross-section, bronchi are identified
ratory disease, cough, nasal discharge, exercise intolerance, as thin-walled radio-opaque rings that gradually reduce in
tachypnea, dyspnea, and dysphagia. Radiography is the diameter towards the periphery.
diagnostic method of choice for evaluating pulmonary
parenchymal disorders, especially those involving the Pulmonary vasculature
axial or deep lung, and mediastinal disorders (Lamb & The pulmonary vessels are visible as a series of linear,
O’Callaghan 1989). Radiography is, however, less valuable tapering soft tissue opacities running in tandem with the
than ultrasonography for detection and assessment of bronchi to the lung periphery. In cross-section they are
pleural and peripheral lung disorders (Ainsworth & Hackett identified as circular soft tissue opacities lying adjacent to
2004). While thoracic radiographs are useful for monitor- the bronchi. When superimposed on the ribs, they appear
ing the progression of pulmonary disease processes, the particularly radio-opaque and may mimic intrapulmonary
radiographic appearance does not correlate well with nodules (Fig. 10.17C). The branches of the pulmonary
the severity of the disease process and the resolution of artery are seen dorsal to the caudal heart base as they
radiographic lesions often lags behind the progression emerge from the main pulmonary artery. Pulmonary veins
of the clinical syndrome (Sweeney 1991). Thus radio- are visible as they enter the left atrium at the caudodorsal
logical observations must be interpreted in the light of aspect of the cardiac silhouette, dorsal to the caudal vena
the clinical findings and ancillary laboratory test results. cava. As the pulmonary veins course towards the caudo-
dorsal aspect of the cardiac silhouette they diverge
Normal radiographic anatomy ventrally, away from the pulmonary arteries and bronchi.
Pulmonary arteries and veins cannot be distinguished from
The thoracic structures that are usually visible on each other in the lung periphery.
radiographs are the trachea, lungs, main-stem bronchi,
cardiac silhouette, aorta, pulmonary vasculature, caudal Mediastinum
vena cava, mediastinum, dorsal margin of the diaphragm, The air-filled trachea is usually the only structure visible in
ribs, vertebrae, and sternum. the soft tissue region of the cranial mediastinum. The heart
base, aorta, and pulmonary vasculature are profiled in
the middle mediastinal region. The aorta, esophagus and
Lungs caudal vena cava are seen in the caudal mediastinum. The
The lungs differ from those of other domestic species esophagus is not normally visible in the thorax unless it
in that they lack distinct lung lobes and deep inter- contains air, fluid or food (Fig. 10.17D).
lobar fissures. However, they are subdivided, somewhat
arbitrarily, into left cranial, left caudal, right cranial, right Diaphragm
caudal, and right intermediate or accessory lobes (Farrow The diaphragmatic outline is identified as a gently curved
1981b). The right accessory lobe is separated from the rest structure in the caudal thorax. The caudal vena cava
of the right lung by the caudal vena cava and the phrenic passes through it roughly at the mid-thoracic level. In adult
nerve. The right accessory lobe overlies the caudal vena horses the ventral half of the diaphragm is often obscured
cava on a lateral radiograph, and its bronchovascular by the cardiac silhouette.
Bronchial pattern
Interpretation of abnormal
radiographic appearance The primary, secondary, and often the tertiary bronchi are
usually visible on radiographs of normal adult horses. The
Assessment of thoracic radiographs requires a complete recognition of an abnormal bronchial pattern is often
examination of all the radiographs, evaluating the posi- appreciated only when severe pathological changes are
tioning, exposure factors, and recognition of the normal present. Thickened bronchial walls appear as prominent,
and abnormal anatomical structures. In addition, the paired, tapering radio-opaque lines, which extend further
location (perihilar, mid or caudal; peripheral or central), into the periphery than usual. In cross-section they appear
distribution (discrete, widespread or localized), and type of as distinct radio-opaque rings with radiolucent centers
radiographic pattern all provide valuable information (Fig. 10.18C,D). A bronchial pattern may be seen in horses
(Sande & Tucker 1997). with chronic airway inflammatory disorders such as
recurrent airway obstruction. Bronchiectasis, remodeling
Radiographic patterns and dilatation of the terminal bronchi in response to
chronic bronchial diseases such as recurrent airway
Pulmonary disease may cause a variety of radiological
obstruction, may appear radiographically as cylindrical or
changes that are broadly divided into four different pat-
saccular dilatations of the bronchial walls (Butler et al
terns, namely alveolar, bronchial, interstitial, and vascular
2000). A bronchial pattern can result from inflammatory
(Butler et al 2000). While the use of these patterns in
and allergic airway disease, and is often seen in combina-
describing lung diseases is somewhat controversial, it gives
tion with interstitial and alveolar infiltrates. The bronchial
clinicians a method of assessing and classifying the
walls of older horses may be more radio-opaque because
radiographic abnormalities. The location and distribution
of mineralization, although the clinical significance of this
of the pattern(s) may help the clinician to formulate a
is questionable.
differential diagnosis. However, radiographic patterns
rarely occur individually, but commonly develop as mixed Interstitial pattern
patterns which are dynamic and which change rapidly.
The normal equine lung has a large interstitial component
Importantly, they are not pathognomonic for any specific
and it is important not to misconstrue the normal
condition and each pattern may result from a variety of
radiographic appearance of the interstitium as evidence
clinical conditions.
of interstitial disease. The interstitial pattern is used to
describe the radiographic appearance of pathological
Alveolar pattern changes affecting the interstitium. Radiographically, inter-
An alveolar pattern occurs as a result of flooding of the stitial patterns can be subdivided into nodular and
normally air-filled alveoli with fluids such as blood, generalized (King 1981). A nodular interstitial pattern is
transudate or exudate, or as a result of a lack of aeration associated with infectious bacterial or mycotic diseases
caused by atelectasis or consolidation. This increases radio- causing abscesses and granulomas, silicosis (Berry et al
opacity in the affected area, thereby reducing radiographic 1991), and neoplasia. The generalized pattern may appear
contrast and obscuring the margins of the pulmonary linear, as a pronounced honeycomb-like network, or ill-
blood vessels. Air-filled bronchi, termed air bronchograms defined and hazy. The resultant generalized increased
(Fig. 10.18A,B), are usually visible as a series of radio- opacity of the lung background is interspersed with
lucent branching tubes surrounded by an ill-defined and radiolucent lung tissue. The generalized pattern is caused
poorly marginated, fluffy soft tissue opacity. This pattern is by fibrosis or cellular or fluid infiltrate in the interstitial
identified most easily in the ventral and caudoventral lung tissue, such as occurs with viral and bacterial pneumonia,
regions. Air bronchograms not only place the disease tuberculosis, allergic lung disease, early pulmonary edema
within the air spaces but also indicate the patency of the and pulmonary fibrosis. The margins of the pulmonary
proximal bronchus. If the alveolar infiltrate is severe, large vessels and bronchial walls are less distinct (Fig. 10.18E,F).
areas of lung may be affected. An interstitial pattern is rarely seen as a distinct entity.
Fig. 10.18. (A,B) Alveolar pattern. (A) This 1-week-old foal has a severe alveolar infiltrate in the ventral lung that obscures the cardiac silhouette
and ventral diaphragmatic outline. (B) A close-up of (A). Air bronchograms (arrows) are evident. Diagnosis: aspiration pneumonia. (C,D) Bronchial
pattern. (C) A 4-month-old foal showing a widespread interstitial infiltration. Peribronchial thickening is evident. (D) A close up of (C). The
bronchial walls are seen in longitudinal (black arrows) and cross-section (white arrow). Diagnosis: pneumonia. (E,F) Interstitial pattern.
(E) A 1-year-old colt with a widespread interstitial pattern. There is an overall increase in lung radio-opacity and the pulmonary vessels are
indistinct. (F) A close up of (E) showing a honeycomb pattern in the lung region just dorsal to the caudal vena cava.
E F
Vascular pattern with thick walls and contain a discernible horizontal

The vascular pattern is rarely seen in horses. Exposure fluid–gas interface, indicating gas-forming anaerobes, or a
factors must be correct because overexposure or under- bronchial fistula (Mair & Lane 1989).
exposure will obliterate or accentuate the pulmonary
vessels, respectively. Furthermore, assessment of the
vascular structures is subjective. An increased vascular Acute respiratory distress syndrome
pattern may be seen in severe left-sided cardiac failure and
in foals with left to right cardiovascular shunts. In contrast, This complex syndrome is associated with severe alveolar
hypovolemia and right to left sided cardiac shunts may and interstitial damage. Consequently, radiographic changes
cause an apparent decreased vascularity. Animals with include an initial interstitial pattern progressing to a
severe emphysema or lung hyperinflation appear to have severe bronchointerstitial infiltration affecting the caudo-
smaller blood vessels (Lamb & O’Callaghan 1989). dorsal lung fields with a subsequent alveolar pattern
(Lester & Lester 2001).
Pneumonia
Recurrent airway obstruction
The radiographic signs of pneumonia are diverse and
depend on the nature, stage, and severity of the disease Radiography of horses with recurrent airway obstruction is
(Barr 2003). Pneumonia caused by infectious agents may rarely diagnostically rewarding, except for the purpose of
result in an interstitial, bronchial or mixed pattern, with or eliminating other differential diagnoses. Acutely affected
without a concomitant alveolar pattern forming patchy cases may be normal radiographically. In chronic cases
lung infiltrates. Consolidation may lead to large coalescing there may be a generalized increase in the background
soft tissue opacities. Other additional radiographic features opacity of the lung fields and a widespread interstitial
that can be associated with pneumonia are pulmonary infiltration with a variable bronchial component. Flattening
abscesses, pleural effusion, pneumothorax, and hilar of the diaphragm as a result of pulmonary hyperinflation
lymphadenopathy. Pneumonia often affects the cranio- may be noted. Comparative studies taken at maximum
ventral or ventral regions of the lungs, which are difficult inspiration and expiration are sometimes useful in horses
to image in adult horses because they are obscured by the with suspected recurrent airway obstruction. Air trapping
cardiac silhouette. will result in little radiological difference between the
inspiratory and expiratory radiographs (Farrow 2002).
● Viral pneumonias are rarely diagnosed radiographically
but they cause radiographic signs of interstitial lung
disease. More commonly, a secondary bacterial infection Atelectasis
has occurred by the time the animal is radiographed
(Sande & Tucker 1997) (Fig. 10.19A,B). Atelectasis, which refers to absence of air in the alveoli,
● Pneumonia in foals caused by Rhodococcus equi is usually may be evident radiographically as a severe alveolar
located in the perihilar region and pulmonary abscessa- pattern, usually in the caudodorsal and/or caudoventral
tion is a common observation (Fig. 10.19C,D). lung fields. Quite marked alveolar infiltration is seen in
● Aspiration pneumonia usually affects the cranial and foals that have been recumbent for prolonged periods
ventral lung lobes (Fig. 10.19E). (Farrow 2002).
● Mycotic pneumonia, which is rare in horses, causes
a nodular interstitial infiltrate that is best seen in the
peripheral lung fields. Mycotic pneumonia must be Exercise-induced pulmonary
differentiated from other granulomatous diseases and hemorrhage (EIPH)
from metastatic neoplasia.
● Hematogenous pneumonia in adults often has a caudo- The typical radiographic presentation of EIPH is a
dorsal distribution (Rush & Mair 2004). generalized interstitial pattern. A triangular-shaped soft
tissue opacity with an alveolar pulmonary pattern is often
seen in the caudodorsal lung, merging with the diaphrag-
Lung abscesses matic shadow (O’Callaghan et al 1987a,b). This soft tissue
infiltrate gradually resolves with time, leading to a mixed
Lung abscesses generally occur secondary to bacterial pulmonary pattern (Fig. 10.21). Pulmonary infarcts may
pneumonia. They are evident as circular soft tissue opaci- appear similar radiographically to EIPH, but the lesion does
ties of varying sizes (Fig. 10.20). They may be cavitated not regress over time (Butler et al 2000).
Fig. 10.19. (A,B) Pneumonia in an 8-month-old foal. There is a widespread interstitial infiltration with a
focal alveolar pattern in the caudoventral (A) and caudodorsal (B) lung fields.
Continued
Pulmonary edema Pleural effusion

Pulmonary edema results in a mixed pattern of interstitial The pleural cavities are not normally identified on thoracic
and alveolar infiltrates with air bronchograms, usually radiographs. A minimum of 500 ml pleural fluid must be
affecting primarily the hilar and caudodorsal regions. present before it produces radiographic signs in horses
(Koblik & Hornof 1985). On standing radiographs, pleural
effusion causes an increased homogeneous opacity in the
Pulmonary bullae ventral thorax, with an uneven horizontal border. The
cardiac silhouette is obscured and the fluid opacity merges
Pulmonary bullae are air-filled cavities within the lung with the diaphragmatic outline (Fig. 10.22). A sharply
tissue. Their thin walls, and homogeneous radiolucent defined horizontal fluid line is only evident if there is
contents, enable differentiation from pulmonary abscesses. concomitant pneumothorax. In other species, including
C D
E
Fig. 10.19, cont’d. (C,D) A 6-month-old foal with Rhodococcus equi infection. Multiple cavitated
abscesses (arrows) are seen throughout the lung fields. (E) Six-week-old foal with aspiration pneumonia
and mega-esophagus. Air outlines the distended esophagus (white arrows) and a fluid–air interface (black
arrows) indicating intra-esophageal fluid is also visible. There is a widespread mixed pulmonary infiltrate
and the diaphragm is flattened because of hyperinflation.
humans and dogs, an obvious radiographic feature of that are visible dorsal to the effusion. This may give the
pleural effusion is separation of the individual lung lobes impression of an increased interstitial pattern, which may
by fluid. This feature is less obvious in horses with pleural be misinterpreted as evidence of pulmonary pathology.
effusion because the equine lung is separated only into left Some authors suggest that radiography is best per-
and right lungs and the accessory lobe of the right lung. formed following pleural drainage to visualize the ventral
However, one of the first signs of pleural effusion in horses thorax and lung field more clearly (Rush & Mair 2004).
is visualization of the ventral margin of the accessory lobe However, the iatrogenic pneumothorax that may occur
of the right lung when it is separated from the surrounding following this procedure may confuse radiographic inter-
organs by the effusion. Pleural effusion causes compression pretation. When thoracic radiographs are taken of foals in
atelectasis, leading to increased opacity of the lung fields the recumbent lateral position pleural effusion may be
Fig. 10.20. Pyogranulomatous pulmonary

abscess. A large well-defined circular soft
tissue opacity (arrows) is visible in the dorsal
lung field.
Fig. 10.21. Exercise-induced pulmonary

hemorrhage. There is a widespread inter-
stitial infiltrate. A focal mixed pattern, repre-
senting a resolving intrapulmonary hemor-
rhage, is seen in the caudodorsal region of
the lung between the diaphragm and the
vertebrae. The blood vessels in the affected
area are obscured by the pulmonary infil-
tration. The ventral margin of the aorta is
indicated by the arrowheads.
seen surrounding and outlining the lungs and separating thorax is unilateral, pulmonary vessels in the normal lung
them from the adjacent thoracic wall. Care should be taken may still be seen in the caudodorsal thorax, partially
to differentiate between cavitated extrapleural abscesses obscuring the collapsed lung edge. The outline of the aorta
and pleural effusion (Fig. 10.23). Ultrasonography is more is accentuated in horses with pneumothorax because it is
sensitive than radiography for confirming the presence surrounded by air (Boy & Sweeney 2000).
of pleural fluid.
Pneumomediastinum
Pneumothorax
Air in the mediastinum outlines structures that are not
The dorsal edge of the partially collapsed lung is retracted normally visible radiographically, including the mediastinal
ventrally from the vertebrae and is evident radiographically blood vessels and the esophagus. In contrast, free air makes
as a curved radio-opaque shadow, running horizontally the trachea more difficult to identify. Air in the esophagus
across the thoracic cavity (Fig. 10.24). If the pneumo- may simulate a pneumomediastinum.
Fig. 10.22. Pleural effusion in a horse with

lymphosarcoma. There is an increased soft
tissue opacity obscuring the cardiac silhouette.
The edge of the opacity has an irregular
horizontal margin (arrow).
Mediastinal masses
Mediastinal masses, including neoplasms, abscesses, lym-
phadenopathy and granulomas, may be seen as soft tissue
opacities which displace the trachea or are seen in the
perihilar region.
Thoracic neoplasia
Primary lung tumors are rare. They are seen as soft tissue
nodules or masses within the pulmonary parenchyma
(Fig. 10.25) that may be difficult to differentiate radio-
graphically from intrapulmonary abscesses or cysts.
Metastatic lung disease may be seen as diffuse infiltrates,
multiple nodules or masses of varying sizes scattered
throughout the pulmonary parenchyma with or without
pleural fluid.
Diaphragmatic hernias
Fig. 10.23. A 6-year-old mare with a large, cavitating, gas-filled Diaphragmatic hernias may result in interruption of the
extrapleural abscess at the level of the mid-dorsal thorax (white normal curved diaphragmatic outline, and the gas cap of
arrowheads). A fluid line (black arrowhead) is visible in the ventral part the stomach being located more cranially than usual.
of the abscess. The pulmonary vessels and caudal vena cava (black Rarely, intestines may be evident within the thoracic cavity
arrows) are seen superimposed on the fluid opacity indicating that the
as gas-filled tubular shadows.
underlying lung is in a normal position.
Fractured ribs
Rib fractures are easily missed on survey radiographs
unless the fracture ends are grossly displaced or callus
formation is evident (Fig. 10.26). In foals, ventrodorsal
views can aid detection of rib fractures and will reveal the
Fig. 10.24. Pneumothorax in a 1-year-old

filly. The lateral radiograph shows an intra-
pleural drain placed in the right pleural
cavity. Air is present in the dorsal thorax and
the partially collapsed lung margins (arrows)
are clearly seen.
Fig. 10.25. This 12-year-old thoroughbred

mare has an ill-defined widespread mixed
pulmonary pattern with indistinct soft tissue
opacities overlying the pulmonary vascula-
ture. A fluid line is visible within the mass
(arrowhead). Post-mortem examination iden-
tified a granular cell tumor. (Black arrows
indicate the cranial edge of the diaphragm.)
associated asymmetry of the thoracic wall (Jean et al Hypertrophic osteopathy

1999). Ultrasonographic examination may be more useful
in defining the presence of rib fractures than radiography. Chronic pulmonary disease may result in hypertrophic
osteopathy, which leads to an irregular periosteal prolif-
Sternal fractures erative reaction affecting the diaphyses of the long bones,
and occasionally the bones of the head, but not joints
Sternal fractures and the associated pleural or subpleural (Mair et al 1996). The distribution is often, but not invari-
hemorrhage may be evident radiographically, particularly if ably, bilaterally symmetrical (Fig. 10.28).
they are displaced (Fig. 10.27).
Fig. 10.26. Rib fracture and pneumonia. This 6-month-old foal had a history of Rhodococcus equi
pneumonia. This lateral radiograph taken with the right side against the cassette (a right lateral view)
shows a healed rib fracture with a large smooth callus (white arrowheads) dorsal to the caudal vena cava.
The fracture involves a rib on the left side as the sharper, less-magnified right rib is superimposed on the
fractured rib. The lung markings are superimposed on the callus. There is a widespread interstitial infiltrate
and prominent bronchial lines (black arrowheads).
Fig. 10.27. A 3-year-old pony with a sternal fracture. The lateral radiograph shows a rectangular
separated fragment of bone (black arrow) surrounded by a radiolucent cavity (white arrow). A discharging
sinus tract is seen as a radiolucent channel exiting ventrally from the sequestered fragment (white
arrowhead). Sclerotic bone encircles the lesion.
A B
Fig. 10.28. A 6-year-old mare with hypertrophic osteopathy. There are asymmetric bony exostoses on the
left (A) and right (B) third metacarpal bones.
REFERENCES Farrow CS 1981b Equine thoracic radiology. Journal of the

American Veterinary Medical Association 179: 776–781
Ainsworth DM, Hackett RP 2004 Disorders of the respiratory Farrow CS 2002 The equine lung. In: Thrall DE (editor)
system. In: Reed SM, Bayly WM, DC Sellon (editors) Textbook of Veterinary Diagnostic Radiology, 4th edn.
Equine Internal Medicine, 2nd edn. WB Saunders, WB Saunders, Philadelphia pp.463–475
Philadelphia, pp.289–353 Fintl C, Dixon PM 2001 A review of five cases of parotid
Barakzai SZ, Tremaine WH, Dixon PM 2006 Use of melanoma in the horse. Equine Veterinary Education
scintigraphy for diagnosis of equine paranasal sinus 13: 17–24
disorders. Veterinary Surgery 35: 94–101 Fubini SL, Todhunter RJ, Vivrette SL et al 1985 Tracheal
Barr BS 2003 Pneumonia in weanlings. Veterinary Clinics of rupture in two horses. Journal of the American Veterinary
North America; Equine Practice 19: 35–49 Medical Association 187: 69–70
Behrens E, Schumacher J, Morris E 1991 Contrast paranasal Gibbs C, Lane JG 1987 Radiographic examination of the nasal
sinusography for evaluation of disease of the para- and paranasal sinus regions of the horse. II: Radiological
nasal sinuses of five horses. Veterinary Radiology and findings. Equine Veterinary Journal 19: 474–482
Ultrasound 32: 105–109 Head KW, Dixon PM 1999 Equine nasal and paranasal sinus
Berry CR, O’Brien TR, Madigan JE et al 1991 Thoracic radio- tumours. Part 1: Review of the literature and tumour
graphic features of silicosis in 19 horses. Journal of classification. Veterinary Journal 157: 261–278
Veterinary Internal Medicine 5: 248–256 Jean D, Laverty S, Halley J et al 1999 Thoracic trauma in
Blythe LL 1997 Otitis media and interna and temporohyoid newborn foals. Equine Veterinary Journal 31: 149–152
osteoarthropathy. Veterinary Clinics of North America; King GK 1981 Equine thoracic radiography. Part II. Air gap
Equine Practice 13: 21–42 rare-earth radiography of the normal equine thorax.
Boulton CH 1985 Equine nasal cavity and paranasal Compendium on Continuing Education for Practicing
sinus disease: a review of 85 cases. Journal of Equine Veterinarians 3: S283–S288
Veterinary Science 5: 268–275 King GK, Martens RJ, Clark DR 1981 Equine thoracic
Boy MG, Sweeney CR 2000 Pneumothorax in horses: 40 cases radiography. Part I. Air gap rare-earth radiography of the
(1980–1997). Journal of the American Veterinary Medical normal equine thorax. Compendium on Continuing
Association 216: 1955–1959 Education for Practicing Veterinarians 3: S278–S282
Butler JA, Colles CM, Dyson SJ et al 2000 Clinical Radiology of Koblik PD, Hornof WJ 1985 Diagnostic radiology and nuclear
the Horse, 2nd edn. Blackwell Scientific, Oxford cardiology: their use in assessment of equine cardiovas-
Farrow CS 1981a Radiography of the equine thorax – cular disease. Veterinary Clinics of North America; Equine
anatomy and technique. Veterinary Radiology 22: 62–68 Practice 1: 289–309
Lamb CR, O’Callaghan MW 1989 Diagnostic imaging of Radiological/pathological correlations. Equine Veterinary
equine pulmonary disease. Compendium on Continuing Journal 19: 419–422
Education for Practicing Veterinarians 11: 1110–1119 O’Callaghan MW, Pascoe JR, Tyler WS et al 1987b Exercise-
Lane JG 2001 Fourth branchial arch defects in thoroughbred induced pulmonary haemorrhage in the horse: results of
horses: a review of 60 cases. Proceedings of the 2001 a detailed clinical, post mortem and imaging study. VIII.
World Equine Airways Society Conference, World Equine Conclusions and implications. Equine Veterinary Journal
Airways Society, Edinburgh, Scotland, CD-ROM 19: 419–422
Lane JG, Gibbs C, Meynink S et al 1987a Radiographic exami- Perkins J 2002 Quantitative and qualitative anatomy of the
nation of the facial, nasal and paranasal sinus regions of equine maxillary and conchal sinuses with particular
the horse: I. Indications and procedures in 235 cases. reference to the nasomaxillary aperture. MSc Thesis,
Equine Veterinary Journal 19: 466–473 University of Edinburgh
Lane JG, Longstaffe JA, Gibbs C 1987b Equine paranasal sinus Priester WA, Mackay FW 1980 The occurrence of tumors in
cysts: a report of 15 cases. Equine Veterinary Journal domestic animals. National Cancer Institute Monograph
19: 534–544 54: 59–99
Lester GD, Lester NV 2001 Abdominal and thoracic radiography Rush BR, Mair TS 2004 Equine Respiratory Disorders. Blackwell
in the neonate. Veterinary Clinics of North America; Science, UK
Equine Practice 17: 19–46 Sande RD, Tucker RL 1997 Radiology of the equine lungs and
Linford RL, O’Brien TR, Wheat JD et al 1983 Radiographic thorax. In: Rantanen NW, Hauser ML (editors) The
assessment of epiglottic length and pharyngeal and Diagnosis and Treatment of Respiratory Disease.
laryngeal diameters in the Thoroughbred. American Proceedings of the 1997 Dubai International Equine
Journal of Veterinary Research 44: 1660–1666 Symposium. Rantanen Design, USA pp.139–157
Mair TS, Gibbs C 1989 Thoracic radiography in the foal. Sweeney CR 1991 Exercise induced pulmonary hemorrhage.
Equine Veterinary Education 1: 56–61 Veterinary Clinics of North America; Equine Practice
Mair TS, Lane JG 1989 Pneumonia, lung abscesses and 7: 93–104
pleuritis in adult horses: a review of 51 cases. Equine Tremaine WH, Dixon PM 2001 A long term study of 277
Veterinary Journal 21: 175–180 cases of equine sinonasal disease. Part 1: Details of
Mair TS, Dyson SJ, Fraser JA et al 1996 Hypertrophic horses, historical, clinical and ancillary diagnostic
osteopathy (Marie’s disease) in Equidae: a review of findings. Equine Veterinary Journal 33: 274–282
twenty-four cases. Equine Veterinary Journal 28: 256–262 Weller Y, Livesey L, Maierl J et al 2001 Comparison of
O’Callaghan MW, Pascoe JR, O’Brien TR et al 1987a Exercise- radiography and scintigraphy in the diagnosis of dental
induced pulmonary haemorrhage in the horse: results of disorders of the horse. Equine Veterinary Journal
a detailed clinical, post mortem and imaging study. VI. 33: 49–58
Ultrasonography of the Respiratory Tract
11 Diana S Rosenstein
traveling. This wave of energy has a wavelength, a

What is Diagnostic Ultrasound?
frequency, and a direction. Frequency is the unit for cycles
Energy in the form of sound is used to create images of of compression and expansion per second and is commonly
internal organs based on the reflection of sound waves at measured in units of Hertz (Hz). Most diagnostic
tissue interfaces. The ultrasound machine uses electricity ultrasound imaging is performed in the 2.5–10 megaHertz
to stimulate piezoelectric crystals in the probe to emit (MHz) range.
sound waves. These waves enter the patient and interact If a sound wave is traveling through a uniform medium,
with the tissues. Some of these waves reflect off the tissues the wave continues to be propagated at a constant velocity
and are detected by the probe to create an electrical signal (frequency × wavelength) and direction. When the wave
that is displayed on a monitor. The appearance of the final reaches an interface of different media, such as an organ
image is determined by many characteristics of the sound parenchyma and capsule, or the edges of two adjacent
waves, the tissues, and the scanning technique. organs, interactions occur that affect the sound wave’s
Ultrasonography is useful in evaluating the equine velocity and direction. There are two basic categories of
thorax as a complementary modality to radiology. The interactions that occur at these interfaces, namely
absence of radiation exposure, the reasonable expense, the attenuation and refraction.
portability of an ultrasound machine, and the sensitivity of Attenuation comprises several interactions that decrease
ultrasound imaging for peripheral lesions are qualities the amount of energy remaining in the sound wave as it
that make this modality an asset in the evaluation of the continues further into the patient. Reflection, absorption,
respiratory system. Pathological changes including pleural and scatter are all types of attenuation.
effusion, pleural adhesions and thickening, pulmonary
masses, pulmonary consolidation, diaphragmatic hernia, ● Reflection is the redirection of the sound wave or
and mediastinal diseases may be well visualized sono- creation of an echo (Fig. 11.1). If the probe detects this
graphically with greater sensitivity than with thoracic echo, it generates a bright spot, contributing to the final
radiography. Lateralization of a pleural or pulmonary image. As in the game of pool, angle of incidence equals
lesion may also be accomplished more readily using
ultrasound than with radiographs. However, sonographic
artifacts and natural attenuation of the sound beam
restrict the diagnostic utility of this modality in the thorax
A B C
to peripheral tissues. Scanning from various locations
around the thorax maximizes the access to these struc-
tures. Transesophageal ultrasound takes advantage of the
digestive tract for access to intrathoracic, particularly
mediastinal, structures. This equipment, however, is not yet
readily available beyond large institutions.
Basic Physics of Diagnostic Ultrasound

and Interactions of Sound with Matter
Artifacts associated with sound transmission have a
tremendous impact on the image, and therefore an under- Fig. 11.1. Angle of incident sound beam determines the angle of
standing of sound propagation and interaction of sound reflected sound. Sound traveling perpendicular to the tissue surface is
reflected back to the transducer (A). Sound traveling at an acute angle
with matter is essential. This form of energy moves as to the tissue surface is reflected away from the transducer (B). Sound
a wave by causing compression and expansion of the reflected from the margin of a round structure is directed away from
molecules that comprise the medium in which it is the transducer (C).
175
176 11 Ultrasonography of the Respiratory Tract
angle of reflection, meaning that the angle at which the at equidistant intervals. This reverberation artifact is seen
original sound wave strikes the tissue interface is equal in the normal thorax as it occurs at the interface of the
to the angle at which the echo is reflected. This concept pleural surface and aerated lung (Fig. 11.2). The complete
is important in explaining why the angle at which a reflection of the sound beam at the soft tissue–air interface
probe is held and the shape of a structure both have a and the reverberation artifact obscure visualization of
significant effect on the sonographic appearance of a deeper structures; therefore, only peripheral pulmonary
structure. A tissue interface is most likely to reflect lesions can be visualized. Consequently, pulmonary lesions
echoes back to the probe when the sound wave strikes that are separated from the visceral pleura by aerated lung
a flat surface at a perpendicular angle. Positioning of will not be visualized.
the probe at an acute angle to the tissue surface or At a soft tissue–bone interface, most of the energy is
imaging of a rounded structure will create reflected reflected and the remaining energy is absorbed, so the
echoes that travel in a direction that will not be received image appears dark from the surface of the bone towards
by the probe and therefore no image of that interface the far field. This dark region is called an acoustic shadow,
will be generated on the monitor (Fig. 11.1). Acoustic and it is commonly seen on thoracic images deep to the
impedance is a fundamental property of each structure ribs. The artifact is obvious in a transverse image with
that is determined by its physical density and velocity the transducer held across two ribs and the inter-
of sound propagation. The difference in acoustic imped- costal space (Fig. 11.2). Although all regions of the thorax
ance between two adjacent tissues determines the
amount of reflection that occurs at this interface.
The large difference in acoustic impedance between
soft tissue and air causes reflection of almost the entire
sound wave, while most of the energy is reflected at a
soft tissue–bone interface. Two adjacent structures of
similar acoustic impedance, such as muscle layers, are SQ
more likely to reflect less energy and refract the beam, R ICM
allowing it to penetrate into deeper tissues.
● Absorption is the transfer of sound energy into heat P
that is retained within the tissue. This type of inter-
RS RV RS
action is intentionally used for therapeutic ultrasound
but is also a component of diagnostic ultrasound. It
does not contribute to creation of the image but does
contribute to the darkening of the far field. A higher
frequency sound wave is more likely to be absorbed than
a lower frequency sound wave; therefore use of a high- A
frequency transducer is limited to imaging of superficial
structures because the beam cannot penetrate into
deeper tissues.
● Scatter is the random distribution of echoes when they
are reflected from a rough surface. The resulting image
does not clearly delineate the margins of the original
structure.
● Refraction is the continuation of a sound wave beyond
an interface, into deeper structures at a new velocity
and wavelength. This type of interaction is necessary to
visualize deeper structures.
Some combination of all these interactions ultimately

creates the final image with characteristic patterns for
organs, pathological changes, and interfering artifacts.
Reverberation is a common artifact in thoracic
sonography. Since most of the beam is reflected off the soft B
tissue–air interface, it returns to the probe with enough
Fig. 11.2. Transverse plane sonographic image of a normal equine
energy to generate another echo off the surface of the thorax – drawing (A) and sonogram (B). SQ = subcutaneous tissue,
transducer, directed back into the body. This repeating cycle ICM = intercostal muscles, R = rib, RS = rib shadow, P = pleura,
of returning echoes generates multiple lines on the image RV = reverberation artifact.
11 Ultrasonography of the Respiratory Tract 177
should be imaged in multiple planes, the shadow artifact

Technique
from the ribs may be avoided by scanning in the longi-
tudinal plane, with the transducer aligned along an inter- Since gas–soft tissue interfaces are highly reflective, the air
costal space (Fig. 11.3). trapped in the horse’s haircoat must be removed to
Sound waves propagate efficiently through a liquid transmit the sound waves from the transducer into the
medium because the molecules within the liquid are readily patient. The standard protocol for patient preparation
compressed and expanded. The sound wave continues to includes clipping the hair from the entire area to be
move forward, so no echoes are generated (anechoic areas) scanned and cleansing the skin with a moist towel.
and the representative region of the image is black. Tissues External landmarks for the thoracic cavity are lines
with a more rigid architecture, such as connective connecting points from the 17th intercostal space (ICS) at
tissue, are more resistant to compression and rarefaction the height of the tuber coxae, extending cranioventrally
of the molecules; therefore acoustic impedance of these to the point of the elbow, continuing dorsally to the
tissues is higher. The larger the difference in acoustic caudoventral margin of the scapula then extending
impedance of adjacent tissues, the more reflective the caudally to the point of origin in the 17th ICS (Fig. 11.4).
interface is to sound (echogenic). Descriptive prefixes are If the haircoat is thin, it may not be necessary to clip the
used to compare the relative echogenicity of structures, hair; however, the probe must be moved in the direction of
including hyper- (more echogenic), hypo- (less echogenic) hair growth to avoid disturbance of the moistened hair and
and iso- (equally echogenic). the development of air pockets. Acoustic coupling gel is
applied to the skin and massaged to further displace air
from the skin surface. Dry or soiled skin will cause poor
contact artifacts. A hyperechoic region in the extreme
near field of the image with distant reverberation or an
overall dark image may be the result of trapped air and
poor contact between the probe and the skin (Fig. 11.5).
Further cleansing, reapplication of more gel or firmer
SQ
pressure of the probe against the horse’s body will help to
ICM resolve this artifact.
P A variety of transducers are appropriate for scanning
the thorax. Superficial structures (within 10 cm of the
RV skin) may be examined with a higher frequency probe
(7.5–10 MHz) for good image resolution. To examine
deeper structures (> 15 cm), a lower frequency probe
(2.5–3.5 MHz) should be used to improve sound-beam
Fig. 11.3. Longitudinal plane image of a normal equine thorax –

drawing (A) and sonogram (B). SQ = subcutaneous tissue, ICM = Fig. 11.4. External landmarks for preparation of the equine thorax for
intercostal muscles, P = pleura, RV = reverberation artifact. a sonographic examination.
The right and left sides of the thorax should be completely

scanned at each examination. Abnormalities should be
labeled and recorded as paper printed images, stored still
or video clips on CD or tape, and written comments in
the medical record.
Normal Anatomy
Normally inflated lungs contain air and are therefore
highly echogenic. The reverberation artifact cast by the
echogenic interface of pleura and aerated lung obscures
the visualization of deeper structures. The adjacent pleural
surfaces glide smoothly against each other as the lungs
change in size with inhalation and exhalation. These
pleural layers appear as one thin echogenic line, as the two
Fig. 11.5. Diagram illustrating two types of poor contact artifacts. surfaces are in contact. Ribs are echogenic at the surface,
Gas, hair or debris causes reverberation that originates at the body
surface–probe interface (single arrow). Weak contact between the
smoothly marginated, convexly curved and cast a dark
probe and body wall or dry skin cause a dark image (double arrow). distant shadow (Fig. 11.2). Structures deep to the ribs
cannot be visualized through these skeletal structures. To
examine the underlying lung, the probe must be angled
cranially or caudally from an adjacent ICS. In the longitu-
penetration, albeit at the sacrifice of image resolution. An dinal plane, the probe is positioned lengthwise between ribs
excellent compromise between these two frequencies is a so that this artifact is eliminated (Fig. 11.3). In the caudal
5-MHz probe, which will provide good quality resolution thorax, the diaphragm may be visualized as a thin, smooth
and adequate penetration for most peripheral pleural and echogenic line of demarcation between the aerated lungs
pulmonary lesions. and the cranial border of the liver.
A linear transducer with a flat surface will provide good
contact with the body wall. If the cord extends from one
end of the transducer, such as the shape of a transrectal
Pleural Effusion
probe, it will be awkward to hold against the thoracic body A small volume of pleural fluid may be imaged in healthy
wall. If the cord extends from the back of the transducer, horses. Separation of the parietal and visceral pleura by
it will be more convenient to manipulate. The image is fluid is seen as a band of hypoechoic material deep to the
rectangular and is usually limited in size to a narrow field intercostal muscles and superficial to the lung (Fig. 11.6).
of view. A curvilinear probe produces a wedge-shaped The pleural layers may be visualized as echogenic lines
image with a wider field of view; however, the curved bordering this fluid but they are not always discernible. The
surface provides less contact with the flat or convex surface echogenicity of the fluid varies with its contents. A fluid of
of the thoracic body wall and therefore the periphery of lower cellularity or protein content is lower in echogenicity
the image may be dark and non-diagnostic. Application while a highly cellular or proteinaceous fluid is more
of additional acoustic gel or more manual pressure of the echogenic. Most equine thoracic sonographic studies are
probe against the body may alleviate this artifact. A round performed with the patient in the standing position.
transducer is convenient for imaging in several planes Gravity will cause the fluid to accumulate ventrally;
in small spaces. This type of probe is ideal for cardiac therefore the ventral thorax is an important region to
sonography as it may be easily rotated to acquire longi- examine for pleural effusion. In the recumbent horse
tudinal and transverse cardiac images between ribs. (usually neonates) it is crucial to examine the lower region
A systematic plan for imaging the entire thorax is of the thorax for effusion. A complete examination must
essential to perform a complete examination. Imaging include scanning of both sides of the chest at every evalua-
along the ICS from dorsal to ventral, progressing from tion, because the mediastinum may be a barrier to the
caudal to cranial across the thorax, is a recommended spread of hemithoracic disease to the contralateral side,
protocol. At each ICS the structures must be scanned in a and because the nature and volume of pleural effusions
transverse plane (transducer crosses adjacent ribs with the may differ greatly between two sides of the same patient.
ICS in the center of the field) and in the longitudinal Measuring the dorsal extent of the fluid at each exami-
plane (transducer is aligned along the ICS, between two nation will provide useful information regarding disease
ribs). Movement of the transducer must be slow enough to progression. If thoracocentesis is performed, then the
allow for examination of the thorax in each location thorax should be scanned following the removal of pleural
through inspiratory and expiratory phases of respiration. fluid to document residual fluid levels. Fibrinous or fibrous
PP
P
PE
VP
C C
A
A
Fig. 11.6. Sonographic image of pleural effusion in the equine thorax

– drawing (A) and sonogram (B). Pleural effusion (PE) separates the B
parietal pleura (PP) and the visceral pleura (VP).
Fig. 11.7. Sonographic image of pleuritis in the equine thorax –
drawing (A) and sonogram (B). Comet tail artifacts (C) originate from
the irregular pleural surface (P). Reproduced with the permission of
bands of tissue may cause loculation of pleural fluid; there- Dr Matthew Davis, Merritt & Associates Equine Hospital, Wauconda,
fore ultrasound guidance may be beneficial for placement IL, USA.
of the needle to maximize access to the fluid.
move across the image as the irregular pleural surfaces

Pleuritis change in position. The underlying lung may be well
The shape of a tissue interface affects the appearance of aerated, resulting in the usual reverberation; however,
the reflected echoes. A roughened texture to the pleural the pleural surface is not a long, continuously smooth edge,
surface causes narrow streaks of reverberation artifacts, so the echogenic lines are narrower. In cases of chronic
commonly named comet tails (Fig. 11.7). Comet tails may pleuritis, adhesions between the visceral and parietal
be identified in some healthy equine lungs, especially in the pleura may restrict the gliding motion during inhalation
ventral margins of the lung field at the end of expiration. and exhalation. The lung appears stuck to the parietal
Thus their significance should be assessed in relation to pleura and fails to move during respiration (Fig. 11.8).
other clinical data. However, numerous widespread comet This lesion is, however, not always recognizable on a
tails should arouse a suspicion of lung or pleural disease. still image and requires patient, slow scanning to identify
During respiratory movement, these artifacts appear to in real-time scanning.
ICM
PA PP
PE
PE
FT
L PE
L
L
VP
RV
HL
A
B Fig. 11.9. Sonographic image of fibrinous pleuritis in the equine

thorax – drawing (A) and sonogram (B). PP = parietal pleura, FT =
Fig. 11.8. Sonographic image of pleural effusion (PE) and pleural fibrinous tags, PE = pleural effusion, VP = visceral pleura,
adhesion (PA) in the equine thorax – drawing (A) and sonogram (B). HL = hepatized lung.
Adhesion of the visceral and pleural surfaces (arrow) restricts move-
ment of the lung (L). ICM = intercostal muscles, RV = reverberation
artifact. Reproduced with the permission of Bruce McGorum.
because of the presence of aerated lung between the body

Effusion with Fibrinous Tags
wall and the central thoracic structures. However, in the
Fibrinous and fibrous bands of tissue may extend from a presence of pleural effusion and hypoinflation of the lungs,
pleural surface into a region of pleural effusion. These the mediastinal structures may be visualized.
bands may appear as floating or waving linear echo-
genicities that sway in the pleural fluid during breathing
(Fig. 11.9). The mediastinum (pericardial diaphrag-
Atelectasis and Consolidation
matic ligament) should not be mistaken for a fibrinous Atelectasis is incomplete aeration of the lung, which may
band as it is recognized in the caudal right thorax, be a primary or secondary disorder. Compression atelec-
extending from the caudal margin of the lung to the tasis occurs when increased external pressure inhibits
diaphragm in the far field (Fig. 11.10). The mediastinum is lung expansion. Pulmonary atelectasis is a common
evident as a long convoluted single echogenic fold that finding in the presence of pleural effusion because the
undulates within the pleural fluid, while fibrin generally lung is unable to fully expand. Bronchial or bronchiolar
occurs as multiple shorter strands. This section of the obstruction may cause regions of alveolar atelectasis. The
mediastinum is not visualized in the normal thorax normal reverberation artifact is absent because the soft
ICM
FT
PE
AL PE
L FT
D
C
FT
M
M
A
A
B
B
Fig. 11.11. Sonographic image of pulmonary atelectasis and fibrinous
Fig. 11.10. Sonographic image of pleural effusion (PE) with fibrinous pleuritis in the equine thorax – drawing (A) and sonogram (B).
tags (FT) and partial lung atelectasis (L) in the equine thorax – drawing ICM = intercostal muscle, PE = pleural effusion, AL = atelectatic lung,
(A) and sonogram (B). Pleural effusion allows for visualization of the FT = fibrinous tag, C = comet tail artifact, M = mediastinum, D =
mediastinum (M). diaphragm. Reproduced with the permission of Dr Matthew Davis,
Merritt & Associates Equine Hospital, Wauconda, IL, USA.
tissue–gas interface is not present. Hypoinflated lung with liquid or solid material. The displacement of gas will
tissue appears similar to liver tissue and may be termed eliminate the normal reverberation artifact from the
“hepatized lung”. The lung parenchyma is moderately affected lung. The sonographic pattern of consolidated
echogenic with tubular, hypoechoic, vascular structures in lung varies with the underlying pathology. If a pulmonary
a branching pattern. Air may be present in the larger mass is present adjacent to the visceral pleura, a nodule
bronchi and bronchioles, depending on the severity of with defined margins may be visualized (Fig. 11.12). If the
the atelectasis. These air-filled bronchi will appear disease is more diffuse, such as an exudative pneumonia,
highly echogenic and circular or linear in shape. Pleural then the lung may appear similar to the hepatized
effusion will enhance visualization of the visceral pleura, lung described with atelectasis. Consolidated lung may
which should be smooth along the flat surface of the have a rounded or irregular margin, in contrast to the
atelectatic lung and sharply marginated at the lobar smooth margin with sharp corners of atelectatic lung.
edges (Figs 11.10 and 11.11). The presence of pleural effusion may enhance visualiza-
Consolidation is the process of becoming firm. In the tion of the visceral pleura for differentiation between
lung, this may occur when air in the alveoli is replaced atelectatic and consolidated lung. A sonographic pattern of
PE CL
A
A
Fig. 11.13. Sonographic image of diffuse pulmonary consolidation in

B
the equine thorax – drawing (A) and sonogram (B). Note the indistinct
Fig. 11.12. Sonographic image of focal pulmonary consolidation (M) demarcation between the consolidated lung (CL) and the adjacent
and pleural effusion (PE) in the equine thorax – drawing (A) and aerated lung (arrow).
sonogram (B).
non-inflated lung that is heterogeneous in echogenicity and focal atelectasis. Sonographic guidance for transthoracic
disorganized in architecture is suggestive of pulmonary fine-needle aspiration or biopsy of a peripheral pulmonary
consolidation (Figs 11.13 and 11.14). mass may provide samples for cytology, histopathology,
and bacteriology.
Pulmonary Mass
Pneumothorax
Ultrasonography is more sensitive than radiography at
detecting small pulmonary masses, but only if they contact Free gas in the pleural space is difficult to identify via
the visceral pleura (Fig. 11.12). The presence of aerated ultrasound examination. The reverberation artifact of
lung between the pleural margin and a deeper mass normally aerated lung appears similar to the artifact
will create the normal reverberation artifact, obscuring from free pleural gas (Fig. 11.16). Critical assessment of
visualization of a deeper lesion. A distinct, echogenic the gliding pleural surfaces may be helpful to identify
peripheral margin to a mass with hypoechoic or echogenic pneumothorax. In pneumothorax, the normal breath-
central material is suggestive of an abscess (Fig. 11.15). A induced gliding movement of the visceral pleura over
mass of soft tissue echogenicity with internal vascular the parietal pleura is absent, and consequently the
structures may be a neoplasm, other focal consolidation or gas-filled pleural space remains stagnant throughout
PE
G
G
F
G
CL
G
A B
Fig. 11.14. Sonographic image of diffuse pulmonary consolidation in (PE) enhances visualization of the irregular lung margin (arrow). Foci of
the equine thorax – drawing (A) and sonogram (B). Pleural effusion gas (G) and fluid (F) are present in the consolidated lung (CL).
RV SP
C
A
B B
Fig. 11.15. Sonographic image of a pulmonary abscess in an equine Fig. 11.16. Sonographic image of pneumothorax in an equine thorax
lung. The hypoechoic center of the abscess (A) is surrounded by a thick – drawing (A) and sonogram (B). Reverberation artifact (RV) origi-
echogenic capsule (C). The interface of this mass with aerated lung nates from the parietal pleural interface with the free pleural gas.
(arrow) is present in the far field of the image. SP = spleen.
the respiratory cycle. Dynamic imaging is essential to

appreciate this lesion, as the still image appears similar FURTHER READING
to that of normal lung. In suspected cases of pneumo- Curry TS, Dowdy JE, Murry RC 1990 Christensen’s Physics
thorax, it is likely to be more efficient to radiograph the of Diagnostic Radiology, 4th edn. Lea & Febiger,
horse first, identify the presence of a pneumothorax, then Philadelphia, pp.323–340
Nyland TG, Mattoon JS 1995 Veterinary Diagnostic Ultra-
ultrasound the horse to determine lateralization of any sound. WB Saunders, Philadelphia
pathological findings. The radiographs will provide a base Reef VB 1998 Equine Diagnostic Ultrasound. WB Saunders,
on which to guide the ultrasound examination. Philadelphia
Scintigraphy of the Equine
Upper Respiratory Tract
12 Safia Barakzai
the risks of radiation exposure to personnel. There is

Introduction
also a requirement for technical expertise when reading
With the increasing availability of radioisotopes, scinti- scintigraphic images. Additionally, in most centers, horses
graphy (nuclear medicine) began to emerge as a diag- are considered “radioactive” and must be isolated for
nostic and occasionally therapeutic discipline in human 24–48 h post injection, thereby delaying further diagnostic
medicine after the Second World War (Weaver 1995). It is procedures or treatment.
unique among the imaging modalities because the images The predominant application of scintigraphy in the
reflect active physiological processes rather than the struc- equine upper respiratory tract is the investigation of
tural features portrayed by radiography, ultrasonography, potential periapical infection of the cheek teeth, which is
computed tomography or magnetic resonance imaging. often associated with secondary sinusitis if the caudal
Scintigraphy involves the intravenous administration of four maxillary cheek teeth are involved, or facial swelling
a gamma-ray-emitting radioisotope, which is bound to a with or without a cutaneous draining tract and/or
tissue-seeking molecule. Technetium-99m (99m Tc), cur- unilateral nasal discharge if the rostral two maxillary
rently the most commonly used radioisotope in the equine cheek teeth are involved. It is particularly useful for
field, is a meta-stable radionuclide which emits a gamma- differentiation of dental sinusitis from primary sinusitis
ray of 140 keV, with a physical half-life of 6 h (Lamb & or sinusitis caused by other lesions such as encapsulated
Koblik 1988). If bone is to be imaged, 99m Tc is linked to a abscesses or sinus cysts. This differentiation is extremely
phosphate or diphosphonate-containing molecule (e.g. important for appropriate treatment of these disorders,
methylene diphosphonate, MDP), which has an affinity as the consequences of extracting a non-diseased tooth
for the hydroxyapatite component of bone (Lamb 1991, are serious.
Weaver 1995). The radioisotope is cleared at a fast rate The complex structure of the equine skull can make
from the blood and soft tissues, and is incorporated selec- radiographic images of this area difficult to assess because
tively into bone in areas of resorption or formation (Lamb of numerous superimposed structures, and early periapical
& Koblik 1988). Patterns of uptake are registered in a infections are particularly difficult to detect radiograph-
sodium iodide crystal within a gamma camera or a hand- ically (Gibbs & Lane 1987, Metcalf et al 1989). In the
held probe, 2–4 h after injection (Lamb 1991, Javer et al more caudally positioned cheek teeth, where secondary
1996, Seeherman 1998). sinusitis is common, infected teeth can be recognized with
Scintigraphy using 99m Tc-MDP was first used as a confidence in only 50–57% of cases (Lane et al 1987a,
diagnostic tool in equine orthopedics by Professor Ueltschi Tremaine & Dixon 2001, Weller et al 2001). Lane et al
in Switzerland in 1975 and since then its use has become (1987a) suggested that the increase in bone density
widespread in equine hospitals and referral centers for the associated with maxillary osteitis superimposed on opaque
diagnosis of lameness. However, only recently have reports sinus contents obscures the underlying dental struc-
of the use of scintigraphy for the detection of disorders of tures and prevents detailed inspection so that subtle
the equine skull in significant numbers of horses begun to abnormalities may be missed. In many cases of sinusitis,
emerge (Weller et al 2001, Archer et al 2003a,b, Barakzai the increased soft tissue opacity within the sinuses may be
et al 2006). The ability of scintigraphy, using 99m Tc bound the result of inflamed and hypertrophied sinus mucosa,
to phosphates, to detect changes in bone before they which occurs secondary to any type of chronic sinus
become radiographically apparent (because increased bone infection (Lane et al 1987a, Tremaine & Dixon 2001).
turnover usually precedes structural change) is one of the In contrast to radiography, scintigraphy has been shown
key advantages of this technique in the equine patient. to have excellent sensitivity (95–96%) and moderate
Disadvantages of scintigraphy include the expense of specificity (79–86%) for detecting dental disease in the
acquiring and setting up a gamma camera and appropriate horse (Weller et al 2001, Barakzai et at 2006). Scintigraphy
software programs, licensing for the use, storage and dis- also has a high specificity (92%) and moderate sensitivity
posal of radioactive waste, appropriate stabling facilities (79%) for detection of equine paranasal sinus disorders
which comply with radiation protection legislation, and (Barakzai et al 2006).
185
186 12 Scintigraphy of the Equine Upper Respiratory Tract
Scintigraphic Protocol
Most equine upper respiratory tract scintigraphy is
performed using the bone marker 99m Tc-MDP. A dose of
1–1.5 MBq/100 kg bodyweight is administered to the
horse via an indwelling jugular catheter. Typically, only
bone-phase images are acquired at 2–4 h post injection,
as pool or soft tissue phase images do not usually pro-
vide any additional useful information and considerably
increase the radiation exposure of personnel (Gayle et al
1999, Weller et al 2001).
The use of 99m Tc-hexamethylpropyleneamine oxime
(HMPAO)-radiolabeled leukocytes has also been described
for equine dental scintigraphy (Weller et al 2001) but
it does not facilitate positive identification of apical infec-
tions because of a lack of anatomical resolution, and it
also incurred considerable extra cost. A less expensive
alternative to Indium-111 or 99Tc-HMPAO-labeled leuko-
cytes may be the use of a 99Tc-labeled antigranulocyte
murine antibody Fab′ fragment (Leukoscan™), which
has been shown to be valuable for the detection of human
bone infection. This antibody fragment is mixed with
Tc-pertechnetate, and injected intravenously, thus remov-
ing the requirement to bleed the patient, separate leuko-
cytes, label them with the radionuclide and then re-infuse
them (as is required for the 99mTc-HMPAO method).
Although the antibody fragment has been used successfully
in equine clinical cases (Barakzai, unpublished observa-
Fig. 12.1. Positioning of the patient (with head resting on a stool) and
tions 2002), the results have not been documented in the gamma camera to obtain lateral images of the skull.
literature to date.
Heavy sedation is usually required to allow close
positioning of the camera next to the horse, and is
achieved using a combination of α2-agonist (e.g. xylazine, summated image. A 128 × 128 matrix is best for acquiring
detomodine or romifidine) and butorphanol. Some horses clear scintigraphic images of the equine head. Counts
are very sensitive to the sounds generated by movement should ideally be over 200,000 for each image, but this
of the camera, and “plugging” the ears of such horses will depend on the dose of Tc administered, the uptake
with cotton wool may reduce auditory stimuli. Blinkers by the tissues, and the interval between injection and
may also be used to prevent the horse moving away from image acquisition.
the camera as it is brought into position, as long as they do
not contain metallic components that will attenuate the Scintigraphic views
gamma rays. Similarly, a rope head collar should be used
because buckles and rings on a standard head collar can Lateral images are obtained with the gamma camera
create artifactual “cold spots.” perpendicular to the floor and parallel to the sagittal plane
The head of the heavily sedated horse should be rested of the head (Fig. 12.1). Depending on the diameter of the
on a stool or similar object (Fig. 12.1), to minimize move- gamma camera and the size of the patient’s head, two
ment induced by sedation and minimize rotation in the lateral views centered at different postitions may be
sagittal plane. Images should be acquired using dynamic necessary to view the entire row of cheek teeth and all of
studies (e.g. 30 consecutive 2-second frames), because the paranasal sinuses. Dorsal views are obtained by
there will be inevitable movements of the horse’s head positioning the camera parallel to the frontal bones
during the acquisition period which, even if small in (Fig. 12.2). Image quality may be enhanced when
magnitude, may cause “blurring” of lesions on a static acquiring dorsal images by positioning a lead shield
study. Dynamic studies should then be motion corrected under the head to attenuate gamma-rays arising from
using a computerized algorithm applied to each dynamic the neck and chest (Ramzan 2003). Oblique views may
frame to find the best fit and superimpose the individual be useful for assisting lesion localization (Ramzan 2003).
frames on each other, resulting in a single corrected In horses suspected of having disorders affecting the
12 Scintigraphy of the Equine Upper Respiratory Tract 187
Table 12.1. Normal scintigraphic appearance of the

cheek teeth in relation to age of horse
Age of horse
(years) Scintigraphic appearance of cheek teeth
<1 No patterns of uptake that allow differentia-

tion of the CT
2 Irregular scintigraphic activity associated with

the CT, but often the apices of the caudal
maxillary CT have IRU
3 Focal areas of intense IRU over all CT apices

and in the interdental bone of 06s–08s
4 More uniform activity over upper 06s–10s, IRU

over upper 11s
5–10 Uniform activity over all CT apices, and clear

delineation of interdental bone.
CT appear as “cold spots” with relatively less
uptake than surrounding bone.
Upper 09s have shorter reserve crown than
others
>10 Clear delineation of CT gradually disappears,

replaced by diffuse pattern of activity as a
result of diminishing length of reserve crowns
and depth of alveoli
Reproduced from Ramzan 2003, with permission.

CT = cheek teeth; IRU = increased radionuclide uptake.
Fig. 12.2. Positioning of the patient (with head resting on a stool) and
gamma camera to obtain dorsal images of the skull.
hemi-mandibles, a ventral view may be obtained by
positioning the camera underneath and parallel to the
horizontal mandibular rami.
Normal Scintigraphic Anatomy TMJ

Age-related variations
Normal patterns of 99m Tc-MDP uptake in the equine head
VR ET
will vary markedly between different age groups because of
the development and eruption of the permanent dentition
and the accompanying active apical bone remodeling.
The scintigraphic changes associated with eruption of the
cheek teeth are shown in Table 12.1. It is important to ZYG CT
remember when assessing scintigrams of young horses
that areas of increased radionuclide uptake (IRU), which
are the result of normal eruption of cheek teeth, are
bilaterally symmetrical, whereas disorders involving cheek
tooth apices are most commonly unilateral.
ID
Lateral views (Fig. 12.3)
Lateral views are often the most useful for identification
Fig. 12.3. Right lateral scintigram of a normal 5-year-old horse
and localization of periapical infections of individual cheek showing cheek teeth (CT), interdental bone (ID), ethmoturbinates (ET),
teeth. The reserve crowns of the cheek teeth appear as temporomandibular joint (TMJ), zygomatic arch (ZYG), and vertical
“cold spots” of reduced uptake of radionuclide and are ramus of the mandible (VR).
surrounded by zones of IRU corresponding to the alveolar teeth. A moderate amount of IRU may also be seen in
bone and interdental (interproximal) bone. The erupted the normal zygomatic arch and temporomandibular joints.
crown is represented by an area of absent radionuclide The premaxilla, frontal, and maxillary bones have diffuse
uptake. The ethmoturbinates can be identified as a region mild radionuclide uptake, and the regions of the rostral
of IRU positioned dorsally and caudally to the sixth and caudal maxillary sinuses (lateral to the caudal four
maxillary cheek tooth, and are located within the frontal cheek teeth) and the ventral conchal sinus (medial to the
sinuses. The normal temporomandibular joints are also caudal four cheek teeth) are not clearly demarcated in
associated with focal areas of marked IRU, as are the the normal horse. It should be noted that slight rotation
atlanto-occipital joints. The ventral and caudal edges of the of the camera or the horse’s head can result in distortion of
mandible and the zygomatic arch can be clearly identified the image and loss of symmetry (Archer et al 2003a).
as areas of high metabolic activity (Weller et al 2001). Care
should be taken when evaluating areas of IRU on lateral
views, as IRU on one side of the head may also be seen on
Scintigraphic Imaging of Disorders of
the contralateral image (termed “strike-through”, Archer
the Equine Upper Respiratory Tract
et al 2003b). However, the affected side should have higher Dental disorders
counts and, additionally, a dorsal or ventral view of the
skull should confirm that the lesion is unilateral and will Scintigraphy using 99m Tc-MDP has been used for the inves-
indicate clearly which side is affected. tigation of human dental disease that cannot be diagnosed
The areas of the rostral and caudal maxillary sinuses radiographically, such as pulpitis, caries, and periodontitis
(dorsal to the caudal four cheek teeth) and the concho- (Tow et al 1978, O’Mara 1985). In humans and dogs,
frontal and frontal sinuses (dorsal and caudal to the caudal scintigraphic abnormalities have been documented before
maxillary sinus) are not clearly demarcated in scintigrams clinical or radiographic evidence of dental disease is present,
of the normal horse. indeed as early as 7 days after initiation of periapical infec-
tion in experimental models (Garcia et al 1974, Tow et al
Dorsal views (Fig. 12.4) 1978). Similarly, horses with evidence of pulpar exposure
on oral examination of the occlusal surface of the cheek
IRU is seen in the alveolar and interdental bone associated teeth, but with no clinical signs of periapical infection,
with the cheek teeth but it is often impossible to identify have been shown to have areas of IRU in the periapical
individual teeth apices with accuracy in dorsal scintigrams. regions of the affected teeth using scintigraphy (Barakzai
The ethmoturbinates are also clearly seen as areas of IRU 2005). Therefore, scintigraphy can be a very useful tech-
immediately caudal and axial to the sixth maxillary cheek nique for identification of early periapical infection in
horses, particularly in cases that have equivocal radiographic
changes. Nonetheless, scintigraphy is most useful for the
diagnosis of periapical infection when used in combination
with other diagnostic techniques such as radiography
and, of course, clinical examination (Metcalf et al 1989,
TMJ
Seeherman 1998, Boswell et al 1999, Weller et al 2001).
Uptake of 99m Tc-MDP that is associated with periapical
ET
infection is typically focal and intense, with IRU located
ZYG over the apical region of the affected tooth (Fig. 12.5).
Region of interest studies performed on cases of periapical
infection have shown IRU of 24–259% greater than the
MS same region on the contralateral side when using right and
left lateral views (Archer et al 2003b, Barakzai 2005).
Because “strike-through” may occur when comparing
MCT two lateral views, region of interest studies taken from the
left and right sides on a dorsal (or ventral) view can show
an even greater quantitative IRU (as high as 700%,
Barakzai 2005) on the affected side. If periapical infection
is accompanied by secondary dental sinusitis, the focal
intense uptake over the affected apex will be surrounded by
a diffuse region of moderately increased activity over the
Fig. 12.4. Dorsal scintigram of a normal 7-year-old horse showing
maxillary cheek tooth row (MCT), area of the maxillary sinuses (MS), affected sinus(es) (Fig. 12.6).
ethmoturbinates (ET), zygomatic arch (ZYG), and temporomandibular After dental extraction, areas of IRU can be present
joint (TMJ). for up to 24 months postoperatively, presumably as a
1 5 Fig. 12.5. Right lateral (A) and dorsal (B)

381 K 430 K scintigrams of a 7-year-old horse with peri-
apical infection of 108 (third right maxillary
cheek tooth) showing focal area of intense
IRU over the apex of this tooth on both
views. The affected tooth can be accurately
identified as 108 on the lateral view (the
cheek teeth numbers are marked in red),
but it is less clear which tooth is affected on
6 the dorsal view.
5
4
3
2
0, 328 0, 304
A OTHER:R SINUS - 128X128 B
OTHER:DORSAL HEAD - 128X128
result of continued remodeling of the dental alveolus rostral and caudal maxillary and frontal sinuses individ-
(Barakzai 2005). ually on scintigrams based on their anatomical relation-
Periodontal disease can cause areas of mild to moderate ship to the cheek teeth and ethmoturbinates.
IRU on scintigrams of the equine skull (Weller et al 2001, In one equine scintigraphic study that included 15 cases
Archer et al 2003b, Barakzai 2005). However, because of primary sinusitis, nine of these cases had a focal area of
this disorder is often bilateral, multifocal and commonly moderate or marked IRU within the sinuses (26–496%
affects older horses where the cheek teeth are not clearly increase compared to contralateral side, Barakzai et al 2006;
delineated, it can be difficult to definitively diagnose Fig. 12.8). One of these horses had an encapsulated abscess
this disorder using scintigraphy. Periodontal disease should at surgery, which corresponded to the area of IRU seen on
be clinically evident from a thorough examination of the scintigrams, but there was no explanation for the focal
the oral cavity, and is usually associated with diastemata, areas of IRU seen in the other horses. This is an important
displacements or major dental overgrowths. Therefore finding, because if these focal areas of IRU that are observed
there is little additional benefit from the use of scintigraphy
in its diagnosis.
Primary sinusitis
Experimental and clinical evidence in the human and
veterinary fields indicate that bony changes occur in cases
of primary sinusitis (Bolger et al 1997, Perloff et al 2000).
Additionally, bony changes associated with sinusitis are
reported to extend not only to bone adjacent to the infected
sinus and those which communicate with it, but may also
affect the bone of the contralateral sinonasal complex
(Perloff et al 2000). Human facial bone scintigraphy with
99m 6
Tc-diphosphonate is of diagnostic value in neoplastic
and inflammatory paranasal sinus lesions, including 5
purulent sinusitis (Bergstedt & Lind 1978, Bergstedt et al 4
1978). When compared to computed tomography (CT), 3
bone scintigraphy was more sensitive in detecting osteitis in
human patients with chronic sinusitis, because bony 2
changes can only be detected on CT when the disease is 1
severe enough to destroy bone, or when there is substantial
bony thickening (Jang et al 2002).
Horses with primary sinusitis may show variable Fig. 12.6. Right lateral scintigram of an 18-year-old horse with
periapical infection of 109 (fourth right maxillary cheek tooth) and
patterns of IRU within the affected paranasal sinuses, but
secondary rostral maxillary sinusitis. There is a focal area of marked IRU
generally IRU is more diffuse and less marked (Archer above the affected tooth, and a more diffuse, moderately increased
et al 2003b, Barakzai 2005) than occurs with periapical uptake in the area of the rostral maxillary sinus, dorsal to this tooth
infection (Fig. 12.7). It should be possible to identify the (arrows). The cheek tooth numbers are marked in black.
Fig. 12.7. Left lateral (A) and dorsal (B)

scintigrams of a horse with primary sinusitis.
The area of IRU is more diffuse (spanning the
rostral and caudal maxillary sinuses), and is
less marked than occurs with periapical
infection of a cheek tooth.
A B
Fig. 12.8. Dorsal (A) and right lateral (B)

scintigrams of a horse with primary sinusitis.
Note the focal area of marked IRU (arrow) in
the caudal maxillary sinus, which, in the
lateral view, is positioned too far dorsal to be
associated with an apical infection of the
cheek teeth. No specific lesion was found
within the caudal maxillary sinus during
sinus surgery, which correlated with this
focal area of IRU.
A B
in cases of primary sinusitis happen to be positioned over Sinus cysts

the apex of a cheek tooth, a false diagnosis of periapical
infection may be made. Careful three-dimensional localiza- Sinus cysts are expansive fluid-filled space-occupying
tion of the focal area of IRU (as seen in the case in lesions that occur uncommonly in the equine sinuses and
Fig. 12.8) should help prevent such false diagnoses. frequently cause bone remodeling or even destruction,
accompanied by a low-grade inflammatory response
Sinus trephination (Dixon 1985, Gibbs & Lane 1987, Lane et al 1987b,
Tremaine et al 1999). Histologically, the cyst wall is lined
Trephination of the frontal sinuses is often used to facilitate by a layer of secretory respiratory-type pseudostratified
direct sinus endoscopy as an auxiliary diagnostic technique epithelium, with plates or spicules of bone frequently
in some cases of equine sinusitis. Trephination of a bone present (Lane et al 1987b). The association of these lesions
would be expected to result in a region of IRU (as a result with bony remodeling and new bone formation (within the
of exposure of hydroxyapatite crystals and instigation of cyst wall) may give a typical appearance on scintigraphic
remodeling and callus formation) if the horse later under- examination, with areas of IRU around the margin of the
went scintigraphy to further investigate the cause of the lesion attributable to uptake of radionuclide by calcified
sinusitis. However, trephination of the frontal sinus per- sections of the cyst wall (Fig. 12.9). However, sinus cysts
formed between 1 day and 6 weeks before scintigraphic can usually be accurately diagnosed with a combination of
examination has been found to have no significant effect radiography, endoscopy, direct sinocentesis and sinoscopy,
on radionuclide uptake in the area of the trephine hole and scintigraphic examination is rarely indicated for the
(Archer 2003b, Barakzai & Dixon 2003). diagnosis of these lesions.
Fig. 12.9. Right lateral (A) and dorsal (B)

scintigrams of a horse with a circular sinus
cyst in the right caudal maxillary sinus.
Note the areas of marked IRU around the
margin of the lesion, associated with uptake
of 99mTc-MDP by calcified sections of the
cyst wall.
A B
Fig. 12.10. Dorsal (A) and lateral (B) scinti-

grams of a horse with a maxillary fracture
that presented with facial swelling and
no known history of trauma. Scintigraphy
allowed differentiation between periapical
infection of a cheek tooth and fracture of
the left lateral maxilla, because the focal
area of marked IRU is positioned lateral to
the left cheek tooth row on the dorsal view.
A B
Progressive ethmoidal hematomas

creating sinus flaps or trephine holes, appear to be
The scintigraphic appearance of progressive ethmoidal associated with little or no IRU (Barakzai & Dixon 2003,
hematomas is not well documented, but a focal intense Barakzai 2005). In contrast, skull fractures which are
IRU is usually seen adjacent to the ethmoturbinates, traumatic in origin are often associated with intense IRU, as
which is sometimes accompanied by a more diffuse IRU as is nasofrontal suturitis, a common sequel of equine skull
a result of secondary sinusitis (Barakzai 2005). However, trauma (Tremaine & Dixon 2001, Barakzai 2003).
progressive ethmoidal hematomas can usually be accu-
rately diagnosed by a characteristic history of low-grade Neoplasia of the head
epistaxis, radiography, endoscopy, and sinoscopy, and
scintigraphic examinations are rarely indicated for the The use of scintigraphy in the evaluation of malignant
diagnosis of these lesions. disease of the human facial bones and sinuses has
been limited. CT is usually performed as part of a staging
Skull fractures (Fig. 12.10) procedure, and will usually demonstrate bony involve-
ment in malignancies. However, scintigraphy remains an
Fractured bones often have a focal intense IRU within extremely sensitive method for demonstration of malignant
hours of the fracture occurring, as a result of exposure of involvement of bones, and a normal bone scan virtually
hydroxyapatite crystals, followed by instigation of bone excludes tumor involvement of bone (O’Mara 1985). It has
remodeling and callus formation (Lamb & Koblik 1988, been suggested that gamma scintigraphy may be a useful
Lamb 1991). IRU is variable with equine skull fractures. additional imaging modality for the early detection of
Stable fractures, such as those caused iatrogenically when sinonasal neoplasia in the horse (Archer et al 2003b).
REFERENCES Lamb CR 1991 The principles and practice of bone scintigraphy

in small animals. Seminars in Veterinary Medicine and
Archer DC, Blake CL, Singer ER et al 2003a The normal Surgery (Small Animal) 6: 140–153
scintigraphic appearance of the equine head. Equine Lamb CR, Koblik PD 1988 Scintigraphic evaluation of skele-
Veterinary Education 15: 243–249 tal disease and its application to the horse. Veterinary
Archer DC, Blake CL, Singer ER et al 2003b Scintigraphic Radiology 29: 16–27
appearance of selected diseases of the equine head. Lane JG, Gibbs C, Meynik SE et al 1987a Radiographic
Equine Veterinary Education 15: 305–313 examination of the facial, nasal and paranasal sinus
Barakzai SZ 2005 Use of scintigraphy for the diagnosis of regions of the horse: I: indications and procedures in
suspected equine dental and paranasal sinus disorders. 235 cases. Equine Veterinary Journal 19: 466–473
MSc Thesis, University of Edinburgh Lane JG, Longstaffe JA, Gibbs C 1987b Equine paranasal sinus
Barakzai SZ, Dixon PM 2003 Effect of sinus trephination cysts: a report of 15 cases. Equine Veterinary Journal
on scintigraphy of the equine skull. Veterinary Record 19: 534–544
152: 629–630 Metcalf MR, Tate LP, Sellett LC 1989 Clinical use of
99m
Barakzai SZ, Tremaine WH, Dixon PM 2006 Use of scintigraphy Tc-MDP scintigraphy in the equine mandible and
for diagnosis of equine paranasal sinus disorders. maxilla. Veterinary Radiology 30: 80–87
Veterinary Surgery 35: 94–101 O’Mara RE 1985 Role of bone scanning in dental and
Bergstedt HF, Carenfelt C, Lind MG 1978 Facial bone scinti- maxillofacial disorders. In: Freeman LM, Weissman HS
graphy. IV. Diagnosis of bone involvement by purulent (editors) Nuclear Medicine Annual. Raven Press,
sinusitis. Acta Radiologica: Diagnosis 20: 379–384 New York, pp.78–91
Bergstedt HF, Lind MG 1978 Facial bone scintigraphy. II. Perloff JR, Gannon MD, Bolger WE et al DW 2000 Bone
Diagnostic potential in neoplastic and inflammatory involvement in sinusitis: an apparent pathway for the
lesions. Acta Radiologica: Diagnosis 19: 993–999 spread of disease. Laryngoscope 110: 2095–2099
Bolger WE, Leonard D, Dick EJ et al 1997 Gram negative Ramzan PHL 2003 The head. In: Dyson SJ, Pilsworth RC,
sinusitis: a bacteriologic and histological study in rabbits. Twardock AR, Martinelli MJ (editors) Equine Scintigraphy.
American Journal of Rhinology 11: 15–25 Equine Veterinary Journal, Newmarket, pp.225–226
Boswell JC, Schramme MC, Livesey LC et al 1999 Use of Seeherman HJ 1998 Clinical applications of bone scanning.
scintigraphy in the diagnosis of dental disease in four In: White NA, Moore JN (editors) Current Techniques in
horses. Equine Veterinary Education 11: 294–298 Equine Surgery and Lameness, 2nd edn. WB Saunders,
Dixon PM 1985 Equine maxillary cysts. Equine Practice Philadelphia, pp.592–605
71: 25–33 Tow DE, Garcia DA, Jansons D et al 1978 Bone scan in dental
Garcia DA, Entine G, Tow DE 1974 Detection of small bone diseases. Journal of Nuclear Medicine 19: 845–895
abscesses with a high resolution cadmium telluride Tremaine WH, Dixon PM 2001 A long term study of 277
probe. Journal of Nuclear Medicine 15: 892–895 cases of equine sinonasal disease. Part 1: Details of horses,
Gayle JM, Redding WR, Vacek JR et al 1999 Diagnosis historical, clinical and ancillary diagnostic findings.
and surgical treatment of periapical infection of the Equine Veterinary Journal 33: 274–282
third mandibular molar in five horses. Journal of the Tremaine WH, Clarke CJ, Dixon PM 1999 Histopathological
American Veterinary Medical Association 215: 829–832 findings in equine sinonasal disorders. Equine Veterinary
Gibbs C, Lane JG 1987 Radiographic examination of the Journal 31: 296–303
nasal and paranasal sinus regions of the horse. Part 2: Weaver MP 1995 Twenty years of equine scintigraphy – a
Radiological findings. Equine Veterinary Journal coming of age? Equine Veterinary Journal 27: 163–165
19: 474–482 Weller R, Livesey L, Maierl J et al 2001 Comparison of
Jang YJ, Koo TW, Chung SY et al 2002 Bone involvement radiography and scintigraphy in the diagnosis of dental
in chronic rhinosinusitis assessed by 99mTc-MDP bone disorders in the horse. Equine Veterinary Journal
SPECT. Clinical Otolaryngology and Allied Sciences 33: 49–58
27: 156–161
Javer AR, Stevens HE, Stillwell M et al 1996 Efficacy of nuclear
scintigraphy in the diagnosis and management of
sinusitis. Journal of Otolaryngology 25: 375–382
Pulmonary Scintigraphy
13 Dominique-Marie Votion and Pierre Lekeux
Introduction Table 13.1. The potential applications of

As a complementary investigation tool, scintigraphy pro- scintigraphic tests in the study and diagnosis
of equine pulmonary disorders
vides a unique method for studying regional lung func-
tion. The numerous potential applications of scintigraphic Evaluation of regional ventilation and perfusion and their
tests in the study and diagnosis of pulmonary disorders relationship
Definition of functional changes induced by pulmonary
are listed in Table 13.1. The purpose of this chapter is to
disorders
assist nuclear medicine practitioners in performing and Diagnosis of an unknown disorder
interpreting the results of lung scintigraphy in horses, Assessment of the extent of a pulmonary disease
primarily for: Monitoring the course of a pulmonary disease
Assessment of the response to therapy
● assessing regional ventilation
Measurement of alveolar clearance
● determining regional ventilation to perfusion ratios
Detection of subclinical RAO
● measuring alveolar clearance. Evaluation of management procedures in horses suffering
from RAO
Assessment of mucociliary clearance, detection of pul-
Assessment of the severity of pulmonary diseases
monary bleeding sites, the study of aerosol deposition Monitoring the course of pulmonary diseases
within the equine lung, and imaging of pulmonary Assessment of the response to therapy
infection and inflammation will be covered briefly as these Assessment of mucociliary clearance
techniques have primarily a research application or they Assessment of changes in mucociliary clearance induced by
are inadequately validated in horses. respiratory disorders
Evaluation of drugs such as mucolytics, expectorants or
mucokinetics
Imaging of Regional Lung Function
Detection and quantification of pulmonary bleeding sites
The properties of the radiopharmaceuticals that are used Diagnosis of EIPH
in lung function imaging are summarized in Table 13.2. Assessment of the severity of EIPH
Monitoring the site and time course of EIPH
Lateral images of the lungs are usually obtained by Assessment of the response to therapy
positioning the horse with the thorax against the face of
Study of aerosol deposition within the lung
the gamma camera. Because of the large surface area of
Evaluation of aerosol delivery systems and techniques
the equine lungs, one cranial and one caudal view per lung Determination of inhaled drug dosage requirements
must be acquired. The computer then integrates the cranial Study of inhaled drug deposition
and caudal views to form a single lateral view for each
Imaging sites of pulmonary infection and inflammation
lung. This integration requires placement of reference Detection and diagnosis of occult pulmonary infections and
radioactive marks at fixed positions on the chest wall inflammation
(Votion et al 1997). Multiple sequential imaging may also Assessment of the severity of pulmonary diseases
be performed, whereby a series of images is recorded for a Monitoring the course of pulmonary diseases
Assessment of the response to therapy
selected time period.
Study of inflammatory cell recruitment in lung disorders
Digital images are recorded in matrices of either
64 × 64, 128 × 128 or 256 × 256 pixels, and images are EIPH = exercise-induced pulmonary hemorrhage; RAO = recurrent airway
stored on the computer for subsequent analysis. When obstruction.
image acquisition is completed, a horse that has received

technetium-99m (99m Tc) radiopharmaceuticals must be activity in each pulmonary zone. These images can reveal,
quarantined for 48 h, by which time the 99m Tc (half-life almost at a glance, pulmonary dysfunction (e.g. a mismatch
6 h) has significantly decayed. in ventilation and perfusion distribution) or an abnormal
Scintigraphic images may be displayed in a color-coded deposition pattern in aerosol studies, although appropriate
fashion according to the relative concentration of radio- image processing yields additional information.
193
194 13 Pulmonary Scintigraphy
Table 13.2. Radiopharmaceuticals used in lung function imaging

Radiopharmaceutical Study Dosage Advantage(s) Disadvantage(s)
Radioactive gas
81m
Kr Ventilation 1.8 liter/min* Easy to administer Limited availability
No risk of environmental contamination Expensive
Low radiation dose
High-quality images
True ventilation images
On-line monitoring of functional changes
Ventilation scanning may be repeated
No horse quarantine required
Dual acquisition with 99mTc-albumin
aggregates or 99mTc-microspheres is
feasible
Perfusion 25 ml/min** On-line monitoring of functional changes Time consuming

More expensive than the
labeled albumin aggregate
and microsphere methods
Artifact due to circulating
activity
Technetium-labeled compounds
99m
Tc-DTPA Ventilation 7.4 MBq/kg The most commercially available Lung clearance (poor
quality of the ventilation
image in horses with lung
disorders)
Alveolar 7.4 MBq/kg Measures alveolar epithelium injury

clearance Detects subclinical inflammation
99m
Tc-Nanocolloid Ventilation 7.4 MBq/kg Negligible lung clearance
99m
Tc-Carbon Ventilation to be defined Probably better ventilation imaging agent Risk of environmental
(Technegas) than liquid aerosols contamination
Requires only a few breaths to be High cost of Technegas
administered generator device
99m
Tc-albumin Perfusion 1.11 MBq/kg The easiest method
aggregates or Imaging of the whole lung without
-microspheres artifact due to circulating activity
Images of perfusion at exercise may be
obtained
* The elution rate suggested is for a generator containing approximately 925 MBq (25 mCi) of its parent isotope.
** Elution of the generator with 5% dextrose in water.
elution is 1.8 liter/min for a generator containing approxi-

Assessment of Regional Ventilation
mately 925 MBq 81Rb. The horse breathes the eluted 81m Kr
Radiopharmaceuticals from the generator continuously, through a tube connected
to a facemask. The 81m Kr may also be delivered directly into
Regional ventilation imaging in horses may be performed the trachea via an intratracheal catheter. Owing to the
using radioactive krypton-81m (81m Kr) gas or radiolabeled short half-life of 81m Kr, there is no safety requirement to
aerosols. Scintigraphy using 81m Kr gas allows assessment of collect exhaled air. Unfortunately, the short half-life of 81Rb
ventilation in a time scale of seconds, whereas radiolabeled (4.58 h) limits 81mKr availability in clinical practice.
aerosol scintigraphy allows static imaging of the lungs but As an alternative to 81mKr, inhaled radiolabeled aerosols
does not provide information about airflow. may be used. Ventilation imaging with aerosols assumes
The 81m Kr is a radioactive noble gas that has a very that the deposition of small inhaled particles follows the
short half-life (13 seconds). It is obtained by eluting a distribution of inhaled air, and that areas of the lungs
rubidium-81 (81Rb)/81m Kr generator with air. The rate of in which no radioactive aerosol particles are deposited
13 Pulmonary Scintigraphy 195
are likely to be unventilated. However, other features of of not being diffusible through the alveolar–capillary
respiratory disorders, such as high respiratory rate and barrier (Isawa et al 1996). However, as the entire dose
airway obstruction, reduce penetration of radiolabeled of Technegas is administered in a few seconds, severe
aerosols into the peripheral lung and favor their deposition atmospheric contamination with Technegas may occur
in central conducting airways. Consequently, the deposition if the animal accidentally disconnects from the delivery
pattern of radiolabeled aerosols does not necessarily match system during administration. During labeled aerosol
the ventilation distribution. On the other hand, the image administration (i.e. liquid aerosols or Technegas), it is
obtained using radiolabeled aerosols is highly sensitive preferable to sedate the horse to minimize the risks of
to ventilation restriction and airflow modification. The accidental disconnection from the delivery system.
radiolabeled aerosols used in equine scintigraphy comprise
compounds labeled with 99m Tc. The 99m Tc radionuclide
readily labels a variety of compounds and is both easily and Imaging of regional ventilation
cheaply obtainable via a molybdenum-99 (99Mo)/99m Tc
Ventilation images obtained using 81m Kr must be acquired
generator. Most scintigraphic assessments of ventilation in
during administration of the radioactive gas because of the
horses have used 99m Tc-diethylene triamine pentaacetic
short half-life of the radiopharmaceutical. However, a great
acid (DTPA) as the 99mTc-labeled compound. However,
advantage of this short half-life is that studies may be
DTPA is absorbed from the lungs by passive diffusion
repeated without carry over of radioactivity from preceding
through the alveolar–capillary barrier. In a number of
studies. This can facilitate on-line visualization of the
diseases, the permeability of this barrier is considerably
course of alterations in ventilation induced by specific
increased and thus 99m Tc-DTPA molecules are absorbed
conditions and interventions, such as following adminis-
more rapidly from the lungs. This property may be useful in
tration of bronchodilators.
the measurement of alveolar clearance, but in ventilation
In contrast, static images of radiolabeled aerosol
studies a significant quantity of radiopharmaceutical may
deposition are acquired after administration of the radio-
have already been cleared from the lungs during the time
pharmaceutical. Approximately 30–60 min is required to
required to acquire the aerosol deposition images. A non-
obtain all views of the lungs.
diffusible compound such as nanocolloid of human
albumin, that shows negligible absorption over time, is
therefore preferable to DTPA. Interpretation of regional
Radiolabeled aerosols are prepared by introducing ventilation scintigrams
sodium pertechnetate [Na+(99m TcO4)–] to lyophilized
reaction vials. The radioactive solution (7.4 MBq/kg body In healthy horses, ventilation is evenly distributed
weight) is then aerosolized using an inhalation device throughout the lung field. Functional modifications in
which must produce aerosol droplets that have an regional ventilation result from airway obstruction
aerodynamic particle size of between 0.5 and 2 μm. caused by bronchospasm, excess mucus in the airway,
Droplets that are smaller than 0.5 μm tend to be exhaled, and thickening of the bronchial airway wall by edema and
whereas droplets exceeding 2 μm tend to impact in the inflammation. When ventilation is imaged with radio-
larger conducting airway rather than reaching the alveoli. labeled aerosols, these abnormalities lead to deposition of
The horse breathes the radioactive aerosol for several aerosol droplets predominantly in the large airways, and
minutes, i.e. the time required to aerosolize and deliver reduced deposition in the terminal airways and alveoli.
the entire dose. Because of potential atmospheric radio- Consequently, aerosol images are considered abnormal
active contamination, the radiolabeled aerosol must be when the ventilation distribution is uneven, with the
administered to the horse via an airtight delivery system, degree of irregularity in aerosol distribution being directly
and exhaled air must be collected through a filter to remove proportional to the severity of functional disturbance
exhaled radioactive particles. (Fig. 13.1). Image analysis may then provide quanti-
An ultrafine dry aerosol called Technegas, which so far tative assessment of ventilation, which allows comparison
has not been used in equine medicine, could potentially of subjects or groups of subjects to reference values
be of use in horses. This ventilation imaging agent is pro- and overcomes problems with subjective interpretation
duced by evaporating sodium pertechnetate at 2500°C on of images.
a carbon surface (Burch et al 1986). The 99m Tc-carbon The extent to which the aerosol has penetrated into the
particles produced have gas-like penetrating characteristics smaller airways and alveoli may be assessed by calculating
but, despite their small size (below 0.2 μm), the dry aerosol the penetration index (PI). The PI has been defined as the
particles adhere to the alveolar walls. In calves, a dose of ratio of radioactivity recorded in the peripheral versus the
20 MBq/kg body weight of sodium pertechnetate yielded central part of the lung. Calculation of PI first necessitates
excellent images of regional ventilation (Coghe et al 2000). accurate delineation of the lung margins, using radioactive
Technegas has the advantage over radiolabeled aerosols gas inhalation images (it is assumed that gases reach the
90 μm) exceeds that of the pulmonary precapillary lumina,

the particles temporarily embolize pulmonary capillaries
and small arterioles according to the distribution of
pulmonary blood flow (Beck 1987). This yields a picture
of pulmonary blood flow distribution at the moment
A B the particles were trapped. Removal of the entrapped
particles occurs over several hours. Care must be taken
Fig. 13.1. Aerosol deposition images of a horse suffering from
during the intravenous injection: the solution must be
recurrent airway obstruction (lateral views of the right lung). Airway
obstruction associated with recurrent airway obstruction impedes gently homogenized before administration, blood must
radioactive aerosol particle penetration into the peripheral lung, and not be withdrawn into the syringe as it may form clots, and
favors patchy dispersal of the radiopharmaceutical (A). Following the tracer must be administered over several respiratory
therapy with aerosolized drugs, lung function is improved and a more cycles to average the pulmonary blood flow distribution,
homogeneous distribution of the radiopharmaceutical is observed (B).
which is influenced by changes in alveolar pressure
associated with breathing (Jarvis et al 1992). In horses, the
procedure appears to be safe because no adverse reaction
alveoli) or perfusion images. Second, within the lung has been reported.
margins, the central (including the major bronchi) and
peripheral (containing mainly lung parenchyma) parts of Imaging of regional perfusion (to determine
the lung must be delineated. the ventilation to perfusion ratio)
Another quantitative index of the aerosol’s ability to
reach the peripheral lung is the “size” of the images When ventilation is imaged with 81m Kr gas, ventilation and
as determined by an isocontour function. This function perfusion images may be obtained simultaneously, because
draws a line between pixels with a value equal to a defined the 140-keV emission of 99mTc and the 191-keV emission
percentage of the maximum pixel value in the image. of 81m Kr can be recorded simultaneously using two
The maximal pixel value in the image is influenced by the different acquisition channels. This reduces the time
degree of aerosol penetration and is higher when more required for imaging and enables ventilation and perfusion
aerosol impacts within the airways. Consequently, the images to be matched perfectly in the acquisition matrices.
isocontour function, for the same defined percentage, tends In contrast, when both ventilation and perfusion images
to draw a smaller deposition image. The percentage of the are obtained using 99m Tc radiopharmaceuticals, ventilation
isocontour function should be set high enough to exclude and perfusion images must be acquired in succession.
background radioactivity. The number of pixels within the Consequently, the radioactivity originating from the first
isocontour line represents the size of the picture. study contaminates the subsequent study. To minimize this
effect, the radioactivity within the lungs in the second
study must exceed that of the first study. Labeled aerosol
Assessment of Regional Lung Perfusion or Technegas imaging should be performed before perfu-
Radiopharmaceuticals sion imaging because it is easier to deliver a larger dose of
99m
Tc perfusion imaging agent than of 99mTc aerosol. With
In horses, perfusion scintigraphy alone has been performed the recommended dosages, the background activity arising
mainly for research purposes, such as investigating from the ventilation study is minimal when compared to
alterations in regional perfusion induced by exercise or that of the perfusion study.
anesthesia. These studies employed either infusion of
81m
Kr gas or labeled entrapped particle methods. However, Assessment of regional ventilation
for clinical investigation of respiratory disorders, a to perfusion ratio
combined ventilation–perfusion study is usually performed.
The easiest way to study the ventilation–perfusion relation- In healthy horses, the radioactivity distribution patterns of
ship is to use images of radiolabeled aerosol deposition and ventilation (Fig. 13.2A) and perfusion (Fig. 13.2B) appear
images of labeled entrapped particles. The latter involves very similar. When respiratory disorders alter one or
administration of 99m Tc-labeled microspheres or albumin both of the functions, a direct visual comparison of the
aggregates into a jugular vein. These microspheres and ventilation and perfusion images can be difficult to
albumin aggregates are supplied as lyophilized kits interpret. This problem can be overcome by the creation of
ready to label by adding sodium pertechnetate. A dose computerized images of the ventilation to perfusion ratio.
of 1.11 MBq/kg body weight gives satisfactory images of When labeled aerosols are used for lung ventilation
equine lung perfusion (Votion et al 1997). As the size of imaging, the creation of ventilation to perfusion ratio
the particles in the suspension (at least 90% of the particles images necessitates the exact matching of ventilation and
have a diameter above 10 μm and all are smaller than perfusion images, using reference markers placed on the
Fig. 13.2. (A,B) Ventilation and perfusion

images (lateral views of the right lung).
On visual inspection, ventilation (A) and
perfusion (B) distribution patterns in healthy
horses are comparable.
A B
chest wall. Furthermore, radioactivity arising from the of hydrophilic molecules is primarily dependent on the
ventilation procedure that contaminates the perfusion scan alveolar epithelial component of this barrier. Therefore,
must be subtracted from the perfusion image, taking into soluble materials deposited in the alveoli passively diffuse
account the duration of time that has elapsed between into the pulmonary circulation and enter the bloodstream
the acquisition of the ventilation and perfusion images, at a rate determined largely by the permeability of the
because the radioactivity originating from the ventilation alveolar epithelium. Elimination of 99mTc-DTPA from the
scan will have been attenuated by radioactive decay when lungs is considered to be an index of alveolar epithelial
compared to the ventilation image used for subtraction. damage. Epithelial injury increases permeability of the
From “pure” ventilation (i.e. 81m Kr or corrected 99m Tc- alveolar epithelium, and hastens 99mTc-DTPA diffusion from
labeled aerosol deposition images) and perfusion images, lungs to blood. The 99mTc-DTPA is prepared as described
ventilation to perfusion ratio images may be created by earlier for ventilation studies.
computer. Considering that the same radioactive dose is
present within the lungs after the ventilation and perfusion Imaging of alveolar clearance
procedures, the mean pixel count of the ventilation images
must be equalized to the mean of the perfusion scans using Numerous factors may influence the measurement of
a corrective factor specific for the left and right lungs (see alveolar clearance rates, and thus a highly standardized
Votion et al 1997 for further details of this procedure). method must be used (Votion et al 1998). Immediately
When the corrective factors have been applied, left and after disconnecting the 99mTc-DTPA delivery system from
right ventilation to perfusion ratio images can be obtained the horse, the gamma camera is placed against the horse’s
by dividing the corresponding pixels in the ventilation left chest wall, and the caudal part of the lung is imaged
image by those of the perfusion image. These ventilation at 30-second intervals for 20 min. The rate of alveolar
to perfusion ratio images permit direct visualization of clearance of hydrophilic solutes precludes the acquisition of
ventilation–perfusion mismatches. Additionally, a histo- additional satisfactory views of the lung. Thus, following
gram of frequency ratio distribution can be produced. In imaging of alveolar clearance, a perfusion image should be
healthy horses, the distribution is tightly centered on the obtained to further identify the lung boundary on the
99m
theoretical ideal value of 1, i.e. ventilation closely matches Tc-DTPA deposition images.
perfusion. This matching ensures efficient gas exchange.
Inequalities of the distribution of ventilation and perfu- Measurement of alveolar clearance
sion ratio are the most common causes of inefficient
gas exchange. Scintigraphy highlights these mismatches The caudal half of the left lung may be outlined on the
99m
within the diseased lungs and enables assessment of the Tc-DTPA deposition scans using the perfusion image.
time course of a disease or its response to therapy (Votion The number of counts recorded by the gamma camera
et al 1999a). in each frame of the caudal lung is used to generate a
(radio)activity versus time curve. The coefficient of time,
estimated by fitting the monoexponential decay curve to
Assessment of Alveolar Clearance the observed counts, measures the regional clearance rate
Radiopharmaceuticals (k). Results may also be expressed in half-time clearance
from lung to blood (t 1 ⁄2 = ln2/k). In healthy horses,
The alveolar–capillary membrane comprises the alveolar the mean value for half-time 99mTc-DTPA alveolar clearance
epithelial layer, the interstitial space, and the capillary is approximately 40 min. One advantage of the alveolar
endothelial layer. This barrier normally prevents plasma, clearance test is the detection of subclinical recur-
cells, and proteins from flooding the air space, thereby rent airway obstruction (RAO; Votion et al 1999b). The
99m
maintaining normal gas exchange. Because intercellular Tc-DTPA alveolar clearance rate is reduced in
junctions of alveolar cells are tighter than those of the RAO-affected horses that have clinical signs of the disease
endothelial cells, resistance to transmembrane diffusion but returns to baseline when horses are in full clinical
remission following their turn-out to pasture. RAO-affected

horses that are maintained in a dust-controlled indoor
environment have intermediate values for 99mTc-DTPA
alveolar clearance rates, despite lacking abnormal clinical
signs. In contrast, clinical examination and conventional
pulmonary function tests are of insufficient sensitivity to
differentiate those horses which were in clinical remission
following turn-out to pasture from those of RAO horses
which were maintained in a dust-controlled indoor
environment. This demonstrates that measurement of
99m
Tc-DTPA alveolar clearance may allow detection of
early functional changes at the alveolar level in horses
with subclinical RAO. Detection of subclinical diseases is
extremely useful for effective environmental and medical
management, and for the prevention of irreversible lung
remodeling. Measurement of 99mTc-DTPA alveolar clear- Fig. 13.3. Exercise-induced redistribution of pulmonary perfusion
ance rates may also be useful in following both the time (lateral view of the left lung). Computed exercise versus resting
course and the severity of lung injury, as well as in perfusion ratio image of lung demonstrating the redistribution of
monitoring the subsequent repair process. pulmonary perfusion to the caudodorsal region of the lung during
exercise.
Research Applications of
Equine Scintigraphy indium-111 (111In)-RBC/99mTc-RBC dual isotopes imaging
Scintigraphic assessment of (Votion & Lekeux 2003) or the radiolabeled peptide tech-
mucociliary clearance nique used to detect deep venous thrombosis (Taillefer
2001) should be evaluated for the detection of EIPH.
Mucociliary clearance of inert insoluble particles may be Scintigraphy, using labeled entrapped particles, showed
imaged with scintigraphy, and the tracheal mucus trans- that pulmonary blood flow is redistributed to the dorso-
port rate can be determined. A dose of 370 MBq radioactive caudal regions of the lungs during exercise (Harmegnies et
inert insoluble particles is deposited within the trachea al 2002; Fig. 13.3). This may contribute to EIPH because
using an endoscope or an intratracheal catheter (Nelson & bleeding arises from the dorsocaudal areas of both lungs.
Hampe 1983). Microspheres or albumin aggregates
labeled with 99m Tc may be used as radiopharmaceuticals. Scintigraphic evaluation of
Sequential imaging of the trachea is used to follow the inhalation therapy
transport of the radioactive material up the trachea. The
tracheal mucus transport rate is then calculated by The response to therapeutic aerosols is considered to be a
dividing the distance moved by the radioactive tracer by function of the dose deposited at the appropriate site in the
the time taken. The method used must be highly stan- lung. This dose is dependent upon the system used to
dardized because of the numerous factors affecting the produce and deliver the aerosol, the physical characteristics
tracheal mucus rate, such as sedation, age, angulation of of the inhaled aerosol, the mode of inhalation, and the
the trachea, and the presence of coughing. The study of geometry of the airways. Scintigraphy can facilitate the
tracheal mucociliary clearance is, however, of little value study of the efficiency of a delivery system (dose delivered,
in routine clinical investigation, mainly because of large regional distribution), the techniques of drug administra-
individual variation. tion (e.g. determination of the optimal time in the respira-
tory cycle to administer a bolus of drug to target a specific
Study of pulmonary perfusion for detection lung zone), the effect of respiratory disorders on aerosol
of lung hemorrhage distribution, and may also help determine the site of action
of drugs. These studies may improve drug targeting.
A method to accurately detect and repeatedly quantify
pulmonary hemorrhage in horses would greatly improve Imaging of pulmonary infection
our knowledge of exercise-induced pulmonary hemorrhage and inflammation
(EIPH). In humans, scintigraphy employing labeled red
blood cells (RBCs) is used to detect low-grade gastroin- In human medicine, lung scintigraphy with gallium-67
testinal bleeding, but unfortunately this method lacks (67Ga) is an established means to assess alveolar inflamma-
sensitivity for detection of EIPH. Other techniques such as tion in a wide range of diffuse lung disorders. Immediately
following its intravenous injection, 67Ga citrate binds

REFERENCES
to transferrin and the metal–protein complex diffuses
passively through the vascular endothelium into the Beck KC 1987 Regional trapping of microspheres in the lung
inflamed tissues. The circulating tracer is subsequently correlates well with regional blood flow. Journal of
Applied Physiology 63: 883–889
bound to iron-binding proteins produced by macrophages Burch WM, Sullivan PJ, McLaren CJ 1986 Technegas – a new
and bacteria within the inflamed tissue. Lung scintigraphy ventilation agent for lung scanning. Nuclear Medicine
with 67Ga could theoretically be used to monitor the Communications 7: 865–871
extent and distribution of alveolar inflammation during Coghe J, Votion D, Lekeux P 2000 Comparison between radio-
the course of equine respiratory disorders and to eval- active aerosol, Technegas and Krypton for ventilation
imaging in healthy calves. Veterinary Journal 160: 25–32
uate the response to therapy. However, the major draw- Fairbairn SM, Page CP, Lees P et al 1993 Early neutrophil but
backs of 67Ga are its poor specificity, its long physical not eosinophil or platelet recruitment to the lungs of
half-life (78 h) and its broad range of gamma-ray emission allergic horses following antigen exposure. Clinical and
that produces poor-quality images. Experimental Allergy 23: 821–828
Alternatively, pulmonary inflammatory foci may be Goupille P, Diot P, Valat JP et al 1995 Imaging of pulmonary
disease in rheumatoid arthritis using J001X scintigraphy:
imaged following the intravenous administration of radio- preliminary results. European Journal of Nuclear
labeled leukocytes, which migrate rapidly into inflam- Medicine 12: 1411–1415
matory sites. Radiolabeled leukocyte scintigraphy may Harmegnies NF, Duvivier DH, Vandenput SN et al 2002
aid the diagnosis and assessment of the severity of occult Exercise-induced pulmonary perfusion redistribution in
inflammatory or septic foci in the equine lung, such as heaves. Equine Veterinary Journal 34(suppl): 478–484
Isawa, T, Lee BT, Hiraga K 1996 High-resolution electron
those caused by Rhodococcus equi infection (Ramzan microscopy of technegas and pertechnegas. Nuclear
et al 2004). Medicine Communications 17: 147–152
Specific inflammatory cell involvement in equine Jarvis KA, Steffey EP, Tyler WS et al 1992 Pulmonary blood
lung diseases may also be studied using scintigraphy. flow distribution in anesthetized ponies. Journal of
Neutrophils, eosinophils, mononuclear cells, and platelets Applied Physiology 72: 1173–1178
Marr KA, Lees P, Page CP et al 1998 Effect of the
can be separated by density gradient centrifugation and 5-lipoxygenase inhibitor, fenleuton, on antigen-induced
subsequently selectively labeled in vitro, without alteration neutrophil accumulation and lung function changes in
in their state of activation. These labeled cells may be horses with chronic obstructive pulmonary disease.
re-injected into the donor horse to follow their distribu- Journal of Veterinary Pharmacology and Therapeutics
tion within the body, and to determine whether they are 21: 241–246
Nelson R, Hampe DW 1983 Measurement of tracheal mucus
recruited to the lung. This technique was used to deter- transport rate in the horse. American Journal of Veterinary
mine the time course of leukocyte recruitment to the lungs Research 44: 1165–1166
of RAO-affected horses following dust exposure, and to Ramzan PHL, Malton RJ, McGladdery AJ 2004 Use of
99m
show that pulmonary leukocyte recruitment coincided technetium hexamethylpropyleneamine oxime labelled
temporally with the exacerbation of airway dysfunction leucocyte scintigraphy in equine medical investigations:
8 cases. Equine Veterinary Education 16: 122–127
(Fairbairn et al 1993). Scanning with labeled leukocytes is Taillefer R 2001 Radiolabelled peptides in the detection of
also particularly useful for investigating the effects of pro- deep venous thrombosis. Seminars in Nuclear Medicine
or anti-inflammatory drugs on pulmonary leukocyte 31: 102–123
recruitment (Marr et al 1998). Votion D, Vandenput S, Duvivier DH et al 1997 Analysis of
A preliminary study suggests that a 99m Tc-anti- equine scintigraphical lung images. Veterinary Journal
153: 49–61
granulocyte monoclonal antibody Fab′ fragment Votion D, Vandenput S, Duvivier DH et al 1998 Scintigraphical
(LeukoScan®, Immunomedics Europe, Amsterdam, the evaluation of alveolar clearance in horses. Veterinary
Netherlands) could be valuable in investigating neutrophil Journal 56: 51–58
recruitment to the equine lung (Votion et al 2000). Votion D, Ghafir Y, Vandenput S et al 1999a Analysis of
Intravenously injected LeukoScan® particles bind to a scintigraphical lung images before and after treatment of
horses suffering from chronic pulmonary disease.
granulocyte antigen and therefore can facilitate visualiza- Veterinary Record 144: 232–236
tion of site(s) of granulocyte accumulation in the lung. Votion D, Vandenput S, Duvivier DH et al 1999b Alveolar
Human macrophages can be specifically labeled in vivo clearance in horses with chronic obstructive pulmonary
with a radiolabeled glycolipid, termed J001X, isolated disease. American Journal of Veterinary Research
from the membrane of Klebsiella pneumoniae. Administered 60: 495–500
Votion DM, Harmegnies NF, Lekeux PM 2000 Feasibility of
as an aerosol, radioactive J001X binds selectively to monitoring neutrophils’ migration into the lung with
macrophages, mainly in their activated state, by a protein- immunoscintigraphy: preliminary study. European
receptor-mediated process. In human medicine, scinti- Journal of Nuclear Medicine 27: 1089.
graphy with J001X facilitates the study of monocyte Votion DM, Lekeux P 2003 A dip into the world of veterinary
recruitment in lung diseases (Goupille et al 1995), but the nuclear medicine: equine lung scintigraphy. In: Birks E
(editor) Clinical Techniques in Equine Practice. Elsevier,
technique remains to be evaluated in horses. Oxford, pp.222–230
Blood Gas Analysis
14 R Eddie Clutton
Introduction Equipment
Technical advances have enabled modern blood gas Technical notes
analyzers to measure a range of hematological variables.
Blood gas interpretation is also easier; advanced analyzer Improvements in blood gas analyzer performance have
software has conferred some devices with primitive diag- occurred because fluorescent optodes (optical electrodes)
nostic abilities. Through text displays, some analyzers can have replaced the traditional glass (pH), Clark (PO2) and
prompt the minimally qualified to perform and report Severinghaus (PCO2) electrochemical cells. Optodes measure
results – providing they can read the on-screen instruc- the intensity of light emitted from fluorescent dyes in
tions. Reduced equipment size, increased robustness and response to illumination from an excitatory light source.
the incorporation of fully rechargeable cells makes field The quantity of light emitted is affected by the concentra-
use feasible, while the use of disposable cartridges has tion of analyte (H+ and O2) to which the dye is exposed.
simplified calibration and improved reliability.
Equipment operation
Optode-based analyzers use single-use cassettes that
Applications contain the elements required for calibration, sample
Arterial blood gas analysis is necessary for investigating measurement, waste containment, and disposal. By
pulmonary function because in measuring arterial tensions physically isolating the blood sample from the analytical
of O2 (PAO2) and CO2 (PaCO2) it quantifies the lung’s ability to hardware, cassette-based systems avoid the single greatest
oxygenate and remove CO2 from pulmonary arterial blood. limitation of older devices, namely equipment failure
Arterial pH (pHa) and PaCO2 values also indicate the lung’s caused by aspiration of blood clots, which form in inad-
influence on acid–base status. Blood gas determinations equately heparinized samples. Currently, a clotted sample
facilitate diagnosis and the management of respiratory only disables the cassette; and its prompt replacement
diseases, such as maladaptive problems and pneumonias delays analysis by no more than 2 or 3 min.
in foals and recurrent airway obstruction in adult horses. Depending on the analyzer, analysis often begins with
They are useful in all but the shortest general anesthesia, the cassette package being “swiped” through a bar-code
during which respiratory dysfunction is inevitable and reader, which provides the software with cassette-specific
occasionally severe. Serial arterial blood gas measure- calibration information. The cassette is then placed into
ment is necessary for the proper management of positive the measurement chamber where it is warmed to 37°C.
pressure ventilation. Calibration verification is then performed on the PCO2
From pH and PaCO2 values, blood gas analyzers compute and PO2 sensors, by passing a precision calibration gas
variables like plasma bicarbonate concentration [HCO3–] mixture across the optode sensors. The pH and electrolyte
and base excess, which assist the diagnosis of metabolic channels are calibrated with analytical grade buffer
disturbances, such as those occurring in gastrointestinal solution contained within the cassette. Once calibration is
disease. Analysis of [HCO3– ] can be used to estimate the verified, the analyzer aspirates blood into the cassette and
duration of primary respiratory disturbances (see below). across the optode sensors. While measurement is in
The analysis of both metabolic and respiratory function progress, the device prompts the supply of information
is important in exercise studies, including tolerance such as body temperature, inspired O2 concentration (FI O2),
testing, and in the diagnosis and management of the barometric pressure (PB) and hemoglobin concentration
mixed metabolic and respiratory disturbances that can [Hb], although some models measure PB and [Hb] directly.
occur in anesthetized horses with colic undergoing The analyzer measures pH and PCO2 and its micro-
exploratory laparotomy. processor derives dependent variables like [HCO3– ], base
201
202 14 Blood Gas Analysis
excess, and total CO2. The oxygen optode measures and jugular vein and adjacent to the recurrent laryngeal nerve
displays PO2, which is used with supplied or co-measured and the vagosympathetic trunk. Sampling is performed in
data to calculate derivatives, such as the alveolar–arterial the distal third of the neck where the artery can often be
O2 tension difference (P(A–a)O2) and percentage hemoglobin palpated as a cord-like structure and fixed with the fingers
saturation. Once measurement is complete, the cassette of one hand while punctured with a 4.5 cm long 19- to
and blood sample are removed from the analyzer and 21-gauge needle held in the other. The needle is inserted at
discarded. The detectors’ output signal is displayed by an angle to, and slightly above, the jugular vein to a depth
liquid crystal as numerical data. The time taken for sample of 1.25–2.5 cm. If the artery is impalpable, then a similarly
presentation, cassette calibration, sample analysis and sized needle is passed at a more cranial site through the
result display varies between devices from 1 to 3 min, midpoint of the jugular vein as it lies in the jugular
which far exceeds the needs for diagnosis, and suits rapid furrow. The needle is directed in a dorsomedial direction to
ventilator adjustment. The fixed temperature at which a depth of 3–4 cm. Accidental jugular puncture is readily
samples are analyzed (37°C) renders blood gas analyzers distinguished from arterial penetration, because darker
sensitive to environmental temperature extremes. Models blood drips from the vein rather than flowing vigorously
operating under specific temperature ranges, such as from the needle. The presence of pulsations before and
16–30°C, require insulating or cooling when operated after collection indicates the unlikelihood of inadvertent
in colder or warmer ambient temperatures (Silverman & venous blood collection or contamination. Accidental
Birks 2002). damage to the recurrent laryngeal nerve or the vagosym-
pathetic trunk is unlikely, but hematomas can occur
Equipment availability especially if repeated sampling is performed at the same
site (Willoughby & McDonell 1979). The carotid artery
The purchase or leasing of modern “point-of-care” is “mobile” in foals and is consequently more difficult
analyzers produced by reputable manufacturers is recom- to puncture. The normally positioned carotid artery is
mended for busy equine practices. Equipment that is unsuitable for cannulation.
regularly maintained and calibrated and protected from
mechanical damage will perform reliably for years. The Transverse facial artery
acquisition of second-hand laboratory desktop equipment
is discouraged. Maintenance contracts, though strongly The transverse facial artery runs rostrally on the surface of
recommended because reliability is poor, are very expen- the masseter muscle, about 1.5 cm ventral to the zygomatic
sive. Importantly, desktop devices cannot be used under arch and parallel to the axis of the palpebral fissure. Lying
field conditions and so blood samples must be returned, only a few millimeters below the skin, it is readily palpated
with altered values if examination is delayed, to the prac- and easy to puncture if the needle is advanced at a shallow
tice laboratory. Local hospitals with surgical/intensive care angle over the artery and parallel to the axis of the rima
units will possess analysis equipment and may examine palpebrarum. Unfortunately, the transverse facial vein
veterinary samples providing blood has been adequately runs in an adjacent parallel course and is equally easy
heparinized. The inconvenience of transporting and sub- to puncture. Hale & Chambers (1989) described severe
mitting samples and waiting for results militates against bradycardia and hypotension in an anesthetized horse
this option for busy practitioners.
Sample Collection Table 14.1. Arterial blood sampling sites

Arterial blood collection is only marginally more difficult in adult horses and foals
than venous blood collection. In conscious adult horses, Adult horses
samples may be taken from a number of sites (Table 14.1), Common carotid artery
with choice being based on personal experience and on Transverse facial artery
Facial artery
the horse’s size, temperament, and age. In foals, the dorsal
Auricular artery
metatarsal, brachial, and palmar arteries are easily punc- Dorsal metatarsal artery
tured and the femoral artery may also be used. Brachial or palmar (digital) arteries
Foals
Carotid artery Dorsal metatarsal artery
Brachial artery
In adult horses, carotid arterial puncture is technically Palmar artery
straightforward and well tolerated. The arteries run on the Femoral artery
dorsolateral aspect of the trachea, medial to the external
14 Blood Gas Analysis 203
that accompanied attempted catheterization of the trans- Palmar (digital) arteries

verse facial artery and which they attributed to accidental
stimulation of the transverse facial nerve. Despite this, the The palmar (digital) arteries are most easily palpated
artery is readily catheterized in adult horses, particularly over the abaxial surfaces of the sesamoid bones. With the
after EMLA (eutectic mixture of local anesthetic) cream foreleg held up, the artery is punctured using a 2.5-cm
application (see below). long 23-gauge needle inserted parallel to the long axis of
the leg (Rose & Rossdale 1981).
Facial artery
Puncture technique
The facial artery is most suitable for blood collection in
unconscious animals. It rounds the ventral border of the The skin overlying the intended puncture site is clipped and
horizontal mandible (where it is readily palpated) and surgically prepared. A 25- to 21-gauge needle and pre-
ascends along the rostral border of the masseter, before heparinized (1 or 2 ml) syringe is advanced beneath that
disappearing with the facial vein under the cutaneous point where fingers of the other hand feel the maximum
faciei muscle. It is rostral to the vein and inadvertent pulsation to be and along the vessel’s axis. Mild negative
puncture of the latter is uncommon. This artery is mobile pressure is applied to the syringe plunger, although larger
in foals and more difficult to puncture, even in anes- needles, such as 19- to 21-gauge used with glass syringes,
thetized subjects. are filled by arterial pressure alone. Samples should be
aspirated over three or four breaths when bradypnea is
Auricular artery present, such as during anesthesia, because PAO2 values
oscillate with breathing. If puncture is unsuccessful, the
The auricular artery is easy to puncture in small ponies, needle tip is withdrawn and redirected. Once sampling is
foals, and recumbent animals but access is more difficult completed, a sterile swab is applied with pressure over the
in conscious tall animals or when the head cannot be puncture site and the needle is withdrawn. Firm pressure
immobilized. Once the convex surface of the pinna is must be sustained for at least 5 min or until there is no
clipped, the artery is identified as a straight vessel coursing evidence of hemorrhage.
approximately two-thirds the distance between the ear base Horses must not be stressed during arterial puncture
and apex and closer to the medial than the lateral margin. otherwise hyperventilation will increase PAO2 and lower
It is readily distinguished from the more tortuous branches PaCO2 and confuse diagnosis. Calm, sympathetic han-
of the auricular vein, which are larger though less turgid dling is recommended. The application of local anesthetic
and which do not pulsate. Applying a loose ligature to the ointment, such as EMLA cream, and then an occlusive
ear base, which enlarges the veins while “damping” arterial polyethylene-lined dressing to the sampling site for
pulsations, facilitates identification. This artery is easily 45–60 min desensitizes the skin and may prove beneficial.
catheterized in foals and adults under direct vision, Alternatively, overlying skin may be infiltrated with non-
especially after EMLA cream has been applied. irritant local anesthetic, such as mepivacaine. Sedatives
may be necessary in restive animals. Acepromazine, a
Dorsal metatarsal artery useful anxiolytic but an unpredictable sedative, is preferred
over α2-agonists because its effects on blood gas values
The dorsal metatarsal artery descends the pelvic limb, are predictable and minor. In contrast, α2-agonist drugs
becoming palpable in the oblique vascular groove on produce unpredictable blood gas changes (Table 14.2).
the dorsolateral aspect of the hock. It then descends super- Arterial cannulation is recommended in animals requir-
ficially in the groove between the cannon and the lateral ing repeated samples, such as maladapted foals. Sedation
splint bone where it is readily palpated, immobilized, is not necessary for this procedure in depressed young-
punctured, and catheterized if necessary. There are no sters. However, if struggling occurs, intravenous diazepam
adjacent veins that could be inadvertently sampled. (10–20 mg) may be needed and O2 can be provided by
mask if clinical signs of dyspnea or hypoxemia appear.
Brachial artery Animals should be restrained in sternal recumbency as
repositioning in lateral recumbency may cause orthopnea
The brachial artery, which courses distally on the medial and lower PAO2 (Kosch et al 1984). If struggling continues,
surface of the brachium, is more superficial in foals than a brief period of inhalation anesthesia with sevoflurane,
adults and has been recommended as a site for repeated halothane or isoflurane delivered by mask may be neces-
sampling in foals. It is mobile in some foals, while others sary, though this is not without risk. The dorsal metatarsal
resent attempted puncture at this site vigorously unless artery may be catheterized using a “cut-down” procedure,
local anesthetic is administered. although the auricular artery is a more convenient site,
Table 14.2. The effects of commonly used sedatives on blood gas values in horses and ponies
Drug Dose Effect Reference
Azaperone 0.4–0.8 mg/kg IM No effect on pH, PaCO2 , PAO2 Lees & Serrano 1976
Acepromazine 0.65 mg/kg IV Reduced response to severe hypoxemia and hypercapnia Muir & Hamlin 1975
Diazepam 0.05–0.4 mg/kg IV No significant changes in PaCO2 or PAO2 Muir et al 1982
Xylazine 0.5 mg/kg IV Altered respiratory patterns Lavoie et al 1992
0.6 mg/kg IV Significant reduction on fR ; insignificant decrease in PAO2 Reitemeyer et al 1986
1.1 mg/kg IV Altered respiratory patterns; apneic periods of 7–70 seconds; Lavoie et al 1992
significant increases in PaCO2 and decreases in PAO2 ;
reduced fR, VM
1.1 mg/kg IV Reduced fR ; unchanged PaCO2 ; transiently and significantly Wagner et al 1991
reduced PAO2 [1.33–2.66 kPa (10–20 mmHg)]
Detomidine 10 μg/kg IV Reduced fR ; unchanged PaCO2 ; transiently and significantly Wagner et al 1991
20 μg/kg IV Reduced fR ; unchanged PaCO2 ; transiently and significantly Wagner et al 1991

Up to 40 μg/kg Significant decrease in PAO2
Medetomidine 5 μg/kg IV Significant increases in PaCO2 ; insignificant decreases in PAO2 Bryant et al 1996
10 μg/kg IV Significant increases in PaCO2 ; insignificant decreases in PAO2 Bryant et al 1996
Romifidine 80 μg/kg IV Significant decreases in PAO2 5 min after injection Clarke et al 1991
Significant elevations in PACO2 90 min after injection
fR = respiratory rate, VM = minute ventilation.
using 20- to 22-gauge catheters. Arterial catheters do of a logical or scientific basis for the assumption that
not remain patent for much longer than 12–48 h unless temperature-corrected values are better than values
continuous (rather than intermittent) flushing with obtained at 37°C.
heparinized saline is performed.
It is widely recommended that the rectal tempera-
ture be taken in animals in which it is likely to deviate
from normal by more than 0.556°C (1°F), and appropriate
Sample Storage and Handling
corrections made to the analysis. These measures are Samples are drawn into 2-ml glass or plastic syringes
deemed necessary because the analyzer, in maintaining whose hub is filled with 1000 IU/ml heparin. Exces-
blood temperature at 37°C during measurement, alters gas sive anticoagulant is undesirable because it lowers pH.
solubility and tension in samples drawn from animals at Commercially available blood gas syringes containing
different temperatures. For example, body temperature freeze-dried heparin and supplied with a gas-tight cap
reductions of 1°C decrease pH by 0.014 units, increase CO2 for use when analysis is delayed are ideal, though expen-
solubility and lower PaCO2 (Hodgson 1987). The relation- sive. Air bubbles must be eliminated from the sample
ship between temperature and PAO2 is complex because and the syringe must be sealed from air using either a
temperature affects the oxyhemoglobin dissociation curve. proprietary syringe cap or a needle whose tip is embedded
If temperature corrections are not made then the high in rubber. Otherwise air contamination will lower PCO2
blood temperatures encountered during exercise (> 40°C) and alter PO2 levels. When appreciable analysis delays
will yield spuriously low readings for PAO2 and PaCO2 while (>30 min) are anticipated, glass syringes should be used
pH values will be excessive (Jones et al 1989). In contrast, and placed on ice after sampling. Previous recom-
blood from hypothermic foals will give high readings for mendations regarding equine blood storage conditions for
PAO2 and PaCO2 and report low pH values (Hodgson 1987). blood gas analysis have erroneously relied on data from
However, there is controversy over the need for tem- other species. Deane et al (2004) studied the effects of
perature correction in the medical intensive care setting storage conditions on equine blood gases; their findings are
(Shapiro 1995) with opponents pointing out the absence summarized in Table 14.3.
Table 14.3. The effects of storage temperature, storage duration and syringe material
on arterial blood gas variables in equine blood
Storage temp. pH PO2 PCO2
Glass 20°C* Significant fall at 60 min Significant fall by 60 min Falls significantly by 120 min
0°C† Significant fall at 120 min Significantly rise at 60 min, Falls significantly by 120 min
significant fall in 120 min
Plastic (Monoject) 20°C Significant fall at 60 min Unaffected at 10 min, Falls significantly by 120 min
falls significantly in 60 min
0°C Significant fall at 120 min Unaffected at 10 min, Falls significantly by 120 min
significant rise at 60 min
Polypropylene (QS-50) 20°C Significant fall at 60 min Unaffected at 10 min, Falls significantly by 120 min
falls significantly in 60 min
0°C Significant fall at 120 min Unaffected at 10 min, Falls significantly by 120 min
significant rise at 60 min
Samples were analyzed at 10, 60 and 120 min. From Deane et al 2004, with permission.
* Room temperature; † iced water.
Table 14.4. Some causes of blood pH changes in horses and foals

Examples
–
Acidosis Metabolic Loss of HCO3 Chronic diarrhea; renal failure; saline overinfusion; secondary to chronic
respiratory alkalosis
Gain of H+ Lactacidemia, e.g. anaerobic exercise, hypovolemic “shock”; renal failure;

secondary to chronic respiratory alkalosis
Respiratory Elevated PCO2 Hypoventilation: (1) neurological (drugs, hypothermia, maladaptive syndromes),
(2) obstructive (laryngeal paralysis), (3) mechanical (chest wall injury,
diaphragmatic hernia). Elevated metabolism
Alkalosis Metabolic Gain of HCO3– Iatrogenic overadministration of HCO3– ; secondary to chronic respiratory acidosis
Loss of H+ Gastrointestinal acid sequestration; secondary to chronic respiratory acidosis
Respiratory Reduced PCO2 Psychogenic hyperventilation, e.g. anxiety, pain; secondary to hypoxemia,
e.g. altitude, intra- and extra-cardiac “shunts”
is of major physiological importance because [H+] is a

Information Provided by
principal determinant of enzyme activity. One consequence
Blood Gases and pH
of this logarithmic relationship is that small pH changes
The interpretation of blood gas values is not always represent large changes in acidity. A “normal” pH of 7.4
an “exact science”. If this were the case then modern corresponds to a [H+] of 40 nmol/liter while a pH of 7.1
analyzers would readily provide their own diagnosis. represents twice this concentration (80 nmol/liter). Minor
Consequently, attempts to interpret blood gas values should pH deviations outwith the “accepted” normal range
always be made with regard to the subject’s medical (7.35–7.45) represent a significant [H+] change, which
history and the findings of physical examination, and not deserves enthusiastic management.
attempted de novo. When describing acid–base changes, the suffix -emia
refers to blood pH. Acidemia exists when pH values
pH are <7.35; pH values >7.45 represent alkalemia. The
suffix -osis describes respiratory or metabolic processes
The blood pH is the negative logarithm (base 10) of which act with a propensity to change blood pH but
the hydrogen ion (proton) concentration [H+] and is a without necessarily prevailing. The principal causes of
convenient means of expressing [H+] or acidity. Blood pH pH changes are described in Table 14.4.
“Safe” pH values for equids have not been established, respiratory failure. This is because CO2 is (1) the normal
•
but ranges of 6.9–7.8 are cited for other mammals. determinant of ventilation, and so hypercapnia elevates VA
Arterial blood gas analysis measures extracellular pH, and resolves itself, and (2) readily diffusible across the
which may not reflect intracellular [H+]. Thus, metabolic alveolar–capillary membrane. However, hypercapnia does
acidosis arising within cells may not immediately induce occur in chronic respiratory diseases including recurrent
extracellular pH changes. In contrast, because CO2 is airway obstruction (Gillespie et al 1964), where elevated
rapidly diffusible, respiratory-induced pH changes rapidly CO2 levels represent a compromise between low plasma
become established in the intracellular environment. pH and a metabolically unaffordable work of breathing.
PaCO2 values have been linked with survival prediction in
Arterial carbon dioxide tension (PaCO2) induced, premature foals (Rose et al 1982).
Breathing 100% O2 does not influence PaCO2. Indeed,
The arterial CO2 tension (PCO2) reflects the balance between when hypoxemic animals with chronic respiratory disease
•
metabolic CO2 production (VCO2) and its elimination by breathe high concentrations of O2 it is not uncommon
the lungs. The latter depends on the minute alveolar for ventilation to transiently cease, causing rapid and
• •
ventilation (VA ). When VCO2 is constant, PaCO2 reliably severe rises in PaCO2. This occurs because in chronic severe
indicates the adequacy of minute alveolar ventilation hypoxemia, PAO2, rather than PaCO2, becomes the principal
• •
(equation 1). Halving VA doubles PaCO2. determinant of VA , and when O2 is provided, the surrogate
• • respiratory stimulus is effectively removed.
Equation 1. PaCO2 (in kPa) = V CO2 /VA × ( PB – 6.25) × 0.83
Hypocapnia (respiratory alkalosis) is present when
A second version (equation 2) is more suitable for use PaCO2 < 4.78 kPa (36 mmHg). It normally reflects hyperven-
during anesthesia because by incorporating FI CO2 it tilation in response to stress or pain, or overenthusiastic
recognizes rebreathing (the re-aspiration of expired CO2) as positive pressure ventilation. When severe cardiopul-
a possible cause of hypercapnia. monary disease causes hypoxemia, PAO2 may become the
•
• • principal determinant of ventilation, in which case VA may
Equation 2. PaCO2 is proportional to FICO2 + V CO2 /VA
become excessive with respect to CO2, causing hypocapnia.
Hypercapnia from rebreathing is possible when foals The same occurs when animals are moved from low to
receive inadequate O2 flows delivered with oversized high altitudes without acclimatization; hypoxemia result-
facemasks. These equations indicate that hypercapnia ing from low PI O2 initiates hyperventilation and causes
•
[PaCO2 > 5.85 kPa (44 mmHg)] results from: respiratory alkalosis (Greene et al 1999). Increased VA and
hypocapnia are the common initial responses to hypoxemia
● decreased alveolar ventilation, such as results from
in foals. However, a failure of PAO2 to improve with time
profound sedation, anesthesia, severe neurological
and O2 therapy, coupled with rising PaCO2 , heralds immi-
depression, hypothermia; severe respiratory disease
nent respiratory failure and indicates the need for positive
● increased CO2 production, such as occurs with pyrexia
pressure ventilation or euthanasia. Hyperventilation is a
● both of above.
normal rapid physiological response to primary metabolic
The mean normal PaCO2 in adult horses is 5.33 kPa acidosis, and serves to increase pH in the face of high
(40 mmHg) but PaCO2 ranges from 4.79 to 6.13 kPa plasma acid levels, such as occur after anaerobic exercise,
(36–46 mmHg). Values in foals are high at birth but or low plasma [HCO3–] as occurs in severe diarrhea. In
then fall, approaching normal levels within a week or so rare circumstances, hypocapnia can indicate reduced
(Table 14.5). Hypercapnia is usually a late feature in metabolic CO2 production, as occurs in severely hypo-
respiratory disease, its presence indicating the onset of thermic, non-shivering foals.
Table 14.5. Arterial blood gas values from horses and foals (mean ± SEM)
PAO2 PaCO2
Age kPa mmHg kPa mmHg
Birth 5.72 ± 0.52 43.0 ± 3.9 7.05 ± 0.24 53 ± 1.8 *

15 min 8.55 ± 0.52 64.3 ± 3.9 6.34 ± 0.17 47.7 ± 1.3 *
30 min 9.31 ± 0.57 70.0 ± 4.3 6.29 ± 0.08 47.3 ± 0.6 *
60 min 10.35 ± 0.69 77.8 ± 5.2 5.82 ± 0.16 43.8 ± 1.2 *
12 h 10.53 ± 0.53 79.2 ± 4.0 5.55 ± 0.13 41.7 ±1.0 *
24 h 11.33 ± 0.78 85.2 ± 5.9 5.69 ± 0.09 42.8 ± 0.7 *
1 week 10.64 ± 0.98 80 ± 7.4 5.61 ± 0.28 42.2 ± 2.1 *
Adult 10.64–14.89 80–112 4.79–6.12 36–46 †
*Rose et al 1982; †Brobst & Parry 1987.

Secondary acid–base effects of CO2 sampling, the PaCO2, and to a lesser extent, the atmospheric
pressure (PB ). This is because these factors are incorporated
Values of pHa and [HCO3–] elucidate the duration of respi- into the alveolar gas equation (equation 4), which predicts
ratory changes and indicate whether they are primary or alveolar O2 tension (PAO2), which in turn is the single most
compensatory changes for primary metabolic disorders. important determinant of PAO2 under non-pathological
The pHa falls in hypercapnia because CO2 forms carbonic conditions.
acid (H2CO3) in plasma (equation 3).
Equation 4. PAO2 = FI O2 (PB – PH2O ) – PaCO2 /0.8
Equation 3. H2O + CO2 ←→ H2CO3 ←→ H+ + HCO3–
The normal value for PB at sea level is 101.3 kPa
However, the magnitude of the pH fall depends on (760 mmHg). (Some blood gas analyzers incorporate
increases in plasma HCO3–. These are initially rapid electronic barometers.) PH2O is the saturated vapor pressure
(occurring within seconds) and result from H2CO3 of water, which is 6.25 kPa (47 mmHg) at 37.5°C. The
dissociation. This corresponds with an initial rapid rise in value for PaCO2 is taken from the blood gas analysis.
[HCO3– ] of 1 mmol/liter per 1.33 kPa (10 mmHg) rise in The value 0.8 is the respiratory quotient (see Chapter 4
PaCO2. Thereafter, [HCO3– ] continues to rise, but at a slower for details).
rate because renal tubular HCO3– reabsorption and H+ This complex approach is necessary because normal or
secretion become active. In foals, renal compensation elevated PAO2 values may be found when animals with
begins in approximately 6–12 h and reaches a maximum severe respiratory disease breathe O2-enriched gases
in 3–5 days. Renal compensation eventually increases (see below). During air breathing, FI O2 = 0.21. However,
plasma [HCO3– ] by 2 mmol/liter per 1.33 kPa (10 mmHg) 100% O2 delivered by tracheal or nasal insufflation, or from
rise in PaCO2. Consequently chronic respiratory acidosis is anesthetic breathing systems, does not always correspond
indicated by a rise in [HCO3– ] of 3 mmol/liter per 1.33 kPa with an FI O2 of 1.0, because O2 may be diluted by atmos-
(10 mmHg) rise in PaCO2. pheric nitrogen, rebreathed CO2 or methane. Oximeters
In respiratory alkalosis, the immediate response of the measure and display the inspired and expired O2 values on
bicarbonate buffer system is to increase plasma CO2 levels. a breath-for-breath basis and circumvent this problem.
At the same time, the glycolytic pathway is activated and However, whilst available and affordable, their use is
produces lactic acid. These processes acutely reduce plasma not widespread.
[HCO3– ] by about 2 mmol/liter per PaCO2 decrement of
1.33 kPa or 10 mmHg below normal. Eventually, the Alveolar–arterial oxygen tension
proximal convoluted tubules cease to reabsorb HCO3–. difference (P(A–a)O2)
The net reduction in HCO3– resulting from these responses
is approximately 5 mmol/liter per 1.33 kPa (10 mmHg) In healthy horses breathing air, the normal P(A–a)O2
reduction in PaCO2 below 5.33 kPa (40 mmHg). is approximately 0.66–1.33 kPa (5–10 mmHg) and repre-
sents normal arterial blood dilution by Thebesian and
Arterial oxygen tension (PAO2 ) bronchial venous blood entering the left heart and pul-
monary veins respectively. Abnormal elevations in P(A–a)O2
PAO2 is the most sensitive measure of the lung’s ability to disclose and quantify imperfect gas exchange in animals
oxygenate blood and consequently the best index of which, through breathing high concentrations of O2, may
deteriorating pulmonary function. Most adult horses have normal or even elevated PAO2 levels.
with recurrent airway obstruction have reduced PAO2 The P(A–a)O2 is calculated from the alveolar gas equation
while pHa or PaCO2 are rarely changed (Dixon et al 1995). (equation 4). For this, the PB, FI O2, PaCO2, and the
Normal values in adults breathing air are 11.99–13.3 kPa respiratory quotient should be known. The measured
(90–100 mmHg). Values in normal term foals vary con- PAO2 is then subtracted from PAO2. For a horse with
siderably, and depend on the gestational and postnatal age normal respiratory function [PaCO2 = 5.3 kPa (40 mmHg)
(Rose et al 1982) and body position, with PAO2 values being and PAO2 = 12.6 kPa (95 mmHg)], breathing room air
higher in foals in sternal, rather than lateral, recumbency (FI O2 = 0.21) at sea-level [PB = 101 kPa (760 mmHg)], PAO2
(Kosch et al 1984). A degree of hypoxemia and respiratory is given by:
acidosis by adult standards is present after birth, but
Example 1. PAO2 = 0.21 (101 – 6.25) – (5.3/0.8)
usually resolves by 12–24 h in full-term foals and slightly
= 19.8975 – 6.625
longer in preterm foals (Rose & Rossdale 1981). Impaired
= 13.3 kPa (or 100 mmHg)
oxygenation is inevitable during general anesthesia in
P(A–a)O2 = 13.3 – 12.6
horses (Whitehair & Willits 1999) as P(A–a)O2 gradients are
= 0.7 kPa (5.3 mmHg)
always increased (Stegman 1986, Thurmon 1990).
However, interpretation of PAO2 demands knowledge of which is normal. Increased P(A–a)O2 has three main causes
the fractional inspired concentration of oxygen (FI O2) at in air-breathing animals. The most important, venous
admixture, arises from “shunt” and/or from blood drain- increasing the confidence with which PvCO2 and pHV values
ing alveolar units with low ventilation/perfusion ratios may be used as accurate estimates of ventilatory adequacy
(see Chapter 4). The two are differentiated by providing and acid–base status. Peripheral venous PO2 does not accu-
an O2-rich (> 90%) mixture to breathe, which eliminates rately indicate PAO2, although if PvO2 values are greater
• •
the hypoxemic effects of VA /Q disturbances and exposes than 7.98 kPa (60 mmHg) it can be assumed that arterial
“shunt” flow. Consequently, breathing 100% O2 improves hypoxemia is absent.
PAO2 in horses with recurrent airway obstruction but will Venous blood drains into, and is mixed in, the pul-
not affect cyanosis in foals with congenital right-to-left monary artery, and its O2 tension reflects whole body O2
•
cardiac anomalies, widespread pulmonary atelectasis, consumption (VO2) and cardiac output. The normal value
consolidation or a persistent fetal circulation. P(A–a)O2 values of PV O2 , 5.33 kPa (40 mmHg) is reduced by (1) arterial
are also increased by reduced mixed venous O2 tensions hypoxemia; (2) low cardiac output; and (3) if “whole body”
(see below) and diffusion limitation, though the latter O2 consumption increases. Increased rectal temperature
is considered unimportant in humans and horses. The and other signs, such as cardiovascular hyperdynamism,
measured P(A–a)O2 value also increases as FI O2 rises for indicate an increased metabolic rate. When these are absent,
• •
any given V /Q situation, and it is imperative that the PV O2 is directly proportional to cardiac output. However,
FI O2 be accounted for when comparisons are made. For pulmonary arterial blood sampling is not feasible in general
example, when an animal breathes 100% oxygen (FI O2 = practice because cardiac catheterization is required.
1.0), PAO2 should rise to 88.1 kPa (663 mmHg), as shown Jugular venous O2 tensions, which are easily obtained,
in Example 2. may have value as premonitory indicators of cardiac arrest
in anesthetized horses (McGoldrick et al 1998). It is
Example 2. PAO2 = 1.0 (101 – 6.25) – (5.3/0.8)
known that while jugular venous O2 tensions are always
= 94.75 – 6.625
0.66–1.33 kPa (5–10 mmHg) higher than mixed venous
= 88.1 kPa (or 663 mmHg)
tensions, both correlate positively with cardiac output.
If an arterial blood sample taken from this animal In horses, mixed venous O2 tension of 5.33–5.99 kPa
indicated PAO2 was 13.3 kPa (100 mmHg) the pres- (40–45 mmHg) corresponds with critically low values for
ence of satisfactory lung function might be assumed. cardiac output (Wetmore et al 1987). In humans, a PV O2
However, calculating P(A–a)O2 reveals a value of 74.8 kPa value of 3.99 kPa (30 mmHg) is held to indicate inad-
(563 mmHg) indicating considerable venous admixture equate tissue oxygenation and is associated with a high
and severe dysfunction. risk of acute cardiac failure. In foals, a jugular venous
Tables are available for the conversion of PAO2 and PO2 < 20 mmHg has been held to indicate the onset of
P(A–a)O2 into estimated shunt flow. Alternatively, iso-shunt hypoxemia or cardiac failure (Kosch et al 1984). Venous
diagrams may be used (Benatar et al 1973). As a rule, when PCO2 values greater than 7.99 kPa (60 mmHg) indicate the
PAO2 exceeds 20 kPa (150 mmHg) and hemoglobin is fully presence of hypercapnia.
saturated, the venous admixture is approximately 1% of When collecting venous samples for the investigation of
cardiac output for every 2.66 kPa (20 mmHg) of P(A–a)O2. metabolic or blood gas data, blood flow through the
Hypoxemia, that is inadequate O2 tension in arterial vein should not be restricted because this lowers values for
blood, is defined as a PAO2 less than 7.98 kPa (60 mmHg). PVO2 and pH while increasing PVCO2.
This value corresponds to the “shoulder” of the oxyhemo-
globin dissociation curve, to the left of which small reduc- Arteriovenous oxygen content differences
tions in PAO2 cause large falls in hemoglobin saturation.
“Hypoxia” describes subnormal O2 tensions at a specified Respiratory dysfunction resulting from left heart dysfunc-
level, for example cerebral or tissue hypoxia. This can result tion is not uncommon in foals. The adequacy of cardiac
•
from hypoxemia but can also occur with normal arterial output relative to whole body oxygen consumption (VO2) is
O2 tensions when tissue perfusion is inadequate, when estimated by calculating the arterial and mixed venous
inadequate levels of functional hemoglobin reduce the oxygen content (C(a–v)O2) difference. This requires taking
blood’s O2 content, or when tissue O2 demand is abnor- arterial and mixed venous blood samples simultaneously.
mally high and exceeds delivery. The causes of hypoxia are The value of C(a–v)O2 – traditional units are ml/dl – is
described in Chapter 4. calculated from:
C (a–v)O2 = {([Hb] × SaO2 × 1.39) + (PAO2 × 0.0225)} –
Venous oxygen tension (PV O2 ) {([Hb] × S vO2 × 1.39) + (Pv O2 × 0.0225)}
In rare circumstances, venous blood samples can be used where C(x)O2 is oxygen content of arterial (a) and venous (v)
when arterial blood is unavailable. During anesthesia, blood, [Hb] is hemoglobin concentration in g/dl (normal
cutaneous vasodilatation and hyperemia cause periph- values are 12–15 g/dl), 1.34 indicates ml O2 bound per g
eral venous blood gas values to approach arterial levels, of hemoglobin, S(x)O2 percentage saturation of hemoglobin
in arterial (a) and venous (v) blood. Arterial PO2 values Kosch PC, Koterba AM, Coons TJ 1984 Developments in
of 13.3 kPa (100 mmHg) correspond to an SaO2 of 1.0. management of the newborn foal in respiratory distress
For venous blood, in which Pv O2 is 5.3 kPa (40 mmHg), 1: Evaluation. Equine Veterinary Journal 16: 312–318
Lavoie JP, Pascoe JR, Kurpershoek CJ 1992 Effect of head and
the value of SvO2 is 0.75. The coefficient 0.0225 indi- neck position on respiratory mechanics in horses sedated
cates the solubility of oxygen dissolved in plasma; units with xylazine. American Journal of Veterinary Research
are ml·dl–1·kPa–1. Normal C(a–v)O2 is 4–6 ml/dl. When 53: 1653–1657
whole body oxygen consumption is constant, decreased Lees P, Serrano L 1976 Effects of azaperone on cardiovascular
cardiac output, prolonged circulation time or sluggish per- and respiratory functions in the horse. British Journal of
Pharmacology 56: 263–269
fusion increases the C(a–v)O2 value. Conversely, increased McGoldrick TME, Bowen IM, Clarke KW 1998 Sudden cardiac
C(a–v)O2 indicates a hypermetabolic state when cardiac arrest in an anaesthetised horse associated with low
output is stable. venous oxygen tensions. Veterinary Record 142: 610–611
Muir WW, Hamlin RL 1975 Effects of acetylpromazine on
ventilatory variables in the horse. American Journal of
REFERENCES Veterinary Research 36: 1439–1442
Muir WW, Sams RA, Huffman RH, Noonan JA 1982
Benatar SR, Hewlett AM, Nunn JF 1973 The use of iso-shunt Pharmacodynamic and pharmacokinetic properties of
lines for control of oxygen therapy. British Journal of diazepam in horses. American Journal of Veterinary
Anaesthesia 45: 711–718 Research 43: 1756–1762
Brobst D & Parry BW 1987 Normal clinical pathology Reitemeyer H, Klein HJ, Deegen E 1986 The effect of seda-
data. In: Robinson NE (editor) Current Therapy in tives on lung function in horses. Acta Veterinaria
Equine Medicine, volume 2. WB Saunders, Philadelphia, Scandinavica 82: 111–120
pp.725–729 Rose RJ, Rossdale PD 1981 Techniques and clinical applica-
Bryant CE, Clarke KW, Thompson J 1996 Cardiopulmonary tion of arterial blood collection in the horse. Equine
effects of medetomidine in sheep and in ponies. Research Veterinary Journal 3: 70–73
in Veterinary Science 60: 267–271 Rose RJ, Rossdale PD, Leadon DP 1982 Blood gas and
Clarke KW, England GCW, Goossens L 1991 Sedative and acid–base status in spontaneously delivered term-induced
cardiovascular effects of romifidine, alone and in com- and induced premature foals. Journal of Reproduction
bination with butorphanol, in the horse. Journal of and Fertility Supplement 32: 521–528
Veterinary Anaesthesia 18: 25–29 Shapiro BA 1995 Temperature correction of blood gas values.
Deane JC, Dagleish MP, Benamou AEM et al 2004 Effects Respiratory Care Clinics of North America 1: 69–76
of syringe material and temperature and duration of Silverman SC, Birks EK 2002 Evaluation of the i-STAT
storage on the stability of equine arterial blood gas vari- hand-held chemical analyser during treadmill and endur-
ables. Veterinary Anaesthesia and Analgesia 4: 250–257 ance exercise. Equine Veterinary Journal Supplement
Dixon PM, Railton DI, McGorum BC 1995 Equine pulmonary 34: 551–554
disease: a case–control study of 300 referred cases. Stegman GF 1986 Pulmonary function in the horse during
Part 3: Ancillary diagnostic findings. Equine Veterinary anaesthesia. A review. Journal of the South African
Journal 27: 428–435 Veterinary Association 57: 49–53
Gillespie JR, Tyler WS, Eberly VE 1964 Blood pH, O2 and CO2 Thurmon JC 1990 General clinical considerations for anes-
tensions in exercised control and emphysematous horses. thesia in the horse. Veterinary Clinics of North America;
American Journal of Physiology 207: 1067–1072 Equine Practice 6: 485–494
Greene HM, Wickler SJ, Anderson TP et al 1999 High-altitude Wagner AE, Muir WW, Hinchcliff KW 1991 Cardiovascular
effects on respiratory gases, acid–base balance and pul- effects of xylazine and detomidine in horses. American
monary artery pressures in equids. Equine Veterinary Journal of Veterinary Research 52: 651–657
Journal Supplement 30: 71–76 Wetmore LA, Derksen FJ, Blaze CA et al 1987 Mixed venous
Hale GJ, Chambers JP 1989 Bradycardia and asystole follow- oxygen tension as an estimate of cardiac output in
ing attempted arterial cannulation in a horse under anesthetized horses. American Journal of Veterinary
general anaesthesia. Journal of the Association of Research 48: 971–976
Veterinary Anaesthetists 16: 10–11 Whitehair KJ, Willits NH 1999 Predictors of arterial oxygen
Hodgson DR 1987 Blood gas and acid–base changes in the tension in anesthetized horses: 1,610 cases (1992–1994).
neonatal foal. Veterinary Clinics of North America; Journal of the American Veterinary Medical Association
Equine Practice 3: 617–629 215: 978–981
Jones JH, Taylor CR, Lindholm A et al 1989 Blood gas Willoughby RA, McDonell WN 1979 Pulmonary function
measurements during exercise: errors due to temperature testing in horses. Veterinary Clinics of North America;
correction. Journal of Applied Physiology 67: 879–884 Large Animal Practice 1: 171–196
Pulmonary Function Testing
15 David J Marlin and Christopher M Deaton
Objective assessment of pulmonary function can be useful A progressive change in a variable lung function should
in the diagnosis and prognosis of disease and in the be viewed as significant. To accurately follow changes
monitoring of response to treatment, and is important in in function within a horse, the factors that can affect
understanding normal lung function and the mechanisms measurements must be carefully controlled.
of disease. In equine medicine, pulmonary function tests
(PFT) have remained the domain of veterinary schools,
research institutes, and referral practices. In human
General Guidelines for Pulmonary
medicine the situation is very different. Measurements that
Function Testing
accurately reflect the functional state of the lung, especially Factors that may affect the values obtained from PFT
peak flow and the forced expiratory volume in one second include diurnal variation (Stadler & Deegen 1986),
(FEV1), can be routinely measured with devices that are time of feeding (McDonell et al 1979), sedation, head
inexpensive, accurate, and widely available. Virtually position (Lavoie et al 1992), excitement, the type of meas-
no calibration or preparation is required. Measurement uring equipment, and the duration of the measurements.
of these simple indices of pulmonary function is possible Equipment must not impose significant resistance nor
in people because they cooperate with the “forced” maneu- significantly increase dead space. Sedation has many
vers. Because horses cannot cooperate, measuring pul- advantages for undertaking PFT in horses. It facilitates the
monary function in the horse is more aligned to the placement of facemasks or esophageal catheters; reduces
situation in infants than in adults. the mechanical noise arising from movement of the
Pulmonary function tests include measurements of measuring devices; makes breathing more regular; reduces
lung volumes, tests of mechanical function, and tests of the reaction of the horse to equipment noise or to inhala-
gas exchange. Each of these can be measured in the resting tion of bronchoconstrictor agents such as histamine; and
or exercising horse or when breathing is stimulated by allows standardization of the head and neck angle. The
use of drugs. latter is an important variable in measurement of total
pulmonary resistance because marked flexion of the neck
increases resistance (Lavoie et al 1992). Unfortunately,
Indications for Measurement upper airway resistance increases over time following
of Pulmonary Function sedation (Tomasic et al 1997), most likely as a result of
When managing a sick horse, the clinician needs to know congestion of the upper airways and relaxation of its
the extent and severity of the functional impairment of the dilator muscles. This is especially exaggerated if the head
lung. This can be most easily assessed by evaluation of position is low.
blood gases (see Chapter 14). In addition, understanding Commonly used equine sedatives include the
the type of functional abnormality can be a diagnostic α2-adrenoceptor agonists such as xylazine, detomidine, and
clue. For example, in a horse with obvious respiratory romifidine. Xylazine reduces pulmonary resistance and
distress of some duration, a finding of normal resistance to increases pulmonary compliance in RAO-affected horses
airflow would rule out a diagnosis of recurrent airway during clinical exacerbation (Broadstone et al 1992) by
obstruction (RAO). If that observation was coupled with a inhibiting acetylcholine release from cholinergic nerves in
low value for lung compliance, the horse is likely to have the airways (LeBlanc et al 1993). However, xylazine has no
a restrictive lung disease such as pulmonary fibrosis. effect on RAO-affected horses in clinical remission or in
Unfortunately, the range of normal values for most PFTs in healthy horses because smooth muscle is already relaxed.
horses is quite large. For this reason, a single measurement Because part of the effect of histamine is mediated via the
of lung function may not be diagnostic unless the changes parasympathetic nervous system, α2-adrenoceptor agonists
in the lung are severe. However, PFTs are useful to follow have the potential to inhibit the response to histamine.
the course of disease because the day-to-day variation This effect may cause erroneous measurements of airway
in lung function within an individual horse is not so great. responsiveness.
211
212 15 Pulmonary Function Testing
Forced oscillatory mechanics measurements offer the

Measurements to Evaluate the Mechanical
advantage that they can be superimposed on normal
Properties of Lungs and Airways
breathing and do not need an esophageal catheter. With
Pulmonary function tests can be used to assess the volume more development, these measurements may be useful
of air being breathed, the effort being used to ventilate the in studies conducted in the field. By contrast, measure-
lung and its mechanical properties, gas exchange and its ments derived from forced expiration offer sensitivity
component parts such as diffusion and ventilation/ but are not practical for large-scale use. Tidal-breathing
perfusion matching, and the distribution of air and blood flow–volume loops are derived during normal breathing
within the lung. As with most diagnostic tests, the simpler and are therefore not very sensitive to small disturbances in
the measurement, the less information obtained. Because lung function. It remains to be determined if inductance
the lung has such a large functional reserve, simple plethysmography offers any advantage over other tests. In
measurements of lung function made in the resting horse humans, end-expiratory lung volume (EELV) is measured
may show little abnormality even when the horse has because it tends to increase with airway obstruction and
extensive disease. decrease in cases of restrictive disease. The EELV has been
When considering what to measure to assess the measured in horses but not frequently enough to make it a
mechanical function of the lung, tidal volume immediately useful diagnostic test.
comes to mind. Because of their need to survive, animals
tend to maintain their tidal volume even when lung disease Measurement of ventilation
is quite severe. However, they do this by generating more
effort with their respiratory muscles and this effort is The most basic test of pulmonary function is the
reflected in the magnitude of the pressure change in the measurement of respiratory airflow at rest, i.e. during quiet
pleural cavity. What is important to the horse is how tidal breathing. From this, variables such as tidal volume
much ventilation it is obtaining for a given amount of (VT), respiratory frequency (fR), minute ventilation
•
effort. For this reason, many measurements of the mechan- (VE = VT × fR ), peak inspired flow (PIF), peak expired flow
ical properties of the lung incorporate measurement of (PEF) and inspiratory (Ti) and expiratory time (Te) may be
pleural or esophageal pressure, the latter being a good obtained. The airflow data may also be used to generate
approximation of the former and far easier to measure. tidal breathing flow–volume loops (Petsche et al 1994,
The maximal change in pleural pressure during tidal Guthrie et al 1995a). The current consensus of opinion
breathing (ΔPplmax) is the simplest measurement of the is that measurements of ventilation in horses at rest are
mechanical properties of the lungs. When coupled with relatively insensitive for the detection of impaired pul-
measurement of flow, this can be used to determine the monary function. However, greater sensitivity may be
total pulmonary resistance (RL), which is an indicator of obtained when measurements of flow are combined with
the degree of obstruction of the airways. Addition of a simultaneous analysis of exhaled carbon dioxide concen-
measure of tidal volume allows calculation of dynamic tration (see volumetric capnography).
compliance (Cdyn). The latter reflects the elastic properties Measurement of ventilation in the resting horse requires
of the lungs and the magnitude of obstruction of the small a facemask, a flow measuring device (pneumotacho-
peripheral airways. graph), a differential pressure transducer (except with
In a continuing search for a more sensitive yet simple ultrasonic devices), a means of calibrating either flow
test of pulmonary function, veterinary scientists have or volume, and a recording and analysis system (see
adapted most tests used in humans for use in horses. Box 15.1).
Box 15.1. Flow measuring devices
The most common device used for measuring respiratory air- For measurements in resting adult horses (approx 400–
flow in the horse is the capillary-type Fleisch pneumotacho- 600 kg) a no.4 or no.5 Fleisch pneumotachograph is appro-
graph (Fig. 1.1) that determines flow from the pressure drop priate. A no.3 device is suitable for anesthetized animals,
across the resistive element according to the Poiseuille equation: small ponies or foals. Many Fleisch-style pneumotachographs
• incorporate a heater that limits condensation by increasing the
P = 128 μ LV ′/πd 4
temperature of the screen by about 10°C above that of exhaled
•
where P is the steady-state pressure drop, V ′ is flow, μ is the breath.
viscosity of the gas, L is length and d is diameter of the tube in Fleisch pneumotachographs must be used with a differential
which the gas is flowing. pressure transducer. The Validyne-style transducer (Fig. 1.1A)
Continued
15 Pulmonary Function Testing 213
A B
Fig. 1.1. (A) From right to left, Validyne pressure transducer, Fleisch No.5 heated pneumotachograph and Validyne carrier demodulator.
(B) Piezoelectric differential pressure transducer mounted directly on a Fleisch No.5 heated pneumotachograph.
has excellent stability, sensitivity, and frequency response while rotameters are used for flow calibration. The calibration
(the ability to follow rapid changes in pressure and flow). should be performed at the same temperature and humidity as
Disadvantages include expense, weight, and position sensitivity the measurements will be made. Flow rates displayed on the
that make them unsuitable for mounting on the pneumo- scale of rotameters are specific to particular conditions.
tachograph. For the latter reason, they are usually mounted Calibrations must cover the expected range of measure-
some distance from the horse and connected by two equal ments. In a 500-kg adult horse with a tidal volume of 1–7 liters,
lengths of stiff tubing. An alternative is to use a piezoelectric- calibration solely with a 2-liter volume syringe is inappropriate.
type transducer which is not orientation sensitive, is lighter Furthermore, before undertaking measurements with new
in weight, and which can be mounted directly onto the equipment or new configurations of existing equipment, it
pneumotachograph or mask resulting in less noise as a result of is advisable to establish linearity for both inspiratory and
the movement of the horse’s head (Fig. 1.1B). expiratory measurements. The stability of the baseline (zero
Ultrasonic pneumotachographs are also available for use flow) following calibration should also be determined. When
in horses (Flowmetrics, BRDL, Birmingham, UK; Exhalyzer V, calibrating equipment for measurements of gas concentra-
Eco Medics, Switzerland). They are designed for use during tions, certified gas mixtures should be used.
exercise and generally lack the sensitivity required for resting
Recording and analysis
measurements. Other possibilities for flow measurement
Most flow measuring devices generate a voltage or digital
include turbine pneumotachographs, pitot-based sensors and
signal proportional to the airflow rate. Some systems incor-
hot wire anemometers, although these are uncommonly used
porate a display of the flow rate. However, in most cases it is
for resting measurements in horses.
desirable to record and analyze the signals. The output from
Calibration of equipment pneumotachographs can be easily interfaced with computers
Calibration should be performed at the start of each day, running data acquisition and analysis hardware [in the form
immediately before making the measurements, and at the end of analog to digital (A/D) converters] and software that has
of the series of measurements on each subject. Measurements been specifically developed for analysis of respiratory signals
should be accepted if the difference between pre- and post- (e.g. Biosystem XA, Buxco Research Systems, Wilmington, NC,
calibrations is less than 10%. Calibration of the pneumotacho- USA; Po-Ne-Mah, Gould Instrument Systems Inc., OH, USA).
graph requires either a volume or flow source that is calibrated Alternatively, some complete systems are available (e.g.
and certified. Syringes are commonly used for volume calibration, Eco Medics).
Facemasks
and form a tight seal so that airflow does not escape
Because many measurements of lung function require the from the mask. There are no commercially available masks
use of facemasks, it is useful to review them here. for equine pulmonary function testing, with the excep-
Facemasks must be rigid, have low dead space, not impinge tion of the Exhalyzer Eco Medics (Duernten, Switzerland)
on the movement of the nares or compress the soft tissue (Fig. 15.1) but it only accepts the Eco Medics ultra-
overlying the nasomaxillary notch, be comfortable, sonic flow meters. The Equine Aeromask (Trudell Medical
Fig. 15.1. The Exhalyzer ultrasonic pneumotachographs and mask

from Eco Medics. (A) Original mask and ultrasonic flow transducer,
(B) recently improved flow transducer. Reproduced with the permis-
sion of Eco Medics.
A
International, London, Ontario, Canada) can be modified it is possible to calculate dynamic compliance (Cdyn) and
for equine pulmonary function testing. Masks are available total pulmonary resistance (RL) (Box 15.2). These are the
in three sizes and can be obtained before they have been most common pulmonary function measurements found in
drilled and fitted for medication delivery devices. They are the equine literature. An increase in RL is indicative of
made of clear, lightweight plastic and can be drilled and airway obstruction that can be the result of narrowing of
fitted with a holder that will accept a pneumotachograph the upper and/or lower airway. As noted above, head
(Fig. 15.2). Another alternative is to construct a mask using flexion can obstruct the upper airway but if horses are
a head from a cadaver as a mold to build a cast (Fig. 15.3). allowed to stand with minimal restraint, this is not usually
The seal to the horse’s head should remain airtight, a problem. In the lower airway, obstruction can be caused
even when the horse moves. Rubber shrouds fashioned by bronchospasm, mucus accumulation within the airway
from tire inner tubes are ideal. The Eco Medics mask lumen, and by airway wall thickening as a result of
incorporates an inflatable rubber ring that ensures a firm inflammation-induced remodeling. Dynamic compliance
and airtight fit to the face. Care should be taken to avoid decreases if the lungs become stiffer, for example as a result
seals that are excessively compliant in applications where of fibrosis or pulmonary edema. Dynamic compliance also
the mask may become pressurized, such as for forced decreases when there is diffuse peripheral airway obstruc-
oscillatory mechanics or for provocation testing when tion such as occurs in horses with RAO.
using conventional mechanics measurements. In recent years it has been acknowledged that measure-
ments of compliance and resistance, especially using
the more simplified analytical approaches, appear to be
Pulmonary Resistance and relatively insensitive to changes in pulmonary function
Dynamic Compliance in horses and there are many technical issues asso-
With the addition of an esophageal pressure measurement ciated with their measurement. This has led a number
(as an index of pleural pressure) to the flow measurement, of research groups to simply present data for maximal
its tip lies within the mid-thorax. The final 10 cm or so

of the catheter has holes placed in a spiral pattern. An
unlubricated condom that is sealed to the catheter with
fine suture material, cotton or silk, covers this perforated
region. Once the catheter is in place, a small amount of air
is introduced into the system (usually 2–3 ml). The volume
introduced must not pressurize the system. The catheter is
then connected to the pressure transducer and recording
system. Technical details are provided in Box 15.3.
A potential problem with making measurements of
esophageal pressure is swallowing, which causes transient
but quite marked changes in esophageal tone and therefore
pressure, often causing the recording to go out of range.
Swallowing is easy to observe on a pressure trace and these
pressure waves are excluded from the analysis. Many
horses swallow frequently with an esophageal catheter in
place and therefore it may not be possible to obtain reliable
measurements in such individuals.
Measurement of the maximal change in pleural pressure
(esophageal pressure) during tidal breathing (ΔPpl MAX)
is the simplest PFT. The ΔPpl MAX is directly proportional to
RL, tidal volume, and airflow rate, and indirectly propor-
tional to Cdyn.
(ΔPpl MAX ) = VT /Cdyn + RL × flow
An increase in ΔPpl MAX is not specific for any type of

lung disease because it can increase if the lungs stiffen, the
airways become obstructed, or if VT and flow increase.
If the diagnosis is known however, changes in ΔPpl MAX
Fig. 15.2. Horse in stocks wearing a modified Aeromask fitted with can be used to track progress of the disease or response
a No.5 heated Fleisch pneumotachograph. To the left of the mask to treatment. In a horse with RAO for example, a reduction
the two thicker plastic tubes are those connected to the differential in ΔPpl MAX after administration of atropine would indi-
pressure transducer (out of picture). The thinner wire is the heater cate bronchodilation. Furthermore, if disease is affecting
connection. To the right of the mask is the esophageal catheter, which
passes through a rubber valve (not visible) into the mask.
gas exchange, and there is a compensatory increase in
ventilation (VT and flow), this is also reflected in the
measurement of ΔPpl MAX. For this reason it provides a good
overall view of the lung’s functional status and therefore
Boehringer-Ingelheim used to market an intrapleural
change in pleural pressure (esophageal pressure) to measurement system, the “Ventigraph”, to measure and
describe the mechanical function of the lung, for example, display esophageal pressure in horses.
in response to inhaled organic dust challenge of RAO-
affected horses. However, measurements of conventional
lung mechanics may still be required for regulatory pro-
Forced Oscillatory Mechanics
cedures, such as in obtaining data to support registration of Forced oscillatory mechanics (FOM) is potentially a very
new pharmaceuticals. attractive PFT because it is non-invasive and appears to
be more sensitive to changes in lung function than
are measurements of Cdyn and RL. Flow and pressure are
Maximal Change in Pleural Pressure measured at the nares in response to impulses applied to
Direct measurement of pleural pressure requires placement the respiratory system (Figs 15.4 and 15.5). When Cdyn and
of a catheter in the pleural cavity. Fortunately, esophageal RL are measured, the horse generates the flow and
pressure provides an accurate estimate of pleural pressure pressure, whereas in the case of FOM, pressure and flow
and is a simple measurement to obtain. A relatively stiff signals are superimposed on the normal breathing pattern
catheter of approximately 2–3 m with an external diameter either as multifrequency impulses or trains of single sine
of around 3–4 mm is inserted down the esophagus so that waves (Figs 15.4 and 15.5).
A B
C D
Fig. 15.3. Mask for pulmonary function testing constructed from then used to make a further mold and cast upon which the masks
fiberglass after a mold was made in plaster of Paris from the head of a were made up by using layers of fiberglass sheets. An inflatable rubber
cadaver. A head was then cast in plaster of Paris from the mold and seal is used to seal the mask around the horse’s head. (A) Top view,
the shape for the mask was built up using modeling material. This was (B) lateral view, (C) rear view, (D) front view.
Box 15.2. Calculation of pulmonary resistance and dynamic compliance
The simplest approach to calculating dynamic compliance may not necessarily be representative of the whole cycle. An
(Cdyn ) is to divide tidal volume by the change in pressure alternative approach is the least squares regression method
between the start and end of inspiration at points of zero flow (Fig. 2.3). Compliance is calculated from the slope of the line
(Fig. 2.1). Total pulmonary resistance (RL) is determined by connecting the highest and lowest volume points (as in the
dividing the change in pressure between two points of equal Mead–Whittenberger approach) on a graphical representation
volume (isovolume, the first during inspiration and the second of a pressure–volume loop, whilst resistance is determined by
during expiration) by the change in flow between the same subtracting a calculated value for elastic recoil pressure (Pel)
two points (Fig. 2.2). The isovolume percentage is normally set from transpulmonary pressure (Ptp) at each different volume (V)
to between 60 and 70%. Use of isovolume values in the range reading:
50–90% makes minimal difference to the value of resistance in Pres = Ptp – Pel
horses with and without methacholine-induced bronchocon-
Pres = ΔPtp – (ΔV/Cdyn)
striction (Marlin, unpublished data).
The Mead–Whittenberger technique shown in Figs 2.1 and Pres (the pressure required to overcome resistive forces) is
2.2 was widely used prior to the introduction of computer- then plotted against flow (V ′) at each volume reading and
based signal acquisition and analysis, although it is still used, linear regression is used to obtain the slope of the line, which
for example, by the Po-Ne-Mah data acquisition and analysis represents RL.
system (Gould Instrument Systems Inc., OH, USA). Whilst this Two more advanced techniques are the Mortola–Saetta
is a simple approach, compliance and resistance are only method and the multiple linear regression (MLR) or covariance
calculated at discrete points within the respiratory cycle and technique (Roy et al 1974).
5
In
Flow 0
Ex Fig. 2.1. Illustration of the calculation of
–5 dynamic compliance (Cdyn) from nasal
Tidal VT (insp) flow and esophageal pressure recordings
volume 5 using the Mead–Whittenberger technique.
In = inspiration; Ex = expiration; VT (insp) =
0 inspiratory tidal volume; P1 and P2 =
P1 pressures
Esophageal 0
pressure (dyn = VT / (P1 – P2).
P2
–5
5 F1
In
Flow 0
Ex F2
–5
60% 60% Fig. 2.2. Illustration of the calculation of
Tidal inspiratory expiratory total pulmonary resistance (RL) from nasal
volume 5 volume volume flow and esophageal pressure recordings
using the Mead–Whittenberger technique.
0 RL = (P2 – P1) / (F1 – F2).
Esophageal 0
pressure P1
P2
–5
Continued
Box 15.2. Calculation of pulmonary resistance and dynamic compliance—cont’d
A
The MLR or covariance technique is based on solving a
simplified general equation of motion for the lung for the
constants EL (elastance or 1/Cdyn ) and RL:
Ptp = EL × V + RL × V ′ + k
ce
Volume
n where Ptp is transpulmonary pressure (represented by esophageal

p lia
Com pressure), V is the volume above elastic equilibrium volume
[this normally corresponds to functional residual capacity (FRC)
under resting conditions in healthy individuals], V ′ is flow and
k is a constant. As Ptp , or rather Pes , and flow are measured and
volume can be obtained by integration, the equation can thus
be solved to obtain EL and RL. With computer-based analysis
Pressure the equation can be solved many times within each breath to
analyze either discrete portions (e.g. inspiratory versus expi-
B Pressure ratory) or over the whole breath cycle. While the method is
+ve stable and less susceptible to waveform noise than other
resistance and compliance methods, it is more difficult to
validate. This is the analytical approach employed in the
Biosystem XA software from Buxco (Buxco Research Systems,
0 Wilmington, NC, USA).
nce
si sta The Mortola–Saetta method is a development of the least
Re
squares regression technique where the simplified equation of
motion (see above) is transformed by dividing throughout by
–ve volume to obtain compliance and by flow to obtain resistance.
Expiratory 0 Inspiratory These equations are solved for multiple points within the
Flow breath and the slope of the regression lines represents com-
pliance and resistance. The whole breath cycle may be used or
Fig. 2.3. (A) Representation of compliance as determined from a plot
of volume as a function of pressure (common to both Mead– separated into inspiratory and expiratory components.
Whittenberger and least squares regression analysis/covariance Whichever method is used should be made clear in pub-
techniques). (B) A plot of flow and pressure to obtain Pres and RL, lications, as this will affect the absolute value and also
where Pres = Ptp – (VT/Cdyn) as in the least squares regression method. potentially the sensitivity to detect changes in response to
Pres = the pressure required to overcome resistive forces; Ptp = trans- disease, inhalation challenges, or other interventions.
pulmonary pressure; RL = total pulmonary resistance; VT = tidal
volume; Cdyn = dynamic compliance.
Box 15.3. Measurement of esophageal pressure
The Validyne pressure transducer can be used with air-filled (Figs 3.1, 3.2 and 3.3). In the case of respiratory signals such as
esophageal catheters but it must have the correct pressure airflow and esophageal pressure, a frequency response up to
range, typically ± 30 or ± 60 cmH2O rather than the ± 3 cmH2O 10–20 Hz is adequate for resting measurements. During exer-
used with a pneumotachograph. By using pressure transducers cise the rates of change of flow and pressure are greater and so
of the same make and model connected to the pneumo- equipment with a higher frequency response may be required.
tachograph and esophageal catheter by similar lengths and Less common for the measurement of esophageal pres-
types of tubing, the risk of signals from flow and esophageal sure are catheter-tip-mounted strain-gauge pressure trans-
pressure being out of phase is minimized. ducers of the type commonly found on intravascular pressure
Whether two separate measuring systems are in phase transducers (e.g. Millar and Gaeltech). These have a much
or not is related to the frequency response of the complete higher frequency response and may be desirable when the rate
measuring and recording system. A system with a good fre- of change in pressure is rapid. Tip-mounted catheters are less
quency response will accurately represent the true input signal subject to noise introduced by movement of the external part
of the catheter between the horse and the pressure transducer. gel or spray on the mucosal surface inside the nares greatly
However, the tip must be covered with a condom to prevent facilitates catheter placement. The tricks used to pass a stomach
direct contact between the transducer and the esophageal tube can be used to pass the esophageal catheter.
wall. Without such a cover, the pressure is only measured An esophageal catheter can make it difficult to seal a
locally where the catheter tip meets the esophageal wall. facemask. A simple approach in our experience is to pass the
To represent pressure changes within the pleural cavity, the catheter through a cable port valve inserted into the mask
esophageal balloon must rest between the base of the heart before inserting the catheter into the horse. When the catheter
and the diaphragm. The catheter can be marked to the approx- is in position the mask can be applied and the port valve
imate length by aligning it from the external nares along the tightened to lock the catheter in position.
path of the esophagus. It can then be inserted and moved to The driving pressure for breathing is the difference between
and fro until the maximal change in pressure is recorded that the pleural (esophageal) and external nares pressure. As the
is free of cardiac artifact. An alternative approach is to use nares are inside the mask, it is appropriate to connect the second
radiography to position the balloon in a standard position. The pressure port of the transducer to the inside of the mask rather
catheter can then be marked at the nares so that it is easily than to leave it open to the atmosphere. However, when the
replaced at the same location. horse is breathing quietly at rest, the difference between mask
Depending on the rigidity of the catheter material, it may be (nares) pressure and external (atmospheric) pressure is minimal
possible to pass the esophageal balloon and catheter directly or and can essentially be ignored. However, when a horse has
it may be facilitated by use of a short stomach tube (about increased ventilation, the imposition of a small resistance by
60 cm long) placed into the rostral esophagus. The use of a the pneumotachograph can create several cmH2O difference in
twitch and/or application of a small amount of local anesthetic pressure between the inside of the mask and the atmosphere.
A
Input signal Output signal
1Hz
Increasing frequency
2Hz
5Hz
Fig. 3.1. (A) Illustration of the concept of frequency
response. At 1 and 2 Hz input frequency the output
frequency is faithfully reproduced. At 5 Hz there is some
10Hz loss of signal amplitude, whilst at 10 Hz the output is
almost completely lost. (B) The frequency response of a
system is often expressed by showing the output
amplitude as a function of the input frequency. In this
example there is no loss of amplitude for frequencies
between 0 and 15 Hz. This system would therefore be
B Frequency response described as having a flat frequency response between
100 0 and 15 Hz. At 20 Hz there is a slight loss of amplitude,
which becomes marked between 25 and 40 Hz. This is
80 sometimes referred to as roll-off. This system would be
Output signal amplitude (%)
suitable to measure resting esophageal pressure but

unsuitable for measuring ventilation during exercise.
60
40
20
0
0 10 20 30 40 50 60 70 80
Frequency (Hz)
Continued
Box 15.3. Measurement of esophageal pressure—cont’d
100
Step change
applied
80 Fig. 3.2. The response of a measuring system can also
τ
be defined in terms of its response to an instantaneous
Signal amplitude
63% of maximum change change from one state to another, e.g. a rapid change
60
from low to high or high to low pressure. The latter can
be achieved for example by placing the measuring port
40 of a pressure transducer inside a balloon and popping it.
This is normally defined as the time taken for the
amplitude of the transducer output to reach 63% (one
20 time constant; tau) of its final steady-state value in
response to a step change input.
0
0 10 20 30 40 50
Time (milliseconds)
(a)
Nasal airflow
Input
signal (b)
Esophageal pressure
(c)
(d)
Nasal airflow
Esophageal pressure
Fig. 3.3. Illustration of the frequency response of two different measurement systems. A common step
change signal (dashed line, right of diagram) is applied to two transducer systems, one for measuring
nasal airflow and one for measuring esophageal pressure. Four possible different outputs from these two
systems are shown on the right of the diagram (labeled a to d): (a) both flow and pressure output signals
faithfully reproduce the input signal; (b) both flow and pressure output signals are “slower” (lower
frequency response) than the input signal but nevertheless are both in phase (they change together);
(c) the flow signal responds faster than the pressure signal (i.e. the frequency response of the flow
measuring system is faster or better than the pressure measuring system); (d) both flow and pressure
signals are similar, except that the esophageal signal is delayed such that they are out of phase.
Although, estimation of respiratory system impedance lometry (IOS; Masterscreen, Jaeger GmbH, Wurzburg,
(Zrs ) using forced oscillation was first described in 1956 Germany; Fig. 15.6) and the other on forced oscillations
(Du Bois et al 1956), FOM is relatively new to equine (FOT) (EMMS, Bordon, Hants, UK; Fig. 15.7). Details of the
pulmonary function testing (Young & Hall 1989, Young & two systems and technical aspects of interpretation of
Tesarowski 1994, Young et al 1997, Mazan et al 1999, results are provided in Box 15.4.
van Erck et al 2003, 2004a,b) and as yet is not in wide- Measurement of FOM produces values for resonant
spread use. At present there are two forced oscillation frequency of the respiratory system and for respira-
systems for use on horses, one based on impulse oscil- tory impedance (Zrs), which is composed of resistance (Rrs)
Raw pressure and flow Airflow (horse)

A
6.0
4.0
2.0
Amplitude
0.0
–2.0
Combined signal of
–4.0 airflow due to
horse breathing
–6.0 and airflow
0 500 1000 1500 2000 generated by FOM
Airflow generated by system
Sample number FOM system
Raw pressure and flow Pressure
Flow Time domain Frequency domain
0.2 Combined airflow
(horse + FOM)
B Airflow
Amplitude
2.0
Pressure
0.0
0 5 10 15 20 25 30 35 40 45 50
Bin
File name C:\FOS\AMP study\ellie histamine 10_02_05 Combined pressure

(horse + FOM) Peak due to Peak due
breathing to FOM
Frequency domain
Fig. 15.4. Screen print from the EMMS FOM system to show the high C Airflow
frequency oscillations of flow and resulting pressure superimposed
on the lower frequency flow and pressure signals generated as the
horse takes two breaths (upper graph). The lower graph shows the Airflow
amplitude of the flow and pressure signals after estimation by fast
Fourier transformation (FFT) and removal of the breathing signal.
Pressure
Ratio of airflow to
and reactance (Xrs) (see Box 15.4). Respiratory resistance pressure generated
from FOM signal
includes all the components of the respiratory tract that Peak due
contribute to friction, essentially the resistance to flow in to FOM
the airways, which depends on airway caliber and the Fig. 15.5. (A) Low frequency signal representing horse’s airflow, higher
architecture of the airways (e.g. branching). In an animal frequency oscillations generated by the FOM system and the two
with RAO for example, Rrs would be increased, the signals combined (right hand side). (B) Combined signals for airflow
and pressure (left hand side) in the time domain and representation in
frequency dependence of resistance exaggerated, and
the frequency domain on the right hand side. (C) Pressure and airflow
reactance more negative, which also has the effect of peaks as a result of breathing of horse are ignored and the peaks
increasing resonant frequency. Reactance reflects the generated from the forced oscillation are used to calculate the
stiffness of the lung. impedance variables.
Forced Expiration
In human medicine, the most commonly used lung connected by a tracheostomy tube (Gillespie 1974). Clearly
function measurements are derived during a forced this was not a technique with practical applications.
exhalation. To create a forced exhalation in horses, it is More recently, forced expirations have been generated in
necessary to connect their airway to a large vacuum sedated horses through a nasotracheal tube (Couetil et al
source. This was first performed in anesthetized horses 2000). Horses are mechanically ventilated and the
within a plethysmograph using a vacuum reservoir lungs are inflated to total lung capacity. At this point,
Fig. 15.6. Impulse oscillometry system (IOS; reproduced with the permission of Dr Carmen Klein).
Impulse generator
Flow (loudspeaker or valve
transducer connected to pressurized
air source)
Mask
Resistor
Pressure
transducer
B
A
Fig. 15.7. (A) Measurement of pulmonary function in an unsedated adult horse using the technique of
forced oscillatory mechanics (FOT; EMMS Ltd). Head and neck angle can be more difficult to standardize
in unsedated horses, but if horses are to be sedated then in addition to standardization of the head and
neck angle, the elevation of the head must be maintained to prevent excessive congestion of the upper
airways, which will result in increased resistance. (B) A diagrammatic representation of the FOM
equipment.
Box 15.4. Measurement of forced oscillatory mechanics
In the impulse oscillometry (IOS) system adapted for use in the

horse, impulses are in the form of “clicks” generated by a loud-
Resistance (Rrs)
speaker and each click contains multiple frequencies in the
range 0.1–50 Hz. In the case of the commercially available
forced oscillometry (FOT) system for horses, the impulses are
of single frequency (although sequential trains of different
frequencies can be applied, usually in the range 1–5 Hz) and
consist of pulses of air produced by a valve connected to a
+ve Fres
compressed air source. With IOS there is little sensation of
Reactance (Xrs)
pressure being applied whilst in the case of FOT, oscillations of
0
pressure are more discernible.
The impedance of the respiratory system ( Zrs ) is a function
of the relationship between pressure and airflow and has two
components: resistance (Rrs ) and reactance ( Xrs ). Rrs is defined –ve
as the component of Zrs where pressure and flow are in-phase Increasing oscillation frequency
(also referred to as the “real” part of Zrs ), whilst Xrs is the out-
of-phase (or “imaginary”) component. Real and imaginary in Fig. 4.1. Schematic representation of respiratory system resistance
this context refer to the result of application of the Fast Fourier (Rrs), reactance (Xrs) and resonant frequency (Fres) as a function of
increasing frequency (illustrating frequency dependence) in a healthy
Transform to convert the signals from the time domain to the horse (black line) and in a subject with airway obstruction (blue line).
frequency domain. Both Rrs and Xrs vary with the frequency of Note that with airway obstruction the frequency dependence of
oscillation being applied (Fig. 15.8). resistance increases, reactance becomes more negative and resonant
The “resistance” of the respiratory system is determined frequency increases.
from the relationship between pressure and flow at each fre-
quency. As an example, if the entrance to the mask were com- pressure lags behind flow and when Xrs is positive, pressure
pletely blocked off then there would be zero flow and very high leads flow. The negative part of Xrs reflects the capacitance
pressure, thus leading to high impedance. In practice with IOS (ability to store energy) of the pulmonary system. It is com-
or FOT there is a limit as to how high the impedance can be posed of the elastic components of both the lung and the chest
because the impulses are applied via a measurement head wall, as well as the viscoelastic properties of the lung itself.
which has a leak resistor to avoid over-pressurization of the The positive part of Xrs relates to the inertial properties of the
airways (Fig. 15.7). At the opposite extreme, if the measuring air within the airways. In healthy subjects at low oscillation
head were open to the air, there would be high flow and frequencies, elastic forces dominate over inertial forces and as
negligible pressure, so impedance would be close to zero. a consequence Xrs is negative (Fig. 4.1), whilst at increasing
In contrast, reactance ( Xrs ) is the ability of the lung to store frequencies inertial forces become increasingly dominant. If
energy and is defined as the degree to which oscillatory reactance is plotted as a function of increasing frequency, then
pressure leads flow, described as the phase angle. Reactance a point is reached when reactance becomes zero. This frequency
can be either positive or negative. When Xrs is negative, is termed the resonant frequency of the respiratory system.
Tidal Breathing Flow–Volume Loop Indices

the airway is connected to a vacuum tank. The resulting
forced expiration is used to generate a flow–volume curve Tidal breathing flow–volume (TBFV) loops have the
(Fig. 15.8) from which is calculated forced vital capacity, advantage that they can be recorded from conscious horses
FEV1, forced expiratory flow at 75–95% exhaled vital wearing a facemask and pneumotachograph to measure
capacity, and peak expiratory flow. Forced expiration is flow (see Box 15.1). Loops are formed by graphically
reported to be more sensitive than conventional measures plotting the volume against airflow for each breath
of lung function in determining the early onset of pul- (Fig. 15.9). A mean TBFV loop is usually generated from
monary dysfunction in RAO-affected horses (Couetil et al between 10 and 60 TBFV loops (Lumsden et al 1993,
2001). The downside of this approach is that it is invasive Connally & Derksen 1994, Petsche et al 1994, Herholz
and technically demanding and would not be considered et al 2003a). TBFV loops have been produced from both
practical in a routine clinical setting. exercising horses and horses at rest (Art & Lekeux 1988,
45
Baseline
40
Saline
35
Baseline Histamine
30 8 mg/dl
Histamine
32 mg/dl
Flow (l/s)
25
Histamine
64 64 mg/dl
20
128 Histamine
128 mg/dl
15
10
0
0 10 20 30 40
Volume (Liters)
Fig. 15.8. Flow–volume curves obtained in a control horse during inhalation challenge with 0–128 mg/dl
histamine. Exhalation begins at zero flow and volume. During the first part of exhalation, flow increases
rapidly and reaches a plateau until late in exhalation when flow decreases rapidly. As the concentration of
histamine increases to 128 mg/dl, airway obstruction causes the forced expiratory volume to decrease
from 40 to 20 liters. In addition, the curve becomes more concave at the end of exhalation. Reproduced
from Couetil et al 2000, with permission.
volume. There is considerable intra- and inter-subject

variation in TBFV loop indices (Guthrie et al 1995a,b).
Expiration
However, inspiratory flow at 50% tidal volume appears to

Flow (20.00 l•s-•div-1)
be a useful indicator of disease severity in RAO (Petsche et

al 1994, Herholz et al 2003a). The TBFV loop is very useful
for identification of the severity of inspiratory flow limita-
b tion in horses with upper airway obstruction caused, for
Inspiration
example, by recurrent laryngeal neuropathy.
a
Volume (4.00 l/div) Respiratory Inductance Plethysmography
Respiratory inductance plethysmography (RIP) provides a
Fig. 15.9. Tidal breathing flow–volume loop of a control horse (a) and non-invasive measurement of lung volume using recording
a horse with recurrent laryngeal neuropathy (b) exercising on a bands around the thorax and abdomen. Plethysmography
treadmill. Inspiration begins at the far right. As the horse inhales, its bands are commercially available (Respibands, Ambulatory
flow rate increases (downward deflection on the graph) to a peak,
decreases and then increases to a second peak late in inhalation.
Monitoring Systems, Ardsley, NY, USA) or can be custom-
At the end of inhalation, the horse has inhaled about 16–20 liters made (Marlin et al 2002). The thoracic band can be placed
(four to five marks on the x-axis). Exhalation is uniphasic. Flow increases at the seventh or eighth rib (Marlin et al 2002) or the 11th
(upward deflection) and then decreases again. The horse with recur- intercostal space (Miller et al 2000, Hoffman et al 2001)
rent laryngeal neuropathy has no problem exhaling but the peak flow and the abdominal band at the level of the 16th, 17th
is dramatically reduced during inhalation.
(Marlin et al 2002) or 18th rib (Miller et al 2000, Hoffman
et al 2001). The RIP has been used to study asynchrony
between thoracic and abdominal movement in foals (Miller
Lumsden et al 1993, Connally & Derksen 1994, Petsche et al 2000). An index of airflow from the RIP bands has
et al 1994, Guthrie et al 1995a,b, Herholz et al 2003a). also been evaluated as a measure of airway obstruction
A range of variables can be generated from a TBFV loop, (Hoffman et al 2001). RIP in conjunction with conven-
including peak inspiratory flow, peak expiratory flow, and tional techniques has been used to diagnose bilateral
inspiratory and expiratory flows at 25% and 50% tidal diaphragmatic paralysis in a pony (Amory et al 1994).
(Aguilera-Tejero et al 1993, 1994, Deaton et al 2002).

A Human
Whichever method is used to measure EELV, it should be
remembered that gas trapped behind closed or obstructed
Flow
airways, within cysts, or in regions of the lung with long
time constants (i.e. poorly and slowly ventilated regions) is
not measured by these dilution techniques. In the body
Tidal plethysmograph method for determining EELV in humans
volume
EELV
and animals, however, trapped gas is included. Technical
FRC details of gas dilution techniques for measurement of EELV
are provided in Box 15.5.
B Horse
Measurement of Airway Responsiveness
Flow Increased airway responsiveness, also referred to as
bronchial or airway hyperresponsiveness (AHR), is an
exaggerated narrowing of the airways in response to
Tidal FRC
endogenous and exogenous stimuli. Human asthmatics
volume typically have AHR; they develop airway narrowing in
EELV response to stimuli that do not affect non-asthmatics.
These stimuli include antigens, cold air, and dusts. It is
Fig. 15.10. (A,B) Representation of the breathing strategy and relative generally accepted that AHR is a consequence of inflam-
positions of functional residual capacity (FRC) and end-expiratory lung mation. While allergic inflammation is a primary cause,
volume (EELV) in human (A) and horse (B). Gray areas represent active viral infections such as influenza and exposure to environ-
phases of breathing (i.e. involving muscular effort) whilst blue areas mental dusts can also temporarily induce AHR. The AHR
represent passive phases (i.e. relaxation and no muscular effort). Note
may be present without other clinical evidence of airway
that EELV and FRC are the same in human but EELV is always lower
than FRC in horses because horses breathe around (above and below) inflammation such as cough or mucus hypersecretion. For
their FRC whilst humans breathe from their FRC. this reason measuring AHR may provide a sensitive means
to detect airway inflammation. Indeed, Klein and Deegen
(1986) demonstrated that AHR to histamine is absent in
horses without respiratory tract disease, present in around
a quarter of horses with low-grade disease and present in
End-expiratory Lung Volume
all horses with severe airway inflammation.
At the end of a tidal exhalation, the lungs still contain a Tests of AHR fall into two categories: those that use
large volume of air that permits continuous gas exchange. agents acting directly on airway smooth muscle to produce
In people, this end-expiratory lung volume (EELV) is bronchoconstriction and those that induce broncho-
identical to functional residual capacity (FRC) and constriction indirectly through stimulation of release of
represents the mechanical equilibrium of the respiratory endogenous mediators. Diagnosis of AHR in horses is
system (Fig. 15.10). During the second phase of their most commonly undertaken using inhaled histamine
exhalation, horses push their respiratory system below FRC or methacholine, which act directly on airway smooth
(see Chapter 2) hence EELV is always smaller than the muscle. Histamine binds to smooth muscle H1 receptors but
mechanically determined FRC (Fig. 15.10). can also augment cholinergic bronchospasm (Olszewski et
In humans, airway obstructions such as bronchiolitis, al 1999). Methacholine, an analog of acetylcholine, binds
bronchopulmonary dysplasia, cystic fibrosis, emphysema, directly to airway smooth muscle muscarinic receptors.
and chronic obstructive pulmonary disease tend to increase Exercise, dry air hyperventilation, distilled water, cold air,
EELV. Restrictive conditions such as fibrosis or loss of mannitol, hypertonic saline, and adenosine monophos-
surfactant in respiratory distress syndrome can decrease phate (AMP) have been used in humans and animals.
EELV. In addition, even in the absence of pathology, EELV Measurement of AHR is described in Box 15.6.
can be elevated by processes such active laryngeal closure
to slow exhalation (braking), inspiratory muscle activity
during expiration, and a high respiratory rate.
Tests of Gas Exchange Properties
There are few reports of measurement of EELV in horses
of the Lung
and the role of changes in EELV in disease is unclear Measurement of arterial blood gas tensions (PAO2 and
(Soma et al 1987). The two methods most applicable for PaCO2) provides the best overall evaluation of pulmonary
determining EELV in horses are multiple breath nitro- gas exchange (Chapter 14). If PAO2 is depressed by an
gen washout (Gallivan et al 1990) and helium dilution amount approximately equal to the elevation in PaCO2, the
Box 15.5. Measurement of end-expiratory lung volume
Multiple breath nitrogen washout the helium dilution method as it can take approximately 10 min
The horse is fitted with a facemask, a heated pneumotacho- to wash out the nitrogen from a horse’s lungs. In contrast it
graph, and a non-rebreathing valve. A reservoir bag contain- only takes around 90 seconds to measure EELV by helium
ing 100% oxygen is connected to the inspiratory port of the rebreathing.
non-rebreathing valve. The exhaled nitrogen concentration is
recorded with a rapid-response analyzer. The washout is halted Helium rebreathing
when the exhaled nitrogen concentration is below 1%. EELV is The horse breathes from a bag of air containing a known
calculated from the following equation (Rollin et al 1996): volume and concentration of helium in air in a closed system.
The helium equilibrates with the air within the horse’s respi-
EELV = {VE × FN2(mixed) / [FN2(initial) – FN2(end)] } – VD
ratory tract over approximately six to twelve breaths. Provided
where VE is the total volume of gas exhaled, FN2(mixed) is there are no leaks in the system, the volume (i.e. respiratory
the fraction of nitrogen in the total volume of gas exhaled, tract and bag) is constant and the volume of helium in the
FN2(initial) is the fraction of nitrogen in the lung prior to system is the same at the beginning and end of the equilibra-
washout, FN2(end) is the fraction of nitrogen in the final breath tion. However, as a result of dilution by air within the respira-
of the washout, and VD is the instrumental dead space. The tory tract, the helium concentration is reduced at the end of
nitrogen fraction in the total volume of exhaled gas can be equilibration (Fig. 5.1).
determined by collecting the exhaled gas into a reservoir bag or The technique requires a tight-fitting facemask, a giant
by integrating the exhaled nitrogen fractions during the three-way valve, a 20–50 liter reservoir bag (Douglas bag), a
breath-by-breath washout. cylinder of medical grade 10% helium in air, a dry-gas meter or
Measurements of EELV in horses using the multiple-breath a volume syringe to measure volume, a thermometer and a
nitrogen washout technique have reasonable within-day repro- helium analyzer. A means of displaying flow and helium con-
ducibility but differ significantly between days (Gallivan et al centration in real-time is helpful for timing valve operation and
1990). The measurement is critically affected by the presence detecting leaks, but is not essential.
of leaks in the equipment, most likely around the facemask. The reservoir bag is flushed several times with the rebreath-
Leaks are more likely to occur when measuring EELV by the ing gas containing helium and is evacuated using a vacuum
multiple-breath nitrogen washout technique compared to source. The bag is then filled to the required volume (60 ml
10%
%
He
0% a b
10 litres
Airflow
(l/s)
–10 litres a b
10
Tidal
volume
(Liters)
a b
0
Fig. 5.1. Changes in respired helium concentration during measurement of EELV in a horse using the
rebreathing (dilution) method. Before point “a” the horse is breathing room air. At point “a” (end expiration)
the valve is closed to air and opened to the bag containing ~10% helium. Over approximately 15 breaths
this equilibrates with the air in the horse’s lung and at point “b”, again corresponding to end expiration,
the valve is closed to the bag and the horse breathes room air again (point “b” to end of trace). Respired
airflow rate and tidal volume are also shown in the middle and lower panels, respectively.
gas/kg body weight) with the resulting gas. This is most easily ment must be repeated. Measurements should always be made
accomplished by filling through a dry-gas meter. The bag is in duplicate and the mean of two measurements that are no
agitated to ensure thorough mixing and connected to the helium more than 10% different should be expressed at BTPS.
analyzer. The aspiration rate of the analyzer must be known or To calculate the EELV, the equilibrated helium concentration
measured and the volume of the bag adjusted for the volume in the bag is measured. The dead space of the connectors and
of gas removed. For example, if the aspiration rate is 500 ml/min mask must be subtracted from the calculated EELV. It should
and the analyzer requires 60 seconds for a stable reading, then also be noted that the volume for EELV includes the volume of
for a desired bag volume of 15 liters, the bag should be filled air in the extrathoracic airways (i.e. trachea and upper airway).
to 15.5 liters. EELV is calculated as follows:
The facemask that is connected to the pneumotachograph
EELV = (VB × Hei / Hee ) – (VB + VD )
and helium analyzer is fitted to the horse and the bag con-
taining the helium and air is attached to the large valve. The where VB is the initial bag volume, Hei and Hee are the initial
horse is allowed to breathe room air through the valve for and equilibrated helium concentrations, respectively, in the
several minutes or until a regular breathing pattern has been bag, and VD is the instrumental dead space, which includes
achieved. By following the flow signal or by observing the the dead space of the mask. If the bag is filled through a
horse, the valve is switched at the end of a breath, i.e. end dry-gas meter from a cylinder, then the initial bag volume (VB )
expiration, so that the horse now breathes from the reservoir will be at conditions close to 0% relative humidity and ambient
bag. The helium concentration is monitored until equilibration barometric pressure. As EELV measurements should be pre-
occurs. Changes in breathing pattern that occur after the horse sented at BTPS, it is necessary therefore to also record the
was switched to the bag may affect the rate of equilibration temperature of the gas entering the dry-gas meter.
but not the volume for EELV measured. Once equilibration has Neon has also been used as a tracer gas to determine EELV
occurred, the valve is switched back to room air and the bag is by rebreathing in ponies (Gutting et al 1991). Sodium cyanide
sealed. The timing of the closing of the valve has no bearing on was injected into the jugular vein at the start of rebreathing to
the measurement of EELV. Leaks in the system have a dramatic stimulate ventilation and speed equilibration of neon between
impact on the value for EELV. If the helium concentration is the rebreathing bag and the horse. EELV was calculated as
monitored continuously, leaks are obvious and the measure- described for helium.
hypoxemia is the result of alveolar hypoventilation and no Ventilation and perfusion

further investigation is necessary. If, however, PAO2 is matching/mismatching
depressed more than PaCO2 is elevated, the animal has
additional causes of hypoxemia such as loss of diffusing Because disease rarely occurs uniformly throughout the
area or, more likely, ventilation/perfusion mismatching. lung, there are regions of normal lung and regions in
Both diffusing capacity and ventilation/perfusion matching which there is airway obstruction and altered compliance.
have been investigated in horses but the methods are These regional changes cause abnormal distribution of
highly technical and useful only as research tools. More airflow within the lung. In addition, disease can also cause
recently, volumetric capnography has been introduced as a abnormal distribution of blood flow. These changes lead to
• •
method to examine ventilation/perfusion inequalities. The the mismatching of ventilation (V ) and blood flow (Q ),
usefulness of this technique awaits broader confirmation. which is the most common cause of hypoxemia in lung
disease. The degree of matching or mismatching between
Carbon monoxide diffusing capacity ventilation and perfusion within the lung can be assessed
using either the multiple inert gas elimination technique
The carbon monoxide (CO) diffusing capacity test (DLCO, (MIGET) or by imaging of ventilation and perfusion
also referred to as CO transfer factor) assesses the efficiency (Votion et al 1997, 1999a) (Chapter 13).
of oxygen transport across the alveolar–capillary mem-
brane and into hemoglobin in red blood cells (Comroe Multiple inert gas elimination technique
1975). Diffusing capacity has been measured in horses
using the single breath (Gillespie & Tyler 1968), steady MIGET requires the infusion of six inert gases (sulfur
state (Mauderley 1974) and rebreathing (Aguilera-Tejero hexafluoride, ethane, cyclopropane, enflurane, diethyl ether
et al 1993) methods. and acetone) dissolved in isotonic sodium chloride solution
Box 15.6. Measurement of airway responsiveness
The standard approach is to administer increasing doses of the of 6 ml/min. The latter can be adjusted using a dial on the unit.
challenge agent by means of a jet, ultrasonic or Piezo nebulizer In the case of jet nebulizers, the output rate and the particle
(Fig. 6.1). It is important to know the particle size distribution of size distribution vary with the pressure used to generate the
the output and the output rate (i.e. ml solution nebulized/min). aerosol. For example, the Sidestream jet nebulizer (Profile
In general terms, particles of less than 5 μm diameter are Respiratory Systems Ltd, Bognor Regis, Sussex, UK) has an
required to penetrate to the small airways. The nebulizer output output of 0.37 and 0.46 g/min at the recommend 80–124 kPa.
is normally quoted as the median mass aerodynamic diameter During a challenge, the concentration of the agent, the out-
(MMAD). For example, for the Ultra-Neb 2000 (DeVilbiss) put rate of the nebulizer, and the duration of nebulization
ultrasonic cup nebulizer, the quoted MMAD is < 4 μm at a rate determine the dose delivered. Whilst many authors often
Fig. 6.1. (A) Histamine being nebulized to

a horse using a Devilbiss Ultraneb 2000
ultrasonic nebulizer. The aerosol is being
nebulized directly into the pneumotacho-
graph, which avoids having to remove the
device and disturb the horse. Note the masks
being worn by technicians. (B) Jet nebulizer
chamber (Sidestream durable nebulizer,
Profile Respiratory Systems Ltd) and com-
pressor; and (C) close-up of nebulizer
chamber.
C
display provocation tests in terms of response (e.g. resistance)

to a nebulized concentration (e.g. 1, 2, 4, 8 mg/ml), it is more
appropriate to express the response as a function of challenge
dose (i.e. concentration × time × output rate).
If the nebulizer does not have a calibrated dial to adjust
flow rate (output), output can be determined by weighing the
nebulizer chamber before and after a measured period of
nebulization. Because the rate of nebulization may vary with
the nature of the solution to be nebulized and also with the
volume within the nebulizer, the calibration should use a similar
duration, volume, and type of solution to that being nebulized
during challenges. Viscous solutions such as hay dust suspen-
sion and some preparations of corticosteroids nebulize poorly
in ultrasonic nebulizers. For these solutions, jet nebulizers may
be preferred. Either jet or ultrasonic nebulizers are suitable for
methacholine and histamine.
Nebulizing the aerosol into an open mask is simple but a lot
of aerosol enters the room. A closed delivery system can be
scavenged of excess aerosol and also allows more precise
control of delivery. Whichever system is used, personnel should
wear suitable fitted facemasks to prevent unnecessary expo-
sure to aerosol. The closed delivery system shown in Fig. 6.2
not only limits exposure of personnel in the room, but also
generates a bolus of aerosol for inhalation by back-filling the
inspiratory arm during expiration or breath pause.
Solutions for provocation testing should be made fresh daily. A
Histamine and methacholine powders should be stored below
0°C and allowed to reach room temperature in a desiccator B
before weighing. Solutions for nebulization should be allowed Face
to reach room temperature. Cold solutions (i.e. solutions stored Inspiratory mask
Exhaust
on ice or direct from the fridge) should not be used as they can valve
induce bronchoconstriction.
It is good practice to first challenge with the vehicle solution
(usually 0.9% saline or 0.9% phosphate-buffered saline) to
Jet nebulizer Expiratory
ensure that the animal does not react to the vehicle itself. This valve
is especially important when an animal reacts to the lowest dose
of a provocative agent that has been administered. Without
Compressor
using a vehicle inhalation challenge, the proportion of the reac-
tion that is as a result of the agent cannot be ascertained.
Fig. 6.2. (A,B) Closed system for bronchoprovocation testing using a
Sample protocol for histamine provocation testing Jet nebulizer.
Requirements
● Equipment for measurement of lung function
● Fit equipment for pulmonary function measurement and
● Nebulizer and delivery system
establish baseline. A good baseline measurement is essential
● Scavenging system or masks for personnel
against which to judge responses. If in doubt about the
● Balance to weigh histamine
quality of the measurement, make several.
● Timer (minutes and seconds).
● Nebulize saline for 2 min.
Protocol ● Measure pulmonary function immediately after nebulization.
● Bronchoprovocation testing can be undertaken in unsedated ● Nebulize the lowest concentration of histamine (e.g. 1 mg/ml)
or sedated horses but the results under the two conditions for 2 min.
should not be compared within or between horses. Testing ● Measure pulmonary function immediately after nebulization.
should not be performed less than 4 h after feeding. ● Repeat with increasing doses of histamine 2, 4, 8, 16, and
● Weigh histamine and make up solutions. 32 mg/ml until the required response is obtained.
Continued
Box 15.6. Measurement of airway responsiveness—cont’d
Determination and expression of response used to indicate the dose of an agent resulting in a doubling
The dose at which an animal first responds provides the level of resistance. The precise values obtained depend on the
of sensitivity whilst the slope of the dose–response curve is health of the animals being studied, the type and efficiency of
the reactivity. The reactivity is commonly expressed as the the nebulizer, the efficacy of the delivery system, the duration
dose of bronchoprovocation agent resulting in a specific reduc- of nebulization, the range of doses used, the timings of the
tion in compliance or increase in resistance. For example, PC20 challenge protocol, and the sensitivity of the pulmonary
is used to indicate the dose of an agent resulting in a 20% function testing equipment.
decrease in pulmonary compliance, whilst PD200 would be
into the jugular vein. For studies performed in the rest- (Herholz et al 2001a,b,c, 2002a,b). Measurements of tidal
ing horse, an infusion rate of 30 ml/min for 60 min has volume and CO2 fraction are recorded and the volumetric
been employed (Hedenstierna et al 1987). At the end of the capnogram is generated off-line. Specific software is
infusion period, mixed expired gas is collected into a available (e.g. SBD-CO2calc, Oberli-Engineering, Berne,
heated mixing chamber and arterial and mixed venous Switzerland) to calculate physiological dead space volume,
blood samples are collected. The retention and excretion alveolar dead space volume and an index of CO2 elimina-
of each gas are determined by the ratios of arterial to tion. Volumetric capnography indices are of sufficient
mixed venous gas concentrations and mixed expired sensitivity to differentiate between healthy horses and
to mixed venous gas concentrations, respectively (Wagner asymptomatic RAO-affected horses (Herholz et al 2003b).
et al 1974). The solubility of each gas in the blood of This technique is attractive as it is non-invasive, can be
each horse is measured using a two-step procedure as performed in unsedated animals, and requires limited
described by Wagner et al (1974). The retention, excretion equipment. However, there is relatively little information
and solubility data are entered into a 50-compartment regarding the sensitivity of this technique in comparison to
lung model with each compartment having a specific other more commonly used pulmonary function tests in
ventilation–perfusion ratio (Nyman & Hedenstierna 1989, the horse, and this test has only become established for use
Nyman et al 1991). Data for ventilation and blood flow are by the group at University of Berne.
plotted against the logarithm of the ventilation–perfusion
ratios. Ventilation–perfusion ratios have been determined Scintigraphy
during exercise as well as at rest using MIGET (Seaman
et al 1995, Funkquist et al 1999, Nyman et al 1999). Imaging of pulmonary ventilation and perfusion can
This research technique has been used to understand the be performed by nuclear scintigraphy using radioactive
matching of ventilation and blood flow in the resting horse tracers; this is fully described in Chapter 13.
and during exercise. It also demonstrated that horses with
RAO have a large volume of lung that receives little blood
flow and that they have a large volume of alveolar dead
Other Measurements of Lung Function
space (Nyman et al 1999). Alveolar clearance
Volumetric capnography The ability of inhaled technetium-99m–diethylene triamine

pentaacetic acid (99mTc-DTPA) to diffuse across the alveolar
Volumetric capnography, which is also referred to as the epithelium, which is a drawback when measuring ven-
single breath test for carbon dioxide (SBT-CO2), has been tilation, has been used to assess alveolar clearance (Votion
used as an index of ventilation/perfusion matching in et al 1998, 1999b). The permeability of the pulmonary
the horse (Herholz et al 2003b). The volumetric capno- vascular endothelium to 99m Tc-DTPA is far greater than
gram is a plot of the fraction of carbon dioxide in exhaled that of the alveolar epithelium such that the rate of clear-
gas against exhaled breath volume (Fletcher et al 1981). ance of 99m Tc-DTPA reflects alveolar epithelial integrity.
Volumetric capnography has been performed using an The alveolar clearance rate appears to be a sensitive
ultrasonic pneumotachograph and an infra-red carbon indicator of alveolar epithelial damage in RAO (Votion
dioxide analyzer in both unsedated and sedated horses et al 1999b).
Mucociliary clearance
REFERENCES
The tracheal mucociliary clearance rate has been deter- Aguilera-Tejero E, Pascoe JR, Amis T C et al 1993 Measure-
mined by following the transport of radiographic or radio- ment of pulmonary diffusing capacity for carbon
active markers up the trachea (Nelson & Hampe 1983, monoxide and functional residual capacity during
Dixon 1992). Colored markers, for example Indian ink rebreathing in conscious thoroughbreds. American
in syrup, can also be placed in the distal trachea and Aguilera-Tejero E, Pascoe JR, Smith BL et al 1994 Evaluation
their transport monitored with a bronchoscope (Turgut & of a technique for detection of pulmonary hemorrhage
Sasse 1989). in horses, using carbon monoxide uptake. American
Amory H, Lomba F, Lekeux PM et al 1994 Bilateral diaphrag-
Pulmonary function measurement matic paralysis in a pony. Journal of the American
during exercise Art T, Lekeux P 1988 Respiratory airflow patterns in ponies at
rest and during exercise. Canadian Journal of Veterinary
Ventilation is the most common indicator of pulmonary Research 52: 299–303
function measured during exercise. Measurements of Broadstone RV, Gray PR, Robinson NE et al 1992 Effects of
ventilation in horses during exercise are most commonly xylazine on airway function in ponies with recurrent
made during treadmill exercise but can be undertaken in airway obstruction. American Journal of Veterinary
the field using the Eco Medics Exhalyzer 5 system or a Research 53: 1813–1817
Butler PJ, Woakes AJ, Smale K et al 1993 Respiratory and
system produced by Cosmed (Rome, Italy). The latter cardiovascular adjustments during exercise of increasing
system still needs careful validation for use in horses. intensity and during recovery in thoroughbred race-
Peak flow, tidal volume, respiratory frequency, minute horses. Journal of Experimental Biology 179: 159–180
ventilation, flow–volume loops and observations on Comroe JH 1975 Pulmonary diffusing capacity for carbon
respiratory–locomotory coupling may all provide infor- monoxide (DLCO). American Review of Respiratory
Diseases 111: 225–228
mation on pulmonary function. Measurements of gas Connally BA, Derksen FJ 1994 Tidal breathing flow-volume
exchange (oxygen uptake, carbon dioxide production loop analysis as a test of pulmonary function in
and respiratory exchange ratio) and indicators of blood exercising horses. American Journal of Veterinary
gas and acid–base status (arterial and mixed venous Research 55: 589–594
blood gases and blood lactate concentration) may also be Couetil LL, Denicola DB 1999 Blood gas, plasma lactate and
bronchoalveolar lavage cytology analyses in racehorses
informative. Measurements made during exercise may with respiratory disease. Equine Veterinary Journal
be helpful to identify mild disease or dysfunction (Connally Supplement 30: 77–82
& Derksen et al 1994, Couetil & Denicola 1999, Courouce- Couetil LL, Rosenthal FS, Simpson CM 2000 Forced expiration:
Malblanc et al 2002). For measurement of ventilation a test for airflow obstruction in horses. Journal of Applied
during exercise the Eco Medics Exhalyzer 5 and the BRDL Physiology 88: 1870–1879
Couetil LL, Rosenthal FS, DeNicola DB et al 2001 Clinical
flowmetrics ultrasonic pneumotachograph systems are signs, evaluation of bronchoalveolar lavage fluid, and
highly suitable because of their very low resistance and assessment of pulmonary function in horses with
dead space (Butler et al 1993). However, to estimate oxygen inflammatory respiratory disease. American Journal of
uptake and carbon dioxide production these systems need Veterinary Research 62: 538–546
to be combined with a respiratory mass spectrometer. Courouce-Malblanc A, Pronost S, Fortier G et al 2002
Physiological measurements and upper and lower
Alternatively, oxygen uptake and carbon dioxide production respiratory tract evaluation in French Standard-
can be measured with open-flow systems, although these bred Trotters during a standardised exercise test on
do not provide any information on ventilation. the treadmill. Equine Veterinary Journal Supplement
34: 402–407
Deaton CM, Marlin DJ, Schroter RC 2002 An improved
technique for measuring functional residual capacity
Conclusions (FRC) in horses. Proceedings of the 20th Veterinary and
Many of the pulmonary function tests that have been Comparative Respiratory Society Symposium, p.50
Dixon PM 1992 Respiratory mucociliary clearance in the
described either lack sensitivity for routine application in horse in health and disease, and its pharmaceutical
equine practice or require expensive and sophisticated modification. Veterinary Record 131: 229–235
equipment and are time consuming and technically Du Bois AB, Brody AW, Lewis DH et al 1956 Oscillation
challenging, which limits their use to referral centers or mechanics of lungs and chest in man. Journal of Applied
in research. However, with the development of new tech- Physiology 19: 653–658
Fletcher R, Jonson B, Cumming G et al 1981 The concept of
niques such as FOM and IOS, it is conceivable that sensi- deadspace with special reference to the single breath
tive, specific and simple pulmonary function testing may test for carbon dioxide. British Journal of Anaesthesia
become more accessible to clinicians in equine practice. 53: 77–88
Funkquist P, Wagner PD, Hedenstierna G et al 1999 Hoffman A, Kuehn H, Riedelberger K et al 2001 Flowmetric
Ventilation-perfusion relationships during exercise in comparison of respiratory inductance plethysmography
standardbred trotters with red cell hypervolaemia. Equine and pneumotachography in horses. Journal of Applied
Veterinary Journal Supplement 30: 107–113 Physiology 91: 2767–2775
Gallivan GJ, Viel L, McDonell WN 1990 An evaluation of Klein HJ, Deegen E 1986 Histamine inhalation provocation
the multiple-breath nitrogen washout as a pulmonary test: method to identify nonspecific airway reactivity
function test in horses. Canadian Journal of Veterinary in equids. American Journal of Veterinary Research
Research 54: 99–105 47: 1796–1800
Gillespie J 1974 The role of the respiratory system during Lavoie JP, Pascoe JR, Kurpershoek CJ 1992 Effect of head and
exertion. Journal of the South African Veterinary neck position on respiratory mechanics in horses sedated
Association 45: 305–309 with xylazine. American Journal of Veterinary Research
Gillespie JR, Tyler WS 1968 Chronic alveolar emphysema in 53: 1652–1657
the horse. Advanced Veterinary Science and Comparative LeBlanc PH, Eberhart SW, Robinson NE 1993 In vitro effects of
Medicine 13: 59–99 alpha 2-adrenergic receptor stimulation on cholinergic
Guthrie AJ, Beadle RE, Bateman RD et al 1995a contractions of equine distal airways. American Journal
Characterization of normal tidal breathing flow-volume of Veterinary Research 54: 788–792
loops for thoroughbred horses. Veterinary Research Lumsden JM, Derksen FJ, Stick JA et al 1993 Use of
Communications 19: 331–342 flow-volume loops to evaluate upper airway obstruc-
Guthrie AJ, Beadle RE, Bateman RD et al 1995b The effects tion in exercising standardbreds. American Journal of
of three models of airway disease on tidal breathing Veterinary Research 54: 766–775
flow-volume loops of thoroughbred horses. Veterinary Marlin DJ, Schrotert RC, Cashman PM et al 2002 Move-
Research Communications 19: 517–527 ments of thoracic and abdominal compartments during
Gutting SM, Forster HV, Lowry TF et al 1991 Respiratory ventilation at rest and during exercise. Equine Veterinary
muscle recruitment in awake ponies during exercise and Journal Supplement 34: 384–390
CO2 inhalation. Respiratory Physiology 86: 315–332 Mauderley JL 1974 Evaluation of the grade pony as a pul-
Hedenstierna G, Nyman G, Kvart C et al 1987 Ventilation- monary function model. American Journal of Veterinary
perfusion relationships in the standing horse: an inert Research 35: 1024–1029
gas elimination study. Equine Veterinary Journal Mazan MR, Hoffman AM, Manjerovic N 1999 Comparison of
19: 514–519 forced oscillation with the conventional method for hista-
Herholz C, Straub R, Busato A 2001a Ultrasound-spirometry mine bronchoprovocation testing in horses. American
and capnography in horses: analysis of measure- Journal of Veterinary Research 60: 174–180
ment reliability. Veterinary Research Communications McDonell WN, Hall LW, Jeffcott LB 1979 Radiographic
25: 137–147 evidence of impaired pulmonary function in laterally
Herholz C, Straub R, Busato A 2001b The variability and recumbent anaesthetised horses. Equine Veterinary
repeatability of indices derived from the single-breath Journal 11: 24–32
diagram for CO2 in horses with chronic obstructive Miller C, Hoffman AM, Hunter J 2000 Thoracoabdominal
pulmonary disease and the effect of lobelin hydrochloride asynchrony failed to grade airway obstructions in foals.
on these indices. Veterinary Research Communications Journal of Applied Physiology 88: 2081–2087
25: 401–412 Nelson R, Hampe DW 1983 Measurement of tracheal mucous
Herholz C, Straub R, Moens Y et al 2001c Statistical shape transport rate in the horse. American Journal of
analysis of volumetric capnograms: evaluation of a new Veterinary Research 44: 1165–1166
approach for the assessment of pulmonary function in Nyman G, Hedenstierna G 1989 Ventilation-perfusion rela-
horses with chronic obstructive pulmonary disease. tionships in the anaesthetised horse. Equine Veterinary
Journal of Veterinary Medicine Series A – Physiology Journal 21: 274–281
Pathology Clinical Medicine 48: 75–84 Nyman G, Lindberg R, Weckner D et al 1991 Pulmonary gas
Herholz C, Straub R, Luthi S et al 2002a Differences in exchange correlated to clinical signs and lung pathology
pulmonary functional indices derived from the single- in horses with chronic bronchiolitis. Equine Veterinary
breath diagram for CO2 (SBD-CO2) in horses related to Journal 23: 253–260
age, sex and usage. Veterinary Research Communications Nyman G, Bjork M, Funkquist P 1999 Gas exchange during
26: 467–478 exercise in standardbred trotters with mild bronchiolitis.
Herholz C, Straub R, Luthi S et al 2002b Validity of Equine Veterinary Journal Supplement 30: 96–101
pulmonary function indices derived from the volumetric Olszewski MA, Zhang XY, Robinson NE 1999 Pre- and post-
capnogram in horses with recurrent airway obstruction junctional effects of inflammatory mediators in horse
(RAO). Research in Veterinary Science 72: 141–146 airways. American Journal of Physiology 277: L327–L333
Herholz C, Straub R, Braendlin C et al 2003a Measure- Petsche VM, Derksen FJ, Robinson NE 1994 Tidal breathing
ment of tidal breathing flow-volume loop indices in flow-volume loops in horses with recurrent airway
horses used for different sporting purposes with and obstruction (heaves). American Journal of Veterinary
without recurrent airway obstruction. Veterinary Record Research 55: 885–891
152: 288–292 Rollin F, Desmecht D, Verbanck S et al 1996 Multiple-breath
Herholz CP, Gerber V, Tschudi P et al 2003b Use of volumetric washout and washin experiments in steers. Journal of
capnography to identify pulmonary dysfunction in horses Applied Physiology 81: 957–963
with and without clinically apparent recurrent airway Roy R, Powers SR Jr, Kimball WR 1974 Estimation of
obstruction. American Journal of Veterinary Research respiratory parameters by the method of covariance
64: 338–345 ratios. Computers in Biomedical Research 7: 21–39
Seaman J, Erickson BK, Kubo K et al 1995 Exercise induced oscillometry measurements in horses. Veterinary Journal
ventilation/perfusion inequality in the horse. Equine 168: 259–269
Veterinary Journal 27: 104–109 Votion D, Vandenput S, Duvivier H et al 1997 Analysis of
Soma LR, Beech J, Gerber NH 1987 Effects of cromolyn in equine scintigraphical lung images. Veterinary Journal
horses with chronic obstructive pulmonary disease. 153: 49–61
Veterinary Research Communications 11: 339–351 Votion D, Vandenput S, Duvivier D H et al 1998 Scinti-
Stadler P, Deegen E 1986 Diurnal variation of dynamic graphical evaluation of alveolar clearance in horses.
compliance, resistance and viscous work of breathing in Veterinary Journal 156: 51–58
normal horses and horses with lung disorders. Equine Votion D, Ghafir Y, Vandenput S et al 1999a Analysis of
Veterinary Journal 18: 171–178 scintigraphical lung images before and after treatment of
Tomasic M, Mann LS, Soma LR 1997 Effects of sedation, horses suffering from chronic pulmonary disease.
anesthesia, and endotracheal intubation on respira- Veterinary Record 144: 232–236
tory mechanics in adult horses. American Journal of Votion D, Vandenput S N, Duvivier D H et al 1999b Alveolar
Veterinary Research 58: 641–646 clearance in horses with chronic obstructive pulmonary
Turgut K, Sasse HH 1989 Influence of clenbuterol on disease. American Journal of Veterinary Research
mucociliary transport in healthy horses and horses with 60: 495–500
chronic obstructive pulmonary disease. Veterinary Wagner PD, Naumann PF, Laravuso RB 1974 Simultaneous
Record 125: 526–530 measurement of eight foreign gases in blood by gas chro-
van Erck E, Votion D M, Kirschvink N et al 2003 Use of the matography. Journal of Applied Physiology 36: 600–605
impulse oscillometry system for testing pulmonary Young SS, Hall LW 1989 A rapid, non-invasive method for
function during methacholine bronchoprovocation in measuring total respiratory impedance in the horse.
horses. American Journal of Veterinary Research Equine Veterinary Journal 21: 99–105
64: 1414–1420 Young SS, Tesarowski D 1994 Respiratory mechanics of
van Erck E, Votion D, Art T et al 2004a Measurement of horses measured by conventional and forced oscillation
respiratory function by impulse oscillometry in horses. techniques. Journal of Applied Physiology 76: 2467–2472
Equine Veterinary Journal 36: 21–28 Young SS, Tesarowski D, Viel L 1997 Frequency dependence
van Erck E, Votion D, Kirschvink N et al 2004b Influence of forced oscillatory respiratory mechanics in horses
of breathing pattern and lung inflation on impulse with heaves. Journal of Applied Physiology 82: 983–987
Treadmill Endoscopy
16 Safia Barakzai
High-speed treadmill examination of the equine athlete research work (Stick & Derksen 1989, Kannegieter & Dore
has become an indispensable tool for assessment of the 1995, Tetens et al 1996, Ducharme et al 2003). In fact
upper respiratory tract (URT), for both clinical and research repeated pre- and post-treatment HSTE represents the
purposes. The use of high-speed treadmill endoscopy gold standard for assessment of the efficacy of any medical
(HSTE) has provided clinicians with a gold standard or surgical treatment for naturally occurring dynamic
for accurately identifying dynamic causes of upper air- disorders of the URT. However, as a result of practical
way obstruction which are not present at rest, such as and economic considerations, this is unfortunately rarely
intermittent dorsal displacement of the soft palate, vocal possible in clinical practice (Franklin et al 2002, Barakzai
fold or arytenoid cartilage collapse, nasopharyngeal col- et al 2003).
lapse, intermittent epiglottal entrapment, axial devia-
tion of the aryepiglottic folds, and epiglottic retrover-
sion. These conditions could previously only be speculated
HSTE Equipment, Patient Preparation,
upon in horses that made abnormal respiratory noises
and Training
during exercise. Endoscopic examination during nasal Conducting a high-speed treadmill examination is a labor-
occlusion or after swallowing at rest, or immediately intensive procedure that requires experienced personnel
post exercise may alert the clinician’s suspicions to and expensive equipment. A minimum of three handlers
the possibility of various disorders occurring at exercise, (plus the endoscopist) are necessary – one to operate the
but they do not accurately replicate the appearance and treadmill, one to steady the horse’s head and one to stand
function of the URT at exercise. However, even treadmill at the side of the horse and encourage it to move forward.
testing does not reproduce racing conditions, so that when It is strongly recommended that handlers positioned in
horses are taken to the point of fatigue on a treadmill, the immediate vicinity of the exercising horse should
the level of exertion may not replicate that of a race. wear safety helmets.
Factors such as the weight of the jockey, the excitement or The treadmill itself should be housed in a room large
stress of race day and varying underfoot conditions cannot enough to safely maneuver both the animal and the
be reproduced in an exercise laboratory, and this may equipment. For racehorses, the treadmill must be capable
explain why an endoscopic diagnosis is not achieved during of speeds of up to 14 m/second and an incline of up to 10°
HSTE for a proportion of horses with a history of abnormal uphill, to replicate racing conditions as accurately as
respiratory noise and poor performance during racing possible (Fig. 16.1). The use of an incline allows the animal
(Lane 1999). to perform increased work effort at submaximal speeds.
“Dynamic” disorders of the URT only become apparent Rails should be present on either side of the treadmill
during exercise because of the dramatically increased belt to maintain the horse’s position and protect handlers.
volume of air moving through the tract at this time – Cooling fans (either fixed overhead or moveable units
from 4 liters/second in a resting horse to approximately which can be positioned in front of the horse) must be
75 liters/second in a galloping horse (Parente 1997). To used in warm weather to increase sweat evaporation in the
transport such sizeable volumes of air in and out of the exercising horse and prevent hyperthermia.
lungs and meet the horse’s increased oxygen requirement, Before any horse is exercised on a treadmill, a full
large subatmospheric pressures must be generated within clinical examination should be performed, including
the respiratory tract during inspiration. These subatmos- examination for lameness, to rule out conditions that
pheric pressures tend to collapse the non-rigid parts of the may render the horse unsuitable for high-speed exercise.
upper airway such as the nasopharynx and larynx, and A resting endoscopic examination may reveal obvious
active muscular effort is required to resist such collapse and structural or functional abnormalities in some horses,
maintain an adequate, functional airway. which will then not require an HSTE examination to make
HSTE is also useful in horses that have previously a definitive diagnosis. Ideally, the horse should be fit at
undergone surgery of the URT, for both clinical cases and the time of examination, as this maximizes the chance of
235
236 16 Treadmill Endoscopy
Fig. 16.1. Horse galloping on the treadmill while undergoing HSTE. Note the uphill incline used to
maximize work effort.
diagnosing a suspected problem, and minimizes the risk of horses should be comfortable working at a variety of
injury or of postexercise myopathy. If the horse is not fit, different gaits (including galloping at close to maximal
this should be taken into account during the exercise speed) with smooth transitions between gaits before
sessions. Shoes should be left on, and loose shoes should HSTE is attempted.
be re-fitted because if the horse “throws” a shoe whilst
exercising on the treadmill, the fast-moving flying metal Exercise test protocol
object can cause serious injury to personnel. Neoprene
exercise boots are worn on all four lower limbs, and rubber There are many variations in testing protocol between the
over-reach boots on the front feet, to prevent injuries clinics that perform HSTE (Morris 1991, Parente 1996,
caused by interference. If a heart rate monitor is to be used, Ducharme et al 1998). Protocols involving evaluat-
this is positioned under the safety harness, which is placed ing horses when exercising at various percentages of
around the horse’s girth. This harness can be attached maximum heart rate (HRmax) require a separate exercise
to the overhead safety “cut-out” line which will stop the test to be performed initially to establish what this value
treadmill belt if for some reason excessive tension is placed is, and are therefore not as useful as alternative methods
upon it, for example if the horse falls or does not keep up for evaluation of clinical cases. Use of a heart rate monitor
with the treadmill speed, causing it to be carried backwards is, however, recommended to determine the horse’s heart
on the belt. A nylon halter or a bridle may be used on the rate relative to its speed. A heart rate of approximately
horse’s head, depending on its temperament and thus the 220 beats/min (bpm) guarantees that the horse is at
amount of control required. Hobbles and harness are maximal exertion (Parente 1996), and heart rates in excess
recommended for pacing standardbreds and other horses of 240 bpm suggest that the test should be terminated
which usually run in such equipment, such as Norwegian (Ducharme et al 1998).
coldblooded trotters. A rapid incremental test is usually considered to be
Horses should be acclimatized to the treadmill before the most useful for clinical HSTE evaluations, particularly
HSTE is performed. This usually requires admission of the for National Hunt-type racehorses, which race over long
horse to the hospital so that between one and three distances. A typical protocol requires a heart rate monitor
training sessions can be scheduled, although in some and is given in Table 16.1.
clinics, treadmill testing is performed on an outpatient For racehorses that sprint over short distances, a
basis. The length of time required to acclimatize to the thorough warm-up period followed by a very rapid acceler-
treadmill varies widely between individual horses, and ation to close to maximal speed (usually 12–14 m/second)
16 Treadmill Endoscopy 237
Table 16.1. A typical protocol for rapid

incremental high speed treadmill testing
Phase 1: Warm up – 2 m/s for 4 min, 4.5 m/s for 1 min, 7 m/s
for 2 min
Phase 2: Walk until heart rate < 70 bpm
Phase 3: Gradually accelerate to 9 m/s, incline treadmill to 3°
(for thoroughbreds).
Then accelerate to 11 m/s for 600 m, 12 m/s for
600 m, 14 m/s for 1,600 m before decelerating to
12 m/s for 600 m.
Most horses will not be capable of completing all these steps
as described, but they should be exercised as close to the
desired speed as possible for the predetermined distances.
Reproduced from Parente 1996, with permission.
Table 16.2. Submaximal exercise test, suitable

for unfit racehorses or yearlings
● The horse is worked at 4 m/s for the first 4 min, of which
3 min is performed on the flat, and the final minute is
performed up a 3°–5° incline.
● The treadmill is then accelerated to 6 m/s for 800 m, 8 m/s
for 800 m and 8.5 m/s for 1,600 m or until the animal
fatigues.
Reproduced from Ducharme et al 1998, with permission.
Fig. 16.2. Attachment of endoscope to the halter using Velcro.
up an incline, which is maintained until the horse begins to

fatigue, may be more useful to mimic racing conditions and
reduce the risk of musculoskeletal injury. Adjunctive diagnostic tests
Unfit racehorses (especially yearlings) or show horses
can be worked using a submaximal test (Table 16.2) There are many additional techniques that can be
(Ducharme et al 1998). performed on horses undergoing HSTE which include
recording of respiratory noises made at exercise, intra-
High-speed treadmill video-endoscopy pharyngeal and intratracheal pressure measurements,
respiratory gas analysis, collection of arterial and venous
Video-endoscopic equipment with either digital or video blood samples, exercise electrocardiograms, and high-speed
recording is essential if HSTE is to be performed because gait analysis (Morris & Seeherman 1991, Parente 1996,
very rapid movements of the nasopharynx and larynx are 1997, Ducharme et al 1998, Franklin et al 2003).
often seen more clearly during a slow-motion playback.
After the horse has undergone a warm-up period, the
treadmill is stopped, a twitch is applied if necessary, and a
Normal Endoscopic Appearance
flexible video-endoscope is passed up the right ventral
of the URT During HSTE
meatus. The end of the endoscope should be positioned During exercise, the arytenoid cartilages should attain and
just rostral to the epiglottis to allow clear visualization of maintain full abduction (most of the corniculate process
the caudal nasopharynx and larynx. Many methods have lies horizontally at 90° to the midline of the rima glottidis)
been used to secure the endoscope in the nasopharynx by bilaterally and no movement of the arytenoid cartilages
attaching it to the head collar, including Velcro straps and (apart from during swallowing) should occur until ven-
use of a latex Penrose drain (Fig. 16.2). Some movement tilation returns to resting levels (Fig. 16.3). The roof of the
of the end of the endoscope within the nasopharynx is nasopharynx is normally displaced ventrally at the end of
inevitable, and high-quality video-endoscopic equipment is expiration (Morris & Seeherman 1988) and this finding
necessary to minimize the detail lost by movement blur. should only be considered abnormal if it obstructs more
Dynamic Obstructions of the URT

Intermittent dorsal displacement
of the soft palate (DDSP)
Intermittent DDSP is the most commonly diagnosed cause
of URT obstruction in horses undergoing HSTE examina-
tion for investigation of poor performance (Morris &
Seeherman 1991, Lane 1999). Parente and Martin (1995)
found that many horses which dorsally displaced their soft
palates during nasal occlusion at rest (Fig. 16.4) did not
experience DDSP at exercise, and conversely, some horses
that did not displace their soft palates during nasal
occlusion at rest did develop DDSP during HSTE. Therefore,
the overall correlation between resting and HSTE findings
with respect to DDSP is poor.
The incidence of ulceration of the caudal border of the
soft palate in horses that experience DDSP at exercise is
historically reported to be high (up to 90%; Hogan et al
2002, Rodgerson 2004). In contrast, studies that have
definitively diagnosed DDSP using HSTE have found a
Fig. 16.3. Normal larynx at exercise. Note the bilaterally symmetrically
fully abducted arytenoids.
much lower incidence of soft palate ulceration in DDSP-
affected horses (10%; Kannegieter & Dore 1995, Parente
et al 2002). It is possible that these differences may reflect
breed differences in the study population of these authors.
Epiglottic hypoplasia and flaccidity have also been reported
than one-third of the rima glottidis (Ducharme et al 1998). to be associated with intermittent DDSP (Tulleners et al
The horse remains able to swallow during strenuous 1997, Robertson 1998), but many such studies have
exercise, during which full adduction of both arytenoids not confirmed using HSTE that DDSP occurs. There are
should occur transiently, followed by a rapid return to the clinical and experimental data showing that the epiglottis
fully abducted position. During swallowing, the constrictor is not essential to maintain the palate in a normal sub-
action of the circular muscles of the pharyngeal walls may epiglottic position (Holcombe et al 1997, Parente et al
be evident very transiently. This can be differentiated from 1998), and other studies that have confirmed all DDSP
cases of circumferential nasopharyngeal collapse by the cases using HSTE have found that epiglottic length and/or
timing and transient duration of the constriction during appearance in the vast majority of these horses is normal
swallowing. Normal horses may swallow several times (Kannegieter & Dore 1995, Rehder et al 1995, Parente et al
during submaximal exercise, but repeated swallowing 2002). In addition, research has shown that contraction
usually indicates an irritating stimulus (Morris 1991). of the hyoepiglotticus muscles (whose activity increases
A B C D
Fig. 16.4. DDSP induced by nasal occlusion at rest. (A) The epiglottis appears to be pulled ventrally by the action of the hyoepiglotticus
muscles. (B) The soft palate begins to billow dorsally during inspiration. (C) The palate flips up over the epiglottis. (D) The caudal border of
the palate has displaced dorsal to the epiglottis, and remains displaced despite numerous attempts at swallowing.
A B C D
Fig. 16.5. Sequence of events related to DDSP. (A) Larynx appears normal at start of exercise. (B) Palatal instability of the soft palate. Note the
moderate bilateral axial displacement of the aryepiglottic folds as the epiglottic tip is lifted dorsally by the billowing soft palate. (C) and
(D) DDSP has now occurred – during inspiration, the displaced palate is “sucked” progressively dorsally, almost completely obstructing the
rima glottidis. Reproduced from Barakzai 2006, with permission.
with increased intensity of breathing) causes confor-

mational changes of the epiglottis in some horses, where
the epiglottis assumes a similar shape to that described in
dynamic epiglottic hypoplasia or epiglottic flaccidity (Dixon
1995, Holcombe et al 2002). It has been hypothesized that
dynamic changes in the appearance of the epiglottis during
nasal occlusion or exercise may simply be a result of the
normal physiologic action of the hyoepiglotticus muscle
and not a conformational abnormality of the epiglottis
(Holcombe et al 2002).
Palatal instability (Fig. 16.5) (vertical “billowing” of the
soft palate without displacement of its caudal border) is a
common endoscopic observation before the occurrence of
DDSP (Kannegieter & Dore 1995, Lane 1999, PM Dixon
personal communication). This wave-like billowing is
thought to begin at the junction of the hard and soft
palates, and progresses caudally (Lane 1999). As the soft
palate “billows” dorsally, it may lift the epiglottis and in
turn cause a degree of axial deviation of the aryepiglottic
folds prior to DDSP occurring (Fig. 16.5; Dart et al 2001,
Rodgerson 2004, PM Dixon personal communication).
Fig. 16.6. The base of the epiglottis has “sunk” below the caudal
Some horses may displace the base of the epiglottis for border of the soft palate prior to DDSP occurring.
a time before the soft palate fully displaces (Fig. 16.6)
(Parente 1997).
After the soft palate becomes displaced dorsal to the
epiglottis, it causes a marked obstruction of the rima
glottidis (Fig. 16.5) and affected horses usually make a palatal cysts may predispose horses to intermittent DDSP,
loud expiratory, and possibly an inspiratory, “gurgle” and and therefore a thorough examination of the entire region
are often unable to continue galloping at high speed. should be completed before electing to perform surgery on
Interestingly, in one study, 38% of horses (and particularly the soft palate or adjacent structures.
standardbreds) that experienced DDSP at exercise on the
treadmill did not have a history of abnormal respiratory Recurrent laryngeal neuropathy (RLN)
noise at exercise (Parente et al 2002). Clinically normal
horses may transiently displace their soft palates at exercise RLN is the second most commonly diagnosed cause of URT
but will typically swallow and replace the palate to a obstruction in horses undergoing HSTE examination for
normal subepiglottic position quickly. investigation of poor performance. Endoscopic grading of
It should be remembered that a large number of other laryngeal function at rest is described in Chapter 34.
disorders such as epiglottal entrapment, subepiglottic cysts, Endoscopic grading of laryngeal function at exercise can
epiglottitis, congenital and iatrogenic soft palate defects and be categorized as grade A (Fig. 16.3), B (Fig. 16.7) or C
A B
Fig. 16.7. Two horses during HSTE with grade B laryngeal function – partial abduction of the left
arytenoid is maintained at maximal exertion in both. (A) No vocal fold collapse has occurred. (B) The left
vocal fold is collapsing axially to cause respiratory obstruction and abnormal noise. Reproduced from
Barakzai 2006, with permission.
(Figs 16.8 and 16.15), and definitions of these grades are completely ruled out on the basis of resting endoscopic
shown in Table 16.3. findings alone, and if abnormal inspiratory sounds are
The endoscopic grade of laryngeal function at rest (I–IV) present during exercise, clinicians who do not have
(see Chapter 34) will usually give an indication of laryn- facilities for treadmill testing should not immediately
geal function at exercise, with the majority of resting grade discount RLN as a cause of URT obstruction in horses with
I and II horses (i.e. those which are able to attain and grade I and II RLN at rest.
maintain full bilateral arytenoid abduction) being classified HSTE is particularly useful for evaluation of horses with
as grade A at exercise (Parente & Martin 1995, Lane resting grade III RLN. One study which evaluated 26
2003), and all those with grade IV RLN at rest being racehorses with resting grade III RLN found that at
classified as grade C at exercise (Morris & Seeherman 1990, maximal exercise (12 m/second for standardbreds and
Hackett et al 1998, Lane 2003). Occasionally, horses with 14 m/second for thoroughbreds), 4% were grade A, 19%
grade I or II RLN at rest may experience some degree of were grade B, and 77% were grade C (Hammer et al 1998).
collapse of the arytenoid cartilage or vocal fold during Conversely, another study (Rakestraw et al 1991) found
HSTE (Kannegieter & Dore 1995, Lane 2003). Therefore that five out of six horses with resting grade III RLN were
the presence of exercise-related dynamic RLN cannot be able to maintain full abduction at exercise, but these horses
A B C
Fig. 16.8. (A–C) Horse with grade C laryngeal function shown during HSTE. There is progressive complete collapse of the left arytenoid across
the midline until it completely obstructs the contralateral side of the rima glottidis during inspiration.
laryngoplasty (Lane 1993, Ducharme et al 1998, Barakzai

Table 16.3. Grading system of laryngeal function*
as assessed in the horse during exercise† & Dixon 2003). Therefore, for horses with resting grade III
RLN, HSTE allows differentiation between horses that
Laryngeal do and do not require surgery, and if surgery is required,
grade Definition
will guide the surgeon as to which surgical procedure may
A Full abduction of the arytenoid cartilages be most suitable (Stick & Derksen 1989, Ducharme et al
during inspiration. 1998, Barakzai & Dixon 2003).
B Partial abduction of the affected arytenoid
cartilages (between full abduction and the Intermittent epiglottal entrapment
resting position).
Entrapment of the epiglottic cartilage in the glossoepiglottic
C Abduction less than resting position including
collapse into the contralateral half of the and aryepiglottic folds is commonly diagnosed in the
rima glottidis during inspiration. resting horse but occasionally occurs intermittently as a
dynamic cause of respiratory obstruction at exercise
*Description generally refers to the left arytenoid cartilage in reference (Morris & Seeherman 1990, 1991, Kannegieter & Dore
to the right. However, this grading system can apply to the right side 1995) (Fig. 16.9). Horses with epiglottal entrapment may
(i.e. right grade III.1-B).
†Updated from Rakestraw et al 1991, with permission. be asymptomatic or demonstrate a range of clinical signs.
Respiratory noise varies from a vibrant expiratory noise to
both inspiratory and expiratory noises or no abnormal
noise at all during fast work (Morris 1991). Similarly, some
cases of epiglottal entrapment do not appear to impair
only ran at a maximum speed of 8.5 m/second. Horses ventilation, even at maximal exercise and this is thought to
with grade B RLN during exercise often have the same or a be related to individual variation in the tightness of the
better degree of arytenoid abduction than that obtained entrapping fold of mucosa (Morris 1991). During inspira-
after laryngoplasty (Dixon et al 2003). It has also been tion, the subatmospheric pressures within the airway
reported that some horses may maintain adequate abduc- are greater dorsal to the entrapping fold than ventral to it,
tion of the arytenoid cartilage during exercise but that and this pressure differential will force the entrapping fold
the vocal fold and laryngeal ventricle of the affected side to be drawn ventrally, towards the epiglottis (Morris &
can collapse axially on inspiration and partially obstruct Seeherman 1990). During expiration, the entrapping mem-
the airway (Fig. 16.7B) (Kannegieter & Dore 1995, Dart branes fill with air, ballooning outwards and significantly
et al 2001). In these cases, vocalcordectomy or ventricu- obstructing airflow in many cases. Epiglottal entrapment,
locordectomy should be an effective surgical treatment whether intermittent or persistent, is frequently associated
and is associated with fewer complications than prosthetic with DDSP during exercise (Kannegieter & Dore 1995).
A B C
Fig. 16.9. Horse with epiglottal entrapment during HSTE: (A) during inspiration, normal epiglottic outline is not visible because of the entrap-
ping mucosal fold; (B) during expiration, the entrapping mucosa fills with air and causes significant airway obstruction; (C) epiglottal entrapment
predisposes to DDSP which has occurred in this photograph. The tip of the entrapped epiglottis can be seen bulging dorsally against the ventral
aspect of the soft palate.
A B
Fig. 16.10. ADAF: (A) bilateral ADAF – the aryepiglottic fold does not pass the line of the vocal fold;
(B) severe bilateral right-sided ADAF – the aryepiglottic fold has moved halfway between the vocal cord
and midline.
Axial deviation of the aryepiglottic Table 16.4. Definition of mild, moderate

folds (ADAF) and severe ADAF (King et al 2001)
In ADAF, the membranous portion of the aryepiglottic Grade % obstruction

fold, extending between the lateral corniculate process of ADAF Definition of ADAF grade of glottis
of the arytenoid cartilage and the lateral edge of the Mild Axial collapse of one or both <20%
epiglottis, deviates axially during inspiration at stren- aryepiglottic folds, with folds
uous exercise (Kannegieter & Dore 1995, King et al 2001). remaining abaxial to the vocal
The aryepiglottic folds are usually tensed between the cords
arytenoids and the epiglottis, and slight loss of abduction of Moderate Axial deviation of one or both 21–40%
the former or elevation of the latter will remove tension aryepiglottic folds less than
from these folds and so predispose to ADAF. This disorder is halfway between the vocal
observed in many exercising horses to a mild, clinically cord and midline
insignificant degree (Fig. 16.10A) but occasionally can be Severe Collapse of one or both 41–63%
characterized as moderate or severe (Fig. 16.10B) and cause aryepiglottic folds more than
significant airway obstruction (Table 16.4). The degree of halfway between the vocal cord
and midline
deviation in some horses can progress from mild through
to severe, depending on the degree of fatigue (King et al
Reproduced from King et al 2001, with permission.
2001). In horses with ADAF during HSTE, concurrent
dynamic upper airway disorders have been reported in
36.5% of cases (King et al 2001). These include axial
collapse of one or both vocal cords, left laryngeal hemi-
paresis, intermittent DDSP, right laryngeal dysfunction and (Fig. 16.11) or dorsoventral (Fig. 16.12) (Parente 1997).
dorsal pharyngeal collapse, although the relationship Collapse of the roof of the nasopharynx is considered
between ADAF and these concurrent dynamic URT dis- abnormal if it obstructs more than one-third of the rima
orders is unknown. glottidis (Ducharme et al 1998). Any lateral collapse of
the nasopharynx that encroaches over the rima glottidis
is also considered abnormal (Ducharme et al 1998). In
Nasopharyngeal collapse more severely affected horses, nasopharyngeal collapse is
usually associated with abnormal respiratory noises, which
The caudal two-thirds of the nasopharynx lack rigid may vary from a low-intensity, low-pitched “grunt” to a
support and rely on neuromuscular function to resist vibrant inspiratory and/or expiratory “snore” or “gurgle”.
collapse during inspiration (Strand & Staempfli 1993). Nasopharyngeal collapse may occasionally be associated
Dynamic nasopharyngeal collapse is, therefore, thought to with flexion of the head and neck, and affected horses may
be related to neuromuscular dysfunction of the naso- appear normal when the head and neck are extended
pharynx. It can be classified as lateral, circumferential during HSTE (Dixon & Barakzai, personal observations).
B
D
Fig. 16.11. Circumferential nasopharyngeal collapse: (A) horse at the start of HSTE, (B) nasopharyngeal collapse begins, (C) and (D) progressive
collapse of the nasopharynx, leaving a very limited airway during every inspiration. Note that this type of collapse can be differentiated from
a normal “swallow” by its timing (instigated during inspiration) and duration (lasts longer than a swallow). Reproduced from Barakzai 2006,
with permission.
Fourth branchial arch defects (4-BAD,

Nasopharyngeal collapse can be induced experimentally by cricopharyngeal–laryngeal dysplasia)
topical local anesthesia of the laryngeal mucosa, and
it has therefore been hypothesized that dysfunction of The vast majority of horses with 4-BAD have abnormalities
the mucosal mechanoreceptors and the branches of the which may be detected during resting endoscopy, but a
superior laryngeal nerve may be involved in this disorder small percentage of affected horses will be normal at rest,
(Holcombe et al 2001). Dysfunction of the stylopharyngeus with a variety of abnormalities evident on HSTE (Lane
muscles may have a role in dorsal naso-pharyngeal collapse 2001). These include dynamic rostral displacement of the
(Tessier et al 2004, Tessier et al 2005). palato-pharyngeal arch (Fig. 16.13), dynamic right-sided
Fig. 16.12. Dorsal nasopharyngeal collapse. Reproduced from Barakzai Fig. 16.13. Dynamic unilateral rostral displacement of the palato-
2006, with permission. pharyngeal arch. This horse had 4-BAD syndrome but was normal
during resting endoscopy. During HSTE, the right palato-pharyngeal
arch became rostrally positioned over the right arytenoid cartilage.
Some ADAF of the right aryepiglottic fold has also occurred.
arytenoid cartilage and vocal fold collapse, bilateral vocal
fold collapse (right > left), bilateral ADAF with DDSP, and
unilateral right-sided ADAF (Lane 2001).
Epiglottic retroversion and axial collapse

of the lateral margins of the epiglottis
Epiglottic retroversion is a rare disorder observed during
HSTE where the epiglottis is retroverted dorsally and
caudally into the rima glottidis on each inspiration (Dixon
1995, Parente et al 1998). In one horse, the epiglottis
appeared to roll up in a tube-like fashion before lifting
dorsally (Parente et al 1998). The few documented cases
have occurred in horses with a history of severe upper
respiratory infection and possible disruption of the normal
hyoid musculature (Parente et al 1998). Although the
epiglottis may become fully retroverted, the soft palate
remains stable in its normal position at all times during the
breathing cycle. This condition can be reproduced by local
anesthesia of the hypoglossal nerve, which innervates the
hyoepiglotticus and geniohyoid muscles that control
epiglottic position (Holcombe et al 1997).
Axial collapse of the lateral margins of the epiglottis
is diagnosed when the left or right sides of the epiglottis
are observed to vibrate or displace axially during inspira- Fig. 16.14. HSTE photograph of a Norwegian coldblooded trotter
tion, often at the same time as production of an abnormal during exercise with induced neck flexion. There is bilateral loss of
abduction of the arytenoid cartilages and bilateral axial collapse of the
respiratory noise. It can occur as a lone abnormality, but
vocal folds and the aryepiglottic folds. The left lateral margin of the
has also been reported to occur with ADAF and bilateral epiglottis is also mildly collapsed in an axial direction. Photograph
arytenoid cartilage and vocal fold collapse (Fig. 16.14) courtesy of E. Strand, Norwegian School of Veterinary Medicine and
(Kannegieter & Dore 1995, Dart et al 2001, Strand et al reproduced from Barakzai 2006, with permission.
A B C
Fig. 16.15. Sequence of photographs from

horse with grade C RLN and ADAF. (A) Begin-
ning of treadmill exercise (this horse was
graded III.2 at rest): the left arytenoid is mod-
erately abducted. (B) Start of canter: the left
arytenoid starts to move axially on inspiration
but is still moderately abducted. (C) The left
vocal fold begins to collapse axially. (D) At
the gallop: the left arytenoid loses abduction
during inspiration and progressively assumes
a more midline position. The vocal fold is still
collapsed axially. (E) At maximal exertion:
ADAF is now also present affecting the right
D E
aryepiglottic fold.
2004). It is sometimes associated with epiglottic hypoplasia et al 2004). Given that arytenoid function is bilaterally
or flaccidity, which is observed during resting endoscopy, normal in affected horses when they are run with their
but also occurs in horses with a normal epiglottic appear- head and neck extended, it is unlikely that this condition is
ance at rest. a manifestation of bilateral laryngeal neuropathy. It is
hypothesized that this abnormality is the result of a failure
Bilateral arytenoid cartilage and vocal of the arytenoid cartilages’ ability to abduct, secondary to
fold collapse conformational changes in the throat region associated
with head flexion and the use of particular tack, in
This disorder has been reported in association with head predisposed horses (Strand et al 2004).
flexion in Norwegian coldblooded trotter racehorses (Strand
et al 2004), but could possibly occur in other breeds which Multiple abnormalities (Figs 16.5 and 16.15)
are exercised with a similar head-carriage. Affected horses
present with a history of abnormal respiratory noise and Multiple abnormalities of the URT have been reported
poor performance, and initial resting endoscopy and HSTE during HSTE in between 7 and 38% of horses presenting
(performed without tension applied to the reins) do not with abnormal respiratory noise or poor performance at
reveal URT abnormalities. When the horses undergo HSTE exercise (Kannegieter & Dore 1995, Dart et al 2001,
wearing full harness race-tack, including a “head-check”, Durando et al 2002, Parente et al 2002). Multiple abnor-
and tension is applied to the bit via long reins, bilateral malities have been found to be more commonly associated
dynamic collapse of both vocal folds and reduced abduc- with abnormal exercising blood gases than single URT
tion of both arytenoid cartilages occurs (Fig. 16.14). disorders (Durando et al 2002). Therefore, treadmill test-
Concurrent moderate ADAF associated with mild to ing has been recommended for horses when an abnormal
moderate dorsoaxial collapse of the lateral edges of the URT is observed at rest, to make a complete diagnosis
epiglottis occurred in two of the five reported cases (Strand (Dart et al 2001).
REFERENCES mechanics in exercising horses. American Journal of

Veterinary Research 62: 1706–1710
Barakzai SZ 2006 Handbook of Equine Respiratory Endoscopy. Holcombe SJ, Cornelisse CJ, Berney C et al 2002 Electro-
WB Saunders, Philadelphia. myographic activity of the hyoepiglotticus muscle and
Barakzai SZ, Dixon PM 2003 Ventriculocordectomy for treat- control of epiglottis position in horses. American Journal
ment of recurrent laryngeal neuropathy: 75 cases in a of Veterinary Research 63: 1617–1621
mixed population of horses. Proceedings of the Havemeyer Kannegieter NJ, Dore ML 1995 Endoscopy of the upper
Foundation Workshop on Idiopathic Laryngeal Hemiplegia, respiratory tract during treadmill exercise: a clinical
R&W Publications, Newmarket, UK pp.71–73 study of 100 horses. Australian Veterinary Journal
Barakzai SZ, Johnson VS, Baird DH et al 2003 The efficacy of 72: 101–107
composite surgery for treatment of dorsal displacement King DS, Tulleners EP, Martin BB et al 2001 Clinical experi-
of the soft palate in 53 racing Thoroughbreds. Equine ences with axial deviation of the ary-epiglottic folds in
Veterinary Journal 36: 175–179 52 racehorses. Veterinary Surgery 30: 151–160
Dart AJ, Dowling BA, Hodgson DR et al 2001 Evaluation of Lane JG 1993 Recurrent laryngeal neuropathy. Proceedings of
high-speed treadmill videoendoscopy for diagnosis of the 15th Bain Fallon Lectures, Australian Equine Veteri-
upper respiratory tract dysfunction in horses. Australian nary Association. Australian Veterinary Association,
Veterinary Journal 79: 109–111 Artamon, pp.173–192
Dixon PM 1995 A review of the role of the epiglottis in equine Lane JG 1996 Larynx. In: Traub-Dargatz JL, Brown CM
upper airway obstruction. Equine Veterinary Education (editors) Equine Endoscopy, 2nd edn. Mosby, St Louis,
7: 131–139 pp.74–96
Dixon RM, McGorum BC, Railton DI et al 2003 Long-term Lane JG 1999 Endoscopy during high speed treadmill exercise:
survey of laryngoplasty and ventriculocordectomy what are the advantages of this technique over endoscopy
in an older, mixed-breed population of 200 horses. Part during quiet breathing? In: Proceedings of the BEVA
1: Maintenance of surgical arytenoid abduction and Specialist Meeting on Equine Sports Science, Bristol, UK
complications of surgery. Equine Veterinary Journal Lane JG 2001 Fourth branchial arch defects in thorough-
35: 389–396 bred horses: a review of 60 cases. Proceedings of the
Ducharme NG, Hackett RP, Stick JA 1998 Treadmill diag- World Equine Airways Symposium and Veterinary and
nostics for upper airway abnormalities. In: White NA, Comparative Respiratory Society Annual Conference,
Moore JN (editors) Current Techniques in Equine Surgery Edinburgh, UK
and Lameness. WB Saunders, Philadelphia, pp.119–121 Lane JG 2003 Differences between resting and treadmill
Ducharme NG, Hackett RP, Woodie JB 2003 Investigations endoscopic findings in regard to RLN. Proceedings of
into the role of the thyrohyoid muscles in the patho- the Havemeyer Foundation Workshop on Idiopathic
genesis of dorsal displacement of the soft palate in Laryngeal Hemiplegia, R&W Publications, Newmarket,
horses. Equine Veterinary Journal 35: 258–263 UK, p.23
Durando MM, Martin BB, Hammer EJ et al 2002 Dynamic Morris EA 1991 Dynamic evaluation of the equine upper
upper airway changes and arterial blood gas parameters respiratory tract. Veterinary Clinics of North America;
during treadmill exercise. Equine Veterinary Journal Equine Practice 7: 403–416
Supplement 34: 408–412 Morris EA, Seeherman HJ 1988 The dynamic evaluation
Franklin SH, Naylor RRJ, Lane JG 2002 The effect of a tongue- of upper respiratory function in exercising horses.
tie in horses with dorsal displacement of the soft palate. Proceedings of the American Association of Equine
Equine Veterinary Journal Supplement 34: 430–433 Practitioners 34: 159–160
Franklin SH, Usmar SG, Lane JG et al 2003 Spectral analysis of Morris EA, Seeherman HJ 1990 Evaluation of upper respi-
respiratory noise in horses with upper airway disorders. ratory tract function during strenuous exercise in
Equine Veterinary Journal 35: 264–268 racehorses. Journal of the American Veterinary Medical
Hackett RP, Ducharme NG, Stick JA 1998 Assessment of Association 196: 431–438
laryngeal and pharyngeal function. In: White NA, Moore Morris EA, Seeherman HJ 1991 Clinical evaluation of poor
JN (editors) Current Techniques in Equine Surgery and performance in the racehorse: the results of 275 evalua-
Lameness. WB Saunders, Philadelphia, pp.117–118 tions. Equine Veterinary Journal 23: 169–174
Hammer EJ, Tulleners EP, Parente EJ et al 1998 Video- Parente EJ 1996 Testing methods for exercise intolerance in
endoscopic assessment of dynamic laryngeal func- horses. Veterinary Clinics of North America; Equine
tion during exercise in horses with grade III left Practice 12: 421–433
laryngeal hemiparesis at rest: 26 cases (1992–1995). Parente EJ 1997 Treadmill endoscopy. In: Traub-Dargatz JL,
Journal of the American Veterinary Medical Association Brown CM (editors) Equine Endoscopy, 2nd edn. Mosby,
211: 399–403 St Louis, pp.106–116
Hogan PM, Paler SE, Congelosi M 2002 Transendoscopic Parente EJ, Martin BB 1995 Correlation between standing
laser cauterization of the soft palate as an adjunctive endoscopic examinations and those made during high-
treatment for dorsal displacement in the racehorse. speed exercise in horses: 150 cases. American Journal of
Proceedings of the American Association of Equine Veterinary Research 41: 170–175
Practitioners 48: 228–230 Parente, EJ, Martin BB, Tulleners EP 1998 Epiglottic
Holcombe SJ, Derksen FJ, Stick JA et al 1997 Effects of bilateral retroversion as a cause of upper airway obstruction in
hypoglossal and glossopharyngeal nerve blocks on two horses. Equine Veterinary Journal 30: 270–272
epiglottic and soft palate position in exercising hoses. Parente EJ, Martin BB, Tulleners EP et al 2002 Dorsal
American Journal of Veterinary Research 58: 1022–1026 displacement of the soft palate in 92 horses during high-
Holcombe SJ, Derksen FJ, Berney C et al 2001 Effect of topical speed treadmill examination (1993–1998). Veterinary
anesthesia of the laryngeal mucosa on upper airway Surgery 31: 507–512
Rakestraw PC, Hackett RP, Ducharme NG et al 1991 Strand E, Hanche-Olsen S, Gronvold A et al 2004 Dynamic
Arytenoid cartilage movement in resting and exercising bilateral arytenoid and vocal fold collapse associated
horses. Veterinary Surgery 20: 122–127 with head flexion in 5 Norwegian Coldblooded Trotter
Rehder BS, Ducharme NG, Hackett RP et al 1995 Measure- Racehorses. Equine Veterinary Education 16: 242–254
ment of upper airway pressures in exercising horses with Tessier C, Holcombe SJ, Derksen FJ et al 2004 Effects of
dorsal displacement of the soft palate. American Journal stylopharyngeus muscle dysfunction on the nasophar-
of Veterinary Research 56: 269–274 ynx in exercising horses. Equine Veterinary Journal
Robertson JT 1998 Dorsal displacement of the soft palate. 36: 318–323
In: White NA, Moore JN (editors) Current Techniques in Tessier C, Holcombe SJ, Derksen FJ et al 2005 Electro-
Equine Surgery and Lameness. WB Saunders, Philadelphia, myographic activity of the stylopharyngeus muscle in
pp.131–135 exercising horses. Equine Veterinary Journal 37: 232–235
Rodgerson D 2004 Treadmill pharyngoscopy and laryn- Tetens J, Derksen FJ, Stick JA et al 1996 Efficacy of prosthetic
goscopy. In: Slovis NM (editor) Atlas of Equine Endoscopy. laryngoplasty with and without ventriculocordectomy as
Mosby, St Louis, pp.225–238 treatments for laryngeal hemiplegia in horses. American
Stick JA, Derksen FJ 1989 Use of videoendoscopy during Journal of Veterinary Research 57: 1668–1673
exercise for determination of appropriate surgical treat- Tulleners E, Stick JA, Leitch M et al 1997 Epiglottic
ment of laryngeal hemiplegia in a colt. Journal of the augmentation for treatment of dorsal displacement
American Veterinary Medical Association 195: 619–622 of the soft palate in racehorses: 59 cases (1985–1994)
Strand E, Staempfli HR 1993 Dynamic collapse of the roof of Journal of the American Veterinary Medical Association
the nasopharynx as a cause of poor performance in a 211: 1022–1028
standardbred colt. Equine Veterinary Journal 25: 252–254
Evaluation of Upper Respiratory
Tract Sounds
17 Frederik J Derksen
exercise, because the large increase in airflow and the large

Introduction
intraluminal pressure swings that occur during exercise
Veterinarians have long recognized that when horses make encourage dynamic airway collapse. Thus, examination of
abnormal respiratory sounds (hereafter referred to as the upper airway in the standing horse is often insufficient
“respiratory noise”) during exercise they often perform for making a diagnosis, and video-endoscopy is often
poorly (Williams 1874). Furthermore, specific respiratory required. Video-endoscopy during exercise requires a high-
noises heard during exercise may indicate the presence speed treadmill, available only at referral institutions.
of distinct respiratory conditions, each with their own Furthermore, examination on the treadmill takes the
pathogenesis and implications for exercise tolerance. For horse out of the environment in which it normally
these reasons, veterinarians of the past listened carefully exercises, and examinations on the treadmill often fail to
for these sounds, and noises such as blowing, snuffling, reveal the cause of the problem identified by the owner.
soft and dry whistling, snoring, roaring, and rattling were Thus, a simple and inexpensive diagnostic technique
described in detail (Williams 1874). Readers of these that can be used in the field would aid in the diagnosis of
accounts, however, have difficulty understanding exactly upper airway disease in horses. Upper airway sound
what sounds are being described, and how these sounds evaluation is such a technique.
relate to specific upper airway conditions cannot be Evaluation of respiratory sound during exercise is also
reliably determined. useful in assessing the effectiveness of surgical procedures
Respiratory sounds do not always occur throughout used in the treatment of upper airway conditions (Derksen
the exercise period. In some instances the sounds are more et al 2001, Brown et al 2003, Brown et al 2004). Upper
obvious at maximum exercise, while in other cases the airway noise is sometimes the only reported clinical sign
sounds are intermittent, or occur as the horse is pulling up. of upper airway obstruction, or it can be accompanied
The listener on the ground therefore is often not in a by exercise tolerance. In show horses, upper airway noise
position to hear these sounds, and the jockey, rider, or is often the most important presenting complaint, as it
driver is distracted by concurrent exercise-related interferes with the aesthetics of riding, and may result in
noises such as those caused by footfall and wind. For reduced grading or even disqualification of the affected
these reasons, in horses with suspected upper airway animal from competition. Thus, in many horses with upper
problems, the history regarding noise production during airway conditions, the objective of surgery is to reduce
exercise is often unreliable and non-specific, and subjective the respiratory noise. In these cases, evaluation of sound
sound evaluation has limited usefulness in reaching a production before and after surgery is a good way to
specific diagnosis. determine surgical success.
In recent years, there has been a growing interest in
respiratory acoustic measurements in people as well as
horses, and advances in computer technology have made
Fundamentals of Sound
sound analysis practical and potentially useful in the A sound wave is the vibration of air. When a sound source
diagnosis of airway disorders (Pasterkamp et al 1997). sets the molecules of the air into vibration, a varying
This chapter will describe how upper airway sound in pressure with the same frequency as the source is pro-
exercising horses can be recorded, analyzed, and used as a duced. Human hearing can detect these varying pressures
diagnostic tool. if the frequency is between 0.02 and 20 kHz and vibrations
Upper airway disorders are common in horses, and are in this frequency range are called sound. In exercising
often difficult to diagnose in the standing animal. For horses, most of the upper airway sound energy is in the
example, dorsal displacement of the soft palate is rarely 0.02–8 kHz range, putting it well within the range of
diagnosed at rest, but it is one of the most common causes human hearing. However, the average human ear is most
of airway obstruction in exercising horses (Raphel 1982, sensitive between 2 and 4 kHz. Thus, while human hearing
Morris & Seeherman 1990, Martin et al 2000). Upper can detect almost the entire frequency range of vibrations
airway obstructions are often more apparent during made by the upper airway, upper airway sounds in the
249
250 17 Evaluation of Upper Respiratory Tract Sounds
2–4 kHz range are most acutely appreciated (Strong & then modified as it passes through the vocal tract. In the
Plintnik 1992). vocal tract, resonant frequencies are emphasized resulting
What is the difference between sound and noise? Noise in bands of sound called formants (Kent 1993).
can be defined as any unwanted or annoying sound, much
as a weed is an unwanted plant. Thus, normal respiratory
sounds made by exercising horses are usually not referred
Methods of Sound Recording
to as noise, while abnormal sounds associated with upper One of the earliest methods of recording respiratory sounds
airway diseases can be considered noises. during exercise in horses involves a radio-stethoscope
Sound has time, frequency, and amplitude charac- (Attenburrow 1978a,b). Using this technique, a micro-
teristics, and analyses of these characteristics can yield phone is placed over the ventral wall of the trachea at any
important information. Time is an important component of point between the fourth and ninth tracheal ring. The
upper airway sound analysis in horses. From a clinical microphone is glued to the skin to prevent the skin and
perspective it is important to know if a particular sound is microphone from rubbing and thus generating friction
made during inhalation or exhalation, because sounds sounds. The advantages of this technique are that it is
associated with different upper airway conditions occur simple, easily used in the field and probably excludes
during specific portions of the respiratory cycle. For example, recording extraneous sounds associated with exercise, such
sounds associated with recurrent laryngeal neuropathy as footfall and wind noise. The disadvantage of this
(RLN) occur throughout inhalation, whereas sounds technique is that it is difficult for the clinician to relate to
associated with dorsal displacement of the soft palate are tracheal sounds, as a human observer does not hear these
predominant during exhalation (Derksen et al 2001). sounds directly.
The frequency components of upper airway sounds also Another method involves placing a small microphone in
contain important information. Upper airway sounds made the nasopharynx (Cable et al 2002). This technique
by exercising horses, like most other sounds, are caused by protects the microphone, and the recording of extraneous
a complex wave. A complex wave is made up of many sounds related to exercise is avoided. However, the naso-
sinusoidal components. The frequency characteristics of pharyngeal position of the microphone is slightly more
these sinusoidal components can be analyzed by use of a invasive, and there may be interference associated with
spectrum analyzer. A spectrum analyzer may be thought of bumping of the microphone on the walls of the naso-
as being composed of many filters, separating complex pharynx. Furthermore, air rushes past the microphone in
waves into discrete sinusoids. A sound spectrum is a graph this position, creating vibrations and unwanted iatrogenic
plotting the frequency components of a given sound on the sounds. Similar to the radio-stethoscope, it is difficult to
horizontal axis, and the sound intensity for each frequency relate to pharyngeal sounds as the human observer
in decibels on the vertical axis (Strong & Plintnik 1992). normally hears sounds emanating from the nostrils.
When evaluating respiratory sounds in exercising horses Respiratory sounds in exercising horses have been
using a spectrum analyzer, it is most useful to evaluate recorded at the nostrils using a facemask incorporating
inspiratory and expiratory sounds separately. airflow transducers, an endoscope, and a microphone
A third characteristic of sound is its intensity (amplitude (Franklin et al 2003). This technique has the advantage
of the sound wave). Because the intensity of upper airway that upper airway endoscopy, measurement of upper
noise made by exercising horses is often part of the owner’s airway flow mechanics, and sound recording can be
complaint, this characteristic of upper airway noise is also performed simultaneously. It is possible, however, that the
important to analyze. presence of the mask and flow measurement equipment
Spectrogram analysis is a sound analysis technique that alters sound recordings. A further disadvantage is that this
evaluates time, frequency, and sound-intensity character- methodology is not suitable for field use.
istics simultaneously. A spectrogram is a three-dimensional In our laboratory we also record respiratory sounds in
plot of frequency on the vertical axis, time along the exercising horses at the nostrils (Derksen et al 2001,
horizontal axis, and sound intensity in the third dimension. Brown et al 2004). A unidirectional microphone with
Sound intensity is often plotted in terms of color, or on a a cardioid pickup pattern is attached via a flexible wand
gray scale. This powerful technique has been commonly to a cavison (Fig. 17.1). This type of microphone centers
used to study human voice and biologic sounds such as the sound pickup toward the front of the microphone,
bird songs, and also to evaluate upper respiratory sounds and helps reduce extraneous sounds such as footfall
made by exercising horses (Wollemann & Olaszy 1977, and track noise that originate behind and to the side
Kent 1993, Heaton et al 1995, Cable et al 2002). of the microphone. The microphone is covered with a
The source of upper airway sounds in exercising horses windscreen, and is placed equidistant between the horse’s
has had limited study to date. In humans, the sound nostrils, approximately 4 cm from the horse’s nose. In this
of speech is generated by vibrations of the vocal fold way, the microphone is as close to the source of sound to
(i.e. turbulent airflow in the upper airway). The sound is be recorded as possible, while avoiding placement of the
17 Evaluation of Upper Respiratory Tract Sounds 251
Fig. 17.2. Spectrogram of respiratory sounds in a normal galloping

horse. Timing is on the abscissa, frequency on the ordinate. The color
indicates sound intensity, with light colors representing high intensity
sounds and dark color representing low intensity sounds. Exhalation is
indicated by an arrow. The upper trace represents the complex sound
wave before separation into frequency and intensity.
Fig. 17.1. Cavison-mounted microphone used to record respiratory

sounds in exercising horses.
microphone in the respiratory air stream. The microphone

Fig. 17.3. Spectrogram of respiratory sounds in a galloping horse with
is attached to an audio recorder with a compression circuit. experimentally induced laryngeal hemiplegia. Notice the bands of
This kind of recorder automatically adjusts the gain, inspiratory sound (formants) centered at approximately 0.3, 1.7, and
decreasing the recording of extraneous noises. The 3.7 kHz. Inspiration is indicated by a star.
advantages of this technique are that it is easily used in the
field and it records respiratory sounds that are also heard
by human observers. In normal exercising horses, expiratory sounds pre-
Simply listening to the audiotape of respiratory sounds dominate and occur throughout exhalation (Fig. 17.2).
made by exercising horses is revealing. The listener can Sound intensity increases as speed increases. During a fast
appreciate factors such as respiratory rate, and consis- canter or gallop, the sound intensity of expiratory sounds
tency, the number of swallows, the frequency of stride is approximately 2.5 times that of inspiratory sounds. Most
lead changes, and whether or not abnormal respiratory of the sound intensity occurs at frequencies below 4 kHz,
sounds are present. Concurrent listening to the audiotape with energy concentrated at frequencies below 0.8 kHz
and viewing the spectrogram is an effective method of (Derksen et al 2001, Franklin et al 2003, Brown et al 2004).
sound evaluation. Horses with RLN or experimentally induced laryngeal
hemiplegia produce a loud inspiratory noise, often with
the same sound intensity as normal expiratory sounds
Sound Spectra of Upper Airway Sounds (Fig. 17.3) (Franklin et al 2003). This noise contains
in Exercising Horses higher frequencies than normal expiratory sounds, and is
Upper airway sound spectrograms of exercising horses vary characterized by three frequency bands called formants.
depending on the measurement technique. The subsequent These formants are centered at approximately 0.3, 1.7, and
spectrogram descriptions will be of respiratory sounds 3.7 kHz (Derksen et al 2001, Brown et al 2003). The
recorded at the external nares. highest frequency formant has the least sound intensity,
and is not present in all RLN-affected horses. Human with dorsal displacement of the soft palate, respiratory
hearing is most acute between 2 and 4 kHz. The sound sounds are normal, whereas in others an inspiratory noise
intensity of the format centered at about 0.3 kHz is in a similar to the noise described for exhalation is also heard.
region where human hearing is less acute, and therefore In these cases, the inspiratory noise is often less loud than
this lower frequency noise does not appear prominent. the expiratory noise. During exercise, affected horses often
In contrast, the formant centered at about 1.7 kHz has swallow frequently, presumably trying to maintain the soft
significant sound intensity, and is in the range of acute palate in its normal position.
human hearing. Therefore this sound formant contributes The source of the upper airway noise in horses with
most to the perception of a high-frequency whistle or roar dorsal displacement of the soft palate is probably vibrations
associated with RLN. The spectral pattern just described of the dorsally displaced soft palate (Franklin et al 2004).
is characteristic of horses with RLN or experimentally The rate and amplitude of soft palate vibration are func-
induced laryngeal hemiplegia (Derksen et al 2001, Brown tions of the airflow velocity, the compliance of the dorsally
et al 2003, Franklin et al 2003). It is possible that this displaced soft palate, and the geometry of the individual
spectral pattern is indeed unique to RLN. If this is the horse’s upper airway. Combined, these factors explain why
case, spectrum analysis of upper airway sounds in exer- some horses with dorsal displacement of the soft palate
cising horses could be used as a definitive diagnostic tool make no noise, whereas in others the noise is also apparent
for this condition. during inhalation. Concurrent listening to the recorded
The source of the inspiratory noise in RLN-affected respiratory sounds made by a horse with dorsal displace-
horses is as yet unclear. It has been reported that the reso- ment of the soft palate, and viewing the spectrogram is an
nant frequency of the lateral ventricle is approximately effective way to diagnose the condition.
1.9 kHz, suggesting that the second formant may arise RLN and dorsal displacement of the soft palate are the
from air moving across the open ventricle during inhalation most common upper airway conditions of horses. Further-
(Attenburrow 1982). This suggestion requires further study. more, both conditions can be experimentally reproduced
Dorsal displacement of the soft palate is an intermittent (Derksen et al 1986, Holcombe et al 1998). Consequently
condition in exercising horses; therefore the abnormal noises associated with these conditions have been studied
noise associated with the condition is also intermittent more than those of the less common conditions. However,
(Franklin et al 2003). In some horses, the abnormal sound upper airway conditions such as pharyngeal collapse,
can be heard throughout the exercise period, while in other epiglottic entrapment, aryepiglottic fold collapse and rostral
horses the soft palate displaces near the end of the exercise, soft palate collapse are also associated with respiratory
or as the horse pulls up. In horses with dorsal displacement noise during exercise. While the associations between
of the soft palate, expiratory sounds are abnormal. The specific conditions and their corresponding spectrogram
loud expiratory noise is characterized by rattling, which patterns must still be made, in the future it is likely that
is visualized on the spectrogram in the time domain as bars each upper airway condition associated with noise pro-
of sound with a periodicity of about 32 ms (Fig. 17.4). duction will have a well-described “voiceprint,” allowing a
Most of the sound energy is below 4 kHz, but ranges up to presumptive spectrogram-based diagnosis of the condition
approximately 10 kHz (Derksen et al 2001). In some horses in the field.
Surgical procedures and noise reduction

in horses with RLN
When selecting from the many surgical options for treating
RLN, veterinary surgeons must weigh the ability of the
surgical procedure to improve upper airway function
and/or reduce the associated respiratory noise, while
minimizing the likelihood and severity of postoperative
complications. Thus, the surgical procedures selected will
vary depending on the intended use of the horse after
surgery, the expectations of its owners regarding noise
reduction, and the risk tolerance of the owner for post-
operative complications.
Surgical procedures used to treat RLN include prosthetic
laryngoplasty, and various combinations of laryngeal
Fig. 17.4. Spectrogram of respiratory sounds in a galloping horse with
experimentally induced dorsal displacement of the soft palate. Note
ventricle and vocal cord excision, often combined with
the vertical bars (“rattling”) during exhalation. Exhalation is indicated laryngoplasty, and nerve-muscle pedicle grafting (Marks
by an arrow. et al 1970, Ducharme & Hackett 1991, Russell & Slone
17 Evaluation of Upper Respiratory Tract Sounds 253
1994, Tetens et al 1996, Hawkins et al 1997, Fulton et al Reduction of respiratory noise “as discerned by the
2003). The source of the RLN-associated noise is not critical ear” is often used to determine the surgical success
clearly understood. Therefore, the efficacy of surgical of prosthetic laryngoplasty (Marks et al 1970). This
procedures to reduce the noise is difficult to predict. Several method of evaluation is distinctly subjective in nature, and
studies have addressed this issue. In one study, bilateral assumes a tight correlation between respiratory noise
ventriculocordectomy effectively reduced respiratory noise and airway obstruction. In fact, in horses with experi-
in horses with experimentally induced laryngeal hemiplegia mentally induced laryngeal hemiplegia, the correlation
(Brown et al 2003). Respiratory noises associated with between residual airway obstruction following prosthetic
the condition were almost completely eliminated, although laryngoplasty and residual noise is weak (Brown et al
spectrum analysis revealed some residual abnormal respi- 2004). Therefore, the residual noise during exercise cannot
ratory sounds (Fig. 17.5). Up to 90 days were required before be used as a predictor of improvement in upper airway
the effect of surgery on noise reduction materialized. function in individual horses following laryngoplasty. As
In recent years, endoscopically guided laser surgery has long as the affected arytenoid cartilage is stabilized by the
become popular in the upper airway. The advantage of this prosthetic laryngoplasty, the degree of arytenoid abduction
technique is that general anesthesia is avoided, thus obtained does not affect upper airway flow mechanics.
reducing the risk to the horse and the cost to the owner. In Interestingly, in one study it was found that the greater the
a recent study we evaluated unilateral laser cordectomy, arytenoid abduction, the louder the residual respiratory
and concluded that the procedure does not effectively noise (Brown et al 2004). Explanation of this observa-
reduce upper airway noise in horses with experimentally tion will require a better understanding of the source of
induced laryngeal hemiplegia. Unilateral laser cordectomy the respiratory noise.
results in removal of the left vocal cord, but not the
laryngeal ventricle. This study suggests therefore that the
laryngeal ventricle rather than the vocal cord may be the REFERENCES
source of laryngeal hemiplegia-associated noise. Attenburrow DP 1978a. The development of a radio-
The most commonly used surgical technique to treat stethoscope for use in the horse at rest and during
RLN is prosthetic laryngoplasty, because this procedure exercise. Equine Veterinary Journal 10: 14–17
returns upper airway flow mechanics to baseline values Attenburrow DP 1978b Respiratory sounds recorded by radio-
stethoscope from normal horses at exercise. Equine
(Tetens et al 1996). Furthermore, the success of this Veterinary Journal 10: 176–179
surgery for returning horses to racing has been well Attenburrow DP 1982 Resonant frequency of the lateral
documented (Russell & Slone 1994, Hawkins et al 1997). ventricle and saccule and whistling. In: Snow DH,
Prosthetic laryngoplasty reduces upper airway noise in Persson SGB, Rose RJ (editors) Equine Exercise Physiology.
horses with laryngeal hemiplegia, but is not as effective as Burlington Press, Cambridge, pp.27–32
Brown JA, Derksen FJ, Stick JA et al 2003 Ventricu-
bilateral ventriculocordectomy in this regard (Brown et al locordectomy reduces respiratory noise in horses
2004). Additionally, respiratory noise reduction occurs with laryngeal hemiplegia. Equine Veterinary Journal
more rapidly than with bilateral ventriculocordectomy 35: 570–574
(Brown et al 2004). Brown JA, Derksen FJ, Stick JA et al 2004 Effect of laryn-
goplasty on respiratory noise reduction in horses
with laryngeal hemiplegia. Equine Veterinary Journal
36: 420–425
Cable CS, Ducharme NG, Hackett RP et al 2002 Sound
signature for identification and quantification of upper
80 airway disease in horses. American Journal of Veterinary
Research 63: 1707–1713
60 Derksen FJ, Stick JA, Scott EA et al 1986 Effect of laryngeal
% improvement
hemiplegia and laryngoplasty on airway flow mechanics

40
in exercising horses. American Journal of Veterinary
Research 47: 16–20
Derksen FJ, Holcombe SJ, Hartmann W et al 2001 Spectrum
20 analysis of respiratory sounds in exercising horses with
experimentally induced laryngeal hemiplegia or dorsal
0 displacement of the soft palate. American Journal of
VC PL LC Veterinary Research 62: 659–664
Ducharme NF, Hackett RP 1991 The value of surgical treat-
Fig. 17.5. Mean percentage improvement of inspiratory sound ment of laryngeal hemiplegia in horses. Compendium
intensity in laryngeal hemiplegia-affected galloping horses 90 days on Continuing Education for Practicing Veterinarians
after treatment with bilateral ventriculocordectomy (VC), prosthetic 13: 472–475
laryngoplasty (PL) and unilateral laser cordectomy (LC). Note that Franklin SH, Usmar SG, Lane JG et al 2003 Spectral analysis of
respiratory noise reduction is most effective after VC, and least respiratory noise in horses with upper airway disorders.
effective after LC. Equine Veterinary Journal 35: 264–268
Franklin SH, Price C, Burn JF 2004 The displaced equine soft Morris EA, Seeherman HJ 1990 Evaluation of upper respira-
palate as a source of abnormal respiratory noise during tory tract function during strenuous exercise in race-
expiration. Equine Veterinary Journal 36: 590–594 horses. Journal of the American Veterinary Medical
Fulton IC, Stick JA, Derksen FJ 2003 Laryngeal reinnervation Association 196: 431–438
in the horse. Veterinary Clinics of North America; Equine Pasterkamp H, Kraman SS, Wodicka GR 1997 Respiratory
Practice 19: 189–208 sounds: advances beyond the stethoscope. American
Hawkins JF, Tulleners EP, Ross MW et al 1997 Laryngoplasty Journal of Respiratory and Critical Care Medicine
with or without ventriculectomy for treatment of left 156: 974–987
laryngeal hemiplegia in 230 racehorses. Veterinary Raphel CF 1982 Endoscopic findings in the upper respiratory
Surgery 26: 484–491 tract of 479 horses. Journal of the American Veterinary
Heaton JT, Farabaugh SM, Brauth SE 1995 Effect of syringeal Medical Association 181: 470–473
denervation in the budgerigar (Melopsittacus undulatus): Russell AP, Slone DE 1994 Performance analysis after
the role of the syrinx in call production. Neurobiology of prosthetic laryngoplasty and bilateral ventriculectomy for
Learning and Memory 64: 68–82 laryngeal hemiplegia in horses: 70 cases (1986–1991).
Holcombe SJ, Derksen FJ, Stick JA et al 1998 Effect of bilateral Journal of the American Veterinary Medical Association
blockade of the pharyngeal branch of the vagus nerve on 204: 1235–1241
soft palate function in horses. American Journal of Strong WJ, Plintnik GR 1992 Music, Speech and Audio.
Veterinary Research 59: 504–508 Soundprint, Provo, UT.
Kent RD 1993 Vocal tract acoustics. Journal of Voice Tetens J, Derksen FJ, Stick JA et al 1996 Efficacy of prosthetic
7: 97–117 laryngoplasty with and without bilateral ventricu-
Marks D, Mackay-Smith MP, Cushing LS et al 1970 Use of a locordectomy as treatments for laryngeal hemiplegia
prosthetic device for surgical correction of laryngeal in horses. American Journal of Veterinary Research
hemiplegia in horses. Journal of the American Veterinary 57: 1668–1673
Medical Association 157: 157–163 Williams W 1874 Respiratory sounds. In: The Principles
Martin BB Jr, Reef VB, Parente EJ et al 2000 Causes of poor and Practices of Veterinary Medicine. MacLachlan and
performance of horses during training, racing, or show- Steward, Edinburgh, pp.451–462
ing: 348 cases (1992–1996). Journal of the American Wollemann M, Olaszy G 1977 Spectrogram analysis of
Veterinary Medical Association 216: 554–558 different alarm calls in gulls and waders. Agressologie
18: 97–102
Sinoscopy of the Paranasal Sinuses
18 Henry Tremaine
is performed via a trephine hole in the frontal or maxillary

Introduction
bones, through which the endoscope (or arthroscope) can
Sinoscopy (or direct sinus endoscopy) is a minimally be inserted to allow inspection of the frontal, dorsal
invasive method for visualization of the equine paranasal conchal caudal maxillary, or rostral maxillary sinuses.
sinuses. Sinoscopy enables examination of most of the The landmarks for the trephine hole are as follows
structures within the paranasal sinuses, the collection of (Fig. 18.1):
intra-sinus biopsies and enables some surgical procedures
● Frontal sinus endoscopy: the trephine opening is made
to be performed on the sinuses of standing sedated horses.
1.5 cm lateral to the midline between a line joining the
Sinoscopy can be performed using a rigid arthroscope
caudal margins of the eye and a line joining the rostral
(Ruggles et al 1993, Chan & Munroe 1995) or much
canthi.
more effectively (and safely for the operator) using a flexible
● Caudal maxillary sinus endoscopy: a trephine hole is
fiberoptic or video endoscope (Worster & Hackett 1999,
created 1.5 cm ventral to the most ventral point of the
Tremaine & Dixon 2001). In one study, sinoscopy was
ventral orbital rim.
diagnostically useful in 70% of the cases where it was used
● Rostral maxillary sinus endoscopy: the trephine hole is
(Tremaine & Dixon 2001).
usually created 2 cm dorsal to the rostral aspect of the
facial crest, and this site should be guided by prior
radiography. Rostral maxillary sinoscopy is only possible
Technique
using this approach in older (>10 years of age) horses,
The horse should be sedated and restrained in stocks. Head whose cheek teeth have erupted sufficiently to prevent
supports are useful to keep the head still during creation of the reserve dental crowns impeding the passage of the
the trephine opening and subsequent sinoscopy. Sinoscopy endoscope.
Fig. 18.1. Areas for trephination for sinoscopy

for examination of the frontal (1), caudal (2)
and rostral (3) maxillary sinuses.
255
256 18 Sinoscopy of the Paranasal Sinuses
To perform sinoscopy, the skin and subcutis at the edge and so avoid damaging the delicate rubber sheath on
trephination site are desensitized with 1–2 ml of local the bending section of the endoscope insertion tube.
anesthetic and a 1.5-cm longitudinal skin and periosteal When using a flexible endoscope (Figs 18.4 and 18.5), the
incision is made before the periosteum is bluntly reflected. trephine hole should be made sufficiently wide (e.g. 3–4 mm
A 1–1.5-cm diameter Galt or Horsley’s trephine or modified wider than endoscope body) to prevent endoscope damage.
drill bit (Figs 18.2 and 18.3) can be used to create the Using the frontal bone approach (Fig. 18.4), the
trephine hole, taking care to avoid damage to deeper struc- endoscope can be passed into the caudal maxillary sinus
tures (especially if performing rostral maxillary trephina- via the frontomaxillary opening (Fig. 18.6) (and vice versa
tion). Trephination is usually accompanied by minimal for a caudal maxillary approach) (Fig. 18.7). Structures
hemorrhage. Any sharp or loose bone fragments are which can normally be observed using this approach
removed from the edge of the trephine hole by rotating the include the interiors of the frontal and dorsal conchal
trephine firmly around its margins, to obtain a smooth sinuses, the frontomaxillary ostium (aperture) (Fig. 18.6),
Fig. 18.2. (A) Modified woodwork drill bits (top and bottom) or Galt trephine (center) are suitable for
creating the trephine opening (trephine hole) for sinoscopy. (B) Close-up of modified woodwork drill bits
(left) and Galt trephine (right).
18 Sinoscopy of the Paranasal Sinuses 257
Fig. 18.3. Creating a sinoscopy portal into the left frontal sinus using a modified 10-mm diameter drill bit.
At this stage, the trephine should be directed more rostrolaterally to allow ease of entry of the endoscope
into the caudal maxillary sinus. Reproduced with the permission of Prof. P.M. Dixon.
Fig. 18.4. An 8-mm flexible endoscope has been inserted into the left frontal sinus and is now being
guided down to the frontomaxillary opening. Reproduced with the permission of Prof. P.M. Dixon.
the intra-sinus (sinusal) (i.e. laterodorsal) aspect of the

ethmoturbinates, the ventral conchal bulla, the infraorbital
canal, the apices of the fifth and sixth cheek teeth (Triadan
110–111, 210–211) (Fig. 18.8), the maxillary septum and
possibly, the opening of the nasomaxillary ostium and the
ostium of the sphenopalatine sinus. In the older horse, it
may be easier to endoscopically examine the ostia of the
sphenopalatine sinuses via maxillary sinoscopy.
Rostral maxillary sinoscopy may be possible via a
maxillary trephine hole, at a site rostral to the maxillary
septum. Sinoscopy of the ventral conchal sinus and
possibly of the rostral maxillary sinus can also be
performed via a frontal sinus sinoscopy and then using
bone rongeurs to perforate the conchal bulla. In younger
horses, the tall reserve crowns of the cheek teeth restrict
the size of the conchomaxillary aperture and prevent
passage of the endoscope between the rostral maxillary and
the ventral conchal sinuses. The applications for rostral
maxillary sinoscopy are limited as the reserve crowns of
the cheek teeth (107–8, 207–8) occupy most of the rostral
maxillary sinus in all except older horses. This feature
severely restricts the ability to effectively maneuver an
endoscope within this compartment and also risks causing
damage to cheek teeth reserve crowns or apices during
sinus trephination.
Sinoscopy of the rostral maxillary sinus has fewer
applications than caudal maxillary sinus sinoscopy, but
Fig. 18.5. Sinoscopy of the left caudal maxillary sinus using a narrow structures which potentially can be observed using this
(9-mm) diameter flexible endoscope. approach include the lumen of the rostral maxillary and
Fig. 18.6. Endoscopic view via a frontal sinus trephine hole showing
the margin of the wide frontomaxillary ostium (arrows) and the Fig. 18.7. Endoscopic view of the frontal sinus obtained by passing an
underlying normal caudal maxillary sinus containing the infraorbital endoscope from the caudal maxillary sinus through the frontomaxillary
canal. Note that the mucosa is thin, its blood vessels are of normal sinus opening. Note the trephine opening also present in the frontal
prominence and exudate is absent from within the sinus lumen. sinus (arrows).
ventral conchal sinuses, the infraorbital canal, and usually in the diagnosis and treatment of cases with primary
the alveoli of the third (caudolateral root) and fourth sinusitis which have accumulations of liquid (Fig. 18.9) or
maxillary cheek teeth (Triadan 108–9, 208–9). inspissated pus (including in the ventral conchal sinus)
Where sinus surgery is later proposed, the sinoscopy (Fig. 18.10), dental secondary sinusitis, sinus cysts (Figs
portal (which is also the site where an irrigation catheter is 18.11 and 18.12), progressive ethmoidal hematoma, sinus
to be placed postoperatively) should be located distant from mycosis (Fig. 18.13), sinus neoplasia (Fig. 18.14), and facial
the proposed margins of the bone flap, to lessen the risk of fractures (Ruggles et al 1993, Tremaine & Dixon 2001).
dehiscence of that aspect of the surgical wound.
Biopsy instruments or probes can be inserted through a
second portal under endoscopic guidance or the sinoscopy
Sinoscopic Findings
portal can be enlarged with rongeurs to allow insertion Careful orientation of the endoscope is necessary to
of a Ferris-Smith or intervertebral rongeur alongside appreciate the intra-sinus topographical anatomy. Normal
the endoscope. The rongeurs can then be used to obtain sinus mucosa is pink in color and small blood vessels can
biopsies, remove bone fragments, or to break down the be viewed through its thin epithelium. Small volumes
caudal aspect of the bulla of the ventral conchal sinus to (few milliliters) of serous or mucoid respiratory secre-
create a portal for insertion of the scope into the ventral tions are occasionally present in the sinus. During normal
conchal sinus and possibly the rostral maxillary sinus or to sinoscopy of the frontal sinus, the dorsolateral aspect of
remove inspissated pus from these sites. the ethmoturbinates is visible ventral to the trephine hole.
Directing the endoscope in a rostral direction reveals the
dorsal conchal sinus, but this orientation of the endoscope
Applications is difficult to achieve if the trephine opening is positioned
Sinoscopy is indicated when clinical examination or too rostral in the frontal bone. By directing the endoscope
ancillary diagnostic tests including nasal endoscopy, ventrally and slightly laterally (abaxially), the wide fronto-
radiography, scintigraphy or computed tomography indi- maxillary opening (Fig. 18.6) is visible. The endoscope
cate a lesion within the paranasal sinuses which merits can be directed ventrally through this ostium to enter the
direct visualization to obtain further diagnostic informa- caudal maxillary sinus.
tion. When large volumes of exudate are present in
the paranasal sinuses, lavage of the sinuses for a few
days, before attempting sinoscopy may enable visualiza-
tion in greater detail. The technique has been of value
Fig. 18.9. Sinoscopy of the caudal maxillary sinus of a horse with

primary sinusitis. This image shows thickening of the sinus mucosa
Fig. 18.8. Close-up view of the caudal maxillary sinus shown in and pus on the floor of the sinus. The small amount of hemorrhage
Fig. 18.6. Note the infraorbital canal (arrow), rostral root of the apex of that occurred during sinoscopy of the frontal sinus has flowed down
the fifth maxillary cheek tooth (210) (A) and some intra-sinus septa, to the caudal maxillary sinus. Reproduced with the permission of
that can be variable in their presence and appearance. Prof. P.M. Dixon.
C
P
Fig. 18.11. Endoscopic view of a small, mucosa-covered cyst-like

lesion in the caudal maxillary sinus (C) with some adhesions to the
Fig. 18.10. Endoscopic view of the rostral maxillary sinus of a horse adjacent (thickened) sinus mucosa.
with sinusitis showing inspissated exudate (P).
Fig. 18.12. A spheroid cystic (C) lesion in the caudal maxillary sinus Fig. 18.13. Sinoscopic image of a progressive ethmoid hematoma
causing almost complete obstruction of the frontomaxillary ostium (PEH) at the caudomedial aspect of the caudal maxillary sinus. Note
(arrows). More rostrally in the caudal maxillary sinus, the ventral also the adjacent mycotic plaque (arrows) that was secondary to
conchal bulla can have a similar appearance. Horses between 3 and the ethmoid hematoma and the adjacent inflamed sinus mucosa.
5 years old can also develop dental eruption cysts over the caudal Reproduced with the permission of Prof. P.M. Dixon.
maxillary cheek teeth leading to smaller lesions of similar appearance.
sinusitis, inspissated pus can be observed in the caudal

maxillary sinus (Fig. 18.10).
In cases of dental sinusitis, the alveolus over an infected
apex may be swollen and hyperemic and may have a sinus
tract or overlying granuloma. In many cases of dental
sinusitis, these features may not be visible because of
widespread mucosal swelling or the presence of pus in
the sinus.
With sinus cysts, which have not expanded to fill the
sinuses, an expanding rounded mass covered by apparently
normal sinus mucosa can be observed and some cysts may
obstruct the frontomaxillary ostium. Penetration of the
T cyst lining, which may be variably thickened or fibrous,
using a lance catheter will yield the honey-colored exudate
which is typical of this lesion.
BF Sinonasal mycoses have been reported as primary
lesions, or secondary to intra-sinus growths and following
sinus surgery. Such lesions, which are usually radiograph-
ically obscure, may be visible sinoscopically (Fig. 18.13).
Intrasinus progressive ethmoidal hematoma when
viewed sinoscopically has a typical multicolored appear-
Fig. 18.14. Sinoscopy showing the frontomaxillary ostium (arrows) of
a horse with sinusitis (thickened, inflamed mucosa with hemorrhagic ance and blood and serosanguineous fluid may be observed
exudates) and an irregular soft tissue mass protruding dorsally from in the floor of the sinuses (Fig. 18.13).
the caudal aspect of the caudal maxillary sinus. A trans-endoscopic Sinus neoplasms are variable in appearance and may be
biopsy (BF) is being performed; this identified a carcinoma (T) that was accompanied by sinusitis and destruction of the conchal
later shown to originate in the sphenopalatine sinus. Reproduced with
bones. Fibro-osseous lesions may appear as firm, rounded
the permission of Prof. P.M. Dixon.
masses that are resistant to attempts to biopsy using
transendoscopic biopsy forceps.
Recurrence of clinical signs such as low-grade nasal
discharges, malodorous discharges, and facial swelling
In the caudal maxillary sinus, the lateral aspect of the occur occasionally after sinus surgery. Sinoscopy enables a
ethmoturbinates can be observed. Centrally in the sinus, minimally invasive assessment of such complications to
the infraorbital canal and the underlying alveoli contain- assist with planning treatment.
ing the apices and roots of the sixth (Triadan 111, 211) Rare complications of sinoscopy are temporary peri-
maxillary cheek teeth can be seen curving in a caudal osteal reaction or osteomyelitis at the trephine site, cellulitis
direction. The alveoli of the fifth cheek teeth (Triadan 110, of overlying soft tissues, and subcutaneous emphysema.
210) lie more rostrally in the maxillary sinus and the
maxillary septum marking the rostral limit of the caudal
maxillary sinus often traverses the rostrolateral root of the REFERENCES
fifth (Triadan 110, 210) cheek tooth. Ventral and axial to Chan C, Munroe G 1995 Endoscopy of the equine paranasal
the frontomaxillary opening is the conchal bulla, formed by sinuses. In Practice 17: 419–422
the thin, cartilaginous, convex caudodorsal aspect of the Ruggles AJ, Ross MW, Freeman DE 1993 Endoscopic exami-
ventral conchal sinus. nation and treatment of paranasal sinus disease in 16
horses. Veterinary Surgery 22: 508–514
In cases with sinusitis, sinoscopic visibility can be Tremaine WH, Dixon PM 2001 A long-term study of 277
impaired by the presence of large volumes of purulent cases of equine sinonasal disease. Part 1: Details of
exudates. Accumulation of purulent material in the ventral horses, historical, clinical and ancillary diagnostic
aspects of the sinus in combination with thickening findings. Equine Veterinary Journal 33: 274–282
and hyperemia of the sinus mucosa are consistent with Worster AA, Hackett RP 1999 Equine sinus endoscopy using
a flexible endoscope: diagnosis and treatment of sinus
sinusitis (Fig. 18.9). The absence of any underlying lesion disease in the standing sedated horse. Proceedings of
such as dental infection or cyst is supportive of a diagnosis the American Association of Equine Practitioners
of primary sinusitis. In some cases of chronic primary 45: 128–130
Computed Tomography of the Equine
Upper Respiratory Tract
19 Martin J Philipp
Computed tomography (CT) is a well-established diagnostic tive atomic number of individual tissues within the field
technique in human medicine. Since the first reports of CT of examination.
in the horse in the mid-1980s (Diehl & Cordey 1983, Allen Image reconstruction is performed by back projec-
et al 1987, O’Callaghan et al 1987), CT has proved to tion, iterative methods or analytical methods, which are
be a valuable tool in diagnosing disorders of the equine described in detail in the literature. The reconstructed
head, proximal cervical vertebral column and distal limbs. image is displayed on a matrix of squares or “pixels”. Each
However, the application of CT in the horse is still limited of these pixels has a specific degree of blackness repre-
by the requirement for special heavy-weight-bearing senting the degree of attenuation in a given position within
CT tables, general anesthesia, and by the limited gantry the patient’s tissues. As a result of the elongation of the
opening of current equipment, in addition to the high cost X-ray beam and the setting of the detector window, each
and thus limited availability of this equipment. pixel represents a voxel – a small block of tissue that has
The word “tomogram” derives from the Greek words been imaged. Thus a pixel is a picture element, while a
tomos and gramma, meaning cut or slice and record. The voxel is a volume element. All acquired attenuation infor-
tomogram is thus a record of slices. CT is an imaging mation within a voxel is averaged and then displayed as a
technique that is based on the attenuation of X-rays within pixel with a certain level of gray shade.
the patient, similar to radiography. However, CT provides Voxel values are normalized to the linear attenuation
cross-sectional images with superior resolution to radio- coefficient of water and are expressed as Hounsfield units
graphs, thus avoiding problems associated with super- (HU). Water is represented by the zero value; air has a
imposition of structures, which is a major limitation of value of –1,000 HU; and cortical bone has a value of
conventional radiography of the equine head. >3,000 HU. Within the body, different tissues and organs
have characteristic HU values.
Gray-scale values of the image can be manipulated to fit
The Principles of Computed Tomography the site and type of tissue examined and this is known as
Acquisition and image reconstruction the window technique. For every gray-scale image the
window width (WW) and the window level (WL) are
Acquisition of CT images requires the rotation of an X-ray defined. Window width describes the range of HU assigned
tube around the patient, during which time multiple to the gray scale of the image. Window level describes the
X-ray projections are recorded. The X-ray projections are HU value represented by the middle gray-scale value.
formed by scanning a thin cross-section of the object with Typical settings for soft tissue imaging are WL 50 and
a narrow X-ray beam. The width of the beam is set by the WW 200. HU values between –150 and +250 are shown
examiner and varies between 1 and 10 mm. Thinner slices as shades of gray, with values under –150 shown as black
result in better spatial resolution but they also result in and values over +250 shown as white. A typical bony
longer acquisition time. A slice thickness of 5 mm has window setting is WL +500 and WW 1,500. Teeth are
proven to be a good setting for imaging the equine head. imaged at WL +1,000 and WW 4,000.
A slice overlap of 1 mm further facilitates multiplanar and CT images are acquired in a transverse plane. With the
three-dimensional reconstruction. help of computers and appropriate software programs, any
The transmitted radiation is measured with radiation- other plane can be reconstructed later for viewing. Raw
sensitive detectors based on either scintillation crystals or data may be processed and presented in many different
xenon gas ionization chambers. A computer processes the ways, allowing enlargement of objects, edge enhancement
projections collected during a 360° rotation to construct and digital subtraction of images to produce native
an attenuation image of the patient. As in conventional images and post-contrast images, calculation of histo-
radiography, attenuation of the X-ray beam depends on grams, and measurement of distance, surface, volume, and
the energy of the X-ray, the depth of the tissues being angles. Most CT units can also perform three-dimensional
imaged, physical density, electron density, and the effec- reconstructions, including surface reconstruction and
263
264 19 Computed Tomography of the Equine Upper Respiratory Tract
volumetric reconstruction. In surface reconstruction, the

examiner may obtain a shaded view of the “surface”
corresponding to a certain HU number (e.g. cortical bone).
In volumetric reconstruction, the computer will display the
pixel corresponding to certain HU values (e.g. muscle) as
translucent, consequently allowing the adjacent pixel also
to be displayed. This allows the examiner to see the
relationship of adjacent tissues (e.g. bone and muscle).
Highly sophisticated CT units also produce color coding
of defined HU intervals. Many tissues and organs in the
body have specific HU numbers. This allows volumetric
reconstruction and distinction of multiple organs and their
position in relation to each other within the body.
Newer CT techniques allow for faster imaging and
for coverage of a larger length of field. These techniques Fig. 19.1. Horse in dorsal recumbency with fixation of its head with
tape and padding. An endotracheal tube is in place for administration
include the use of spiral CT and multi-channel or multi- of anesthetic gases. Reproduced with the permission of the section of
slice CT. In spiral CT, the patient is moved through the diagnostic imaging/radio-oncology, Vetsuisse faculty of the University
gantry while the X-ray tube and detectors function of Zürich, Switzerland.
continuously, and an orange peel-like transverse image is
created. The pitch of the scan is defined by the speed with
which the patient is moved through the gantry. In multi-
slice CT, multiple rows of detectors are installed and more
than one slice can be imaged at once. Both of these For CT examination of the head and the proximal
techniques significantly reduce scanning time. cervical vertebral column, the patient is positioned in
Data are stored on electronic devices such as magneto- dorsal recumbency (Fig. 19.1). The patient is fixed and held
optical (MO) disks or CD ROMs and selected images may in position with radiolucent padding and tape or rope. Care
be printed as hard copies. Storage of raw data allows must be taken to avoid overextension of the patient’s neck
subsequent reconstruction to be performed. during anesthesia, as this may lead to laryngeal paralysis
(Dixon et al 2001). Precise axial positioning of the horse is
Positioning of equine patients crucial for acquisition of diagnostic images. The image
plane should be perpendicular to the patient’s axis and to
CT imaging in the horse must always be performed under the hard palate. Good patient fixation is also needed to
general anesthesia to facilitate precise positioning and to minimize motion artifact induced by breathing.
avoid movement of the patient during image acquisition.
Acquisition time is largely dependent on slice thickness Contrast media
settings and the type of CT-scanner used. The time required
for a head scan can vary from approximately 30 seconds Intravenous contrast media can be used to provide direct
using a multi-slice spiral scanner to 30 min using a planar visualization of perfused tissues. Perfused tissue shows up
single-slice scanner. as hyperdense areas in contrast to non-perfused tissues,
Many protocols have been used for induction and which remain the same density. This technique is valuable
maintenance of general anesthesia in horses. Both inhala- if the clinician wishes to know if an imaged area is
tion anesthesia and intravenous anesthesia may be used perfused or not, for example to differentiate a fluid-filled
in CT. The different protocols used, and their relative cystic mass from a soft-tissue neoplasm with vasculariza-
merits, are described in detail elsewhere in the literature tion extending throughout the mass (Fig. 19.2). After
on veterinary anesthesia. The size and weight of horses performing the initial (native) CT scan, the same sequence
means that custom-made CT tables are necessary. These is repeated following administration of contrast medium.
tables may be coupled in a fixed manner to the small Essentially the same contrast media can be used in CT
animal or human table that is provided with the CT system imaging as in conventional radiography and the risks and
or may be separate units. However, as the table must allow precautions are the same. For intravenous administration
very precise and repeatable positioning of the patient in of contrast media for CT studies, tri-iodinated, water-
the gantry, it must be sturdy, of sophisticated construction soluble compounds are used. They are administered as an
to allow fixation of the patient in different positions, and intravenous bolus at a dose of 370 mg iodine/kg body
have sufficient padding to prevent injuries resulting from weight. They are distributed by the vascular system and
prolonged recumbency of the patient. later excreted by the urinary system. Perivascular leakage
19 Computed Tomography of the Equine Upper Respiratory Tract 265
Fig. 19.2. Transverse CT image of an equine skull at

the level of Triadan 09 (fourth cheek tooth) following
administration of intravenous contrast medium. This
image shows a fluid-filled mass within the right
maxillary sinus that is causing marked displacement
of the medial sinus wall and nasal septum to the left
and gross distortion of the nasal concha bilaterally.
Note the hyperdense rim surrounding the intra-sinus
mass and its fluid-filled, hypodense center. Thickening
of the overlying maxillary bone is present with irregu-
larity of its surface. Diagnosis: paranasal sinus cyst.
Reproduced with the permission of the section of
diagnostic imaging/radio-oncology, Vetsuisse faculty
of the University of Zürich, Switzerland.
should be avoided, as most ionic preparations are locally CT of the equine head allows superior visualization of
irritant. Renal vascular effects and renal damage induced bony structures, soft tissue structures, and paranasal
by contrast media are well studied in humans and cavities. Detailed cross-sectional CT anatomy of the equine
dogs (Porter 1993). Maintaining the patient’s hydration head has been described elsewhere (Morrow et al 2000,
status can minimize these adverse renal effects. Although Smallwood et al 2002). The bony structures of the equine
extremely rare, severe side effects such as cardiac arrest head are always visualized with CT. The nasal cavity and
and anaphylaxis have been described following administra- the adjoining paranasal sinuses have good image contrast
tion of tri-iodinated, water-soluble compounds. Contrast because of the adjacent air and bone; thus paranasal
agents with low osmolarity may have fewer adverse effects. sinuses and their communications are always identifiable
Additionally, in equine imaging, cost is the main limitation in CT (Arencibia et al 2000, Lattimer 2002). The size
in the use of intravenous contrast media. and shape of the communications of nasal and paranasal
cavities in normal horses show some degree of variation.
The size of the conchomaxillary, nasomaxillary, and
Role of CT in the Evaluation of the Equine sphenomaxillary openings are more consistent than the
Upper Respiratory Tract frontomaxillary opening, which can vary between horses
Clinical indications for CT scanning of the equine head (Probst et al 2005). The frontomaxillary opening lies in a
are nasal discharge, swellings of the nasomaxillary and dorsal plane and provides drainage from the conchofrontal
pharyngeal regions, epiphora, and nasal obstruction, sinuses to the caudal maxillary sinus. The location of the
especially when other ancillary techniques such as frontomaxillary opening varies depending on the age of
endoscopy and radiography are not diagnostic. CT allows the horse. In younger horses the opening extends from the
precise presurgical evaluation of the size and location second to the fourth cheek teeth (Triadan 07–09). In older
of upper respiratory tract lesions and so allows optimal horses, the opening extends from the fifth cheek tooth
planning of surgical procedures. CT may also be used in (Triadan 10) to 20 mm past the last cheek tooth (Triadan
a postsurgical setting to ensure correct and complete 11) (Probst et al 2005). This should be taken into
repulsion of teeth, especially if the extracted tooth is consideration when removing diseased teeth in horses
fractured (Fig. 19.3). (Kainer 1993).
CT has an important role in the diagnosis of disorders

of the equine head, including fractures, osteitis, dental
disease, progressive ethmoid hematoma, maxillary sinus
cyst, neoplasia of the nasal cavity, intracranial neoplasia,
abscesses, temporohyoid arthropathy, and disorders of the
ear canal such as otitis media and interna (Tietje et al
1996, Vink-Nooteboom et al 1998, Gardelle et al 1999,
Henninger et al 2003). The few larger clinical publications
on CT of the equine head include descriptions of the CT
features of cholesterol granulomas of the choroid plexus
(Vink-Nooteboom et al 1998), and dental alveolitis and
sinusitis (Henninger et al 2003).
Sinusitis
Investigation of paranasal sinusitis is undoubtedly the most
common indication for CT examination of the horse’s head
and CT has proven to be a powerful tool for evaluation of
underlying dental disease or intra-sinus masses. Henninger
et al (2003) recently described CT findings in horses with
maxillary sinusitis. Evidence of sinusitis on CT scans
Fig. 19.3. CT of equine skull following oral extraction of Triadan 08
(third cheek tooth). A fragment of the extracted tooth is present at the includes thickening of the sinus mucosa (>5 mm thick)
ventromedial aspect of the distorted alveolus. Secondary inflammation and fluid accumulation within the sinus. In that study, the
with gas inclusion and mucosal thickening is also present in the ventral rostral maxillary sinus was found to be more frequently
conchal sinus. Reproduced with the permission of the section of affected than the larger caudal maxillary sinus (Henninger
diagnostic imaging/radio-oncology, Vetsuisse faculty of the University
et al 2003). Early in the course of sinusitis, changes have
of Zürich, Switzerland.
been found in the ventral aspect of the rostral maxillary
sinus (Henninger et al 2003). The frontomaxillary aperture
may be markedly narrowed or completely obstructed in
some cases of sinusitis (Henninger et al 2003). Displace-
Normal cheek teeth have hyperdense enamel with ment of the infraorbital canal is another common feature
slightly less dense dentine and cementum. The pulp of maxillary sinusitis, and commonly occurs in com-
appears hypodense, with the pulp canal being more opaque bination with thickening and sclerosis of its bony wall.
near the occlusal surface because of secondary dentine In chronic sinusitis, inflammatory polyps may be seen
filling. Once formed, the tooth roots are homogeneous within the sinuses. Chronic sinus inflammation also leads
(contain only cement), the overlying sinus is air-filled and to remodeling of the maxillary bone, with thickening,
normally has only a thin (<5 mm) respiratory mucosa endosteal sclerosis and irregular surfaces, or less com-
lining it, and the maxillary bone is of homogeneous monly, bony destruction.
appearance with a smooth surface and a sharply defined An early sign of apical infection of the caudal maxillary
facial crest. The rostral cheek teeth (Triadan 06–08) cheek teeth (within the maxillary sinuses) is the appear-
are somewhat longer (8.5–10 cm in length) than the ance of a small, soft tissue mass around the tooth apex,
caudal cheek teeth (Triadan 09–11) (5–8.5 cm in length) that represents an apical granuloma (Fig. 19.4). Later
(Henninger et al 2003). The fourth cheek tooth (09) is in the course of disease, a periapical gas inclusion and
consistently shorter than the neighboring teeth (because it sometimes fragmentation of the affected tooth apex
erupted first) and is often positioned close to the rostral (or root if it is formed) may indicate apical (tooth root)
aspect of the facial crest. infection (Fig. 19.5). Widening of the periodontal space
When evaluating CT scans of young horses, we must indicating destruction of the periodontal ligament is also
appreciate the significant changes that occur in the cross- usually seen in advanced dental disease. Dental disease is
sectional anatomy of the head as the foal matures. The often accompanied by areas of lucency or opacification in
paranasal sinuses expand during postnatal development. the adjacent alveolar bone (Fig. 19.6) and remodeling of
Deciduous and permanent teeth show remarkable changes the maxillary bone is seen in severe periapical disease. The
in their eruption and development, and fibrous sutures maxillary bone may show thickening, endosteal sclerosis,
between individual bones of the skull may now be recog- and an irregular surface in the presence of chronic
nized. The CT anatomy of the head of the foal has been inflammation. The facial crest is involved in around 50% of
described in detail by Smallwood et al 2002. severe cases of maxillary cheek tooth infection (Henninger
Fig. 19.4. This CT shows an apical infection of Triadan 10 (fourth

cheek tooth). There is apical granuloma formation, and periapical gas
inclusion, within a distended and disrupted alveolus that has some
focal calcified material deposition (reactive cementoma or new bone
formation). Note the opacity of the adjacent ventral and dorsal conchal
sinuses as a result of secondary (dental) sinusitis. Reproduced with the
permission of the section of diagnostic imaging/radio-oncology,
Vetsuisse faculty of the University of Zürich, Switzerland.
Fig. 19.6. This CT image shows extensive changes to Triadan 208

(third left upper cheek tooth) including narrowing and loss of density
of this tooth, widening of the periodontium on its lateral aspect
and absence of its alveolus on the medial aspect. There are also gas
inclusions in the dental pulp canals, destruction of the maxillary bone,
facial swelling and sinus tract formation. Metal skin clips were used for
positioning. Diagnosis: apical infection. Reproduced with the permis-
sion of the section of diagnostic imaging/radio-oncology, Vetsuisse
faculty of the University of Zürich, Switzerland.
et al 2003). Facial swelling and sinus tracts are seen more

often in cases involving the rostral three maxillary cheek
teeth. CT has been reported to positively identify infected
teeth where radiography has been negative or equivocal.
Fig. 19.5. This CT image shows chronic apical infection of Triadan 109
(fourth upper right cheek tooth). There is gross destruction of the
apex, with loss of the roots. Irregular widening of the periodontium is Progressive ethmoidal hematoma
present as a result of destruction and even total loss of alveolar bone,
except at the apical area, where it appears distended. Spread of In CT, progressive ethmoidal hematoma presents as a soft
infection has caused displacement and partial destruction of the
tissue mass (around 30 HU) originating from the ethmo-
infraorbital canal. There is also thickening of the mucosal lining of the
maxillary and ventral conchal sinuses. Reproduced with the permission turbinates (Fig. 19.7). In most cases the ethmoturbinates
of the section of diagnostic imaging/radio-oncology, Vetsuisse faculty are enlarged or have extensive displacement or destruc-
of the University of Zürich, Switzerland. tion. The mass may extend from the rostral aspect of the
Fig. 19.7. This CT image shows a soft tissue

mass in the frontal sinus that has arisen
from the dorsolateral aspect of the adjacent
ethmoturbinates. Partial destruction of the
affected ethmoid is present. Diagnosis: pro-
gressive ethmoidal hematoma. Reproduced
with the permission of the section of diagnos-
tic imaging/radio-oncology, Vetsuisse faculty
of the University of Zürich, Switzerland.
ethmoturbinates into the ipsilateral nasal meatus or contrast media, only peripheral enhancement of the mass
caudally into the nasopharynx. These lesions may also is seen (i.e. uptake by the two layers of respiratory mucosa
extend from the lateral, dorsal, and ventral aspect of the and underling stroma of the cyst wall) and the fluid-filled
ethmoturbinates into the caudal maxillary, frontal, and lumen of the cyst remains unchanged (Fig. 19.2).
sphenopalatine sinuses, respectively. Destruction of the
nasal septum has also been described (Tietje et al 1996). Neoplasia
Thickening of bony structures in contact with the mass
and fluid accumulation in the sinuses are other common The CT appearance of neoplasm of the upper respiratory
findings. After application of intravenous contrast media, tract is highly variable, depending on the nature, extent,
mild uniform enhancement of the progressive ethmoidal and location of the neoplasm. Adenocarcinomas and
hematoma is seen. squamous cell carcinomas often present as highly aggres-
sive masses with extensive destruction of surrounding
Paranasal sinus cyst structures. Their CT appearance is highly irregular with
very variable HU counts. Fluid-filled areas and areas of
The CT appearance of paranasal sinus cysts is of a uniform mineralization may also be present. Depending on the
mass of about 10–20 HU. Most paranasal sinus cysts tissue of origin, the mass may also penetrate and destroy
develop within the caudal maxillary sinus and less the nasal septum and invade the contralateral nasal cavity.
commonly in the rostral maxillary or frontal sinuses. Destruction of the hard palate and invasion of the oral
Mineralization of the cyst wall (Lane et al 1987) may cavity may occur but many carcinomas may have extended
appear as dense spikes surrounding the cyst on the CT from the oral cavity into the sinuses. Following intravenous
image. Extensive midline deviation of the medial wall of administration of contrast media, excessive and often
the sinus, and distortion of adjacent structures is common. highly irregular enhancement of the tumor mass is seen.
Dental distortion and malocclusion have been described
(Tucker & Farrell 2001). Fluid accumulation in sinuses Dentigerous cysts
outwith the cyst is common because of obstruction of
normal sinus drainage. In longstanding cases, the sur- Dentigerous cysts or temporal cysts are congenital abnor-
rounding bone may be thickened and have a roughened malities that comprise epithelium-lined cavities variably
surface. The thinning of adjacent bone beneath expanding containing elements of dental origin. They are usually
lesions in some cases may be the result of local secretion of located on the temporal bone and discharge via a tract along
prostaglandins (Tremaine & Dixon 2001). Rarely, bone the pinna. Other locations on the equine head have been
destruction may occur. After intravenous administration of rarely reported, including locations within the paranasal
Fig. 19.9. Fracture of vertical ramus of the right hemimandible. There

is extensive soft tissue swelling in the pharyngeal region with
displacement and compression of the guttural pouch (hematoma)
Reproduced with the permission of the section of diagnostic
imaging/radio-oncology, Vetsuisse faculty of the University of Zürich,
Fig. 19.8. Transverse CT image of an equine skull at the level of Switzerland.
Triadan 09. An irregular mass fills the entire left maxillary sinus and
compresses its medial wall off the nasal septum. The intra-sinus mass
contains multiple tooth-like structures. There is also some fluid
accumulation in the dorsal part of the maxillary sinus, probably as a
result of impaired sinus drainage cause by the above mass. Diagnosis: The presence of the endotracheal tube also prevents
dentigerous cyst. Reproduced with the permission of the section of
assessment of the spatial relationship of pharyngeal and
diagnostic imaging/radio-oncology, Vetsuisse faculty of the University
of Zürich, Switzerland. laryngeal structures, unless there is marked asymmetry or
soft tissue swelling present in this area.
In CT images, the guttural pouches appear as two
symmetrical gas-filled structures, but their walls are not
sinuses. The CT appearance of dentigerous cysts is highly visualized. The stylohyoid bone is clearly seen as a bony
variable. They present as fluid-filled structures of varying structure with smooth and regular outlines, dividing each
size, possibly containing calcified dental structures with pouch into a medial and lateral compartment. The left
very high HU counts (3000–4000 HU) (Fig. 19.8). The and right guttural pouches can be seen to meet in the
degree of distortion of adjacent structures such as tem- midline and form a thin septum. The auditory tube can be
poral bone, ethmoturbinates, nasal septum or maxil- seen as a gas-filled structure passing in a caudal direc-
lary bone depends on the size and location of the cyst. tion just ventral to the pterygoid bone. Interbreed differ-
Obstruction of the sinus and secondary sinusitis may ences in the size and extension of the two guttural pouch
occur. After intravenous administration of contrast media, compartments have been reported (Sasaki et al 1999).
peripheral enhancement is usually seen, but the cyst itself The presence of a horizontal fluid–gas interface within
does not enhance. the guttural pouches indicates guttural pouch hemor-
rhage (trauma, mycosis), mucus accumulation or empyema
Diseases of the pharynx, larynx, (usually following Streptococcus equi infection) (Fig. 19.9).
and guttural pouch The HU count of this fluid may give some indication of the
type of fluid present within the pouch (whole blood 50 HU,
CT evaluation of the pharynx and larynx is somewhat blood clots 50–80 HU, mucus 10–25 HU). The retropha-
limited by the fact that the patient is under general ryngeal areas should be carefully examined for signs of soft
anesthesia and usually has an endotracheal tube in situ. tissue masses representing lymphadenopathy.
Fractures of the stylohyoid bone are easily recognized as Kainer RA 1993 Clinical anatomy of the equine head.
a sequel to trauma, mycotic osteopathy (Tucker & Farrell Veterinary Clinics of North America; Equine Practice
2001) or temporohyoid osteoarthropathy (Walker et al 9: 1–23
Lane JG, Longstaffe JA, Gibbs C 1987 Equine paranasal sinus
2002). In the latter cases, CT has proven to be a powerful cysts: a report of 15 cases. Equine Veterinary Journal
diagnostic tool. 19: 537–544
Lattimer JC 2002 Equine nasal passages and sinuses. In:
Thrall DE (editor) Textbook of Veterinary Diagnostic
Fractures of the skull Radiology, 4th edn. WB Saunders, Philadelphia, pp.87–98
Morrow KL, Park RD, Spurgeon TL et al 2000 Computed
Diagnosis of fractures of the equine skull may be extremely tomographic imaging of the equine head. Veterinary
difficult using conventional radiography. This is mainly the Radiology and Ultrasound 41: 491–497
result of superimposition of multiple bony structures over O’Callaghan MW, Pascoe JR, Tyler WS et al 1987 Exercise-
the site of interest. Fractures of any part of the head and induced pulmonary haemorrhage in the horse: results of
the cranial cervical vertebral column may be visualized a detailed clinical, post mortem and imaging study. IV.
Changes in the bronchial circulation demonstrated by CT
by CT. The usefulness of CT in the diagnosis of skull scanning and microradiography. Equine Veterinary
fractures in the equine patient has been well documented Journal 19: 405–410
(Ramirez 1998, Gardelle et al 1999). In cases where there Porter GA 1993 Effects of contrast agents on renal func-
is only minimal fracture displacement, or where incomplete tion. Investigative Radiology 28 (Supplement 5): S1–S5;
fractures have occurred, it is advised to set slice thick- discussion S6
Probst A, Henninger W, Willmann M 2005 Communications
ness at no greater than 3 mm and to allow for overlap of normal nasal and paranasal cavities in computed
of slices of at least 1 mm. This allows for better spatial tomography of horses. Veterinary Radiology and
resolution in planar reconstruction and three-dimensional Ultrasound 46: 44–48
reconstruction. Ramirez O, Jorgensen JS, Thrall DE 1998 Imaging basilar skull
fractures in the horse: a review. Veterinary Radiology and
Ultrasound 39: 391–395
REFERENCES Sasaki M, Hayashi Y, Koie H et al 1999 CT examination of the
guttural pouch (auditory tube diverticulum) in Przewalski’s
Allen JR, Barbee DD, Boulton CR et al 1987 Brain abscess horse (Equus przewalski). Journal of Veterinary Medicine
in a horse: diagnosis by computed tomography and and Science 61: 1019–1022
successful surgical treatment. Equine Veterinary Journal Smallwood JE, Wood BC, Taylor WE et al 2002 Anatomic
19: 552–555 reference for computed tomography of the head of the
Arencibia A, Vazquez JM, Rivero M et al 2000 Computed foal. Veterinary Radiology and Ultrasound 43: 99–117
tomography of normal cranioencephalic structures Tietje S, Becker M, Bockenhoff G 1996 Computed tomographic
in two horses. Anatomy Histology and Embryology evaluation of head diseases in the horse: 15 cases.
29: 295–299 Equine Veterinary Journal 28: 98–105
Diehl M, Cordey J 1983 Bone densitometry: using the axial Tremaine WH, Dixon PM 2001 A long-term study of 277
Isotom tomograph on healthy and diseased navic- cases of equine sinonasal disease. Part 1: details of
ular bone in horses in vitro. Berliner and Munchener horses, historical, clinical, and ancillary diagnostic
Tierarztliche Wochenschrift 96: 305–307 findings. Equine Veterinary Journal 33: 274–282
Dixon PM, McGorum BC, Railton DI et al 2001 Laryngeal Tucker RL, Farrell E 2001 Computed tomography and mag-
paralysis: a study of 375 cases in a mixed-breed popula- netic resonance imaging of the equine head. Veterinary
tion of horses. Equine Veterinary Journal 33: 452–458 Clinics of North America; Equine Practice 17: 131–144
Gardelle O, Feige K, Geissbuhler U et al 1999 Possibilities for Vink-Noooteboom M, Junker K, van den Ingh TS et al 1998
computer tomography of the equine head based on two Computed tomography of cholesterinic granulomas in
cases with a fracture of the base of the skull. Schweizer the choroid plexus of horses. Veterinary Radiology and
Archiv fur Tierheilkunde 141: 267–272 Ultrasound 39: 512–516
Henninger W, Frame EM, Willmann M et al 2003 CT features Walker AM, Sellon DC, Cornelisse CJ et al 2002 Temporohyoid
of alveolitis and sinusitis in horses. Veterinary Radiology osteoarthropathy in 33 horses (1993–2000). Journal of
and Ultrasound 44: 269–276 Veterinary Internal Medicine 16: 697–703
Thoracoscopy and Lung Biopsy
20 Joel Lugo and John F Peroni
Introduction
An added benefit is that thoracoscopy can be easily
Thoracoscopy is a minimally invasive endoscopic surgical accomplished in the standing horse, thereby limiting the
procedure that allows video-assisted examination of the risks associated with combining open thoracic surgery and
thoracic cavity (Landreneau et al 1993). The procedure is general anesthesia.
performed by inserting a rigid endoscope and additional The advantages of thoracoscopy in assessing pleuritis
operative instrumentation through the intercostal spaces. and pneumonia were elucidated in a report of 28 cases
A unilateral pneumothorax is induced after perforation of (Vachon & Fischer 1998). In horses affected by pleuro-
the thoracic wall and the thoracic anatomical structures pneumonia, clinicians were able to view the cranioventral
are observed after collapse of the ipsilateral lung. regions of the thorax, thereby allowing accurate place-
In 1985 Mackey and Wheat tested the technique on ment of thoracic drains without compromising pulmonary
10 horses using a 130° rigid endoscope and then used or cardiac structures and facilitating debridement of
thoracoscopy in five horses with pleuropulmonary disease necrotic lung tissue and resection of affected pulmonary
(Mackey & Wheat 1985). The authors advocated using segments. As evident from this clinical report, thora-
thoracoscopy as an adjunctive diagnostic procedure to coscopy is most often employed in those chronic cases of
provide a more accurate prognosis. A subsequent report pleuropneumonia that are unresponsive to standard
described eight clinical cases and six normal horses antimicrobial therapy and pleural drainage. In these cases,
(Mansmann & Bernard-Strother 1985). These authors thoracoscopy allows the aggressive debridement of non-
combined a description of the normal thoracic anatomy viable lung tissue, the evaluation and resection of pleural
with a series of clinical cases of chronic thoracic disease. In adhesions, and the establishment of the most appropriate
contrast with the study by Mackey and Wheat, these site for ventral drainage. The procedure can also be
authors used a 110-cm long flexible, fiberoptic endoscope, performed in selected cases of acute pleuropneumonia,
which proved useful for the examination of the most when breakdown of immature adhesions and establish-
ventral aspect of the chest cavity. ment of drainage are necessary, and in cases in which an
Thoracoscopy in the horse has since gained popularity. endoscopically guided thoracic lavage may aid in resolu-
In 1998, 28 clinical cases were described that had tion of acute pleuritis. Care should be taken to avoid using
been diagnosed and treated using thoracoscopy (Vachon the technique on horses with acute pleuropneumonia,
& Fischer 1998). The procedures were performed in because the inflammatory response associated with the
the standing horse and also under general anesthesia procedure or possible iatrogenic hemorrhage may disturb
for the diagnosis and treatment of thoracic neoplasia, the pleural environment enough to allow exacerbation of a
pleuropneumonia (adhesion breakdown and intrathoracic low-grade infection.
drain placement), thoracic abscessation, pericarditis, and The investigation of thoracic neoplasia is another
diaphragmatic hernia. indication for thoracoscopy. The procedure has allowed the
ante-mortem diagnosis of thoracic neoplasia and the col-
lection of tissue biopsy samples for histological diagnosis.
Indications
Both flexible and rigid endoscopes have been used to
Thoracoscopy is most efficiently employed as a com- diagnose pleural metastatic invasion by gastro-esophageal
plementary procedure to traditional diagnostic imaging squamous cell carcinoma, hemangiosarcoma and cholan-
methods, such as ultrasonography and radiography giocellular carcinoma (Ford et al 1987, Rossier et al 1990,
(Ahmed & Jones 2004). The identification and investiga- Mueller et al 1992).
tion of pulmonary, pleural, and mediastinal disease is Other reported thoracoscopy-assisted procedures are
greatly enhanced by an unobstructed and direct view diaphragmatic hernia repair (Malone et al 2001), assess-
of the intrapleural structures but, most importantly, ment of the thoracic portion of the esophagus for obstruc-
thoracoscopy presents the clinician with the option of tion and stricture evaluation, and the investigation of the
converting from a diagnostic to a therapeutic procedure. nature and location of thoracic wounds (Peroni 2003).
271
272 20 Thoracoscopy and Lung Biopsy
endoscopy is the ease with which the endoscope can be

Equipment and Technique
moved within the thorax. Flexible endoscopes tend to
The equipment used for thoracoscopy in the horse is follow gravity when placed in the chest and invariably fall
the same as that required for laparoscopy, including an toward the most ventral region of the thorax. As often
endoscope coupled to a video camera. Commonly a 58-cm occurs during upper airway endoscopy, flexible endoscopes
long, 10-mm diameter rigid endoscope is used (30° Hopkins require at least two individuals to advance the unit and
endoscope). The endoscope is attached to a video camera simultaneously maneuver the camera located in the tip of
and light source. The video camera used is a standard the endoscope. In contrast, with the rigid endoscope the
endoscopic camera that is commonly used for arthroscopy surgeon is in control of both position and field of view. The
and laparoscopy. A 300-watt xenon light source is recom- 58-cm long endoscope with its 30° optical viewing angle is
mended. The endoscope is inserted through the chest wall ideally suited for a broad view of the thorax and also allows
via a trocar/cannula unit, which can be disposable or non- the delivery of high-intensity xenon light for optimizing
disposable and of variable length (Fig. 20.1). Screw-in detail. One advantage of the flexible fiberoptic endoscopes
cannulae are safer to insert into the chest because they may be the fact that the tip of the endoscope can be
do not require a trocar, thereby eliminating iatrogenic maneuvered 360°, which may be convenient in closed
pulmonary trauma. Importantly, the cannula must be spaces such as walled-off pleural abscesses.
equipped with a side port with a stopcock to allow attach- In preparation for thoracoscopy, horses are usually
ment of tubing for insufflation and suction. Insufflation is premedicated with flunixin meglumine (1 mg/kg q 12 h)
not usually required for thoracoscopy; however a CO2 and systemic broad-spectrum antibiotics. In elective
insufflation (e.g. laparoflator) may be employed to distend thoracoscopy, prophylactic perioperative antibiotic therapy
the thorax and improve visualization of thoracic contents may include an aminoglycoside and β-lactam antibiotic
of foals, which have a more compliant chest wall than combination administered for 24 h. In the standing horse,
adults. A CO2 laparoflator may also be employed to thoracoscopy can be completed safely using local anes-
facilitate surgical exposure during thoracoscopy performed thesia and systemic analgesia/sedation (either xylazine or
under general anesthesia. A suction unit is mandatory to detomidine combined with butorphanol). Detomidine is
re-establish the normal subatmospheric pleural pressure a selective α2-adrenergic receptor agonist favored over
following completion of thoracoscopy. Additional trocar/ xylazine for thoracoscopy because its effects are of longer
cannula units of varying length and size may be used to duration and profoundly sedative (Daunt et al 1993).
introduce accessory instrumentation in the thorax or to Detomidine can be safely administered as a continuous
change the insertion point of the endoscope. infusion and has proven to be safe both in normal horses
The use of a rigid endoscope is generally preferred for and in horses with recurrent airway obstruction under-
intrapleural procedures although a flexible endoscope has going thoracoscopy and lung biopsy (Peroni et al 2000,
been used (Mackey & Wheat 1985). The advantage of rigid Lugo et al 2002).
Fig. 20.1. Cannula placed in the dorsocaudal

aspect of the left thorax during thora-
coscopy performed in the standing horse.
Suction tubing is shown attached to the side
port of the cannula.
20 Thoracoscopy and Lung Biopsy 273
Horses are restrained in stocks and the hemithorax is and lateral surface of the heart. In clinical practice, general
clipped over an area extending from the caudal aspect of anesthesia has been used to accomplish window pericardec-
the shoulder to the last rib and from the dorsal thorax to tomy in horses with constrictive pericardial effusion and
the ventral thorax at the level of the elbow joint. This also exploration of thoracic wounds involving the ventral
area is aseptically prepared. Local anesthetic is infused aspect of the chest (Vachon & Fischer 1998).
subcutaneously into the site of the endoscope portal, either
at the 8th, 10th, or 12th intercostal space, just ventral to
the serratus dorsalis muscle. The authors consider that
Complications of Thoracoscopy
entering the thorax via the 10th and 12th intercostal Thoracoscopy is well tolerated and has been associated
spaces is most effective to facilitate comfortable exploration with minimal cardiopulmonary complications in healthy
of the thorax. An ipsilateral pneumothorax is induced by horses (Peroni et al 2000). Despite the relatively low inci-
making a 2-cm skin and subcutaneous tissue incision and dence of complications, the clinician should be aware of
inserting a stainless steel, blunt cannula into the pleural the consequences of inducing a pneumothorax, especially
space. Upon cannula placement a characteristic sound in horses with underlying lung disease. Even in horses
of air rushing into the chest can be heard with each with severe pneumonia, however, the incidence of intra-
breath, indicating the development of a pneumothorax. or post-operative problems is low.
Following removal of the cannula, a sharp 10-mm Creation of an iatrogenic pneumothorax is a necessary
diameter trocar/cannula unit is inserted through the skin feature of thoracoscopy and horses should be carefully
incision into the thoracic cavity to serve as the endoscope monitored during the procedure, particularly if lung
portal. The rigid endoscope is connected to a video camera disease has significantly impaired ventilation–perfusion
and light source and is then placed through the portal to matching. Lung collapse can further exacerbate gas
explore the hemithorax. exchange and the surgeon should undertake precautionary
Approximately two-thirds of the thoracic cavity, includ- measures that may reduce the risk of hypoxemia. The lung
ing major portions of the lungs, mediastinum, thoracic can be gradually collapsed by intermittently opening
aorta, esophagus, diaphragm, and sometimes the base of and closing the teat cannula used to create the pneumo-
the heart/pericardium can be visualized (Klohnen & Peroni thorax. Transient exacerbation of pulmonary compromise,
2000). The cranioventral region of the thoracic cavity is evidenced by tachypnea, can be alleviated by re-inflation of
more difficult to observe because the collapsed lung tends the lung (Vachon & Fischer 1998). In addition, the degree
to fall cranially, thereby obstructing the view of the most of lung collapse can be varied during the procedure by
ventral region of the chest. During the exploratory phase of applying suction to the pleural space. It is important
thoracoscopy it may be necessary to make additional to regulate the degree of pneumothorax depending upon
accessory portals to facilitate introduction of additional the anatomical region to be inspected and the overall
operative instrumentation needed to complete procedures cardiopulmonary status of the horse (Peroni et al 2001).
such as lung biopsy (see below). When placing multiple Nasal insufflation with 100% oxygen may be an additional
portals, the rules of appropriate triangulation technique useful procedure to implement during thoracoscopy.
used in arthroscopy and laparoscopy should be followed to Although rare, other possible complications include
maximize hand–eye coordination and efficient instrument lung perforation upon entry into the chest and intra-
manipulation. pleural hemorrhage. Pulmonary injury can be avoided if
Upon completion of thoracoscopy, the normal subatmos- appropriate measures are taken such as using guarded or
pheric pleural pressure is re-established by applying suction screw-in type cannulae and, most importantly, ensuring
to the pleural space via sterile tubing connected to the that adequate lung collapse has been achieved before
endoscopic portal unit. First, all cannulae are removed entering the pleural space. The most common reason for
with the exception of the endoscope portal and, while hemorrhage is perforation of an intercostal blood vessel.
suction is applied, it is useful to leave the endoscope in The intercostal artery and vein are located along the
the dorsal thorax to observe complete lung inflation over caudal edge of each rib and inadvertent perforation of
about 15–20 seconds. Skin incisions are closed with a these structures can be prevented by careful insertion of
simple interrupted pattern using non-absorbable suture the cannula along the cranial edge of the rib. In horse
material or staples. with chronic pleuritis, mature fibrous adhesions may
Thoracoscopy is generally performed in the standing form between the visceral and parietal pleurae, which
horse. Most procedures can be accomplished safely in this mechanically limit lung collapse during creation of the
manner and the decision to proceed with general anes- pneumothorax. Preoperative knowledge of this complica-
thesia should be carefully weighed. Horses with pleuro- tion is important and can be accomplished via a careful
pulmonary disease are not the best candidates for general ultrasound examination. Depending on the location of
anesthesia; however, in certain cases it may be necessary to fibrin tags and adhesions the surgeon may choose to
explore the ventral lung surfaces, ventral thoracic cavities, strategically place the endoscope portal so that the most
unobstructed view of the chest can be obtained. Typically,

adhesions form in the mid and lower thorax; therefore, a
more dorsally placed endoscope can facilitate exploration.
Lung Biopsy
Despite the numerous diagnostic modalities available for
investigation of equine thoracic diseases, accurate diag-
nosis and prognosis of some pleuropulmonary diseases
often require direct evaluation of the pulmonary tissue.
Transendoscopic bronchial pinch lung biopsy (Fig. 20.2)
(Mair 1992) and percutaneous lung biopsy (Schatzmann
et al 1974, Raphel & Gunson 1981, Savage et al 1998)
have been used in horses. More recently, thoracoscopically
guided pulmonary wedge resection has been described
(Lugo et al 2002). The most common indications for lung
biopsy include suspicion of infiltrative disease, neoplasia
and interstitial disease, and for pulmonary research (Nyman
et al 1991, Naylor et al 1992, Savage et al 1998). Lung
biopsy should be performed with care or avoided in horses
with pulmonary abscesses and bacterial pneumonia and Fig. 20.2. Transendoscopic bronchial pinch biopsy. Reproduced with
pleuropneumonia, because the infectious process may be the permission of P.M. Dixon, University of Edinburgh.
disseminated to other areas of the lung and pleural cavity.
Transendoscopic pinch biopsy ninth intercostal space, approximately 10 cm above a

horizontal line to the point of the elbow. Alternatively, if
A technique for transendoscopic biopsy of the airway a specific site of lung tissue is to be sampled, ultrasono-
mucosa has been described (Mair 1992, Buechner-Maxwell graphic and radiographic evaluation may help to localize
et al 1996). We were unable to find studies that evaluated the site of interest. The skin, subcutaneous tissue, and inter-
this procedure in a controlled manner and compared his- costal muscles are infiltrated with local anesthetic solution
tological and microbiological results with those obtained and the skin is surgically prepared. A Tru Cut biopsy needle
via more common diagnostics techniques. (Travelonol Laboratories, Deerfield, IL, USA) 15 cm long
After the horse is restrained in stocks and sedated with a 2-cm specimen notch is inserted through a stab
(xylazine or detomidine), a >150-cm endoscope is passed incision made just cranial to the rib. The biopsy needle is
through the ventral meatus of the nasal cavity to the level rapidly advanced into the lung and the tissue sample
of the bifurcation of the trachea into a main-stem is collected. Biopsy samples are immediately placed in
bronchus. Twenty to thirty milliliters of local anesthetic formalin for fixation. Because of the elastic nature of the
diluted in 25 ml saline is instilled through the endo- lung, the chamber of the biopsy needle is seldom filled;
scope biopsy channel to provide topical anesthesia of therefore, multiple samples are usually collected. Following
the bronchial mucosa. The endoscope is then passed into biopsy, horses should be rested for 2–3 days. The main
a bronchus and wedged. The bronchial tissue sample is drawback of this procedure is that frequently the samples
obtained using endoscopic biopsy forceps, which are obtained are small and may not be of diagnostic value.
introduced through the operating channel of the endo- Complications described following percutaneous lung
scope. Multiple biopsy samples can be obtained. The biopsy biopsy include sudden collapse, epistaxis, pneumothorax,
sample is immediately placed in 10% formalin and/or in and fatal pulmonary hemorrhage (Costa et al 2000).
media for bacterial and fungal culture. Indeed, in a survey reported by Savage et al (1998), 33 of
44 respondents had seen a complication at least once, and
Percutaneous lung biopsy approximately 3% of the horses died after the procedure.
The percutaneous technique described by Raphel and Thoracoscopically guided wedge

Gunson (1981) has become the standard method for lung resection lung biopsy
biopsy in horses because it is reasonably safe, easily
performed, and inexpensive. The technique is performed Thoracoscopically guided wedge resection lung biopsy is
with the horse standing, sedated, and restrained in stocks. safe, well tolerated, and provides a minimally invasive
A 10-cm square of skin is clipped between the seventh and method for lung biopsy in horses, avoiding the complications
20 Thoracoscopy and Lung Biopsy 275
Costa LR, Seahorn TL, Moore RM et al 2000 Correlation of

clinical score, intrapleural pressure, cytologic findings of
bronchoalveolar fluid, and histopathologic lesions
of pulmonary tissue in horses with summer pasture-
associated obstructive pulmonary disease. American
Daunt DA, Dunlop CL, Chapman PL et al 1993 Cardio-
pulmonary and behavioral responses to computer-driven
infusion of detomidine in standing horses. American
Ford TS, Vaala WE, Sweeney CR et al 1987 Pleuroscopic
diagnosis of gastroesophageal squamous cell carcinoma
in a horse. Journal of the American Veterinary Medical
Association 190: 1556–1558
Klohnen A, Peroni JF 2000 Thoracoscopy in horses. Veterinary
Clinics of North America; Equine Practice 16: 351–362
Landreneau RJ, Mack MJ, Keenan RJ et al 1993 Strategic
Fig. 20.3. A wedge resection of the lung being performed. planning for video-assisted thoracic surgery. Annals of
Thoracic Surgery 56: 615–619
Lugo J, Stick JA, Peroni J et al 2002 Safety and efficacy of a
seen with other techniques. Unlike percutaneous lung technique for thoracoscopically guided pulmonary wedge
resection in horses. American Journal of Veterinary
biopsy, this method of lung biopsy provides a tissue sample Research 63: 1232–1240
that is adequate for histologic examination. With this Mackey VS, Wheat JD 1985 Endoscopic examination of the
technique, the sample obtained contains few artifacts, equine thorax. Equine Veterinary Journal 17: 140–142
increasing the reliability of lung biopsies for both clinical Malone ED, Farnsworth K, Lennox T et al 2001 Thoracoscopic-
and research purposes. Other advantages are that the assisted diaphragmatic hernia repair using a thoracic rib
resection. Veterinary Surgery 30: 175–178
specimen obtained can comprise both normal and diseased Mansmann RA, Bernard-Strother S 1985 Pleuroscopy in
tissue, and that complications reported with other tech- horses. Modern Veterinary Practice 66: 9–17
niques can be prevented. Furthermore, if a larger tissue Mair T 1992 Diagnostic techniques of the lower respira-
sample is desired, multiple wedge resections can be per- tory tract diseases. In: Robinson NE (editor), Current
formed. The tissue sample is generally obtained from the Therapy in Equine Medicine, 3rd edn. WB Saunders,
Philadelphia, pp.302–303
caudodorsal aspect of the caudal lung lobe and is thus Mueller PO, Morris DD, Carmichael KP et al 1992
useful for diagnosis of peripheral lung lesions or diffuse Antemortem diagnosis of cholangiocellular carcinoma in
pulmonary diseases. a horse. Journal of the American Veterinary Medical
Lung biopsy via thoracoscopy is performed with the Association 201: 899–901
horse standing and using chemical restraint as described Naylor JN, Clark EG, Clayton HM 1992 Chronic obstruc-
tive pulmonary disease: usefulness of clinical signs,
above. After the endoscope is placed in the pleural cavity, a bronchoalveolar lavage, and lung biopsy as diagnostic
site for lung biopsy is selected. One accessory instrument and prognostic aids. Canadian Veterinary Journal
portal is placed one or two intercostal spaces cranial and 33: 591–598
15 cm ventral to the endoscope, and the other instrument Nyman G, Lindberg R, Weckner D et al 1991 Pulmonary gas
portal is usually placed through the 15th intercostal space exchange correlated to clinical signs and lung pathology
in horses with chronic bronchiolitis. Equine Veterinary
approximately 10 cm ventral to the endoscope portal. The Journal 23: 253–260
caudal aspect of the caudal lung lobe is grasped with Peroni JF 2003 Laparoscopic assessment of abdominal trauma
endoscopic forceps, and using commercially available in horses. Compendium on Continuing Education for the
endoscopic stapling equipment, the wedge resection sample Practicing Veterinarian 24: 490–494.
is obtained (Fig. 20.3). The sample of tissue is with- Peroni JF, Robinson NE, Stick JA et al 2000 Pleuropulmonary
and cardiovascular consequences of thoracoscopy per-
drawn and the biopsy site is evaluated for hemostasis. formed in healthy standing horses. Equine Veterinary
The normal subatmospheric pressure of the pleural cavity Journal 32: 280–286
is re-established by removing the air via suction and the Peroni JF, Horner NT, Robinson NE et al 2001 Equine
skin incisions are closed as described above. thoracoscopy: normal anatomy and surgical technique.
Raphel CF, Gunson DE 1981 Percutaneous lung biopsy in the
horse. The Cornell Veterinarian 71: 439–448
REFERENCES Rossier Y, Sweeney CR, Heyer G et al 1990 Pleuroscopic
diagnosis of disseminated hemangiosarcoma in a horse.
Ahmed N, Jones D 2004 Video-assisted thoracic surgery: state Journal of the American Veterinary Medical Association
of the art in trauma care. Injury 35: 479–489 196: 1639–1640
Buechner-Maxwell V, Christmann M, Murray M et al 1996 A Savage CJ, Traub-Dargatz JL, Mumford EL 1998 Survey of the
transendoscopic biopsy of the horse’s airway mucosa. large animal diplomates of the American College of
Journal of Equine Veterinary Science 16: 375–379 Veterinary Internal Medicine regarding percutaneous
lung biopsy in the horse. Journal of Veterinary Internal Vachon AM, Fischer AT 1998 Thoracoscopy in the horse:
Medicine 12: 456–464 diagnostic and therapeutic indications in 28 cases.
Schatzmann U, Straub R, Gerber H et al 1974 Percutaneous Equine Veterinary Journal 30: 467–475
lung biopsy in the horse. Veterinary Record 94: 588–590
Post-mortem Examination
21 Kenneth C Smith
cology, histology, and immunohistochemistry. For these

Introduction
subsequent examinations to yield the most useful infor-
Careful and comprehensive post-mortem examination is mation, it is important that any changes present on
a fundamental method of diagnosis for many cases of dissection have been recognized and described in full.
equine respiratory disease, and is also critical in clinico- Photographs of such changes also assist the histopathol-
pathological audit. As expertise in equine medicine, sur- ogist in interpretation of microscopic changes.
gery, and diagnostic imaging progresses, so it is important
that pathology advances at a similar rate, to capitalize Post-mortem examination of adult horses
on technological advances. Classical techniques of veteri-
nary pathology (morbid anatomy and histopathology) The method outlined in this chapter is one used routinely
are now augmented and enhanced by the armory of in the author’s laboratory in Newmarket for post-mortem
modern molecular diagnostics [immunophenotyping, examination of the respiratory tract, and is based upon
in situ hybridization and polymerase chain reaction (PCR)], examination of the horse supported in dorsal recumbency.
and it is likely that techniques such as tissue microarray The method commences after external examination of
analysis will also form part of the routine toolbox of the the carcass, removal and examination of the abdominal
veterinary pathologist in coming years (Bodrossy & viscera, and removal of the head by transection of the
Sessitsch 2004). Such novel techniques rest upon a atlanto-occipital joint (Rooney & Robertson 1996).
foundation of sound post-mortem technique and tissue
sampling, which are outlined in this chapter. Examination of the diaphragm and pleura
Following removal of the abdominal contents, the
diaphragm is incised to test for subatmospheric intra-
Method of Post-mortem Examination
pleural pressure. Where pneumothorax is present, the
Selection of post-mortem method expected in-rush of air into the thoracic cavity upon
incision of the diaphragm does not occur. Pneumothorax
Several techniques of equine post-mortem examination in horses is a rare disorder but can be acquired secondary
have been described (Rooney & Robertson 1996). The to traumatic damage to the trachea, esophagus, lungs,
method used is one of personal preference for the patholo- chest wall or diaphragm. If a diaphragmatic defect is
gist, but should in any event permit full examination of all present then it is important to determine whether this
of the body organs in a standardized and reproducible is congenital, acquired or a post-mortem change. Con-
manner. To gain maximal information from a post-mortem genital diaphragmatic hernias generally involve the dorsal
examination it is preferable wherever possible that the diaphragmatic quadrant in foals, have smooth edges, and
carcass be referred to an experienced equine pathologist may be associated with visceral herniation. Acquired and
with access to full laboratory facilities as soon as possible presumably post-traumatic diaphragmatic hernias, by
after death or euthanasia. The pathologist should be given contrast, have ragged edges with hemorrhage and often
access to all the clinical and laboratory data relating to the occur on the left side of the diaphragm. Post-mortem
horse before commencing the post-mortem examination, rupture of the diaphragm can occur in horses that are
and it is often of value to both individuals if the attending examined several hours after death, as a consequence of
clinician observes all or part of the post-mortem examina- post-mortem gastrointestinal tympany (usually involving
tion. Where referral of the carcass to a specialist institute is the large bowel). Post-mortem rupture is not accompanied
not feasible, it is nonetheless important that the veterinary by hemorrhage, although post-mortem discoloration of
surgeon in the field undertakes a systematic and compre- tissue often necessitates microscopic examination of the
hensive examination, taking contemporaneous notes and torn diaphragmatic edges to make an absolute distinction.
photographs of any changes found. Samples should be After assessing diaphragmatic integrity, the central
collected for other analyses such as microbiology, toxi- portion of the diaphragm is removed by incising around
277
278 21 Post-mortem Examination
the periphery and the thoracic contents are inspected and soft tissue attachments in the thoracic inlet. The lungs
in situ from the caudal aspect of the cavity. In the majority and heart together with the anterior mediastinum
of horses the integrity of the caudal mediastinum main- (including the thymus if present) are removed through the
tains a barrier between the left and right sides of the diaphragmatic opening and via the abdominal cavity, by
thoracic cavity so that if the diaphragm is incised in an passing the trachea/esophagus back through the thoracic
anti-clockwise fashion from right to left then air enters inlet, having released the heart within the pericardial sac
only the right pleural cavity until the incision is continued from its ventral attachments. The volume of fluid in the
beyond the midline to incise the mediastinum. Pneumo- pericardial sac is noted, and, if appropriate, cytology or
thorax may thus be defined as left- or right-sided. Some microbiology samples are collected as described for pleural
horses have fenestrations within the caudal mediastinum fluid samples, before the pericardial sac is detached. Once
that allow air movement between the left and right sides, the thoracic viscera have been exteriorized into the abdom-
resulting in bilateral pneumothorax. These fenestrations inal cavity, the aorta is transected at the diaphragm and
are difficult to detect on dissection, and will be missed the thoracic viscera are drawn backwards by pulling on the
unless careful observation of air movement is made on trachea and freeing any other soft tissue attachments. The
incision around the diaphragm. parietal surface of the pleura is then inspected, and the
A sample of pleural fluid can be obtained aseptically as ribs are checked for evidence of injury. Fractured ribs are
the diaphragm is removed. In an adult horse, there is a unusual in adult horses, but common in foals as a con-
small volume (usually 5–15 ml) of clear yellow fluid in sequence of birth trauma, classically affecting the fourth to
each side of the pleural cavity. This fluid becomes pro- ninth ribs and carrying an attendant risk of laceration to
gressively discolored red as a result of hemolysis if post- the contained thoracic organs by the fractured rib ends
mortem examination is delayed. Excessive fluids, changes (Schambourg et al 2003).
in fluid color or consistency, or the presence of pleural In some cases, lateral exposure of the chest may be
adhesions, are indications for collection of pleural fluid preferred, after removing the rib cage by sawing through
for cytological and bacteriological analysis. Pleural fluid the ribs at their cranial and caudal extremities, to permit
should be collected into: detailed dissection of thoracic organs in situ. This tech-
nique is of value in cases where congenital anomalies
● an ethylenediaminetetraacetic acid (EDTA) container for
or other lesions affecting blood vessels or other struc-
cytological assessment
tures of the thoracic inlet and anterior mediastinum are
● a container with an equal volume of neutral buffered
suspected (particularly anomalies of the first and second
formalin for cytology if any delay in analysis is anticipated
ribs and associated blood vessels) (K.E. Whitwell, personal
● a sterile container for protein measurement and
communication).
bacteriology.
The trachea is inspected for evidence of deformity and
Cytological and bacteriological analyses of pleural fluid then opened by cutting along the groove between the
are discussed in Chapter 9. Inflammation of the pleural cartilages on the dorsal aspect down to the main-stem
surfaces (pleuritis) may occur in pleuropneumonia, giving bronchi, and then continuing the incision along the main
rise to thickening and discoloration of the pleurae, with bronchial divisions. The mucosal surfaces and lumina of
accumulation of exudate in the pleural cavities. It is often the trachea and main-stem bronchi are then inspected, and
difficult to recover microorganisms from pleural fluid materials are collected for microbiology (including virus
collected from horses that have already received antibiotic isolation, PCR, aerobic and anaerobic bacterial culture)
therapy, and pleural fluid smears demonstrating exuda- and histology, as guided by the clinical history and macro-
tive inflammatory change should be scrutinized carefully scopic findings. If endoscopic examination of the airways
for microorganisms using appropriate special stains. Meso- was performed before death, the post-mortem appearance
thelioma is rare in horses, as in other domestic animals. of the airways should be correlated with the endoscopic
Published reports of mesothelioma describe massive findings. Apart from tracheal collapse in ponies and donkeys,
pleural effusion, in which malignant cells may be recog- primary lesions affecting the trachea are uncommon.
nized on cytology, with multifocal, shaggy, plaque-like
thickenings of pleural surfaces (Colbourne et al 1992, Examination of the lungs
Stoica et al 2004). As the lungs are such large organs, and the distribution of
lesions within the lungs often correlates with different
Examination of the trachea types of insult, care needs to be taken that all lobes of each
Following collection of pleural fluid, the thoracic organs lung receive adequate examination by inspection of color
are removed by separating the trachea and esophagus changes, palpation for changes in consistency and serial
from the neck, having incised through the trachea and incision of the parenchyma for evidence of focal lesions.
esophagus below the larynx, bluntly dissected the trachea Areas of suspected lung consolidation should be tested for
and esophagus from the cervical muscle and connective flotation in water or formalin. It is good practice to collect
tissue, and transected the brachiocephalic blood vessels samples for routine histology from each of the lung
21 Post-mortem Examination 279
lobes (left and right apical, middle and caudal, and right a history of long-distance travel), with the remainder
accessory), to include both dorsal and ventral areas, and to having infection secondary to aspiration of food or saliva,
include additional labeled samples from any areas with thoracic trauma, generalized infection, airway disease,
visible abnormalities. These samples may be collected into neoplasia or thrombo-embolism (Mair & Lane 1989).
individual formalin-filled universal bottles, or identified Opportunistic infections may occur, with pulmonary
within larger tubs of formalin by individually attached abscessation resulting from penetration of the lungs via
parcel labels. A systematic method for examination and the chest wall, mediastinum or diaphragm, or extension
bacteriological sampling of the different levels of the of infection to the lungs from the tracheobronchial
respiratory tract and the lung lobes has been described lymph nodes in cases of Streptococcus equi infection (see
and presented in the context of the normal respiratory Chapter 23). Cases of bacterial infection secondary to
microflora of horses (Blunden & Mackintosh 1991). long-term corticosteroid therapy have also been recorded
Pulmonary edema, congestion, and accumulation of (Mair 1996). Further to sporadic cases of opportunist
stable froth in the trachea and main-stem bronchi are bacterial infection, there is good evidence that Streptococcus
common incidental findings in horses that are euthanased pneumoniae is also able to act as a primary pathogen,
with barbiturates or similar compounds, and may also resulting in focal pneumonia under experimental condi-
occur in the agonal stages of a variety of diseases that tions (Blunden et al 1994).
terminate in cardiac failure. Histological examination of Mycobacterial infection in horses is uncommon, and it
the lungs is critical in such cases to establish the duration appears that the horse has a high innate resistance to
of the edema and congestion. This is carried out by tubercle bacilli (Luke 1958). Most reported infections
assessment of the number and degree of vacuolation have involved Mycobacterium bovis but M. avium and
of bronchoalveolar macrophages, which may contain M. tuberculosis have also been recorded. Infection is
hemosiderin in cases of chronic cardiogenic edema (“heart generally by the alimentary route, and the lesions in
failure cells”) or exercise-induced pulmonary hemorrhage the lungs and tracheobronchial lymph nodes are typically
(EIPH). The presence of these cells is useful in aging firm, gray, and smooth, rather than caseous. Histologically,
congestive or hemorrhagic lesions. Studies on EIPH have there is initial granulomatous inflammation that progresses
shown that the numbers of these cells do not increase to fibrosis. Acid-fast bacilli may be very difficult to find,
significantly within alveoli until around 1 week after the requiring multiple Ziehl–Neelsen-stained sections, and the
start of hard training, and that they decrease around lesions may be mistaken for sarcomas on macroscopic
3 weeks after training ceases (Meyer et al 1998). Discussion examination.
of cardiac pathology is beyond the scope of this chapter, Verminous pneumonia may occur as a result of infec-
and the reader is referred to standard textbooks of equine tion with Dictyocaulus arnfieldi in horses pastured with
cardiology (Darke et al 1996). donkeys, but this and other parasitic infestations are rare
Severe viral pneumonia is rare in adult horses. As in animals on routine anthelmintic therapy. With the wide-
equine influenza and equine herpesvirus-1 (EHV-1) and spread use of effective anthelmintics it is unusual to observe
EHV-4 are rarely fatal, and often subclinical, knowledge of aberrant strongyle lesions affecting the lungs or vascula-
the pathology of the respiratory disease is largely based ture of the thoracic cavity, excluding cases of neglect.
upon historical or experimental studies (Jones & Maurer Various immune-mediated conditions may involve the
1943, Kydd et al 1994a,b). Certain isolates of EHV-1 are lungs, including multisystemic eosinophilic epitheliotropic
capable of causing primary severe respiratory infection, as disease and idiopathic pulmonary eosinophilia. These
is the recently characterized Hendra virus (formerly equine conditions are sporadic, and their etiology is ill-defined,
morbillivirus) (Barclay & Paton 2000). With the exception although it is speculated that host immune reactions
of these highly virulent agents, horses presented for post- to prior endoparasitism are important in at least a propor-
mortem examination following an episode of viral infection tion of cases. The most important immune-mediated pul-
often demonstrate secondary bacterial infection by the time monary disease affecting the lungs in adult horses is
of necropsy. Uncomplicated viral infection of the lungs can- recurrent airway obstruction. Clinical and immunopatho-
not be diagnosed solely by gross examination, and is often logical features of this disorder are well defined (Robinson
difficult to distinguish from edema of differing etiologies. et al 1996), and the histological lesion is a generalized
Histological examination of sections of lung is critical in chronic bronchiolitis with epithelial hyperplasia, goblet cell
conjunction with virus isolation and PCR in such cases. metaplasia, smooth muscle hypertrophy, peribronchiolar
Bacterial infections of the lung in adult horses are rarely fibrosis and infiltration by lymphocytes and plasma cells
fatal, although they are often associated with impaired (Kaup et al 1990). Neutrophils are often (but not consis-
respiratory performance, as exemplified by Streptococcus tently) prominent within airway lumina, airway epithelium
zooepidemicus and other airway infections in young race- and peribronchiolar spaces, sometimes accompanied by
horses in training. In a review of 45 horses with bacterial smaller numbers of eosinophils. There is often peribron-
pneumonia and/or pulmonary abscesses it was found that chiolar mast cell hyperplasia. This histological lesion does
the infection was primary in 11 horses (eight of which had however overlap with other types of chronic small airway
inflammation, including inflammatory airway disease, and nodular thickening of the mucosa. This change is not
there is a need for an objective grading system to facili- specific for particular etiological agents, and generally
tate histological diagnosis of probable recurrent airway regresses with age.
obstruction in horses without a full medical history. A history of unilateral nasal discharge is an indication
Exercise-induced pulmonary hemorrhage occurs to for full examination of the nasal cavity and paranasal
some degree in the majority of horses during race training. sinuses, which requires removal of bone from the maxilla
The severity ranges from the presence of small amounts of to fully expose the maxillary sinuses, and facilitate tooth
blood in the trachea and main-stem bronchi on post-race apex inspection. Rhinitis in horses may be caused by viral
endoscopy, to severe epistaxis that is occasionally life- infection (including equine rhinoviruses, EHV-1, and
threatening. Incidental lesions of EIPH are apparent on EHV-4), bacterial infection (particularly involving infection
post-mortem examination of the lungs of many racehorses with S. zooepidemicus), fungal infection (such as Aspergillus
as gray/brown plaques and discolored subpleural foci on fumigatus, Cryptococcus neoformans or Rhinosporidium seeberi),
the dorsocaudal portions of the caudal lung lobes. Histo- or by immune-mediated processes such as allergy. The
logically these lesions correspond to areas of bronchiolitis, nature of the inflammatory reaction (serous, catarrhal,
fibrosis, neovascularization of arterial branches, and hemo- purulent, ulcerative, pseudomembranous, hemorrhagic or
siderin accumulation in alveoli and interstitial septa. granulomatous) is important in determining the likely
Neoplasia affecting the lower respiratory tract of horses etiology and duration of the condition, with acute rhinitis
is uncommon. The most frequently reported primary generally presenting as a serous exudate that progresses
pulmonary tumor of the horse is the granular cell tumor to become catarrhal and then purulent. In subacute to
(myoblastoma), which occurs in older animals. It may be chronic rhinitis, localized mucosal hyperplasia, edema and
associated with coughing and pulmonary insufficiency, or reduced venous drainage may rarely predispose to the
occur as an incidental finding. The cell of origin of this development of nasal polyps that present as soft mottled
type of tumor is uncertain, but current opinion favors a pedunculated masses protruding into the nasal cavity.
Schwann cell precursor (Kagawa et al 2001). These lesions must be distinguished histologically from
neoplasms. Sinusitis may occur as an extension from
Examination of the upper respiratory tract purulent rhinitis or periodontal or dental apical infections,
Examination of the upper respiratory tract is achieved as and is of particular importance in this species owing to the
follows. The head is detached from the neck at the atlanto- size and complexity of the paranasal sinuses and their
occipital joint, leaving the soft tissues posterior to the limited capacity for drainage. Empyema is the usual gross
guttural pouches intact. The skin is reflected from the head, finding in cases of chronic sinusitis, and histological exami-
permitting examination for subcutaneous bruising or skull nation and appropriate microbiology are necessary to
trauma. The rostral portions of the upper and lower achieve an etiological diagnosis.
jaws are removed by transverse cuts (by bandsaw or A history of epistaxis should prompt close inspection of
handsaw) just caudal to the incisor teeth. This then enables the guttural pouches for mycotic plaques, which appear
parasagittal bisection of the head, just slightly abaxial of as white/gray plaque-like thickening of the wall of the
the midline, to minimize damage to the brainstem and affected pouch, with erosion of underlying blood vessels.
midline central nervous system structures. The nasal The causal organism, often Aspergillus spp., may be iden-
septum is removed from the side of the nasal cavity, where tified by fungal culture from the plaques and/or by direct
it is still intact, to enable complete inspection of right and demonstration of fungal hyphae in tissue sections using
left turbinates. The remainder of the upper respiratory appropriate special staining. The principal differential diag-
tract, including larynx, guttural pouches and lymphoid nosis for epistaxis originating from the upper respiratory
tissues, and the oral cavity are examined at this stage, and, tract is progressive ethmoid hematoma, which represents
if appropriate, samples are collected for microbiology a hemorrhagic variant of nasal polyp. This condition is
and histology. recognized at post-mortem examination as a friable fleshy
The most important condition affecting the equine mass occupying the ethmoturbinate region and extending
larynx is recurrent laryngeal neuropathy. Atrophy of proximally into the nasal cavity or into the paranasal
the cricoarytenoideus dorsalis muscle is recognized at sinuses. Histological examination may be necessary to
post-mortem examination as reduced mass and pallor distinguish progressive ethmoid hematoma from rare cases
of the affected muscle, with histological changes typical of of hemangiosarcoma, adenocarcinoma or other neoplasia
neurogenic myofiber atrophy. The pharynx may contain occurring in this region of the nasal cavity.
cysts (e.g. glossopharyngeal or subepiglottic), but these are The guttural pouches are also key areas for examination
usually incidental findings. Histological examination of the in cases of acute or chronic S. equi infection. Collection of
wall of the cyst may assist in determining the embryonic swabs or cultures from the guttural pouches is important
origin. Pharyngitis is rare in adult horses, although the in the identification of carrier animals. Horses with clinical
majority of young horses demonstrate follicular hyper- signs of S. equi infection may demonstrate abscessation of
plasia of pharyngeal lymphoid tissues that is recognized as the submandibular and retropharyngeal lymph nodes,
Fig. 21.1. Guttural pouch of a pony infected

with Streptococcus equi. Note abundant
purulent material filling pouch: guttural
pouch empyema. Reproduced with the per-
mission of Dr Richard Newton, Animal Health
Trust, Newmarket, UK.
in association with guttural pouch empyema (Fig. 21.1). stances, surgical procedures, diagnostic procedures, and
Cervical and tracheobronchial lymph nodes may also resuscitation attempts. EHV-1 infection in late-term fetuses
demonstrate abscessation, and clinical signs may then and neonatal foals typically causes a constellation of lesions
include upper and lower respiratory tract obstruction. that includes hepatosplenomegaly, perirenal edema, and
Asymptomatic carriers of S. equi generally have nodules of body cavity effusions. Transudative pleural effusion is a
inspissated caseous material, termed chondroids, within particularly important diagnostic aid that has been docu-
one or both guttural pouches. Bacteria or bacterial nucleic mented since the first reports of this pathogen in the 1930s
acids are generally detectable within chondroids using (Westerfield & Dimock 1946, Allen et al 1999) (Fig. 21.2).
culture or PCR analysis. Other viral infections of the fetus and neonate are equine
Sinonasal neoplasms occur sporadically in horses and viral arteritis and equine adenovirus, the latter particularly
are generally malignant. Squamous cell carcinomas pre- in cases of severe combined immunodeficiency in Arab
dominate, with occasional reports of other tumors such as foals (McChesney et al 1973). Bacterial infections may be
fibrosarcoma and adenocarcinoma. pre- or post-natal, the former often being associated with
placentitis and generally being associated with pathogens
Post-mortem examination of fetuses such as Escherichia coli or S. zooepidemicus. Histological and
and foals microbiological examination of the lungs is essential to
distinguish bacterial infection in neonates from uncom-
The method outlined above is not appropriate for the plicated primary atelectasis, as occurs in cases of dystocia.
examination of equine fetuses and foals up to 6 months of Meconium inhalation within airways and alveoli is a useful
age, where infectious disease is a particular concern indicator of intrapartum stress in such cases.
(Smith et al 2003). The respiratory tract and associated Postnatal bacterial infections occurring in the first few
structures of fetuses and neonatal foals may be examined weeks of life may involve a similar range of organisms to
as follows. The carcass is placed in right-sided recumbency those infecting foals in the first days of life. The most
and the left limbs and body wall are reflected dorsally to important bacterial infection occurring in older foals
expose the viscera. Before further handling of the tissues, (1–6 months of age) is Rhodococcus equi. Post-mortem
virology and then bacteriology samples are taken. The diagnosis of R. equi pneumonia is achieved by the recog-
abdominal and then thoracic cavities are inspected and the nition either of multiple caseous abscesses within the
organs are examined individually, firstly in situ and then on lungs of foals with the chronic form of the disease or of
a table. Particular attention is paid to evidence of birth diffuse to multifocal suppurative pneumonia in the acute
trauma (ribs, limb joints, cranium, brain, cervical spine) in form (Yager 1987). The causal organism is a Gram-positive
stillborn, late-term or neonatal foals; congenital abnor- pleomorphic rod bacterium that is often identified within
malities; sites of infection in neonates (guided by clinical phagocytic cells on tissue sections. Foals aged between
history); state of aeration of lungs; viral-type lesions in 1 and 6 months of age may also present to the patholo-
the lungs of aborted fetuses or neonates; and evidence gist with a history of acute-onset respiratory distress, and
of veterinary intervention, such as administration of sub- demonstrate post-mortem lesions of interstitial pneumonia.
Fig. 21.2. Equine fetus aborted as a result

of EHV-1 infection. Note abundant straw-
colored fluid in pleural cavity.
Sections of lung demonstrate diffuse alveolitis with hyaline to the clinical signs exhibited by the horse, and by the gross
membrane formation and/or type 2 pneumocyte hyper- post-mortem findings. Fixation is generally by immersion
plasia. A proportion of these cases are associated with in 10% neutral buffered formalin, but more specialized
Pneumocystis carinii infection (Ewing et al 1994, Peters fixatives such as paraformaldehyde may be required for
et al 1994), while various theories have been advanced to specific procedures such as in situ hybridization. Methods of
explain the remainder, including viral and toxic disease. perfusion fixation are rarely employed in adult horses,
owing to technical difficulties. Samples for bacteriology and
virology must be collected with good aseptic technique to
Summary of Post-mortem avoid cross-contamination. It is good practice to retain
Sample Collection unfixed specimens from the upper and lower respiratory
Table 21.1 summarizes those samples that should be col- tract, both in virus transport medium and frozen in sterile
lected in the comprehensive examination of the respiratory containers, should subsequent virological, toxicological or
tract. The sampling protocol should be modified according genetic analysis be undertaken.
Table 21.1. Suggested minimal sampling set for full post mortem examination
of the respiratory tract of an adult horse
Method Collection medium Samples for collection
Histopathology and Neutral buffered formalin Nasal mucosa (turbinate and septum), nasopharynx, tonsil (nasal and
immunohistochemistry* lingual), guttural pouch, lymph node (submandibular, retropharyngeal,
cervical, tracheobronchial), trachea (proximal, middle and distal),
main-stem bronchus, lung (left and right apical, middle and caudal
lobes, right accessory lobe)
Virology and PCR Virus transport medium Pooled samples from nasal and nasopharyngeal mucosa. Pooled samples
from respiratory tract-associated lymph nodes. Pooled samples from left
and right lungs
Bacteriology Unfixed tissue samples Nasal mucosa, guttural pouch, trachea, main-stem bronchus and left
or unfixed swabs and right lung
Other (e.g. serology Unfixed tissue samples Serum and snap-frozen samples of lung
toxicology)
*Some antibodies are optimized for snap-frozen rather than fixed tissue: check with laboratory in advance.
PCR = polymerase chain reaction.
that the carcass be accompanied by a full medical history,

including any ante-mortem laboratory results. Travel
history is fundamental, and it is important that the exam-
ining pathologist is well acquainted with infectious diseases
occurring in the country of origin of imported horses.
Molecular Pathology
Pathology has kept pace with other developments in
veterinary diagnostics through the increasing application
of new molecular techniques to post-mortem diagnosis. Of
greatest value in routine diagnostic pathology are
immunohistochemical methods, both for the phenotyping
of inflammatory and neoplastic cells (Mair et al 1988,
Kelley & Mahaffey 1998, Blunden & Gower 1999), and for
the detection of infectious agents (Kydd et al 1994a,b,
Fig. 21.3. Equine tracheal explant infected with equine influenza virus
(H3N8) and immunostained for viral antigen expression using a Lopez et al 1996) (Figs 21.3 and 21.4). The majority of
polyclonal antiserum and indirect immunoperoxidase method with these techniques are now applicable to routinely processed
DAB as chromogen and Mayer’s hematoxylin as counterstain. and fixed material but it is always worthwhile to retain
Epithelial cells infected with influenza stain brown. Magnification a specimen of unfixed tissue for cryostat sections if the
×400.
fixation stability of the target antigens is not known.
PCR techniques are also applied routinely to material
collected at post-mortem examination, and these tech-
Health and Safety in the
niques can often be adapted to the examination of archived
Post-mortem Room
formalin-fixed paraffin-embedded tissues. Owing to the
Health and safety considerations should be followed in the speed, economy, and sensitivity of PCR diagnosis, these
examination of horses with suspected zoonoses (use of methods have largely superseded routine virus isolation
facemasks or respirators; avoidance of mechanical saws for infectious disease diagnosis. PCR-based techniques are
that could aerosolize tissue debris). These guidelines should of particular value in screening tissues for latent viral
be clarified with the regulatory authorities of the appro- infections (Edington et al 1994). In situ hybridization is a
priate country (e.g. Health and Safety Executive in the more technically demanding technique than immunohis-
United Kingdom). For proper health and safety precautions tochemistry, and generally less used for routine diagnostic
to be followed in a post-mortem examination it is essential investigations. It is of value in the detection of infectious
Fig. 21.4. Immunoperoxidase staining of

nasal mucosa of pony following EHV-1
infection. Cells containing EHV-1 antigens
are immunostained brown. Note disorganiza-
tion and erosion of mucosa, with associated
inflammation. Reproduced with the permis-
sion of Dr Julia Kydd, Animal Health Trust,
Newmarket, UK.
agents where specific antibodies are not available or where Kaup FJ, Drommer W, Deegen E 1990 Ultrastructural findings
latency results in highly restricted nucleic acid transcrip- in horses with chronic obstructive pulmonary disease
tion and undetectable protein expression. (COPD). I: Alterations of the larger conducting airways.
Kelley LC, Mahaffey EA 1998 Equine malignant lymphomas:
Conclusion morphologic and immunohistochemical classification.
Veterinary Pathology 35: 241–252
Close communication between experienced equine patholo- Kydd JH, Smith KC, Hannant D et al 1994a Distribution of
gists and respiratory clinicians is key to the successful equid herpesvirus 1 in the respiratory tract of ponies:
implications for vaccination strategies. Equine Veterinary
investigation of equine respiratory disorders. A systematic Journal 26: 466–469
post-mortem examination of the equine respiratory tract is Kydd JH, Smith KC, Hannant D et al 1994b Distribution of
recommended in all cases of respiratory disease that do not equid herpesvirus 1 in the respiratory tract associated
respond to logical therapy, and classical methods should be lymphoid tissue: implications for cellular immunity.
supplemented and extended wherever appropriate by Equine Veterinary Journal 26: 470–473
Lopez JW, del Piero F, Glaser A et al 1996 Immunoperoxidase
modern molecular techniques. histochemistry as a diagnostic tool for detection of
equine arteritis virus antigen in formalin fixed tissues.
Acknowledgment Luke D 1958 Tuberculosis in the horse, pig, sheep and goat.
I am grateful to my colleagues Katherine Whitwell and Veterinary Record 70: 529–536
Mair TS 1996 Bacterial pneumonia associated with corti-
Tony Blunden for teaching me the techniques described in costeroid therapy in three horses. Veterinary Record
this chapter. 138: 205–207
Mair TS, Lane JG 1989 Pneumonia, lung abscesses and
pleuritis in adult horses: a review of 51 cases. Equine
REFERENCES Veterinary Journal 21: 175–180
Mair TS, Stokes CR, Bourne FJ 1988 Immunohistochemical
Allen GP, Kydd JH, Slater JD et al 1999 Recent advances in study of the local humoral immune system of the equine
understanding of the pathogenesis, latency and immu- respiratory mucosa. Research in Veterinary Science
nology of EHV-1 abortion. In: Wernery U, Wade JF, 45: 160–165
Mumford JA et al (editors) Proceedings of the Eighth McChesney AE, England JJ, Rich LJ 1973 Adenoviral infection
International Conference on Equine Infectious Diseases. in foals. Journal of the American Veterinary Medical
R&W Publications, Newmarket pp.129–146 Association 162: 545–549
Barclay AJ, Paton DJ 2000 Hendra (equine morbillivirus). Meyer TS, Fedde MR, Gaughan EM et al 1998 Quantifica-
Veterinary Journal 160: 169–176 tion of exercise-induced pulmonary haemorrhage with
Blunden AS, Mackintosh ME 1991 The microflora of the lower bronchoalveolar lavage. Equine Veterinary Journal
respiratory tract of the horse: an autopsy study. British 30: 284–288
Veterinary Journal 147: 238–250 Peters SE, Wakefield AE, Whitwell KE et al 1994 Pneumocystis
Blunden AS, Gower SM 1999 A histological and immuno- carinii pneumonia in thoroughbred foals: identification of
histochemical study of the humoral immune system of a genetically distinct organism by DNA amplification.
the lungs in young Thoroughbred horses. Journal of Journal of Clinical Microbiology 32: 213–216
Comparative Pathology 120: 347–356 Robinson NE, Derksen FJ, Olszewski MA et al 1996 The
Blunden AS, Hannant D, Livesay G et al 1994 Susceptibility pathogenesis of chronic obstructive pulmonary disease of
of ponies to infection with Streptococcus pneumoniae horses. British Veterinary Journal 152: 283–306
(capsular type 3). Equine Veterinary Journal 26: 22–28 Rooney JR, Robertson JL 1996 Respiratory system. In: Rooney JR,
Bodrossy L, Sessitsch A 2004 Oligonucleotide microarrays in Robertson JL (editors) Equine Pathology, 1st edn. Iowa
microbial diagnostics. Current Opinion in Microbiology State University Press, Iowa, pp.23–56
7: 245–254 Schambourg MA, Laverty S, Mullim S et al 2003 Thoracic
Colbourne CM, Bolton JR, Mills JN et al 1992 Mesothelioma in trauma in foals: post mortem findings. Equine Veterinary
horses. Australian Veterinary Journal 69: 275–278 Journal 35: 78–81
Darke PGG, Bonagura JD, Kelly DF 1996 Post mortem Smith KC, Blunden AS, Whitwell KE et al 2003 A survey of
examination of the cardiovascular system. Color Atlas of equine abortion, stillbirth and neonatal death in the
Veterinary Cardiology. Mosby-Wolfe, London, pp.10–20 UK from 1988 to 1997. Equine Veterinary Journal
Edington N, Welch HM, Griffiths L 1994 The prevalence of 35: 496–501
latent Equid herpesviruses in the tissues of 40 abattoir Stoica G, Cohen N, Mendes O et al 2004 Use of immuno-
horses. Equine Veterinary Journal 26: 140–142 histochemical marker calretinin in the diagnosis of a
Ewing PJ, Cowell RL, Tyler RD et al 1994 Pneumocystis carinii diffuse malignant metastatic mesothelioma in an
pneumonia in foals. Journal of the American Veterinary equine. Journal of Veterinary Diagnostic Investigation
Jones TC, Maurer FD 1943 The pathology of equine influenza. Westerfield C, Dimock WW 1946 The pathology of equine
American Journal of Veterinary Research 4: 15–31 virus abortion. Journal of the American Veterinary
Kagawa Y, Hirayama K, Tagami M et al 2001 Immunohisto- Medical Association 109: 101–111
chemical analysis of equine pulmonary granular cell Yager JA 1987 The pathogenesis of Rhodococcus equi pneu-
tumours. Journal of Comparative Pathology 124: 122–127 monia in foals. Veterinary Microbiology 14: 225–232
Viral Infections of the Equine
Respiratory Tract
22 James Wood, Kenneth C Smith, Janet M Daly
and J Richard Newton
Introduction
comparing epidemic coughing in young racehorses with
This chapter describes features of the most commonly the then recently isolated swine influenza virus, showed for
encountered equine respiratory viruses (equine influenza the first time that the disease was the result of a filterable
viruses, equine herpesviruses and equine arteritis virus) virus and that it was experimentally reproducible. The
and their control, as well as those of less widespread but disease had many pseudonyms, including “laryngotracheo-
nevertheless important infections such as Hendra virus bronchitis”, “infectious bronchitis”, “infectious catarrh”,
and African horse sickness. A few comments are made at “Hoppengarten cough”, “Gulf Stream disease”, “epizootic
the end of the chapter about other viruses with effects cough”, and “Newmarket cough”. Influenza became recog-
on the respiratory tract. nized as a highly contagious respiratory disease char-
acterized by acute pyrexia and a harsh dry cough that
Outbreaks of disease rapidly spread both within and between groups of young
horses, particularly in racing yards. There were few deaths
A common feature of all viruses covered here is their or complications when horses were rested and recovery
ability to cause outbreaks of disease as a result of their usually occurred in 2–3 weeks.
contagious nature. Despite this, clinical cases may appear The first identification of the viral family causing this
in either individual animals or as outbreaks in large disease was in 1955 when it was shown that horses in a
populations of animals, or indeed anywhere between these respiratory disease epidemic in Sweden seroconverted to a
two extremes, depending on the specific infection, the soluble human influenza virus antigen. Shortly afterwards,
individual level and “herd” immunity, how the animals are an influenza virus was isolated for the first time from
managed and also, critically, on chance effects. coughing horses in Czechoslovakia and this prototype virus
Some insight can be gained into etiology from clinical was the Prague/56 H7N7 virus (see below for description
presentation and epidemiological features but clinical cases of how viruses are classified). Retrospective serological
or outbreaks of equine respiratory disease are still often surveys demonstrated that the virus had been the cause
attributed to infection with a virus, or with “the virus” of disease in many areas of the world. Serological and
without any specific etiological investigations. Optimal virological monitoring of epidemic respiratory disease
treatment and advice on management and prevention demonstrated that this prototype virus continued to
cannot be given without knowledge of specific cause and be responsible for disease outbreaks in predominantly
while etiological investigations can sometimes be hard to young horses in many countries between 1957 and 1963.
justify in individual cases, they should be encouraged In January 1963 there was an outbreak of rapidly
when dealing with disease in groups. Our experience, and spreading acute respiratory disease among horses at
that of others, is that it is often impossible to differentiate several racetracks in Miami, USA. A characteristic of this
cases of disease caused by equine influenza, equine outbreak that differentiated it from earlier outbreaks
herpesvirus, and Streptococcus equi var. equi on clinical was that it affected all ages rather than predominantly
grounds alone. Although stating the obvious, hemato- younger horses. A novel subtype, H3N8, was isolated and
logical investigation of outbreaks does not provide a was subsequently responsible for an equine influenza pan-
reliable insight into etiology. demic. A serological survey of H3N8 antibodies following
the epidemic of H7N7 influenza in the UK in 1963 demon-
strated that British horses were completely susceptible to
Equine Influenza Virus
the new virus and an epidemic was predicted. Despite the
Historical context start of production of a vaccine, insufficient stocks were
available before the disease was first seen in February 1965
A disease of horses clinically indistinguishable from on two studs in Sussex. The stud had recently received
influenza and referred to as a “distemper” was described as mares from France, where the disease had been present for
long ago as 1732. In the 1930s German researchers about 1 month.
287
SECTION 3 : Infectious Respiratory Diseases
288 22 Viral Infections of the Equine Respiratory Tract
Virology indicate that the viruses are antigenically unrelated and

values approaching 100 indicate that viruses are
Influenza viruses are pleomorphic, spherical or filamentous antigenically indistinguishable. When this method is
virions with a diameter of 80–120 nm. They have a seg- applied to reports of reciprocal HI tests with equine H3N8
mented, single-stranded RNA genome of negative sense. viruses, a number of conclusions can be drawn. It is clear
The eight gene segments code for two surface glyco- that the species in which the antisera are prepared has a
proteins, the hemagglutinin (HA) and neuraminidase (NA), marked effect on the apparent relatedness of two viruses.
the internal matrix protein and nucleoprotein, and other Horse sera are relatively cross-reactive, particularly when
structural and non-structural proteins involved in virus taken from repeatedly vaccinated animals whereas ferrets
replication. The RNA segments are closely associated with develop the most strain-specific antibody response. Where
the nucleoprotein and are surrounded by the matrix ferret sera have been used to examine the same pair of
protein, which is closely associated with the lipid envelope viruses in different laboratories, the antigenic relatedness
containing the two surface glycoproteins. HA is the major based on R-values is, on the whole, very similar, suggesting
surface glycoprotein making up approximately 25% of that this approach is a reliable method of quantifying
the virus protein as compared to 5% for NA. These glyco- antigenic differences.
proteins are the principal determinants for cell entry in Minor antigenic drift has been identified within the
infection (HA) and for exit from the cell after virus replica- H7N7 subtype, while more extensive drift into two distinct
tion (NA). Influenza virus is enveloped and, as such, does lineages has been observed in H3N8 viruses (Fig. 22.1)
not remain infectious for long outside the host (generally (Daly et al 1996, Lai et al 2001). As a result of this feature
<7 days even in favorable conditions) and is rapidly inacti- of influenza viruses, the formulation of human influenza
vated by sunlight and disinfectants (Hannant et al 1996). vaccines is reviewed on an annual basis and in most years
There are three types of influenza viruses, A, B, and C, is changed to reflect the virus strains most representative of
all of which are classified in the Orthomyxovirus family. those in worldwide circulation.
The antigenic character of the nucleoprotein and matrix A formal surveillance system was established for equine
proteins determines the virus type. All equine influenza influenza in 1995 (Mumford 1999). An international
viruses are type A. The HA and NA define subtypes within panel of experts, including representatives from the Office
a virus type. Among all influenza viruses, 16 HA and nine International des Epizooties (OIE) and the World Health
NA subtypes have been identified. In the viruses that Organization (WHO) influenza reference laboratories,
naturally infect horses, only H7N7 and H3N8 have been reviews data collected on outbreaks of influenza, vaccine
recognized. performance in the field, and antigenic and genetic
Antigenic drift occurs when mutations in the HA gene characteristics of new virus isolates annually. The expert
sequence result in amino acid substitutions. As with other surveillance panel makes recommendations on the need to
RNA viruses, influenza virus replication is highly error- update vaccine strains, which are published in the OIE
prone, and therefore newly synthesized viral genes have a Bulletin. The criteria used for deciding on the need to
high frequency of mutation. Many of these mutations are update equine influenza vaccine strains are based largely
either inconsequential or are detrimental to the virus but on those used for human influenza vaccine strain selection,
mutations affecting the antigenic sites of the HA (and NA) i.e. detection of changes in the HA as characterized by HI
can lead to the virus not being recognizable by pre-existing tests using ferret and horse antisera, genetic sequencing of
antibodies generated by infection or vaccination with an the HA1 gene and vaccine breakdown in the field.
earlier strain. Immunological pressure, such as from vacci- Improved surveillance in the field, standardization of
nation, may influence antigenic drift (Mumford 1999). the potency of vaccines (see later) and the introduction
Phylogenetic relationships between viruses are estab- of this vaccine strain selection system have enabled
lished either using evidence from RNA sequencing of the the development of a fast-track licensing system in the
HA gene or by antigenic analysis using hemagglutination European Union (EU) for equine vaccines containing
inhibition (HI) tests using ferret or equine sera. Historically, updated strains. While recommendations for equine
antigenic drift in equine H3N8 viruses has been examined influenza vaccines are reviewed on an annual basis,
in HI tests employing postinfection or postvaccination sera changes are not required so frequently.
prepared in a number of different species. Conclusions Major or subtype changes in the surface glycoproteins
about the antigenic relatedness of equine H3N8 viruses can occur as a result of the reassortment of viral genome
and the significance of observed differences with respect to segments with those from other influenza viruses, or intro-
the immunity induced have varied. duction from other host species, particularly aquatic birds,
Antigenic differences between equine influenza strains the major reservoir host for influenza viruses. New viruses
have been examined using R-values calculated from generated by this process (frequently termed “antigenic
reciprocal tests between pairs of viruses and matching shift”) may result in pandemics because all populations will
antisera. Using this expression, R-values approaching 0 tend to be completely susceptible, as was seen with the
22 Viral Infections of the Equine Respiratory Tract 289
Leicester/1/00
Taby/91 Hong Kong/92 Leicester/2/00
Borlange/91 Lambourn Grosbois/98
/92
American-like Avesta Holland/1/95
viruses Newmarket/2/93 /93 Newmarket/95
Berlin/94
Moulton/98 Roma/91
Snailwell/98
Edinburgh/98 Saskatoon/90 Visingso
/90
Dubai/41/95
Philippines/97 Sussex/89
Kentucky/96 European-like
Newmarket/1/93 viruses
Switzerland/2/95
Kentucky/96
Brno/97 Arundel/91 Czechoslovakia/95
Alaska/91 Kentucky/91 Suffolk/89 Italy/788/91
Soderala/94
Kentucky/94
Kentucky/95
Alvdalen/96
Florida/93 Argentina/99
Kentucky/97 Kentucky/99 Kentucky/92
South Skara/88
Argentina/1/93 Kentucky/90 Kentucky/87
American Argentina/94
viruses
Kentucky/86
Santiago/85
Kentucky/81
Newmarket/76 Aby/84
Fontainebleau/79
Romania/80
France/67
Tokyo/71
Algiers/72
La Plata/88
Miami/63
Fig. 22.1. Phylogenetic tree of equine influenza A (H3N8) viruses based on amino acid sequences of HA1
molecules.
emergence of H3N8 viruses in Miami in 1963 and with associated with hemorrhagic pneumonia and significant
human influenza viruses on three occasions in the 20th mortality (Crawford et al 2005). Transmission in the
century. An entirely avian H3N8 virus transferred to canine population is now widespread in the USA.
horses in Jilin province in China in 1989 (Shortridge et al
1995). The resulting outbreak was associated with a Clinical signs and pathogenesis
mortality of up to 20% and a morbidity of up to 80%.
This compares with a mortality rate of around 2% in an In controlled experimental infection studies in horses,
outbreak caused by a conventional equine H3N8 virus the incubation period usually varies between 1 and 3 days
elsewhere in China in 1993–4. The avian-derived H3N8 with a range of 18 h to 5 days, with the length of the
virus did not persist in the equine population and has not incubation period being inversely related to the virus dose
been detected since that time. (Mumford 1999). Coughing and fever are the most com-
Recent investigations in North America have implicated mon clinical signs of equine influenza in naive animals,
an equine-derived H3N8 virus as the cause of outbreaks the cough being dry, harsh and initially non-productive.
of severe respiratory disease in kenneled greyhounds, Coughing is frequent during the first week of infection and
These foals developed primary viral pneumonia and they

40.5
had very high temperatures (41–42°C), stopped sucking,
Mean rectal temperature (ºC)
40.0
had increased heart rates, and manifested signs of severe
39.5 respiratory distress, including tachypnea (80–90 breaths
39.0 per minute) and soft gurgling sounds on auscultation of
38.5 the thorax. Many became weak and died 7–10 days later.
38.0 Influenza is also a cause of mortality in donkeys
37.5 and mules. Necropsies performed on donkeys affected
Challenge in the H3N8 outbreak in Britain in 1969 revealed acute
37.0
1 2 3 4 5 6 7 8 9 10 11 bronchopneumonia complicated by secondary bacterial
Day
infection. Secondary complications and sequelae to equine
influenza are common in stressed or neglected animals.
Fig. 22.2. Mean daily rectal temperatures (mean ± 95% confidence Bacterial infections, including Streptococcus equisimilis,
intervals around the mean) following experimental influenza virus Streptococcus zooepidemicus, Escherichia coli, Staphylococcus
infections in naive Welsh mountain ponies conducted at the Animal
Health Trust (pyrexia is defined as > 38.5°C and is indicated by the
spp., Pseudomonas spp., Pasteurella spp., Aerobacter spp.,
broken line). Actinobacillus equuli, and Bordetella bronchiseptica, result in
purulent nasal discharges, pharyngitis, conjunctivitis, and
sometimes bronchopneumonia.
During an outbreak of equine influenza in the UK
in uncomplicated cases, given sufficient rest, will disappear during 2003, there were reports of unusually severe
within 1–3 weeks. There is usually a mild rhinitis and clinical signs among unvaccinated animals. Two influenza-
no obvious swelling of the submandibular lymph nodes. infected horses developed neurological signs, and one was
The nasal discharge is initially serous but frequently euthanased. Post-mortem examination of the brain of that
becomes mucopurulent as a result of secondary bacterial horse revealed viral-type, non-suppurative encephalitis,
infection. In populations of partially immune, vaccinated and influenza virus antigen was demonstrated by the
horses where clinical signs are not necessarily typical of immunostaining of sections of nasal mucosa but was
influenza, one of the most common signs is nasal dis- not demonstrated in the brain (Daly et al 2006). Experi-
charge, which rapidly spreads among horses. mental infection of ponies not previously exposed to equine
Pyrexia is a feature of natural outbreaks of equine influenza virus with a strain representative of the 2003
influenza virus infection in naive horses. Experimental outbreak resulted in more severe clinical signs and higher
infections with equine influenza viruses have allowed levels of cytokines in nasal secretions than observed for
specific clinical signs to be more precisely characterized earlier strains of equine influenza virus (unpublished data).
with respect to time since infection. Daily rectal tempera- In the absence of an alternative explanation, the possibility
ture data in naive ponies experimentally challenged with that infection with a highly pathogenic strain of equine
various H3N8 influenza viruses are shown in Fig. 22.2 influenza virus had given rise to neurological complications
(data courtesy of J. Daly and L. Spencer). In general, H3N8 was suspected on the basis of the findings.
infections produce more severe clinical disease with higher Outbreaks of clinically mild influenza do occur among
and more prolonged pyrexia than H7N7 infections, as vaccinated horses that have incomplete immunity, par-
H3N8 viruses appear to be more pneumotropic than H7N7 ticularly if vaccine strains have become outdated. In
viruses. Peak temperatures in H7N7 and H3N8 infections such outbreaks, the mild signs may not be recognized or
have been reported as 40.4°C and 41.2°C, respectively. diagnosed as influenza. In two longitudinal studies of
Continuous fever beyond 4 or 5 days accompanied by respiratory disease in racehorses, in Canada and the UK,
pronounced mucopurulent nasal discharge is attributable influenza was associated with signs of upper respiratory
to secondary bacterial infection. Other signs of influenza tract disease (Morley et al 1999, Newton et al 2003). In
infection may include anorexia, dyspnea, and myalgia, other outbreaks, the first sign noted was poor training and
and there may be icterus in some cases. Cardiac damage racing performance. It is clear from experimental work that
may occur, particularly in older animals and in those that subclinical infections can occur and indeed are common
have been worked during the acute phase of the disease under the cover of partial immunity (see later).
(Gerber 1970). Hematological changes during equine influenza infec-
Mortality rates are usually very low in uncomplicated tions are non-specific and variable. Anemia, leukopenia
cases, with the exception of young foals that have not and lymphopenia are often observed in the first 3–7 days
acquired maternal-derived immunity. Death in foals with an increased neutrophil : lymphocyte ratio in the
occurred during H3N8 outbreaks in Britain in 1965 and first 2 or 3 days after infection. Monocytosis may also
South Africa in 1986, particularly in foals that were born be observed during early convalescence from about day 7
while their dams were suffering from the acute disease. after infection.
A B C
Fig. 22.3. Scanning electron micrographs of (A) normal equine epithelium 6 days post-influenza infection, showing disruption and
tracheal ciliated epithelium, (B) equine tracheal ciliated epithelium loss of cilia from the tracheal epithelium. Reproduced with the
2 days post-influenza infection, showing disruption and loss of cilia permission of A.S. Blunden and J.A. Mumford.
from the tracheal epithelium, and (C) equine tracheal ciliated
Equine influenza virus, as well as causing pathology of hens’ eggs are inoculated via the amniotic (6- to 8-day-old
the upper respiratory tract, also extensively damages embryos) or allantoic (8- to 12-day-old embryos) routes.
the ciliated epithelial cells lining the conducting airways. Amniotic and allantoic fluids are harvested after incuba-
This leads to disruption of normal mucociliary clearance tion for 48–72 h at 34°C and examined for hemaggluti-
with consequent accumulation of mucus and bacteria nating activity using chick erythrocytes.
in the airways and exposure of the lamina propria The adoption of more widespread vaccination has made
and irritant receptors, all leading to frequent coughing. the diagnosis of influenza infection less straightforward,
Figure 22.3 shows disruption and loss of cilia from the with clinical signs being less severe, blood samples from
tracheal epithelium at different stages of experimental acute cases already possessing moderate levels of serum
influenza infection. antibody, and the quantities of live virus retrievable from
the respiratory tract being greatly reduced. The develop-
Diagnosis ment of sensitive and rapid enzyme-linked immunosorbent
assays (ELISA) for the detection of influenza nucleoprotein
The characteristic clinical features of equine influenza in antigen in extracts from nasopharyngeal swabs has greatly
susceptible animals (rapidly spreading disease manifested improved the ability to diagnose influenza in previously
by a harsh, dry cough, high temperature, and nasal dis- vaccinated horses (Cook et al 1988, Livesay et al 1993).
charge) are sufficiently characteristic to permit a tentative In addition, ELISA may be more appropriate where sub-
clinical diagnosis. However, in animals that have previously mission of specimens in a good state of preservation to
experienced the infection or that have waning vaccinal laboratories for virus isolation may not be practical when
immunity, it is difficult to differentiate influenza from other the distances are great or the temperatures are unfavorable
respiratory infections. In such situations, or where equine for maintaining viability of the virus. The nucleoprotein
influenza has not occurred in the locality in the recent is antigenically similar in all influenza A viruses and
past, laboratory diagnosis, involving rapid antigen detec- thus this assay cannot be used to differentiate H3N8 and
tion, virus isolation or serology, is required. H7N7 subtypes. Detailed subtyping of the infecting virus
Specimens for virus detection and/or isolation should be requires its isolation, although the identity of the HA
collected as soon as possible after the onset of pyrexia and can be determined through the examination of host
coughing, as the period of virus excretion may be as short serological responses. Viral antigen can also be detected
as 1–2 days in animals with pre-existing immunity. Virus directly in nasal secretions by immunofluorescence of
may be cultured from nasopharyngeal secretions collected infected cells or the viral genome can be detected and
into virus transport medium, usually by swabbing of the sequenced by polymerase chain reaction (PCR).
nasopharynx or by transendoscopic tracheal lavage. The Antibody to influenza virus may be detected by its ability
transport medium should not contain fetal calf serum, to inhibit the agglutination of chick erythrocytes mediated
which inhibits influenza virus growth, and samples should by the influenza virus HA. The HI test is subtype specific,
be submitted on ice to the laboratory as quickly as possible. and is much more sensitive for antibody to H7 viruses than
Influenza virus can be cultured in embryonated it is to H3 virus antibody when whole virus is used in
hens’ eggs or in susceptible mammalian cells such as the assay. The sensitivity of the test for antibody to the
Madin–Darby canine kidney (MDCK) cells. Embryonated H3 viruses may be enhanced by disruption of the virus
with detergent. In HI tests a fourfold or greater increase world. Australia, New Zealand, and Iceland are the only
in antibody titer between acute and convalescent sera countries that are known to have remained entirely free
is regarded as significant and indicative of infection. from the infection and Japan has not experienced a large
Although an ELISA has been developed for the detection epidemic since 1972. The disease is considered endemic in
of serum antibodies to equine influenza, this has been of the USA, UK, and other European countries, based on the
limited benefit in horses that have received multiple doses occurrence of almost annual outbreaks.
of vaccine. There are many different factors that influence the
Subclinical infections may occur in vaccinated horses epidemiology of equine influenza. Some relate to the
but they do not necessarily stimulate a fourfold increase in intrinsic properties of the virus, some to the pathogenesis
HI antibody, and such animals may be a source of infection of the disease, the immune system of the horse and, not
to other horses. Significant increases in antibody may least, to the equine population structure and activity of the
be detected using the single radial hemolysis (SRH) test equine industry. A key factor in the spread of equine
(Morley et al 1995). In that test, influenza virus is coupled influenza in the last two decades has been the increase in
to sheep erythrocytes with chromium chloride, and agarose transportation of horses over long distances by air. Horses
gels are prepared containing these sensitized cells and incubating the disease, or those that are clinically or
guinea-pig complement. Equine serum, inactivated by heat- subclinically infected, can introduce the infection into a
ing at 56°C for 30 min, is introduced into wells in the gels susceptible population if they are not quarantined
and incubated for 18–20 h at 37°C. The diameters of the adequately. Examples of this have been seen in the UK,
resultant zones of hemolysis are measured. The repro- South Africa, Hong Kong, Dubai, Puerto Rico, and the
ducibility of the assay allows the identification of infections Philippines. In some areas of the world, quarantine
that stimulate no more than a twofold increase in antibody. procedures have been virtually ignored to facilitate the
The SRH assay has also been widely used in both experi- international movement of horses for racing, competition
mental and field studies of vaccine efficacy, and correlation and breeding purposes, particularly among thoroughbreds.
between vaccine-induced SRH antibody and protective In addition, inadequate immunization from vaccination
immunity from whole virus inactivated vaccines is well leaves horses with partial immunity and can merely result
established (Mumford & Wood 1992, Newton et al 2000b). in the suppression of clinical signs. This may make
infections difficult to recognize clinically while still allowing
Epidemiology virus excretion. Such horses probably play an important
role in the maintenance and spread of equine influenza.
Equine influenza is a highly contagious disease charac- However, countries such as Australia, New Zealand, Dubai,
terized by rapid spread in susceptible populations and Hong Kong, and Japan all now have extremely stringent
morbidity rates are consequently high. In one outbreak in quarantine requirements, even for major competitions, to
1965, only 11 out of 634 susceptible horses resisted the prevent the introduction of equine influenza infection to
disease, giving a morbidity rate of 98.2%. Detailed analysis their susceptible horse populations. In most of these
of outbreaks in 1963 suggested that the basic reproduction countries, vaccination is used in conjunction with strict
rate, or R0, in a North American racetrack was around quarantine and post-import testing.
10.2, consistent with its highly contagious nature (Glass et Influenza viruses produce a frequent and harsh cough,
al 2002). (R0 is a term used to quantify transmissibility and which is an efficient way of spreading the virus in aerosols
represents an estimate of the average number of secondary and over distances of many meters or more. Although it is
cases of an infection produced directly by an index on believed that influenza is transmitted almost exclusively
introduction into a naive population.) Despite this, detailed directly between horses, evidence from the South African
computer modeling, supported by subsequent clinical outbreak in 1986 indicated that people and contami-
observations, suggests that many outbreaks often die out as nated vehicles could transmit the virus indirectly (Guthrie
a result of chance effects after only a few animals have et al 1999). Virus excretion in fully susceptible horses
been infected, especially in vaccinated populations. Thus, lasts between 7 and 10 days, although infected animals
influenza should be considered even when outbreaks do not are rarely infectious for more than 7 days. Data from
affect all the susceptible animals in a population. experimental infections suggests that large amounts of
Equine influenza has been reported in many parts of the virus may be shed continuously over the infectious period,
world, including North and South America, the West with >103 EID50 (50% egg infective dose per ml of swab
Indies, Europe, countries of the former USSR, North Africa, extract) influenza virus being recovered from single daily
the Middle East, India, Singapore, Japan, and Mongolia. nasopharyngeal swabs. Coughing may persist for longer
The introduction of equine influenza into South Africa in than virus excretion, but the short incubation period also
1986, India in 1987, Hong Kong in 1992, Dubai in 1995, contributes to the rapid spread of infection. Long-term
and Puerto Rico and the Philippines in 1997 were other carriers (>10–14 days) of equine influenza are not thought
milestones in the transmission of this virus throughout the to occur.
Immunity to equine influenza is short-lived, with clinical the single radial immunodiffusion (SRD) test, was intro-
immunity lasting little more than a year. Immunity to duced. In addition, the SRH assay for measuring antibody
infection may be even more short-lived, therefore, allowing to HA in equine serum is significantly more reproducible
re-infection to occur without clinical signs within a matter than the HI or other tests. Detailed studies of vaccine
of months after a previous infection (Hannant et al 1988). potency in horses have demonstrated a direct relationship
There is no evidence that the occurrence of equine between HA content in vaccines, measured in μg by SRD,
influenza is influenced by climatic conditions. Outbreaks and HA antibody levels, measured by SRH, stimulated by
of disease, particularly in the USA and some parts of inactivated vaccines. Adjuvants vary in their ability to
Europe, are primarily related to the mixing and movement induce greater antibody levels at given levels of HA as
of horses and to the introduction of young stock onto measured by SRD.
racetracks where the infection may be endemic. Vaccine evaluation by experimental challenge infection
Features of equine influenza are similar in other equid of horses was slow to progress because of difficulties
species, such as donkeys, mules, and zebras. A high mor- encountered in reproducing clinical disease. These
tality rate has been reported in donkeys in some, but not all difficulties have been overcome by using nebulized aerosols
outbreaks. Indigenous equids are likely to provide important in known naive animals (Mumford & Wood 1992). This
foci of susceptible animals for equine influenza viruses in delivery system mimics a natural infection by producing
regions where their widespread vaccination is impractical. infectious droplets (diameter <5 μm) capable of reaching
the upper and lower airways and avoids a concentration
Prevention and control of challenge inoculum at the site of sampling in the
nasopharynx. Using this challenge method, a series of
Management procedures aimed at limiting the severity of experiments to measure the protection afforded by
disease and the spread of infection, whether on a local or inactivated virus vaccines with a variety of adjuvants and
international basis, require sensitive diagnostic techniques antigen presentation systems has been performed. The SRD
for rapid detection of clinical and subclinical infection, test has been used to standardize inactivated vaccines, the
effective vaccines, and a coordinated strategy for the use of SRH test has been used to measure antibody responses in
both. Equine influenza vaccines were first developed in the the horse, and challenge infections were used to assess
1960s and are used widely for control of equine influenza protection against infection and disease in animals with
but, in spite of intensive vaccination programs in some different defined immunological backgrounds. These
groups of horses, equine influenza infections remain a studies have shown good correlation between vaccine-
serious problem. While H7N7 vaccines were generally suc- induced antibody levels directed against HA and protective
cessful, the H3N8 component of inactivated vaccines has immunity against infection with antigenically similar
not been so effective and reasons for vaccine breakdown viruses (“homologous” viruses), with an effect of challenge
have been the subject of intense investigations. Research dose. A threshold of SRH antibody levels required to pre-
has focused on vaccine potency, the use of different adju- vent infection varied between >120 mm2 and >154 mm2,
vants, vaccination schedules, and antigenic drift. During with the threshold increasing incrementally with the
the last decade, progress has been made in all these areas infectious viral dose. Field studies have validated this
of investigation, providing new approaches to the control of challenge system as being representative of field challenges
equine influenza. (Newton et al 2000b). Vaccinated racehorses in the UK
with pre-exposure SRH levels ≥140 mm2 during outbreaks
Vaccine potency did not become infected, whereas those with lower anti-
body levels did. In South Africa in 1986, pre-infection SRH
The principal markers for resistance to influenza virus antibody levels of around 160 mm2 were associated with a
infection derived from whole virus inactivated or 90% protection rate.
subunit vaccines are circulating antibodies specific for Many commercially available equine influenza vaccines
the HA and NA glycoproteins. Progress in assessing the contain inactivated whole virus with an adjuvant, includ-
protective efficacy of early vaccines was hampered by a ing mineral oil, alhydrogel and carbomer and some are
lack of reliable methods to measure the HA content of based on viral subunits [e.g. ISCOMs (immunostimulatory
vaccines and the host’s antibody response to the HA and complexes) or micelles combined with Quil A; Wood et al
of a reproducible challenge method in horses. Improved 1983a, Mumford et al 1988, 1994a,b,c]. Antibody responses
methods of measuring vaccine potency, antibody responses, stimulated by vaccines containing aluminum phosphate or
and protection against infection have been developed, hydroxide were more durable than those induced by
facilitating progress in vaccine standardization and design. aqueous vaccines of equivalent antigenic content. Even
Based on experience with human influenza viruses, a with adjuvant, mean antibody levels tended to decline to
reliable in vitro potency test for the measurement of low levels by 16–20 weeks after the second and third doses
immunologically active HA in equine influenza vaccines, of vaccine, although this again was affected by antigenic
content. In contrast, the incorporation of a polymer adju- and consequently generate a rapid anamnestic response
vant was found to stimulate antibody that remained at upon field exposure to equine influenza virus. The inci-
a high level for at least 6 months after the third dose of dence of free and cell-associated virus is thereby reduced
vaccine. Similarly, vaccination with three doses of ISCOMs and recovery is enhanced. Live attenuated and live vectored
containing 15 μg HA resulted in the level of SRH anti- equine influenza vaccines that should more closely mimic
body persisting at around 70 mm2 for 15 months following natural infection have become commercially available.
the third dose. One vectored product is a live recombinant vaccine,
The historical lack of standardization of vaccines from based on a canarypox vector that expresses the HA genes of
different sources, and the undemanding standards of some equine influenza viruses. The recombinant virus undergoes
licensing authorities, has resulted in the use of products an abortive infection in mammalian cells so that no
with inadequate potency in terms of ability to stimulate progeny viruses are made but the expressed viral antigens
antibody to the HA (Wood et al 1983a,b, 1986, 1988). A are processed endogenously and presented as peptides
large double-blind field trial using a commercial killed via major histocompatibility complex class I by the host
vaccine failed to demonstrate a significant difference cell in the same manner as occurs in natural infection.
in the rate of disease between vaccinated and unvacci- Canarypox-vectored vaccines induce cellular immune
nated animals in the face of a naturally occurring out- responses to human immunodeficiency virus and probably
break of disease in a population of horses stabled at a do the same for equine influenza, although the data to
racetrack in North America (Morley et al 1999). The demonstrate this are only just becoming available with the
situation is improving with the establishment of European advent of new assays.
Pharmacopoeia international reference preparations to A cold-adapted, temperature-sensitive, modified live
standardize the serological tests used in potency evaluation virus equine influenza vaccine, delivered intranasally, is
of vaccines, and the introduction of federal regulations on commercially available in the USA (Chambers et al 2001,
equine influenza vaccines in Europe and, more recently, in Lunn et al 2001, Townsend et al 2001). The safety and
the USA. Inactivated vaccines currently available in Europe efficacy of the vaccine has been demonstrated in experi-
(in 2005) generally induce high peak antibody responses mental studies but the vaccine does not provide sterile
(>150 mm2 SRH) with good duration after the third dose immunity, particularly 6 months after a single dose.
and some vaccines from North America do the same. There is no correlation between concentrations of serum
antibody induced by vaccination and protection against
Natural immunity and live vaccines infection, but anamnestic responses can be demonstrated
at 7 days post infection. Primed animals have some circu-
Immunity provided by inactivated influenza virus vaccines lating antibody but serum antibody cannot be used as a
is dependent on high levels of circulating antibody to HA measure of efficacy of such live virus vaccines. The ability
and, in the absence of such antibody, vaccinated horses are to provide alternative correlates of immunity has lagged
susceptible to infection (Newton et al 1999, 2000b). In behind the development of these alternative vaccination
contrast, infection with influenza induces longer term strategies.
immunity independent of circulating antibody against
HA. For example, ponies with low or undetectable anti-HA Optimizing vaccination schedules
antibodies were clinically protected from challenge infec-
tion more than 1 year after natural infection (Hannant The early vaccination schedules for inactivated virus
et al 1988). This suggests an important difference in the vaccines required two primary doses 4–6 weeks apart
immune response following infection compared with followed by annual booster doses. Where vaccination is
vaccination using inactivated virus. Additional compo- compulsory in major European thoroughbred racing
nents of the immune response that may be involved are authorities, the current minimum requirements are of a
cell-mediated immunity and mucosal antibody responses primary course of two doses 4–6 weeks apart and a
local to the site of infection. 6-month booster followed by annual boosters. Extensive
Equine influenza virus infection has been demonstrated experience and mathematical models validated against
to generate virus-specific mucosal immunoglobulin A (IgA) experimental and field data have demonstrated that
and serum IgGa and IgGb responses, whereas a paren- vaccination dramatically reduces both the incidence and
terally administered inactivated virus vaccine induced size of epidemics, with larger outbreaks of equine influenza
only a serum IgG(T) response. The qualitative differences being exceptional amongst groups of vaccinated animals
between the immune responses that follow infection or but with substantial seasonal fluctuation associated
vaccination with inactivated virus suggest that improve- with levels of antibody declining after boosters (Fig. 22.4)
ments can be made in vaccine design. Ideally, vaccines (de la Rua-Domenech et al 1999, Glass et al 2002, Park
should induce broadly reactive, local and systemic, anti- et al 2003). Thus the vaccination policy ensures a suffi-
body and cellular immune responses, establish memory cient level of overall herd immunity to prevent large-scale
0.5 240 Autumn yearling sales

A
Probability of epidemic
220
0.4
200
0.3 180
160
SRH titer (mm2)

0.2
140 140 mm2
0.1
120
0 100
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52
80
Week (starting Jan 1)
60
40
0.5 20
B 0
Probability of epidemic
0.4 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Jan 1 Dec 31
0.3 Week of 1996
Cohort 1a Cohort 1b Cohort 2
0.2
Cohort 3 (n=5) Cohort 3 (n=3) Horses in training
0.1
0 Fig. 22.5. Mean Suffolk/89 SRH responses in four cohorts of yearlings

1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 and one cohort of horses in training following booster vaccination in
Week (starting Jan 1) 1996. Reproduced with permission from Newton et al (2000b).
Fig. 22.4. Comparison of the probability of (A) a 3% outbreak

or larger, and (B) a 10% outbreak or larger under the commonly
240
Mean standardized serum SRH antibody titer (mm2)
used vaccination policy (black line) and the alternative 6-monthly

vaccination strategy (blue line). Reproduced with permission from 220 SRH = 172*e–0.0053days
Park et al (2003). 200
180
160
outbreaks that are likely to lead to cancellation of race 140
meetings and other equestrian events. In contrast, a 120
program of three doses followed by annual vaccination 100
probably does not provide sufficient immunity to protect
80
all young horses from the disease or individual training
60
yards from small outbreaks of influenza. In particular,
40
horses following this regimen will have low antibody
20
titers for several months between their second and
0
third vaccinations. Also, SRH antibody levels in yearling 0 50 100 150 200 250 300 350 400 450 500
thoroughbreds on studs in Newmarket declined below a Time since last vaccination (days)
protective level within 4 months of a booster vaccination
(Fig. 22.5) (Newton et al 2000b). Importantly, this also Fig. 22.6. The scatter plot of mean SRH antibody levels (y) plotted
coincided with the autumn sales, a recognized risk period against time since last vaccination (x) for 140 thoroughbred yearlings.
Reproduced with permission from Newton et al (2000a).
for transmission of influenza in young thoroughbreds.
Later observations in yearlings entering training yards
in Newmarket confirmed that antibody levels at this time
were influenced by both time elapsed since the last vacci- frequency of vaccination in horses aged 2 years and
nation and the total number of vaccines that had been upwards to include 6-monthly boosters would offer a
previously administered (Fig. 22.6) (Newton et al 2000a). significant increase in protection over annual vaccination,
Additional 6-month booster vaccination benefits particularly in the latter half of the year (Park et al 2003).
horses that may be at high risk during this interval. Timing of the age at first vaccination may be critical to
Intensive vaccination regimens, involving booster doses the subsequent development of antibody. Maternal anti-
every 30–60 days, have been practiced in the USA but too body generally inhibits the development of neonatal
frequent administration of a potent vaccine could be antibody synthesis, and it has often been assumed that
detrimental. Using a mathematical model to assess the these antibodies have decayed to an insignificant level by
risk of an outbreak occurring in a thoroughbred popu- 3–4 months. The temptation is to vaccinate elite stock
lation in a typical flat-racing training yard, increasing the before the loss of maternal antibodies to avoid any window
of susceptibility. Foals born to mares vaccinated during the efficacy in terms of ability to eliminate virus excretion
gestation period have high levels of maternal antibody correlated directly with the degree of antigenic related-
within 2 days of birth. It has been suggested that not only ness between vaccine and challenge strain. Following
does vaccination in the face of maternal antibody interfere a meeting of OIE and WHO experts on newly emerging
with the development of active immunity but that repeat strains of equine influenza, it was recommended that
vaccination in the face of maternal antibodies could induce equine influenza vaccines be updated to include a 1989
tolerance (Cullinane et al 2001). It is recommended that isolate, and that efforts be made to increase surveillance
mares should be vaccinated against equine influenza in and virus characterization.
the last 4–6 weeks of pregnancy to ensure the transfer of Phylogenetic analysis of HA sequences revealed that
protective levels of antibody in the colostrum, and that equine H3N8 viruses, which had been evolving as a single
foals should not be vaccinated until their maternal lineage, apparently diverged into two distinct lineages
antibodies have waned (i.e. not until 6 months of age or during the mid-1980s (Fig. 22.1) (Daly et al 1996, Lai et al
they are seronegative). 2001). Viruses in one lineage were predominantly isolated
from horses in Europe, whereas viruses in the other lineage
Vaccine strain selection were predominantly from horses on the American con-
tinent. It was apparent, however, that American lineage
Surveillance of antigenic drift is a cornerstone of global viruses had been introduced into Europe on at least one
influenza control programs based on vaccination. Epi- occasion. The genetic divergence of American and European
demiological investigation of disease outbreaks also provides lineage viruses was reflected in their antigenic reactivity,
important information on vaccine efficacy and the need to raising the question of the potential importance of geograph-
update vaccine strains. Field studies, backed up by detailed ical variations in antigenic character for vaccine efficacy.
experimentation, have confirmed the need for inclusion of Field observations have supported the hypothesis that
antigenically relevant strains in vaccines (Daly et al 1996, antigenic differences between viruses of the American and
2003, 2004, Newton et al 1999). When antigenic drift is European lineages are sufficient to have an adverse effect
occurring, cross-protection between vaccine and challenge on vaccine efficacy. In contrast to outbreaks described
viral strains will diminish over time. above, in which high levels of antibody were protective in
Experimental studies have demonstrated that increas- outbreaks with viruses homologous to those in vaccines,
ingly higher levels of protective immunity are required during an outbreak caused by an American lineage virus in
from outdated vaccines to achieve minimal protection 1998, when the vaccines used contained only European
(Yates & Mumford 2000, Daly et al 2004). Generally, lineage viruses, a quarter of horses with antibody levels
after antigenic drift has occurred, transmission between higher than 140 mm2 became infected (Newton et al
inadequately vaccinated animals will occur before clinical 1999). The importance of continued antigenic drift in
signs are observed. When circulating field strains become causing vaccine breakdown has been evidenced by the
sufficiently different from vaccine strains, they can cause increasing number of isolations of “American-like” H3N8
clinical disease irrespective of the frequency of administra- viruses from horses in Europe that have been immunized
tion and response to vaccination, as was seen in Europe in with vaccines containing only “European-like” strains.
1989 (Livesay et al 1993). Further vaccination and experimental challenge studies in
The widespread epidemic that was caused by a variant of ponies suggested that vaccines containing virus from the
the H3N8 subtype in the USA and Europe during 1979–80 American lineage may not be as effective in protecting
first raised the possibility that antigenic drift could play a against infection as the homologous vaccine against
major role in the epidemiology of equine influenza. During challenge with virus from the European lineage, but
the 1989 outbreak of influenza in the UK, only horses with differences were not marked.
very high levels of vaccine-induced antibody were pro- Data from these experiments, in particular those that
tected against infection, raising the possibility that there quantitatively describe protective antibody thresholds, have
had been significant antigenic changes in the 1989 isolate been used to set the parameters for mathematical models.
that prevented its neutralization by antibody stimulated These models have demonstrated how transmission of
by vaccines containing Miami/63, Fontainebleau/79 or equine influenza was markedly enhanced in the presence
Kentucky/81. Sequencing of the HA1 gene and antigenic of antigenic drift. Small changes observed experimentally
analysis suggested that there were significant differences at the individual pony level can have large effects when
between a representative 1989 strain and the vaccine scaled up to the population level in mathematical models
strains in use at the time. The hypothesis was tested by (Park et al 2004).
vaccinating groups of ponies with monovalent vaccines Experts of OIE/WHO have recommended that if future
containing either of the vaccine strains or a 1989 strain equine vaccines are to be effective then they should contain
and experimentally challenging them with a 1989 virus. representatives from both the American and the European
Although all vaccines provided clinical protection, vaccine lineages.
International control groups of horses, it has become common practice for mass
vaccination to be implemented in the face of an outbreak,
The ever-increasing international movement of horses for particularly in racing centers with large numbers of young,
competition and breeding purposes presents a challenge valuable horses. Anecdotal reports suggest that this is
with regard to the control of equine influenza. Several effective in reducing adverse clinical effects of influenza
explosive outbreaks of equine influenza attributable to infection, probably by both stimulating immunity before
the introduction of infected animals into susceptible infection and reducing the amount of virus shed.
indigenous populations have been described during the last
20 years. As a result of economic and competitive issues, it
Equine Herpesvirus-1 and -4
is desirable for the disruption to training programs caused
by quarantine to be kept to a minimum when horses are Historical context
moved. There is, therefore, a reliance on surveillance of
influenza in the population that the animals are leaving Equids are host to at least 11 taxonomically grouped
and on the effectiveness of vaccines to prevent viral herpesviruses. Asinine herpesviruses 1, 2, and 3 (Browning
shedding. When these measures fail, and subclinically et al 1988, Kleiboeker et al 2002), which principally infect
infected horses shedding virus are transported, the short donkeys, are synonymous with equine herpesviruses (EHV)
quarantine periods that are often used fail to prevent 6, 7, and 8. Six of the 11 are classified as Alphaherpes-
introduction of infection. virinae (EHV-1, -3, -4, and -9, and asinine herpesviruses 1
Regulations relating to the movement of animals based and 3) and five as Gammaherpesvirinae (EHV-2 and -5,
on the use of improved diagnostic techniques and vacci- and asinine herpesviruses 2, 4, and 5). EHV-9 was originally
nation policies that recognize the limitations of current named gazelle herpesvirus 1 (GHV-1) (Roizmann et al 1992).
products are now in place. The Code Commission of the The association between EHV-1 infection and abortion
OIE recommends that importing countries that are free of was first recognized in Kentucky in 1932 (Dimock et al
equine influenza should require that all horses traveling 1936). At that time, the virus was termed equine influenza
from endemic areas are fully vaccinated and have received virus because of the influenza-like symptoms that it
their last booster dose within 2–8 weeks of travel. A simple produced, and it was not until 1954 that it was shown that
additional measure that can be implemented is the screen- herpesviral respiratory disease in young horses (equine
ing of antibody using the SRH assay, which can identify rhinopneumonitis) and equine abortion in pregnant mares
potentially susceptible animals that require re-vaccination were caused by the same agent, identified as EHV-1. In
to boost their antibody levels before traveling. The advent of 1959, major antigenic differences between EHV-1 strains
more rapid diagnostic tests for equine influenza means that were noted by workers in Japan, and meticulous obser-
animals can be screened for virus shedding while still in vations of herpesviral disease in the closed pony herd
quarantine at their destination before being released into maintained at the Pirbright research station in the UK
potentially susceptible local populations. in the 1970s subsequently led to the concept that the
EHV-1 strains associated with abortion and respira-
Treatment of clinical cases tory disease were different virus subtypes (Burrows et al
1984b). Restriction endonuclease fingerprinting subse-
During the febrile stage of influenza, horses may be quently demonstrated that the two subtypes were geneti-
treated with non-steroidal anti-inflammatory drugs while cally distinct viruses that were renamed EHV-1 (formerly
antibiotics such as penicillin may be useful to combat subtype 1, associated with abortion) and EHV-4 (formerly
secondary infections. Horses recovering from equine subtype 2, associated with respiratory disease). These
influenza, even after mild or subclinical disease, should be differences in clinical outcome are not absolute though:
given adequate rest before training is resumed to avoid EHV-1 can also cause respiratory disease, and EHV-4
subsequent chronic respiratory disease (Gross et al 1998, occasionally causes abortion. Certain strains of EHV-1 also
2004). As a guide, the number of weeks of rest that is cause neurological disease, ranging from mild ataxia to
recommended is the same as the number of days that the quadriplegia (Allen et al 1986).
animal suffered from pyrexia, with a minimum of 2 weeks EHV-2 and EHV-5 are closely related gammaherpes-
rest and slow resumption of work thereafter. Although viruses. EHV-2 is considered to be ubiquitous in horses, and
antiviral therapy with matrix inhibitors amantadine and it is therefore difficult to associate the presence of virus
cimantadine has been used in experimentally infected with specific clinical syndromes. Nonetheless, studies in
horses, the risk of fatal side effects, impracticality and the USA, Europe and Australia have shown an increased
prohibitive expense all mean that it is not used routinely prevalence of EHV-2 in foals with clinically apparent lower
(Rees et al 1997, 1999). The newer neuramidase inhibitors respiratory tract disease than in normal foals (MJ Murray
have not been tested in horses. Because of the availability et al 1996), in addition to demonstrating the virus in
of rapid diagnosis and longer duration of outbreaks in large samples from foals with keratoconjunctivitis (Collinson et al
ENVELOPE: TEGUMENT:
viral glycoproteins structural and trans-activating
proteins
CAPSID:
packages viral genome
Fig. 22.7. Ultrastructural features of an EHV-1 virion. Reproduced with the permission of Dr Nick
Davis-Poynter.
Virology
1994). Respiratory tract infection with EHV-2 has also
been suggested as a predisposing factor for Rhodococcus equi EHV-1 and EHV-4 are alphaherpesviruses of the varicello-
infection in foals, perhaps through immunosuppression virus subfamily, being most closely related to the virus
(Nordengrahn et al 1996). Molecular studies have also that causes chickenpox and shingles in people. The virus
suggested that EHV-2 may have a role in reactivating particle consists of an inner crystalline DNA nucleocapsid,
EHV-1 and EHV-4 infections from latency (Edington 1992). surrounded by an amorphous tegument layer composed of
More detailed investigation of EHV-2 and EHV-5 in experi- structural and trans-activating proteins, and an outer enve-
mental challenge studies will however be necessary to lope bearing major immunogenic glycoproteins (Fig. 22.7).
establish the importance of these viruses as respiratory In common with other enveloped viruses such as influenza,
pathogens in the field. EHV-1 and EHV-4 are quickly inactivated in the environ-
The asinine herpesviruses have not been studied in ment by sunlight and disinfectants (Allen et al 1986, Crabb
the same detail as the other equine herpesviruses, and & Studdert 1995).
their classification is in flux, but it is likely that major Both EHV-1 and EHV-4 have been completely sequenced
aspects of the pathogenicity, latency and immunogenicity (Telford et al 1992, 1998). Each virus has 76 genes, and
of the asinine viruses are similar to those of their equine there is considerable sequence homology between the two
counterparts. Thus, asinine herpesviruses 4 and 5 are viruses, with the degree of amino acid identity for
gammaherpesviruses that have been associated with individual viral proteins ranging from 55 to 96%. This
interstitial pneumonia in young donkeys and would be has two important practical outcomes: diagnostic tests
expected to behave in a similar manner in their natural for EHV-1 and EHV-4 often cross-react, and there is
hosts to EHV-2, whereas asinine herpesvirus 3 is an alpha- immunological cross-protection between the two viruses.
herpesvirus that shares some sequence homology with Recent exploitation of sequence data for EHV-1 by
EHV-1 and is primarily associated with upper respiratory workers in Newmarket (Nugent et al, submitted) has
tract disease. Closer collaboration between researchers enabled grouping of EHV-1 strains into six major strain
dealing with donkeys and horses will be necessary to groups (Fig. 22.8) on the basis of sequence variability of a
establish whether cross-infection with equine and asinine single gene (ORF68). The six major strain groups show
herpesviruses is important in causing clinical disease. a degree of geographical restriction, with group 2 viruses
We have isolated what appeared to be both asinine being the most widespread, and occurring in North and
and equine herpesviruses from donkeys suffering severe South America, Europe and Australia. Group 5 viruses
clinical disease. predominantly occur in North America, and viruses
71 GB80_1_2, GB83_1_1, GB83_3_1, GB83_4_2,

66 US85_1_1 1
AR85_1_1
AR90_1_1, AR90_2_1, AR91_1_1, AR91_2_2, AR91_3_1,

AR96_1_1, AR00_1_1, AU82_1_2, FR97_1_1, FR99_1_1,
FR99_2_1, FR99_5_1, GB79_1_2, GB86_2_1, GB99_1_2,
GB03_2_2, US76_1_1, US83_2_1, US84_1_1, US85_2_2,
US85_4_1, US86_2_2, US86_3_2, US90_1_1, US99_1_1,
US00_1_1, US03_1_2, US03_2_2, US03_3_2, US03_4_2,
US03_7_2
2
US70_1_2
US89_1_1
US03_5_2
US79_1_1
AR79_1_1
AU02_1_1, BE94_1_1, BE95_1_2, BE97_1_1, BE99_1_1,

BE03_1_2, FR02_1_2, GB83_2_1, GB88_2_2, GB91_2_1,
GB93_2_1, GB00_2_1, GB01_1_1, GB03_1_1, GB03_3_2,
GB03_4_2, GB03_5_2, GB02_1_1, GB04_1_1, GB04_3_1,
GB04_5_1,
NL95_1_2,
GB04_10_2, GB04_11_2, GB04_14_1, GB05_1_1,
NL99_1_2, US86_1_1, US90_2_1, US90_3_1, 3
US92_1_1
60 GB89_1_1, GB89_2_1
BE99_2_2
CA89_1_2, PL68_1_0, US41_1_2, US72_1_0, US75_1_1,

US81_1_1, US82_1_2, US83_3_2, US85_3_1, US99_2_2,
88 US99_3_2, US01_1_2, US01_2_1, US02_1_2, US03_8_2,
US03_10_2, US03_11_2 5
63 US03_6_2, US03_9_2
51
GB00_1_1
FR00_1_1, GB81_2_1, GB81_3_1, GB04_12_2, GB04_13_2,

GB04_15_2, US86_4_2
4
GB86_3_2
69
66 GB85_1_1, GB91_1_1, GB01_2_1
6
GB87_1_1
Fig. 22.8. A phylogram of ORF68 DNA sequence for 106 EHV-1 isolates, classified into six major strain groups, is shown. The unrooted tree was
constructed using MEGA version 2.1 (Kumar et al 2001), using the neighbor-joining method (distance according to the number of nucleotide
differences). Bootstrap values above 50 are shown (from a total of 100 iterations). Clusters of isolates within each of the six major strain groups
are indicated (boxes). The scale bar denotes one nucleotide difference. Isolates were coded according to their country of origin (C), year of
outbreak (Y), a unique identifier for the outbreak (x: 1, 2, 3 etc) and the pathogenic features of the outbreak (p: 0 – attenuated vaccine strain;
1 – non-neuropathogenic; 2 – neuropathogenic) according to the scheme CCYY_x_p. Countries of origin are designated AR (Argentina),
AU (Australia), BE (Belgium), CA (Canada), FR (France), GB (Great Britain), NL (Netherlands), PL (Poland) and US (USA).
in groups 3, 4, and 6 predominantly occur in Europe. or abortigenic disease. Simultaneously, in the initial stages
Furthermore, molecular epidemiological studies for addi- of nasal and conjunctival epithelial infection, EHV-1 gains
tional variable genes has shown a significant associa- access to neurons of the trigeminal nerve and reaches the
tion between a particular genetic mutation (of the DNA trigeminal ganglion by 48 h p.i., before or synchronously
polymerase) and strains of EHV-1 isolated from outbreaks with the onset of viremia (Slater et al 1994). EHV-1 is
of neurological disease. These are important break- generally cleared from the respiratory tract within 3 weeks
throughs, which will revolutionize our understanding of after primary infection and after 1–2 weeks following
EHV-1 molecular epidemiology, pathogenesis, and preven- subsequent infections.
tion, as well as facilitating more targeted diagnostic tests The detailed pathogenesis of EHV-4 infections has not
and control procedures. been elucidated but primary infection results in naso-
pharyngeal shedding for 7–10 days and for a shorter time
Pathogenesis of herpesviral (≤ 5 days) following secondary infection or recrudescence.
respiratory disease It is likely that the initial steps in EHV-4 infection of the
respiratory tract are similar to those in EHV-1 infection, but
Since uncomplicated herpesviral respiratory disease is in contrast to EHV-1, dissemination generally terminates at
rarely fatal, most information on the pathogenesis of the the local lymph nodes. Most EHV-4 isolates do not infect
respiratory disease has been obtained from experimental endothelial cells or cause cell-associated viremia and
studies performed as part of long-term vaccine research therefore are not associated with abortion and neurological
programs in the UK and USA. Both EHV-1 and EHV-4 disease. Exceptionally, however, cell-associated viremia can
initially infect and replicate in epithelial cells of the upper be detected and more virulent isolates of EHV-4 also have a
respiratory tract following inhalation of infectious aerosols capacity to infect endothelial cells in fetuses and foals
or contact with infected fomites. EHV-1 can also infect the (Matsumura et al 1992, Blunden et al 1995). EHV-4
conjunctival epithelium, presumably via aerosol contact. infections are generally cleared from the respiratory tract
Initial steps in infection of the respiratory tract are rapid: within 7–20 days after first infection and within 2–7 days
in primed adult ponies, occasional infected epithelial cells in subsequent infections.
can be detected by immunoperoxidase staining in the
nasopharynx, trachea, and bronchi as early as 12 h after Clinical signs of respiratory disease
experimental intranasal infection (Kydd et al 1994b). As a
result of this primary replication, infectious virus may be Experimental studies have shown a short incubation period
shed in nasal mucus transiently (2–4 days) in animals with for EHV-1 respiratory disease, which is usually 1–3 days
previous exposure to EHV-1 but shedding can persist for at duration. In the field, the incubation period may be longer
least 15 days post infection (p.i.) in naive animals (Gibson (up to 10 days), although the relative contributions of
et al 1992). Virus then spreads quickly (within 48 h) to infectious virus dose, pathogenicity and host immunity
monocytes and large and small lymphocytes in the sinuses in determining incubation period are not known (Ostlund
of the respiratory tract-associated lymph nodes (Kydd 1993). Young horses infected with EHV-1 show clinical
et al 1994a). Progression of infection over days 4–6 p.i. signs of upper respiratory tract infection (rhinitis or
involves the formation of multiple erosions in the nasal pharyngitis), with some animals developing concur-
mucosa and nasopharynx, with viral antigen expression in rent tracheobronchitis. Older horses, which are partially
degenerating epithelial cells, local lymphocytes, monocytes immune as a result of earlier infections with EHV-1 or
and endothelial cells of nasal blood vessels. Infection of EHV-4, generally show a reduced duration and severity of
epithelial cells, endothelial cells and leukocytes in the lungs respiratory tract disease, which is often subclinical. Indeed,
can be observed from day 2 to day 13 p.i., with a peak on the first sign of EHV-1 infection in mature horses may be
day 9 when occasional mural non-occlusive thrombi may abortion or neurological disease (Fig. 22.9).
occur in the pulmonary interstitium. Infection of such Useful information on the outcome of EHV-1 infection in
diverse cell types leads ultimately to leukocyte infection young horses has been gained from work with specific
and progression to cell-associated viremia, thereby dis- pathogen-free foals, which are immunologically naive
seminating virus to sites of secondary replication including (Gibson et al 1992). If infected with EHV-1 by intranasal
the pregnant uterus. Viremia develops from day 3 p.i. in inoculation, specific pathogen-free foals show a biphasic
both primed and naive animals but in the latter persists pyrexia, with peaks of rectal temperature on days 1–2 p.i.
for up to 21 days (Scott et al 1983). The viremia primarily and on days 6–7 p.i. The total duration of pyrexia can
involves T cells (of CD5/CD8 phenotype) (Lunn et al 1991), be 8–10 days, and the foals are depressed and anorexic
and the interaction between infected circulating lym- over this period. There is a nasal and ocular discharge,
phocytes and endothelial cells in the central nervous which is initially serous but becomes mucoid and muco-
system and genital tract is fundamental in determining purulent over the first week of infection. The discharge
whether respiratory infection is succeeded by neurological is associated with viral rhinitis and conjunctivitis that
Fig. 22.9. A recumbent horse exhibiting

typical signs of severe paralytic EHV-1.
become complicated by secondary bacterial infection. discussed above) that no signs whatsoever, even in horses
Viral infection of regional lymph nodes results in lym- competing, are observed. For example, EHV-1 has been
phadenopathy, which is most readily detected as swelling isolated from samples taken from horses 48 h prior to them
of the submandibular lymph nodes. Retropharyngeal winning races.
lymph node enlargement is also present in most cases, Treatment of herpesviral respiratory disease using
but is not detectable on palpation. The lymph node antiviral compounds is rarely reported, largely because
enlargements are maximal over days 7–10 p.i. and may of the lack of published data on the efficacy of these
be persistent over several weeks. If infection spreads to compounds in horses, and the fact that the productive
involve the lower respiratory tract in young foals then phase of viral infection has often ceased by the time
clinical signs may be more severe: the foals are markedly the clinical signs are recognized. There are occasional
depressed, tachypneic and dyspneic, lose interest in the reports of the use of acyclovir in the treatment of young
mare and may stop suckling. EHV-4 causes upper respi- foals with EHV-1 respiratory disease or EHV-2-associated
ratory tract disease which is clinically indistinguishable ocular disease (MJ Murray et al 1998), but these studies
from that caused by EHV-1 and, on occasion, can also have generally been uncontrolled, and the number of
cause bronchopneumonia (Coignoul et al 1984a). Since animals involved has been too small for meaningful
both EHV-1 and EHV-4 infections principally cause clin- statistical analysis.
ical signs ascribable to upper respiratory tract disease,
coughing is not usually a prominent clinical sign (this Diagnosis
is in contrast to influenza infection, where coughing is
common). Where coughing does occur secondary to EHV-1 and EHV-4 respiratory disease may be diagnosed by
herpesviral infection it is often suspected that suboptimal detection of virus in nasopharyngeal swabs collected in
stable air quality or inadequate rest following pyrexia may the acute phase of disease, particularly over the first few
be contributory factors. days of infection when the horse is pyrexic. Virus may be
As well as the disease described above, EHV-1 and EHV-4 demonstrated by isolation on tissue culture or detection of
have been associated with around 5% of cases of inflam- specific viral DNA by PCR (Sharma et al 1992). Tracheal
matory airway disease in young racehorses. There is no washes collected during the early stages of infection may
evidence that the low proportion of cases associated with also demonstrate degenerative changes in epithelial cells,
EHV infection take any longer to resolve than the other with viral antigen detectable by immunofluorescence.
95% of cases of inflammatory airway disease – which have However, in practice, since clinical signs are generally mild
an average duration of around 2 months. The economic and often subclinical, diagnosis is often retrospective and
losses associated with respiratory disease are related based upon serology. In the 1950s and 1960s assays were
not only to the lost training days during the acute stages developed to measure serum antibodies with virus neutral-
of infection, but also to the longer term effects on izing (VN) and complement fixing (CF) activity in vitro (Doll
performance. Some infections can be so mild (for reasons & Bryans 1962, Thomson et al 1976). These diagnostic
techniques demonstrated seroconversions of both VN and Epidemiology

CF antibodies starting approximately 2 weeks after field
or experimental infection with EHV-1. VN antibodies are Host range and international
long-lived, persisting for up to 1 year after infection and distribution of infection
largely type-specific (i.e. EHV-1 or EHV-4), being directed The natural host range and reservoir of infection for
primarily against the major envelope glycoproteins B and C EHV-1 and EHV-4 are generally restricted to members of
(gB and gC). In contrast CF antibodies are short-lived, the Equids, although for EHV-1, non-equine species, for
usually becoming undetectable by 3 months after infection. example onager and deer, may be involved. The full host
The CF antibody test is therefore useful, particularly when range for EHV-4 has not yet been elucidated. EHV-1 and
applied to pairs of sera collected at least 14 days apart, as EHV-4 have a worldwide geographical distribution, are
an indicator of recent EHV-1 infection. However, the ubiquitous in the USA, UK, and Australia and are con-
epitopes recognized by CF antibodies are cross-reactive sidered significant equine pathogens in these countries.
with both EHV-1 and EHV-4 proteins, so this response is In common with influenza, the international movement of
inaccurate for differentiation of type. A type-specific ELISA horses for racing, breeding, and competition has facilitated
using fusion proteins expressing variable regions of a the global spread of these viruses.
different envelope glycoprotein, gG, has been developed and
applied extensively to epidemiological studies of EHV-1 Prevalence of infection
and EHV-4 field infection in Australia (Foote et al 2004). Both EHV-1 and EHV-4 infections become established early
Since mortality associated with EHV-1 or -4 respiratory in life in most equids. These viruses, along with EHV-2,
disease is low, it is unusual to make this diagnosis by appear on stud farms every breeding season, with young
post-mortem examination of adult horses, unless as part horses generally acquiring infection as foals, often while
of the investigation of herpesviral neurological disease. still under the cover of maternal immunity. Indeed,
Adult horses presenting with hind limb ataxia and incon- recent studies in Australia have demonstrated shedding
tinence suggestive of EHV-1 infection may be diagnosed in of EHV-4 by foals as young as 11 days (Foote et al 2004).
life by detection of circulating virus-infected leukocytes Frequent episodes of re-infection or reactivation of latent
in heparinized blood samples, and will generally have virus occur during the first 12–18 months of life, when
high CF antibody titers to both EHV-1 and EHV-4 in associated clinical signs of respiratory disease may be recog-
samples collected soon after the onset of neurological nized. Both serological and PCR-based studies suggest that
disease (Edington et al 1986). Post-mortem diagnosis the majority of horses then harbor EHV-1 and EHV-4
generally requires immunohistochemistry to demonstrate throughout life, and experience repeated re-infections or
viral antigen expression at sites of vasculitis in the central reactivations, many of which events are not associated
nervous system. Antigen has often been cleared from the with clinical signs of disease.
respiratory tract by the time that lesions are established
in the central nervous system. Route of infection
The pathologist will often be required to investigate For both EHV-1 and EHV-4 the route of infection is via the
EHV-1 as a cause of pneumonia in neonatal and suckling upper respiratory tract by virus-infected fomites or aerosol.
foals (Prickett 1970, Smith et al 2003). Foals infected Transmission of virus to susceptible animals occurs either
with EHV-1 show hyperemia, vesiculation, necrosis, and from horses with acute or reactivated EHV respiratory
ulceration of the mucosa of the upper respiratory tract, infections or from contact with aborted fetuses. The source
with miliary dark-red foci in the lungs. Microscopically, of infectious virus in the first two examples is respiratory
these lesions correspond to foci of necrotizing to exuda- tract secretions, whilst from pregnant mares, the aborted
tive rhinitis and terminal bronchiolitis or alveolitis. Viral fetus and placenta are rich in infectious virus.
inclusion bodies may be detected in degenerating epithelial
cells of the upper and lower respiratory tract, broncho- Latency and reactivation
alveolar macrophages and lymphoid cells within mucosa- In common with other alphaherpesviruses, infection
associated lymphoid tissue and local lymph nodes. These with EHV-1 and EHV-4 results in the establishment of
respiratory tract lesions may occur in primary post- latency, which is often lifelong and ensures persistence
natal infection of foals, and also form part of the multi- of infection in horse populations through periodic reacti-
systemic viral lesions seen in aborted fetuses or sick vations (Edington 1992, Edington et al 1994). After EHV-1
neonatal foals with the congenital form of the disease. infection of the respiratory tract, latent infection is estab-
In the case of the abortigenic disease, diagnosis is achieved lished in the lymphoreticular system, both in circulating
by detailed post-mortem examination of the aborted lymphocytes and in lymph nodes, and in sensory ganglia
fetus and placenta, detecting infectious virus, DNA or such as the trigeminal ganglion. The sites of latent infec-
antigens by a combined application of virus isolation, PCR tion may be detected by PCR or by prolonged co-cultivation
and immunohistochemistry. of indicator cells with cells from the tissues of interest.
Horse latently infected

with EHV-1 or EHV-4
Establishment Reactivation of
of viral latency virus from latency
Recruitment of Nasal shedding

new hosts of infectious
into cycle virus
Infection of young horses
Fig. 22.10. The cycle of primary infection, latency and reactivation of EHV-1 infections in horses.
Reproduced with the permission of Professor George Allen.
Using these techniques, it is generally easier to detect latent mare that has no history of recent EHV-1 respiratory
virus in lymphoreticular tissues than ganglia. Sites of EHV- disease in in-contact horses. The central role of latency and
4 latency also involve sensory ganglia and lymphoreticular reactivation in maintaining EHV-1 in horse populations is
tissues, including circulating lymphocytes (despite the illustrated in Fig. 22.10.
rarity of EHV-4 viremia) (Borchers et al 1997).
Reactivation of EHV-1 or -4 infection may result in Immune responses to EHV-1
viremia (thereby rendering the affected horse at risk of and EHV-4 infection
abortion or paralysis) and/or shedding of infectious
virus in respiratory tract secretions (thus infecting new, Both antibody-mediated (humoral) and cell-mediated
susceptible horses). Reactivation of latent EHV-1 and -4 immune responses are stimulated by EHV-1 or EHV-4
infections in field situations has been observed following infection, and generally lead to recovery within 2 or
transport, handling, re-housing and weaning, and reactiva- 3 weeks, although immunity to re-infection is short-lived,
tion has been achieved experimentally by treatment with lasting 3–6 months (Allen et al 1999). Repeated infec-
corticosteroids. Modern management of horses, especially tions may, however, substantially increase the duration
long-distance travel in racing and competition horses, of immunity.
results in frequent reactivation of latent infections. Impor- The antibody responses may be divided into systemic
tantly, clinical respiratory disease is often absent following and mucosal types, with the former having received
reactivation and such horses are therefore silent shedders more detailed study in relation to diagnostic testing and
of virus. This presents obvious management difficulties: assessment of immunity. Thus it has been known for
new cases of EHV respiratory disease develop in suscep- several decades that, following infection with EHV-1 or
tible, in-contact horses that have had no apparent contact EHV-4, CF and VN antibodies may be detected in serum
with horses with respiratory disease. Similarly, abortion as samples. CF antibody lasts only 60–90 days, whereas VN
a result of EHV-1 reactivation may occur in a pregnant antibody is longer lived and can be detected 12 months
after infection. There is antigenic cross-reactivity and a Research into EHV-1 and EHV-4 immunology is now
degree of cross-protection between EHV-1 and EHV-4, entering an exciting phase, with the development of
although the extent of cross-reactivity and cross-protection sensitive assays for cellular responses that correlate
varies between virus isolates and between studies. In with protection. Foremost among these is the detection
general, studies have shown that cross-protection is greater of cytotoxic T lymphocyte (CTL) precursors as a measure of
after multiple infections (with either virus) than single T cells capable of lysing virus-infected cells (Allen et al
infections. It is also noteworthy that repeated infections can 1995, Kydd et al 2003). This cytotoxic immune response is
substantially increase the overall duration of immunity. major histocompatibility complex class I restricted and
Mucosal antibody secretion represents a first line of mediated by CD8+ lymphocytes, and is not mediated by
defense against EHV-1 or EHV-4 infection of the respiratory lymphokine-activated killer cell activity. CTL activity and
tract, although detailed study of this arm of the immune CTL precursor frequency increase after EHV-1 infection
system has been relatively neglected. Nevertheless, virus- and are of long duration. This may be up to 1 year in
specific antibody has been detected in the respiratory tract, multiply infected ponies, although perhaps less in younger
and antibody with VN activity has been detected in animals. Identification of those viral genes and proteins
mucosal secretions collected from horses for a few weeks most important in stimulating CTL activity in horses is now
after EHV-1 infection (Allen et al 1999, Breathnach et al an attainable goal, and is critical in rational vaccine design
2001). These mucosal antibodies are primarily of the IgA (Allen et al 1999).
isotype. Effective protection at the mucosal surface is also
likely to involve cytokine responses, although there are
similarly sparse data on these. Putative type I interferon Control of EHV-1 and EHV-4
secretion has been detected in nasal secretions and serum
during the first 10 days after experimental EHV-1 infection, Management of control
and synthesis of interferon-γ has been shown to increase in EHV-1 and EHV-4 can infect both bloodstock and horses
both CD4+ and CD8+ peripheral blood T lymphocytes in training but greater emphasis has been placed on
collected at 10 days p.i. (Edington et al 1989). the control of EHV-1 because of its abortigenic potential
Cell-mediated immune responses are vital in recovery in pregnant mares. In the UK, the Horserace Betting Levy
from EHV-1 or -4 infection. This is because both viruses Board (HBLB) publishes a Code of Practice recommending
become intracellular within hours of contact with host precautions to prevent or limit infection of pregnant mares
cells, thereby evading the neutralizing effects of serum with EHV-1 (available online on www.hblb.org.uk). The
antibodies. However, attainment of a robust cellular Code is not mandatory but is adhered to in the thorough-
immune response to infection is complicated by the fact bred industries in Britain, France, and Ireland. Similar
that EHV-1 (and to a lesser extent EHV-4) is capable of management practices are used in North America (Ostlund
replicating in lymphocytes and impairing their function. 1993). Elsewhere, EHV-1 management is less formal.
It has been shown that lymphocytes collected from Since EHV-1 and -4 are present as latent infections in
animals infected experimentally with virulent strains of the majority of horses, it is not feasible to prevent infection
EHV-1 have a reduced ability to respond optimally to either being introduced into horse populations. Management
inactivated virus or mitogen for periods varying between procedures may nevertheless have a major impact in
2 and 10 weeks. This period of impaired lymphocyte limiting spread of infection, and associated clinical disease
function is succeeded by a phase of increased lymphocyte such as abortion, within populations. Infectious EHV-1
responsiveness to antigen, which then declines to baseline virions are present in aerosols shed from the respiratory
levels by 3 months p.i. (Hannant et al 1991). The basis of tract and may also be present in other body fluids (tears,
the impaired lymphocyte function has been studied in vitro, saliva, urine, feces, mucosal surfaces, blood, lymph) during
by measuring the proliferation of lymphocytes (either the acute phase of disease. The aborted fetus and placenta
resting or mitogen-stimulated) in response to live or are also highly infectious. Where abortion occurs within
inactivated EHV-1. This has shown that lymphocytes that 2 weeks of respiratory infection or reactivation, the mare
have been exposed to live EHV-1, either in vivo or in vitro, herself may shed virus from her respiratory tract. Reacti-
fail to proliferate in response to incubation with live virus vation of latent virus to result in nasopharyngeal shedding
in vitro. It is likely therefore that one factor contributing and/or abortion also complicates control measures. There-
to the immunodepression is viral replication within fore, horses of all ages and either sex must be considered
the lymphocytes, which interferes with the ability of the potential sources of infection. This is particularly impor-
infected cells to enter mitosis and thereby to proliferate in tant when planning the husbandry of pregnant mares, and
response to viral antigens. Thus, EHV-1, and presumably measures to limit contact between young horses that may
EHV-4, have evolved sophisticated mechanisms to subvert be shedding EHV-1 infection and pregnant mares that are
the function of key effector cells responsible for viral susceptible to EHV-1 abortion are of paramount impor-
clearance and recovery. tance, particularly in the last trimester of pregnancy.
Disease prevention is often divided into three areas, Clinical treatment of diagnosed cases of EHV respiratory
namely management, hygiene and vaccination. Adherence disease should include rest from strenuous exercise and
to the principles outlined in the HBLB Code of Practice, particular care with the management of stabled horses to
summarized below, remains the mainstay of successful minimize stress and dust inhalation, which may require a
control of EHV-1 on equine breeding premises. change of bedding. In many cases in horses-in-training,
secondary bacterial infections are not particularly evident,
but where they are, they should be treated aggressively
Summary of measures to be taken on breeding with standard antibacterial therapy.
premises following EHV-1 abortion
● Isolate mare, destroy bedding and disinfect box.
Control by vaccination
● Stop horse movement on and off the stud.
During the decade from 1941, several EHV vaccines were
● Notify local breeders’ association.
tested by intramuscular administration in pregnant mares.
● Divide close contact pregnant mares into small groups.
Both inactivated vaccines prepared from virus grown in
● Contact owners of mares that are at the infected stud equine fetal tissues and live vaccines derived from hamster-
or are due to be sent there. adapted virus were used in these early studies. Unfortu-
● Contact studs to which mares have been sent or are nately, adverse side effects were common features of these
due to be sent. vaccines (although intranasal delivery of the live vaccine to
● Pregnant mares should remain on the stud until young horses did protect them from challenge infection
foaling. 1 month later). Subsequently, a planned infection program
● Do not move any horse for 28 days from last abortion. was initiated in Kentucky to immunize pregnant mares
● Non-pregnant mares can move earlier than 28 days if against virus abortion (Doll & Bryans 1963). Vaccination of
they have been isolated from pregnant mares and 9,480 pregnant mares during the next decade was asso-
handled by separate staff, and if blood samples at ciated with a reduction of the incidence of abortion from
14-day intervals do not indicate seroconversion. 15% in unvaccinated animals to 0.93%, although the
● Aborting mares should be isolated from pregnant effect of the vaccine is impossible to separate from the
mares for 56 days. effects of management changes implemented over this
● The following year, aborted and in-contact mares period. However, safety problems continued because there
should foal in isolation, preferably at home. was a suggestion of vaccine-induced abortions. In the
● Review vaccination policy. 1960s, a new attenuated virus was developed from a high-
titer porcine-cell-culture-adapted virus that had been first
isolated from an aborted fetus and then passaged in
With regard to horses-in-training, EHV-1 and EHV-4 hamsters (isolate RAC-H), resulting in a virus that had
are responsible for only a low incidence of respiratory impaired capacity to replicate but nonetheless retained
disease. In naive young-stock, disease is obvious but after some immunogenicity (Mayr & Pette 1968). Derivatives of
several infections and/or vaccination the infection is this isolate are still in commercial use in northern Europe
subclinical, which in the athletic horse may be responsible today. Attempts were made to enhance further the efficacy
for loss of performance. Although less infectious than of the vaccine in the 1970s, by further passage of the
equine influenza virus, both EHV-1 and EHV-4 spread porcine-cell-culture-adapted virus in rabbit kidney cells and
between animals at grass or in nose-to-nose contact with then equine dermal cells to reach a final passage of p263.
each other. Spread around training yards also occurs and The resultant vaccine became available in North America
appears to be facilitated where airspaces are shared, as in and parts of Europe, but safety problems were identified,
American Barn housing systems. with abortion occurring in 50% of pony mares experi-
Good animal husbandry and management in training mentally challenged with the vaccine virus (Dutta &
yards can alert the trainer and veterinary surgeon to a Shipley 1975). Largely as a result of this concern about
horse with subclinical disease. Many yards now monitor the safety of live virus vaccines, workers in Lexington
rectal temperatures daily and use regular hematological in the 1980s demonstrated serviceable immunity to EHV-1
examinations and cytology on tracheal washes as a means in pregnant mares (successful foaling and reduction in
of early detection of infectious disease. This information virus shedding) using a formalin-inactivated, whole virus
gives the trainer the option of reducing the workload or adjuvanted vaccine, which was administered intramus-
even resting the animal while investigations are continued. cularly. These results were substantiated by a large field
Strict isolation of all acutely infected animals, perhaps trial of the same vaccine after it became commercially
detected by early diagnosis of pyrexia, can be an effective available as Pneumabort K (Bryans & Allen 1982). The
means of limiting spread of infection around a training accumulated frequency of EHV-1 abortions among vacci-
establishment. nated mares was 1.6/1000 (14/8,638) as compared with a
frequency of 6.8/1000 (140/20,732) in the remainder of promoter, the required gene sequence and a polyadenyla-
the study population. However, subsequent studies in the UK tion/transcriptional termination sequence. On administra-
were not so encouraging: Burrows and colleagues showed tion of the plasmid DNA vector by intramuscular injection
that intramuscular vaccination with this inactivated or bombardment of DNA-coated gold beads intradermally,
vaccine in yearlings and 2-year-old pregnant pony mares the antigen is expressed in situ, leading to the induction
was associated with reduced viremia, but that there was no of antigen-specific immunity, including vigorous cellular
difference in the occurrence of abortion between vacci- immune responses. The immune response generated after
nated and unvaccinated controls (Burrows et al 1984a). DNA vaccination can also be modulated by the inclusion of
Towards the end of the 1990s in the UK, the use of the cytokine sequences. In the horse, one potential advantage
earlier inactivated product was generally replaced by of DNA vaccination may be induction of immunity in foals,
the use of a similar, but carbomer-adjuvanted, inactivated even under cover of colostrally derived antibodies.
product (Heldens et al 2001). Typically, this vaccine is used It is highly likely that, whatever progress is made with
in pregnant mares in the 5th, 7th, and 9th months of their the development of new vaccines, the use of novel products
gestation. The vaccine is also licensed for protection against will never replace the important role that management
respiratory disease, when 6-monthly boosting of all suscep- practices play in the prevention and control of disease
tible horses is recommended. Another inactivated vaccine associated with EHV-1 and EHV-4.
is licensed in the UK for protection against EHV-1 and
EHV-4 respiratory disease and equine influenza, but is not
licensed for protection against abortion. Neither vaccine is
licensed for protection against neurological disease.
Equine Arteritis Virus
Notwithstanding safety concerns, it is predictable that Historical context
live virus vaccines will be more effective than inactivated
vaccines in stimulating protective immune responses The symptoms of the disease “pink-eye”, now known
associated with CTL. To balance the risk of such viruses as equine viral arteritis (EVA), were first reported over
reverting to virulence against the benefit of stimulating 100 years ago, but there was clearly some confusion with
more robust immunity, efforts have been directed towards other equine viral diseases as the condition was also
constructing live attenuated viruses with deletions in referred to as “equine influenza”. Early workers described
specific genes associated with pathogenicity. Several such the clinical signs as including “weakness, watering of the
deletion mutants have been constructed, and vaccine trials eyes, injected conjunctiva, swelled legs, and diffuse swelling
are underway in experimental ponies. The results are on the under-part of the abdomen”. There was also recog-
awaited with interest, although success may be confounded nition that the disease could be spread from stallions to
by the paradox that those genes associated with patho- mares at covering and that this spread continued for a
genicity, and thereby deleted from the vaccines, may also be long period after stallions were first affected. Abortion
the most immunogenic. was sometimes observed and it was recognized that strict
The route of vaccine administration will also condition isolation could successfully control the disease.
the type of immune response that is stimulated. Given that The next major advance in the understanding of EVA
EHV-1 and -4 initially infect the respiratory tract, it is came when the causative agent, equine arteritis virus
logical to predict that stimulation of immunity at the (EAV), was first isolated from horses during an outbreak of
respiratory mucosal surface, by intranasal administration severe respiratory disease and abortion on a standardbred
of vaccine, may be more successful that parenteral admin- stud farm in the town of Bucyrus, Ohio in 1953 (Bryans et
istration. The attraction of mucosal vaccines is that the al 1957). The observation that different disease outbreaks
induction of a layer of antibody with VN activity should often presented with differing severity of signs then led
neutralize inhaled virus particles before epithelial cell to speculation that different strains of EAV could exist.
infection occurs. This may prove useful for vaccinating in- Differences in virulence between isolates were recognized
contact horses in the face of an ongoing outbreak or to and this was further modified and exploited through the
protect bloodstock passing through the sale ring by limiting development of a modified virus strain in a live vaccine
the spread of disease. This technique has been studied for (Doll et al 1968, McCollum 1969). Following its initial
influenza virus vaccination, using cholera toxin as an isolation, the morphological and physicochemical prop-
adjuvant to enhance immunogenicity, but awaits applica- erties of EAV were described by the early 1970s, by which
tion to EHV-1, although it has been shown to be successful time it had been appreciated that there were two different
in bovine herpesvirus 1 infection in cattle. viruses capable of causing abortion in mares (i.e. EHV
DNA vaccines also offer promise as a means of intro- and EAV). Around the same time, detailed observations on
ducing immunogenic viral genes into animal cells, without the respiratory form of the disease were made in Kentucky
the risk of viral replication and consequent disease. Such during experimental infections which contributed to
vaccines consist of a bacterial plasmid with a strong viral understanding of the pathogenesis of EVA (McCollum et al
1971). The serological assays of CF and VN were developed prevent EVA (McCollum 1976). However, virus-specific
and described by the mid-1970s (Senne et al 1985). These CD8+ CTL responses are stimulated by EAV (Castillo-
techniques allowed accurate diagnosis and surveillance of Olivares et al 2003a) and high levels of protection have
EVA in many areas of the world. been achieved in the absence of a strong VN antibody
using a GL deletion mutant vaccine, indicating that alter-
Virology and immunity native effector mechanisms of immunity (CTL responses)
are important for protection (Castillo-Olivares et al 2003b).
EAV is the prototype member of the family Arteriviridae, a In chronically infected stallions, EAV replication, which is
group of small enveloped, single-stranded RNA viruses. restricted to cells of the accessory sex glands, persists for
Other members of this family are lactate dehydrogenase- several months or years, despite high levels of circulating
elevating virus, simian hemorrhagic fever virus, and porcine VN antibody (Timoney et al 1987).
reproductive and respiratory syndrome virus.
EAV has an icosahedral nucleocapsid that contains a Clinical signs and pathogenesis
12.7-kilobase polyadenylated infectious RNA molecule
surrounded by a lipid bilayer envelope. The genome contains EAV replicates primarily in the endothelium of small arteries
nine recognized open reading frames (ORFs 1a, 1b, 2a, 2b and in macrophages. Secondary sites of virus replication
and 3–7), of which the two largest (1a and 1b) encode the include the epithelia of adrenals, kidney, liver, seminiferous
viral replicase. Five structural proteins have been charac- tubules, and mesothelium. The result of infection is
terized, namely the nucleocapsid protein (N, encoded by variable and depends on the virus strain, the age of the
ORF 7), two glycosylated envelope proteins (GL and GS, host and environmental factors (Timoney & McCollum
encoded by ORFs 5 and 2b, respectively) and two non- 1991). Affected animals may or may not develop a syn-
glycosylated envelope proteins (M and E), encoded by drome that is typically characterized by one or a combina-
ORFs 6 and 2a, respectively (de Vries et al 1992). Recently, tion of the following clinical signs: pyrexia (up to 41°C),
GP3 and GP4, encoded by ORFs 3 and 4, have been demon- depression, conjunctivitis, palpebral edema, ocular and
strated to form part of the virion envelope (Wieringa et al nasal discharges, edema of the periorbital region or ventral
2002). Proteins N, M and GL are the major antigens parts of the body, urticarial skin rash and lymph node
of EAV (Balasuriya et al 1995, Chirnside et al 1995, swelling (Fig. 22.11). An important sequel of infection
MacLachlan et al 1998). Although ORF 3 is also thought in the pregnant mare is abortion. Typically this occurs
to encode an immunogenic protein (Hedges et al 1999), around 2 weeks after acute infection and often, but not
all hitherto known neutralizing epitopes are contained invariably, follows illness in the mare. It is not always
within the putative ectodomain of GL (Balasuriya et al associated with fetal infection, although it is possible to
1997). The enveloped virus is easily inactivated by lipid recover virus from the tissues in some fetuses (Johnson
solvents and disinfectants (Castillo-Olivares et al 2001). et al 1991). If neonatal foals become infected, signs
Animals that recover from EAV infection develop a including fever, leukopenia and pneumonia can be severe
long-lasting immunity against the disease, although and there is significant mortality. At necropsy, an inter-
not always against re-infection. It is thought that this stitial pneumonia and an arteritis are frequently present
immunity is mediated mainly by VN antibodies, since their (Del Piero et al 1997). In the outbreak in the UK in 1993,
appearance in serum, usually within a week of infection, two foals on the index stud were born prematurely
coincides with the elimination of virus from circulation. following illness in their dams; one died from pneumonia
Furthermore, passive transfer of colostral antibodies from and another was weak, with its dam having little milk
immune mares to foals has been found to moderate or following a severe illness.
A B C
Fig. 22.11. Horses with clinical EVA demonstrating (A) edema of the sheath, (B) conjunctivitis, blepharitis, and uveitis, and (C) severe
periorbital edema.
Importantly, the nature and severity of the clinical signs al 1999). The VN test should be undertaken as described in
are not affected by the route of infection – mares infected the standard protocol in the OIE Manual of Standards for
venereally will demonstrate identical signs to those infected Diagnostic Tests and Vaccines (Timoney 2000).
via the respiratory route. More recently, problems have been reported with serum
Infection with EAV typically produces a viremia that cytotoxicity when undertaking the VN test in old mares
persists for up to 20 days (McCollum et al 1971), although that have been repeatedly immunized with tissue-culture-
experimental studies with some strains of virus have grown equine herpesvirus vaccines (Newton et al 2004).
demonstrated a cell-associated viremia for several weeks Factors like this and issues such as cost and speed of assay
longer than this (J. Castillo-Olivares and N. Davis-Poynter, have directed attention towards replacing the VN test with
personal communication). During this period, all bodily an ELISA. Excellent data on a prototype ELISA based on GL
secretions may be infectious, including ocular and nasal have been published (Nugent et al 2000) and while this
discharges, saliva, urine, milk, feces, and semen. The virus assay is not yet commercially available, efforts are being
has been isolated from nasal discharges for up to 16 days made to introduce it and inter-laboratory trials are under-
after infection. After the acute period, the infection is way. However, several commercially available ELISAs have
eliminated from geldings, mares, and sexually immature poor specificity and/or sensitivity, are not supported by
colts (McCollum et al 1971). However, the infection may good published data or inter-laboratory comparisons, and
persist in the accessory glands of the adult male repro- their use cannot be supported in any setting.
ductive tract for longer periods and around 30% of infected Virus can be detected in blood samples or nasopharyn-
stallions have been reported to be persistent carriers geal swabs collected from acute cases, either through its
(Timoney et al 1987). Virus is shed in the semen and infects growth in tissue culture in a wide range of cell types, or
mares, whether covered naturally or inseminated with through detection of its RNA through reverse transcrip-
frozen or chilled semen. tion (RT)-PCR. Semen samples (which are frequently toxic
The clinical signs presented, and their severity, vary to cells in tissue culture) are usually pretreated before
widely between outbreaks and between animals within inoculation by short-term sonication followed by centri-
outbreaks. In many occasions, EAV causes subclinical fugation to sediment the spermatozoa. Monolayer cul-
infections. Of particular significance for the equine industry tures should be inoculated in duplicate (at least) with
is the capacity of EAV to cause abortion in pregnant mares tenfold serial dilutions of the sonicated seminal plasma, or
and to establish persistent infection in stallions (Fukunaga buffy coat collected from heparinized blood samples. The
1994). Infection is also transmitted by nasal secretions virus can be difficult to isolate or detect in tissue culture
during the acute phase of the disease as well as through in the laboratory and not all strains are always imme-
semen of chronically infected stallions. The latter animals diately cytopathic.
are asymptomatic virus carriers and can introduce the Diagnosis of EVA in the fetus is problematic, as a high
disease to naive equine populations, as demonstrated in proportion of fetuses aborted during this infection are
the 1993 outbreak in the UK. virologically negative, with placental separation occurring
secondary to viral replication in the pregnant uterus
(Coignoul et al 1984b). Confirmation of EVA infection
Diagnosis in the aborting mare is necessary in such cases. Where
transplacental spread of EAV to the fetus occurs then
The appearance of disease suggestive of EVA in mares lesions of vasculitis may be detected in the fetal organs,
1–2 weeks after mating should lead to suspicion of EVA, as and viral antigen may be demonstrated by immuno-
should respiratory transmission of a disease with these histochemistry in a similar manner to EHV-1 abortion
clinical features. However, diagnosis of the disease can (Del Piero 2000).
only be made following laboratory confirmation, either by
detection of virus or viral RNA, or through demonstration Detection of persistently infected
of a four-fold or greater increase in specific antibody levels. (“shedding”) stallions
The current international standard and OIE-recognized Detailed studies of persistently infected stallions have been
serological assay still remains the virus or serum neutral- undertaken, reflecting the key role that these animals play
ization test (VN or SNT) (Timoney 2000). The CF test has in the persistence and transmission of EAV, in particular by
been used in the past, but has no advantages over VN Professor Peter Timoney at the Gluck Equine Research
for routine use. There have been problems regarding inter- Center in Kentucky (Timoney et al 1986, 1987, Timoney
laboratory differences with VN tests which were addressed, & McCollum 2000). All persistently infected stallions
at least in some European laboratories, through sharing of have a titer of 1 : 4 or greater in VN tests and the VN test
reagents (in particular of virus strains with given passage performed on serum is a well-validated first screening test
histories and positive control antisera) and protocols to determine if stallions have been infected. Care should be
following a formal inter-laboratory comparison (Edwards et taken to use only laboratories experienced in this assay.
In stallions that have detectable neutralizing antibody, by treatments aimed at preserving semen quality (e.g.
efforts should be directed to determine whether or not they chilling or freezing) and shipping semen is a most effec-
are persistently infected. Virus is thought to be shed con- tive means of spreading the infection over long distances
tinuously in the semen and can be found in any fraction, so (Timoney & McCollum 1993).
if sensitive methods are used, it should be possible to deter- The infection is not highly contagious by the respiratory
mine whether or not a stallion is a shedder through exami- routes, certainly transmitting less rapidly and readily than
nation of one semen sample. Semen should be delivered diseases like influenza. Respiratory spread usually requires
chilled to the laboratory, preferably within 12 h of collec- fairly close contact and even then may not occur, although
tion, although frozen semen straws can also be used. major respiratory outbreaks have been described, including
Where possible, a combination of validated RT-PCR and on major North American racetracks. In outbreaks on
virus isolation techniques should be employed to determine stud farms that involve both venereal and respiratory
whether or not the sample is infected. infection, the venereal route is usually the more important
Most stallions will shed virus in the first few weeks of the two. Care must also be taken to prevent contact
following infection, but the proportion infected then between susceptible mares and aborted fetuses and other
decreases over several weeks to around 30%. Some stallions products of parturition, as these can also act as important
will shed virus for many years – effectively for their lifetime. sources of infection.
The testing of semen can be repeated if it is felt that the Infection on stud farms is frequently introduced by the
stallion may have ceased to shed. If laboratory tests suggest use of infected semen. Once mares are acutely infected,
that stallions have ceased shedding or if there is any then infection can spread to close contacts via the respi-
question relating to these results, the shedding status of a ratory route. If pregnant mares become infected, abortion
stallion can be determined by test mating at least two or neonatal foal death can occur and if mares due for
naive, proven seronegative mares. The mares should be covering are infected, then they can pass the infection on to
placed in strict isolation before the test mating and then other resident stallions. Typically, a large proportion of the
tested serologically 2 weeks later. They should then be clinical cases observed during an outbreak will be derived
covered at least twice a day for two consecutive days (i.e. from venereally transmitted infections. A representation of
each mare should be covered at least four times), kept in a typical epidemic lifecycle on a stud farm is shown in
strict isolation and then retested 14–28 days later to Fig. 22.12. The route of transmission from naive mare to
determine if they have seroconverted (see the HBLB Code of nursing foal, perhaps following insemination by infected
Practice for details). semen, is unclear and could involve milk or close
respiratory contact; it is, however, most efficient.
Although not particularly well characterized, epidemio-
Epidemiology logical investigations of outbreaks suggest that there are
marked differences between strains of virus in their ability
EAV spreads readily by both the respiratory and the to spread via the respiratory route (as well as differences in
venereal routes. The outbreak in Kentucky in 1984 led virulence, which may be related) (Moore et al 2002). This
to a major breakthrough in the understanding of the can lead to very different patterns of infection from that
epidemiology of EVA that provided an explanation for described above being observed on some stud farms. For
the postcoital infections that had been described at the example, we investigated, in conjunction with the local
turn of the century. Testosterone-dependent persistence of veterinarians, spread of infection on a very well-managed
EAV infection localized in the accessory sexual organs UK warmblood stud farm where one of the two resident
was found to occur in around one-third of infected stallions had been shedding virus in its semen for a number
sexually mature stallions and was reproduced experi- of years (as represented in Fig. 22.13). All infections had
mentally (Holyoak et al 1993, McCollum et al 1994). This been entirely subclinical. Interestingly, other than spread
understanding of the epidemiology of EVA offered for from all maiden mares covered by the shedder to their
the first time the realistic prospect of control and even suckling foals, there had been, over several years, no
elimination of this disease from endemically infected horse respiratory spread to other animals from acutely infected
populations. However, treatment of persistently shedding mares or their foals. This was evident from finding that
stallions with testosterone antagonists has not yet pro- all mares that had ever been covered by the shedder
duced consistently useful results (Fortier et al 2002). were seropositive and that all of those only covered by
Spread through the venereal route is highly efficient the other, seronegative, stallion remained seronegative. The
and the fundamental role of persistently infected stallions mares had been kept as a single band over several years,
in the spread and persistence of this infection cannot be emphasizing the highly variable transmissibility of EAV
overemphasized. It has been estimated that around 90% of under different circumstances. Such results are consistent
susceptible mares will become infected for each mating with the variation seen between isolates in vitro (Moore
or insemination with infected semen. Virus is preserved et al 2002, 2003).
Off stud
Shedding stallion Stallions
Semen
Off stud
Mares Mares
Fetuses and neonatal foals
Foals Foals
Venereal spread
Respiratory spread
Fig. 22.12. Representation of the typical spread of EAV on a stud farm.
There are marked differences between different breeds in the first few years of the 21st century in both France
in the prevalence of infection and also between breeds in and Ireland (see below under Control). These outbreaks
different countries. The two extremes are the thorough- emphasize the importance of ongoing disease control and
bred, in which the infection is generally rare and fairly surveillance in preventing this infection.
tightly controlled, and the standardbred, in which the
infection is generally common and relatively uncontrolled. Prevention and control
The infection has also been reported to be common in
warmblood breeds. That these breed differences are Prevention and control programs for EVA need to focus on
frequently consistent between continents emphasizes the the pivotal role that the shedding stallion plays in the
critical role played by reproduction in the spread of transmission of this infection. Protecting stallions from
infection with EAV. Until recently, the infection had not infection can be based on vaccination, on quarantine of all
caused many problems in major European thoroughbred animals having contact with stallions or on a combination
populations, but subclinical outbreaks have occurred of the two. The avoidance of natural covering by stallions
Second stallion
not infected
Shedding stallion 2nd Stallion
All mares
covered by No respiratory spread to
stallion other mares or foals
positive
All mares only

covered by negative
stallion all negative
Mares Mares
Spread to all
foals of
maiden
mares
No abortions or
neonatal death
Foals Foals
Venereal spread
No spread
Respiratory spread
Fig. 22.13. Restricted pattern of spread of EAV on a warmblood stud farm.
through the use of artificial breeding techniques, so that tation of infected stallions from outside the EU are
stallions have no contact with incoming mares, is a highly prevented by legislation, but where there is no require-
effective means of preventing spread but is currently ment to test stallions before movement within the EU.
not possible in thoroughbreds. Considerable care should In addition, the disease is notifiable in Britain (only in
always be taken to ensure that stallions being used for stallions), Ireland, and other countries and statutory
artificial insemination are not infected; transmission of disease control procedures provide an important means of
virus through semen is an entirely avoidable means of controlling animals and their owners when there is no
spreading the infection over particularly long distances. compliance with voluntary control measures.
Because of the role of stallions, extensive efforts are
made by governments to ensure that infected stallions and
semen are not traded between different countries. A major Vaccination
exception to this is the situation within the EU, in which Tissue culture-adapted and formalin-inactivated whole
intracommunity trade of EAV-infected semen and impor- virus vaccines have been used to control EAV infection. The
live vaccine was attenuated by serial passages in horse (Chirnside et al 1995). A fusion protein and a synthetic
kidney (HK), rabbit kidney (RK) and equine dermal (ED) peptide, both derived from GL, induce neutralizing anti-
cells. Despite occasional isolation of the attenuated virus bodies when injected into rabbits and ponies, thus demon-
after vaccination (Fukunaga et al 1982, Timoney et al strating the potential of the subunit approach. Further
1988), no reversion to virulence was observed after sequen- studies demonstrated that other GL-based antigens also
tial passages of the vaccine virus in horses (Doll et al 1968, induced strong neutralizing antibody responses and could
McCollum 1969). However, vaccination of pregnant mares confer protection in ponies against experimental infection
is not recommended. The commercial live virus vaccine (Castillo-Olivares et al 2001). The combined use of the
(passage history HK-131/RK-80/ED-24) and its less atten- GL-based subunit vaccine and a differential diagnostic test
uated earlier versions have been shown to be effective for against EAV would allow the discrimination of vaccinated
clinical protection (McCollum 1969, 1986, Timoney & from naturally infected horses. Other EAV antigens, such
McCollum 1988). These animals also demonstrated reduc- as N and M, are frequently recognized by sera from
tions in duration of virus excretion from nasal secretions EAV-infected horses and initial steps to develop ELISA
and in duration of viremia. diagnostic tests based on these antigens have been taken
An experimental, non-adjuvanted, formalin-inactivated (MacLachlan et al 1998); so a GL-based subunit vaccine
whole virus vaccine was shown to stimulate high levels of could be generally administered to horse populations
VN antibody after repeated inoculations with high titer without compromising disease surveillance by serological
virus preparations (Fukunaga et al 1996, 1997). Clinical screening. Such an approach should be very useful in those
trials with this vaccine showed a reduction in clinical signs, areas of low EAV prevalence, or for international trade
nasal excretion of virus and viremia in vaccinated horses, or for the control of outbreaks of EAV by enabling the
which appear to correlate with the VN antibody titer at the protection of susceptible populations by vaccination and,
time of challenge. In 1993, an adjuvanted killed virus vac- at the same time, permitting the surveillance of disease
cine was licensed in the UK under an Animal Test Certificate, progression by serological testing.
based on some experimental efficacy data. It has subsequently
been fully licensed in several European countries and has Control
been widely used since then. No significant adverse effects
have been detected with the widespread use of this product Most attention is given to the prevention of EVA on stud
in stallions and there has been no evidence of vaccine farms because of the huge costs that EAV can cause in this
breakdown, although it is unclear how often vaccinated setting. Using artificial insemination to prevent contact
animals have experienced field infections. between uninfected stallions and visiting brood mares can
Both commercially available products have principally be a most effective means of protecting stallions, but is not
been used in stallions and a particular challenge arises currently possible in registered thoroughbreds. Protection
with the vaccination of stallions with them. These animals of stallions through vaccination is the cornerstone of
develop circulating neutralizing antibody that is indistin- many stud-based control programs. Serological and clinical
guishable from that induced by infection. Therefore, all surveillance in brood-mare populations is also vital to
stallions to be vaccinated should have a sample taken to protect studs that use covering from potential challenges to
demonstrate that they are seronegative at the time of vacci- their stallions and from outbreaks of abortion. A detailed
nation. Wherever possible, they should then be boosted at description of the formal disease prevention program
least annually and possibly, in the case of those receiving employed in Europe is in the HBLB Code of Practice, along
the whole virus inactivated product, every 6 months for the with a program for EHV-1 (www.hblb.org.uk).
first few years (J. Cardwell, J.R. Newton and J. Wood, unpub- Briefly, it is recommended that all mares should be
lished observations). Ideally, they should also be serologically screened serologically within 28 days of mating. Seropositive
monitored to ensure that they have not become infected animals, if not previously identified as such, should be
under the cover of vaccination. Most trading countries will isolated and retested 14–28 days later to determine if the
accept vaccinated stallions if they have been shown to be infection is still active. If the animal was managed as part of
seronegative at the time of first vaccination and then a group, then investigations in this group may at times be
regularly boosted, although some still require testing of necessary. Animals being imported from higher risk areas
semen samples for virus in all seropositive animals. should be placed in isolation on arrival and tested serologi-
The development of a subunit vaccine for EAV would cally after 14 days. Stallions should preferably be vaccinated.
enable differentiation between vaccinated and infected Where unvaccinated, they should be screened at least
animals. Immunodominant proteins of EAV have now been annually at the start of the breeding season. Where vacci-
identified and bacterially expressed glutathione S-transferase nated they should be boosted at least annually and, preferably,
(GST) fusion proteins of ORFs 2b–7 have been screened serologically monitored for changes in titer as well.
by ELISA with EAV-positive equine sera; GL has been Considerable care should be taken to ensure that
demonstrated to be the most immunoreactive polypeptide stallions being brought on to premises for either natural
covering or semen collection are not infected before arrival. Virology and immunity
Animals being used for semen collection should not be
mixed with others of lower health status after their arrival Several different picornaviruses have been isolated from
on the collection station. Frozen semen can be proven free horses (Plummer 1962, Studdert & Gleeson 1977,
from infection by showing that stallions are seronegative Mumford & Thomson 1978, Fukunaga et al 1983) and
both before and 28 days after the last date of collection. most have been rhinoviruses, isolated from the respiratory
Chilled semen is harder to certify, but stallions should be tract, mouth, blood, and feces.
shown to be uninfected within 2 weeks of collection, The rhinoviruses were originally grouped into three
having been kept in isolation during this period. categories, equine rhinovirus-1 (ERV-1), ERV-2 and ERV-3.
Despite the existence of these control programs, out- ERV-1 has now been reclassified as equine rhinitis A virus
breaks of EAV infection can still occur. For example, exten- (ERAV) (Varrasso et al 2001). ERV-2 has been renamed
sive and entirely subclinical spread of EAV occurred in equine rhinitis B virus (ERBV) and has been reclassified as
several studs in Normandy in northern France in 2000, an Erbovirus, a new genus in the Picornaviridae (Hinton &
resulting in at least two thoroughbred stallions serocon- Crabb 2001). ERV-3 has also recently been classified as an
verting; one of these stallions became a long-term shedder Erbovirus and named ERBV2 in view of its close sequence
of the virus and has subsequently had to be used under homology with ERBV (Huang et al 2001). ASPV, which
stringent restrictions. Less information has been made shares the properties of enteroviruses and rhinoviruses,
available on some EAV infections in the thoroughbred has not been reconsidered in recent years.
population in Ireland in 2003 when a problem became Infection with ERAV stimulates a long-lasting neutral-
apparent after a prospective “shuttle” stallion was rou- izing antibody response which is thought to prevent further
tinely tested in late summer before export and was found disease, although repeated infections in racehorses in
to be unexpectedly EAV seropositive. Further serological training can occur (Mumford 1994). Infection with ERAV
screening demonstrated evidence of subclinical infec- does not stimulate cross-reactive neutralizing antibody
tion on at least three stud farms, but in contrast to the to either ERBV or ASPV (Mumford & Thomson 1978,
French outbreak, no stallions were reported to have Steck et al 1978, Mumford 1994). There is little informa-
become shedders. tion on cell-mediated immune responses to other equine
This increasing number of EVA outbreaks reported in picornaviruses.
Europe, and those that continue elsewhere, identify that
the use of high value (in economic or breeding terms) Clinical signs and pathogenesis
stallions that have unfortunately become shedders must
be considered. There is extensive experience in the USA Both natural and experimental infection of seronegative
(Timoney & McCollum 1991) and increasingly elsewhere horses with ERAV has been associated with pyrexia
as well, that suggests that, with care and considerable (<40.4°C) for up to 5 days, nasal discharge and swelling
attention to biosecurity, these animals can be used safely of retropharyngeal lymph nodes and a moist cough
with no general threat to the equine population. Mares (Plummer 1962, Plummer & Kerry 1962). Natural infec-
should be seropositive prior to covering and should be kept tions may frequently be subclinical, particularly in sero-
in strict isolation for at least 28 days after covering. positive animals (Studdert & Gleeson 1978).
As we move forward in this new millennium, recent EVA Although ERBV infections may sometimes cause slight
outbreaks serve to remind us that the international move- pyrexia and mild respiratory signs (Steck et al 1978), infec-
ment of horses or their semen still poses a real threat. The tions are usually subclinical and infection of gnotobiotic
situation for EVA is exacerbated because different nations foals failed to induce clinical signs of respiratory disease
currently have very different attitudes to this disease. (Mumford & Thomson 1978). There is little or no informa-
tion on the ability of ERBV2 to cause disease.
ASPV was initially isolated from a thoroughbred
racehorse in training, although it was not showing signs of
Equine Rhinitis Viruses respiratory disease at the time (Mumford & Thomson
Historical context 1978). Experimental infection of a gnotobiotic foal failed
to produce signs of respiratory disease, but seroconversion
Equine rhinitis virus A and B, previously classified as did occur and virus was recovered from the animal.
equine rhinovirus-1, -2, and -3, are common in horse Serological investigations of naturally occurring outbreaks
populations but knowledge of their epidemiology, patho- of respiratory disease have produced confusing results
genesis and association with disease is rather limited. The and there is little evidence that this virus is a cause of
viruses have recently been reclassified and other equine equine respiratory disease, although the very limited
picornaviruses, such as “acid-stable picornavirus” (ASPV), amount of work reported precludes firm conclusions from
may yet also be reclassified. being drawn.
Diagnosis Hendra Virus

Equine rhinitis virus infections may be diagnosed by Historical context
isolation of virus in tissue culture, detection of viral RNA
by PCR (Li et al 1997) or through demonstration of viral In September 1994 there was an outbreak of acute severe
seroconversion using either CF or VN tests (Mumford respiratory disease in racehorses stabled in the Hendra
& Thomson 1978). suburb of Brisbane, Queensland, Australia. During the out-
break, which lasted around 20 days, 18 horses were clini-
Epidemiology cally affected and 14 died or were euthanased. Two human
contacts, the trainer (who later died of a pneumonic condi-
ERAV has a worldwide distribution. Infection can spread by tion) and a stable hand, became ill, with the latter sub-
respiratory contact and outbreaks of disease associated sequently slowly recovering (Selvey et al 1995). Following
with ERAV have been reported (Mumford 1994, Li et al notification to the Department of Primary Industries, a
1997). Prolonged excretion of ERAV in urine in racehorses veterinary team conducted an exhaustive investigation of
is common, particularly in 2- and 3-year-olds (McCollum & the outbreak. Quarantine and movement restrictions were
Timoney 1992) and is probably an important source immediately implemented, all horseracing in Queensland
of infection. was halted, and all equine deaths were made notifiable
Many foals in the UK remain seronegative to ERAV and (Mackenzie et al 2003). The investigation did not demon-
racehorses usually experience their first ERAV infection strate infection with any known equine infectious agents,
in their second or third year, whilst in training (Powell but quickly identified a previously unrecognized virus
et al 1974). A similar situation has also been reported (initially termed equine morbillivirus and now referred to
elsewhere, including North America (Holmes et al 1978). as Hendra virus – HeV).
During outbreaks, ERAV is highly contagious and trans- A program of extensive experimental and in vitro studies,
mission rates in naive populations may approach 100% many conducted at the Commonwealth Scientific and
(Holmes et al 1978, Studdert & Gleeson 1978). Initial Industrial Research Organization (CSIRO) and complicated
infections are usually associated with clinical signs by the extensive care required when working with such
(Burrows 1979, Li et al 1997, Klaey et al 1998), but dangerous category 4 pathogens in large animals, have
repeated infections with ERAV, detectable in racehorses fulfilled Koch’s postulates and confirmed the etiology
using the CF test (Mumford & Thomsen 1978), are (K Murray et al 1995, 1998, Hooper et al 2001). Detailed
frequently not associated with signs of disease. Most foals epidemiological studies have demonstrated that this is a
become infected with ERBV during the first few months of rare, incidental infection in horses, being endemic in fruit
life (Holmes et al 1978, Burrows 1979) and repeated bats in the region (Westbury 2000). Only a few other cases
infections are frequently observed. It is clear that infec- have been diagnosed in either horse or humans since that
tions with ERBV and ERBV2 are common in Australia, time, but far more extensive outbreaks of disease caused by
where they have been most often studied (Huang et al the closely related Nipah virus in pigs and people have
2001). Most infections are not associated with obvious occurred over Southeast Asia.
clinical signs.
Virology
Prevention
Initially described as a morbillivirus, the viruses isolated
No commercially available equine rhinovirus vaccines from both horses and people in the initial outbreak were
currently exist. However, ERAV infection stimulates strong shown to be closely related on the basis of two-way cross-
clinical immunity and immunization with inactivated virus neutralization assays (K Murray et al 1995). Hendra and
stimulates VN antibody and protection against experi- the related Nipah virus have now been classified in the
mental infection (Burrows 1979). Henipah genus of the Paramyxoviridae as they were not
As a result of the lack of commercially available typical of the morbillivirus group. The viruses are pleomor-
vaccines, controlled infection programs with ERAV in phic and enveloped, with two or three glycosylated trans-
racehorses have been suggested as a means of ensuring membrane proteins. The viruses have single-stranded RNA
that disease does not occur shortly before important race with negative polarity, of 5 × 106 to 7 × 106 b. p. (base pairs),
meetings, but so far these have not been reported (Klaey which can encode 10–12 proteins. The function of these
et al 1998). are not described here, and readers are referred to more
No information is available on stimulation of immunity detailed descriptions (Rodriguez & Horvath 2004). The
to ERBV or ERBV2, but natural infection is often associated virus will grow in a wide variety of different cell types.
with prolonged excretion (Fukunaga et al 1983) and virus Virions are labile and are rapidly inactivated by heat, lipid
neutralizing antibody levels are not maintained at high solvents, and detergents. HeV shares between 80 and 90%
levels, suggesting that natural immunity may be poor. sequence homology with the closely related Nipah virus.
Clinical signs and pathogenesis Australia with the death of an adult thoroughbred mare
within 24 h of becoming ill. There was no evidence of
Following a typical incubation period of 8–11 days, not spread of infection to another mare in the same paddock in
extending beyond 16 days, similar clinical signs develop in a residential area of Cairns and no other contact with
both the natural disease and that induced by either other horses.
inoculation of laboratory-grown virus or lung from field Investigations that followed the earlier outbreaks of HeV
cases. These signs consist of a high temperature (up to demonstrated no evidence of infection in any other people
41°C) with anorexia and depression, accompanied by or horses, suggesting that a wildlife reservoir might exist.
signs of a primary viral interstitial pneumonia including After investigation of many other species, a seroprevalence
hyperpnea and dyspnea, sweating, congested mucous of >20% was demonstrated in pteroptid bats in eastern
membranes, and copious frothy nasal discharge. Ataxia Australia (Halpin et al 2000). Three species of these large
may be present, along with head pressing in terminal cases frugiverous bats, otherwise known as fruit bats or flying
and subcutaneous edema in a few animals (K Murray et al foxes, are found around coastal regions of Australia and
1995, 1998). Death often rapidly ensues, although the they are generally assumed to be the reservoir hosts of this
outbreak in Hendra was also associated with significant virus. Detailed understanding of its persistence in bats does
levels of subclinical infection. not exist, but the isolation of virus from bat uterine fluids
The primary pathology in horses is in the lung, where (Halpin et al 2000) and the demonstration of vertical
massive subpleural edema and distension of lymphatics transmission in bats (Williamson et al 1998) have led to
accompanies the interstitial pneumonia, along with suggestions that transmission of infection may occur
thoracic and pericardial fluid effusion. Virus can be found around birth. These animals often give birth to their young
in blood vessel walls and in pulmonary epithelium; on the ground and it may be that inquisitive horses come
pulmonary capillary endothelium is extensively damaged, into contact with infection at this time.
leading to the edema, and giant cell syncytia are present Field investigations, supported by experimental studies,
in lung capillaries and arterioles. More detailed reviews have demonstrated that the virus is not highly conta-
of pathology in horses and cats are available (Hooper gious between horses. Transmission of the virus between
et al 2001). horses generally required close contact, as it did for trans-
mission between horses and people. Cats can be infected
Diagnosis experimentally and can transmit the infection to horses.
Importantly, infection occurs in the kidneys of many infected
The infection can be diagnosed by detection of the virus horses and virus can be detected in urine (Williamson et al
in tissue culture, detection of viral RNA by RT-PCR 1998). Infection did not spread from experimentally
(Guillaume et al 2004), demonstration of typical histo- infected grey-headed fruit bats to horses in contact with
logical lesions, supported by immunoperoxidase staining or them, but the bats were not breeding at the time.
by demonstration of seroconversion. A VN assay was used These studies and observations demonstrate that, as the
in all initial investigations, but an ELISA has been used disease is not very contagious, it should generally be easy
more recently, particularly for screening of healthy animals to control, but they emphasize the care that must be taken
for international trade purposes. in managing cases and suspect cases and their fomites
Diagnosis should not be attempted by field veterinarians and bedding. A greater challenge is to improve our under-
and suspicion of disease should always be notified to standing of the transmission of HeV in fruit bats and how
competent authorities because of its extremely high case this might be controlled.
fatality rate in human contacts.
Prevention and control
Epidemiology
Fruit bats are common in Australia and the high sero-
Since the original outbreak, very few other cases have prevalence of HeV in them suggests that elimination
been diagnosed in horses or humans, despite extensive from this wildlife reservoir would be problematic. While
retrospective and prospective investigations. In October stabling of horses during the fruit bat reproductive season
1995 a farmer in northern Queensland, 1000 km from the can be proposed in theory, it is hard to envisage how this
original outbreak, died in hospital following a progressive can be achieved in practice. Nonetheless, it is important to
neurological illness associated with Hendra virus infection. note the rarity of transfer of the infection to horses. It is
In August 1994 the farmer had assisted with necropsies on critical that clinical cases are diagnosed at the earliest
two horses, diagnosed then as poisoning but retrospec- possible stage so that appropriate precautions can be taken
tively diagnosed with HeV infection. He had suffered mild for handlers and veterinary staff (Mackenzie et al 2003).
meningoencephalitis soon after but had recovered without Diagnosed cases of HeV infection in horses should be
apparent complication before later relapsing. A further destroyed because of the unacceptable human health risks
case of equine HeV infection occurred in January 1999 in of managing such animals in the field.
Control procedures implemented in Europe after the group. There is a marked contrast between several sero-
initial outbreaks included a demonstration that horses logical studies of respiratory disease in horses. Several
traveling from Australia, particularly from the northeast, studies have reported a PI3 seroprevalence of 0% in race-
should be demonstrated to be Hendra-seronegative within horses (Canadian standardbred racehorses and thorough-
2 weeks of travel. This requirement has now lapsed and the bred racehorses in Chile and Japan). In contrast, a sero-
generally high clinical expression of infection and the short prevalence of 3–33% has been reported in racehorses and
incubation period provide a reasonable safeguard that riding horses in different parts of Europe. No serological
subclinically affected horses do not travel. studies of PI3 infection in horses in the UK have been
The control of the Hendra outbreaks and the subse- published and given the widespread occurrence of this
quent investigations provide an excellent example of how a virus in other species, further studies of this infection in
novel and fatal viral zoonosis can be effectively investigated horses are warranted.
collaboratively between veterinary and medical specialists
and then controlled and monitored.
African Horse Sickness
Parainfluenza-3 Historical context
Clinical signs African horse sickness (AHS) is typically a peracute or

acute infectious, but non-contagious, disease of Equids
Parainfluenza-3 (PI3) was first isolated from a horse in transmitted by Culicoides midges. The outcome is highly
Canada in 1961 (Ditchfield et al 1963). The virus was dependent on the equid species infected and while the
associated with an outbreak of severe upper respiratory mortality rate in naive horses is between 70 and 95%, it
disease in one group of horses. Temperatures were raised varies between 50 and 70% in mules and is very low
(38.6–39.7°C) and these pyrexias were accompanied by in South African donkeys, although donkeys from the
anorexia, seropurulent nasal discharges, and dyspnea. Middle East may experience a mortality rate of up to 10%
Conjunctivitis was seen in 22 of 48 affected animals and (Coetzer & Erasmus 1994). Clinical signs are not gener-
bronchitis was observed in five. In most cases the disease ally recognized in zebras. Rates of transmission through
was self-limiting within 7–9 days. Since then, there have South African donkeys and zebras, in which the infection
been few reports of any association between this virus and is usually subclinical, can however be high (Lord et al
respiratory disease in horses, despite several reports of 1997a, 2002).
serological evidence of infection. PI3 was isolated from AHS is common in most countries in sub-Saharan
horses with lung disease in China (Zhu et al 1989). Africa and is the only OIE list A disease of horses. AHS
One study of respiratory disease in children found that causes sporadic, but socio-economically devastating,
specific degenerative changes of respiratory epithelium, epidemics in other countries such as Morocco and Ethiopia
termed ciliocytophthoria, were a sensitive and specific indi- (Coetzer & Erasmus 1994). It is an important reason why
cator of PI3 infection (Naib et al 1968). These findings Equids have not been more widely used as draught
have been extrapolated to the horse and ciliocytophthoria, animals in Africa and so continues to have significant
which is not uncommon in both acute (Whitwell & Greet socio-economic impact in the African continent. Also,
1984) and chronic (Beech 1975) respiratory disease in many affected horses have considerable monetary value
the horse, is now regarded by many as indicative of “viral” either as performance horses or in their use in other forms
infection (Beech 1975, Whitwell & Greet 1984), even of recreation. Furthermore, exportation of horses from
though it appears to be a specific feature of PI3 infection areas where AHS occurs can only be accomplished, if at
in humans and it has never been associated with PI3 all, following strict quarantine and testing procedures. The
infection in the horse. virus caused massive mortality in the 19th century in
imported horses, with outbreaks in 1854/5 and 1891/2
Diagnosis being associated with the deaths of 70,000 and 25,000
horses respectively.
PI3 infection may be diagnosed by isolation of virus from
Major outbreaks of the disease outside the hyper-
respiratory secretions or through demonstration of
endemic areas occurred in Egypt in 1928, 1943, 1953,
seroconversion (Ditchfield et al 1963). The initial virus
1958, and 1971, in Yemen in 1930, and across the Middle
isolates were obtained with the use of primary rhesus
East in 1944. In 1959, an outbreak caused by serotype 9
monkey kidney cell lines. The HI test is the most commonly
occurred in Iran and between 1960 and 1961 this spread
used serological test in the horse (Ditchfield et al 1963).
through the Persian Gulf area into Afghanistan, Pakistan,
Epidemiology India and Turkey, killing in excess of 300,000 animals
(Coetzer & Erasmus 1994). The disease occurred in several
In the initial outbreak in Canada, infection was widespread North African countries in 1965, spreading across the
and antibody to PI3 was found in all adults in the affected straits of Gibraltar into Spain in 1966. Further outbreaks
occurred between 1987 and 1991 in Spain, Portugal, and endothelium (Mellor & Hamblin 2004). Virus strains vary
Morocco, the infection having been introduced into in their organ tropisms (Gomez-Villamandos et al 1999).
the region by a group of zebra from Namibia (Lubroth In the pulmonary form, a fever (up to 41°C) lasting up
1988, Hamblin et al 1991b). The disease also occurred to 2 days is followed by development of severe dyspnea,
in Saudi Arabia in 1989, after an absence of 30 years paroxysmal coughing, and a copious nasal discharge of
(Mellor et al 1990). frothy, serofibrinous fluid (Coetzer & Erasmus 1994). The
disease is characterized by a massive pulmonary edema
Virology and hydrothorax, often with several liters of fluid accumu-
lating. Death can occur within a few hours of onset of
AHS virus (AHSV) is in the genus Orbivirus in the family signs and less than 5% of animals with this form, which is
Reoviridae. It shares many properties with other orbi- the typical form in young susceptible animals, survive.
viruses such as bluetongue virus and equine encephalosis The cardiac or edematous form is chiefly characterized
virus and is a double-stranded RNA unenveloped virus clinically by subcutaneous swelling of the neck and head,
with a segmented genome. The viruses are highly resistant particularly the supra-orbital fossa. At post-mortem, yellow
to disinfection and other forms of inactivation. gelatinous edema of subcutaneous and intermuscular
There are nine serotypes of AHSV, the last of which connective tissues is the most obvious feature. Microscopic
was isolated in 1960 (Howell 1962). Serotype is deter- pathology in cardiac tissues can be hard to detect, other
mined by the surface glycoprotein VP3. Antisera raised than for serotype 9, where foci of myocyte degeneration
to homologous virus may cross-neutralize different sero- and necrosis occur. In more severe cases, in which mortality
types, although the extent of cross-protection in natural is more likely, all cranial soft-tissue structures are affected,
mammalian hosts, other than the zebra (Lord et al 1997b), along with the shoulders, neck, and chest. Petechial
has not been formally evaluated to any extent. The cross- hemorrhages are a poor prognostic indicator. Mortality
neutralization between antisera produced against different from the cardiac form, which is milder than the pulmonary
strains of orbiviruses depends to a great extent on the form, is around 50% (Coetzer & Erasmus 1994).
species in which the antisera have been produced (Howell Horsesickness fever is the most common form in horses
1962, Howell et al 2002). In AHSV, there is cross-neutral- with pre-existent immunity to one or more serotypes. It
ization between serotypes 6 and 9, 5 and 8 and, to a lesser is the mildest form of the disease and is probably very
extent, between strains 1 and 2 and strains 3 and 7 (Coetzer underdiagnosed. It is characterized by a pyrexia (39–40°C)
& Erasmus 1994). These cross-reactions can complicate the lasting 1–6 days and some edema of the supra-orbital
interpretation of postinfection serology, especially after fossa. The pyrexia may also be accompanied by transient
infection with a number of different serotypes. Clinical loss of appetite, slight dyspnea, and increased heart rate.
evidence suggests that there is a lack of intratypic varia-
tion, but this has not been evaluated formally either Diagnosis
through molecular or serological means.
In most cases, in endemic or epidemic areas, clinical
Clinical signs and pathogenesis diagnosis of AHS will often be correct. Confirmation of
diagnosis of AHS, as for most viral diseases, can be
The incubation period following AHSV infection in sus- accomplished by either serological means detecting rises in
ceptible hosts is typically 5–7 days. The clinical signs are antibody levels, or by virus detection through isolation or
markedly affected by the host species and its immune status. the detection of specific viral RNA using PCR. In AHS,
Experimentally, the incubation period may vary between serologic methods commonly used in diagnostic labora-
2 and 10 days and disease severity depends markedly on tories include a group-specific ELISA which enables
virus dose and virulence. There are four different forms of detection of antibodies following infection with any of the
the disease: the pulmonary form (“Dunkop”), the cardiac nine viral serotypes (Hamblin et al 1990, House et al
form (“Dikkop”), the mixed form, and horsesickness fever. 1990) or through specific serotype VN assays (Howell
Although the mixed form is probably the commonest, it is 1962, House et al 1990). Virus can be isolated from
rarely diagnosed because pulmonary or cardiac signs usually tissues or blood samples from acutely affected animals
predominate in individual animals (Coetzer & Erasmus 1994). using a variety of different cell culture systems (e.g. BHK
After inoculation by biting Culicoides, initial multiplica- or Vero) and characterized in neutralization or other
tion occurs in the regional lymph nodes, followed by a assays (House et al 1990, Coetzer & Erasmus 1994); for
disseminating viremia with subsequent infection of target example antigen detection ELISA (Hamblin et al 1991c)
organs (Mellor & Hamblin 2004). Replication of AHSV in and PCR assays have been reported which are either
these organs, particularly in capillary endothelium, is group-specific (Zientara et al 1993, Sailleau et al 1997) or
associated with a secondary cell-associated viremia of serotype-specific (Sailleau et al 2000). AHSV can also be
variable duration and with clinical signs. Much of the detected in midge species by virus isolation or ELISA
pathology results from increased permeability of capillary (Hamblin et al 1991a).
Postinfection serology has been used in epidemiological and the rate of virogenesis are temperature dependent
investigations in donkey (Hamblin et al 1991b, Williams (Mellor et al 1998, Paweska et al 2002). AHSV serotype 4
et al 1993, el Hasnaoui et al 1998, Lord et al 2002) replication is low at temperatures <15°C. While the
and zebra (Barnard & Paweska 1993, Lord et al 1997a) vector’s lifespan is extended at lower temperatures (Mellor
populations, although the cross-reactions between sero- et al 1998) or at lower night-time wind speeds (Baylis et al
types can complicate the interpretation of the results, 1998b), the rate of virogenesis decreases so that at environ-
particularly for the more cross-reactive types (Lord et al mental temperatures of 10°C virus becomes undetectable,
1997a, 2002). although there is some, apparently non-replicative, per-
sistence of virus at these temperatures (Mellor et al 1998).
Epidemiology and prevention If the ambient temperature increases, the virus will repli-
cate and vectors will be able to transmit the virus. The rates
In addition to the sporadic, but internationally reported, of infection and titers of infectivity of different Culicoides
epidemics of AHS, cases in horses occur every year in spp. vary substantially and are also affected by the strain
South Africa, despite the practice of widespread vaccina- and specific isolate of virus (Venter et al 1998); such
tion with a polyvalent attenuated vaccine (Coetzer & variability is likely to exist for AHSV but has not yet been
Erasmus 1994). There was a major outbreak caused by characterized.
serotype 2 in the Transkei region of the Eastern Cape Quantitative studies of the epidemiology of AHS in
Province from November 2000 to May 2001, in which over different provinces of South Africa have produced estimates
1,000 horses died. These horses were in poor rural areas, of the “force of infection” of AHSV serotypes as a whole,
where they were typically used for transport and work, and for two separate time periods (Lord et al 1996). However,
the outbreak had a substantial economic impact. there are no published estimates of serotype-specific trans-
The distribution and spread of AHSV is determined to a mission rates or of forces of infection, despite these being
great extent by the distribution of its insect vector. In most fundamental measures (Lord et al 1997b) and despite there
parts of Africa and southern Europe, there is a large body being evidence that transmission may vary between sero-
of evidence that indicates that the major role is played types (Lord et al 1998). Elegant, deterministic mathe-
by Culicoides imicola (Coetzer & Erasmus 1994, Mellor & matical models of large-scale AHSV transmission, which
Boorman 1995), as is also the case for the closely related included the role of two mammalian hosts (horse and
bluetongue virus (Baylis et al 2001, Purse et al 2005). donkey) and one vector species (C. imicola) in viral trans-
Extensive work has had considerable success in predict- mission, have been published (Lord et al 1996, 1997b).
ing the distribution of C. imicola, and hence of AHS and Control is currently hampered by an insufficient under-
bluetongue, from satellite data (Baylis et al 1997, 1998a, standing of the quantitative aspects of transmission that
2001, Rawlings et al 1997, Purse et al 2005). The distri- are required for scientifically based control programs. For
bution of this species is dependent to a great extent example, given sometimes large populations of donkeys
on the phase of the annual “normalized difference vege- and the fact that donkey populations can experience high
tative index” (NDVI) cycle (Baylis et al 2001). NDVI is rates of AHSV infection (Lord et al 2002), immunization of
a composite measure and is influenced by a variety of donkeys (Lord et al 1997b, 1998, el Hasnaoui et al 1998,
factors, including soil type, rainfall, and environmental Hamblin et al 1998) has been suggested as critical in the
temperatures. success of vaccination (to eradicate) programs. Despite
Investigations of some recent outbreaks of AHS in South this, donkeys have largely been ignored in previous epi-
Africa have implicated C. bolitinos in transmitting some demics in non-endemic areas, probably because of their
strains of AHSV (Meiswinkel & Paweska 2003) in regions low economic value and the fact that they are clinically
where C. imicola was absent. There is less published unaffected by AHS and the uncertainty of the precise role
material on the usefulness of satellite imagery to predict that they can play in the epidemiology of AHS.
the distribution of C. bolitinos in South Africa, or of the Recent spread of the closely related bluetongue virus
more recently identified northern European bluetongue through the Mediterranean area (Mellor & Wittmann
vectors C. pulicaris and C. obsoletus (Capela et al 2003, 2002, Purse et al 2005) has been associated with remark-
Caracappa et al 2003, Purse et al 2005). able and rapid spread of the shared primary insect vector,
The transmission of orbiviruses by Culicoides is under transmission by novel vectors and overwintering in new
genetic control and is strongly influenced by environmental northern regions. This experience suggests that AHS may
temperatures, because of the requirement for virogenesis also cause unforeseen problems in these regions and that
in the vector after feeding on an infected mammalian efforts should be made now to understand and quantify the
host, followed by feeding again on another susceptible host transmission of the virus and manage its control (Anon
(Mellor et al 1998). The temperature dependence of the 1997, The Royal Society 2002).
virogenesis in bluetongue virus is affected by the virus As is the case for bluetongue virus, the only currently
serotype and the species of Culicoides (Paweska et al 2002). available vaccine against AHSV is a live attenuated vac-
For AHS and bluetongue, both the infection rate of midges cine. As a result of the possible reversion to virulence in
vaccinated animals and transmission by vectors and the 1996). Antibodies to equine adenovirus-2 also appear
possible reassortment with field virus, this is not the ideal to be common (Studdert 1996). However, despite this,
vaccine for use in naive areas. An inactivated monovalent structured studies in both foals (Hoffman et al 1993,
vaccine was used as an adjunct to control during the most Dunowska et al 2002) and young thoroughbred race-
recent outbreak in southern Europe. Currently, however (as horses (Burrell et al 1996, Christley et al 2001, Newton
of 2006), the license for this product has lapsed and it is no et al 2003, Wood et al 2005) have failed to demonstrate
longer commercially available in Europe. any association between clinical respiratory disease and the
Management factors that reduce exposure to midge bites presence of adenovirus or seroconversion to this agent.
are a most effective means of preventing the disease in Occasional outbreaks of respiratory disease or pyrexia in
horses, and stabling without the use of lights at night has adult animals associated with adenovirus infection do
long been recognized to be highly effective in areas where undoubtedly occur, but, in the authors’ experience, are
C. imicola is implicated in the transmission, even if the not common.
stabling is open and not insect proof. However, the feeding Infection with equine adenovirus is common, but the
behavior of northern European Culicoides species may differ virus does not generally appear to be an important cause
and this means of prevention may not be as effective in of equine disease, particularly in the adult. The advent of
non-C. imicola areas. genetic tests that have markedly reduced the numbers
of Arab foals being produced with SCID reduces the
apparent significance of equine adenovirus further.
Adenovirus
There are several reports of the isolation of equine
adenovirus from foals (Wilks & Studdert 1972, Studdert
Conclusion
et al 1974, Dutta 1975, Whitlock et al 1975, Konishi et al This chapter illustrates the rapid advances that have been
1977) and, less frequently, from adult horses, with pneu- made in equine respiratory virology in the last decades, and
monia or signs of upper respiratory disease (unpublished identifies new challenges for the future. There is a need for
observations). In some reports, the infection has been improved, more rapid, and internationally validated diag-
associated with diarrhea (Studdert & Blackney 1982) or a nostic tests that will allow consistent and early diagnosis
loosening of fecal material (Powell et al 1974). Generally, of disease and early implementation of control. Further
all isolates have been remarkably antigenically similar improvements in our understanding of viral disease
(Studdert 1978), but one study reported the isolation of a epidemiology, pathogenesis, virulence determinants, and
distinct isolate from cases of diarrhea (Studdert & Blackney correlates of immunity are also required. Such advances
1982). The typical isolates are referred to as equine would enable better models of disease to be developed
adenovirus type 1 and the isolate from cases of diarrhea is and subsequently lead to the marketing of effective and
referred to as equine adenovirus type 2. safer vaccines. Improved and multidisciplinary approaches
The infection can be diagnosed by isolation of virus, to surveillance and control of equine diseases are also
detection of viral DNA, or by demonstration of seroconver- required, particularly in the light of the increasing
sion using serum neutralization tests or HI assays. international movement of horses and not least because
Equine adenovirus is a very important cause of mor- of the potential for novel inter-species and zoonotic viral
bidity and mortality in Arabian foals suffering from severe transmission. Key to all of these advances is good commu-
combined immunodeficiency (SCID) (Whitlock et al 1975, nication between all those with interests in the disease,
Thompson et al 1976, Perryman et al 1978). In addition, from the clinician dealing with the suspect case and
the virus has been isolated from the spinal cord of a few working with the official to prevent the disease in the
horses with cauda equina neuritis (Edington et al 1984), population, through epidemiologists to laboratory diag-
but its role, if any, in this rare disease remains unclear. nosticians and basic researchers who should provide the
Experimental infection studies have demonstrated that necessary tools to the pharmaceutical industry to develop
the virus can cause signs of respiratory disease, including the necessary commercially available products.
mild nasal discharge, rhinitis, tracheitis, bronchopneu-
monia, and an interstitial pneumonia (McChesney et al
1974, Pascoe et al 1974, Gleeson et al 1978). Signs of REFERENCES
disease were worsened in colostrum-deprived foals and also Allen GP, Bryans JT, Pandey R 1986 Molecular epizootiology,
diminished in foals aged > 2 months compared to those pathogenesis, and prophylaxis of equine herpesvirus-1
aged 48 hours. Clinical signs had largely resolved, even in infections. Veterinary microbiology molecular and clini-
colostrum-deprived animals, within 10 days (McChesney cal perspectives. Progress in Veterinary Microbiology and
et al 1974). Immunology 2: 78–144
Allen G, Yeargan M, Costa LR et al 1995 Major histocom-
Different serological surveys have demonstrated that patibility complex class I-restricted cytotoxic T-lymphocyte
antibodies to equine adenovirus-1 are common in many responses in horses infected with equine herpesvirus 1.
horse populations, often being close to 100% (Studdert Journal of Virology 69: 606–612
Allen GP, Kydd JH, Slater JD et al 1999 Advances in under- Burrell MH, Wood JL, Whitwell KE et al 1996 Respiratory
standing of the pathogenesis, epidemiology and immu- disease in thoroughbred horses in training: the relation-
nological control of equine herpesvirus abortion. In: ships between disease and viruses, bacteria and environ-
Proceedings of the Eighth International Conference on ment. Veterinary Record 139: 308–313
Equine Infectious Diseases, Dubai. R&W Publications Ltd, Burrows R 1979 Equine rhinovirus and adenovirus infec-
Newmarket UK tions. In: Proceedings of the 24th Annual Convention
Anon. 1997 African horse sickness. Conclusions and recom- of the American Association of Equine Practitioners.
mendations of a scientific meeting. Bulletin of the Office St. Louis, MI, pp.299–306
of International Epizootics 4: 406–411 Burrows R, Goodridge D, Denyer M S 1984a Trials of an
Balasuriya UB, Timoney PJ, McCollum WH et al 1995 inactivated equid herpesvirus I vaccine: challenge with a
Phylogenetic analysis of open reading frame 5 of field subtype 1 virus. Veterinary Record 114: 369–374
isolates of equine arteritis virus and identification of Burrows R, Goodridge D, Wittmann G 1984b Studies of
conserved and nonconserved regions in the GL envelope persistent and latent equid herpesvirus 1 and herpesvirus
glycoprotein. Virology 214: 690–697 3 infections in the Pirbright pony herd. In: Gaskell RM,
Balasuriya UB, Patton JF, Rossitto PV et al 1997 Neutralization Rziha HJ (editors) Latent Herpesvirus Infections in
determinants of laboratory strains and field isolates of Veterinary Medicine. Series: Current Topics in Veterinary
equine arteritis virus: identification of four neutralization Medicine and Animal Science, vol 27. Martinus Nijhoff,
sites in the amino-terminal ectodomain of the G(L) Dordrecht, pp.307–319
envelope glycoprotein. Virology 232: 114–128 Capela R, Purse BV, Pena I et al 2003 Spatial distribution of
Barnard BJ, Paweska JT 1993 Prevalence of antibodies against Culicoides species in Portugal in relation to the trans-
some equine viruses in zebra (Zebra burchelli) in the mission of African horse sickness and bluetongue viruses.
Kruger National Park, 1991–1992. Onderstepoort Journal Medical and Veterinary Entomology 17: 165–177
of Veterinary Research 60: 175–179 Caracappa S, Torina A, Guercio A et al 2003 Identification of
Baylis M, El Hasnaoui H, Bouayoune H et al 1997 The spatial a novel bluetongue virus vector species of Culicoides in
and seasonal distribution of AHS and its potential Sicily. Veterinary Record 153: 71–74
Culicoides vectors in Morocco. Medical and Veterinary Castillo-Olivares J, de Vries AA, Raamsman MJ et al 2001
Entomology 11: 203–211 Evaluation of a prototype sub-unit vaccine against
Baylis M, Bouayoune H, Touti J et al 1998a Use of climatic equine arteritis virus comprising the entire ectodomain of
data and satellite imagery to model the abundance of the virus large envelope glycoprotein (G(L)): induction of
Culicoides imicola, the vector of African horse sickness virus-neutralizing antibody and assessment of protection
virus, in Morocco. Medical and Veterinary Entomology in ponies. Journal of General Virology 82: 2425–2435
12: 255–266 Castillo-Olivares J, Tearle, JP, Montesso F et al 2003a. Detec-
Baylis M, Touti J, Bouayoune H et al 1998b Studies of the tion of equine arteritis virus (EAV)-specific cytotoxic
mortality rate of Culicoides imicola in Morocco. Archives CD8+ T lymphocyte precursors from EAV-infected ponies.
of Virology (Supplement) 14: 127–136 Journal of General Virology 84: 2745–2753
Baylis M, Wittman EJ, Mellor PS et al 2001 Prediction of areas Castillo-Olivares J, Wieringa R, Bakonyi T et al 2003b Genera-
around the Mediterranean at risk of bluetongue by tion of a candidate live marker vaccine for equine
modelling the distribution of its vector using satellite arteritis virus by deletion of the major virus neutraliza-
imaging. Veterinary Record 149: 639–643 tion domain. Journal of Virology 77: 8470–8480
Beech J 1975 Cytology of tracheobronchial aspirates in Chambers,TM, Holland RE, Tudor LR et al 2001 A new modi-
horses. Veterinary Pathology 12: 157–164 fied live equine influenza virus vaccine: phenotypic sta-
Blunden AS, Smith KC, Binns MM et al 1995 Replication of bility, restricted spread and efficacy against heterologous
equid herpesvirus 4 in endothelial cells and synovia of a virus challenge. Equine Veterinary Journal 33: 630–636
field case of viral pneumonia and synovitis in a foal. Chirnside ED, de Vries AA, Mumford JA et al 1995 Equine
Journal of Comparative Pathology 112: 133–140 arteritis virus-neutralizing antibody in the horse is
Borchers K, Wolfinger U, Lawrenz B et al 1997 Equine induced by a determinant on the large envelope glyco-
herpesvirus 4 DNA in trigeminal ganglia of naturally protein GL. Journal of General Virology 76: 1989–1998
infected horses detected by direct in situ PCR. Journal of Christley RM, Hodgson DR, Rose RJ et al 2001 A case–control
General Virology 78: 1109–1114 study of respiratory disease in Thoroughbred race-
Breathnach CC, Yeargan MR, Sheoran AS et al 2001 The horses in Sydney, Australia. Equine Veterinary Journal
mucosal humoral immune response of the horse to infec- 33: 256–264
tive challenge and vaccination with equine herpesvirus-1 Coetzer JAW, Erasmus B 1994 African horse sickness.
antigens. Equine Veterinary Journal 33: 651–657 In: Coetzer JAW, Thompson GR, Tutsin RC (editors)
Browning GF, Ficorilli N, Studdert MJ 1988 Asinine herpes- Infectious Diseases of Livestock, with Special Reference
virus genomes: comparison with those of the equine to Southern Africa. Oxford University Press, Oxford,
herpesviruses. Archives of Virology 101: 183–190 pp.460–475
Bryans JT, Allen GP 1982 Application of a chemically Coignoul FL, Bertram TA Cheville NF 1984a Pathogenicity of
inactivated, adjuvanted vaccine to control of abortigenic equine herpesvirus 1 subtype 2 for foals and adult pony
infection of mares by equine herpesvirus 1. Develop- mares. Veterinary Microbiology 9: 533–542
ments in Biological Standardization 52: 493–498 Coignoul FL, Cheville NF 1984b Pathology of maternal genital
Bryans JT, Crowe ME, Doll ER et al 1957 Isolation of a tract, placenta, and fetus in equine viral arteritis.
filterable agent causing arteritis of horses and abortion Veterinary Pathology 21: 333–340
by mares; its differentiation from the equine abortion Collinson PN, O’Rielly J, Ficorilli N et al 1994 Isolation of
(influenza) virus. Cornell Veterinarian 47: 3–41 equine herpesvirus type 2 (equine gammaherpesvirus 2)
from foals with keratoconjunctivitis. Journal of the Dutta SK 1975 Isolation and characterization of an adeno-
American Veterinary Medical Association 205: 329–331 virus and isolation of its adenovirus-associated virus in
Cook RF, Sinclair R, Mumford JA 1988 Detection of influenza cell culture from foals with respiratory tract disease.
nucleoprotein antigen in nasal secretions from horses American Journal of Veterinary Research 36: 247–250
infected with A/equine influenza (H3N8) viruses. Journal Dutta SK, Shipley WD 1975 Immunity and the level of
of Virological Methods 20: 1–12 neutralization antibodies in foals and mares vaccinated
Crabb BS, Studdert MJ 1995 Equine herpesvirus 4 (equine with a modified live-virus rhinopneumonitis vaccine.
rhinopneumonitis virus) and 1 (equine abortion virus). American Journal of Veterinary Research 36: 445–448
Advances in Virus Research 45: 153–190 Edington N 1992 Latency of equine herpesviruses. In:
Crawford PC, Dubovi EJ, Castleman WL et al 2005 Transmission Proceedings of the Sixth International Conference on
of equine influenza virus to dogs. Science 310: 482–485 Equine Infectious Diseases, Cambridge. R&W Publica-
Cullinane A, Weld J, Osborne M et al 2001 Field studies on tions, Newmarket, pp.195–200
equine influenza vaccination regimes in thoroughbred Edington N, Wright JA, Patel JR et al 1984 Equine adeno-
foals and yearlings. Veterinary Journal 161: 174–185 virus 1 isolated from cauda equina neuritis. Research in
Daly JM, Lai ACK, Binns MM et al 1996 Antigenic and genetic Veterinary Science 37: 252–254
evolution of equine H3N8 influenza A viruses. Journal of Edington N, Bridges CG, Patel JR 1986 Endothelial cell infection
General Virology 77: 661–671 and thrombosis in paralysis caused by equid herpesvirus-
Daly JM, Yates RJ, Browse G et al 2003 Comparison of 1: equine stroke. Archives of Virology 90: 111–124
hamster and pony challenge models for evaluation of Edington N, Bridges CG, Griffiths L 1989 Equine interferons
effect of antigenic drift on cross protection afforded following exposure to equid herpesvirus-1 or -4. Journal
by equine influenza vaccines. Equine Veterinary Journal of Interferon Research 9: 389–392
35: 458–462 Edington N, Welch HM, Griffiths L 1994 The prevalence of
Daly JM, Yates PJ, Newton JR et al 2004 Evidence supporting latent Equid herpesviruses in the tissues of 40 abattoir
the inclusion of strains from each of the two co- horses. Equine Veterinary Journal 26: 140–142
circulating lineages of H3N8 equine influenza virus in Edwards S, Castillo-Olivares J, Cullinane A et al 1999
vaccines. Vaccine 22: 4101–4109 International harmonisation of laboratory diagnostic
Daly JM, Whitwell KE, Miller J et al 2006 Investigation of tests for equine viral arteritis. In: Proceedings of the
equine influenza cases exhibiting neurological disease: Eighth International Conference on Equine Infec-
coincidence on association. Journal of Comparative tious Diseases, Dubai. R&W Publications, Newmarket,
Pathology (in press) pp.359–362
de la Rua-Domenech R, Reid SW, Gonzalez-Zariquiey AE et al el Hasnaoui H, el Harrak M, Zientara S et al 1998 Serological
1999 Modelling the spread of a viral infection in equine and virological responses in mules and donkeys following
populations managed in Thoroughbred racehorse train- inoculation with African horse sickness virus serotype 4.
ing yards. Preventative Veterinary Medicine 47: 61–77 Archives of Virology (Supplement) 14: 29–36
de Vries AA, Chirnside ED, Horzinek MC et al 1992 Structural Foote CE, Love DN, Gilkerson JR et al 2004 Detection of EHV-1
proteins of equine arteritis virus. Journal of Virology and EHV-4 DNA in unweaned Thoroughbred foals from
66: 6294–6303 vaccinated mares on a large stud farm. Equine Veterinary
Del Piero F 2000 Equine viral arteritis. Veterinary Pathology Journal 36: 341–345
37: 287–296 Fortier G, Vidament M, DeCraene F et al 2002 The effect of
Del Piero F, Wilkins PA, Lopez JW et al 1997 Equine viral GnRH antagonist on testosterone secretion, spermato-
arteritis in newborn foals: clinical, pathological, sero- genesis and viral excretion in EVA-virus excreting
logical, microbiological and immunohistochemical obser- stallions. Equine reproduction VIII. In: Proceedings of the
vations. Equine Veterinary Journal 29: 178–185 Eighth International Symposium on Equine Reproduction
Dimock WW, Edwards PR 1936 The differential diagnosis of Theriogenology 58. Elsevier, New York, pp.425–427
equine abortion with reference to a hitherto unknown Fukunaga Y 1994 Equine viral arteritis: diagnostic and
form of epizootic abortion in mares. Cornell Veterinarian control measures. Journal of Equine Science 5: 101–114
26: 231–240 Fukunaga Y, Wada R, Hirasawa K et al 1982 Effect of
Ditchfield J, Zbitnew A, MacPherson LW 1963 Association of the modified Bucyrus strain of equine arteritis virus
Myxovirus Para-Influenzae 3 (RE 55) with upper respira- experimentally inoculated into horses. Bulletin of Equine
tory infection of horses. Canadian Veterinary Journal Research Institute, Japan 19: 97–101
4: 175–180 Fukunaga Y, Kumanimodo T, Kamada M et al 1983 Equine
Doll ER, Bryans JT 1962 Incubation periods for abortion in picornavirus: isolation of virus from the oral cavity of
equine viral rhinopneumonitis. Journal of Biochemistry healthy horses. Bulletin of the Equine Research Institute
(Tokyo) 140: 351–354 20: 103–109
Doll ER, Bryans JT 1963 A planned infection program for Fukunaga Y, Wada R, Kanemaru T et al 1996 Immune
immunizing mares against viral rhinopneumonitis. potency of lyophilized, killed vaccine for equine viral
Cornell Veterinarian 53: 249–262 arteritis and its protection against abortion in pregnant
Doll ER, Bryans JT, Wilson JC et al 1968 Immunization against mares. Journal of Equine Veterinary Science 16: 217–221
equine viral arteritis using modified live virus propagated Fukunaga Y, Wada R, Imagawa H et al 1997 Venereal
in cell cultures of rabbit kidney. Cornell Veterinarian infection of mares by equine arteritis virus and use
48: 497–524 of killed vaccine against the infection. Journal of
Dunowska M, Wilks CR, Studdert MJ et al 2002 Equine Comparative Pathology 117: 201–208
respiratory viruses in foals in New Zealand. New Zealand Gerber H 1970 Clinical features, sequelae and epidemiology
Veterinary Journal 50: 140–147 of equine influenza. In: Proceedings of the Second
International Conference on Equine Infectious Diseases. Hedges JF, Balasuriya UB, MacLachlan NJ 1999 The open
Karger AG, Basel, pp.63–80 reading frame 3 of equine arteritis virus encodes an
Gibson JS, Slater JD, Awan AR et al 1992 Pathogenesis of immunogenic glycosylated, integral membrane protein.
equine herpesvirus-1 in specific pathogen-free foals: Virology 264: 92–98
primary and secondary infections and reactivation. Heldens JG, Hannant D, Cullinane AA et al 2001 Clinical and
Archives of Virology 123: 351–366 virological evaluation of the efficacy of an inactivated
Glass K, Wood JL, Mumford JA et al 2002 Modelling equine EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4).
influenza 1: a stochastic model of within-yard epidemics. Vaccination/challenge experiments in foals and pregnant
Epidemiology and Infection 128: 491–502 mares. Vaccine 19: 4307–4317
Gleeson LJ, Studdert MJ, Sullivan ND 1978 Pathogenicity and Hinton TM, Crabb BS 2001 The novel picornavirus Equine
immunologic studies of equine adenovirus in specific- rhinitis B virus contains a strong type II internal
pathogen-free foals. American Journal of Veterinary ribosomal entry site which functions similarly to that of
Research 39: 1636–1642 Encephalomyocarditis virus. Journal of General Virology
Gomez-Villamandos JC, Sanchez C, Carrasco L et al 1999 82: 2257–2269
Pathogenesis of African horse sickness: ultrastructural Hoffman AM, Viel L, Prescott JF et al 1993 Association of
study of the capillaries in experimental infection. Journal microbiologic flora with clinical, endoscopic, and pul-
of Comparative Pathology 121: 101–116 monary cytologic findings in foals with distal respiratory
Gross DK, Hinchcliff KW, French PS et al 1998 Effect of tract infection. American Journal of Veterinary Research
moderate exercise on the severity of clinical signs asso- 54: 615–1622
ciated with influenza virus infection in horses. Equine Holmes DF, Kemen MJ, Coggins L 1978 Equine rhinovirus
Veterinary Journal 30: 489–497 infection – serological evidence of infection in selected
Gross DK, Morley PS, Hinchcliff KW et al 2004 Pulmonary United States horse populations. In: Proceedings of the
ultrasonographic abnormalities associated with naturally Fourth International Conference on Equine Infectious
occurring equine influenza virus infection in standard- Diseases, Lyon. Veterinary Publications, Princeton, NJ,
bred racehorses. Journal of Veterinary Internal Medicine pp.315–319
18: 718–727 Holyoak GR, Little TV, McCollam WH et al 1993 Relationship
Guillaume V, Lefeuvre A, Faure C et al 2004 Specific detection between onset of puberty and establishment of persistent
of Nipah virus using real-time RT-PCR (TaqMan). Journal infection with equine arteritis virus in the experimentally
of Virological Methods 120: 229–237 infected colt. Journal of Comparative Pathology 109: 29–46
Guthrie AJ, Stevens KB, Bosman PP 1999 The circumstances Hooper P, Zaki S, Daniels P et al 2001 Comparative pathology
surrounding the outbreak and spread of equine influenza of the diseases caused by Hendra and Nipah viruses.
in South Africa. Review of Science and Technology Microbes and Infection 3: 315–322
18: 179–185 House C, Mikiciuk PE, Berninger ML 1990 Laboratory diag-
Halpin K, Young PL, Field HE et al 2000 Isolation of Hendra nosis of African horse sickness: comparison of serological
virus from pteropid bats: a natural reservoir of Hendra techniques and evaluation of storage methods of samples
virus. Journal of General Virology 81: 1927–1932 for virus isolation. Journal of Veterinary Diagnostic
Hamblin C, Graham SD, Anderson EC et al 1990 A competitive Investigation 2: 44–50
ELISA for the detection of group-specific antibodies to Howell PG 1962 The isolation and identification of further
African horse sickness virus. Epidemiology and Infection antigenic types of African horsesickness virus. Onder-
104: 303–312 stepoort Journal of Veterinary Research 29: 139–149
Hamblin C, Mellor PS, Boned J 1991a The use of ELISA for the Howell PG, Groenewald D, Visage CW et al 2002 The classi-
detection of African horse sickness viruses in Culicoides fication of seven serotypes of equine encephalosis virus
midges. Journal of Virological Methods 34: 221–225 and the prevalence of homologous antibody in horses in
Hamblin C, Mellor PS, Graham SD et al 1991b Antibodies South Africa. Onderstepoort Journal of Veterinary Research
in horses, mules and donkeys following monovalent 69: 79–93
vaccination against African horse sickness. Epidemiology Huang JA, Ficorilli N, Hartley CA et al 2001 Equine rhinitis B
and Infection 106: 365–371 virus: a new serotype. Journal of General Virology
Hamblin C, Mertens PP, Mellor PS et al 1991c A serogroup 82: 2641–2645
specific enzyme-linked immunosorbent assay for the Johnson B, Baldwin C, Timoney P et al 1991 Arteritis in
detection and identification of African horse sickness equine fetuses aborted due to equine viral arteritis.
viruses. Journal of Virological Methods 31: 285–292 Veterinary Pathology 28: 248–250
Hamblin C, Salt JS, Mellor PS et al 1998 Donkeys as reservoirs Klaey M, Sanchez-Higgins M, Leadon DP et al 1998 Field case
of African horse sickness virus. Archives of Virology study of equine rhinovirus 1 infection: clinical signs and
(Supplement) 14: 37–47 clinicopathology. Equine Veterinary Journal 30: 267–269
Hannant D, Mumford JA, Jessett DM 1988 Duration of Kleiboeker SB, Schommer SK, Johnson PJ et al 2002 Asso-
circulating antibody and immunity following infec- ciation of two newly recognized herpesviruses with
tion with equine influenza virus. Veterinary Record interstitial pneumonia in donkeys (Equus asinus). Journal
122: 125–128 of Veterinary Diagnostic Investigation 14: 273–280
Hannant D, O’Neil T, Jessett DM et al 1991 Evidence for non- Konishi SI, Harasawa R, Mochizuki M et al 1977 Studies on
specific immunosuppression during the development equine adenovirus. I. Characteristics of an adenovirus
of immune responses to equid herpesvirus-1. Equine isolated from a thoroughbred colt with pneumonia.
Veterinary Journal Supplement 12: 41–45 Nippon Juigaku Zasshi 39: 117–125
Hannant D, Mumford JA 1996 Equine influenza. In: Studdert Kumar S, Tamura K, Jakobsen IB, Nei M 2001 MEGA2:
MJ (ed.) Virus Infections of Equines. Elsevier, Amsterdam, molecular evolutionary genetics analysis software.
pp.285–293 Bioinformatics 17: 1244–1245
Kydd JH, Smith KC, Hannant D et al 1994a Distribution infections among horse populations. Journal of Veterinary
of equid herpesvirus-1 (EHV-1) in respiratory tract Medical Science 54: 207–211
associated lymphoid tissue: implications for cellular Mayr A, Pette J 1968 1st experiments concerning the vacci-
immunity. Equine Veterinary Journal 26: 470–473 nation of horses against rhino-pneumonia (viral abortion
Kydd JH, Smith KC, Hannant D et al 1994b Distribution of of mares) with a live vaccine from cell cultures. Bulletin
equid herpesvirus-1 (EHV-1) in the respiratory tract of of the Office of International Epizootics 70: 133–140
ponies: implications for vaccination strategies. Equine McChesney AE, England JJ, Whiteman CE et al 1974 Experi-
Veterinary Journal 26: 466–469 mental transmission of equine adenovirus in Arabian
Kydd JH, Wattrang E, Hannant D 2003 Pre-infection frequen- and non-Arabian foals. American Journal of Veterinary
cies of equine herpesvirus-1 specific, cytotoxic T lympho- Research 35: 1015–1023
cytes correlate with protection against abortion following McCollum WH 1969 Development of a modified virus strain
experimental infection of pregnant mares. Veterinary and vaccine for equine viral arteritis. Journal of the
Immunology and Immunopathology 96: 207–217 American Veterinary Medical Association 155: 318–322
Lai AC, Chambers TM, Holland RE et al 2001 Diverged McCollum WH 1976 Studies of passive immunity in foals to
evolution of recent equine-2 influenza (H3N8) viruses equine viral arteritis. Veterinary Microbiology 1: 45–54
in the Western Hemisphere. Archives of Virology McCollum WH 1986 Responses of horses vaccinated with
146: 1063–1074 avirulent modified-live equine arteritis virus propagated
Li F, Drummer HE, Ficorilli N et al 1997 Identification of in the E. Derm (NBL-6) cell line to nasal inoculation with
noncytopathic equine rhinovirus 1 as a cause of acute virulent virus. American Journal of Veterinary Research
febrile respiratory disease in horses. Journal of Clinical 47: 1931–1934
Microbiology 35: 937–943 McCollum WH, Timoney PJ 1992 Studies on the seropreva-
Livesay GJ, O’Neill T, Hannant D et al 1993 The outbreak of lence and frequency of equine rhinovirus-I and -II infec-
equine influenza (H3N8) in the United Kingdom in 1989: tion in normal horse urine. In: Proceedings of the Sixth
diagnostic use of an antigen capture ELISA. Veterinary International Conference on Equine Infectious Diseases,
Record 133: 515–519 Cambridge. R&W Publications, Newmarket, pp.83–87
Lord CC, Woolhouse ME, Rawlings P et al 1996 Simulation McCollum WH, Prickett ME, Bryans JT 1971 Temporal
studies of African horse sickness and Culicoides imicola distribution of equine arteritis virus in respiratory
(Diptera: Ceratopogonidae). Journal of Medical Entomology mucosa, tissues and body fluids of horses infected by
33: 328–338 inhalation. Research in Veterinary Science 12: 459–464
Lord CC, Woolhouse ME, Barnard BJ 1997a Transmission and McCollum WH, Little TV, Timoney PJ et al 1994 Resistance
distribution of virus serotypes: African horse sickness in of castrated male horses to attempted establishment of
zebra. Epidemiology and Infection 118: 43–50 the carrier state with equine arteritis virus. Journal
Lord CC, Woolhouse ME, Mellor PS 1997b Simulation studies of Comparative Pathology 111: 383–388
of vaccination strategies in African horse sickness. Meiswinkel R, Paweska JT 2003 Evidence for a new field
Vaccine 15: 519–524 Culicoides vector of African horse sickness in South
Lord CC, Woolhouse ME, Barnard BJ 1998 Transmission and Africa. Preventative Veterinary Medicine 60: 243–253
distribution of African horse sickness virus serotypes in Mellor PS, Boorman J 1995 The transmission and geograph-
South African zebra. Archives of Virology (Supplement) ical spread of African horse sickness and bluetongue
14: 21–28 viruses. Annals of Tropical Medicine and Parasitology
Lord CC, Venter GJ, Mellor PS et al 2002 Transmission patterns 89: 1–15
of African horse sickness and equine encephalosis Mellor PS, Wittmann EJ 2002 Bluetongue virus in the
viruses in South African donkeys. Epidemiology and Mediterranean Basin 1998–2001. Veterinary Journal
Infection 128: 265–275 164: 20–37
Lubroth J 1988. African horse sickness and the epizootic in Mellor PS, Hamblin C 2004 African horse sickness. Veterinary
Spain 1987. Equine Practice 10: 26–33 Research 35: 445–466
Lunn DP, Holmes MA, Gibson J et al 1991 Haematological Mellor PS, Hamblin C, Graham SD 1990 African horse sickness
changes and equine lymphocyte subpopulation kinetics in Saudi Arabia. Veterinary Record 127: 41–42
during primary infection and attempted re-infection Mellor PS, Rawlings P, Baylis M et al 1998 Effect of tempera-
of specific pathogen free foals with EHV-1. Equine ture on African horse sickness virus infection in Culicoides.
Veterinary Journal 23: 35–40 Archives of Virology (Supplement) 14: 155–163
Lunn DP, Hussey S, Sebing R et al 2001 Safety, efficacy, and Moore BD, Balasuriya UB, Hedges JF et al 2002 Growth
immunogenicity of a modified-live equine influenza virus characteristics of a highly virulent, a moderately virulent,
vaccine in ponies after induction of exercise-induced and an avirulent strain of equine arteritis virus in
immunosuppression. Journal of the American Veterinary primary equine endothelial cells are predictive of their
Medical Association 218: 900–906 virulence to horses. Virology 298: 39–44
Mackenzie JS, Field HE, Guyatt KJ 2003 Managing emerging Moore BD, Balasuriya UB, Watson JL et al 2003 Virulent and
diseases borne by fruit bats (flying foxes), with particular avirulent strains of equine arteritis virus induce different
reference to henipaviruses and Australian bat lyssavirus. quantities of TNF-alpha and other proinflammatory cyto-
Journal of Applied Microbiology 94 Suppl: 59S–69S kines in alveolar and blood-derived equine macrophages.
MacLachlan NJ, Balasuriya UB, Hedges JF et al 1998 Sero- Virology 314: 662–670
logic response of horses to the structural proteins of Morley PS, Hanson LK, Bogdan JR et al 1995 The relationship
equine arteritis virus. Journal of Veterinary Diagnostic between single radial hemolysis, hemagglutination
Investigation 10: 229–236 inhibition, and virus neutralization assays used to detect
Matsumura T, Sugiura T, Imagawa H et al 1992 Epizootio- antibodies specific for equine influenza viruses. Veterinary
logical aspects of type 1 and type 4 equine herpesvirus Microbiology 45: 81–92
Morley PS, Townsend HG, Bogdan JR et al 1999 Efficacy of a Newton JR, Wood JL, Chanter N 2003 A case control study of
commercial vaccine for preventing disease caused by factors and infections associated with clinically apparent
influenza virus infection in horses. Journal of the respiratory disease in UK Thoroughbred racehorses.
American Veterinary Medical Association 215: 61–66 Preventative Veterinary Medicine 60: 107–132
Mumford JA 1994 Equine rhinovirus infections. In: Coetzer Newton JR, Geraghty RJ, Castillo-Olivares J et al 2004
JAW, Thomson GR, Tustin RC, Kriek NPJ (editors) Evidence that use of an inactivated equine herpes-
Infectious Diseases of Livestock with Special Reference virus vaccine induces serum cytotoxicity affecting
to South Africa. Oxford University Press, Oxford, vol. II, the equine arteritis virus neutralisation test. Vaccine
pp.820–822 22: 4117–4123
Mumford JA 1999 The equine influenza surveillance program. Nordengrahn A, Rusvai M, Merza M et al 1996 Equine
Advances in Veterinary Medicine 41: 379–387 herpesvirus type 2 (EHV-2) as a predisposing factor
Mumford JA, Thomson GR 1978 Studies on picornaviruses for Rhodococcus equi pneumonia in foals: prevention of
isolated from the respiratory tract of horses. In: Pro- the bifactorial disease with EHV-2 immunostimulating
ceedings of the Fourth International Conference on complexes. Veterinary Microbiology 51: 55–68
Equine Infectious Diseases, Lyon. Veterinary Publications, Nugent J, Sinclair R, deVries AA et al 2000 Development and
Princeton, NJ, pp.419–429 evaluation of ELISA procedures to detect antibodies against
Mumford JA, Wood J 1992 Establishing an acceptability the major envelope protein (G(L)) of equine arteritis
threshold for equine influenza vaccines. Developments in virus. Journal of Virological Methods 90: 167–183
Biological Standardization 79: 137–146 Ostlund EN 1993 The equine herpesviruses. Veterinary Clinics
Mumford JA, Wood JM, Folkers C et al 1988 Protection against of North American; Equine Practice 9: 283–294
experimental infection with influenza virus A/equine/ Park AW, Wood JL, Newton JR et al 2003 Optimising vaccina-
Miami/63 (H3N8) provided by inactivated whole virus tion strategies in equine influenza. Vaccine 21: 2862–2870
vaccines containing homologous virus. Epidemiology and Park AW, Wood JL, Daly JM et al 2004 The effects of strain
Infection 100: 501–510 heterology on the epidemiology of equine influenza
Mumford JA, Jessett DM, Rollinson EA et al 1994a. Duration of in a vaccinated population. Proceedings of the Royal
protective efficacy of equine influenza immunosti- Society of London. Series B, Biological Sciences 271:
mulating complex/tetanus vaccines. Veterinary Record 1547–1555
134: 158–162 Pascoe RR, Harden TJ, Spradbrow PB 1974 Letter: Experi-
Mumford JA, Wilson H, Hannant D et al 1994b Antigenicity mental infection of a horse with an equine adenovirus.
and immunogenicity of equine influenza vaccines con- Australian Veterinary Journal 50: 278–279
taining a Carbomer adjuvant. Epidemiology and Infection Paweska JT, Venter GJ, Mellor PS 2002 Vector competence of
112: 421–437 South African Culicoides species for bluetongue virus
Mumford JA, Wood J, Jessett DM et al 1994c Efficacy of H3N8 serotype 1 (BTV-1) with special reference to the effect of
influenza vaccines prepared from virus cultured in eggs temperature on the rate of virus replication in C. imicola
or mammalian cells. In: Equine infectious diseases VII: and C. bolitinos. Medical and Veterinary Entomology
Proceedings of the Seventh International Conference, 16: 10–21
Tokyo. R&W Publications, Newmarket, pp.342–343 Perryman LE, McGuire TC, Crawford TB 1978 Maintenance
Murray K, Selleck P, Hooper P et al 1995 A morbillivirus of foals with combined immunodeficiency: causes and
that caused fatal disease in horses and humans. Science control of secondary infections. American Journal of
268: 94–97 Veterinary Research 39: 1043–1047
Murray K, Dunn K, Murray G 1998 Hendra virus (equine Plummer G 1962 An equine respiratory virus with entero-
morbillivirus): the outbreaks, the disease and lessons for virus properties. Nature 195: 519–520
preparedness. In: Proceedings of the Eighth International Plummer G, Kerry JB 1962 Studies on an equine respiratory
Conference on Equine Infectious Diseases, Dubai. R&W virus. Veterinary Record 74: 967–970
Publications, Newmarket, pp.3–10 Powell DG, Burrows, R, Goodridge D 1974 Respiratory viral
Murray MJ, Eichorn ES, Dubovi EJ et al 1996 Equine herpes- infections among thoroughbred horses in training during
virus type 2: prevalence and seroepidemiology in foals. 1972. Equine Veterinary Journal 6: 19–24
Equine Veterinary Journal 28: 432–436 Prickett ME 1970 The pathology of disease caused by
Murray MJ, del Piero F, Jeffrey SC et al 1998 Neonatal equine equine herpesvirus-1. Proceedings of the Second Interna-
herpesvirus type 1 infection on a thoroughbred breeding tional Conference on Equine Infectious Diseases. Karger,
farm. Journal of Veterinary Internal Medicine 12: 36–41 Basel
Naib ZM, Stewart JA, Dowdle WR et al 1968 Cytological Purse BV, Mellor PS, Rogers DJ et al 2005 Climate change and
features of viral respiratory tract infections. Acta Cytologica the recent emergence of bluetongue in Europe. National
12: 162–171 Review of Microbiology 3: 71–181
Newton JR, Verheyen, K, Wood JL et al 1999 Equine influenza Rawlings P, Pro MJ, Pena I et al 1997 Spatial and seasonal
in the United Kingdom in 1998. Veterinary Record 145: distribution of Culicoides imicola in Iberia in relation to
449–452 the transmission of African horse sickness virus. Medical
Newton JR, Lakhani KH, Wood JL et al 2000a Risk factors for and Veterinary Entomology 11: 49–57
equine influenza serum antibody titres in young Rees WA, Harkins JD, Woods WE et al 1997 Amantadine and
thoroughbred racehorses given an inactivated vaccine. equine influenza: pharmacology, pharmacokinetics and
Preventive Veterinary Medicine 46: 129–141 neurological effects in the horse. Equine Veterinary
Newton JR, Townsend HG, Wood JL et al 2000b Immunity to Journal 29: 104–110
equine influenza: relationship of vaccine-induced anti- Rees WA, Harkins JD, Lu M et al 1999 Pharmacokinetics and
body in young Thoroughbred racehorses to protection therapeutic efficacy of rimantadine in horses experi-
against field infection with influenza A/equine-2 viruses mentally infected with influenza virus A2. American
(H3N8). Equine Veterinary Journal 32: 65–74 Journal of Veterinary Research 60:888–894
Rodriguez JJ, Horvath CM 2004 Host evasion by emerg- Telford EAR, Watson MS, McBride K et al 1992 The DNA
ing paramyxoviruses: Hendra virus and Nipah virus v sequence of equine herpesvirus-1. Virology 189: 304–316
proteins inhibit interferon signalling. Viral Immunology Telford EAR, Watson MS, Perry, J et al 1998 The DNA
17: 210–219 sequence of equine herpesvirus-4. Journal of General
Roizmann B, Desrosiers RC, Fleckenstein B et al 1992 The Virology 79: 1197–1203
family Herpesviridae: an update. The Herpesvirus Study The Royal Society 2002 Infectious Diseases of Livestock. Royal
Group of the International Committee on Taxonomy of Society, London
Viruses. Archives of Virology 123: 425–449 Thompson DB, Spradborw PB, Studdert M 1976 Isolation of
Sailleau C, Moulay S, Cruciere C et al 1997 Detection of an adenovirus from an Arab foal with a combined
African horse sickness virus in the blood of experi- immunodeficiency disease. Australian Veterinary Journal
mentally infected horses: comparison of virus isola- 52: 435–437
tion and a PCR assay. Research in Veterinary Science Thomson GR, Mumford JA, Campbell J et al 1976 Serological
62: 229–232 detection of equid herpesvirus 1 infections of the
Sailleau C, Hamblin C, Paweska JT et al 2000 Identification respiratory tract. Equine Veterinary Journal 8: 58–65
and differentiation of the nine African horse sickness Timoney PJ 2000 Equine viral arteritis. In: Manual of
virus serotypes by RT-PCR amplification of the serotype- Standards for Diagnostic Tests and Vaccines. Lists A and
specific genome segment 2. Journal of General Virology B Diseases of Mammals, Birds and Bees. Office Interna-
81: 831–837 tional des Epizooties, Paris, pp.582–594
Scott JC, Dutta SK, Myrup AC 1983 In vivo harboring of Timoney PJ, McCollum WH 1988 Equine viral arteritis –
equine herpesvirus-1 in leukocyte populations and sub- epidemiology and control. Journal of Equine Veterinary
populations and their quantitation from experimentally Science 8: 54–59
infected ponies. American Journal of Veterinary Research Timoney PJ, McCollum WH 1991 Equine viral arteritis:
44: 1344–1348 current clinical and economic significance. In: Proceed-
Selvey LA, Wells RM, McCormack JG et al 1995 Infection of ings of the thirty-sixth annual convention of the American
humans and horses by a newly described morbillivirus. Association of Equine Practitioners, Lexington, KY
Medical Journal of Australia 162: 642–645 Timoney PJ, McCollom WH 1993 Equine viral arteritis in
Senne DA, Pearson JE, Carbrey EA 1985 Equine viral arteritis: perspective in relation to international trade. Journal of
a standard procedure for the virus neutralization test and Equine Veterinary Science 13: 50–52
comparison of results of a proficiency test performed at Timoney PJ, McCollum WH 2000 Equine viral arteritis:
five laboratories. In: Proceedings of the United States further characterisation of the carrier state in stallions.
Animal Health Association 89: 29–34 Journal of Reproduction and Fertility Supplement
Sharma PC, Cullinane AA, Onions DE et al 1992 Diagnosis of 56: 3–11
equid herpesviruses -1 and -4 by polymerase chain Timoney PJ, McCollum WH, Murphy TW et al 1987 The
reaction. Equine Veterinary Journal 24: 20–25 carrier state in equine arteritis virus infection in the
Shortridge KF, Chan WH, Guan Y 1995 Epidemiology of the stallion with specific emphasis on the venereal mode of
equine influenza outbreak in China, 1993–94. Veterinary virus transmission. Journal of Reproduction and Fertility
Record 136: 160–161 Supplement 35: 95–102z
Slater JD, Borchers K, Thackray AM et al 1994 The trigeminal Timoney PJ, McCollum WH, Roberts AW 1988 Current strate-
ganglion is a location for equine herpesvirus 1 latency gies for the control of equine viral arteritis. Proceedings of
and reactivation in the horse. Journal of General the United States Animal Health Association 92: 211–218
Virology 75: 2007–2016 Timoney PJ, McCollum WH, Roberts AW et al 1986 Demon-
Smith KC, Blunden AS, Whitwell KE et al 2003 A survey of stration of the carrier state in naturally acquired equine
equine abortion, stillbirth and neonatal death in the arteritis virus infection in the stallion. Research in
UK from 1988 to 1997. Equine Veterinary Journal Veterinary Science 41: 279–280
35: 496–501 Townsend HG, Penner SJ, Watts TC et al 2001 Efficacy of
Steck F, Hofer B, Schaeren B et al 1978 Equine rhinoviruses: a cold-adapted, intranasal, equine influenza vaccine:
new serotypes. In: Proceedings of the Fourth Interna- challenge trials. Equine Veterinary Journal 33: 637–643
tional Conference on Equine Infectious Diseases, Lyon. Varrasso A, Drummer HE, Huang JA et al 2001 Sequence
Veterinary Publications, Princeton, NJ, pp.321–328 conservation and antigenic variation of the structural
Studdert MJ 1978 Antigenic homogeneity of equine adeno- proteins of equine rhinitis A virus. Journal of Virology
viruses. Australian Veterinary Journal 54: 263–264 75: 10550–10556
Studdert MJ 1996 Equine adenovirus infections. In: Studdert MJ Venter GJ, Paweska JT, Van Dijk AA et al 1998 Vector
(ed.) Virus Infections of Vertebrates, vol. 6, Virus Infec- competence of Culicoides bolitinos and C. imicola for South
tions of Equines. Elsevier Science, Amsterdam, pp.67–80 African bluetongue virus serotypes 1, 3 and 4. Medical
Studdert MJ, Gleeson LJ 1977 Isolation of equine rhinovirus and Veterinary Entomology 12: 378–385
type 1. Australian Veterinary Journal 53: 452 Westbury HA 2000 Hendra virus disease in horses. Review of
Studdert MJ, Gleeson LJ 1978 Isolation and characterisation of Science and Technology 19: 151–159
an equine rhinovirus. Zentralblatt für Veterinärmedizin B Whitwell, KE and Greet, TR 1984. Collection and evaluation of
25: 225–237 tracheobronchial washes in the horse. Equine Veterinary
Studdert MJ, Blackney MH 1982 Isolation of an adenovirus Journal 16: 499–508
antigenically distinct from equine adenovirus type 1 from Whitlock RH, Dellers RW, Shively JN 1975 Adenoviral
diarrheic foal feces. American Journal of Veterinary pneumonia in a foal. Cornell Veterinarian 65: 393–401
Research 43: 543–544 Wieringa R, de Vries AA, Raamsman MJ et al 2002 Charac-
Studdert MJ, Wilks CR, Coggins L 1974 Antigenic comparisons terization of two new structural glycoproteins, GP(3)
and serologic survey of equine adenoviruses. American and GP(4), of equine arteritis virus. Journal of Virology
Journal of Veterinary Research 35: 693–699 76: 10829–10840
Wilks CR, Studdert MJ 1972 Isolation of an equine adeno- Wood JM, Mumford J, Schild GC et al 1986 Single-radial-
virus. Australian Veterinary Journal 48: 580–581 immunodiffusion potency tests of inactivated influenza
Williams R, Du Plessis DH, Van Wyngaardt W 1993 Group- vaccines for use in man and animals. Developments in
reactive ELISAs for detecting antibodies to African Biological Standardization 64: 169–176
horsesickness and equine encephalosis viruses in horse, Wood JM, Mumford JA, Dunleavy U et al 1988 Single radial
donkey, and zebra sera. Journal of Veterinary Diagnostic immunodiffusion potency tests for inactivated equine
Investigation 5: 3–7 influenza vaccines. In: Proceedings of the 5th Interna-
Williamson MM, Hooper PT, Selleck PW et al 1998 Trans- tional Conference on Equine Infectious Diseases. University
mission studies of Hendra virus (equine morbillivirus) in Press of Kentucky, Lexington, KY, pp.74–79
fruit bats, horses and cats. Australian Veterinary Journal Yates P, Mumford JA 2000 Equine influenza vaccine effi-
76: 813–818 cacy: the significance of antigenic variation. Veterinary
Wood JL, Newton JR, Chanter N et al 2005 Association Microbiology 74: 173–177
between respiratory disease and bacterial and viral Zhu XR, Wang CR, Shen BY et al 1989 Microbiological
infections in British racehorses. Journal of Clinical examination of horses with chronic obstructive pulmonary
Microbiology 43: 120–126 disease in Hexi district, Gansu province. Acta Veterinaria
Wood JM, Mumford J, Folkers C et al 1983a Studies with et Zootechnica Sinica 20: 238–241
inactivated equine influenza vaccine. 1. Serological Zientara S, Sailleau C, Moulay S et al 1993 Diagnosis and
responses of ponies to graded doses of vaccine. Journal of molecular epidemiology of the African horse sickness
Hygiene 90: 371–384 virus by the polymerase chain reaction and restriction
Wood JM, Schild GC, Folkers C et al 1983b The standard- patterns. Veterinary Research 24: 385–395
ization of inactivated equine influenza vaccines by single-
radial immunodiffusion. Journal of Biological Standard-
ization 11: 133–136
Bacterial Infections of the Equine
Respiratory Tract
23 Josh Slater
from the horse’s inflammatory defenses, including preven-

Equine Streptococci
tion of opsonization by complement (C3b), and thus confers
Streptococci are the most important respiratory bacterial resistance to phagocytosis. Streptococci secrete a variety of
pathogens of the horse and are the major etiological proteins, referred to as exotoxins, that are cytolytic to host
agents, either as single infections or mixed infections with cells including respiratory epithelium and leukocytes.
other pathogens, of all four of the major equine bacterial
respiratory syndromes: Differentiating equine streptococci
● strangles
Most equine streptococcal clinical isolates are β-hemolytic
● bronchopneumonia in foals up to 6–8 months old
and belong to Lancefield group C (Fig. 23.2), the exception
● inflammatory airway disease
being S. pneumoniae which is α-hemolytic and does not
● pneumonia/pleuropneumonia in mature horses.
have a Lancefield group antigen. The Group C streptococci
There are four principal equine streptococci: are closely related to each other (Lancefield 1933, Quinn
et al 1994, Chanter et al 1997) but can be differentiated
● Streptococcus equi subsp. equi
by their biochemical properties. Between-subspecies and
● Streptococcus equi subsp. zooepidemicus
● Streptococcus dysgalactiae subsp. equisimilis
● Streptococcus pneumoniae.
General features of the equine streptococci are listed Box 23.1. General features of the equine streptococci
in Box 23.1.
A typical equine streptococcus is shown schematically ● Gram-positive cocci approximately 1 μm in diameter
in Fig. 23.1. The scanning electron micrograph shows ● Occur as pairs or chains depending on the culture environ-
chains of S. equi colonizing equine ciliated respiratory ment: usually as pairs (diplococci) in the animal but as
epithelium (×2,000). The streptococcal cell wall consists elongated chains in vitro; diplococci are more virulent
of peptidoglycan and teichoic acid. A variety of surface ● Facultative anaerobes
proteins (including M-like proteins and lipoproteins) are ● Catalase and oxidase negative
anchored to the cell wall by their C terminus, their N ● Non-motile and non-spore-forming (therefore limited
terminus, or by other chemical interactions. These proteins environmental persistence and reservoir of infection)
are fibrillar structures that project into the environment ● β-hemolysis (complete) on blood agar plates (except
around the bacterium and are responsible for many of S. pneumoniae which is α-hemolytic)
the interactions between the bacterium and the horse’s ● Lancefield Group C (except S. pneumoniae which has no
epithelium and immune system. Although the functions of Lancefield group antigen)
all the surface proteins have not been determined, they ● Opportunist pathogens of the respiratory tract
are known to be responsible for certain key events in ● Cause both mucosal respiratory infections and invasive
pathogenesis including adhesion to respiratory epithelium, systemic disease
evasion of phagocytosis and immunogenicity. The bacterial ● Host range varies from strictly Equids (S. equi subsp. equi)
cell is surrounded by a loose network of polysaccharides to a variety of animal species and humans (S. equi subsp.
known as a capsule, through which the surface proteins zooepidemicus; S. pneumoniae)
project. With the exception of S. pneumoniae, the capsule ● Variety of virulence and defense mechanisms including the
of equine streptococci consists of hyaluronic acid. Since antiphagocytic capsule and surface (M) protein
hyaluronic acid is a polysaccharide found in mammalian ● Variably transient immunity following natural infection;
tissues, it is not recognized as foreign by the horse, i.e. it is some species have huge antigenic diversity between strains
non-immunogenic and opsonizing antibodies are not raised with little cross-protection
against the capsule. The capsule also protects the bacterium
327
328 23 Bacterial Infections of the Equine Respiratory Tract
Other surface proteins e.g. lipoprotein
Cell wall
Surface M protein
Capsule
Fig. 23.1. Principal features of an equine streptococcus.
within-subspecies differentiation is also possible by genetic formation in red blood cells resulting in osmotic lysis. Three
“fingerprinting” at chromosome level (restriction fragment patterns of hemolysis occur.
length polymorphisms and pulsed field gel electrophoresis)
● α-Hemolysis: growth on blood plates causes incomplete
or nucleotide level using polymerase chain reactions
destruction of blood cells. This produces dark green
(PCR) for amplification of single gene (16s and 23s rRNA
discoloration around bacterial colonies, reflecting the
and M protein) or multiple gene sequences (multilocus
presence of biliverdin and other hemoglobin breakdown
sequence typing).
products.
● β-Hemolysis: growth on blood plates causes complete
Hemolysis
destruction of blood cells, resulting in transparency of
Hemolysis occurs around streptococcal colonies growing the region surrounding bacterial colonies.
on blood agar plates because of production of the cytolytic ● γ-Hemolysis: no observable destruction of blood cells
toxin streptolysin. Streptolysin causes transmembrane pore surrounding bacterial colonies.
Streptococcus dysgalactiae
subspecies dysgalactiae
Group C streptococci subspecies equisimilis
Streptococcus equi
Streptococcus equi
subspecies zooepidemicus
Streptococcus equi
subspecies equi
Fig. 23.2. Lancefield group C.

23 Bacterial Infections of the Equine Respiratory Tract 329
Table 23.1. Sugar fermentation patterns

of the equine group C streptococci
Sugar
Species Trehalose Sorbitol Lactose Ribose
Streptococcus equi – – – –
subspecies equi
Streptococcus equi – + + +
subspecies
zooepidemicus
Streptococcus + – ± +
dysgalactiae
subspecies equisimilis
Fig. 23.3. Streptococcus equi: Gram-stained smears show chains of

Gram-positive cocci. Colony smears show elongated chains as in this
case, while smears from nasal discharge or abscesses show shorter
chains and often diplococci (magnification ×100).
Pathogenic equine streptococci are hemolytic and most
are β-hemolytic. Non-hemolytic streptococci may be isolated
from the equine upper respiratory tract (URT) but are
regarded as commensals without pathogenic potential.
Lancefield groups
Lancefield grouping is a serological method for classifying
streptococci into one of 20 groups (designated by a letter)
based on the presence of polysaccharide and teichoic acid
antigens in the bacterial cell wall (Lancefield 1933). The
technique is now performed using commercial latex agglu-
tination test kits, which allow rapid detection of clinically
important streptococcal groups. Some streptococci, for
example S. pneumoniae, have not been assigned to a group
because their antigen extracts fail to react with group
antisera. With the exception of S. pneumoniae all the equine
streptococci belong to Lancefield group C.
Fig. 23.4. Streptococcus equi colonies are generally mucoid and

Biochemical properties
β-hemolytic on blood agar plates.
The equine streptococci are all oxidase and catalase
negative. The group C streptococci are differentiated on the
basis of their ability to ferment the sugars salicin, sucrose, ably homogeneous, apparently clonal, organism which
trehalose, sorbitol, lactose, and ribose. They all ferment appears to have evolved comparatively recently from
salicin and sucrose; S. equi subsp. equi does not ferment the closely related S. equi subsp. zooepidemicus (Chanter
any other sugars but S. equi subsp. zooepidemicus and et al 1997). Different isolates from diverse geographical
S. equi subsp. equisimilis ferment at least two other sugars locations demonstrate antigenic homogeneity on gel
(Table 23.1). diffusion precipitin analysis, immunoblot of M-protein
(SeM) and serum neutralization experiments. Genetic
homogeneity of S. equi has also been demonstrated through
Streptococcus equi subsp. equi chromosomal DNA “fingerprinting” and sequence com-
General features parisons of the 16s and 23s rRNA intergenic spacer
regions of different strains. However, detailed genetic
Streptococcus equi subsp. equi (S. equi) is the cause of analysis has shown that the previously held belief that
strangles. It is a Gram-positive, chain-forming (Fig. 23.3), S. equi is a single serotype with no genetic variation is
Lancefield group C β-hemolytic streptococcus (Fig. 23.4). incorrect (Al-Ghamdi et al 2000, Takai et al 2000). At
Streptococcus equi is prevalent worldwide and is a remark- least seven different genetic subtypes with particular
geographical distributions have been identified, allowing colonization and the subsequent steps in pathogenesis
molecular epidemiology and the tracing of subtype trans- cannot progress. Adhesion almost certainly involves mul-
mission during and between outbreaks to be performed tiple components on the bacterial surface. Our under-
(Al-Ghamdi et al 2000, Takai et al 2000). standing of the molecular events and regulation of S. equi
adhesion is incomplete. Although several S. equi adhesins
Pathogenesis and virulence factors have been identified and characterized, there are many
surface proteins to which functions have not been ascribed
The pathogenesis of S. equi infections has not been and it is likely, based on sequence homology, that many of
completely elucidated at a cellular level and, although these are involved with host cell adhesion. Like most
some bacterial virulence mechanisms have been iden- bacteria, S. equi possesses adhesins that bind to host extra-
tified, the detailed bacterial mechanisms employed in the cellular matrix molecules (these adhesins are referred to
processes of adhesion to respiratory epithelium, invasion as microbial surface components recognizing adhesive
into the lamina propria, entry into lymphatics, and evasion matrix molecules – MSCRAMMs). These include the
of phagocytosis are incompletely understood. fibrinogen-binding proteins SFS and FNE (Lindmark &
Acquisition of S. equi infection appears to be mainly via Guss 1999, Lindmark et al 2001). It is not clear whether
infected droplets directly from other horses or indirectly via the hyaluronic acid capsule functions as an adhesin or
fomites rather than by aerosol transmission. Acquisition whether, by virtue of its negative charge and physical
may be via nasal or oral routes. Following entry, bacteria masking of surface proteins, it acts to prevent adhesion.
adhere to, and colonize, the epithelium in the URT, possibly Studies with S. pyogenes have suggested that the capsule
preferentially in the nasopharynx and pharyngeal tonsil acts as a ligand for CD44 receptors on human cell lines, but
region although this has not been demonstrated in vivo. experiments with non-capsulated isolates of S. equi have
Invasion through the epithelium into the lamina propria either found no difference in adhesion or an increase in
and lymphatics appears to occur rapidly because bacteria adhesion compared to encapsulated isolates. Evasion of
can be isolated from drainage lymph nodes within hours host defenses (opsonophagocytosis) is central to patho-
of infection (Timoney 1988a). S. equi efficiently evades genesis, enabling bacterial persistence despite neutrophil
phagocytosis despite efficient chemotaxis of neutrophils chemotaxis, and drives abscess formation. Streptococcus
to the sites of infection. The continued survival of bac- equi possesses three antiphagocytic mechanisms: capsule,
teria within lymph nodes drives further recruitment of M protein, and exotoxins. The hyaluronic acid capsule is
neutrophils and abscess formation. In most horses bac- a polymer of N-acetylglucosamine and glucuronic acid.
teria are confined to the lymph nodes draining the head It interferes with opsonization (Anzai et al 1999) by
(submandibular, parotid, retropharyngeal, and cervical preventing the formation of C3b convertase and hence the
lymph nodes). In a minority of cases S. equi is released in deposition of C3b on the bacterial surface. The M protein
efferent lymph and gains entry to the blood circulation via SeM, in common with all streptococcal M proteins, binds
the thoracic duct, with systemic dissemination of bacteria fibrinogen and is antiphagocytic by inhibiting opsonization
resulting in metastatic abscessation. Bacterial antigens (Galan & Timoney 1987, Timoney et al 1997) by blocking
(either whole bacteria or bacterial surface proteins) in the C3b deposition on the bacterial surface (fibrinogen is bound
circulation can trigger purpura hemorrhagica, an immune- by the N terminus thus masking the C3b binding site) and
complex-mediated vasculitis, the pathogenesis of which is by binding the Fc portion of IgG, preventing Fc binding to
not completely understood. Although classically associated
with S. equi infection, it can be triggered by a variety of
bacterial antigens, and some horses may have no history Box 23.2. Known virulence mechanisms of S. equi
of exposure to infectious agents (Pusterla et al 2003).
Immune complexes contain immunoglobulin A (IgA) ● Bacterial cell wall
complexed to streptococcal M protein. Affected horses – Peptidoglycan
generally have high IgA titers and low IgG titers, with IgG ● Hyaluronic acid capsule
titers only rising in the convalescent phase. The reason for ● Surface proteins
the apparent association with IgA and the late rise in IgG – Extracellular matrix binding proteins
in affected horses is not clear. – Antibody binding proteins
Several virulence factors have been identified and char- – M protein
acterized in S. equi and the genome sequencing projects for ● Exotoxins
S. equi and S. zooepidemicus (www.sanger.ac.uk) have enabled – Hyaluronidase
rapid progress to be made in identifying other virulence – Streptolysin
mechanisms (Box 23.2; Harrington et al 2002). – Streptokinase
Adhesion is the first and key step in pathogenesis: – Pyrogenic exotoxins
without bacterial adhesion to the epithelium of the URT,
Fc receptors on neutrophils (Boschwitz & Timoney 1994). the UK. Morbidity is high and may approach 100% in
SeM is a 58-kDa coiled fibrillar protein and, unlike most susceptible populations (Yelle 1987, Dalgleish et al 1993,
streptococcal M proteins, it is highly conserved showing no Hamlen et al 1994). Mortality is generally considered to be
antigenic and little sequence variation. Although isolates only 2–3% but rates of up to 20% have been recorded in
with truncated M proteins have been isolated from the individual outbreaks (Sweeney et al 1987, Spoormakers et
guttural pouches of carrier horses, these isolates appear al 2003). The estimates of disease prevalence are likely to
to retain immunogenicity and virulence despite their be inaccurate because of the lack of compulsory reporting
M protein truncations (Chanter et al 2000). Survival in the in the UK, for example, and the stigma attached to S. equi
host also requires a variety of nutrient acquisition mecha- infections among horse owners means that detailed and
nisms. Streptococcus equi possesses several ATP binding comprehensive epidemiological data are not available.
cassette (ABC) transporter systems and associated surface Streptococcus equi is mainly transmitted via infected
lipoproteins, which appear to be important in pathogenesis. droplets either by direct horse-to-horse contact (George et al
It produces a number of exotoxins that interfere with 1983) or indirectly by fomites including personnel (hands,
horse leukocyte function. These include four pyrogenic clothing, and footwear) and equipment (tack, feed utensils,
exotoxins (SePE-H, -I, -K, -L) and an antichemotactic/ and water buckets/troughs). Aerosol transmission over
cytotoxic leukotoxin (Muhktar & Timoney 1988). Invasion extended distances as occurs for the respiratory viruses,
into the lamina propria is assisted by degradative enzymes such as influenza virus, does not appear to be an important
including hyaluronidase and the hemolytic cytotoxin feature of S. equi transmission. Horses with clinical S. equi
streptolysin-S (Flanagan et al 1998), although this step in disease are a major source of contagion and shed bacteria
pathogenesis is poorly understood. (determined by both culture and PCR) continuously or,
more commonly, intermittently in nasal discharge and
Transmission lymph node pus. The duration and magnitude of shedding
is unrelated to the severity of clinical signs. Although
Streptococcus equi infections occur in equids of all ages, detailed epidemiological data from field outbreaks are not
although severe clinical disease is more prevalent in young available, it is likely that bacterial shedding is initially
animals or in those not previously exposed (Todd 1910, continuous and becomes intermittent with increasing time
Sweeney et al 1987, 1989, Yelle 1987, Hamlen et al 1994). post infection (p.i.). Bacterial shedding also occurs during
In establishments where there is a large population and convalescence (George et al 1983, Timoney 1988b, Grant
frequent introduction of new individuals, the risk of S. equi et al 1993, Newton et al 2000) for up to 3–4 weeks after
outbreaks increases (Box 23.3). In particular, overcrowd- the cessation of clinical signs. In a small proportion of
ing and coexisting disease may enhance susceptibility recovered horses, a carrier state is established (defined as
(Todd 1910, Yelle 1987, Jorm 1990, Hoffman et al 1991, shedding of bacteria by an apparently healthy horse for
Dalgleish et al 1993). Whilst the incidence of strangles more than 1 month after cessation of clinical signs) with
varies both geographically and temporally, it has been intermittent shedding of bacteria in nasal secretions.
estimated that S. equi infection accounts for approximately Bacterial carriage may continue for several months or even
30% of all reported equine infections worldwide (Todd years (Newton et al 1997). Carrier horses are probably the
1910, Dalgleish et al 1993, Harrington et al 2002) and is major reservoir of S. equi infection and almost certainly
the most commonly reported equine bacterial infection in account for strangles outbreaks on establishments follow-
ing the introduction of new animals (George et al 1983,
Newton et al 1997) or the reappearance of clinical disease
Box 23.3. Risk groups for S. equi outbreaks months to years after previous outbreaks on particular
premises. The existence and importance of an environmental
● Low risk – Closed populations that do not travel reservoir of infection has been the subject of debate.
– Horses kept on private premises which do not mix with Streptococcus equi is not a hardy organism and survives
other horses; no or infrequent travel to events, competi- for only short periods (less than 10 days) if desiccated or
tions, shows exposed to ultraviolet light. Survival in the environment
● Medium risk – Closed populations that travel will depend on ambient temperature, humidity, rainfall,
– Horses kept in closed yards but which travel to events, and ultraviolet light. Bacteria survive for longer periods (up
competitions, shows and race meetings to 2 months) in water or in pus smeared onto wood or tack
● High risk – Open populations (Jorm 1991). However, these experiments were performed
– Livery yards, studs, dealer yards in controlled conditions of high humidity and low tempera-
– Frequent mixing of new arrivals and age groups; stabling ture and almost certainly overestimate survival times in the
allows contact between horses; communal feed and environment. Irrespective of the duration of environmental
water troughs survival, the contagiousness of S. equi decreases exponen-
tially with time and transmission from the environment is
and the previous immune experience of the horse. Pyrexia

(up to 42°C) is the earliest clinical sign and persists for
2–3 weeks p.i. Affected horses are depressed and anorexic
for 1–2 weeks, possibly longer if complications develop.
Nasal discharge becomes increasingly purulent (Fig. 23.5)
and persists for 2–4 weeks. Bacterial shedding continues
for a considerable period after resolution of pyrexia and
overt clinical signs of disease. The duration of bacterial
shedding, and hence contagiousness, is typically in the
range of 3 to 8 weeks after infection but can be even longer
in some horses.
Lymph node enlargement is palpable from 2–3 days after
infection and clinically apparent abscesses usually develop
2–3 weeks later (Yelle 1987, Wilson 1988, Timoney
1993). Histological evidence of abscessation is present from
1–2 days p.i. Abscesses usually develop in the submandi-
bular and retropharyngeal lymph nodes (Fig. 23.6). Their
Fig. 23.5. Streptococcus equi infection (“strangles”) causes a moder- superficial position makes submandibular abscesses com-
ate to profuse bilateral mucopurulent nasal discharge. paratively easy to diagnose and manage (Fig. 23.7). Retro-
pharyngeal abscesses are more difficult to diagnose because
of their deeper position. Retropharyngeal abscesses may
thus only likely with freshly (less than 1 week) discharged burst and drain externally (over the lateral laryngeal
bacteria. Nevertheless, care should be taken with the stable region) or internally (dorsally into the guttural pouches).
and feed environment especially communal water troughs. Large, unruptured retropharyngeal abscesses can cause
Streptococcus equi is readily inactivated by commonly used moderate or marked airway compression with ventral
disinfectants including bleach, quaternary ammonium deviation of the trachea (Fig. 23.8) and occlusion of the
compounds, chlorhexidine, and Virkon, thus greatly facili- nasopharynx, resulting in inspiratory dyspnea and possibly
tating environmental control. stertorous inspiratory noise (Sweeney et al 1987). Guttural
pouch empyema may develop secondary to rupture and
Clinical signs drainage of retropharyngeal abscesses into the guttural
pouch (see Fig. 28.2). However, retropharyngeal absces-
Severe “classical” strangles sation is not a prerequisite because bacteria gain access
The incubation period is variable (1–14 days), even follow- to the pouches directly from the nasopharynx via the
ing experimental challenge, and is probably dependent on pharyngeal ostia of the auditory tubes. Guttural pouch
the strain of bacterium, the size of the infecting inoculum, empyema causes intermittent, mostly unilateral, purulent
Fig. 23.6. Streptococcus equi infection. This

Welsh Mountain Pony has a resolving retro-
pharyngeal lymph node abscess. This photo-
graph was taken approximately 4 weeks
after the onset of clinical signs.
Fig. 23.7. Streptococcus equi infection. Abscesses initially develop in

the lymph nodes draining the head. This horse has a draining sub-
mandibular lymph node abscess. Abscesses can also develop in the
parotid and retropharyngeal lymph nodes. Reproduced with the
permission of Prof. D. Paul Lunn, CSU. Fig. 23.8. Streptococcus equi infection. Large, non-ruptured retropha-
ryngeal lymph nodes may compress the nasopharynx and trachea
causing dyspnea. This radiograph shows ventral deviation of the trachea
by a large retropharyngeal lymph node abscess. Reproduced with the
permission of Prof. D. Paul Lunn, CSU.
nasal discharge. There is usually no obvious guttural
pouch swelling externally. The pouch may be painful on
percussion or palpation. Chondroids (balls of inspissated
pus that contain viable bacteria) may develop in chronic diarrhea, coughing, dyspnea, and seizures (Spoormakers
cases of guttural pouch empyema. Persistent (months to et al 2003). The S. equi antigens in the circulation can
years) guttural pouch infection may develop in a small trigger purpura hemorrhagica, an immune complex-
proportion (<10%) of recovered horses, with a carrier mediated, aseptic, leukocytoclastic vasculitis, causing
remaining in an estimated 50% of outbreaks (Newton et al petechial hemorrhages and well-demarcated subcutaneous
1997, 2000). These animals are often asymptomatically edema (Fig. 23.9). There may be oozing of serum from the
infected and shed bacteria intermittently, often in small skin or even skin necrosis and sloughing. Vasculitis and
numbers, in the respiratory tract secretions. Infection may edema occur in organ systems throughout the body includ-
be established in the sinuses, causing clinical signs of ing the viscera, musculature, and kidneys, causing a
sinusitis (unilateral nasal discharge with or without pain variety of other signs to occur including depression, pyrexia,
and dullness on sinus percussion). The sinuses may also be tachycardia, tachypnea, reluctance to move, colic, epistaxis,
sites for chronic carriage as well as, or instead of, the and weight loss (Galan & Timoney 1985a,b).
guttural pouches. Other strangles-related clinical signs include agalactia,
In most cases bacteria do not disseminate beyond the although this is believed to be secondary to pyrexia
head but in a small proportion of horses the bacteria and anorexia and not as a direct consequence of S. equi
disseminate widely via the blood and lymphatics causing invading the udder and causing disease.
metastatic abscessation (“bastard strangles”) in the abdomen
(abdominal lymph nodes, viscera, and peritoneum), thorax “Atypical” strangles
(thoracic lymph nodes, lungs, pleura, and mediastinum), In most outbreaks in the UK a minority of horses develop
central nervous system, eye, skeletal and cardiac muscle, classical strangles. The majority of horses exhibit milder
tendon and joint sheaths (Sweeney et al 1987). Metastatic clinical signs and experience a transient, self-limiting
abscessation causes clinical signs relating to the region infection. In some horses infection is subclinical. This
where the abscesses develop together with more generalized milder form of S. equi infection is referred to as “atypical”
and non-specific signs including weight loss, intermittent strangles (Woolcock 1975, Prescott et al 1982, Grant et al
pyrexia, and anorexia. It is generally a chronic, progressive 1993). It resembles a URT viral infectious disease with
syndrome with obvious clinical signs developing weeks to pyrexia, depression, lymph node enlargement, and nasal
months after infection and frequently resulting in death discharge and is frequently not recognized as S. equi
(Sweeney et al 1987). Clinical signs are often insidiously infection if appropriate samples are not collected for
progressive and initially vague, including intermittent microbiology. The more serious sequelae of “classical”
pyrexia, depression, and weight loss. Later, organ- or strangles (lymph node abscesses, guttural pouch empyema,
region-specific clinical signs may appear, including colic, metastatic abscessation, and purpura hemorrhagica) do
influenza virus, equine herpesvirus, equine viral arteritis,

and equine rhinitic virus. Hematology will usually reveal a
leukocytosis with neutrophilia from 7 to 10 days p.i., but
this is not diagnostic for S. equi infections. Horses with
purpura hemorrhagica show anemia, neutrophilia, hyper-
proteinemia, hyperfibrinogenemia, hyperglobulinemia, and
raised muscle enzymes (creatine kinase and aspartate
transaminase).
Serology to detect antibody against SeM is commercially
available but lacks specificity because of cross-reaction
with other streptococcal M proteins, especially the
S. zooepidemicus M protein. Confirmation of S. equi infection
requires culture of viable bacteria or detection of bacterial
DNA by PCR, using a nested PCR and primers amplifying a
region of SeM (Timoney & Artiushin 1997, Newton et al
2000). Bacterial culture can be performed on nasal, naso-
pharyngeal, and abscess swabs; nasal washes; guttural
pouch lavages; and abscess aspirates. Sample type, quality
and handling after collection are important considerations
because bacterial shedding is often intermittent and the
number of viable bacteria is variable. Samples should be
kept cool and processed as soon as practicable. Swabs
should be stored in charcoal and can be posted to diag-
nostic laboratories. Nasal and guttural pouch lavages are
performed with approx 50 ml phosphate-buffered saline
via a 10-cm length of rubber tubing inserted into the
nasal cavity (nasal lavage) or transendoscopically (guttural
pouch lavage). The sample can be pelleted before culture
to increase sensitivity. Samples need to be processed the
same day if possible, making them less suitable for postal
delivery. Lavages provide a superior sample to swabs
Fig. 23.9. Streptococcus equi infection. Purpura hemorrhagica is an because a greater surface area of epithelium is sampled.
immune-mediated vasculitis with mucosal and visceral hemorrhages False negatives (i.e. negative results in horses infected with
and subcutaneous edema. This horse has large plaques of proximal
S. equi) occur with both culture and PCR. The sensitivity
limb and ventral trunk edema. Reproduced with the permission of
Prof. D. Paul Lunn, CSU. of culture of single samples is low (between 20 and 40%).
The sensitivity of PCR is higher (between 50 and 80%).
Combining these tests increases the sensitivity further.
not develop in the milder “atypical” form of strangles. It is Guttural pouch empyema causes chronic, principally
not clear why there are two forms of the disease, but unilateral, nasal discharge. There is usually no pouch
bacterial strain differences, horse genetic differences, and distension or pain apparent on palpation. Endoscopy
previous immune exposure of the horse, are probably all confirms the diagnosis. Lateral radiographs can be used to
contributory factors. Bacteria isolated from “atypical” cases demonstrate a fluid line in the pouch but are most useful
retain their virulence and are capable of causing more for identifying retropharyngeal lymph node enlarge-
severe disease in other horses. ment and abscessation. Ultrasonography is also useful
for assessing retropharyngeal lymph node enlargement
Diagnosis and abscessation. Streptococcus equi carriage occurs most
frequently in the guttural pouches but also occurs in other
Outbreaks of URT infectious disease with high morbidity, sites, including the paranasal sinuses. Guttural pouch
pyrexia, depression, purulent nasal discharge, coughing, carriage is frequently asymptomatic and occurs without
and lymphadenopathy progressing to abscessation, espe- frank empyema. On endoscopy there may be small quanti-
cially in yards with movement and mixing of horses, is ties of pus in the pouches, chondroids, discharging lymph
strongly suggestive of classical strangles (Timoney 1993). nodes or areas of epithelial inflammation. In some cases
The milder “atypical” disease is difficult to diagnose with the pouches appear grossly normal (Fintl et al 2000).
certainty on clinical grounds alone because it resembles Pouch carriage is confirmed by endoscopic guttural pouch
other causes of URT infectious disease, including equine lavage using 30–50 ml saline.
Sinus carriage may also be asymptomatic, although PCR on a single nasopharyngeal swab has a sensitivity of
there may be clinical signs of sinusitis. Diagnosis is by sinus 53% rising to 80% for three swabs at weekly intervals. The
radiography, sinoscopy, and lavage. Metastatic abscessation sensitivity of guttural pouch lavages is higher with a
can be difficult to diagnose because abscesses can form at predicted sensitivity of 80–90% for carrier detection when
almost any anatomical site, often in regions that are diffi- both culture and PCR are performed. The implication of
cult to examine physically or to image. Affected animals these data is that whilst serial nasopharyngeal swab
show intermittent pyrexia, depression, illthrift, and weight samples are the most practical means of identifying
loss with variable leukocytosis and neutrophilia. There may carriers in a large herd, single guttural pouch lavages
be signs relating to the abscessed organ(s) or more general provide a useful alternative in small groups of animals.
signs including colic (for abdominal abscesses), thoracic
pain, dyspnea and tachypnea (for thoracic abscesses), and Management
seizures or other cerebral signs (for central nervous system
abscesses). Ultrasonography, radiography, abdominocen- The three aims of managing an outbreak of strangles are
tesis, and thoracocentesis can be useful diagnostic aids and (1) prevent spread of infection to new premises; (2) limit
magnetic resonance imaging has been used to diagnose spread of infection within the infected premises; and (3)
central nervous system abscesses. ensuring that carriers are identified and treated at the end
Horses with mild “atypical” disease are easily misiden- of the outbreak. Currently, the UK does not have a
tified as not being infected with S. equi unless a careful compulsory reporting, tracing, testing or isolation/move-
clinical assessment is made. It should be remembered that ment restriction policy for S. equi. However, movement of
in some outbreaks the majority of S. equi-positive (by horses on and off the infected premises should be
culture or PCR) horses are apparently healthy or exhibit suspended to reduce the risk of infection spread elsewhere.
subtle clinical signs only. Very importantly, convalescent Personnel should be briefed about the risk of indirect
horses can continue to be PCR positive for S. equi for transmission and precautions should be taken with hand
extended periods (up to 4 weeks) after viable bacteria can washing, clothing, footwear, and tack. Management of
no longer be isolated. In other words, positive results clinical cases requires strict isolation and barrier nursing.
on PCR in the early convalescent phase should not be On suspicion of S. equi infection, the yard should be divided
interpreted as evidence for continued infection or the into clean (unaffected) and dirty (affected) areas and horses
presence of a carrier state. should be assigned to one group or the other based on
Although the majority of URT infectious disease clinical signs (initially pyrexia). Daily checks should be
with lymph node abscessation are the result of S. equi made and as the outbreak progresses some horses from the
infection, other Lancefield group C streptococci, especially unaffected group that were incubating disease will require
S. zooepidemicus, can also be involved either in combination movement into the affected group. Ideally different staff
with S. equi or as sole infections. Detection of carriers is not should attend each group but where this is not possible
easy or inexpensive and requires a committed owner and staff should attend the “clean” area first. Dedicated boots,
clinician (Newton et al 1997, 2000). The ability to identify overalls, and latex gloves should be worn when attending
carriers serologically would provide a valuable, effective the dirty area. Bedding should be disinfected before disposal
and simple management aid. However, serology based on from the dirty area. Environmental contamination by
SeM does not distinguish carriers from normal convales- S. equi can be readily contained by any of the commonly
cent horses. Diagnosis, as for clinical cases, requires culture used disinfectants including bleaches, phenolic compounds,
of viable bacteria or demonstration of bacterial DNA from quaternary ammonium compounds disinfectants, and
nasopharyngeal swabs or guttural pouch lavages. Carriers Virkon. Feeding utensils should not be shared and
shed bacteria intermittently and in low numbers, making particular attention should be paid to communal water
reliable detection difficult. Nasal swabs do not provide a troughs. These should be emptied and disinfected.
sample of sufficient diagnostic quality. Large, gauze naso- Woodwork (fencing and stable partitions) should also be
pharyngeal swabs provide a much better sample because disinfected to reduce any possible environmental bacterial
they absorb a large volume of secretion from the region reservoir. The apparent lack of aerosol transmission of
close to the pharyngeal ostia of the guttural pouches. The S. equi means that physical separation of the two groups by
sensitivity of nasopharyngeal swabs increases with serial a solid barrier to prevent direct horse-to-horse contact
sampling and if bacterial culture is combined with should be sufficient to prevent spread between groups.
PCR (Newton et al 2000). The sensitivity of a single naso- Affected horses should be kept in clean, dry, well-
pharyngeal swab is low (approximately 30%) but is ventilated, and dust-free stables and fed damp, palatable
improved if three nasopharyngeal swabs are collected at feed. Antibiotic treatment of clinical cases is controversial
weekly intervals. Further nasopharyngeal swabs are likely with some clinicians advocating that antibiotics should
to increase sensitivity. PCR on a single nasopharyngeal never be used for fear of prolonging the clinical disease,
swab improves sensitivity to 50%. Combining culture and reducing immunity or increasing the risk of metastatic
this produces the highest bacterial cure rate and resistance

appears to be uncommon. Other antibiotics including
cephalosporins, fluoroquinolones, and tetracyclines can be
used. Potentiated sulfonamides should be avoided because,
although S. equi is usually sensitive in vitro, this antibiotic
combination is ineffective in abscesses because of the high
concentrations of folic acid present in pus.
At least 1 month after the end of the outbreak the yard
should be screened for carriers using either serial naso-
pharyngeal swabs or guttural pouch lavages. Carriers can
be successfully treated by guttural pouch lavage and
antibiotic treatment (Verheyen et al 2000). Chondroids
should be removed endoscopically using a polyp basket
Fig. 23.10. Retropharyngeal lymph node abscesses that fail to rupture
(or surgically if they cannot be retrieved via the naso-
and drain can cause significant airway compression and dyspnea. This pharyngeal ostium). The affected pouch should be lavaged
horse required a tracheotomy to alleviate its dyspnea. Reproduced daily with approximately 2 liters of saline via an indwell-
with the permission of Prof. D. Paul Lunn, CSU. ing Foley catheter (Fig. 23.11). Benzylpenicillin should be
instilled into the pouch after each lavage and lavaging
should continue until the pouch is negative on culture
(PCR should not be used to test whether treatment has
abscessation. There are however no experimental or field been successful because this does not distinguish dead
data to support these beliefs (Sweeney et al 2005). from live bacteria). Horses with purpura hemorrhagica
Antibiotics may be used in early cases with pyrexia and should be treated with corticosteroids [dexamethasone
depression, especially in foals, to improve welfare and 0.1 mg/kg twice a day intravenously (q 12 h IV)]. Penicillin
reduce the period of bacterial shedding. “In-contact” [22,000 IU/kg q 12 h intramuscularly (IM) or four times a
horses can also be treated with antibiotics provided they day (q.i.d.) IV] should also be used if active S. equi infection
can be moved to a clean area. Antibiotics should not be is suspected. Supportive therapy, including IV fluids, is
used in horses with developing abscesses: these should be very important.
managed by hot fomentation to encourage drainage. Large
non-ruptured retropharyngeal lymph node abscesses may Prevention
require needle drainage under ultrasound guidance if the
airway is compromised and the horse develops inspiratory The American College of Veterinary Internal Medicine
dyspnea. If drainage cannot be effected a temporary (ACVIM; Sweeney et al 2005) has published a consensus
tracheotomy may be required until the abscess resolves statement containing guidelines for the treatment, control,
(Fig. 23.10). The antibiotic of choice is penicillin because and prevention of S. equi. In the UK, the Horserace Betting
Fig. 23.11. Guttural pouch empyema follow-

ing S. equi infection. This horse’s right gut-
tural pouch is being lavaged via an indwelling
Foley catheter.
none of these products has been licensed for use in Europe.

Box 23.4. Principles of S. equi control
The failure of killed and subunit IM vaccines to pro-
vide effective immunity is probably because the route of
● Maintain biosecurity
administration, antigen preparation, and hence type
– ACVIM Consensus Statement and HBLB Code of Practice
of immune response stimulated are inappropriate (Jacobs
on Strangles
et al 2000) because mucosal immunity (osponizing mucosal
● Maximize individual/yard immunity
IgA and IgG) is principally required to provide protec-
– Vaccination
tive immunity (Galan & Timoney 1985a,b, Sheoran et al
1997). Whilst live attenuated intranasal vaccines have the
potential to present a near full complement of bacterial
antigens to the horse’s immune system in a physiologically
Levy Board (HBLB) publishes a Code of Practice on correct context, it has proved difficult to achieve a balance
strangles detailing the management measures required to between attenuation and maintenance of immunogenicity.
control infection (www.hblb.org.uk) (Box 23.4). There have been concerns, for example, about the occur-
The management measures detailed in the ACVIM rence of side effects and even the induction of clinical
Consensus Statement and the Strangles Code of Practice pub- disease following vaccination with the Pinnacle vaccine
lished by the HBLB (www.hblb.org.uk) are the cornerstone strain. In 2005 the first European-licensed commercial
of prevention and are designed to maintain biosecurity: strangles vaccine was launched (Equilis Strep-E, Intervet,
Milton Keynes, UK). This is a live attenuated (genetically
● stop movements on and off the premises if disease occurs
modified) vaccine and is delivered intramucosally into the
● quarantine and test new arrivals
lip. The genetic modification is deletion of a metabolic
● investigate and isolate new clinical cases promptly; use
pathway gene (aroA) required for aromatic amino acid
rectal temperatures to identify new cases
synthesis, which is required for growth in a mam-
● screen convalescent horses to identify and treat carriers.
malian background. This vaccine has a comparatively
New arrivals should be kept quarantined until confirmed short duration of protection and requires revaccina-
free from S. equi infection by culture and PCR of three tion at 3-month intervals to maintain immunity in an
nasopharyngeal swabs collected at weekly intervals. endemically infected area, although this interval can
Suspected new clinical cases should be isolated, investi- be extended to 6-monthly in a non-endemically infected
gated (by bacteriology), and treated promptly. Yards with area provided immediate revaccination is carried out
endemic infection should screen all horses to identify between 3 and 6 months if disease appears in that area.
carriers by nasopharyngeal swabs and/or guttural pouch The delay between vaccination and appearance of protec-
lavage. Carriers should be isolated and treated until con- tive immunity means that vaccination of naive animals in
firmed bacteriologically negative by culture and returned to the face of an outbreak is unlikely to be effective. The effect
the herd. For horses whose management presents a of vaccination on carrier animals is unknown but is
low–medium risk of S. equi infection (i.e. “closed” yards or unlikely to influence the carrier state.
horses from “closed” yards that travel to competitions/
events/race meetings) the Code of Practice can usually be Prognosis
successfully implemented and provides effective control of
disease, reducing the need to vaccinate. However, in many The prognosis for S. equi infections is variable, although
“open” yards (e.g. studs, dealer and livery yards) the Code mortality is generally low and most horses make a com-
of Practice is difficult to implement. It is in these situa- plete recovery. The prognosis for mild disease (“atypical
tions that vaccination forms an important part of S. equi strangles”) is good although it is not known whether
control measures. carriers arise following this form of the disease. For the
There has, however, been limited success in developing more severe disease (“classical strangles”) the prognosis
safe and efficacious S. equi vaccines (Hoffman et al 1991, depends on whether complications develop. The majority of
Smith 1994, Jacobs et al 2000). In the USA and Australia horses recover once abscesses have resolved but up to 10%
commercial vaccines consisting of inactivated whole of cases develop complications that delay recovery or may
bacteria (Equivac-S®, CSL Limited, Victoria, Australia), be fatal. Data on the duration of protective immunity after
M-protein extracts (StrepVax II™, Boehringer Ingelheim, recovery from natural infection is scant but British Army
St. Joseph, MO, USA), enzyme extracts of S. equi (Strepguard™, records suggest that long-lasting (approximately 5 years
Intervet, Millsboro, DE, USA), all administered IM, and most duration) immunity develops in most (> 75%) recovered
recently a live, attenuated, intranasal vaccine (Pinnacle™ horses (Todd 1910). It should be remembered that this
I.N., Fort Dodge, IA, USA) have been developed (Walker & observation relates to large, endemically infected herds and
Timoney 2002). The efficacy and/or safety or all of these the duration of immunity may be shorter in the modern
vaccines has been questioned (Timoney 1988a, 1999) and management settings.
Clinical signs
Bacterial Infectious Diseases
Foals show typical, progressive clinical signs of LRT
of the Lower Respiratory Tract infectious disease: variable pyrexia, depression, coughing,
The respiratory tract is not sterile but is populated by a and bilateral purulent or blood-tinged purulent nasal
dynamic population of Gram-positive and Gram-negative discharge. Nasal discharge may not be copious because
bacteria including Streptococcus spp., members of the mucociliary clearance is generally impaired and a scant
Pasteurellaceae and Mycoplasma spp. that are capable of nasal discharge should not be taken as an indication
responding rapidly to changes in the airway environment that there is little discharge in the trachea and bronchial
and to host defenses. In healthy horses bacterial coloniza- tree. As the disease progresses, foals develop tachypnea,
tion is heaviest in the nares and nasopharynx and dyspnea, and eventually respiratory distress. Affected foals
decreases along the trachea so that the airway beyond the must be handled sympathetically because they have
carina is normally sterile. reduced respiratory capacity. Auscultation is worthwhile.
Bacterial infections of the lower respiratory tract (LRT) There is often pooling of discharge within the trachea
occur in horses and ponies of all ages but are of particular at the thoracic inlet, which produces coarse crackles in
importance in foals, young racehorses in training, and the trachea. Auscultation of the lung field may identify
mature race and sport horses. The clinical disease caused crackles and wheezes, especially in the cranioventral lung.
by bacterial LRT infections is different in each age group Adventitious sounds may not always be audible and a re-
(Table 23.2). Bacterial involvement in neonatal septicemia breathing test can be performed to accentuate these. This
and neonatal bacterial pneumonias is dealt with in procedure should not be performed in foals with severe
Chapters 24 and 45. In older foals (up to 8–9 months) disease or marked dyspnea. In advanced disease some areas
bacterial LRT infections are common and generally cause of the lung may have reduced or absent breath sounds on
bronchopneumonia. In young racehorses in training bac- auscultation and decreased resonance on percussion indi-
terial LRT infections are also common and cause chronic, cating pulmonary abscess/consolidation or pleural effusion.
low-grade tracheobronchitis (inflammatory airway disease).
In mature race and sport horses bacterial LRT infection Pathology
is not common and causes sporadic, potentially fatal, Pathological changes occur mostly in cranioventral regions
pneumonia and pleuropneumonia. of the lung: the affected lung is consolidated and red. There
is copious mucopurulent or purulent discharge within the
Disease summaries bronchi, bronchioles, and alveoli. Consolidation may be
diffuse or occur in focal patches. Cut sections of lung will
Bronchopneumonia in foals generally ooze mucopus or pus from the airway. There may
Overview be fibrin tags on the visceral pleura. With chronic disease
Pneumonia is common in foals up to 8–9 months old, the discharge often becomes more mucopurulent. Localized
and is generally caused by airway-resident bacteria that pulmonary abscesses and focal adhesions may develop
act as opportunistic pathogens when host airway defenses between the visceral and parietal pleurae. Bacterial infec-
are compromised. Most affected foals have mixed infection may extend through consolidated regions of lung to
tions involving one or more of the following: Streptococcus reach the pleurae and produce pleural effusion.
zooepidemicus, S. pneumoniae, Actinobacillus equuli, Pasteurella
caballi and Mycoplasma sp. Other bacteria can also be Diagnosis
involved including Bordetella bronchiseptica, Escherichia coli The clinical findings of pyrexia, depression, coughing,
and Klebsiella sp. A variety of events damage airway dyspnea, tachypnea (especially when handled, stressed or
defenses including respiratory virus infections, Parascaris running) with variable nasal discharge, and abnormal
equorum and Dictyocaulus arnfieldi migration and stresses lung auscultation are highly suggestive of pneumonia.
that include other intercurrent illnesses, transport, Microbiological samples are required to identify which
weaning, and general anesthesia. bacterial species are present and their antibiotic sensitivity.
Table 23.2. Clinical disease syndromes caused by bacterial LRT infections by age group
Age group Disease caused Morbidity Mortality Prognosis
Foals Bronchopneumonia Can be high Can be high Variable – moderate to poor
Thoroughbred racehorses Inflammatory airway disease High Low Good

in training
Adults Pneumonia and pleuropneumonia Low Can be high Moderate

Bronchopneumonia usually involves mixed infections of disease in these types of animals. The disease has a strong
mostly aerobic Gram-positive (mainly streptococci) and association with commensal airway bacteria that act as
Gram-negative bacteria (Pasteurellaceae, possibly with opportunistic pathogens, but up to 40% of cases do not
Mycoplasma sp.). The features of the different bacteria have a clear association with bacteria and other factors,
involved are discussed in the following sections. Samples e.g. hypersensitivity to airborne allergens or hyperreactivity
for bacteriological investigation should be collected with to airborne irritants, may be involved in these cases.
care. For foals with moderate to severe disease that are A variety of bacteria are associated with IAD including
struggling to maintain ventilation, endoscopy and tracheal S. zooepidemicus and S. pneumoniae along with A. equuli,
or bronchoalveolar lavage may be too invasive and may P. caballi and Mycoplasma sp.
reduce ventilation to dangerously low levels. Transtracheal
(percutaneous) lavage is less invasive. Clinical signs
Clinical signs are highly variable. In many cases infection
Management is subclinical and detected only on endoscopic examina-
Affected foals should be isolated (along with the mare) to tion. Clinical signs, when present, are usually subtle and
limit contagion to others in the group. They should be restricted to poor performance, intermittent coughing, and
handled with care and kept in a clean, dry, well-drained, mucopurulent nasal discharge. Importantly, horses with
and well-ventilated dust-free stable environment. Since IAD do not have dyspnea, depression, pyrexia or other
bronchopneumonia in foals is usually the result of indications of systemic illness. Disease occurs both sporad-
mixed infections a broad-spectrum antibiotic regimen ically and as outbreaks, suggesting that there can be con-
should be used. Streptococci are almost always involved tagious transmission from affected horses to other suscep-
(S. zooepidemicus and also S. pneumoniae) and regimens tible horses in the group. This presumably is a function of
should contain penicillin (22,000 IU/kg q 12 h IM or q.i.d. the large bacterial loads present in the airway of affected
IV) together with an aminoglycoside [usually gentamicin horses with transmission via infected respiratory droplets
6.6 mg/kg once a day (s.i.d.) IM or IV] to provide cover and discharges. Affected horses are often unremarkable on
against Gram-negative bacteria. With the exception of clinical examination but tracheal crackles may be audible
Bacteroides fragilis, which is inherently penicillin resistant, at the thoracic inlet. There are usually no abnormalities
anaerobic bacteria are usually sensitive to penicillin. on auscultation of the lung fields. Endoscopy reveals a
Metronidazole can be used to provide additional spectrum variable quantity of mucopus within the trachea and
against penicillin-resistant anaerobes. Alternative anti- possibly extending beyond the carina into the left and right
biotics include oxytetracycline (5 mg/kg IV s.i.d. or q 12 h), bronchial trees. Copious volumes of mucopus may be
ceftiofur (5 mg/kg q 12 h IM or IV) or enrofloxacin (5 mg/kg present at the thoracic inlet (Fig. 23.12).
s.i.d. IV). Oxytetracycline and enrofloxacin are effective
against Mycoplasma sp. Trimethoprim–sulfonamides can
also be used but their efficacy is reduced in pus, which
restricts their value for treatment of foals with large
volumes of exudate. Prevention centers on limiting stock-
ing density, maintaining good air hygiene, controlling
pulmonary parasites, and reducing transport and other
management stresses. There are no vaccines against the
bronchopneumonia-causing bacteria of foals.
Inflammatory airway disease

Overview
Inflammatory airway disease (IAD) is a common condition
affecting young racehorses in training. It may also affect
older performance horses of all breeds. IAD is characterized
by neutrophilic airway inflammation and accumulation of
mucopurulent exudate within the trachea and bronchial
tree. As awareness of this disease has increased so have
diagnosis rates. The prevalence of IAD appears to be
between 10 and 20% in most groups of horses in training
but may be as high as 50%. IAD may also be common in
housed groups of young ponies and horses of other breeds, Fig. 23.12. Endoscopic image of a horse with inflammatory airway
including sport horses, subjected to training or other disease showing a high volume of tracheal mucopus which, on cyto-
management stresses, although there are few data about logical examination, contained increased numbers of neutrophils.
Gram-negative bacteria (Actinobacillus sp., P. caballi) and

Box 23.5. Quantitative bacteriology
Mycoplasma sp. are also commonly involved. If treatment
commences before the results of culture and sensitivity are
● A means of enumerating the number of bacteria present in
known, penicillin (22,000 IU/kg q 12 h IM or q.i.d. IV)
tracheal lavage samples
together with gentamicin (6.6 mg/kg s.i.d. IM or IV) is a
● Allows the clinical significance of bacterial isolates to be
suitable broad-spectrum regimen. The regimen may require
determined
modification once microbiology results are known; for
● Viable counts of > 103 cfu/ml are likely to be significant
example infection with S. zooepidemicus alone does not
Method require gentamicin treatment. With the exception of
● Mix tracheal lavage sample thoroughly Bacteroides fragilis, which is inherently penicillin resistant,
● Perform serial tenfold dilutions of the sample anaerobic bacteria are usually sensitive to penicillin.
● Spread 100 μl of each dilution onto suitable culture plates Metronidazole can be used to provide additional spectrum
(usually sheep blood agar) against penicillin-resistant anaerobes. Alternative anti-
● Incubate, and count colonies to provide a viable count per biotics include oxytetracycline (5 mg/kg IV s.i.d. or q 12 h),
ml of tracheal lavage ceftiofur (5 mg/kg q 12 h IM or IV) or enrofloxacin (5 mg/kg
s.i.d. IV). Oxytetracycline and enrofloxacin are effective
against Mycoplasma sp. Trimethoprim–sulfonamides can
also be used but have reduced efficacy in pus. Where an
allergic etiology is suspected horses should be treated with
Diagnosis corticosteroids by inhalation [beclomethasone 1–3 μg/kg
Clinical signs and endoscopic findings are suggestive of q 12 h or three times a day (t.i.d.); fluticasone 2–4 μg/kg
IAD. Confirmation of a possible bacterial etiology requires q 12 h or t.i.d.] or systemically (dexamethasone 0.1 mg/kg
microbiological culture of tracheal lavage samples followed s.i.d. IM or IV). Sodium cromoglycate can be used in horses
by antibiotic sensitivity testing of isolates. The features of with increased mast cells in tracheal or bronchoalveolar
the different bacteria involved are discussed in the follow- lavage fluids. Bronchodilators (clenbuterol 0.8 μg/kg IV
ing sections. It is essential that quantitative bacteriology q 12 h or by inhalation; ipratropium bromide 1 μg/kg
(Box 23.5) be performed when assessing microbiological by inhalation t.i.d.; salmeterol 1 μg/kg by inhalation t.i.d.)
samples from suspected cases of IAD. This is because can be used. Horses refractory to antibiotic treatment are
whenever mucociliary clearance is impaired and muco- sometimes treated with immunomodulators. Prevention
purulent discharge accumulates in the airway, resident centers on limiting stocking density, maintaining good air
bacteria are able to grow to increased titers. Consequently, hygiene, controlling pulmonary parasites, and reducing
simply demonstrating that bacteria are present in a transport and other management stresses.
tracheal lavage sample is insufficient evidence of bacterial
infection and IAD: it is the number of bacteria present that
is important. Bacterial counts of less than 103 colony- Pneumonia and pleuropneumonia
forming units (cfu) per ml of lavage should not be regarded Overview
as significant. Titers greater than 103 cfu/ml, and espe- Pneumonia and pleuropneumonia in adult horses are
cially greater than 105 cfu/ml, are convincing evidence of caused by resident commensal bacteria that cause disease
bacterial involvement. Tracheal lavage and broncho- opportunistically (see Chapter 46). Disease occurs follow-
alveolar lavage cytology reveal airway neutrophilia possibly ing events that suppress mucosal immunity and damage
with increases in mast cells. Phagocytosed and free bacteria airway defenses, allowing resident microbes to multiply and
may be visible. induce disease. These events include a variety of stresses
such as long-distance transport, overcrowding in barns
Management with poor air hygiene, hospitalization (especially being
IAD should be treated as a contagious disease and horses cross-tied for lengthy periods), and general anesthesia. In
should be divided into affected and non-affected groups. adult horses, in contrast to foals, primary virus infec-
Training should be suspended and horses should be tions are an uncommon predisposition to pneumonia or
stabled in a dry, well-drained, and well-ventilated dust-free pleuropneumonia. The disease often presents as a peracute
environment. Straw should not be used for bedding and fibrinous pleuropneumonia but may also progress to
hay, if used, should be soaked and fed wet. Horses should chronic pneumonia with regions of consolidated lung and
be kept at pasture whenever possible. Where bacteria are pulmonary abscess. The acute form that follows transport
involved in IAD they are mostly present as mixed infections is referred to as “equine shipping fever” and is analogous to
and should therefore be treated using a broad-spectrum the similarly named disease in farm animals. Equine
antibiotic regimen. Streptococci (S. zooepidemicus and also shipping fever is common in horses that are kept for
S. pneumoniae) are the most prevalent bacteria involved but racing and competition, especially sport horses and some
thoroughbred and standardbred racehorses, because they dyspnea and tachypnea: horses with localized regions of
are frequently subjected to long-distance travel. A wide pneumonia may not show obvious dyspnea at rest whereas
variety of aerobic and anaerobic Gram-positive and Gram- horses with large volumes of pleural effusion show marked
negative bacteria are associated with pneumonia/pleuro- respiratory distress. Coarse crackles can often be heard in
pneumonia. Aerobes include S. zooepidemicus, S. pneumoniae, the trachea at the thoracic inlet as a result of pooling of
A. equuli, P. caballi and Mycoplasma sp. Anaerobes include exudate in this region. In horses without pleural effusion
Clostridium sp., Fusobacterium sp. and Bacteroides sp. The crackles and wheezes can usually be heard in the affected
majority of cases are caused by S. zooepidemicus alone or in lung regions. A rebreathing test can be performed with
combination with other bacteria. caution in horses without severe clinical signs to accen-
tuate abnormal sounds. Horses with pleural effusion show
Pathogenesis more obvious clinical signs: there may be signs of pleural
The regulation of resident microbial populations by host pain (pain when walking and standing with elbows
defenses is incompletely understood but involves physical abducted), breathing sounds are absent in the ventral lung
defenses such as the mucociliary escalator, non-specific field, and the ventral thorax is dull on percussion because
immunity such as complement and phagocytes as well as of the pleural effusion. Cardiac sounds are muffled and,
specific immunity mediated by B and T lymphocytes. occasionally, pleural friction rubs can be heard. Re-
Transport, especially in poor air hygiene and with the breathing tests should not be performed on horses with
head tied in an upright position, reduces mucociliary clear- pleural effusion. Other clinical signs relating to sepsis and
ance and a variety of stresses reduce the efficiency of endotoxemia may develop including circulatory collapse,
phagocytosis by neutrophils and macrophages. Bacteria are abdominal pain, and laminitis.
responsive to the local airway environment and possess a
variety of sophisticated sensing systems that up-regulate Diagnosis
virulence mechanisms when host defenses change (dis- The history and clinical examination findings are sugges-
cussed for each bacterium in the following sections of this tive. Thoracic ultrasound is extremely useful and identifies
chapter). It is mainly the cranioventral regions of the lung the volume, location, and nature of the pleural exudate. It
that are affected. Pathological changes initially occur in will identify pleural adhesions and pocketing of pleural
the airway with bronchopneumonia and mucopurulent fluid. Pulmonary abscesses, consolidation, atelectasis, and
exudate in the bronchi, bronchioles, and alveoli. Affected fibrosis can be identified if the affected region of the lung
regions rapidly become consolidated, giving them a red is superficial or if there are adhesions between the parietal
appearance, and within these regions pulmonary infarction and visceral pleura. Thoracic radiography is useful for
and necrosis can develop, resulting in a serosanguineous assessment of abscessation and consolidation/collapse
suppurative exudate. In horses that develop pleuropneu- within deeper regions of the lung that are not accessible by
monia, bacteria invade the consolidated lung and migrate ultrasound. Identification of the bacteria involved requires
to the surface of the lung causing fibrinous pleurisy with culture of airway and pleural fluid samples. Horses with
extensive fibrin deposition on the visceral pleural surface severe disease may not tolerate endoscopic examination
and a variable volume pleural serosanguineous purulent and less invasive collection of samples, for example trans-
effusion. Adhesions may develop between the visceral tracheal (percutaneous) lavage, may have to suffice. It is
and parietal pleural surfaces and cause pocketing of important to culture pleural fluid because this is, initially
pleural fluid. More chronic changes develop in some at least, an anaerobic environment and the population(s)
horses including pulmonary abscesses, bronchiectasis, of bacteria present may be different from those in the
and fibrosis. airway. However, the most prevalent bacteria involved are
Streptococcus sp. and these are facultative anaerobes
Clinical signs allowing them to colonize and grow both in the airway
Onset of clinical signs is generally acute and occurs within and the pleural space. Pleural fluid can be collected by
hours of the stressful event that compromised the airway thoracocentesis (Fig. 23.13) which should, ideally, be
defenses. Clinical signs are more acute, severe, and rapidly ultrasound guided to ensure accurate sampling of fluid
progressive with pleuropneumonia than pneumonia. The pockets and avoid lung puncture. Thoracocentesis gener-
severity of the clinical signs is proportional to the amount ally yields a purulent exudate with a high nucleated cell
of lung affected, the degree of pulmonary necrosis, and the count (mainly neutrophils), raised protein content and free
volume of pleural effusion. Affected horses show pyrexia, and intracellular bacteria (Fig. 23.14). A Gram stain is
depression, some coughing, and variable mucopurulent useful but Pasteurellaceae and Mycoplasma sp. are difficult
nasal discharge that may be blood-tinged. Nasal discharge to visualize microscopically because of their small size
varies because of poor mucociliary clearance. Thus the and poor stain uptake. Quantitative bacteriology is useful
scant nasal discharges often belie the large volumes of to provide some indication of the likely clinical signifi-
exudate that accumulate in the airway. There is variable cance of bacterial isolates but is less important than
stabled in a dry, well-drained, and well-ventilated dust-

free environment. They should not be bedded on straw,
and hay, if used, should be soaked and fed wet. Pleural
drainage is vital (Fig. 23.13) and supportive IV fluid
therapy for pleural fluid loss and endotoxemia are essential.
Non-steroidal anti-inflammatory drugs improve welfare
and assist in control of the endotoxin-mediated systemic
inflammatory response. Mixed bacterial infections, which
generally include the streptococci, are often involved and
the antibiotic regimen should therefore provide broad-
spectrum activity. A sensible initial regimen is peni-
cillin (22,000 IU/kg q 12 h IM or q.i.d. IV) together with
gentamicin (6.6 mg/kg s.i.d. IM or IV) and metronidazole
(20 mg/kg q.i.d. orally). This may need to be modified
Fig. 23.13. Drainage of pleural fluid from a case of pleuropneumonia. when the results of bacterial culture and sensitivity are
known. Ceftiofur (5 mg/kg q 12 h IM or IV), oxytetracycline
(5 mg/kg s.i.d. or q 12 h IV) or enrofloxacin (5 mg/kg s.i.d.
in IAD. The isolation of anaerobes appears to be asso- IV) can also be used; the latter two are active against
ciated with a poorer prognosis than infections associated Mycoplasma sp. A variety of acute and more chronic com-
only with aerobes. plications may develop. Acute complications include pneu-
mothorax as a result of communication between necrotic
Management lung and the pleural space. More chronic complica-
Pneumonia and pleuropneumonia are usually sporadic tions include pulmonary abscess, mediastinal abscess,
diseases in individual horses with only a small risk of pleural adhesions, pulmonary atelectasis, and fibrosis.
contagious transmission. However, there are anecdotal Great improvements have been made in long-distance
reports of transmission within hospital yards and it horse transport and better understanding of air hygiene
appears sensible to treat affected horses as contagious and requirements, maximum journey times, and management
take appropriate barrier precautions, especially avoiding has greatly reduced the prevalence of equine shipping
direct horse-to-horse contact and taking care with fomites. fever. Disease in hospitals is difficult to prevent except that
Pleuropneumonia in particular requires aggressive horses should be closely monitored for pneumonia/
management and careful monitoring. Affected horses pleuropneumonia after surgical procedures. There are no
require detailed and frequent assessment and conscientious vaccines against the bacteria that cause pneumonia/
nursing. They should be handled sympathetically and pleuropneumonia in adult horses.
Fig. 23.14. Pleural fluid from pleuropneu-

monia cases is purulent and frequently san-
guineous. This pleural fluid yielded a pure
culture of S. equi subsp. zooepidemicus.
•Decreased mucociliary clearance

•Compromised mucosal immunity
•Healthy mucociliary system decreased opsonization,
•Normal mucosal immunity phagocyte chemotaxis or
efficient opsonization, phagocytosis
phagocyte chemotaxis and •Poor air hygiene
phagocytosis •Management stress
•Good air hygiene •Susceptible horse genotype
•No management stress •Up-regulation of bacterial
•Resistant horse genotype virulence factors
•Down-regulation of bacterial
virulence factors
Harmless (non- Harmful (disease-

disease-causing) causing)
resident pathogen
Fig. 23.15. Change in behavior of opportunist pathogens.
Bacteria as opportunist LRT pathogens 1993, 1997, 2005, Christley et al 2001, Ward et at 1998).
A similar spectrum of Gram-positive and Gram-negative
Almost all cases of bacterial LRT disease are caused by bacteria are isolated from foals with bronchopneumonia,
opportunist pathogens that are part of the normal resident horses in training with IAD, and adult horses with
airway flora of many horses. The traditional view of bac- pneumonia/pleuropneumonia, even though the clinical
terial LRT disease as strictly secondary to primary viral presentations of these diseases are different. Streptococcus
infection or pulmonary parasitic migration is almost zooepidemicus is the most prevalent pathogen isolated from
certainly incorrect, although this does apply in some cases, all age groups. In foals S. pneumoniae, Pasteurella sp. and
particularly foals. It is now apparent that bacterial LRT Actinobacillus sp. are also commonly involved although a
disease in all age groups, especially horses in training and variety of other bacteria including Bordetella bronchiseptica,
adults, often occurs without a preceding viral infection, in Klebsiella sp. and E. coli can also be isolated. IAD is most
response to changes in dynamics of the resident air- strongly associated with S. zooepidemicus, S. pneumoniae,
way bacterial population (Newton et al 2003, Wood et al Actinobacillus sp. and Mycoplasma equirhinis infections, but
2005). The triggers that change the behavior of oppor- a large number of other Gram-positive and Gram-negative
tunist bacterial pathogens from non-disease-causing bacteria may be isolated from affected horses. Mixed Gram-
residents to disease-causing pathogens are poorly under- positive/negative and aerobic/anaerobic infections are
stood and probably act in combination. It is highly likely common in pneumonia and pleuropneumonia in mature
that management stresses (overcrowding, poor air hygiene, horses. Streptococcus zooepidemicus, S. pneumoniae, Staphylo-
transport, general anesthesia, hospitalization) act by coccus aureus, Actinobacillus sp., Pasteurella sp., Enterobacter sp.
compromising airway defenses and changing the balance and E. coli are frequently isolated aerobes whilst Bacteroides sp.,
of airway flora (Anzai et al 2002). There is emerging Fusobacterium sp., Clostridium sp., and Peptostreptococcus sp.
evidence that the genotype of the horse may also play a are common anaerobes. Mycoplasma spp. are also impli-
role in LRT disease susceptibility. The advent of bacterial cated as causes of bacterial LRT disease, especially IAD,
genome sequencing and studies of functional genomics usually in association with one or more of the bacteria
has started to unravel the complexities of the regulation listed above but also as single infections (Wood et al 1997).
of bacterial growth, regulation/expression of virulence Mycoplasma equirhinis is most strongly associated with IAD
factors and host–pathogen interactions. Understanding (Wood et al 2005), but other species, including M. felis,
is far from complete but it is now clear that the bac- may also be involved (Wood et al 1997).
teria involved in equine LRT disease are sophisticated
pathogens whose behavior is under complex regulatory
control (Fig. 23.15).
Streptococcus equi subsp. zooepidemicus
Most bacterial LRT infections in horses involve mixed Key factors concerning S. equi subsp. zooepidemicus are
populations of bacteria and mycoplasmas (Wood et al listed in Box 23.6.
Box 23.6. Key facts for Streptococcus equi Box 23.7. Streptococcus zooepidemicus
subsp. zooepidemicus virulence factors
● Gram-positive Lancefield group C β-hemolytic cocci approxi- ● Bacterial cell wall

mately 1 μm in diameter – Peptidoglycan
– Occur as pairs but mostly as chains, depending on cul- ● Hyaluronic acid capsule
ture environment – Isolates usually capsulated in vivo but non-capsulated
– Facultative anaerobes in vitro
– Catalase and oxidase negative ● Surface proteins
– Non-motile and non-spore forming (therefore limited – Extracellular matrix binding proteins
environmental persistence and reservoir of infection) – Antibody binding proteins
● Closely related to S. equi subsp. equi (> 98% genome – M protein
homology with almost identical protein profiles) but has ● Exotoxins
very different biological behavior, i.e.: – Hyaluronidase
– Not host (equine) restricted, infects wide range of – Streptolysin
mammals – Streptokinase
– Mucosal resident and opportunistic pathogen of the – Pyrogenic exotoxins
respiratory tract
– Causes mainly mucosal rather than invasive disease
– Opportunistic pathogen of other sites including skin,
tivitis and keratitis), joints and bone, reproductive tract
cornea, joints, bone, udder, and genitourinary tract
(metritis), and lymph nodes (abscesses) (Hoffman et al
● Culture on horse blood agar plates; selective plates can be
1993). It is also a common cause of septicemia in foals. It
used (horse blood agar supplemented with nalidixic acid
is the most prevalent bacterial pathogen in equine LRT
and colistin sulfate)
disease and opportunistically causes bronchopneumonia
Disease profile in foals, IAD in horses in training, pneumonia/pleuro-
Opportunist pathogen causing: pneumonia in adults, and equine shipping fever (Racklyeft
● Bronchopneumonia in foals & Love 2000, Christley et al 2001, Newton et al 2003,
● IAD in horses in training Wood et al 2005).
● Pneumonia and pleuropneumonia (including equine ship-
ping fever) in adult horses

Virulence factors
Virulence mechanisms
● Bacterial cell wall Steptococcus zooepidemicus is almost identical at a genome
● Hyaluronic acid capsule level to its clonal derivative S. equi with an estimated
● Surface proteins 98% DNA homology between the two subspecies. Despite
● Exotoxins this similarity, the disease profiles of the two bacteria
are markedly different. Streptococcus equi is highly host
Antibiotic resistance adapted, is a primary pathogen of the upper respiratory
Generally sensitive to penicillin and related antibiotics; tract only, is not part of the normal resident URT flora, and
resistance to penicillins is seldom a clinical problem. Also causes invasive disease. In contrast, S. zooepidemicus infects
sensitive to a variety of other antibiotics including tetra- a wide range of hosts and causes disease in most organ
cyclines, trimethoprim–sulfonamide combinations and peptide systems. It is a URT resident and causes mainly mucosal,
antibiotics rather than invasive, disease. The small genome differences
Prevention between these two bacteria are therefore likely to encode
● Transient immunity following natural infection the virulence factors responsible for their different patho-
● No vaccines available genicities and may provide fundamental clues of the
molecular basis of streptococcal biology.
Streptococcus zooepidemicus has been comparatively
Clinical disease poorly studied but appears to possess a very similar panel of
virulence factors to S. equi (Box 23.7).
Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) The peptidoglycan cell wall is a pyrogen and is a key
disease is not confined to the respiratory tract. Overall it is molecule responsible for bacterial recognition by the
the most frequently isolated equine bacterial pathogen and horse’s immune system.
causes disease in most organ systems including skin The hyaluronic acid capsule is an important anti-
(cellulitis and abscesses), conjunctiva and cornea (conjunc- phagocytic mechanism along with the M protein. However,
unlike S. equi where hyaluronic capsule is constitutively adults are triggered by stresses that compromise airway
produced by most isolates, capsule production is variable in defenses including long-distance transport and general
S. zooepidemicus. It appears to be regulated in response to anesthesia. The triggers for induction of IAD are unknown
the environment so that isolates taken directly from the but probably include training stress, crowded environ-
horse’s respiratory tract are generally capsulated but lose ments, and poor air hygiene (Robinson 1997, 2003,
their capsule on culture in the laboratory. Colonies of Christley et al 2001, Newton et al 2003, Wood et al 2005).
S. zooepidemicus have a flat matt appearance on culture There is emerging evidence that horse genotype plays a
plates and are therefore usually different from the rounded, role in disease susceptibility, possibly related to transferrin
shiny, gloss colonies of S. equi. haplotype. Streptococcus zooepidemicus causes a rapidly
Streptococcus zooepidemicus has a similar range of progressive, severe, purulent, necrotizing hemorrhagic
adhesins to S. equi including a number of MSCRAMMs, e.g. pneumonia often accompanied by pleuritis (Oikawa et al
fibronectin binding proteins (Lindmark et al 1996). 1994). In the horse, but not in vitro, the bacteria efficiently
In contrast to the near homogeneous S. equi M protein resist phagocytosis by virtue of their hyaluronic acid
SeM, the S. zooepidemicus M protein SzP shows considerable capsule and are able to persist within the lung despite
variation at both DNA and protein levels (central and phagocyte (mainly neutrophil but also macrophage)
N-terminal regions) between isolates (Walker & Timoney chemotaxis to the site of infection. The extensive cellular
1998). Since the hypervariable SzP is the major immunogen damage (epithelial desquamation, necrosis), hemorrhage,
recognized by the horse’s immune system, there is wide interstitial changes, and pulmonary consolidation are
variation in antigenicity between isolates resulting in little likely to be caused both by exotoxins (especially pro-
cross-protection. SzP is antiphagocytic and prevents C3b teolytic enzymes) and also immunopathology mediated
and IgG opsonization by binding fibrinogen, thus masking by antigen–antibody complexes binding to pulmonary
the C3b binding site, and also by binding the Fc portion of endothelium (Divers et al 1992, Yoshikawa et al 2003).
IgG, making it unavailable to Fc receptors on phagocytes The reasons for the variation in disease severity caused by
(Timoney et al 1997). S. zooepidemicus in different age groups of horse are not
Streptococcus zooepidemicus produces many of the same clear. Similarly there is no information about the possible
exotoxins as S. equi including the hemolytic cytotoxin molecular basis for the differences in pathogenicity between
streptolysin-S and hyaluronidase. It does not produce S. zooepidemicus isolates. It does appear, however that varia-
homologs of the S. equi pyrogenic exotoxins SePE-I and tion in SzP is not responsible for differences in pathogenicity
PsPE-H or the mitogenic leukotoxin. A combination of (Walker & Runyan 2003). Bronchopneumonia in foals and
exotoxins is likely to be responsible for the severe necro- pneumonia/pleuropneumonia/equine shipping fever in
tizing pneumonia that this bacterium produces in foals and adults are sporadic diseases with low morbidity and high
adult horses with shipping fever (Oikawa et al 1994). mortality. In contrast, IAD occurs as outbreaks with high
morbidity and very low mortality. It is possible that the
Pathogenesis difference is, in part, because horses in training experience
less severe compromise to their respiratory tract defenses than
Streptococcus zooepidemicus colonizes the nasopharynx (and sick foals or adults subject to transport or anesthetic stress.
other mucosal sites) in normal horses and is part of the
respiratory tract’s resident flora. The transition from Diagnosis
commensal to disease-causing states is associated with
colonization more distally along the trachea from the Diagnosis is by culture of nasal/nasopharyngeal swabs or
nasopharynx (Anzai et al 2002). As with the other strepto- tracheal/bronchoalveolar lavage samples on blood agar at
cocci, colonization is dependent on binding to epithelial 37°C in 5% CO2. Tracheal/bronchoalveolar lavage samples
cells by adhesins, including MSCRAMMs. Streptococcus should be collected with great care in horses with dyspnea
zooepidemicus is an opportunistic pathogen causing disease and should not be collected from horses with severe
when conditions within the respiratory tract favor dyspnea. Colonies are β-hemolytic, Lancefield group C
bacterial growth. The molecular events regulating the (determined by latex agglutination) and usually non-
switch in behavior from mucosal resident to opportunist capsulated. Confirmation of identity is by sugar fermenta-
pathogen are poorly understood but are likely to be tion tests (S. zooepidemicus ferments sorbitol, lactose, and
multifactorial, highly regulated, and involve changes in ribose but not trehalose).
both host and bacterium (Fig. 23.15).
The factors that trigger S. zooepidemicus-associated Management
bronchopneumonia in foals include primary respiratory
viral infections, poor maternal transfer of immunity, Most isolates are susceptible to the penicillins and these
overcrowding, debilitation, transport, and anesthesia. should be regarded as front-line antibiotics because they
Pneumonia/pleuropneumonia and equine shipping fever in produce a rapid bactericidal effect and achieve the highest
bacteriological cure rates. Other antibiotics including tetra-

Box 23.8. Key facts for Streptococcus pneumoniae
cyclines and macrolides can also be used. Although sensi-
tive to trimethoprim–sulfonamide combinations in vitro, the
● Primarily a human pathogen – equine isolates are a distinct
efficacy of these antibiotics is greatly reduced in the pres-
clonal group
ence of pus because of the high concentrations of folic acid
● Gram-positive cocci, usually occurring as diplococci, with
present in pus.
no assigned Lancefield group
● Capsule polysaccharide defines serotype
Streptococcus pneumoniae – All equine isolates are serotype 3
● Naturally transformable – take up DNA from other bacteria
Key factors concerning S. pneumoniae are listed in Box 23.8.
including:
– Acquisition of new virulence and antibiotic-resistance
Clinical disease
genes
Streptococcus pneumoniae is a major human pathogen that is ● Equine isolates have a variety of culture, biochemical, and
a common cause of pneumonia, otitis media, bacteremia, genetic differences from human isolates:
and meningitis. It is a sporadic cause of bronchopneu- – Equine isolates form elongated chains whereas human
monia in foals (Meyer et al 1992) and also pneumonia/ isolates form diplococci (a pair of cocci)
pleuropneumonia in adults (Chaffin & Carter 1993, Seltzer – Equine isolates are bile insoluble, human isolates are bile
& Byars 1996, Carr et al 1997). Streptococcus pneumoniae soluble
has been identified as one of the principal bacteria, – Equine isolates are non-hemolytic, human isolates are
along with S. zooepidemicus and Actinobacillus sp., asso- α-hemolytic
ciated with IAD in horses in training (Chapman et al 2000, – Equine isolates do not undergo autolysis, human isolates
Wood et al 2005). do
Disease profile
Equine S. pneumoniae isolates
● Common cause of pneumonia, otitis media, and
There are over 80 S. pneumoniae capsular serotypes that meningitis in humans
infect humans but all equine isolates characterized to date ● Causes bronchopneumonia in foals and associated with
belong to capsular serotype 3 (Whatmore et al 1999). IAD in horses in training
Molecular characterization of equine isolates by restriction
Virulence factors
fragment length polymorphism of virulence factor and
● Adhesins
housekeeping encoding genes suggests that equine isolates
● Toxins, but equine isolates lack pneumolysin and autolysin
represent a tight clonal group and are closely related to,
● Capsule
but distinct from, human isolates. There is no evidence that
● Cell wall
equine S. pneumoniae isolates are zoonotic because farm
workers are generally infected with non-equine strains. Antibiotic resistance
There are several important differences between human ● Emerging penicillin resistance in humans, little information
and equine S. pneumoniae isolates. Equine isolates lack two on equine isolates
of the key virulence factors present in human isolates:
Prevention
pneumolysin and autolysin.
● No equine vaccines available
Pneumolysin, encoded by ply, is a hemolytic cytotoxin
responsible for disrupting host cell membranes by binding
cell-membrane-associated cholesterol and creating pores in
host cell membranes, resulting in cell lysis. Unlike the isolates do possess other virulence factors found in human
hemolysins produced by S. equi and S. zooepidemicus, isolates including neuraminidases A and B (encoded by
pneumolysin is not secreted from the bacterial cell but is a nanA, nanB), surface protein A (encoded by pspA) and
cytoplasmic protein released when bacteria lyse. hyaluronidase (encoded by hyl). However, equine isolates
Autolysin, a bile acid (dedeoxycholic acid) activated possess unique alleles for these virulence genes providing
enzyme encoded by lytA, cleaves the peptidoglycan further evidence that isolates from horses form a sub-
bacterial cell wall, lyses the bacteria and releases population distinct from human isolates.
pneumolysin from the cell. The genes ply and lytA are
adjacent within the S. pneumoniae chromosome. However, Pathogenesis
equine isolates lack both pneumolysin and autolysin
activity as the result of a 7-kilobase chromosomal dele- In a proportion of humans and horses, S. pneumoniae
tion of the 3′ region of lytA and the 5′ region of ply, colonizes the nasopharynx and forms part of the
along with the interspersed chromosomal region. Equine resident flora. Colonization is dependent on binding to
epithelial cells by specific surface proteins (adhesins and The apparent limited duration of natural immunity, the
MSCRAMMs). Steptococcus pneumoniae possess a variety of large inter-isolate antigenic variation as a result of SzP
surface adhesins including pneumococcal surface protein A variability and limited extent of cross-protection between
(PspA), pneumococcal surface adhesin, S. pneumoniae isolates do not auger well for the development of vaccines
protein A, and choline-binding protein A. At least one of against this bacterium. It seems unlikely that vaccination
these (PspA) is present in equine isolates. It is an oppor- against S. equi will provide cross-protection against oppor-
tunist pathogen of the respiratory tract. The reasons for tunistic S. pneumoniae infections.
the switch from a carriage to disease-causing phenotype
and the regulatory mechanisms controlling this are not
fully understood but involve changes to host airway
defenses, mucosal immunity, and up-regulation of bacterial
virulence factors.
subsp. equisimilis
Streptococcus pneumoniae produces a variety of toxins, LRT infections with S. dysgalactiae are less common than
the best studied of which is pneumolysin. Human, but not those associated with S. zooepidemicus. Like S. zooepidemicus
equine, isolates produce pneumolysin which, although it is an opportunist pathogen and is part of the resident
regarded as important for virulence in humans and some airway flora in many horses. It also belongs to Lancefield
animal models because of cytotoxic activity, is presumably group C and is β-hemolytic but it is genetically dis-
not important in horses. The polysaccharide capsule is an tinct from both S. equi and S. zooepidemicus. In the diag-
important virulence factor. It is antiphagocytic and acts by nostic laboratory it is distinguished from S. equi and
blocking complement (C3b) and antibody opsonization of S. zooepidemicus by sugar fermentation. There is little
the bacterial cell, thus preventing neutrophil binding detailed information on virulence factors and patho-
to the bacteria and allowing bacterial persistence in the genesis although the bacterium possesses a similar array of
face of neutrophil chemotaxis to the site of infection. The virulence factors as S. equi and S. zooepidemicus including
capsule is a complex and varied polymer of sugars, amino hyaluronic acid capsule, M protein, a variety of adhesins,
acids, and choline; variations in its composition allow and exotoxins including hyaluronidase and fibrinolysin.
different capsular serotypes to be identified. Variation in The pathogenesis of S. dysgalactiae disease is assumed to be
capsular composition also accounts for variations in viru- similar to that for S. zooepidemicus.
lence; whilst acapsular isolates are non-virulent, the
virulence of capsulated isolates varies considerably, with
serotype 3 being one of the most pathogenic serotypes in
humans. The cell wall components lipoteichoic acid and
The Pasteurellaceae (Actinobacillus
peptidoglycan also contribute to pathogenesis by triggering
and Pasteurella sp.)
inflammation. The key facts for the Pasteurellaceae are listed in Box 23.9.
Diagnosis Clinical disease

Diagnosis is by culture of nasal/nasopharyngeal swabs or The Pasteurellaceae (Pasteurella family) comprise Pasteurella,
tracheal lavage samples on blood agar at 37°C in 5% CO2. Actinobacillus, and Haemophilus sp. They are ubiquitous
Equine colonies are usually non-hemolytic, optochin commensals of the URT in all animals and are opportunist
sensitive and are not bile soluble. Further characteriza- pathogens causing LRT disease when host defenses are
tion is by slide agglutination test to detect pneumococcal impaired allowing bacterial growth. In horses Actinobacillus
capsule antigen and serotyping using antibody directed equuli and Pasteurella caballi are commensals of the
against the polysaccharide capsule. URT, especially the nasopharynx and oral cavity, and
are important causes of LRT disease (Ward et al 1998).
Management Haemophilus sp. are rarely implicated in equine LRT disease.
In addition to LRT disease in horses of all ages (Wood et al
Most strains are susceptible to the penicillins and these 1993, Rycroft & Garside 2000), A. equuli is a common
should be regarded as front-line antibiotics because they cause of neonatal septicemia (Raisis et al 1996) and has
produce a rapid bactericidal effect and achieve the highest been associated with a wide range of other infections
bacteriological cure rates. However, penicillin resistance including peritonitis, arthritis, endocarditis, enteritis,
has recently appeared in human isolates as a result of mastitis, and abortion in horses of all ages (Hillyer et al
β-lactamase production and mutations in penicillin- 1990, Peremans et al 1991, Golland et al 1994). Pasteurella
binding proteins. Resistance to these antibiotics is uncom- caballi has been isolated mainly from cases of LRT disease
mon although penicillin-resistant isolates have occasionally in foals, IAD and pneumonia/pleuropneumonia in adult
been reported. There are no equine S. pneumoniae vaccines. horses (Wood et al 1993).
and joint ill while A. equuli subsp. haemolyticus is hemolytic

Box 23.9. Key facts for Pasteurellaceae
and is associated mainly with LRT disease and infections
of other organ systems in older horses. Actinobacillus species
General features
other than A. equuli can also be isolated from cases of
● The Pasteurellaceae family consists of the genera Pasteurella,
equine LRT disease including Actinobacillus genomospecies
Actinobacillus, and Haemophilus
1 and 2 (A. lignieresii). However, it is common practice for
● Actinobacillus sp. and Pasteurella sp. cause LRT disease in
diagnostic laboratories to simply report the isolation of
horses
Actinobacillus sp. and not to identify to species level.
● Aerobic, medium (Actinobacillus sp.) or small (Pasteurella
The most commonly isolated Pasteurella sp. is P. caballi
sp.), Gram-negative rods that frequently stain as coccobacilli
and this has been associated with LRT disease in horses of
(especially Pasteurella sp.)
all ages. Actinobacillus and Pasteurella sp. are commensal
Disease profile bacteria of the URT, nasopharynx, and oral cavity and are
● Primarily respiratory pathogens; Actinobacillus sp. also opportunistic pathogens: biochemical and genetic analysis
cause septicemia in foals and have been associated with a reveals no differences between A. equuli isolates from
wide range of infections in older horses healthy and diseased horses (Sternberg & Brandstrom
● Ubiquitous commensals of the URT and cause respiratory 1999). They are medium (A. equuli) or small (P. caballi)
disease opportunistically when host defenses are impaired Gram-negative rods that often stain as coccobacilli because
(e.g. by stress, transport, training or, occasionally, primary of preferential uptake of stain at the bacterial poles. They
respiratory virus infections) grow on sheep blood agar and produce moderate-sized
● Along with S. zooepidemicus and S. pneumoniae, infec- gray–white colonies. Actinobacillus equuli is either non-
tions by the Pasteurellaceae are responsible for the majority hemolytic (A. equuli subsp. equuli) or hemolytic (A. equuli
of bacterial LRT disease in foals, horses in training and subsp. haemolyticus). Pasteurella caballi is non-hemolytic.
mature horses
Culture characteristics Virulence factors

● Cultured on sheep blood agar
Little is known about virulence factors for A. equuli and
● Catalase and oxidase positive
P. caballi. For other species within the Pasteurellaceae,
● Actinobacillus sp. can be hemolytic or non-hemolytic
the bacterial capsule confers resistance to phagocytosis.
● Pasteurella caballi is non-hemolytic
Lipopolysaccharide, located within the outer membrane of
Virulence determinants the cell wall, is believed to contribute to virulence and
● Capsule to be responsible for the severe clinical signs associated
● Cell wall with septicemia. Although there is no detailed informa-
– Lipopolysaccharide tion about the role of capsule and lipopolysaccharide in
● Secreted proteins A. equuli and P. caballi virulence, it is reasonable to suppose
– Hemolysins that these play a role in pathogenesis. It is also likely that
– Leukotoxins these bacteria produce a variety of exotoxins that dam-
age host defenses, including epithelial cytotoxins, tissue
Antibiotic resistance
degradative (proteolytic) enzymes, and leukotoxins, and,
● Usually sensitive to aminoglycosides and tetracyclines
although these have not been characterized, A. equuli
Prevention cultures do produce a toxin that damages equine neu-
● There are no equine vaccines trophils (Sternberg & Brandstrom 1999). There has been
considerable interest in the hemolytic activity of A. equuli
because of the different disease-causing profiles of the non-
hemolytic (mainly associated with neonatal septicemias)
General features and hemolytic (associated with respiratory and other
diseases in older horses) subspecies and the observation
Historically the common species of Actinobacillus isolated that serum from convalescent horses contains antibody
from horses have been classified as A. equuli, variants directed against hemolysin (Rycroft & Garside 2000).
of A. equuli, A. suis and Bisgaard taxon 11 (Blackall et al Actinobacillus equuli produces a hemolysin belonging to the
1997). The application of DNA sequence comparisons has RTX family of pore-forming toxins (Berthoud et al 2002).
permitted the adoption of a more rational classification The RTX toxins have a series of calcium-binding, glycine-
system. The common equine isolates are now classified as rich peptide repeat units (hence “Repeats in ToXin”) and
either A. equuli subsp. equuli or A. equuli subsp. haemolyticus form pores in host cell membranes destroying the cell or
(Christensen et al 2002). The A. equuli subsp. equuli is impairing its function. RTX toxins act as virulence factors
non-hemolytic and causes mainly neonatal foal septicemia and are directed against the host’s immune cells. High
concentrations kill effector cells in the immune system Pasteurella caballi also grows on sheep blood agar and
(neutrophils, macrophages, and lymphocytes) and low produces similar-sized gray–white, non-hemolytic colonies
concentrations impair phagocytosis and oxidative burst that are oxidase positive, catalase and urease negative and
killing by phagocytes. The A. equuli hemolysin AqxA is that ferment glucose, lactose, maltose, and mannitol.
encoded by the aqxCABD operon (Berthoud et al 2002) and
exhibits selective toxicity to equine leukocytes (Kuhnert Management
et al 2003). Although not characterized, it is likely that
P. caballi also possesses RTX toxins that may resemble the Most isolates are sensitive to aminoglycosides and these,
LktA leukotoxin of other pasteurellas. RTX toxins are thus particularly gentamicin, are generally used as first-choice
candidates as major virulence factors in A. equuli and antibiotics. Resistance to aminoglycosides is not a
P. caballi but it is likely that virulence is multilayered and major clinical problem. A variety of other antibacterials,
conferred by a wide variety of determinants which have yet for example oxytetracycline, ampicillin, trimethoprim–
to be characterized. sulfonamide, cephalosporins, and fluoroquinolones, may be
effective and can be considered as alternatives. Pasteurella
Pathogenesis caballi is often sensitive to penicillin, an unusual feature for
Gram-negative bacteria. There are no equine vaccines
The factors that allow switching of behavior of A. equuli for these organisms.
and P. caballi from respiratory tract commensals to
opportunistic pathogens are not understood but, as is the
case with the other opportunistic respiratory tract bacterial
Mycoplasma spp.
pathogens, they likely involve complex interactions between The key facts for Mycoplasma spp. are listed in Box 23.10.
the horse’s respiratory tract defenses, mucosal immunity
and up-regulation of bacterial virulence factors in response Clinical disease
to changes in the airway environment. Primary virus infec-
tion, injury to respiratory defenses by poor environmental The mycoplasmas are commensal inhabitants of the URT
air hygiene, transport, and general anesthesia stress all and cause disease opportunistically when host defenses are
contribute to create conditions that favor bacterial growth. impaired. They may cause disease as single agents
It is likely that a variety of (uncharacterized) exotoxins (Hoffman et al 1992, Wood et al 1997), but are more
cause epithelial injury exposing the extracellular matrix frequently present as mixed infections with the Streptococci
and providing additional surfaces for bacteria to colonize sp. and Actinobacillus sp. (Wood et al 2005). There are at
and nutrients for growth. Bacteria resist phagocytosis and least seven species of mycoplasmas that colonize the equine
thus persist at the site of infection by means of capsule and URT (Allam & Lemcke 1975) and cause opportunistic LRT
a variety of exotoxins including hemolysin and leukotoxin. disease. Several of these species, such as Mycoplasma felis,
The role of lipopolysaccharide has not been determined but infect other animals as well as horses, while M. equirhinis
it is likely to drive a widespread inflammatory cascade and appears to infect horses only.
is probably partly responsible for the severe systemic signs
associated with A. equuli septicemia. The reasons for the General features
more severe manifestations of A. equuli infection in neonatal
foals (septicemia) compared to older foals and adults (bron- Mycoplasmas are very small bacteria and have many
chopneumonia, IAD, and pneumonia/pleuropneumonia) unusual features (Razin et al 1998). They lack the rigid
are not clear. peptidoglycan cell wall present in other bacteria and
possess only a flexible cytoplasmic membrane with some
Diagnosis resemblance to the outer membrane of Gram-negative
bacteria. This is a bilayer but, unlike the symmetrical
Actinobacillus sp. and P. caballi are difficult to identify on phospholipid bilayer of the Gram-negative bacteria, it is
Gram-stained nasal/nasopharyngeal swabs and tracheal/ asymmetrical with an outer layer of lipoproteins and an
bronchoalveolar lavage samples because of their small size inner layer of phospholipids. The flexible cytoplasmic
and weak uptake of stain. Colonies of A. equuli grow on membrane gives mycoplasmas their distinctive elongated,
sheep blood agar and produce gray–white sticky colonies bipolar, asymmetric shape. One pole is used to attach to
(approximately 2 mm in diameter) which are either hemo- host cells and the other pole is responsible for the
lytic (subsp. haemolyticus) or non-hemolytic (subsp. equuli). gliding movement of these bacteria. They are extracellular
Identification to species level is by demonstration of Gram- bacteria, but grow in close contact with host cells and
negative rods or coccobacilli that are catalase, oxidase, and appear to require host cells for nutrient acquisition,
urease positive and ferment lactose, maltose, mannitol, especially the amino acid arginine, which is used as an
melibiose, sucrose, and trehalose but not arabinose. energy substrate.
ous biosynthetic pathways including the tricarboxylic

Box 23.10. Key facts for Mycoplasma spp.
acid pathway, oxidative phosphorylation, and lipid and amino
synthesis. As a consequence, mycoplasmas are highly fas-
General features
tidious organisms with specific nutrient requirements for
● The mycoplasmas are very small bacteria with the smallest
growth and rely on the animal host to provide many of the
known bacterial genomes
nutrients required for their growth. Their strict nutrient
● They stain poorly, especially with Gram stain; they stain
requirements mean they are found in close association
best with Giemsa
with host cells, typically on the mucous membrane surface
● Consist of two genera: Acholeplasma and Mycoplasma,
in the respiratory tract. They are generally not invasive
with at least seven Mycoplasma species causing equine
bacteria although some species can invade tissues.
LRT disease
Adhesion to respiratory epithelial cells is regulated by
● Species are separated by biochemical profiles and sero-
an organelle (the “attachment organelle”) at one pole of
logical typing
the bacterium together with surface adhesin proteins
Disease profile (“cytadhesins”) embedded within the outer layer of the cell
● Cause opportunist LRT disease in foals, horses in training membrane. A number of these adhesins appear be essential
and mature horses, usually in combination with other for the architecture of the attachment organelle and to
(Gram-positive and Gram-negative) bacteria act as accessory proteins, possibly by providing a scaffold
● Occasionally present as single agents in cases of LRT for the localization and/or maturation of other adhesin
disease proteins (Waldo et al 2005). Several of these mycoplasmal
● The principal equine respiratory pathogens are Mycoplasma adhesin proteins have been characterized including
equirhinis and Mycoplasma felis adhesin MHP1, ciliary adhesin, adhesin P97, and adhesin-
● Mycoplasma equirhinis appears to be associated with like protein P146 from M. hyopneumoniae; adhesin P1
equine respiratory disease only from M. pneumoniae (Krause & Balish 2004); LppS from
● The mycoplasmas also cause opportunistic disease in other M. conjunctivae (Belloy et al 2003); and binding and
sites including the eye and genital tract activation of plasminogen from bovine Group 7 myco-
plasmas (Bower et al 2003). Some surface proteins are
Culture characteristics
known to confer virulence, such as MIA (mycoplasma
● Highly fastidious and require nutrient-rich commercial
immunodominant protein; Tu et al 2005). Specific surface
growth media
adhesin proteins have not been described for M. equirhinis
● Species within the genus Acholeplasma require sterol for
but this mycoplasma is likely to possess a similar array
growth
of adhesins.
● Species within the genus Mycoplasma do not require sterol
Although mycoplasma infection does cause cytotox-
for growth
icity, there is little information about possible exotoxins,
● Both M. equirhinis and M. felis use glucose and hydrolyze
although it seems highly likely that they do produce
arginine
cytotoxins. The outer layer of lipoproteins may act as
Virulence determinants recognition molecules for the horse’s immune system and
● Adhesins drive the inflammatory response. It also seems likely that
● Toxins they produce mitogenic leukotoxins, e.g. M. arthriditis T-cell
● Evasion of phagocytosis mitogen superantigen (Cole & Atkin 1991), although few
Antibiotic resistance of these have been characterized. Hydrogen peroxide
● Sensitive to tetracyclines, macrolides, and aminoglycosides production by Mycoplasma sp. is directly cytotoxic to host
● Resistance is not a clinical problem cells and is important in virulence (Khan et al 2005).
Like many bacteria, mycoplasmas are able to avoid
Prevention phagocytosis and persist at the site of infection despite
● There are no equine vaccines phagocyte chemotaxis. The mechanisms allowing phago-
cytosis evasion have not been elucidated but are likely
to be different from those of other bacteria because the
Virulence factors mycoplasmas do not possess a capsule.
Mycoplasmas have the smallest of all known bacterial Pathogenesis

genomes, less than 1 Mbp in size, and thus encode fewer
than 1000 genes (Razin et al 1998). Not surprisingly Mycoplasmas are present as part of the normal airway
they are comparatively simple organisms and lack many flora in many horses and disease generally occurs opportu-
of the metabolic and regulatory genes possessed by nistically. In farm animals, mycoplasmas can be transmitted
other bacteria. They lack the genes involved in numer- contagiously by aerosol (Cardona et al 2005), possibly over
large distances (Goodwin 1985). Contagious transmission Anzai T, Timoney JE, Kuwamoto Y et al 2002 Polymerase
is also possible in horses and is responsible for group chain reaction-restriction fragment length polymorphism
outbreaks of disease (Wood et al 1997). Mycoplasmas analysis of the SzP gene of Streptococcus zooepidemicus
isolated from the respiratory tract of horses. American
attach to ciliated host epithelial cells using the adhesion Journal of Veterinary Research 63: 1298–1301
organelle and associated adhesion proteins located at the Belloy L, Vilei EM, Giacometti M et al 2003 Characteriza-
adhesion pole of the bacterial cell. Like the Bordetellae, tion of LppS, an adhesin of Mycoplasma conjunctivae.
attachment to ciliated cells causes ciliostasis and epithelial Microbiology 149: 185–193
cell depolarization. Induction of ciliostasis allows further Berthoud H, Frey J, Kuhnert P 2002 Characterization of Aqx
and its operon: the hemolytic RTX determinant of
bacterial attachment and colonization of the airway. Actinobacillus equuli. Veterinary Microbiology 87: 159–174
Mycoplasmas induce cytotoxicity, by release of hydrogen Blackall PJ, Bisgaard M, McKenzie RA 1997 Characterisation
peroxide and a range of exotoxins, and induce an intense of Australian isolates of Actinobacillus capsulatus, A.
inflammatory response, possibly in response to the outer equuli, P. caballi and Bisgaard taxa 9 and 11. Australian
layer of lipoproteins, which initiates most of the airway Veterinary Journal 75: 52–55
Boschwitz JS, Timoney JF 1994 Inhibition of C3 deposition on
and pulmonary pathology. The host immune response is Streptococcus equi subsp. equi by M protein: a mechanism
effectively avoided by uncharacterized phagocytosis evasion for survival in equine blood. Infection and Immunity
mechanisms and leukotoxins. 62: 3515–3520
Bower K, Djordjevic SP, Andronicos NM et al 2003 Cell surface
antigens of Mycoplasma species bovine group 7 bind
Diagnosis to and activate plasminogen. Infection and Immunity
71: 4823–4827
Direct microscopy of nasal/nasopharyngeal swabs and Cardona AC, Pijoan C, Dee SA 2005 Assessing mycoplasma
tracheal/bronchoalveolar lavage samples is usually not hyopneumoniae aerosol movement at several distances.
diagnostic because of the weak and inconsistent stain Veterinary Record 156: 91–92
uptake by mycoplasmas and their pleiomorphism. In Carr EA, Carlson GP, Wilson WD et al 1997 Acute hemor-
rhagic pulmonary infarction and necrotizing pneumonia
culture, mycoplasmas produce “fried-egg” microcolonies in horses: 21 cases (1967–1993). Journal of the American
(< 0.6 mm) on agar plates. They are digitonin sensitive Veterinary Medical Association 210: 1774–1778
and urease negative. Identification of mycoplasmas to Chaffin MK, Carter GK 1993 Equine bacterial pleuropneu-
the species level is achieved by further biochemical monia. I: Epidemiology, pathophysiology and bacterial
characteristics. Fluorescent antibody and enzyme-linked isolates. Compendium on Continuing Education for the
Practicing Veterinarian 15: 1642–1650
immunosorbent assays can be used in tissue sections to Chanter N, Collin N, Holmes N et al 1997 Characterization of
detect mycoplasma antigens. Serology can be used to detect the Lancefield group C Streptococcus 16S-23S RNA gene
species-specific antibodies against Mycoplasma in convales- intergenic spacer and its potential for identification
cent horse serum. and sub-specific typing. Epidemiology and Infection
118: 125–135
Chanter N, Talbot NC, Newton JR et al 2000 Streptococcus equi
Management with truncated M-proteins isolated from outwardly
healthy horses. Microbiology 146: 1361–1369
Mycoplasmas are resistant to the penicillins but are sen- Chapman PS, Green C, Main JP et al 2000 Retrospective study
sitive to a variety of antibiotics, the most suitable for equine of the relationships between age, inflammation and the
use being the tetracyclines and fluoroquinolones. Antibiotic isolation of bacteria from the lower respiratory tract of
thoroughbred horses. Veterinary Record 146: 91–95
resistance is not a major clinical problem, possibly because Christensen H, Bisgaard M, Olsen JE 2002 Reclassification of
the small genome size of the mycoplasmas limits their equine isolates previously reported as Actinobacillus
capacity for gene acquisition. There are no equine myco- equuli, variants of A. equuli, Actinobacillus suis or Bisgaard
plasma vaccines. taxon 11 and proposal of A. equuli subsp. equuli subsp.
nov. and A. equuli subsp. haemolyticus subsp. nov.
International Journal of Systematic and Evolutionary
REFERENCES Microbiology 52: 1569–1576
Christley RM, Hodgson DR, Rose RJ et al 2001 A case-control
Al-Ghamdi GM, Kapur V, Ames TR et al 2000 Use of repeti- study of respiratory disease in Thoroughbred race-
tive sequence-based polymerase chain reaction for horses in Sydney, Australia. Equine Veterinary Journal
molecular epidemiologic: analysis of Streptococcus equi 33: 256–264
subspecies equi. American Journal of Veterinary Research Cole BC, Atkin CL 1991 The Mycoplasma arthritidis T-cell
61: 699–705 mitogen, MAM: a model superantigen. Immunology
Allam NM, Lemcke RM 1975 Mycoplasmas isolated from Today 12: 271–276
the respiratory tract of horses. Journal of Hygiene Dalgleish R, Love S, Pirie HM et al 1993 An outbreak of strangles
74: 385–407 in young ponies. Veterinary Record 132: 528–531
Anzai T, Timoney JF, Kuwamoto Y et al 1999 In vivo Divers TJ, Timoney JF, Lewis RM et al 1992 Equine glomeru-
pathogenicity and resistance to phagocytosis of lonephritis and renal failure associated with complexes of
Streptococcus equi strains with different levels of capsule group-C streptococcal antigen and IgG antibody. Veterinary
expression. Veterinary Microbiology 67: 277–286 Immunology and Immunopathology 32: 93–102
Fintl C, Dixon PM, Brazil TJ et al 2000 Endoscopic and bac- Khan LA, Miles RJ, Nicholas RA 2005 Hydrogen peroxide
teriological findings in a chronic outbreak of strangles. production by Mycoplasma bovis and Mycoplasma
Veterinary Record 147: 480–484 agalactiae and effect of in vitro passage on a Mycoplasma
Flanagan J, Collin N, Timoney J et al 1998 Characterization of bovis strain producing high levels of H2O2. Veterinary
the haemolytic activity of Streptococcus equi. Microbial Research Communications 29: 181–188
Pathogenesis 24: 211–221 Krause DC, Balish MF 2004 Cellular engineering in a
Galan JE, Timoney JF 1985a Immune complexes in pur- minimal microbe: structure and assembly of the ter-
pura hemorrhagica of the horse contain IgA and M minal organelle of Mycoplasma pneumoniae. Molecular
antigen of Streptococcus equi. Journal of Immunology Microbiology 51: 917–924
135: 3134–3137 Kuhnert P, Berthoud H, Straub R et al 2003 Host cell specific
Galan JE, Timoney JF 1985b Mucosal nasopharyngeal activity of RTX toxins from haemolytic Actinobacillus
immune responses of horses to protein antigens of equuli and Actinobacillus suis. Veterinary Microbiology
Streptococcus equi. Infection and Immunity 47: 623–628 92: 161–167
Galan JE, Timoney JF 1987 Molecular analysis of the M Lancefield RC 1933 A serological differentiation of human and
protein of Streptococcus equi and cloning and expression other hemolytic streptococci. Journal of Experimental
of the M protein gene in Escherichia coli. Infection and Medicine 57: 571–595
Immunity 55: 3181–3187 Lindmark H, Guss B 1999 SFS, a novel fibronectin-binding
George JL, Reif JS, Shideler RK et al 1983 Identification of protein from Streptococcus equi, inhibits the bind-
carriers of Streptococcus equi in a naturally infected herd. ing between fibronectin and collagen. Infection and
Journal of the American Veterinary Medical Association Immunity 67: 2383–2388
183: 80–84 Lindmark H, Jacobsson K, Frykberg L et al 1996 Fibronectin-
Golland LC, Hodgson DR, Hodgson JL et al 1994 Peritonitis binding protein of Streptococcus equi subsp. zooepidemicus.
associated with Actinobacillus equuli in horses: 15 cases Infection and Immunity 64: 3993–3999
(1982–1992). Journal of the American Veterinary Lindmark H, Nilsson M, Guss B 2001 Comparison of the
Medical Association 205: 340–343 fibronectin-binding protein FNE from Streptococcus equi
Goodwin RF 1985 Apparent reinfection of enzootic-pneumonia- subspecies equi with FNZ from S. equi subspecies
free pig herds: search for possible causes. Veterinary zooepidemicus reveals a major and conserved difference.
Record 116: 690–694 Infection and Immunity 69: 3159–3163
Grant ST, Efstratiou A, Chanter N 1993 Laboratory diagnosis Meyer JC, Koterba A, Lester G et al 1992 Bacteraemia
of strangles and the isolation of atypical Streptococcus and pneumonia in a neonatal foal caused by Strepto-
equi. Veterinary Record 133: 215–216 coccus pneumoniae type 3. Equine Veterinary Journal
Hamlen HJ, Timoney JF, Bell RJ 1994 Epidemiologic and 418: 407–410
immunologic characteristics of Streptococcus equi infec- Muhktar MM, Timoney JF 1988 Chemotactic response of
tion in foals. Journal of the American Veterinary Medical equine polymorphonuclear leucocytes to Streptococcus
Association 204: 768–775 equi. Research in Veterinary Science 45: 225–229
Harrington DJ, Sutcliffe IC, Chanter N 2002 The molecular Newton JR, Wood JL, Dunn KA et al 1997 Naturally occurring
basis of Streptococcus equi infection and disease. Microbes persistent and asymptomatic infection of the guttural
and Infection 4: 501–510 pouches of horses with Streptococcus equi. Veterinary
Hillyer MH, Mair TS, Holmes JR 1990 Bacterial endocarditis in Record 140: 84–90
a Shire mare. Equine Veterinary Education 2: 5–7 Newton JR, Verheyen K, Talbot NC et al 2000 Control of
Hoffman AM, Staempfli HR, Prescott JF et al 1991 Field strangles outbreaks by isolation of guttural pouch
evaluation of a commercial M-protein vaccine against carriers identified using PCR and culture of Streptococcus
Streptococcus equi infection in foals. American Journal of equi. Equine Veterinary Journal 32: 515–526
Veterinary Research 52: 589–592 Newton JR, Wood JL, Chanter N 2003 A case control study of
Hoffman AM, Baird JD, Kloeze HJ et al 1992 Mycoplasma felis factors and infections associated with clinically apparent
pleuritis in two show-jumper horses. Cornell Veterinarian respiratory disease in UK Thoroughbred racehorses.
82: 155–162 Preventative Veterinary Medicine 60: 107–132
Hoffman AM, Viel L, Prescott JF et al 1993 Association of Oikawa M, Kamada M, Yoshikawa Y et al 1994 Pathology of
microbiologic flora with clinical, endoscopic, and pul- equine pneumonia associated with transport and
monary cytologic findings in foals with distal respiratory isolation of Streptococcus equi subsp. zooepidemicus.
tract infection. American Journal of Veterinary Research Journal of Comparative Pathology 111: 205–212
54: 1615–1622 Peremans K, Verschooten F, De Moor A et al 1991 Mono-
Jacobs AA, Goovaerts D, Nuijten PJ et al 2000 Investigations articular infectious arthritis in the horse. Journal of
towards an efficacious and safe strangles vaccine: sub- Equine Veterinary Science 11: 27–32
mucosal vaccination with a live attenuated Streptococcus Prescott JF, Srivastava SK, deGannes R et al 1982 A mild form
equi. Veterinary Record 147: 563–567 of strangles caused by an atypical Streptococcus equi.
Jorm LR 1990 Strangles in horse studs: incidence, risk factors Journal of the American Veterinary Medical Association
and effect of vaccination. Australian Veterinary Journal 180: 293–299
67: 436–439 Pusterla N, Watson JL, Affolter VK et al 2003 Purpura
Jorm LR 1991 Laboratory studies on the survival of Strepto- haemorrhagica in 53 horses. Veterinary Record 153:
coccus equi subspecies equi on surfaces. In: Plowright W, 118–121
Rossdale PD, Wade JF (editors) Equine Infectious Diseases Quinn PJ, Carter ME, Markey BK et al 1994 Clinical Veteri-
VI: Proceedings of the VI International Conference. nary Microbiology, 1st edn. Mosby-Year Book Europe,
R & W Publications, Newmarket, pp.39–43. London.
Racklyeft DJ, Love DN 2000 Bacterial infection of the lower Timoney JF 1999 Equine strangles: 1999. Proceedings of the
respiratory tract in 34 horses. Australian Veterinary Association of American Equine Practitioners 45: 31–37
Journal 78: 549–559 Timoney JF, Artiushin SC 1997 Detection of Streptococcus equi
Raisis AL, Hodgson JL, Hodgson DR 1996 Equine neo- in equine nasal swabs and washes by DNA amplification.
natal septicaemia: 24 cases. Australian Veterinary Veterinary Record 141: 446–447
Journal 73: 137–140 Timoney JF, Artiushin SC, Boschwitz JS 1997 Comparison
Razin SD, Yogev D, Naot Y 1998 Molecular biology and of the sequences and functions of Streptococcus equi
pathogenicity of mycoplasmas. Microbiology and Molecular M-like proteins SeM and SzPSe. Infection and Immunity
Biology Reviews 62: 1094–1156 65: 3600–3605
Robinson NE 1997 Pathogenesis and management of airway Todd AG 1910 Strangles. Journal of Comparative Pathology
disease. Proceedings of the American Association of and Therapeutics 28: 212–229
Equine Practitioners 43: 106–115 Tu AH, Clapper B, Schoeb TR et al 2005 Association of a
Robinson NE 2003 Inflammatory airway disease: defining the major protein antigen of Mycoplasma arthriditis with
syndrome. Conclusions of the Havemeyer Workshop. virulence. Infection and Immunity 73: 245–249
Equine Veterinary Education 15: 61–63 Verheyen K, Newton JR, Talbot NC et al 2000 Elimination of
Rycroft AN, Garside LH 2000 Actinobacillus species and their guttural pouch infection and inflammation in asympto-
role in animal disease. Veterinary Journal 159: 18–36 matic carriers of Streptococcus equi. Equine Veterinary
Seltzer KL, Byars TD 1996 Prognosis for return to racing Journal 32: 527–532
after recovery from infectious pleuropneumonia in Waldo RH, Jordan JL, Krause DC 2005 Identification and
Thoroughbred horses: 70 cases (1984–1989). Journal complementation of a mutation associated with loss of
of the American Veterinary Medical Association 208: Mycoplasma pneumoniae virulence-specific proteins B and
1300–1301 C. Journal of Bacteriology 187: 747–751
Sheoran AS, Sponseller BT, Holmes MA et al 1997 Serum Walker JA, Timoney JF 1998 Molecular basis of variation
and mucosal antibody isotype responses to M-like in protective SzP proteins of Streptococcus zooepidemicus.
protein (SeM) of Streptococcus equi in convalescent American Journal of Veterinary Research 59: 1129–1133
and vaccinated horses. Veterinary Immunology and Walker JA, Timoney JF 2002 Construction of a stable non-
Immunopathology 59: 239–251 mucoid deletion mutant of the Streptococcus equi Pinnacle
Smith H 1994 Reactions to strangles vaccination. Australian vaccine strain. Veterinary Microbiology 89: 311–321
Veterinary Journal 71: 257–258 Walker RL, Runyan CA 2003 Identification of variations in
Spoormakers TJ, Ensink JM, Goehring LS et al 2003 Brain SzP proteins of Streptococcus equi subspecies zooepidemicus
abscesses as a metastatic manifestation of strangles: and the relationship between protein variants and
symptomatology and the use of magnetic resonance clinical signs of infection in horses. American Journal of
imaging as a diagnostic aid. Equine Veterinary Journal Veterinary Research 64: 976–981
35: 146–151 Ward CL, Wood JLN, Houghton SB et al 1998 Actinobacillus
Sternberg S, Brandstrom B 1999 Biochemical fingerprint- and Pasteurella species isolated from horses with lower
ing and ribotyping of isolates of Actinobacillus equuli airway disease. Veterinary Record 143: 277–279
from healthy and diseased horses. Veterinary Microbiology Whatmore AM, King SJ, Doherty NC et al 1999 Molecular
66: 53–65 characterization of equine isolates of Streptococcus
Sweeney CR, Whitlock RH, Meirs DA et al 1987 Complications pneumoniae: natural disruption of genes encoding the
associated with Streptococcus equi infection on a horse virulence factors pneumolysin and autolysin. Infection
farm. Journal of the American Veterinary Medical and Immunity 67: 2776–2782
Association 191: 1446–1448 Wilson DW 1988 Streptococcus equi infections (strangles) in
Sweeney CR, Benson CE, Whitlock RH et al 1989 Description horses. Equine Practice 10: 12–25
of an epizootic and persistence of Streptococcus equi Wood JLN, Burrell MH, Roberts CA et al 1993 Strepto-
infections in horses. Journal of the American Veterinary cocci and Pasteurella spp. associated with disease of the
Medical Association 194: 1281–1286 equine lower respiratory tract. Equine Veterinary Journal
Sweeney CR, Timoney JF, Newton JR et al 2005 Streptococcus 25: 314–318
equi infections in horses: Guidelines for treatment, control Wood JL, Chanter N, Newton JR et al 1997 An outbreak of
and prevention of strangles. Journal of Veterinary Internal respiratory disease in horses associated with Mycoplasma
Medicine 19: 123–134 felis infection. Veterinary Record 140: 388–391
Takai S, Anzai T, Yashiro H et al 2000 Detection of DNA Wood JL, Newton JR, Chanter N et al 2005 Association
restriction fragment polymorphisms in Streptococcus equi. between respiratory disease and bacterial and viral
Veterinary Record 146: 159–161 infections in British racehorses. Journal of Clinical
Timoney JF 1988a Protecting against strangles: a contem- Microbiology 43: 120–126
porary view. Equine Veterinary Journal 20: 392–394 Woolcock JB 1975 Studies in atypical Streptococcus equi.
Timoney JF 1988b Shedding and maintenance of Streptococcus Research in Veterinary Science 19: 115–119
equi in typical and atypical strangles. In: Powell DG Yelle MT 1987 Clinical aspects of Streptococcus equi infection.
(editor) Equine Infectious Diseases V: Proceedings of the Equine Veterinary Journal 19: 158–162
V International Conference. The University Press of Yoshikawa H, Yasu T, Ueki H et al 2003 Pneumonia in horses
Kentucky, Lexington, Kentucky, pp.28–33 induced by intrapulmonary inoculation of Streptococcus
Timoney JF 1993 Strangles. Veterinary Clinics of North equi subsp. zooepidemicus. Journal of Veterinary Medical
America; Equine Practice 9: 365–374 Science 65: 787–792
Rhodococcus equi Foal Pneumonia
24 Noah D Cohen and Ronald J Martens
presence without the remainder of the plasmid is not re-

Introduction
sponsible for virulence (Giguere et al 1999). The 85–90-kb
Pneumonia is an important cause of disease and death virulence-associated plasmid is not commonly associated
in foals. Although conflicting data exist, pneumonia with R. equi isolated from diseased, non-equine hosts,
caused by Rhodococcus equi is considered to be the most including human patients with acquired immunodefi-
common cause of severe pneumonia among foals from ciency syndrome.
1 to 6 months of age (Hoffman et al 1993, Takai 1997). Pneumonia caused by R. equi appears to occur sporadi-
The disease is of veterinary importance for a number of cally at some breeding farms, other farms appear to have
reasons: regular recurrent problems with the disease (hereafter
referred to as endemic farms), while some breeding farms
● Prevalence and case-fatality rates can be high (Chaffin
do not experience problems with the disease (Prescott
et al 2003a).
1991). Although data regarding temporal fluctuations
● Treatment is generally prolonged, expensive, associated
in prevalence of R. equi pneumonia at a large number of
with adverse effects, and not uniformly successful
endemic farms are lacking, evidence exists of year-to-year
(Giguere 2001).
variation in the prevalence. There are a number of putative
● Rhodococcus equi pneumonia may negatively impact
explanations for changes in the prevalence of R. equi
future athletic performance (Ainsworth et al 1998).
pneumonia between years at a farm, including health and
● Breeding farms reputed to have a problem with R. equi
other management practices and climatic conditions. The
pneumonia often suffer loss of clients.
variation in prevalence among farms and years makes it
The purpose of this chapter is to review the epidemi- difficult to obtain accurate estimates of the prevalence of
ology, clinical signs, diagnosis, treatment, prognosis, and the disease. The median prevalence at 32 affected farms in
control and prevention for this disease. Texas was 7% (range 1–100%), and more than half the
farms had ≤ 10% of foals affected; the case mortality
proportion was 29% (Chaffin et al 2003a). The prevalence
Epidemiology
at 65 affected farms in the USA (including Texas) among
Rhodococcus equi is a Gram-positive, soil-saprophytic, facul- 5,230 foals was 13%, and the case mortality rate was
tatively intracellular pathogen that survives and proliferates only 8%.
in alveolar and other macrophages. The bacterium has a The reasons that some farms are affected recurrently
worldwide distribution. It shares many microbiologic and and more severely than others remain unclear. Epidemi-
pathogenic characteristics with Mycobacterium tuberculosis, ology of infectious diseases is often considered in light of
the causative agent of tuberculosis in humans (Prescott the effects of the environment, agent, and host. A possible
1991). Similar to M. tuberculosis, the ability of R. equi to explanation for variation in prevalence of disease among
replicate within, and destroy, macrophages is the basis for farms is that environmental exposure is greater at affected
its pathogenicity and for the resulting granulomatous than unaffected farms. However, conflicting data exist
lesions. The presence of an 85–90-kilobase (kb) plasmid regarding this hypothesis. The prevalence of R. equi in the
has been strongly associated with virulence, on the basis of feces of mares was similar for two farms with recent cases
clinical and experimental observations (Takai et al 1991a, of R. equi (14%) and an unaffected control farm (31%)
Takai 1997). This plasmid encodes the production of in Kansas (Debey & Bailie 1987). In a study of two breed-
several virulence-associated protein antigens (e.g. VapA ing farms in Japan, prevalence of virulent organisms was
and VapC–VapH) (Byrne et al 2001). VapA is surface- greater among foals at an R. equi-endemic farm than
expressed, while VapC, VapD, and VapE are secreted. among foals at an unaffected farm, but there was no
The expression characteristics of VapF, VapG, and VapH difference in the prevalence of virulent isolates in the feces
have not yet been described. VapA, which has been most of dams of foals from the two farms (14% and 16%,
extensively studied, is associated with virulence, but its respectively) (Takai et al 1991b). In a study of 66 farms in
355
356 24 Rhodococcus equi Foal Pneumonia
Texas, R. equi was isolated from the soil of 85% of affected link infections to a given site or region on the basis of analy-
farms and 73% of unaffected farms, and virulent R. equi sis of isolates by use of genotyping of chromosomal DNA.
was isolated from the soil of 32% of affected farms and Considered together, the preceding findings indicate
21% of unaffected farms (Martens et al 2000). These that host factors rather than environmental factors or
differences were not significant, indicating that culturing farm-specific virulent strains may explain why some foals
soil to recover R. equi or virulent R. equi could not be used are affected while others remain unaffected at farms in
to differentiate affected from unaffected farms. This study, which there is exposure of foals to virulent (VapA-positive)
however, did not quantify the number of organisms in soil isolates. Data regarding foal-level risk factors associ-
samples. In Japan, studies using the combination of ated with R. equi pneumonia are scant. It has been pro-
quantitative culture and subsequent detection of either the posed that percutaneous invasion by third-stage larvae of
VapA protein or its plasmid indicate that there is greater Strongyloides westeri facilitates invasion by the bacterium
environmental contamination at endemic farms than and subsequent disease development. To date, studies of
at unaffected farms (Takai et al 1991b). Although it is foal-level factors have only identified characteristics that
plausible that increased environmental exposure increases relate to farm management as predisposing to disease
risk of infection and disease, one must also consider that (Chaffin et al 2003c). Given that horses older than foals
infected animals are more likely to shed the organism in appear to be resistant to infection, and given that R. equi
their feces and that greater environmental contamination is most often an opportunistic infectious disease in other
may be a result rather than a cause of disease. The timing species, it is plausible that the immunity of affected foals
of assessment of such exposure is important because there is different from that of foals that do not develop R. equi
appear to be seasonal influences on shedding and the pneumonia. Recently, it was determined that foals with
organism is amplified in the intestinal tract of foals, and ratios of peripheral blood CD4+ : CD8+ lymphocytes that
their shedding increases with age (Takai 1997). were < 3 during the first month of life were significantly
The environment and characteristics of affected farms more likely to develop R. equi pneumonia than foals from
differ from those of unaffected farms. Generally, affected the same farm that had ratios ≥ 3 (Chaffin et al 2004).
farms are larger in size, population, and, often, stocking Further studies are needed to elucidate underlying immu-
density than unaffected farms (Chaffin et al 2003a); how- nologic differences between affected and unaffected foals.
ever, this may simply indicate that these farms have more Anecdotally, some mares at endemic farms are known to
opportunity to have individuals affected with any disease. have multiple affected foals. If true, this observation has at
The desirable health management practices (such as rou- least two explanations: (1) there is a genetic contribution to
tinely testing and treating foals for failure of passive predisposition to susceptibility; or (2) mares may be a
transfer of immunity) that are commonly used at breeding source of infection for their foals. Evidence exists that
farms are not effective for controlling or preventing R. equi iron is important for the growth of R. equi and for expres-
pneumonia (Chaffin et al 2003b). To date, evidence indi- sion of the virulence factor VapA. Sources from which, and
cates that soil geochemistry does not differ between affected mechanisms by which, R. equi acquires iron in vivo may
and unaffected farms (Martens et al 2002a). contribute to the pathogenesis of infection. Evidence exists
Isolates of R. equi have been compared using DNA that transferrin genotypes differ between affected and
fingerprinting (genotyping) methods. Restriction frag- unaffected foals. Polymorphisms in certain genes such
ment length polymorphisms have been used to identify as the Nramp1 gene have been associated with suscep-
geographic differences in the distribution of virulence tibility to intracellular bacteria, including organisms closely
plasmids of R. equi isolates from five countries. While this related to R. equi such as mycobacteria. However the
method may be useful for molecular epidemiologic studies authors have recently demonstrated that mice in which
of virulent R. equi, it is not highly discriminating and thus the Nramp1 gene is functionally deleted were not more
cannot be used to provide strong evidence of a link susceptible to infection with virulent R. equi than wild-type
between isolates from a given region. Using pulsed-field mice possessing the gene. Polymorphisms in the Nramp1
gel electrophoresis (a more discriminating genotyping gene have been described in horses, and it is possible that
method), it is generally not possible to establish a genotypic other genes related to the host immune response are
link among isolates on the basis of source, time-point, associated with predisposition to R. equi pneumonia.
or location (Cohen et al 2003). Isolates from different It is also possible that mares are a source of R. equi for
continents may be as similar to one another as isolates their foals. Rhodococcus equi can be isolated commonly
from the same country or region within the country. from the feces of mature horses and the organism can
Furthermore, isolates from the same farm are rarely multiply in the feces of horses (Takai 1997). Although the
identical over time and the isolates found at farms may bacterium can survive and multiply in soil, it has been
change over time. Thus it appears that diverse arrays of proposed that R. equi is maintained primarily in the intes-
isolates of R. equi that are capable of causing disease are tinal tract of horses. In a study of 43 foals from two farms
widely distributed. Consequently, it will rarely be possible to in Japan (Takai et al 1986), the prevalence of fecal shedding
24 Rhodococcus equi Foal Pneumonia 357
was high among foals both from an R. equi-endemic farm

(94%) and a farm with no history of R. equi pneumonia
(73%). Evidence exists that there can be seasonal variations
of fecal shedding of R. equi by mares, with increases occur-
ring during the spring. The mean number of organisms
shed by mares during the five 1-week periods before and
after foaling was similar. Given the high prevalence of fecal
shedding by dams, the large volume of feces passed by adult
horses, the increased prevalence of shedding by mares
reported in the spring (foaling season), and the fact that
many foals are coprophagic, it is plausible that the dam
may be an important source of infection for foals.
The age at which foals become infected is unknown.
Knowing this information is important because it has
implications for control and prevention. Current dogma Fig. 24.1. Mesenteric pyogranuloma caused by Rhodococcus equi in a
asserts that foals become infected at around the time foal (being held by the surgeon’s left hand). These lesions often
progress in the face of appropriate antimicrobial therapy, and foals
maternal antibody wanes. The principal rationales for this
with intra-abdominal pyogranulomas generally have a poor prognosis.
hypothesis are that administration of hyperimmune plasma
is partially protective (see section on Control and Preven-
tion, p. 362) and that the distribution of ages at onset of
R. equi is similar to the timing of declining maternal generally appears to progress over a period of weeks. Foals
antibody concentrations in foals. Although this thinking may become lethargic, lose their appetite, become febrile,
is plausible and possibly correct, it may also be wrong. and have increases in respiratory rate and effort. The pres-
Evidence exists that immunoglobulin can modulate cell- ence of cough and nasal discharge is inconsistent. Some
mediated immunity, such that the protective mechanism foals appear to experience either a more rapid progression
of hyperimmune plasma administration might not relate to of the disease or a more rapid progression to severe pul-
strictly humoral effects. Although the typical age at onset monary disease, sometimes in association with concurrent
of pneumonia caused by R. equi is coincident with the age infection with Pneumocystis carinii.
at which maternal antibody is approaching its nadir in Extrapulmonary disorders also commonly occur with
foals, development of this pyogranulomatous disease is R. equi infection of foals. Approximately two-thirds of
likely insidious and therefore infection is likely to occur affected foals admitted to a teaching hospital had at least
weeks before the development of clinical signs. Our group one extrapulmonary disorder (Chaffin & Martens 1997).
has advanced an alternative hypothesis, namely that foals Intra-abdominal problems are among the more common
become infected very early in life (Horowitz et al 2001). extrapulmonary disorders, and include intra-abdominal
Consistent with this hypothesis, R. equi can be isolated lymphadenitis, granulomatous enterocolitis/typhlitis, diar-
from the feces of foals < 1 week of age, indicating that foals rhea, and peritonitis. Approximately 50% of affected foals
are exposed early in life (Takai et al 1986). The concept of that were examined post-mortem had intra-abdominal
early infection first occurred to one of the authors (R.J.M.) lymphadenitis/lymphatic abscessation (Fig. 24.1) (Zink
when he observed that it was easier to experimentally infect et al 1986). Clinical signs associated with intra-abdominal
foals before 2 weeks of age than it was to infect older foals, abscesses are often non-specific, and include failure to
suggesting that younger foals might be particularly sus- thrive, lethargy, fever, and diarrhea. Intra-abdominal lesions
ceptible to infection. Irrespective of susceptibility, we have caused by R. equi may progress in the face of successful
reported epidemiologic evidence that is consistent with treatment of pneumonia caused by the bacterium.
foals being infected very early in life. This evidence was Another common extrapulmonary disorder is polysyno-
based on the distribution of the ages of onset and ages of vitis (Fig. 24.2), possibly as the result of immune-complex
death being logarithmically normal, consistent with infec- deposition, and most commonly involving the tarsocrural,
tion at or around the time of birth (Horowitz et al 2001). femoropatellar and carpal joints. Lameness is generally
mild such that joint effusion is often the only clinical sign
observed. Dissemination (presumably hematogenous) can
Clinical Signs occasionally result in osteomyelitis or septic arthritis.
Rhodococcus equi is most commonly recognized as causing Clinical signs are referable to the site of the affected
pneumonia in foals. Clinical signs are often insidious, such bone; for example, ataxia has been reported in associa-
that early signs of disease are subtle, inconsistent, and tion with vertebral body osteomyelitis in foals and cauda
non-specific, including low-grade fever, exercise intoler- equina syndrome has been reported in association with
ance, and a mildly increased respiratory rate. The disease diskospondylitis and a paravertebral abscess in a foal.
Table 24.1. Extrapulmonary disorders occurring with

Rhodococcus equi infection
Common
Abdominal lymphadenitis
Granulomatous enterocolitis/typhlitis with or without
diarrhea
Peritonitis
Less common
Osteomyelitis
Septic arthritis
Diskospondylitis
Paravertebral abscessation
Pleuritis
Uveitis/keratouveitis/panophthalmitis
Mediastinal lymphadenitis
Hepatic pyogranuloma
Immune-mediated hemolytic anemia
Immune-mediated thrombocytopenia
Pericarditis
Guttural pouch empyema
Granulomatous laryngitis
Septic sinusitis
Pyogranulomatous dermatitis
Telogen effluvium
Pyelonephritis
Fig. 24.2. Polysynovitis affecting the tarsocrural joints of a foal with

Rhodococcus equi pneumonia.
findings, clinicopathologic testing, and diagnostic imaging
of the thorax. The disease is most commonly reported in
A number of other extrapulmonary disorders have been foals aged 1–3 months, but we and others have seen cases
reported (see Table 24.1). with mild lesions in foals as young as 10–17 days of age
One important aspect of extrapulmonary disorders is (Prescott et al 1989, Horowitz et al 2001). Farm history
that they may become manifest before signs of respiratory is important because it will influence the probability that
tract disease; extrapulmonary disorders for which this is a foal with certain findings has R. equi pneumonia, and
most common include immune-mediated polysynovitis, consequently, the extent of diagnostic efforts by the veteri-
diarrhea, osteomyelitis, and septic arthritis. Extrapulmonary narian. For example, typical radiographic findings in a foal
disorders may also be identified during the course of from an endemic farm may be considered by a given
diagnostic evaluation or treatment, and some are only veterinarian to be sufficient basis for a diagnosis of the
identified at necropsy. Some extrapulmonary disorders disease in that foal. Extrapulmonary findings often occur
ultimately result in death or euthanasia, even if the with R. equi pneumonia, and their occurrence can provide
associated pneumonia has been treated successfully. an indication for further testing. Abnormal lung sounds
are, in our experience, an insensitive diagnostic method,
particularly early in the course of disease. This lack of
Diagnosis of R. equi Pneumonia sensitivity is likely because the disease is insidious such that
Determining a diagnosis of R. equi pneumonia can be abnormal lung sounds may not be found until infection is
accomplished in a number of ways, depending on the quite advanced.
status of the individual foal (severity of disease), the disease Non-specific diagnostic testing should include a com-
history of the farm, the resources and needs of the farm, plete blood count because many, but by no means all, foals
and the resources and needs of the veterinarian. Diagnostic with R. equi pneumonia have leukocytosis, hyperfibrino-
methods include non-specific and R. equi-specific approaches. genemia or both (Giguere et al 2003, Chaffin et al 2004).
Absence of these findings, however, would not preclude a
Non-specific testing diagnosis of the disease.
Diagnostic imaging should include ultrasonography,
Results of non-specific diagnostic methods may provide an radiography, or both. Each method has strengths and
indication for specific diagnostic testing. Non-specific find- limitations. Radiography of foals between 1 and 3 months
ings include the signalment, history, physical examination of age can be performed in the field. Radiography can
Fig. 24.3. Radiographic findings in a foal

with severe Rhodococcus equi pneumonia.
Numerous interstitial opacities caused by
pyogranulomas appear throughout the lungs.
The prognosis for foals with such radiographic
findings is poor.
detect lesions that are either axial or abaxial (Fig. 24.3). of no value for either diagnosis or early detection of R. equi
Disadvantages of radiography include the need for special pneumonia (Martens et al 2002b). There are a number of
equipment and adequate personnel, exposure of personnel reasons why these tests have poor diagnostic accuracy.
to radiation, costs associated with the procedure, the time They measure exposure, and thus cannot differentiate foals
required to perform and evaluate the results, technical that are exposed from foals that are actively infected. Given
limitations of performing the technique in larger foals, and the ubiquitous nature of the organism and the fact that it
the finding that early radiographic lesions can be subtle can be found at affected and unaffected farms, exposure is
and less characteristic of R. equi pneumonia than more widespread. Furthermore, the tests cannot differentiate
advanced cases. Ultrasonography may reveal abnormalities between antibodies that are maternally derived and those
of the abaxial lung (Fig. 24.4). With experience, thoracic
ultrasonography of a foal can be performed in a matter
of minutes and, when the peripheral lung is involved,
ultrasonography may be more sensitive than radiography.
Disadvantages of ultrasonography include the potential
to miss central pulmonary lesions surrounded by normal
aerated lung, the need for experience to perform the tech-
nique with diagnostic accuracy, the need for special equip-
ment and adequate personnel, costs associated with the
procedure, and the time required to perform (including
clipping a foal’s coat when necessary) and evaluate the
results. Radiographic or sonographic findings can be strongly
suggestive of R. equi pneumonia and often provide a basis
for more specific testing.
Rhodococcus equi-specific testing

Because they are relatively non-invasive, a variety of
serologic tests have been developed, including enzyme-
Fig. 24.4. Ultrasonographic image of a small, abaxial pyogranuloma
linked immunosorbent assays, an indirect hemagglu-
(circular hypoechoic area) in the right eighth intercostal space of a foal
tination inhibition test, agar gel immunodiffusion, and with Rhodococcus equi pneumonia. The top of the figure is at the
synergistic hemolysis inhibition tests. Recent evidence foal’s skin surface (abaxial) and the bottom of the image is axial; dorsal
indicates that serologic testing of single or paired samples is is to the left and ventral to the right of the figure.
produced by the foal. Indeed, many mature horses have synovitis, uveitis, anemia). Presence of extrapulmonary
serologic evidence of exposure to the organism. Further- disorders should prompt testing for pneumonia as well
more, paired titers may be of less value for an insidious as specific testing to determine the causes of the extra-
disease like R. equi pneumonia because foals will have been pulmonary lesion(s). There is no reason to believe that
infected for weeks or months before signs become apparent. serologic testing will be more useful for an extrapulmonary
It is generally considered that detection of R. equi [either disorder than for R. equi pneumonia.
by microbiologic culture or by polymerase chain reaction Culturing R. equi from the feces of foals is not reliable for
(PCR)] from fluid collected by tracheobronchial aspiration diagnosing enteric infection (Takai et al 1986). Although
(TBA) in combination with cytologic evidence of sepsis in serial quantitative culturing has been advocated, the
the TBA fluid is needed to definitively diagnose R. equi reliability of this approach has not been tested, and it is not
pneumonia. This approach likely provides strong evidence very practical to sequentially culture feces. Furthermore,
for the disease, but it is important to consider limitations in culturing feces does not appear to be reliable for diagnosing
the sensitivity and specificity of these methods. Micro- R. equi pneumonia, as only 17% (5/30) of foals with R. equi
biologic culture cannot differentiate between virulent and pneumonia were fecal-culture positive in one study
avirulent isolates. Reported sensitivities of TBA culture in (Ardans et al 1986). Detecting the organism in aspirates
foals with spontaneous disease, fatal disease, or experi- of intra-abdominal abscesses and infected bone can be
mental infection range from 57% to 100%. Foals without diagnostic. For suspected immune-mediated disorders, such
disease that are exposed to R. equi may yield positive results as polysynovitis, cytologic or microbiologic culture results
on culture. In one study, 35% (77/216) of foals had generally do not provide evidence of sepsis. Indeed, absence
culture-positive TBA fluid, but lacked clinical signs of of evidence of sepsis is a basis for considering these lesions
respiratory disease, suggesting low specificity (Ardans et al to be non-septic.
1986); however, the extent to which these foals might
have had subclinical pneumonia is unknown. Cytologic
evidence of septic pneumonia (large number of degenerate
Treatment of R. equi Pneumonia
neutrophils with intracellular rod-like organisms) and Antimicrobials
Gram-stain results consistent with R. equi pneumonia
(large number of pleomorphic, Gram-positive rods) should In vitro, a wide variety of antimicrobials is effective against
be considered in establishing a diagnosis. Consideration of R. equi. However, because of the intracellular location of
farm history and findings of diagnostic imaging can also R. equi and its development within pyogranulomatous
help influence the probability that a positive TBA result lesions, drugs that are effective in vitro may not be effective
is truly indicative of disease. Evidence exists that gene in vivo. The efficacy of any antimicrobial for treatment of
amplification of DNA extracted from TBA fluid using the this disease has not been demonstrated using a controlled
PCR and primers for a segment of the VapA gene (specific trial. There are retrospective data to suggest that the com-
for virulent organisms) may be more sensitive than culture bination of penicillin and gentamicin is therapeutically
(Sellon et al 2001). Limitations of this method include its ineffective (Sweeney et al 1987).
limited availability and the fact that the high sensitivity Recommended doses of antimicrobials for treatment
may result in amplification of environmental “contaminants” of R. equi are summarized in Table 24.2. Erythromycin in
that can be found at both affected and unaffected farms. combination with rifampin is considered the standard
Performing a percutaneous TBA can pose significant risk treatment for R. equi (Hillidge 1987, Sweeney et al 1987).
to foals with marked respiratory compromise. Performing a Their combination is synergistic in vitro and in vivo, and
TBA via endoscopy may be less stressful for some foals and the combination reduces the likelihood of resistance to
technically easier for veterinarians (regardless of the status either drug. Doses of rifampin range from 5 to 10 mg/kg
of the foal). Double-guarded, triple-lumen transendoscopic by mouth (PO) once or twice daily. In the USA, the
TBA catheters are commercially manufactured for obtain- drug is available as capsules for human use. Doses for
ing specimens for microbiologic culture. To date, it appears erythromycin range from 15–25 mg/kg four times a day
that culturing the organism or using PCR for detection to 25–37.5 mg/kg twice a day (Lakritz & Wilson 2002).
from nasal swabs or nasopharyngeal swabs are not reliable There are different formulations of erythromycin for oral
for diagnosis of R. equi pneumonia (Sellon et al 2001). use; intravenous (IV) use is not recommended because
of gastrointestinal and other side effects. Erythromycin
ethylsuccinate is not well absorbed in foals and should be
Diagnosis of R. equi avoided. Erythromycin estolate is bioavailable in foals. In
Extrapulmonary Disorders the USA, erythromycin phosphate is manufactured as a
Some of the extrapulmonary disorders are directly attrib- powder for use in poultry. It is relatively inexpensive, and
utable to infection (e.g. a large intra-abdominal abscess) at least as bioavailable as erythromycin estolate. Erythro-
whereas others may be immune-mediated (e.g. poly- mycin stearate appears to be well absorbed in adult horses,
Table 24.2. Summary of recommended doses of antimicrobials for treatment of Rhodococcus equi
Drug Dosage Comments
Erythromycin 15–25 mg/kg; PO; q 6–8 h Many formulations are effective (see text), but ethylsuccinate should be
(base and salts) avoided
Erythromycin 37.5 mg/kg; PO; q 12 h Side effects of erythromycin include an environmentally mediated
(base and salts) hyperthermia, diarrhea in the foal, and diarrhea in the dam
Azithromycin 10 mg/kg; PO; q 24 h for 5–7 days; Can cause similar side effects as erythromycin; some people use q 24 h for
then 10 mg/kg; PO; q 48 h duration of treatment
Clarithromycin 7.5 mg/kg; PO; q 12 h May be more effective than other macrolides; likely to cause similar side
effects to erythromycin
Rifampin 5–10 mg/kg; PO; q 12 h Must be used in combination with a macrolide
and is less expensive than the estolate formulation. such as elevations in liver enzymes or hyperthermia,
Erythromycin base is available as enteric-coated tablets should be expected with clarithromycin.
made for human beings. Microencapsulated base in gelatin Newer classes of antimicrobials may become available or
granules is reported to have better bioavailability than necessary as resistance to other antimicrobials develops.
the coated tablets. The volume of the suspension can be For example, linezolid is a member of a new class of anti-
large and this formulation is expensive. However, it has microbials, the oxazolidinones. Pharmacokinetics in horses
desirable properties, including good bioavailability, the or foals are lacking for this drug. It is used to treat R. equi
pro-drug is absorbed intact, and it may produce enhanced and other Gram-positive infections in human beings,
intracellular concentration of the active metabolite including methicillin-resistant Staphylococcus aureus, and
(erythromycin A). consequently its use in veterinary medicine may be
Side effects associated with erythromycin include restricted or discouraged.
environmentally modulated hyperthermia and diarrhea in Duration of treatment of R. equi is generally prolonged.
foals, and diarrhea in the dam; the latter can be severe and The earlier the infection is diagnosed, the shorter the
often fatal (Gustafsson et al 1997, Stratton-Phelps et al duration of treatment is likely to be (this is the rationale for
2000). Resistance to both erythromycin and rifampin has screening). Foals with radiographically apparent lesions
been reported for isolates of R. equi from both foals and should be treated for a minimum of 3 weeks. Monitoring
human beings. cases with radiography or ultrasonography can be helpful.
Use of azithromycin (10 mg/kg; PO; q 24 h for 5–7 days In general, treatment should be extended at least a few
then q 48 h) has greatly increased. Advantages of the days past resolution of ultrasonographic or radiographic
drug include once daily or every-other-day dosing and lesions. Monitoring the white blood cell count or fibrinogen
persistently high intracellular concentrations. Often, it is concentration can be used, but these are imprecise, and we
used in combination with rifampin. If it proves to be more recommend treating at least 2 weeks beyond reduction of
effective than erythromycin, it is conceivable that the dura- either parameter to the reference range and evidence that
tion of treatment might be reduced. The drug is a human the foal is clinically healthy. Serologic testing is of no value
pharmaceutical, is expensive, and adverse reactions include for monitoring affected foals. There is some evidence that
diarrhea, elevated liver enzymes, and, rarely, hyperthermia. monitoring serum amyloid A is of value.
Additionally, the syndrome of inappropriate antidiuretic
hormone secretion attributed to azithromycin has been Other treatments
reported in a human patient. Clarithromycin (7.5 mg/kg;
PO; q 12 h) is another macrolide that has been reported to There are also ancillary treatments that can be admin-
be effective for treating R. equi pneumonia (Giguere 2001). istered to affected foals. The benefits of hyperimmune
Anecdotally, data from a retrospective study indicate that plasma as adjunctive therapy remain unknown, but should
clarithromycin may be more effective than other macrolides be considered. The use of non-steroidal anti-inflammatory
for treating R. equi pneumonia (Giguere et al 2004). It may drugs to reduce fever and pulmonary inflammation may
be combined with rifampin, and side effects include diar- be of benefit for some foals. Administration of intranasal
rhea. Because its use has been limited to date, it is unclear oxygen may help foals with severe respiratory distress.
whether other common macrolide-associated side effects, The benefit of bronchodilators for treating foals with
this disease is unknown. Nebulization of antimicrobials,

Control and Prevention
bronchodilators, and mucolytic agents may be of benefit
for some foals. Combinations of some medications (e.g. For farms with foals affected by R. equi pneumonia, we have
aminophylline and erythromycin) may have interactions suggested an approach to control and prevention that
that result in adverse effects. Avoiding exposure of foals to addresses three areas, namely:
high heat and humidity (if possible) may help to avoid
● treatment of affected foals
macrolide-associated hyperthermia, and also may make
● screening for early detection of infection or disease in
pneumonic foals more comfortable.
foals without clinical signs
● preventing infection or disease in foals.
This approach to control and prevention entails con-
Treatment of Extrapulmonary Disorders sidering the farm, rather than individual foals, as the
Treatment with erythromycin or another macrolide in unit for evaluation. It is important to consider that pro-
combination with rifampin is indicated for intra-abdominal grams for control and prevention must be developed to
pyogranulomas; however, many of these lesions appear to accommodate the specific needs and resources of a given
progress in the face of treatment that is effective for R. equi farm. Resources that a farm is willing and able to commit
pneumonia. The prognosis for intra-abdominal pyogranu- will vary, and the duration and extent of the pneumonia
lomas is generally poor. Typically, polysynovitis lesions problem will influence how much money and other
resolve with successful treatment of the accompanying resources owners/managers will be willing to expend.
pneumonia. The authors have occasionally used system- Nevertheless, the first occurrence of R. equi pneumonia
ically administered corticosteroids as adjunctive therapy. on a farm could represent the beginning of recurrent
Limiting, but not eliminating, exercise may be of benefit problems. Veterinarians should consider a foal with R. equi
for affected foals. Appropriate therapy for other septic pneumonia as an individual patient in need of care, as a
conditions, such as drainage of abscesses or curettage for source of virulent organisms, and as a signal that the farm
osteomyelitis, may be needed. Some manifestations such as of origin may experience new and/or ongoing problems
uveitis may be immune-mediated or non-responsive to with the disease. Owners and farm managers should be
antimicrobials, but may resolve solely with successful advised that, as is the case for treatment, no program for con-
treatment of the accompanying pneumonia. trol and prevention should be expected to be 100% effective.
Treatment of affected foals

Prognosis for R. equi Infections Treatment of affected foals has been discussed previously.
Prognosis for foals with R. equi infection varies with the Whether affected foals should be isolated from other foals
severity and anatomic location of the infection, and appears and pregnant mares is unclear. As noted, virulent isolates
to vary among farms and admitting clinics (Ainsworth et al of the organism can be found in the soil of farms with or
1998, Chaffin et al 2003a). Generally, case fatality propor- without a history of R. equi pneumonia (Martens et al
tions are low (< 30%) but may be considerably higher 2000), and the source of infection for foals remains uncer-
at some farms. Early detection of disease and prompt tain. Exposure is likely widespread at affected farms and
implementation of treatment will improve prognosis for has probably occurred for many foals by the time cases
foals affected with R. equi pneumonia. Foals admitted of R. equi pneumonia are identified. However, foals can
to a group of teaching hospitals that were tachycardic amplify the organism in their intestinal tracts, thereby
and in respiratory distress at admission had a poorer enhancing contamination of the environment. Because
prognosis (Ainsworth et al 1998). Foals with more severe such environmental contamination may increase exposure
radiographic abnormalities are less likely to survive to the agent, it may be advisable to isolate affected foals. In
(Ainsworth et al 1998). The prognosis for foals with intra- the case of farms with resident and transient populations,
abdominal lymphadenitis and granulomatous enterocolitis/ it seems appropriate to minimize mixing of groups so that
typhlitis is guarded to poor (Chaffin & Martens 1997), but affected transient horses and foals do not contaminate the
treatment may occasionally be successful. environment of resident horses and vice versa.
Foals that survive R. equi appear to be less likely than the
general population of contemporary thoroughbred or Screening for earlier detection
standardbred foals in the USA to start at least one race. of infection or disease
However, standardbred and thoroughbred foals that survive
and race do not appear to have reduced performance A variety of methods exist for screening foals at farms with
(Ainsworth et al 1998). The impact of R. equi on activities a history of R. equi pneumonia to detect disease or infection
other than racing has not been systematically evaluated. at an earlier point in time; however, none of them is ideal
in terms of accuracy, cost, and labor. The rationale for in affected foals (Chaffin & Martens 1997). Rectal tempera-
screening is the belief that earlier initiation of specific tures of foals can be monitored twice daily. Febrile foals
treatment will improve the prognosis for recovery. The should be either treated or tested further. Performing
various methods for screening often need to be applied physical examination (including thoracic auscultation)
repeatedly. The individual screening methods can be twice weekly has been demonstrated to be effective for
employed sequentially, individually, or in parallel, depend- early recognition and reduction of mortality attributed to
ing on the needs and resources of the individual farm. R. equi pneumonia at an endemic farm (Prescott et al
Using a single screening test and initiating treatment on 1989). However, in our experience, thoracic auscultation
the basis of a positive result might be best for a farm with alone is an insensitive tool for early detection of foals with
recurrent high prevalence of disease or one with limited R. equi pneumonia.
resources. In contrast, farms with greater resources or Results of complete blood counts can be used for screen-
more sporadic disease occurrence might use a sequence ing purposes. Foals with leukocytosis (i.e. > 13,000 white
of screening tests to ensure a higher probability that a blood cells per liter) or increased concentration of fibrino-
foal selected for treatment has the disease. Variation in gen (> 400 mg/dl) should be considered either for further
resources and preferences renders it impossible either to testing or for treatment. Evidence exists that fibrinogen
prescribe methods for control and prevention that are concentration is a relatively insensitive indicator of R. equi
suitable for all farms or to predetermine the approach to infection (Giguere et al 2003). Serologic tests lack sensitivity
screening that is best for a particular farm. The plan for and specificity both for screening (early detection) and
each farm must be determined after consideration of the diagnosis of R. equi pneumonia (Martens et al 2002b).
specific needs and wishes of each farm, and following Radiography, ultrasonography, or both can be useful for
consultations between the veterinarian, farm owners, and screening to detect foals with early or subclinical R. equi
farm managers. pneumonia. Diagnostic imaging is relatively specific
because it may reveal pulmonary lesions. The radiographic
Screening tests are not the same appearance of pulmonary lesions is often strongly sugges-
as diagnostic tests tive of R. equi pneumonia, and in any case antimicrobial
therapy for R. equi pneumonia is generally effective for
The distinction between a diagnosis based on a screening streptococcal organisms which are the other common
test (an epidemiologic diagnosis) and a diagnosis based on cause of lung abscesses in foals (Hoffman et al 1993).
definitive diagnostic testing (a clinical diagnosis) should be A positive result of a screening test would be interpreted
explained to all interested parties. Positive results of a as an indication for either further screening or initiating
screening test for early detection of R. equi would be a basis treatment. The decision to initiate treatment must include
for initiating treatment for R. equi; however, positive results consideration of the aforementioned adverse effects of
of a screening test do not represent a definitive diagnosis of antimicrobials. An example of a sequential screening pro-
either R. equi infection or its disease. A useful screening test gram would be one in which foals were visually inspected
is one in which the probability of disease is very high and had rectal temperatures recorded twice daily; any foal
among those with a positive test result (i.e. high positive that appeared abnormal or was febrile would have a
predictive value) and very low among those with negative complete blood count performed; any foal with a leuko-
test results (i.e. high negative predictive value). The higher cytosis or hyperfibrinogenemia would be treated with anti-
the prevalence of disease at a farm, the higher the positive microbials (or subjected to radiography or ultrasonography).
predictive value of a screening test’s result. Thus, a positive However, some veterinarians may prefer to subject foals
result for a screening test, such as leukocytosis, for R. equi that are identified as positive by screening tests to more
pneumonia would need to be interpreted differently for a definitive diagnostic testing to reduce the rate of false-
foal at a farm with a recurrent history of pneumonia positive screening results. It should be recognized, however,
caused by R. equi than it would be for a foal at a farm that the goal of screening is not to obtain a definitive
without a history of R. equi pneumonia. For the former, but diagnosis, and accurate diagnosis early in the course of
not the latter, the result would be a reasonable basis for infection is difficult and false-negative results can occur in
treating the foal for R. equi pneumonia. more definitive diagnostic testing.
Visual inspection of foals at an affected farm is recom-
mended as an initial screening test. Pneumonia caused by
R. equi is insidious and clinical signs are often absent in
Preventing Disease
foals with early infection or disease; however, foals that Hyperimmune plasma
have increased respiratory effort or lethargy should be
further evaluated. Visual inspection may also reveal extra- To date, the only method proven to prevent pneumonia
pulmonary disorders such as polysynovitis. These extrapul- caused by R. equi is transfusion of hyperimmune plasma
monary disorders are often the initial clinical signs detected (Martens et al 1989), but it is not without limitations.
Plasma administration is costly and labor-intensive, is generally lacking. In the USA, the disease is not associ-
associated on rare occasions with transfusion reactions or ated with poor health management practices. Rather, the
injury to the foal during handling, and is not universally disease often occurs on farms that provide health man-
successful. The volume of plasma that should be admin- agement deemed to be desirable, indicating that these
istered and the time(s) of administration for optimal strategies are inadequate for preventing R. equi pneumonia
protection are unknown. We recommend administration of (Chaffin et al 2003b).
1 or 2 liters of hyperimmune plasma to a foal during the Removing manure from foaling stalls, pens, and pad-
first few days of life and again during the third week of life. docks could decrease environmental contamination and
The rationale for this approach is that we believe exposure the level of exposure of susceptible foals because R. equi is
and infection occur early in life and that younger foals are shed in the feces of mares and foals and multiplies within
more susceptible to infection than older foals (see above). feces (Takai 1997). Frequent cleaning of foaling stalls may
Although hyperimmune plasma is expensive, the costs of help to decrease contamination and the opportunity for
prophylactic administration of plasma to many foals can be infection; however, the organism is a soil saprophyte that
lower for some farms than the costs of treatment and can be found both at farms affected with the disease and
the lost value of any foals that succumb to the disease. at farms not affected with the disease. The organism is
Assessing the cost–benefit ratio for use of plasma for seldom recovered from soil at a depth greater than 30 cm
prevention may be beneficial, using methods such as (Takai 1997). Removal and replacement of topsoil in stalls
decision-tree analysis. Such an analysis requires estimation and pens is impractical and soil might rapidly become
of the average value of foals produced, the expected re-contaminated.
prevalence of disease, the case fatality rate, and the average Methods used for disposal of manure might reduce
cost of treating R. equi pneumonia. Farms with a high exposure to R. equi. Directly spreading feces containing
prevalence of disease, high case fatality rate, or both will virulent R. equi on pastures may increase contamination of
often have a net financial benefit from administration of the environment. Composting manure before spreading it
1 or 2 liters of hyperimmune plasma to all foals. on pastures or disposing of manure without applying it to
pastures is recommended; however, evidence to support
Vaccination these recommendations is lacking.
The stocking density of horses, particularly the density
To date, evidence is lacking that vaccination of mares or of foaling mares and foals, is likely to increase the risk of
oral administration of colostrum from R. equi-immunized R. equi pneumonia. Efforts to reduce the stocking density
mares to neonatal foals is effective for preventing disease. of mares and foals should be considered on farms that have
A product containing concentrated serum which was a high density of breeding horses and endemic R. equi
developed to prevent failure of passive transfer was pneumonia. A systematic cost–benefit analysis would have
reported to increase serum antibody titers against R. equi to be conducted to determine whether the financial benefits
and to delay by 2–3 weeks the time of seroconversion to of decreased disease and death outweigh the costs of lost
R. equi among foals (Davis et al 1995). Controlled trials revenue associated with reducing the number of horses or
demonstrating the efficacy of this product have not been increasing the pasture area.
reported. Given that colostrum from immunized mares is Keeping resident and transient populations separated
not protective (Martens et al 1991, Mueller & Madigan may help to reduce transmission. Although evidence that
1992), claims of efficacy for oral products should be viewed this approach specifically prevents transmission and spread
with considerable caution. Vaccination of foals or dams has of R. equi pneumonia is lacking, it is a generally useful
not been demonstrated in controlled trials to be effective principle for control of infectious diseases at farms with
for preventing R. equi pneumonia. Novel strategies for resident and transient populations. Whether there is benefit
vaccination, such as development of DNA vaccines to in isolating mares and foals returning to unaffected farms
promote mucosal immunity, may eventually prove to be from R. equi-endemic farms is unclear. Virulent isolates of
effective. Alternatively, vaccination may be ineffective if this organism can be found in the soil of unaffected farms,
foals are infected very early in life such that infection would and duration or pattern of shedding by infected horses is
have occurred before the development of an effective ill-defined. As a general principle for control of infectious
immune response. diseases, isolating mares and foals returning from facili-
ties where there are horses of diverse origins and ages
Environmental and management is advisable.
considerations As inhalation is considered the principal mode of trans-
mission of R. equi pneumonia, improving ventilation may
Environmental factors often influence the risk of infec- decrease the risk of R. equi pneumonia. Anecdotally and
tious diseases. A number of management factors have been in a recent survey of farms in the USA, a dusty environ-
implicated in relation to R. equi pneumonia but evidence is ment was associated with farms having R. equi infections.
Diminishing dust in the environment may help to reduce Davis J, Gaskin JM, Hietala SK et al 1995 Oral administra-
the risk of R. equi pneumonia. Applying water sprinklers tion of concentrated equine serum to newborn foals
to pens and small paddocks can reduce dust. Rotation of prevents failure of passive transfer of immunoglob-
ulin and provides passive transfer of immunity for
paddocks to avoid overgrazing, reducing the density of Rhodococcus equi. Proceedings of the American Associa-
horses (and foals) in paddocks or pens, and reseeding tion of Equine Practitioners 41: 176–177
paddocks or pens may diminish dust levels by promoting Debey MC, Bailie WE 1987 Rhodococcus equi in fecal and
grass growth. environmental samples from Kansas horse farms.
Veterinary Microbiology 14: 251–257
Giguere S 2001 Rhodococcus equi pneumonia. Proceedings
Chemoprophylaxis of the American Association of Equine Practitioners
47: 456–467
Chemoprophylaxis for R. equi pneumonia has not been Giguere S, Hondalus MK, Yager JA et al 1999 Role of the
evaluated in foals. Given that hyperimmune plasma is 85-kilobase plasmid and plasmid-encoded virulence-
not completely effective and has the other aforementioned associated protein in intracellular survival and viru-
lence of Rhodococcus equi. Infection and Immunity
limitations, and that vaccination is unlikely to be effective 67: 3548–3557
if foals are infected early in life, this approach merits fur- Giguere S, Hernandez J, Gaskin J et al 2003 Evaluation of
ther investigation. white blood cell concentration, plasma fibrinogen con-
centration, and an agar gel immunodiffusion test for early
identification of foals with Rhodococcus equi pneumonia.
REFERENCES Journal of the American Veterinary Medical Association
222: 775–781
Ainsworth DM, Eicker SW, Yeager AE et al 1998 Associa- Giguere S, Jacks S, Roberts GD et al 2004 Retrospective
tions between physical examination, laboratory, and comparison of azithromycin, clarithromycin, and eryth-
radiographic findings and outcome and subsequent romycin for the treatment of foals with Rhodococcus equi
racing performance of foals with Rhodococcus equi pneumonia. Journal of Veterinary Internal Medicine
infection: 115 cases (1984–1982). Journal of the 18: 568–573
American Veterinary Medical Association 213: 510–515 Gustafsson A, Baverud V, Gunnarson A et al 1997 The
Ardans AA, Hietala SK, Spensley MS et al 1986 Studies of association of erythromycin ethylsuccinate with acute
naturally occurring and experimental Rhodococcus equi. colitis in horses in Sweden. Equine Veterinary Journal
Proceedings of the American Association of Equine 29: 314–318
Practitioners 32: 129–144 Hillidge CJ 1987 Use of erythromycin-rifampin combination in
Byrne BA, Prescott JF, Palmer GH et al 2001 Virulence plasmid treatment of Rhodococcus equi pneumonia. Veterinary
of Rhodococcus equi contains inducible gene family Microbiology 14: 337–342
encoding secreted proteins. Infection and Immunity Hoffman AM, Viel L, Prescott JF et al 1993 Association of
69: 650–656 microbiologic flora with clinical, endoscopic, and pul-
Chaffin MK, Martens RJ 1997 Extrapulmonary disorders monary cytologic findings in foals with distal respiratory
associated with Rhodococcus equi pneumonia in foals: tract infection. American Journal of Veterinary Research
retrospective study of 61 cases (1988–1996). Proceed- 54: 1615–1622
ings of the American Association of Equine Practitioners Horowitz ML, Cohen ND, Takai S et al 2001 Application
43: 79–80 of Sartwell’s model (lognormal distribution of incuba-
Chaffin MK, Cohen ND, Martens RJ 2003a Evaluation of tion periods) to age at onset and age at death of foals
equine breeding farm characteristics as risk factors for with Rhodococcus equi pneumonia as evidence of peri-
development of Rhodococcus equi pneumonia in foals. natal infection. Journal of Veterinary Internal Medicine
Journal of the American Veterinary Medical Association 15: 171–175
222: 467–475 Lakritz J, Wilson WD 2002 Erythromycin and other macrolide
Chaffin MK, Cohen ND, Martens RJ 2003b Evaluation of antibiotics for treating Rhodococcus equi pneumonia in
equine breeding farm management and preventative foals. Compendium on Continuing Education for Practicing
health practices as risk factors for development of Veterinarians 24: 256–261
Rhodococcus equi pneumonia in foals. Journal of the Martens RJ, Martens JG, Fiske RA 1989 Rhodococcus equi foal
American Veterinary Medical Association 222: 476–485 pneumonia: protective effects of immune plasma in
Chaffin MK, Cohen ND, Martens RJ et al 2003c Foal-related experimentally infected foals. Equine Veterinary Journal
risk factors associated with development of Rhodococcus 21: 249–255
equi pneumonia on farms with endemic infection. Martens RJ, Martens JG, Fiske RA 1991 Failure of passive
Journal of the American Veterinary Medical Association immunization by ingestion of colostrum from immunized
223: 1791–1799 mares to protect foals against Rhodococcus equi pneu-
Chaffin MK, Cohen ND, Martens RJ et al 2004 Hematologic monia. Equine Veterinary Journal 12 (suppl): 19–22
and immunophenotypic factors associated with develop- Martens RJ, Takai S, Cohen ND et al 2000 Association of
ment of Rhodococcus equi pneumonia of foals at equine disease with isolation and virulence of Rhodococcus equi
breeding farms with endemic infection. Veterinary from farm soil and foals with pneumonia. Journal of the
Immunology and Immunopathology 100: 33–48 American Veterinary Medical Association 217: 220–225
Cohen ND, Smith KE, Ficht TA et al 2003 Epidemiologic Martens RJ, Cohen ND, Chaffin MK et al 2002a Association
study of pulsed-field gel electrophoresis of isolates of of Rhodococcus equi foal pneumonia with farm soil
Rhodococcus equi obtained from horses and horse farms. geochemistry. American Journal of Veterinary Research
American Journal of Veterinary Research 64: 153–161 63: 95–98
Martens RJ, Cohen ND, Chaffin MK et al 2002b Evaluation of Journal of the American Veterinary Medical Association
5 serologic assays to detect Rhodococcus equi pneumonia 217: 68–73
in foals. Journal of the American Veterinary Medical Sweeney CR, Sweeney RW, Divers TJ 1987 Rhodococcus equi
Association 221: 825–833 pneumonia in 48 foals: response to antimicrobial therapy.
Mueller NS, Madigan JE 1992 Methods of implementation of Veterinary Microbiology 14: 326–329
an immunoprophylaxis program for the prevention of Takai S 1997 Epidemiology of Rhodococcus equi infections: a
Rhodococcus equi pneumonia: results of a 5-year field review. Veterinary Microbiology 56: 167–176
study. Proceedings of the American Association of Takai S, Timori S, Tsubaki S 1986 Quantitative fecal culture
Equine Practitioners 38: 193–201 for early diagnosis of Corynebacterium (Rhodococcus) equi
Prescott JF 1991 Rhodococcus equi: an animal and human enteritis in foals. Canadian Journal of Veterinary Research
pathogen. Clinical Microbiology Reviews 4: 20–34 50: 479–484
Prescott JF, Machangu R, Kwiecien J et al 1989 Prevention of Takai S, Sekizaki T, Ozawa T et al 1991a Association between
foal mortality due to Rhodococcus equi pneumonia on an a large plasmid and 15- to 17-kilodalton antigens in
endemically affected farm. Canadian Veterinary Journal virulent Rhodococcus equi. Infection and Immunity
30: 871–875 59: 4056–4060
Sellon DC, Besser TE, Vivrette SL et al 2001 Comparison of Takai S, Ohbushi S, Koike K et al 1991b Prevalence of virulent
nucleic acid amplification, serology, and microbiologic Rhodococcus equi in isolates from soil and feces of horses
culture for diagnosis of Rhodococcus equi pneumonia in from horse-breeding farms with and without endemic
foals. Journal of Clinical Microbiology 39: 1289–1293 infections. Journal of Clinical Microbiology 29: 2887–2889
Stratton-Phelps MS, Wilson WD, Gardner IA 2000 Risk of Zink MC, Yager JA, Smart NL 1986 Corynebacterium equi
adverse effects in pneumonic foals treated with eryth- infections in horses: 1958–1984: a review of 131 cases.
romycin versus other antibiotics: 143 cases (1986–1996). Canadian Journal of Veterinary Research 27: 213–217
Diseases of the Nasal Cavities
25 Jim Schumacher and Padraic M Dixon
airflow from the affected naris while at rest. Failure to

High Blowing (False Nostril Flutter)
dilate the nostrils and nasal collapse during inspiration
High blowing is a loud, vibratory expiratory noise that may be apparent when the horse exercises.
is associated with turbulence in the nasal vestibule caused
by vibration of both the true and false nostrils. Some horse Diagnosis
may produce high blowing noises at the start of exercise or
when excited. These noises are not associated with respira- Unilateral nostril paralysis is usually obvious, because the
tory impairment, and so are not clinically important. Some horse has a deviated muzzle and sometimes a dropped
owners even find them desirable. ear and ptosis on the affected side, depending on the level
Sometimes, while high blowing, the horse’s nostrils can of the site of nerve damage. Mild, bilateral nasal collapse
be seen to vibrate. High blowing noises usually disappear caused by bilateral facial paralysis may be more difficult
when the horse is strenuously exercised. Although the to recognize. The condition may be confirmed if the horse’s
noise caused by high blowing is not clinically important, it tolerance to exercise improves and abnormal noises dis-
must be recognized and differentiated from abnormal appear when the nostrils are dilated by abducting the alar
respiratory noise caused by disease. cartilages with sutures (Beard 1996). An affected nostril
may be seen to collapse when the contralateral nostril is
occluded to increase inspiratory pressure (Torre 2000, 2003).
Nasal Paralysis
Severe, bilateral facial paralysis associated with generalized
The nostrils are comma-shaped when the horse is at rest, neuromuscular dysfunction is usually associated with other
but during strenuous exercise the nostrils become circular clinical signs, such as generalized muscular weakness.
as the musculature of the nostrils contracts to increase the
size of the nasal vestibule. Nasal collapse is usually the Treatment and prognosis
result of trauma to one or both dorsal buccal branches of
cranial nerve VII (i.e. facial nerves) caused by trauma Nasal collapse resulting from neuropraxia of cranial nerve
to the side of the head or improper padding beneath the VII or its branches caused by a blunt trauma to the side of
head when the horse is anesthetized and positioned in the head usually resolves spontaneously within days to
lateral recumbency. Damage to a facial nerve resulting months. Anti-inflammatory therapy, with corticosteroids
in nasal collapse can also be caused by mycosis of a gut- and/or non-steroidal anti-inflammatory drugs, may hasten
tural pouch or by temporohyoid osteoarthropathy. Unilat- recovery. If nasal collapse does not resolve, airflow through
eral nasal collapse can occur after injury to the dorsal the affected nostril can be improved by removing the alar
buccal branch of cranial nerve VII during dental extraction fold (see Alar Fold Stenosis, p. 373) and/or by implanting a
performed through a buccotomy. Mild, bilateral paralysis prosthesis to provide rigid support to the naris (Hawkins
can be caused by harness that is too tight or by a bitless et al 1995). Prostheses used to prevent nasal collapse
bridle. Severe, bilateral facial paralysis causing bilateral include autogenous auricular cartilage (Torre 2003) and
nasal collapse can occur in association with disorders stainless steel mesh (Torre 2000). Removing the lateral
causing generalized neuromuscular dysfunction, such as alae or creating a permanent tracheostomy may also improve
botulism or lead poisoning. the horse’s respiratory capacity, but these procedures are
disfiguring.
Clinical signs
Horses suffering from unilateral or bilateral nasal collapse
Vasomotor Rhinitis
exhibit exercise intolerance and make an abnormal respi- Vasomotor rhinitis is a non-inflammatory, non-allergic,
ratory noise that can be localized to the nostrils. A unilat- physiological disorder of the nasal mucosa characterized
erally affected horse may have a detectable decreased by a bilateral watery nasal discharge, sneezing, obstruction
369
SECTION 4 : Disorders of the Upper Respiratory Tract
370 25 Diseases of the Nasal Cavities
Fig. 25.1. The nostril of a horse suffering

from grass sickness that has developed
rhinitis sicca, with excoriation and crusting
of the nasal mucosa.
to nasal airflow, nasal pruritus, and loss of sense of smell vasculature. Sodium cromoglycate stabilizes mast cells and
(Lane & Mair 1987, McGorum & Dixon 1990, Ayars may reduce nasal inflammation by preventing excessive
2000). The disorder may be caused by an imbalance in the release of histamine. Nasal administration of drugs is often
autonomic control of nasal mucosal function that results resented by horses, and long-term nasal administration of
in hyperreactivity of the nasal mucosa to exogenous and an adrenergic agonist may eventually result in desensitiza-
endogenous stimuli. The disorder occurs commonly in tion of the nasal vasculature to the adrenergic agent.
human beings, but apparently horses are seldom affected.
Rhinitis Sicca
Clinical signs and diagnosis
Rhinitis sicca is a common disorder of horses suffering
Clinical signs of vasomotor rhinitis include bilateral serous from chronic grass sickness and is characterized by
nasal discharge, nose rubbing, snorting, and head shaking swelling, excoriation, and exudation of the nasal mucosa,
(Lane & Mair 1987, McGorum & Dixon 1990). Clinical presumably as a result of disturbed autonomic control of
signs in human beings may be triggered by changes in the nasal vasculature and mucosal glands. The crusted
temperature and humidity, certain odors, and physical or and inflamed nasal mucosa is usually visible at the nostrils
emotional stress, and the same may be true of horses. In a (Fig. 25.1). Depending on the degree of nasal obstruction,
report of an affected horse, clinical signs were induced by affected horses may make “snuffling” respiratory sounds
exercise or by stress (McGorum & Dixon 1990). Clinical at rest, and occasionally horses with severe nasal obstruc-
signs of unilateral vasomotor rhinitis in another horse tion need a tracheostomy. Rhinitis sicca may adversely
were associated with unilateral Horner syndrome and affect olfaction, which may further depress appetite and,
probably resulted from damage to the sympathetic inner- therefore, worsen the prognosis for severely affected horses.
vation of the nasal mucosa (Lane & Mair 1987). Diagnosis The disorder resolves over a period of months, if the horse
of vasomotor rhinitis is based on clinical signs, elimination survives (Milne et al 1994).
of other causes of chronic rhinitis, and remission of signs
after treatment.
Apical Infection of a Rostral Cheek Tooth
with Intranasal Drainage
Treatment
The apices of the first, second, and third cheek teeth
Horses affected with vasomotor rhinitis can be treated (Triadan 106–108 and 206–208) are embedded in the
by nebulization with an adrenergic agonist, such as rostral portion of the maxillary bone (Fig. 25.2) and lie
xylometazoline, or with sodium cromoglycate (McGorum completely or partially outside the paranasal sinuses.
& Dixon 1990). Adrenergic agents may reduce nasal Periapical infection of these teeth usually results in facial
congestion and discharge by constricting the nasal swelling and sometimes in a discharging tract on the side of
25 Diseases of the Nasal Cavities 371
DM Treatment
DC Treatment involves extraction of the affected tooth and

sealing of the oral aspect of the oronasal fistula, using a
MM material such as bone cement (polymethylmethacrylate) or
dental wax. Some surgeons have attempted endodontic
VC treatment of affected horses, but the efficacy of this treat-
ment has not been critically assessed. If the intranasal granu-
SB loma is large, it should be excised. The draining tract soon
resolves after the source of infection has been removed.
VM
Oronasal Fistula
An oronasal fistula is characterized by the presence of a
direct, epithelial-lined communication between the oral
and nasal cavities that allows the ingress of oral contents
into the nasal cavity. The usual cause of an oronasal fistula
is failure of the alveolus of a rostral cheek tooth to heal
completely after the tooth has been repulsed. The non-
Fig. 25.2. Transverse section of an equine skull at the level of the healing alveolus often contains dental or alveolar remnants
second cheek teeth (Triadan 07) showing the dorsal meatus (DM), and is incompletely filled with infected granulation tissue
dorsal concha (DC), middle meatus (MM), ventral concha (VC), ventral
and feed.
meatus (VM), and swell body (SB). The swell body is distended by
blood in the live horse and protrudes into the middle meatus. Affected horses have a unilateral, malodorous, purulent
nasal discharge that often contains feed material. Some
affected horses have a rostral maxillary swelling on the
affected side. During oral examination, the non-healed
alveolus appears as a deep cavity, and a metal probe inserted
the face. It may also occasionally result in formation of a into the oral aspect of the alveolus can be observed or pal-
tract that drains medially into the nasal cavity, leading to pated where it emerges in the nasal cavity. Digital palpation
a unilateral, purulent, foul-smelling nasal discharge and of the rostrolateral wall of the affected nasal cavity may
sometimes formation of a nasal granuloma (Tremaine & reveal a tract or a granuloma. Rhinoscopy may be useful in
Dixon 2001a,b). identifying the nasal aspect of the fistula or associated food
and pus (Fig. 25.3), if the fistula is situated beyond the
Clinical signs reach of a finger. Dental or alveolar remnants can often
be observed radiographically in the unhealed alveolus.
Clinical signs of a nasal tract caused by periapical infection
of a maxillary cheek tooth include halitosis, purulent nasal Treatment
discharge, and sometimes, rostral maxillary swelling.
Pain associated with disease of the clinical crown of the Treatment is initially directed at promoting alveolar heal-
affected tooth may cause quidding in a small proportion of ing by removing dental and osseous fragments and the
affected horses. A large nasal granuloma may cause a epithelial lining of the tract using a long-handled, right-
detectable decrease in airflow from the affected nasal cavity. angled curette inserted per os. Intranasal granulation tissue
Nasal endoscopy may reveal exudate, feed material, or a is removed by curettage using a straight-handled curette
granuloma within the rostrolateral aspect of the nasal inserted per nasum. A wax plug can be placed several
cavity. The tall reserve crowns of young horses may cause centimeters into the oral portion of the alveolus to prevent
the draining tract to be obscured by the ventral concha. the ingress of feed into the alveolus. An acrylic prosthesis is
better suited for this purpose because it can be attached
Diagnosis onto the tooth in front or behind the vacated alveolus.
The restriction of hay or haylage in the diet for a few
Careful oral examination may reveal an abnormality of the weeks can reduce the amount of time spent masticating
crown of one of the maxillary premolars, such as occlusal and so prevent dislodgement of the alveolar prosthesis. If
exposure of the pulp, infundibular caries, or fracture. the alveolus fails to heal using these measures, the fistula
Radiographic examination of the dental apices is necessary can be closed using a plug of transposed muscle (Orsini
to confirm periapical infection but when radiographic et al 1992) or a sliding mucoperiosteal flap (Barakzai &
changes are equivocal, scintigraphy is useful. Dixon 2005) (Fig. 25.3).
Fig. 25.3. The larger image shows creation of a sliding muco-

periosteal hard palate flap to repair a chronic oronasal fistula (arrows)
that developed after repulsion of two cheek teeth. The commissures
of the lips have been incised (arrowheads) for surgical access. The
smaller image shows inspissated pus and feed material seen during
nasal endoscopy of a similarly affected horse.
Epidermal Inclusion Cysts of the

Nasal Diverticulum
Epidermal inclusion cysts (or epidermoid cysts) of the nasal
diverticulum are uncommonly encountered, spherical
cystic structures, lined by epithelium, located between the
skin and the mucous membrane in the dorsocaudal aspect
of the nasal diverticulum (i.e. false nostril), rostral to the
nasoincisive notch (Head & Dixon 1999, Tremaine et al Fig. 25.4. Epidermal inclusion cyst (i.e. false nostril cyst) in the right
1999, Tremaine and Dixon 2001a). These lesions are a nasal diverticulum (i.e. false nostril). The smaller image shows the
intact, excised cyst.
congenital malformation resulting from aberrant loca-
tion of epithelial tissue. They are sometimes erroneously
identified as an atheroma (i.e. a sebaceous cyst) because
they contain a thick, gray, greasy material that resembles Pathology
sebum (Tremaine et al 1999). Epidermal inclusion cysts
can occur elsewhere in the body other than the nasal Histologic examination of an epidermal inclusion cyst
diverticuli, and an occasionally reported site is the brain reveals a well-differentiated, stratified squamous epithe-
(Kelly & Watson 1976, Gordon 1978). lium, 4–30 cells deep, with a thick band of surface keratin
and acellular debris (Gordon 1978, Head & Dixon 1999).
Clinical signs The subepithelial connective tissue is infiltrated with a
mixed population of cells, mainly lymphocytes (Tremaine
Although present at birth, a cyst may only become et al 1999). Keratinized and non-keratinized squamous
apparent when continuous exfoliation of squamous cells cells are seen during microscopic examination of the
from its lining causes the cyst to slowly or rapidly expand. contents of the cyst.
A cyst is usually first noted by the time the affected horse
is 2 years old. Cysts range from 2 to 5 cm in diameter Diagnosis
and usually bulge laterally to distort the contour of the
nostril, rather than medially into the lumen of the nasal Diagnosis is based on the pathognomonic location and
diverticulum (Fig. 25.4) (Robertson & Rooney 1997). They gross appearance of the lesion and is confirmed by aspi-
are soft, fluctuant, and mobile in the subcutaneous tissue, rating its contents, which are odorless, greasy, and
and painless on palpation. They do not obstruct respiration dark-to-light gray (Robertson & Rooney 1997, Head &
and are of cosmetic significance only (Lane 1998). Dixon 1999).
Fig. 25.5. An epidermal inclusion cyst being

removed with a laryngeal burr.
Treatment lumen of the cyst after aspirating its contents (Frankeny

2003). The cyst enlarges within 24 h after injection and
Affected horses are treated only to improve cosmesis. then, within 7 days, begins to regress until it is no longer
The usual treatment is excision of the entire cyst with the visible. After several weeks, all that is left of the cyst is a
horse sedated and standing, using local anesthesia, firm, leathery mass attached to the nasal diverticulum by a
through a skin incision created over the cyst. The cyst is stalk. The desiccated mass is removed by severing the stalk.
thin-walled, and inadvertent perforation of the cyst Reported complications of the procedure are mild and
hampers complete excision. temporary and include signs of nasal irritation, swelling of
Another technique of excision that does not require the cyst, and mucoid nasal discharge (Frankeny 2003).
meticulous dissection is to remove the cyst using a laryn-
geal burr (Schumacher et al 1997). The technique is per-
Alar Fold Stenosis (Nasal Flutter)
formed after anesthetizing the infraorbital nerve of the
affected side or after infiltrating local anesthetic solution The alar fold is a mucocutaneous structure located in the
into the subcutaneous tissue overlying the rostral aspect dorsorostral aspect of the nasal cavities (Fig. 25.6) that
of the cyst within the nasal diverticulum. After scrubbing extends caudally from the laminar portion of the alar
the nasal diverticulum, a 1-cm stab incision is made into the cartilage to the rostral aspect of the ventral nasal concha
rostroventral aspect of the cyst, and the cyst’s contents are (Sisson & Grossman 1953, Boles 1979, Schummer et al
expressed into the cavity of the false nostril. A laryngeal 1979). It divides the external naris into a small, upper
burr is inserted into the lumen of the cyst and rotated to nasal diverticulum (i.e. the false nostril) and a large, lower
engage the cyst’s lining (Fig. 25.5). The burr is retracted, opening (i.e. the true nostril). Its dorsolateral surface
everting the wall of the cyst, which is then excised. If the is covered with skin and forms the ventral and medial
thin cyst lining tears, the burr is reinserted, rotated, and aspects of the nasal diverticulum. The mucous membrane
retracted to remove residual tissue. The incision is left of the ventromedial surface of the fold is continuous with
unsutured to heal by second intention. the nasal mucosa.
The cyst can also be removed by chemically destroying During deep inspiration, the alar cartilage, which is
its lining. One such technique is to swab the cavity of the attached to the alar fold, is elevated by action of the trans-
cyst daily with a sclerosing agent, such as tincture of versus nasi muscle (Foerner 1967). This tightens the alar
iodine, through an incision in the rostroventral aspect fold, which closes the entrance to the false nostril. Malfun-
of the cyst (Haynes 1984). Recurrence of the cyst is a ction of the transversus nasi muscles or excessive size of
frequent complication of this technique. A more effective the alar folds allows air to enter the nasal diverticula,
method of chemical ablation is to instill 2–4 ml of a 4% which causes obstruction of the nasal cavities, a condition
solution of formaldehyde (i.e. 10% formalin) into the referred to as alar fold stenosis. Relative obstruction of the
Fig. 25.6. Sagittal section of a normal equine

E MM skull with the nasal septum removed show-
ing the ethmoturbinates (E), dorsal concha
(DC), middle meatus (MM), ventral concha
AF N (VC), alar fold (AF), and (true) nostril (N).
DC
VC
nasal cavities by alar folds that are anatomically and of the alar cartilages may be evident, and the nasal diver-
functionally normal can occur if the nasal vestibula are ticula may be deeper than normal (Foerner 1967). In
abnormally narrow (Boles 1979, Haynes 1984). addition to causing an abnormal respiratory noise, the
condition may impair exercise tolerance (Vasey et al 1995).
Signalment
Diagnosis
Flaccidity of the alar folds (i.e. alar fold stenosis) was
originally described as a cause of a loud, objectionable The diagnosis can be confirmed by temporarily retracting
respiratory noise that occurred during exercise, or some- the alar folds with sutures and then exercising the horse
times even at rest, in some American Saddlebred horses to determine if this prevents the noise (Fig. 25.7). The horse
that may have been genetically predisposed to the condition is restrained with a nose twitch, and local anesthetic
(Foerner 1967). Standardbred horses also appear to be at solution is injected into the alar folds. To retract the folds,
risk of alar fold stenosis, perhaps because of the confor- heavy suture material is placed in a horizontal mattress
mation of the rostral aspect of their premaxillae and pattern through each alar fold within the external nares,
associated soft tissue structures (Hawkins et al 1995). just caudal to the alar cartilages, and the sutures are tied
Noise attributed to the alar folds may also occur in together over a gauze roll situated over the nasal bones.
young male horses, especially miniature horses, even Tension on the sutures retracts the alar folds and closes
though their alar folds are anatomically and functionally the nasal diverticula. Alleviation of noise with the folds
normal, because unerupted maxillary canine teeth may retracted and recurrence of the noise with the sutures
contribute to narrowing of the nasal vestibule (Boles 1979). removed confirm the diagnosis of alar fold stenosis.
After the maxillary canine teeth erupt, the tendency for the
alar folds to produce abnormal noise decreases. (Note: Treatment
Eruption of the cheek teeth of 2- to 4-year-old miniature
horses is sometimes associated with nasal obstruction so Both alar folds and the medial wall of the nasal diverticula
severe that tracheostomy is necessary.) are resected with the horse anesthetized and positioned
in dorsal or lateral recumbency (Foerner 1967). The pro-
Clinical signs cedure can be performed through the external nares or by
incising the lateral alae of the nostrils to expose the alar
Alar fold stenosis causes a continuous, muffled rattling or folds. Dorsal recumbency provides adequate access to both
vibrating noise emanating from the area of the nostrils alar folds, if the procedure is performed through the
during both inspiration and expiration, but the noise is nostrils. Lateral recumbency provides better exposure to an
most pronounced during expiration (Foerner 1967). Affected alar fold, if the lateral ala of the nostril is incised, but to
horses may make abnormal respiratory noise at rest, but resect both alar folds using this approach, the horse must
others require intense exercise to elicit the noise. Drooping be turned over during surgery.
Fig. 25.7. The role of the alar folds in pro-

duction of abnormal respiratory noise can
be determined by temporarily retracting the
alar folds with suture placed through each
alar fold (A). The sutures are tied together,
under tension, over a gauze roll situated over
the nasal bones, to retract the alar folds (B).
Remission of noise with the folds retracted
confirms the diagnosis of alar fold stenosis.
A B
The alar fold is uncurled and resected, using scissors,

along its longitudinal limits, from the alar cartilage to the
cartilaginous portion of the ventral concha (turbinate).
Severe hemorrhage created by excision stops when the
mucosal edge of the incision is joined to the correspond-
ing skin edge with a continuous suture pattern using
absorbable suture. The horse can be returned to work in
approximately 2 weeks.
Prognosis
The prognosis after surgery is favorable, both for resolution
of abnormal respiratory noise and return to the previous
level of exercise (Vasey et al 1995). Horses with normal
sized nasal cavities appear to receive the greatest benefit
from resection of the alar folds (Hawkins et al 1995). If
the horse is exercise intolerant and/or produces a noise at
rest because of the inadequate size of the rostral portion of
the nasal cavities, excision of the folds may provide some
relief but should not be expected to totally relieve the signs.
Wounds of the Nostrils

Because the horse is an obligate nasal breather, its nostrils
must dilate effectively during strenuous exercise, and con-
Fig. 25.8. This horse sustained a 10-cm long laceration to its left
sequently, wounds of the nostrils must be managed care-
nostril that was not sutured. Consequently, the lateral, flaccid skin flap
fully to maintain normal nostril morphology. Obstruction was sucked into the nostril during deep inspiration causing airflow
to nasal airflow can result from scar formation caused by obstruction and abnormal noise.
poor surgical technique in suturing a nostril laceration or
from failure to surgically appose the laceration (Fig. 25.8).
nasal bones, and vomer bone (Valdez et al 1978, McKellar
& Collins 1993, Baker 1999, Puchol et al 2004). The
Wry Nose (Campylorrhinus Lateralis) deformity is accompanied by deviation of the nasal septum,
Wry nose, or campylorrhinus lateralis, is a congenital which occasionally results in severe nasal obstruction.
shortening and deviation of the maxillae, premaxillae, The inability of a mare, especially a primiparous mare, to
distend its uterus to accommodate a developing foal may

cause fetal malpositioning, which may be responsible for
the condition (Vandeplassche et al 1984).
Signalment
Wry nose occurs occasionally in all breeds, but the inci-
dence seems to be highest in the Arabian breed, leading to
speculation that the condition may be heritable (Baker
1999). Male and female foals are equally affected, and the
malformation affects the right and left sides with equal
frequency (Vandeplassche et al 1984).

The deviation may be mild to severe (e.g. up to 90°) and
may be accompanied by a protrusion (“hump”) on one
of the nasal bones (Fig. 25.9). Excessive arching of the
nasal bones (i.e. Roman nose) and of the hard palate may
accompany wry nose (J. Easley, personal communica-
tion). The affected foal may also suffer from cleft palate.
Premaxillary deviation causes malocclusion of all or some
of the incisor teeth, and all or a portion of the mandibular
incisors may be visible. The tongue may protrude, and feed
may be retained in the oral cavity producing a fetid odor
(Puchol et al 2004). Deviation of the rostral portion of the
facial bones can complicate deglutition, and the affected
foal may be unable to nurse (McKellar & Collins 1993).
Severe deviation may result in respiratory impairment,
even when the foal is resting.
Treatment
Fig. 25.9. This foal is severely affected with wry nose (campylorrhinus
A mildly affected foal needs no immediate treatment, but lateralis).
severely affected foals require intensive nursing care,
and euthanasia may even be necessary. Administration of
nutrition through a nasogastric tube may be necessary if
the foal is unable to nurse, but often a foal unable to nurse formed after the premaxillary/maxillary osteotomies have
is able to drink milk replacer from a bucket. Serum concen- healed, airflow through the nares is improved by removing
tration of immunoglobulins should be assessed to deter- a portion of the deviated nasal septum, and the nasal
mine if the foal has received colostrum. bones are straightened.
A mild deformity may resolve spontaneously as the foal Distraction osteogenesis has also been used to correct
grows (Vandeplassche et al 1984). Surgical correction is deviation of the premaxillae/maxillae (Puchol et al 2004).
usually performed in two stages and involves straightening Using this technique, the premaxillae/maxillae are par-
the maxillae/premaxillae and nasal bones and removing tially transected with a saw at their point of maximum
the affected part of the nasal septum (Valdez et al 1978, curvature, through small incisions at the midpoint between
McKellar & Collins 1993). During the first stage of repair, the dorsal and ventral aspect of the premaxillae/maxillae.
the premaxillae/maxillae are transected at their point Steinmann pins are inserted perpendicularly across the
of maximum curvature, and an autogenous rib graft is premaxillae/maxillae, rostral and caudal to the osteotomies.
inserted into the space created on the concave side of the A double connecting bar is attached on the convex side of
deformity when the incisors are realigned. The severed the face, and a monolateral distraction external skeletal
premaxillae/maxillae are stabilized with Steinmann pins fixator is attached on the concave side. The rostral and
inserted into their medullary cavity or with an external caudal pins on the concave side of the face are distracted
fixator. During the second stage of repair, usually per- 1.0 mm apart every 24 h, and clamps that attach the
Steinmann pins with the double connecting bar on the (Silverman et al 1977). The heritability of the condition in
convex side of the face are slackened and retightened every horses has not been evaluated, and teratogenic causes have
other day to accommodate the pressure generated by bone not been identified.
distraction on the concave side.
Prevalence
Prognosis
The condition is rarely reported, but the scarcity of reports
The cosmetic results of surgery are poor if the premaxillae may not be indicative of the condition’s true prevalence.
and maxillae are abnormally short, or if removing a large Bilateral choanal atresia may often go undetected because
portion of the nasal septum causes the nasal bones to of the rapid death of the foal after birth and failure to
collapse. The nasal bones are more likely to collapse after perform a detailed post-mortem examination. Some foals
surgery if the foal is less than 6 months old (Tulleners & that are assumed to have been stillborn may have actually
Raker 1983). The cosmetic result of distraction osteo- died after birth as a result of bilateral choanal atresia
genesis is reported be superior to that of conventional (Crouch & Morgan 1983).
surgical correction (Puchol et al 2004).
Clinical signs
Choanal Atresia Complete, bilateral choanal atresia may not be recognized
Choanal atresia, also known as posterior nasal atresia or unless the birth is attended or a complete necropsy is
imperforate buccopharyngeal septum, is a congenital mal- performed. If the birth is attended, severe inspiratory
formation in which one or both nasal cavities fail to difficulty and ballooning of the guttural pouches may
communicate with the nasopharynx (Crouch & Morgan be noted (Sprinkle et al 1984). If the condition is unilateral
1983, Aylor et al 1984, Goring et al 1984, Hogan et al or bilateral but incomplete, it may go undetected until
1995, Lane 1998). The condition occurs as the result the horse is put into training and noted to be exercise intol-
of persistence of the buccopharyngeal septum, which erant or to make an abnormal respiratory noise (Lane
separates the nasal and nasopharyngeal cavities during 1998). Unilaterally affected horses may have a unilateral
embryonic development. The boundaries of the obstruct- nasal discharge and unilateral nostril flare during exercise
ing tissue in affected human beings, and presumably in (Hogan et al 1995).
affected foals, are the body of the sphenoid bone dorsally,
the medial pterygoid lamina laterally, the caudal edge of Diagnosis
the nasal septum medially, and the caudal aspect of the
hard palate ventrally (Hengerer & Stome 1982). Diagnosis is based on clinical signs, inability to advance a
Choanal atresia may be unilateral or bilateral, and the nasogastric tube or catheter into the nasopharynx, and
obstructing septum may be complete or incomplete, and endoscopic or contrast radiographic examination of the
bony or membranous (Crouch & Morgan 1983, Aylor et al nasal cavities. During rhinoscopic examination, which is
1984, Goring et al 1984, Hogan et al 1995, Lane 1998). the most practical and useful means of diagnosing the
Although the obstructing tissue of human beings is usually condition, an obstructing membrane is seen at the level
bony (Hengerer & Stome 1982), that of horses seems to of the caudal nares, or the entrance between one or both
usually be membranous, based on the few reports of the nasal cavities and the nasopharynx may appear to be nar-
condition in this species (Hogan et al 1995). The condition rowed (Lane 1998). The ethmoturbinates may be atretic
results in partial or complete inability to breathe though and distorted.
the nose. The horse is an obligate nasal breather, and so Contrast radiography, using a contrast medium intro-
when the condition is bilateral and complete, the foal duced into the nasal cavities through the external nares,
is at immediate risk of suffocation, unless it receives a defines the caudal extent of the nasal cavities and shows
temporary tracheostomy. Choanal atresia in human beings the location of the obstructing tissue. Computed tomography,
is sometimes accompanied by other facial deformities, such if available, may aid evaluation.
as an arched hard palate and thickened vomer bone,
especially if the condition occurs bilaterally (Silverman Treatment
et al 1977, Hengerer & Stome 1982), but accompanying
abnormalities in affected horses have not been reported. Treatment of foals affected with complete and bilateral
This anomaly in human beings has sometimes been choanal atresia involves performing an emergency tra-
seen in multiple family members (Maniglia & Goodwin cheostomy to bypass the obstruction, which can then be
1981). It has been induced in offspring of baboons by removed when the foal’s condition is stable. The persistent
administrating triamcinolone acetonide to pregnant females septum can be removed using an intranasal approach or
through a facial bone flap (Aylor et al 1984, Goring et al tight; and bacterial infection of the septal cartilage asso-
1984, Hogan et al 1995). The transpalatine approach ciated with severe respiratory infection (Tulleners & Raker
used to access the caudal choanae of human infants is 1983). Rarely, the septum can be thickened as a result of
impractical for use in the horse because of the length of mycotic infection or neoplasia. Septal deviation is caused by
the horse’s maxillary region (Goring et al 1984, Hogan congenital malformation, such as wry nose, or from an
et al 1995). The intranasal approach should be reserved expanding mass, such as a neoplasm or cyst, within the
for those horses with membranous obstruction (Hogan paranasal sinuses or a nasal cavity. Occasionally, nasal
et al 1995). If the obstruction is bony, or if a membranous perforations occur that can cause continuous whistling
obstruction is exceptionally thick, the area of obstruction type noises (without airflow obstruction) even at rest in
should be approached through a facial bone flap. affected horses.
Using an intranasal approach with endoscopic guidance,
obstructing membranous tissue can be perforated with a Clinical signs
probe; destroyed by electrocoagulation or laser; or excised
using laparoscopic scissors and forceps (Aylor et al 1984, The most common clinical signs displayed by a horse with
Goring et al 1984, Hogan et al 1995). Cicatrization with nasal septum deformity are respiratory difficulty during
subsequent closure, the most common complication of exercise and production of abnormal respiratory noise
resection of choanal obstruction, is prevented by inserting without apparent respiratory impairment (Tulleners &
a tube through the nasal cavity into the nasopharynx and Raker 1983). Asymmetry of the face may be noted if the
maintaining the tube in this position for 4–6 weeks. septal abnormality is caused by wry nose, by an expanding
The obstructing membranous or bony buccopharyngeal mass within the paranasal sinuses, or by trauma to the
septum can be excised through facial bone flaps, which nasal and frontal bones.
provide surgical access to the caudal aspect of the nasal
cavities, but the foal is likely to develop facial deformity and Diagnosis
dental malocclusion after this surgery because of decreased
growth of the maxillae caused by disruption of the facial Most septal abnormalities can be seen or palpated, and an
suture lines (Aylor et al 1984, Goring et al 1984). Horses uneven flow of air through the nasal cavities can often be
affected with life-threatening choanal atresia can be detected at the external nares (Tulleners & Raker 1983).
treated by permanent tracheostomy, if removal of the Septal deformity or thickening can usually be palpated
nasal obstruction is not feasible or if an attempt at removal by simultaneously inserting an index finger into each
has failed. nasal cavity and feeling the septum between the fingers.
Rhinoscopic examination and dorsoventral radiographic
projections of the nasal region can be used to determine
Deformity of the Nasal Septum the extent of the abnormality. Septal deformity results in
The nasal septum is a cartilaginous plate extending ros- narrowing of one or, usually, both nasal cavities, and diffi-
trally from the ethmoidal turbinates to the alar cartilages culty may be encountered when inserting the endoscope
that separate the right and left nasal cavities (Figs 25.2 and into the nasal cavities. The septal cartilage and soft tissues
25.6) (Sisson & Grossman 1953, Schummer et al 1979). surrounding it are visible on a dorsoventral radiographic
The septum is positioned on the midline perpendicular to projection, but precise positioning is required to observe
the frontal and nasal bones. From its dorsal border, the septal deformity (Stilson et al 1985).
parietal cartilage curves outward on each side for a short
distance and lies on the lateral aspect of the nasal bones at Treatment
the incisive notch. The ventral border of the nasal septum
rests on the bony groove of the vomer bone and palatine Deformity of the nasal septum seldom resolves after it
processes of the premaxillae. The septum is cartilaginous, becomes clinically evident; therefore, the usual treatment
except at its caudal extent, where it becomes osseous as it of affected horses is excision of the accessible portion of
blends with the perpendicular plate of the ethmoid and the deformed septum. Only the rostral three-quarters of the
vomer bones. The cartilage of the septum is covered with a septum is accessible for removal (Tulleners & Raker 1983).
highly vascular mucosa. Septal deformity seldom advances to the point of being life-
Deformities of the nasal septum include deviation and threatening, and so resection may not be necessary if the
thickening and are associated with obstruction of airflow horse is not expected to perform athletically.
through the nasal cavities. Causes of nasal septum thick- Because the horse may lose a large quantity of blood
ening include congenital cystic degeneration (Tulleners & during the procedure, the hematocrit and coagulation
Raker 1983); hamartoma formation (Servantie & Sautet profile should be determined before surgery. Replacing
1986); trauma from fracture of the nasal and frontal bones, blood during surgery is usually not necessary, but if the
amyloidosis (see Nasal Amyloidosis), or a halter that is too horse is anemic or if the surgeon is inexperienced in this
procedure, having at least 4 liters of blood available for occur when the septum is removed using a guarded chisel
transfusion may be prudent. The horse should receive a (Tulleners & Raker 1983).
balanced electrolyte solution intravenously during surgery To remove the septum using obstetrical wire, three
to avoid hypovolemia caused by severe hemorrhage. separate wires are placed around the septum to make the
Both common carotid arteries can be ligated temporarily ventral, dorsal, and caudal septal incisions. Placement of
to control hemorrhage while the septum is being removed the caudal and ventral wires requires insertion of the
(Freeman et al 1990), but this procedure prolongs surgery, surgeon’s hand into the horse’s mouth, and so for conve-
is sometimes ineffective in reducing severe hemorrhage, nience, gas anesthesia can be administered through an
and may damage one or both recurrent laryngeal nerves or endotracheal tube placed through a tracheostomy.
vagosympathetic trunks, which lie adjacent to the common To situate the ventral wire, the ends of a length of
carotid arteries (Greet 1992, Tremaine & Dixon 2001b). obstetrical wire are inserted into the nasopharynx on
The nasal septum is excised with the horse anesthetized either side of the septum through the ventral nasal meatus
and positioned in lateral recumbency. A small trephine hole so that the ends of the wire can be grasped over the caudal
(i.e. 15–25 mm in diameter) is made on the midline of the edge of the soft palate and exteriorized through the mouth.
face through the nasal bones at a site just rostral to the If the horse is too small to insert a hand into the caudal
conchofrontal sinuses. This site is located where the nasal aspect of the mouth, the ends of the wire can be grasped,
bones begin to diverge and is several centimeters caudal to using endoscopic guidance, with a long forceps or with a
an imaginary line drawn between the rostral aspects of the wire snare inserted through the biopsy chamber of the
facial crests. The nasal bones can be exposed through a endoscope. To prevent damaging the nasal mucosa with
curvilinear incision through the skin and periosteum, the ends of the wire, each end of the wire should be
which are reflected. Removing a circular section of the sheathed in a male dog urinary catheter. The two ends of
nasal bones exposes the parietal cartilage of the septum, the wire loop protruding from the mouth are tied together,
which is excised with a scalpel to expose the right and left the knot is covered with tape to protect the mucosa, and
nasal cavities. This opening into the nasal cavities provides the knotted loop of wire is pushed back into the mouth
access for the caudal and dorsal septal incisions. and over the back edge of the soft palate. The knot is
The dorsal, ventral, and caudal septal incisions can be exteriorized by pulling on the wire emerging from one of
made using a guarded chisel, a cartilage scissor, or the external nares. Tension on the wire secures the loop at
obstetrical wire (Bemis 1916, Tulleners & Raker 1983). the caudoventral aspect of the septum at the junction of
Hemorrhage associated with removal of the nasal septum the hard and soft palates (Fig. 25.10).
using obstetrical wire is less than that encountered when To situate the wire for the dorsal septal incision, the
using a chisel or scissor because when using obstetrical sheathed ends of a second length of obstetrical wire are
wire, three of the four incisions required to remove the sep- inserted on either side of the septum at the trephine site
tum can be made simultaneously. This allows the septum to and directed rostrally through the dorsal meatus of each
be removed rapidly, so that the nasal cavity can be packed nasal cavity so that the ends emerge at the external nares.
to stop excessive hemorrhage. Using obstetrical wire also Tension on the ends of the loop secures the loop at the
eliminates trauma to the adjacent turbinates, which can caudodorsal aspect of the septum.
A B
Fig. 25.10. Nasal septum resection. (A) Sagittal section of a head showing the loop at the caudoventral
aspect of the septum at the junction of the hard and soft palates. (B) Sagittal section of a head showing
the jaws of an intestinal forceps placed into the nasopharynx at a 60° angle to the nasal bones. The wire
loop is situated caudal to the jaws of the forceps for the caudal septal incision.
To situate the wire for the caudal septal incision, the

sheathed ends of a third length of obstetrical wire are
inserted on either side of the septum at the trephine site
and directed caudoventrally into the nasopharynx so that
the ends of the wire can be grasped with fingers at the
caudal edge of the soft palate and exteriorized through the
mouth. The two ends of the wire loop exteriorized through
the mouth are tied together, the knot is covered with tape
to protect the mucosa, and the knotted loop of wire is
pushed back into the mouth and over the back edge of the
soft palate into the nasopharynx. By pulling on one strand
of wire emerging from the trephine hole, the knot is
exteriorized.
The caudal incision should be made at a 60° angle to
the nasal bones (towards the nasopharynx), and to achieve
this angle, the blades of a straight Doyen intestinal forceps
are inserted through the trephine hole, one jaw on either
side of the septum, and directed caudoventrally into the
nasopharynx until the jaws of the forceps contact the soft
palate. As the loop of wire for the caudal incision is pulled Fig. 25.11. Endoscopic view of the healed, caudal aspect of the
from the mouth into the nasopharynx, the loop comes to incised edge of the septum. The thickened septal stump lies in the
rest caudal to the jaws of the forceps (Fig. 25.10). nasopharynx, rather than between the turbinates and so causes no
The caudal, ventral, and dorsal septal incisions are made nasal obstruction.
simultaneously by the surgeon and two assistants with the
three loops of wire. When the dorsal and ventral incisions
approach the alar cartilages, the rostral aspect of the
septum is incised, with a scalpel, to connect these two the nasopharynx can result in obstruction of the nasal
incisions. The rostral incision should be curved rostrally cavity by the healed edge of the caudal portion of the
and should be at least 3 cm from the rostral limit of the septum. By incising the caudal aspect of the septum at a
septum so that support for the alar cartilages and external 60° angle to the nasal bones, the thickened septal stump
nares is maintained. The septum is then removed through resides in the nasopharynx, rather than between the
either naris using a heavy Vulsellum forceps, and the nasal conchae (Fig. 25.11).
cavity is packed tightly with rolled gauze. Most horses continue to make an abnormal respira-
The nostrils may be sutured closed to retain the packing, tory noise at exercise after the nasal septum is resected
and the cutaneous–periosteal flap is replaced and secured (Tulleners & Raker 1983), but full respiratory capacity
with skin staples. The endotracheal tube is replaced with a is restored. Collapse of the bridge of the nose near the
tracheostomy tube either before or after the horse has nasal diverticula may occur, especially when surgery is
recovered from anesthesia. Gauze packing is removed after performed on horses less than 6 months old. Respiratory
24–48 h. Because horses are obligate nasal breathers, impairment resulting from collapse of the nose can
dislodgement or occlusion of the tracheotomy tube before sometimes be alleviated by resection of the alar folds (see
the packing is removed causes the horse to asphyxiate. The section on Alar Fold Stenosis, p. 373).
nasal cavity typically develops a profuse, foul-smelling
discharge after several days. Mucosal surfaces heal within
4–6 weeks, and the horse can resume work 8 weeks
after surgery.
Mycotic Nasal Infection
Mycotic infection of the nasal mucosa of horses is caused
Prognosis most commonly by the normally saprophytic fungus
Aspergillus fumigatus (Greet 1981, McGorum et al 1992,
Longer term complications associated with nasal septum Tremaine et al 1999) and less commonly by Pseudallescheria
resection include excessive formation of granulation at boydii, a saprophytic fungus that has been isolated from
either the rostral or caudal aspect of the cut edge of the soil, sewage, and poultry and cattle manure (Brearley et al
septum, persistent respiratory noise, collapse of the nasal 1986, McGorum et al 1992, Davis et al 2000). These fungi
bones, and exercise intolerance (Tulleners & Raker 1983). are generally regarded as secondary invaders of damaged
The incised edge of the septum thickens as it heals; tissue, so the mechanism by which they infect the mucosa
therefore, failure to angle the caudal incision toward of the nasal cavities is not clear, except in cases where
mucosal damage was incurred by accidental trauma, by

expanding growths, or by sinonasal surgery (Tremaine &
Dixon 2001a). Horses confined to a stable containing moldy
hay or straw are most likely to develop mycotic nasal plaques
(Greet 1981, McGorum et al 1992, Tremaine et al 1999).
Signalment
There is no breed or sex predisposition for development of
mycotic nasal plaques (Tremaine & Dixon 2001a), but the
disease occurs most commonly in horses that are stabled
on hay and straw, especially following sinonasal surgery
(McGorum et al 1992). The condition is more commonly
reported in Europe than in North America.
Clinical signs
Mycotic nasal plaques characteristically cause a chronic,
malodorous, unilateral nasal discharge that may be blood-
tinged, mucoid, purulent, or mucopurulent (Greet 1981,
Brearley et al 1986, McGorum et al 1992, Davis et al
Fig. 25.12. Endoscopic image of nasal cavity of a horse that has a
2000). Uncommonly, they may cause gross epistaxis. fistula into its maxillary sinus. This shows an extensive mycotic plaque
Affected horses often have an ipsilateral submandibular caused by Aspergillus infection.
lymphadenopathy. Rhinoscopy reveals mycotic plaques,
which can vary in size and color and which may be
associated with an accumulation of a thick, tenacious,
yellow discharge (McGorum et al 1992). Extensive destruc- Treatment
tion of the conchae is sometimes observed during rhinoscopy
(McGorum et al 1992, Tremaine & Dixon 2001a). Treatment of horses affected with nasal mycosis includes
correcting the predisposing causes, removing the mycotic
Diagnosis plaques and associated diseased tissue, and administer-
ing an antimycotic drug topically to the affected area
Diagnosis of mycotic nasal plaques is based on clinical signs, (Greet 1981, McGorum et al 1992, Tremaine et al 1999).
endoscopic identification of mycotic plaques (Fig. 25.12), Large mycotic plaques and diseased tissue are removed
cytologic examination of exudate or sections of plaques, transendoscopically (Davis et al 2000, Tremaine & Dixon
histologic examination of lesions, and culture of a heavy 2001b), and exposed tissue is lavaged transendoscopically
and pure growth of potentially pathogenic fungi (Greet or through a catheter inserted into the ipsilateral para-
1981, McGorum et al 1992). Failure to identify a mycotic nasal sinuses, with a concentrated solution of an anti-
plaque does not eliminate mycotic nasal plaques as a cause mycotic drug, once or twice daily, for 1–2 weeks (McGorum
of clinical signs (Greet 1981). Histologic examination of et al 1992). Antifungal drugs locally effective against
lesions and cytologic examination of exudate from horses Aspergillus spp. include itraconazole, fluconazole, enilcona-
infected with Aspergillus spp. or Pseudallescheria boydii zole, miconazole, ketoconazole, natamycin, and clotri-
reveals fungal hyphae and conidiophores (McGorum et al mazole. Ancillary treatment is usually unnecessary but
1992, Davis et al 2000). Results of fungal culture of exudate could include systemic administration of sodium iodide
or microscopic examination of plaques should be inter- (67 mg/kg, intravenous, once daily) for 2–5 days and then
preted cautiously because fungal spores and hyphae are oral administration of organic iodide (ethylenediamine
commonly found in the respiratory tract of normal horses. dihydroiodide) (40 mg/kg, once daily) indefinitely (Scott
Cytologic examination and culture of plaques are more & Miller 2003).
reliable than cytologic examination and culture of nasal
discharge. Serologic evaluation of horses affected with
nasal mycosis does not reveal antibodies to Aspergillus
fumigatus serotypes (McGorum et al 1992), but immuno-
Fungal Granulomas
histochemistry performed on infected tissue may confirm Fungal diseases incriminated in the development of granu-
the identity of Aspergillus fumigatus as the causative agent lomas in the nasal cavities of horses include rhinosporidiosis,
(des Lions et al 2000). conidiobolomycosis, cryptococcosis, and coccidioidomycosis.
Although fungal granulomas of the nasal cavity are gener-

ally uncommonly observed, they are encountered with
some frequency in certain geographic regions.
Rhinosporidiosis is a chronic fungal infection of people,
cattle, horses, mules, and other species caused by Rhino-
sporidium seeberi and characterized by nodular or polypoid
growths on the nasal, vaginal, ocular, or oral mucosa
(Smith 1961, Myers et al 1964, Londero et al 1977, Gillespie
1981). The disease does not become generalized and does
not ordinarily endanger life. Only the nasal form has been
reported to occur in horses. Rhinosporidium seeberi seems to
favor temperate regions, and there appears to be positive
correlation between the amount of contact of the horse
with stagnant water and the frequency of occurrence of
the infection. The few reported cases of the disease in
horses in the USA have been located in southeastern states,
perhaps because of the warm, wet climate of this region
(Smith 1961, Myers et al 1964). The source of infection
and method of spread have not been determined, but the
disease is probably not contagious.
Fig. 25.13. A sessile lesion of rhinosporidiosis (arrow) on the nasal
Conidiobolomycosis of horses, also known as rhino-
septum at the right external naris.
phycomycosis or entomorphomycosis, is a pyogranulo-
matous disease of the upper respiratory tract caused by
infection of the mucosa and submucosa by the fungus
Conidiobolus coronatus. Conidiobolomycosis is part of the
pyogranulomatous disease complex known as equine monly found in soil that is enriched by bird droppings
phycomycosis (Bridges 1972, Murray et al 1978, Miller & (Ainsworth & Austwick 1959, Gillespie 1981). Respiratory
Campbell 1982, Miller et al 1983, Owens et al 1985, infection is acquired by the inhalation of contaminated
Alfaro & Mendoza 1990, Campbell 1990). The other dis- dust. Transmission from one host to another has not
eases of the phycomycosis complex are pythiosis, caused been clearly demonstrated (Ainsworth & Austwick 1959,
by invasion of a protistal organism, Pythium insidiosum, Corrier et al 1984).
and basidiobolomycosis, caused by invasion of the fungus Coccidioidomycosis is a granulomatous disease caused
Basidiobolus haptosporus (Murray et al 1978, Miller & by infection with the fungus Coccidioides immitis. Other
Campbell 1982, Miller et al 1983, Owens et al 1985, names for the disease include valley fever, San Joaquin
Campbell 1990). Pythiosis and basidiobolomycosis occur in fever, and desert fever (Zontine 1958). The disease in horses
tropical and subtropical regions and primarily affect the may be manifested as a nasal granuloma or by generalized
skin and subcutis, whereas conidiobolomycosis can also debilitation (Zontine 1958, Hodgin et al 1984). The disease
occur in more temperate climates and is found exclusively is endemic in arid and semiarid regions in North, Central,
in the upper respiratory tract (Miller & Campbell 1982). and South American countries (Ainsworth & Austwick
Conidiobolus coronatus is found in soil and decaying 1959, Gillespie 1981). The usual mode of infection is by
organic material and in insects (Miller 1983). Infection by inhalation of the organism. The disease is not transmitted
the fungus most likely occurs while the horse is grazing. from animal to animal.
Mucosal damage, perhaps damage caused by bacterial or
viral infection of the respiratory epithelium, may provide Clinical signs
entry for the infective fungal conidia (Hanselka 1977),
but whether or not the epithelium must be damaged for Clinical signs of fungal granuloma include stertorous
the organism to enter is not known. Infection does not breathing, dyspnea caused by restricted airflow, halitosis,
seem to be associated with immunodeficiency (Steiger & sneezing, dysphagia, epistaxis, and sanguinous, mucoid, or
Williams 2000). mucopurulent discharge from the affected nasal cavity.
Cryptococcosis is a granulomatous fungal disease, usually Granulomas can sometimes be seen at the external nares,
of the skin, meninges and brain, or respiratory system, but rhinoscopy may be necessary to observe the lesions.
caused by the yeast-like organism Cryptococcus neoformans With rhinosporidiosis, pedunculated or sessile polypoid,
(Gillespie 1981, Corrier et al 1984). The most frequently pinkish-tan nodules, usually less than 3 cm in diameter,
reported site of infection in horses is the nasal cavity. may be visible on the nasal mucosa, usually close to
Cryptococcus neoformans is a ubiquitous saprophyte com- the external nares (Fig. 25.13) (Smith 1961, Myers et al
measuring up to 400 μm in diameter, and each containing

numerous endospores measuring 5–10 μm in diameter, are
dispersed throughout the nodule.
Microscopic examination of granulomas of conidiobolo-
mycosis reveals granulation tissue infiltrated by numerous
eosinophils, neutrophils, macrophages, plasma cells, lym-
phocytes, giant cells, and hyphae surrounding necrotic
masses (Hutchins & Johnston 1972, French et al 1985,
Zamos et al 1996). Special stains, such as Gomori’s silver
stain, may be required to identify hyphae.
The granuloma caused by Cryptococcus neoformans has
a yellow to yellowish-gray appearance, and cut sections
of the mass contain many cysts filled with a gelatinous
material (Watt 1970, Corrier et al 1984). Microscopic
examination of sections of lesions caused by Cryptococcus
neoformans reveals an inflammatory response consisting of
a mixed population of inflammatory cells and periodic acid
Schiff-positive, thickly encapsulated yeast bodies, 5–30 μm
in diameter (Watt 1970, Corrier et al 1984).
The granulomatous nasal lesions caused by Coccidioides
Fig. 25.14. Endoscopic view of the nasopharynx of a horse affected
with conidiobolomycosis. The granulomatous lesion on the left wall of
immitis are smooth with a glistening surface (Hodgin et al
the nasopharynx (arrows) extended into the left nasal cavity. 1984). Microscopic examination of the lesions reveals a
pyogranulomatous reaction containing spherical bodies, or
spherules, 20–50 μm in diameter, often surrounded by
focal accumulations of inflammatory cells (DeMartini &
Riddle 1969, Hodgin et al 1984). The spherules have a
1964, Londero et al 1977, Gillespie 1981), and during double-contoured cell wall and can be found extracellularly
rhinoscopy, smaller, nodular granulomatous lesions may and within giant cells. Spherules resemble an oocyst of a
be found scattered throughout the nasal cavities (Londero coccidium, and it is from this resemblance that the fungus
et al 1977). The nodules bleed easily and are stippled with derives its name (Gillespie 1981). Large spherules contain
1-mm diameter, white or yellow dots (Myers et al 1964, endospores, 2–5 μm in diameter.
Londero et al 1977, Gillespie 1981, Allison et al 1986).
Conidiobolus coronatus causes small growths, 1–3 cm Diagnosis
in diameter, within the nasal cavity and slightly larger
growths, 1–5 cm in diameter, on the external nares (Pascoe Fungal granulomas must be differentiated from ethmoidal
1981). Lesions can sometimes be seen to contain small hematomas, neoplasia, and nasal granulomas caused
granules, 2–5 mm in diameter (French et al 1985). Lesions by periapical infection of a maxillary premolar. Diagnosis
caused by Conidiobolus coronatus do not appear to be as of fungal granuloma and identification of the causative
pruritic as lesions caused by pythiosis (Hutchins & Johnston organism are usually based on clinical signs, gross and
1972). Lesions of cryptococcosis or coccidiodomycosis may histologic appearance of the lesions, and identification of
appear as a glistening, gelatinous mass during rhinoscopy the causative organism, either within lesions or by culture.
(Fig. 25.14) (Roberts et al 1981, Corrier et al 1984, Hodgin Granulomas caused by Rhinosporidium seeberi and
et al 1984). Coccidioides immitis could be confused during cytologic or
histologic examination of infected tissue because both
Pathology organisms have a somewhat similar appearance in tissue
(Allison et al 1986). Rhinosporidium seeberi cannot be cul-
Granulomas caused by rhinosporidiosis are covered by a tured on conventional, artificial culture media (Ainsworth
thin, shiny epithelial membrane and contain white or & Austwick 1959, Gillespie 1981).
yellow dots, which represent aggregates of sporangia Diagnosis of conidiobolomycosis can be confirmed by
(Smith 1961, Myers et al 1964, Londero et al 1977, identifying characteristic hyphae of the causative organism
Gillespie 1981). Microscopic examination of granulomas during histologic examination of a lesion. Conidiobolus
reveals hyperplastic epithelium covering highly vascular coronatus can be cultured with ease on ordinary media, but
fibrous connective tissue, which is heavily infiltrated with samples from suspected lesions are usually sent to labora-
inflammatory cells, especially neutrophils and eosinophils. tories with personnel experienced in isolating and identi-
Numerous sporangia in various stages of development, fying organisms causing phycomycosis (Newton & Ross
1993). Conidiobolomycosis can also be identified by poly- (Hanselka 1977, French et al 1985, Zamos et al 1996,
merase chain reaction (Grooters & Gee 2002) or by an Taintor et al 2003). Parenteral administration of ampho-
immunodiffusion test, using serum from the affected horse tericin B is expensive, and prolonged use can result in
(Kaufman et al 1990, Steiger and Williams 2000). nephrotoxicosis and thrombophlebitis.
Diagnosis of cryptococcosis can be confirmed by identi- Ancillary treatment of horses affected with condio-
fying Cryptococcus neoformans during cytologic examination bolomycosis includes systemic administration of sodium
of nasal exudate, by serology, or by culture (Watt 1970, iodide (67 mg/kg, intravenous, once daily) for 2–5 days
Pearson et al 1983, Corrier et al 1984). Examination of and then oral administration of organic iodide (ethylene-
nasal exudate stained with periodic acid–Schiff or India ink diamine dihydroiodide) (40 mg/kg, orally, once daily) in-
reveals the characteristic thickly encapsulated budding definitely (Scott & Miller 2003). The mechanism of action
yeast bodies. Culture of Cryptococcus neoformans requires of iodide against Conidiobolus coronatus is not known.
3–5 days (Corrier et al 1984). The latex agglutination Treatment of horses with a nasal granuloma caused by
test has been used to diagnose cryptococcosis in people and Cryptococcus neoformans is usually unsuccessful (Corrier et
cats (Medleau et al 1990) and would likely be useful in al 1984). The disease is difficult to resolve because the
diagnosing the condition in horses. gelatinous capsule that surrounds the yeast masks
the attached opsonic antibody, protecting the organisms
Treatment from phagocytosis. Therapy has included excision of the
granuloma, cryotherapy, and parenteral treatment of the
Treatment for rhinosporidiosis is by excision of the lesions affected horse with sodium iodide and an antibiotic, most
(Smith 1961, Myers et al 1964, Hodgin et al 1984). commonly amphotericin B (see earlier discussion on treat-
Surgical margins should be wide to avoid recurrence. ment of horses with conidiobolomycosis for dosages). The
Freezing the entire lesion or the base of the lesion after difficulty in resolving infection and the potential threat to
excision may be effective (authors’ experience). Therapeutic human health may justify euthanasia of infected horses.
results have been obtained in dogs, when surgical excision However, there is no clear evidence that cryptococcosis is
was not possible, by administering dapsone (diamino- transmissible from one host to another or from animals to
diphenylsulfone), a drug used for treatment of leprosy human beings (Roberts et al 1981).
(Allison et al 1986). Therapy with dapsone can, how- The treatment of horses affected with coccidioidomy-
ever, result in hemolytic anemia, agranulocytosis, and cosis is by antifungal therapy (see earlier discussion on
methemoglobinemia. The use of dapsone for treatment treatment of horses with conidiobolomycosis for drugs and
of affected horses has not been reported. Experience in dosages) in conjunction with surgical removal of lesions.
human patients affected with rhinosporidiosis is that the Long-term, oral administration of itraconazole (2.6 mg/kg,
infection is locally persistent, and that repeated surgical q 12 h) was apparently effective in the treatment of a horse
removal of recurring polyps is often required (Ainsworth & affected with coccidioidomycosis (Foley & Legendre 1992),
Austwick 1959). even though this drug has been shown to be absorbed
Treatment of horses affected by conidiobolomycosis poorly from the horse’s gastrointestinal tract (Korenek
includes excision of lesions and parenteral and topical et al 1994).
administration of antifungal drugs. Complete excision of
nasal and nasopharyngeal lesions of conidiobolomycosis
may be difficult because lesions within these locations may
be surgically inaccessible. Although horses with pythiosis
Nasal Amyloidosis
have been treated successfully with a vaccine made from Amyloidosis is a group of diseases characterized by the
Pythium insidiosum (Miller 1981), immunotherapy as a deposition of a homogeneous, extracellular proteinaceous
treatment for horses with conidiobolomycosis does not seem substance, amyloid, in tissue (Husby 1988). The two major
to be effective (authors’ experience, Taintor et al 2004). types of amyloid are amyloid AA, which is derived from a
Horses affected with conidiobolomycosis have been serum α-globulin, a normal acute-phase protein produced
treated successfully with orally administered fluconazole by the liver, and amyloid AL, which consists of monoclonal
(5 mg/kg, q 12 h, for 6 weeks) (Taintor et al 2004), but immunoglobulin light chains and fragments of light
parenteral treatment of affected horses with the similar chains. Amyloid AA may be deposited in various tissues
antifungal drugs, ketoconazole or itraconazole, is less likely when its concentration in serum is chronically elevated by
to be successful because these drugs are absorbed poorly inflammation or antigenic stimulation (Husby 1988,
from the horse’s gastrointestinal tract (Korenek et al Mould et al 1990).
1994). Affected horses have also been treated successfully Nasal amyloidosis is a disease peculiar to horses. Lesions
with parenteral and intralesional administration of ampho- are reported to be composed of amyloid AL, but the cause
tericin B (0.2–1.0 mg/kg, intravenous, in 1 liter 5% dextrose of deposition of amyloid AL in the nasal cavity of horses
over 20–30 min every other day or 10–20 mg/lesion) is idiopathic and is usually not associated with any
Fig. 25.15. A nodular mass composed of

amyloid at the right external naris.
underlying disease (Shaw et al 1987, van Andel et al nucleated giant cells. Amyloid is deposited within and
1988, Mould et al 1990, Kasper et al 1994, Robertson & around blood vessels, the basement membrane of glands,
Rooney 1997). An inhaled toxicant or antigenic stimulus and within the connective tissue (Smith et al 1972,
may be the inciting cause (Kasper et al 1994). Robertson & Rooney 1997). A specific stain for amyloid is
Congo red, which stains the amyloid orange-red (Shaw et al
Signalment 1987, Kasper et al 1994).
Too few horses affected with nasal amyloidosis have been Diagnosis
reported to conclude that the disease has an age, breed, or
sex predilection. Nasal amyloidosis must be differentiated from nasal
neoplasia and nasal fungal granulomas. Diagnosis is based
Clinical signs on the gross and histologic appearance of the lesion.
Clinical signs of nasal amyloidosis include the presence of Treatment

multiple, nodular, mucosa-covered masses at the external
nares (Fig. 25.15). The nasal septum and alar folds may be Medical therapy appears to be ineffective, consequently
thickened. During endoscopic examination of the upper removal of the masses (or affected structures, such as
portion of the respiratory tract, the lesions may be the alar folds or nasal septum) is the only treatment
seen extending into the nasopharynx (Shaw et al 1987, (Shaw et al 1987, Kasper et al 1994, Hawkins et al 1995).
Kasper et al 1994). The masses are often ulcerated and Removal of lesions of nasal amyloidosis apparently effects
bleed easily after gentle, digital manipulation. A com- cure, and the masses are unlikely to recur (Shaw et al 1987,
mon clinical sign of horses with amyloid deposits in the Husby 1988, Kasper et al 1994). Masses may be surgically
nasal cavities is epistaxis. Other signs include respiratory inaccessible or so extensive, however, that complete removal
obstruction, abnormal respiratory noise, and decreased is not possible.
athletic performance.
Pathology Neoplasia
On cut section, the lesions have a pale yellow, waxy appear- The most common nasal neoplasm of horses is the car-
ance (Shaw et al 1987, Kasper et al 1994). Microscopically, cinoma (Schuh 1986), and the three most common intra-
the nasal mucosa is intact. The submucosa contains an nasal carcinomas are the adenocarcinoma, squamous cell
acellular, amorphous, homogeneous, pale, eosinophilic carcinoma, and undifferentiated carcinoma. Because of
material (i.e. amyloid) and a few histiocytes and multi- the variety of tissue found in the nasal cavities, other
neoplasms, such as fibroma, myxoma, chondroma, osteo-

sarcoma, fibrosarcoma, neurofibroma, hemangiosarcoma,
and lymphoma, may also occur, although less commonly.
Prevalence
Sinonasal neoplasia of horses is encountered uncommonly,
compared to sinonasal neoplasia of other species (Head &
Dixon 1999). Horses with sinonasal neoplasia represent
only about 0.2% of all referred horses (Dixon & Head
1999), and comprise only 8–19% of all horses with sino-
nasal disease (Boulton 1985, Tremaine & Dixon 2001a).
Signalment
Old horses are more at risk for nasal neoplasia in general
and are especially at risk for neoplasia of epithelial origin
(Madewell et al 1976, Dixon & Head 1999). Although
fibro-osseous nasal tumors can be found in horses of any Fig. 25.16. Endoscopic view of the left nasal cavity of a horse. Because
of its location, the carcinoma within the ethmoidal labyrinth could be
age, they are found most frequently in young horses.
mistaken during examination for a progressive ethmoidal hematoma.
Clinical signs
Clinical signs of nasal neoplasia typically become apparent
slowly and insidiously and can include stertorous respi- 1986). Histologic grading of nasal carcinomas is of little
ration, reduced airflow from the affected nasal cavity, and value, though, because grading is subjective and results
unilateral nasal discharge, which can be purulent, muco- vary with the site of sampling, and because the correlation
purulent, sanguineous, or serosanguineous (Dixon & Head between the degree of differentiation and the tendency to
1999). Because horses with nasal neoplasia commonly metastasize is poor (Schuh 1986, Head & Dixon 1999).
have mucopurulent nasal discharge, primary bacterial The malignant nature of most intranasal carcinomas
rhinitis or paranasal sinusitis is often mistakenly diagnosed. is reflected by their local invasiveness; however, despite
Other signs include ipsilateral enlargement of the sub- their locally aggressive nature most sinonasal tumors are
mandibular lymph nodes, epiphora, and, with growth of slow to metastasize to regional lymph nodes (Head & Dixon
the tumor, distortion of the nasal or maxillary bones. 1999). Metastasis usually only occurs late in the course of
Ipsilateral enlargement of submandibular lymph nodes is the disease.
usually caused by reactive lymphadenopathy associated
with local infection and tumor necrosis, rather than by Differential diagnosis
neoplastic involvement. Distortion of the nasal cavity by
the neoplasm may cause the nasal septum to deviate into Nasal neoplasia must be differentiated from granulomas
the contralateral nasal cavity. Affected horses may exhibit caused by periapical infection of a maxillary premolar,
signs of systemic disease, including lethargy, anorexia, and nasal amyloidosis, and nasal mycotic granulomas. A nasal
weight-loss. The neoplasm may be visible at the external neoplasm may occasionally bear some resemblance to a
naris, but usually endoscopy is required to observe the progressive ethmoidal hematoma (Fig. 25.16).
mass. Some nasal squamous cell carcinomas develop in
the hard palate and then invade the nasal cavity (and Diagnosis
paranasal sinuses); therefore, oral examination of horses
suspected of having sinonasal neoplasia may reveal a prolif- Definitive diagnosis of nasal neoplasia is based on results of
erating lesion on the hard palate (Dixon & Head 1999). cytologic and histologic examination of biopsy specimens.
Cytologic examination of a fine-needle aspirate from a
Pathology nasal mass may be helpful in obtaining a diagnosis, but
care should be taken not to misinterpret dysplastic cells
Squamous cell carcinoma, the most common nasal found in severely inflamed mucosa as being neoplastic.
neoplasm, is classified by its cytologic features and degree Biopsy samples should be obtained from deep within the
of keratinization as being either well-differentiated, tumor to avoid sampling the overlying surface epithelium
moderately differentiated, or poorly differentiated (Schuh (Scarratt & Crisman 1998, Head & Dixon 1999).
Despite the use of radiography and endoscopy, the site

of origin of most sinonasal tumors cannot be deter-
mined (Dixon & Head 1999). Computed tomography and
magnetic resonance imaging offer more information
about the origin and extent of neoplasia than does plain
radiography and may aid the planning of an effective
strategy for radiotherapy.
Treatment
Most horses affected with neoplasia of the nasal cavity are
eventually euthanased because success of treatment is
poor. Nasal neoplasms are relatively inaccessible, and
because they are invasive, their margins are often poorly
defined. The advanced stage of disease when recognized
and the anatomical complexity and vascularity of the
area involved make complete surgical excision or cryo-
therapy difficult or impossible. If immediate euthanasia
is not a satisfactory option, the therapeutic objective is Fig. 25.17. A polyp is visible at the left external naris of this horse.
Reproduced with the permission of Dr Mark Crabill.
usually to palliate clinical signs. For example, horses
experiencing difficult breathing as a result of occlusion
of the nasal cavities by the neoplasm can be treated by
temporary tracheostomy or by creating a permanent
tracheal fistula. breathing, and dyspnea (Nickels 1993, Watt & Beck 1997).
Horses with sinonasal carcinoma have been treated A polyp may be visible at the external nares (Fig. 25.17),
successfully using fractionated, cobalt-60 radiotherapy, but rhinoscopy may be required to observe the mass.
but multiple treatments with the horse anesthetized are
necessary, and the equipment required is not readily Pathology
available (Walker et al 1998). Even this form of therapy
should be considered palliative, not curative. Polyps are covered by nasal mucosa and are composed of
fibrous and myxomatous tissue that contains numerous
Prognosis capillaries and is infiltrated by leukocytes, chiefly neu-
trophils and lymphocytes (Smith et al 1972). The histo-
Treatment of affected horses is usually not successful, and logic appearance of polyps indicates an inflammatory
the disease is eventually fatal. The life expectancy of an etiology and is similar to that of granulation tissue found
affected horse depends on the type of neoplasm and the in wounds.
owner’s tolerance of the clinical signs. The course of
disease is usually protracted. Diagnosis
Diagnosis is based on clinical signs and gross and histologic
appearance of the lesion, but distinguishing between
Nasal Polyps a benign neoplasm and an inflammatory polyp may be
A polyp is an uncommonly reported, smooth, mucosa- difficult. Radiography of the skull may aid in determining
covered growth on a mucosal surface caused by a hyper- the extent and origin of the polyp.
plastic response of the mucosa or associated lymphoid
tissue, usually to inflammatory or allergic stimulation Treatment
(Smith et al 1972, Head & Dixon 1999).
Treatment of affected horses is to remove the polyp.
Clinical signs Pedunculated polyps can be removed with a snare using
endoscopic guidance (Watt & Beck 1997). Both pedun-
Polyps vary in size and may entirely fill the nasal cavity in culated and sessile polyps can be removed transendo-
which they are located. They may be solitary or multiple, scopically using electrocautery or a laser. Large polyps in
but most are pedunculated (Smith et al 1972, Head & the caudal portion of the nasal cavity can be accessed
Dixon 1999). Clinical signs usually develop insidiously through an osteoplastic nasal flap. The prognosis for
and may include unilateral nasal discharge, stertorous resolution is good with removal of the lesion.
Fig. 25.18. (A) An osteoma (o) within the

left nasal cavity of a horse. (B) An endo-
scopic view of the nasal cavity after the
osteoma was excised.
A B
Osteomas
bone (Pool 1978, Atallah & Jay 1981). The proportions of
Osteomas are smooth, solitary osseous growths protruding these two types of bone vary according to the rate of
from the surface of a bone, typically a bone formed by growth of the osteoma. Well-developed Haversian canal
intramembranous ossification (Spjut et al 1971, Pool systems can be identified as the osteoma remodels (Head &
1978, Aegerter & Kirkpatrick 1979). They are regarded by Dixon 1999).
some pathologists to be hamartomas and as such, are
present at or soon after birth and represent a benign, Diagnosis
disordered overgrowth of mature bone.
Diagnosis is based on physical examination of the horse, endo-
Signalment scopic examination of the nasal cavities, and radiographic
examination of the skull. Diagnosis can be confirmed by
Although female horses can be affected by sinonasal histological examination of a biopsy specimen, but because
osteoma (Steinman et al 2002), in nearly all reports, of their hardness, most osteomas are difficult to biopsy.
horses affected with sinonasal osteoma have been male An osteoma causing no clinical signs may be discovered
(Freeman et al 1990, DelPiero et al 1997). The cause of incidentally during radiographic examination of the skull
the preponderance of osteoma occurrence in male horses is performed for reasons other than clinical signs caused by
not known, but the same predilection of osteomas for men the osteoma (Scrutchfield et al 1994).
is also reported (Spjut et al 1971).
Treatment and prognosis
Clinical signs
Removal of an osteoma from the nasal cavity may require
Most osteomas are probably present at birth, although creation of a nasal flap and therefore may be more difficult
years may elapse before clinical signs are recognized (Head than removal of an osteoma from the paranasal sinuses
and Dixon 1999). Clinical signs of nasally located (authors’ experience). If removed completely, osteomas do
osteomas (Fig. 25.18) are those produced by any expansile, not recur. Incomplete removal does not appear to stimulate
space-occupying lesion in the nasal cavity and include growth, but the probability of growth of the remnants
mucopurulent nasal discharge, epiphora, restricted airflow, remains. If the osteoma was not completely removed, the
and facial distortion (Schumacher et al 1988). horse should be monitored periodically for regrowth of the
osteoma by radiographic and endoscopic examination (Pool
Pathology 1978, Atallah & Jay 1981).
Osteomas may be sessile or pedunculated and are expansile

rather than infiltrative. An osteoma may demonstrate slow
Osteodystrophia Fibrosa
but progressive growth and then may cease growth and Osteodystrophia fibrosa is a nutrition-induced, skeletal
remain quiescent for years (Pool 1978). They apparently disease characterized by deposition of non-mineralized,
do not undergo malignant transformation. Histologically, fibrous tissue in affected bones (Joyce et al 1971). This
osteomas are composed of a central core of cancellous disease causes thickening of the mandible, maxilla, conchae,
bone surrounded by a peripheral layer of dense compact and other facial bones, resulting in bilaterally symmetrical
enlargement of the head. Other names for the disease

include miller’s disease, bighead, and bran disease.
Osteodystrophia fibrosa is a manifestation of nutritional
secondary hyperparathyroidism caused by diets that are
low in calcium or by diets with three or more times as
much phosphorus as calcium, regardless of whether the
calcium content is deficient (Joyce et al 1971). The disease
was previously caused by diets high in bran (hence the
terms, miller’s disease and bran disease), but now it occurs
most commonly in horses eating large amounts of certain
tropical grasses (Clarke et al 1996). Excessive dietary
phosphorus, by unknown mechanisms, inhibits calcium
absorption and causes hypocalcemia (Clarke et al 1996).
Sustained dietary intake of excessive phosphorus results in
decreased concentration of ionic calcium in the serum and
subsequent stimulation of secretion of parathormone
(Joyce et al 1971). The abnormally high concentration of
parathormone causes bone resorption and deposition of
fibrous tissue, preferentially in the skull.
Prevalence
Osteodystrophia fibrosa of horses is now an uncommon
disease in Western countries because of improved dietary
knowledge, but it occurs in subtropical climates where Fig. 25.19. A prominent feature of this horse affected with osteo-
certain plants predispose horses to this dietary disorder dystrophia fibrosa is the bilaterally symmetrical enlargement of the
facial bones immediately dorsal and rostral to the facial crests.
(Clarke et al 1996). Young, growing horses are most
commonly affected.
Clinical signs
by numerous, large, multinucleate osteoclasts are found
The most prominent feature of the affected horses is within the fibrous tissue, which may have patchy cystic
bilaterally symmetrical, firm, pyramidal enlargement of the degeneration (Head & Dixon 1999). The parathyroid
facial bones immediately dorsal and rostral to the facial glands may show features of hypertrophy and hyperplasia
crests and thickening of the horizontal rami of the (DelPiero et al 1997).
mandible (Fig. 25.19) (Clarke et al 1996). Gross thicken-
ing of the maxillary bones, conchae, and hard palate by Diagnosis
supraperiosteal deposition of fibro-osseous tissue occludes
the nasal cavities, and severely affected horses may become Diagnosis of osteodystrophia is based on observed charac-
dyspneic. Severely affected horses may also have loosen- teristic skeletal changes (Joyce et al 1971). Radiographic
ing of the teeth and difficulty in masticating, which may examination may reveal loss of trabeculation of long bones
lead to cachexia. In advanced cases of osteodystrophia and increased radiolucency of all bones. Diagnosis of the
fibrosa, other skeletal areas may be affected, and these condition can sometimes be assisted by detecting a low
lesions may predispose the horse to lameness as a result concentration of calcium and a high concentration of
of fractures, avulsion of ligaments, and limb deformity phosphorus in the urine. Concentrations of these minerals
(Clarke et al 1996). in the serum are usually normal because of the compen-
satory activity of the parathyroid glands (Joyce et al 1971).
Pathology
Treatment and prognosis
The maxillary, ventral conchal, and conchofrontal sinuses
of horses affected by osteodystrophia fibrosa are filled Horses affected with osteodystrophia fibrosa should be
with firm, slightly spongy tissue (Clarke et al 1996). During treated by correcting the dietary calcium : phosphorus ratio
histologic examination of affected tissue, dense, highly to between 1.5 and 1. Although dietary management may
cellular fibrous tissue arranged in whorls and streams is partially resolve some of the skeletal lesions, severely
seen replacing cortical bone. Osseous trabeculae surrounded affected horses may fail to show significant improvement
in respiratory capacity (Joyce et al 1971, Clarke et al 1996). Davis PR, Meyer GA, Hanson RR, Stringfellow JS 2000
Resection of deformed, occluding nasal conchae through Pseudallescheria boydii infection of the nasal cavity of a
trephination holes has been described (Berge & Westhues horse. Journal of the American Veterinary Medical
1966), but permanent tracheostomy may be necessary to DelPiero F, Wilkins PA, Langsetmo I, Fubini SL 1997 An
restore respiratory capacity. Facial deformity is not likely unusual cause of unilateral facial deformity in a yearling
to resolve. horse. Equine Practice 19: 8–11
DeMartini JC, Riddle WE 1969 Disseminated coccidioidomy-
cosis in two horses and a pony. Journal of the American
REFERENCES Veterinary Medical Association 155: 149–156
des Lions JA, Guillot J, Legrand E, Bisseaud O, Jensen HE 2000
Aegerter E, Kirkpatrick JA Jr 1979 Orthopedic Diseases, Aspergillosis involving the frontal sinus in a horse.
3rd edn. WB Saunders, Philadelphia, pp.1–5 Equine Veterinary Education 12: 248–250
Ainsworth GC, Austwick PKC 1959 Fungal Diseases of Dixon PM, Head KW 1999 Equine nasal and paranasal
Animals. Commonwealth Agricultural Bureau, Farnham sinus tumours: part 2: a contribution of 28 case reports.
Royal, pp.44–45 Veterinary Journal 157: 279–294
Alfaro AA, Mendoza L. 1990 Four cases of equine bone lesions Foerner JJ 1967 The diagnosis and correction of false nostril
caused by Pythium insidiosum. Equine Veterinary Journal noises. Proceedings of the American Association of
22: 295–297 Equine Practitioners 13: 315–327
Allison N, Willard MD, Bentinck-Smith J, Davis K 1986 Nasal Foley JP, Legendre AM 1992 Treatment of coccidioidomycosis
rhinosporidiosis in two dogs. Journal of the American osteomyelitis with itraconazole in a horse. Journal of
Veterinary Medical Association 188: 869–871 Veterinary Internal Medicine 6: 333–334
Atallah N, Jay MM 1981 Osteomas of the paranasal sinuses. Frankeny RL 2003 Intralesional administration of formalin for
Journal of Laryngology and Otology 95: 291–304 treatment of epidermal inclusion cysts in five horses.
Ayars G 2000 Nonallergic rhinitis. Immunology and Allergy Journal of the American Veterinary Medical Association
Clinics of North America 20: 283–302 223: 221–222
Aylor MK, Campbell ML, Goring RL, Hillidge CJ 1984 Freeman DE, Orsini PG, Ross MW, Madison JB 1990 A large
Congenital bilateral choanal atresia in a Standardbred frontonasal bone flap for sinus surgery in the horse.
foal. Equine Veterinary Journal 16: 396–398 Veterinary Surgery 19: 122–130
Baker GJ 1999 Abnormalities of development and eruption. French DD, Haynes PF, Miller RI 1985 Surgical and medical
In: Baker FJ, Easley JR (editors) Equine Dentistry, 1st edn. management of rhinophycomycosis (conidiobolomycosis)
WB Saunders, Philadelphia, pp.49–59 in a horse. Journal of the American Veterinary Medical
Barakzai SZ, Dixon PM 2005 Sliding muco-periosteal hard Association 186: 1105–1107
palate flap for treatment of a persistent oro-nasal fistula. Gillespie JH 1981 Hagan and Bruner’s Infectious Diseases of
Equine Veterinary Education 17: 287–291 Domestic Animals, 7th edn. Cornell University Press,
Beard W 1996 Upper respiratory causes of exercise intoler- Ithaca, NY, pp.372–376
ance. Veterinary Clinics of North America; Equine Practice Gordon LR 1978 Cytology and histology of epidermal
12: 435–453 inclusion cysts in the horse. Journal of Equine Medicine
Bemis H 1916 Removal of the nasal septum. Journal of the and Surgery 2: 370–372
American Veterinary Medical Association 2: 397–399 Goring RL, Campbell M, Hillidge CJ 1984 Surgical correction
Berge E, Westhues M 1966 Veterinary Operative Surgery. of congenital bilateral choanal atresia in a foal.
Williams and Wilkins, Baltimore, pp.140–142 Veterinary Surgery 13: 211–216
Boles C 1979 Abnormalities of the upper respiratory tract. Greet TRC 1981 Nasal aspergillosis in three horses. Veterinary
Veterinary Clinics of North America; Equine Practice Record 109: 487–489
1: 89–111 Greet TRC 1992 Outcome of treatment in 23 horses with
Boulton CH 1985 Equine nasal cavity and paranasal cavity progressive ethmoidal hematoma. Equine Veterinary
disease: a review of 85 cases. Journal of Equine Veterinary Journal 24: 468–471
Science 5: 268–275 Grooters A, Gee MK 2002 Development of a nested poly-
Brearley JC, McCandlish IA, Sullivan M, Dawson CO 1986 merase chain reaction assay for the detection and iden-
Nasal granuloma caused by Pseudallescheria boydii. tification of Pythium insidiosum. Journal of Veterinary
Equine Veterinary Journal 18: 151–153 Internal Medicine 16: 147–152
Bridges CH 1972 Mycotic diseases. In: Catcott EJ, Smithcors JF Hanselka DV 1977 Equine nasal phycomycosis. Veterinary
(editors) Equine Medicine and Surgery, 2nd edn. American Medicine/Small Animal Clinician 72: 251–253
Veterinary Publications, Wheaton, IL, pp.119–135 Hawkins JF, Tulleners EP, Evans LH, Orsini JA 1995 Alar fold
Campbell CK 1990 Pythiosis. Equine Veterinary Journal resection in horses: 24 cases (1979–1992). Journal of the
22: 227–228 American Veterinary Medical Association 206: 1913–1916
Clarke CJ, Roeder PL, Dixon PM 1996 Nasal obstruction Haynes PF 1984 Surgery of the equine respiratory tract. In:
caused by nutritional osteodystrophia fibrosa in a group Jennings PB (editor) The Practice of Large Animal
of Ethiopian horses. Veterinary Record 138: 568–570 Surgery, Vol. 1. WB Saunders, Philadelphia, pp.388–487
Corrier DE, Wilson SR, Scrutchfield WL 1984 Equine crypto- Head KW, Dixon PM 1999 Equine nasal and paranasal sinus
coccal rhinitis. Compendium on Continuing Education tumours. Part 1: review of the literature and tumour
for the Practicing Veterinarian 6: S556–S558 classification. Veterinary Journal 157: 261–278
Crouch GM, Morgan SJ 1983 Bilateral congenital choanal Hengerer AS, Stome M 1982 Choanal atresia: a new embry-
atresia in a foal. Compendium on Continuing Education ologic theory and its influence on surgical management.
for the Practicing Veterinarian 5: 206–211 Laryngoscope 92: 913–921
Hodgin EC, Conaway DH, Ortenburger AI 1984 Recurrence of with immunotherapy of equine phycomycosis. Journal
obstructive nasal coccidioidal granuloma in a horse. of the American Veterinary Medical Association 182:
Journal of the American Veterinary Medical Association 1227–1229
184: 339–340 Milne EM, Woodman MP, Doxey DL 1994 Use of clinical
Hogan PM, Embertson RM, Hunt RJ 1995 Unilateral choanal measurements to predict the outcome in chronic cases of
atresia in a foal. Journal of the American Veterinary grass sickness (equine dysautonomia). Veterinary Record
Husby G 1988 Equine amyloidosis. Equine Veterinary Journal Mould JR, Munroe GA, Eckersall PD, Conner JG, McNeil PE
20: 235–238 1990 Conjunctival and nasal amyloidosis in a horse.
Hutchins DR, Johnston KG 1972 Phycomycosis in the horse. Equine Veterinary Journal Supplement 10: 8–11
Australian Veterinary Journal 48: 269–278 Murray DR, Ladds PW, Johnson RH, Pott BW 1978 Metastatic
Joyce J, Pierce K, Romane W, Baker JM 1971 Clinical study of phycomycosis in a horse. Journal of the American
nutritional secondary hyperparathyroidism in horses. Veterinary Medical Association 172: 834–836
Journal of the American Veterinary Medical Association Myers DD, Simon J, Case MT 1964 Rhinosporidiosis in a horse.
158: 2033–2042 Journal of the American Veterinary Medical Association
Kasper CA, Fretz PB, Allen AL, Clark EG 1994 Nasal 145: 345–347
amyloidosis: a case report and review. Equine Practice Newton JC, Ross PS 1993 Equine pythiosis: an overview of
16: 25–30 immunotherapy. Compendium on Continuing Education
Kaufman L, Mendoza L, Standard PG 1990 Immunodiffusion for the Practicing Veterinarian 15: 491–493
test for serodiagnosing subcutaneous zygomycosis. Nickels FA 1993 Diseases of the nasal cavity. Veterinary
Journal of Clinical Microbiology 28: 1887–1890 Clinics of North America; Equine Practice 9: 111–121
Kelly DF, Watson WJ 1976 Epidermoid cyst of the brain in the Orsini PG, Ross MW, Hamir AN 1992 Levator nasolabialis
horse. Equine Veterinary Journal 8: 110–112 muscle transposition to prevent an orosinus fistula after
Korenek NL, Legendre AM, Andrews FM 1994 Treatment tooth extraction in horses. Veterinary Surgery 21: 150–156
of mycotic rhinitis with itraconazole in three horses. Owens WR, Miller RI, Haynes PF, Snider TG 1985
Journal of Veterinary Internal Medicine 8: 224–227 Phycomycosis caused by Basidiobolus haptosporus in two
Lane JG 1998 Disorders of the ear, nose and throat. In: Mair T, horses. Journal of the American Veterinary Medical
Love S, Schumacher J, Watson E (editors) Equine Medicine Association 186: 703–705
Surgery and Reproduction. WB Saunders, Philadelphia, Pascoe RR 1981 Equine Dermatoses. University of Sydney,
pp.81–117 Sydney, p.29
Lane JG, Mair TS 1987 Observations on headshaking in the Pearson EG, Watrous BJ, Schmitz JA, Sonn RJ 1983 Crypto-
horse. Equine Veterinary Journal 19: 331–336 coccal pneumonia in a horse. Journal of the American
Londero AT, Santos MN, Freitas CJ 1977 Animal rhino- Veterinary Medical Association 183: 577–579
sporidiosis in Brazil. Report of three additional cases. Pool RR 1978 Tumors of bone and cartilage. In: Moulton JE
Mycopathologia 60: 171–173 (editor) Tumors of Domestic Animals, 2nd edn. University
Madewell BR, Priester WA, Gillette EL, Snyder SP 1976 of California Press, Berkeley, CA, pp.99–103
Neoplasms of the nasal passages and paranasal sinuses Puchol JL, Herran R, Durall L, Lopez J, Diaz-Bertrana C 2004
in domesticated animals as reported by 13 veterinary Use of distraction osteogenesis for the correction of
colleges. American Journal of Veterinary Research deviated nasal septum and premaxilla in a horse.
37: 851–865 Journal of the American Veterinary Medical Association
Maniglia A, Goodwin W 1981 Congenital choanal atresia. 224: 1147–1150
Otolaryngologic Clinics of North America 14: 167 Roberts MC, Sutton RH, Lovell DK 1981 A protracted case of
McGorum BC, Dixon PM 1990 Vasomotor rhinitis with cryptococcal nasal granuloma in a stallion. Australian
headshaking in a pony. Equine Veterinary Journal Veterinary Journal 57: 287–291
22: 220–222 Robertson JL, Rooney JR 1997 The pathology of the equine
McGorum BC, Dixon PM, Lawson GHK 1992 A review of ten respiratory system. In: Rantanen N, Hauser ML (editors)
cases of mycotic rhinitis. Equine Veterinary Education Proceedings of the 2nd International Dubai Equine
4: 8–12 Symposium. Mathew Rantanen Design, Wildomar, CA,
McKellar GM, Collins AP 1993 The surgical correction of a pp.189–239
deviated anterior maxilla in a horse. Australian Scarratt WK, Crisman MV 1998 Neoplasia of the respiratory
Veterinary Journal 70: 112–114 tract. Veterinary Clinics of North America; Equine Practice
Medleau L, Greene CE, Rakich M 1990 Evaluation of keto- 14: 451–473
conazole and itraconazole for treatment of disseminated Schuh JC 1986 Squamous cell carcinoma of the oral,
cryptococcosis in cats. American Journal of Veterinary pharyngeal, and nasal mucosa in the horse. Veterinary
Research 51: 1454–1458 Pathology 23: 205–207
Miller RI 1981 Treatment of equine phycomycosis by Schumacher J, Smith BL, Morgan SJ 1988 An osteoma of the
immunotherapy and surgery. Australian Veterinary paranasal sinuses of a horse. Journal of the American
Journal 57: 377–382 Veterinary Medical Association 192: 1449–1450
Miller RI 1983 Equine phycomycosis. Compendium on Schumacher J, Moll HD, Schumacher J, Crabill M 1997
Continuing Education for the Practicing Veterinarian A simple method to remove an epidermal inclusion
5: 472–478 cyst from the false nostril of horses. Equine Practice
Miller RI, Campbell RS 1982 Clinical observations on equine 19: 11–13
phycomycosis. Australian Veterinary Journal 58: 221–226 Schummer A, Nickel R, Sack WO 1979 The Viscera of the
Miller RI, Wold D, Lindsay WA, Beadle RE, McClure JJ, Domestic Mammals, 2nd edn. Paul Parey, Berlin &
McClure JR, McCoy DJ 1983 Complications associated Hamburg, p.304
Scott DW, Miller WHJ 2003 Equine Dermatology. Elsevier paralysis of the nostril in a racing Standardbred. Equine
Science, St Louis, MO, pp.311–312 Veterinary Education 15: 10–14
Scrutchfield WL, Schumacher J, Walker M, Crabill M 1994 Tremaine WH, Clarke CJ, Dixon PM 1999 Histopathological
Removal of an osteoma from the paranasal sinuses of a findings in equine sinonasal disorders. Equine Veterinary
standing horse. Equine Practice 16: 24–28. Journal 31: 296–303
Servantie J, Sautet JY 1986 Hamartoma of the nasal septum Tremaine WH, Dixon PM 2001a A long-term study of 277
in a yearling. Equine Practice 8: 11–14 cases of equine sinonasal disease. Part 1: details of horses,
Shaw DP, Gunson DE, Evans LH 1987 Nasal amyloidosis in historical, clinical and ancillary diagnostic findings. Equine
4 horses. Veterinary Pathology 24: 183–185 Veterinary Journal 33: 274–282
Silverman S, Merten DF, Anderson JH, Hendrickx AG 1977 Tremaine WH, Dixon PM 2001b A long-term study of 277
Radiographic diagnosis of choanal atresia induced cases of equine sinonasal disease. Part 2: Treatments
prenatally with triamcinolone in the baboon (Papio cyno- and results of treatments. Equine Veterinary Journal
cephalus). Journal of Medical Primatology 6: 284–297 33: 283–289
Sisson S, Grossman JD 1953 The Anatomy of Domestic Animals, Tulleners EP, Raker CW 1983 Nasal septum resection in the
4th edn. WB Saunders, Philadelphia, pp.517–563 horse. Veterinary Surgery 12: 41–47
Smith HA 1961 Rhinosporidiosis in Texas horse. Southwest Valdez H, McMullan WC, Hobson HP, Hanselka DV 1978
Veterinarian 15: 22–24 Surgical correction of deviated nasal septum and
Smith HA, Jones TC, Hunt RD 1972 Veterinary Pathology, premaxilla in a colt. Journal of the American Veterinary
4th edn. Lea & Febiger, Philadelphia, pp.261, 325, 1336 Medical Association 173: 1001–1004
Spjut HJ, Dorfman HD, Fechner RE, Ackerman, LV 1971 van Andel AC, Gruys E, Kroneman J, Veerkamp J 1988
Tumors of Bone and Cartilage. Armed Forces Institute of Amyloid in the horse: a report of nine cases. Equine
Pathology, Washington, DC, pp.17–119 Veterinary Journal 20: 277–285
Sprinkle FP, Crowe MW, Swerczek TW 1984 Choanal atresia in Vandeplassche M, Simoens P, Bouters R, De Vos N,
foals. Modern Veterinary Practice 65: 306 Verschooten F 1984 Aetiology and pathogenesis of
Steiger RR, Williams MA 2000 Granulomatous tracheitis congenital torticollis and head scoliosis in the equine
caused by Conidiobolus coronatus in a horse. Journal of foetus. Equine Veterinary Journal 16: 419–424
Veterinary Internal Medicine 14: 311–314 Vasey JR, McKinnon AO, Axon JE, Hazard GH, Lescun TB 1995
Steinman A, Sutton GA, Lichawski D, Johnston DE 2002 Nasal flutter as a cause of poor performance in race
Osteoma of paranasal sinuses in a horse with inspiratory horses – a review of 22 cases (1981–1995). Veterinary
dyspnoea. Australian Veterinary Journal 80: 140–142 Surgery 24: 444
Stilson AE Jr, Herring DS, Robertson JT 1985 Contribution of Walker MA, Schumacher J, Schmitz DG, et al 1998 Cobalt 60
the nasal septum to the radiographic anatomy of the radiotherapy for treatment of squamous cell carcinoma
equine nasal cavity. Journal of the American Veterinary of the nasal cavity and paranasal sinuses in three horses.
Medical Association 186: 590–592 Journal of the American Veterinary Medical Association
Taintor J, Schumacher J, Newton J 2003 Conidiobolomycosis 212: 848–851
in horses. Compendium on Continuing Education for the Watt BC, Beck BE 1997 Removal of a nasal polyp in a standing
Practicing Veterinarian 25: 872–876 horse. Canadian Veterinary Journal 38: 108–109
Taintor J, Crowe C, Hancock S, Schumacher J, Livesey L 2004 Watt DA 1970 A case of cryptococcal granuloma in the
Treatment of conidiobolomycosis with fluconazole in two nasal cavity of a horse. Australian Veterinary Journal
pregnant mares. Journal of Veterinary Internal Medicine 46: 493–495
18: 363–364 Zamos DT, Schumacher J, Loy JK 1996 Nasopharyngeal
Torre F 2000 Use of a stainless steel mesh combined with conidiobolomycosis in a horse. Journal of the American
resection of the alar fold for correction of unilateral Veterinary Medical Association 208: 100–101
paralysis of the nostril in a Standardbred filly. Equine Zontine WJ 1958 Coccidioidomycosis in the horse; a case
Veterinary Education 12: 234–236 report. Journal of the American Veterinary Medical
Torre F 2003 Use of an autogenous cartilage graft from Association 132: 490–492
the auricular cartilage in the treatment of unilateral
Disorders of the Paranasal Sinuses
26 Henry Tremaine and David E Freeman
nosa, Bacteroides spp., Peptostreptococcus spp. (Ruggles et al

Introduction
1993, Tremaine & Dixon 2001a), Streptococcus equi var. equi
Inflammation of the equine paranasal sinuses is a rela- (Mansmann & Wheat 1973), and Escherichia coli (Mason
tively uncommon disease that may be caused by primary 1975a, Schumacher et al 1987), although as noted, the
bacterial or mycotic infections (Mason 1975a), or can be etiologic importance of these isolates is often unclear.
secondary to dental disease (van der Velden & Verzijlenberg Nasal endoscopy of horses with sinusitis usually reveals
1984, Scott 1987, Tremaine & Dixon 2001a), facial trauma, purulent exudate in the caudal nasal cavity draining from
sinus cysts, progressive ethmoid hematoma or sinonasal the nasomaxillary ostia of the rostral and/or caudal maxil-
neoplasia (Mansmann & Wheat 1973, Gibbs & Lane 1987, lary sinuses (“drainage angle”) (Fig. 26.1). Marked accu-
Tremaine & Dixon 2001a). Equine sinusitis is usually mulation of exudate in the ventral conchal sinus can result
unilateral but bilateral disease has been reported (Coumbe in swelling of the ventral concha, which may eventually
et al 1987, Lane 1993, Tremaine & Dixon 2001a). There prevent passage of the endoscope up the affected nasal
is apparently no breed, age or gender predisposition to cavity. Displacement of the nasal septum can occur in
sinusitis. Clinical signs of any type of sinusitis usually cases with gross distension of this sinus. Straight lateral
include unilateral purulent nasal discharge, ipsilateral radiographs of horses with primary sinusitis frequently
submandibular lymph node enlargement, and epiphora. reveal multiple fluid lines in some of the paranasal sinuses.
Less common signs include facial swelling, exophthalmos, Oblique radiographs are necessary to separate the left
abnormal respiratory noises, head shaking, and exercise and right rows of maxillary cheek teeth for radiographic
intolerance (Lane 1993, Tremaine & Dixon 2001a).
Primary Sinus Empyema

(Primary Sinusitis)
Primary sinusitis is the result of obstruction of the normal
nasomaxillary drainage with resulting accumulation of
mucus in the sinus, which later becomes infected. Some
cases occur following upper respiratory tract infections
that cause inflammation, increase mucus production
within the sinuses, and decrease drainage of secretions
from the sinuses into the nasal cavity via the anatomically
narrow nasomaxillary ostia. The nasal discharge in
primary sinusitis is traditionally stated to be purulent
and odorless (Mason 1975a), but malodorous nasal dis-
charges can occur with primary sinusitis (Tremaine &
Dixon 2001a), especially in association with inspissation
of purulent material in the ventral conchal sinuses
(Schumacher et al 1987).
Culture of exudates from primary sinusitis cases often
yields a mixed bacterial growth that is of unclear etiologic
significance. Isolated bacteria include Streptococcus equi
var. zooepidemicus (Schumacher et al 1987, Ruggles et al
Fig. 26.1. Endoscopic view of the caudal aspect of the middle meatus
1993), Corynebacterium spp., (Schumacher & Crossland (“drainage angle”) in a horse with sinusitis down which purulent
1994), Staphylococcus spp. (Mason 1975a, Schumacher exudate from the maxillary sinuses is draining through the naso-
et al 1987, Tremaine & Dixon 2001a), Pseudomonas aerugi- maxillary ostia (arrowheads).
393
394 26 Disorders of the Paranasal Sinuses
6
1 RMS
VM
7 2
3
Fig. 26.3. Transverse section of the skull of an aged horse at the level
9 of the fourth cheek tooth (109, 209) showing the voluminous rostral
maxillary sinus (RMS) and the ventral nasal meatus (VM).
8 sinusitis (of > 2 months duration) frequently have gross

thickening of the sinus mucosa, which can further restrict
normal nasomaxillary drainage and such cases may only
show a transient improvement to antibiotic treatment
(Tremaine & Dixon 2001a). Treatment by sinus irrigation
may be performed in these cases, via a sutured irriga-
tion tube or Foley catheter placed via a trephine opening
into the frontal or caudal maxillary sinuses (for lavage
of the frontal and caudal maxillary sinuses), or into the
rostral maxillary sinus (for lavage of the rostral maxillary
and ventral conchal sinuses). Such cases may respond to
lavage with 5–10 liters of water, saline or dilute disinfec-
tants such as 0.05% povidine-iodine solution, once to twice
daily for 5–10 days.
Fig. 26.2. Front view of a transverse section of the right paranasal Cases with gross thickening of the sinus mucosa, and in
sinuses and nasal passage through tooth 109 at the level of the most particular cases with accumulations of inspissated pus
rostral end of a frontonasal bone flap. 1 = frontal sinus; 2 = dorsal
in the sinus, may require surgical debridement and possibly
conchal sinus; 3 = rostral maxillary sinus; 4 = ventral conchal sinus;
5 = dorsal meatus; 6 = middle meatus; 7 = nasolacrimal duct; sinonasal fistulation to improve drainage. An outline of
8 = ventral meatus; 9 = infraorbital nerve in the infraorbital canal. sinus anatomy and surgical approaches is presented in
Arrow points to opening from the rostral maxillary sinus into the Figs 26.2–26.4. The frontal, maxillary, and ventral conchal
middle meatus. Rectangle is the point of fracture for a frontonasal sinus are all most easily approached via a large nasofrontal
bone flap and includes the point of separation from the underlying
bone-flap osteotomy (Freeman et al 1990) (Figs 26.4 and
reflection of the dorsal nasal concha. The arrowhead is the lateral
edge of the bone flap. Note the reserve dental crown occupies a large 26.5) where the bone is preserved or a smaller osteotomy
portion of the sinus cavities in this young horse and along with the where the bone is discarded (Figs 26.6–26.9). Even when
infraorbital canal limits access to the sinuses. radiographs or computed tomographic images demonstrate
that the inflammation mainly involves the maxillary
sinuses, a frontonasal flap is the preferred approach for a
number of reasons (Freeman et al 1990). When the lesion
examination of the dental apical areas. Dorsoventral is in the maxillary sinus, the frontal approach is far enough
radiographs are particularly useful for demonstrating from it to allow creation of the flap without disturbing the
distension of, and exudate within, the ventral conchal sinus lesion (e.g. sinus cyst), and yet close enough to allow its
(see Chapter 10). easy removal. It also provides a sufficiently clear view of
Acute cases of primary sinusitis may spontaneously the sinus interior to allow complete examination.
resolve or may respond to antimicrobial drug admin- The incisions necessary for this type of flap do not
istration, with the organisms commonly isolated frequently involve muscles or large blood vessels, and the size and
being sensitive to penicillin. Chronic cases of primary position of the flap can be designed to suit the lesion, even
26 Disorders of the Paranasal Sinuses 395
A C
4
6
5 5
7
2
8
1 6
11 2
3
10
9 1
3
2
1
Fig. 26.4. Approaches to the sinuses through a frontonasal bone flap (broken line in A) and maxillary
bone flap (broken line in B), and (C) expanded dorsal view of sinuses. 1 = rostral maxillary sinus;
2 = caudal maxillary sinus; 3 = ventral conchal sinus; 4 = sphenopalatine sinus; 5 = frontal sinus;
6 = ethmoidal labyrinth; 7 = frontomaxillary opening; 8 = dorsal conchal sinus (5 and 8 combine to form
the conchofrontal sinus); 9 = infraorbital canal; 10 = bony maxillary septum; 11 = caudal bulla of ventral
conchal sinus. Reproduced from Freeman 2003, with permission.
6 4
5
2 3
1
Fig. 26.5. Interior of the right conchofrontal sinus as viewed through

a frontonasal bone flap in a cadaver specimen. For demonstration
purposes, the entire flap has been removed. The rostral part of the
head is to the left and the lateral margin is uppermost. 1 = reflec-
tion of dorsal nasal concha which has retained some of the bony
attachment to the underside of the flap; 2 = dorsal conchal sinus;
3 = ethmoid labyrinth; 4 = caudal maxillary sinus; 5 = medial edge of
the frontomaxillary opening; 6 = caudal bulla of the ventral conchal
sinus. Reproduced from Freeman et al 1990, with permission.
allowing access to the nasal passage if necessary (Freeman

et al 1990). If the bone flap is constructed so that it is
hinged on the dorsal midline, it will lie out of the surgeon’s
way when fully opened. The frontonasal flap can also be Fig. 26.6. A curvilinear incision has been made through the skin and
used for repulsion of cheek teeth, but access to 109 and periosteum which have then been reflected back, to enable a right-sided
209 (the fourth maxillary cheek teeth) is limited using nasofrontal bone osteotomy to be made in a standing sedated horse.
this approach. Alternatively, a caudal maxillary osteotomy
may be used in older (>10 years) horses (Fig. 26.10), but
the reserve crowns of the maxillary cheek teeth limit the
access to the sinuses via this approach in younger animals. of retention of sinus osteotomy flaps, published reports do
A maxillary approach to the rostral maxillary sinus gives not confirm this to be a frequent occurrence, especially with
even more restricted access to the sinus lumen because of larger flaps. Alternatively, despite the loss of a 5-cm disc of
the position of the reserve crowns of the third and fourth bone, albeit over a flat surface, the cosmetic results after dis-
maxillary cheek teeth (Triadan 08s and 09s). carding the flap are usually acceptable (Quinn et al 2004).
Bone flap osteotomies may be created under general At sinusotomy, inspissated pus and grossly thickened
anesthesia or in the standing sedated horse (Scrutchfield mucosa are removed and the sinus can then be irrigated
et al 1994, Quinn et al 2004). After making a rectangular postoperatively (Fig, 26.9). If sinonasal drainage appears
or curved incision through the skin and periosteum, the to be compromised, it may be improved by creation of a
bone flap is created with an oscillating saw, chisel or fistula through the dorsomedial wall of the ventral concha
Gigli wire; the larger, three-sided bone flap may then be into the nasal cavity. Even when performed on the less
hinged back on its (fourth) uncut side, to fracture the bone, vascular, dorsal aspect of the medial conchal wall, this
whilst retaining the flap’s intact skin, subcutaneous tissue fistulation will usually be accompanied by profuse hemor-
and periosteal attachments. Alternatively, an axial-based rhage. To control hemorrhage after such fistulation a
curvilinear incision may be made and the skin and perio- 3-inch (7.6-cm) elasticated stockinet can be introduced
osteum can be reflected. The osteotomy can be created into the sinus via the nasal cavity (Fig. 26.11). To place
using a 5-cm diameter trephine with the disc of bone being this packing, an assistant passes a Chambers’ mare
discarded (Figs 26.6–26.8). The skin and periosteum are catheter up the nasal passage until it can be digitally
closed over the osteotomy ensuring that a 5–10-mm shelf directed into the sinus by the surgeon. A length of
of bone is present peripheral to the osteotomy on which umbilical tape is tied to the end of the catheter in the sinus
the periosteum can be laid, to help prevent dehiscence. and this end is drawn out of the nostril while the other
Although sequestration of the flap has been cited as a risk remains within the sinus. Then saline-soaked gauze
Fig. 26.7. A large (5-cm) diameter trephine is being used to create a large bone flap into the left frontal
sinus in this horse, enabling surgical access to the dorsal conchal, frontal and caudal maxillary sinuses. The
bone flap is discarded and the flap later closed by apposing the skin and periosteum.
Fig. 26.8. Copious quantities of purulent exudate flowing from a nasofrontal bone flap osteotomy in a
horse with chronic sinus empyema.
Fig. 26.9. The skin flap and periosteum are supported by a rim of
frontal bone and are apposed using interrupted sutures (arrowheads).
A maxillary trephine opening has then been made to allow post-
operative irrigation of the maxillary sinuses through a Foley catheter.
BF
Fig. 26.10. A large maxillary bone flap (BF) has been created in this Fig. 26.11. Diagram outlining the postsurgical packing of a paranasal
horse using an oscillating bone saw. This approach gives exposure to sinus to reduce hemorrhage following sinonasal fistulation.
the caudal and rostral maxillary sinuses. The ventral conchal sinus
is variably accessible dorsal to the infraorbital canal. This horse has
extensive, inflamed soft tissue swelling within its caudal maxillary
sinus.
bandage is placed within the “sock” of stockinet in

accordion-fashion until the sinuses are packed.
The umbilical tape is tied around the redundant portion
of stockinet, and the gauze within it, and used to draw
them through the nostrils. The free end of stockinet, and
gauze within it, are sutured to the roof of the false nostril
with a heavy mattress suture over a butterfly of gauze
sponge, and any excess packing is trimmed flush with the
nostril. Alternatively, packing can be brought out through
a trephine hole in adjacent intact bone. The purpose of the
stockinet “sock” is to prevent migration of the packing into
the pharynx, where it can be swallowed. It has been
suggested that the upright position of the head when
the procedure is performed in the standing horse results in
less bleeding, although profuse hemorrhage can accom-
pany fistulation of the venous conchal sinuses in stand-
ing horses. The necessity and efficacy of this sinonasal
fistulation has been questioned (J. Schumacher, personal
communication) and it is possible that sinonasal fistulation
could alter mucociliary clearance and diminish intrasinus
retention of endogenous (possibly bactericidal) nitric oxide.
Fig. 26.12. Computed tomography transverse image of skull of a
The bone flap is replaced in situ (if retained) and may be young horse at the level of the rostral maxillary sinuses, showing
secured with one or two wire sutures inserted into pre- unilateral distortion of the overlying maxillary and nasal bones caused
placed drill holes in the flap and adjacent bone, although by an expansive soft tissue density mass within the sinus. Reproduced
this may be unnecessary. The periosteum is closed with with the permission of Dr Wolfgang Henninger, University of Veterinary
Medicine, Vienna.
absorbable sutures and the skin is closed with staples or
non-absorbable sutures. A lavage cannula or Foley catheter
sutured into a separate trephine opening in the frontal
sinus or caudal maxillary sinus allows postoperative B. melaninogenicus, B. oralis and Fusobacterium mortiferum
irrigation of the sinuses. The prognosis for resolution of have been cultured from nasal discharge with such infec-
chronic sinusitis, including cases involving the ventral tions (Mackintosh & Colles 1987), but their precise
conchal sinus after surgical debridement, and where etiologic role remains unclear.
necessary, creation of sinonasal drainage is excellent Radiography is an insensitive technique for detection
(Tremaine et al 2001b, Quinn et al 2004). of dental infections, especially in younger horses, because
the radiographic changes associated with anatomical
development of cheek teeth apices (i.e. blunt apices,
Dental Sinusitis absence of roots, wide periodontal spaces and absence of
Sinusitis commonly occurs with apical infections of the lamina dura denta in this region) are similar to the
caudal maxillary cheek teeth (Triadan upper 08s–11s) radiographic signs of early apical infection (see Chapter 10).
(Mason 1975a, van der Velden & Verzijlenberg 1984, In such cases, the presence of apical infection can some-
Lane 1993) and such dental infections caused 53% of times be confirmed by gamma scintigraphy, which is more
sinusitis cases in one study (Tremaine & Dixon 2001a). sensitive than radiography in selected cases, particularly in
Dental sinusitis occurs most frequently in horses aged the early stages of the disease (Weller et al 2001) (see
4–7 years (Dixon et al 2000b). Maxillary cheek teeth apical Chapter 12). Computed tomography and magnetic reso-
infections commonly occur following anachoresis (blood- nance imaging are also increasingly used to obtain highly
borne infections of apices) (Dacre 2004) but also occur detailed images of structures within the equine head and
secondarily to idiopathic dental fractures (lateral slab or thus make an early and accurate diagnosis of apical infec-
saggital), or with severe diastemata, and sometimes in tions (Tiejte at al 1998, Morrow et al 2000, Henninger
conjunction with supernumerary cheek teeth (Dixon et al et al 2003) (Fig. 26.12).
1999, 2000a, Dacre 2004). Nasal discharge is frequently Sinusitis secondary to maxillary dental apical infections
fetid when associated with dental secondary sinusitis, usually necessitates removal of the affected cheek tooth
and also with intranasal tracts and granulomas result- before resolution of the sinusitis will occur. Because of
ing from infection of the first or second (or occasionally difficulty with the extraction of cheek teeth and the major
third) maxillary cheek tooth (Triadan 106–108, 206–208) long-term consequences following such extractions, this
(Lane 1994). Anaerobes including Bacteroides fragilis, procedure should never be undertaken lightly. Definite
diagnosis of dental involvement in sinusitis using radio- et al (1992), Aspergillus fumigatus was cultured from six,
graphy, scintigraphy or computed tomography is essential Pseudallescheria boydii from one, and Penicillium spp. from
before embarking on tooth removal. Anecdotal reports a single case. Pseudallescheria boydii, an opportunistic
suggesting that endodontic therapy of infected pulp per os, saprophyte, has also been isolated from a frontal sinus
effectively sealing the oral cavity from the sinus, will result lesion (Johnson et al 1975).
in resolution of the sinus (T. Johnson, personal commu- Aspergillus fumigatus is ubiquitous in dead vegetation
nication) have not been critically evaluated. including hay and straw. The mechanism of infection of
Infected cheek teeth may be removed via oral extraction, the nasal chambers or paranasal sinuses of horses by
repulsion or via a lateral buccotomy. The latter tech- normally saprophytic fungi is not clear, but previous
nique can be used for the rostral three maxillary cheek trauma from surgery or nasogastric tube passage may be a
teeth but not for the caudal maxillary cheek teeth. factor in some cases (Watt 1970, Greet 1981, Tremaine &
Extraction per os is associated with considerably reduced Dixon 2001b).
complications compared to repulsion, and additionally, Mycotic sinonasal infections caused by other fungal
may be accomplished in the standing horse (Tremaine organisms are common in warm humid climates. These
2004b, Dixon et al 2005). Dental extractions involving the have involved infection with Cryptococcus neoformans (Watt
maxillary cheek teeth that cannot be achieved by oral 1970, Corrier et al 1984), Coccidioides immitis (DeMartini &
extraction (e.g. badly fractured or carious cheek teeth) can Riddle 1969, Hodgkin et al 1984), Rhinosporidium seeberi
be performed under general anesthesia via a bone-flap (Myers et al 1964), Conidiobolus coronatus (Entomophthora
osteotomy or via trephine opening. Intraoperative imag- coronata) (Bridges et al 1962, Hanselka 1977, Zamos et al
ing to ensure accurate alignment of the punch with the 1996), Conidiobolus lamprauges (Humber et al 1989) and
affected tooth before repulsing the tooth is advised, to avoid Hyphomyces destruens (Hutchins & Johnston 1972). Such
iatrogenic damage to adjacent structures. mycotic granulomas are characterized by the presence of
If dental extraction is performed per os in horses with necrotic foci or “kunkers” within proliferative granulation
dental sinusitis, lavage of the affected paranasal sinuses tissue. Nasal infections by these lesions are described in
should also be performed post extraction. Intraoperative detail in Chapter 25.
radiographs should be taken after dental removal (espe- Sinus mycosis has also been reported secondary to other
cially by repulsion) to attempt to identify the possible intrasinus lesions such as progressive ethmoidal hematoma
presence of intraalveolar bone or dental fracture frag- and can also occur following sinus surgery for other dis-
ments that are likely to sequestrate. Following oral extrac- eases such as progressive ethmoidal hematoma, sinus cysts
tion the alveolus can be temporarily packed with an or following head trauma (McGorum & Dixon 1992,
antibiotic-soaked swab (Dixon et al 2005), but following Tremaine & Dixon 2001a).
repulsion a more robust alveolar packing is required, Mycotic sinus infections commonly cause a unilateral
such as an acrylic plug attached to adjacent cheek teeth, nasal discharge, which may vary from mucopurulent,
to prevent the development of an oromaxillary fistula. purulent to sanguineous, and is frequently malodorous
Unsuccessful treatment of sinusitis can be attributed to (McGorum et al 1992, Tremaine & Dixon 2001a).
oromaxillary fistula, persistent alveolar osteitis, abscesses The treatment of superficial mycotic lesions with anti-
within the overlying sinus, failure to remove all the infected mycotic drugs including nystatin (Campbell & Peyton
tooth and infected or loose alveolar bone, and failure to 1984), enilconazole or natamycin (McGorum et al 1992)
treat obligate anaerobes with appropriate antibiotics such by topical application directly or via an endoscope carries a
as metronidazole (De Moor & Verschooten 1982, Mackintosh good prognosis although recurrence is possible. Surgical
& Colles 1987). The presence of small alveolar sequestra, removal of large intrasinus fungal granulomas or plaques
which are not identifiable on postoperative radiographs, or of any underlying cause such as sequestra, cysts or pro-
are an occasional cause for persistent clinical signs of gressive ethmoidal hematoma lesions, followed by sinus
sinusitis. These apparently develop later as the result of irrigation with a topical antifungal such as natamycin or
damage to alveoli by the repulsion process. The long-term miconazole, usually results in rapid resolution of the lesions.
prognosis for both primary and dental sinusitis cases is
good (Tremaine & Dixon 2001b).
Halicephalobus gingivalis Infection
Halicephalobus gingivalis is a saprophytic nematode found in
Mycotic Sinusitis decaying humus and infection through an unknown route
Equine sinonasal diseases associated with fungal infection can involve the sinuses, central nervous system, and, to a
are rare in the horse in the UK. Greet (1981) first described lesser extent, the kidney in certain geographical regions
three cases of mycotic rhinitis in horses caused by (Pearce at al 2001). Infection of the sinuses produces a
Aspergillus fumigatus, and subsequent reports are sparse. mass of gray–yellow fibrous tissue that obliterates the
Of ten cases of sinonasal mycosis described by McGorum sinuses and their walls, loosens teeth and distorts sinus
architecture. Infection can be unilateral or bilateral, can sinus cysts can expand into the nasal cavity, causing
involve both the upper and lower jaws, and can spread compression of the nasal septum and bilateral nasal air-
from there to the kidneys and cerebellum (Freeman 1991a). flow obstruction.
Predominant clinical signs of H. gingivalis infection Diagnosis of sinus cysts is assisted by endoscopy, which
are facial distortion with firm swellings in the maxilla, may reveal distortion of nasal conchae. Radiographic
unilateral or bilateral nasal discharge, marked dyspnea and features of sinus cysts include the presence of a rounded,
stridor, difficulty in eating, and weight loss (Pearce et al expansive, soft tissue density lesion in the frontal or maxil-
2001). The condition can be confused with squamous cell lary sinuses. Distortion and thinning of the surrounding
carcinoma but the female rhabditiform nematodes and bones may be evident as the lesion increases in size, and
their larvae and eggs can be seen in clusters or scattered secondary distortion of adjacent dental apices within
throughout a biopsy specimen. Surgical debulking, intra- the sinuses may be present. The contents of the cysts fre-
operative lavage with ivermectin, and subsequent oral quently appear radiographically as a homogeneous soft
ivermectin was successful in one horse with a periorbital tissue density shadow. The radiodense capsule may contain
granuloma (Freeman 1991a). However, the response to spicules of mineralized tissue (Fig. 26.14) and extralesional
ivermectin is not always favorable and the prognosis fluid lines may be present if secondary sinus empyema is
appears to be poor, especially because of risk of spread to present (Tremaine & Dixon 2001a). Centesis of the lesion
other organs. via needle aspiration (e.g. using a 16-gauge needle inserted
into areas of thinned, swollen bone) or via a sinusotomy is
diagnostic, yielding a viscous, usually sterile, translucent
Sinus Cysts yellow fluid which is odorless and may contain some
Sinus cysts are expansive fluid-filled space-occupying leukocytes (Dixon 1985, Lane et al 1987, Tremaine &
lesions which develop within the sinuses (Leyland & Baker Dixon 2001a, Beard & Hardy 2003). Treatment of the
1975, Dixon 1985, Lane et al 1987) of young to old
horses. Congenital intrasinus cysts have also been reported
(Sanders-Shamis & Robertson 1987, Beard et al 1990).
Equine sinus cysts most commonly occur in the maxillary
sinuses but they can also occur in the other sinuses.
The etiology of these lesions is unclear and no breed or
sex predisposition has been identified. It has been suggested
that they are developmental in origin (Beard et al 1990),
or associated with dental tissues (Boulton 1985), but
little evidence for this theory has been found, although
one case described by Dixon (1985) was attached to dental
alveoli. A common etiology between these lesions and
ethmoid hematomas has been suggested (Lane et al 1987)
as both lesions histologically contain areas of hemorrhage
and hemosiderophages, but little factual evidence for this
association has been found (Tremaine et al 1999). Sinus
cysts are frequently associated with a nasal discharge and
facial swelling (Fig. 26.13). The nasal discharge varies from
mucoid, mucopurulent to purulent, and is thought to be
the result of sinus infection secondary to obstruction of
normal sinonasal drainage. A consistent clinical feature
caused by the expansive nature of sinus cysts is distortion
of the frontal, maxillary, and conchal bones (Lane et al
1987, Caron 1991, Freeman 1991b, Tremaine & Dixon
2001a). This may result in gross facial swelling and
exophthalmos as a result of thinning of the overlying
maxillary or frontal bones, and nasal obstruction as a
result of the expansion of the lesion within the sinuses and
conchae. Horses are affected unilaterally in almost all
cases, but expansion of a frontal sinus cyst with lysis of the
intersinus septum and expansion into the contralateral Fig. 26.13. The large swelling of the left side of this 8-year-old horse’s
frontal sinus, resulting in bilateral clinical signs, can occur rostral maxillary area (arrows) is the result of bone remodeling in
(H. Tremaine, personal observations). Large maxillary response to an expanding cyst within the maxillary sinuses.
lesion by surgical drainage may be effective in some cases

(O’Connor 1930, Dixon 1985, Lane et al 1987) but total
removal of the lesion via a nasofrontal or maxillary
osteotomy approach, under general anesthesia or standing
chemical restraint, is the treatment of choice (Fig. 26.15)
(Dixon 1985, Lane et al 1987, Tremaine & Dixon 2001b).
Histologic examination of sinus cysts has revealed
extensive resorption and remodeling of the bones sur-
rounding the cyst, replacement of the normal bony septa
within the sinus by fibrous tissue, and replacement of the
loose intrasinus connective tissue with bony spicules
(Tremaine et al 1999). The cysts themselves are lined by
ciliated columnar respiratory epithelium with focal areas
of ulceration, areas of submucosal calcification and of
subepithelial hemorrhage, and chronic inflammation may
be present (Lane et al 1987, Tremaine et al 1999).
Progressive Ethmoidal Hematoma

Progressive ethmoidal hematomas are observed most
commonly in the nasal cavity arising from the ethmo-
turbinates. Less commonly, lesions arise in the frontal
or maxillary sinuses. The etiology, clinical signs, and
treatment of these lesions are discussed in Chapter 27.
Cases with clinical signs typical of progressive ethmoidal
hematoma (i.e. low-grade chronic, unilateral epistaxis)
and with endoscopic evidence of drainage of small volumes
of blood from the sinonasal drainage areas and which do
not reveal a lesion in the nasal cavities should be subjected
to careful examination of the sinuses by radiography,
Fig. 26.14. Radiograph showing distortion of the sinuses as the result
sinoscopy or sinusotomy (Fig. 26.16).
of a sinus cyst with an increased soft tissue density radio-opacity
(arrows) throughout the sinus.
Fig. 26.15. Frontal sinus bone flap osteotomy

showing a partially removed sinus cyst wall
(yellow arrows) with a residual pool of honey-
colored exudates (blue arrow) typical of this
type of lesion.
A group of fibro-osseous lesions, often of overlapping

Sinus Neoplasia
histologic classification, have been reported in the para-
Neoplasia of the nasal and paranasal sinuses is a relatively nasal sinuses of horses. These include osteomas, which
rare condition in the horse (Cotchin 1956, Madewell et al have been found in the frontal and maxillary sinuses
1976, Sundbergh et al 1977, Priester & Mackay 1980) and (Gorlin et al 1963, Schumacher et al 1988, Dixon & Head
there are only a few multiple case studies of equine sinus 1999), osteochondromas (Adair et al 1994), fibromas
neoplasia (Cotchin 1967, Madewell et al 1976, Stunzi & (Barber et al 1983) and fibrosarcomas (Hultgren et al
Hauser 1976, Hilbert et al 1988, Dixon & Head 1999). 1987, Dixon & Head 1999). Tumors of dental tissue origin
Although the sinuses are lined by ciliated respiratory with involvement of the maxillary sinuses have been
mucosa, squamous cell carcinomas are probably the most reported, although such neoplasms more frequently
common sinus neoplasia (Head & Dixon 1999). These affect the mandibular or rostral maxillary cheek teeth
lesions are usually direct extensions of lesions originating (Pirie & Dixon 1993) and such lesions, although more
in the oral cavity (usually the lateral aspects of the hard common in older animals, have been described in foals
palate) or from metaplastic epithelium within the sinuses (Roberts et al 1978).
themselves (Reynolds et al 1979, Hill et al 1989, Head & Clinical signs associated with neoplasia are similar to
Dixon 1999). They display rapid local expansion and those of other expansive lesions affecting the paranasal
induce considerable necrosis of adjacent tissue. sinuses and include nasal discharge (purulent or muco-
Other tumor types recorded with paranasal sinus purulent, occasionally hemorrhagic), facial swelling (Fig.
involvement include spindle cell sarcoma, mastocytomas, 26.17), epiphora, and nasal obstruction. However, as a
hemangiosarcoma, angiosarcoma and lymphosarcoma consequence of the large space into which sinus lesions
(Lane 1985, Adams et al 1988, Richardson et al 1994, can expand, facial swelling and other signs may be absent
Malikides et al 1996, Dixon & Head 1999). until an advanced stage. Head shaking, exophthalmos, and
Fig. 26.16. Nasofrontal sinus bone flap surgery showing an intrasinus Fig. 26.17. This pony has a rapidly expanding maxillary tumor, which
progressive ethmoidal hematoma (arrows), which was not detectable caused loosening and secondary apical infections of the adjacent
on nasal endoscopy and which is covered by inspissated pus. maxillary cheek teeth.
epistaxis are less commonly observed (Hill et al 1989,

Tremaine & Dixon 2001a).
The diagnosis of intrasinus neoplasia requires, as
for other sinus lesions, clinical and oral examination,
radiography, sinoscopy, and possibly scintigraphy and
computed tomography. Wherever possible, histopathology
of biopsy specimens should be performed to confirm the
diagnosis and help establish a prognosis.
Surgical resection of benign lesions, such as osteomas,
via a nasofrontal flap, may carry a good long-term
prognosis (Schumacher et al 1988, Head & Dixon 1999,
Tremaine & Dixon 2001b). However, the aggressive nature
and the complex anatomical location of most sinonasal
tumors usually prevent complete resection and conse-
quently, a poor prognosis is present following surgical
treatment of these lesions (Dixon & Head 1999). Excep-
tions include osteomas which are usually amenable to Fig. 26.18. This figure shows a horse with a large depressed maxillary
treatment because they are benign (some may not even fracture (arrow on fixed side of depressed fracture) undergoing
be true neoplasms but hamartomas), grow slowly, have surgical repair of this injury. Fractured bones such as this can be
pedunculated or sessile attachments over a small base, and elevated and stabilized with wire with a good cosmetic outcome.
tend to form well-circumscribed lesions rather than
infiltrate (Freeman 1991b).
Beta-radiotherapy with cobalt-60 has been attempted fragments should be wired to stable adjacent bone. The
with limited success for soft tissue sinus neoplasms. In one fracture fragments can also be exposed through a large
report, the results of aggressive radiotherapy of advanced curvilinear skin flap, especially if an open fracture is
squamous cell carcinomas in three horses was encour- present and intrasinus access is required. Blood clots and
aging, because radiation-induced complications were loose bone fragments are removed and the sinus cavity is
mild, and survival duration and quality of life were good flushed liberally with saline. All small fragments without
(Walker et al 1998). full periosteal attachments should also be removed. Follow-
ing repair of the bone and skin wounds, the head should be
bandaged so as to cover the wound, if possible, and the
Traumatic Injuries of the horse should be recovered from general anesthesia either
Paranasal Sinuses with assistance or wearing a padded headguard. Healing
Fractures involving the premaxilla are common in foals after repair of sinus injuries is usually excellent, particu-
(Hardy 1991) and depression fractures of the frontal and larly if the skin remains intact (Tremaine 2004b) although
maxillary sinuses have been commonly reported in suture exostoses may remain.
adult horses (Sullins & Turner 1982, Tremaine & Dixon In horses with long-standing, healed depression frac-
2001a). Traumatic hemorrhage into the sinuses may tures, fluorocarbon polymer and carbon fiber can be used
lead to a profuse short-term epistaxis, which is often to restore the facial contour (Valdez & Rook 1981), or the
followed by an unexpectedly prolonged (> 4 weeks) inter- healed maligned areas can be cut with a bone saw, elevated
mittent low-grade epistaxis. Open sinus fractures fre- and then wired into a more anatomically normal position.
quently lead to secondary sinusitis (Dixon 1993a), and the However, a better cosmetic appearance can be obtained by
presence of intrasinus sequestra may result in chronic primary open reduction of such large depressed factures
suppuration with persistent sinusitis (Lane 1993). Repair of shortly after injury, rather than by facial reconstruction
these fractures is possible by elevating the depressed later. If severe or open sinus fractures are not treated,
bone flap (Fig. 26.18) and, if it is unstable once elevated, complications such as sinusitis, sequestra formation, facial
immobilizing it in the reduced position with stainless steel deformity, abnormal bone growth in young horses, and
wires. To facilitate elevation of the fracture fragments, nasal obstruction can be expected.
holes can be drilled in adjacent undamaged bone and
a periosteal elevator, Steinmann pins, or Langenbeck
retractors can be passed through these to pry up depressed
Nasofrontal Suture Exostoses
fragments. If the elevated fragments wedge firmly together Swellings of the nasofrontal region of the head as a result
in their normal position and form a stable union it may of periostitis of the suture lines between the nasal and
be unnecessary to wire them (Turner 1979), but large frontal bones, and more rarely the nasal, lacrimal,
and malar bones have been described (Gibbs & Lane 1987, Barber SM, Clark EG, Fretz PB 1983 Fibroblastic tumour of the
Speirs 1992, Trotter 1993, Tremaine & Dixon 2001a). premaxilla in two horses. Journal of the American
They occur in many breeds but the incidence appears Veterinary Medical Association 182: 700–702
Beard WL, Hardy J 2003 Diagnosis of conditions of the para-
to be particularly high in thoroughbreds and thorough- nasal sinuses of the horse. Equine Veterinary Education
bred crosses (Dixon 1991). Although most are possibly 13: 265–273
traumatic in origin, including following sinonasal surgery, Beard WL, Robertson JT, Leeth B 1990 Bilateral congenital
especially after a large nasofrontal osteotomy, the exact cysts in the frontal sinus of a horse. Journal of the
etiology of such lesions remains unknown in other cases. American Veterinary Medical Association 196: 453–454
Boulton CH 1985 Equine nasal cavity and paranasal sinus
Affected horses present with bilateral, firm, non-painful disease: a review of 85 cases. Journal of Equine Veterinary
swellings, rostral to the eye, accompanied by epiphora Science 5: 268–275
in some cases. Differentiation from facial fractures and Bridges CH, Romane WM, Emmons CW 1962 Phycomycosis
sinusitis is usually possible clinically and radiologically. of horses caused by Entomophthora coronata. Journal of the
Radiographs frequently demonstrate proliferative peri- American Veterinary Medical Association 140: 673–677
Campbell ML, Peyton LC 1984 Muscle flap closure of a
osteal changes of the widened and incompletely closed frontocutaneous fistula in a horse. Veterinary Surgery
suture line. The swellings usually remodel and regress 13: 185–188
gradually without treatment, but in some cases continued Caron JP 1991 Diseases of the nasal cavity and paranasal
instability has resulted in progressive increases in the size of sinuses. In: Colahan PT, Mayhew IG, Merritt AM, Moore
these swellings. JN (editors) Equine Medicine and Surgery. American
Veterinary Publications, Goleta, CA, pp.386–397
Clarke CJ, Roeder PL, Dixon PM 1996 Nasal obstruction
Miscellaneous Sinus Disorders caused by nutritional osteodystrophia fibrosa in a group
of Ethiopian horses. Veterinary Record 139: 568–570
Frontal sinus eversion is probably a congenital defect that Corrier DE, Wison SR, Scrutchfield WL 1984 Equine crypto-
forms a hard, slow-growing protuberance over, and com- coccal rhinitis. Compendium on Continuing Education
for the Practicing Veterinarian 6: 556–558.
municating with, the frontal sinus (Martin & McIlwraith Cotchin E 1956 Neoplasms of the Domesticated Animals.
1981). The bony protuberance can be removed through a Commonwealth Agricultural Bureaux, Buckingham, UK
large elliptical incision and the resulting defect in the Cotchin E 1967 Spontaneous neoplasms of the upper respira-
frontal bone can be repaired with synthetic polypropylene tory tract in animals In: Muir CS, Shanmugaratnam K
mesh (Marlex) and skin. (editors) Cancer of the Naso-Pharynx. Medical Examina-
tion Publishing Co, Flushing, NY, pp.203–259
Osteodystrophia fibrosa or secondary nutritional hyper- Coumbe KM, Jones RD, Kenward JH 1987 Bilateral sinus
parathyroidism can develop in horses on a high phosphorus empyema in a six year-old mare. Equine Veterinary
diet, such as bran, or on some tropical grasses (Clarke et al Journal 19: 559–560
1996) and can be attributed to relative calcium deficiency Dacre IT 2004 A pathological, histological and ultrastruc-
(Freeman 1991b). It is rare under modern management con- tural study of diseased equine cheek teeth. PhD thesis,
University of Edinburgh
ditions. Conchal necrosis (De Moor & Verschooten 1982) DeMartini JC, Riddle WE 1969 Disseminated coccidiomycosis
may be caused by advanced mycotic rhinitis (Tremaine & in two horses and a pony. Journal of the American
Dixon 2001b) that usually responds to removal of the Veterinary Medical Association 155: 149–156
affected concha by intranasal curettage and lavage. De Moor Von A, Verschooten F 1982 Empyem und Nekrose
The reserve tooth crowns of young (2- to 4-year-old) der Nasenmuscheln beim Pferd (Empyema and necrosis
of the nasal conchae in a horse). Deutsche Tierarztliche
Welsh and miniature ponies and other smaller pony breeds Wochenschrift 89: 275–281
can project a considerable distance into the nasal and sinus Dixon PM 1985 Equine maxillary cysts. Equine Practice
cavities and cause firm, painless, bilateral swellings in the 7: 25–33
maxillary bones that should not be confused with injuries Dixon PM 1991 Swellings of the head region in the horse. In
or disease. Facial lumps or “horns” can be seen in horses as Practice 13: 257–263
Dixon PM 1993a Nasal cavity. In: Equine Respiratory Endoscopy.
symmetrical painless prominences of the nasal and frontal Boehringer Ingelheim, Bracknell, pp.22–29
bones and possibly are caused by an embryologic fault. Dixon PM 1993b Ethmoturbinates. In: Equine Respiratory
Endoscopy. Boehringer Ingelheim, Bracknell, pp.43–48
Dixon PM, Head KW 1999 Equine nasal and paranasal
REFERENCES sinus tumours: part 2: A contribution of 28 case reports.
Adair HS, Duncan RB, Toal RL 1994 Solitary osteochondroma Dixon PM, Tremaine WH, Pickles K et al 1999 Equine
of the nasal bone in a horse. Cornell Veterinarian dental disease Part 2: A long term study of 400 cases:
84: 25–31 disorders of development and eruption and variations in
Adams R, Calderwood-Mays MB, Peyton LC 1988 Malignant position of the cheek teeth. Equine Veterinary Journal
lymphoma in three horses with ulcerative pharyngitis. 31: 519–528
Journal of the American Veterinary Medical Association Dixon PM, Tremaine WH, Pickles K et al 2000a Equine dental
193: 674–676 disease Part 3: A long term study of 400 cases: disorders
of wear, traumatic damage and idiopathic fractures, Lane JG 1993 Management of sinus disorders, part 1. Equine
tumours and miscellaneous disorders of the cheek teeth. Veterinary Education 5: 5–9
Equine Veterinary Journal 32: 9–18 Lane JG 1994 A review of dental disorders of the horse, their
Dixon PM, Tremaine WH, Pickles K et al 2000b Equine dental treatment and possible fresh approaches to management.
disease Part 4: A long term study of 400 cases: apical Equine Veterinary Education 6: 13–21
infections of cheek teeth. Equine Veterinary Journal Lane JG, Longstaffe JA, Gibbs C 1987 Equine paranasal sinus
32: 182–194 cysts: a report of 15 cases. Equine Veterinary Journal
Dixon PM, Dacre I, Dacre K et al 2005 Standing oral 19: 534–544
extraction of cheek teeth in 100 horses (1998–2003). Leyland A, Baker JR 1975 Lesions of the nasal and paranasal
Equine Veterinary Journal 37: 105–112 sinuses of the horse causing dyspnoea. British Veterinary
Freeman DE 1991a Nasal passages. In: Beech J (editor) Equine Journal 131: 339–346
Respiratory Disorders. Lea and Febiger, Philadelphia, Mackintosh ME, Colles CM 1987 Anaerobic bacteria
pp.253–274 associated with abscesses in the horse and donkey. Equine
Freeman DE 1991b Paranasal sinuses In: Beech J (editor) Equine Veterinary Journal 19: 360–362
Respiratory Disorders. Lea and Febiger, Philadelphia, Madewell BR, Priester WA, Gillete EL et al 1976 Neoplasms of
pp.275–305 the nasal passages and paranasal sinuses in domestic
Freeman DE 2003 Sinus disease. Veterinary Clinics of North animals as reported by 13 veterinary colleges. American
America; Equine Practice 19: 209–243 Journal of Veterinary Research 37: 851–856
Freeman DE, Orsini PG, Ross MW et al 1990 A large fronto- Malikides N, Reppas G, Hodgson JL et al 1996 Mast cell
nasal flap for sinus surgery in the horse. Veterinary tumours in the horse: four case reports. Equine Practice
Surgery 19: 122–130 18: 12–17
Gibbs C, Lane JG 1987 Radiographic examination of the Mansmann RA, Wheat JD 1973 The diagnosis and treatment
nasal and paranasal sinus regions of the horse. Part 2: of equine upper respiratory diseases. In: Proceedings of
Radiological findings. Equine Veterinary Journal the 18th Annual Convention of the American Associa-
19: 474–482 tion of Equine Practitioners. Lexington, KY, pp.388–487
Gorlin RJ, Meskin LH, Brodey R 1963 Odontogenic tumours in Martin GS, McIlwraith CW 1981 Repair of a frontal sinus
man and animals, pathological classification and clinical eversion in a horse. Veterinary Surgery 10: 149
behaviour – a review. Annals of the New York Academy Mason BJE 1975a Empyema of the equine paranasal sinuses.
of Science 108: 722–771 Journal of the American Veterinary Medical Association
Greet TRC 1981 Nasal aspergillosis in three horses. Veterinary 167: 727–731
Record 109: 487–489 Mason BJE 1975b Spindle-cell sarcoma of the equine
Hanselka DV 1977 Equine nasal phycomycosis. Veterinary para-nasal sinuses and nasal chamber. Veterinary Record
Medicine/Small Animal Clinician 72: 251–253 96: 287–288
Hardy J 1991 Upper respiratory obstruction in foals, wean- McGorum BC, Dixon PM, Lawson GHK 1992 A review of ten
lings, and yearlings. Veterinary Clinics of North America; cases of mycotic rhinitis. Equine Veterinary Education
Equine Practice 7: 105–122 4: 8–12
Head KW, Dixon PM 1999 Equine nasal and paranasal sinus Meschter CL, Allen D 1984 Lymphosarcoma within the nasal
tumours. Part 1: review of the literature and tumour cavities of an 18 month old filly. Equine Veterinary
classification. Veterinary Journal 157: 261–278 Journal 16: 475–476
Henninger W, Frame M, Willman M et al 2003 CT features of Morrow K, Park RD, Spurgeon, TL et al 2000 Computed
alveolitis and sinusitis in horses. Veterinary Radiology tomography of the equine head. Veterinary Radiology
and Ultrasound 44: 269–276 and Ultrasound 41: 491–497
Hilbert BJ, Little CB, Klein K et al 1988 Tumours of the Myers DD, Simon J, Case MT 1964 Rhinosporidiosis in a horse.
paranasal sinuses in 16 horses. Australian Veterinary Journal of the American Veterinary Medical Association
Journal 65: 86–88 145: 345–346
Hill FWE, Moulton JE, Schiff PH 1989 Exophthalmos in a O’Connor JJ 1930 Operations. Dollar’s Veterinary Surgery.
horse resulting from an adenocarcinoma of the Bailliere, Tindall and Cox, London, pp.222–231
paranasal sinus. Journal of South African Veterinary Pearce SG, Bouré LP, Taylor JA et al 2001 Treatment of a
Medicine Association 60: 104–105 granuloma caused by Halicephalobus gingivalis in a horse.
Hodgkin EC, Conaway DH, Ortenburger AI 1984 Recurrence Journal of the American Veterinary Medical Association
of obstructive nasal coccidioidal granuloma in a horse. 219: 1735–1738
Journal of the American Veterinary Medical Association Pirie RS, Dixon PM 1993 Mandibular tumours in the horse:
184: 339–340 a review of the literature and 7 case reports. Equine
Hultgren BD, Schmotzer WB, Watrous BJ et al 1987 Veterinary Education 5: 287–294
Nasal–maxillary fibrosarcoma in young horses: a light Priester WA, Mackay FW 1980 The occurrence of tumors in
microscopic study. Veterinary Pathology 24: 194–196 domestic animals. National Cancer Institute Monograph
Humber RA, Brown CC, Korngay RW 1989 Equine zygomy- 54: 59–99
cosis caused by Conidiobolus lamprauges. Journal of Clinical Quinn G, Lane JG, Kidd JF 2005 Fronto-nasal flap surgery in
Microbiology 27: 573–576 standing horses. Equine Veterinary Journal 37: 138–142
Hutchins DR, Johnston KG 1972 Phycomycosis in the horse. Reed SM, Boles CL, Dade AW et al 1979 Localised equine nasal
Australian Veterinary Journal 48: 269–277 coccidiomycosis granuloma. Journal of Equine Medicine
Johnson GR, Schiefer B, Pantekoek JFCA 1975 Maduromycosis and Surgery 3: 119–123
in a horse in Western Canada. Canadian Veterinary Reynolds BL, Stedham MA, Lawrence JM et al 1979 Adeno-
Journal 16: 341–344 carcinoma of the frontal sinus with extension to the
Lane JG 1985 Palatine lymphosarcoma in two horses. Equine brain in a horse. Journal of the American Veterinary
Veterinary Journal 17: 465–467 Medical Association 174: 734–736
Richardson JD, Lane JG, Nicholls PK 1994 Nasopharyn- Tietje S, Becker M, Bockenhoff G 1998 Computed tomographic
geal mast cell tumour in a horse. Veterinary Record evaluation of head diseases in the horse: 15 cases.
Roberts MC, Groenendyk S, Kelly WR 1978 Ameloblastic Tremaine WH 2004a The management of head fractures in
odontoma in a foal. Equine Veterinary Journal 10: 91–93 horses. In Practice 26: 142–149
Ruggles AJ, Ross MW, Freeman DE 1991 Endoscopic exami- Tremaine WH 2004b Oral extraction of equine cheek teeth.
nation of normal paranasal sinuses in horses. Veterinary Equine Veterinary Education 16: 151–159
Surgery 20: 418–423 Tremaine WH, Dixon PM 2001a A long-term study of 277
Ruggles AJ, Ross MW, Freeman DE 1993 Endoscopic exami- cases of equine sinonasal disease. Part 1: details of
nation and treatment of paranasal sinus disease in 16 horses, historical, clinical and ancillary diagnostic
horses. Veterinary Surgery 22: 508–514 findings. Equine Veterinary Journal 33: 274–282
Sanders-Shamis M, Robertson JT 1987 Congenital sinus cyst Tremaine WH, Dixon PM 2001b A long-term study of 277
in a foal. Journal of the American Veterinary Medical cases of equine sinonasal disease. Part 2: treatments
Association 190: 1011–1012 and results of treatments. Equine Veterinary Journal
Schumacher J, Crossland LE 1994 Removal of inspissated 33: 283–289
purulent exudate from the ventral conchal sinus of three Tremaine WH, Clarke CJ, Dixon PM 1999 Histopathological
standing horses. Journal of the American Veterinary findings in equine sinonasal disorders. Equine Veterinary
Medical Association 205: 1312–1314 Journal 31: 296–303
Schumacher J, Honnas C, Smith B 1987 Paranasal sinusitis Trotter GW 1993 Paranasal sinuses. Veterinary Clinics of
complicated by inspissated exudate in the ventral conchal North America; Equine Practice 9: 153–169
sinus. Veterinary Surgery 16: 373–377 Tulleners EP, Raker C 1983 Nasal septum resection in the
Schumacher J, Smith BL, Morgan SJ 1988 Osteoma of horse. Veterinary Surgery 12: 41–47
paranasal sinuses of a horse. Journal of the American Turner AS 1979 Surgical management of depression fractures
Veterinary Medical Association 192: 1449–1450 of the equine skull. Veterinary Surgery 8: 29
Scott EA 1987 Sinusitis. In: Robinson NE (editor) Current Valdez H, Rook JS 1981 Use of fluorocarbon polymer and
Therapy in Equine Medicine 2. WB Saunders, Philadelphia, carbon fiber for restoration of facial contour in a horse.
pp.605–607 Journal of the American Veterinary Medical Association
Scrutchfield WL, Schumacher J, Walker M et al 1994 Removal 178: 249–251
of an osteoma from the paranasal sinuses of a standing van der Velden MA,Verzijlenberg K 1984 Chronic puru-
horse. Equine Practice 16: 24–27 lent maxillary sinusitis in horses. Tijdschrift voor
Speirs VC 1992 Diseases of the paranasal sinuses. In: Dergeneesekunde 109: 793–799
Robinson NE (editor) Current Therapy in Equine Medicine Walker MA, Schumacher J, Schmitz DG et al 1998 Cobalt 60
3. WB Saunders, Philadelphia, pp.217–224 radiotherapy for treatment of squamous cell carcinoma
Stunzi H, Hauser B 1976 Tumours of the nasal cavity of the nasal cavity and paranasal sinuses in three horses.
(International histological classification of tumours Journal of the American Veterinary Medical Association
of domestic animals). Bulletin of the World Health 212: 848–851
Organisation 53: 257–263 Watt DA 1970 A case of cyptococcal granuloma in the
Sullins KE, Turner AS 1982 Management of fractures of the nasal cavity of a horse. Australian Veterinary Journal
equine mandible and premaxilla (Incisive bone). Com- 46: 493–494
pendium on Continuing Education for the Practicing Weller R, Livesey L, Maierl J et al 2001 Comparison of
Veterinarian 4: S480–S489 radiography and scintigraphy in the diagnosis of dental
Sundbergh JP, Burustein T, Page EH et al 1977 Neoplasms of disorders in the horse. Equine Veterinary Journal
equidae. Journal of the American Veterinary Medical 33: 49–58
Association 170: 150–152 Zamos DT, Schumacher J, Loy JK 1996 Nasopharyngeal
Taylor J 1955 The horse. The Head and Neck. Oliver & Boyd, conidiobolomycosis in a horse. Journal of the American
London Veterinary Medical Association 208: 100–101
Progressive Ethmoidal Hematoma
27 Jim Schumacher and Padraic M Dixon
Progressive ethmoidal hematoma (PEH), first described by 1985, Bell et al 1993b), and horses with PEH represent
Cook & Littlewort (1974), is an idiopathic, slowly expand- about 8% of referral horses with disease of the nasal
ing, non-neoplastic mass found in the nasal cavity or passages and paranasal sinuses (Tremaine & Dixon 2001b).
paranasal sinuses of horses; it has been described as a
hemorrhagic polyp (Head & Dixon 1999). The mass
usually originates from the submucosa of one of the larger
Signalment
ethmoturbinates (i.e. endoturbinates 1–5) (Figs 27.1 and PEH has been reported to occur in most breeds except
27.2) (Cook & Littlewort 1974, Boles 1979, Specht et al standardbreds, with thoroughbred and Arabian horses
1990, Bell et al 1993a), and the most ventral aspect of the most commonly affected (Bell et al 1993a). There is no
ethmoidal labyrinth, which protrudes into the caudal apparent gender difference in prevalence of PEH (Bell et al
portion of the nasal cavity, is the most common site of a 1993a); however, females may be more likely to be
PEH (Bell et al 1993a, Head & Dixon 1999) (Figs 27.3 and bilaterally affected than males (Rothaug & Tulleners
27.4). Less commonly, lesions arising from the sinusal 1999). Horses of any age may develop PEH, but horses less
(intrasinus) portion of the ethmoidal labyrinth grow into
the paranasal sinuses, especially the maxillary or frontal
sinuses. PEH lesions may occasionally arise from the
submucosa of areas of the paranasal sinuses other than
the ethmoidal labyrinth (Cook & Littlewort 1974, Sullivan
et al 1984, Freeman et al 1990, Specht et al 1990, Greet
1992, Bell et al 1993a), but Cook & Littlewort (1974)
surmised that only PEHs that arise from the ethmoidal
labyrinth are capable of achieving a large size.
Recurrent hemorrhage and the development of a large
fibrous skeleton can cause the PEH to expand along the
lines of least resistance into the ipsilateral nasal passage
(Fig. 27.4), nasopharynx or paranasal sinuses, inducing
varying degrees of pressure (often minimal) on adjacent
tissues. The cause of PEH is unknown, but the disease may 2
originate from a congenital or acquired hemangiomatous
lesion, which predisposes to repeated hemorrhage into the
submucosa of the ethmoidal labyrinth (Platt 1975). The
blood supply to the ethmoid region is complex with a dual
arterial supply present in the ethmoid labyrinth (Bell et al
1995), resulting in a complex network of vessels. However,
so far, the description of PEH as a primary vascular lesion
remains speculative (Tremaine et al 1999).
Prevalence Fig. 27.1. Nasal endoscopic view of the normal equine ethmo-
turbinates. Note the varying size of the individual endoturbinates
The prevalence of PEH in the general equine population is (ethmoturbinates), with endoturbinate number two (2) being largest.
unknown, but has been recorded as approximately one In other normal horses endoturbinate number two can be two to three
horse per 2,500 (0.04%) at referral hospitals (Boulton times this diameter.
409
410 27 Progressive Ethmoidal Hematoma
Fig. 27.2. Transverse section of a normal equine skull at the level of the ethmoturbinates showing the
tightly coiled endoturbinates, vertical septum between left and right ethmoturbinates, and the overlying
conchofrontal sinuses. Note the cavities (small sinuses) present within the larger, ventrally situated
endoturbinates.
Fig. 27.3. Transverse section of a skull of a horse suffering from bilat-

eral PEH. Most of the ethmoturbinates on the left side have been
replaced by a large PEH lesion, whilst on the right side, the ventro-
medial aspect of the ethmoturbinates is similarly affected.
Fig. 27.4. A PEH viewed on endoscopy of the left nasal cavity. This
PEH is multicolored with focal areas of bright red, indicating areas of
recent hemorrhage. The brown–green areas are caused by hemo-
siderin within the PEH, at sites where older hemorrhages have
occurred. The caudal aspect of the middle meatus (“drainage angle”)
is indicated by arrows.
27 Progressive Ethmoidal Hematoma 411
than 3 years old are seldom affected although a case of anemia (Cook & Littlewort 1974, Specht et al 1990,
neonatal PEH has been reported (Colbourne et al 1997). Greet 1992, Laing & Hutchins 1992, Bell et al 1993a,
The average age of affected horses is about 10 years (Platt Schumacher et al 1997, Tremaine & Dixon 2001a).
1975, Bell et al 1993a, Schumacher et al 1997, Rothaug &
Tulleners 1999, Tremaine & Dixon 2001a).
Differential Diagnosis
Other causes of equine epistaxis include mycosis of a
Clinical Signs guttural pouch, paranasal sinus or nasal cavity, facial and
Small PEH lesions may be subclinical (Laing & Hutchins sinus trauma (e.g. maxillary or nasal bone fracture), and
1992, Schumacher et al 1997, Rothaug & Tulleners rupture of the longus capitus muscles, all of which usually
1999), because the limited amount of hemorrhage from cause more acute and severe hemorrhage (except sinonasal
them can be accommodated by the normal, caudally mycosis). Lower grade epistaxis can, however, occur with
directed mucociliary flow and then swallowed. The most upper or lower respiratory tract neoplasia, infection of a
common clinical sign caused by a PEH is a chronic, nasolacrimal duct (dacryohemorrhea), exercise-induced
intermittent, low-volume, hemorrhagic or serohemor- pulmonary hemorrhage, pleuropneumonia, disseminated
rhagic discharge from the affected, and sometimes the intravascular coagulation, thrombocytopenia, and nasal
unaffected, nasal passage, that is caused by ulceration amyloidosis (Schumacher et al 1992, Bell et al 1993a).
of the mucosa covering the lesion (Cook & Littlewort Masses located in a nasal cavity or the paranasal sinuses
1974, Greet 1992, Behrens et al 1993, Bell et al 1993a, that may grossly resemble PEH include neoplasms, sinus
Schumacher et al 1997, Tremaine & Dixon 2001a). The cysts, polyps, and fungal granulomas, such as those caused
nasal discharge is usually spontaneous but rarely may by Cryptococcus neoformans (Bell et al 1993a, Tremaine &
be induced by exercise (Cook & Littlewort 1974, Behrens Dixon 2001b).
et al 1993). PEH is the most common cause of low-grade
(perhaps a few drops per day), chronic (possibly of many
months duration) unilateral epistaxis or mucohemorrhagic
Diagnosis
nasal discharge in horses (Boles 1979, Tremaine & Dixon PEH can be provisionally diagnosed by its endoscopic
2001a). A lesion may rarely cause a purulent nasal dis- appearance of a smooth, red to green mass originating
charge as a result of induced local damage to the adjacent from the nasal portion of the ethmoidal labyrinth (Fig.
tissue, or obstruction of paranasal sinus drainage. 27.4) (Schumacher et al 1992). The ethmoidal labyrinth
A large PEH within the nasal cavity may reduce airflow from which the PEH arises may be obscured by the bulk of
through that nasal cavity and so result in stertorous the PEH. Rarely, the PEH may protrude caudally beneath
breathing at exercise (Hanselka & Young 1975, Leyland & the ventral border of the vomer bone into the contra-
Baker 1975, Specht et al 1990, Laing & Hutchins 1992, lateral nasal cavity obscuring the contralateral ethmoidal
Colbourne et al 1997, Schumacher et al 1997) and rarely, labyrinth, giving the false impression that the horse has a
large PEH lesions may be visible at the nostril (Schumacher separate PEH in each nasal cavity. The PEH acquires its
et al 1997, Frees et al 2001). A PEH originating on the color from the hemoglobin underlying its mucosal lining
nasal portion of the ethmoidal labyrinth usually expands and so may be of varying shades of red, green, gray, and
rostrally into the nasal cavity, but rarely it may expand yellow, often with focal differences in coloring, depending
caudally into the nasopharynx, and even grow around the on the time of the most recent hemorrhage (which causes
caudal edge of the nasal septum into the contralateral red lesions) that later turn to hemosiderin (green-colored)
nasal cavity (Schumacher et al 1997) causing bilateral (Platt 1975, Head & Dixon 1999). White, fungal plaques,
nasal obstruction that may cause stertorous breathing and including those caused by secondary infection with
even dyspnea at rest. As a lesion within the paranasal Aspergillus spp., may occasionally cover the dorsal surface
sinuses expands, it may push the medial wall of the dorsal of the lesion, especially of PEHs within a paranasal sinus
and ventral conchal sinuses into the ipsilateral nasal cavity (authors’ personal observation). Even if clinical signs have
and, less commonly, in the case of a very large intrasinus been unilateral, both nasal cavities should be examined
PEH, it may cause facial deformity. Facial swelling is endoscopically because about 15% of affected horses are
much less likely with PEH lesions than with sinus cysts or affected bilaterally (Bell et al 1993a, Schumacher et al
sinonasal neoplasia (Tremaine & Dixon 2001a). 1997, Rothaug & Tulleners 1999).
Other reported clinical signs associated with PEH A PEH that originates from the sinusal portion of the
include ipsilateral submandibular lymphadenopathy, head ethmoidal labyrinth is not seen during nasal endoscopy,
shaking, head shyness, halitosis (as a result of local unless the PEH protrudes into the nasal cavity through the
necrosis of PEH lesions or secondary infection), exoph- dorsal or ventral ethmoidal meati (Cook & Littlewort 1974)
thalmos, episodes of choking and ptyalism (as the result or through the nasomaxillary aperture (Behrens et al
of extension of PEH to the nasopharynx), and low-grade 1993). Hemorrhagic or serohemorrhagic discharge from a
PEH
Fig. 27.5. Endoscopy of the caudal aspect of the right nasal cavity of a Fig. 27.6. View at sinoscopy of a maxillary sinus showing a large
horse with an intrasinus PEH. Notice the normal morphology of these green-tinged PEH within its lumen, with minimal inflammation of the
ethmoturbinates. Two streaks of blood (arrowheads) can be seen sinus mucosa.
flowing from the “drainage angle” of the right maxillary sinus.
Gross and Histologic Appearance

PEH within the paranasal sinuses can sometimes be seen
emerging from the ventral or dorsal ethmoidal meati (Cook While the history and clinical signs are sometimes
& Littlewort 1974) or through the nasomaxillary aperture pathognomonic, the endoscopic appearance of PEH lesions
(“drainage angle”) (Fig. 27.5) (Cook & Littlewort 1974, is usually diagnostic. Histological examination of the
Etherington et al 1982, Tremaine & Dixon 2001b). A PEH lesion confirms the diagnosis, or at least eliminates the
originating within the paranasal sinuses can usually be presence of other similar appearing masses of the nasal
observed by sinoscopy of the caudal maxillary or concho- cavity. A uterine biopsy forceps, directed to the lesion
frontal sinuses (Fig. 27.6) (see Chapter 18) (Tremaine & using endoscopic guidance, can be used to obtain adequate
Dixon 2001b). tissue for histological diagnosis because a transendoscopic
The extent of a PEH can be determined by endoscopic, biopsy instrument does not usually retrieve a sufficient
radiographic or computed tomographic imaging (Greet sample size for diagnosis (Colbourne et al 1997; authors’
1992, Tietje et al 1996, Colbourne et al 1997). A PEH at personal observation). The biopsied lesion often collapses
the more common rostroventral ethmoidal labyrinth site is because of leakage of the semi-liquid contents, leaving only
best imaged on lateral radiographic projections, centered the remaining capsule.
on the medial canthus of the eye. The PEH appears as an Macroscopically, PEHs have a smooth surface, and as
abnormal opacity of soft tissue density, rostral to the noted, range from purple–red to green–yellow in color. PEHs
ethmoidal labyrinth (Cook & Littlewort 1974, Schumacher are usually covered by a flattened columnar or cuboidal
et al 1997, Tremaine & Dixon 2001b). Superimposition of ciliated epithelium, containing mucous glands, and occa-
the eyes and ethmoidal labyrinths may prevent radiographic sionally by stratified squamous epithelium, which is often
identification of small PEH lesions (Rothaug & Tulleners focally ulcerated with a localized underlying inflammatory
1999, Tremaine & Dixon 2001b); in these cases, computed response. The cut surface of a PEH is reddish-brown
tomography can be useful (Tietje et al 1996, Colbourne and, on section, the lesions often collapse because of their
et al 1997). Skull radiography after administration of a liquid contents. Deeper tissues contain areas of recent
water-soluble, radiographic contrast medium into the hemorrhage, with a variable inflammatory infiltrate of
paranasal sinuses may help delineate the margins of an plasma cells, lymphocytes, and, less commonly, neutrophils
intrasinus PEH (Behrens et al 1991), but sinoscopy could (Tremaine et al 1999). Hemosiderophages and multi-
as readily be performed and would likely provide a more nucleate giant cells are often numerous (Platt 1975,
definitive diagnosis. Tremaine et al 1999). The degree of fibroplasia can vary
PEH
PEH
Fig. 27.7. View of the nasofrontal region of an anesthetized horse

through a small nasofrontal flap revealing a PEH lying within the rostral
aspect of the frontal sinus.
C
Fig. 27.9. This endoscopic image shows an intrasinus PEH with a
needle-tipped transendoscopic catheter (C) deeply inserted into it to
allow intralesional formalin therapy.
C
1992, Behrens et al 1993); ablating the lesion using

a cryogen (Meagher 1986) or laser (Meagher 1990);
surgically debulking the lesion and then ablating its
base with a cryogen or laser (Tate 1991, 1996, Rothaug &
Tulleners 1999); or injecting formaldehyde solution into
the lesion (Schumacher et al 1997, Marriott et al 1999,
Tremaine & Dixon 2001b). Successful removal of a PEH
Fig. 27.8. This surgically excised PEH has collapsed, which is usual. The using a snare placed around the base of the lesion under
green–brown colored, smooth mucosal capsule (C) of the PEH lesion is endoscopic guidance has also been reported (Hanselka &
identifiable, as is the internal stroma containing free blood and some Young 1975, Boulton 1985).
dark colored, more organized stroma.
Surgical ablation
from loose connective tissue and fibrin containing few Surgical ablation was the main treatment for PEH lesions
fibroblasts in some cases, to a dense fibrous connective until a decade or so ago, when it was largely replaced
tissue stroma in other cases (Tremaine et al 1999). by the less invasive treatments described below. A PEH
arising from the sinusal portion of the ethmoidal labyrinth
can be exposed and excised through a frontonasal
Treatment osteoplastic (bone) flap (Figs 27.7–27.9) (Cook & Littlewort
There are various treatment options for PEH. Treatment of 1974, Freeman et al 1990, Specht et al 1990, Greet 1992,
horses whose lesion does not protrude beyond the external Behrens et al 1993, Tremaine & Dixon 2001b) created as
lamina of the ethmoidal bone is often not necessary, described by Blackford et al (1985) or Freeman et al
because lesions this small often cause no clinical signs of (1990), following which the floor of the dorsal conchal
disease (Schumacher et al 1997). However, if treatment is sinus is fenestrated (using a scissors or a rongeur) into
not performed, these horses should be monitored for the middle meatus of the nasal cavity and the PEH is
clinical signs and endoscopically examined periodically then excised (Greet 1992). This surgery is usually per-
because the lesion is considered to be progressive. Rarely, a formed with the horse anesthetized, and there is often
PEH may disappear spontaneously (Laing & Hutchins marked blood loss. Intrasinus PEH lesions can similarly
1992, authors’ personal observation). Horses affected by be excised through a frontonasal or maxillary osteoplastic
PEH can be treated by excising the lesion (Cook & Littlewort flap with the horse anesthetized or sedated and standing
1974, Specht et al 1990, Greet 1992, Laing & Hutchins (Schumacher et al 2000).
Severe, intraoperative hemorrhage is the most common hemorrhage) if an intrasinus PEH has been removed. The
complication of excision of a PEH. Creating a frontonasal end of the gauze is exited through a separate trephine
flap to expose the paranasal sinuses and sinusal portion of opening created adjacent to the osteoplastic flap and the
the ethmoidal labyrinth generally causes relatively little gauze is pulled out 24–48 h later and an indwelling lavage
hemorrhage, but perforating the floor of the dorsal conchal system is then inserted for 5–7 days of sinus lavage.
sinus and excising the PEH are usually accompanied by Both the nasal cavity and the paranasal sinuses are
severe hemorrhage. The use of suction may improve postoperatively packed to control hemorrhage if the PEH
visibility. Methods of decreasing hemorrhage include the has been removed from the nasal portion of the ethmoidal
use of electrocautery and application of gauze sponges labyrinth. They can be packed separately, using separate
soaked in cold, physiological saline solution, with or rolls of gauze, if a separate trephine hole is created (see
without epinephrine, to the hemorrhaging tissue. above), or the sinuses and nasal cavity can be packed with
Removing a PEH with the horse standing and its head a continuous roll of gauze. When using one continuous
elevated may decrease the severity of hemorrhage by roll of gauze, one end of the gauze is introduced into the
lowering the blood pressure at head level as compared to nasal cavity with a long grasping forceps and is then pulled
recumbency (Schumacher et al 2000) and also eliminates into the paranasal sinuses through the created sinonasal
anesthetic risk. However, these advantages must be weighed fistula. The end of the gauze exiting the nasal cavity should
against the problems that could be encountered during be sutured to the nostril to prevent complete loss of the
surgery if the horse hemorrhages severely while its head gauze in case the horse accidentally swallows the pack. To
cannot be properly restrained. Horses selected for standing decrease the likelihood of the pack being swallowed, the
surgery of paranasal sinuses and nasal passage must be nasopharynx can be inspected endoscopically through the
docile and must not resent manipulations of their head. contralateral nasal cavity to ensure that the pack has not
To prevent cardiovascular problems associated with been pushed into the nasopharynx. Inserting the gauze
severe hemorrhage and hypovolemia, the horse should pack into an elastic, tubular stocking (Tubular Stockinette,
receive a balanced electrolyte solution intravenously during Baxter Healthcare Corporation, Deerfield, IL, USA) inserted
surgery. Replacing blood during surgery is seldom necessary, into the nasal cavity prevents the gauze from being
but if the surgeon is inexperienced in this procedure, swallowed (Greet 1992, Lane 1993) as described in detail
having at least 4–6 liters of compatible blood available for in Chapter 26.
transfusion or having a compatible donor on standby may Although some surgeons prefer to remove the packing
be prudent. Very rarely, an anemic horse should receive as late as 72–96 h after surgery (Freeman et al 1990), the
blood from a suitable donor during or before surgery. packing can usually be removed safely at 24 h, because
A technique for controlling hemorrhage in anesthetized longer duration of packing can lead to local infection at the
horses is to temporarily occlude both common carotid site of surgery (authors’ personal observation). Repacking
arteries in the mid-neck region (Wynn-Jones et al 1986, of the nasal cavity may occasionally be required if severe
Freeman et al 1990). An umbilical tape ligature is placed and prolonged hemorrhage is encountered immediately
loosely around each artery before sinusotomy, with the after removal of the packing. After packing removal, the
horse anesthetized (Wynn-Jones et al 1986, Lane 1993). paranasal sinuses can be lavaged to remove blood clots
The ligatures are tightened while the lesion is excised, to through a trephine opening created adjacent to the fron-
temporarily occlude the arteries. Both common carotid tonasal flap for about 5 days post surgery. Gravity flow,
arteries can be occluded for at least 15 min without rather than pressurized flow, should be used when lavaging
causing neurological deficits because the ventral spinal the paranasal sinuses particularly in the first 24–48 h of
artery, which contributes a large amount of the blood lavage after creation of an osteoplastic flap to avoid forcing
supply to the circle of Willis, prevents cerebral ischemia fluid into the subcutaneous tissue at the sinusotomy,
during bilateral carotid occlusion (Wynn-Jones et al 1986, which may increase the incidence of wound infection and
Lane 1993). Temporarily ligating the common carotid dehiscence around the edges of the flap. One of us (PMD)
arteries prolongs surgical time, is sometimes ineffective uses an extremely dilute solution of povidone iodine to
in reducing severe hemorrhage (Greet 1992, Laing & lavage the sinuses.
Hutchins 1992, Tremaine & Dixon 2001b), and may result Fatal postoperative complications associated with sur-
in damage to the adjacent recurrent laryngeal nerve (may gical excision of a PEH include meningoencephalitis (Greet
result in permanent laryngeal dysfunction) or vagosym- 1992, Rothaug & Tulleners 1999) and intracranial hemor-
pathetic trunk (may result in bradycardia and apnea) rhage (Tremaine & Dixon 2001b). Meningoencephalitis
(Wynn-Jones et al 1986, Lane 1993). can occur from damage to the cribriform plate or tracking
Postoperatively, only the paranasal sinuses require of infection through the plate (Greet 1992). Less serious
packing (using rolled gauze, either dry or saturated with a complications are infection and dehiscence of the cuta-
dilute [e.g. 1 : 10,000] solution of epinephrine to control neous incision, usually at the rostral margin of the incision
(Freeman et al 1990, Greet 1992); sequestration of a to its origin than is possible using surgical ablation alone
section of the osseous portion of the frontonasal flap; (Tulleners 1996). A study by Rothaug and Tulleners (1999)
suture periostitis; and opportunistic fungal infection at the found no difference in the incidence of recurrence with this
surgical site (Greet 1992, Tremaine & Dixon 2001b). technique compared to surgical excision alone.
Cryotherapy Chemical ablation

A cryogen, such as liquid nitrogen, delivered as a spray or A PEH can be ablated with a 4% aqueous solution of
through a probe, can be administered nasally to ablate formaldehyde gas (10% formalin) (Schumacher et al 1997,
small PEHs after applying a topical anesthetic to the nasal Marriott et al 1999, Tremaine & Dixon 2001b). Formalin
cavity (Meagher 1990). Cryogenic ablation of a PEH results can be injected into a PEH located on the nasal portion of
in minimal hemorrhage, and the cryogen can be adminis- the ethmoidal labyrinth, in a standing sedated horse, using
tered with the horse sedated and standing, using endo- a transendoscopic polypropylene catheter. The end of the
scopic guidance. Only small lesions on the nasal portion of tubing can be cut diagonally to penetrate the PEH capsule,
the ethmoidal labyrinth can be ablated in this manner, and or the lesion can be injected using commercially available
treatment may be more palliative than curative. polypropylene tubing with a retractable, swaged-on needle.
Liquid nitrogen can also be applied, through a probe or A small PEH can be injected by inserting the needle into
as a spray, to the origin of a PEH after a PEH has been the center of the mass; however, to inject a large lesion, the
excised (Cook & Littlewort 1974, Meagher, 1990, Specht short needle plus a few centimeters of the catheter are
et al 1990). Control of hemorrhage, at least temporarily, inserted into the center of the lesion.
is required because hemorrhage prevents the effective The PEH is injected with formalin until it expands and
application of the cryogen (Meagher 1990). Conflicting begins to leak solution. Horses often snort and become
reports exist as to the efficacy of this treatment. Meagher agitated by leakage of formalin solution over their nasal
(1990) found that it decreased the incidence of recurrence cavity; having some 50-ml syringes filled with lukewarm
while Specht et al (1990) found no such advantage. One water allows the area to be immediately lavaged to relieve
major complication associated with this technique is that this discomfort. The lesion is injected at 3- to 4-week inter-
freezing the cribriform plate could result in brain damage, vals until it is eliminated or becomes so small and deep
especially if the cribriform plate has been thinned or within the ethmoidal recess that the lesion can no longer
destroyed by pressure from the expanding PEH (Cook & be injected (Schumacher et al 1997). Usually, only two to
Littlewort 1974, Meagher 1990). five treatments, performed at 3- to 4-week intervals, are
required to eliminate a lesion, regardless of the lesion’s size.
Laser ablation A lesion originating on the sinusal portion of the
ethmoidal labyrinth can also be injected with formaldehyde
A PEH less than 5 cm in diameter that originates on the solution, using endoscopic guidance or direct visualiza-
nasal portion of the ethmoidal labyrinth can be photo- tion, through a trephine hole in the caudal maxillary or
ablated using a neodymium : yttrium–aluminum–garnet conchofrontal sinus. Injecting solely the nasal portion of a
(Nd:YAG) laser transendoscopically with the horse stand- PEH that resides both in the nasal cavity and the adjacent
ing, following topical local anesthesia of the nasal cavity paranasal sinuses may cause both the sinusal and nasal
(Meagher 1990, Tulleners 1992) as described in Chapter portions of the lesion to resolve (Schumacher et al 1997).
39 –Laser Surgery of the Upper Respiratory Tract. Lesions No complications were associated with chemical abla-
are best photoablated at 60 watts using a non-contact tion of PEHs of three horses in one study (Marriott et al
technique (Tulleners 1992). Treatments should be at least 1999) or of six horses in another study (Tremaine and
7 days apart to permit the devitalized tissue to slough. Dixon 2001b). In another report, however, one of 21 affected
Horses with even small PEHs may require 12 to 14 horses treated by chemical ablation developed laminitis
applications of the laser, and because of the high cost of within 24 h after each of three treatments (Schumacher
a Nd:YAG laser, this form of treatment is available only et al 1997). The association between intralesional injec-
at large referral centers (Tate 1991, 1996, Rothaug & tion of formalin and the development of laminitis may
Tulleners 1999). have been coincidental because the horse had suffered
Laser ablation can be performed to the base of a PEH periodically from laminitis before PEH treatment. In
after the lesion has been excised through a frontonasal flap another report, one horse affected with a large PEH was
(Rothaug & Tulleners 1999). The origin of the PEH is euthanased when it developed severe CNS depressing and
destroyed in contact fashion at 18–20 watts. Laser-assisted ataxia within minutes of the intralesional injection of
excision of PEHs may result in fewer recurrences than formalin (Frees et al 2001). Neurological abnormalities
surgical removal, because the PEH can be transected closer developed because erosion and necrosis of the cribriform
plate by the PEH had resulted in an abnormal commu- unilaterally to be 8% (median time of follow-up was
nication between the nasal cavity and the ventral cranial 26 months; range 3–110 months). The studies by Rothaug
vault, allowing formalin to migrate to the frontal lobe of and Tulleners (1999), Cook and Littlewort (1974) and
the brain. Specht et al (1990) did not indicate whether or not horses
At this recommended concentration, formalin desiccates that had no recurrence of clinical signs were examined
and coagulates the PEH by hydrolyzing protein (Osol & endoscopically. Determining the treatment method that
Farrar 1947, Schumacher et al 1997). While complica- has the lowest incidence of recurrence, based on results of
tions have been associated with intravenous injection of retrospective studies, is difficult because the long-term
formaldehyde solution, including restlessness, lacrimation, results obtained are difficult to compare.
salivation, elevation of the tail, and tenesmus (Roberts Rothaug and Tulleners (1999) recommended endo-
1943), these complications have not been reported after scopic examination of both nasal cavities of affected horses
intralesional injection of PEH with formalin (Schumacher every 3–6 months for at least 5 years after treatment
et al 1997, Marriott et al 1999, Tremaine & Dixon 2001b). to determine if the lesion has reappeared, but the length
Ablating PEHs using formalin avoids general anesthesia; of time after which a lesion is unlikely to recur has not
complications associated with surgical ablation, such as been determined. Recurrence has been observed as long
severe hemorrhage and infection of the cutaneous incision; as 3–4 years after surgical removal and the authors
problems associated with ablation by laser, such as avail- recommend bilateral nasal endoscopy at least annually
ability of equipment; and problems associated with cryo- for this period.
therapy, such as availability of equipment and lesions
being too large to be effectively frozen. Owners should be
informed of the potential, but relatively rare, complications REFERENCES
of this form of treatment, such as colic, laminitis, and
Behrens E, Schumacher J, Morris E 1991 Contrast paranasal
severe neurological deficits. sinusography for evaluation of disease of the paranasal
sinuses of five horses. Veterinary Radiology 32: 105–109
Behrens E, Schumacher J, Ford T 1993 Progressive ethmoidal
Prognosis hematomas in eight horses (1986–1990). Texas Veterinary
Axial deviation of the medial wall of the dorsal and ventral Medical Journal 55: 16–18
Bell BTL, Baker GJ, Foreman JH 1993a Progressive ethmoid
conchal sinuses, caused by a PEH contained within the hematoma: background, clinical signs, and diagnosis.
paranasal sinuses, usually resolves rapidly after the PEH Compendium on Continuing Education for the Practicing
has been removed. Even a deviated nasal septum may Veterinarian 15:1101–1110
return to its normal position (Colbourne et al 1997, Bell BTL, Baker GJ, Foreman JH 1993b Progressive ethmoid
authors’ personal observation). Facial distortion caused by hematoma: characteristics, cause, and treatment. Com-
pendium on Continuing Education for the Practicing
an expanding intrasinus PEH is also likely to improve after Veterinarian 15:1391–1398
PEH removal. Bell BTL, Baker GJ, Abbott LC et al 1995 The macroscopic
Regardless of the elected treatment method, the vascular anatomy of the equine ethmoidal area. Anatomia
prognosis for long-term resolution of a PEH is guarded to Histologia Embryologia 24: 39–45
poor. Incomplete excision may account for recurrence of Blackford JD, Goble DO, Henry RW et al 1985 Triangulated
flat technique for nasofrontal surgery. Veterinary Surgery
PEH in some horses, or new PEHs may develop at a site 14: 287–294
adjacent to or distant from (e.g. contralateral ethmoidal Boles C 1979 Abnormalities of the upper respiratory tract.
complex) the original PEH (Rothaug & Tulleners 1999). Veterinary Clinics of North America; Large Animal
Cook and Littlewort (1974) found that signs of disease Practice 1: 89–111
reappeared in five of 12 horses (41.6%) at 3–44 months Boulton CH 1985 Equine nasal cavity and paranasal sinus
disease: a review of 85 cases. Journal of Equine Veterinary
after surgery and believed it likely that the final proportion Science 5: 268–275
of lesions that recurred would have been higher if the time Colbourne CM, Rosenstein DS, Steficek BA et al 1997 Surgical
of follow-up had been extended. In a study by Specht et al treatment of progressive ethmoidal hematoma aided by
(1990), PEH reappeared in four of nine horses (44.4%) computed tomography in a foal. Journal of the American
after surgery (mean time of follow-up was 61 months). In a Veterinary Medical Association 211: 335–338
Cook WR, Littlewort MC 1974 Progressive hematoma of the
study by Greet (1992), three of 21 horses (i.e. 14.3%) with ethmoid region in the horse. Equine Veterinary Journal
PEH that were treated by surgical ablation had reappear- 6: 101–107
ance of lesions 7–32 months after surgery. Resolution Etherington WG, Vasey JR, Horney FD 1982 Ethmoid hema-
of disease was determined by owner questionnaire, and toma of the equine. Canadian Veterinary Journal 8: 231
not all horses were examined endoscopically to confirm Freeman DE, Orsini PG, Ross MW et al 1990 A large fronto-
nasal bone flap for sinus surgery in the horse. Veterinary
resolution of the lesion. Rothaug and Tulleners (1999) Surgery 19: 122–130
found the incidence of disease recurrence in seven horses Frees KE, Gaughan EM, Lillich JD et al 2001 Severe compli-
affected bilaterally to be 43% and that of 12 horses affected cation after administration of formalin for treatment of
progressive ethmoidal haematoma in a horse. Journal Schumacher J, Yarbrough T, Pascoe J et al 1997 Trans-
of the American Veterinary Medical Association 219: endoscopic chemical ablation of progressive ethmoidal
950–952 hematomas in standing horses. Veterinary Surgery
Greet TRC 1992 Outcome of treatment in 23 horses with 27: 175–181
progressive ethmoidal haematoma. Equine Veterinary Schumacher J, Dutton DM, Murphy DJ et al 2000 Paranasal
Journal 24: 468–471 sinus surgery in sedated, standing horses. Veterinary
Hanselka DV, Young MF 1975 Ethmoidal hematoma. Veteri- Surgery 29: 173–177
nary Medicine and Small Animal Clinician 70: 1289–1291 Specht TE, Colahan PT, Nixon AJ et al 1990 Ethmoidal
Head KW, Dixon PM 1999 Equine nasal and paranasal sinus hematoma in nine horses. Journal of the American
tumours. Part 1: Review of the literature and tumour Veterinary Medical Association 197: 613–616
classification. Veterinary Journal 157: 261–278 Sullivan M, Burrel MH, McCandish IA 1984 Progressive
Laing JA, Hutchins DR 1992 Progressive ethmoidal haema- haematoma of the maxillary sinus in a horse. Veterinary
toma in horses. Australian Veterinary Journal 69: 57–58 Record 114: 191–192
Lane JG 1993 The management of sinus disorders of horses – Tate LP 1991 Applications of lasers in equine upper respira-
Part 2. Equine Veterinary Education 5: 69–73 tory surgery. Veterinary Clinics of North America; Equine
Leyland A, Baker JR 1975 Lesions of the nasal and paranasal Practice 7: 165–195
sinuses of the horse causing dyspnoea. British Veterinary Tate LP 1996 Transendoscopic neodymium:yttrium–aluminum–
Journal 131: 339–346 garnet laser ablation of progressive ethmoid hematoma
Marriott MR, Dart AJ, Hodgson DR 1999 Treatment of in the horse. American Society of Laser Medicine and
progressive ethmoidal haematoma using intralesional Surgery Abstracts Supplement 8: 45
injections of formalin in three horses. Australian Veterinary Tietje S, Becker M, Bockenhoff G 1996 Computed tomographic
Journal 77: 371–373 evaluation of head diseases in the horse: 15 cases.
Meagher DM 1986 The evaluation and surgical treatment of Equine Veterinary Journal 28: 98–105
ethmoid hematomas in the horse. Veterinary Surgery Tremaine WH, Dixon PM 2001a A long-term study of 277
15: 128 cases of equine sinonasal disease. Part 1: Details of
Meagher DM 1990 Ethmoid hematoma. In White NA, horses, historical, clinical and ancillary diagnostic
Moore JN (editors) Current Practice of Equine Surgery. findings. Equine Veterinary Journal 33: 274–282
Lippincott, Philadelphia, pp.227–230 Tremaine WH, Dixon PM 2001b A long-term study of 277
Osol A, Farrar GE 1947 The Dispensatory of the United cases of equine sinonasal disease. Part 2: Treatments
States of America, 24th edn. Lippincott, Philadelphia, and results of treatments. Equine Veterinary Journal
pp.483–486 33: 283–289
Platt H 1975 Haemorrhagic nasal polyps of the horse. Journal Tremaine WH, Clarke CJ, Dixon PM 1999 Histopathological
of Pathology 115: 51–55 findings in equine sinonasal disorders. Equine Veterinary
Roberts SJ 1943 The effects of various intravenous injections Journal 31: 296–303
on the horse. American Journal of Veterinary Research Tulleners EP 1992 Nasal passages. In: Auer J (editor) Equine
4: 226–239 Surgery. Saunders, Philadelphia, pp.443–446
Rothaug PG, Tulleners EP 1999 Neodymium:yttrium– Tulleners EP 1996 Instrumentation and techniques in
aluminum–garnet laser-assisted excision of progressive transendoscopic upper respiratory tract laser surgery.
ethmoid hematomas in horses: 20 cases (1986–1996) Veterinary Clinics of North America; Equine Practice
Journal of the American Veterinary Medical Association 12: 373–395
214: 1037–1041 Wynn-Jones G, Jones RS, Church S 1986 Temporary bilateral
Schumacher J, Dean PM, Welch R 1992 Dacryohemorrhea as carotid artery occlusion as an aid to nasal surgery in the
a cause of epistaxis from two horses. Journal of the horse. Equine Veterinary Journal 18: 125–128
Disorders of the Guttural Pouches
(Auditory Tube Diverticuli)
28 G Barrie Edwards and Tim Greet
Anatomy
artery (ICA; Fig. 28.1). The facial nerve (VII) passes for a
The guttural pouches, which are not present in any domes- short distance over the caudodorsal aspect of the lateral
ticated animals other than Equids, are paired ventral compartment.
diverticuli of the eustachian tubes extending from the The external carotid artery (ECA) lies along the wall of
nasopharynx to the middle ear. Their location, configura- the lateral compartment and, after giving off the superficial
tion, and anatomical relationships contribute to the variety temporal artery, continues as the maxillary artery along
of clinical signs demonstrated when the pouches are the roof of the guttural pouch. The lateral retropharyngeal
involved in a disease process. lymph nodes contact the lateral wall of the medial com-
Each pouch is an air-filled space with a capacity of partment, and the medial retropharyngeal lymph nodes
300–500 ml in adults. The two pouches are in contact contact the medial compartment’s ventral wall. Each
ventral to the longus capiti muscles, where the mem- pouch communicates with the pharynx through a slit-like
branous portion of their medial wall separates them. The opening on the pharyngeal wall, rostroventral to the
pouch is reflected around the dorsal border of the pharyngeal recess. A thin plate of fibrocartilage is located
stylohyoid bone, which courses through its caudolateral in the mucosa of the medial aspect of the ostium. The
aspect, dividing it into a small lateral compartment and a pharyngeal opening into the pouch lies halfway up from
larger medial compartment. The medial compartment the base of the pouch. Therefore, when a horse’s head is in
is two to three times the size of the lateral compartment the upright position, the ostium only provides an overflow
and extends more caudally and ventrally. The lateral outlet for the escape of fluid, which may accumulate in the
compartment is related to the ramus of the mandible pouch. However, the ostia open during swallowing,
laterally, and the ventral aspect of the medial compartment allowing effective drainage when the horse is grazing.
is laterally related to the mandibular and parotid salivary Dilatation of the ostia also results in an exchange of air
glands (Sisson 1975). The pouches are lined by ciliated
epithelium, but non-ciliated microvillous and mucus-
producing cells are also evident on electron microscopy
(Pirie et al 1990). The lining of the pouch contains a large
number of lymphocytic follicles, and its lumen contains a
complex microflora of bacteria, fungi, and viruses. The
walls of the guttural pouch are thin and intimately
associated with many vital structures, including the
pharynx, larynx, esophagus, parotid and mandibular L M i
salivary glands, and the retropharyngeal lymph nodes. The
e
associated neurovascular anatomy is extensive and
complex. The roof of the guttural pouch directly contacts s
a large area of the ventral surface of the skull from n
the occipital condyles to the mandibular articulation.
In the center of this area are the foramen lacerum
and the tympanic bulla, and structures that enter and
leave the foramen lacerum must cross the pouch. A fold
of mucous membrane extending from the roof of the
pouch along the caudal aspect of the medial compartment
contains the glossopharyngeal (IX), vagus (X), accessory
Fig. 28.1. Endoscopic view of the right guttural pouch. s = stylohyoid
(XI), and the hypoglossal (XII) nerves, as well as the bone; L = lateral compartment; e = external maxillary artery; M =
pharyngeal branches of IX and X, the sympathetic trunk medial compartment; i = internal carotid artery; n = IX, X, XI cranial
with the cranial cervical ganglion, and the internal carotid nerves.
419
420 28 Disorders of the Guttural Pouches (Auditory Tube Diverticuli)
during breathing, which exposes the pouches to airborne guttural pouch is facilitated by counter-clockwise rotation
infectious agents. It has been shown experimentally that of the endoscope once the lead wire has passed under the
ventilation of the guttural pouch cools the blood in the ICA cartilaginous flap. Such rotation is not required when
(Baptiste et al 2000), and the normal exchange of air introducing the endoscope into the left guttural pouch.
during breathing may be a brain-cooling mechanism to
dissipate the heat that is generated by muscular exertion. Radiographic Examination
The main disorders of the guttural pouches are
tympany, mycosis, empyema, chondroids, diverticulitis, On an erect, lateral projection, centered one-third of the
and neoplasia. way down the caudal border of the vertical ramus of the
mandible, the normal guttural pouches appear as dark
triangular areas, extending rostrally and caudally to this
Diagnosis border, with their apex located below the petrous temporal
Guttural pouch disease is suggested by a history of nasal bone and their base lying dorsal to the larynx and
discharge (mucopurulent material or blood), parotid area nasopharynx. The stylohyoid bones can be seen running in
swelling, dyspnea, and evidence of cranial nerve and a rostroventral to dorsocaudal direction through the
cranial sympathetic trunk dysfunction. Distension of the pouches. The air that normally fills the guttural pouches
pouch may be characterized by external swelling medial provides contrast for good diagnostic radiographic images,
to the parotid salivary gland and by nasopharyngeal com- enabling identification of gas–fluid interfaces or loss of air
pression. Most guttural pouch diseases do not, however, contrast as the result of the presence of inspissated pus,
cause external swelling. Guttural pouch disease can be enlarged lymph nodes, and tumors (Cook 1973). The
definitively diagnosed by endoscopic examination of the degree of nasopharyngeal compression caused by disten-
nasopharynx and pouch, by lavage of the pouch, and by sion of the pouch can be radiographically evaluated.
radiographic examination of the parotid region.
Surgical Approaches to the
Physical Examination Guttural Pouch
External palpation in the parotid area is helpful to detect Historically, several surgical approaches have been used for
swellings caused by tympany, empyema, abscessation the treatment of diseases affecting the guttural pouch.
of adjacent lymph glands, or neoplastic foci, particularly The ideal surgical approach should afford the best access,
within the parotid lymph nodes. Occasionally, guttural with minimal risk of damage to adjacent structures.
pouch mycosis may produce painful foci deep to the base The guttural pouches are difficult to approach surgically,
of the ear, when the head of the stylohyoid bone or the because of the numerous important neural and vascular
tympanohyoid articulation have become involved. structures that surround them. All approaches, other than
the “Whitehouse” approach, are usually performed with
Endoscopy the horse anesthetized and placed in lateral recumbency
with the affected pouch uppermost; for the “Whitehouse”
Non-specific evidence of guttural pouch disease, such as approach, the horse is placed in dorsal recumbency;
nasopharyngeal collapse and the presence of blood or however, this latter approach can be performed with the
purulent material draining from the pharyngeal orifice, can horse standing.
be found on endoscopic examination of the nasopharynx.
However, blood or pus from other respiratory sources can Hyovertebrotomy
occasionally be aspirated into the guttural pouch ostia
during swallowing and can appear to be draining from The hyovertebrotomy approach is the most commonly
there. Endoscopy of the guttural pouch usually allows all employed surgical approach to the guttural pouches. It is
the anatomical structures within the pouch to be exam- used primarily for identification of the carotid artery
ined, unless it is filled with blood, pus, or chondroids. prior to intra-arterial balloon catheterization and/or the
Passage of an endoscope into each guttural pouch is placement of surgical ligatures around the ICA or any
simplified by using a wire leader or biopsy instrument other vessels affected by guttural pouch mycosis. Less
introduced through the biopsy channel, which is invariably commonly this approach is used to provide access to the
eccentrically located, to raise the cartilage flap before dorsal aspect of the pouch, so allowing inspection of the
advancing the endoscope into the pouch. To achieve this, pouch and possible removal of its contents. This approach
the endoscope must be introduced via the ventral meatus is often performed to aid creation of ventral drainage
and directed caudodorsally to enter the pouch. If the from the pouch (see below). An approximately 10-cm long,
biopsy channel of the endoscope is located at the 5 o’clock curved incision is made parallel and cranioventrad to
position, introduction of the endoscope into the right the wing of the atlas. Occasionally, a moderately sized
28 Disorders of the Guttural Pouches (Auditory Tube Diverticuli) 421
superficial vein is encountered here, but this vein can countless generations of veterinary students. It is, however,
usually be reflected or ligated. The parotid fascia imme- the least used of surgical approaches because it provides
diately below the skin in this region is very dense and limited access to the pouch, unless the pouch is grossly
must be incised with a scalpel or scissors. However, dissec- distended, such as may occur with marked tympany or
tion deep to this level must be carried out using blunt empyema, and also because it requires dorsal reflection of
instrumentation or digitally, to avoid injury to the many the parotid salivary gland and its duct, which then
neural or vascular structures in this area. The dorsal aspect interferes with access to the lateral compartment of the
of the parotid salivary gland is usually retracted rostrally guttural pouch in many horses.
out of the surgical field using a strong, self-retaining
retractor, such as a rib retractor, which is placed between Modified Whitehouse approach
the parotid gland and the wing of the atlas, or by using
hand-held retractors. This ensures a clear view of the This approach is similar to that used for laryngoplasty and
loose, fibrous-areolar tissue that surrounds the vessels and is performed by making a 7–10-cm skin incision ventral to
nerves deep in this site and also exposes the dorsal aspect of the linguofacial vein. The skin incision is continued by
the guttural pouch. blunt dissection deep to the vein to reveal the lateral
If the intention is to identify the appropriate artery aspect of the larynx and the related thyropharyngeal and
before inserting a balloon catheter and/or ligating it, the cricopharyngeal muscles. As with the previously described
vessels should be carefully separated from the surrounding approaches, pointing the tip of a flexible endoscope
fascia and the adjacent nerves must be identified and (previously inserted into the ipsilateral guttural pouch)
preserved. The use of aneurysm needles can be very helpful toward the wall of the lateral compartment helps to
in identifying the carotid arterial trifurcation, and in allow- identify the guttural pouch deep within the incision, thus
ing separation of the arteries from surrounding tissue. allowing the wall of the medial compartment of the pouch
Digital identification of an arterial pulse is useful but to be safely penetrated.
if there is any doubt about whether a structure is an The modified Whitehouse is the preferred approach for
artery or a nerve, the “needle test” can be employed with establishing optimal drainage of purulent material from the
complete safety. This involves the gentle insertion of a pouch, and allows removal of large or firm chondroids. It is
25-gauge needle into the structure in question. If inserted the most direct approach and allows flexible, safe, surgical
into a nerve, no blood will emerge, but if inserted into an access to the contralateral pouch through the midline
artery, a small spurt of arterial blood will be obtained that septum, which is best identified by trans-septal illumination
can be readily controlled after needle removal. from an endoscope inserted into the contralateral pouch.
If the guttural pouch is to be surgically entered using The incision in the lateral wall of the medial compart-
this approach, passing an endoscope into the pouch ment is usually left to heal by second intention. However, if
beforehand is helpful, because light from the lens of the the mucosa is to be closed, great caution must be observed
endoscope is transmitted through the wall of the pouch, to avoid the closely related, vital neural structures.
allowing its easy identification. This allows the lining,
which is usually covered with the same loose areolar tissue Whitehouse approach
as the nerves and vessels, to be grasped with rat-tooth
forceps. The lumen is then carefully penetrated, and the This approach has been used both for ligating the ICA and
incision is expanded digitally to minimize the risk of injury for establishing drainage of purulent material, but in the
to adjacent neural or vascular structures. The pouch authors’ view, it is less than ideal for either purpose.
mucosa can be sutured or left to heal by second intention. Using this approach, the horse is positioned in dorsal
If it is to be repaired, a continuous suture of absorbable recumbency, and a 20–25-cm long ventral midline incision
suture material such as polyglactin can be used, taking is made from the basihyoid bone in a caudad direction to
great care to avoid damaging any nerve or blood vessel. the trachea. The sternohyoid muscles are separated, and
The parotid fascia and subcutaneous tissues can readily be the larynx and trachea are pushed to one side to allow
apposed using a continuous suture of the same material. ventral access to the medial compartment of either
The skin is usually closed with stainless steel staples. guttural pouch, taking great care to avoid the pharyngeal
branch of the vagus nerve and the cranial laryngeal nerve,
Viborg’s triangle which are both in the surgical field.
If the intention is to ligate the ICA, it may be necessary
This anatomical landmark is formed by the intersection of to use long-handled instruments because the artery is
the tendon of the sternocephalicus muscle, the caudal situated very deep in the wound using this approach.
aspect of the mandible, and the linguofacial vein. It is Ligating the ICA in the roof of the medial compartment
named after the Danish veterinary surgeon Erik Viborg, without damaging the closely associated cranial sym-
and is the site of a surgical approach remembered by pathetic nerve and causing Horner syndrome is almost
impossible. In the authors’ view, arterial ligation is far more

satisfactorily achieved via a hyovertebrotomy approach.
In general, direct surgical approaches into the guttural
pouch should be avoided whenever possible, because of the
high risk of life- or career-threatening iatrogenic nerve
injury. Whenever a surgical approach is used, inserting an
endoscope into the appropriate pouch to allow the wall to
be identified by transmural illumination can make the
procedure much safer, as previously noted. If an animal is
dyspneic as a consequence of guttural pouch empyema,
pouch drainage may be considered as an emergency
procedure and can be performed in the standing patient.
However, in such cases it may be preferable to provide relief
by performing a temporary tracheotomy, before taking a
more considered approach to guttural pouch drainage
(e.g. by large volume lavage of the affected pouch via an
indwelling catheter). Additionally, the dyspnea in some of
these patients may be the result of ventral nasopharyngeal
compression caused by grossly swollen lymph nodes, which
may not be resolved by pouch drainage.
The hyovertebrotomy approach is the most commonly
used guttural pouch surgical approach used to prevent
fatal epistaxis in cases of guttural pouch mycosis. Access
via a hyovertebrotomy incision is adequate for both
proximal ligation of the affected artery and for insertion Fig. 28.2. Guttural pouch tympany.
of a balloon catheter via a small arteriotomy incision.
All arteries can be approached by that method but if
the maxillary artery is involved an approach must also The presenting signs of the condition are variable but a
be made to the greater palatine artery just rostral to marked, often fluctuating, air-filled swelling of the parotid
the premolar arcade to insert a balloon catheter, as and ventral laryngeal areas is the usual predominating
later described. feature (Fig. 28.2), and the term “bullfrog” is sometimes
Septal fenestration or ostial enlargement in cases of used as a colloquial description because of this appearance.
guttural pouch tympany can be performed via a modified The swelling is usually more marked on one side, because
Whitehouse (laryngoplasty type) approach. However, the condition is usually unilateral. However, the naturally
ostial enlargement can be carried out far more safely deformable nature of the soft tissues of the pharynx often
via chronic catheterization of the affected pouch, or by results in some swelling on the contralateral side, which
transendoscopic laser surgery. To summarize, surgical can make identification of the affected side by clinical
approaches to the guttural pouch by whatever method examination alone more difficult. In a small but significant
should be used only when no other alternative treatment proportion of affected horses, the swelling is bilaterally
is available. symmetrical because the condition is bilateral.
In addition to the above swelling, most affected foals
make adventitious “snoring” noises, particularly when
Disorders of the Guttural Pouch suckling. In bilateral cases, severe dyspnea may be the most
Guttural pouch tympany dramatic feature. A variable degree of nasal return of
milk is commonly noted but, as with the respiratory
History and clinical signs noise, the volume of return can vary with the degree of
This is a relatively uncommon condition typically affecting nasopharyngeal distension present at that time. In the
young foals, but horses up to 1-year-old can be affected. most severely affected animals this can result in aspira-
Although Arabian foals appear to be over-represented in tion pneumonia.
the population affected by this disorder, the authors have The swelling often fluctuates during the course of 24 h,
encountered the condition in horses and ponies of many and some foals may appear to recover during the day
breeds. The condition may have a genetic component while being turned out to grass with their dam; presumably
(Blazyczek et al 2004b). Fillies appear to be much more the degree of tympany is reduced by the more frequent
commonly affected than colts but the condition is seen in swallowing efforts associated with suckling and inter-
both sexes (Blazyczek et al 2004a). mittent grazing. Another variable feature of guttural pouch
Fig. 28.3. Guttural pouch tympany. Lateral

radiographic projection of the head showing
a grossly distended, air-filled guttural pouch
extending caudally to the ventral straight
muscles of the neck.
tympany is the degree of retention of mucus within the a characteristic manner, confirming that the primary
affected pouch; in some cases, the guttural pouch becomes condition is one of tympany rather than empyema.
secondarily infected, producing an empyema. Standing lateral radiographic projections of affected
The cause of guttural pouch tympany is unknown. horses show marked enlargement of the affected pouch
Some authors believe a “ball-valve effect” of the pharyn- (Fig. 28.3). On occasions, there may be a radiodense fluid
geal ostium of the guttural pouch, perhaps related to the shadow with a typical “fluid line” (much as in a case of
mucosal rim within the cartilaginous flap of the ostium, is paranasal sinusitis). The normal air shadow of the guttural
responsible. However, the authors have never seen any pouches can extend as far caudad as the ventral tubercle
anatomical deformity of this structure. Additionally, in of the first cervical vertebra (Cook 1973), but in cases of
unilateral cases, there is no apparent anatomical difference tympany this shadow is usually massively enlarged
between the normal and affected sides, indicating a possible (Fig. 28.3). The radiological appearance of the guttural
functional basis for this disorder. Interestingly, the authors pouches produces a complex shadow because of super-
have noted the condition occasionally developing in more imposition of the smaller lateral and the larger medial
mature animals. Whilst it is impossible to be sure whether compartment of each pouch. However, it is usually possible
the problem has gone unnoticed earlier in life, it seems to distinguish between unilateral and bilateral tympany
highly improbable because the presenting signs are cases on radiological features alone.
usually obvious.
Treatment
Endoscopic and radiological features The aim of treatment is to alleviate guttural pouch
The clinical signs of guttural pouch tympany are usually distension by enlarging the pharyngeal opening of the
diagnostic; however, both endoscopic and radiological guttural pouch, or if the foal is affected unilaterally, by
confirmation are valuable. An endoscopic view of the creating communication between adjacent pouches
nasopharynx in affected foals usually reveals significant through the septum. It is also possible to create drainage
luminal obstruction caused by collapse of the naso- of air from the pouches directly into the nasopharynx,
pharyngeal roof, as a result of distension of the overlying through the pharyngeal recess (as described later). Treat-
pouch. The nasopharynx may be obviously asymmetric ment is necessary, other than in the most mildly affected
if the foal is unilaterally affected, but even in some animals, to relieve airway obstruction and/or dysphagia.
unilaterally affected foals nasopharyngeal collapse is In unilateral cases the distended pouch can be drained
surprisingly symmetrical. Inserting the endoscope into the effectively by creating a defect in the common septum.
affected guttural pouch usually causes an instant and Traditionally, this has been achieved using conventional
dramatic pouch deflation. As noted above, other than surgery via any of the surgical approaches described above,
the occasional presence of mucus or purulent material but it is most easily achieved via a modified Whitehouse
within the pouch, no structural abnormalities are observed. approach. The advent of surgical lasers has encouraged the
Unless the pouch is filled with exudate, it will deflate in use of a neodymium : yttrium–aluminum–garnet (Nd:YAG)
or diode laser to create the defect under endoscopic control

(Tate et al 1995). Whilst requiring expensive equipment
and specialist training, this method of treatment is usually
effective. However, great care must be observed when firing
the laser because there is the potential to injure vital
structures in the contralateral pouch. One foal treated
using Nd:YAG laser had effective drainage of the distended
pouch but was found dead in a pool of blood approximately
7 days postoperatively (authors’ personal observations).
Clearly a blood vessel in the lateral compartment of the
contralateral pouch had been damaged by the laser beam
but it was only when the wall of the vessel sloughed,
approximately 1 week later, that the vascular injury
became apparent.
Another reported technique using a transendoscopic
laser is to create a fistula in the pharyngeal recess to
provide drainage to one or both pouches. The authors have
no first hand experience of this technique but it is obvious
that great caution should be observed to avoid damage to
vital structures and it is desirable that a contact laser
be used. Fig. 28.4. Angiogram showing a large aneurysm (large arrow) of the
Without doubt, the simplest and safest approach to the internal carotid artery in the roof of the medial compartment. The
treatment of foals affected with guttural pouch tympany is internal carotid artery and the occipital artery have a common trunk
the prolonged catheterization of the pharyngeal ostium of (small arrow).
the pouch. A Foley catheter inserted into the pouch can be
retained by inflating the balloon with water. Retention of
the catheter within the pouch for 4–6 weeks results in less frequently, on the lateral wall of the lateral compart-
inflammation and remodeling of the overlying cartilagi- ment where the ECA and maxillary artery are located.
nous flap, leaving the ostium permanently open and the Greet (1987) reported that all 35 cases in his series had
pouch deflated. This technique can be used in unilateral or lesions over the ICA while Freeman & Ross (1987) suggest
bilateral cases. The obvious shortcoming of this simple and that at least a third of horses with epistaxis caused by GPM
safe technique is the propensity for foals or their dams to bleed from fungal erosions of the ECA and its branches.
remove the indwelling catheters. This can occur when the GPM is an opportunistic infection requiring appro-
foal or its dam pulls on, or treads on the exposed end of the priate environmental conditions or predisposing factors to
catheter. Such displacement can cause considerable owner colonize the mucous membrane of the pouch. Colles &
frustration because the catheter can only be replaced Cook (1983) showed that 18 out of 25 horses with
by a veterinarian under endoscopic guidance. The other GPM had aneurysms of some of the arteries that ran
previously described techniques may be employed if this through their guttural pouch. In some cases, angiography
technique of prolonged catheterization fails. will show aneurysmal dilatation of the diseased arteries
(Fig. 28.4), but aneurysm formation does not appear
Guttural pouch mycosis to precede or follow arterial invasion consistently and,
therefore, is not necessarily involved in the pathogenesis of
Guttural pouch mycosis (GPM) is a fungal infection that arterial infection.
invades the mucosa and, frequently, the closely associated Typically, the mycotic infection causes formation of
various neurovascular structures. Aspergillus spp, particu- a diphtheritic membrane that is closely attached to the
larly Aspergillus fumigatus and A. nidulans and Candida spp. underlying tissues and has an irregular surface elevated
are the most commonly incriminated organisms. There is above the mucosal surface. The size of the lesion may vary
no apparent age, sex, breed or geographic predisposition from less than 1 cm in diameter to one which covers most
to this disease, although it is seen most frequently in of the medial and lateral compartments (Fig. 28.5). It may
stabled horses during the warmer months of the year and be brown, yellow, green, black, or white and is composed of
is seldom recorded in warmer climates. The lesion, which is necrotic tissue, cell debris, fungal mycelia, and a variety of
usually, but not always, unilateral, is usually found at one bacteria. The fungal mycelia can be found throughout the
of two characteristic sites. The majority of lesions develop depth of the diphtheritic membrane and also invading the
on the roof of the medial compartment over the petrous adjacent tissues, including nerves and arteries (Fig. 28.6).
temporal bone and the distal segment of the ICA, or much The associated inflammation can also extend to underlying
Clinical signs of GPM

Mycotic infection of the guttural pouch usually progresses
unsuspected until invasion of neurovascular structures
results in hemorrhage or neurological deficits, although in
retrospect, the owner may occasionally report a preceding
fetid smell from the nose, resentment to handling the base
of the ear, or neck pain or stiffness.
The most common clinical sign is moderate to severe
epistaxis, caused by erosion of the ICA in most cases, or
less commonly, of the external carotid and maxillary
arteries. The first episode of severe epistaxis is often
preceded by minor hemorrhages resulting in a small
quantity of blood at one or both nostrils. If undiagnosed
and untreated, exsanguination is the probable final
outcome. It is unusual for the first episode of severe
epistaxis to be fatal but the course of the disease from first
to final hemorrhage rarely spans more than 3 weeks and
may be a matter of days.
Dysphagia as a result of damage to the motor or sensory
Fig. 28.5. Guttural pouch mycosis. Endoscopic view showing an
(or both) pharyngeal branches of IX, X and XI is the most
extensive lesion located predominantly on the roof of the medial
compartment but extending over the stylohyoid bone into the lateral frequent neuropathological sequel to GPM. The severity of
compartment. the dysphagia in GPM cases probably requires damage
to all three cranial nerves. The study by Klebe et al (2005)
showed that although the glossopharyngeal nerve (IX) has
important sensory and motor contributions to pharyngeal
bone, stimulating formation of extensive exostoses. Lesions function during swallowing, it is not essential in otherwise
on the medial wall of the medial compartment can erode normal horses. Damage to X with laryngeal hemiplegia
through the septum to affect the other pouch. Rarely, is the next most frequent cranial nerve deficit but is rarely
necrosis of the floor of the pouch can result in abscess the only sign observed by the owner. GPM may produce a
formation that can spread to the supraorbital fossa or wide range of other signs referable to the head and neck,
create a fistula through the nasopharyngeal recess into the including dorsal displacement of the soft palate, facial
nasopharynx. Dorsocaudal extension of GPM can cause paralysis, lingual hemiplegia, Horner syndrome, stiffness of
atlanto-occipital infection (Dixon & Rowlands 1981, the upper neck, reluctance to lower the head to the ground,
Walmsley 1988). parotid pain, otorrhea, epiphora, and photophobia.
Fig. 28.6. Guttural pouch mycosis. Histo-

logical section of the internal carotid artery
showing invasion of its wall by fungal hyphae;
periodic acid–Schiff stain.
A B
Fig. 28.7. Guttural pouch mycosis. (A) Bilateral epistaxis – the trunk involvement, thus incriminating the internal carotid artery as the
hemorrhage was more copious from the left nostril. (B) The lateral source of the hemorrhage.
view shows ptosis and sweating below the ear, indicating sympathetic
Diagnosis of epistaxis caused by GPM on the affected side, and distension of the overlying pouch
Whenever a horse presents with spontaneous epistaxis, the may also be evident. Blood may also be seen at the other
possibility of GPM should always be explored, because ostium (Fig. 28.8). While this could indicate a bilateral
delayed treatment may result in a fatal outcome. When problem, in most cases it is the result of aspiration of blood
severe, hemorrhage will be bilateral but it will be more during swallowing, when severe hemorrhage was occur-
copious from the nostril on the affected side (Fig. 28.7). ring, or is the result of the presence of a septal fistula.
In many cases, the bleeding will have stopped by the time Some clinicians (GBE) prefer to delay occluding the ICA
the horse receives veterinary attention or does so soon until endoscopy of the pouch is possible to confirm where
afterwards. However, if it continues unabated, steps must the fungal plaque is and thus identify which artery is
be taken to prevent exsanguination. Acepromazine may be involved. Therefore endoscopy may be delayed for 1–3 days,
administered to lower the blood pressure, but while this is because visibility is poor after a recent hemorrhage and
often successful, it is not without risk, and once it is because introduction of the endoscope may dislodge the
administered, the horse should be left quietly in its stable. blood clot and precipitate another episode of severe
Any attempt to move it may result in fatal collapse. hemorrhage. Feeding the horse off the ground or leading it
An alternative but unevaluated treatment that has been out to graze facilitates drainage of blood during this period.
used by some veterinarians is the intravenous administra- However, there is always the risk that the horse may
tion of 50 ml of 10% formalin in 2 liters of physiological hemorrhage again (even fatally) within 48–72 h, before the
saline solution. pouch has cleared of blood.
A definitive diagnosis can only be made by endoscopic In view of the risk of delaying surgery, other clinicians
examination of the interior of the pouch but this procedure will immediately proceed with arterial occlusion without
should not be performed until the bleeding has stopped, endoscopic confirmation of which artery is affected. Whilst
and the horse’s general condition has stabilized. After the the administration of intravenous hypertonic saline or a
hemorrhage has stopped, endoscopy of the nasopharynx blood transfusion may be essential with severe hypovolemia,
will usually identify which pouch is involved. A finger-like these measures risk precipitating further hemorrhage from
blood clot can usually be seen emerging from the ostium the damaged artery and some clinicians (GBE) prefer not
the week or so following surgery, severe, sometimes fatal,

hemorrhage may occur because of retrograde flow.
Although prevention of back-flow by ligation of the vessel
either side of the mycotic lesion via a modified Whitehouse
approach to the pouch has been described, poor surgical
access to, and also great difficulty in identifying, the artery,
which is obscured by the mycotic plaque or hematoma,
may result in failure to occlude the vessel, or the ligature
may incorporate the sympathetic trunk, causing Horner
syndrome (Owen 1974).
Occlusion of the distal segment with a balloon-tipped
catheter, combined with proximal ligation of the ICA, is
superior to ligation alone (Freeman & Donawick 1980a,b).
In the majority of horses, the ICA and the occipital artery
are separate, but closely related, branches of the common
carotid artery. The ICA branches off the common carotid
artery more caudally and passes beneath the occipital
artery in the direction of the base of the ear (Fig. 28.9). In
some cases, periarterial edema resulting from the more
proximal inflammatory process helps to identify the ICA.
Fig. 28.8. Guttural pouch mycosis. Endoscopic view of nasopharynx The occipital artery passes dorsally in a more caudal
showing a large blood clot at the ostium on the affected left side and direction. In a small proportion of horses, the two vessels
a small amount of previously aspirated blood at the right ostium. have a common trunk. Usually, the bifurcation of the
common trunk of the caudally directed occipital artery and
the cranially directed ICA is within the field of view, but the
bifurcation can be more cranial than the surgical site. The
to do so, unless absolutely essential. In the case of horses ICA is isolated near its origin from the common carotid
showing evidence of involvement of the sympathetic trunk artery, dissected free from the surrounding tissue, and
(i.e. ptosis and unilateral head sweating) it can be con- ligated. A small incision is made into its lumen distal
fidently assumed that the ICA is involved (Fig. 28.7). When to the ligature and a balloon-tipped catheter is inserted
evidence of Horner syndrome is absent, the decision to for a distance of 13 cm. In a 450-kg horse, this places
ligate the ICA may be taken on the basis that it is involved the balloon tip at the second flexure of the sigmoid
far more frequently than the external carotid or maxillary and, therefore, distal to the mycotic lesion (Fig. 28.9). The
arteries. Of the 125 cases reported in the literature between balloon is inflated with physiological saline solution, and
1968 and 1987, 120 involved lesions of the ICA. the catheter is secured in position by a ligature placed
distal to the site of insertion. The catheter is ligated and
Treatment options transected a few centimeters caudal to its point of entry
The natural progress of primary arterial disorders is toward into the artery, and the redundant part is buried in the
thrombosis, but this is a slow process with or without deeper tissues when the incision is closed.
antimycotic treatment. As a result of the risk of further Occasionally, the tip of the catheter may pass through
hemorrhage before thrombosis occurs, surgical occlusion the defect in the ICA causing severe hemorrhage. In such
of the affected artery is advised. None of the vessels cases, withdrawing the catheter for a short distance before
commonly involved is an end artery so the potential exists advancing it again may enable the catheter to be passed
for retrograde flow (e.g. from the circle of Willis) following along the artery beyond the defect. If the catheter cannot
ligation only, on the cardiac side of the lesion. be advanced beyond the defect, it should be inserted
through the arterial defect into the guttural pouch; then
Ligation of the internal carotid artery the balloon should be inflated and the catheter pulled back
The ICA can be exposed at its origin from the common firmly against the external wall of the artery and fixed in
carotid artery via the previously described hyovertebrotomy this position with a ligature just distal to its site of insertion
approach. This extradiverticular ligation has the advantage into the artery.
that the affected pouch is not invaded but the ligature is Embolization microcoils can also be placed in the
some distance from the lesion in the arterial wall. Such affected artery to bring about therapeutic occlusion
ligation of the ICA close to its origin may be sufficient to (Leveille et al 2000). These microcoils have been used to
prevent a fatal hemorrhage. However, if adequate throm- occlude the ICA as well as branches of the ECA. They are
bosis of the vessel does not occur beyond this site during commonly placed with the aid of dynamic fluoroscopy,
12
10
9
11
14
8
6 4
7
13
5
2 3
Fig. 28.9. Diagram of the major arteries related to the left guttural pouch and sites of balloon-catheter
occlusion. 1 = common carotid artery; 2 = external carotid artery; 3 = internal carotid artery (ICA);
4 = occipital artery; 5 = linguofacial trunk; 6 = maxillary artery; 7 = caudoauricular artery; 8 = superficial
temporal artery; 9 = transverse facial artery; 10 = external ophthalmic artery; 11 = caudal alar foramen;
12 = balloon located at sigmoid flexure of ICA; 13 = balloon located in the major palatine artery
immediately caudal to caudal alar foramen; 14 = balloon inserted into the transverse facial artery at arrow
and directed into the ECA, where it is inflated close to the floor of the guttural pouch. Redrawn from
Smith and Barber, 1984, Caron et al, 1987 and Freeman, 1992, with permission.
although they can be positioned using a technique similar sterile environment of the guttural pouch, the passage of a
to that used to place a balloon-tipped catheter. Contrast catheter, contrast material or lavage fluid past the lesion
arteriography will confirm correct placement of the has the potential to cause thrombi, bacteria or fungi to flow
microcoils and occlusion of the intended artery, but will toward the brain. Ragle (2003) reported that one horse
add expense and time to the procedure. out of more than 30 treated using microcoil techniques
Although complication rates as high as 46% have been developed neurological signs 9 days after surgery because
reported with use of long indwelling catheters, most of a brain abscess caused by Streptococcus equi. At other
complications, such as incisional infection or catheter clinics, horses have died from brain infarction following
breakage, are not life-threatening. Because an infected arterial occlusion, but this sequel has also been recorded in
artery with a transmural lesion is in contact with the non- untreated horses with GPM.
A B
Fig. 28.10. Guttural pouch mycosis. (A) Method of insufflating Higginson’s syringe. (B) Endoscopic view immediately after insufflation
nystatin powder into the guttural pouch using a Neilson’s catheter and showing the powder dispersed throughout the pouch.
Aspergillus fumigatus and A. nidulans are opportunistic, guttural pouch. Successful entry of the catheter into the
angiotrophic pathogens and require damage to the mucosal pouch leaves the end of the catheter at the nostril, whereas
barrier to permit binding to fibrinogen on the mucosal if the catheter has not entered the pouch, the tip will
surfaces. Resolution of mycotic plaques can occur after engage the back of the pharynx leaving several centimeters
arterial thrombosis with no other treatment, regardless of the catheter protruding from the nostril. Once the end
of whether the thrombosis occurs as the result of surgery of the catheter is in place in the guttural pouch, the anti-
or naturally. Nevertheless, one author (GBE) considers mycotic agent is placed in the end of the enema syringe
that topical application of antimycotic medication, in from which the plastic tip has been removed. The enema
conjunction with arterial occlusion, is of considerable syringe is attached to the catheter, and the balloon of the
benefit in accelerating the resolution of infection, and in syringe is compressed sharply twice. This results in a cloud
preventing the development of additional neurological of antifungal powder leaving the two openings at the end of
disorders, particularly when the lesion is extensive, whilst the Neilson’s catheter to effectively coat the whole of the
the other author (TWG) does not. interior of the guttural pouch (Fig. 28.10). The insufflation
Difficulty in applying antimycotic agents (e.g. nystatin, process may be repeated by detaching the Higginson’s
miconazole, or ketoconazole) to the lesion on the roof of syringe and refilling it with the antifungal agent. The
the medial compartment of the pouch has been a major procedure, which is well tolerated by the horse, is repeated
reason for topical therapy not being used more frequently. daily for 7–10 days.
However, insufflation of one of these drugs in powder form If a mycotic lesion in the lateral wall of the lateral pouch
via a Neilson’s catheter, using a Higginson’s enema syringe, has led to epistaxis, the ECA and its branches must be
coats the whole of the lining of the pouch with the drug. occluded. Although the ECA can be ligated distal to the
The catheter is placed along the side of the horse’s face origin of the linguofacial trunk through a hyovertebrotomy
with the tip level with the lateral canthus of the eye and is approach, this procedure is generally unsuccessful because
then held between finger and thumb at the nostril. It the external carotid and maxillary arteries have numerous
is now passed along the ventral nasal meatus, with the collateral channels that allow retrograde flow to the
curved tip directed ventrally until the finger and thumb perforated segment.
holding it are at the nostril. The catheter is then rotated The palatine artery, which is a large continuation of the
through 90°, so that the curved tip is in contact with the maxillary artery, is the most likely source of retrograde
lateral wall, and it is advanced through the ostium into the flow to the ECA and its branches. This artery can be
occluded by inserting a 6-F Fogarty venous thrombectomy

catheter into its lumen 3 cm caudomedial to the upper
corner incisor tooth (Triadan 103, 203) (Freeman et al
1989). The catheter is passed retrograde for approximately
40 cm in a 450-kg horse. The balloon is partially inflated
with saline, and the catheter is gently retracted until some
resistance is felt, at which point it is assumed that the
balloon is wedged at the caudal alar foramen. It is subse-
quently fully inflated with saline. At this site, the balloon
should obstruct all retrograde flow to the maxillary artery.
Normograde flow can be prevented either by ligation
of the ECA distal to the origin of the linguofacial trunk,
which requires deep dissection, or by inserting a balloon-tip
catheter through the transverse facial artery (Freeman et al
1989). To perform the latter procedure, a catheter is
inserted into the transverse facial artery 3 cm rostral to
the articular tubercle of the temporal bone and advanced
in retrograde fashion until its tip enters the ECA, which
is approximately 12 cm from the arteriotomy site in a
450-kg horse. The balloon is inflated with saline and
the redundant ends of the catheters in the transverse Fig. 28.11. Guttural pouch mycosis. Endoscopic view of nasopharynx
showing presence of food material as a result of pharyngeal
facial and palatine arteries are taped and incorporated
hemiplegia, and left recurrent laryngeal neuropathy.
in a stockinget hood. The catheters are removed after
7–10 days (Fig. 28.9).
Management of horses with mation at the site of the mycotic plaque. Occasionally, a
neurological damage black focus in a mycotic plaque overlying the ICA may be
The second most common clinical sign of GPM is seen, indicating that slight hemorrhage has occurred. In
dysphagia manifested in its severe form as discharge of these cases arterial ligation should be performed because
masticated food, saliva, and water from the nostrils and is of the risk of a severe hemorrhage before the mycotic
caused by mycotic damage of the pharyngeal branches of infection has resolved.
the glossopharyngeal and vagus nerves. The glossopharyn- Horses with neurological deficits caused by GPM are
geal nerve is vulnerable because of its prominent position treated by topical treatment of the lesion with nystatin as
in the fold of mucous membrane that contains the other described. Although Church et al (1986) suggested that
cranial nerves and the ICA. the prognosis for horses with this complication is hopeless,
On endoscopy, food material can be seen in the nasal Cook (1968) reported that seven of 17 affected horses
cavities or nasopharynx, and there may also be laryn- recovered from dysphagia, and Lane (1989) reported
geal hemiplegia (confirming involvement of the vagus) recovery of five of 17 dysphagic horses following success-
(Fig. 28.11). Persistent dorsal displacement of the soft ful treatment of the mycotic lesion. The period from
palate may also be noted. Collapse of the roof of the naso- onset of dysphagia to resolution of coughing and nasal
pharynx may be evident in a proportion of horses with reflux of ingesta ranged from 3 to 14 months. Dysphagia is
GPM. Failure of the guttural pouch ostium on the affected the most difficult aspect of GPM to manage and requires
side to open when swallowing is stimulated by touching the considerable patience and vigorous supportive therapy to
epiglottis is more convincing evidence of neuromuscular meet the nutritional requirements of affected horses.
dysfunction of the nasopharynx. Radiological assessment It is not clear from the literature how often horses with
of deglutition by fluorography or even by simple contrast laryngeal hemiplegia regain normal function. Cook (1987)
radiography of the pharynx can also confirm the diagnosis considered that this type of laryngeal hemiplegia was
of pharyngeal dysphagia. invariably permanent, but Greet (1987) described a single
Examination of the interior of the pouch will reveal case that recovered laryngeal motility spontaneously.
mycotic plaques that are often extensive, extending from Horses that fail to recover laryngeal motility can be
the roof of the medial compartment and obscuring the surgically treated as if they had the idiopathic form of
nerves. In the authors’ experience, it is rare for a horse to laryngeal paralysis. Some horses with Horner syndrome
exhibit both dysphagia and epistaxis. This suggests that the and facial paralysis may slowly regain normal function of
ICA may become occluded as the result of chronic inflam- the affected nerves.
LN
A B
Fig. 28.12. Endoscopic images of a horse with strangles that is suffering from upper airway obstruction
because of bilateral collapse of the nasopharynx. (A) An abscessed lymph node (LN) on the floor of a
guttural pouch that is discharging pus, (B) the depression on the nasopharyngeal roof caused by these
abscessed lymph nodes. (Figure courtesy of P.M. Dixon.)
Guttural pouch empyema in nature, swelling in the parotid region is absent. However
if dysfunction of the guttural pouch drainage occurs, the
Because they share a common respiratory mucosa with the purulent material becomes thicker and in chronic cases
rest of the airway, inflammation of the guttural pouch can develop the consistency of cottage cheese. Drainage of
mucosa accompanies most upper respiratory tract bacterial this viscous material into the nasopharynx is poor, and
and viral infections. However, the normal mucosal defense accumulation of exudate may eventually result in gross
mechanism and mucociliary clearance mechanism that distension of the affected pouch, displacing air from the
serve to drain the guttural pouches usually allow rapid normal pouch and causing compression of the roof of the
resolution of this inflammation. Failure of mucus and/or nasopharynx, and even severe obstructive dyspnea and
pus within the pouches to drain satisfactorily leads to dysphagia. If dyspnea is severe, the head and neck are
guttural pouch empyema (GPE). Empyema of the guttural extended to reduce resistance to airflow (Fig. 28.13), and
pouches can affect horses of any age but usually occurs in although a harsh inspiratory noise may be audible, very
young animals. Upper respiratory infections, especially little movement of air can be felt at the nostrils. So-called
those caused by Streptococcus equi, and rupture of abscessed chondroids, a longer term sequel to inspissation, are ovoid
retropharyngeal lymph nodes into the guttural pouch are masses of variable size caused by compression of the pus
the most commonly implicated causes of GPE (Fig. 28.12). within the guttural pouch by head movement.
Topical guttural pouch treatment with irritant drugs,
fracture of the stylohyoid bone, and congenital stenosis of Diagnosis
the pharyngeal orifice are much less frequent causes. Endoscopy will often show thick, purulent material at
the pharyngeal ostium of the affected pouch or pouches.
Clinical signs In severe cases, the nasopharyngeal lumen is almost
The clinical signs of GPE include intermittent purulent to completely obliterated because of depression of its roof by
mucopurulent nasal discharge, parotid swelling and pain, the grossly distended guttural pouch (Fig. 28.14). Any
extended head carriage, and difficulty in swallowing and attempt at passing the endoscope into the pouch is usually
breathing. thwarted by the inspissated material.
The most common clinical sign of GPE is a muco- Lateral radiographic images of the head will confirm the
purulent nasal discharge, often persisting after the other loss of air contrast with the guttural pouch. If the purulent
signs of the upper respiratory tract infection have resolved. material is still fluid, an air–fluid interface will be evident,
Usually only one pouch is involved, which results in an while in cases with inspissated pus the guttural pouch will
asymmetric nasal discharge, with the heavier discharge appear as a large, radiodense area with little or no gas
emanating from the ipsilateral naris. The discharge may be present at its apex. The degree of pharyngeal obstruction
intermittent and usually increases when the horse lowers can best be evaluated, and is greatest, if the radiograph is
its head. External pressure on the parotid area when the taken during inspiration, when subatmospheric pressure
head is lowered frequently results in a marked increase in produces further collapse of the airway. Chondroids can
the volume of discharge. The pouches can expand a great usually be recognized as marble-like densities within the
deal before enlargement can be seen externally. In the pouch, aided by the contrast provided by the air present
acute stages, when the mucopurulent material is quite fluid above them (Fig. 28.15). Distension of the parotid region
Fig. 28.13. Typical posture adopted by a

horse with airway obstruction caused by
severe guttural pouch distension.
and compression of the pharynx are often less marked in for example because abscessed retropharyngeal lymph
horses with chondroids compared to horses with GPE or nodes are present in the floor of the pouch or the purulent
abscessed retropharyngeal lymph nodes. material is too thick to drain freely, daily irrigation of the
pouch with 500 ml of physiological saline or even tap
Treatment of horses affected with GPE water is indicated. This procedure is facilitated by placing
Non-surgical treatment an indwelling Foley catheter or a coiled catheter created
In patients with acute GPE, treatment with systemic from a 10-French polypropylene male dog catheter (White
antibiotics coupled with feeding off the floor to encourage & Williamson 1987) into the affected pouch(es). The catheter
natural drainage of the guttural pouches often brings is threaded with 18-gauge wire and the end is coiled
about resolution within 10–14 days. There is some con- around a 5-ml syringe case four times and all are then
troversy concerning the administration of antibiotics to placed in boiling water for 10 min, then cold water for a
horses with strangles. If this treatment is unsuccessful, further 10 min to obtain a permanent spiral configuration.
A B
Fig. 28.14. Guttural pouch empyema. (A) Lateral radiographic complete obstruction of the nasopharynx. (B) Endoscopic view of the
projection showing opacity of the guttural pouch and almost nasopharynx in the same horse.
Fig. 28.15. Guttural pouch empyema. Lateral

radiograph of the guttural pouch showing a
large number of chondroids.
The catheter is straightened with the wire still in place and

placed into the guttural pouch. Removal of the wire causes
the end of the catheter to resume its spiral shape and it is
then retained within the pouch.
This lavage technique has been used to remove chon-
droids, when the chondroids are small and few in number
(Adkins et al 1997). Daily lavage is necessary to bring
about dissolution of the aggregated masses of purulent
material. Care should be taken to avoid using hydrogen
peroxide or antiseptic solutions because they are irritant
and can possibly damage the cranial nerves but the addi-
tion of acetyl cysteine can be beneficial. Transendoscopic
removal of chondroids using a snare has been reported, but
is difficult and very time-consuming unless small numbers
of chondroids are present.
Surgical treatment of horses affected with GPE

Horses with a large number of chondroids or a large
amount of inspissated pus require surgical evacuation of
the pouch, and those showing severe dyspnea as a result of
pharyngeal compression should be treated promptly. No
attempt should be made to administer a general anesthetic
until a temporary tracheotomy tube has been inserted. The
authors insert a 14-mm, cuffed endotracheal tube in the
mid-cervical trachea, just before induction of anesthesia
(Fig. 28.16), and use this tube to administer the gaseous
anesthetic. If inserted higher in the trachea, the tube tends
to encroach on the surgical site.
The objective of surgical treatment is the complete Fig. 28.16. Guttural pouch empyema. Endotracheal tube placed in the
removal of all the exudate. Retention of semi-solid material trachea prior to induction of anesthesia.
or a single chondroid may predispose the horse to a recur- avulsion fracture of the basisphenoid bone where these
rence of GPE, and will probably result in the horse being a muscles attach to it. Rearing over backwards and trauma
carrier of Streptococcus equi subsp. equi in those cases where to the base of the skull are often associated with rupture of
this is the causal organism. Several surgical approaches these two muscles. On endoscopic examination blood may
have been employed, but the authors consider the modified be seen emerging from the ostia of one or both guttural
Whitehouse approach, described earlier, to be the most pouches and the guttural pouch may be blood-filled. It is
effective. When the pouch is very distended, there is little important to inspect both the rectus capitis muscles
difficulty in identifying it in the depth of the incision. endoscopically (if visible) and the occipital and basisphenoid
If the pouch is less distended, introducing air into it via bones radiographically to distinguish this condition
an endoscope or an enema syringe attached to a Neilson’s from GPM.
catheter can be helpful. Once the pouch is entered, its
contents are carefully removed. A spoon is often useful for Temporohyoid osteoarthropathy
this purpose, particularly for removal of chondroids. Gentle
handling of the pouch wall is imperative to avoid iatrogenic Temporohyoid osteoarthropathy is a disorder that can
neurovascular injury. Inspissated material can be removed result in acute onset of vestibular disease, which is often
by copious lavage and suction. The pouch should be exam- accompanied by facial paralysis. Other clinical signs include
ined very carefully to ensure that no material, particularly head shaking and pain associated with palpation of the
chondroids, is left behind. base of the ear. Endoscopic examination of the guttural
An indwelling Foley catheter can be inserted via the pouch is useful because osseous proliferation or healing
surgical incision to allow daily lavage of the pouch. After it fractures of the proximal third of the stylohyoid bone often
has been removed, the surgical wound is left open to drain accompanies the disease. Temporohyoid osteoarthropathy
and heal by second intention. was thought to originate from a low-grade otitis media,
Endoscopic examination of the pouch after treatment which then progressed to an osteitis of the tympanic bulla
of empyema reveals thickening of the mucous mem- and temporohyoid joint (Power et al 1983, Blythe & Watrous
brane lining that tends to have a dull, yellowish appear- 1997), but otitis is now not considered to be present in
ance; this may obscure the underlying vessels and nerves, most such cases.
which are normally clearly visible. After the infection is Vestibular disease and facial nerve (all branches) paralysis
resolved, the mucous membrane will regain its normal occur when osseous proliferation impinges on the VII
appearance and any dysphagia (that was probably (facial) and VIII (vestibulocochlear) nerves, or if the
mechanical rather than neurological) will soon resolve. petrous temporal bone fractures, as described below. The
Very rarely, some degree of dysphagia will remain that may spontaneous development of cranial nerve VII and/or VIII
be neurological in origin. dysfunction in horses should prompt an examination of
the guttural pouch. Progression of the disease leads to
ankylosis of the temporohyoid joint. With the loss of
Chronic diverticulitis mobility of the joint, the normal forces generated from
movement of the tongue and larynx and transmitted
As noted earlier in this chapter, chronic inflammation of
through the bones of the hyoid apparatus can cause an
the guttural pouch mucosa is common in horses with
acute stress fracture of the petrous temporal bone, or, less
chronic GPE, but similarly thickened mucosa may also be
frequently, a mid-shaft fracture of the stylohyoid bone that
encountered even though the horse has no history to
will also be endoscopically evident in the guttural pouch.
suggest prior streptococcal respiratory infection. Cases of
Blythe et al (1994) and Blythe and Watrous (1997)
chronic diverticulitis without the presence of empyema
described a technique for partial resection of the stylohyoid
may present as a series of neuropathies where a combi-
bone that created a pseudoarthrosis to prevent the sequelae
nation of deficits of the glossopharyngeal, vagus, facial,
of petrous temporal bone fracture. Following regrowth of
spinal accessory, and sympathetic nerves may be present.
the stylohyoid and recurrence of symptoms, Pease et al
Endoscopy reveals a similar roughened thickening of the
(2004) developed an alternative technique of ceratro-
guttural pouch lining, suggesting that the nerve pathways
hyoidectomy, which they considered to be a safer, easier,
are damaged by extension of the inflammatory process
and more permanent procedure.
within the wall of the pouch.
Otitis media/interna caused by bacterial infection is not
commonly encountered in horses, and fungal infection is
Other disorders of the guttural pouch even rarer (Firth 1977). Although treatment of horses
with otitis media/interna caused by bacterial infection with
Guttural pouch hemorrhage can also be associated with antimicrobial therapy is reported to be successful (Mayhew
rupture of the rectus capitis ventralis and longus capitus 1989), there are no reports of successful treatment of
muscles (i.e. the ventral straight muscles of the head) or fungal-induced otitis media (Newton & Knottenbelt 1999).
Baptiste KE, Naylor JM, Bailey J et al 2000 A function for

guttural pouches in the horse. Nature 403: 382–383
Blazyczek I, Hamann H, Deegan E et al 2004a Retrospective
analysis of 50 cases of guttural pouch tympany. Veterinary
Record 154: 261–264
Blazyczek I, Hamann H, Ohnesorge B et al 2004b Inheritance
of guttural pouch tympany in the Arabian horses.
Journal of Heredity 95: 195–199
Blythe LL, Watrous BJ 1997 Temporohyoid osteoarthropathy
(middle ear disease) In: Robinson NE (editor) Current
Therapy in Equine Medicine, 4th edn. Saunders,
Blythe LL, Watrous BJ, Shires GM et al 1994 Prophylactic
partial styloidostectomy for horses with osteoarthropathy
of the temporohyoid joint. Journal of Equine Veterinary
Science 14: 32–37
Caron JP, Fretz PD, Bailey JV et al 1987 Balloon tipped catheter
occlusion for prevention of haemorrhage caused by
GPM: 13 cases (1982–1985). Journal of the American
Church S, Wyn-Jones G, Parks AH et al 1986 Treatment
Fig. 28.17. Endoscopic view of a guttural pouch with melanomas. of guttural pouch mycosis. Equine Veterinary Journal
18: 362–365
Colles CM, Cook WR 1983 Carotid and cerebral angiography
Neoplasia in the horse. Veterinary Record 113: 483–489
Cook WR 1968 The clinical features of guttural pouch
Neoplasia of the guttural pouch is uncommon. Reported mycosis in the horse. Veterinary Record 83: 336–345
tumors include parotid melanoma, squamous cell carci- Cook WR 1973 The auditory tube diverticulum (guttural
pouch) in the horse: its radiographic examination. Journal
noma (Trigo & Nickels 1981, Moulton 1990), round cell of American Veterinary Radiology Society 14: 51–71
sarcoma (Cook 1973), fibroma (Merriam 1972), heman- Cook WR 1987 Diseases of the auditory tube diverticulum
gioma (Greene & O’Connor 1986), and hemangiosarcoma (guttural pouch). In: Robinson NE (editor) Current Therapy
(Raker 1982). in Equine Medicine, 2nd edn. Saunders, Philadelphia,
Clinical signs of neoplasia include non-specific signs pp.612–618
Dixon PM, Rowlands AC 1981 Atlanto-occipital joint infection
of guttural pouch disease. Endoscopy may reveal dorsal associated with guttural pouch mycosis in a horse.
pharyngeal compression, mucopurulent discharge, drainage Equine Veterinary Journal 13: 260–262
from the pharyngeal ostium, or single or multiple masses Fintl C, Dixon PM 2001 A review of five cases of parotid
within the pouch. melanoma in the horse. Equine Veterinary Education
Melanotic lesions are often present in the guttural 13: 17–24
Firth EC 1977 Vestibular disease and its relationship to facial
pouches of gray horses (Fintl & Dixon 2001), more par- paralysis in the horse; a clinical study of 7 cases.
ticularly in the lateral compartment (Fig. 28.17). At Australian Veterinary Journal 53: 560–565
this site two distinct types of lesion can be identified. Freeman DE 1992 Guttural pouches In: Auer JA (editor)
The first are benign-looking, small, flat, irregular patches Equine Surgery. Saunders, Philadelphia, pp.480–488
of black pigment, often in large numbers that are located Freeman DE, Donawick WJ 1980a Occlusion of the inter-
nal carotid artery in the horse by means of a balloon
on the walls of the major vessels. These are probably not tipped catheter: evaluation of a method designed to
tumors but represent abnormal accumulations of normal prevent epistaxis caused by guttural pouch mycosis.
melanocytes (i.e. a hamartoma). Larger, well-defined tumor- Journal of the American Veterinary Medical Association
like masses of black tissue represent a more serious and an 176: 232–235
obviously neoplastic disorder (Knottenbelt 1994). These Freeman DE, Donawick WJ 1980b Occlusion of the internal
carotid artery in the horse by means of a balloon tipped
masses are often located high in the lateral compartment. catheter. Clinical use of a method to prevent epistaxis
Their significance is equivocal, but extension from the caused by GPM. Journal of the American Veterinary
pouch to the parotid lymph nodes and lymphoid tissue of Medical Association 176: 236–240
the salivary gland is possibly responsible for the externally Freeman DE, Ross MW, Donawick WJ, Hamir AN 1989
obvious form of the disease. Alternatively, spread may Occlusion of the external carotid and maxillary arteries
in the horse to prevent haemorrhage from guttural
occur in the opposite direction (Fintl & Dixon 2001). pouch mycosis. Veterinary Surgery 18: 39
Greene HJ, O’Connor JP 1986 Haemangioma of the guttural
REFERENCES pouch of a 16 year old Thoroughbred mare. Clinical and
pathological findings. Veterinary Record 118: 445
Adkins AR, Yovich JV, Colborne CM 1997 Non-surgical Greet TRC 1987 Outcome of treatment in 35 cases of gut-
treatment of chondroids of the guttural pouch of the tural pouch mycosis. Equine Veterinary Journal 19:
horse. Australian Veterinary Journal 75: 332–333 483–487
Klebe EA, Holcombe SJ, Rosenstein D et al 2005 The effect of osteoarthropathy and an alternative surgical technique
bilateral glasso-pharyngeal nerve anaesthesia on swallow- in 5 cases. Equine Veterinary Journal 36: 546–550
ing in horses. Equine Veterinary Journal 37: 65–70 Pirie M, Pirie HM, Wright NG 1990 A scanning electron
Knottenbelt DC 1994 Conditions of the respiratory tract – microscopic study of the equine upper respiratory tract.
neoplastic disorders. In: Knottenbelt DC, Pascoe RR (editors) Equine Veterinary Journal 22: 333–337
A Colour Atlas of Diseases and Disorders of the Horse. Power HT, Watrous BJ, deLaHunta A 1983 Facial and vesti-
Mosby Wolfe, London, p.155 bulocochlear nerve disease in six horses. Journal of the
Lane JG 1989 The management of guttural pouch mycosis. American Veterinary Medical Association 183: 1076–1080
Equine Veterinary Journal 21: 321–324 Ragle CA 2003 Guttural pouch disease. In: Robinson NE
Leveille R, Hardy J, Robertson JT et al 2000 Transarterial coil (editor) Current Therapy in Equine Medicine, 5th edn.
embolisation of the internal and external carotid and Saunders, Philadelphia, pp.386–390
maxillary arteries for prevention of haemorrhage from Raker CW 1982 The nasopharynx. In: Mannsmann RA,
guttural pouch mycosis in horses. Veterinary Surgery McAllister ES (editors) Equine Medicine and Surgery. CA
29: 389–397 American Veterinary Publications, Santa Barbara, p.756
Mayhew IG 1989 Head tilt, circling, nystagmus and other Sisson S 1975 Sense organs and common integument – Ear.
signs of vestibular abnormalities. Large Animal Neurology: In: Getty R, Sisson S, Grossman (editors) The Anatomy
A Handbook for Veterinary Clinicians. Lea and Febiger, of Domestic Animals, 5th edn. Saunders, Philadelphia,
Philadelphia, pp.179–192 pp.723–725
Merriam JG 1972 Guttural pouch fibroma in a mare. Smith DM, Barber SM 1984 Guttural pouch haemorrhage
Journal of the American Veterinary Medical Association associated with lesions of the maxillary artery in two
161: 487 horses. Canadian Veterinary Journal 25: 239
Moulton JE 1990 Tumours of the respiratory system In: Tate LP, Blikslager AT, Little ED 1995 Transendoscopic laser
Moulton JE (editor) Tumours in Domestic Animals, 3rd edn. treatment of guttural pouch tympany in eight foals.
University of California Press, Los Angeles, p.318 Veterinary Surgery 24: 367–372
Newton SA, Knottenbelt DC 1999 Vestibular disease in Trigo RJ, Nickels FA 1981 Squamous cell carcinoma of a horse’s
two horses; a case of mycotic otitis media and a case guttural pouch. Modern Veterinary Practice 62: 456
of temporohyoid osteoarthropathy. Veterinary Record Walmsley, JP 1988 A case of atlanto-occipital arthropathy
145: 142–144 following guttural pouch mycosis in the horse. The use of
Owen R 1974 Epistaxis prevented by ligation of the internal radioisotope bone scanning as an aid to diagnosis. Equine
carotid artery in the guttural pouch. Equine Veterinary Veterinary Journal 20: 219–220
Journal 6: 143–149 White SL, Williamson L 1987 How to make a retention catheter
Pease AP, van Bierliet J, Dykes NL et al 2004 Complications of to treat guttural pouch empyema. Veterinary Medicine
partial stylohyoidectomy for treatment of temporohyoid 82: 76–82
Disorders of the Nasopharynx
and Soft Palate
29 Susan J Holcombe and Norm G Ducharme
Introduction Dorsal pharyngeal muscles

The physiologically distinct functions of breathing, degluti- The actions of the dorsal pharyngeal constricting muscles
tion, and vocalization in the horse rely on the carefully and the stylopharyngeus muscle are responsible for
orchestrated action and anatomic arrangement of the stiffening and dilating the nasopharynx (Kuna et al 1999,
nasopharynx, the common conduit through which both air Feroah et al 2000, Kuna 2001). The middle pharyngeal
and ingesta pass. Simply conceived, it is a muscular tube constrictor (hyopharyngeus muscle) and superior pharyn-
suspended rostrally from the pterygoid and palatine bones, geal constrictors (palatopharyngeus and pterygopharyngeus
and anchored caudally on portions of the hyoid apparatus muscles) form the dorsal and caudolateral pharyngeal
and the laryngeal cartilages. Its main body lacks the walls (Fig. 29.1) (Kuna et al 1999, Feroah et al 2000). The
structural support of bones or cartilage. During strenuous contraction and shortening of these muscles form a sphinc-
exercise, airflow velocities and airway pressures fluctuate ter, which moves the food bolus caudally into the esophagus
tremendously, and appropriate sensory and motor activity during swallowing. During breathing, these muscles have
must occur to maintain airway patency. Failure of these tonic and phasic expiratory activities that help to support
anatomic structures or neuromuscular activities results in the nasopharynx (Kuna et al 1999, Kuna 2001).
a constellation of clinical disorders, ranging from dysphagia The major dilating muscle of the dorsal nasopharynx
to exercise intolerance. is the stylopharyngeus muscle (Feroah et al 2000). This
muscle originates on the axial aspect of the distal por-
tion of the stylohyoid bone and courses rostroventrally to
Anatomy of the Nasopharynx
ramify into the wall of the dorsal nasopharynx, by passing
While the nasopharynx may be simply conceptualized as between the pterygopharyngeus and palatopharyngeus
a muscular tube, it is an anatomically and functionally muscles (Fig. 29.2). Contraction of the stylopharyngeus
complicated structure composed of multiple muscle groups, muscles retracts the pharyngeal wall dorsally, to receive a
innervated by several cranial nerves, and subject to the food bolus into the pharynx during swallowing (Sisson
activity, anatomy, and the effects of pathological changes 1975a). In a similar manner during breathing, contrac-
of surrounding structures. At the microscopic level, the tion of the stylopharyngeus muscle retracts the nasopha-
nasopharyngeal mucosa is comprised of a pseudostrati- ryngeal wall dorsally, thereby supporting the dorsal wall
fied columnar epithelium interspersed with goblet cells, of the nasopharynx and preventing dynamic collapse of
lymphoid follicles and sensory receptors of the glosso- this structure during inspiration (Fig. 29.3) (Feroah et al
pharyngeal (CN IX) and trigeminal (CN V) cranial nerves. 2001). Experimentally creating stylopharyngeus muscle
These are principally tactile receptors important for air- dysfunction causes collapse of the dorsal nasopharynx
way protection, stimulating the swallowing (gag) reflex, and inspiratory obstruction in exercising horses (Tessier
and for airflow detection and stimulating airway dilation et al 2004).
during inhalation.
The muscular conduit itself comprises groups of con- Soft palate
strictor muscles: i.e. the superior pharyngeal constrictors
(palatopharyngeus and pterygopharyngeus), the middle The nasopharynx is demarcated by the soft palate, which
pharyngeal constrictor (hyopharyngeus), and the caudal completely divides the pharynx into nasal and oral com-
pharyngeal constrictors (thyropharyngeus and cricopha- partments in the horse. Because the horse is an obligate
ryngeus). The stability of this muscular conduit depends on nasal breather, it is critically important that the soft palate
the appropriate conformation and function being present in remains ventral to the epiglottis (except during swallow-
the surrounding tissue structures. Each of these structures ing) to allow unimpeded nasal breathing. The soft palate
will be considered in detail. extends caudally from the hard palate to the base of the
437
438 29 Disorders of the Nasopharynx and Soft Palate
Fig. 29.1. Illustration of the lateral projection of a horse’s

head depicting the nasopharyngeal constricting and dilating
muscles. Cp = cricopharyngeus muscle; Pp = palatopha-
ryngeus muscle; Ptp = pterygopharyngeus muscle; SH =
stylohyoid bone; Sp = stylopharyngeus muscle; Thop =
thyropharyngeus muscle.
SH
Styloglossus
muscle Sp.
Thop
Ptp Cp
Pp
Hyopharyngeus
muscle
Geniohyoid
muscle Sternohyoid
muscle
Genioglossus
muscle
SH
SP
Fig. 29.3. Endoscopic image of the nasopharynx of a horse during

inhalation showing the depressions (arrows) that form in the dorsal
Fig. 29.2. Endoscopic image of the left guttural pouch showing the nasopharyngeal wall as both of the stylopharyngeus muscles contract,
origin of the stylopharyngeus muscle (SP) on the stylohyoid bone (SH) lifting the nasopharyngeal wall dorsally. This is especially evident
within the medial compartment. immediately after swallowing.
29 Disorders of the Nasopharynx and Soft Palate 439
Tensor veli palatini

muscle
Hamulus
Levator veli palatini

muscle
Nasal mucosa
Palatine aponeurosis
Oral mucosa
Glandular layer
Palatinus
muscle
Fig. 29.4. Illustration of the cross-sectional anatomy of the soft palate.
larynx and consists of the oral mucous membrane, which

contains ductile openings of the palatine glands, the
palatine glands, the palatine aponeurosis, palatinus and
palatopharyngeus muscles, and the nasopharyngeal
mucous membrane (Fig. 29.4) (Sisson 1975a). The caudal
free margin of the soft palate continues dorsally, on either
side of the larynx, forming the lateral pillars of the soft
palate. These pillars unite dorsal to the larynx, forming P
the posterior pillar of the soft palate (the palatopharyn-
geal arch) (Fig. 29.5).
The position of the soft palate is determined by the
coordinated activity of groups of antagonistic muscles,
which include the levator veli palatini, tensor veli palatini,
palatinus, and palatopharyngeus muscles (Fig. 29.4) (Sisson LP
1975a, Kuehn et al 1982). The levator veli palatini muscle
acts to elevate the soft palate during swallowing and
vocalization. The action of the levator veli palatini muscle
can be seen during endoscopic examination of the upper
airway when the gag reflex is stimulated. A “sling” forms
within the nasopharynx as the nasopharynx contracts into
a sphincter (Fig. 29.6). The tensor veli palatini is a flat,
CFM
fusiform muscle that travels with the levator veli palatini
muscle along the lateral walls of the nasopharynx and the Fig. 29.5. Endoscopic image of the nasopharynx of a horse while the
lateral lamina of the guttural pouch (Sisson 1975a). Its soft palate is displaced. Note the caudal free margin (CFM) of the soft
tendon is reflected around the hamulus of the pterygoid palate, the lateral pillars (LP) and the palatopharyngeal arch (P).
NS
SP
Fig. 29.6. Endoscopic image of the nasopharynx of a horse as the

Fig. 29.7. Endoscopic image of the rostral portion of the nasopharynx
levator veli palatini muscles are contracting (arrow). Notice the “sling”
showing the action of the tensor veli palatini muscle tensing and
that forms within the nasopharynx.
depressing the rostral portion of the soft palate (SP). NS = nasal
septum.
bone, where it is lubricated by a bursa. The tendon then

ramifies in the palatine aponeurosis (Sisson 1975a).
Contraction of this muscle tenses the palatine aponeurosis
and, therefore, the rostral portion of the soft palate, and so
depresses this portion of the soft palate toward the tongue
(Fig. 29.7) (Kuehn et al 1982, Sisson 1975a). Contraction
of the tensor veli palatini muscle also aids in opening
the pharyngeal opening of the guttural pouch (Fig. 29.8) R
(Baptiste 1997).
The palatinus muscle (uvula retractor muscle) consists L
of two fusiform muscles that lie on either side of midline, in
the soft palate beneath the nasopharyngeal mucosa,
extending caudally from the hard palate (Sisson 1975a).
The muscles attach to the caudal aspect of the palatine
aponeurosis and terminate near the caudal free margin of
the soft palate. A small muscle bundle arising from the
lateral aspect of each muscle continues a short distance
caudodorsally into the palatopharyngeal arch. Contraction
of the palatinus muscle shortens the soft palate (Sisson
1975a, Kuehn et al 1982). SP
The palatopharyngeus muscle originates from the
palatine aponeurosis and the lateral border of the palatinus Fig. 29.8. Endoscopic image of the nasopharynx during swallowing
muscle (Sisson 1975a). It travels caudally along the lateral showing opening of the right (R) and left (L) ostia of the guttural
pouches, as a result of contraction of the tensor veli palatini muscles.
wall of the nasopharynx to the pharyngeal raphe, forming
SP = soft palate.
part of the superior constrictor muscle group. Contraction
of this muscle shortens the soft palate and draws the
larynx and esophagus toward the base of the tongue. Tongue
Dysfunction of the palatinus and palatopharyngeus mus-
cles has been implicated in the pathogenesis of intermittent The tongue is integral to positioning the hyoid apparatus,
dorsal displacement of the soft palate and dysphagia in one of the key support structures of the nasopharynx.
horses (Holcombe et al 1998). There are three intrinsic tongue muscle: the genioglossus,
Fig. 29.9. Illustration of the cross-sectional anatomy

of the hyoid region.
Mandible Hyoepiglotticus
muscle
Genioglossus Basihyoid
muscle bone
Geniohyoideus Hyoglossus Sternohyoid
muscle muscle muscle
hyoglossus, and styloglossus. The genioglossus is the largest tion, and enhanced pharyngeal stability in several species
intrinsic tongue muscle and originates from the medial (Brouillette & Bradley 1980, Fuller et al 1999). Therefore,
surface of the mandible, just caudal to the symphysis it seems that tongue depression may be the critical force
(Fig. 29.9) (Sisson 1975a) and its muscle fibers radiate needed to dilate and stabilize the nasopharynx in horses.
rostrally toward the tip of the tongue, dorsally, and distally This is perhaps why the use of a tongue-tie has been shown
toward the root of the tongue. The hyoglossus is a flat wide to be ineffective in expanding the dimensions of the naso-
muscle that lies in the lateral portion of the base of the pharynx or preventing dorsal displacement of the soft
tongue (Sisson 1975a). It originates from the lateral aspect palate in some affected horses (Cornelisse et al 2001,
of the basihyoid bone and from portions of the stylohyoid Franklin et al 2002).
and thyrohyoid bones (Sisson 1975a). The styloglossus
muscle originates at the distal lateral aspect of the Hyoid muscles
stylohyoid bone and travels the length of the tongue, along
its lateral aspect (Sisson 1975a). Near the tip of the tongue Other muscles that attach to the hyoid apparatus and
the paired muscle meets and ramifies with fibers of other critically affect the nasopharyngeal architecture include
tongue muscles. the geniohyoideus, sternohyoideus, sternothyroideus, omo-
Contraction of the styloglossus retracts the tongue. Con- hyoideus, and thyrohyoideus muscles. The geniohyoideus
traction of the genioglossus muscle protracts the tongue muscle is a fusiform, paired muscle that lies on the ventral
and pulls the basihyoid bone rostrally. The genioglossus surface of the tongue (Fig. 29.9) (Sisson 1975b). The
also acts with the hyoglossus muscle to depress and geniohyoideus originates from the medial surface of
retract the tongue. Hyoglossus and genioglossus activity the mandible (near the origin of the genioglossus muscle)
are synchronous with respiration, and activity of these caudal to the symphysis and it inserts on the basihyoid
muscles correlates well with increases in pharyngeal bone. The omohyoideus, sternohyoideus and sternothy-
airway size during breathing (Brouillette & Bradley 1980, roideus muscles are accessory respiratory muscles that
Mathew et al 1984a, Fregosi & Fuller 1997, Fuller et al insert on the manubrium and extend cranially. These
1999). Hypoxia, hypercapnia, and airway occlusion muscles are called accessory muscles of respiration because
cause parallel increases in electrical activity of the pro- their respiratory activity is somewhat silent during resting
trudor and retractor muscles of the tongue. Indeed, retrac- breathing but increases with exertion and exercise. The
tion and depression of the tongue improves airflow, func- sternothyroideus inserts on the caudal abaxial aspect of
the thyroid cartilage, and the sternohyoideus inserts on the

basihyoid bone and the lingual process of the hyoid Inflammatory Disorders
apparatus. Contraction of these muscles results in caudal Follicular pharyngeal hyperplasia (pharyngitis)
traction of the hyoid apparatus and larynx, dilating
the pharyngeal region (Sisson 1975b). The omohyoideus Etiology
muscles originate on the subscapular fascia near the Young horses very commonly develop follicular pharyngeal
shoulder joint and also insert on the basihyoid bone and hyperplasia. The location of the nasopharynx at the
the lingual process of the hyoid apparatus. Contraction of entrance of the airway exposes it to multiple types of
these muscles produces caudal traction of the hyoid irritant particles, allergens, and viral or bacterial agents.
apparatus (Castro et al 1999). The local lymphoid tissue responds to these stimuli
The thyrohyoideus is a flat rectangular muscle that by secreting mucus to entrap inhaled particles and by
originates on the lateral surface of the thyroid cartilage producing local immunoglobulins. As young horses begin
lamina and inserts on the caudal part of the thyrohyoid their performance careers, enter training barns, and travel,
bone (Sisson 1975b). On contraction, it moves the hyoid they become exposed to multiple new infectious, irritant,
bone caudally or the larynx rostrally and dorsally (Sisson and antigenic stimuli.
1975b). In studies evaluating the electromyographic Thus, this type of pharyngitis is very common in young
activity of some “extrinsic” nasopharyngeal muscles horses and its prevalence decreases as horses age, as
during exercise, Ducharme et al (2003) observed decreased documented by Hobo et al (1995) who reported a 37%
thyrohyoideus muscle activity prior to soft palate displace- prevalence of pharyngitis (grade 3–4) in 2-year-old
ment in one horse. Investigations by Tsukroff et al (1998) thoroughbred racehorses that decreased to nearly 0% in
reveal that transection of a combination of thyrohyoideus, horses aged 6 years or more. Auer et al (1985) reported
omohyoideus, sternohyoideus, and hyoepiglotticus muscles that 68 out of 70 young thoroughbred racehorses had
results in dorsal displacement of the soft palate in horses. evidence of pharyngeal lymphoid hyperplasia, or pharyn-
The soft palate displacement observed was associated with gitis. Similar to Hobo’s work, they found that 2-year-old
a more caudal positioning of the basihyoid bone. In sub- horses had the most severe pharyngeal inflammation
sequent studies, thyrohyoideus muscle resection caused when compared to other age groups. In the study by Auer
intermittent dorsal displacement of the soft palate in et al (1985), none of the affected horses had a history of
7 out of 10 exercising horses (Ducharme et al 2003). diminished racing performance. The results of this study
Additionally, the insertion of a thyrohyoideus muscle pros- suggest that pharyngeal lymphoid hyperplasia may be a
thesis (created by placing a suture through the basihyoid normal response to new inhaled environmental irritants or
bone and the thyroid cartilage) returned airway function to antigens or infectious agents in young horses. Therefore,
normal such that dorsal displacement of the soft palate because pharyngitis is frequently self-limiting and has not
no longer occurred in any of these horses (Ducharme et al been definitively associated with poor performance, this
2003). These data clearly suggest that more cranial posi- disease is usually not treated. However, there are anecdotal
tioning of the larynx relative to the hyoid bone improves concerns that pharyngitis may be a prelude to dynamic
soft palate stability during exercise and that thyrohyoideus upper airway obstruction and the sequelae of nasopharyn-
muscle dysfunction may be a cause of intermittent dorsal geal inflammation may be more performance limiting than
displacement of the soft palate in horses. the initial bout of pharyngitis. Some clinical evidence sug-
In summary, it is not clear how deficits of individual gests that regional inflammation of the upper airway may
muscle groups result in diminished airway patency, though predispose individuals to obstructive upper airway disease,
this causal relationship has been well studied in laboratory such as nasopharyngeal collapse, dorsal displacement of
animals and humans. Nasopharyngeal patency results the soft palate, and aryepiglottic fold collapse.
from a synergistic association of extrinsic muscles with
opposing actions that affects the position of the larynx
and hyoid bone. Indeed the hyoid moves rostrally when the Diagnosis
geniohyoid and genioglossus muscles contract and in It is important to evaluate the extent of pharyngeal
the opposite direction when the sternohyoid and sternothy- follicular hyperplasia, which can be classified into five
roid muscles contract (Sisson 1975a, Kuna et al 1999, grades (including 0) based on the degree of severity (Raker
Feroah et al 2000, 2001, Kuna 2001, Ducharme et al & Boles 1978). A pharynx with a few small white follicles
2003, Tessier et al 2004). The complex results of the over the dorsal walls is classified as grade 1 (Fig. 29.10).
activity of these muscles yield a more cranioventral Numerous small follicles interspersed with occasional
position of the basihyoid bone, and an increase in the hyperemic follicles on the dorsal pharyngeal wall and
diameter and stability of the nasopharynx in exercising extending ventrally over the lateral nasopharyngeal walls
horses (Rehder 1992, Castro 1999, Tessier et al 2004). characterize grade 2 pharyngitis. This degree of follicular
A B C
D E
Fig. 29.10. Grading pharyngitis. A score of between 0 and 4 can be used to grade pharyngeal lymphoid
hyperplasia. Here, the five endoscopic images show (A) grade 0 pharyngitis, (B) grade 1 pharyngitis,
(C) grade 2 pharyngitis, (D) grade 3 pharyngitis, and (E) grade 4 pharyngitis.
hyperplasia is normal for 2-year-old horses. Grade 3 pharyn- culturing the pharyngeal area may be warranted, though
gitis is diagnosed when more hyperemic follicles coalesce growth of certain Streptococcus spp. would be expected in
over the entire dorsal and lateral walls of the nasopharynx. nasopharyngeal swabs of normal horses.
Grade 3 pharyngitis is often seen in association with
other abnormalities such as epiglottic flaccidity and dorsal
displacement of the soft palate. The most severe form Treatment
of pharyngitis is grade 4 and is characterized by large, Generally, pharyngitis of grade 2 or less is not treated if
edematous, hyperemic follicles that frequently coalesce this follicular pharyngitis is the only clinical complaint.
into broad-based and polypoid aggregates. One reason If pharmacological therapy is to be administered, anti-
why culture and sensitivity of the nasopharynx is rarely inflammatory therapy may prove useful in the treatment
performed in horses with follicular pharyngeal hyperplasia of this pharyngitis. Systemic and inhaled corticosteroids
is because specific bacterial nasopharyngeal infections have been used to treat pharyngitis. Following a thorough
[such as β-hemolytic group A streptococcal infections in physical examination, complete blood count, and fibrino-
children (Gerber & Shulman 2004)] are rarely a concern in gen assay to rule out possible bacterial or viral infection,
horses with pharyngeal hyperplasia. However, if a horse systemic corticosteroid therapy may be initiated. Therapies
with follicular hyperplasia is showing signs of clinical include prednisolone [oral dose of 0.6 mg/kg once a day
illness, such as depression, fever, and inappetence, (s.i.d.) for 7 days, followed by 0.3 mg/kg s.i.d. for 7 days,
and then 0.3 mg/kg every other day for five treatments]
or dexamethasone [0.02–0.04 mg/kg per os (PO) or intra- ER
venous (IV), s.i.d for 3 days, then 0.01–0.02 mg/kg PO or
IV, s.i.d. for 3 days, and then every other day for 3 days NS
of treatment]. Topical anti-inflammatory therapies have
also been used, including administration of 20 ml of a
mixture comprising 250 ml glycerin, 250 ml dimethyl-
sulfoxide 90%, nitrofurazone 500 ml, and 50 ml pred-
nisolone (25 mg/ml) that can be sprayed on the naso-
pharynx twice daily. If the pharyngitis is bacterial in origin
or accompanies infectious pulmonary disease, appropriate
antimicrobial therapy should be used.
If a viral etiology is suspected, treatment may incor-
porate interferons, a family of proteins that have antiviral
and immunomodulatory activity. Oral administration of a
low dose (0.1 IU/kg) of human interferon-α once daily for
5–7 days reduces tracheal and nasopharyngeal exudate
in racehorses with inflammatory airway disease. Oral SP
administration of human interferon-α may modulate
the activity of oropharyngeal lymphoid tissue in the
oropharynx. The horse should be rested during this
time, and either turned out in a pasture or worked lightly Fig. 29.11. Endoscopic image of the rostral portion of the naso-
for 6–8 weeks. The airway inflammation often resolves pharynx showing collapse of the rostral portion of the soft palate into
the airway. SP = soft palate; NS = nasal septum; ER = ethmoid region.
within 7–10 days.
Functional Disorders genesis of nasopharyngeal collapse and in more severe

Nasopharyngeal collapse forms of nasopharyngeal dysfunction such as dysphagia.
Despite this long list of disorders known to cause naso-
Factors that affect the nerves and muscles that control the pharyngeal collapse, the precise etiology of nasopharyngeal
nasopharynx may result in dorsal, lateral, or circum- collapse in individual cases is usually unknown.
ferential nasopharyngeal collapse as a result of changes in
the compliance of this region. Fitness and maturity of
development of the musculature contribute to the stability Models of nasopharyngeal collapse
of the nasopharynx and appropriate neural function is Research models of the collapse of various regions of the
critical to maintain airway responses and tone. Therefore, nasopharynx have been created which may aid our
horses with clinical signs of nasopharyngeal collapse understanding of the pathogenesis of these disorders but
should be evaluated for neuromuscular or primary muscle they have not yet led to an effective treatment. Instability
disorders, such as equine protozoal myoencephalitis, of the rostral portion of the soft palate, or “billowing” of
selenium and vitamin E deficiency, and hyperkalemic the soft palate occurs following bilateral tenectomy of the
periodic paresis (HYPP). In quarter horses, HYPP disrupts tendons of the tensor veli palatini muscles (Holcombe et al
the normal tone of the nasopharyngeal musculature even 1997). As mentioned previously, when this muscle con-
at rest (Carr et al 1996). Medications such as muscle tracts, it tenses the palatine aponeurosis, depressing the
relaxants and sedatives are known to alter nasopharyn- rostral portion of the soft palate slightly and maintaining
geal muscle function. Mechanical pharyngeal disorders, its stability during inspiration. Following tenectomy, the
including those caused by the presence of cysts within the rostral portion of the soft palate is unable to resist the
soft palate, cleft palate tumors, or scarring from chronic collapsing subatmospheric pressures that occur in the
inflammatory conditions, may prevent subepiglottic posi- nasopharynx during inspiration, and, as a result, the
tioning of the caudal edge of the soft palate and result in rostral aspect of the soft palate billows dorsally into the
generalized dysfunction of the nasopharynx. Inflammation airway during inhalation and obstructs airflow (Fig. 29.11)
of the nasopharynx that affects the pharyngeal plexus (Holcombe et al 1997). Horses with dorsal billowing of the
of nerves, the principal motor innervation to the naso- soft palate make a respiratory noise during exercise. This
pharyngeal muscles, has been implicated in the patho- dysfunction has occasionally been described as a prelude
during treadmill exercise and at rest while the nares were

occluded (Holcombe et al 2001). The collapse was circum-
DP
ferential in most cases, consistent with the presentation of
most clinical cases.
Diagnosis
Horses with nasopharyngeal collapse have a history of
exercise intolerance and inspiratory respiratory noise,
which escalates with increasing exercise intensity. Observa-
tion of nasopharyngeal collapse when both nostrils are
obstructed in the resting horse supports this diagnosis, but
horses can have induced nasopharyngeal collapse during
nasal occlusion and still have appropriate nasopharyngeal
function during exercise. This may occur because the local
reflex contraction of nasopharyngeal muscles, stimulated
by nasal occlusion, results primarily from stimulation of
receptors within the laryngeal mucosa. During exercise,
multiple factors affect the activity of upper airway dilating
muscles, including locomotion, neuroendocrine stimuli,
Fig. 29.12. Endoscopic image of the nasopharynx showing collapse of hypercarbia and hypoxemia (Bartlett 1979, Brouillette
the dorsal pharyngeal wall. Note that the corniculate processes of the & Thach 1979). In normal horses, the roof of the naso-
arytenoid cartilages are not visible. DP = dorsal pharynx. pharynx slightly projects ventrally into the lumen of the
nasopharynx at the end of expiration, as a result of positive
end-expiratory pressure within the guttural pouches, and
this finding should not be considered abnormal (Rehder
1992). The floor of the guttural pouch forms part of the
to dorsal displacement of the soft palate. However, in roof of the nasopharynx and therefore positive pressure
experimental horses and clinical cases, dysfunction of the within the guttural pouches results in mild collapse of the
rostral soft palate can occur without dorsal displacement of roof of the nasopharynx. Additionally, if a horse has been
the soft palate as a sequel (Holcombe et al 1997). sedated for endoscopic examination, evaluation of naso-
Collapse of the dorsal nasopharynx may be induced by pharyngeal function has no diagnostic value because
anesthetizing the glossopharyngeal nerves and so creating the effect of sedation on muscular function may yield
stylopharyngeus dysfunction (Tessier et al 2004). Follow- an erroneous result. In conclusion, a definitive diagnosis
ing this procedure, horses suffered collapse of the dorsal of nasopharyngeal collapse can only be made during
nasopharynx when the nares were occluded and also treadmill video-endoscopy although in the future, respira-
during treadmill exercise as inspiratory pressures increased tory sound analysis may prove to be a useful diagnostic
(Fig. 29.12). The nasopharyngeal collapse did cause aid (see Chapter 17).
inspiratory obstruction based on upper airway pressure
measurements. However, the degree of collapse produced
by this model was modest in contrast to clinical cases of Treatment
nasopharyngeal collapse, which frequently exhibit circum- There is no current treatment for nasopharyngeal collapse.
ferential or more lateral collapse of the airway (Fig. 29.13). Frequently, horses are exercised with their tongues tied
The etiology of clinical nasopharyngeal collapse remains and/or wearing figure-of-eight nosebands in an attempt to
unknown, though abnormalities of afferent innerva- help stabilize the airway. This treatment strategy is rarely
tion may play a causal role. Numerous mucosal pressure effective. Occasionally, the disease is self-limiting, for
receptors cover the laryngeal mucosa and these mechano- example in horses that are not fully fit or are suffering
receptors can sense subatmospheric pressures within the intercurrent short-term disease, and some of these horses
airway (Sant’Ambrogio et al 1983, Mathew et al 1984b). will recover normal nasopharyngeal function without
Increased activity of these receptors reflexly enhances the treatment. If the horse has suffered from a respiratory viral
tone of upper airway dilating and stabilizing muscles, thus infection or pharyngitis, alleviating the airway inflam-
preventing dynamic collapse of the airway (Mathew et al mation may improve nasopharyngeal function within a few
1984b). Following topical anesthesia of the laryngeal weeks to months. Horses that are HYPP-positive respond to
mucosa, horses exhibited collapse of the nasopharynx both acetozolamide therapy (Carr et al 1996).
GP
LPW
C
SP
E
SP
A B
Fig. 29.13. (A) Endoscopic image of a horse during an episode of ryngeal opening of the guttural pouch. (B) Endoscopic image of the
nasopharyngeal collapse. Note how the nasopharynx collapses into a nasopharynx showing collapse of the lateral wall of the nasopharynx
sphincter. SP = soft palate. C = right vocal cord; GP = left nasopha- (LPW) as well as bulging of the soft palate (SP) around the epiglottis (E).
Nasopharyngeal paralysis, possibly the most severe form dilatation of intraneural capillaries to heavy leukocytic
of nasopharyngeal collapse, can occur along with dysphagia infiltration of the nerves and necrosis (DeLahunta 1977).
(the inability to swallow). Differential diagnoses for Chromatolysis and degenerative swelling and vacuolization
nasopharyngeal paralysis in the horse include many of the of neurons in the cranial cervical ganglion occur in some
same diseases speculated to cause nasopharyngeal collapse. animals (DeLahunta 1977).
The list includes botulism, equine protozoal myoencephali-
tis, equine herpesvirus 1 infection, guttural pouch mycosis, Dorsal displacement of the soft palate (DDSP)
guttural pouch empyema, and iatrogenic inflammation of
the guttural pouch caused by lavage with caustic solutions Horses with intermittent DDSP are exercise intolerant and
(DeLahunta 1977, Mayhew 1989). Horses with nasopha- most (70–80%) affected horses will make an abnormal
ryngeal paralysis frequently have persistent or permanent noise during exhalation at fast work (Derksen 2001). The
dorsal displacement of the soft palate. Inflammation from displaced soft palate billows dorsally during exhalation as
fungal (guttural pouch mycosis) or streptococcal infection air flows beneath the soft palate (Fig. 29.14). Horses often
(guttural pouch empyema) that may affect branches of the produce a “snoring” noise when the soft palate is displaced,
vagal and glossopharyngeal nerves may result in ipsilateral and this is caused by a low frequency fluttering of the
hypesthesia of the pharyngeal mucosa and pharyngeal caudal margin of the soft palate during expiration (Derksen
paresis with dysphagia (DeLahunta 1977, Kipper & Frees 2001, Franklin et al 2004). However, in approximately
1993). In one study, 12 of 35 cases of guttural pouch 30% of horses with DDSP, noise is not reported (Franklin
mycosis had dysphagia (Greet 1987). Following treatment, et al 2004). The caudal edge of the soft palate in each horse
one horse had continuing low-grade dysphagia, five horses has a different stiffness, and this may be why 20–30% of
died or were euthanased following treatment for guttural horses are “silent displacers” (Franklin et al 2004). Dorsal
pouch mycosis and six recovered completely. The total displacement of the soft palate should still be considered
recovery from pharyngeal dysphagia in these horses as a possible diagnosis in horses with a sudden decrease
suggested that the underlying neurological deficit is often in performance and no history of respiratory noise.
neuropraxia rather than necrotizing inflammation of This disease is more common in racehorses, especially
nerves (DeLahunta 1977, Greet 1987). Microscopic study 2- to 4-year-olds, but in Europe it is also common in older
of affected nerves from horses with guttural pouch mycosis National Hunt racehorses (P.M. Dixon, personal communi-
revealed active neuritis. The involvement ranges from cation). It is an uncommon disease of show hunters and
slight swelling of myelin sheaths and Schwann cells with western pleasure horses but does affect horses that carry
RCP
SP
A B
Fig. 29.14. (A) Endoscopic image of the nasopharynx of a horse on measured with the tracheal catheter (C). Notice how the caudal free
a treadmill during an episode of dorsal displacement of the soft margin of the soft palate billows across the airway, obstructing the
palate. This image was taken during inspiration, documented by sub- rima glottidis. SP = soft palate; RCP = right corniculate process of
atmospheric pressure measured with the tracheal catheter (C). (B) This the arytenoid cartilage.
image was taken during exhalation, documented by positive pressures
their head and neck in a flexed position, such as upper level Dysfunction of nasopharyngeal muscles has been impli-
dressage horses and saddlebreds. cated in the pathogenesis of DDSP. In a study evaluating
Dorsal displacement of the soft palate is an expira- the electromyographic activity of some “extrinsic” naso-
tory upper airway obstructive syndrome that can cause pharyngeal muscles during exercise, Ducharme et al (2003)
increased expiratory impedance, decreased minute ven- observed decreased thyrohyoideus muscle activity prior to
tilation, hypoxia, and hypercarbia (Rehder et al 1995, soft palate displacement in one horse. In the same study,
Holcombe et al 1998). When the soft palate displaces with bilateral resection of the thyrohyoideus muscles caused
respect to the epiglottis during exercise, it undergoes dorsal intermittent DDSP during exercise (Ducharme et al 2003).
and ventral excursion during the respiratory cycle. During Creating a thyrohyoideus prosthesis by imbricating the
inhalation, the soft palate rests dorsal to the epiglottis but thyroid cartilage to the basihyoid bone (“tie-forward
does not cause obstruction because inspiratory pressures procedure”) corrected DDSP in these horses. The specific
maintain it in a relatively stable position on the floor of the function of the thyrohyoideus muscle in preventing DDSP
nasopharynx. However, during exhalation the soft palate is not well understood, but because contraction of the
billows dorsally into the nasopharyngeal lumen, thus thyrohyoideus muscles apposes the larynx and basihyoid
diverting some flow of air through the oropharynx and bone, we can infer that the position of the larynx relative
mouth. This flow pattern is associated with decreased to the soft palate is likely to be important in the patho-
expiratory airflows and increased expiratory impedance genesis of DDSP.
(Rehder et al 1995, Holcombe et al 1998). Some horses Neuromuscular dysfunction of the structures control-
suffering from DDSP exhibit the characteristic sign of ling the position of the soft palate may occur secondary to
mouth breathing during exhalation, recognized by flutter- inflammation of the upper airway. Some of the nerves that
ing of the cheeks as air is diverted underneath the soft are important in coordinating nasopharyngeal function
palate through the mouth. course through the guttural pouch to the pharyngeal
The cause of intermittent DDSP is unknown, but many plexus, which ramifies within the dorsal wall of the
theories exist to explain the etiology of this condition which nasopharynx. As previously discussed with respect to
is likely multifactorial. Some theories focus on dysfunction nasopharyngeal collapse, infection or inflammation of this
of the nerves and muscles that control the soft palate, and area could affect the innervation and thus the function of
others concern the stability and proximity of the epiglottis the intrinsic soft palate muscles. The pharyngeal branch
and larynx to the soft palate. of the vagus nerve provides motor innervation to the
palatinus and palatopharyngeus muscles, two muscles evaluate the horse’s response to displacement. Soft palate
that control the position of the caudal portion of the displacement can be induced in some horses by obstructing
soft palate. Experimentally desensitizing the pharyngeal the nostrils during endoscopy, thus challenging nasopha-
branch of the vagus nerve bilaterally caused persistent ryngeal stability. Alternatively, passing the endoscope into
DDSP and dysphagia in horses (Holcombe et al 1998). the proximal aspect of the trachea will induce temporary
Biopsies taken of the palatinus muscle from horses with displacement of the soft palate in most horses.
DDSP showed evidence of chronic denervation including Evidence of trauma, inflammation, or pathology of the
fiber type grouping, mild atrophy, moth-eaten fibers and palate or epiglottis may support a diagnosis of DDSP.
target fibers (Holcombe 2001). It is therefore possible that Ulcers on the axial aspect of the caudal free edge of the soft
denervation atrophy of the palatinus may cause DDSP palate also indicate that DDSP occurred during exercise. An
in some horses. epiglottis that is abnormal (flaccid, short or hypoplastic) or
Some authors have implicated anatomical aberrations deviated to one side provides some evidence to support
such as epiglottic hypoplasia (reduced size or rigidity of a diagnosis of DDSP, although the association may not
epiglottis) in the pathogenesis of DDSP. These authors be causal because DDSP seems to occur independent of
speculate that in some horses the epiglottis is not epiglottic conformation. In addition, a “choke ring”, i.e.
sufficiently rigid to maintain its position dorsal to the soft bruising of the roof of the nasopharynx in the area of the
palate. No conclusive evidence exists to support epiglottic guttural pouch openings (in the mid portion of the naso-
hypoplasia as the cause of DDSP, and its association with pharynx), is consistent with DDSP.
DDSP and poor racing performance has not been confirmed A complete examination of the caudal portion of the
(Stick et al 2001). However, epiglottic malformation or soft palate to evaluate its contour, which should be some-
chondritis have been reported to result in permanent or what concave, as well as an assessment of possible masses
persistent DDSP. Other anatomical abnormalities such as or cysts should also be performed. Subepiglottic cysts and
the presence of masses or cysts on the caudal free edge of masses can be located underneath the soft palate, so the
the soft palate or beneath the epiglottis may impede patient should be observed during repeated swallows and
subepiglottic placement of the soft palate, resulting in efforts should be made to induce the cyst to move to a
DDSP. Epiglottic entrapment with epiglottic deformity visible location.
can also cause intermittent or persistent DDSP in horses. Previous attempts at surgical correction of DDSP should
These horses are not dysphagic and a lateral radiograph be noted. Evidence of such surgery includes indentation
of the laryngeal region or per os endoscopy or palpation of in the cervical musculature, where a sternothyrohyoid
the epiglottis (under sedation or anesthesia) can confirm the myectomy was performed. It is more difficult to identify
diagnosis. Relieving the epiglottic entrapment will correct horses that have had excision of the caudal margin of the
the DDSP in some horses. Unfortunately, re-entrapment, soft palate or sternothyroid tenectomy and myectomy at
epiglottic deformity, and chondritis, as well as the con- the muscle’s origin. Local palpation and/or clipping the
tinuation of persistent or intermittent DDSP represent hair over the ventral aspect of the cricoid cartilage may
alternative outcomes following treatment of the epiglottic permit identification of a surgical scar indicative of a prior
entrapment. laryngotomy procedure.
Diagnosis at rest Diagnosis during exercise

The presence or absence of DDSP during an endoscopic The current gold standard for diagnosis of DDSP is obser-
examination of the nasopharynx at rest does not neces- vation of intermittent DDSP during strenuous exercise
sarily correlate with the development of DDSP during using high-speed treadmill video-endoscopy (Fig. 29.14).
strenuous exercise on a high-speed treadmill (Parente et al Following acclimation to the treadmill, horses are exer-
1994). In the practice situation however, the diagnosis cised at incrementally increasing speed until fatigue
must often be made based on history and endoscopy of (usually 13–14 m/s at a 0° incline). One successful strategy
the soft palate and epiglottis at rest. Some horses have used by some clinicians involves exercising the horse at
permanent DDSP at rest, thus preventing epiglottic maximum speed for 30–60 seconds, decreasing the speed
examination. The epiglottis must be evaluated using the to a moderate level for 30 seconds, and then increasing the
previously described, alternative techniques in those speed to maximum speed. This protocol is sometimes
horses. If the horse displaces its soft palate dorsal to the effective because some horses exhibit DDSP during changes
epiglottis and, despite multiple swallows, maintains the in exercise intensity. However, the absence of DDSP at
palate in a displaced position, it may be assumed that exercise does not rule out this diagnosis because the
the horse is likely to exhibit DDSP during exercise. There- condition is intermittent in nature and therefore not
fore, a potentially useful strategy is to induce DDSP and always demonstrable with treadmill evaluation. The use of
sound recordings with spectral analysis frequency peaks in Surgical treatment alternatives are numerous and
the 20–80 Hz range is considered good evidence of DDSP include staphylectomy or trimming the caudal free margin
(Derksen 2001, Franklin et al 2004). of the soft palate, various myectomy and tenectomy proce-
dures (sternohyoid and sternothyroid, alone or in combina-
tion), epiglottic augmentation, multiple tension palatoplasty,
Treatment thermal and laser procedures to cauterize the soft palate,
In 2-year-old horses, or any horse that has active or and the tie-forward procedure (Cook 1981, Harrison &
previous upper or lower airway inflammation, the initial Raker 1988, Peloso et al 1992, Ahern 1993, Anderson
therapy should focus on decreasing this inflammation. If et al 1995, Llewellyn 1997, Hogan et al 2003, Woodie et al
bacterial upper airway infection is diagnosed, systemic anti- 2005b). These procedures are performed alone or in various
biotics (usually penicillin G, ceftiofur or sulfamethoxazole– combinations e.g. staphylectomy, sternothyrohyoideus
trimethoprim) may be administered along with non-steroidal myeotomy, and ventriculectomy (Barakzai et al 2003).
anti-inflammatory drugs. Upper airway inflammation is
treated in a plethora of different ways, including systemic
administration of corticosteroids (dexamethasone); non- Staphylectomy
steroidal anti-inflammatory medication; topical anti- Staphylectomy or trimming the caudal free margin of the
inflammatory throat sprays containing agents such as soft palate was developed by Dr Quinlan in 1949 (Cook
glycerin, dimethyl sulfoxide, and nitrofurazone; systemic 1981). Theoretically, this procedure is therapeutic for
administration of interferon; and guttural pouch lavage two reasons: it reduces the amount of soft palate tissue
with balanced polyionic solutions with or without dimethyl available to cause airway obstruction during episodes of
sulfoxide and corticosteroids. Oral interferon (50–200 IU/day DDSP and it may increase the stability of the palate,
for 10–14 days) has also been used. because of scarring of the caudal free margin. Staphylectomy
An appropriate treatment regimen for moderate to is performed through a laryngotomy incision, with the
severe nasopharyngeal inflammation without bacterial horse anesthetized and placed in dorsal recumbency. A
infection might initially include systemic corticosteroids laryngotomy is performed by incising the cricothyroid
such as prednisolone (not prednisone) or dexamethasone ligament and underlying mucosa along the midline and
and topical anti-inflammatory pharyngeal spray for extending the incision from the cricoid cartilage to the
2–4 weeks. A common pharyngeal spray administered thyroid cartilage (Fig. 29.15). Care should be taken not to
transnasally at the rate of 20 ml, q 12 h consists of glycerin incise the thyroid or cricoid cartilage. The caudal free
250 ml, 250 ml dimethyl sulfoxide 90%, nitrofurazone edge of the soft palate is identified, and a crescent section of
500 ml, prednisolone 50 ml (25 mg/ml). Horses should be the soft palate (0.5–1.5 cm at the midline and tapering to
rested (light training without fast speed work) for each side) is resected using Satinsky or Metzenbaum
10–30 days and the upper airway function should be scissors. The laryngotomy incision can be closed or left
re-evaluated periodically over this time. Normal function to heal by second intention. If closure is elected, the
may not return for 3–4 months, if the cause of the DDSP cricothyroid membrane and epithelium are re-apposed
was neuromuscular dysfunction related to airway inflam- using 3.5 metric polyglactin 910 in a simple continuous
mation. Owners and trainers of 2-year-old horses should pattern. Suture placement in the cartilages should be
consider waiting until the following year before pursuing avoided to minimize granuloma formation. Closure of the
any surgical treatment of DDSP because maturity may rest of the laryngotomy is optional, but may increase
alleviate the need for treatment. morbidity because of local incisional infection and poten-
Tack modifications such as the use of a bit that main- tial septic mediastinitis. Perioperatively, parenteral non-
tains the position of the tongue (i.e. a “W” bit, Serena bit), steroidal anti-inflammatory drugs and broad-spectrum
tongue-ties, and the figure-of-eight noseband are tradi- antibiotics are administered for 3–7 days. Training can
tional approaches that may be of value in reducing the resume within 2–3 days for standardbreds and 2–3 weeks
occurrence of DDSP (Barakzai & Dixon 2005). There is no for thoroughbreds. The prognosis for improvement in
evidence to support the use of a tongue-tie in the pre- racing performance following this procedure is approxi-
vention of DDSP or the improvement of airway mechanics mately 60% (Anderson et al 1995).
in exercising horses (Cornelisse et al 2001, Franklin et al
2002). An external device, called a “Cornell Throat Support
Device”, is being tested in the field and focuses on prevent- Sternothyrohyoid myectomy
ing caudal movement of the basihyoid bone and larynx This procedure was first proposed by Cook to prevent
during exercise. In experimental treadmill studies, the caudal retraction of the larynx (Cook 1981). When per-
device has been shown to be effective in six out of seven formed with the horse standing and sedated, local
horses (Woodie et al 2005a). anesthetic is infiltrated subcutaneously at the junction of
Fig. 29.15. Laryngotomy approach. SH = ster-

nohyoideus muscles; CTM = cricothyroid mem-
brane; TC= thyroid cartilage; CC = cricoid
cartilage.
SH
CTM
CC
TC
the mid and proximal cervical areas. Alternatively it can elevated and its proximal aspect is transected. The muscle
be performed under general anesthesia with the horse in is grasped, pulled cranially, and transected distally
dorsal recumbency. A 10-cm ventral midline skin incision (Fig. 29.16). Next, the smaller sternothyroid muscles are
is made and extended through the subcutaneous fascia exposed and resected. The incision is closed primarily.
to expose the sternohyoid muscle. Using curved forceps, a The surgical site may be bandaged until the skin sutures
7.5- to 10-cm section of the sternohyoid muscles is are removed to minimize swelling, and non-steroidal
Fig. 29.16. Sternothyrohyoideus myectomy

being performed in a standing horse. SH =
sternohyoideus muscle.
SH
anti-inflammatory and broad-spectrum antimicrobial

therapy may be given as described above. Stall rest with
daily hand walking is recommended for 2 weeks. Training
can be resumed 2 weeks after surgery.
If resection of the omohyoid muscle is elected, the horse
SH
must be placed in dorsal recumbency under general anes-
thesia. The omohyoideus is separated from the linguofacial
and jugular vein and partial resection is performed as STT
described for the sternothyroid/hyoid muscles. Careful
evaluation and ligation of all vessels is made to prevent
later hematoma formation, which would be more clinically
significant because of the amount of dead space resulting
from the partial resection of the sternohyoid, sternothyroid,
and omohyoid muscles bilaterally. The subcutaneous tissue LI
and skin are closed after placement of Penrose drains.
Currently, the omohyoideus muscle is rarely resected
because of the morbidity associated with this procedure.
Complications are usually minor and are related to Fig. 29.17. Tendon of insertion of the sternothyroideus muscle (STT)
incisional seromas or abscesses that require appropriate attaching to the thyroid cartilage. SH = sternohyoideus muscle;
drainage. This latter complication is more common if LI = laryngotomy incision.
the omohyoid muscles are removed. There are no notable
long-term complications except for the cosmetic defect
associated with the lack of strap muscle at the operated tomy and myectomy above. The prognosis for resolution of
site. The prognosis for improved performance following DDSP following combined staphylectomy and sternothyroid
sternothyrohyoid myectomy is approximately 60% (Harrison tenectomy is approximately 60% (Anderson et al 1995).
& Raker 1988, Anderson et al 1995).
Epiglottic augmentation
Combined staphylectomy and Epiglottic augmentation was developed because of the
sternothyroideus tenectomy anecdotal association of a flaccid epiglottis and DDSP in
This technique was introduced by Llewellyn and Petrowitz standardbreds (Peloso et al 1992, Tulleners et al 1997).
in 1997 (Llewellyn 1997). The combined staphylectomy The purpose of this procedure is to stiffen the epiglottic
and sternothyroid tenectomy procedure causes scarring of cartilage of horses to maintain the soft palate in a sub-
the caudal free margin of the soft palate and also prevents epiglottic position. However, epiglottic augmentation is
caudal traction of the larynx. The horse is placed under currently infrequently performed, because of lack of a
general anesthesia in dorsal recumbency, and a 10-cm proven association between epiglottic length and DDSP, an
ventral midline incision is made centered over the cricothy- absence of objective evidence of its success, and, prac-
roid membrane. The incision is extended through the tically, because surgical grade Teflon is rarely available
subcutaneous tissue and paired sternohyoid muscles on at present.
the midline. A self-retaining retractor is placed to laterally A laryngotomy is performed to provide access to the
displace the sternohyoid muscles and blunt dissection is epiglottis. The epiglottic cartilage is inverted into the lumen
performed lateral to the thyroid cartilage exposing the of the larynx by grasping one of the aryepiglottic folds with
tendon of insertion of the sternothyroideus muscle on Allis forceps and pulling this tissue toward the laryngotomy
the thyroid cartilage (Fig. 29.17). incision, exposing the ventral surface of the epiglottis.
Transection of the sternothyroid tendon is performed Between 3 and 7 ml Teflon paste (Mentor Polytef® paste
1 cm caudal to its insertion on the thyroid cartilage to for injection, Mentor O&O, Inc., Norwell, MA, USA) are
prevent inadvertent incision of the vascular pedicle of the injected submucosally. One of the authors (N.G.D.) prefers
cranial thyroid artery. A section of the muscle and its to inject 3 ml Teflon paste along the midline followed by
tendon is usually removed and the procedure is performed digital redistribution/flattening over the ventral surface of
bilaterally. The cricothyroid membrane can then be incised the epiglottis. Postoperatively, parenteral anti-inflammatory
and a staphylectomy can be performed as described above, agents are given for 5–7 days. Training can resume in
although currently, staphylectomy is fairly unpopular and 2–6 weeks. Prognosis for improved performance following
infrequently performed. Perioperative medications and epiglottic augmentations is approximately 60% (Tulleners
rehabilitation instructions are as described for staphylec- et al 1997).
Partial sternothyroidectomy and laser cautery hole in the basihyoid bone approximately 1 cm rostral to its
of caudal aspect of the soft palate caudal border. The sutures (no. 2 or no. 5 USP polybend
Partial sternothyroidectomy and laser cautery of caudal suture, Fiberwire®) are first passed through the hole in the
aspect of the soft palate has been described by Hogan et al basihyoid bone. One suture is then placed through the left
(2003). First, bilateral sternothyroid tenectomy is per- wing of the thyroid cartilage near the insertion site of the
formed as described above. Next, a laser is used per nasum sternothyroideus muscle. A second suture is placed within
to induce fibrosis on the caudal aspect of the soft palate. 1 cm of it to increase the strength of the fixation in the
The resulting fibrosis is thought to increase the stiffness of thyroid cartilage by dividing the stress on the cartilage
the caudal soft palate, allowing the soft palate to maintain between two points. The procedure is repeated in the right
a subepiglottic position. The laser portion of this procedure thyroid cartilage placing the suture in the same direc-
is performed in the sedated, standing horse. Briefly the tion. After suture placement, the horse’s nose is lifted so
endoscope is passed through the right nasal passage and that the head is at a 90° angle to the neck to facilitate tying
the soft palate is locally anesthetized with a topical the sutures.
application of 10 ml mepivacaine. A 600-μm bare laser Both before and after tying the sutures, a sterile, stainless
fiber is passed through the biopsy channel and directed steel ruler is used to measure the distance between the
at the caudal free edge of the soft palate. Using 15 watts caudal aspect of the basihyoid bone and rostral aspect of
of power and contact technique, the fiber is applied for the thyroid cartilage (the “BT distance”) and the distance
1–2 seconds at 2- to 4-mm intervals along the entire free between the caudal aspect of the basihyoid bone and
edge of the palate and extending approximately 1.5 cm cranial aspect of the cricoid cartilage (the “BC distance”)
rostrally. If an ulcer is present along the caudal free edge of (Fig. 29.18). The first suture is tied so that the rostral
the palate, the soft palate is displaced and the ulcer is aspect of the thyroid cartilage is dorsal to the basihyoid
cauterized directly with the laser fiber (Hogan et al 2003). bone and extends up to 1 cm rostral to the caudal border of
Postoperative rehabilitation includes hand walking for the basihyoid bone. The second suture is tied to match that
3 days followed by resumption of jogging or galloping. tension. The head is replaced in its normal resting position,
Perioperative medications include topical pharyngeal spray and the BT and BC distances are remeasured. Because the
for 14 days, phenylbutazone (4 mg/kg PO) for 5 days, and a rostral aspect of the thyroid cartilage is either at the level
decreasing regimen of oral prednisolone for 2–3 weeks. of, or rostral to, the caudal aspect of the basihyoid bone,
Horses return to normal work 1 week after surgery if endo- the postoperative BT distance is expressed as a negative
scopic examination of the surgical area is normal (Hogan value. The sternohyoideus muscles are re-apposed with
et al 2003). The prognosis for resolution of DDSP following a single continuous suture pattern that incorporates
this procedure is 90% (Hogan et al 2003). the loose fascia over the ventral aspect of the larynx. The
subcutaneous tissues and skin are closed in a routine
Laryngeal tie-forward manner (Woodie et al 2005b).
We have performed the tie-forward procedure based on Perioperatively, horses receive broad-spectrum antibiotics
experimental data suggesting that the optimal position of (ampicillin 10 mg/kg, IV t.i.d. and gentamicin 6.6 mg/kg,
the larynx during exercise is slightly dorsal to the basihyoid IV s.i.d. for 24 h followed by trimethoprim–sulfamethoxazole
bone (Woodie et al 2005b). The horse is placed under 30 mg/kg, PO, q 12 h) and phenylbutazone (2.2 mg/kg,
general anesthesia in dorsal recumbency, and endotracheal PO, q 12 h) for 5–7 days. With the horse standing, a lateral
intubation is performed. A 15-cm ventral midline incision radiograph of the larynx is obtained to verify the position
is made, extending from the rostral aspect of the basihyoid of the larynx. Feeding at shoulder height is recommended
bone to 1 cm caudal to the cricoid cartilage. The paired to prevent early stress on the surgery site. Training
sternohyoideus muscles are separated bluntly on the resumes 2 weeks after surgery, pending satisfactory exami-
midline, and dissection is extended to the ventral aspect of nation at the time of suture removal. The tie-forward
the larynx. The entire ventral aspect of the larynx is freed procedure has a prognosis of 86% for improved racing
from surrounding tissue. The dissection is extended performance (Woodie et al 2005b).
laterally to expose the tendon of insertion of the sternothy-
roideus muscles. Pharyngeal cysts
A small, self-retaining retractor is placed at the rostral
aspect of the incision to facilitate exposure of the basihyoid Pharyngeal cysts occur most commonly in the sub-
bone, and a larger retractor (e.g. Balfour) is placed in the epiglottic region but have been reported within the soft
caudal aspect of the incision to facilitate exposure of the palate and on the dorsal wall of the nasopharynx
lateral aspects of the thyroid cartilage. A curette is used to (Fig. 29.19) (Haynes et al 1990, Koch & Tate 1978).
remove the muscle insertion and expose the ventral aspect Subepiglottic cysts are likely remnants of the thyroglossal
of the basihyoid bone. A 3.2-mm drill bit is used to create a duct which forms as a ventral epithelial out-pouching from
Fig. 29.18. Intraoperative view of laryngeal

tie-forward after placement of sutures. Note
the 3.2-mm drill hole in the base of the
basihyoid bone through which both sutures
are passed. The other ends of the sutures
are placed in the caudal laminae of the right
and left thyroid cartilages. C = cricoid car-
tilage; T = thyroid cartilage; B = basihyoid
bone. Refer to text for explanation of arrows.
C B
T
the floor of the primitive pharynx and grows caudally,

forming a vesicle that divides over the trachea into two
lobes of the embryonic thyroid gland (Koch & Tate 1978).
Normally, the duct atrophies early in embryonic develop-
ment, but rarely it persists, allowing cysts to form along its
length. Cysts that form within the dorsal nasopharyngeal
wall are remnants of the craniopharyngeal duct, the
embryonic precursor of the adenohypophysis or anterior
pituitary gland (Koch & Tate 1978). The craniopharyngeal
duct originates from Rathke’s pouch. Persistence of por-
tions of the craniopharyngeal duct presumably perpetuates
cyst formation within the pharyngeal walls. Cysts within
the soft palate are rare and probably form as the result of
the obstruction of mucus-secreting glands within the soft
palate and walls of the nasopharynx, or they may have a
C
traumatic etiology (Haynes et al 1990).
Pharyngeal cysts are more commonly diagnosed in male
horses than females and are most commonly reported in
young horses, between 2 and 4 years of age (Koch & Tate
1978). Clinical signs include respiratory noise, coughing,
SP
exercise intolerance, nasal discharge, dysphagia, aspiration
of feed and aspiration pneumonia, and dorsal displacement
of the soft palate (Koch & Tate 1978). The diagnosis is Fig. 29.19. Endoscopic image of the nasopharynx of a horse with a
soft palate cyst that was causing persistent dorsal displacement of
most commonly made by endoscopic examination of the
the soft palate. SP = soft palate; C = cyst.
nasopharynx, which reveals a raised, well-circumscribed
mass covered by mucosa. Occasionally, subepiglottic cysts
move from the nasopharynx to the oropharynx during
swallowing. If a subepiglottic cyst is anticipated but not

seen during endoscopic examination, the horse should be
made to swallow multiple times in an attempt to displace
the cyst into the nasopharynx. Additionally, radiography of
the laryngeal and pharyngeal region can help to diagnose
pharyngeal cysts. Contrast radiography of the region,
performed by administering 60 ml of contrast material
orally just prior to taking the lateral radiograph, can also
help to document the size and position of the cyst within
the pharynx (Haynes et al 1990).
Treatment of pharyngeal cysts includes surgical
excision, which can be performed through a laryngotomy,
transorally, or by use of non-contact laser ablation. The
entire cyst must be extirpated because if some of the lining
is left in situ, the cyst will likely recur. Surgical dissection of
the cyst from the surrounding mucosa is facilitated by
leaving the cyst intact and not aspirating the cystic SP
contents before removal. Prognosis following removal of SP
subepiglottic cysts is good with a reported return to athletic E
activity of 75% (Koch & Tate 1978). Less information is OP
available regarding the prognosis for return to athleticism
following removal of soft palate and pharyngeal wall cysts, Fig. 29.20. Endoscopic image of the nasopharynx of a horse with a
though one report of two cases of soft palate cysts stated cleft palate. E = epiglottis; SP = soft palate; OP = oropharynx.
that both horses were unable to race but were useful as
performance horses (Haynes et al 1990).
Neoplasia of the nasopharynx and mesenchyme flow with subsequent establishment of

osteogenic and myogenic blastemata (Sandy 2003). This
Neoplasia of the nasopharynx is rare with lymphosarcoma significant level of matrix turnover is partly regulated by
and squamous cell carcinoma being most commonly the matrix metalloproteinases and may be affected by
reported. Clinical signs include dysphagia, nasal discharge, abnormalities in gene function (Sandy 2003). The etiology
anorexia, and cachexia (Jones 1994, Sullivan & Parente of cleft palate is still largely unknown, but mutations in
2003). Treatment is limited to surgical debulking of the candidate genes have been identified in a small proportion
mass, because excision is usually not possible, followed by of cases (Wong & Hagg 2004). In other species, toxins and
intralesional chemotherapy (Jones 1994, Sullivan & medications can affect the fusion of the palatine process.
Parente 2003). Clinical evidence of cleft palate includes nasal discharge
of milk during nursing and coughing as a result of aspira-
tion of milk. Diagnosis of cleft palate is made by palpation
Cleft Palate of a deficit in the soft palate or by endoscopic observation of
Cleft palate or palatoschisis is a rare congenital anomaly the cleft palate, including observing the oropharynx beneath
affecting 0.01–0.02% of foals and represented 4% of the edges of the soft palate (Fig. 29.20). Differential diag-
608 deformities diagnosed at necropsy in neonatal foals nosis for nasal regurgitation of milk includes immature
(Bowman et al 1982, Crowe & Swerczek 1985). Defects of nasopharyngeal function, whereby the foal has not com-
the nasopharynx are categorized as secondary cleft palate pletely developed a coordinated swallowing reflex, which
or clefts of the soft and possibly also the hard portions of will usually develop given time. In both cases, aspiration
the palate. Defects of the caudal portion of the soft palate pneumonia, failure of passive transfer, and rhinitis are
are most commonly diagnosed in horses, especially those potential complications.
affecting the caudal free margin of the soft palate (Bowman Treatment of dysphagic foals should be restricted to
et al 1982, Crowe & Swerczek 1985). Cleft palates result surgical repair of the cleft palate or euthanasia. Before
principally from failure of the palatine processes to fuse. surgical correction is attempted, the presence of concur-
The development of the equine palate starts at approxi- rent congenital defects, such as cardiac anomalies, gastro-
mately 47 days’ gestation and requires development of intestinal defects, and nasal septum deviations should
the palatal shelves from the maxillary processes of the be ruled out. Attempts to medically manage a foal with a
first arch, shelf elevation, medial edge epithelial breakdown cleft palate and dysphagia are unrewarding and perhaps
inhumane. The result, at best, is an unthrifty horse with

chronic pneumonia. Surgical approaches to the soft palate
include transoral, pharyngotomy, and mandibular sym-
physiotomy, the last of these being most commonly used
and providing the best exposure (Bowman et al 1982,
Crowe & Swerczek 1985). Defects in the soft palate are R
closed in three layers. Tension on the soft palate can
be reduced by performing osteotomy of the hamulus of
the pterygoid bone, bilaterally, to decrease the pull of the
tensor veli palatini muscles, or by performing tension-
relieving incisions of the palate and lateral pharyngeal
walls (Bowman et al 1982). Defects in the hard palate are
uncommon in foals and such defects are closed with a
mucoperiosteal sliding flap combined with soft palate C
reconstruction (Bowman et al 1982).
Complications of cleft palate repair include dehiscence
of the palate reconstruction as a result of the inherent
tension on the repair and motion of the foal’s tongue,
mandibular osteitis and osteomyelitis, aspiration pneumonia,
continued dysphagia, and stunted growth of the foal.
Additionally, even if the above complications do not
occur, there is little factual evidence that surgically treated Fig. 29.21. Endoscopic image of the nasopharynx of a horse with a
foals can establish normal epiglottis–soft palate relation- nasopharyngeal cicatrix (C). R = nasopharyngeal opening of right
ships and become elite athletes. guttural pouch.
Nasopharyngeal Scarring or Cicatrix

Nasopharyngeal cicatrization has most frequently been REFERENCES
diagnosed in horses located in the southwestern USA, Ahern TJ 1993 Oral palatopharyngoplasty; a survey of one
in particular horses from the Texas Panhandle area hundred post-operative raced horses. Equine Veterinary
(Schumacher & Hanselka 1987, McClure et al 1994). Science 13: 670–672
Anderson JD, Tulleners EP, Johnston JK et al 1995
Clinical signs of nasopharyngeal cicatrix include respira- Sternothyrohyoideus myectomy or staphylectomy for
tory stridor at rest or during exercise, exercise intolerance, treatment of intermittent dorsal displacement of the
and, in some horses, abnormal vocalization. One review of soft palate in race horses: 209 cases (1986–1991).
47 cases of nasopharyngeal cicatrix reported that the Journal of the American Veterinary Medical Association
disease occurred 2.7 times more frequently in females than 206: 1909–1912
Auer DE, Wilson RG, Groenendyk S 1985 Pharyngeal
males with an age range from 6 to 20 years (Schumacher lymphoid hyperplasia in Thoroughbred racehorses in
& Hanselka 1987). Diagnosis of nasopharyngeal cicatrix is training. Australian Veterinary Journal 62: 124–126
made based on endoscopic examination of the upper Baptiste K 1997 Functional anatomy observations of the
airway. In addition to the cicatrix, which appears as a pharyngeal orifice of the equine guttural pouch (auditory
transverse circumferential scar within the nasopharynx, tube diverticulum). Veterinary Journal 153: 311–319
Barakzai SZ, Dixon PM 2005 Conservative treatment for race-
most horses also have lesions of the arytenoid or epiglottic horses affected with intermittent dorsal displacement of
cartilages and the nasopharyngeal openings of the guttural the soft palate. Veterinary Record 36: 337–341
pouches (Fig. 29.21) (Schumacher & Hanselka 1987). The Barakzai SZ, Johnson VS, Baird DH et al 2003 The efficacy of
cicatrix is generally not the cause of the airway obstruc- composite surgery for treatment of dorsal displacement
tion, which is usually caused by arytenoid chondritis or of the soft palate in 53 racing Thoroughbreds. Equine
epiglottic deformity, and therefore the cicatrix is usually Bartlett D 1979 Effects of hypercapnia and hypoxia on
not treated (Schumacher & Hanselka 1987). However, laryngeal resistance to airflow. Respiratory Physiology
three horses treated for nasopharyngeal cicatrix by sharp 37: 293–302
transection of the cicatrix were able to resume athletic Bowman KF, Tate LP Jr, Evans LH et al 1982 Complications
activity (McClure et al 1994). The etiopathogenesis of this of cleft palate repair in large animals. Journal of the
condition is not known but is assumed to be a sequela to Brouillette RT, Thach BT 1979 A neuromuscular mechanism
ulcerative pharyngitis and laryngitis (Schumacher & maintaining extrathoracic airway patency. Journal of
Hanselka 1987). Applied Physiology 46: 772–779
Brouillette RT, Bradley TT 1980 Control of genioglossus Hobo S, Matsuda Y, Yoshida K 1995 Prevalence of upper
muscle inspiratory activity. Journal of Applied Physiology respiratory tract disorders detected with a flexible video-
49: 801–808 endoscope in thoroughbred racehorses. Journal of
Carr EA, Spier SJ, Kortz GD et al 1996 Laryngeal and Veterinary Medical Science 57: 409–413
pharyngeal dysfunction in horses homozygous for hyper- Hogan PM, Palmer SE, Congelosi M 2003 Transendoscopic
kalemic periodic paralysis. Journal of the American laser cauterization of the soft palate as an adjunctive
Veterinary Medical Association 209: 798–803 treatment for dorsal displacement of the soft palate in the
Castro HA, Resende LA, Berzin F et al 1999 Electromyographic racehorse. In: Proceedings of the American Association
analysis of the superior belly of the omohyoid muscle of Equine Practitioners 48: 228–250
and anterior belly of the digastric muscle in tongue and Holcombe SJ 2001 New thoughts on URT anatomy: rele-
head movements. Journal of Electromyography and vancy. Proceeding from the 29th Annual Surgical Forum.
Kinesiology 9: 229–232 American College of Veterinary Surgeons, Washington,
Cook WR 1981 Some observations on form and function of DC, pp.59–62
the equine upper airway in health and disease: I. The Holcombe SJ, Derksen FJ, Stick JA et al 1997 Effect of bilateral
pharynx. Proceedings of the American Association of tenectomy of the tensor veli palatini muscle on soft palate
Equine Practitioners 27: 355–391 function in horses. American Journal of Veterinary
Cornelisse CJ, Holcombe SJ, Derksen FJ et al 2001 Effect of a Research 58: 317–321
tongue-tie on upper airway mechanics in horses during Holcombe SJ, Derksen FJ, Stick JA et al 1998 Bilateral
exercise. American Journal of Veterinary Research nerve blockade of the pharyngeal branch of the
62: 775–778 vagus nerve produces persistent soft palate dysfunction
Crowe MW, Swerczek TW 1985 Equine congenital defects. in horses. American Journal of Veterinary Research
American Journal of Veterinary Research 46: 353–358 59: 504–508
DeLahunta A 1977 Veterinary Neuroanatomy and Clin- Holcombe SJ, Derksen FJ, Berney C et al 2001 Effect of topical
ical Neurology, 1st edn. WB Saunders, Philadelphia, anesthesia of the laryngeal mucosa on upper airway
pp.104–107,370 mechanics in exercising horses. American Journal of
Derksen FJ 2001 Spectrum analysis of respiratory sounds in Veterinary Research 62: 1706–1710
exercising horses with experimentally induced laryngeal Jones DL 1994 Squamous cell carcinoma of the larynx and
hemiplegia or dorsal displacement of the soft palate. pharynx in horses. Cornell Veterinarian 84: 15–24
American Journal of Veterinary Research 62: 659–664 Kipper A, Frees K 1993 Hypoglossal neuritis with associated
Ducharme NG, Hackett RP, Woodie JB et al 2003 Investigation lingual hemiplegia secondary to guttural pouch mycosis.
into the role of the thyrohyoid muscles in the patho- Veterinary Pathology 30: 547–556
genesis of dorsal displacement of the soft palate. Equine Koch DB, Tate LP 1978 Pharyngeal cysts in horses.
Veterinary Journal 35: 258–263 Journal of the American Veterinary Medical Association
Feroah TR, Forster HV, Pan LG et al 2000 Reciprocal 173: 860–862
activation of hypopharyngeal muscles and their effect Kuehn DP, Folkins JW, Cutting JW 1982 Relationships between
on upper airway area. Journal of Applied Physiology muscle activity and velar position. Cleft Palate Journal
88: 611–626 19: 25–35
Feroah TR, Forster HV, Pan L et al 2001 Effect of slow wave Kuna ST 2001 Effects of pharyngeal muscle activation on
and REM sleep on thyropharyngeus and stylopharyngeus airway size and configuration. American Journal of
activity during induced central apneas. Respiratory Respiratory and Critical Care Medicine 164: 1236–1241
Physiology 124: 129–140 Kuna ST, Smickely JS, Vanoye CR 1999 Respiratory-related
Franklin SH, Naylor JR, Lane JG 2002 The effect of a tongue- pharyngeal constrictor activation on pharyngeal airway
tie in horses with dorsal displacement of the soft palate. function. Journal of Applied Physiology 86: 411–417
Equine Veterinary Journal Supplement 34: 430–433 Llewellyn HR 1997 Sternothyroideus myotomy for the
Franklin SH, Price C, Burn JF 2004 The displaced equine soft treatment of dorsal displacement of the soft palate.
palate as a source of abnormal respiratory noise during Proceedings of the American Association of Equine
expiration. Equine Veterinary Journal 36: 590–594 Practitioners 43: 239–243
Fregosi RF, Fuller DD 1997 Respiratory-related control of McClure SR, Schumacher J, Snyder JR 1994 Trans-
extrinsic tongue muscle activity. Respiratory Physiology nasal incision of restrictive nasopharyngeal cicatrix in
110: 295–306 three horses. Journal of the American Veterinary Medical
Fuller DD, Williams JS, Janssen PL et al 1999 Effect of Association 205: 461–463
coactivation of tongue protrudor and retractor muscles Mathew OP, Abu-Osba YK, Thatch BT 1984a Genioglossus
on tongue movements and pharyngeal airflow mechanics muscle responses to upper airway pressure changes:
in the rat. Journal of Physiology 519: 601–613 afferent pathways. Journal of Applied Physiology:
Gerber MA, Shulman ST 2004 Rapid diagnosis of pharyngitis Respiration and Environmental Exercise Physiology
caused by group A streptococci. Clinical Microbiology 52: 445–450
Review 17: 571–580 Mathew OP, Sant’Ambrogio G, Fisher JT et al 1984b Laryngeal
Greet TR 1987 Outcome of treatment in 35 cases of guttural pressure receptors. Respiratory Physiology 57: 113–122
pouch mycosis. Equine Veterinary Journal 19: 483–487 Mayhew IG 1989 Large Animal Neurology: A Handbook
Harrison IW, Raker CW 1988 Sternothyrohyoideus myectomy for Veterinary Clinicians, 1st edn. Lea and Febiger,
in horses: 17 cases (1984–1985). Journal of the American Philadelphia, pp.166–177
Veterinary Medical Association 193: 1299–1302 Parente EJ, Martin BB, Tulleners EP et al 1994 Upper
Haynes PF, Beadle RE, McClure JR et al 1990 Soft palate cysts respiratory dysfunctions in horses during high-speed
as a cause of pharyngeal dysfunction in two horses. exercise. Proceedings of the American Association of
Equine Veterinary Journal 22: 369–371 Equine Practitioners 40: 81–82
Peloso JG, Stick JA, Nickels FA et al 1992 Epiglottic augmen- performance in Thoroughbred yearlings: 427 cases
tation by use of polytetrafluoroethylene to correct dorsal (1997–2000). Journal of the American Veterinary
displacement of the soft palate in a Standardbred horse. Medical Association 219: 962–966
Journal of the American Veterinary Medical Association Sullivan EK, Parente EJ 2003 Disorders of the pharynx.
201: 13931395 Veterinary Clinics of North America; Equine Practice
Raker CW, Boles CL 1978 Pharyngeal lymphoid hyperplasia 19: 159–167
in the horse. Journal of Equine Medicine and Surgery Tessier C, Holcombe SJ, Derksen FJ et al 2004 Effects of
2: 202–207 stylopharyngeus muscle dysfunction on the naso-
Rehder RS 1992 Equine upper airway and guttural pouch pharynx in exercising horses. Equine Veterinary Journal
pressures during exercise. MS thesis, Cornell University 36: 318–323
Rehder RS, Ducharme NG, Hackett RP et al 1995 Measure- Tsukroff S, Ducharme NG, Bertram JE et al 1998 Relationship
ment of upper airway pressures in exercising horses with of basihyoid bone and thyroid cartilage in exercising
dorsal displacement of the soft palate. American Journal horses. Proceedings of the 1st World Equine Airway
of Veterinary Research 56: 269–274 Symposium, Guelph Ontario, Canada, CD-ROM
Sandy JR 2003 Molecular, clinical and political approaches to Tulleners E, Stick JA, Leitch M et al 1997 Epiglottic
the problem of cleft lip and palate. Surgeon 1: 9–16 augmentation for treatment of dorsal displacement of
Sant’Ambrogio G, Mathew OP, Fisher JT et al 1983 Laryngeal the soft palate in racehorses: 59 cases (1985–1994).
receptors responding to transmural pressure, airflow and Journal of the American Veterinary Medical Association
local muscle activity. Respiratory Physiology 54: 317–330 211: 1022–1028
Schumacher J, Hanselka DV 1987 Nasopharyngeal cicatrices Woodie JB, Ducharme NG, Hackett RP et al 2005a Can an
in horses: 47 cases (1972–1985). Journal of the American external device prevent dorsal displacement of the soft
Veterinary Medical Association 191: 239–242 palate during strenuous exercise? An experimental
Sisson S 1975a Equine myology. In: Getty R (editor) Sisson model. Equine Veterinary Journal 37: 425–429
and Grossman’s the Anatomy of Domestic Animals, Woodie JB, NG Ducharme, P Kanter et al 2005b Surgical
5th edn. WB Saunders, Philadelphia, pp.386–387 mobilization of the larynx (Laryngeal tie-forward) as a
Sisson S 1975b Equine digestive system. In: Getty R (editor) treatment for DDSP: a prospective study 2001–2003.
Sisson and Grossman’s the Anatomy of Domestic Animals, Equine Veterinary Journal 37: 418–423
5th edn. WB Saunders, Philadelphia, pp.471–475 Wong FK, Hagg U 2004 An update on the aetiology of oro-
Stick JA, Peloso JG, Morehead JP et al 2001 Endoscopic facial clefts. Hong Kong Medical Journal 10: 331–336
assessment of airway function as a predictor of racing
Epiglottic Fold Entrapment
30 Kira L Epstein and Eric J Parente
between 0.74% (Raphel 1982) and 2.1% (thoroughbred

Introduction
racehorses) (Sweeney et al 1991). In horses undergoing
The epiglottis is a triangular-shaped, elastic cartilage that treadmill examination for investigation of poor performance
helps to protect the airway during swallowing. The tip of or abnormal respiratory noise, the reported incidence of
the triangle points rostrally and in a normal horse, the epiglottic entrapment ranges from 2.1% (1/46) (Morris &
epiglottis sits dorsal to the soft palate during breathing. The Seeherman 1990) to 9.5% (8/92) (Kannegieter & Dore 1995).
epiglottis has a characteristic scalloped border and has a
vascular pattern on its dorsal surface. The aryepiglottic
folds are bands of tissue coursing from the corniculate
Diagnosis
process of the arytenoids to the free edge of the epiglottis, Clinical signs
and they join the glossoepiglottic fold under the epiglottis.
Epiglottic entrapment is the result of the aryepiglottic Horses with epiglottic entrapment may make abnormal
membrane enveloping the rostral aspect of the epiglottis, respiratory noises and/or have exercise intolerance;
and when so affected, the vascular pattern and scalloped alternatively, they may be asymptomatic. The presence of
edge can no longer be seen and a free edge of tissue is clinical signs is greatly dependent upon the extent of the
noted just in front of the glottis (Fig. 30.1). Entrapping
membrane thickening has been reported to occur in
20–98% of affected horses, while ulceration has been
reported to occur in 45–50% of epiglottic entrapments
(Tulleners 1990, Ross et al 1993). Entrapment can occur
persistently, or may be observed intermittently at rest
and/or during treadmill examination (Lumsden et al 1994,
Kannegieter & Dore 1995).
Epiglottic entrapment has also been associated with
hypoplasia of the epiglottis and dorsal displacement of the
soft palate. Two studies comparing radiographic epiglottic
length have shown significantly shorter epiglottic length in
horses with epiglottic entrapment when compared to
normal horses (Lindford et al 1983, Tulleners 1991). In
one study, 31% of thoroughbreds and 36% of standard-
breds with epiglottic entrapment were judged to have a
hypoplastic epiglottis (Tulleners 1991). Additionally, dorsal
displacement of the soft palate can occur concurrently
with an entrapment (Boles et al 1978, Tate et al 1990,
Lumsden et al 1994, Kannegieter & Dore 1995).
Epiglottic entrapment is primarily a disease of racing
thoroughbreds and standardbreds, although it is also
reported in older thoroughbreds and in other breeds. In
a study of 102 horses with epiglottic entrapment, one
12-year-old thoroughbred was affected (Tulleners 1990).
Another study of 56 horses with epiglottic entrapment
Fig. 30.1. Simple epiglottic entrapment with a clear outline of the
included one Appaloosa and one American Saddlebred epiglottic shape beneath the entrapping membrane. The normal
(Lumsden et al 1994). The incidence of epiglottic entrap- vascular pattern and scalloped edge of the epiglottis are obscured by
ment in randomly evaluated horses has been reported to be the entrapping membrane.
459
460 30 Epiglottic Fold Entrapment
abnormality of the entrapping membrane and the presence

of intercurrent respiratory problems. Some clinicians feel
that an entrapment may precipitate dorsal displacement of
the soft palate in certain horses, thus resulting in more
significant noise and performance-limiting problems. It
has been speculated that the membrane may be tightly
adhered to the epiglottis in horses that are asymptomatic,
and therefore it does not cause respiratory obstruction
(Kannegieter & Dore 1995). Billowing of the entrapping
membrane during expiration may cause increased airflow
turbulence. This may cause abnormal respiratory noise and
a decrease in the nasopharyngeal cross-sectional area,
which may lead to increased upper airway inspiratory
resistance and thus to increased airflow pressures, resulting
in exercise intolerance (Morris & Seeherman 1990).
Objective assessments of the impact of epiglottic entrap-
ment on respiratory function are scarce. Measurement of
inspiratory upper airway pressure at maximal exercise in
horses with uncomplicated epiglottic entrapment showed
only slight increases (3–5 cmH2O), compared with normal
horses. However, in one horse with an ulcerated and thick-
ened entrapping membrane, the increase in inspiratory Fig. 30.2. An epiglottic entrapment with a blunted rostral tip (arrows)
upper airway pressure was moderate (15 cmH2O) (Williams probably indicates that the tip of the epiglottis is rolled up into
et al 1990). In a study of cardiorespiratory and metabolic the entrapment. Even with surgical correction, epiglottic deformity
may persist.
responses to exercise, values from one horse with epiglottic
entrapment were similar to those of a normal horse (King
et al 1994). Despite the minimal impact on respiratory
function noted during treadmill testing in the above limited (Fig. 30.3). If entrapment is suspected, but the epiglottis is
studies, it is uncommon to compete a horse with epiglottic not entrapped at the time of the endoscopic examina-
entrapment. tion, the horse should be induced to swallow, to try and
reproduce the entrapment, or a high-speed treadmill
Endoscopy examination should be performed.
It is important to differentiate the endoscopic appear-
Horses with a history of exercise intolerance and/or ance of epiglottic entrapment from that of (primary) dorsal
abnormal respiratory noise should be evaluated by resting displacement of the soft palate and epiglottitis. In a study
endoscopy, and also by high-speed treadmill examination if of 20 horses with epiglottitis, 11 had been referred with a
necessary. A diagnosis of epiglottic entrapment is based on diagnosis of epiglottic entrapment but only one actually
the characteristic endoscopic appearance of an entrapped had concurrent epiglottic entrapment (Hawkins & Tulleners
epiglottis when the scalloped border and dorsal vascular 1994). With epiglottitis, endoscopic findings may include
pattern are not visible because of the presence of the thickening, edema, and/or discoloration of the epiglottis,
entrapping membrane. Instead, the outline of the trian- ulceration and/or reddening of the epiglottic mucosa,
gular shape of the epiglottis is apparent under the exposed cartilage at the epiglottic tip, the presence of
smoother, rounded margins of the entrapping membrane. granulation tissue on the lingual surface of the epiglottis,
As mentioned previously, variable degrees of thickening and/or dorsal angulation of the epiglottis. However, it is
and ulceration may be present on the entrapping important to recognize that with epiglottitis, the dorsal
membrane. If the rostral tip of the epiglottis appears vascular pattern and scalloped border of the epiglottis,
blunted within the entrapment, it is likely that the tip of while distorted, are visible. With primary dorsal displace-
the epiglottis is folded back on itself under the membrane ment of the soft palate the caudal edge of the soft palate is
(Fig. 30.2). This may result in a persistent epiglottic visible and the epiglottis is hidden.
deformity even after the entrapment has been resolved. If a
concurrent dorsal displacement of the soft palate is Assessment of epiglottic hypoplasia
present, two free edges of membrane may be seen rostral to
the glottis (caudal aspects of the soft palate and entrap- Both radiography and endoscopy can be useful in assess-
ping membrane), and a focal bulging of the soft palate ing epiglottic hypoplasia (reduced size), which should not
may be caused by the apex of the underlying epiglottis be confused with epiglottic flaccidity. A technique for
30 Epiglottic Fold Entrapment 461
techniques have been described for the surgical treatment

of epiglottic entrapment. Axial division of the entrapping
membrane can be performed in a sedated standing horse
with endoscopic guidance and local anesthesia using a
curved bistoury or hook knife transnasally (Honnas &
Wheat 1988, Greet 1995). Transendoscopic electrosurgery
(Jann & Cook 1985, Sullins 1991), or transendoscopic laser
surgery [neodymium : yttrium–aluminum–garnet (Nd:YAG)
or diode lasers] (Tate et al 1990, Tulleners 1990, 1991,
Greet 1995, Parente 2002) may also be used. Alterna-
tively, axial division can be performed in an anesthetized
horse under endoscopic guidance using a curved bistoury
transorally (Ross et al 1993, Lumsden et al 1994).
Resection of the entrapping membrane can be performed
via laryngotomy or pharyngotomy under general anes-
thesia (Ordidge 1977, Honnas & Wheat 1988, Lumsden
et al 1994). This resection can also be performed with elec-
trosurgery or transendoscopic laser using local anesthesia
in sedated standing horses with endoscopic guidance
(Sullins 1991, Parente 2002).
Performing standing surgeries alleviates the risks
associated with anesthesia and recovery and can often be
Fig. 30.3. A concurrent epiglottic entrapment and dorsal displacement
performed on an outpatient basis. Electrosurgery and laser
of the soft palate. There are two separate edges of tissue visible, the
entrapment (arrowhead), and the free edge of the palate (arrow) from surgery require specialized and expensive equipment as
the displacement. There is also a bulging of the soft palate caused by well as surgical technique and safety training. Additional
the entrapped epiglottis below it. aftercare and convalescence are required for healing of
laryngotomy or pharyngotomy wounds following open
surgical methods of resection.
Currently, the most commonly used surgical techniques
radiographic assessment of epiglottic length has been in the USA are axial division with a laser in the sedated
described by Lindford et al (1983) with good correlation to standing horse or axial division with a curved bistoury in
post-mortem measurements. A lateral radiograph of the an anesthetized horse.
pharyngeal region taken with the horse’s head in a rest-
ing position can be used to measure the thyroepiglottic Axial division with a laser
length. Adjustments must be made for magnification and
for the additional distance from the base of the epiglottis to The most commonly used lasers for this procedure are
the thyroid cartilage to accurately assess the epiglottic Nd:YAG and diode lasers. They produce light of similar
length. In a study by Tulleners (1991), radiographic wavelength and the laser fibers are compatible with
thyroepiglottic length in horses with epiglottic entrapment transendoscopic use, and both provide good hemostasis
and endoscopically apparent epiglottic hypoplasia was (Chapter 39). They can be used in a contact or non-contact
significantly shorter than in horses with epiglottic manner, although contact is more generally used. The
entrapment and an endoscopically normal epiglottis. Thus, diode laser has the advantage of being easily portable and
most clinicians now rely solely on the endoscopic appear- can be used with a standard electrical outlet. Proper eye
ance of the epiglottis. protection should be worn when operating any laser.
Before beginning surgery, the horse should be properly
sedated, placed in standing stocks, and local anesthetic
Treatment should be applied transendoscopically to the epiglottis.
Local anti-inflammatory medication and rest may be Sedation can be achieved with an α2-agonist such as
effective treatments for simple entrapments when diag- xylazine (suggested dose 0.44 mg/kg) or detomidine (sug-
nosed early. However, more often, entrapments diagnosed gested dose 0.006–0.01 mg/kg) intravenously. Depending
during resting endoscopy are treated surgically. In one on the length of the procedure, additional half doses of the
study, four of 38 horses with epiglottic entrapment were sedation may be required. Acepromazine (suggested dose
treated with an anti-inflammatory pharyngeal spray alone, 0.01 mg/kg) can also be administered, depending on the
with resolution of the entrapment without any further disposition of the horse and clinician preference. Opioids
treatment in three of them (Greet 1995). A variety of such as butorphanol are avoided by some clinicians because
horses may sometimes have excessive head movement most rostroventral portion of the membrane can be difficult
following administration. Once sedated, local anesthetic to divide because the membrane starts to retract beneath
solution is applied, using a transendoscopic catheter. the epiglottis toward the end of the procedure. Therefore,
The entrapping membrane is divided along its midline several passes in the rostral region should be made in the
using repeated passes of the laser fiber with mild pressure initial stages. The laser should be activated only while the
contact from a caudal to rostral direction (Fig. 30.4). The fiber is being moved to avoid excessive charring of tissue.
A B
Fig. 30.4. (A) The laser fiber has made the first axial cut through the
entrapping membrane in contact fashion. (B) Progression through
the layers of membrane and retraction of the membrane back under-
neath the epiglottis is apparent. (C) The completed surgery with the
C
membranes just barely visibly under the epiglottis.
Care should be taken to avoid inadvertent contact with and forceps. The aryepiglottic fold is grasped bilaterally with
thermal damage to the dorsal surface and tip of the a second and third Allis tissue forceps to allow more
epiglottis. Changing the horse’s head position may be even tension and better visualization of the epiglottis.
helpful to allow appropriate placement of the laser fiber. Metzenbaum scissors, electrocautery, or a laser can be used
Stimulation of swallowing and application of ventral for resection of the entrapping membrane. The epiglottic
pressure on the epiglottis with the endoscope tip may help cartilage should be identified by palpation and visualiza-
retract the membrane ventrally when the cut is completed. tion before resection, to prevent it being cut. Ideally,
If the membrane does not recede under the epiglottis after the membrane should be resected within 2–3 mm of the
complete axial division, some of the entrapping membrane epiglottic tip and 1–1.5 cm to either side of the midline
can be resected with the laser or alternatively, the horse (Stick et al 1999). The membrane can be distorted very
can be treated successfully with local and systemic anti- easily with tension and great care should be exercised not
inflammatory medication. to resect an excessive amount of tissue, which may
increase the incidence of dorsal displacement of the soft
Axial division with a curved bistoury palate postoperatively.
This procedure can be performed in the standing sedated

horse or under general anesthesia with a short-acting
Aftercare
injectable anesthetic such as ketamine. With the horse in Following axial division, horses should be starved for
lateral recumbency, a mouth speculum is placed and the several hours to allow the sedation or anesthesia to wear
tongue is retracted and the medial aspect of the upper off, and so prevent dysphagia and subsequent aspiration.
cheek teeth should be rasped (floated). The surgeon Antimicrobials may be indicated in cases of thickened or
manually displaces the soft palate through the mouth and ulcerated entrapping membranes, or following a laryn-
an endoscope is passed through the mouth to allow gotomy procedure. A combination of non-steroidal anti-
visualization of the epiglottis. Under endoscopic guidance, inflammatories (phenylbutazone or flunixin meglumine
the curved bistoury (shorter than the transnasal bistoury) typically) and corticosteroids can be administered, based on
can be positioned between the dorsal surface of the clinician preference. Additionally, topical anti-inflammatory
epiglottis and the entrapping membrane on the midline. therapy such as pharyngeal sprays containing various
The sharp point of the bistoury should penetrate the combinations of dimethyl sulfoxide and/or corticosteroids
aryepiglottic fold immediately rostral to the apex of the can be applied twice daily by transnasal catheter. In horses
epiglottis and tension must be maintained at all times to treated without laryngotomy, stall rest is recommended for
avoid repositioning of the bistoury. At this time, the approximately 7–14 days. Repeat endoscopy should ideally
endoscope can be removed or operated by an assistant, be performed before returning the horse to race training to
because the surgeon will need both hands. One hand is check that healing is progressing appropriately.
inserted into the mouth to apply ventral pressure and
guard the point of the bistoury, preventing damage to the
base of the tongue, as the bistoury is pulled rostrally by the
Prognosis
other hand. Complete division should be confirmed Rates of postoperative recurrence of entrapment vary
endoscopically. depending on the surgical technique performed (Fig. 30.5).
As mentioned, the curved bistoury has been used per The re-entrapment rates are as follows: 5–15% after trans-
nasum in sedated standing horses, but there is significant nasal axial division using a curved bistoury or hook knife
additional risk of inadvertent damage to the soft palate, (Honnas & Wheat 1988, Greet 1995); approximately 10%
esophagus or other structures if the horse swallows during after transoral axial division using a curved bistoury (Ross
the procedure and therefore this technique is no longer et al 1993, Lumsden et al 1994); approximately 5% after
recommended. transendoscopic laser axial division (Tulleners 1990); as
high as 40% (two of five horses) after transendoscopic
Resection through a laryngotomy electrosurgical axial division (Jann & Cook 1985); and as
high as 36% after resection via laryngotomy or pharyn-
For resection of an epiglottic entrapment through a gotomy (Lumsden et al 1994). Dorsal displacement of the
laryngotomy, horses are placed under general anesthesia in soft palate has been reported in 5–10% of cases following
dorsal recumbency. While a pharyngotomy approach can transoral axial division using a curved bistoury (Ross et al
be used to access the ventral aspect of the epiglottis, it is 1993, Lumsden et al 1994); in 15% of cases following
much preferred to use a routine laryngotomy approach. transendoscopic laser division (Tulleners 1990); and in 9%
One side of the aryepiglottic fold is grasped with Allis tissue of cases following resection via laryngotomy or pharyn-
forceps to retrovert the epiglottis into view. Care should be gotomy (Lumsden et al 1994). Damage to the tip of the
taken to avoid grasping the epiglottic cartilage with the epiglottis is a potential complication with use of the bistoury,
laryngotomy. A significant advantage of transendoscopic

laser resection is the normal anatomical positioning of the
epiglottis while resecting the tissue using this technique,
versus resection through a laryngotomy when the epiglottis
is in a distorted, retroverted position. Regardless of which
technique is employed, epiglottic deformity as a result of
chronic entrapment will often negatively affect the post-
operative prognosis.
REFERENCES
Boles CL, Raker CW, Wheat JD 1978 Epiglottic entrapment by
arytenoepiglottic folds in the horse. Journal of the
Greet TRC 1995 Experiences in treatment of epiglottal
entrapment using a hook knife per nasum. Equine
Hawkins JF, Tulleners EP 1994 Epiglottitis in horses: 20 cases
(1988–1993). Journal of the American Veterinary
Medical Association 205: 1577–1580
Honnas CM, Wheat JD 1988 Epiglottic entrapment. A trans-
nasal surgical approach to divide the aryepiglottic fold
Fig. 30.5. Recurrent epiglottic entrapment after axial division with axially in the standing horse. Veterinary Surgery 17:
a curved bistoury. Note incomplete axial cut that resulted in the 246–251
re-entrapment. Jann HW, Cook WR 1985 Transendoscopic electrosurgery
for epiglottal entrapment in the horse. Journal of the
Kannegieter NJ, Dore ML 1995 Endoscopy of the upper
respiratory tract during treadmill exercise: a clinical
and with laser or electrosurgical procedures. As noted, study of 100 horses. Australian Veterinary Journal
transnasal axial division with the bistoury has caused the 72: 101–107
potentially severe complication of inadvertent injury to the King CM, Evans DL, Rose RJ 1994 Cardiorespiratory and
soft palate, which may necessitate euthanasia. metabolic responses to exercise in horses with various
Concurrent upper respiratory disorders, including abnormalities of the upper respiratory tract. Equine
epiglottic hypoplasia and mucosal ulceration, may com- Lindford RL, O’Brien TR, Wheat JD et al 1983 Radiographic
plicate the correction of epiglottic entrapment and worsen assessment of epiglottic length and pharyngeal and
the prognosis. In a study of 51 horses with epiglottic laryngeal diameters in the Thoroughbred. American
entrapment, horses with concurrent upper airway abnor- Journal of Veterinary Research 44: 1660–1666
malities (including, dorsal displacement of the soft palate, Lumsden JM, Stick JA, Caron JP et al 1994 Surgical treatment
for epiglottic entrapment in horses: 51 cases (1981–1992).
subepiglottic cyst, arytenoid chondropathy, and left recur- Journal of the American Veterinary Medical Association
rent laryngeal neuropathy) were significantly less likely to 205: 729–735
return to racing than horses with uncomplicated epiglottic Morris EA, Seeherman HJ 1990 Evaluation of upper respi-
entrapment (Lumsden et al 1994). In a study on trans- ratory tract function during strenuous exercise in
endoscopic Nd:YAG laser axial division, three out of four racehorses. Journal of the American Veterinary Medical
horses with re-entrapment and nine out of nine horses Ordidge RM 1977 Epiglottic entrapment in the horse.
with postoperative dorsal displacement of the soft palate Veterinary Record 100: 365–366
were judged to have a hypoplastic epiglottis (Tulleners Parente EJ 2002 Transendoscopic axial division of epiglottic
1990). However, a later study showed no significant asso- entrapment. Clinical Techniques in Equine Practice
ciation between performance before and after surgery and 1: 9–12
Raphel CF 1982 Endoscopic findings in the upper respiratory
the presence of epiglottic hypoplasia (Tulleners 1991). tract of 479 horses. Journal of the American Veterinary
It has been suggested that severe ulceration, thickening, Medical Association 181: 470–473
or scarring of the entrapping membrane may make axial Ross MW, Gentile DG, Evans LH 1993 Transoral axial division,
division more difficult, and resection via laryngotomy or under endoscopic guidance, for correction of epiglottic
pharyngotomy may be indicated in those cases (Ross et al entrapment in horses. Journal of the American Veterinary
1993, Lumsden et al 1994). However, with experience, Stick JA, Tulleners EP, Robertson JT et al 1999 Larynx. In:
resection of the tissue via transendoscopic laser surgery Auer JA, Stick JA, (editors) Equine Surgery, 2nd edn.
may yield a better prognosis than resection through a Saunders, Philadelphia, pp.349–368
Sullins KE 1991 Standing endoscopic electrosurgery. Veterinary entrapment in standing horses. Journal of the American
Clinics of North America; Equine Practice 7: 571–581 Veterinary Medical Association 196: 1971–1980
Sweeney CR, Maxson AD, Soma LR 1991 Endoscopic findings Tulleners EP 1991 Correlation of performance with endo-
in the upper respiratory tract of 678 Thoroughbred scopic and radiographic assessment of epiglottic hypo-
racehorses. Journal of the American Veterinary Medical plasia in racehorses with epiglottic entrapment corrected
Association 198: 1037–1038 by use of contact neodymium:yttrim aluminum garnet
Tate LP, Sweeney CL, Bowman KF et al 1990 Transendoscopic laser. Journal of the American Veterinary Medical
Nd:YAG laser surgery for treatment of epiglottal entrap- Association 98: 621–626
ment and dorsal displacement of the soft palate in the Williams JW, Meagher DM., Pascoe JR et al 1990 Upper airway
horse. Veterinary Surgery 19: 356–363 function during maximal exercise in horses with obstruc-
Tulleners EP 1990 Transendoscopic contact neodymium: tive upper airway lesions. Effect of surgical treatment.
yttrium aluminum garnet laser correction of epiglottic Veterinary Surgery 19: 142–147
Fourth Branchial Arch Defects
31 J Geoffrey Lane
(Dixon et al 1993) involved a 7-year-old thoroughbred

Introduction and Definition
which showed sudden-onset dyspnea and was later
Congenital and developmental deformities of the equine euthanased because of severe aerophagia. From this
larynx are not common and those which have been limited list of reports the impressions might be gained that
described have generally comprised defects of the cartilage the disorder is so rare, and that the diagnosis is so straight-
skeleton which supports the moving components – the forward, that it is scarcely worthy of specific attention.
arytenoid cartilages and vocal folds – and of the extrin- However, more recently a series of 60 cases of 4-BAD in
sic musculature which links the larynx to the upper thoroughbreds and eight cases in other breeds has been
esophagus. In the human embryo, the muscles and car- reviewed (Lane 2003) and that study forms the basis for
tilages of the larynx form from the fourth and sixth this contribution.
branchial arches (Hast 1972, Zaw-Tun & Burdi 1985). The term 4-BAD was suggested as a more appropriate
The extrinsic structures, which include the wing of the description because it implies that there is a syndrome of
thyroid cartilage and the associated cricothyroid articu- deformities that may afflict the derivatives of the fourth
lation, the cricothyroid muscle and the upper esophageal branchial arch (Lane 1993). It had previously been sug-
sphincter muscles (i.e. the thyropharyngeus and crico- gested (Goulden et al 1976) that failure of development of
pharyngeus muscles) all stem from the fourth arch. The these structures might offer an explanation for RDPA.
intrinsic laryngeal muscles, and the cricoid and arytenoid However, in isolation, the term RDPA is misleading because
cartilages form from the sixth branchial arch. There is no it does no more than describe the endoscopic tip of an
reason to suspect that the equine larynx develops in a dif- iceberg and gives little intimation of the major underlying
ferent fashion from the human larynx, and the syndrome congenital structural deformities.
which is described here consists of aplasia, or varying The presenting signs of 4-BAD reflect the structures
degrees of hypoplasia, of one or more of the cartilaginous which are defective and fall into two broad groups – dynamic
or muscular structures derived from the fourth arch, unilat- obstructions to airflow producing abnormal respiratory
erally or bilaterally, and is termed the fourth branchial arch noises during exercise, and incompetence of the upper
defect syndrome or, in its abbreviated form, 4-BAD (Lane esophageal sphincter causing involuntary aerophagia,
1993). This congenital laryngeal deformity is not rare, but occasionally leading to tympanitic colic.
it has possibly been underdiagnosed in the past through Normal abduction of the arytenoid cartilages and vocal
misinterpretations of the endoscopic findings or through folds is compromised when the mechanical stability
a failure to use other diagnostic techniques, specifically afforded by the cartilage box structure of the larynx is
laryngeal palpation. defective. Thus, when there is no stable union between the
The 4-BAD syndrome has most often been described in thyroid and cricoid cartilages the forces applied through
isolated case reports in the equine veterinary literature contraction of the cricoarytenoideus dorsalis muscle(s)
under other titles and may be subject to a number of may be transmitted via the vocal fold(s) to draw the body
misconceptions. Under the guise of rostral displacement of of the thyroid caudally rather than to abduct the vocal
the palatopharyngeal arch (RDPA) there have been process(es) laterally. Such futile cricoarytenoideus dorsalis
descriptions of 13 previous cases; these have involved eight activity might give the false impression on endoscopy of
thoroughbreds (Cook 1974, Goulden et al 1976, Blikslager laryngeal hemiparesis in animals with unilateral defects, or
et al 1999), three warmbloods (Wilson et al 1986), one of laryngeal paresis in bilaterally diseased horses. RDPA
Haflinger (Deegen & Klein 1987), and one Hanovarian is more easily explained: the caudal pillars of the soft
(Klein et al 1989). The ages at presentation ranged from palate are normally anchored at the esophageal aditus and
3 months to 6 years and the clinical signs predominantly are not visible by endoscopy per nasum because they are
related to abnormal respiratory noises (seven cases), dys- hidden behind the apices of the corniculate processes of
phagia (one case) and recurring colic (one case). A further the arytenoid cartilages. When the muscular support
case, described as “cricopharyngeal laryngeal dysplasia” of the proximal esophagus is absent, the pillars lose this
467
468 31 Fourth Branchial Arch Defects
anchorage and become passively displaced rostral to the 4-BAD most commonly exists as a right unilateral
apices of the corniculate processes. Involuntary aerophagia disorder and, although some cases are bilaterally afflicted,
is inevitable when the proximal esophagus cannot be right-sided defects arise at least six times more frequently
maintained in a closed state and there is continuity than on the left side alone (Lane 2003). In 60 afflicted
between the airspaces of the nasopharynx and the upper thoroughbreds bilateral defects of the fourth branchial
esophagus. It should not be surprising that horses with arch were identified in 15 horses, the anomalies were
4-BAD are occasionally afflicted with tympanitic colic. restricted to the right side in 39 cases, and to the left side in
Normal deglutition depends upon contraction of the crico- six of the patients.
and thyro-pharyngeal musculature to initiate primary A pretraining survey of almost 3,500 thoroughbred
waves of esophageal peristalsis, but in 4-BAD-afflicted yearlings yielded seven animals afflicted with 4-BAD,
horses the transfer of ingesta through the esophagus intimating that the prevalence of the condition is in the
is dependent upon secondary peristaltic waves alone. order of two per 1,000 foaled in this breed (Lane 2003).
Nevertheless, dysphagia is an unusual presenting sign, This survey was performed over 16 years on behalf of an
possibly because there is no obstruction to the passage owner–breeder and, apart from selection for genetic excel-
of ingesta. lence, the group as a whole had not been subjected to any
prior screening process when the above examinations were
performed. To put this incidence of 4-BAD into context, the
Clinical Manifestations same survey led to the identification of five yearlings with
Although the overwhelming majority of horses identified subepiglottal cysts, five with idiopathic right-sided laryn-
with 4-BAD have been thoroughbreds, it is likely that any geal malfunction, and two with epiglottal entrapment.
breed can be afflicted. Apart from the isolated case reports
mentioned above and the previously noted 60 thorough- Diagnosis and Differential Diagnosis
breds, the only major review of the disorder included one
Dartmoor pony (aged 5 months at the time of presenta- Palpation
tion), two Welsh Section A ponies (5 months and 11 months),
Palpation is a straightforward but effective technique in the
one Warmblood (5 months), two Irish Draught horses
diagnosis of 4-BAD. Its purpose is to identify defects of the
(2 and 4 years), one Cob (5) and one part-bred hunter
laryngeal cartilage skeleton. The technique depends upon
(6 years) (Lane 2003). There appears to be no sex predis-
assessing the space between the cricoid and thyroid car-
position to this congenital laryngeal defect.
tilages. Normally this space is restricted to a small gap
The circumstances in which the diagnosis of 4-BAD was
ventrally, corresponding to the cricothyroid ligament. As
made in the 60 thoroughbreds were as follows:
the fingers pass laterally in normal horses, the wings of the
● referred for clinical investigation of abnormal respira- thyroid cartilage can be felt overlapping the cricoid ring.
tory noise (37) A large gap is present on the defective side(s) of those
● referred for investigation of dysphagia (1) horses with absence of one or both wings of the thyroid
● identified at prepurchase examination, including sales (Fig. 31.1). The overwhelming majority of 4-BAD-afflicted
arbitration panel (8) horses can be identified by palpation alone – a positive
● identified during routine stud pretraining or presales finding was achieved in 55 out of 58 horses where the find-
screening (13) ings were documented, with 11 bilateral gaps, 39 right-
● incidental finding during investigation of unrelated sided defects, and only five with left unilateral defects
disease (1) identified (Lane 2003). However, the total number of cases
with positive findings included three horses where palpa-
Thus, the most frequent presenting sign is abnormal
tion was used retrospectively after surgery had confirmed a
respiratory noise at exercise, which was present in 50
defect of the thyroid cartilage (see below).
out of these 60 horses. The solitary case with dysphagia
was a foal that was concurrently afflicted with a unilateral
hypoplasia of the soft palate. Six of the non-thoroughbreds Endoscopy
were referred for investigation of stridor at exercise, one Endoscopy of the upper respiratory tract will reveal
had shown recurrent tympanitic colic and the last non- reduced arytenoid motility on the afflicted side(s) and/or
thoroughbred (an asymptomatic entire male) was identified RDPA. Sometimes, in bilateral cases where a comparison
during a prebreeding survey. One reason why thorough- between right- and left-sided movements is sought, evi-
breds may be overrepresented in the diagnosis of 4-BAD dence of reduced laryngeal function is more difficult to
could be that afflicted horses in less athletic breeds are not establish. Similarly, because recurrent neuropathy is an all
exerted to the point where untoward respiratory sounds are too familiar disorder afflicting the left side of the equine
evident and veterinary attention may not be sought unless larynx, the correct diagnosis of 4-BAD may be overlooked
other less frequent signs, such as colic, arise. in left-sided unilaterally afflicted horses. Reduced motility
31 Fourth Branchial Arch Defects 469
Fig. 31.1. The appearance of the laryngeal

cartilages of a horse unilaterally afflicted
with 4-BAD on the right side: (A) view of
the normal left side, (B) view of the defec-
tive right side. Note the absent wing of the
thyroid cartilage and the resultant wide
cricothyroid space (arrow).
on the right side of the larynx is always more likely to Endoscopy during high-speed treadmill endoscopy
sound alarm bells (Fig. 31.2) and 4-BAD is the most provides a definitive means to identify the structures that
common cause of such a finding (Tulleners et al 1996). are intruding into the airway during forceful respiration.
RDPA may be obvious to the extent that it is possible to As is frequently the case with dynamic collapse of the
see an open esophageal aditus (Fig. 31.3) but it is, on occa- upper respiratory tract, the obstructions are often complex
sions, more subtle with no more than a “lipping” of the with partial collapse of the arytenoid cartilage and axial
displaced palatal arch over the apices of the corniculate deviation of the aryepiglottal fold being the most common
processes. RDPA will be evident only in those horses which combination. Such information may be helpful if surgical
have aplasia or hypoplasia of the thyropharyngeus and/or correction of the respiratory obstruction is to be considered.
cricopharyngeus muscles, which accounts for slightly more
than half of cases – present in 30 of the 59 horses where Radiography
the technique was applied (Lane 2003). However, overall
endoscopy provided positive findings in 58 out of the 59 Radiography of the pharynx and larynx takes advantage
cases of 4-BAD where it was applied, the exception being a of the excellent contrast that exists in this area and seeks
horse with very minor defects that were only confirmed by to show a continuous column of air between the naso-
a combination of endoscopy during treadmill exercise and pharynx and the upper esophagus. This can only arise
surgical exploration. when the upper esophageal sphincter muscles are defective,
Fig. 31.3. Endoscopic view of the larynx of a 2-year-old filly presenting

Fig. 31.2. Endoscopic view of the larynx of a 7-year-old gelding pre- with abnormal inspiratory noise at exercise. Note the rostral displacement
senting with abnormal inspiratory noise at exercise. Note the reduced of the caudal pillars of the soft palate and the open esophageal aditus.
abduction by the right arytenoid cartilage and vocal fold. Congenital
defects of the cartilages and musculature were only discovered when
prosthetic laryngoplasty was mistakenly attempted.
otherwise the esophageal aditus remains closed and no

air enters. In lateral projections of cases of 4-BAD with
RDPA the rostrally displaced palatal pillars are seen as a
“dew drop” dorsal and slightly rostral to the corniculate
processes of the arytenoids and large volumes of air are
present in the esophagus (Fig. 31.4). Clearly, radiography
will only yield positive results in those cases where RDPA
is identifiable on endoscopy. Thus, in clinical practice
radiography may be regarded as a luxury rather than a
necessity in the diagnosis of 4-BAD. There will be no
radiological abnormalities in those afflicted horses showing
reduced arytenoid motility but no RDPA (Lane 2003). Fig. 31.4. Lateral radiograph of pharynx and larynx of the same
Dynamic fluoroscopic studies of deglutition (e.g. using 2-year-old filly shown in Fig. 31.3 showing a rostrally displaced palato-
pharyngeal arch (single arrow) and an air column in the proximal
a bran mash impregnated with barium sulfate as the con-
esophagus (double arrows).
trast medium) may be used to assess the influence of 4-BAD
on deglutition. In normal horses, primary esophageal peris-
talsis is triggered by the closure of the upper esophageal
sphincter after the passage of food and fluid boluses from Exploratory surgery/autopsy
the oropharynx to the proximal esophagus has occurred.
However, in horses with defective thyropharyngeus and Clearly the full extent of the anatomical anomalies present
cricopharyngeus musculature, this mechanism cannot in any individual 4-BAD-afflicted horse can only be con-
apply, with the result that ingesta is moved caudally by firmed by exploratory laryngeal surgery or autopsy. One or
secondary waves of peristalsis initiated by stretch receptors other of these procedures was applied to 11 of 60 horses
in the esophageal wall after a mass of ingesta has been (Lane 2003). In the two horses with endoscopic evidence of
propelled caudally by the pharyngeal “stripping wave”. left laryngeal dysfunction, but without RDPA, an incorrect
31 Fourth Branchial Arch Defects 471
diagnosis of recurrent laryngeal neuropathy was made nature of the underlying disorder because there have been
and it was only when prosthetic laryngoplastic surgery reports of resection of rostrally displaced palatal pillars
was attempted that the defective laryngeal structures either by sharp instrumentation or with a cutting laser. It
were discovered. One horse with a right-sided 4-BAD was comes as no surprise that the results of these techniques
similarly misdiagnosed preoperatively and the deformity were universally disappointing (Blikslager et al 1999).
was only confirmed at surgery. In all three horses, a The racing performance statistics of the afflicted horses
palpable defect between the cricoid and thyroid cartilages are incomplete but of 51 affected cases that were raced,
on the affected side had been overlooked before surgery but seven horses won races and three others were placed. One
was confirmed postoperatively. horse won six races between the ages of 2 and 6 years.
A full autopsy was performed on six afflicted horses. The However, none of the horses has won a group, listed or
most consistent findings consisted of maldevelopment stakes race and the majority of the successes were achieved
of one or both wings of the thyroid cartilage and con- over short distances (Lane 2003). It is concluded that
sequently absence of the cricothyroid articulation(s). These 4-BAD is likely to be a performance-limiting disorder and
are the features that lend themselves to diagnosis by that afflicted horses cannot be recommended for purchase
palpation. The frequency of aplasia or hypoplasia of the whenever they are identified before sale.
cricothyroid musculature cannot be estimated other than
at autopsy. In all six horses the cricothyroid muscles were
symmetrical in appearance – normal in two, vestigial in
Discussion and Conclusions
two, and aplastic in two. The cricopharyngeus muscular Fourth branchial arch defects constitute an important
sphincter was generally absent or hypoplastic (Lane 2003). syndrome which may arise in any breed of horse but
which is more likely to be identified in racehorses simply
Differential diagnosis because they are subjected to the greatest athletic exertion
where any respiratory impediment will cause performance
The 4-BAD syndrome should be considered as an alter- limitation. Most afflicted horses present with abnormal
native diagnosis in cases presented as stereotypic “wind- respiratory noise during exercise. An incidence of two cases
sucking” behavior. Frequently those involved in the routine per 1,000 thoroughbreds foaled (0.2%) means that all
stable care of afflicted horses will report hearing “belching” clinicians involved in equine practice will encounter horses
sounds corresponding to the passage of air out of the with 4-BAD from time to time. Indeed, the condition is
esophagus. Clearly, no horse should be subjected to any form more common in thoroughbreds than other better recog-
of therapy for stereotypic aerophagia until the possibility of nized entities such as subepiglottal cyst and epiglottal
4-BAD has been eliminated by palpation and endoscopy. entrapment, although it is conceded that the latter disorder
The most likely cause for diagnostic confusion lies with is frequently acquired in later life.
those horses that show reduced laryngeal function on one Previous reports have often used the term RDPA as if it
or both sides but without RDPA, and that might otherwise were a diagnosis in its own right rather than an endoscopic
be diagnosed as being afflicted with recurrent laryngeal finding pointing to a serious underlying laryngeal deformity.
neuropathy if endoscopy is used and palpation is not. As with many obstructive disorders of the upper respi-
Horses with right-sided 4-BAD account for the majority of ratory tract, an overdependence on endoscopy of the
cases with reduced right-sided laryngeal motility. However, resting horse, to the exclusion of other simpler techniques
it is correct clinical practice to explore other possibilities by such as palpation and an exercise test, is likely to lead
checking the course of the recurrent nerve at the level of to a failure to achieve a complete or correct diagnosis.
the ipsilateral auditory tube diverticulum, examining the Laryngeal palpation should routinely be used to identify
ipsilateral neck for evidence of scarring, and assessing the defects of the cartilage skeleton in horses with 4-BAD
filling of the ipsilateral jugular vein. as well as to assess the presence or absence of atrophy of
Horses that have recently been subjected to laryngeal the intrinsic musculature in cases of recurrent neuropathy,
surgery or have sustained trauma in this region may and investigate the presence of scars from previous surgical
develop swelling in the area of the cricopharynx that can interferences.
displace the caudal pillars of the soft palate forwards, It is difficult to explain the clear overrepresentation of
resembling RDPA. Sedation also causes relaxation of the right-sided 4-BAD. It seems improbable that there are equal
nasopharyngeal muscles that may mimic RDPA. numbers of right- and left-sided cases and that the left
4-BAD-afflicted horses are simply being misdiagnosed as
recurrent neuropathy. If this were the case many more
Treatment and Prognosis structural defects would have been encountered during
At present, no surgical remedy has been devised to replace routine prosthetic laryngoplasty surgery. In a previous
or reconstruct the deficient structures. However, in the past report of right laryngeal “hemiplegia” (Tulleners et al
there have clearly been misunderstandings regarding the 1996) seven out of 11 thoroughbreds were found to have
congenital malformations of the laryngeal cartilages. Dixon PM, McGorum BC, Else RW 1993 Cricopharyngeal-
Indeed, 4-BAD should be considered as a likely explanation laryngeal dysplasia in a horse with sudden clinical
whenever right-sided laryngeal dysfunction is identified in onset of idiopathic laryngeal hemiparesis. New Zealand
clinical practice. Goulden BE, Anderson LJ, Davies AS, Barnes GRG 1976
Regardless of the severity of the defects, preliminary Rostral displacement of the palatopharyngeal arch: a
studies of race performance records suggest that afflicted case report. Equine Veterinary Journal 8: 95–98
horses are less likely to become effective athletes than Hast MH 1972 Early development of the human laryngeal
non-affected horses. This has medicolegal implications for muscles. Annals of Otology, Rhinology and Laryngology
81: 524
veterinarians, who should be vigilant for this condition at Klein H-J, Deegen E, Stockhofe N, Wissdorf H 1989 Rostral
prepurchase examinations of horses, and for bloodstock displacement of the palatopharyngeal arch in a seven-
auctioneers, who should take this performance-limiting month-old Hanoverian colt. Equine Veterinary Journal
disorder into account when drafting their veterinary con- 21: 382–383
ditions of sale. An increased awareness of the simplicity of Lane JG 1993 Fourth branchial arch defects in the horse.
In: Dyson SJ, Lane JG (editors) Proceedings of the 15th
a definitive diagnosis by palpation alone in almost all cases Bain-Fallon Memorial Lectures. Australian Equine Veteri-
would be helpful. nary Association, Artamon, pp.49–50
Lane JG 2003 Non-RLN upper respiratory tract disorders
found in a survey of 3497 Thoroughbred yearlings. In:
Dixon PM, Robinson NE, Wade JF (editors) Havemeyer
REFERENCES Foundation Monograph Series. R & W Publications,
Newmarket, pp.49–50
Blikslager AT, Tate LP, Tudor R 1999 Transendoscopic laser Tulleners EP, Ross MW, Hawkins J 1996 Management of right
treatment of rostral displacement of the palatopharyn- laryngeal hemiplegia in horses: 28 cases. ACVS Abstract
geal arch in four horses. Journal of Clinical Laser in Veterinary Surgery 25: 439
Medicine and Surgery 17: 49–52 Wilson RG, Sutton RH, Groenendyk S 1986 Rostral displace-
Cook WR 1974 Some observations on diseases of the ear, nose ment of the palatopharyngeal arch in a Thoroughbred
and throat in the horse, and endoscopy using a flexible yearling. Australian Veterinary Journal 63: 99–100
fibreoptic endoscope. Veterinary Record 94: 533–541 Zaw-Tun HA, Burdi AR 1985 Re-examination of the origin
Deegen E, Klein, H-J 1987 Rostrale verlagerung des arcus and early development of the human larynx. Acta
palatopharyngicus beim pferd. Pferdeheilkunde 3: 303–308 Anatomica (Basel) 122: 163–184
Idiopathic Recurrent Laryngeal
Neuropathy: Etiopathogenesis
32 Caroline Hahn and Joe Mayhew
Introduction
the axolotl), then separate arytenoid and cricoid cartilages
Idiopathic recurrent laryngeal neuropathy (RLN) is a (newt), primitive thyroid cartilages (alligators and their
prominent disease of domestic horses that is character- feathered relatives, the birds) and finally the complex
ized by the distal degeneration of axons in the recurrent mammalian larynx. As the survival of equids depended on
laryngeal nerve supplying the larynx, and paresis or their athletic capability to escape predators they evolved a
paralysis of the left vocal fold. Respiratory impairment larynx that when fully abducted has an aperture that is
and inspiratory stridor (“roaring”) ensue and the athletic larger than the trachea itself; this is in sharp contrast to the
performance of affected animals can be significantly human larynx, which allows for speech but when abducted
impaired. It is widely reported throughout the world in is only half the diameter of the trachea).
both temperate and tropical climates (Cahill & Goulden An appreciation of the anatomy of laryngeal inner-
1987). In addition, a large proportion of clinically unaf- vation is a prerequisite to understanding the pathological
fected horses have histological changes of the intrinsic changes characteristic of RLN. The main source of laryn-
laryngeal musculature and recurrent laryngeal nerves geal innervation of the equine larynx is the ipsilateral
characteristic of RLN (Cook 1989). recurrent laryngeal nerve. Motor neurons of the recurrent
Despite the fact that “roaring” was described in the 18th laryngeal nerve are in the nucleus ambiguus in the caudal
century, a great deal remains to be learned about the brainstem. This nucleus was recently localized in the horse
pathogenesis and precise pathological changes of RLN. (Hackett 2000) and was found to be a loosely organized
Fundamental questions, such as whether or not RLN is a column of cells in the ventrolateral medulla oblongata. A
manifestation of a polyneuropathy, whether the cause somatotopic distribution of adductor and abductor motor
involves a mechanical component, and whether there is a neurons was not apparent but neurons innervating the
prenatal onset, have not been resolved and the etiology cricoarytenoideus lateralis muscle were observed through-
remains a mystery. out the nucleus, whereas neurons innervating the cricoary-
tenoideus dorsalis (the only laryngeal abductor) tended to
be situated more rostrally.
Anatomy
Nucleus ambiguus axons loop around the parasympa-
The mammalian larynx acts as a modified air valve with a thetic nucleus of the vagus to emerge from the brainstem
number of functions, including protection of the lower as axons of the internal branch of the accessory nerve,
respiratory tract and phonation, and the curious anatomy cranial nerve (CN) XI. They only join the vagus nerve (CN
of this organ has its origin in the evolution of air-breathing X) on leaving the skull through the jugular foramen and
animals. tympano-occipital fissure (Fig. 32.1).
The lungfish evolved the ability to breathe air directly Growth of the head and neck during embryogenesis,
from the external environment about 400 million years and differential degeneration of the sixth aortic arch, result
ago, perhaps because its watery home was periodically in extremely long nerves with the left and right nerves
subject to drought (Ewings 1949). A simple larynx-like slit having different pathways. The left nerve loops around the
behind the gills developed to allow air into the swim aorta while the right takes a shorter route around the right
bladder when the fish was exposed to the atmosphere, subclavian artery. Including its vagal course, the total
and to keep water out when it was submerged. As the length from neuronal cell body to larynx of the left recur-
lungfish’s descendants moved on to land, this swim bladder rent laryngeal nerve can be up to 250 cm, making it twice
evolved into lungs, a multi-compartment organ with a as long as other motor nerves in the horse and 31 cm
large surface area whose sole function was gas exchange. longer than the right recurrent laryngeal nerve.
The larynx in the meantime developed adductor and The normal recurrent laryngeal nerve consists of
abductor muscles and lateral cartilages (such as found in medium-sized myelinated fibers with only scattered, smaller
473
474 32 Idiopathic Recurrent Laryngeal Neuropathy: Etiopathogenesis
Glossopharyngeal Vagus
(CN IX)
Accessory nerve
(CN XI)
Vagus nerve
CN XI Recurrent laryngeal nerve
Cranial laryngeal nerve
CN IX
Fig. 32.1. The recurrent laryngeal nerve is supplied by axons originating in the caudal nucleus ambiguus.
Redrawn from de Lahunta, 1983, with permission.
Pathological Changes
diameter fibers present. Myelinated axons in the recurrent
laryngeal nerve segregate as fascicles within the vagus The lesions associated with RLN have been well char-
nerve. After these fascicles separate from the vagus as the acterized at the light and electron microscopic levels
recurrent laryngeal nerve however, the axons that are (Cole 1946, Duncan & Griffiths 1974, Duncan et al 1978,
targeted to innervate a particular intrinsic laryngeal 1991a,b, Cahill & Goulden 1986a,b,c,d,e).
muscle are not discretely clustered within the recurrent The principal pathological changes are found in the
laryngeal nerve at its origin in the thorax, but instead are recurrent laryngeal nerve and are characterized by a
mixed among the fascicles throughout its length. This progressive loss of large myelinated fibers in the distal
implies that focal, non-selective damage (“compression”) of nerve (Fig. 32.2). It is worth pointing out, however,
the recurrent laryngeal nerve is unlikely to be the cause of that the same trend, including the presence of whorled
the different severities of lesions found in specific laryngeal
muscles of RLN cases.
Although the recurrent laryngeal nerve is classically
thought of as a motor nerve, primary afferent (“dorsal root
ganglia”) recurrent laryngeal nerve neurons have been
demonstrated in the proximal and distal vagal ganglia. The
distal vagal ganglion is poorly described in the horse but
histologically consists of scattered neurons in the vagus
nerve at its bifurcation with the cranial laryngeal nerve.
Involvement of sensory axons in horses with recurrent
laryngeal neuropathy has not been established. The recur-
rent laryngeal nerve then courses cranially to provide motor
innervation to the paired intrinsic laryngeal muscles, with
the exception of the cricothyroideus muscle, which is inner-
vated by the cranial laryngeal nerve (de Lahunta 1983).
The complexity and length of this pathway is likely to Fig. 32.2. Plastic-embedded 1-μm section of left recurrent laryngeal
underlie the pathological changes in RLN. nerve showing loss of myelinated fibers.
32 Idiopathic Recurrent Laryngeal Neuropathy: Etiopathogenesis 475
Fig. 32.3. Longitudinal section of left recurrent laryngeal nerve Fig. 32.4. Left cricoarytenoideus lateralis muscle. There is fibrosis,
showing Wallerian degeneration (thin arrow) with myelin digestion myofiber angular atrophy, and hypertrophy with multiple fibers having
chambers, axonal and myelin debris and macrophages. The thick internal nuclei.
arrow points to proliferating Schwann cells, the so-called bands of
Büngner.
fibrillary structures (Renaut bodies) that has been reported seen in lower motor neuron soma secondary to the axonal
in RLN cases, has been shown in “normal” horses (Lopez damage is influenced by the proximity of the lesion, which
Plana et al 1993). Axonal loss has been found to be in the case of RLN may be over 1 m away. Chromatolysis
greatest in the distal portions of the left and right recurrent or neuronal loss in the nucleus ambiguus would however
laryngeal nerves but has also been noted proximal and be anticipated if the axonal changes were the result of
distal to the aorta and in the vagus nerve. Changes noted somatic (cell body) lesions, as has been described in Bouvier
in the right recurrent laryngeal nerve are less severe than des Flandres (Venker-van Haggen 1980) and Siberian
those found in the left. Lesions are presumed to be found Husky dogs (O’Brien & Hendriks 1986). Unfortunately,
principally in motor axons and it is unknown if sensory there has been no systematic work in the horse evaluat-
fibers in the recurrent laryngeal nerves are also affected. ing the peripheral or central pathological changes that
Vagal sensory ganglionic cell bodies should be examined for accompany damage to long axons. Ultrastructural exami-
neuronal chromatolysis. nation of nucleus ambiguus neurons has been attempted
The primary lesion may be axonal in nature, as indi- but is complicated greatly by the difficulty of identifying
cated by collapsed myelin sheaths, increased relative myelin the boundaries of the nucleus in the medulla oblongata. It
sheath thickness (potentially as a result of axonal atrophy), was believed that there was a difference in the number of
regenerating Schwann cell membrane clusters and para- neurons in horses with RLN compared to normal horses
nodal and internodal accumulations of axonal debris and but the small number of animals examined did not allow a
organelles. The latter may be an indication that a defect in statistical comparison (S. Hackett, personal communica-
the axonal transport systems results in the eventual distal tion). There have been no histochemical techniques applied
axonal degeneration. Signatures of proliferating Schwann to identify somal changes secondary to the hypothesized
cells (Büngner’s bands and onion bulbs) are commonly transport disorder.
found (Fig. 32.3), as are myelin digestion chambers con- Lesions in the laryngeal muscles innervated by the
taining central axon fragments. Teased fiber preparations recurrent laryngeal nerves are characteristic of neurogenic
show a marked variation in internodal length and diameter disease (Fig. 32.4). Denervation of the adductor mus-
indicating chronic demyelination and attempted remyelina- cles precedes abductor involvement and typical changes
tion. This could be the result of either a primary myelin include scattered angular fibers and groups of atrophied
deficit or, perhaps more likely, underlying axonal damage. fibers adjacent to hypertrophied fibers with central nuclei
Evidence of damage to the cell bodies of the recurrent (Duncan & Griffiths 1974, Duncan et al 1991a). The crico-
laryngeal nerve has been sought; however, neither Cahill arytenoideus lateralis is among the earliest and most severely
and Goulden (1986e) nor S. Hackett and C.W. Cummings affected muscles (Lopez Plana et al 1993). The chronic or
(personal communication) were able to identify lesions in repetitive nature of the disease is further exemplified by the
the nucleus ambiguus in the brainstem of affected horses. presence of muscle fiber type grouping, because muscle
This is perhaps not surprising because the chromatolysis fiber type is controlled by the innervating neuron.
476 32 Idiopathic Recurrent Laryngeal Neuropathy: Etiopathogenesis
These pathological changes have been classified as a mally (“dying back”), is the most common lesion seen in
distal axonopathy, with the greater damage in the left peripheral nerve diseases caused by a wide variety of toxic,
recurrent laryngeal nerve being explained by its greater metabolic, and infectious insults. Some of these processes
length. One hypothetical cause of distal axonopathy is a affect the cell body, and it may be that the axonal dying-
defect in the neuronal soma, because the axon depends on back process is initiated to conserve energy: how a cell
the cell body for metabolic support and trophic influences. can eliminate part of itself while leaving the rest intact is
Indeed, many of the peripheral nerve lesions that are unknown. Localized axonal degeneration that resembles
typically found in equine motor neuron disease, a disease dying back can also occur in cell culture if the distal
primarily affecting the cell body, are also observed in portion of the axon is deprived of nerve growth factor and
RLN including axonal atrophy, proliferated Schwann cell a similar process may be involved in disease states. Other
cords (Büngner’s bands), loss of myelinated fibers and an forms of axonal degeneration that seem distinct from
increase in endoneurial collagen. typical dying back occur in various human neurodegen-
erative diseases such as Alzheimer’s, Parkinson’s, and
Huntington’s diseases.
Hypothetical Etiologies Pathological changes of the recurrent laryngeal nerve in
Despite many years of work we appear to be no closer to RLN have been described in great detail using both light
clarifying the etiology of this common equine disease. and electron microscopy, but the tools of the burgeoning
Hypotheses range from mechanical causes, such as tension science of molecular pathology have not been utilized: a
and stretch to the recurrent laryngeal nerve and its blood detailed examination of changes in gene regulation and
supply during neck movement, growth, or growth of cytokine expression will have to be applied if further details
the head and neck during embryonic development, to of the pathogenesis are to be uncovered.
environmental factors including toxins (reviewed by
Cahill & Goulden 1987). Compression of the nerve as it
loops around the aorta might be expected to result in
REFERENCES
nerve lesions at that site; however, this has not been
noted, and toxins have been viewed as unlikely causes of Cahill JI, Goulden BE 1986a Equine laryngeal hemiplegia. I. A
RLN as the neuropathological changes appear to be limited light microscopic study of peripheral nerves. New Zealand
to the recurrent laryngeal nerves. The effect of nerve Cahill JI, Goulden BE 1986b Equine laryngeal hemiplegia. II.
stretch on the blood supply of the recurrent laryngeal An electron microscopic study of peripheral nerves. New
nerve (the vasa nervorum) has not been evaluated. Zealand Veterinary Journal 34: 170–175
A hypothetical etiology for RLN is an inherited axonopathy Cahill JI, Goulden BE 1986c Equine laryngeal hemiplegia. III.
or myelinopathy. Comparable pathological changes have A teased fibre study of peripheral nerves. New Zealand
indeed been noted in foals (Duncan 1992, Harrison et al Cahill JI, Goulden BE 1986d Equine laryngeal hemiplegia.
1992) and clinical signs of left-sided hemiplegia have been IV. Muscle pathology. New Zealand Veterinary Journal
demonstrated to be clinically progressive (Dixon et al 2002). 34: 186–190
There have however been no reports of left hemiplegic horses Cahill JI, Goulden BE 1986e Equine laryngeal hemiplegia.
progressing to develop right-sided clinical signs (P.M. Dixon, V. Central nervous system pathology. New Zealand
personal communication), and horses affected with RLN Cahill JI, Goulden BE 1987 The pathogenesis of equine laryn-
clearly do not show classical clinical signs of polyneu- geal hemiplegia – a review. New Zealand Veterinary
ropathy such as mega-esophagus, tetraparesis, and somatic Journal 35: 82–90
muscle atrophy. However, involvement of other long Cole CR 1946 Changes in the equine larynx associated with
peripheral nerves (common, deep and superficial peroneal laryngeal hemiplegia. American Journal of Veterinary
Research 7: 69–77
and tibial nerves) has been reported by some workers Cook WR 1989 Recent observations on recurrent laryn-
(Cahill & Goulden 1986a, Kannegieter 1989), but was not geal neuropathy in the horse: applications to practice.
found by Duncan et al (1978). Similarly, neurogenic muscle Proceedings of the Annual Convention of the American
changes have been reported to exist in the extensor Association of Equine Practitioners, pp.427–478
digitorum longus (Cahill & Goulden 1986d) in three out of de Lahunta A 1983 Veterinary Neuroanatomy and Clinical
Neurology. WB Saunders, Philadelphia
four horses suffering from RLN. The above observations, Dixon PM, McGorum BC, Railton DI et al 2002 Clinical
however, are isolated, uncontrolled and have not taken into and endoscopic evidence of progression in 152 cases of
account that age-related pathological changes can be equine recurrent laryngeal neuropathy (RLN). Equine
demonstrated in the distal limb nerves of horses (Wheeler Veterinary Journal 34: 29–34
1987). A detailed study of the peripheral nerves in RLN- Duncan ID 1992 Determination of the early age of onset of
equine recurrent laryngeal neuropathy. 2. Nerve pathology.
affected and control animals has not been undertaken. Acta Neuropathologica (Berlin) 84: 316–321
It should be remembered that axonal degeneration, Duncan I D, Griffiths I R 1974 Pathological changes in
characterized by distal degeneration that spreads proxi- equine laryngeal muscles and nerves. Proceedings of the
32 Idiopathic Recurrent Laryngeal Neuropathy: Etiopathogenesis 477
Nineteenth Annual Convention of the American Associa- Harrison GD, Duncan ID, Clayton MK 1992 Determination of
tion of Equine Practitioners, pp.97–113 the early age of onset of equine recurrent laryngeal
Duncan ID, Griffiths IR, Madrid RE 1978 A light and electron neuropathy. 1. Muscle pathology. Acta Neuropathologica
microscopic study of the neuropathy of equine idiopathic (Berlin) 84: 307–315
laryngeal hemiplegia. Neuropathology and Applied Kannegieter N 1989 A study of distal hindlimb muscles and
Neurobiology 4: 483–501 nerves in normal and laryngeal hemiplegic horse. PhD
Duncan ID, Amundson J, Cuddon PA et al 1991a Preferen- Thesis, Massey University, New Zealand
tial denervation of the adductor muscles of the equine Lopez Plana C, Sautet JY, Pons J et al 1993 Morphometric
larynx. I: Muscle pathology. Equine Veterinary Journal study of the recurrent laryngeal nerve in young “normal”
23: 94–98 horses. Research in Veterinary Science 55: 333–337
Duncan ID, Reifenrath P, Jackson KF et al 1991b Preferen- O’Brien JA, Hendriks J 1986 Inherited laryngeal paralysis.
tial denervation of the adductor muscles of the equine Analysis in the husky cross. Veterinary Quarterly 8:
larynx. II: Nerve pathology. Equine Veterinary Journal 301–302
23: 99–103 Venker-van Haggen AJ 1980 Investigations on the patho-
Ewings V 1949 The Comparative Anatomy and Physiology of genesis of hereditary laryngeal paralysis in the Bouvier.
the Larynx. William Heinemann, London PhD thesis, University of Utrecht, The Netherlands
Hackett S 2000 The equine nucleus ambiguus: myotopic and Wheeler SJ 1987 Structure and function of equine peripheral
neurotopic representations of motor and sensory compo- nerve: morphology, morphometry and clinical electro-
nents of the recurrent laryngeal nerve. PhD Thesis, physiology. PhD Thesis, Royal Veterinary College, UK
Cornell University, USA
Laryngeal Paralysis with Known
and Suspected Causes
33 Bruce C McGorum
Introduction Postanesthesia Laryngeal Paralysis

This chapter reviews the current state of knowledge Unilateral or bilateral, total laryngeal paralysis is a rare,
regarding the small proportion of horses with laryngeal but potentially fatal, complication of general anesthe-
paralysis for which a known or suspected cause can sia (Abrahamsen et al 1990, Dixon et al 1993, 2001,
be identified, given as 6% by Goulden & Anderson (1981) Southwood et al 2003). Proposed predisposing factors
and 11% by Dixon et al (2001). The remainder of horses include dorsal recumbency with hyperextension of the
with laryngeal paralysis are termed idiopathic recurrent neck and a dependent head position, pre-existing RLN,
laryngeal neuropathy (RLN) cases, because their laryn- large body size, prolonged duration of anesthesia, hypo-
geal paralysis has no known or suspected cause (see tension, hypoventilation, hypoxemia, and postanesthetic
Chapter 32). myopathy. Contributory factors may include postop-
erative laryngeal edema and inflammation, and laryn-
geal dysfunction associated with xylazine administration
(Southwood & Gaynor 2003). Postoperative laryngeal
Laryngeal Paralysis Resulting paralysis is probably caused by excessive extension of the
from Nerve Damage head and neck, which could induce neural stretch injury or
Most commonly, non-RLN laryngeal paralysis is a sequel cause neural hypoxia via occlusion of the vasa nervorum.
to localized injury to the vagus or recurrent laryngeal Alternatively, nerve damage may be a consequence of
nerves at any site along their long and circuitous path- compression of the recurrent laryngeal nerve between the
way. Such injury may occur in disorders of the guttural endotracheal tube and a rigid structure in the neck, such
pouch, pharynx, neck, and cranial mediastinum as indi- as the vertebrae. Affected horses develop an acute-onset,
cated in Table 33.1. life-threatening laryngeal obstruction, with inspiratory
dyspnea, stridor, and cyanosis. Extreme distress makes
them difficult and dangerous to handle, and the condition
Table 33.1. Disorders that cause laryngeal paralysis via can be rapidly fatal. Laryngeal obstruction may occur
local injury to the vagus/recurrent laryngeal nerve following extubation, when the horse is encouraged to
stand during recovery, or during vocalization when the
Disorders of the guttural pouch
horse is walking to the stall following recovery (Southwood
Guttural pouch mycosis
Trauma et al 2003). The laryngeal obstruction may also lead
Disorders of the pharynx
to potentially fatal pulmonary edema and hemorrhage
Trauma (see Chapter 43). Treatments have included emergency
Neoplasia tracheal reintubation via the oral or nasal cavities, place-
Disorders of the neck ment of a temporary tracheostomy tube, supplemental
Perivascular/perineural irritant injection reactions intranasal oxygen, anti-inflammatory drugs, and in horses
Trauma with secondary pulmonary edema, furosemide. Horses that
Iatrogenic nerve damage during laryngeal, esophageal,
survive the acute obstruction have variable recovery of
tracheal, thyroid, and vertebral surgery
laryngeal function; some horses show complete resolution
Disorders of the cranial mediastinum
Neoplasia
within 24 h, while others have permanent laryngeal dys-
Abscesses function. Southwood et al (2003) recommend avoiding
Unknown site and nature of injury hyperextension of the neck during anesthesia, and having
Postanesthesia bilateral laryngeal paralysis (nerve stretching an emergency tracheostomy kit available when recovering
or compression?) horses that may be predisposed to this disorder. Previously
reported cases of postanesthetic death from pulmonary
479
480 33 Laryngeal Paralysis with Known and Suspected Causes
in seven of 50 horses with primary hepatic disease, all

Table 33.2. Generalized neuromuscular disorders
that cause laryngeal paralysis of which had encephalopathy and hyperammonemia
(McGorum et al 1999). Because all horses had a loud
Hepatopathy inspiratory stridor, many were referred for investigation
Lead toxicosis
of suspected primary upper respiratory tract obstruction.
Delayed organophosphate-induced neurotoxicity
Australian stringhalt This suggests that hepatopathy causes preferential dysfunc-
Plant poisoning tion of the recurrent laryngeal nerve compared to other
Hyperkalemic periodic paresis peripheral nerves. Endoscopy of affected horses reveals
total bilateral paralysis, with both arytenoids being passively
adducted to the midline during inspiration (Fig. 33.1).
Ponies appear to be more commonly affected than horses.
edema may in fact have been the result of bilateral This may reflect the increased frequency of liver failure in
laryngeal paralysis with secondary pulmonary edema ponies compared with horses, or a true predisposition of
(Tute et al 1996). ponies to develop this type of bilateral laryngeal paralysis.
The laryngeal dysfunction may be temporary, resolving
with restoration of hepatic function, but worsening again
Generalized Neuromuscular Disorders when the encephalopathy recurs.
That Cause Laryngeal Paralysis The pathogenesis of this complication is unknown.
Non-RLN laryngeal paralysis may be a manifestation of To date, no gross or histopathological lesions have been
generalized neuromuscular disorders (Table 33.2). Such identified in the laryngeal muscles, recurrent laryn-
disorders commonly cause bilateral laryngeal paralysis. geal nerve or other peripheral nerves of affected horses.
Reported cases have involved horses with hepatic failure
Laryngeal paralysis associated and encephalopathy; whether it occurs in horses with
with hepatopathy compensated liver disease is unknown. While laryngeal
paralysis has been reported in horses with pyrrolizidine
Hepatopathy is a common cause of bilateral laryngeal alkaloid-induced hepatopathy (Pearson 1991, McGorum
paralysis (Mayhew 1989, Pearson 1991, McGorum et al et al 1999), the causal role of pyrrolizidine alkaloids,
1999). Indeed bilateral laryngeal paralysis was recorded which may be neurotoxic per se (Huxtable et al 1996),
A B
Fig. 33.1. Endoscopic view of the larynx of a pony with bilateral airway is a result of an emergency tracheostomy. Following this proce-
laryngeal paralysis which was associated with liver failure. (A) This dure, the arytenoids remained relatively motionless in the resting
image, captured during inspiration, reveals passive adduction of the position, indicating bilateral paralysis.
arytenoids with resultant closure of the glottis. (B) The blood in the
33 Laryngeal Paralysis with Known and Suspected Causes 481
in laryngeal dysfunction is unclear. Since the laryngeal

REFERENCES
paralysis may be transient, and since no neuropathology
has been identified, it probably reflects neuromuscular Abrahamsen EJ, Bonahon TC, Bednarski RM et al 1990
dysfunction rather than neuromuscular pathology. Such Bilateral arytenoid cartilage paralysis after inhala-
tion anaesthesia in a horse. Journal of the American
dysfunction could potentially occur by mechanisms akin Veterinary Medical Association 197: 1363–1365
to those that cause hepatic encephalopathy. Alternatively, Carr EA, Spier SJ, Kortz GD et al 1996 Laryngeal and
this form of laryngeal paralysis may represent a periph- pharyngeal dysfunction in horses homozygous for
eral neuropathy, which is a common complication of hyperkalemic periodic paralysis. Journal of the American
hepatic disease in humans. The pathogenesis of peripheral Veterinary Medical Association 209: 798–803
Dixon PM, Railton DI, McGorum BC 1993 Temporary bilateral
neuropathy in humans with liver disease is incompletely laryngeal paralysis in a horse associated with general
understood but may involve (1) metabolic inhibition of anaesthesia and post anaesthetic myositis. Veterinary
axonal membrane function, (2) metabolic damage to Record 132: 29–32
Schwann cells, and/or (3) disordered insulin metabolism Dixon PM, McGorum BC, Railton DI et al 2001 Laryngeal
akin to diabetic neuropathy. paralysis: a study of 375 cases in a mixed-breed popula-
tion of horses. Equine Veterinary Journal 33: 452–458
Duncan ID, Brook D 1985 Bilateral laryngeal paralysis in the
Toxic peripheral neuropathies causing horse. Equine Veterinary Journal 17: 228–233
laryngeal paralysis Goulden BE, Anderson LJ 1981 Equine laryngeal hemiplegia
part II: some clinical observations. New Zealand Veterinary
Various toxic peripheral neuropathies may also cause Journal 29: 194–198
Hutyra G, Marek F, Manninger T 1938 Paralysis of the recur-
laryngeal paralysis (Table 33.2). These disorders are readily rent laryngeal nerve. In: Special Pathology and Thera-
differentiated from RLN because the laryngeal paralysis is peutics of the Diseases of Domestic Animals, 4th edn.
commonly bilateral and it is clearly part of a generalized Bailliere, Tindall & Cox, London, vol. 3, pp.401–410
disorder that affects multiple peripheral nerves. Delayed Huxtable RJ, Yan CC, Wild S et al 1996 Physicochemical and
organophosphate-induced toxicity causes neurodegen- metabolic basis for the differing neurotoxicity of the
pyrrolizidine alkaloids, trichodesmine and monocrotaline.
eration, primarily of long axons in peripheral nerves and Neurochemical Research 21: 141–146
spinal cord. The resultant laryngeal paralysis may be Mayhew IG 1989 Large Animal Neurology. Lea & Febiger,
permanent (Rose et al 1981, Duncan & Brook 1985). London, p.95
Ingestion of Lathyrus spp. and Cicer arietinum (chickpea) McGorum BC, Murphy D, Love S et al 1999 Clinicopatho-
may cause laryngeal paralysis. The toxic agents include logical features of equine primary hepatic disease: a
review of 50 cases. Veterinary Record 145: 134–139
β-N-oxalylamino-L-alanine, an excitatory amino acid Pearson EG 1991 Liver failure attributable to pyrrolizidine
that causes neuropathy with distal axonal degeneration. alkaloid toxicity and associated with inspiratory dyspnea
Interestingly, experimental studies indicate that, even after in ponies: three cases (1982–1988). Journal of the
prolonged ingestion of Lathyrus sativus (Indian vetch), American Veterinary Medical Association 9: 1651–1654
only a minority of horses develops laryngeal dysfunction Rose RJ, Hartley WJ, Baker W 1981 Laryngeal paralysis in
Arabian foals associated with oral haloxon administra-
(Hutyra et al 1938), suggesting that factors other than tion. Equine Veterinary Journal 13: 171–176
toxin ingestion contribute to the clinical outcome. Sojka JE, Hope W, Pearson D 1996 Lead toxicosis in 2
Sojka et al (1996) described laryngeal dysfunction in horses: similarity to equine degenerative lower motor
around 13% of horses with lead toxicosis. neuron disease. Journal of Veterinary Internal Medicine
10: 420–423
Southwood LL, Baxter GM, Wagner AE 2003 Severe post-
Hyperkalemic periodic paresis anesthetic upper respiratory tract obstruction in horses:
8 cases (1993–2001). Veterinary Surgery 32: 602
Hyperkalemic periodic paresis, a generalized myasthenic Southwood L L, Gaynor J S 2003 Postanesthetic upper
disorder, often results in episodic upper airway obstruc- respiratory tract obstruction. In: Robinson NE (editor)
tion. While the nature of airway obstruction in this dis- Current Therapy in Equine Medicine 5. Saunders,
St Louis, pp.391–393
order appears to be variable, obstruction is attributed Tute AS, Wilkins PA, Gleed RD et al 1996 Negative pressure
to laryngeal spasm or paralysis in approximately half of pulmonary edema as a post-anesthetic complication
affected horses. Appropriate medical treatment may ame- associated with upper airway obstruction in a horse.
liorate the severity and incidence of upper airway dysfunc- Veterinary Surgery 25: 519–523
tion associated with this disorder (Carr et al 1996).
Recurrent Laryngeal Neuropathy: Clinical
Aspects and Endoscopic Diagnosis
34 Brian H Anderson
Introduction and Definition

repair, including collateral axonal sprouting and reinner-
Paralysis of the equine larynx can be bilateral or unilat- vation of previously denervated muscle (demonstrated
eral, and either partial or total. Unilateral, left-sided paraly- by fiber-type grouping) are evident (Duncan et al 1974,
sis is most common and is termed laryngeal hemiplegia 1977, Anderson 1984, Cahill & Goulden 1986d). When
if complete paralysis is present and laryngeal hemiparesis if axonal loss and muscle atrophy are extensive and repair
partial paralysis is present. Two studies showed that a processes are insufficient, abductory dysfunction of the left
definitive cause was established in only 6% (Dixon et al side of the larynx occurs. The term RLN is now preferred to
2001) and 11% (Goulden & Anderson 1981a) of cases of “idiopathic laryngeal hemiplegia” because RLN describes
laryngeal paralysis (or partial paralysis). Documented the full range of pathology and associated clinical disease
causes of unilateral laryngeal paralysis include injury to which can vary from mild to severe. Laryngeal hemiplegia
the left or right recurrent laryngeal nerve by inadvertent is therefore the end-stage of neuropathy of the recurrent
perivascular injection of irritant medication, trauma to the laryngeal nerve.
neck, guttural pouch mycosis, thyroid carcinoma, strangles, Inability to abduct the arytenoid cartilage sufficiently
abscessation of the head and neck, and thymic lymphosar- and/or maintain abduction reduces the cross-sectional area
coma. In addition, organophosphate poisoning, plant toxic- of the rima glottidis, consequently obstructing inspiratory
ity, lead poisoning, liver disease, and sequelae to general airflow and causing abnormal inspiratory noise because of
anesthesia have been associated with bilateral laryngeal increased air turbulence. This abnormal inspiratory noise
paralysis (Cahill & Goulden 1987, Barber 1981) However, is referred to as “roaring” or “whistling” and horses so
in the remaining vast majority of cases, which are pre- afflicted are termed “roarers” and “whistlers” respectively.
dominantly left-sided hemiparesis, the cause is unknown Reduced volumes of oxygen reach the pulmonary capil-
and the disease is termed recurrent laryngeal neuropathy laries and the resultant hypoxemia causes premature
(RLN) (formerly idiopathic laryngeal hemiplegia) fatigue during strenuous exercise.
Although the etiology of RLN remains unknown, the Most RLN-affected horses are presented to practicing
pathology has been well described and is discussed in clinicians because abnormal respiratory “noises” and in
detail in Chapter 32, but it is briefly reviewed here to many cases impaired athletic performance are noted by
emphasize the relationship between neuromuscular pathol- owners and trainers. The diagnosis of severe RLN is not
ogy of the larynx and the clinical signs demonstrated difficult but the detection of mildly affected horses is more
by affected individuals. Neuropathy of the left recurrent troublesome, as is the ability to predict possible progression
laryngeal nerve, and to a lesser extent the right, is the of this disorder or the clinical effect of this disease on
primary pathological feature of RLN (Duncan et al 1974, affected horses.
1978, Cahill & Goulden 1986a,b,c). Progressive loss of
large myelinated nerve fibers in the distal part of the left
recurrent laryngeal nerve results in atrophy of the intrinsic
Clinical Aspects
laryngeal muscles innervated on this side. Although the Prevalence
adductor muscles of the arytenoid cartilage are affected
earlier and more profoundly (Duncan et al 1991a), it is Obtaining an accurate figure of the prevalence of RLN
atrophy of the dorsal cricoarytenoid muscle (DCAM) that is difficult and the results depend on the criteria and
results in significant clinical signs. This muscle is the methods used to determine the presence of this dis-
only abductor of the arytenoid cartilage and vocal fold order. Various endoscopic surveys conducted primarily on
and its dysfunction results in a significant reduction in thoroughbred horses estimate significant RLN to be present
airflow in exercising horses. Histopathological examination in some 2.6–8.3% of adult horses (Lane et al 1987). In a
of horses with RLN shows that a repetitive, progressive more recent endoscopic survey (using a five-point grading
denervation/reinnervation process occurs. Attempts at system), which reported on the distribution of RLN in
483
484 34 Recurrent Laryngeal Neuropathy: Clinical Aspects and Endoscopic Diagnosis
3,494 unbroken elite thoroughbred yearlings examined thoroughbred horses the histopathological changes typical
over 15 years, significant RLN (including laryngeal hemi- of RLN increased dramatically in prevalence and severity
plegia) was recorded in 0.45% of cases (Lane 2003a). Horses in horses at 1–2 years of age (Anderson 1984) which
with equivocal evidence of RLN (grade 3) comprised 17.7% supports the view that RLN is a disease of “childhood”
of the horses examined (Lane 2003a). In selected popula- (Cook 1970).
tions, such as those in public auction sales of thoroughbred Despite these findings the age at which clinical signs of
yearlings, significant RLN was recorded in 0.18% of horses RLN occur can be variable. For example, RLN is often
(Anderson 2002) when endoscopy alone was used for diagnosed in unbroken yearling thoroughbreds examined
diagnosis, but in 0.65% of horses (Ellis et al 2004) when at the time of sale. More commonly, however, clinically
the examination for the presence of a characteristic inspi- significant RLN becomes evident with the start of stren-
ratory noise during exercise was also undertaken. uous work. In thoroughbreds, particularly those intended
In a further study (Duncan et al 1974) of mixed breeds for flat racing, the clinical signs of RLN most commonly
of horses, which used histopathological criteria for the occur when training and racing begins in 2- to 3-year-old
diagnosis of RLN, 30% of apparently clinically normal horses. In hunters and National Hunt racehorses, which
horses had evidence of neurogenic atrophy of the left are not broken until aged 4–5 years, the median age for
intrinsic laryngeal muscles. Of these horses, 77% were diagnosis of RLN was 6 years (Dixon et al 2001). In
14.2 hands or taller. In another study (Anderson 1984), in summary, RLN can affect animals at almost any age but
which all the horses were thoroughbreds, 80% of clinically the most commonly noted time of clinical disease is
normal horses over 1.5 years of age without endoscopic between 1 and 6 years of age.
evidence of abnormal laryngeal movements had evidence
of neurogenic atrophy of the left intrinsic laryngeal muscles.
These horses have been referred to as subclinical cases.
Diagnosis
RLN is suspected when there is a history of exercise
Breed, height, and body weight intolerance and an abnormal respiratory noise evident at
exercise. Palpation of the larynx is performed to detect
In general, RLN affects heavier, taller breeds such as draft evidence of atrophy of the DCAM, although this muscle
breeds, warmbloods, and thoroughbreds, and is rarely may be atrophied in many large horses with normal
found in ponies. In one study, the odds ratios by breed for laryngeal function. Confirmation of RLN is achieved
the development of significant RLN in descending order by endoscopic examination of the larynx at rest or, if
were draft breeds, warmbloods, Tennessee walkers, saddle- necessary, during exercise on a treadmill (Ducharme &
breds, thoroughbreds, standardbreds and quarter horses Hackett 1991).
(Beard & Hayes 1993). A clinical and endoscopic survey of
Clydesdale horses showed that 9% (i.e. four of 48) horses History and presenting clinical signs
had laryngeal paralysis (Goulden et al 1985). Approxi-
mately 95% of horses affected with clinically significant RLN-affected horses are frequently reported to make an
RLN are over 160 cm tall at the withers (Cook 1965, abnormal respiratory noise during exercise and have
Goulden & Anderson 1981b, Dixon et al 2001). reduced exercise capacity.
Respiratory noise and RLN

Gender
In athletic horses, principally racehorses, an abnormal
A number of clinical and endoscopic surveys have indi- respiratory noise, typically described as a “whistle” or
cated that higher grades of RLN are more common in “roar”, is reported when exercising at higher speeds, i.e.
males than females but conclusive evidence is lacking cantering or galloping in larger breeds and fast trotting or
(Goulden & Anderson 1981b, Dixon et al 2001). Histo- pacing in standardbred racehorses. Such noises are seldom
pathological changes typical of RLN are more frequent in heard at the trot except in severely affected (hemiplegia)
male as compared to female horses (Anderson 1984). horses. Sometimes there is a history of sudden appearance
of a noise in horses, which often coincides with the onset of
Age of onset training. In young racehorses it is not uncommon for
the noise to start immediately upon resumption of train-
Histological changes typical of RLN have been recorded ing following a break between the second and third years
in fetuses (Gunn 1973) and in male draft horse foals as (Goulden & Anderson 1981a). In other cases the onset of
young as 2 weeks of age, lending weight to the theory abnormal respiratory noise is insidious.
that the disease is hereditary and/or congenital (Duncan In draft breeds used for showing, an abnormal respi-
1992, Harrison et al 1992). In a survey of predominantly ratory noise is often reported but in those used for pulling
34 Recurrent Laryngeal Neuropathy: Clinical Aspects and Endoscopic Diagnosis 485
competitions an abnormal respiratory noise and exercise and the degree of dysfunction relates to the severity of
intolerance may be reported (Beard & Hayes 1993). RLN (Christley et al 1997). The end result is that oxygen
Because of the low speeds at which sport horses such demand exceeds oxygen supply and fatigue sets in. In many
as showjumpers and dressage horses perform, RLN is cases, horses are competitive for most of the race but in the
frequently not a performance-limiting disorder. However, final 400–600 m they do not accelerate and may weaken,
at elite levels it can be, and often the associated abnor- with the rest of the field passing them. Even though
mal respiratory noise is, objectionable to owners and com- obviously affected horses can be competitive over short
petition judges. RLN can impair three-day event horses distances, e.g. 1000–1200 m, the longer the race (1600 m or
from competing successfully over cross-country courses more), the more difficulty RLN-affected horses will have.
because of the intensity and duration of exercise required.
Vocalization changes may also be noted. A softer neigh or Assessment of respiratory sounds
whinny can be heard as a result of incomplete adduction of
the affected arytenoid cartilage. Horses that are suddenly Galloping and cantering horses normally have a 1 : 1
frightened may have a prolonged, instead of a short, coupling between stride and respiration with inspiration
“grunt” as a result of forced expiration against an incom- and expiration completed within one stride cycle. When the
pletely closed glottis. This is the basis of the “grunt to the leading limb strikes the ground to complete the stride cycle,
stick” test (Speirs 1992). Thoroughbred yearlings sold at expiration occurs. In normal animals there is little if any
public auction sales often whinny when being paraded in audible sound heard on inspiration, unless the listener is
the sales ring, especially colts. An abnormal whinny may close to the horse. Thus, when listening to a horse gallop a
alert the potential purchaser to the presence of underlying single expiratory sound is usually noted. In horses affected
RLN. Because RLN is not the only cause of abnormal with RLN, an additional audible noise is usually heard
respiratory noises, riders or drivers should be questioned during inspiration. Therefore, two noises are noted and this
carefully on the nature of any abnormal respiratory noise biphasic sound has been compared to that heard when
reported. The following questions should be asked: sawing wood. Although the quality of the inspiratory sound
has been described in a variety of ways, two different
● What does the noise sound like? RLN-induced noises are
sounds are commonly heard. The first is a finer, higher
often musical in nature in mildly affected cases and with
pitched sound which is described as a “whistle”, often heard
faster work may become harsher “wood-sawing” type
early on in exercise or throughout exercise in less severely
noises.
affected cases. The other is a coarse/harsh, lower pitched
● Is the abnormal noise heard during inspiration, expira-
sound that is usually louder and is referred to as a “roar”,
tion or both? It should be noted, however, that many
hence the description “whistlers” or “roarers”. The precise
owners and trainers will not be able to accurately differ-
source of the abnormal inspiratory noise within the larynx
entiate between inspiratory and expiratory noises (Dixon
has not been identified but air turbulence caused by air
et al 2001).
moving across an incompletely abducted or collapsed
● At what level of exercise does the noise start and stop? Is
arytenoid cartilage and an open laryngeal ventricle or
it continuous or intermittent? Does it stop immediately
collapsed vocal fold are involved (Attenburrow 1982).
on slowing down or does it continue even when the
When examining racehorses it is preferable to be posi-
horse is standing quietly? With RLN, the noises tend to
tioned down-wind, and listening and watching the horse
occur only during strenuous exercise and are contin-
can help to determine if the abnormal sounds are made on
uous until the exercise slows down or stops, after which
inspiration or expiration, if they are continuous through-
they will disappear within seconds.
out the exercise period or intermittent, and if they stop
abruptly with cessation of exercise or can still be heard post
Exercise intolerance and the physiological exercise. On cold days the expired breath is clearly visible
effects of RLN and respiratory sounds can be matched to expiration and
It has long been recognized, especially in racehorses, inspiration. With thoroughbred racehorses the horse is
that RLN causes decreased exercise performance. It has warmed up over 1000 m or so, starting with trotting and
been shown that, compared to unaffected horses, those then cantering. Hard galloping is then performed over
with RLN suffer from a number of ventilatory alterations a further 400–600 m to stress the horse and increase
including an increase in inspiratory impedance (a measure respiratory rate. In the standardbred, the horse is jogged at
of resistance to airflow), increased inspiratory and expira- lower speed initially until warmed up but usually is fast
tory trans-upper airway driving pressures, reduced peak worked over 2000 m, aiming to complete the last 400 m in
inspiratory airflow and hypoventilation. In addition, exer- 28 seconds. The rider/driver should then pull the horse up
cising horses with significant RLN are more hypoxemic, as quickly as possible and jog or canter back to the listener.
hypercapnic and acidotic compared to normal horses In a minority of horses with RLN the abnormal inspiratory
noise can still be heard for up to a minute or so but it External examination and palpation
usually disappears within seconds after the horse is of the larynx
brought to a stop. Palpation of the larynx immediately
after exercise may reveal fremitus, and auscultation of the All horses suspected of suffering from RLN should have
ventral aspect of the larynx with a stethoscope may reveal the larynx palpated. During palpation of the larynx the
increased inspiratory noise. An abnormal inspiratory noise clinician should also check for evidence of previous upper
can be accentuated at this time in some horses with RLN respiratory tract surgery. If a ventral laryngotomy has been
using the arytenoid depression maneuver. The test can be performed, fibrosis and thickening of the tissues ventral to
performed bilaterally or unilaterally and detects reduced the cricothyroid membrane may be obvious, especially if
abductor tone (Mackay-Smith & Marks 1968, Spiers 1992). the laryngotomy closed by secondary intention. A scar
By placing fingers of each hand on the muscular processes may also be evident especially if the area is clipped. If
of the arytenoid cartilages and applying pressure in the a prosthetic laryngoplasty has been performed, a scar
medial, rostral, and ventral directions, inspiratory noise is parallel and ventral or dorsal to the linguofacial vein may
readily demonstrated in affected individuals. The ease with be evident in a minority of cases, but clipping the hair over
which stridor is induced can be compared between sides by this site is usually necessary to detect such scars.
depressing the muscular process of each side independ- Further evidence for the presence of RLN can be
ently. In horses with left-sided RLN inspiratory noise can be obtained by comparing the percutaneously palpated promi-
demonstrated more easily on the left side compared to the nence of the muscular process of the arytenoid cartilage
right (Mackay-Smith & Marks 1968). These tests can also between left and right sides. The muscular processes in
be performed in the resting horse. The results of these tests most horses can be palpated 2–3 cm caudal to the vertical
should be interpreted with caution however, because it is ramus of the mandible and medial to the tendon of the
possible to induce a similar inspiratory noise in some sternocephalicus muscle using the flexed index finger
normal horses (Cook 1988). of both hands (Fig. 34.1), except in horses with a ros-
In sport horses, yearlings or horses not fit enough to trally positioned larynx that lies between the mandibles
gallop, lunging or riding at the canter may be enough (“cock-throttled”; Hawe et al 2001). The muscular process
to elicit abnormal respiratory noises (Lane et al 1987). A of the normal arytenoid cartilage feels like a rounded
15-m diameter circle is sufficient and horses should be “flesh-covered knuckle”. Overlying the muscular process
exercised hard enough to achieve 1 : 1 stride and respi- are the cricopharyngeus and thyropharyngeus muscles and
ration coupling. The horse should be worked in both associated with it are the insertions of the dorsal cricoary-
directions for approximately 5 min (Gerring 1985). The tenoid, lateral cricoarytenoid, and transverse arytenoid
examiner should be positioned close to the horse, on muscles (intrinsic laryngeal muscles). Because RLN results
the perimeter of the circle. The inspiratory noise made in atrophy of the intrinsic laryngeal muscles a more obvious,
by a horse with severe RLN and complete paralysis is more pointed and firmer muscular process can be palpated
characteristic. However, in less severely affected horses, in horses with RLN.
abnormal inspiratory noise may be less obvious, especially Some authors place great importance on this technique
at submaximal exercise. Moreover, abnormal inspiratory and even believe the diagnosis of RLN by this method is
noises can be produced by obese or unfit horses or be more accurate than by endoscopic examination of laryn-
the result of other upper respiratory tract abnormalities geal movements. Cook reported that RLN could be diag-
such as soft palate displacement, axial deviation of the nosed by palpation in up to 100% of horses selected at
aryepiglottic folds or epiglottic entrapment. random (Cook 1988). Laryngeal palpation is useful in
More accurate assessment of respiratory sounds made detecting totally hemiplegic horses and when an endoscope
at exercise has recently been achieved using various is unavailable; it also supports a diagnosis of RLN where
microphone recording systems positioned at the nostrils laryngeal endoscopy is equivocal but an inspiratory noise is
using a facemask, in the nasopharynx or external to the heard at exercise. In one study (Anderson et al 1997) the
nostrils via a flexible wand attached to a cavison (see percentage of horses that had a more prominent muscular
Chapter 17). Spectrogram analysis of the recorded sound process on the left side and had abnormal arytenoid move-
can be performed and spectral patterns characteristic for ments (39% of 18) was significantly higher (P = 0.006)
specific upper airway disorders including RLN and dorsal than that for horses in which both sides were of similar
displacement of the soft palate (DDSP) have been identified prominence and in which abnormal arytenoid movements
(see Chapter 17). This diagnostic tool is potentially of great were recorded (10% of 78). In addition, it has been noted
benefit to practitioners who may be able to use it under that many larger horses have some degree of left-sided
field conditions. However, further work is required to verify intrinsic laryngeal muscle wasting but that laryngeal
the accuracy of sound analysis in differentiating between dysfunction is absent (Hawe et al 2001).
various upper airway disorders and within each disorder, Maldevelopment of one or both wings of the thyroid
between disease of varying severity. laminae and the absence of the cricothyroid articulation(s)
Fig. 34.1. Technique used to palpate the left

and right muscular processes of the arytenoid
cartilages.
may be determined digitally and indicate the presence In the normal horse during quiet breathing, the
of a congenital laryngeal disorder such as cricopharyn- arytenoid cartilages are positioned at approximately 15°
geal laryngeal dysplasia (fourth branchial arch defect to the midline of the rima glottidis (Fig. 34.2). Full sym-
syndrome) (Lane 1993a; see Chapter 31). metrical and synchronous abduction and adduction of
the arytenoid cartilages indicates normal laryngeal func-
Endoscopic diagnosis tion. When both arytenoid cartilages are bilaterally, fully
abducted in normal horses, as seen after swallowing or
Endoscopy of the larynx is essential to confirm the pres-
ence, and determine the severity, of RLN. An endoscopic
examination of the pharynx and larynx is indicated in all Table 34.1. Definitions of terminology used to
or some of the following situations: describe endoscopically observed laryngeal
movements (Robinson 2004)
● owner/trainer/jockey/driver/rider reports an unusual or
excessive respiratory noise during exercise Abduction Movement of the corniculate process of the
arytenoid cartilage away from the midline of
● as part of the prepurchase examination
the rima glottidis
● as part of the examination of horses which are perform-
ing poorly. Adduction Movement of the corniculate process of the
arytenoid cartilage toward the midline of
the rima glottidis
Examination of laryngeal movements
Full abduction Most of the corniculate process lies
The technique and requirements for endoscopy of the upper
horizontally (90° to the midline of the rima
respiratory tract during exercise on a high-speed treadmill glottidis) (Fig. 34.3)
have been detailed in Chapter 16 – Treadmill Endoscopy. A
description of the evaluation of laryngeal function for Asymmetry A difference in position of the right and left
corniculate processes of the arytenoid
evidence of RLN is presented below but the appearance of cartilages relative to the midline of the rima
normal laryngeal function is first briefly reviewed. glottidis
Normal laryngeal movements Asynchrony Movement of the corniculate processes of

the arytenoid cartilages at different times.
It is important that the endoscopist observes the full range This can include twitching, shivering and
of arytenoid cartilage movements (Table 34.1) before delayed or biphasic movement of one
deciding if there is evidence for adductor and/or abductor arytenoid cartilage as compared to the other
muscle dysfunction.
Fig. 34.2. Diagram of the endoscopic appearance of the arytenoid Fig. 34.3. Diagram of the endoscopic appearance of full and sym-
cartilages in the resting position during quiet breathing. metrical bilateral arytenoid abduction as observed following nasal
occlusion or swallowing in the resting horse. Much of the corniculate
cartilage is in contact with the nasopharyngeal roof.
following bilateral nasal occlusion, the abaxial borders of
most of the corniculate processes of the arytenoid carti-
lages are in contact with the dorsal nasopharyngeal wall Swallowing can be induced by transendoscopic flushing
and are positioned at approximately 90° to the midline of of the endoscope lens or more effectively by flushing water
the rima glottidis (Fig. 34.3). In strenuously exercising down the biopsy channel. The palate is displaced dorsally
normal horses, video-endoscopy shows that the arytenoid as the horse swallows and on replacement, full and sym-
cartilages are further abducted and almost all are in metrical abduction of the arytenoid cartilages occurs in the
contact with the dorsal nasopharyngeal wall and are normal horse. In horses with more severe degrees of RLN,
essentially at 90° to the midline of the rima glottidis (Fig. the left arytenoid cartilage is positioned on or near the
34.4). Bilaterally symmetrical adduction can be observed midline of the rima glottidis at rest (Fig. 34.6) and no
during phonation, swallowing, coughing or during bilateral abduction is observed following swallowing. The degree
nasal occlusion in normal horses (Fig. 34.5). of abduction achieved, however, can vary from slightly
more than the normal resting position (Fig. 34.7) to where
Techniques to stimulate laryngeal movement the abaxial margin of the corniculate process is at approxi-
To accurately assess abnormalities in laryngeal function it mately 75° to the midline (Fig. 34.8). In other horses with
is necessary to view the entire range of laryngeal move- lower grades of RLN, full abduction may be achieved after
ments. In some horses the arytenoid cartilages may be held swallowing, but is very transient.
in complete symmetrical abduction for the duration of the To perform the nasal occlusion maneuver, both nostrils
examination. These horses are considered to be func- are occluded by placing the hand over the nasal bone
tionally normal. In others, the arytenoid cartilages are and while the thumb compresses one nasal cavity the
held in the resting position with very little movement fingers compress the other. This temporary asphyxiation
present. To stimulate abduction and adduction all horses (if held for 30 seconds or more) results in deep respira-
should be made to swallow and a nasal occlusion maneu- tory efforts that causes near-maximal arytenoid cartilage
ver should be performed. It is recommended that three full abduction frequently followed by complete arytenoid car-
and symmetrically maintained abductions of the arytenoid tilage adduction. This technique induces subatmospheric
cartilages be observed before determining that laryngeal tracheal and pharyngeal pressures that are equal to or
function is normal. exceed those occurring during maximal exercise but
Fig. 34.4. Diagram of the endoscopic appearance of full and sym- Fig. 34.5. Diagram of the endoscopic appearance of bilaterally sym-
metrical bilateral arytenoid abduction as observed during strenuous metrical adduction of the arytenoid cartilages that can be observed
exercise on a treadmill with a video-endoscope in the pharynx. Most of during phonation, swallowing, coughing or during bilateral nasal
corniculate cartilage is in contact with the nasopharyngeal roof. occlusion in normal horses.
without the associated airflow; nevertheless it is useful for was the use of nasal occlusion. All nine racehorses that
assessing upper airway neuromuscular function (Holcombe could achieve full symmetrical arytenoid cartilage abduc-
et al 1996). Horses affected with RLN are frequently tion following swallowing, but could not do so after nasal
unable to fully and symmetrically abduct the left arytenoid occlusion, were able to maintain full abduction when
cartilage during this procedure. Evidence of adductor exercising on a treadmill at 12–14 m/s. Conversely, when
muscle dysfunction can also be observed in some RLN cases 14 racehorses which could not achieve full symmetrical
when incomplete adduction of the left arytenoid cartilage arytenoid cartilage abduction after swallowing were evalu-
is noted. ated in the same manner, only two maintained full abduc-
One drawback to the procedure is that some horses, tion during exercise.
particularly thoroughbred yearlings, do not tolerate this When performing post-sale endoscopic examination of
procedure and can become violent, striking with the yearlings it is not uncommon to observe full symmetrical
front feet or attempting to jump out of stocks. In such abduction of both arytenoid cartilages following swallow-
horses an inability to abduct both arytenoid cartilages ing, but incomplete abduction of the left arytenoid carti-
should be interpreted with caution because of the short- lage during nasal occlusion (B.H. Anderson, unpublished
ened duration of nasal occlusion. Another difficulty is observations). If the nasal occlusion maneuver was the
interpretation of laryngeal function when full abduction only test applied then a false-positive result for the presence
is not achieved following nasal occlusion but is achieved of clinically significant RLN would cause an error in
following swallowing. To examine this, Parente and col- decision-making on the suitability for sale.
leagues performed endoscopy of the upper respiratory tract Reflex adduction of either or both arytenoid cartilages is
at rest and then during intensive treadmill exercise in 150 evoked using the “slap test”. In horses with intact spinal
horses (Parente & Martin 1995). The ability to fully and reflexes a sharp slap to the saddle region caudal to the
symmetrically abduct both arytenoid cartilages after wither results in adduction of the contralateral arytenoid
swallowing was a more accurate predictor of maintaining cartilage under endoscopic observation. Adduction of the
full arytenoid abduction during strenuous exercise than contralateral arytenoid cartilage may also be detected.
Fig. 34.6. Diagram of the endoscopic appearance of the larynx in a Fig. 34.7. Diagram of the endoscopic appearance of the arytenoid
horse with severe RLN at rest. Note the left arytenoid cartilage is posi- cartilages in a horse with incomplete abduction of the left arytenoid
tioned on or near the midline of the rima glottidis. during deeper breathing. This can vary (see Fig. 34.8) and in this case
left arytenoid cartilage abduction is only slightly more than the normal
resting position.
If the reflex is absent or reduced compared to the right

side RLN is suspected. The response to this test must be performing strenuous exercise on a treadmill, peak inspi-
interpreted with respect to arytenoid abduction and by ratory and expiratory flows are lower because the respira-
itself is not reliable because it is abolished in frightened tory rate does not reach those obtained during exercise
or tense horses, weakens or disappears with continued (Weishaupt et al 1998).
slapping, and varies according to the force of the slap. In Examination immediately after exercise can also be
addition, in some horses with marked arytenoid abductor useful and is a recommended technique for prepurchase
muscle dysfunction a positive adductor response might examination of the athletic horse. If it is possible to endo-
still be present (Greet et al 1980, Hawe et al 2001). In scope the horse within minutes of galloping, when the
addition, positive thoracolaryngeal reflexes have been noted effects of elevated respiratory rate and airflow on the upper
in horses with advanced neuropathology of the lateral airways are still present, evidence of DCAM dysfunction
cricoarytenoid muscle (Newton-Clarke et al 1994). may be visible.
Increasing the respiratory rate in the resting horse by
chemical means has been used to assess the efficiency of Abnormal laryngeal movements
DCAM function. Doxapram hydrochloride (Archer et al In many horses without clinically evident respiratory
1991) (40 mg/kg intravenous) and lobeline hydrochloride abnormalities, laryngeal movements are frequently neither
(0.2 mg/kg intravenous) have both been used to stimulate bilaterally symmetrical nor synchronous. Indeed figures
hyperventilation. The degree of abduction achieved after cited from endoscopic surveys of selected or non-selected
doxapram hydrochloride administration was less than that populations of mainly thoroughbred horses indicate that
produced after nasal occlusion in one study and doxapram asynchronous and/or asymmetrical laryngeal movements
administration did not cause hyperventilation in all horses (excluding obvious or marked paralysis) are present in
(Archer et al 1991). The use of lobeline hydrochloride is more 50–78% of all horses examined (Baker 1982, Cook 1988,
reliable and induces hyperventilation for 90–150 seconds Stick et al 2001, Lane 2004a). The cause(s) of these
and although tidal volumes are similar to those in horses bilateral differences in arytenoid movements and their
● Resting asymmetry of the rima glottidis – usually only

significant if full and symmetrical arytenoid abduction
cannot be obtained or sustained.
● Inefficient abductor muscle function, which with more
severe degrees of RLN, full and symmetrical arytenoid
abduction may not be achieved and even if achieved, the
affected arytenoid cartilage adducts towards the mid-
line of the rima glottidis before the opposite arytenoid
cartilage following swallowing or nasal occlusion. Alter-
natively, abductor muscle fatigue is evident and observed
as a failure to maintain full abduction and the affected
cartilage slowly adducts towards the midline of the rima
glottidis before the opposite arytenoid cartilage.
● Inability to obtain full arytenoid abduction.
● Total immobility of the affected arytenoid cartilage.
● Open laryngeal ventricle and “slack” vocal fold as a
result of loss in muscle tone.
● Vocal fold trembling, hesitation or flutter – usually of
little clinical significance.
Grading laryngeal movements

Various subjective grading systems have been used to
describe laryngeal movements observed endoscopically
in horses breathing quietly at rest (Cook 1988, Ducharme
Fig. 34.8. This diagram shows the endoscopic appearance of the et al 1991, Dixon et al 2001, Lane 2004b). Using a static
larynx in a horse in which the left arytenoid cartilage is incompletely system to describe and categorize a dynamic process, in
abducted during deeper breathing. It is more abducted than in which an infinite range of laryngeal movements is possible,
Fig. 34.7. Note that the abaxial margin of the corniculate process is at
has limitations. Describing normal movements and those
approximately 75° to the midline.
as a result of paralysis is simple but a wide range of
potentially abnormal laryngeal movements can occur and
grading can never be precise. While a uniformly accepted
significance, in relation to the horses’ exercise tolerance,
system for describing laryngeal function is useful, of more
has been the subject of much debate. Because horses with
benefit to clinicians is one that could grade clinically
varying degrees of asymmetrical laryngeal movements
significant variations in laryngeal function and which
have also been shown to have intrinsic laryngeal muscle
could accurately predict how the larynx will function
damage it is generally considered that endoscopically
during exercise.
observed abnormal laryngeal function is directly related
Recently, a general consensus was reached amongst
to RLN (Duncan et al 1977, 1991b, Duncan & Baker
clinicians and researchers on an endoscopic laryngeal
1987). However, a precise correlation between the two is
grading system (Table 34.2) that should be useful in
not established and other physiological causes, e.g. the
clinical practice (Robinson 2004). It is an amalgamation
thoracolaryngeal adductory reflex, may account for some
of a number of common grading systems (Cook 1988,
asynchronous and asymmetrical laryngeal movements.
Ducharme et al 1991, Dixon et al 2001, Lane 2004b).
In addition, the different lengths of the left and right
The system described will be helpful in communication
recurrent laryngeal nerves, the influence of excitement,
between clinicians on grading, and hopefully when making
time of day, duration of examination, day of examination,
decisions on the necessity for surgical intervention, in
and the repeatability and reliability of endoscopic exami-
prepurchase examinations, and to determine if further
nations could all cause variation in endoscopically observed
diagnostic information is needed using video-endoscopy
laryngeal movements (Ducharme et al 1991, Anderson
of the upper respiratory tract during treadmill exercise.
et al 1997, Embertson 1997).
However, application over a large number of horses is
The effect of RLN on the movement of the arytenoid
required to assess the system’s clinical accuracy. In par-
cartilages can result in the following (Duncan et al 1977,
ticular, a large number of horses with each grade of
1991b, Duncan & Baker 1987):
laryngeal function will need to be examined on the tread-
● Loss of adductor function precedes loss of abductor mill under exercise conditions to assess the accuracy of the
function and may be demonstrated by the “grunt to the resting laryngeal function grades to be used as a predictor
stick” test. of laryngeal function during strenuous exercise.
Table 34.2. Subjective grading system of laryngeal function performed in the standing unsedated horse*
Grade Description Sub-grade
I All arytenoid cartilage movements are

synchronous and symmetrical and full
arytenoid cartilage abduction can be
achieved and maintained.
II Arytenoid cartilage movements are a. Transient asynchrony, flutter or delayed movements are seen.
asynchronous and/or larynx is asymmetric b. There is asymmetry of the rima glottidis much of the time due to
at times but full arytenoid cartilage reduced mobility of the affected arytenoid and vocal fold but there
abduction can be achieved and maintained. are occasions, typically after swallowing or nasal occlusion, when full
symmetrical abduction is achieved and maintained.
III Arytenoid cartilage movements are a. There is asymmetry of the rima glottidis much of the time due to
asynchronous and/or asymmetric. Full reduced mobility of the arytenoid cartilage and vocal fold but there
arytenoid cartilage abduction cannot be are occasions, typically after swallowing or nasal occlusion, when full
achieved and maintained. symmetrical abduction is achieved but not maintained.
b. Obvious arytenoid abductor muscle deficit and arytenoid cartilage
asymmetry. Full abduction is never achieved.
c. Marked but not total arytenoid abductor muscle deficit and arytenoid
cartilage asymmetry with little arytenoid cartilage movement. Full
abduction is never achieved.
IV Complete immobility of the arytenoid

cartilage and vocal fold.
* Description generally refers to the left arytenoid cartilage in reference to the right. However this grading system can apply to the right side
(i.e. right grade IIIa)
Clinical interpretation of laryngeal movement considered to have normal laryngeal function at rest will
grades and the diagnosis of RLN show dynamic axial collapse of the affected arytenoid
cartilage during strenuous exercise on the treadmill
As stated previously, the diagnosis of RLN requires clinical
(Morris 1991, Kannegieter & Dore 1995, Lane 2004c).
interpretation of laryngeal function in conjunction with an
In the study by Lane (2004c), 19 of 338 horses (or
animal’s exercise performance history, the nature of any
5.6%) referred for investigation of poor performance
possible abnormal exercise-related respiratory sounds
(often with a history of abnormal respiratory noise)
present and when they occur, and palpation of the larynx
that were graded I or IIa at rest showed dynamic col-
for the presence of muscular atrophy. An evaluation of
lapse of the left arytenoid cartilage or vocal fold under
the larynx that depends on endoscopy alone is incomplete
exercise conditions.
and the diagnosis of RLN from endoscopy alone should
● Horses with laryngeal movement grades IIb, IIIa, and
be made with caution. Unfortunately, in some circum-
IIIb may or may not have compromised respiratory
stances endoscopy and laryngeal palpation findings are all
function at exercise. In general, however, inability to
that the veterinarian has to make a diagnostic decision,
achieve full abduction of the affected arytenoid cartilage
e.g. in the yearling racehorse at purchase time.
during examination (grade IIIb) is likely to be associated
Based on the above grading system, the following clin-
with compromised respiratory function during exercise
ical decisions can be made.
and poor performance (Stick et al 2001). In one study
● Horses with grades IIIc and IV have significant RLN and (Lane 2004c) 83% of horses with this resting laryn-
all make a characteristic abnormal inspiratory noise at geal grade had axial dynamic collapse of the affected
exercise. Treadmill video-endoscopy is seldom warranted. arytenoid cartilage during strenuous exercise.
Surgical treatment is indicated (see Chapter 35). ● The functional significance of full arytenoid abduction
● Horses with laryngeal movements graded I and IIa that is not maintained symmetrically (grade IIIa)
should be considered functionally normal. However, can be difficult to determine. Limited treadmill endo-
if an abnormal respiratory noise is heard at exercise, scopic examinations of horses with this laryngeal grade
and especially if there is evidence of DCAM atrophy, indicate that some 75% of such horses can maintain
treadmill video-endoscopy is warranted. A number of full symmetrical abduction under exercise conditions
studies have shown that a small percentage of horses (Lane 2004c).
show that the disease is characterized by repetitive

Table 34.3. Grading system of laryngeal function
as assessed in the horse during exercise* denervation and reinnervation of the intrinsic laryngeal
muscles, suggesting that it is a progressive disorder.
Laryngeal Anderson (1984) found that these pathological changes
grade Definition
dramatically increase in prevalence and severity in
A Full abduction of the arytenoid cartilages during thoroughbred horses during the yearling to 2-year-old
inspiration. period. Presumably, if asynchronous arytenoid move-
B Partial abduction of the affected arytenoid
ments are related to these pathological changes, then
cartilages (between full abduction and the resting progression of asynchrony to hemiplegia is most likely to
position). be found in animals of this age. In one study (Anderson
et al 1997), 109 young thoroughbred and standardbred
C Abduction less than resting position including
collapse into the contralateral half of the rima horses were endoscopically examined on two occasions,
glottidis during inspiration. 16 months apart. At the initial examination most horses
were less than 2 years old. A change in laryngeal function
* Description generally refers to the left arytenoid cartilage in reference from that considered normal to that indicative of RLN was
to the right. However this grading system can apply to the right side recorded in 12% of horses. The development of severe RLN
(i.e. right grade IIIa)
(complete left-sided paralysis) was recorded in one horse
that initially had low-grade RLN, a rate of progression
of 5%. In this study it was interesting to note that 43% of
the horses did not change laryngeal grades, 29% were
When there is a mismatch between endoscopic, histori- given a “better” grade and 28% were given a “worse” grade
cal, and clinical findings, high-speed treadmill endoscopy at re-examination. While the repeatability of endoscopic
is indicated to evaluate the function of the larynx during laryngeal grading has limitations and could affect the
strenuous exercise. In addition, such an examination is used: results of this study, 29% of the changes in grading were
of 2 RLN grades. The authors concluded that some of the
● to evaluate the efficiency of a previous surgical
apparent improvement in laryngeal function might be
procedure
the result of regeneration of nerve fibers and compensatory
● in the general evaluation of poor performance
hypertrophy of unaffected muscle fibers in the DCAM.
● potentially, to arbitrate on a sales dispute or to assess the
Changes in laryngeal function over a 12-month period
likelihood of future problems in a horse to be purchased.
in young thoroughbreds have also been reported by
The endoscopic grading of laryngeal function during others (Lane 2004a). In this study, video-endoscopy was
exercise has been reported (Rakestraw et al 1991) and is used to record the laryngeal function in 197 foals. At
presented in Table 34.3. re-examination 12 months later, 187 yearlings were avail-
Hammer et al (1998) used this exercise grading system able. The video-endoscopic records were reviewed blindly.
to categorize 26 horses which all showed evidence of The results showed marked inconsistencies in the two age
laryngeal hemiparesis at rest (full abduction of the left groups. The laryngeal function of 129 of the 159 foals
arytenoid cartilage could not be achieved or maintained – (81%) with normal laryngeal function initially remained
denoted grade III). Of the 26 horses, 20 (77%) had grade C in this group, 20 of the 159 (13%) were recorded in the
laryngeal function during strenuous exercise. Of the equivocal group for RLN and one of the 159 (0.63%)
remaining horses, five had grade B laryngeal function and showed endoscopic evidence of RLN. Conversely, when nine
one had grade A. The use of treadmill endoscopy on this foals with marked abductor deficiency (grade 4 of 5) on
group of horses was helpful in determining the need for initial examination were re-examined 12 months later,
surgical intervention. However, the success of treatment one (11%) was considered normal (grade 2 of 5), five
varied according to the laryngeal function observed during (56%) were considered equivocal (grade 3 of 5) and three
exercise. Horses with grade C function during exercise (33%) remained grade 4. While it was concluded that
were treated by prosthetic laryngoplasty with reasonable endoscopy of foals is not reliable and decisions on whether
results (50% success). However, when this procedure was to buy or reject horses should not be solely based upon
performed on horses with grade B function the results were this technique, it is possible that some of the variation
poor (25% success). in laryngeal function could be the result of reinnerva-
tion of denervated laryngeal muscles or, alternatively, of
denervation of functionally normal intrinsic laryngeal
Clinical Progression of RLN musculature over this period.
Historical and anecdotal evidence from experienced veteri- Two studies have examined the possibility of progres-
narians indicates that some cases of RLN can be progression of RLN in older horses. Baker (1982) examined 168
sive. Histopathological examination of horses with RLN thoroughbred national hunt horses endoscopically, most
over 5 years old, at annual intervals on at least three Baker GJ 1982 Laryngeal asynchrony in the horse: definition
occasions. Laryngeal movements were classified as normal, and significance. In: Snow DH, Persson SGB, Rose RF
asynchronous, and laryngeal hemiplegia. The conclusion (editors) Equine Exercise Physiology. Granta Publications,
Cambridge, pp.46–52
from the survey was that laryngeal asynchrony is not Barber SM 1981 Paralaryngeal abscess with laryngeal hemi-
clinically significant and that horses with asynchrony do plegia and fistulation in a horse. Canadian Veterinary
not progress to hemiplegia. More recently, Dixon et al Journal 22: 389–392
(2002) reported on endoscopic and/or clinical progres- Beard WL, Hayes HM. 1993 Risk factors for laryngeal
sion of RLN in older National Hunt and sport horses hemiplegia in horses. Preventative Veterinary Medicine
17: 57–63
(predominantly thoroughbreds). Fifty-two of the 351 Cahill J, Goulden B 1986a Equine laryngeal hemiplegia:
horses examined (15%) showed evidence of progression of Part I, a light microscopic study of peripheral nerves.
the degree of laryngeal dysfunction over a median period New Zealand Veterinary Journal 34: 161–169
of 12 months (range 1.5–48 months) with the onset of Cahill J, Goulden B 1986b Equine laryngeal hemiplegia:
progression occurring at a median age of 7 years. Part II, an electron microscopic study of peripheral nerve.
New Zealand Veterinary Journal 34: 170–175
The results of the endoscopic surveys by Anderson et al Cahill J, Goulden B 1986c Equine laryngeal hemiplegia:
(1997) and Dixon et al (2002), both of which involve Part III, a teased fibre study of peripheral nerves. New
predominantly thoroughbreds, indicate that the pro- Zealand Veterinary Journal 34: 181–185
gression of RLN with clinically significant arytenoid Cahill J, Goulden B 1986d Equine laryngeal hemiplegia:
abductor dysfunction can occur in between 5 and 15% Part IV, muscle pathology. New Zealand Veterinary
Journal 34: 186–190
of horses, respectively. The age of onset of the deteriora- Cahill J, Goulden B 1987 The pathogenesis of equine laryngeal
tion in arytenoid function is, however, markedly different. hemiplegia – a review. New Zealand Veterinary Journal
The reason for this is unknown. In addition, Dixon et al 35: 82–90
(2002) reported that the time or rate at which progression Christley RM, Hodgson DR, Evans DL, Rose RJ 1997 Cardio-
can develop may be as short as 6 weeks. In other cases respiratory responses to exercise in horses with different
grades of idiopathic laryngeal hemiplegia. Equine
deterioration can take months to years. This has important Veterinary Journal 29: 6–10
implications for the examination of horses for sale and Cook WR 1965 The diagnosis of respiratory unsoundness in
also for determining the most appropriate treatment the horse. Veterinary Record 77: 516–28
for such cases. Cook WR 1970 A comparison of idiopathic laryngeal paralysis
In contrast to the above study by Anderson et al (1997), in the horse and man. Journal of Laryngology and
Otology 84: 819–835
Dixon et al (2002) found no evidence of improvement in Cook WR 1988 Diagnosis and grading of hereditary recurrent
laryngeal function in the clinical cases examined. laryngeal neuropathy in the horse. Journal of Equine
In summary, in the majority of horses, laryngeal func- Veterinary Science 8: 432–455
tion remains constant over time, but in some horses, laryn- Dixon PM, McGorum BC, Railton DI, Hawe C, Tremaine WH,
geal function can deteriorate quickly over a few weeks or Pickles K, McCann J 2001 Laryngeal paralysis: a study
of 375 cases in a mixed-breed population of horses
more slowly over some years. Equine Veterinary Journal 33: 452–458
Dixon PM, McGorum BC, Railton DI, Hawe C et al 2002
Clinical and endoscopic evidence of progression of 152
REFERENCES cases of equine recurrent laryngeal neuropathy (RLN).
Anderson LJ 1984 A study of some muscles of the equine Ducharme NG, Hackett RP 1991 The value of surgical treat-
larynx and soft palate. Unpublished PhD thesis. Massey ment of laryngeal hemiplegia in horses. Compendium on
University, Palmerston North Continuing Education for the Practicing Veterinarian
Anderson BH 2002 Update on post-sale endoscopic exami- 13: 472–475
nation of horses in New Zealand. Proceedings of the Ducharme NG, Hackett RP, Fubini SL, Erb HN 1991 The
Annual Seminar of the Equine Branch of New Zealand reliability of endoscopic examination in assessment
Veterinary Association (Publication No 222). Massey of arytenoid cartilage movement in horses. Part II.
University, Palmerston North, pp.99–105 Influence of side of examination, reexamination, and
Anderson BH, Kannegieter NJ, Goulden BE 1997 Endoscopic sedation. Veterinary Surgery 20: 180–184
observations on laryngeal symmetry and movements in Duncan ID 1992 Determination of the early age of onset
young racing horses. New Zealand Veterinary Journal of equine recurrent laryngeal neuropathy. 2. Nerve
45: 188–192 pathology. Acta Neuropathologica 84: 316–321
Archer RM, Lindsay WA, Duncan ID 1991 A comparison of Duncan ID, Baker GJ 1987 Experimental crush of the equine
techniques to enhance the evaluation of equine laryngeal recurrent laryngeal nerve: a study of normal and aberrant
function. Equine Veterinary Journal 23: 104–107 re-innervation. American Journal of Veterinary Research
Attenburrow DP 1982 Resonant frequency of the lateral 48: 431–438
ventricle and saccule and whistling In: Snow DH, Persson Duncan ID, Griffiths IR, McQueen A, Baker GO 1974
SGB, Rose RF (editors) Equine Exercise Physiology. Granta The pathology of equine laryngeal hemiplegia. Acta
Publications, Cambridge, pp.27–32 Neuropathologica (Berlin) 27: 337–348
Duncan ID, Baker GJ, Heffron CJ, Griffiths IR 1977 A corre- Lane JG 1993a Fourth branchial arch defects. In: Dyke TM
lation of the endoscopic and pathological changes in (editor) Proceedings of the fifteenth Bain-Fallon Memo-
subclinical pathology of the horse’s larynx. Equine rial Lectures. Australian Equine Veterinary Association,
Veterinary Journal 23: 22–225 Artarmon, NSW, pp.209–212
Duncan ID, Griffiths IR, Madrid RE 1978 A light and electron Lane JG 1993b Equine recurrent laryngeal neuropathy (RLN):
microscopic study of the neuropathy of equine idio- current attitudes to aetiology, diagnosis and treatment.
pathic laryngeal hemiplegia. Neuropathology and Applied In: Dyke TM (editor) Proceedings of the fifteenth Bain-
Neurobiology 4: 483–501 Fallon Memorial Lectures. Australian Equine Veterinary
Duncan ID, Reifenrath P, Jackson KF, Clayton M 1991a Association, Artarmon, NSW, pp.173–192
Preferential denervation of the adductor muscles of the Lane JG 2004a Long-term longitudinal study of laryngeal
equine larynx. II: Nerve pathology. Equine Veterinary function in 187 foals. In: Dixon PM, Robinson NE,
Journal 23: 99–103 Wade JF (editors) Proceedings of a Workshop on Equine
Duncan ID, Amundson J, Cuddon PA et al 1991b Preferential Recurrent Laryngeal Neuropathy, Havemeyer Foundation
denervation of the adductor muscles of the equine Monograph Series No 11. R&W Publications, Newmarket,
larynx. I: Muscle pathology. Equine Veterinary Journal pp.31–32
23: 94–98 Lane JG 2004b 5-point grading system for endoscopy of
Ellis D, Greet TRC Lane JG 2004 Sales: problems in diagnosis horses during quiet breathing. Proceedings of a Work-
of RLN – UK perspective. In: Dixon PM, Robinson NE, shop on Equine Recurrent Laryngeal Neuropathy,
Wade JF (editors) Proceedings of a Workshop on Equine Havemeyer Foundation Monograph Series No 11. Eds
Recurrent Laryngeal Neuropathy, Havemeyer Foundation PM Dixon, NE Robinson JF Wade, pp.24–25
Monograph Series No 11. R&W Publications, Newmarket, Lane JG 2004c Differences between resting and treadmill
pp.39–41 endoscopic findings in regard to RLN. In: Dixon PM,
Embertson RM 1997 Evaluation of the upper respiratory tract Robinson NE, Wade JF (editors) Proceedings of a Work-
of the immature horse. In: Rantanen NW, Hauser ML shop on Equine Recurrent Laryngeal Neuropathy,
(editors) Proceedings of the Dubai International Equine Havemeyer Foundation Monograph Series No 11. R&W
Symposium. The Diagnosis and Treatment of Respiratory Publications, Newmarket, pp.47–48
Disease. Matthew R Rantanen, Bonsall, pp.399–405 Lane JG, Ellis DR, Greet TR 1987 Observations on the exami-
Gerring EL 1985 Differential diagnosis of equine respiratory nation of Thoroughbred yearlings for idiopathic laryn-
noises. In Practice pp.109–117 geal hemiplegia. Equine Veterinary Journal 19: 531–536
Goulden BE, Anderson LJ 1981a Equine laryngeal hemiplegia, Mackay-Smith MP, Marks D 1968 Clinical diagnosis of laryn-
Part II: some clinical observations. New Zealand Veterinary geal hemiplegia in horses. Proceedings of the American
Journal 29: 194–198 Association of Equine Practitioners, pp.227–235
Goulden BE, Anderson LJ 1981b Equine laryngeal hemiplegia, Morris E 1991 Dynamic evaluation of the equine upper
Part I: Physical characteristics of affected animals. respiratory tract. Veterinary Clinics of North America;
New Zealand Veterinary Journal 29: 151–154 Equine Practice 7: 403–416
Goulden BE, Anderson LJ, Cahill HI 1985 Roaring in Newton-Clarke MJ, Divers TJ, Valentine BA 1994 Evaluation of
Clydesdales. New Zealand Veterinary Journal 33: 73–76 the thoraco-laryngeal reflex (“slap test”) as an indicator
Greet TR, Jeffcott LB, Whitwell KE, Cook WR 1980 The slap of laryngeal adductor myopathy in the horse. Equine
test for laryngeal adductory function in horses with Veterinary Journal 26: 355–357
suspected cervical spinal cord damage. Equine Veterinary Parente E, Martin B 1995 Correlation between standing
Journal 12: 127–131 endoscopic examinations and endoscopic examina-
Gunn HM 1973 Further observations on laryngeal skeletal tion during high-speed exercise in horses: 150 cases.
muscle in the horse. Equine Veterinary Journal 2: 77–80 Proceedings of the American Association of Equine
Hammer EJ, Tulleners EP, Parente EJ, Martin BB 1998 Video- Practitioners 24: 436
endoscopic assessment of dynamic laryngeal function Rakestraw PC, Hackett RP, Ducharme NG et al 1991 A com-
during exercise in horses with grade-III laryngeal hemi- parison of arytenoid cartilage movement in resting and
paresis at rest: 26 cases (1992–1995). Journal of the exercising horses. Veterinary Surgery 20: 122–127
American Veterinary Medical Association 212: 399–403 Robinson NE 2004 (Chairperson) Consensus statements on
Harrison GD, Duncan ID, Clayton MK 1992 Determination of equine recurrent laryngeal neuropathy: Conclusions of
the early age of onset of equine recurrent laryngeal the Havemeyer Workshop. September 2003, Stratford-
neuropathy. 1. Muscle pathology. Acta Neuropathologica upon-Avon. Equine Veterinary Education 16: 333–336
(Berlin) 84: 307–315 Speirs VC 1992 Larynx. In: Auer JA (editor) Equine Surgery,
Hawe C, Dixon PM, Mayhew IG 2001 A study of an electro- 1st edn. WB Saunders, Philadelphia, pp.467–480
diagnostic technique for the evaluation of equine recur- Stick JA, Peloso JG, Morehead JP et al 2001 Endoscopic
rent laryngeal neuropathy. Equine Veterinary Journal assessment of airway function as a predictor of racing
5: 459–465 performance in Thoroughbred yearlings: 427 cases
Holcombe SJ, Derksen FJ, Stick JA et al 1996 Effect of nasal (1997–2000). Journal of the American Veterinary Medical
occlusion on tracheal and pharyngeal pressures in horses. Association 219: 962–967
American Journal of Veterinary Research 57: 1258–1260 Weishaupt MA, Kästner SBR, Greishaber, von Plocki K 1998
Kannegieter NJ, Dore ML 1995 Endoscopy of the upper respi- Airflow limitations in laryngeal hemiplegia: chemical
ratory tract during treadmill exercise: a clinical study of versus exercise induced hyperventilation. Proceedings of
100 horses. Australian Veterinary Journal 72: 101–107 the World Equine Airways Symposium 2: 40
Surgical Treatment of Laryngeal
Hemiplegia and Hemiparesis
35 Christine M Adreani and Eric J Parente
Laryngoplasty: Surgical Technique

because of the many adjacent vital structures. The use of a
Laryngoplasty was first described by Marks et al (1970), as hand-held retractor in the dorsal portion of the incision
an alternative technique to ventriculectomy and arytenoidec- allows better exposure of the larynx. The cricopharyngeus
tomy for the treatment of recurrent laryngeal neuropathy and thyropharyngeus muscles are separated along their
(RLN) in athletic horses. The authors noted that although aponeurosis to expose the intrinsic laryngeal muscles and
ventriculectomy was the standard technique for treating the muscular process of the arytenoid.
horses with RLN, this procedure was not very successful in The suture prosthesis is first placed through the dorso-
treating race and performance horses. The technique of caudal edge of the cricoid cartilage between the cartilage
laryngoplasty was developed to “reconstruct the laryngeal and the laryngeal mucosa. The point of the needle should
lumen in its anatomic position of maximal inspiratory be carefully walked off the caudal edge of the cricoid to
dilatation” (Marks et al 1970). To do this, they proposed avoid inadvertent damage to nearby structures such as the
replacing the atrophied cricoarytenoideus dorsalis muscle carotid artery or esophagus, and should be placed as close
with a prosthesis that would “maintain the muscular to the dorsal midline as possible (at the site of the caudal
process of the arytenoid in caudad retraction”. The pros- cricoid “notch”). Once through the cricoid cartilage, the
thesis, therefore, joins the dorsocaudal edge of the cricoid needle is passed under the cricopharyngeus muscle and
cartilage and the muscular process of the arytenoid cartilage. then passed through the muscular process of the arytenoid
The choice of suture material used for the prosthesis in a caudomedial to rostrolateral direction. The trailing
varies depending on surgeon preference. A large diameter, end of the suture is then passed under the cricopharyngeus
non-absorbable, monofilament or coated suture material is muscle. A second prosthesis can then be placed. Intra-
preferable. Marks et al (1970) used braided Lycra® for the operative endoscopy is often used at this time to ensure that
prosthesis because they believed the elastic properties of the suture has not penetrated the laryngeal lumen and
this suture were necessary. Subsequent descriptions of the to ensure that an appropriate degree of arytenoid abduc-
procedure have replaced this multifilament, inflammatory tion is present, as the individual sutures are tightened and
material with materials such as No. 5 coated polyester, knotted (Fig. 35.1). Generally it is appropriate to abduct the
No. 2 nylon or stainless steel wire. arytenoid into a position of 80–90% of maximal abduction
Horses are positioned in lateral recumbency, with in racehorses, with lesser abduction (60–80% of maximal
the affected side dorsally and the head and neck extended. abduction) being appropriate in non-performance horses.
A 3-liter bag of fluid placed under the larynx will help The degree of abduction has been semi-quantitatively
to elevate it towards the surgeon. It is often beneficial to graded by a number of systems including that illustrated
position a video-endoscope in the ipsilateral nostril before in Fig. 35.2. The apparent degree of abduction intraopera-
the beginning of surgery to provide an image of the larynx tively is always slightly greater than that seen on resting
for later use. After preparation of the skin for aseptic endoscopy the following day in the standing horse. This
surgery, an 8- to 10-cm incision is made ventral and may be because of some immediate decrease in abduction
parallel to the linguofacial vein, centered at the palpable or the overestimation of abduction in the horse under
caudal edge of the cricoid cartilage. A plane of dissection anesthesia, possibly because the pharyngeal vault is
is established between the linguofacial vein and the relaxed onto the margin of the corniculates while the horse
omohyoideus muscle, and a combination of sharp and is under anesthesia. Once the sutures are knotted, the
blunt dissection is used to expose the caudal pharyngeal pharyngeal constrictor muscles are re-apposed using 2–0
constrictor muscles (thyropharyngeus and cricopha- absorbable sutures. Closure of the subcutaneous and skin
ryngeus). Careful attention should be paid to hemostasis incisions is then performed in a routine fashion.
as this surgical site is prone to large seroma formation Two variations to the standard laryngoplasty procedure
because of the extensive dissection used for this procedure have been employed by the authors. With appropriate posi-
and the inability to close the large dead space created tioning, the arytenoid muscular process can be approached
497
498 35 Surgical Treatment of Laryngeal Hemiplegia and Hemiparesis
at the caudal margin of the cricopharyngeus muscle. This

obviates the need for the dissection and closure between
the cricopharyngeus and thyropharyngeus muscles, saving
surgical time. More importantly, it minimizes the potential
of subsequent suture loosening from interposed fascia. A
second alternative is to approach the cricoarytenoid joint
underneath the attachment of the cricoarytenoideus
dorsalis to the muscular process and ablate this joint with a
rotating burr. This procedure causes ankylosis of the
cricoarytenoid joint and more rigid fixation of the
arytenoid experimentally (Parente 2004).
Horses should be treated perioperatively with antimicro-
bials and anti-inflammatory medications. Sequential endo-
scopic evaluation of the degree of arytenoid abduction
should be performed postoperatively, especially before the
horse is discharged from the hospital.
Postoperative care
Most horses experience some degree of dysphagia and
coughing immediately postoperatively (Speirs 1972, Hawkins
Fig. 35.1. Intraoperative endoscopic view of the larynx during laryn-
et al 1997, Dixon et al 2003a). Therefore, they should be
goplasty as the left arytenoid is being surgically abducted.
Grade 1 Grade 2 Grade 3
Grade 4 Grade 5
Fig. 35.2. Semi-quantitative grading of the degree of laryngoplasty abduction. Reprinted from Dixon et al,
2003a, with permission.
35 Surgical Treatment of Laryngeal Hemiplegia and Hemiparesis 499
fed off the ground to help minimize aspiration of feed were significantly improved following surgical correction,
material. The incision should be carefully examined daily arterial blood gas and pH values were not the same as
for signs of excessive swelling or drainage, indicative of in normal horses, in spite of endoscopic evidence of full
excessive seroma formation or wound infection. arytenoid abduction postoperatively.
Horses should be confined to their stall with hand walk- Upper airway flow mechanics, measured in horses exer-
ing for 4–6 weeks following surgery. A further endoscopic cising on a treadmill, show a predictable decrease in peak
examination should then be performed to assess healing of inspiratory flow and increase in inspiratory resistance
the vocal cordectomy and the position of the affected following experimental recurrent laryngeal neurectomy
arytenoid before the horse resumes training (Fig. 35.3). (Derksen et al 1986). These alterations were reversed by
prosthetic laryngoplasty, leading to the conclusion that
laryngoplasty supported the arytenoid cartilage and so
Efficacy of Surgical Intervention: limited dynamic collapse of the laryngeal airway during
Experimental Studies inspiration. Likewise, Shappell et al (1988) showed that the
The effects of prosthetic laryngoplasty on upper airway increases in inspiratory impedance and inspiratory trans-
function and arterial blood gases and pH parameters upper airway pressure that occurred following experi-
have been examined in numerous experimental studies. mental recurrent laryngeal neurectomy were abolished
Overall, prosthetic laryngoplasty has been shown to restore by laryngoplasty. Tetens et al (1996) tested upper airway
abnormalities in the above parameters that are present in function in horses exercising at 75 and 100% of maximal
horses with RLN or in experimental recurrent laryngeal heart rate on a treadmill and found that inspiratory
neurectomy to values found in normal exercising horses. impedance was increased and flow was decreased following
Arterial blood gases measured in a horse with left RLN recurrent laryngeal neurectomy. Tetens et al (1996) also
before and 48 h after laryngoplasty demonstrated that found that these values were restored to preneurectomy
the hypoxemia and hypercapnia initially observed after levels after laryngoplasty.
galloping were reversed postoperatively (Bayly et al 1984). A limitation in the interpretation of these studies, how-
Similar results were obtained by Tate et al (1993) in a ever, is that horses were studied at submaximal exercise
study of four horses with RLN where blood gas tensions levels, and consequently airflow rates were not as high as
and acid–base status were evaluated before and after occur in horses exercising at racing speeds. Williams et al
corrective surgery. In that study however, although the (1990a) addressed this limitation by recording upper airway
acidosis and hypoxemia that developed during exercise pressures in thoroughbred horses galloping on a racetrack.
In this study, horses with experimental recurrent laryngeal
neurectomy had a 2.5-fold increased peak inspiratory upper
airway pressure as compared to preneurectomy levels.
Laryngoplasty reduced the peak inspiratory pressure, but
values were still significantly elevated over control (pre-
neurectomy) levels. In a separate study of horses clinically
affected with left RLN, Williams et al (1990b) showed that
clinically affected horses had airway pressures similar to
those with experimental recurrent laryngeal neurectomies.
Laryngoplasty in the RLN-affected horses restored upper
airway function to within the normal range.
While the effect of laryngoplasty on respiratory noise is
generally evaluated in a subjective manner, recent work
has shown that noise can be qualitatively and quantita-
tively studied using spectrogram analysis in exercising
horses. Brown et al (2004) used exercising standardbreds
that had received a recurrent laryngeal neurectomy,
followed by laryngoplasty, to study the effect of surgery on
inspiratory sound level and the three formants of inspi-
ratory sound intensity (see Chapter 17). These authors
found that sound level and intensity were increased follow-
ing neurectomy, and that the first inspiratory formant
was restored to its preneurectomy value by 30 days post
Fig. 35.3. Endoscopic examination 1 month postoperatively following laryngoplasty. Sound levels, as well as the second and third
left-sided laryngoplasty and vocal cordectomy. The left arytenoid is in a formants of respiratory sounds, were significantly improved
well-abducted position and the cordectomy site is well healed. by laryngoplasty but did not return to baseline levels.
Interestingly, the degree of arytenoid abduction post- after surgery dropped in class or distance after surgery,
operatively was positively correlated with postoperative and that their earnings dropped 2.6-fold over this period.
noise production. Hawkins et al (1997) found that 56% of thoroughbred and
standardbred racehorses that raced three or more times
before and after surgery had improved performance index
Efficacy of Surgical Intervention: scores postoperatively, and that 77% of horses raced at
Outcome in Clinical Cases least once after surgery. In a retrospective study designed to
The reported success rates for prosthetic laryngoplasty vary compare the success rate of laryngoplasty in experienced
widely depending on the criteria used to define success. In and inexperienced thoroughbred racehorses, Strand et al
general, success rates for draft and sport horses are better (2000) used a performance index which was obtained from
than those reported for racehorses, leading to the overall a verified regression model for standardizing the racing
conclusion that even with surgical correction, there still performance of thoroughbreds. Experienced racehorses
may be respiratory limitations to high-speed exercise in improved their performance index following surgery
some horses. compared to the period immediately preceding laryngo-
In the first published report of prosthetic laryngoplasty, plasty but did not reach their previous baseline values for
Marks et al (1970) reported on 121 horses treated with performance index or earnings. Nevertheless, they raced
this procedure. Eighty-eight per cent of these surgeries distances of similar length before and after surgery, and
were reported to be “completely successful”, with success 45% of experienced racehorses ran a personal best time
being defined as the presence of maximal abduction of the after surgery.
affected arytenoid during postoperative resting endo- Age at the time of surgery does not seem to affect the
scopy. Speirs (1972) reported on eight thoroughbreds that outcome of laryngoplasty in racehorses. When a perform-
had been treated with prosthetic laryngoplasty. Five were ance index was used to compare outcome in 2-year-old
reported to be in race training and free of respiratory noise. standardbred and thoroughbred racehorses to that in
One horse was racing, but still made a noise, and the other 3-year-old horses of the same breeds, no effect of age at
two horses were reported to have reduced racing perform- the time of surgery was observed (Hawkins et al 1997).
ance. Subsequent reports have refined the criteria for Likewise, horses that were either 2 years old or had fewer
success by focusing on various aspects of functional than two starts at the time of surgery had a career per-
outcome following surgery. formance index equal to that of the older, experienced
horses (Strand et al 2000). Younger, inexperienced horses
Outcome in racehorses require significantly more time after surgery to their first
race (165 days) than older experienced horses (120 days)
When postoperative racing performance was subjectively (Strand et al 2000).
evaluated by owner/trainer, improvement was found in The effect of the endoscopic degree of preoperative
48–69% of horses (Russell & Slone 1994, Hawkins et al hemiplegia on surgical outcome has been evaluated in
1997, Kidd & Slone 2002). Interestingly, the perceived several retrospective studies, and the results are some-
success rate was higher in thoroughbred racehorses aged 2 what conflicting (Hawkins et al 1997, Hammer et al 1998,
years or more (70% success) when compared to those aged Davenport et al 2001). Hawkins et al (1997) reported on
3 years or above (25% success) (Russell & Slone 1994). the postoperative findings of 230 thoroughbred and
Several objective analyses of racing performance follow- standardbred racehorses divided nearly equally between
ing laryngoplasty have been reported, with varying results grades III and IV RLN, where the grading system used
depending on the method of comparison of performance (Hackett et al 1991) was a four-grade system based on
before and after surgery (Speirs et al 1983, Russell & Slone resting endoscopy in which a grade IV was unable to move
1994, Hawkins et al 1997, Strand et al 2000, Kidd & Slone one arytenoid, and a grade III was able to move the
2002). A large Australian study (Speirs et al 1983) described arytenoid but not achieve full abduction. In spite of the
the results of laryngoplasty in 100 racing thoroughbreds large number of cases of each grade of RLN, no effect of
in a survival analysis which compared the postoperative grade on postoperative performance index was observed.
racing results of these horses to those of 400 control When horses with grade III laryngeal hemiplegia are
horses of similar age, breed, sex, and occupation. The further subdivided, based on the degree of arytenoid
survival analysis took into account total races, wins, wins movement during high-speed treadmill exercise, a differ-
plus placings, and earnings. It showed no significant ence in surgical success was reported between those horses
difference between the 100 horses treated with laryngo- that have some ability to abduct the left arytenoid (grade
plasty and the control horses, leading the authors to IIIb) and those that have complete dynamic collapse of
conclude that laryngoplasty “restored racehorses to the the arytenoid (grade IIIc) (Hammer et al 1998). Only
standard set by their peers”. one in four horses with grade IIIb laryngeal hemiplegia
In a study of 40 racehorses, Russell & Slone (1994) were reported to have an improved performance index
found that 78% of thoroughbreds that raced before and postoperatively, whereas nine of 18 horses with grade IIIc
improved their racing performance postoperatively. No procedure. When combined with ventriculocordectomy,
statistical analysis was performed and while these results laryngoplasty resulted in 73% of horses (sports horses and
appear to indicate that horses with worse preoperative racehorses) making no abnormal upper respiratory noise
function have a better outcome, it is more likely that all during exercise (Dixon et al 2003b). Similarly, respiratory
horses have a similar postoperative performance outcome, noise was eliminated in 72% of draft horses treated with
but those horses that are paralyzed have a greater disparity laryngoplasty and ventriculectomy or ventriculocordec-
between their preoperative and postoperative performances tomy (Kraus et al 2003). These results contrast somewhat
than horses that still have partial function preoperatively. with those found in racehorses, in which 25–47% of
Consequently, there is no evidence to support the theory horses treated with laryngoplasty and ventriculocordec-
that waiting until a horse is completely paralyzed before tomy still make a noise while exercising at long-term
pursuing surgery will improve the surgical outcome. follow-up (Russell & Slone 1994, Hawkins et al 1997). This
A suspected reason for the apparent lack of improve- difference may be the result of the higher intensity exercise
ment in some horses with partial laryngeal function at and the resulting increased respiratory effort made by
the time of surgery is that they are more likely to have an racehorses when compared to performance breeds.
unsuccessful surgery. The primary reason for laryngoplasty Dixon et al (2003b) published a comprehensive evalua-
failure is inability of the prosthesis to maintain abduction. tion of the outcome of laryngoplasty and ventriculocordec-
Some authors suspect that the major causes for prosthesis tomy in an older, mixed-breed group of 200 horses. While
failure are repetitive contraction of the remaining muscles many horses included in the study were National Hunt
that results in subsequent loosening of the suture, or that racehorses and therefore analogous to flat racehorses, the
the suture cuts through the cartilage. In an effort to inves- majority were hunters, eventers, show jumpers, draft horses,
tigate the contribution of the cricoarytenoideus dorsalis and multi-discipline sport horses. Six weeks postoperatively,
muscle movement to laryngoplasty failure, Davenport et al 91% of the treated horses began to resume training.
(2001) compared postoperative racing performance in Interestingly, the degree of postoperative abduction at
horses with grade III laryngeal hemiplegia that were treated 6 weeks had little effect on whether or not the horse
with laryngoplasty, ventriculocordectomy, and ipsilateral returned to full work, except that horses with no detect-
recurrent laryngeal neurectomy to horses without the able abduction were much less likely to resume full work.
neurectomy. By eliminating any movement of the existing Ninety-five per cent of horses with a high degree of abduc-
intrinsic muscles via the neurectomy, the authors were able tion, 91% of horses with moderate abduction, and 88% of
to determine that residual movement of the muscles caused horses with slight abduction returned to full work, but only
by an intact, partially functional recurrent laryngeal nerve 25% of horses with no residual abduction returned to
did not affect the postoperative performance. Therefore, a full work. When owners/trainers were asked to evaluate
difference in success following laryngoplasty between their horses’ level of exercise performance at a mean of
horses with grade III and grade IV laryngeal hemiplegia 12 months after surgery, 64% reported a marked increase
would not be expected. in performance and another 11% reported a slight or
moderate increase.
Outcome in non-racing breeds A report of surgical treatment for laryngeal hemiplegia
in draft horses implied that laryngoplasty held no advan-
Surgical success in draft and sport horses is generally tage over ventriculectomy alone (Bohanon et al 1990),
higher than that reported in racehorses, regardless of the suggesting that the additional surgery time required for
criteria used to define success (Russell & Slone 1994, Kidd laryngoplasty posed an unnecessary increased anesthetic
& Slone 2002, Dixon et al 2003b). The perceived success risk to draft horses. Kraus et al (2003) described the
rate, based on owner/trainer surveys, in non-racing breeds outcome of laryngoplasty and ventriculectomy or ventricu-
ranges between 86 and 93%. While exercise intolerance locordectomy in 104 competitive draft horses, and although
must be alleviated enough to allow the horse to fulfill its the incidence of anesthetic-related complications was
intended purpose, elimination of abnormal respiratory higher than that reported for light breed horses, these
noise is often equally important for the competitive show complications were still relatively rare. Postanesthetic
horse. An objective comparison of performance before and myopathy or neuropathy occurred in 7% of cases and
after surgery is difficult in this population of horses because prolonged anesthetic recoveries occurred in 4%; only one
of the wide range of expectations on the part of the anesthetic-related death was reported. Overall, surgical
owner/trainer in terms of athletic function and presence of correction was highly successful in this study, with 92% of
respiratory noise. Nevertheless, several large studies have horses having improved exercise tolerance postoperatively
evaluated the success of laryngoplasty in addressing the and 72% of horses being able to be used for their intended
performance-limiting problems seen in the non-racehorse. purpose of competitive driving.
When success was defined as a significant reduction or Regardless of the breed, occupation, or criteria for
absence of noise, Baker (1983) reported that laryngoplasty success used, the grade of preoperative laryngeal dysfunc-
was successful in 58% of 316 horses treated with the tion does not appear to have a significant effect on surgical
A B
Fig. 35.4. (A) Excessive laryngoplasty abduction of this left arytenoid prosthesis, with the arytenoid now in a more adducted position. The
led to dysphagia and excessive coughing in this horse. (B) Endoscopic aspiration problem was resolved.
examination after a second surgery was performed to replace the
outcome in non-racehorses (Russell & Slone 1994, Dixon The horse’s inability to protect its airway adequately while
et al 2003a,b, Kraus et al 2003). A greater degree of post- eating likely results in the persistent aspiration of feed
operative surgical abduction resulted in a larger number material. The dorsal laryngeal wall and the trachea of
of postoperative complications such as coughing, but in humans have been shown to contain numerous irritant
the longer term did not appear to be correlated with receptors (Guyton & Hall 2000) which, when stimulated,
postoperative performance (Russell & Slone 1994, Dixon result in a cough reflex, although horses appear to have a
et al 2003a,b). less sensitive upper respiratory tract than humans and
many other domestic animals. Some aspiration of feed
material is likely the result of dysphagia caused by the
Postoperative Complications surgically abducted arytenoid failing to protect the air-
Cough: short-term and chronic way during swallowing. Dysphagia may also result from
pharyngeal constrictor muscle dysfunction following
Coughing, both immediately postoperatively and chroni- surgery (Greet et al 1979). Dissection between the caudal
cally, is a common complication of laryngoplasty surgery pharyngeal constrictor muscles and inadvertent damage
(Marks et al 1970, Raker 1975, Speirs et al 1983, Russell & to the cranial laryngeal nerve may result in this dysfunc-
Slone 1994, Hawkins et al 1997, Dixon et al 2003a). tion. Some surgeons have reasoned that this is why, in a
Although there is wide variation in the reported incidence minority of horses that cough postoperatively, removal of
of postoperative coughing, up to 43% of horses treated the prosthesis does not result in elimination of the clinical
with laryngoplasty may develop coughing at some point. signs (Raker 1975, Greet et al 1979).
The cause is likely multifactorial. The presence of coughing In some cases with maximal surgical abduction of the
postoperatively does not necessarily preclude improved arytenoid and subsequent dysphagia and coughing, a
athletic performance (Russell & Slone 1994, Hawkins et al second surgery is required to loosen the prosthesis
1997) but it is considered a common and undesirable side (Fig. 35.4A,B). Dixon et al (2003a) reported that eight
effect of laryngoplasty. of 200 horses required a second surgery within a week of
The presence of a maximal degree of arytenoid abduc- the first surgery, and another six of the remainder required
tion postoperatively is significantly associated with coughing a second surgery within 6 weeks of the first to alleviate
and dysphagia (Russell & Slone 1994, Dixon et al 2003a). persistent dysphagia and coughing; there was immediate
resolution of the dysphagia and coughing in all cases is sutured closed (Hawkins et al 1997), likely because of
following prosthesis loosening. the excellent ventral drainage afforded by the location of
Many cases of postoperative dysphagia and coughing this incision.
will spontaneously resolve within a few weeks of surgery, Meticulous postoperative local wound care aids in reduc-
possibly because of loosening of the prosthesis and/or ing the likelihood of soft tissue infection around unsutured
adaptation of the swallowing reflex. However, if the dys- laryngotomy incisions (Stick et al 1999). Laryngoplasty
phagia and coughing persist, there are several manage- wound infections usually resolve with drainage, combined
ment changes that should be considered postoperatively with antimicrobial and possibly anti-inflammatory therapy.
before removing the prosthesis. Continuing to feed the Suture removal is rarely required (Hawkins et al 1997).
horse off the ground and moistening the hay or changing Incisional seromas and minor wound swelling are more
the horse’s diet to include a greater percentage of processed common wound complications than infection in laryngo-
feed is often beneficial. Removing all feed several hours plasty (Hawkins et al 1997, Speirs et al 1983, Dixon et al
before exercise and rinsing out the horse’s mouth with 2003a). The reported incidence for minor swelling and/or
water will remove most feed stored in the mouth. Generally seroma formation is 7–30%. The higher number was
if these methods do not improve the horse in several weeks, reported in 1983 when Lycra suture material was used for
suture removal or replacement is recommended. Removal laryngoplasty (Speirs et al 1983). Therefore, some reported
of the suture alone may not be enough to resolve the swellings might have been the result of inflammation
coughing. To gain relaxation of the arytenoid at the time of associated with the prosthesis. Dixon et al (2003a) found
surgery in more chronic cases, or particularly if there has that 17% of cases had reported swellings or discharge asso-
been postoperative wound infection, it may be necessary ciated with the laryngoplasty incision, and that more than
to dissect the muscular process free from the fibrous half of these resolved within 2 weeks of surgery. One horse
adhesions that often form between the arytenoid and in this study developed a retrolaryngeal abscess that caused
the adjacent wing of the thyroid cartilage, and possibly perilaryngeal swelling and loss of left arytenoid abduction.
even to surgically disarticulate the cricoarytenoid joint. The abscess was drained, but this failed to restore arytenoid
abduction. Careful attention to hemostasis and avoiding
Wound and prosthesis infection large lymphatic vessels should help avoid excessive wound
swellings and seromas (Stick et al 1999).
Among the first reported complications of laryngoplasty
were wound infection, excessive wound inflammation, and Loss of arytenoid abduction
the formation of sinus tracts caused by the prosthesis
(Raker 1975). These complications, which occurred in Failure of the prosthesis to maintain abduction of the
15% of cases, were noted shortly after the laryngoplasty arytenoid is another major complication of laryngoplasty,
procedure was first described using a braided Lycra® both in the immediate postoperative period and in the long
suture material. Lycra has been associated with inflam- term. Although two studies (Russell & Slone 1994, Kidd
mation and delayed healing more frequently than other & Slone 2002) reported that no horses had complete
types of suture (Raker 1975), and the multifilament loss of abduction at long-term follow-up, the incidence
nature of this suture made it more prone to harboring of laryngoplasty failure because of the loss of arytenoid
infection. Currently, most surgeons use either monofila- abduction in other studies is 2–15% (Marks et al 1970,
ment or coated suture materials, which aids in reducing Raker 1975, Baker 1983, Hawkins et al 1997, Dixon et al
the occurrence of prosthesis infection. 2003a, Kraus et al 2003). Loss of abduction can be caused
The reported incidence of wound infection with by suture loosening or breakage, suture cutting through
laryngoplasty is between 0.5 and 6% (Hawkins et al 1997, the arytenoid or cricoid cartilage, or avulsion of the mus-
Strand et al 2000, Davenport et al 2001, Kidd & Slone cular process of the arytenoid (Russell & Slone 1994,
2002, Dixon et al 2003a, Kraus et al 2003). This inci- Kidd & Slone 2002). The majority of cases in which there
dence is similar to that seen with other clean, elective is total loss of arytenoid abduction (arytenoid collapse)
equine surgical procedures (Santschi 1999). Laryngotomy at the follow-up examinations are thought to be caused
incisions, used to perform ventriculectomies concurrently by sutures cutting through the muscular process of the
with laryngoplasty, are often left open to heal by second arytenoid (Baker 1983, Johnson 1985) and in vitro studies
intention, and lie in close proximity to clean laryngoplasty have supported this conclusion (Dean et al 1990, Herde
incisions. A significant correlation between laryngotomy et al 2001). Dixon et al (2003a) reported that of 200
and laryngoplasty wound problems was observed in 200 horses treated with laryngoplasty using stainless steel
horses that were treated with both laryngoplasty and wire, ten required a second surgery within 7 days for
ventriculocordectomy (Dixon et al 2003a). Nevertheless, excessive loss of arytenoid abduction because of pros-
the incidence of laryngotomy wound infections is low, thesis loosening/migration (five horses), broken prosthesis
regardless of whether or not the cricothyroid membrane (three horses) or avulsion of the muscular process of the
arytenoid (two horses). An additional nine horses required

a second surgery because of excessive loss of abduction
within 6 weeks of the first surgery.
Most studies do not reveal the exact cause of arytenoid
collapse because determining this information would
require a second laryngoplasty procedure which owners
may find financially unacceptable. Because the exact cause
of failure is unknown in many cases, it is difficult to draw
conclusions about the factors responsible for failure of
surgical arytenoid abduction. Nevertheless, several in vitro
studies on isolated equine larynges have demonstrated
that the age of the horse and the type of suture material
used (polyester versus polytetrafluoroethylene) have no
significant effect on laryngoplasty failure.
Schumacher et al (2000) investigated the use of a stain-
less steel cable with stress-reducing washers as a pros-
thesis in cadaver larynges to minimize the risk of suture
loosening or pull out. The authors concluded that the cable
required significantly more force than polyester suture to
result in failure. Despite the encouraging results with this
system, it was not practical to use it successfully in vivo.
If a horse experiences a loss of abduction that limits Fig. 35.5. Before the use of intraoperative endoscopy, suture penetra-
its exercise performance, a repeat laryngoplasty should tion of the lumen was not diagnosed until postoperatively. This figure
shows a granulomatous reaction around a laryngoplasty suture pene-
be considered. Although some clinicians advocate an
trating the laryngeal lumen.
arytenoidectomy rather than a repeat laryngoplasty, the
success rate of repeat laryngoplasty by experienced sur-
geons is comparable to that of an initial laryngoplasty
(Tulleners 1994), and it is likely to be more successful than to the airway, resulting in a chronic cough. More recent
a partial arytenoidectomy. If the failure is secondary to publications have cited this as a potential complication, but
muscular process avulsion and there is no remaining car- do not report on any cases in which this occurred. The lack
tilage to place the suture through, the partial arytenoidec- of cases reported may be the result of the common use of
tomy should be considered. intraoperative endoscopy to evaluate the airway lumen
after suture placement, allowing removal of any that do
Aspiration pneumonia penetrate the lumen before completing the surgery.
While chronic coughing and dysphagia are far more Postoperative changes in
common following laryngoplasty than is aspiration pneu- corniculate cartilages
monia, this latter complication is life-threatening and
requires removal of the prosthesis if the horse is to be Granuloma formation and chondritis are rare complica-
salvaged for any purpose. The incidence of aspiration of tions of laryngoplasty with Dixon et al (2003a) reporting
small amounts of feed, based on postoperative endo- a 1% incidence of such problems. Other morphological
scopic evidence of feed material in the airway, is 3–10% changes to the arytenoids can also occur following laryn-
(Russell & Slone 1994, Hawkins et al 1997, Strand et al goplasty (Figs 35.6 and 35.7). Some of these complications
2000). Relatively few of these cases, however, go on to may be the result of trauma induced by the endotracheal
develop fulminant bacterial pulmonary infection (Dixon tube. With concurrent use of vocal cordectomy, excision
et al 2003a). of the vocal process of the corniculate could also predis-
pose to such lesions, as could inadvertent damage to the
Suture penetration into airway corniculate cartilages during laser cordectomy.
Inadvertent penetration of the airway mucosa with the

prosthesis as it is placed in the cricoid cartilage can result
Ventriculectomy and Ventriculocordectomy:
in an intraluminal, granulomatous inflammatory reac-
Surgical Technique
tion or surgical wound infection (Fig. 35.5) (Raker 1975), Ventriculectomy has been performed through a laryngo-
especially with braided sutures. The inflammation asso- tomy incision for many years with the horse standing and
ciated with the intraluminal suture may serve as an irritant sedated, or under general anesthesia in dorsal recumbency.
Fig. 35.6. Laryngeal endoscopy of a horse that underwent left-sided Fig. 35.7. At a routine laryngeal endoscopy of a racehorse that had
laryngoplasty 1 year earlier and raced successfully. At a revisit because received left-sided laryngoplasty several months earlier and also raced
of lameness, routine endoscopy now shows an area of normal successfully, the left corniculate cartilage is atrophied and distorted
corniculate cartilage that is devoid of mucosa. There is also some and unusual ulcerations are also present on the adjacent aryepiglottic
excessive fibrosis at the caudal aspect of the vocal cordectomy site. fold. This case was treated medically and continued to race for another
year but eventually developed left-sided arytenoid chondritis.
As this procedure is often performed in conjunction with To address this, an alternative approach has been
laryngoplasty, it is usually performed under general anes- described (Brown et al 2003). The defect created by
thesia on the ipsilateral lateral ventricle. There is no removing the ventricle is extended to include the most
current evidence demonstrating the necessity to perform rostral edge of the vocal cord. This edge of the vocal cord is
a bilateral ventriculectomy, but it is occasionally chosen then sutured to the rostral lateral margin of the ventricle
by the surgeon to minimize the possibility of abnormal defect. By doing so, the cord is pulled laterally, and there-
noise postoperatively. If a bilateral ventriculectomy is fore should not be displaced into the airway during exercise
performed, caution should be exercised to leave an intact and so affect airflow through the glottis.
mucosal strip between the two cords. If not, webbing across With either procedure, the cricothyroid ligament may be
the ventral glottis may develop. either closed with interrupted absorbable suture or left
The standard approach for ventriculectomy has been open to heal by second intention. The area around and
through a laryngotomy. The horse is positioned in dorsal rostral to the laryngotomy should be cleaned daily and
recumbency with the head and neck extended. After skin Vaseline applied until it ceases discharging to prevent skin
preparation, a ventral midline incision is made between the scalding from the drainage. An open laryngotomy usually
thyroid notch and the rostral ventral edge of the cricoid heals within 3 weeks, and those in which the cricothyroid
cartilage. The cricothyroid membrane is then penetrated ligament is closed will heal slightly sooner.
to enter the laryngeal cavity. A burr is placed deep into More recently, ventriculocordectomy has been performed
the ventricles and rotated to engage the membrane. It using a laser via video-endoscope through the nasal or
is then gently retracted up toward the laryngotomy oral cavity (Chapter 39) with the horse either standing
site to evert the ventricle, which is then resected with and sedated, or under general anesthesia in lateral recum-
Metzenbaum scissors. The ventricle is usually allowed to bency. When performed under standing sedation, the vocal
heal by second intention. The proposed mechanism of folds should be desensitized with topical local anesthetic
decreasing turbulence in the airway by stabilizing the vocal such as Cetacaine. A laser fiber [neodymium:yttrium–
cord has not been supported clinically because the cord is aluminum–garnet (Nd:YAG) or diode] is passed through the
not “lateralized” after such a procedure. biopsy channel of the endoscope and a transnasal grasping
five horses with laryngeal hemiplegia induced by recur-

rent laryngeal neurectomy. The horses were exercised on
a treadmill 30 days after left ventriculectomy, at which
stage inspiratory impedance, airflow, and upper airway
pressure were unchanged when compared to values
obtained immediately after the neurectomy. The same
horses were then treated with a laryngoplasty, and exer-
cised on a treadmill 14 days later. Respiratory mechanics
values were now found to be restored to baseline levels,
leading the authors to conclude that any adhesions formed
between the vocal cord and the laryngeal wall by the
ventriculocordectomy were insufficient to prevent the
dynamic collapse of the affected arytenoid which had
occurred during exercise. Stabilization of the arytenoid by
laryngoplasty, however, was able to prevent this collapse.
One limitation of this study is that the design made it
impossible to compare the effects of laryngoplasty alone to
laryngoplasty plus ventriculectomy. Because the two
procedures were not evaluated at the same time point
post ventriculectomy, the 14 days of additional healing
time for the ventriculectomy may also have contributed to
the improved results found after laryngoplasty.
Fig. 35.8. Endoscopic view of a larynx 1 day after laryngoplasty and The absence of an effect of ventriculectomy on upper
left-sided, laser vocal cordectomy. airway flow mechanics was confirmed in another experi-
mental study (Tetens et al 1996) in exercising standard-
breds with induced left laryngeal hemiplegia. Horses were
treated with laryngoplasty alone or laryngoplasty plus
ventriculocordectomy. Regardless of surgical treatment,
forceps is used to grasp and rotate the vocal fold and part of inspiratory flow mechanics were restored to preneurectomy
the ventricle axially. The laser is used in contact fashion to levels 60 days postoperatively. In contrast to Shappell’s
excise the vocal fold and the everted part of the ventricular study (Shappell et al 1988), a bilateral ventriculocordec-
mucosa, which are removed through the nasal cavity with tomy was performed in this study, and the cut edge of the
the grasping forceps once freed from the surrounding vocal fold was sutured to the vestibular fold. Neither
tissue (Fig. 35.8). experimental study addressed the issue of inspiratory noise
production. Another limitation is that the treadmill speed
at which the horses were exercised in both cases was
Efficacy of Ventriculectomy/ below the maximal speed at which a thoroughbred race-
Ventriculocordectomy Surgery: horse performs. It is not known whether the addition of
Experimental and Clinical Studies ventriculectomy/ventriculocordectomy to laryngoplasty
Most surgeons perform a ventriculectomy or ventriculo- would improve airway mechanics under more intense
cordectomy in conjunction with laryngoplasty but there is exercise conditions.
controversy regarding the value of these procedures in In another experimental study of induced left laryngeal
eliminating the clinical signs of laryngeal hemiparesis/ hemiplegia in standardbreds, Brown et al (2003) performed
hemiplegia (Shappell et al 1988, Bohanon et al 1990, a bilateral ventriculocordectomy, and then measured
Tetens et al 1996, Hawkins et al 1997, Kidd & Slone upper airway pressures and respiratory sounds during
2002, Brown et al 2003). It is generally accepted that ven- treadmill exercise at maximum heart rate. These authors
triculectomy/ventriculocordectomy significantly decreases found that although airway pressures were still increased
the inspiratory noise associated with laryngeal hemi- over preneurectomy levels at 90 days after ventriculo-
paresis/hemiplegia but most experimental and clinical cordectomy, the pressures had significantly decreased
evidence leads to the conclusion that these procedures compared to immediately postneurectomy levels. This
must be combined with prosthetic laryngoplasty to sig- effect of ventriculocordectomy was not observed 30 days
nificantly improve airway mechanics and thus exercise postoperatively, leading to the conclusion that scar forma-
performance (Brown et al 2003). tion between the remnant of the vocal fold and the lateral
The effect of ventriculectomy on upper airway flow laryngeal wall required up to 90 days, which may explain
mechanics was investigated by Shappell et al (1988) in why earlier studies failed to demonstrate an effect of
ventriculocordectomy on airway pressure. In addition, improved performance in 59% of the horses that had
these authors performed a spectrogram analysis of three a mild degree of paresis of the left arytenoid, and so a
inspiratory sound formants 30, 90, and 120 days after laryngoplasty with its potential complications were conse-
ventriculocordectomy. They found that the two formants quently avoided.
constituting much of the inspiratory sound intensity
returned to baseline values by 90 days postoperatively, and
that there were no detectable abnormal respiratory noises REFERENCES
present at that time. Baker GJ 1983 Laryngeal hemiplegia in the horse. Com-
The addition of a ventriculectomy procedure to laryn- pendium on Continuing Education for the Practicing
goplasty in racehorses does not appear to improve post- Veterinarian 5: S61–S67
operative racing performance compared to laryngoplasty Barakzai SZ, Dixon PM. 2004 Ventriculo-cordectomy for treat-
alone. Hawkins et al (1997) found that the perform- ment of recurrent laryngeal neuropathy: 75 cases in a
mixed population of horses. In: Dixon PM, Robinson, NE,
ance index in thoroughbred and standardbred race- Wade J (editors) Proceedings of Havemeyer Foundation
horses was similar, whether or not the horses received a Monograph Series No. 11: Equine Recurrent Laryngeal
ventriculectomy in addition to laryngoplasty. Likewise, Neuropathy. R & W Publications, Newmarket, pp.71–73
there was no statistically significant difference in post- Bayly WM, Grant BD, Modransky PD 1984 Arterial blood gas
operative respiratory noise production, according to an tensions during exercise in a horse with laryngeal
hemiplegia before and after corrective surgery. Research
owner/trainer survey (Hawkins et al 1997). In this study, in Veterinary Science 36: 256–258
however, there was a strong surgeon bias toward ven- Bohanon TC, Beard WL, Robertson JT 1990 Laryngeal hemi-
triculectomy, and only 19% of horses studied received plegia in draft horses: a review of 27 cases. Veterinary
laryngoplasty alone. Surgery 19: 456–459
When a mixed group of horses (race and performance) Brown JA, Derksen FJ, Stick JA et al 2003 Ventriculocordec-
tomy reduces respiratory noise in horses with laryngeal
were treated with ventriculocordectomy at the time of hemiplegia. Equine Veterinary Journal 35: 570–574
laryngoplasty, only 8.7% were reported to make a respi- Brown JA, Derksen FJ, Stick JA et al 2004 Effect of laryn-
ratory noise postoperatively (Kidd & Slone 2002). This is in goplasty on respiratory noise reduction in horses with
contrast to the 47% of horses treated by the same surgeon laryngeal hemiplegia. Equine Veterinary Journal 36:
that made a postoperative respiratory noise when treated 420–425
Davenport CLM, Tulleners EP, Parente EJ 2001 The effect
by ventriculectomy alone (Russell & Slone 1994). On of recurrent laryngeal neurectomy in conjunction
the other hand, in draft horses treated with ventriculec- with laryngoplasty and unilateral ventriculocordec-
tomy or ventriculocordectomy in conjunction with laryn- tomy in thoroughbred racehorses. Veterinary Surgery
goplasty, no difference in postoperative performance score 30: 417–421
was observed, whether or not the vocal cord was resected Dean PW, Nelson JK, Schumacher J 1990 Effects of age and
prosthesis material on in vitro cartilage retention of
(Kraus et al 2003). laryngoplasty prostheses in horses. American Journal
Ventriculectomy alone has been successful in treat- of Veterinary Research 51: 114–117
ing clinical signs of laryngeal hemiplegia in draft horses, Derksen FJ, Stick JA, Scott EA et al 1986 Effect of laryngeal
with signs of exercise intolerance and noise production hemiplegia and laryngoplasty on airway flow mechanics
eliminated in 80% of the treated horses (Bohanon et al in exercising horses. American Journal of Veterinary
Research 47: 16–20
1990). However, another study of draft horses used Dixon PM, McGorum BC, Railton DI et al 2003a. Long-term
for competitive pulling found that seven of 104 horses survey of laryngoplasty and ventriculocordectomy
that had been previously treated with ventriculectomy or in an older, mixed-breed population of 200 horses. Part
ventriculocordectomy alone before laryngoplasty were 1: Maintenance of surgical arytenoid abduction and
unable to work satisfactorily until they later received a complications of surgery. Equine Veterinary Journal
35: 389–396
prosthetic laryngoplasty (Kraus et al 2003). These authors Dixon PM, McGorum BC, Railton DI et al 2003b. Long-term
noted that signs of laryngeal hemiplegia were alleviated survey of laryngoplasty and ventriculocordectomy in an
in 72% of draft horses treated with ventriculectomy or older, mixed-breed population of 200 horses. Part 2:
ventriculocordectomy combined with laryngoplasty. Owners’ assessment of the value of surgery. Equine
It is logical that the ventriculocordectomy alone with- Veterinary Journal 35: 397–401
Greet TRC, Baker GJ, Lee R 1979 The effect of laryngoplasty
out a laryngoplasty may best be reserved for horses that on pharyngeal function in the horse. Equine Veterinary
can maintain moderate abduction of the arytenoid during Journal 11: 153–158
exercise. It may be difficult to ascertain which horses Guyton AC, Hall JE 2000 Pulmonary ventilation. In: Guyton
maintain abduction without a treadmill endoscopic exami- AC, Hall JE (editors) Textbook of Medical Physiology,
nation, but performing a ventriculocordectomy does not 10th edn. Saunders, Philadelphia, pp.441–442
Hackett RP, Ducharme NG, Fubini SL et al 1991 The reliability
preclude a laryngoplasty at a later date if the ventriculo- of endoscopic examination in assessment of arytenoid
cordectomy is not effective. In a study by Barakzai and cartilage movement in horses. I. Subjective and objective
Dixon (2004), a sutured unilateral ventriculocordectomy laryngeal evaluation. Veterinary Surgery 20: 174–179
Hammer EJ, Tulleners EP, Parente EJ et al 1998 Video- Schumacher J, Wilson AM, Pardoe C et al 2000 In vitro
endoscopic assessment of dynamic laryngeal function evaluation of a novel prosthesis for laryngoplasty of
during exercise in horses with grade-III left laryngeal horses with recurrent laryngeal neuropathy. Equine
hemiparesis at rest: 26 cases (1992–1995). Journal of the Veterinary Journal 32: 43–46
American Veterinary Medical Association 212: 399–403 Shappell KK, Derksen FJ, Stick JA et al 1988 Effects of
Hawkins JF, Tulleners EP, Ross MW et al 1997 Laryngoplasty ventriculectomy, prosthetic laryngoplasty, and exercise
with or without ventriculectomy for treatment of left on upper airway function in horses with induced left
laryngeal hemiplegia in 230 racehorses. Veterinary laryngeal hemiplegia. American Journal of Veterinary
Surgery 26: 484–491 Research 49: 1760–1765
Herde I, Boening KJ, Sasse HHL 2001 Arytenoid cartilage Speirs VC 1972 Abductor muscle prosthesis in the treat-
retention of laryngoplasty in horses – in vitro assessment ment of laryngeal hemiplegia in the horse. Australian
of effect of age, placement site, and implantation Veterinary Journal 48: 251–254
technique. Proceedings of the American Association of Speirs VC, Bourke JM, Anderson GA 1983 Assessment of the
Equine Practitioners 47: 115–119 efficacy of an abductor muscle prosthesis for treatment of
Johnson JH 1985 Laryngeal surgery: techniques and results. laryngeal hemiplegia in horses. Australian Veterinary
Proceedings of the American College of Veterinary Journal 60: 294–299
Surgeons 13: 60 Stick JA, Tulleners EP, Robertson JT et al 1999 The larynx.
Kidd JA, Slone DE 2002 Treatment of laryngeal hemiplegia in In: Auer JA, Stick JA (editors) Equine Surgery, 2nd edn.
horses by prosthetic laryngoplasty, ventriculectomy, and Saunders, Philadelphia, pp.355–360
vocal cordectomy. Veterinary Record 150: 481–484 Strand E, Martin GS, Haynes PF et al 2000 Career
Kraus BM, Parente EJ, Tulleners EP 2003 Laryngoplasty with racing performance in Thoroughbreds treated with pros-
ventriculectomy or ventriculocordectomy in 104 draft thetic laryngoplasty for laryngeal neuropathy: 52 cases
horses. Veterinary Surgery 32: 530–538 (1981–1989). Journal of the American Veterinary
Marks D, Mackay-Smith MP, Cushing LS et al 1970 Use of Medical Association 217: 1689–1696
a prosthetic device for surgical correction of laryngeal Tate LP, Corbett WT, Bishop BJ et al 1993 Blood gas tensions,
hemiplegia in horses. Journal of the American Veterinary acid–base status, heart rates, and venous profiles in
Medical Association 57: 157–163 exercising horses with laryngeal hemiplegia before and
Parente EJ 2004 Improvements in laryngoplasty. In: Dixon PM, after corrective surgery. Veterinary Surgery 22: 177–183
Robinson, NE, Wade J (editors) Proceedings Havemeyer Tetens J, Derksen FJ, Stick JA et al 1996 Efficacy of laryn-
Foundation Monograph Series No. 11: Equine Recurrent goplasty with and without bilateral ventriculocordec-
Laryngeal Neuropathy. R & W Publications, Newmarket, tomy as treatments for laryngeal hemiplegia in horses.
pp.66–67 American Journal of Veterinary Research 57: 1668–1673
Raker CW 1975 Complications related to the insertion of a Tulleners EP 1994 Management of failed laryngoplasty: 25
suture to retract the arytenoid cartilage to correct horses (1988–1993). Veterinary Surgery 23: 419
laryngeal hemiplegia in the horse. Archives of Veterinary Williams JW, Pascoe JR, Meagher DM et al 1990a Effects of
Surgery 4: 64–66 left recurrent laryngeal neurectomy, prosthetic laryngo-
Russell AP, Slone DE 1994 Performance analysis after pros- plasty, and subtotal arytenoidectomy on upper airway
thetic laryngoplasty and bilateral ventriculectomy for pressure during maximal exertion. Veterinary Surgery
laryngeal hemiplegia in horses: 70 cases (1986–1991) 19: 136–141
Journal of the American Veterinary Medical Association Williams JW, Meagher DM, Pascoe JR et al 1990b Upper
204: 1235–1241 airway function during maximal exercise in horses with
Santschi EM 1999 Diagnosis and management of surgical site obstructive upper airway lesions: effect of surgical treat-
infection and antimicrobial prophylaxis. In: Auer JA, ment. Veterinary Surgery 19: 142–147
Stick JA (editors) Equine Surgery, 2nd edn. Saunders,
Equine Laryngeal Reinnervation
36 Ian C Fulton
Introduction
or without some attached omohyoideus muscle, as the
Experiments with laryngeal reinnervation in animals were donor, three techniques of laryngeal reinnervation were
reported as early as 1946 (McCall & Hoerr 1946) and the investigated: the NMP graft (Ducharme et al 1989a), nerve
nerve–muscle pedicle (NMP) graft technique of laryngeal implantation (Ducharme et al 1989b) and nerve anasto-
reinnervation was first demonstrated successfully in dogs mosis (Ducharme et al 1989c). All three methods produced
in 1973 (Hengerer & Tucker 1973). Laryngeal muscles histological evidence of reinnervation. However, only the
that had been denervated for 6 months could be reinner- nerve anastomosis technique, joining the first cervical
vated using the NMP graft technique, with success of nerve to the distal segment of the left recurrent laryngeal
the reinnervation determined by visual and histological nerve, produced significant clonic movement of the left
assessment (Lyons & Tucker 1974). Clinical use of the arytenoid cartilage, although this was believed to be insuf-
NMP graft method of laryngeal reinnervation in humans ficient to allow maximal exercise to be performed.
was first reported in 1976 in five patients with bilateral Further research into equine laryngeal reinnervation
laryngeal paralysis (Tucker 1976). Success rates up to 90% focused on the NMP graft technique using standard-
with unilateral laryngeal paralysis and 80% for bilateral bred horses with experimentally induced left laryngeal
laryngeal paralysis have since been reported in humans hemiplegia (Fulton et al 1991). That study not only iden-
(Tucker & Rusnov 1981). tified successful reinnervation of the cricoarytenoideus
Initial attempts at equine laryngeal reinnervation were dorsalis (CAD) muscle by histological examination (Fulton
conducted in ponies with experimentally induced left et al 1992), but also found that laryngeal reinnervation
laryngeal hemiplegia by Ducharme et al (1989a,b,c). allowed upper airway function in horses with experimen-
Using the first or second cervical nerve (Fig. 36.1), with tally induced laryngeal hemiplegia to return to normal.
Fig. 36.1. Path of the first cervical nerve

(arrows) as it travels from the alar foramen
of the atlas and a common branching pat-
tern before implanting into the omohyoideus
muscle
509
510 36 Equine Laryngeal Reinnervation
While endoscopic evidence of CAD muscle reinnervation

can be detected as early as 4 months after reinnerva-
tion surgery, return of full upper airway function during
exercise can take up to 6–12 months. The major advantage
of laryngeal reinnervation is the absence of perma-
nent alteration to the laryngeal architecture resulting in
minimal postoperative complications compared with pros-
thetic laryngoplasty.
Since 1991, the NMP graft technique has been used by
the author in horses with grade 3 or grade 4 recurrent A
laryngeal neuropathy (RLN) (Hackett et al 1991). The
author has operated on 182 horses in total, including 164
thoroughbreds, 11 standardbred and 7 warmblood horses.
Surgical Technique
Laryngeal reinnervation using the NMP graft technique
is performed with the horse under general anesthesia in
right lateral recumbency for cases of left RLN. A 15-cm
skin incision is made along the ventral border of the
linguofacial vein, with the center of this incision being in
a direct line with the middle of the left wing of the atlas. Fig. 36.2. The surgical approach with the linguofacial vein retracted
The first cervical nerve exits from a foramen in the wing of dorsally, lymph nodes (A) which are often enlarged in yearlings, and
the distal branches of the first cervical nerve (arrows).
the atlas and passes over the lateral aspect of the larynx
before branching and entering the omohyoideus muscle
(Fig. 36.1). Careful dissection of the subcutaneous tissues
is performed, sometimes requiring an incision through the
(subcutaneous) panniculus muscle to expose the linguo- markedly the vigorous contraction of the omohyoideus
facial vein. A ventral branch of the linguofacial vein is muscle that occurs when the nerve–muscle pedicle is
often present near the midpoint of the exposed vein formed, thus avoiding trauma to the nerve–muscle interface.
(Fig. 36.2). Double ligation of this branch is essential to A small block of muscle, approximately 3 mm3, is dis-
allow further dissection to expose the body of the first sected from the omohyoideus muscle with the branch of
cervical nerve. Once ligated, elevation of the linguofacial the first cervical nerve attached. An abundance of motor
vein provides an easily identifiable plane of dissection endplates exists in the muscle fibers around the point of
between the omohyoideus muscle and the skin/subcu- entry of the distal nerve branches (Fulton et al 2003). As
taneous fascia and linguofacial vein. Elevation of the skin/ many as five pedicles can be harvested for transplantation,
subcutaneous fascia and linguofacial vein can be main- depending on the number of nerve branches identified.
tained with a broad, malleable retractor. A single cruciate suture of 2–0 polydioxanone is used to
The first cervical nerve is a 2–4 mm wide, white, band- reduce hemorrhage from each omohyoideus muscle pedicle
like structure lying over the lateral aspect of the larynx. site. Branches of the first cervical nerve that need to be
In 1- to 2-year-old horses, lymph nodes frequently overlie transected for dorsal repositioning of the nerve are cut
the nerve, increasing the difficulty of dissection of the dis- as long as possible so that they can be directly used as
tal nerve and its branches. Accurate dissection of the distal donor nerves also (without muscle pedicle). Implantation
segment of the first cervical nerve from its loose connective of transected nerve ends into atrophied skeletal muscles
tissue allows identification of two or three distal branches, can result in reinnervation via axonal sprouting (Hall
which can be followed to their point of entry into the et al 1988).
omohyoideus muscle. Elevation of the proximal aspect of The bundle of nerve–muscle pedicles and transected
the first cervical nerve with a small hooked retractor allows nerve branches are carefully placed within the caudal
for fine dissection of the nerve from the surrounding aspect of the surgical field while the existing plane of
connective tissue, which allows easier repositioning of the dissection is continued proximally to expose the dorsal
nerve over the dorsal aspect of the larynx, after the muscle aspect of the larynx. Access to the left CAD muscle is
pedicles have been created. When the sites of muscle inser- improved by rotating the larynx laterally. A narrow, hooked
tion of the distal nerve branches have been exposed, the retractor is placed through the septum between the
surgical field is flooded with local anesthetic. This reduces left cricothyroideus and cricopharyngeus muscles and
36 Equine Laryngeal Reinnervation 511
Fig. 36.3. A hooked retractor (large arrow) placed through the septum between the thyropharyngeus (T)
and cricopharyngeus (C) muscles, is placed over the lateral wing of the thyroid cartilage to rotate the
larynx exposing the dorsal aspect of the larynx. The Weitlaner retractor is placed with one arm in the dorsal
border of the cricopharyngeus muscle and the other in the connective tissue overlying the larynx to expose
the cricoarytenoideus dorsalis muscle. The nerve muscle pedicle grafts (small arrows) are sutured into slits
created parallel with the atrophied fibers of the cricoarytenoideus dorsalis muscle.
is hooked over the wing of the left thyroid cartilage to the pockets and then retrieved. The needle is then passed
help maintain this rotation (Fig. 36.3). Using a 20-mm through the muscle fibers of the pedicle graft (or through
endotracheal tube for anesthesia makes rotation of the the perineurium of transected nerve branches) and then
larynx easier. Dissection through either the caudal portion passed back down into the base of the pockets to exit
of the cricopharyngeus muscle or the fascia overlying through the muscle surface, next to the original insertion
the CAD muscle will allow placement of a blunt tipped point. The pedicle grafts and nerve implants are distributed
Weitlaner retractor to maintain access to the CAD muscle as evenly as possible in the muscle belly. However, the
(Fig. 36.3). A plexus of vessels commonly overlies the CAD length of the nerve branches will dictate how far apart
muscle and hemorrhage from these vessels reduces visi- pedicles can be placed in relation to each other. After
bility of the CAD muscle and so of the implantation site. suturing the pedicles and nerve implants in place, the
Control of such hemorrhage is often more easily achieved laryngeal retractor is removed to allow the larynx to rotate
by pressure, using gauze swabs, rather than by ligation. back to its natural position and an examination is made to
The left CAD muscle in RLN horses is usually pale in color ensure that there is not excessive tension on the first
and shows various degrees of atrophy, with atrophy in cervical nerve.
grade 4 RLN horses more obvious than in grade 3 horses. No attempt is made to close the potential dead space
In grade 3 RLN horses, the CAD often has a striped appear- over the dorsal and lateral aspects of the larynx. The sub-
ance, with pale denervated muscle fibers lying next to more cutaneous and subcuticular layers are closed using 2–0
normal appearing muscle fibers. polydioxanone and a simple interrupted 2–0 monofilament
A long vascular forcep is used to create a deep, slit-like non-absorbable suture is used for the skin. During wound
opening in the CAD muscle belly, parallel with the fibers of closure, examination for leaking lymphatic vessels (com-
the CAD muscle, and the pedicle grafts are inserted into monly seen in younger horses) should be made, especially
these individual pockets. A polydioxanone suture (4–0) is along the border of the omohyoideus muscle. Failure to
used to suture the pedicle graft into the pocket of the CAD ligate these will lead to significant postoperative seroma
muscle with minimal tension applied to the knot. The formation. A stent bandage is sutured over the incision and
needle is passed from the muscle surface into the base of a firm adhesive elastic bandage is placed around the neck,
in front of and behind the ears, to apply pressure over the ment of the left arytenoid cartilage may only be seen once
incision area, and so help minimize seroma formation. or twice during several attempts at stimulating either of
Ventriculectomy via laryngotomy has not been per- these reflexes.
formed by the author immediately following the NMP graft, An abductory movement of the left arytenoid cartilage
primarily to reduce possible disruption of the fine NMP is a positive indicator of reinnervation of the CAD muscle.
grafts by further surgical manipulation of the larynx. Prior Once these movements have been identified, it is recom-
to 2000, ventriculectomy was only performed in horses mended that training continue as normal. If no evidence of
deemed to be making excessive noise after surgery. Now, all movement is seen at the first revisit, turning the horse out
horses undergo standing, unilateral laser vocal cordectomy again for another 8 weeks is advised. Another 6 weeks of
the day following laryngeal reinnervation surgery. the previously described training program is performed
before further laryngeal assessment, usually at least
9 months following surgery. Some horses may take up to
Postoperative Management 12 months to show evidence of successful reinnervation.
Immediate postoperative care includes confinement for Information from direct stimulation of the first cervical
2 weeks in stalls where horses cannot easily rub the neck nerve in horses suggests that reinnervation probably
incision. Procaine penicillin and gentamicin are routinely occurs in most horses by 4–5 months after surgery. The
given for 4 days after surgery. These prophylactic broad- problem appears to be not whether reinnervation has
spectrum antibiotics are used because of the loss of the occurred or not, but whether sufficient regeneration of the
protective mucosal tissue associated with the laser cordec- CAD muscle has occurred to provide stable abduction of
tomy. Phenylbutazone is administered for 7 days postopera- the left arytenoid cartilage during exercise.
tively. The neck bandage is removed after 48–72 h. Sutures The best evidence of successful reinnervation in an
are removed after 14 days. individual horse is derived from treadmill endoscopy or
After 2 weeks of stall rest, a further 2 weeks of confine- treadmill upper airway flow mechanics studies but only a
ment in a yard, followed by paddock turnout for 12 weeks small number of research cases and a few clinical cases
is recommended. Training resumes 16 weeks postopera- have undergone this evaluation. In treadmill studies,
tively. This timing is based on the results of reinnervation horses with movement of the left arytenoid cartilage visible
studies in dogs (Hengerer & Tucker 1973), humans (Tucker at rest following NMP graft surgery can maintain a level
1976) and horses (Fulton et al 1991), where evidence of of arytenoid abduction during vigorous exercise (Fulton
reinnervation has been identified 12–16 weeks postopera- et al 1991, Dart et al 2001). If movement of the affected
tively. When horses resume training, short episodes of fast arytenoid could not be demonstrated in the standing
exercise are introduced as early and as frequently as horse using the reflexes described earlier, dynamic col-
possible. Since the omohyoideus muscle is an accessory lapse of the arytenoid cartilage would be expected to occur
muscle of respiration, considerable respiratory effort must during exercise.
be induced to activate the first cervical nerve, hence the
recommendation that horses gallop over 300–400 m every
second day of training to help promote physiotherapy of
Surgical Complications
the reinnervated muscle. Complications are uncommon following laryngeal reinner-
After 6 weeks of training we advise endoscopic assess- vation surgery. The most frequent has been seroma forma-
ment of the larynx. At rest, the function of the left tion 3–5 days following surgery, no doubt partly as a result
arytenoid cartilage commonly appears identical to before of the potential dead space that exists dorsal and lateral to
the surgery; this is because the first cervical nerve is the larynx following an NMP graft procedure (also follow-
inactive at rest, resulting in absence of CAD muscle con- ing laryngoplasty). The use of a sutured stent bandage and
traction. Two diagnostic reflexes have been identified compressive neck bandage, described earlier, markedly
to stimulate contraction of the omohyoideus muscle and reduces this complication. Seroma formation may also be
also the newly innervated CAD in the standing horse predisposed to by inadvertently cutting lymphatic vessels
at rest. The first requires stretching the head and neck during surgery. Many seromas resolve without intervention
upwards as high as possible while observing the larynx but some require open drainage and daily lavage and these
with the endoscope. If reinnervation has been successful horses are also given a short course of procaine penicillin.
there is often a spontaneous abductory movement of A small number of seromas become infected necessitating
the left arytenoid cartilage as the head is elevated. The antibiotic treatment based on culture and sensitivity
second reflex involves pulling back rapidly and firmly results. Based on the results of both clinical and research
with a finger on the commissure of the lips. Again, a cases, these complications do not appear to compromise the
sudden abduction of the left arytenoid cartilage occurs if success of the NMP graft (Fulton 1990).
reinnervation has been successful. This reflex can be Other infrequent complications include a single case of
stimulated from the left or right side of the head. Move- laryngeal obstruction, which occurred at recovery from
36 Equine Laryngeal Reinnervation 513
anesthesia and was successfully treated by passage of a Group B

nasotracheal tube. One horse developed a large hematoma Of the 88 horses operated on, 65, aged 1–3 years (mean
2 h after surgery that required the incision to be reopened 1.8 years) were available for long-term follow-up. Twenty
in the standing horse and a blood vessel in the omohy- of these unraced horses were considered failures based
oideus muscle to be ligated. Three horses that apparently on their inability to start a race. Seventy-six per cent (43 of
had successful reinnervation have subsequently begun 65) had evidence of laryngeal reinnervation based on
making noise and performing poorly again. One horse endoscopic assessment. Sixty-six per cent also started in at
that had competed in high-level 3-day event competitions least one race, with these horses racing a mean of 10.6
for 5 years suddenly began making a loud inspiratory times. Of the 43 horses that raced, 27 (63%) won at least
noise and showing evidence of marked exercise intoler- one race. Since the Group B horses had no prior perform-
ance as a result of sudden-onset deterioration in left ance level to allow for performance comparisons after
laryngeal function. surgery, the prize money earned per start was compared
with the national average for the same age group. Those
horses treated with an NMP graft for left RLN earned a
Results of Clinical Cases similar amount of prize money per start in all age groups
Thoroughbreds except as 3-year-olds, when NMP graft horses earned
considerably more per start than the national average.
To date, 164 thoroughbred horses have been operated on After laryngeal reinnervation many horses will make
by the author using the NMP graft. Ninety-six of these an audible inspiratory “noise” early in training. However,
horses had grade 4 RLN and 68 had grade 3 RLN. While in horses with successful reinnervation this “noise” often
many of the horses had been presented for poor perform- reduces progressively as training continues. This is believed
ance associated with noise, a number of unraced horses to be the result of a time-related progressive increase
had been presented after diagnosis of RLN following in muscle regeneration of the reinnervated CAD. Recent
yearling sale endoscopy. To appraise success of the surgery information suggests that respiratory noise during exercise
technique, horses were placed into one of two groups. cannot be easily equated to degree of airway obstruc-
tion (Brown et al 2004) so trainers are encouraged to
● group A – raced prior to surgery – 76 horses
continue training even if noise is heard early in the
● group B – unraced prior to surgery – 88 horses.
retraining period.
Group A Standardbreds
To date 65 of the 76 horses aged 2–6 years (mean
A total of 11 standardbred horses, all with grade 4 LRN,
3.2 years) have had long-term assessment and 86%
have been treated using an NMP graft. Six of the horses
had evidence of reinnervation as described earlier. Ninety-
raced following surgery, three were retired with unrelated
five per cent started in one or more races and Group A
problems, one died and one was considered a failure. Three
horses raced a mean of 12.5 times each. Fifty-four per cent
of the six horses earned more money in total after surgery
(35 of 65) won one or more races after surgery. The
than before (mean of nine races presurgery and of 15 races
average length of time from surgery to their first race was
postsurgery). The trainers indicated that in five of these six
7.5 months for grade 3 (Hackett at al 1991; i.e. laryngeal
horses they were satisfied with the decrease in noise and
asymmetry) horses, and 8.6 months for grade 4 (Hackett
improvement in racing performance.
et al 1991; i.e. hemiplegic) horses.
Objective assessment of the success of the NMP graft
was undertaken by calculating four parameters before
Warmbloods
and after surgery. A performance ranking for both total Seven horses with grade 4 LRN have been treated with the
starts and per start was calculated by allocating points, NMP graft, without vocal cordectomy being performed.
dependent on race position at finish as well as total prize Five of these seven horses have performed at a higher level
money and prize money per start. Fifty-eight per cent after surgery. A horse that was 12 years old at the time of
(38 of 65) of horses had an improved total performance surgery and had been affected with left RLN for 4 years,
ranking and performance ranking per start after surgery. had endoscopic evidence of reinnervation 5 months after
Fifty-one per cent (33 of 65) of horses had higher total surgery. All five horses have been reported to have a
prize money after surgery while 57% (37 of 65) earned markedly reduced noise level during exercise.
more money per start after surgery. Twenty-two horses In another report, 18 eventing and hunt horses received
raced and won over the same distance before and after an NMP graft and 14 were available for follow-up. Six
surgery allowing comparison of race times. Eighty-six per horses (43%) were considered failures and eight (57%)
cent (19 of 22) of these horses had better race times over were subjectively judged by their owners to have improved
the same distance after surgery. performance (Tyler 2000).
upper respiratory tract dysfunction in horses. Australian

Overview Veterinary Journal 79: 109–112
The NMP graft technique can be used to successfully Ducharme NG, Horney FD, Partlow GD et al 1989a Attempts
to restore abduction of the paralysed equine arytenoid
reinnervate the CAD muscle of horses with RLN. Seventy- cartilage I. Nerve-muscle pedicle transplants. Canadian
six per cent of unraced horses and 84% of raced horses Journal of Veterinary Research 53: 202–210
demonstrated endoscopic evidence of CAD reinnerva- Ducharme NG, Horney FD, Hullard TJ et al 1989b Attempts to
tion. Assessment of results indicates that the NMP graft restore abduction of the paralysed equine arytenoid
technique is as efficacious as prosthetic laryngoplasty when cartilage II. Nerve implantation (Pilot study). Canadian
racing performance is measured. In one study, 77% of Ducharme NG, Viel L, Partlow GD et al 1989c Attempts to
horses raced after prosthetic laryngoplasty with 56% restore abduction of the paralysed equine arytenoid
racing at an improved level (Hawkins et al 1997). Another cartilage III. Nerve anastomosis. Canadian Journal of
study found that 94% of horses raced after prosthetic Veterinary Research 53: 216–223
laryngoplasty, with 45% demonstrating improved perform- Fulton IC 1990 The effectiveness of a nerve muscle pedicle
graft for the treatment of equine left laryngeal hemi-
ance (Strand et al 2000). Following treatment of pre- plegia. Thesis, Michigan State University
viously raced horses with the NMP graft, 95% went on to Fulton IC, Derksen FJ, Stick JA et al 1991 Treatment of left
race one or more times; 58% had improved performance laryngeal hemiplegia in standardbreds using a nerve
scores and 57% earned more prize money per start after muscle pedicle graft. American Journal of Veterinary
surgery. The time period from surgery to first race is longer Research 52: 1461–1467
Fulton IC, Derksen FJ, Stick JA et al 1992 Histologic evaluation
following NMP graft than prosthetic laryngoplasty. The of nerve muscle pedicle graft as a treatment for left
age, breed, and use of the horse will determine if sufficient laryngeal hemiplegia in Standardbreds. American
time is available to wait for muscle regeneration follow- Journal of Veterinary Research 53: 592–595
ing laryngeal reinnervation. The primary advantage of Fulton IC, Stick JA, Derksen FJ 2003 Laryngeal reinnervation
the NMP graft technique is the absence of potentially in the horse. Veterinary Clinics of North America; Equine
Practice 19: 189–208
chronically debilitating complications that can occur after Hackett R, Ducharme N, Fubini S et al 1991 The reliability
prosthetic laryngoplasty. of endoscopic examination in assessment of arytenoid
cartilage movement in horses. Part 1. Subjective and
objective laryngeal evaluation. Veterinary Surgery
The Future 20: 174–179
Hall SJ, Trachy RE, Cummings CW 1988 Facial muscle
Based on results from a pilot study (Fulton et al 2003), reinnervation: A comparison of neuromuscular pedicle
external nerve stimulation has the potential to decrease with direct implant. Annals of Otology, Rhinology and
time from reinnervation surgery to the first race and Laryngology 97: 229–233
more importantly, to increase the strength of the reinner- Hawkins JF, Tulleners EP, Ross MW et al 1997 Laryngoplasty
vated CAD muscle by more effective physiotherapy via with or without ventriculocordectomy for treatment of
left laryngeal hemiplegia in 230 racehorses. Veterinary
nerve stimulation. Other research is currently investi- Surgery 26: 484–491
gating the use of growth factors that may increase the Hengerer AS, Tucker HM 1973 Restoration of abduction in the
speed of reinnervation of the CAD muscle. In people, nerve paralysed canine vocal fold. Archives of Otolaryngology
anastomosis is now considered by some surgeons to be 97: 247–250
the method of choice for unilateral vocal cord paralysis Lyons RM, Tucker HM 1974 Delayed restoration of abduction in
the paralyzed canine larynx. Archives of Otolaryngology
(Crumley 1991). Given the results in a small group of 100: 176–179
ponies (Ducharme et al 1989c), nerve anastomosis may be McCall JW, Hoerr NL 1946 Reinnervation of a paralysed vocal
worthy of further research. cord. Laryngoscope 56: 527–535
Strand E, Martin GS, Haynes PF et al 2000 Career racing per-
formance in Thoroughbreds treated with prosthetic laryn-
goplasty for laryngeal neuropathy: 52 cases (1981–1989).
REFERENCES Journal of the American Veterinary Medical Association
217: 1689–1696
Brown JA, Derksen FJ, Stick JA et al 2004 Effect of laryn- Tucker HM 1976 Human laryngeal reinnervation. Laryngoscope
goplasty on respiratory noise reduction in horses 86: 769–779
with laryngeal hemiplegia. Equine Veterinary Journal Tucker HM, Rusnov M 1981 Laryngeal reinnervation for
36: 420–425 unilateral vocal cord paralysis: long term results. Annals
Crumley RL 1991 Update: ansa cervicalis to recurrent laryn- of Otolaryngology 90: 457–459
geal nerve anastomosis for unilateral laryngeal paralysis. Tyler R 2000 Experiences with the nerve muscle pedicle graft.
Laryngoscope 101: 384–388 Proceedings of the British Equine Veterinary Association
Dart AJ, Dowling BA, Hodgson DR et al 2001 Evaluation of Congress. Equine Veterinary Journal Ltd, Newmarket
high-speed treadmill videoendoscopy for diagnosis of pp.86–87
Arytenoid Chondropathy
37 Eric J Parente
Arytenoid chondropathy is a disease process affecting one the axial aspect of the arytenoid, just dorsal to the vocal
or both arytenoid laryngeal cartilages that may be process. There are often coexisting superficial ulcer-
secondary to inflammation and swelling of the arytenoid ated (“kissing”) lesions, or granulation tissue, on the axial
cartilage. This disorder can cause decreased mobility and aspect of the apposing arytenoid, that may appear more
varying degrees of respiratory obstruction. The chon- significant than the lesion on the affected arytenoid. Rarely,
dropathy is likely the consequence of ascending inflam- lesions are absent at the axial aspect of the arytenoid but
mation and/or infection into the body of the arytenoid more caudally positioned ulcerative lesions are present
cartilage through a mucosal disruption on the axial side of within the laryngeal lumen that are difficult to observe
the cartilage at the level of the glottis. Potential causes of because of swallowing (and subsequent glottic closure)
this disorder are discussed in Chapter 38. Arytenoid chon- during the examination. Affected horses may have a
dropathy is more commonly seen in the racing thorough- history of poor performance and exercise-induced respira-
bred but can be observed in all breeds and ages. tory noise similar to that of a “roarer” but horses usually
make no abnormal noises at rest.
There is usually some degree of concurrent compro-
Diagnosis mised abduction of the affected arytenoid. Laryngeal
Clinical history, palpation of the larynx, and resting hemiplegia may have preceded the chondrosis, further
endoscopy are used to diagnose arytenoid chondropathy. contributing to the reduced abduction. The concurrent
The findings will vary slightly, depending on whether swelling of the arytenoid cartilage results in mechanical
the chondropathy is diagnosed in the acute, subacute, or restriction of the movement of the arytenoid because
chronic stage. In the acute stage, dramatic laryngeal it is laterally limited by the wing of the thyroid carti-
and perilaryngeal inflammation and edema are seen on lage. Observation of an immobile cartilage may lead to
resting endoscopy. Infrequently there will be an associ- an erroneous diagnosis of a typical case of recurrent
ated cellulitis in the perilaryngeal region and palpation laryngeal neuropathy (RLN); consequently it is essential
of the larynx may be difficult. Horses may be presented to differentiate laryngeal paralysis from a structurally
as emergencies because of severe respiratory distress abnormal chondritic arytenoid or cricopharyngeal laryn-
and stridor, and they often have a history of recent fast geal dysplasia (fourth brachial arch defect) before consid-
galloping before the flare-up. Mucosal abnormalities may ering treatments. These disorders should be differentiated
have been observed at previous endoscopic examinations by resting endoscopy and palpation of the larynx. An
but may not have caused any clinical abnormalities until immobile hemiplegic arytenoid will normally have no space
the acute stage. The severity of the mucosal swelling between it and the palatopharyngeal arch, making the rim
during the acute phase prohibits accurate assessment of the arch difficult to visualize on resting endoscopy. If
of the more long-term conformational changes to the car- there is a space present lateral to the corniculate process,
tilage and may even make it difficult to determine which and the palatopharyngeal arch can be clearly seen, this
arytenoid is affected. The final shape and function of indicates that a structural enlargement of the arytenoid is
the arytenoid cannot be determined until after the com- pushing the palatopharyngeal arch laterally (Fig. 37.1).
pletion of aggressive medical treatment. External laryngeal palpation may also help diagnose
While it is simple to make a diagnosis of arytenoid arytenoid chondropathy. While a horse with RLN should
chondrosis in the acute phase, it is sometimes more difficult have a very prominent muscular process, the horse with
to do so in chronic cases. In the chronic stages, there is no arytenoid chondropathy will have a less prominent and less
laryngeal edema but abnormalities of the shape of the defined muscular process. Obtaining an accurate diagnosis
corniculate process can be seen endoscopically. Carti- is critical to ensure that a laryngoplasty is not mistakenly
laginous protrusions are often observed endoscopically on attempted on a horse with arytenoid chondropathy.
515
516 37 Arytenoid Chondropathy
Fig. 37.1. Chondropathy of the left arytenoid. Note the abnormal cor- Fig. 37.2. Arytenoid chondritis in the acute stage with excessive
niculate shape, cartilaginous projection on left arytenoid, abnormal edema limiting the ability to assess eventual arytenoid structure
appearance of palatopharyngeal arch behind left arytenoid (large and function.
arrow), and kissing granulation tissue on right arytenoid (arrowhead).
Treatment
Medical treatment
In the acute inflammatory stage, arytenoid chondropathy
should be treated aggressively with intravenous antimicro-
bial and anti-inflammatory drugs (Fig. 37.2). It is difficult to
obtain a representative bacterial culture to target treatment
so broad-spectrum antimicrobials are commonly used,
such as potassium penicillin (22,000 IU/kg four times a
day) and gentamicin (6.6 mg/kg once a day), in addition to
phenylbutazone (4.4 mg/kg twice a day), and dexametha-
sone (0.025–0.05 mg/kg once a day) intravenously. It is
uncommon to have to perform an emergency tracheostomy
but the horse should be kept in a quiet environment and
monitored closely because respiratory distress can be
induced with excitement. An emergency tracheotomy kit
should be available by the stall. Tracheotomy is reserved for
horses that cannot be maintained in a quiet environment
and those which have respiratory stridor at rest. Fig. 37.3. The larynx of the same horse as in Fig. 37.2 after a 1-week
Within a few days of initiating treatment there is course of intravenous antimicrobial and anti-inflammatory drugs.
usually dramatic improvement, with a decrease in the
laryngeal soft tissue swelling observed endoscopically
(Fig. 37.3). However, surgical treatment should be delayed, treatment and stall rest, endoscopic re-evaluation and
because many horses will continue to improve for 30 days decisions for possible further treatment can be made.
with further rest and oral antimicrobial treatment. There Surgical treatment may be initiated earlier in those horses
are occasional cases that improve so dramatically that they which do not show dramatic improvement within the first
never require surgery. Following 1 month of antimicrobial few days of intravenous antimicrobial treatment, those
37 Arytenoid Chondropathy 517
with gross purulent material exiting their arytenoid, arguable whether it is worthwhile attempting to salvage a
and those with swelling of the laryngeal saccule (which mucosal flap on the axial side of the arytenoid to achieve
indicates accumulation of purulent material abaxial to primary mucosal closure after the arytenoid is removed
the arytenoid). (Tulleners et al 1988b, Barnes et al 2004) but it is recom-
The decision to pursue surgery after intensive medical mended by this author because it reduces the postoperative
management is dependent on the degree of response to development of granulation tissue.
therapy and the intended use of the horse. Several horses To form the mucosal flap, dorsoventral mucosal inci-
have gone back to racing after medical treatment alone, sions are made at the caudal border of the arytenoid, and
despite the corniculate processes of their arytenoids having at its rostral border just caudal to the corniculate. These
a slightly abnormal endoscopic appearance. However, all incisions are connected with a horizontal incision along
of these horses could maintain good abduction bilat- the ventral border of the arytenoid. The mucosa is slowly
erally (E. Parente, personal observation). Horses that have dissected free from the arytenoid and is left attached
granulation tissue persisting on their arytenoid following dorsally. The abaxial border of the arytenoid is then freed of
the above medical management are best treated by laser its muscular attachments using primarily blunt dissection
excision of this tissue followed by rest. Several weeks are to minimize hemorrhage. The muscular process is isolated
required for the mucosa to cover the defect before resuming and transected. The arytenoid is then elevated with Allis
exercise. If laryngeal function is still compromised beyond forceps, and freed completely by cutting the remaining
what is necessary for the horse’s athletic purpose, a partial corniculate mucosa rostrally and sectioning any remaining
arytenoidectomy should be considered. Before this surgery dorsal attachments and the cricoarytenoid joint capsule
is pursued for an athletic horse, it is essential to determine caudally. Mucosae are positioned together to plan their
that the normal-looking arytenoid has full abductory closure, and excess mucosa is excised. The caudal edge of
function. The prognosis is significantly worse for bilateral the mucosal flap is reapposed to the laryngeal mucosa in a
disease even after unilateral partial arytenoidectomy simple continuous pattern with 3–0 absorbable suture, in a
(Tulleners 1988a, Parente 2003). dorsal to ventral direction. The rostral edge of the mucosal
flap is apposed similarly to the remaining mucosa lying
abaxial to the corniculate, in a line parallel with the caudal
Surgical treatment edge. The most difficult part to suture is the dorsal aspect of
the vertical incisions, and closure of this area is important
Different forms of arytenoidectomies have been described to prevent the formation of postoperative granulation
(Belknap et al 1990, Tulleners 1990, Hay et al 1993), tissue. The ventral aspect of the mucosal wound is left open
but partial arytenoidectomy has been shown to provide for drainage. Bleeding should be minimal once the mucosal
the least postoperative obstruction (Belknap et al 1990, edges are apposed. After closing the mucosal flap the vocal
Williams et al 1990, Lumsden et al 1994). A temporary cord and ventricle are removed. This leaves an opening at
tracheotomy is required to administer the inhalant anes- the ventral aspect of the arytenoidectomy site for drainage
thesia for a partial arytenoidectomy, because the surgery of submucosal hemorrhage or blood clots lying abaxial to
is performed through a laryngotomy. Usually the glottis is the final mucosal flap. Granulating “kissing” lesions on the
wide enough to permit passage of an endotracheal tube, so opposite arytenoid should be debrided at this time. If
the tracheotomy can be performed under general anes- extensive purulent material is present abaxial to the
thesia. The endotracheal tube is then switched to the arytenoid, or if there is excessive loss of mucosa, a primary
tracheotomy site so it does not pass through the larynx. A closure is not performed. At the conclusion of surgery, the
cleaner, smaller tracheotomy can be performed in this endotracheal tube is replaced with an equivalent sized
manner. However, if there is any risk that endotracheal tracheotomy tube for recovery from general anesthesia.
intubation may be problematic, then the tracheostomy An endoscopic examination should be performed the
should be performed before induction of general anes- morning following surgery (Fig. 37.4). A moderate open-
thesia. When performing a tracheotomy under general ing to the glottis should be seen, and blocking the tra-
anesthesia, care should be taken to avoid placing the cheotomy tube while watching the horse’s respiratory
tracheotomy too far cranially because the relative position effort can be used to assess if the horse can breathe easily
is deceiving when the horse is under anesthesia with the through its larynx. The tracheotomy tube can usually
head extended. If the tracheotomy is placed too far be removed at this time. The horse should be maintained
cranially it may become obstructed during recovery. on perioperative antimicrobials and anti-inflammatories
To perform an arytenoidectomy, a standard laryngotomy for 1 week and maintained in a stall for 1 month with
approach (Chapter 35) is first made. A headlamp is useful only hand grazing. The tracheotomy and laryngotomy
for illumination while working within the larynx, and sites are left open to heal by second intention. All feed-
placing an endoscope transnasally with its tip placed in ing should be from the ground to minimize the risk of
front of the larynx can also provide supplemental light. It is aspiration.
518 37 Arytenoid Chondropathy
Fig. 37.4. Endoscopic examination the day following left partial Fig. 37.5. The final appearance of a successful left partial arytenoidec-
arytenoidectomy. The mucosal flap is sutured in this case and there is tomy.
ample glottic space enabling removal of the tracheotomy tube.
Complications
Endoscopy should be performed 1 month following
surgery to examine for the presence of intralaryngeal There are several potential complications of this surgery.
granulation tissue. If present, it can be transendoscopi- The most common complication after arytenoidectomy is
cally removed with a laser on an outpatient basis. Once the presence of aspiration and coughing. The risk may
there is complete mucosal healing, the horse should be dramatically decreased by less traumatic dissection
receive one further month of rest before resuming exer- of the arytenoid from the lateral musculature at the time of
cise (Fig. 37.5). surgery, because many of these adductor muscle bellies
play a protective role by narrowing the glottis during swal-
lowing, even in the absence of the arytenoid body. Somewhat
Prognosis surprisingly, a minor degree of aspiration does not preclude
The reported prognosis for arytenoid chondropathy a successful racing career. Another complication is the
following treatment is extremely variable, and is dependent development of postoperative granulation tissue, which
upon the extent and duration of the disease before occurs in approximately 15% of the horses, or the presence
treatment, and to the actual type of treatment performed of excessive residual mucosa within the glottis (Parente
(Speirs 1986, Tulleners 1988a, Dean & Cohen 1990, 2003). Granulation tissue, or excessive mucosa, should be
Parente 2003, Barnes et al 2004). Horses that have a removed using a transendoscopic laser at 1 month after
chronic, non-active chondropathy can function quite arytenoidectomy and the surgical site will then often
adequately at low levels of exercise without surgical resolve without further complications. If not removed in its
intervention. Horses with concurrent severe hemiplegia early stages, intraluminal granulation tissue may miner-
or those with more severe chondropathy will likely require alize and make subsequent excision much more difficult.
surgical intervention to provide an adequate airway for Postoperative respiratory noise during exercise can also
any athletic function. After unilateral partial arytenoidec- occur following arytenoidectomy. The presence of post-
tomy, most racehorses will return to athletic function and operative respiratory noise is most likely from residual
have significant earnings (Parente 2003). In contrast, arytenoid/corniculate mucosa impinging on the glottis
horses with severe bilateral disease are unlikely to return to during fast work, provided the affected cartilage has
any significant athletic function (Parente 2003). been removed and no concurrent disorders (e.g. RLN) are
37 Arytenoid Chondropathy 519
present. There appear to be no reports on results of partial Hay WP, Tulleners EP, Ducharme NG 1993 Partial ary-
arytenoidectomy in show horses where noise would be a tenoidectomy in the horse using an extralaryngeal
fault, but generally, the prognosis is considered worse for approach. Veterinary Surgery 22: 50–56
Lumsden JM, Derksen FJ, Stick JA et al 1994 An eval-
abnormal noise production than for exercise performance. uation of partial arytenoidectomy as a treatment for
A treadmill examination may be beneficial to determine equine laryngeal hemiplegia. Equine Veterinary Journal
the source of any noise. Inspiratory axial deviation of the 26: 125–129
adjacent aryepiglottic fold that is no longer held abaxial by Parente EJ 2003 Partial arytenoidectomy for treatment
the corniculate process of the arytenoid is another likely of failed laryngoplasty or arytenoid chondritis in race-
horses. Proceedings of the 49th Annual Convention
cause of abnormal noise after partial arytenoidectomy. This of American Association of Equine Practitioners,
tissue, or any excessive residual arytenoid mucosa imping- pp.373–376
ing on the airway, can be identified by high-speed treadmill Speirs VC 1986 Partial arytenoidectomy in horses. Veterinary
endoscopy and the offending tissue removed as needed. Surgery 15: 316–320
Tulleners EP, Harrison IW, Raker CW 1988a Management of
arytenoid chondropathy and failed laryngoplasty in
REFERENCES horses: 75 cases (1979–1985). Journal of the American
Barnes AJ, Slone DE, Lynch TM 2004 Performance after Tulleners EP, Harrison IW, Mann P et al 1988b Partial
partial arytenoidectomy without mucosal closure in 27 arytenoidectomy in the horse with and without mucosal
thoroughbred racehorses. Veterinary Surgery 33: 398–403 closure. Veterinary Surgery 17: 252–257
Belknap JK, Derksen FJ, Nickels FA et al 1990 Failure of Tulleners EP 1990 Arytenoidectomy. In: White NA, Moore JN
subtotal arytenoidectomy to improve upper airway flow (editors) Current Practice of Equine Surgery. Lippincott,
mechanics in exercising standardbreds with induced Philadelphia, pp.255–261
laryngeal hemiplegia. American Journal of Veterinary Williams JW, Pascoe JR, Meagher DM et al 1990 Effects of
Research 51: 1481–1487 left recurrent laryngeal neurectomy, prosthetic laryngo-
Dean PW, Cohen ND 1990 Arytenoidectomy for advanced plasty, and subtotal arytenoidectomy on upper airway
unilateral chondropathy with accompanying lesions. pressure during maximal exertion. Veterinary Surgery
Veterinary Surgery 19: 364–370 19: 136–141
Miscellaneous Disorders of the
Larynx and Epiglottis
38 Padraic M Dixon
Congenital Defects of the Larynx

(1992) found a fluid-filled cyst, 3–4 cm in diameter, lying
A number of congenital defects of the equine larynx between the medial aspect of a laterally displaced thyroid
(including the epiglottis) have been described, with cartilage and the lateral aspect of deformed cricoid and
cricopharyngeal–laryngeal dysplasia (fourth branchial arytenoid cartilages. Following surgical excision of the cyst
arch defect) being most frequently recorded. This disorder and laryngoplasty, the horse remained asymptomatic.
is described in detail in Chapter 31. Subepiglottic cysts are Histology of the excised cyst showed it to have a mucosal
also relatively common in standardbreds (Stick & Boles lining with features of a paralaryngeal accessory bronchial
1980) and are described in Chapter 29). Hypoplasia of the cyst (i.e. lined with tracheal/bronchial type mucosa).
epiglottis has also been recorded in horses (Rooney & A wide range of human congenital laryngeal defects has
Robertson 1996). This can be of varying degrees from been described. Laryngomalacia, a disorder in which
aplasia, or gross hypoplasia, as illustrated by Lane (1997), the laryngeal inlet collapses on inspiration, accounts for
to slight shortening of the epiglottis as determined 60–70% of all congenital laryngeal defects (Lusk 1991),
by lateral pharyngeal radiography (Linford et al 1983, but this defect does not appear to have been described in
Tulleners 1991a). Horses with an abnormally shortened horses. Other common human congenital laryngeal defects
epiglottis are prone to dorsal displacement of the soft include absent or bifid epiglottis, laryngeal cysts, laryngeal
palate, as described in Chapter 29. Whitton & Kannegieter clefts (deficient separation from the esophagus) and laryn-
(1995) described four cases of epiglottic deformity in adult geal paralysis as a result of congenital central nervous
horses, two of which appeared to have a developmental system disorders, including hydrocephalus, meningocele
deformity of the mid-epiglottic region, with a deep unilateral and nucleus ambiguus dysgenesis (Lusk 1991), none of
infolding in one, and axial folding of both epiglottic borders which have been reported in the horse.
in the other. Yarborough et al (1999) described persistent
frenulum of the epiglottis in four foals.
Lees et al (1987) recorded a developmental laryngeal
web (stenosis) in a 10-day-old quarterhorse foal with
Bilateral Arytenoid Cartilage
respiratory distress and dysphagia. A thick band of fibrous
and Vocal Fold Collapse
tissue adjoined both vocal folds, occluding the ventral Bilateral arytenoid cartilage and vocal fold collapse have
aspect of the rima glottidis. The foal also had a short, been recorded in Norwegian coldblooded trotter racehorses
vertically angulated epiglottis, permanent soft palate that have no evidence of neurological laryngeal disease
displacement that caused dysphagia, and abnormally (Strand et al 2004). This phenomenon could also account
shaped arytenoids and lateral ventricles. The foal was for some of the undiagnosed abnormal noises that are
euthanased and necropsy showed a hypoplastic larynx recorded in other breeds that are exercised with head
with arytenoids that could not abduct because of a thick, flexion. Diagnosis of this disorder is by high-speed treadmill
mucosa-covered, fibrous web. Byars (2004) described a video-endoscopy, while the horse is wearing appropriate
neonatal foal with marked laryngeal obstruction caused tack (as discussed in Chapter 16).
by a congenital cyst on the right aryepiglottic fold that Hyperkalemic periodic paresis, an inherited generalized
was successfully excised using a diode laser. A further myasthenic disorder of quarterhorses, can also cause
congenital laryngeal deformity recorded in the horse is intermittent upper airway obstruction, attributed to laryn-
paralaryngeal accessory bronchial cyst (Baxter et al 1992), geal spasm and nasopharyngeal muscle dysfunction (Carr
a deformity that has been well described in humans. Whilst et al 1996). More generalized skeletal muscle dysfunction
performing laryngoplasty in a 3-year-old thoroughbred may also be present, and the disorder may respond to
with left-sided recurrent laryngeal neuropathy, Baxter et al appropriate medical treatment.
521
522 38 Miscellaneous Disorders of the Larynx and Epiglottis
of the laryngeal lumen can also occur. For this reason,

External Laryngeal Trauma
intensive antibiotic therapy and cartilage debridement are
The equine larynx is anatomically well protected from indicated with open laryngeal wounds (Miles-Foxen 1980).
trauma and consequently severe external laryngeal trauma
rarely occurs in this species, as compared to humans where
laryngeal damage is common in car accidents and with
Laryngeal and Epiglottic Inflammation
assaults such as knife wounds and blows (Miles-Foxen The tight junction between the laryngeal submucosa and
1980, Sanders & Billers 1991). Laryngeal trauma is also underlying fibrocartilage limits the degree of mucosal
well recorded in dogs, usually as a result of choke chain inflammation and swelling that can occur in the larynx.
abuse and gunshot wounds (Manus 1965, Nelson & Wykes This evolutionary feature is of obvious benefit to the host
1985). Occasionally a horse may damage its larynx after by preventing glottic obstruction. Even in horses with viral
trapping its head, such as when trying to feed from sheep respiratory infections or strangles, which may have gross
or cattle feeders. If a horse escapes from its rider and gets inflammation of the surrounding nasopharyngeal mucosa,
its bridle or reins caught in a fence or other fixed struc- marked swelling of the laryngeal, and in particular of the
ture, it can severely traumatize its neck and larynx trying epiglottic, mucosa is rare (Dixon 1995).
to free itself. Inflammation of the larynx, mainly of the medial
External laryngeal trauma can cause inflammation and aspects of the arytenoids, often occurs following intubation
edema of the larynx, which can result in fatal airway for general anesthesia, and similar inflammation also
obstruction. Cartilage fractures and submucosal hemor- occurs in the trachea (Holland et al 1986). This inflam-
rhage can follow direct laryngeal trauma (Miles-Foxen mation can occur within 1 h of intubation and lesions
1980), which can also lead to acute respiratory obstruc- can include focal mucosal hyperemia, submucosal hemor-
tion. In such cases, an immediate temporary tracheotomy rhage or ulceration. This inflammation invariably begins
should be performed below the level of any intercurrently to regress within 24–48 h (Holland et al 1986). More
damaged trachea. Non-steroidal anti-inflammatory drugs marked bruising, and even arytenoid mucosal tears
and/or corticosteroids should be administered, along and hemorrhage can occur with difficult intubations, such
with antibiotics if there are open wounds. Damage to the as in horses with laryngeal paralysis. Serial endoscopic
overlying skin or internally to the laryngeal mucosa caused examinations of such cases following surgery have shown
by cartilage fractures will invariably lead to emphysema of this inflammation to be self-resolving within days in
the laryngeal region that may spread extensively. virtually all cases (P.M. Dixon, personal observations).
Of greatest long-term concern with laryngeal trauma Similar arytenoid bruising and even ulceration are also
is the presence of laryngeal mucosal damage. Extensive well recorded in humans following prolonged intubation
mucosal loss, particularly in the presence of concurrent (Bradley 1997).
fractures of the laryngeal cartilages, may lead to extensive Gross inflammation of the larynx including the
granulation tissue formation in the larynx and possibly to epiglottis can occur with smoke inhalation (from both
permanent fibrotic webs (laryngeal stenosis) (Dixon et al thermal and chemical insults) and severe concurrent
1994), as described later in this chapter. damage to other upper respiratory tract sites and also to
If fractures of the laryngeal cartilages are non-displaced the lungs can contribute to the respiratory embarrass-
and the overlying mucosa and skin are intact, no long-term ment in such cases. The treatment of horses with smoke
laryngeal obstruction should ensue. However, if the cricoid inhalation pulmonary injury is covered in Chapter 43.
cartilage is fractured and displaced, some degree of per- Occasionally horses will develop severe edema of the
manent laryngeal obstruction is likely, because this ring- head that can also involve the larynx; causes include
shaped cartilage is the scaffold of the larynx. Accurate insect and snake bites to the head and upper neck,
assessment of traumatic laryngeal cartilage damage is urticarial reactions of the head region, angioedema, and
difficult, especially when extensive perilaryngeal swelling purpura hemorrhagica. Focal laryngeal inflammation can
and emphysema are present. Assessment is best performed occur with purpura hemorrhagica following strangles
by computed tomography or magnetic resonance imaging vaccination (Byars 2004). Generalized head swelling can
scans, but if these imaging modalities are unavailable, also occur as the result of adverse reactions to drugs
assessment by clinical, radiographic, ultrasonographic and (e.g. penicillin) or vaccines. Obstruction to venous and
even surgical exploration may be necessary. Bearing in lymphatic drainage of the head, including that caused by
mind the need to preserve the laryngeal mucosa, displaced head or neck neoplasia (Fig. 38.1), or bilateral jugular
cartilage fragments can be realigned and stabilized with phlebitis may also cause gross swelling of the head. Some
steel sutures, whilst loose and necrotic tissue should be degree of head edema can develop in horses under general
resected. Following penetrating wounds of the larynx, anesthesia, particularly if their head is maintained in a
chronic chondropathy with cartilage necrosis are common dependent position for prolonged periods, such as in horses
sequelae in humans, and secondary fibrotic obstruction having prolonged esophageal lavage for esophageal choke.
38 Miscellaneous Disorders of the Larynx and Epiglottis 523
AE
Fig. 38.2. Laryngeal endoscopy of a pony with marked inspiratory

stridor. Both arytenoids are swollen and erythematous, with edema
and distortion of the aryepiglottic folds, especially on the right side
(AE). There appear to be adhesions between the mucosa of the right
arytenoid and the palatopharyngeal arch (arrow). These laryngeal
changes were caused by inflammation associated with an adjacent
thyroid neoplasm.
labored breathing, neck extension, and distress. As

previously noted, concurrent edema of the nasal cavity
and nostrils may exacerbate the respiratory obstruction in
such cases. Horses with laryngeal obstruction should be
carefully clinically evaluated, and unless they are in severe
respiratory distress, they should also be endoscopically
examined to confirm the site and extent of the airway
obstruction. Intranasal oxygen therapy (if tolerated) and
an emergency temporary tracheotomy (Fig. 38.1) (see
Fig. 38.1. This pony has gross bilateral swelling of the head region Chapter 40) are indicated in cases with severe dyspnea.
secondary to neoplasia of the mandibular region. The pony is unable
For less severe cases of laryngeal inflammation, rest and
to dilate its grossly swollen nostrils and marked edema of the eyelids is
also present, preventing full eye opening. A temporary tracheostomy non-steroidal anti-inflammatories can be employed, with
tube is in place because of life-threatening nasal and laryngeal edema. regular 24-h monitoring for evidence of increasing air-
way obstruction. An emergency tracheostomy tube and
appropriate surgical equipment should be immediately
available by the stall.
Marked swelling of the nasal mucosa is also a feature of

some of these cases with postanesthetic head edema.
Epiglottic Inflammation
As noted elsewhere (Chapter 33), some horses develop Inflammation of the epiglottis alone can develop (primarily
dyspnea following anesthesia because of bilateral laryngeal in racehorses) in a number of situations, including some
paralysis following general anesthesia. horses with epiglottic entrapment (Chapter 30) and in
Horses with acute head edema may develop significant most horses following surgical correction of epiglottic
perilaryngeal and laryngeal edema (Fig. 38.2) and can entrapment (even if minimal epiglottic inflammation
therefore develop inspiratory dyspnea and stridor, with was present pre-surgery). Some horses may consequently
develop a permanent deformity of the epiglottis following

its entrapment and surgical correction (Whitton &
Kannegieter 1995, Dixon & Collins 2004). Severe epiglottic
inflammation can also develop following resection of sub-
epiglottic mucosa to treat dorsal displacement of the soft
palate (DDSP) and in particular following subepiglottic
injections of polytetrafluoroethylene (Teflon) paste or
collagen to stiffen a “hypoplastic” epiglottis to help prevent
DDSP (Tulleners et al 1997, Stick et al 1999). Trauma from
a nasopharyngeal foreign body (usually a twig) entrapped
on the lateral aspect of the larynx can also cause laryn-
geal, and especially epiglottic, trauma and inflammation
(Dixon 1995).
Less severe degrees of idiopathic epiglottic inflammation
have been described in racehorses, especially thorough-
breds showing poor exercise performance (Hawkins &
Tulleners 1993, Davenport-Goodall & Parente 2003). This
inflammation may be related to abnormal epiglottic–soft
palate contact, as can occur in horses with DDSP, and
some such cases may respond to rest. Tulleners (1997)
also proposed that epiglottic inflammation in American
racehorses might be caused by the inhalation of dirt from Fig. 38.3. Swollen epiglottis of a 12-year-old pony that suddenly
developed exercise intolerance and near permanent dorsal displace-
racetracks or be the result of the stresses of race training.
ment of the soft palate. The ventral aspect of the epiglottis and caudal
Ulceration of the subepiglottic area (glossoepiglottic fold), aspect of the soft palate (arrows) are inflamed and ulcerated. This
which is detectable by elevating the epiglottis with a mal- epiglottic inflammation did not respond to 9 months of rest along with
leable rod per nasum, is also increasingly recognized in some prolonged phenylbutazone therapy. The initial cause of this epiglottitis
racehorses with similar histories, and concurrent ulcera- may have been nasopharyngeal foreign body damage or a self-
resolving epiglottic entrapment.
tion of the caudal aspect of the soft palate is also apparent
in some of these cases (Blea & Arthur 2003). Marked
inflammation of these areas with sudden-onset permanent
DDSP can occur rarely in any breed of horse (Fig. 38.3).
In humans, primary bacterial infection with Haemophilus marked nasopharyngeal and laryngeal obstruction that
influenzae type B, and less commonly with Streptococcus spp. resulted in dyspnea, dysphagia, and aspiration (Fig. 38.4).
and Staphylococcus spp., can cause acute inflammation The cause of the underlying epiglottitis was not determined
of both the nasopharynx and larynx. Of most clinical and the inflammation resolved fully following crystalline
importance is peracute epiglottitis as a result of severe penicillin, gentamicin, and flunixin therapy.
cellulitis of the epiglottic mucosa and submucosa that A sequel to human epiglottitis is the development of an
can prove fatal within hours of onset (Bastian 1991). epiglottic abscess (Bastian 1991). In horses, dorsal epiglottic
A mortality of 6.1% was recorded in human epiglottitis abscessation is a rare idiopathic disorder, presenting endo-
cases managed conservatively (antibiotics, with or without scopically as well-circumscribed, smooth swellings of the
corticosteroid therapy) as compared to 0.9% in cases that dorsal surface of the epiglottis. Treatment is by drainage,
additionally received a tracheotomy or intubation to bypass using a transendoscopic needle or biopsy forceps, or using
the obstructed glottis (Cantrell et al 1978). transendoscopic laser as described by Tulleners (1991b).
In contrast to humans, acute epiglottitis is rare in
horses. Barclay et al (1982) recorded acute epiglottitis in a
3-year-old thoroughbred that presented with acute-onset
Idiopathic Laryngeal Mucosal
stridor and dysphagia. Endoscopy revealed marked swelling
Ulceration and Granulomas
of the epiglottis, with ulceration of its tip. The epiglottitis Mucosal ulceration and granulomas are commonly
partly resolved following 2 days of penicillin and phenylbu- present on the arytenoids of horses affected with chon-
tazone therapy, and fully resolved after 5 days of systemic dropathy, as described in detail in Chapter 37. Arytenoid
corticosteroid therapy. A peracute case of epiglottitis in granulomas, without obvious underlying chondropathy,
an 8-day-old foal was described by Dacre et al (2004), can also occasionally occur following laryngoplasty (Dixon
which presented with dyspnea, coughing, and dysphagia of et al 2003). More commonly, granulomas can form fol-
2 days’ duration. Endoscopy showed marked inflammation lowing intraluminal surgery of the larynx (e.g. following
of an almost vertically positioned epiglottis to be causing partial arytenoidectomy or at the dorsal aspect of a vocal
Fig. 38.4. (A) Nasopharyngeal endoscopy of

a dyspneic foal that has gross inflammation
and swelling of its epiglottis (E) that is dor-
sally deviated and whose tip is touching the
nasopharyngeal roof. This deviation is the
result of the swollen epiglottis becoming
trapped by the caudal aspect of the soft
palate (arrowheads). (B) On occasions, the
soft palate could relocate beneath the
epiglottis, and the latter then resumed a
more normal, horizontal position. Repro-
E
duced with the permission of Dr K. Dacre.
A B
cordectomy site) but these are usually self-resolving

(Haynes 1978, Dixon et al 1994).
Focal, bilateral areas of arytenoid erythema often occur
in horses after tracheal endoscopy (tracheoscopy) or bron-
choscopy, especially in the presence of normal laryngeal
function, where forceful glottic closure on an intralaryn-
geal endoscope induces local mucosal bruising, usually on
the ventromedial aspects of the corniculate cartilages,
i.e. the vocal processes. Laryngospasm, which can be G
life-threatening in other species when intralaryngeal
endoscopy is performed without sedation or local anes-
thesia, seldom if ever occurs in horses, probably because
they have a relatively insensitive larynx. As noted earlier,
endotracheal intubation can cause inflammation of the VC
equine glottis in addition to more severe laryngeal bruis-
ing if intubation was difficult. Mucosal ulcers can also
occasionally occur in horses with bilateral laryngeal paraly-
sis as a result of abnormal contact between the arytenoids.
In addition to the aforementioned types of laryngeal
inflammation, idiopathic mucosal ulceration or granu-
loma formation has been reported in horses in which
Fig. 38.5. Laryngeal endoscopy of a 3-year-old thoroughbred race-
the underlying arytenoid cartilages appear normal and horse that had laryngoplasty, left vocal cordectomy (VC) and
in which normal laryngeal function is present (Hay right-sided ventriculectomy for recurrent laryngeal neuropathy
& Tulleners 1993, Embertson 1998, Stick et al 1999, circa 6 months earlier. More recently, an arytenoid granuloma (G)
Kelly et al 2003, Anderson 2004, Byars 2004). Such focal has developed, dorsal to the left vocal process, a common site for
idiopathic arytenoid granuloma formation. There is no distortion of
arytenoid mucosal lesions usually occur medially (axially)
the arytenoids, indicating that arytenoid chondropathy is not present.
on the vocal processes, just above the dorsal insertion of
the vocal folds. These mucosal lesions are sometimes
erroneously referred to as arytenoid chondritis, despite the
underlying arytenoids being of normal shape and size, mation and repetitive injury later inducing granulation
unlike in most cases of arytenoid chondropathy (Figs 38.5 tissue formation (Bradley 1997). Whilst usually small
and 38.6). Unilateral arytenoid granulomas often have a (< 3 cm in diameter), larger granulomas have been illus-
corresponding (“kissing”) mucosal ulcer on the medial trated that can cause marked laryngeal obstruction even
aspect on the opposite arytenoid, which is believed to be at rest (Byars 2004).
caused by contact. These equine mucosal and granulo- Embertson (1998) described the occurrence of idio-
matous arytenoid lesions are likely to be related, as is pathic, small, reddened areas of the corniculate process
the case in humans where arytenoid granulomas are or vocal process of unknown origin in thoroughbred year-
believed to begin as mucosal ulcers, with continued inflam- lings in Kentucky. Intercurrent respiratory disease with
Fig. 38.6. On the left, the arytenoid granu-

loma shown in Fig. 38.5 is almost completely
dissected free and hanging into the glottis,
following diode laser (L) resection. The right
image shows the larynx immediately follow-
ing removal of the granuloma.
L L
laryngeal mucosal swelling and arytenoid mucosal trauma et al (2000) described acute laryngeal obstruction caused
caused by endoscopy, coughing or exercise testing at sales by a large unilateral arytenoid granuloma in a pregnant
could account for these mucosal lesions. mare that was successfully removed using a transendo-
Kelly et al (2003) reported 21 cases of arytenoid mucosal scopic electrosurgical snare.
lesions in 3,312 thoroughbred yearlings in Australia Hay & Tulleners (1993) described arytenoid granulomas
(0.63% prevalence), this disorder being the most com- in 25 horses, with an underlying arytenoid chondropathy
mon upper airway abnormality found in these horses. present in 17 of these cases (following partial arytenoidec-
Nineteen of the 21 cases had mucosal ulceration (13 tomies in three cases). However, minimal or no underlying
bilateral, six unilateral), one horse had bilateral arytenoid arytenoid swellings, or laryngeal abductory deficits were
granulomas (with concurrent total left recurrent laryn- present in the other eight cases. Interestingly, 18 of the 22
geal neuropathy) and one had unilateral arytenoid (82%) “primary” granulomas were right-sided, and all
granulomas and ulceration. The mucosal ulcers were originated axially on the arytenoid between the vocal and
2–6 mm in diameter and were usually located at the corniculate processes. Using a neodymium:yttrium–
rostroventral aspect of the arytenoids, just above the aluminum–garnet (Nd:YAG) laser, the base of the lesion
vocal process. Of 18 yearlings that were followed up, was excised circumferentially creating a 1- to 2-mm deep
15 recovered fully following antimicrobial and anti- concave defect. The granuloma was grasped with bron-
inflammatory therapy combined with box rest, and the choesophageal forceps before it was fully removed. All eight
other three later developed mucosal granulomas, with cases without significant arytenoid swelling responded
arytenoid chondropathy developing subsequently in one. to this contact laser excision. Stick et al (1999) have
It was hypothesized that the cause of these lesions was a also noted that removal of larger laryngeal granulomas
respiratory mucosal infection with secondary traumatic can help the healing of underlying mucosal lesions. It is
damage to focal areas of the arytenoids by abnormally unclear if the eight cases of Hay and Tulleners (1993)
forceful contact with the contralateral arytenoid during described above were early stage arytenoid chondropathy
coughing or fast exercise. Kelly et al (2003) dismissed cases or simply idiopathic mucosal ulceration with later
endoscopic trauma as a cause of these lesions because they granuloma formation.
expected endoscopically induced lesions to be more ros- Arytenoid contact ulcers are common in feedlot cattle,
trally positioned. However, as noted above, closure of the with an incidence of 13% in one large abattoir study
larynx can induce mucosal bruising on the medial aspects (Jensen et al 1980). Respiratory infection with laryngeal
of the arytenoids. It is also likely that such horses would mucosal inflammation and excessive coughing (Jensen et al
have undergone frequent laryngeal endoscopy before and 1980) or focal infarct (Dillman 1972) has been proposed as
during yearling sales. the cause of these lesions. Excessive vocalization during the
Anderson (2004) reported that, in addition to endo- breeding season is believed to be the cause of laryngeal
scopically recording arytenoid chondropathy in thorough- inflammation in male sheep (especially in Texel and Suffolk
bred yearlings in New Zealand, arytenoid mucosal ulcera- breeds) in Britain (C. Penny, personal communication
tion without apparent concurrent chondropathy was 2004). Likewise, excessive vocalization associated with
also observed. These usually bilateral, idiopathic arytenoid transport and mixing with new horses could also be a
ulcers were present on the medial aspect of the arytenoid potential cause of focal trauma to the arytenoid mucosa
near the vocal process. These lesions appear identical to in young horses, for example at times of sales. The fact
those described in Australia by Kelly et al (2003). Booth that these obvious lesions are rarely recorded in other
countries with large, well-evaluated equine populations,

Miscellaneous Arytenoid Swellings
such as Britain and Ireland, is interesting, and suggests
that some of the predisposing factors for the develop- Shapiro et al (1979) described laryngeal obstruction and
ment of idiopathic arytenoid ulceration are absent in these stridor in an aged horse that were caused by bilateral,
two countries. irregular enlargements of all of the laryngeal cartilages, in
In humans, arytenoid granulomas can occur following particular by medial swellings of the thyroid cartilage, that
mucosal injury caused by endoscopy or endotracheal intu- prevented arytenoid abduction. The lesions were histologi-
bation, especially if intubation is prolonged, as can occur cally described as hypertrophic ossification of the laryngeal
in patients maintained on ventilators and also following cartilages, with osseous metaplasia that extended well
laryngeal surgery (Bradley 1997). The majority of endo- beyond the normal borders of the cartilages. The marked
tracheally induced human laryngeal granulomas resolve inflammatory nature of the cartilaginous changes, in
spontaneously within 8–14 weeks after extubation. A addition to the reported cartilage calcification in this case,
second type of contact ulcer of the human arytenoid differs greatly from the normal ossification of equine
(usually of the vocal process) is caused by excessively laryngeal cartilages, which can develop in horses as young
forceful apposition of the two arytenoids (Sanders & Billers as 2 years (P.M. Dixon, personal observations) but more
1991, Bradley 1997) and this type of lesion may be commonly develops in older horses. This normal ossifica-
unilateral or bilateral. The lesions tend to occur in older tion first appears in the thyroid cartilage, then the dorsal
males, particularly in those that use forceful speech in their lamina of the cricoid and the arytenoid muscular processes
work (e.g. lawyers, clergy). Chronic coughing, gastro- (Rooney & Robertson 1996).
esophageal reflux, and smoking are additional risk factors
(Bradley 1997). This type of human laryngeal contact
Parasitic Laryngeal Inflammation
ulcer usually responds to voice rest, and later voice
re-education. Failure to respond usually indicates the Lane et al (1986) described a parasitic infection of the
presence of underlying arytenoid inflammation. Human larynx in a horse imported from Central America that was
arytenoid granulomas are commonly excised by sharp caused by Besnoitia bennetti (a coccidian type organism).
dissection and laser application to the mucosal wound to The affected horse had multiple papillomatous lesions
control hemorrhage. These arytenoid mucosal lesions differ (ranging from 0.3 to 2 cm in diameter) on its arytenoids,
from the vocal cord nodules that can develop, especially epiglottis, and aryepiglottic and vocal folds, although normal
in young children (“screamer’s nodules”) or older female laryngeal movement was present. Histology showed the
singers (“singers nodules”) (Sanders & Billers 1991), as the lesions to be composed of subepithelial connective tissue
result of excessive vocalization. containing the parasite, covered by acanthotic epithelium.
In conclusion, it is likely that continued inflammation
of idiopathic arytenoid ulceration in horses leads to ary-
tenoid granuloma formation as has been recorded in
Laryngeal Foreign Bodies
humans (Bradley 1997). It also appears likely that some
arytenoid granulomas will progress to arytenoid chon- The height of the horse makes it unlikely that inhalation of
dropathy, as has also been reported in humans (Sanders plant material will occur whilst running, in contrast to
& Billers 1991). shorter mammals such as dogs in which inhalation of ears
(awns) of grass and corn are commonly described. Never-
theless, 10- to 15-cm long, branched twigs will occasion-
Perilaryngeal Infections ally become inhaled and may lodge in the nasal concha or,
Barber (1981) described a 3-year-old thoroughbred filly more commonly, in the laryngopharynx lateral to the
that developed bilateral nasal discharge and swelling of the arytenoids, laryngeal lumen, lateral ventricles, or in the
left laryngeal area. Following an emergency tracheostomy trachea. Horses are very selective eaters but occasionally
and 2 weeks of antibiotic therapy, endoscopy showed shorter twigs (e.g. hedge clippings) will be ingested,
left-sided laryngeal paralysis, a swollen left arytenoid and masticated, and partially swallowed before becoming
drainage of pus into the laryngeal lumen. Radiography entrapped in the oropharynx, laryngopharynx or larynx
showed a gas-capped abscess superimposed over the larynx (T. Greet, personal communications 2005). Pieces of wire
and rostral trachea indicating a communicating abscess. in forage may also be ingested and also may become
Surgical drainage via a left-sided paramedian ventral entrapped in the oropharynx, laryngopharynx or larynx.
approach was successful in resolving the abscess. The If sharp and pointed, such ingested twigs or wire may
author has also treated a horse with a dorsal laryngeal become deeply embedded in the nasopharyngeal wall
abscess caused by an ingested piece of wire that involved a during swallowing or as the result of spasm of the naso-
common carotid artery, and which resolved with foreign pharyngeal muscles. Likewise, similar objects may become
body removal and drainage. embedded in the larynx as a result of laryngospasm.
Fig. 38.7. (A) Nasopharyngeal endoscopic

image of a horse with sudden-onset dys-
phagia and distress which shows a Y-shaped
twig embedded in the roof of the pharynx,
just lateral to right arytenoid. The foreign
body caused gross, fibrinous inflammation
of the punctured nasopharynx and inflam-
mation of the adjacent arytenoids and
epiglottis. (B) The twig that was removed
per os. The structural damage caused to the
epiglottis in this horse caused long-term
intermittent soft palate displacement.
B
Fig. 38.8. (A) Endoscopic image of the caudal

nasopharyngeal and laryngeal area of a pony
with severe dyspnea and stridor. There is
severe bruising of the nasopharyngeal area
and epiglottis, and the laryngeal lumen
appears to be almost fully occluded by a
spherical mass. Following emergency tra-
cheostomy, a laryngotomy showed a polyp-
like mass protruding from the right lateral
ventricle, which was surgically excised at its
base. (B) The excised polyp (transected).
B
Laryngeal or perilaryngeal foreign bodies may become ventricles and cause a granulomatous reaction at this site,
dislodged and then swallowed or coughed out. Consequently, with the granuloma protruding into the laryngeal lumen
laryngeal (especially epiglottic) trauma of unknown origin (Fig. 38.8). In the case shown in Fig. 38.8 the lateral ven-
can reasonably be attributed to such foreign body damage. tricle granuloma was removed via a laryngotomy but
When embedded at the side of the larynx or in its lumen, clinical signs recurred some months later as the result of
foreign bodies will cause sudden-onset paroxysmal cough- regrowth of a similar-sized polyp. Radiography showed a
ing, dysphagia, and anorexia accompanied by malodorous piece of wire in the ventricle. At a second surgery, the polyp
breath. Depending on the degree of laryngeal inflammation was removed and exploration of the ventricle revealed
that occurs, dyspnea and stridor may also develop. Clinical the embedded wire that had caused the granuloma forma-
examination will usually be unrewarding in early cases, tion (Fig. 38.9). The wire was removed and there was
unless malodorous breath and/or dysphagia (as manifested permanent resolution of the laryngeal inflammation. In
by nasal discharge containing food) are present. Later, with contrast, Ordridge (1988) reported a horse with a 5-cm
the onset of marked laryngeal inflammation, stridor may long twig in a laryngeal lateral ventricle for an estimated
be present even at rest, and deep palpation of the laryngeal 3 weeks, where minimal laryngeal inflammation occurred.
area may be resented and may also induce coughing. The twig was successfully removed using a snare of thick
Diagnosis is best made by nasopharyngeal endoscopy, nylon fishing line inserted transendoscopically.
when the foreign body, possibly covered by food, mucus or Although radiography can only detect radio-opaque
fibrin can be visualized, in addition to swollen, reddened, foreign bodies, it is nevertheless a worthwhile technique to
and possibly fibrinous inflammation of the larynx and use in cases of pharyngeal or laryngeal swelling, and in
laryngopharynx or nasopharynx (Fig. 38.7). The epiglottis horses with sudden-onset dysphagia or stridor of unknown
in particular can be extensively inflamed and torn. Smaller etiology. Perilaryngeal or peripharyngeal metallic foreign
foreign bodies may become entrapped in the lateral bodies may be detected radiographically in some of these
Fig. 38.9. The upper airway obstruction in the pony described in

Fig. 38.8 recurred after several months and endoscopy showed
regrowth of a polyp from the right lateral ventricle. Radiography at
that stage showed a piece of wire embedded in the lateral ventricle.
The polyp and the wire fragment (embedded in granulation tissue)
Fig. 38.10. Endoscopic view of the larynx of a horse with marked
were removed, leading to permanent resolution of the laryngeal
ventral glottic stenosis, which occludes most of the laryngeal lumen
obstruction.
(arrows). The ventral aspect of the right corniculate process (C) has
been resected. This laryngeal web developed following bilateral vocal
cordectomy, and the web became taller and thicker following surgical
resection.
cases, as may perilaryngeal abscesses and gas pockets. The

latter lesions may be caused by non-opaque foreign bodies,
hematogenous infections or trauma. can also be removed via a high cervical tracheostomy by
A horse with an inhaled foreign body is obviously inserting grasping forceps retrograde to the larynx under
treated by removal of the foreign body. As these objects are nasopharyngeal endoscopic guidance (Voss & Seahorn
often large and also deeply embedded into the pharynx or 2004), but the postoperative risks are greater for tra-
larynx, attempted removal with transendoscopic biopsy or cheostomy than laryngotomy when used for this purpose.
grasping forceps may be unsuccessful or may break the
foreign body, possibly leaving some of it embedded in situ.
The use of long, rigid grasping forceps (such as bron-
Laryngeal Stenosis
choesophageal forceps) per nasum can be successful in Laryngeal stenosis (laryngeal webbing or cicatrix) of horses
suitably sedated horses with use of topical local anesthesia. can be congenital, as described earlier. More commonly in
If a perilaryngeal or laryngeal foreign body cannot be the horse these webs are acquired following extensive
retrieved per nasum in adult horses, the use of heavy endolaryngeal mucosal injury, when granulation tissue
sedation, transendoscopic lavage of the nasopharynx and protrudes so extensively from denuded mucosa on opposite
larynx with local anesthetic, and the use of a full mouth sides of the larynx that it prevents normal mucosal
speculum will usually allow their manual removal per os. healing. This granulation tissue then contacts granulation
To perform such procedures, the medial (palatal) aspect of tissue on an opposite surface and the two sides join
any sharp upper cheek teeth should be rasped, to protect together in the laryngeal lumen. This bridge of granulation
the operator’s hands. The wet hand should be pushed tissue then develops into a fibrous fold across the larynx,
caudally into the oropharynx, and then directed dorso- which later becomes covered with mucosa (Fig. 38.10)
caudally, displacing the soft palate and elevating the (Langman et al 1989, Bastian 1991, Dixon et al 1994).
epiglottis. The laryngeal structures can then be palpated Laryngeal stenosis is common in humans, where it usually
and a caudally positioned nasopharyngeal, laryngopharyn- involves the narrowest intralaryngeal areas (i.e. glottic
geal or laryngeal foreign body can be grasped and removed stenosis) or areas just caudal to the larynx (i.e. subglottic
via the oral cavity. Alternatively, per os retrieval can be stenosis) and is congenital in about 40% of cases (Flexon
performed with the horse under general anesthesia (Greet et al 1989, Lusk 1991). Acquired glottic stenosis in
2003), possibly using rigid instruments passed per nasum humans most commonly develops following extensive
to assist removal. mucosal injury caused by prolonged nasotracheal intu-
A laryngotomy can be performed to remove deeply bation (Langman et al 1989), or as a sequel to serious
embedded laryngeal foreign bodies, such as those trapped trauma, e.g. from steering wheel trauma in car accidents,
in the lateral ventricles. Intralaryngeal foreign bodies knife and gunshot wounds (Sanders & Billers 1991) or
injuries from ingested caustic chemicals or hot liquids of the underlying mucosal deficit (e.g. by mucosal sliding
(Koufman et al 1988, Flexon et al 1989, Bastian 1991). techniques when possible) to remove the stimulus for fur-
In the dog, ventral glottic stenosis was a common ther granulation, and thus for webbing, to occur (Langman
postoperative sequel when bilateral partial laryngectomy or et al 1989). Intralaryngeal stents (sutured through the
vocal cordectomy was used to treat bilateral laryngeal body of the larynx) have also been widely used in humans
paralysis, particularly when these were performed via to restrict the regrowth of excised webs. An intralaryngeal
laryngotomy that added further mucosal injury, ventral to round stent limits the development of excessive granulation
the two vocal cordectomy sites (Lane 1982, Harvey 1983, tissue by applying topical, circumferential pressure to this
Matushek & Bjorling 1988). Laryngeal stenosis also occurs site, yet hopefully allowing epithelial migration over the
in dogs following external laryngeal trauma, e.g. from mucosal deficit. Although a stent overlying the resected
forceful use of choke chains, or gunshot and bite injuries surgical site will in itself damage the regrowing epithelium,
(Manus 1965, Nelson & Wykes 1985). it appears to retard the development of granulation tissue
Laryngeal stenosis has rarely been recorded in the horse to an even greater degree, thus hopefully allowing mucosal
in comparison to other species, although its incidence may closure. This mucosal closure will be by secondary inten-
increase with the use of non-contact (e.g. Nd:YAG) or even tion, as primary healing of laryngeal mucosa is difficult to
contact laser surgery to perform bilateral cordectomy or achieve (Bradley 1997).
ventriculectomy (Fig. 38.11). The increase in the number Another type of intralaryngeal stent that is more com-
of foal intensive-care units (Koterba et al 1975) may also monly used to treat laryngeal stenosis in human beings
increase the incidence of glottic stenosis in foals under- (Flexon et al 1989, Langman et al 1989) and dogs (Nelson
going long-term ventilation by nasotracheal intubation, as & Wykes 1985, Peterson et al 1987) is termed a keel stent;
occurs in human neonatal intensive care units. it consists of a plastic or metal base plate which is sutured
The principles of treating laryngeal webbing include to the ventral aspect of the thyroid cartilage at the laryn-
excision of the web and then promotion of rapid healing gotomy site. The base plate has a thin, right-angled plate
(keel) attached to it that protrudes sagittally through
the laryngotomy site into the laryngeal lumen. After web
resection, this keel prevents granulation tissue from oppo-
site sides of the larynx from joining and then, hopefully,
the separate areas of granulation tissue will retract and
eventually epithelialize.
As noted earlier under congenital laryngeal defects,
Lees et al (1987) recorded a developmental laryngeal web
in a 10-day-old foal, with all other recorded equine laryn-
geal webbing cases being acquired disorders. Harrison and
Raker (1988) reported two cases of equine laryngeal
stenosis involving the dorsal aspect of the glottis that
developed following bilateral arytenoidectomy to treat
arytenoid chondropathy. Treatment of the stenosis was not
attempted in either case. Dixon et al (1994) reported three
cases of ventral glottic stenosis in horses, two of which
occurred following bilateral vocal cordectomy as the result
of coalescence of granulation tissue from the vocal
cordectomy sites. These cases also had arytenoid rigidity
because of extensive fibrosis, which involved all of the
ventral laryngeal area. Repeated resection of the fibrous
web in one case resulted in more extensive development of
granulation tissue at the resection sites, resulting in a
Fig. 38.11. Endoscopic image of a horse with a thick fibrous web
taller, thicker web. A further resection of the web was
attached to the ventral aspect of the right vocal fold (arrows), the performed accompanied by suturing a stent (made from a
laryngeal floor and to the remnant of the left vocal fold (single arrow- 40 mm length, 30 mm diameter soft plastic endotracheal
head). This horse had a left-sided, laser vocal cordectomy several tube) over the web excision site. The stent was held in
months previously but inadvertent damage to the floor of the larynx position within the larynx for 4 weeks by external sutures
and to the axial aspect of the right vocal fold led to extensive mucosal
damage. Subsequent granulation tissue formation at these sites joined
through the laryngeal walls. This stenting procedure
later to become a fibrous web. As well as physically obstructing the greatly reduced the web size permanently, and in the long
glottis, the fibrous web also restricted arytenoid abduction. term allowed this horse to perform moderate exercise.
A further case with a thin “V”-shaped, ventral web that in the standing horse. Proceedings of the American
occurred following severe external trauma (which is rare in Association of Equine Practitioners 49: 295–300
horses because the larynx is anatomically well protected Booth TM, Hainisch EK, Knottenbelt DC et al 2000 Endo-
scopic electrosurgical excision of laryngeal granulation
from external trauma) responded to resection of the larger tissue in a standing pregnant mare. Veterinary Record
side of this web and some mobilization and suturing of the 147: 418–420
underlying mucosal deficit, with long-term total absence of Bradley PJ 1997 Arytenoid granuloma – Editorial review.
respiratory noise and the development of normal exercise Journal of Laryngology and Otology 111: 801–803
tolerance. Lane (1997) also reported a case of ventral Byars TD 2004 Pharyngoscopy and laryngoscopy In: Slovis
NM (editor) Atlas of Equine Endoscopy. Mosby, St Louis,
glottic stenosis following bilateral vocal cordectomy via a MO, pp.55–81
ventral laryngotomy to treat laryngeal paralysis. Cantrell RW, Bell RA, Morioka WT 1978 Acute epiglottitis:
intubation versus tracheostomy. Laryngoscope 88: 994
Carr EA, Spier SJ, Kortz GD et al 1996 Laryngeal and pharyn-
Laryngeal Tumors geal dysfunction in horses homozygous for hyperkalemic
periodic paralysis. Journal of the American Veterinary
Neoplasia of the equine larynx is rare (Cotchin 1977, Medical Association 209: 798–803
Rooney & Robertson 1996) with only occasional reports of Cotchin 1977 A general survey of tumours in the horse.
laryngeal tumors, mainly squamous cell carcinomas Equine Veterinary Journal 9: 16–21
(Cotchin 1977) and lymphosarcomas (Lane 1985, Dixon Davenport-Goodall CLM, Parente EJ 2003 Disorders of the
1995) in the literature. Lane (1997) described a 9-year-old larynx. Veterinary Clinics of North America; Equine
Practice 19: 169–187
horse with stridor and exercise intolerance as the result of Dacre KJ, Pirie RS, Prince DR 2004 Primary epiglottitis with
a pedunculated laryngeal lymphosarcoma attached near associated dysphagia in a foal. Equine Veterinary
the right ventricle. The tumor recurred within 3 months of Education 16: 296–301
surgical removal. Most cases of laryngeal lymphosarcoma Dillman RC 1972 Laryngitis in feedlot calves and its relation-
are not treated because of the inaccessibility of lesions and ship to Haemophilus somnus complex. Proceedings of the
United States Animal Health Association 66: 498–501
the presence of concurrent tumors elsewhere in the upper Dixon PM 1995 A review of the role of the epiglottis in equine
respiratory tract. Trotter et al (1990) described a 5-year-old upper airway obstruction. Equine Veterinary Education
American quarterhorse with a 2-week history of respira- 7: 131–139
tory distress caused by a 3-cm diameter chondroma on the Dixon PM, Collins N 2004 The equine epiglottis. Equine
medial aspect of the left arytenoid that was successfully Veterinary Education 16: 299–301
Dixon PM, Railton DI, McGorum BC 1994 Ventral glottic steno-
surgically removed. Sarli et al (2001) described a heman- sis in 3 horses. Equine Veterinary Journal 26: 166–170
gioma protruding submucosally into the laryngeal lumen Dixon PM, McGorum BC, Railton DI et al 2003 A long-
that caused airflow obstruction with exercise intolerance term survey of laryngoplasty in an older, mixed-breed
and abnormal noise production. The lesion was success- population of 200 horses. 1: Maintenance of surgical
fully removed surgically. arytenoid abduction and complications of surgery.
Embertson RM 1998 Evaluation of the upper respira-
REFERENCES tory tract in weanlings and yearlings. In: White NA,
Moore JN (editors) Current Techniques in Equine Surgery
Anderson BH 2004 Non-RLN URT disorders identified during and Lameness, 2nd edn. WB Saunders, Philadelphia,
post sale endoscopic examinations of 5559 TB yearlings pp.122–127
(1997–2002) in New Zealand. In: Dixon PM, Robinson Flexon PB, Cheney ML, Montgomery WW et al 1989 Manage-
NE, Wade JF (editors) Equine Recurrent Laryngeal ment of patients with glottic and subglottic stenosis
Neuropathy, Havemeyer Foundation Monograph Series resulting from thermal burns. Annals of Rhinology and
No. 11. R & W Publications (Newmarket), Newmarket, Laryngology 98: 27–30
pp.51–54 Greet TRC 2003 Endoscopic retrieval of foreign bodies. Equine
Barber SM 1981 Paralaryngeal abscess with laryngeal hemi- Veterinary Education 15: 232
plegia and fistulation in a horse. Canadian Veterinary Harrison IW, Raker CW 1988 Dorsal glottic stenosis after
Journal 22: 389–392 bilateral arytenoidectomy in two horses. Journal of the
Barclay WP, Phillips TN, Foerner JJ 1982 Acute epiglottidis American Veterinary Medical Association 192: 202–204
in a horse. Journal of the American Veterinary Medical Harvey CE 1983 Partial laryngectomy in the dog. I. Healing
Association 181: 925 and swallowing function in normal dogs. Veterinary
Bastian RW 1991 Acute inflammatory diseases of the larynx. Surgery 12: 192–196
In: Ballenger JJ (editor) Diseases of the Nose, Throat, Ear, Hawkins JF, Tulleners EPI 1993 Epiglottitis in the horse: 20
Head and Neck, 14th edn. Lea and Febiger, Philadelphia, cases (1998–1993). Veterinary Surgery 22: 383
pp.605–615 Hay WP, Tulleners E 1993 Excision of intralaryngeal granu-
Baxter GM, Allen D, Farrell RL 1992 Paralaryngeal accessory lation tissue in 25 horses using a neodymium:YAG laser
bronchial cyst as a cause of laryngeal paralysis in a (1986–1991). Veterinary Surgery 22: 129–134
horse. Equine Veterinary Journal 24: 67–69 Haynes PF 1978 Surgical failures in upper airway respiratory
Blea JA, Arthur RM 2003 How to evaluate and treat surgery. Proceedings of the American Association of
ulceration of the glosso-epiglottic fold (subepiglottic area) Equine Practitioners 24: 223–249
Holland M, Snyder JR, Steffey EP et al 1986 Laryngotracheal Peterson SL, Smith MM, Senders CW 1987 Evaluation of a
injuries associated with nasotracheal intubation in the stented laryngoplasty for cranial glottic stenosis in four
horse. Journal of the American Veterinary Medical dogs. Journal of the American Veterinary Medical
Association 189: 1447–1450 Association 191: 1582–1584
Jensen R, Lauerman LH, Braddy PM et al 1980 Laryngeal Rooney JR, Robertson JL 1996 The respiratory system. Equine
contact ulcers in feedlot cattle. Veterinary Pathology Pathology, 1st edn. Iowa State University Press, Ames, IA,
17: 667–671 pp.24–56
Kelly G, Lumsden JM, Dunkerly G et al 2003 Idiopathic Sanders I, Billers H 1991 Trauma to the larynx. In: Ballenger
mucosal lesions of the arytenoid cartilages of 21 JJ (editor) Diseases of the Nose, Throat, Ear, Head and
Thoroughbred yearlings: (1997–2001). Equine Veterinary Neck. Lea and Febiger, Philadelphia, pp.602–604
Journal 35: 276–281 Sarli G, Torre F, Simoni P et al 2001 Diagnosis, surgical
Koterba AM, Drummond WH, Kosch P 1975 Intensive care of treatment and histological characterisation of a laryn-
the neonatal foal; Symposium on neonatal equine disease. geal haemangioma in a Standardbred horse. Ippologia
Veterinary Clinics of North America; Equine Practice 12: 7–12
1: 3–34 Shapiro J, White NA, Schlafer DH et al 1979 Hypertrophic
Koufman JA, Branch ME, Ryu JH 1988 A comparison of ossification of the laryngeal cartilages of a horse. Journal
the carbon dioxide and neodymium: YAG lasers in a of Equine Medicine and Surgery 3: 370–374
canine model of acquired subglottic stenosis. Journal of Stick J, Boles C 1980 Subepiglottic cyst in three foals. Journal of
Otolaryngology 17: 223–226 the American Veterinary Medical Association 177: 62–64
Lane JG 1982 Ear, Nose and Throat and Oral Surgery of the Stick JA, Tulleners EP, Robertson JT et al 1999 The larynx.
Dog and Cat. Wright PSG, Bristol, pp.112–113 In: Auer J, Stick JA (editors) Equine Surgery, 2nd edn.
Lane JG 1985 Palatine lymphosarcoma in two horses. Equine WB Saunders, Philadelphia, pp.349–375
Veterinary Journal 17: 465–467 Strand E, Hanche-Olsen S, Gronvold AMR et al 2004 Dynamic
Lane JG 1997 Larynx. In: Traub-Dargatz JL, Brown CM (editors) bilateral and vocal fold collapse associated with head
Equine Endoscopy. Mosby, St Louis MO, pp.74–96 flexion in 5 Norwegian Coldblooded Trotter racehorses.
Lane JG, Lucke VM, Wright AI 1986 Parasitic laryngeal papil- Equine Veterinary Education 36: 235–241
lomatosis in a horse. Veterinary Record 119: 591–593 Trotter GW, Aanes WA, Snyder SP 1990 Laryngeal chon-
Langman AW, Lee KC, Dedo HH 1989 The endoscopic Teflon droma in a horse. Journal of the American Veterinary
keel for posterior and total glottic stenosis. Laryngoscope Medical Association 178: 829–830
99: 571–577 Tulleners E 1991a Correlation of performance with endo-
Lees MJ, Scuh JCL, Barber SM et al 1987 A congenital laryn- scopic and radiographic assessment of epiglottic hypopla-
geal web in a Quarterhorse filly. Equine Veterinary Journal sia in racehorses with epiglottic entrapment corrected by
19: 561–563 use of contact neodymium:yttrium aluminium garnet
Linford RL, O’Brien TR, Wheat JD et al 1983 Radiographic laser. Journal of the American Veterinary Medical
assessment of the epiglottic length and pharyngeal and Association 198: 621–626
laryngeal diameters in the Thoroughbred. American Tulleners E 1991b Use of transendoscopic contact neo-
Journal of Veterinary Research 44: 1660–1666 dymium:yttrium aluminum garnet laser to drain dorsal
Lusk RP 1991 Congenital malformations of the larynx. epiglottic abscesses in two horses. Journal of the American
In: Ballenger JJ (editor) Diseases of the Nose, Throat, Veterinary Medical Association 198: 1765–1767
Ear, Head and Neck. Lea and Febiger, Philadelphia, Tulleners E 1997 Epiglottitis. In: Robinson NE (editor) Current
pp.570–588 Therapy in Equine Medicine 4. WB Saunders, Philadelphia,
Manus AG 1965 Canine epihyoid fractures. Journal of the pp.407–409
American Veterinary Medical Association 147: 129–132 Tulleners TP, Stick JS, Leitch M et al 1997 Epiglottic augmen-
Matushek KJ, Bjorling DE 1988 A mucosal flap technique for tation for treating dorsal displacement of the soft palate
correction of laryngeal webbing: results in four dogs. in racehorses: 59 cases (1985–1994). Journal of the
Veterinary Surgery 17: 318–320 American Veterinary Medical Association 211: 1022–1028
Miles-Foxen EH 1980 Injury of the larynx and trachea. Voss E, Seahorn T 2004 Tracheobronchoscopy. In: Slovis NM
In: Miles-Foxen EH (editor) Diseases of the Ear, Nose (editor) Atlas of Equine Endoscopy. Mosby, St Louis,
and Throat. Blackwell Scientific Publications, Oxford, pp.97–118
pp.159–160 Whitton RC, Kannegieter NJ 1995 Deformity of the epiglottis
Nelson AW, Wykes PM 1985 Upper respiratory system. In: in 4 horses. Equine Veterinary Education 7: 127–130
Slatter DH (editor) Textbook of Small Animal Surgery, Yarborough TB, Voss E, Herrgesell EJ et al 1999 Persistent
Vol. I. WB Saunders, Philadelphia, pp.979–985 frenulum of the epiglottis in four foals. Veterinary Surgery
Ordridge RM 1988 Twig removal. Veterinary Record 123: 608 28: 287–291.
Laser Surgery of the Upper
Respiratory Tract
39 Eric J Parente
without any fixed relationship to each other, meaning

Introduction
that they are incoherent. If all waves are lined up together
Lasers have been used in the biomedical field for over so their peaks and valleys match, they are said to be in
40 years, but their use in equine respiratory surgery phase, or coherent. Laser light is coherent.
began in the mid-1980s when it was found that laser To truly understand lasers, basic atomic physics must
light could be transmitted down a small diameter fiber be reviewed. An atom consists of a positive nucleus sur-
that could be passed through the biopsy channel of rounded by negative electrons. A neutral atom of a given
an endoscope (Tate 1991). The first such laser was the element has the same number of positive charges (protons)
neodymium:yttrium–aluminum–garnet (Nd:YAG) laser in its nucleus and negative charges (electrons) around the
and with its use, equine transendoscopic laser surgery nucleus. When electrons are in orbits close to the nucleus,
was born. the atom is in its lowest energy level, which is termed the
Before the advent of laser surgery, many procedures ground or resting state. If an electron absorbs energy in the
performed on the larynx or pharynx of the horse required form of heat or light, the electrons will jump or make a
an open surgical approach under general anesthesia. A quantum leap into a higher orbit (i.e. further away from
distinct advantage of transendoscopic laser surgery was the nucleus) and assume an excited state. Atoms in an
that the surgery could be performed without a skin incision excited state tend to return to the resting or ground state
and without general anesthesia. Additional features were and in so doing, they spontaneously emit energy in the
increased visualization of the surgical field, increased sur- form of photons or light. In 1917, Einstein proposed that
gical precision, better hemostasis, and ultimately shorter there was a difference between spontaneous and stimulated
hospitalization and convalescence periods for the patient. emission of light. His theory was eventually applied in
the invention of the laser. He predicted that when elec-
trons in higher orbits or energy levels were bombarded by
The Principles of Lasers
particular types of photons, they would decay to a lower
Laser is an acronym for “light amplification of stimulated energy level, emitting a photon in the process. The stimu-
emission of radiation”. The light emitted by lasers works lating photon, instead of being absorbed, would continue
according to the basic properties of light and electro- to be propagated. The end result is two photons or quanta
magnetic radiation, and like white light, laser light consists of energy with identical wavelengths. A chain reaction
of particles (photons) traveling through space in unique ensues, resulting in stimulated emission of photons.
waveforms. Visible light has an electromagnetic spectrum Since atoms tend to be in a ground state, they are more
of wavelength of approximately 400–700 nm and each likely to absorb an encountered photon than to stimulate
color of visible light has its own characteristic wave- the emission of a second one. Therefore to reach a state of
length. Laser light is very different from the light produced producing a sustained stimulated emission, more atoms
by more common white light sources, such as incandes- need to be in higher energy levels than in the ground state.
cent bulbs, fluorescent lamps, or sunlight, for several This condition is known as “population inversion” and is
different reasons. created by exposing atoms to a source of energy, a process
Laser light can be within the visible spectrum of light that is termed “pumping”. The energy source used to
but differs significantly from white light because of its create the population inversion can be heat, light or
monochromicity, direction, and coherence. Laser light electricity. Once the population inversion occurs, atoms
consists of a single wavelength, or an extremely narrow decay to their lower energy levels and release photons. The
range of wavelengths and is therefore considered “mono- spontaneously emitted photons collide with atoms in the
chromatic”, while white light is a mixture of different higher energy states, resulting in stimulated emission,
wavelengths. Light emitted from bulbs or headlights which begins the chain reaction.
diverges rapidly, while laser light has a very narrow cone of There is a general four-grade (classes I–IV) classification
divergence. Finally, light waves can travel through space system for laser power and safety. Classes I and II are low
533
534 39 Laser Surgery of the Upper Respiratory Tract
risk lasers with < 1 milliwatts (mW) of power. Class III lasers which laser is used and also how it is used (such as
are the “cold” or therapeutic lasers. All surgical lasers are absorption spectrum, scatter, thermal conductivity, and
class IV (> 0.5 W). While the power is measured in watts, local circulation). The interaction of laser energy with
the power density is termed “irradiance” and refers to the tissue is by a thermal effect. If tissue is heated to over 60°C,
amount of power per unit surface area. Irradiance = laser protein is coagulated, and if tissue is heated to greater than
power output/laser beam size; therefore a larger beam size 100°C, it begins to be vaporized. When the laser is used in
will have a smaller irradiance. The total energy applied is contact fashion there is more focused energy application,
measured in joules, i.e. laser output × exposure time. The less loss of power and less lateral thermal damage. With
“energy fluence” is equal to Joules/laser beam size, and non-contact use of lasers, there will be a greater margin of
measures the total amount of energy directed to the tissue ablation and coagulation. Therefore, a contact technique
during a treatment. where the fiber touches the tissue will provide a more
precise cut with less lateral damage, while a non-contact
technique is more successful at ablating highly vascular
Components of Surgical Lasers tissue, such as ethmoid hematomas. Furthermore, a non-
and Tissue Interactions contact laser can be used focused or unfocused. The
The components of a laser system are an active medium, a unfocused beam will have a decreased irradiance but an
power source, an optical resonator, and an output coupler increased treated area, leading to a greater margin of
(partially transmitting mirror). The active medium is the coagulation. To cut tissues precisely, the use of a contact
material that determines the wavelength of the laser. technique and keeping tension on the tissue will minimize
The medium can be a gas, a liquid, a solid material, or a lateral thermal damage. Also some lasers can be used in a
junction between two slabs of semiconductor materials. continuous, pulsed or superpulsed mode. The pulsed modes
The power source is the pump that puts the atoms into a will again minimize the extent of lateral thermal energy
population inversion state and the particular type is but in most cases a continuous technique is effective
determined by the lasing medium that is being used. The without excessive collateral damage.
optical resonator can be thought of as mirrors on either Several different laser fibers are available with diameters
side of the medium, which reflect the light back into the of 400–1,000 μm. Most often, a 600–800 μm fiber (e.g.
medium for “amplification.” The output coupler allows a quartz or silica) is used. While special tips are also available
portion of the laser light between the two mirrors to leave for laser fibers, using a bare fiber is satisfactory. The
the laser resonator in the form of a beam. The fraction of cladding surrounding the laser fiber will burn back with
the coherent light allowed to escape varies greatly from one use and the exposed fiber will soon become brittle. The fiber
laser to another. should periodically be broken off back to the level of the
Laser light interacts with tissue in several ways. It can cladding to help prevent fibers breaking in the airway.
be absorbed, transmitted, or reflected. The reflected light
can be specular (like a mirror) or scattered (diffuse). It can
be transmitted through the tissue without having any
Laser Systems
effect, or it can be absorbed and transformed into heat Lasers are often referred to by the medium they contain,
energy. The amount of absorption is dependent upon the which determines the laser wavelength that is generated.
wavelength of the light and the chromophore content of Two lasers are presently used commonly in the equine
the tissue (such as hemoglobin, keratin, protein, water, upper respiratory tract, namely the diode laser and the
and melanin content). Each chromophore has its own Nd:YAG. These lasers have similar wavelengths of around
absorption spectrum for different wavelengths of light. The 1,000 nm and the primary reason for their use is because
thermal energy created through absorption can result they can be transmitted through a silica or quartz fiber
in coagulation, cutting, or ablation of tissue. The primary that can be passed through the biopsy channel of a video-
colors of lasers (blue, green and red) are different to endoscope. A narrow diameter hollow fiber is currently
pigment colors (blue, green, and yellow) and light of one being developed so that the CO2 laser can be used trans-
primary color will be absorbed by the other two colors. endoscopically, but this fiber has had limited clinical use to
Therefore, the red pigment of hemoglobin readily absorbs date (Anastassiou et al 2004).
the blue-green frequencies of the argon laser, making the The diode laser is created by producing a charge across
argon laser effective for coagulation and ablation of two slabs of semiconductor materials and it has a wave-
superficial vascular lesions. length of 800–1,100 nm. It is a solid-state system that does
Whether lasers incise, coagulate, or vaporize tissue is not require a cooling system, requires only a standard US
both dependent upon factors that can be controlled (such household electrical current (110 V), is small (under 7 kg),
as power density, duration of application, wavelength, and and is less expensive than the Nd:YAG laser. A disadvantage
use of a contact versus non-contact technique), and also is that the maximum power is usually less than 30 W.
on factors that cannot be controlled but which influence A bare fiber technique as previously described is most
39 Laser Surgery of the Upper Respiratory Tract 535
Fig. 39.1. The bronchoesophageal grasping forceps that have been bent to the contour of the nasal
passage. The insert is a close-up of the jaws.
commonly used and the fiber can be cleaved (extended tip mixture of helium and oxygen, with less than 40% oxygen
broken off) as the cladding is burned back during use. (FI O2 < 0.4). This gaseous mixture significantly diminishes
The Nd:YAG laser is yttrium–aluminum–garnet (fake the risk of spontaneous ignition without compromising the
diamond) doped with neodymium (medium), which uses a patient (Driessen et al 2002).
xenon flash lamp or tungsten filament lamp for excitation To prevent injury to personnel, several precautions
of the medium; it is a larger machine that usually requires should be taken. The surgery should be performed in a
240 V. It has a wavelength of 1,064 nm. While it is slightly closed room with signs posted to prevent unauthorized
more difficult to operate than the diode laser, the Nd:YAG personnel from entering the room during laser procedures.
can operate at a higher power setting of up to 100 W. Ocular injury is the most significant risk and specialized
Since the wavelength is similar, the coagulation and pene- glasses to block the specific wavelength of laser light being
tration properties of the Nd:YAG are very similar to those used should be worn by all personnel in the room. Noxious
of the diode laser. fumes as well as microbes may be released into the local
environment if a large amount of tissue is being ablated in
a non-contact fashion and therefore an adequate smoke
Preoperative Preparation evacuation system may be necessary. Smoke evacuation
There are three major issues to consider before performing may be necessary for visualization while performing laser
laser surgery, namely patient safety, personnel safety, and procedures in horses under general anesthesia. If the
having appropriate instrumentation for the envisaged surgery is being performed in a standing sedated horse, the
procedure. Most patient safety issues will be addressed by horse’s breathing acts to ventilate the airway and remove
appropriate use of the laser and by minimizing the use of most laser-created smoke or laser plume.
excessive energy to perform the procedure. Appropriate Finally, appropriate equipment must be available. As
restraint can be achieved easily with intravenous sedation mentioned, it is uncommon that suction for smoke evac-
(xylazine 0.44 mg/kg, or detomidine 0.006–0.01 mg/kg) uation or hemorrhage is necessary, particularly in proce-
and topical anesthetic administered by a transendoscopic dures performed in standing sedated horses but it is often
catheter. Depending on the length of the procedure, addi- required if working with horses under general anesthesia.
tional sedation may be required later. In the author’s If suction is needed, modifications should be made to the
opinion, opioids such as butorphanol should be avoided suction tubing to atraumatically place it into the upper
because some horses will develop head twitching follow- respiratory tract. A 600-mm long bronchoesophageal
ing their administration. It is not recommended that the grasping forceps (Richard Wolfe Medical Instruments,
horse’s head be restrained with cross ties because altera- Vernon Hills, IL) is very useful for manipulation of tissues
tion of the horse’s head position is frequently required during upper respiratory laser surgery. These forceps are
during laser surgery of the upper airways. If the laser has bent to the curve of the upper respiratory tract (Fig. 39.1)
to be used while the animal is under general anesthesia, and can be passed up the contralateral nostril from the
there is risk of spontaneous ignition of the oxygen in the video-endoscope. It is beneficial to apply topical anesthetic
endotracheal tube. Rather than attempting to shield to the nasal passage or perform an infraorbital nerve block
the tube, the inhalant gas mixture can be changed to a on the side that the forceps will be passed.
Multiple thin cuts should be repeated in the same plane,

Postoperative Treatment
extending from the center of the caudal margin of the
Depending on the specific procedure performed, little entrapping membrane towards the tip of the epiglottis to
postoperative medication or rest may be required before perform the axial division. It is wise to make one or two
returning the horse to training. The horse should initially axial strokes from the ventral surface of the entrapped
be maintained in a stall with hand walking only. Following epiglottis towards its tip in the early part of the division,
simple laryngeal procedures, a topical anti-inflammatory before this part of the entrapping membrane moves
medication applied via a nasal catheter can be used ventrally under the soft palate. The strokes should be
twice daily for 1 week. Systemic anti-inflammatory drugs made in smooth, slow motions of 1–2 seconds duration, by
(phenylbutazone 4.4 mg/kg and dexamethasone 0.04 mg/kg) withdrawing the laser fiber toward the biopsy channel. As
are usually given only once perioperatively. Most horses each stroke is made, the membrane will peel back, exposing
should have a further endoscopic examination to ensure its deeper layers, and the entire membrane will begin to
there are no remaining abnormalities, before returning to slide rostrally and ventrally.
exercise at 2–3 weeks postoperatively. Swallowing should be induced to encourage the
For more complex laser procedures, or procedures per- membrane to move under the epiglottis and thereby
formed on very fibrotic tissues, postoperative management maintain tension on the tissue. If the membrane recedes
can be more complex. Usually more rest time will be completely under the epiglottis, the horse is induced to
required before returning the horse to exercise and post- swallow again to ensure the entrapment does not return.
operative antimicrobial treatment is often administered, The procedure can be considered completed if the entrap-
although it is uncommon for infection to develop at a laser ment does not return after multiple swallows. Usually
surgery site within the respiratory tract. While the surgical between 1,000 and 3,000 joules of energy are sufficient to
site is essentially sterile at the time of surgery and generally accomplish the entire procedure. If after the division is
has an excellent blood supply, it is an open wound that will complete, the membranes do not recede under the
become contaminated quickly. Furthermore, some chronic epiglottis, they can be initially treated medically and should
ulcerated tissues become fibrotic with a compromised resolve within 7–10 days. Alternatively, the sectioned
blood supply and have the potential for foreign material entrapping folds can be resected by grasping them with a
(food) to become lodged within them. Complications most 600-mm long bronchoesophageal grasping forceps and
commonly occur following laser treatment of chronic then using the laser in contact fashion. If the epiglottis is
epiglottic entrapment. normal in size, recurrence of entrapment is minimal. If the
epiglottis is hypoplastic, up to 10% of affected horses may
later have problems with dorsal displacement of the soft
Procedures
palate (Tulleners 1990).
Epiglottic entrapment
Axial deviation of the aryepiglottic folds
Epiglottic entrapments can be simple, with just a thin
entrapping membrane, or more complicated, with thicker, Axial deviation of the aryepiglottic folds (ADAF) has been
ulcerated entrapping tissue and possibly the tip of the recognized as a cause of dynamic upper respiratory
epiglottis rolled up in the entrapment. These variations do obstruction in horses since high-speed treadmill exercise
not affect the initial approach of an axial division of the testing was introduced for the evaluation of poor perform-
membrane that is performed in the standing sedated horse, ance. The membranous portions of the aryepiglottic folds
but may affect the treatment at the conclusion of the collapse axially, giving an hourglass appearance in front of
division (Parente 2002). A power setting of 16–18 W is the laryngeal airway, and they can occlude the glottis
sufficient when a laser is used in contact fashion. After during the deep inspirations of fast work. The problem can
sedation of the horse, local anesthetic is applied and the be unilateral or bilateral and the folds may have a varying
video-endoscope is positioned with its tip just 1–2 cm degree of axial collapse. Horses affected with significant
rostral to the tip of the epiglottis. The laser fiber is then ADAF not only finish races poorly but make an abnormal
advanced out of the endoscope for 2–3 cm. Before enabling noise during inspiration at exercise, which may sound
the laser, the surgeon should ensure that the fiber can be similar to the noise associated with recurrent laryngeal
dragged from the caudal edge of the entrapping membrane neuropathy. Resting endoscopy is normal, and the cause of
to the tip of the epiglottis, while keeping light pressure on the stridor and poor exercise performance cannot be deter-
the membrane with the tip of the fiber, as this will be the mined without treadmill endoscopy.
cutting stroke used for the division. If this stroke cannot be Transendoscopic laser excision of the aryepiglottic fold
made, the horse’s head position should be adjusted or the tissue that impinges on the glottis is best performed in the
endoscope should be withdrawn and re-inserted via the standing sedated horse utilizing the laser in contact fashion.
ventral meatus, and not more dorsally. After topical anesthetic is applied, the video-endoscope is
horizontally through the membrane by sweeping the fiber

from side to side and cutting the tissue in a rostral to
caudal direction, immediately adjacent to its epiglottic
attachment. The grasping forceps are then rotated to
apply traction to the aryepiglottic fold in a rostromedial
direction. A vertical incision is then made from dorsal to
ventral, incising the tissue adjacent to its attachments on
the corniculate process. The vertical incision is extended
ventrally to intersect the initial horizontal incision and the
resected tissue is then removed with the grasping forceps.
The video-endoscope and forceps are positioned in the
opposite sides for excision of the contralateral aryepiglottic
fold when performing a bilateral excision.
No complications have been documented following this
surgical procedure, and in particular, no adverse effects on
deglutition or laryngeal or pharyngeal function have been
reported. In a retrospective study of racehorses affected
with ADAF, 75% of horses treated by laser excision showed
improved performance (King et al 2001).
Pharyngeal cysts/masses
Fig. 39.2. The aryepiglottic fold being grasped and manipulated with Cysts can develop anywhere on the wall of the nasopha-
the forceps to simulate axial deviation of the aryepiglottic fold before rynx, but most commonly occur on its dorsal surface.
resection of the tissue. Pharyngeal cysts usually contain a yellow viscous fluid
and often rupture during their surgical resection, and it
is therefore important to ablate the entire cyst lining to
inserted via the nasal passage ipsilateral to the target prevent recurrence. The cyst can be grasped with bron-
aryepiglottic fold. The tip of the endoscope is placed a few choesophageal forceps inserted through the opposite nostril
centimeters rostral to the surgical site and held in place and traction can then be applied to the cyst while it
there by an assistant. Bronchoesophageal forceps are is resected. The cyst is easily resected using the laser in
passed via the nasal passage contralateral to the target contact fashion, by stroking the fiber across the junction of
aryepiglottic fold and are controlled by a second assistant. the cyst with the pharyngeal wall. Other pharyngeal
The free margin of the membranous portion of the ary- masses that would be extremely difficult to resect using
epiglottic fold is grasped midway between the arytenoid standard surgical approaches can be approached similarly
and the epiglottis and manipulated medially to reproduce with the laser (Fig. 39.3).
the ADAF deviation and to determine the margins of An alternative approach is to ablate the cyst with the
tissue to be resected (Fig. 39.2). The first cut is directed laser in non-contact fashion. Initially, the cyst is blanched
Fig. 39.3. (A) A granulomatous mass extend-

ing from the lateral pharyngeal wall in pony
causing laryngeal obstruction. The inciting
cause was unknown. (B) The same pony
2 days after laser excision of the mass per-
formed with standing sedation and local
anesthetic.
A B
at a power setting of 40 W to prevent puncture, with the lateral nostril to the lesion and the laser fiber is dragged
fiber held perpendicular to, and just millimeters away across the base of the granulation tissue in short strokes
from, the cyst. With a sweeping motion of the fiber, the cyst until it is almost completely loose, before attempting
is slowly blanched. The laser is then set to a higher setting to grasp it. The grasping forceps are then passed up
of 100 W and the cyst is vaporized (Tate 1991). the contralateral nostril and the tissue is grasped under
video-endoscopic guidance. Once grasped, just one or two
Subepiglottic cysts/granulation tissue more passes with the laser fiber should release the tissue for
removal. Grasping the granulation tissue early in the
Laser surgery of subepiglottic cysts can be challenging procedure will just shred it, and will also stimulate the
to perform. When the cyst is endoscopically visible above horse to swallow frequently. Recurrence is uncommon and
the soft palate, the horse can be sedated and the area the prognosis is good if there is no significant underlying
anesthetized as previously described. Care should be taken laryngeal cartilage pathology (Hay & Tulleners 1993).
not to cause the horse to swallow after the nasopharynx An alternative approach has been described in which
is anesthetized, until the cyst is firmly grasped with the laser fiber is passed through a cannula inserted
the grasping forceps. Once the cyst is grasped, it can be through the thyroid notch, i.e. the ventral aspect of the
manipulated using tension, repulsion, and rotation so that larynx. Again this is performed under video-endoscopic
its base can be visualized and then it can be resected with guidance. This technique has the advantage of facilitating
the laser fiber in contact fashion. If the cyst is accidentally resection of intracartilagenous tracts or abscesses that
punctured during the procedure, the lining membrane could not be treated via the standard per nasum trans-
can still be visualized and resected. The subepiglottic endoscopic approach (Sullins 2002).
tissue is highly elastic and care should be taken to avoid
removing too much adjacent tissue with the cyst. If the Vocal cordectomy
cyst cannot be displaced above the soft palate for resection,
the horse should be placed under general anesthesia and a Vocal cordectomy (cordectomy) is often performed as an
similar procedure can be performed through the horse’s adjunctive procedure along with a laryngoplasty, or is the
oral cavity (Tulleners 1991). As noted, suction is required sole treatment for cases of milder recurrent laryngeal
for smoke evacuation during laser procedures under neuropathy in non-racehorses. It can be performed in
general anesthesia. contact fashion, under general anesthesia or in the stand-
Infrequently, horses will develop exuberant subepiglottic ing horse, based on the clinician’s preference (Hawkins
granulation tissue at the site of subepiglottic cyst resection. & Andrews-Jones 2001, Ducharme et al 2002, Parente
This granulation tissue is presumed to be a non-healing, 2002). Disadvantages of performing the procedure under
contaminated wound and resection or vaporization of the anesthesia include the requirement of using heliox (to
abnormal tissue is required. Resection can be performed in diminish the risk of spontaneous ignition of the oxygen
the standing sedated animal, but, because of the friable within the endotracheal tube) and also the increased tech-
nature of the tissue, the resection is often incomplete. nical difficulty of having to perform surgery in the restricted
Any residual granulation tissue should be vaporized in nasopharyngeal space of anesthetized horses. Yet, with
non-contact fashion at a power setting of 40 W. Again, experience, a complete resection can be performed under
care should be taken to avoid causing excessive collateral general anesthesia in less than 10 min, with less lateral
thermal damage to adjacent normal tissues, in particular thermal damage than occurs with other techniques.
the epiglottic cartilage. The horse is placed under general anesthesia with the
vocal cord to be resected uppermost, and the horse is
Intralaryngeal granulation tissue nasotracheally intubated via the ventrally positioned
nostril. Oxygen concentration is decreased with helium to
Removal of intralaryngeal granulation tissue with a laser preclude the risk of ignition of the gases within the
can be an effective treatment, provided there is no endotracheal tube. A speculum is placed in the horse’s
significant underlying pathology of the arytenoid carti- mouth and the horse’s palate is manually displaced; suc-
lage or continued trauma to the arytenoid secondary to tion tubing is placed just rostral to the more ventral vocal
hemiplegia. Laser excision is also a very effective way cord. The video-endoscope and the bronchoesophageal
to remove any granulation tissue present after partial forceps are inserted through the mouth, and the targeted
arytenoidectomy. vocal cord is grasped. If it cannot be grasped because of the
The horse is sedated and locally anesthetized as vertical orientation of the cord and the forceps jaws, an
previously described. Non-contact laser ablation would initial cut is made through the cord just below the vocal
likely result in excessive and unappreciated thermal process with the laser. This results in a free horizontal
damage to the larynx, and so contact laser excision is plane of tissue that can be grasped. The forceps are rotated
recommended. The video-endoscope is passed up the ipsi- clockwise and used to move the cord away from the
saccule. The laser fiber is used to cut the vocal fold in dorsal and caudal to the normal guttural pouch opening.
contact fashion, in a dorsal to ventral direction. The most This defect may close later over many months, but may
ventral and rostral aspect of the cord has a significant also persist, and there has been no reported increased risk
blood vessel that can obstruct vision of the medial surface of guttural pouch infection in horses with this perma-
of the cord if it hemorrhages; thus this portion of the cord nent fistula.
is not cut until beginning the medial cut. The forceps are
derotated to separate the two vocal cords slightly and the Guttural pouch empyema
targeted cord is repelled caudally. This allows visualization
and application of tension on the medial side of the cord so Cases of guttural pouch empyema can be managed in
it can be transected. This is performed in a rostral to caudal many ways, depending on the extent of the disease. Most
direction, freeing the entire cord, so it can be removed cases can be managed with a combination of medical
with the forceps. A 4 × 4 gauze sponge tied to 40 cm of treatment (isolation to prevent the spread of strangles and
umbilical tape can be placed in the defect with the forceps feeding from ground level) and transendoscopic removal
to provide hemostasis while proceeding with a possible of any chondroids through the normal pouch opening.
laryngoplasty. The gauze is removed just before the horse Infrequently a surgical approach, such as the modified
enters the recovery stall. Whitehouse, is required (see Chapter 28). Another alterna-
If the procedure is performed standing, a contact tive is to create a large enough opening into the guttural
(Ducharme et al 2002) or non-contact (Hawkins & pouch from the nasopharynx to remove inspissated material
Andrews-Jones 2001) laser resection technique can be (Tate et al 1995, Hawkins et al 2001). This salpingo-
used. While there are no histology reports for postsurgical pharyngeal fistula can be created in the standing sedated
cordectomy sites of horses undergoing contact cordectomy, horse as described above. Not only will this fistula allow
these wounds are presumed to heal quicker than removal of chondroids with the endoscope but also any
the reported 47 days following non-contact surgery. The small amounts of material remaining after surgery will
risk of complications is minimal with only four of 106 naturally empty over several weeks (Fig. 39.5).
horses having complications associated with non-contact
ventriculectomy in a study by Bristol et al (1994). Horses Progressive ethmoid hematoma
that have a contact laser vocal cordectomy can resume
work within 1 month of surgery. Intralesional treatment of progressive ethmoidal hematoma
(PEH) with 10% formalin is probably the most common
Guttural pouch tympany current treatment of those hematomas that are readily
A standard method of treatment of unilateral guttural

pouch tympany is to establish a fenestration through the
median septum or create an opening from the auditory
tube into the nasopharynx (salpingopharyngeal fistula).
Both of these procedures are more readily performed with
the laser than other techniques (Tetens et al 1994, Tate
et al 1995) in the anesthetized or standing sedated animal.
The septal fenestration is performed transendoscopically
with the laser in contact mode at 16–18 W. A Chambers’
catheter should be passed up the contrateral nostril and
directed into the unaffected guttural pouch under video-
endoscopic guidance. The endoscope is then passed into the
affected guttural pouch. The Chamber’s catheter is used to
tent the median septum and then a 2- to 3-cm diameter
defect is made in the septum with the laser. Care should be
taken to create the defect rostrodorsally in the septum to
minimize the risk of any inadvertent nerve or vascular
damage (Fig. 39.4).
If the disease is bilateral, a salpingopharyngeal fistula
should be created. Again, the catheter is used to enter the
guttural pouch but this time the catheter is used to tent
the auditory tube so it can be seen within the naso-
pharynx. A hole is then cut from the nasopharynx into Fig. 39.4. Septal fenestration within the guttural pouch as a treatment
the guttural pouch using the laser. The hole should be for unilateral guttural pouch tympany.
was to use the laser in contact fashion intraoperatively

during a flap sinusotomy. They used a power setting of
18–20 W and they reported a success rate of close to 70%
for unilateral lesions and 50% for bilateral lesions
Soft palate displacement

Inducing soft palate alterations with the laser to reduce
snoring in people and displacement in horses has been
investigated recently (Hogan et al 2002, Wang et al 2002).
The theory behind such surgery is to cause an alteration of
collagen within the tissue that results in shortening and
stiffening of the soft palate. Hogan et al (2002) reported
on 52 racehorses that were suspected to be experiencing
intermittent dorsal displacement of the soft palate during
exercise. They used a diode laser transendoscopically set
at 15 W and applied it for 1–2 seconds at 2- to 4-mm
intervals along the free margin of the palate. These horses
also underwent a sternothyroid tenectomy and were given
anti-inflammatory medications for several weeks, but were
returning to exercise within days. Based on owner/trainer
Fig. 39.5. A fistula created by transendoscopic laser surgery between assessment as well as racing times, they reported a 90%
the pharynx and the right guttural pouch to assist in the treatment of improvement in performance with this combined therapy.
guttural pouch empyema.
Complications of Laser Surgery

The most likely complication of laser surgery is collateral
visible endoscopically. This treatment can be employed thermal damage that may result in irreparable damage to
fairly successfully on both large and small PEHs, but adjacent tissues. The absorption coefficient with laser light
recurrence (and formation of new lesions) is common with in the spectrum of the diode and Nd:YAG is not as great as
this disorder. An alternative to intralesional injection is with the CO2 laser; thus there will be greater scatter and
transendoscopic laser ablation (Tate 2002). A diode laser heat transfer to adjacent tissues with use of the diode and
cannot be used because high power is needed for non- Nd:YAG lasers. While the adjacent tissues may look normal
contact ablation, and an Nd:YAG is recommended. at the end of the procedure, there can be a delayed
The power should be set at 100 W in continuous mode, necrosis, because of the thermal energy transferred to
and the laser should be directed at the center of the lesion these tissues. This is in part why contact surgery is pre-
initially, to cause cavitation. Once cavitation is created, the ferred in many situations, to concentrate the energy in a
laser fiber can be used to slowly enlarge the cavitation smaller focal spot. Yet, even with contact surgery, excessive
in concentric circles. Since there is significant scatter energy can be applied to the tissues. This problem can often
irradiation that will cause marked lateral thermal damage, be avoided with experience and proper technique. Other
the perimeter of the PEH should not be targeted. This complications are extremely rare and more specifically
technique will minimize the risk of adverse effects on associated with the particular procedure that is being
adjacent normal mucosa while still causing necrosis of the performed.
perimeter of the lesion. Once a significant amount of char
develops during the laser treatment, surgery should be
stopped. The char will prevent absorption of energy to
Conclusion
the underlying targeted tissue. The laser treatment should The transendoscopic use of lasers has revolutionized our
be repeated every other day to allow removal of char and approaches to upper respiratory surgery. It is a minimally
necrotic tissue before further treatments. A success rate invasive approach that yields excellent results with a
approximating 70% has been reported using this tech- shorter convalescence period and that can often be
nique on both primary lesions and lesions recurring performed on an outpatient basis. As new technology
after surgery. develops with different lasers and improved video-
Rothaug and Tulleners (1999) also reported using the endoscopic equipment, even more procedures will be
Nd:YAG laser for treatment of PEHs but their technique performed transendoscopically.
REFERENCES Parente EJ 2002 Transendoscopic axial division of epiglot-

tic entrapment. Clinical Techniques in Equine Practice
Anastassiou C, Dellemann G, Weisberg O et al 2004 Fibers 1: 9–12
deliver CO2 laser beams for medical applications. Rothaug PG, Tulleners EP 1999 Neodymium:yttrium-aluminum-
Photonics Spectra 12: 162–164 garnet laser-assisted excision of progressive ethmoid
Bristol DG, Palmer SE, Tate LP 1994 Complications of Nd:YAG hematomas in horses: 20 cases (1986–1996). Journal
laser ventriculectomy in the horse. Veterinary Surgery of the American Veterinary Medical Association 214:
23: 397 1037–1041
Driessen B, Nann LE, Klein LV 2002 Use of a helium/oxygen Sullins KE 2002 Noninvasive removal of equine uroliths:
carrier gas mixture for inhalation anesthesia during laser laser lithotripsy. Clinical Techniques in Equine Practice
surgery in the airway of the horse. In: Steffey EP (editor) 1: 36–38
Recent Advances in Anesthetic Management of Large Tate LP 1991 Application of lasers in equine upper respiratory
Domestic Animals. International Veterinary Information surgery. Veterinary Clinics of North America; Equine
Service, Ithaca (www.ivis.org) Practice 7: 165–195
Ducharme NG, Goodrich L, Woodie B 2002 Vocal cordectomy Tate LP 2002 Noncontact free fiber ablation of equine
as an aid in the management of horses with laryngeal progressive ethmoid hematoma. Clinical Techniques in
hemiparesis/hemiplegia. Clinical Techniques in Equine Equine Practice 1: 22–27
Practice 1: 17–21 Tate LP, Blikslager AT, Little EDE 1995 Transendoscopic laser
Hawkins JF, Andrews-Jones L 2001 Neodymium:yttrium treatment of guttural pouch tympanities in 8 foals.
aluminum garnet laser ventriculocordectomy in stand- Veterinary Surgery 24: 367–372
ing horses. American Journal of Veterinary Research Tetens J, Tulleners EP, Ross MW et al 1994 Transendoscopic
62: 531–537 contact neodymium:yttrium aluminum garnet laser
Hawkins JF, Frank N, Sojka JE et al 2001 Fistulation of the treatment of tympany of the auditory tube diverticulum
auditory tube diverticulum (guttural pouch) with a in two foals. Journal of the American Veterinary Medical
neodymium:yttrium-aluminum-garnet laser for treatment Association 204: 1927–1929
of chronic empyema in two horses. Journal of the Tulleners EP 1990 Transendoscopic contact neodymium:
American Veterinary Medical Association 218: 405–407 yttrium aluminum garnet laser correction of epiglottic
Hay WP, Tulleners EP 1993 Excision of intralaryngeal granu- entrapment in standing horses. Journal of the American
lation tissue in 25 horses using a neodymium: YAG laser Veterinary Medical Association 196: 1971–1980
(1986–1991). Veterinary Surgery 22: 129–134 Tulleners EP 1991 Evaluation of peroral transendoscopic
Hogan PM, Palmer SE, Congelosi M 2002 Transendoscopic contact neodymium:yttrium aluminum garnet laser
laser cauterization of the soft palate as an adjunctive and snare excision of subepiglottic cysts in horses.
treatment for dorsal displacement in the racehorse. Journal of the American Veterinary Medical Association
In: Proceedings of the 48th Annual Convention of the 198: 1631–1635
American Association of Equine Practitioners, Orlando, Wang Z, Rebeiz EE, Shapshay SM 2002 Laser soft palate
FL, pp.228–230 “stiffening”: an alternative to uvulopalatopharyngoplasty.
King DS, Tulleners EP, Martin BB Jr et al 2001 Clinical Lasers in Surgery and Medicine 30: 40–43
experiences with axial deviation of the aryepiglottic folds
in 52 racehorses. Veterinary Surgery 30: 151–160
Tracheal Disorders
40 Padraic M Dixon, Jim Schumacher
and Niamh Collins
Introduction
vertebra. In some horses, the esophagus may lie more
Primary tracheal disorders are uncommon in horses; ventral to the trachea at around the sixth cervical vertebra,
however, the tracheal mucosa is sometimes grossly sometimes even lying below the level of the trachea at this
inflamed in horses with pulmonary disorders, and with site. The esophagus then moves back to the left side of the
virtually all types of equine pulmonary disease the trachea trachea in the lower cervical area, remaining so until the
will invariably contain excessive volumes of abnormal level of the fourth thoracic vertebra, when it moves dorsal
respiratory secretions (Dixon et al 1995, McGorum et al to the trachea, and then to the right of the medial plane,
2000). Consequently, endoscopic examination of the before passing through the diaphragm (Hare 1975).
trachea for the above findings should be part of a full The paired thyroid glands, which are often mobile and of
equine pulmonary examination variable size in horses, lie on the lateral aspects of the first
few tracheal rings. The strap muscles (sternothyrohyoideus
muscles) lie ventrally to the cervical trachea throughout
Anatomy of Trachea
most of its length and are fused midline, at an indistinct
The equine trachea is a rigid but flexible tube that is circa junction beneath the rostral aspect of the trachea. At this
75–80 cm long in adult horses of the larger breeds and site they are overlain by the variably thick panniculus
extends from the larynx to the carina where it divides into (cutaneous colli) muscle. Anatomical knowledge of these
the two main-stem bronchi at the level of the fifth to sixth structures is important to enable an emergency tracheostomy
intercostal spaces. The trachea has a median position in to be performed efficiently. More distally down the neck, the
the neck and also in the rostral thorax, where it lies in a sternothyrohyoideus becomes the separate sternohyoideus
fold of mediastinum, but at its termination, the trachea is and sternothyroideus muscles. The paired omohyoideus
slightly displaced to the right by the adjacent aortic arch. muscles are fleshy, ribbon-like muscles that are positioned
The equine trachea is composed of 48 to 60 individual ventrolateral to the trachea more rostrally, where they
tracheal rings of hyaline cartilage. Each individual tracheal blend with the sternothyrohyoideus and cover the first
ring is circa 10–12 mm wide, and is 2–3 mm thick dorsally few tracheal rings and the larynx (Figs 40.1 and 40.2).
and 5–7 mm thick ventrally. The space enclosed by each Distal to the third or fourth tracheal rings, these muscles
tracheal ring is circa 6 cm wide and 5 cm deep (dorso- diverge laterally towards the scapula. Lower down the neck
ventrally) in adult thoroughbred horses but the shape and the omohyoideus muscles lie between the carotid artery
size of the trachea can vary slightly, depending on the and the jugular vein and they also separate the jugular
degree of trachealis muscle contraction. The rostral two to vein from the trachea for much of their length. Whilst the
four tracheal rings are often slightly laterally flattened, and omohyoideus muscles have to be divided midline to perform
if this flattening is extreme, it can be termed “scabbard a laryngotomy, they have diverged lateral to the trachea
trachea”. These laterally flattened tracheal rings can be at the usual tracheostomy site (third to fifth tracheal rings).
recognized by their palpable, protruding ventral ridge, but In general the trachea is relatively superficial rostrally and
there is rarely clinical airflow obstruction at this site. The becomes progressively deeper under the thicker cervical
next few cervical tracheal rings may be circular in outline, muscles in the distal neck.
but the more distal cervical tracheal rings usually have a Running bilaterally along the dorsolateral aspect of the
more oval shape, with a slight dorsoventral flattening. The trachea are many vital structures including the carotid
thoracic portion of the trachea is often more cylindrical in artery, sympathetic trunk, vagus and recurrent laryngeal
shape and may return to a slightly laterally flattened nerves, and tracheal lymph ducts and cervical lymph nodes.
appearance where it contacts the aortic arch. The arterial supply to the trachea is segmental, from
The longus capitis muscles lie on the dorsal aspect of branches of the common carotid and the bronchoesophageal
both the cervical and thoracic trachea. At its origin, the arteries. Its venous drainage is provided by branches of the
esophagus is situated dorsally to the trachea, and it moves jugular and bronchoesophageal veins. Sensory innervation
to the left of the trachea at the level of the fourth cervical of the trachea is via the recurrent laryngeal nerves and
543
544 40 Tracheal Disorders
Fig. 40.1. Transverse section of the equine neck at the level of

the fourth cervical vertebra showing the anatomical relation-
ships of the trachea to adjacent structures. (From a drawing
by M. Camburn.)
Right Left
Brachiocephalicus
Esophagus
Carotid artery and

associated nerves
Jugular vein
Omohyoideus
Trachea Sternocephalicus
Skin Sternothyrohyoideus
Cutaneus coli
Fig. 40.2. Diagram of the ventral aspect of the cervical

trachea and its relationships to the surrounding super-
ficial muscles. The incision site for a tracheostomy is
indicated. (From a drawing by M. Camburn.)
Thyroid cartilage
Cricoid cartilage
First tracheal ring
Omohyoideus
Incision site for

tracheostomy
Sternothyrohyoideus
Sternocephalicus
40 Tracheal Disorders 545
other branches of the vagus; parasympathetic innervation especially in the “sump-like” depression in the rostral
is by branches of the vagus; and sympathetic innervation is thoracic trachea (Dixon et al 1995). Lowering of the head
by branches of the adjacent cervical sympathetic trunk. may play an important part in mucociliary clearance,
Lymphatic drainage is via the adjacent tracheal lymphatic especially in the presence of impaired mucociliary clear-
trunk (Sisson & Grossman 1953). ance and abnormal respiratory secretions, and preventing
Equine tracheal rings are incomplete dorsally, with the a horse from doing so by tying its head up for prolonged
free ends of these rings sometimes overlapping in the periods, such as occurs during prolonged air or road travel,
cervical trachea but seldom meeting in the thoracic may seriously compromise normal mucociliary clearance
trachea. The free ends of the tracheal rings are connected and thus predispose to pulmonary infections.
by the dorsal tracheal ligament, which is composed of the
transversely oriented trachealis smooth muscle that is
attached to the inner (concave) surface of the tracheal
Endoscopy of the Trachea (Tracheoscopy)
rings, along with adjacent loose, areolar-containing con- With some pulmonary diseases, in particular with viral
nective tissue and the tracheal adventitia more dorsally respiratory infections of the lower respiratory tract, and
(Bradley 1923). This elastic structure of the dorsal aspect especially with aspiration tracheitis, e.g. choke or post
of the trachea allows it to expand slightly during deep laryngoplasty, the normally pale pink tracheal and
breathing, whilst the normally rigid nature of the tracheal bronchial mucosa may be swollen, reddened and have
rings prevents inspiratory collapse of the cervical trachea more prominent blood vessels. With most cases of chronic
and expiratory collapse of the intrathoracic trachea. pulmonary disease, in particular recurrent airway obstruc-
The tracheal adventitia is the outer layer of the fascia tion, excessive volumes of mucopurulent respiratory
that covers the cartilaginous rings and the intervening secretions will be seen endoscopically in the tracheal lumen,
muscular and ligamentous structures of the larynx. It is but the tracheal mucosa will be of normal appearance,
attached to the deep tracheal fascia, which extends the unless significant coughing is present, in which case the
length of the trachea to join the endothoracic fascia at the mucosa may be inflamed.
thoracic inlet (Hare 1975, Schummer et al 1979). Each
tracheal ring is covered by and connected to adjacent rings Tracheal cartilaginous nodules
by an intimately attached fibroelastic ligament, which is
termed the annular ligament when it lies in the spaces Small, white nodular cartilaginous protrusions are endo-
between the tracheal rings. This arrangement of semi-rigid scopically detected on the luminal aspects of tracheal
cartilaginous rings and elastic annular ligaments, along cartilages, often throughout the length of the trachea,
with the loose attachment of the tracheal adventitia to particularly in ponies (Chapter 1, Fig. 1.9B). No clinical
other tissues, gives the trachea great flexibility during head significance should be attached to this developmental
and neck movement. This movement is exemplified by the anomaly.
human trachea sliding in and out of the thorax during
neck flexion. The cricotracheal ligament which attaches Post general anesthesia
the first tracheal ring to the cricoid cartilage has a similar mucosal inflammation
structure to the annular ligaments but is wider and under
less tension. Definitive differentiation of the cricotracheal Following endotracheal intubation, inflammation will
ligament from the annular ligament between the first and always be present in the equine trachea (Holland et al 1986).
second tracheal rings is essential during laryngotomy. If very excessive cuff pressure is used, there is a risk of
The trachea is lined by a pale mucosa, containing severe ischemia of the tracheal mucosa (Touzot-Jourde et al
numerous mucous and serous glands; it may have fine 2005), and even of ischemic necrosis of the tracheal
longitudinal folds. Ciliated epithelial cells are the predomi- mucosa and deeper tissue with subsequent development of
nant cell type in the equine large bronchi and trachea circumferential granulation tissue and later stricture, as is
(Pirie et al 1990) with each cell containing about 200 cilia well documented in humans (Grillo et al 1995).
that beat 15–20 times/second. These cilia transport the
mucus from the lungs proximally to the nasopharynx Extramural tracheal and
where it is normally swallowed. In the equine trachea, bronchial compression
mucus is transported at a velocity of 13–20 mm/min (as
reviewed by Dixon 1992), which is similar to tracheal The cervical trachea can be compressed by grossly enlarged
mucus velocities in other mammals. In pulmonary disease, or abscessed adjacent lymph nodes (discussed later).
as a result of the increased production of more viscous Mediastinal tumors or grossly abscessed mediastinal lymph
respiratory secretions combined with decreased mucociliary nodes may also cause compression of the intrathoracic
clearance (primarily because of the loss of cilia), the trachea, or of one or both main-stem bronchi, and cause
respiratory secretions will accumulate in the trachea, stridor and dyspnea.
Temporary tracheal collapse said to significantly obstruct tracheal airflow and thus
cause turbulence with resultant “noises” and reduced
In horses with severe expiratory dyspnea as the result exercise performance (Pouret 1966, Goulden 1977). Goulden
of pulmonary disease, the raised intrathoracic pressure (1977) noted that affected horses had cricotracheal
during expiration can cause a temporary collapse of the membranes up to 5 cm wide. This disorder is reputed to
intrathoracic trachea, particularly of its dorsal ligament. occur in thoroughbreds, which race with their head
Such temporary and often near total tracheal collapse and neck in extension, thus tensing their cricotracheal
can also be seen in all horses if they cough during ligament. Consequently, it is difficult to imagine how this
bronchoscopy. prolapse occurs during fast exercise, unless there is gross
slackness of this ligament or abnormally negative inspira-
Left-sided intrathoracic tracheal deviation tory pressures within the rostral trachea, such as are
caused by an intercurrent upper respiratory tract obstruc-
A variable bulging of the caudal left side of the intra- tion. Surprisingly, this disorder does not appear to be
thoracic trachea, circa 10 cm in front of the carina, is reported in standardbreds, which often race with their
visible endoscopically in some horses. This is caused by the necks flexed.
adjacent aorta pressing on the trachea and is of no clinical The reported treatment of cricotracheal membrane
significance. On close observations the tracheal wall at this prolapse is to perform a transverse skin incision over the
site may be seen to pulsate in time with the heartbeat. cricotracheal ligament followed by resection (imbrication)
of much of the ventral aspect of this membrane and
Tracheal venous congestion closure using mattress sutures. The aim of surgery is to
leave a residual cricotracheal membrane circa 1.5 cm wide
On endoscopy, the vasculature of the equine tracheal (Goulden 1977). There is little factual evidence on the
mucosa is not normally very prominent, but small, paired significance of cricotracheal membrane collapse in exer-
veins can usually be seen running up the lateral borders. cising horses, nor of the response of affected horses to the
Smaller venules or capillaries are visible on close inspection above treatment.
of the mucosa, especially around the carina. In horses with
obstructed venous return to this area, such as from an
Lateral Tracheal Flattening
intrathoracic mass or because of congestive heart failure,
the lateral veins will become very prominent and possibly Lateral tracheal flattening (scabbard trachea) occurs to
tortuous, and more prominent vessels will be apparent some degree in the first few tracheal rings of many
in the mucosa. Dyspnea, associated with the presence of thoroughbreds and thoroughbred crosses but rarely, if ever,
frothy respiratory secretions and free fluid in the bronchi, will this deformity cause clinical airflow obstruction. This
may also occur in congestive heart disease. condition can be recognized by palpation of the ventral
aspect of the trachea in this region through the overlying
Endoscopic appearance of the carina muscles; distinctive ridges can be palpated on the ventral
midline aspect of the deformed rings. Endoscopy will
The normally sharp appearance of the carina and of the confirm this slight lateral flattening of the upper tracheal
bronchial bifurcations may become rounded and blunt as a lumen, and will invariably show an adequate airway. No
result of mucosal swelling. The lumina of the main bronchi treatment is required for this deformity.
may narrow because of mucosal inflammation and/or
bronchospasm, and this finding can be subjectively assessed
Dorsoventral Tracheal Collapse
endoscopically. In cases of pulmonary abscessation, it may
be possible to identify exudate consistently flowing from an Dorsoventral tracheal collapse is commonly recorded
affected larger bronchus. in many breeds of toy dogs (Dallman et al 1988, White
1995, Rudorf et al 1997) and can also occur in goats
(Jackson et al 1986), and sheep and cattle (P.M. Dixon,
Cricotracheal Membrane personal observations). In Equids, this developmental dis-
(Ligament) Prolapse order mainly occurs in small ponies, especially Shetlands
The cricotracheal membrane is normally wider and under (Delahanty & Georgi 1954, Dixon 1988, Simmons et al
less tension than the tracheal annular ligaments. There 1988, Mair & Lane 1990) and miniature horses (Simmons
are a limited number of clinical reports suggesting that et al 1988, Couteil et al 2004) but also occurs in larger
excessive length and slackness of the cricotracheal liga- breeds of ponies (Carrig et al 1973) and donkeys (Mair &
ment may allow it to prolapse deeply into the airway lumen Lane 1990, P.M. Dixon, personal observations). In many
as a result of the subatmospheric inspiratory airway small ponies, the disorder remains undiagnosed because of
pressures that occur during fast exercise. This prolapse is both the lesser degrees of tracheal collapse and the usual
Fig. 40.3. Dorsal view of the intrathoracic

trachea from a donkey which shows an
abnormal vertical alignment of the (normally
overlapping) free ends of the tracheal rings
on both sides over seven tracheal rings (arrow-
heads). In this area the dorsal ligament is
inserted circa 3–4 cm ventrally from the free
ends of the tracheal rings.
low workload of these animals and thus it is an incidental that an inherited defect in chondrogenesis is present.
post-mortem finding in many small ponies. This disorder There do not appear to be any studies of tracheal cartilage
appears to have a high prevalence in donkeys where it is composition in Equids. However, most ponies develop
usually asymptomatic, unless severe tracheal deformity or clinical signs of tracheal collapse in middle age (Freeman
intercurrent pulmonary disorder, such as advanced 1991), thus indicating that some degenerative process of
pulmonary fibrosis, is also present (P.M. Dixon, personal the tracheal cartilage or connective tissue (including
observations). separation of the dorsal ligament from the cartilage) may
Dorsoventral tracheal collapse is usually caused by play a role in the pathogenesis of this disorder, in addition
a cartilage ring deformity, such that the normal rounded to the apparently developmental cartilage deformity. Some
or oval tracheal ring is replaced classically by a flatter tra- deformed rings in ponies may be excessively ossified (Mair
cheal ring with a greatly reduced dorsoventral distance & Lane 1990). The presence of chronic airway disease,
(Figs 40.3 and 40.4) that is further reduced by excessive which may cause tracheal mucosal thickening and also
movement of the slack and enlarged dorsal tracheal increase intrapleural pressure swings, and neuromuscular
ligament (Delahanty & Georgi 1954, Carrig et al 1973, problems causing loss of tone of the trachealis muscle have
Dixon 1988). Many ponies and donkeys with tracheal also been implicated in the pathogenesis of this disorder
collapse will have not only some dorsoventrally flattened in dogs (Hobson 1976, White 1995). Carrig et al (1973)
tracheal rings (especially in their lower cervical trachea) proposed the latter as a potential etiology for tracheal
but also other types of ring deformities at different sites collapse in ponies. A grading system has been used to
(Fig. 40.4) that can also restrict the tracheal lumen size structurally classify the severity of the disorder in dogs but
(Mair & Lane 1990, P.M. Dixon, personal observation). The because of a greater variation in tracheal ring shape in
free ends of some affected tracheal rings may protrude ponies with this disorder such a grading system is unlikely
dorsally with the dorsal ligament attached 2–4 cm from the to be of clinical value.
free ends of the tracheal rings and thus greatly decreasing The typical clinical signs in ponies are dyspnea and
the lumen of the trachea (Figs 40.3 and 40.4). In other stridor, which commonly occur in hot or humid weather
affected cases with tracheal rings of relatively normal and may regress in autumn. This stridor may be very loud,
shape, there appears to be separation of the dorsal liga- with Delahanty & Georgi (1954) reporting a pony that
ment from the dorsal aspect of the tracheal rings. This made sounds like a truck horn that could be heard over
defect normally involves the mid and distal cervical, as 800 m away! The stridor is loudest when auscultated
well as the intrathoracic trachea, and may occasionally directly over areas of tracheal obstruction. Severe dyspnea
involve the main-stem bronchi (Fig. 40.4). Some affected may occur even at rest, because hyperventilation will
ponies may also have some degree of tracheal rotation, exacerbate the partial tracheal obstruction in a self-
with the dorsal aspect of trachea facing dorsolaterally perpetuating cycle. Exercise-induced pulmonary hemor-
(P.M. Dixon, personal observation). rhage may occur in severe cases, presumably because of
The equivalent disorder in dogs has been associated with increasingly subatmospheric intrathoracic pressures.
hypocellularity and decreased chondroitin sulfate content Coughing may also occur and it is unclear if this is the
of the tracheal cartilage (Dallman et al 1988), suggesting result of tracheal inflammation caused by abnormal
A B
Fig. 40.4. (A) Cross-section of trachea showing separation of the positioned free aspect of the tracheal rings. (C) Dorsal view of the
dorsal ligament from the tracheal rings that are aligned normally trachea of a pony showing a relatively normal configuration of the
on the left-hand side but slightly vertically misaligned on the right- tracheal cartilages in the cervical and rostral thoracic area. There is a
hand side (arrow). The ventrally positioned dorsal ligament greatly more vertical alignment and separation of the free ends of the tracheal
reduces the cross-sectional area of the tracheal lumen. (B) Cross- rings in the mid thoracic region leading to a flattening of the trachea
section of the intrathoracic trachea of a donkey, showing the dorsal (arrows). There is also dorsoventral flattening of the left main
ligament attached at an abnormal, ventral site on the vertically bronchus (lower bronchus in figure).
contact of dorsal and ventral tracheal mucosa, or of be difficult, as the deeper, distal cervical trachea is most
underlying pulmonary disease that may have precipitated commonly affected. Additionally, some small ponies such
the clinical problem. In contrast, small dogs primarily as Shetlands have very thick skin and much subcutaneous
present with coughing rather than stridor, with one report fat, which make palpation difficult. As noted above, some
noting stridor in only 20–30% of dogs (White 1995). affected ponies do not have this classical dorsoventral
Palpation of a collapsed cervical trachea may reveal a flattening, but have relatively normally shaped tracheal
distinct, even sharp, edge on the lateral aspect of a trachea rings (possibly vertically aligned free ends of the tracheal
at the site where the rounded, lateral aspect of a normal rings), with separation of the dorsal ligament, while others
trachea should be palpated. Additionally, the deformed have tracheal rotation and thus palpable abnormalities.
trachea will usually not roll away with digital pressure. Endoscopy of affected cases will show the normal
Palpation of the lateral edges of the flattened trachea can circular/oval appearance of the tracheal lumen to be
replaced by a wider, flatter and restricted lumen. Addition- An endoscopically introduced, expanding intraluminal
ally, excessive dynamic movement of the dorsal tracheal stent has been recently used in a 7-month-old miniature
wall and even airway occlusion may be observed during horse foal to correct a life-threatening 7-cm-long segment
deep breathing, with inspiratory narrowing of the cervical of collapsed distal cervical and rostral thoracic trachea
tracheal lumen and expiratory narrowing of the intra- (Couteil et al 2004). The folded, self-expanding, metallic
thoracic tracheal lumen. The mucosa may be red and stent was placed in position under general anesthesia and
swollen so further compromising the tracheal lumen. expanded in situ. The stent later migrated distally but
Lateral radiographs of the distal cervical and thoracic was repositioned endoscopically. Lower airway infection
trachea may be diagnostic, demonstrating the flattened developed some months later, possibly caused by disruption
appearance of the trachea (Dixon 1988), but this may give of tracheal mucociliary clearance caused by multiple
a misleading normal appearance if a collapsed intra- nodules of granulation tissue protruding through the
thoracic trachea is radiographed during inspiration, or a mesh. Following antibiotic therapy and later, removal of
collapsed cervical trachea is radiographed during expira- the large nodules by electrocautery, resolution of the lower
tion. Radiography can also be misleading in cases where airway infection occurred and thus the repair was
tracheal rotation is present along with collapse, where considered successful.
a widened (but collapsed) trachea will be found on lat-
eral radiographs. The use of an image intensifier or of
serial radiographs, taken at determined times of the res- Other Congenital Defects of the Trachea
piratory cycle, could overcome the above limitations.
Congenital defects of the trachea, other than tracheal
Ultrasonography has been successfully used in the diag-
collapse, are rare in horses with only a few other types of
nosis of tracheal collapse in dogs (Rudorf et al 1997).
deformities recorded, including a few reports of accessory
Treatment of such cases should initially be conservative,
or ectopic pulmonary tissue. For example, Davis et al (1991)
by restricting exercise and keeping affected cases indoors in
recorded an accessory cervical tracheal bronchus in a
cool boxes in hot weather and treating any intercurrent
3-day-old foal. The foal presented with a large, air-filled sac
respiratory disease. Acutely affected horses will benefit
in its cervical region caused by a rudimentary accessory
from intranasal oxygen therapy that will reduce hyper-
lung that contained cartilaginous tissue and ciliated
ventilation and thus decrease the degree of tracheal
epithelium. Peek et al (1995) reported a combined tracheal
collapse. Severely affected cases may be hyperthermic,
and esophageal duplication cyst in a 4-month-old Arabian
which increases the metabolic rate and thus respiratory
foal with a slowly developing cervical swelling that was
rate, causing a vicious circle. Cooling down such ponies
successfully resected.
with a cold-water hose until their temperature is normal
is beneficial. Parenteral corticosteroid therapy is also
indicated in severely affected cases, to reduce the secondary
tracheal mucosal inflammation that is likely to be present.
External Tracheal Trauma
Surgical correction of affected cartilaginous cervical Tracheal trauma is usually caused by blunt trauma, such
tracheal rings (as is commonly performed in miniature as kicks to the rostral neck region that can cause severe
dogs) such as placing external stents (made from appro- tracheal damage, particularly from compression of the
priately sized plastic tubing strips) over deformed tracheal trachea between a hoof and the cervical vertebral body.
rings (Simmons et al 1988) or inserting stainless steel Tracheal trauma can cause tearing of the mucosa and of
sutures into every third tracheal ring along with plication the overlying annular ligaments, and fracture of tracheal
(tucking in) of the slack dorsal membrane (Delahanty & rings. Penetrating tracheal injuries occur less commonly,
Georgi 1954) has been performed in ponies with limited such as by horses running into sharp objects including
success. However, in many ponies, altering the shape of the fence posts. In dogs and humans, sudden and severe chest
tracheal rings may not be successful, because separation trauma against a closed glottis can cause a massive
of the dorsal ligaments from the cartilage rings is the increase in intratracheal pressure leading to tracheal
primary problem. Additionally, careful evaluation will rupture (Feat et al 2002) that often occurs at the junction
usually reveal involvement of the intrathoracic trachea of the distal trachea and main-stem bronchi but this injury
and, because only three or four intrathoracic rings can be does not appear to have been reported in horses.
exteriorized rostrally to the distal cervical area for surgical A common presenting sign in horses with tracheal
correction, this may be of limited benefit to the horse. rupture is extensive subcutaneous emphysema and swelling
Whilst intrathoracic surgery to correct more caudal over the rostral aspect of the neck (Scott 1978, Caron &
tracheal deformities is technically feasible, it is not prac- Townsend 1984, Fubini et al 1985). External skin wounds
tical. Thus the sole correction of affected cervical tracheal are not always present. The emphysema may later spread
rings is unlikely to be of major clinical benefit if widespread to involve the head, trunk, and even limbs. Horses may later
intrathoracic tracheal collapse is concurrently present. become stiff, and possibly febrile from secondary infection,
and epistaxis and coughing may also occur (Caron & Fractures of the tracheal rings with gross distortion of
Townsend 1984). In addition to possibly having a ruptured the trachea may also occur and it may be difficult to
trachea, horses with emphysematous cervical swellings evaluate the degree of cartilage ring damage in the pres-
should always be suspected of suffering from a ruptured ence of major local inflammation and emphysema. If
esophagus from identical trauma (Risnes & Mair 2003, available, computed tomography or magnetic resonance
P.M. Dixon, personal observation). Because the esophagus imaging of such lesions is the optimal method of assessing
may lie ventrolateral, or even ventral, to the trachea at cartilage damage. If life-threatening tracheal obstruction
around the level of the sixth cervical vertebra in some occurs, a temporary tracheostomy can be performed more
horses, it is prone to trauma at this site. Penetrating skin distally, depending on the site of the tracheal damage. If
wounds of the axilla can also lead to marked emphysema of the site of a traumatic tracheal obstruction is so distal
the cervical area, but clinical examination will readily dif- that a temporary tracheostomy cannot be performed, a
ferentiate this type of injury from cervical tracheal or more proximal tracheostomy can be performed and an
esophageal injury. endotracheal tube can be inserted through the tra-
Cervical radiography of horses with tracheal or cheostomy and then manipulated through the damaged
esophageal rupture will show extensive gas-infiltration lumen into the thoracic trachea. Such tubes should be
subcutaneously, and along the fascial planes of the neck, made of soft rubber without sharp edges to help prevent
in addition to variable soft tissue or fluid-filled swellings of exacerbation of any mucosal ulceration and the subse-
the rostral and ventral neck regions. Thoracic radiography quent development of a circumferential stricture. Addi-
will also reveal pneumomediastinum and possibly pneu- tionally, such tubes should not have an inflated cuff
mothorax. Endoscopy (tracheoscopy) will confirm if tra- because the lumen of such tubes will soon accumulate dry
cheal trauma has occurred, with evidence of mucosal exudates (both from tracheal wound exudate and normal
tears, mainly on the dorsal and ventral aspects of the lower airway secretions) that will then cause an
trachea (especially overlying the annular ligaments); intraluminal obstruction that could prove fatal if the cuff
possible prolapse of submucosal tissue into the tracheal on the tube is inflated. Finally, these tubes should not be
lumen; distortion or partial occlusion of the lumen as a advanced to the level of the carina, in case they enter a
result of cartilage ring fractures; and/or local inflammation main-stem bronchus and bypass airflow to the other main-
(Caron & Townsend 1984, Fubini et al 1985, authors’ stem bronchus, causing a unilateral lung collapse with
personal observations). Esophageal endoscopy to examine serious consequences.
the integrity of the esophagus should always be performed Granulation tissue will usually develop at sites of
on horses with neck swelling and emphysema that have mucosal damage but if focal it will contract when it
had suspected neck injury. If the esophagus is ruptured, subsequently becomes covered in mucosa. However, if the
the prognosis is poor. The accumulated saliva, food and trauma has damaged the cervical tracheal mucosa
exudates should be drained ventrally and the esophageal circumferentially, or over most of its circumference, there is
wound left to heal by secondary intention, possibly with an a risk that the granulation tissue that develops over these
indwelling nasogastric tube in the distal esophagus for wounds may develop into a ring, or into a broad band of
2–3 weeks, along with appropriate supportive therapy. fibrous tissue over the following months, as occurs with
If the cervical swelling and emphysema are solely the laryngeal mucosal trauma (Chapter 38). A circumferential
result of tracheal rupture, the prognosis is much better. In fibrotic ring is more serious than a partial circumference
many instances of tracheal trauma with emphysema, the transtracheal band, because fibrotic rings may progres-
small tears of the tracheal mucosa will heal spontaneously. sively contract into a smaller stricture that may even-
In addition to tetanus prophylaxis, non-steroidal anti- tually reduce the tracheal lumen to 1–2 cm in diameter
inflammatory agents should be administered to such cases (Fig. 40.5), leading to respiratory obstruction with stridor
to decrease the traumatic inflammation, along with broad- at rest, and possibly death by asphyxiation. After allow-
spectrum antibiotics to reduce the potential spread of ing the traumatic tracheal inflammation to subside, it
pathogenic bacteria with entrapped air along the fascial may become obvious in other cases that resection of the
planes. The emphysema present in such cases will usually damaged tracheal rings is required, as described later. If
resolve in 1–2 weeks, but may remain for up to a month in such damage involves only two or three tracheal rings, it
some horses (Caron & Townsend 1984). may be possible to fully resect the damaged segment, and
Large rents in the tracheal mucosa with extensive then appose the ends of the trachea. If more extensive
herniation of soft tissue into the tracheal lumen can be damage occurs (i.e. if more than four tracheal rings are
sutured as described by Fubini et al (1985), who dissected involved), it will be difficult to appose the normal tracheal
the trachea free at the injury site and rotated it to allow segments without having excessive tension on the suture
suture repair of a progressively enlarging intratracheal line. Such wounds will be prone to dehiscence and the later
hernia of the dorsal aspect of the trachea that contained development of granulation tissue, leading to further
trachealis muscle and subcutaneous tissue. fibrosis at the anastomosis sites. The prognosis for horses
and also following tracheostomy. These may enlarge to

such an extent (up to 7–10 cm in diameter), that they
cause almost total tracheal lumen obstruction (Fig. 40.6).
Such solid swellings may also extensively distort adjacent
tracheal rings. Following excision of these cartilaginous
swellings, including the involved tracheal ring(s), mucosal
stricture or tracheal collapse (as a result of the absence
of tracheal ring structural support) may then develop.
Consequently, such cases should have the affected rings
fully removed and an end-to-end tracheal anastomosis
performed, if feasible.
Focal Intraluminal Tracheal Lesions

Apart from granuloma formation post tracheostomy, focal
intraluminal tracheal lesions are rare in horses. Charlton &
Tulleners (1991) reported infected/necrotic midcervical
tracheal proliferative lesions in two adult horses follow-
ing intratracheal antibiotic administration in one, and
following a transtracheal aspiration in the other. The
masses were resected using a transendoscopic laser in one
Fig. 40.5. Upper cervical trachea of a horse that sustained a kick injury
horse and combination of transendoscopic laser and con-
to this region some months previously. At the time of injury, extensive
emphysema and inflammation were present over the neck. The horse ventional surgery in the other.
made an apparent clinical recovery, but subsequently developed
stridor and exercise intolerance. The traumatic circumferential mucosal
injury has healed with a fibrous stricture that has a diameter of circa Tracheal Resection and
2 cm at the site of the stenosis. Reconstruction Techniques
The trachea is flexible and mobile in its fascial attachments
with such wide areas of traumatically damaged cartilage and so, in humans, excellent mobilization of the trachea
rings is very poor, unless the damage is in the rostral can be achieved using tension-relieving sutures, allowing
cervical trachea and a permanent tracheostomy can be over half of the trachea to be resected with primary
placed more distally. anastomosis achieved. The adjacent vital structures, in
Solid, chondroma-type swellings occasionally develop particular the recurrent laryngeal nerves, must be iden-
several months after traumatic damage to tracheal rings tified and protected during tracheal resection. Tate et al
Fig. 40.6. The ventral sections of two tra-

cheal rings from either side of a temporary
tracheostomy in a horse with Streptococcus
equi var. equi (strangles) retropharyngeal
abscesses. These firm, non-suppurative car-
tilaginous swellings enlarged over several
months following the tracheostomy and
caused gross tracheal obstruction (1 cm
markers).
(1981) successfully resected three tracheal rings in each of for 24 h. The horse raced successfully as a 2-year-old.
three normal horses using the following technique, but Yovich & Stashak (1984) used a similar repair to support
removal of five rings in a further horse was unsuccessful tracheal rings that were deformed and eroded by a lipoma
because of excessive tension on the suture line. A 40-cm in an aged gelding.
ventral midline skin and cutaneous colli incision is made,
the sternothyrohyoideus muscles are separated, and careful
blunt dissection is continued to fully isolate the trachea.
Extramural Tracheal Compression
Where possible, the affected tracheal cartilages are resected Occasionally, enlarged lymph nodes compress the trachea
submucosally, without entering the tracheal lumen. Once causing stridor. These lymph node abscesses are usually
the affected tracheal area is resected, the endotracheal tube caused by S. equi infection (Randall & Myers 1973) and
is immediately advanced down to the distal segment. The may involve the upper cervical chain, compressing the
mucosa is folded back over the two adjacent normal proximal cervical trachea. They can also involve the distal
tracheal rings and sutured to their margins. The thick cervical trachea at the chest entrance (Randall & Myers
adventitia of the equine trachea will hold sutures whilst 1973, Rigg et al 1985, Tessier et al 1996, P.M. Dixon, per-
mucosal and cartilage sutures are being placed. The sonal observation). Diagnosis is by a history, and possibly
tracheal ends are temporarily maintained in place with by intercurrent clinical signs, of strangles and confirmation
towel clips while steel wire or monofilament nylon partial can be by needle aspiration and/or ultrasonography of
thickness, cartilaginous sutures are inserted. Tate et al cervical swellings. Following local anesthesia of the over-
(1981) also performed this technique on two clinical cases. lying skin and subcutaneous tissues (except in emergen-
One clinical case with post-tracheostomy cicatrix had five cies), the abscessed lymph nodes should be drained. The
tracheal rings removed, with the use of a martingale to cavity of the abscess should then be digitally explored and,
restrict neck movement postoperatively and a return to if loculated, it should be opened into a common chamber.
work at 8 weeks post surgery. A second clinical case died The abscess cavity should then be lavaged with dilute
within 2 days of surgery as a result of myopathy. Necropsy povidone iodine solution, having ensured that the drainage
on this case showed the tracheal anastomosis to be airtight. wound is large enough to prevent premature closure (Rigg
No iatrogenic laryngeal paralysis was observed in the four et al 1985). As viable S. equi bacteria are commonly pres-
experimental and two clinical cases operated on by Tate ent in these abscesses, the clinical examination of such
et al (1981). cases, and in particular endoscopy and surgical drainage,
More extensive tracheal resection was performed by must be carried out with strict attention to hygiene and
Carrig et al (1973) who resected 45 cm of cervical trachea all protective clothing, equipment and premises must be
in a horse with tracheal collapse and replaced it with a thoroughly cleaned and sterilized.
reinforced polyvinylchloride corrugated hose that was Mediastinal tumors, mainly lymphosarcomas, or other
inserted 3 cm into both ends of the resected trachea. cranial thoracic tumors including primary lung tumors, or
However, 3 months after surgery, granulation tissue formed grossly abscessed mediastinal lymph nodes may also cause
at the proximal end of the prosthesis and was surgically compression of the intrathoracic trachea, or of one or both
removed. Subsequently (61 ⁄ 2 months later), the pony was main-stem bronchi and thus cause wheezing and dyspnea.
euthanased because of the reformation of intraluminal Such an endoscopic finding should lead to a careful
granulation tissue at the proximal end of the prosthesis. thoracic examination, including radiography and ultra-
Robertson & Spurlock (1986) operated on a 6-month- sonography. Thoracic tumors are usually untreatable
old standardbred foal that had had four midcervical in the horse.
tracheal rings fully sectioned midline for a tracheostomy at
2 months of age because of a Streptococcus equi cervical
abscess. The cut rings had later inverted into the lumen
Tracheobronchial Foreign Bodies
with fibrous tissue formation that connected the cut Inhaled foreign bodies are common in humans and
ends obstructing the lumen. A fifth adjacent ring had a dogs, but less common in horses because of their height.
chondromatous thickening ventrally. The four inverted O’Connor (1950) described a range of laryngeal and
cartilages were partially sectioned on each side of the tracheal foreign bodies in horses and stated that a fatal
deformity and monofilament nylon sutures were inserted bronchopneumonia could develop if the foreign body
in the rings ventral to the cartilage incisions. External was not coughed up. As noted (Chapter 38), long thin
support made from 2- to 5-cm wide sections of a 60 ml twigs or other long plant material will very occasionally
polypropylene syringe barrel that was cut in half longi- be inhaled and, if they manage to bypass the larynx,
tudinally were sutured over the ventral half of the they will become entrapped at the carina or in the main-
deformed trachea, through appropriately placed holes. The stem bronchi (Lane 1981, Urquhart et al 1981, Brown
wound was fully closed and a suction drain was inserted & Collier 1983, Ferrucci et al 2003), predominantly the
right main-stem bronchus (Freeman 1991, P.M. Dixon,

personal observation). If the branches, short leaves or
thorns of these plants are directed rostrally, they will
become progressively embedded in the airway wall like
fishhooks, and are unlikely to be coughed out. Indeed,
it is even difficult to retrieve such foreign bodies
transendoscopically.
A history of sudden onset of continuous coughing is a
very prominent finding in these cases. Malodorous breath
will often be present. Other signs of pulmonary disease,
such as increased respiratory rate or the presence of
Fig. 40.7. This 6–7 cm long plant stem with caudally facing thorns was
abnormal lung sounds, are usually absent, at least initially,
deeply embedded in the right main bronchus of a horse. For almost a
unless secondary lung infection occurs. If significant pul- year the horse coughed, had malodorous breath and intermittent
monary infection develops, abnormal lung sounds and purulent nasal discharge that temporarily responded to antibiotics. All
possibly purulent, or blood-tinged, nasal discharge may signs resolved following the removal of the foreign body using
occur. No response or only a temporary response (decreased transendoscopic biopsy forceps.
nasal discharge) may occur following antibiotic therapy.
Radiography may show a localized interstitial pattern
caudal to the ventral cava (Brown & Collier 1983). Tracheostomy in the Horse
Endoscopically, local airway inflammation and purulent
A “tracheostomy” is a surgical opening into the trachea,
respiratory secretions may obscure a foreign body, espe-
with or without the use of a tracheostomy tube to keep this
cially shorter pieces of vegetation that are fully embedded
opening patent. The term “tracheotomy” was originally
within a main-stem bronchus. These types of object may
introduced by Heister in 1718 for this procedure (Wright
significantly obstruct airflow and also obstruct the nor-
1914, Stevenson & Guthrie 1949) and this term is now
mal drainage of respiratory secretions from the affected
used by some to describe the surgical procedure of creat-
bronchus and so induce severe, focal pulmonary infec-
ing a tracheostomy, although many authors includ-
tion. If the foreign body is not visible, culture of purulent
ing Woolridge (1928) use these words interchangeably.
exudate from the affected area will often reveal high
Tracheostomies have long been used in humans, with
numbers of a wide range of organisms that are unrespon-
descriptions of this procedure in a Hindu text of 2000 BC,
sive to antibiotic therapy. Such bacteriological findings in
although Hippocrates later condemned this procedure
the presence of focal, purulent pulmonary disease should
because of the fear of carotid artery damage (Spector
suggest that some predisposition to the local pulmonary
1991). In horses, the benefits of tracheostomy have been
infection is present. In such cases, the affected area should
recognized for over 150 years with Youatt (1846) stating:
be transendoscopically lavaged to help determine if a
bronchial foreign body or tumor is present. The respiratory canal is occasionally obstructed, to an
When identified, bronchial foreign bodies may be annoying and dangerous degree. It has been anxiously
removed using transendoscopic grasping or basket forceps. inquired whether there might not be established an
As noted, cranially facing branches and thorns will artificial opening for the passage of the air, when the
make the recovery of such vegetation difficult trans- natural one could no longer be used. It has now been
endoscopically, and the midline stem may become inad- ascertained that it is both a simple and safe operation.
vertently progressively broken off when grasped with the
There are three basic types of equine tracheostomy:
forceps. With persistence, most bronchial foreign bodies
will eventually become loose and retrievable (Fig. 40.7). ● Temporary tracheostomy – this is usually an emergency
If a solid area of the plant stem cannot be grasped, basket procedure where a smaller diameter tracheostomy tube
forceps (as used to retrieve guttural pouch chondroid) can is inserted, usually for a matter of days, to bypass an
be pushed down the bronchus beside the plant and then acute upper airflow obstruction.
opened to ensnare part or all of the plant. If still unsuc- ● Permanent tracheostomy – this is an elective proce-
cessful, a distal cervical tracheostomy can be performed dure in which a larger metal tracheostomy tube is
under general anesthesia and a long, rigid grasping instru- used to bypass a permanent upper airway obstruction.
ment (that will have to be bent significantly to permit its The term “permanent tracheostomy” is not absolute
entry into the thoracic trachea and main-stem bronchi) because, for ease of management, many “permanent”
can be used under flexible endoscopy guidance, to grasp tracheostomy tubes are removed at the end of each
and retrieve the foreign body (Urquhart et al 1981, Brown working season and then replaced at the beginning of
& Collier 1983). the following season.
● Permanent tracheal fistula (stoma) – this has also been develop temporary bilateral laryngeal paralysis during
used to create a permanent bypass of the upper air- recovery from general anesthesia following any type of
ways in both clinical and experimental cases (Shappell surgery (Dixon et al 1993; see Chapter 33). Equipment for
et al 1988). an emergency tracheostomy should be readily available for
this eventuality. A temporary tracheostomy may also be
The horse has a large relatively superficial trachea used for horses with acute hepatic encephalopathy-induced
more rostrally, which readily facilitates tracheostomy. bilateral temporary laryngeal paralysis and in chronic
Additionally, because of the low sensitivity of the equine grass sickness cases, which have severe rhinitis sicca (Milne
upper trachea, as compared to some other species, horses et al 1994). A temporary tracheostomy can be used to
will tolerate the presence of a tracheostomy tube in situ permit inhalation anesthesia during major head surgery,
very well, with little coughing, even immediately after e.g. arytenoidectomy. A distal temporary tracheostomy
its placement. allows retrieval of bronchial foreign bodies and removal
(or biopsy) of polyps and tumors of the lower trachea
and bronchi.
Indications for temporary tracheostomy
Severe upper airway obstructions can be caused by acute Indications for permanent tracheostomy
upper respiratory infections, most commonly strangles
infection with accompanying large retropharyngeal Horses with inoperable nasal and sinus neoplasia can
abscesses. Other causes include nasopharyngeal cellulitis be maintained with a “permanent” tracheostomy for weeks
(e.g. following foreign body damage), or less commonly to months, for example to enable a valuable stallion to
following viral or other infections in younger horses and complete a breeding season or allow a pregnant mare
foals that have relatively smaller upper airways, and also to foal. Some miniature horses have a temporary, but
usually have pre-existing lymphoid hyperplasia of their severe, bilateral nasal obstruction as the result of
nasopharynx. Upper respiratory infections can occasionally encroachment of maxillary cheek teeth eruption cysts
cause an epiglottitis, which can cause significant upper into the nasal cavity, and may need a permanent tra-
airflow obstruction as described in Chapter 38. Acute upper cheostomy tube for 12 months or so until these structures
airway obstructions can also occur following anaphylactic reduce in size (J. Easley, personal communication 2002).
reactions to insect stings or snake bites to the head or However, the ethics of this procedure are questionable.
upper neck, in adverse injection reactions in the neck Major deformations of the nasal cavity and nasopharyn-
region that can cause laryngeal obstructions, or to smoke geal cicatrix formation can also be bypassed with a
inhalation. Trauma to the head or throat regions may tracheostomy, as can severe acquired tracheal obstruc-
also cause serious perilaryngeal inflammation, e.g. horse tions of the upper cervical trachea. Dorsoventral tracheal
throwing a rider and later causing self trauma to head collapse in ponies is not amenable to this treatment
after getting its bridle caught in a fence. because the distal cervical and intrathoracic trachea are
Such severe upper respiratory obstruction causes usually worst affected.
anxiety, greatly increased respiratory effort, tachypnea, In the UK, Ireland, and a limited number of other
tachycardia, hyperthermia, stridor, nostril flaring, and countries, a permanent tracheostomy can be used in
extension of the head and neck. Arterial blood gas analysis performance horses (e.g. racehorses, hunters) to bypass
reveals marked hypoxemia (PAO2 < 60 mmHg) and hyper- performance-limiting upper respiratory obstruction, such
capnia (PaCO2 > 50 mmHg). With more severe airway as after failure of surgery to treat laryngeal paralysis
obstruction, worsening hypoxemia (PAO2 < 40 mmHg) and or dorsal displacement of the soft palate. A permanent
hypercapnia, cyanosis and depression will develop. The tracheostomy tube may be fitted in a horse with upper
accessory muscles of respiration (including the sterno- respiratory airflow problems, to assess the animal’s athletic
thyrohyoideus and orbicularis oris) may begin to contract ability with the obstruction bypassed, and consequently
during respiration and then death will shortly ensue. to determine if conventional surgery is likely to be worth-
A prophylactic temporary tracheostomy is indicated while. Some owners and trainers find a permanent tra-
following major upper respiratory tract surgery, such cheostomy aesthetically objectionable and do not permit
as bilateral arytenoidectomy or correction of tracheal their use. Some racing authorities, including those of most
stenosis. A temporary tracheostomy is unnecessary after American states, do not allow racehorses to run with a
vocal cordectomy or ventriculectomy unless postoperative tracheostomy and in general this treatment is currently
inflammation occurs to such a degree as to markedly uncommonly performed. Additionally, it is unclear if the
obstruct the laryngeal lumen. Under these rare circum- unfiltered, unhumidified and unheated air entering the
stances a temporary tracheostomy tube can be inserted trachea at right angles via a tracheostomy has any adverse
through the laryngotomy wound. Horses occasionally effects on pulmonary function.
A B
Fig. 40.8. Performing a tracheostomy. (A) For insertion of a temporary tracheostomy tube, the skin and
the cutaneous colli muscle are incised vertically and the sternothyrohyoideus muscles are separated at
the midline and retracted to expose the underlying trachea. The annular ligament between two tracheal
rings is then incised to permit insertion of the tube. (B) For insertion of a permanent tracheostomy tube,
the strap muscles have been further retracted with Lane’s forceps. An elliptical segment of the dorsal
aspect of the tracheal ring below the tracheal ligament incision has been resected to allow the insertion
of a (wide) permanent tracheostomy tube. The pale dorsal wall of the trachea is visible in the center of
the wound.
Surgical procedure hemostats; there should be minimal hemorrhage from

dissection of the deeper layers.
A temporary tracheostomy is usually an emergency It is helpful if an assistant laterally retracts the cuta-
procedure that is performed on the standing horse under neous colli muscle and skin with tissue forceps, to reveal
local anesthesia. Thankfully, the anatomy of this area the underlying sternothyrohyoideus muscles (Fig. 40.8).
is relatively simple (Figs 40.1 and 40.2), with no vital Provided that the skin and panniculus muscle incisions are
structures overlying the standard tracheostomy site. Unless midline (they may be off-center in emergency tracheos-
the airflow obstruction is in the mid-cervical trachea, tomies), the junction (sometimes ill-defined) between
the usual tracheostomy site is the upper third of the the paired bodies of these muscles can usually be identified
cervical trachea, commonly at the third to the fifth as a pale fibrous line which can usually be avascularly
tracheal rings (Woolridge 1928), where the trachea is divided with scissors (Share-Jones 1908). Separation of
most superficial. Additionally, if tracheostomy-induced these muscles over a 7- to 8-cm length then reveals
granulation/chondroma-type tissue causes subsequent the trachea (Fig. 40.8), to which they are loosely attached
tracheal obstruction, a second tracheostomy can be created by sparse connective tissue, and also exposes the paired
more distally. A tracheostomy tube is also less likely to be omohyoideus muscles on the lateral aspects of the trachea.
rubbed on or trapped in doors or fences at this site, as If the omohyoideus overlie the tracheostomy site, these
compared to one located in the mid-neck region. muscles can be bluntly dissected off the trachea to more
A midline area, circa 15 cm long and 7 cm wide, fully expose its anterior surface. In emergency situations,
overlying the chosen tracheal site is shaved and the skin there may be insufficient time to follow the above pro-
is prepared for surgery; 20–30 ml local anesthetic is cedures and one may have to make a deep midline incision
infiltrated midline subcutaneously into the underlying through the skin and both muscle layers, down to the
muscles and directly over the trachea. The animal’s head tracheal surface, without skin preparation or anesthesia.
is then elevated to make the trachea more promi- If a more rostral tracheostomy must be performed, this
nent, provided that this manipulation does not worsen the will involve sectioning between the omohyoideus muscles,
dyspnea in animals with gross laryngeal obstructions. where the line of demarcation between these paired, thin
It is also essential to have the head absolutely straight muscles is very indistinct.
to ensure a midline incision. A 10-cm midline skin and
subcutaneous incision will expose the underlying cuta-
neous colli (panniculus) muscle. There is no distinct mid- Temporary tracheostomy procedure
line division of this muscle over the trachea and so it must As the horse’s head is normally elevated during this
be incised midline beneath the skin incision. If present (and surgery, it is important to ensure that the external skin
if time allows), hemorrhage from small arteries in the wound and the tracheal incision site overlie each other.
skin and panniculus muscle should be controlled with Before making the annular ligament incision, the horse’s
Fig. 40.9. This horse has a temporary tra-

cheostomy tube inserted into its rostral
trachea following extensive laryngeal surgery
that might have caused severe laryngeal
obstruction. In this case the temporary tube
has been sutured to the skin because it
is likely to be in this position for only 24 h.
Note the nylon loop (arrow) which was
sutured around the tracheal ring imme-
diately distal to the tracheostomy site (with a
shorter loop encircling the more proximal
tracheal ring), to facilitate easy reinsertion of
the tracheal tube if required.
head should be lowered to its normal resting position to cleaning and so minimizing the risk of its accidental
select the optimum annular ligament incision site, which is insertion subcutaneously, or between the muscles and the
usually the most distal annular ligament exposed. A trachea by inexperienced personnel. Gaping skin wounds
transverse stab incision is made into the annular ligament can be loosely sutured, but marked inflammation always
and, in horses with severe dyspnea, this will induce a loud occurs and tightly suturing the tissues around the
inspiratory noise, as air rushes into the trachea. Using tracheostomy tube will restrict exudate drainage and
straight scissors, this incision is extended on both sides, promote local abscess formation or cellulitis and also
to create an opening large enough for the temporary promote the development of subcutaneous emphysema. A
tracheostomy tube. This incision should not be continued temporary tracheostomy tube should be left in place no
more than 180° through the circumference of the annular longer than necessary and, if possible, should be gradually
ligament in case the carotid artery or associated nerves reduced in size to allow air to flow around it before its
are transected, and also to prevent tracheal stenosis final removal.
following removal of the temporary tracheostomy tube.
The temporary tracheostomy tube should be of soft
silicone or plastic because the older style metal temporary Permanent tracheostomy procedure
tracheostomy tubes can cause severe mucosal damage, To fit a permanent tracheostomy tube, the trachea is
especially where their distal end contacts the ventral exposed as described above. Because the annular spaces in
trachea. The largest tube that can be comfortably fitted the horse are not large enough to accommodate a wide
through the tracheostomy incision should be manipulated metal permanent tracheostomy tube, parts of two adjacent
through this opening and down the trachea. If a tem- tracheal rings (Fig. 40.10) have to be removed to insert
porary tracheostomy tube is unavailable, one can readily be these tubes through the tracheal wall. A variety of instru-
fashioned from the sawn barrel of a 30- or 50-ml syringe, ments for accurately removing portions of tracheal rings
a section of nasogastric tube or a plastic pipe, with holes (including Spooner’s or McKenny’s tracheotomes) were
drilled or burned into their wider parts to allow them to be previously used when these procedures were more com-
taped or sutured to the neck. monly performed, but they are now largely unavailable.
It is helpful to insert two heavy monofilament nylon Following incision of the chosen annular ligament, the
suture loops circa 15 cm long, encircling the tracheal rings midline of one of the adjacent tracheal rings is firmly
immediately above and below the tracheostomy (Fig. 40.9). grasped with large curved artery forceps. An elliptical
With moderate traction on these loops, the tracheal incision is then made with a scalpel or less readily
incision can be both exteriorized and dilated to facilitate with heavy, sharp curved scissors. A firm grip should be
tracheostomy tube reinsertion following removal for maintained on the tracheal ring both to allow proper
Fig. 40.10. (A) A permanent tracheostomy

tube had been fitted to this horse. The ven-
tral aspect of the wound (arrowheads) was
not sutured to help prevent the develop-
ment of post-tracheosotomy emphysema.
(B) Tracheal specimen demonstrating the
removal of an elliptical part of two adjacent
tracheal rings to allow placement of a per-
manent tracheostomy tube.
A B
control of the curved cartilage incision (the incision will inspected and cleaned if necessary two to four times,
tend to run straight and so can fully cut through the depending on degree of exudate accumulation present
tracheal ring) and also to prevent inhalation of the excised within the tube; twice daily examination and cleaning
piece of cartilage. should suffice thereafter.
One should attempt to remove 75% of the width of With temporary tracheostomies it is very helpful if a
tracheal ring (Share-Jones 1908) and avoid cutting fully spare temporary tube is available so that they can be imme-
through a tracheal ring, because following removal of the diately exchanged for cleaning. The soiled tracheostomy
tracheostomy tube, the transected ends may invert into and tube should be soaked in a biological detergent, cleaned
partially occlude the tracheal lumen, particularly if two or inside with a flexible bottle-brush, followed by thorough
more rings are transected. This problem can be particu- rinsing in water to remove all chemicals. The skin beneath
larly serious in foals, for example where a temporary the tracheostomy should be cleaned of blood, dried, and
tracheostomy has been performed using a temporary then coated in petroleum jelly immediately after tube
tracheostomy tube which has been found to be too large to insertion. Thereafter, the area below the tracheostomy
fit through an annular space, with subsequent transection should be cleaned, dried and again coated in petroleum
of tracheal rings to enable its insertion. jelly twice a day to facilitate skin cleaning and prevent
excoriation. Horses with a temporary tracheostomy should
Aftercare: temporary tracheostomy be kept indoors in a box where they cannot rub and
dislodge the tube. After the primary airway obstruction
Depending on its vaccination status, the animal should be has resolved, the temporary tracheostomy tube and the
given tetanus antitoxin. Broad-spectrum antibiotics should two nylon loops are removed. The tracheostomy wound,
be administered for 2–3 days to reduce the inevitable which is inevitably contaminated, should always be
postoperative local infection that develops and so lessen the allowed to heal by secondary intention, which usually
volume of exudate that causes a major problem in the first takes 2–4 weeks.
few days postoperatively by blocking the tracheostomy All horses will develop localized emphysema following a
tube. It is absolutely imperative that the tube’s lumen be tracheostomy and, consequently, subcutaneous crepitus
kept fully patent, otherwise the blocked tracheostomy tube will always be palpable around these wounds. However, the
will act as an additional airflow obstruction to the one emphysema may extend up the neck to the larynx and
being bypassed and further compromise airflow. Temporary head (Fig. 40.11), or caudally down to the ventral neck,
tracheostomy tubes with cuffs should not have the cuffs especially when the tracheostomy skin wounds are sutured
inflated (except during anesthesia or in intensive-care cases excessively tight. Such horses are usually otherwise
that are being ventilated) because intraluminal blockage asymptomatic and little effective treatment is needed or
of the tube may suffocate the horse. On the first day follow- indeed can be given for this emphysema. Removing skin
ing insertion, temporary tracheostomy tubes should be sutures above or below the tracheostomy that have become
Fig. 40.11. This horse had a permanent

tracheostomy fitted 24 h previously, and has
since developed extensive emphysema of
the head and neck. Note the finger of the
examiner deeply depressing the emphy-
sematous subcutaneous tissues.
excessively tight because of postoperative inflamma- tracheostomy tubes should be temporarily removed two or
tion may be of value in some cases. Performing minimal three times daily (e.g. whilst cleaning tubes) and the wound
dissection during the placement of tracheostomy tubes surfaces should be debrided of necrotic tissue using swabs
will decrease dead space and help reduce the spread of soaked in dilute povidone iodine. Metronidazole (local and
emphysema. systemic) and penicillin should be administered until the
Pneumothorax is a well-recognized complication of malodor and excessive discharge resolve.
tracheostomy in humans, partly as a result of the short
human neck and consequently of the risk of tracheal tubes Aftercare: permanent tracheostomy
being inadvertently misplaced rostral to the trachea
and into the mediastinal space. Boy and Sweeney (2000) In heavier type horses, particularly if a permanent tra-
reported pneumothorax following temporary tracheostomy cheostomy has to be re-fitted lower down the neck, where
in three horses, and Kelly et al (2003) recorded pneu- there is greater muscle cover by the sternocephalicus and
mothorax in an 18-month-old filly following an emergency also by the larger (and at this site) separate bodies of the
tracheostomy performed 2 h after sinus cyst excision. Kelly sternothyroideus and sternohyoideus muscles, postopera-
et al (2003) proposed that the subcutaneous emphysema tive inflammation can cause complications (Dixon 1988).
dissected along the facial planes and migrated into the Woolridge (1928) noted that when a permanent tra-
mediastinal space to cause pneumomediastinum and then cheostomy is fitted there is always inflammation of the
extended through the pleura to cause pneumothorax. This tracheostomy site and therefore the neck on the tube used
mechanism is well described in humans, especially children during this period should be 1–1.5 cm longer than the skin
(Swift & Rogers 1987, Waldron et al 1990). to tracheal lumen thickness. The inevitable postoperative
As noted previously, all tracheostomy wounds are swelling of the tissues overlying the trachea can cause
contaminated with microorganisms and all will have such pressure on the permanent tracheostomy tube that
inflammation and exudation of the exposed muscles, it cannot be dismantled and removed for cleaning with-
subcutaneous and cutaneous tissues. Secretions will also be out considerable force. This inflammation may also cause
present in the tracheal lumen, especially in horses with the internal flange of the tube to press on the tracheal
pre-existing pulmonary disease. As a tracheostomy will mucosa, and cause pressure necrosis of the mucosa and
interfere with conditioning of inhaled air, this may even cartilage. This is one reason for the development of
predispose to temporary lower airway inflammation that tracheal granulation, scar tissue, chondroma-type swell-
may be responsible for increased production of tracheal ings, and septic chondritis (Woolridge 1928) which can
respiratory secretions, in the short term at least. A small cause local tracheal obstruction. This inflammation can
percentage of cases will develop foul-smelling, anaerobic also cause the external flange of the tube to press on the
or mixed infections of the tracheostomy wound that lead skin and can even cause the flange to sink below the skin
to copious, malodorous, purulent exudate. In these cases, surface and eventually become totally embedded in scar
one should ensure maximal drainage of the wound by tissue. An appropriate diameter, longer-necked permanent
removing sutures in the ventral aspect of the wound. The tracheostomy tube which can accommodate the tissue
A B
Fig. 40.12. (A) Intratracheal endoscopy image taken after removal of a forming a fistula (arrowheads). (B) Intratracheal view of a tracheal
permanent “tracheostomy tube”. The tracheostomy wound did not fistula showing an open curette being used to remove the conjoining
heal because the external epithelium had grown into the trachea. epithelial surfaces at the fistula (arrowheads) and so allow the wound
Epithelium, with hair on it, is present on the margins of the wound to close by granulation.
swelling without causing undue pressure on the tracheal Post-tracheostomy airway obstruction
mucosa or skin surface should therefore be used in this
situation. In some animals it may be necessary to resort to Following removal of a temporary or permanent tra-
removal of sections of these overlying muscles before fitting cheostomy tube, excessive granulation tissue (Fig. 40.13),
the tube, especially if it must be fitted lower down the neck. which can possibly develop into a web (Fig. 40.14) and/or
The removal for cleaning of permanent tracheostomy cartilaginous proliferation (Fig. 40.6), may continue
tubes by owners who have little regard for the gentle and to develop at the tracheostomy site. If excessive, this may
hygienic handling of tissues can be another factor in lead to significant airflow obstruction. This is more com-
the exacerbation of postoperative inflammation and the mon following a permanent tracheostomy. Sectioning the
development of intratracheal granulomas/chondromas. annular ligament over more than 180° of the tracheal
After permanent tracheostomy the surgeon should, if circumference during a temporary tracheostomy procedure
possible, remove and fully clean the tube daily for the first risks immediate damage to the carotid artery, vagosym-
few days and then instruct the owner how to clean it in situ pathetic trunk and recurrent laryngeal nerve, and in the
daily with a blunt-ended blade, such as a round-ended long term risks tracheal obstruction by causing a band of
table knife. Animals that have been shown to have tracheal healed mucosa to protrude into the rostral half of the
granuloma formation should not have their tubes removed tracheal lumen (Freeman 1991). Following a permanent
for cleaning at any stage, with all cleaning being done tracheostomy, a permanent tracheal obstruction may occur
in situ. In all cases where a permanent tube is removed for if tracheal rings are fully cut to accommodate the tra-
cleaning, it should be replaced as quickly as possible because cheostomy tube. Following removal of the permanent tube,
local inflammation can make replacement impossible even the cut ends and attached mucosa may fold back into the
within a few hours. tracheal lumen and cause a permanent obstruction.
If a permanent tube is removed at the end of a season’s
work or on retirement to stud, the wound will normally
heal over fully within weeks. If full healing does not occur,
Permanent Tracheal Fistulation
this usually indicates the development of continuity A permanent tracheal fistula (stoma) has long been used to
between the tracheal mucosa and skin, i.e. a tracheal create a permanent bypass of the upper airways in both
fistula. This can generally be treated by freshening up the clinical (McClure et al 1995) and experimental (Shappell
edges of the fistula (Fig. 40.12). et al 1988) horses, as is commonly performed in ruminants
Fig. 40.13. Endoscopic image of the rostral trachea of a horse that Fig. 40.14. A ventral tracheal stenosis (web) (arrowheads) that
had a temporary tracheostomy tube fitted for 1 week, some months developed following placement of a temporary tracheostomy in the
previously. Damage to the tracheal mucosa around the tracheostomy upper trachea for 1 week.
site led to granulation and scar tissue formation, causing clinically
insignificant tracheal obstruction at this time. Some tracheal cartilage
swelling may also be present that can progress to form tumor-like
tracheal obstructions (see Fig. 40.6).
(less its cartilages) is extended into a (double) “Y”-shaped

incision at each end of the wound. The flaps of the trachea
with chronic laryngeal infections (Goulding et al 2003). are everted and sutured directly to the skin. If excessive
Smaller tracheal fistulas will contract in size and may tension is present (often at the caudal aspect of the
become blocked with dried tracheal secretions so larger wound), the medial aspects of the sternothyrohyoideus
fistulas are desirable if they are required for the long term. muscle can be resected. Such fistulas have been maintained
For this procedure, a vertical midline incision as described for 32 months in experimental ponies (Shappell et al 1988).
above can be made (Shappell et al 1988) with later resec- Unlike permanent tracheostomies, these large fistulas will
tion of some of the sternothyrohyoideus muscles if exces- predispose horses to the development of pulmonary disease
sive tension is present on the trachea to skin sutures. An (Shappell et al 1988) and, when used in clinical cases, they
alternative approach, as used in ruminants, is to fully sometimes have to be reversed to treat such pulmonary
resect all tissues above the tracheostomy site (McClure et al infections.
1995). For this technique, a 3 × 6 cm rectangular section of
skin and subcutaneous tissue and cutaneous colli (often
very thin this far rostrally) is removed from the ventral
Tracheal Tumors and Growths
midline neck, beginning 3 cm behind the larynx. Local Malignant tracheal tumors are rare in all species, with
anesthesia of the tracheal mucosa is reported to reduce for example the incidence of human tracheal tumors
coughing and make patients more comfortable during being only 2.7 cases per million people per year, mainly
this procedure. squamous cell carcinomas and adenoid cystic carcinomas.
The overlying sternothyrohyoideus muscles are clamped Sweeney (1997) illustrated intratracheal squamous cell
and resected at both ends of the skin resection, exposing carcinomas in an 18-year-old Arab cross and a 35-year-old
the rostral aspect of the second to fifth tracheal rings. Morgan horse. Benign lesions including papillomas,
Parallel incisions are made through the cartilages only, fibromas, chondromas, and adenomas are more common
on the lateral aspects of the exposed tracheal rings, (Spector 1991). Wenger & Caron (1988) reported tracheal
1.5–2.0 cm (depending on size of horse) to each side of the mastocytosis in an Arabian cross that presented with a
midline; then, the rostral aspects (circa 30% of circum- stridor of 3 days duration. The stridor was loudest during
ference) of the incised tracheal rings are dissected free and eating, which was thought to be the result of the
resected. The vertical incision in the center of the trachea esophageal food bolus compressing the dorsal tracheal
tracheal lesions in two horses Journal of the American

Collins NM, Barakzai S, Dixon PM 2005 Tracheal obstruction
by an eosinophilic polyp in a horse. Equine Veterinary
Education 17: 128–131
Couteil LL, Gallatin LL, Blevins W et al 2004 Treatment of
tracheal collapse with an intraluminal stent in a
miniature horse. Journal of the American Veterinary
Dallman MJ, McClure RC, Brown EM 1988 Histochemical
study of normal and collapsed tracheas in dogs. American
P
Davis DM, Honnas CM, Hedlund CS et al 1991 Resection of a
cervical tracheal bronchus in a foal. Journal of the
Delahanty DD, Georgi JR 1954 A tracheal deformity in a pony.
Journal of the American Veterinary Medical Association
125: 42–44
Dixon PM 1988 Tracheostomy in the horse. In Practice
10: 249–253
Dixon PM 1992 Respiratory mucociliary clearance in the
horse in health and disease, and its pharmaceutical
modification. Veterinary Record 131: 229–235
Dixon PM, Railton DI, McGorum BC 1993 Temporary bilateral
laryngeal paralysis in a horse associated with general
Fig. 40.15. Endoscopy of the distal cervical trachea of a horse with anaesthesia and post anaesthetic myositis. Veterinary
severe dyspnea showing a bi-lobed pedunculated mass (a polyp “P”) Record 132: 29–32
attached by a pedicle (arrowheads) to the dorsal trachea. This mass is Dixon PM, Railton DI, McGorum BC 1995 Equine pulmonary
almost totally obstructing the tracheal lumen. disease: a case control study of 300 referred cases. Part
3: Ancillary diagnostic findings. Equine Veterinary
Journal 27: 428–435
Feat S, Le Clech G, Riffaud L et al 2002 Complete cervical
ligament, thereby further compromising the tracheal tracheal rupture in children after closed trauma. Journal
of Pediatric Surgery 37: 1–3
lumen. Endoscopy revealed a large, rounded mass attached Ferrucci F, Croci C, Zucca E et al 2003 Use of a trans-
to the left dorsolateral aspect of the trachea, 5 cm distal to endoscopic technique to remove a bronchial foreign body
the larynx. The mass was removed via a laryngotomy in a Standardbred colt. Equine Veterinary Education
and its identity was confirmed histologically. Collins et al 15: 228–232
(2005) reported an eosinophilic polyp of the distal cervical Freeman DE 1991 Trachea. In: Beech J (editor) Equine
Respiratory Disorders. Lea & Febiger, Philadelphia,
trachea in a 12-year-old Irish draft cross that presented pp.389–402
with coughing and stridor (Fig. 40.15). The lesion was Fubini SL, Todhunter RJ, Vivrett SL et al 1985 Tracheal rup-
successfully resected using a distal cervical tracheostomy. ture in two horses. Journal of the American Veterinary
Goulden BE 1977 Some unusual cases of abnormal respira-
tory noises in horses. New Zealand Veterinary Journal
REFERENCES 25: 398–390
Goulding R, Schumacher J, Barrett DC et al 2003 Use of
Boy MG, Sweeney CR 2000 Pneumothorax in horses: 40 cases a permanent tracheostomy to treat laryngeal chon-
(1980–1997). Journal of the American Veterinary dritis and stenosis in a heifer. Veterinary Record 152:
Medical Association 216: 1955–1959 809–811
Bradley CO 1923 The Head and Neck. Topographical Anatomy Grillo HC, Donahue DM, Mathisen DI et al 1995 Postintu-
of the Head and Neck of the Horse. W Green, Edinburgh. bation tracheal stenosis. Treatment and results. Journal
p.7 of Thoracic and Cardiovascular Surgery 109: 486–493
Brown CM, Collier MA 1983 Tracheobronchial foreign body Hare WC 1975 Equine respiratory system. In: Getty R (editor)
in a horse. Journal of the American Veterinary Medical Sisson and Grossman’s The Anatomy of the Domestic
Association 182: 280–281 Animals, 5th edn. WB Saunders, Philadelphia, pp.498–523
Caron JP, Townsend HGG 1984 Tracheal perforation and Hobson HP 1976 Total ring prosthesis for the surgical
widespread subcutaneous emphysema in a horse. correction of collapsed trachea. Journal of the American
Canadian Veterinary Journal 25: 339–341 Animal Hospital Association 12: 822–828
Carrig CB, Groenendyk S, Seawright AA 1973 Dorsoventral Holland M, Snyder JR, Steffey EP et al 1986 Laryngotracheal
flattening of the trachea in a horse and its attempted injury associated with nasotracheal intubation in the
treatment. Journal of the American Radiographic Society horse. Journal of the American Veterinary Medical
14: 32–36 Association 189: 1447–1450
Charlton C, Tulleners E 1991 Transendoscopic contact Jackson PG, White RA, Dennis R et al 1986 Tracheal collapse
neodymium: yttrium aluminum garnet laser excision of in a goat. Veterinary Record 119: 160
Kelly G, Prendergast M, Skelly C et al 2003 Pneumothorax as Share-Jones JT 1908 The Surgical Anatomy of the Horse, Part
a complication of tracheostomy in a horse. Irish I. Bailliere, Tindall, Cox, London, pp.73–77
Veterinary Journal 56: 153–156 Simmons TR, Peterson M, Parker J et al 1988 Tracheal
Lane JG 1981 Fibreoptic endoscopy. In Practice 3: 24–30 collapse due to chondrodysplasia in a miniature horse
Mair TS, Lane JG 1990 Tracheal obstructions in two horses foal. Equine Practice 10: 39–42
and a donkey. Veterinary Record 126: 303–304 Sisson S, Grossman JD 1953 The Anatomy of the Domestic
McClure SR, Taylor TS, Honnas CM et al 1995 Permanent Animals. WB Saunders, Philadelphia, p.533
tracheostomy in standing horses: techniques and results. Spector GJ 1991 Respiratory insufficiency, tracheostenosis
Veterinary Surgery 24: 231–234 and airway control. In: Ballenger JJ (editor) Diseases of
McGorum BC, Dixon PM, Radostitis OM et al 2000 Clinical the Nose, Throat, Ear, Head and Neck. Lea & Febiger,
examination of respiratory system. In: Radostitis OM, Philadelphia, pp.530–569
Mayhew IG, Houston DM (editors) Veterinary Clinical Stevenson RS, Guthrie D1949 History of Otolaryngology.
Examination and Diagnosis. WB Saunders, London, E & S Livingstone, Edinburgh, pp.17, 31
pp.299–348 Sweeney CR 1997 Trachea and bronchi. In: Traub-Dargatz JL,
Milne EM, Woodman MP, Doxey DL 1994 Use of clinical Brown CM (editors) Equine Endoscopy, 2nd edn. Mosby,
measurements to predict the outcome in chronic cases of St Louis pp.97–105
grass sickness (equine dysautonomia). Veterinary Record Swift AC, Rogers JH 1987 The outcome of tracheostomy
134: 438–440 in children. Journal of Laryngology and Otology
O’Connor JJ 1950 Operations on the head and neck. In: 101: 936–939
Dollar’s Veterinary Surgery, 4th edn. Bailliere, Tindall, Tate LP, Koch DB, Sembrat RF et al 1981 Tracheal
Cox, London, pp.308–314 reconstruction by resection and end-to-end anastomosis
Peek SF, DeLahunta A, Hackett RP 1995 Combined in the horse. Journal of the American Veterinary Medical
oesophageal and tracheal duplication cyst in an Arabian Association 178: 253–258
filly. Equine Veterinary Journal 27: 475–478 Tessier GJ, Neuwirth LA, Merritt AM 1996 Peritracheal
Pirie M, Pirie HM, Cranston S et al 1990 An ultrastructural abscess as the cause of tracheal compression and severe
study of the equine lower respiratory tract. Equine respiratory distress in a horse. Equine Veterinary
Veterinary Journal 22: 338–342 Education 8: 127–130
Pouret E 1966 Laryngeal ventriculectomy with suturing Touzot-Jourde G, Stedman NL, Trim CM 2005 The effects
of the laryngeal saccules. In: Proceedings of the 12th of two endotracheal tube cuff inflation pressures on
Annual meeting of the American Association of Equine liquid aspiration and tracheal wall damage in horses.
Practitioners, p.207 Veterinary Anaesthesia and Analgesia 32: 23–29
Randall RW, Myers VS 1973 Partial tracheal stenosis in Urquhart KA, Gerring EL, Shepherd ML 1981 Tracheobron-
a horse. Veterinary Medicine: Small Animal Clinician chial foreign body in a pony. Equine Veterinary Journal
68: 264–266 13: 262–264
Rigg DL, Ramey DW, Reinerston EL 1985 Tracheal com- Waldron J, Padgham ND, Hurley SE 1990 Complications of
pression secondary to abscessation of cranial mediastinal emergency and elective tracheostomy – a retrospective
lymph nodes in a horse. Journal of the American study of 150 consecutive cases. Annals of the Royal
Veterinary Medical Association 186: 283–284 College of Surgeons of England 72: 218–220
Risnes I, Mair TS 2003 Traumatic oesophageal rupture in Wenger IE, Caron JP 1988 Tracheal mastocytosis in a horse.
horse complicated by subsequent rupture of the common Canadian Veterinary Journal 29: 563–565
carotid. Equine Veterinary Education 35: 120–125 White R 1995 Unilateral arytenoid lateralisation and extra-
Robertson JT, Spurlock GH 1986 Tracheal reconstruction luminal polypropylene ring prostheses for correction of
in a foal. Journal of the American Veterinary Medical tracheal collapse in the dog. Journal of Small Animal
Association 189: 313–314 Practice 36: 151–158
Rudorf H, Herrtage ME,White RA 1997 Use of ultrasonography Woolridge GH 1928 Encyclopaedia of Veterinary Medicine,
in the diagnosis of tracheal collapse. Journal of Small Surgery and Obstetrics. Volume II. Frowde H, Hodder,
Animal Practice 38: 513–518 Stoughton, London, pp.949–954
Scott EA 1978 Ruptured trachea in the horse: a method of Wright J 1914 A History of Laryngology and Otology. Lea &
surgical reconstruction. Veterinary Medicine: Small Febiger, Philadelphia, p.65
Animal Clinician 73: 485 Youatt W 1846 The Anatomy and Diseases of the Neck and
Schummer A, Nickel R, Sack WO 1979 The Viscera of the Neighbouring Parts: Tracheotomy. The Horse, new
Domestic Animals. Springer-Verlag, New York, pp.238, edition. C Knight, London, pp.219–220
276 Yovich JV, Stashak TS 1984 Surgical repair of a collapsed
Shappell KK, Stick JA, Derksen FJ et al 1988 Permanent trachea caused by a lipoma in a horse. Veterinary
tracheostomy in Equidae: 47 cases (1981–1986). Journal Surgery 13: 217–221
of the American Veterinary Medical Association 192:
939–942
Recurrent Airway Obstruction (Heaves)
and Summer-pasture-associated Obstructive
41 Pulmonary Disease
Jean-Pierre Lavoie
Introduction and Case Definition Etiology and Pathogenesis

It has been known since antiquity that stabled horses have The strong association between environment and both
an increased risk of developing a chronic, recurrent, and RAO and SPAOPD is well established. While it is now
debilitating respiratory syndrome. The terms that have recognized that inflammation of the distal airways is
been used to describe this syndrome are numerous and central to these syndromes, the mechanisms by which the
relate to the clinical presentation (heaves, broken-wind, environment leads to chronic airway inflammation and to
chronic obstructive pulmonary disease, recurrent air- the clinical signs of respiratory diseases remain poorly
way obstruction), the suggested etiologies (allergic airway defined. The finding that only a subset of horses will
diseases, hay sickness), or the lung pathology (emphysema, develop RAO or SPAOPD was the basis for the “allergy”
chronic bronchiolitis, small airway disease). The variable hypothesis, in which predisposed individuals mount an
terminology and inconsistent case definitions have led to antigen-specific inflammatory response (hypersensitivity
conflicting reports and considerable confusion concern- reaction) to components of environmental dust. However,
ing the etiopathogenesis, diagnosis, and therapy of equine it has recently been suggested that RAO may result from a
chronic respiratory diseases. A recent consensus statement, non-specific inflammatory response to inhaled pro-
from clinicians and researchers interested in the field of inflammatory agents including molds, endotoxins,
equine respiratory diseases, recommended the use of particulates and noxious gases which are present in the
heaves or recurrent airway obstruction (RAO) to describe a breathing zone of stabled horses (Table 41.1). The etiology
syndrome of mature horses with chronic airway obstruc-
tion (periods during which labored breathing is present),
reversible by dust control in the environment or the use of
Table 41.1. Pro-inflammatory agents present in the
bronchodilators (Robinson 2001). In this chapter, both breathing zone of stabled horses that could contribute
terms will be used interchangeably. As major differences to development of airway inflammation
exist between equine RAO and human chronic obstructive
Bacteria Endotoxin
pulmonary disease (poorly reversible airway obstruction
Lipoteichoic acid
occurring primarily in smokers), this latter term is no longer Peptidoglycan
appropriate to describe this condition of horses (Robinson Bacterial DNA
2001). The term inflammatory airway disease (IAD) is Short formylated peptides
used to describe a condition of horses with lower airway Proteases
Toxins
inflammation which does not result in episodes of labored
breathing. Presently, the relationship between IAD and Molds Allergens
RAO is unknown. Glucans
Proteases
While RAO is observed in horses that are stabled and fed Mycotoxins
hay, a similar clinical presentation is observed in some
Forage mites Allergens
horses when pastured; the condition is reversible by hous-
Proteases
ing affected horses in a dust-free stable. This syndrome has
been called summer-pasture-associated obstructive pul- Plant debris
monary disease (SPAOPD) and shares many clinical and Inorganic dust components
pathological similarities with RAO. SPAOPD and RAO do Noxious gases Ammonia
not appear to be mutually exclusive and horses with heaves Hydrogen sulfide
may also develop airway obstruction when pastured in the Methane
absence of hay or straw exposure (Mair 1996b).
565
SECTION 5 : Disorders of the Lower Respiratory Tract
566 41 Recurrent Airway Obstruction (Heaves) and Summer-pasture-associated Obstructive Pulmonary Disease
of SPAOPD is unknown. While inhaled pollens or out- an IgE-mediated mast cell response is not central to the
door molds are a probable cause, tracheal secretions from pathogenesis of heaves. Furthermore, the increase in
affected horses do not have increased concentrations of allergen-specific IgE in horses with RAO may be the result
mold-specific or pollen-specific immunoglobulin G (IgG) of environmental or genetic factors which are unrelated to
and IgE antibodies (Seahorn et al 1997). The possibility disease pathogenesis (Eder et al 2001). An early-phase
that SPAOPD results from ingestion of a pasture-derived response is also not a feature of SPAOPD. Antigen-specific
pneumotoxin has not been eliminated. IgE for various fungi, thermophilic actinomycetes, and a
forage mite in tracheal fluids of horses with SPAOPD were
Hypersensitivity reactions not elevated, suggesting that if an allergic response is
implicated, it may be the result of unrelated environmental
Type I hypersensitivity reaction (allergy) allergens (Seahorn et al 1997). The “late-phase response”
Because exacerbation of clinical signs can be provoked by occurs 6–9 h after allergen provocation and is reminiscent
the inhalation of dusty hay, researchers have postulated of the time-course of recruitment of neutrophils and
that heaves is an allergic reaction to inhaled molds and development of airway obstruction in RAO (Fairbairn et al
fungi. A number of anecdotal findings support this 1993b). While it was previously believed that the late-
hypothesis, including the observation that some RAO- phase response resulted primarily from the release of
affected horses in midwestern USA may become completely mediators by sensitized mast cells, it is now recognized
asymptomatic when moved to central USA, even when that T cells, particularly CD4+ T cells, play a key role in
exposed to locally produced moldy hay (N.E. Robinson, coordinating the asthmatic late-phase response. The under-
personal communication). An emphasis has been directed lying mechanisms by which T cells initiate and propagate
toward the possible roles of Faenia rectivirgula (formerly the inflammatory response include the elaboration of
Micropolyspora faeni), Aspergillus fumigatus and Thermoacti- T helper type 2 (Th2)-type cytokines and chemokines and
nomyces vulgaris, as they are abundant in poor quality hay the interaction with pulmonary leukocytes. Recent reports
(Woods et al 1993). Consistent with this possibility, inhala- suggest involvement of Th2-type cytokines in RAO and
tion of F. rectivirgula or A. fumigatus caused airway obstruc- SPAOPD (see under Lymphocytes below).
tion in animals with RAO, but not in controls (McPherson In summary, the absence of an early response after
et al 1979b, Derksen et al 1988). Inhalation challenge inhalation challenges or following natural exposure to
with timothy hay extracts did not elicit clinical exacer- moldy hay indicates that a classical type I hypersensitivity
bation in affected horses, suggesting that the condition reaction to molds is not central to RAO pathogenesis.
does not result from an allergic response to the hay per se Whether molds or other pro-inflammatory components of
(Lowell 1964). moldy hay may elicit a late-phase response independently
Studies of atopic human asthmatics and various animal from mast cell degranulation remains to be elucidated.
models of allergic pulmonary disease have highlighted
a typical biphasic response when sensitized animals are Type III hypersensitivity (Arthus) reaction
exposed to inhaled allergens. The “early-phase response” Type III hypersensitivity reactions to inhaled allergens
occurs within minutes after susceptible subjects have result from local pulmonary deposition of immune
inhaled an allergen. It is initiated by the activation of cells complexes and the resultant activation of the complement
bearing allergen-specific IgE, primarily mast cells, through system. This reaction requires presensitization, which is
activation of FcεRI receptors. Mast cell activation leads demonstrable by the presence of precipitating antibodies
to liberation of numerous pro-inflammatory mediators, against the offending antigen in the serum of affected
which induce mucus secretion, vasodilation, microvascular individuals. Farmer’s lung disease in humans, a condition
leakage, and airway smooth muscle contraction. Together, associated with a type III hypersensitivity reaction to
these changes result in a narrowing of the airway lumen F. rectivirgula and other thermophilic actinomycetes, shares
and airflow obstruction that typically last less than 45 min many epidemiological similarities with RAO. As in RAO, it
to 1 h. Involvement of IgE-mediated mast cell degranu- affects middle-aged farmers and the disease peaks at the
lation in RAO is supported by the positive passive cuta- time of year when farmers feed stored hay to farm animals.
neous anaphylaxis test observed using sera from horses Similar to RAO, there is a neutrophilic inflammation in the
with heaves (Eyre 1972), the 30-min response after airway secretions of affected patients. Initial reports indi-
intradermal injection of molds and fungi (Halliwell et al cating that RAO-affected horses have high serum precipita-
1979), and the elevated levels of IgE in bronchoalveolar ting antibodies to F. rectivirgula and that they develop
lavage fluid (BALF) (Halliwell et al 1993, Schmallenbach wheals 4 h after intradermal injection of mold extracts
et al 1998) and serum (Eder et al 2000) of affected horses. suggested that RAO involved type III hypersensitivity
However, an early-phase response is not a clinical feature of (Halliwell et al 1979). However, the lung pathology in
RAO, as hours or days of stabling are usually required farmer’s lung disease is strikingly different to that in RAO,
before airway obstruction ensues. This suggests that with the former being a bronchiolitis and alveolitis with
41 Recurrent Airway Obstruction (Heaves) and Summer-pasture-associated Obstructive Pulmonary Disease 567
granuloma formation and extensive fibrosis leading to a cell wall of molds, yeasts, and certain bacteria and plants,
restrictive respiratory pattern. Also, fever, which is a char- can induce inflammation of the airways by non-immune-
acteristic finding in farmer’s lung disease, is not a feature of mediated mechanisms. In horses, hay dust suspensions
heaves. Furthermore, RAO-affected horses that responded with a higher content of β-glucan are more likely to induce
to inhalation challenge with F. rectivirgula often lack serum- airway inflammation, supporting the concept that molds
precipitating antibodies, suggesting that the latter are are involved in the pathogenesis of RAO (Pirie et al 2002).
indicative of high exposure to the antigen as a result of However, whether immune mechanisms are involved or not
poor air hygiene, rather than of an impaired immune in this response remains to be determined.
response (Lawson et al 1979). For these reasons, a type III
hypersensitivity reaction is not currently considered to be Noxious gases
central to RAO pathogenesis. Stabled animals are exposed to various noxious gases that
can induce airway inflammation, including ammonia,
Non-antigen-specific inflammatory responses hydrogen sulfide and methane. However, while the threshold
concentrations of these gases that are required to induce
Typical stabling conditions expose horses to a mixture of inflammation in equine airways is unknown, their levels
irritant gases and airborne dusts which have been shown in stables are generally lower than those in environ-
to cause airway inflammation in humans. Among these, ments used for food-producing animals (Clarke et al 1987).
the contribution of endotoxins, molds, and particulates to Nevertheless, because horses with RAO have non-specific
RAO has been recently investigated. airway hyperresponsiveness, these gases may exacerbate
airway obstruction in affected horses.
Endotoxins
Inhalation of endotoxin by humans and animals induces Bacterial and viral infection
inflammatory lung disease that has many similarities with
RAO. Experimental endotoxin inhalation causes a dose- There is currently no evidence indicating that RAO is an
dependent airway neutrophilia, both in RAO-affected and infectious process. The bacteria that are often present
control horses, but airway dysfunction occurs only in in the tracheal secretions of RAO-affected horses likely
horses with RAO (Pirie et al 2001). However, the concen- reflect colonization of the airways as a result of impaired
tration of endotoxins required to cause airway obstruction mucociliary clearance because histological and cytological
is much greater than the level of exposure occurring findings are not indicative of infection. It had been sug-
during natural hay and straw challenges. Furthermore, the gested, based on circumstantial evidence, that influenza
potency of nebulized hay dust suspension to induce airway and other respiratory infections may predispose horses
neutrophilia and airway obstruction is not related to its to develop RAO.
endotoxin content (Pirie et al 2002). These findings suggest
that although endotoxins may contribute to airway
inflammation in horses, other components of stabled dust,
Pathophysiology
such as molds, are more important for the etiopathogenesis Airway obstruction, inflammation, mucus accumulation,
of RAO (Pirie et al 2001). An additional argument against and tissue remodeling have been shown to contribute to
an important role of inhaled endotoxin in RAO is the the pathophysiology of RAO.
recent observation that concentrations of airborne endo-
toxin in horse stables in Scotland, where RAO is prevalent, Airway obstruction
are similar to those in stables in Australia, where RAO is
comparatively rare (Malikides 2004). The greater response Airway smooth muscle
to inhaled endotoxin in horses with RAO compared with Bronchospasm is a key feature in RAO, as indicated by the
control horses is nonetheless reminiscent of the finding marked improvement in clinical signs and pulmonary
that human asthmatics are more sensitive to inhaled function within minutes of administration of broncho-
endotoxin than healthy control subjects. It has been dilators. Airway smooth muscle contraction is controlled by
proposed that atopy may enhance the sensitivity to inhaled the autonomic nervous system, centrally, via local axonal
endotoxins in asthmatic subjects through the activation of reflexes, and through activation of receptors for a number
airway macrophages and granulocytes. of circulating excitatory and inhibitory molecules that
are present on the smooth muscle cell membrane. Anti-
Molds cholinergic agents and β2-adrenergic agents have similar
The contribution of mold components, including allergens, bronchodilator potency, suggesting that bronchospasm is
glucans, proteases, and mycotoxins, to allergic airway mediated predominantly via muscarinic receptors (Robinson
inflammation is well known in animals and humans. It has 2001). Bronchorelaxation also appears to be defective
been demonstrated that β-D-glucan, a component of the in RAO, due to a reduced inhibitory non-adrenergic
non-cholinergic (NANC) response (Yu et al 1994). Despite oxygen species (superoxide, H2O2, OH– ), proteases (elastase,
these findings, RAO is not considered to be the result of a collagenase, metalloproteinase-9), lipid mediators (LTB4,
primary defect of the airways or their neuromuscular platelet-activating factor, thromboxane A2, LTA4 ), micro-
control mechanisms (reviewed by Robinson 2001). bicidal products (lactoferrin, myeloperoxidase, lysozyme),
Numerous inflammatory mediators, including serotonin, and nitric oxide. The concentrations of many of these
endothelin-1, histamine, and leukotriene D4 (LTD4), increase mediators are increased in the airways of RAO-affected
tension in equine smooth muscle cells and cause bron- horses. Neutrophils also produce potent pro-inflammatory
choconstriction. However, while they may contribute to cytokines such as TNF-α, IL-1β, and IL-6, and the
increased cholinergic airway tone, the latter two mediators chemokines IL-8 and MIP-2 (Joubert et al 2001). These are
are not believed to be major contributors to bronchospasm likely to play an active role in the pathogenesis of RAO.
as neither antihistamines nor leukotriene antagonists are However, neutrophils are unlikely to be direct contribu-
effective for the treatment of heaves (Marr et al 1998a, tors to bronchospasm as their secretory products do not
Olszewski et al 1999, Lavoie et al 2002b). increase equine airway smooth muscle tone in vitro
(Olszewski et al 1999).
Airway inflammation It has been shown that stabling may also lead to airway
neutrophil infiltration in horses without RAO, and that this
Pulmonary inflammation is central to the pathogenesis of may occur in the absence of clinical signs of airway disease
chronic lung diseases and to the development of airway (Tremblay et al 1993, Holcombe et al 2001). However,
obstruction. The contribution of the various leukocytes to neutrophils from these horses appear to be in a reduced
this inflammatory response is emerging. state of activation compared to those of RAO animals
(Tremblay et al 1993).
Neutrophils
Airway neutrophilia is a characteristic feature of RAO Lymphocytes (Th1/Th2 paradigm)
and SPAOPD. Neutrophils accumulate in the airways of Recent studies, using molecular tools and murine models,
RAO-affected horses within 6 h after exposure to moldy have highlighted the complex interactions involved in
hay (Fairbairn et al 1993b, Pirie et al 2001). The airway the modulation of inflammatory lung diseases. Most
neutrophilia persists thereafter if RAO-affected horses are cells present within the lung, including epithelial cells,
continually exposed to stable dust (Jean 1996). Blood myocytes, and neurons, in addition to traditional inflam-
and airway neutrophils are activated in RAO, further matory cells, contribute to this modulation. Among these,
supporting their contribution to lung inflammation T cells (CD4+ cells, more specifically Th2 cells) play a
(Tremblay et al 1993, Marr et al 1997, Pellegrini et al central role in allergic airway inflammation by secreting
1998). However, the mechanisms responsible for their cytokines including IL-4, IL-5, IL-9, and IL-13. Th1 cells
activation and recruitment into the airways, as well as their are important for cell-mediated immunity because they
contribution, if any, to bronchospasm, mucus accumu- produce interferon (IFN)-γ, IL-2, and other cytokines.
lation, and airway remodeling, remain poorly understood. The cytokines produced by each subset of cells act in a
Interleukin-8 (IL-8) is a neutrophil chemokine that may paracrine fashion to promote the growth of their own
be important in the recruitment of neutrophils to the phenotype. Thus, once a particular pathway has been
airways in RAO. IL-8 is synthesized by many cells in entered, the response will be skewed toward that cell line.
the lung, including neutrophils, macrophages, epithelial However, complete polarization into either type of response
cells, endothelial cells, and smooth muscle cells, and its appears to be very uncommon during natural animal
expression is increased in RAO (Franchini et al 2000). In diseases. The current belief is that the balance between the
human asthmatics, the levels of IL-8 correlate both with Th1- and Th2-type responses, rather than the complete
neutrophil numbers and the degree of lung dysfunction. polarization into either phenotype, is important for the
Other cytokines and chemokines that promote tissue modulation of airway inflammation.
neutrophilia, such as macrophage inflammatory protein The polarization of uncommitted T cells (Th0) into
(MIP)-2, IL-1β and tumor necrosis factor-α (TNF-α), either a Th1 or a Th2 response is the result of complex
are also up-regulated in RAO (Franchini et al 2000, interactions between immune cells, including interac-
Giguere et al 2000). Inhalation of LTB4 induces airway tions between the T-cell receptor/CD3 complex and the
neutrophilia, suggesting that it may also contribute to antigen/major histocompatibility complex on antigen-
neutrophil recruitment in equine airway diseases (Marr presenting cells and the presence of additional signals
et al 1998b). Bronchoalveolar lavage (BAL) granulocytes of produced by costimulatory or accessory molecules. Although
horses with heaves have delayed apoptosis, which may the capacity of equine T helper cells to differentiate into
contribute to the airway neutrophilia (Turlej et al 2001). Th1 and Th2 subsets has not been thoroughly investigated,
When activated, neutrophils may cause lung injury by in vitro culture of equine CD4+ T cells following chronic
releasing as many as 50 histotoxins, including reactive allergenic stimulation has induced a Th2 cytokine profile
characterized by an increased expression of IL-4 mRNA eosinophils predominate in equine allergic pulmonary
and a decreased expression of IL-2 mRNA (Aggarwal & diseases (Bowles et al 2002). Furthermore, mRNA expres-
Holmes 1999). Furthermore, consistent with the capacity sion of IL-17, a cytokine secreted by activated T cells that
of horses to develop a Th2-type cell response, ovalbumin indirectly promotes maturation, chemotaxis, and activa-
inhalation by sensitized ponies increased the BAL cell tion of neutrophils, was increased in horses with heaves
mRNA expression of the Th2-type cytokines IL-4 and following exposure to moldy hay (Debrue et al 2004).
IL-13, and decreased the expression of IFN-γ, a Th1 There is also evidence that Th2-type cytokines are impli-
cytokine (Bowles et al 2002). cated in the modulation of the neutrophilic inflamma-
Lower airway inflammation, reversible airway obstruc- tory response. Injection of IL-4 into humans causes a
tion, and bronchial hyperresponsiveness are characteristic neutrophilia (Gilleece et al 1992) and accelerates the
of both equine heaves and human asthma. Asthma is maturation of myelocytes into neutrophils (Bober et al
associated with a predominant Th2-type cytokine expres- 1995). Functional IL-4 receptors are present on human
sion in BAL cells and it had been postulated that a similar neutrophils and their activation leads to cytoskeletal
process occurs in RAO and SPAOPD. Consistent with this, rearrangements, de novo protein synthesis, and inhibition
BAL cells from horses with RAO which had been stabled for of neutrophil apoptosis (Girard et al 1997). Also, horses
several months had an increased expression of the mRNA with RAO have significantly increased numbers of neu-
for Th2-type cytokines IL-4 and IL-5, when compared to trophils that express IL-5 and IL-9 receptors compared to
control horses, while the expression of IFN-γ mRNA was control horses (Al-Dewachi et al 2002). These results
decreased (Lavoie et al 2001). These changes were not provide a possible mechanism by which Th2-type cytokines
detected when the horses were at pasture, but started could play a role in heaves by stimulating neutrophils
within 24 h of exposure to moldy hay (Cordeau et al to release various pro-inflammatory mediators, thereby
2004). Furthermore competitive reverse transcription– amplifying the inflammatory response.
polymerase chain reaction (RT-PCR) revealed increased However, while the above findings support the contri-
expression of IL-4 mRNA in RAO-affected horses after bution of Th2-type cytokines to RAO, other studies have
3 weeks of exposure to moldy hay (Giguere et al 2002). reported contradictory results. The concurrent increases in
Real-time RT-PCR analysis of BAL and peripheral blood the mRNA expression of both IL-4 and IFN-γ noted in some
cells from horses affected with SPAOPD also demonstrated studies suggested a mixed Th1 and Th2 response (Beadle
that clinical disease was associated with elevated levels of et al 2002, Giguere et al 2002, Ainsworth et al 2003).
mRNA for IL-4 (Beadle et al 2002). These findings were In another study, increased IFN-γ without changes in
consistent with the concept that RAO and SPAOPD are Th2-type cytokines suggested a predominant Th1-type
associated with a predominant Th2-type cytokine response. response (Ainsworth et al 2003). The apparently contra-
IL-4 promotes development and growth of the Th2 cell dictory conclusions of these studies may be explained by
phenotype and is essential for the induction of B-cell differences in the methods used for tissue collection and
isotype switching to IgE production (Lasky & Brody 1997). cytokine measurements, duration of exposure to moldy hay
The increase in IL-4 mRNA expression in heaves is before the sampling (chronicity of inflammatory response)
coherent with the elevated levels of antigen-specific IgE and differences in factors such as deworming, vaccination,
in serum and BAL of horses with heaves (Halliwell et al and the quantity and composition of airborne dust in the
1993, Schmallenbach et al 1998, Eder et al 2000). The environment. These findings also highlight the complexity
significance of the increased IL-5 mRNA expression that of the factors that determine the heaves phenotype and
was noted in these studies is less clear, since increased suggest that multiple pathways may lead to this syndrome.
expression of IL-5 mRNA is usually associated with tissue Clearly, more work will be required before a definite
eosinophilia, which is an inconsistent finding in heaves. conclusion can be reached concerning the contribution of
The recent finding that horses with RAO have high levels Th1/Th2-type cytokines to heaves.
of the transcription factor nuclear factor-κB (NF-κB),
consisting mainly of truncated p65 homodimers rather Mast cells
than classic p65–p50 heterodimers, may contribute to the Liberation of pro-inflammatory mediators by mast cells
lack of BAL eosinophilia in heaves (Bureau et al 2000a), following cross-linkage of their membrane-bound IgE
as loss of the p50 locus in knockout mice ablates the receptors is central to acute allergic responses. Within
eosinophilic airway response (Yang et al 1998). minutes after exposure to an allergen, sensitized mast cells
While a Th2-type response is typically associated with release vasoactive molecules, proteases, cyclooxygenase
tissue eosinophilia, pooling of neutrophils in the lower metabolites, cytokines, and chemokines. Among those,
airways of affected horses is characteristic of RAO. histamine contributes to the initial bronchospasm, vascular
Interestingly, allergen inhalation by sensitized ponies leakage, and increased mucus secretion and serves as a
resulted in a predominant Th2-type response and BAL surrogate marker of mast cell activation. In RAO-affected
neutrophilia, suggesting that neutrophils rather than horses, allergen challenge increased the concentration of
histamine in the pulmonary epithelial lining and decreased

BAL mast cell numbers, presumably attributable to their
degranulation (Derksen et al 1988, McGorum et al 1993b).
Furthermore, pulmonary mast cells from RAO-affected
horses degranulate more than mast cells from control
horses in response to in vitro fungal antigen challenge,
suggesting presensitization of mast cells from RAO-affected
horses (Hare et al 1999).
Eosinophils
Bronchoalveolar eosinophilia is uncommon in RAO and
peribronchial eosinophilic infiltrates are inconsistent find-
ings, indicating that eosinophils are not pivotal in RAO
pathogenesis.
Fig. 41.1. Marked goblet cell hyperplasia and mucus accumulation in
a bronchiole from an RAO-affected horse that failed to improve with
Macrophages turning out to pasture and corticosteroid administration. The mucus
Macrophages are a family of antigen-presenting cells that appears to plug the bronchioles and pools of mucus may be seen in
contributes to tissue damage and repair in various inflam- adjacent alveoli.
matory conditions through phagocytosis and the produc-
tion of a wide range of molecules. Pulmonary macrophages
have been divided into four categories based primarily on
their anatomical locations, but only those macrophages heaves (Bureau et al 2000a,b). Also, bronchial epithelial
that can be retrieved by BAL (presumably of the alveolar cells of horses with SPAOPD have increased immunoreac-
type) have been studied in RAO. BAL macrophages from tivity to inducible nitric oxide synthase (iNOS) (Costa et al
RAO-affected horses have a higher density than those from 2001). The iNOS-derived nitric oxide (NO) may contribute
control horses, suggesting an elevated state of activation to the amplification of the airway inflammation, and may
(Tremblay et al 1993). Compared to the general popula- possibly down-regulate Th1 cells, favoring immune devia-
tion, high-density macrophages are generally more cyto- tion towards a Th2-type response. Furthermore, goblet cell
toxic and release more pro-inflammatory mediators hyperplasia and increased mucin accumulation contribute
including superoxide anion, IL-1 and thromboxane B2. to airway obstruction and clinical exacerbation.
Equine macrophages also have the capacity to produce
pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8 and Mucus accumulation
MIP-2, which are potent chemoattractants for neutrophils
(Franchini et al 1998, Joubert et al 2002). Airway mucus accumulation is a consistent finding in
horses with RAO and is associated with neutrophilic
Epithelial cells, smooth muscle, and other airway inflammation and coughing (Robinson et al 2003).
parenchymal and mesenchymal cells When RAO-affected horses have been pastured for several
While the contribution of leukocytes to inflammation weeks and most components of lower airway disease,
has long been recognized, there is emerging informa- including bronchospasm and inflammation, have resolved,
tion highlighting the critical role of mesenchymal and mucus accumulation persists at higher levels than in
parenchymal cells in the modulation of airway inflam- healthy horses (Jefcoat et al 2001). This persistent mucus
mation and tissue remodeling. Epithelial cells are important accumulation may contribute to the residual lung function
in many lung diseases as a consequence of their role as a deficits noted in RAO horses when they are in remission.
physical and functional barrier to inhaled gases and While poorly documented, mucus plugging of airways may
particles and because of the extensive array of receptors also occur in some severely affected heaves horses that are
they possess and mediators they produce. While our relatively unresponsive to environmental change and to
understanding of the role of epithelial cells in RAO and therapy (Fig. 41.1).
SPAOPD is limited, emerging information indicates that A 5-h duration hay and straw challenge resulted in
they may be important modulators of the inflammatory increased tracheal secretions in RAO-affected horses but
response. For instance, bronchial epithelial cells of horses not in controls (Pirie et al 2001). Mucus accumulation in
with heaves have an increased expression of transcription RAO exacerbation is accompanied by decreased mucus
factor NF-κB, a regulator of inflammatory gene expression. clearability resulting from a large increase in mucus
The bronchial activity of NF-κB is correlated with airway viscoelasticity (Gerber et al 2000). Both in exacerba-
function and BAL neutrophilia, and may therefore play a tion and in remission of RAO, there are quantitative and
key role in both airway inflammation and obstruction in qualitative changes in the carbohydrate side chains of
inflation (Beech 1991). Exudate is commonly found within

the airways. Severely affected horses may have emphysema,
both vesicular and interlobular. Right ventricular hyper-
trophy, a common sequel to chronic lung disease in other
species, is not a characteristic finding in RAO, although the
weight of the right ventricle wall may be increased com-
pared to that of the left ventricle (Dixon et al 1982).
Histopathology
In RAO and SPAOPD, mucus, neutrophils, and cellular
debris are commonly present within the airway lumina
(Figs 41.1 and 41.2). The mucus may appear to plug the
bronchioles and pools of mucus may be seen in adjacent
Fig. 41.2. Photomicrograph of the distal airways of a horse with RAO. alveoli (Thurlbeck & Lowell 1964, Kaup et al 1990). The
Peribronchiolar infiltrates with primarily mononuclear cells and distal airways are the primary site of the microscopic
increased smooth muscle mass are present. There are mucus and
inflammatory cells within the airway lumen.
lesions. Common findings include inflammation of the
distal airway wall, epithelial metaplasia and desquamation,
increased smooth muscle mass, and peribronchial fibrosis.
Inflammation of the airway wall is mainly the result of
chronic bronchiolitis with predominantly lymphocytic and
airway mucins, and in particular of α-1,2-fucose (Jefcoat plasmacytic infiltration of the bronchiolar and peribron-
et al 2001). This may be linked both to mucus charac- chiolar regions (Thurlbeck & Lowell 1964, Winder & von
teristics and to the expression of specific mucin genes. Fellenberg 1987, Nyman et al 1991). Goblet cell hyperpla-
MUC5AC, a signature mucin in airway disease of humans sia and metaplasia, and fibrosis of bronchiolar submucosa
and experimental models, but not MUC2, shows robust and alveoli are also common. Aggregates of lymphocytes
expression in large and small airways of RAO-affected and forming small nodules and follicles around the vasculature
control horses (Gerber et al 2003). of the small airways may also be seen (Winder & von
Fellenberg 1987). Peribronchial fibrosis and accumulations
Airway remodeling of eosinophils and mast cells are inconsistent findings. The
large airways may have loss of ciliated epithelial cells, and
Features of airway remodeling in RAO that decrease the peribronchial inflammation of varying severity may be
caliber of the airway lumen include increased smooth observed focally (Kaup et al 1990). All sizes of airways
muscle mass, peribronchial fibrosis and epithelial cell show increased airway smooth muscle mass but this is
hyperplasia (Fig. 41.2). These features may contribute to most marked in the distal airways (Herszberg et al 2004).
progressive impairment in airway function in affected Emphysema (enlarged air spaces resulting from destruc-
horses. The increased smooth muscle mass, in particular, tion of alveolar walls) has been reported in RAO, although
may accentuate airway obstruction due to passive narrow- alveolar hyperinflation as the result of air trapping is
ing of the airway lumen and increased force of muscle more common (Thurlbeck & Lowell 1964, Gerber 1973).
contraction. Furthermore, while the role of airway smooth Furthermore, the subpleural emphysema occasionally seen
muscle has been traditionally restricted to the control of in horses with heaves must be interpreted with caution as
regional ventilation, new evidence indicates that smooth it may also be observed in older horses without respira-
muscle is capable of secreting various cytokines, chemokines, tory disease (Thurlbeck & Lowell 1964). Nevertheless,
and growth factors that may be important in RAO. areas of alveolar emphysema are associated with markedly
increased numbers of Kohn’s pores, allowing increased
collateral ventilation (Kaup et al 1990). Fibrosis, epithelial
Pathology cell metaplasia, and mononuclear cell infiltrates of the
Gross pathology alveolar region may be present in areas with peribronchial
inflammation (Winder & von Fellenberg 1987, Kaup et al
Macroscopic findings in RAO and SPAOPD are variable and 1990). The changes observed in the alveolar regions are
not homogeneously distributed throughout the lungs. The believed to be the result of bronchiolar obstruction and
lungs may be grossly normal, may be slow to collapse or extension of the bronchiolar inflammation to the adjacent
may appear hyperinflated, primarily in the cranial lobes alveoli. When bronchiectasis is present, the cartilaginous
and in the periphery of the caudal lobes. Their normally plates of the dilated bronchus may be widely separated from
pink color may be abnormally pale as a result of hyper- each other and the chondrocytes may appear disorganized.
The number of elastic fibers in the lamina propria may be farm, 17%, 48%, and 67% of the progeny had chronic
greatly reduced (Lavoie et al 2004). pulmonary disease when, respectively, none, one or both
SPAOPD is characterized by an accumulation of mucus, parents had the disease (Marti et al 1991). Similarly, on a
degenerated and sloughed epithelial and inflammatory cells Lippizaner stud farm, 6%, 35% or 44% of the progeny had
(predominantly neutrophils) within the airways, and respiratory diseases when none, one or two parents had a
variable peribronchial smooth muscle hypertrophy and history of chronic respiratory diseases. The study also
inflammation (Costa et al 2000). Fibrosis and emphysema showed that the offspring from an affected stallion had an
are not prominent features of SPAOPD. increased risk of developing chronic respiratory disease
when stabled in a poorly ventilated barn or when fed poor
Clinicopathological correlations quality hay, suggesting that the phenotype is determined by
environmental and genetic risk factors.
In RAO, a good structural–functional relationship has been
observed between bronchiolar alterations in necropsy
specimens and clinical disease severity (Viel 1983, Kaup
Clinical Manifestations
et al 1990). As the histological changes are focal and Natural history
heterogeneously distributed, transthoracic lung biopsy
results may not necessarily correlate with the necropsy RAO and SPAOPD are both seasonal disorders, but they
findings. However, in one study, clinical scores were corre- occur at different times of the year. As RAO is associated
lated with the severity of peribronchial mast cell and bron- with exposure to hay and straw, it is more common when
chiolar neutrophilic infiltrations in lung biopsies (Naylor et horses are stabled during the winter. In contrast, clinical
al 1992). In SPAOPD, histological findings in transthoracic exacerbation of SPAOPD occurs during the warm summer
lung biopsies were highly correlated with those found in months, mainly from June to September, when horses are
post-mortem tissue samples (Costa et al 2000). grazing (Mair 1996b, Seahorn et al 1996). Horses with
SPAOPD usually recover in autumn and are commonly
unaffected during winter. However, those horses that have
Epidemiology both RAO and SPAOPD may have respiratory disease
Prevalence throughout the year, and present a significant diagnostic
and managemental challenge. Both conditions usually
The true prevalence of RAO and SPAOPD, as currently recur from year to year if horses are exposed to the
defined, is unknown. However, chronic pulmonary disorders appropriate environments.
are the most common cause of premature loss through
disease in the Swiss horse population (Gerber 1973). Respiratory manifestations
Breed, sex, gender, and age When in disease remission, horses with RAO and SPAOPD
appear clinically healthy at rest and their respiratory
Horses with RAO and SPAOPD are usually 7 years of age or rate and breathing patterns are usually indistinguishable
older and all breeds and genders are affected. Results from those of unaffected horses. However, because of lung
from a large retrospective epidemiological study conducted remodeling and persistent low-grade airway inflammation
in a North American referral center suggested that females and mucus accumulation, affected horses may remain
may be at increased risk of developing RAO, a finding exercise intolerant or present with an occasional cough at
anecdotally reported 150 years ago (Dun 1859, Couetil & the onset of exercise or when eating. Auscultation during
Ward 2003). However, in most reported studies, both sexes normal tidal breathing is often unremarkable although
were equally affected. There is also conflicting evidence during forced rebreathing some horses may have wheezes
concerning breed predilection, with thoroughbreds being throughout the lung fields and expiratory crackles primarily
either the most likely or the least likely breed to be affected at the periphery of the lungs. Interestingly, a period of clin-
with RAO (McPherson et al 1979a, Couetil & Ward 2003). ical remission of between 1 and 3 months’ duration did
not improve morphological changes in lung biopsies from
Genetic factors RAO horses, suggesting that altered airway morphology
may persist even when clinical signs have resolved (Kvart
It has long been suggested that RAO is a heretable con- et al 1986).
dition, but only recently has a genetic predisposition to During periods of disease exacerbation, the clinical
chronic respiratory diseases been documented in German signs of horses with RAO and SPAOPD are non-specific
warmbloods and Lippizaner horses (Dun 1859, Marti et al and include serous, seromucous or mucopurulent nasal
1991). In a study of German warmbloods on a large stud discharge, coughing, exercise intolerance, and labored
breathing. The frequency and severity of the coughing During severe clinical exacerbations, crackles and
episodes increases as the disease progresses; thus severely wheezes may be auscultated without the use of a rebreath-
affected horses have paroxysmal bouts of deep non- ing bag and thoracic auscultation may detect areas with
productive coughing. In severe cases, an increased res- decreased audibility of breath sounds. Percussion of the
piratory rate, extended neck and head, flared nostrils thorax may occasionally reveal increased resonance of
(Fig. 41.3) and double expiratory effort are evident. A the ventral and caudal borders of the lung fields as a result
“heave line” caused by hypertrophy of the external abdom- of air trapping.
inal oblique muscles may develop. The anus may “pump”,
as a result of forced expiration, and flatulence may occur, Other manifestations
especially when the horse coughs. The appearance and
severity of the clinical signs tend to wax and wane in RAO. Importantly, horses with mild to moderate RAO and
The duration of the exacerbations varies from days to SPAOPD have good appetite and remain alert and afebrile.
weeks and some horses may be asymptomatic at rest Severe cases may develop weight loss, likely as a result of
between exacerbations even if they are maintained in the the increased energy expenditure resulting from the
same deleterious environment. As some horses may require increased work of breathing (Mazan et al 2004). Horses
exposure to moldy hay for 1 month before showing signs of with recurrent fever episodes and severe clinical airway
heaves (Grünig et al 1989), short duration exposure to obstruction may have secondary bacterial bronchopneu-
moldy hay may be ineffective for the detection of heaves- monia or bronchiectasis (Mair 1996a, Lavoie et al 2004).
susceptible horses in a prepurchase situation. Heart rate and cardiac output usually remain within
Fig. 41.3. RAO-affected horse with respiratory distress. Note the characteristic extended position of the head and neck and the dilated nostrils.
normal ranges, although tachycardia and pulmonary both peak inspiratory and expiratory flow. In severe
hypertension are common during clinical exacerbation cases, the rapid contraction of thoracic muscles at the
(Nuytten et al 1988, Seahorn et al 1996). This increase in beginning of expiration is followed by a more prolonged
pulmonary vascular resistance is likely the result of contraction of abdominal muscles at the end of expira-
hypoxemia as it is closely correlated to PAO2 in horses with tion, which cause the typical doubled expiratory efforts
RAO (Nuytten et al 1988). observed of RAO.
Using standard respiratory mechanics techniques

(measurement of esophageal pressures and flow rates),
Assessment of Lung Function lung function parameters of horses with heaves in clinical
Clinical scores remission are not significantly different from those of
normal horses. However, airflow limitation appears to
Clinical scores have been developed to estimate the severity be only partially reversible in some horses with RAO,
of airway obstruction in horses with both RAO and especially when using more sensitive measuring tech-
SPAOPD. These are more useful for the identification of niques, such as determination of airway hyperrespon-
group differences for research purposes than for quanti- siveness, forced oscillation, forced expiration, and volu-
fying the degree of airway obstruction in individual horses. metric capnography.
They are based on grading the clinical signs commonly Airway hyperresponsiveness describes an excessive response
found during severe exacerbation of RAO such as cough, of the airways to intrinsic chemical mediators, such as his-
nasal flaring, nasal discharges, abdominal muscle excur- tamine, or to synthetic analogs of acetylcholine, such as
sion, and movement of the anus. A simple clinical scoring methacholine and carbachol. The cause of airway hyper-
system which graded nasal flaring and abdominal effort responsiveness in RAO is unknown but may include reduced
was found to correlate well with, but be less sensitive than, airway caliber as a result of airway remodeling (increased
standard lung mechanics measurements in RAO (Rush airway smooth muscle mass, goblet and epithelial cell
et al 1998b, Robinson et al 2000). In SPAOPD, a simple hyperplasia, and peribronchial fibrosis), impaired inhibitory
scoring system based on nasal flare and abdominal lift mechanisms that normally limit smooth muscle contraction,
was strongly correlated with maximal change in pleural and sensitization of cholinergic nerves and smooth muscle
pressure (Costa et al 2000). by inflammatory mediators to facilitate smooth muscle
contraction (Robinson 2001). This characteristic feature of
Respiratory mechanics RAO is of clinical relevance because affected horses have
increased susceptibility to develop airway obstruction in
Lung function measurement facilitates objective assess- response to a wide range of specific (such as mold or pollen
ment of the degree of airway obstruction. It is primarily allergens) and non-specific (such as cold air, dry air, exer-
used in research settings because it requires special- cise, irritant dusts) triggers (Obel & Schmiterlöw 1948).
ized equipment and expertise, and has a low sensitivity. While RAO-affected horses have increased airway hyper-
Sequential respiratory mechanics measurements are espe- responsiveness even when stabled in a low-dust environ-
cially useful to assess treatment efficacy. ment (Votion et al 1999, van Erck et al 2003), when they
Robinson et al (2000) reviewed the changes in lung are at pasture their airway responsiveness is indistinguish-
function that occur in heaves: able from that of controls (Derksen et al 1985, Fairbairn
et al 1993a, Votion et al 1999).
the diffuse obstruction of the airways leads to increased Forced oscillation techniques are more sensitive and less
pulmonary resistance due to airflow and tissue resistance invasive than standard respiratory mechanics measure-
and increased dynamic elastance (or decrease in dynamic ments for the diagnosis of heaves (Mazan et al 1999,
compliance), which reflects peripheral airway obstruc- van Erck et al 2003). These techniques may gain popu-
tion, parenchymal tissue remodeling and an uneven larity for the evaluation of equine lung function follow-
distribution of ventilation. To maintain ventilation, a ing the commercial availability of a system measuring
greater effort by the respiratory muscles is applied to the impulse oscillometry, a forced oscillation method that
thoracic wall to expand and compress the lungs, resulting generates pulse-shape signals in a wide range of fre-
in an increase in the variation of pleural pressure during quencies (IOS MasterScreen, Jaeger GmbH, Wurzburg,
each respiration. Also, while the tidal volume remains Germany). Similarly, the forced expiration technique and
generally unaffected or is only mildly decreased, increased volumetric capnography are more sensitive that standard
ventilation is achieved by increasing the respiratory rate respiratory mechanics for the detection of airway obstruc-
and changing breathing strategy by moving air at the end tion (Couetil et al 2000). Whole body plethysmography has
of inhalation and the beginning of expiration, when the also been used to study airway function of horses with
airways are at their widest. This leads to increases in SPAOPD (Beadle 1985); however, the technical difficulties
associated with this method have limited its use in of the horses with RAO have < 25% neutrophils in BAL,
both clinical and research settings. Respiratory inductance suggesting that there is insignificant intra-horse variability
plethysmography is more practical and may prove helpful in neutrophil counts given continuous dust challenge
for the assessment of airway function in field studies (Jean 1996). This finding is in agreement with the recent
(Hoffman et al 2001). proposal that > 25% neutrophils in BAL is necessary in a
research setting for a horse to qualify as being affected
Gas exchange with RAO (Robinson 2001). However, in advanced cases,
labored breathing is occasionally observed in horses with
Arterial hypoxemia is a characteristic finding during clin- only mild (10–20%) airway neutrophilia. As stabling of
ical exacerbation of RAO that reflects uneven distribution both young (Holcombe et al 2001) and older horses which
of ventilation as the result of diffuse but variable airway are free of clinical respiratory disease (Tremblay et al
obstruction. Arterial blood gas analysis allows assessment 1993) may induce an airway neutrophilia, the results of
of the degree of respiratory dysfunction in severely affected BAL cytology should be interpreted in conjunction with
RAO horses and assessment of the response to therapy. the history and other clinical findings. Importantly, the
However, the degree of hypoxemia is poorly correlated with airway neutrophilia in RAO and SPAOPD should not be
pulmonary mechanics (Nuytten et al 1988). In severe interpreted as evidence of bacterial infection, even if
cases, PAO2 values less than 50 mmHg may be observed and degenerate neutrophils with karyolysis and cytoplasmic
may be accompanied by hypercapnia, although PaCO2 vacuolation are also noted. In addition to the airway neu-
usually remains within normal limits (Willoughby & trophilia, large amounts of mucus and increased numbers
McDonnel 1979, Kvart et al 1986). Arterial acidemia is of exfoliated epithelial cells may be seen within the air-
rare because of the compensatory metabolic alkalosis ways. The presence of fungal elements in BAL cell prepa-
(Picandet et al 2004). rations suggests impaired mucociliary clearance and/or
The prolonged nitrogen washout in horses with RAO exposure to high levels of airborne organic dust, rather
is consistent with the presence of small airway disease than fungal infection of the airways. Curschmann’s spirals,
and correlates with the severity of histological lung which are coils of inspissated mucus fibrin, may be observed
changes (Willoughby & McDonnel 1979, Viel 1983). (Fig. 41.4). RAO-affected horses rarely have increased
Increased dead space ventilation and ventilation of high numbers of metachromatic cells and eosinophils in their
• •
VA/Q regions were not correlated with clinical signs or airway secretions (Winder et al 1990, Vrins et al 1991).
lung biopsy (Nyman et al 1991). However, there was a Tracheal aspirates comprise secretions from both the
strong correlation between the extent of bronchiolar peripheral and central airways throughout the lungs.
• •
epithelial hyperplasia and ventilation of high VA/Q regions Neutrophil counts in tracheal aspirates are poorly corre-
and dead space (Nyman et al 1991). Alveolar clearance, lated with BAL neutrophil counts and with lung histology
measured using scintigraphy, is a sensitive technique in RAO (Larson & Busch 1985, Derksen et al 1989, Winder
to quantify the ventilation–perfusion mismatch in RAO et al 1990, Traub-Dargatz et al 1992). Furthermore, the
(Votion et al 1999). neutrophil percentages found in tracheal washes of normal
horses vary widely, and the cytological features observed
in RAO are non-specific and occur in a number of other
inflammatory lung diseases. The presence of bacteria in
Laboratory Findings tracheal aspirates from RAO- and SPAOPD-affected horses,
Pulmonary cytology and bacteriology in the absence of clinical signs of bacterial infection (fever,
anorexia, depression), most likely represents secondary
Cytological examination of respiratory tract secretions is colonization of the large airways and reduced mucociliary
commonly used for the diagnosis of equine lower air- clearance, rather than primary bacterial infection.
ways diseases. Since RAO is associated with diffuse lung
pathology, the cytological findings of BAL samples from Hematology and serum biochemistry
different lung segments show good correlation (McGorum
et al 1993a, Jean 1996). The hemogram, leukogram, and fibrinogen concentration
Macrophages and lymphocytes are the predominant cell are usually within reference ranges in RAO and SPAOPD.
populations in BAL from normal horses and the propor- Mild and inconsistent increases in packed cell volume,
tions of other cell types are negligible (Fig. 41.4). RAO and as the result of elevated mean erythrocyte corpuscular
SPAOPD are characterized by a BAL neutrophilia (RAO volume, have been reported in some horses with chronic
neutrophils > 25%, controls ≤ 5%), the degree of which respiratory diseases (Gerber 1973). These analyses may,
is poorly correlated with the severity of clinical signs however, be performed to aid detection of secondary
(Grünig et al 1989). In a study where BAL was performed bacterial infection in severely affected horses that are
at monthly intervals for 3 months, on no occasion did any febrile or unresponsive to therapy.
A C
B D
Fig. 41.4. BAL cytology from a control horse (A,B) and a horse with control, there are numerous neutrophils (white arrows) in the RAO-
RAO (C,D). While lymphocytes and macrophages predominate in the affected horse. A Curschmann’s spiral (black arrow) is also present (D).
Imaging techniques et al 1978, Seahorn & Beadle 1993). Localized radiolucent

areas, suggestive of emphysematous bullae, occur rarely in
Endoscopy advanced cases. The presence of single or multiple dis-
Endoscopy of the lower airways of horses with RAO and tended bronchi is indicative of bronchiectasis (Fig. 41.5).
SPAOPD generally reveals variable amounts of mucopus
within the trachea. The tracheal carina may be thickened Other imaging techniques
and the tracheal and bronchial mucosa may be hyperemic Thoracic ultrasonography of RAO-affected horses is
(Mair 1996b). Dynamic collapse of the intrathoracic air- usually unrewarding, although the surface of the visceral
ways may occur during coughing. The presence of dis- pleura may have irregular echogenicity. Scintigraphic
tended and irregular bronchial walls suggests bronchiectasis, determination of the alveolar clearance rate is a sensitive
a sequel of severe RAO (Lavoie et al 2004). method of detecting lung damage that facilitates detec-
tion of RAO-affected horses even when they are clinically
Radiography asymptomatic (Votion et al 1999).
Radiographic examination of the thorax is often unre-
markable but may reveal an increased bronchointerstitial Immunological testing
pattern. Flattening or concavity of the diaphragm is
indicative of alveolar hyperinflation, and may be reversible Intradermal allergen testing is an accepted method for the
when affected horses attain clinical remission (McPherson detection of allergen hypersensitivity in atopic humans and
Table 41.2. Criteria commonly used for the clinical

diagnosis of RAO and SPAOPD
Signalment Horses are usually 7 years of age or older
No sex or breed predispositions
History Respiratory problem of > 3 months’ duration

Period of labored breathing (nasal flaring,
expiratory effort), reversible with broncho-
dilator, corticosteroids, pasture (RAO) or
stabling (SPAOPD)
Clinical Horses are afebrile, bright, and alert unless in

findings respiratory distress
Labored breathing with doubled expiratory
effort and heaves line may be present
Crackles and wheezes are audible on thoracic
auscultation
BAL cytology >25% neutrophils during disease exacerbation

Normal cytology when in disease remission
Thoracic Not performed routinely

radiography May be used to exclude other conditions such
as pneumonia or neoplasia
Usually normal chest, but bronchointerstitial
patterns, hyperinflation, and emphysematous
bullae may be present
Bronchiectasis in severe cases
as a non-invasive method for the diagnosis of airway

inflammatory diseases. To date, this methodology is not
Fig. 41.5. Thoracic radiograph of a horse with cylindrical bronchiec-
tasis. Multiple cavitary lesions are present throughout the lung field used in clinical settings.
and the bronchial walls are thin and regular.
Diagnosis and Differential Diagnosis

domestic animals. Horses with RAO have immediate Diagnosis
(30–60 min), late-phase (4–6 h), and delayed (24–48 h)
reactions to environmental allergens. However, intradermal In clinical practice, a diagnosis of RAO and SPAOPD
testing is not discriminating of health status because most (Table 41.2) is generally based on the signalment
horses have positive skin reactions to common barn (horses > 7 years of age), history (bright, alert, coughing
allergens, although horses with heaves tend to have a episodes of > 3 months’ duration, normal appetite, absence
greater number of positive skin reactions at both 30 min of pyrexia) and results of clinical examination (double
and 4 h. A radioallergosorbent test and two enzyme-linked expiratory effort, dilated nostrils, abnormal breath sounds
immunosorbent assays are commercially available in the on auscultation of the cervical trachea and both hemi-
USA, but they failed to reliably detect allergen hyper- thoraces). The diagnosis can be confirmed by demon-
sensitivity when compared to intradermal testing (Lorch strating airway neutrophilia and the reversibility of airway
et al 2001). For these reasons, intradermal mold antigen obstruction with environmental dust control or with bron-
testing and the evaluation of serum antibody titers against chodilators (Table 41.3). Inhaled bronchodilators are well
common environmental antigens appear to be of little tolerated in horses and may improve the clinical signs of
value in the diagnosis of equine RAO. airway obstruction within minutes of administration.
Analysis of exhaled markers Differential diagnosis

of inflammation
A thorough history and clinical examination usually suffice
Analysis of inflammatory mediators or related molecules in to differentiate RAO from other conditions that may cause
breath condensate and exhaled breath is being evaluated clinical signs of lower airway disease.
Table 41.3. Medications recommended for the treatment of acute exacerbations of RAO
and SPAOPD: suggested dosages are indicative only
Medication Dosage
Corticosteroids
Dexamethasone 0.04–0.1 mg/kg q24h IV

0.164 mg/kg q24h PO, preferably before feeding
Dexmethasone-21-isonicotinate 0.04 mg/kg q3 days IM
Isoflupredone acetate 0.03 mg/kg q24h IM
Triamcinolone acetonide 20–40 mg* IM
Beclomethasone dipropionate (CFC) 3,500 μg/horse, q12h in MDI (Equine Aeromask®)

Beclomethasone dipropionate (HFA) 1,320 μg/horse, q12h in MDI (3M Equine Aerosol Delivery System®)
Fluticasone propionate (CFC) 2,000 μg/horse, q12h in MDI (Equine Aeromask®)
Bronchodilators
Clenbuterol 0.8–3.2 μg/kg PO q12h

0.8 μg/kg IV
Aminophylline 5–10 mg/kg PO q12h
Fenoterol 1–2 mg/horse, q1h, in MDI (Equine Aeromask®)
Albuterol 0.8–2 μg/kg, q1h, in MDI (3M Equine Aerosol Delivery System‚ Equine Aeromask®)
Pirbuterol 1.3 μg/kg q7h, in MDI (3M Equine Aerosol Delivery System‚ Equine Aeromask®)
Salmeterol 0.5–1 μg/kg, q6h, in MDI (Equine Aeromask®)
Ipratropium bromide 180–450 μg/horse, q6h, using a mechanical nebulizer

0.4–1 μg/kg, q6h, in MDI (Equine Aeromask®)
2,400 μg/horse, q6h, using a DPI (EquiPoudre®)
Cromones
Sodium cromoglycate 80 mg/horse, q24h for 4 days using a mechanical nebulizer

200 mg/horse, q12h, in MDI (Equine Aeromask®)
* The usual dose for a horse that weighs 450–500 kg.

CFC, chlorofluorocarbon; DPI, dry powder inhaler; HFA, hydrofluoralkane; MDI, metered-dose inhaler.
IAD Viral infection

IAD and RAO share a number of clinical, cytological, The short duration of the respiratory symptoms resulting
and functional similarities. However, the lack of labored from viral infections allows their differentiation from RAO.
breathing in IAD permits differentiation from RAO.
The differences between the two disorders are further Chicken hypersensitivity pneumonitis
highlighted in Table 42.1 in Chapter 42. This uncommon condition develops when horses share
stabling with chickens, especially when the chickens roost
Bronchopneumonia above the stables (Mansmann et al 1975). The clinical
Manifestations of sepsis, such as fever, depression, signs of this disorder resemble those of RAO, and include
decreased appetite, and weight loss, are usually present coughing, obvious airway obstruction, and rapid reversal of
in bacterial or fungal bronchopneumonia and pleuro- clinical signs when horses are removed from the causal
pneumonia but are absent in RAO. However, in horses with allergens.
severe exacerbation of heaves, or when bronchiectasis is
present, febrile episodes, anorexia and weight loss may Neoplasia
occur. In these horses complete blood count, plasma Thoracic neoplasia may present with numerous clin-
fibrinogen estimation, and thoracic radiography may be ical signs, some of which may resemble RAO. Thoracic
necessary to exclude the presence of bacterial infections. radiography and ultrasonography, cytological analysis
Table 41.4. Practical management of RAO

1. The clinical signs of RAO are reversible, but chronic cases may develop incompletely reversible lung dysfunction
2. Reduce airborne dust levels
a. Most effective means to control the clinical signs and prevent the progression of RAO
b. May take up to 6 weeks before clinical signs subside
c. Remove hay from diet
d. Turning horse out to pasture without hay supplement is ideal
e. Pelleted hay and cubes are practical but may be associated with development of stereotypic behavior
f. Hay silage may be associated with botulism in certain countries
g. Use low dust bedding such as wood shavings or shredded paper
h. Ensure adequate stable ventilation
i. Prevent exposure to dust particles (house horse away from hay stores, remove horse from stable while mucking out the stall)
3. Corticosteroids
a. Most effective drugs
b. Clinical signs will return if not combined with environmental dust control
c. May be associated with severe side effects
d. Inhaled corticosteroids are preferable for prolonged therapy, however:
(i) Expensive and time consuming
(ii) Inadequate administration techniques may result in treatment failure
(iii) Mask is poorly tolerated when labored breathing is present
4. Bronchodilators
a. Offer symptomatic relief only
b. Should be combined with environmental dust control and/or corticosteroid therapy
c. Variable efficacy in horses with labored breathing
d. May improve the delivery of inhaled corticosteroids to the small airways
of lower airway specimens and histological findings of and cleaning of the stable) and increasing ventilation to
transthoracic or bronchial biopsies may help confirm remove the airborne dust (Clarke et al 1987, Woods et al
the diagnosis. 1993). The replacement of hay and straw by less dusty feed
and bedding material is central to the management of
Lungworm horses with RAO. Pelleted or cubed hay, hay silage and
Horses with Dictyocaulus arnfieldi infection may have clin- hydroponic hay are well tolerated and relatively free of
ical signs similar to those of RAO, including paroxysmal dust, although mild degrees of inflammation and abnormal
coughing, crackles and wheezes on thoracic ausculta- lung function may persist when horses are fed grass silage
tion, and increased respiratory effort (George et al 1981). and bedded on wood shavings, as indicated by increased
Clinical diagnosis of lungworm is based on a history of airway responsiveness (Vandenput et al 1998a, Votion et al
contact with mules or asses and, occasionally, the presence 1999). Soaking hay in water for 2–4 h before feeding
of eosinophils and immature D. arnfieldi in tracheal aspirates. may control heaves in some horses, while it affords only
The resolution of the clinical signs with appropriate para- partial or no improvement in others (Beech 1991). Wood
siticidal drugs may further help to differentiate lungworm shavings, shredded paper, peanut kernels, and peat moss
infection from RAO. are good substitutes for straw, although a recent study
failed to find differences in airway function in heaves-
susceptible horses fed silage that were bedded on good
Treatment of RAO and SPAOPD quality straw or shavings (Vandenput et al 1998b). This
(Tables 41.3 and 41.4)
may be explained by the finding that good quality straw
Environmental control has low dust particle content (Vandenput et al 1997).
Other common recommendations include use of a box stall
Reduction of exposure to environmental dust is essential away from the hay chute, removing the horse from the
for the successful long-term management of horses with stable when cleaning the box stall, and watering the aisles
RAO and SPAOPD. In RAO, remission of clinical signs and before sweeping to decrease the airborne dust. Proper
airway inflammation is best achieved by pasturing affected ventilation is also important, although identifying the
horses all year long. When this is not possible, exposure to optimal ventilation system to minimize dust levels is
airborne stable dust can be diminished by changing the problematic.
feedstuff and bedding, decreasing the degree of agitation of The reversal of clinical signs of RAO with strict environ-
the source material (which occurs primarily during eating, mental changes may start within a few days but may take
up to 3–4 weeks (Thomson & McPherson 1984). The corticosteroids have proven efficacy for the acute manage-
remission time correlates with age and the duration and ment of clinical exacerbations of RAO (Table 41.3). After
severity of illness (Thomson & McPherson 1984). In a the clinical signs have subsided, drugs are empirically
study where clinical cases of heaves were re-evaluated after administered at decremental doses and on alternate days
6 weeks of environmental dust control, only seven of 73 until an effective maintenance dose is reached or treat-
horses had BALF neutrophil ratios exceeding 8% (Dixon et ment can be discontinued. Prolonged systemic adminis-
al 1995). Horses kept permanently outdoors and fed grass tration of corticosteroids is to be avoided because of the
or hay substitutes usually remain free of clinical signs, widely feared, but poorly documented, side effects such
airway inflammation, bronchial reactivity, and abnormal as laminitis and enhanced susceptibility to infections.
alveolar clearance. However, supplementing horses with With recommended dosages of corticosteroids, pulmonary
hay while at pasture may lead to airway neutrophilia, even inflammation often persists and, unless a strict environ-
in the absence of abnormal airway function at rest mental regimen is concurrently implemented, the clinical
(Tremblay et al 1993). Horses do well when kept outdoors, signs of RAO are likely to recur rapidly following the
even in very cold conditions, provided they have enough cessation of drug administration.
food, fresh water (heated water tub), and shelter. Reported adverse effects of systemic corticosteroid
Environmental control is also central to the success- administration to RAO-affected horses include adrenal
ful management of SPAOPD. Affected horses should be suppression, altered bone metabolism, laminitis, bacterial
removed from pasture and placed in a low-dust environ- pneumonia, neutrophilia, lymphopenia, and eosinopenia.
ment (Beadle 1983). As with RAO, it may take several days To date, the only adverse effect attributed to inhaled
before an improvement in clinical signs is noted. However, corticosteroids is a decrease in serum cortisol (Rush et al
in some cases, and in horses with labored breathing, 1997). While the clinical significance of the adrenal
stabling alone may not be sufficient and administration of suppression remains to be determined, laminitis and
bronchodilators and corticosteroids may also be required bacterial pneumonia appear to be very uncommon when
(Mair 1996b, Seahorn et al 1996). corticosteroids are used for the treatment of heaves.
Systemic corticosteroids
Medications DEXAMETHASONE Dexamethasone is the most commonly
used corticosteroid for the treatment of RAO in North
Medications are required for the control of RAO when
America. While clinical improvements may be observed
appropriate environmental dust control cannot be fully
within a few hours of therapy (Cornelisse et al 2004), a
implemented or when more rapid relief of airway obstruc-
delay of a week or longer can be expected before achieving
tion is required (see Chapter 7).
the maximal improvement in lung function when con-
current dust control measures are not implemented. In
Anti-inflammatory agents horses with labored breathing, dexamethasone may be
combined with a bronchodilator to provide more rapid
As inflammation is believed to play a central role in the
symptomatic relief. Episodes of severe airway obstruction
pathophysiology of RAO, a number of anti-inflammatory
have been effectively treated with dexamethasone [initial
agents have been evaluated for the treatment of RAO
dose 0.04–0.1 mg/kg, q24h intravenously (IV)] (Rush et al
including corticosteroids, phosphodiesterase inhibitors,
1998b, Lavoie et al 2002a). Intramuscular administration
anti-leukotriene therapies, and other non-steroidal anti-
of dexamethasone-21-isonicotinate (0.04 mg/kg) every
inflammatory drugs.
3 days was considered effective in eight of nine horses
(Robinson et al 2002). A single oral administration of a
Corticosteroids dexamethasone solution formulated for intravenous use
Corticosteroids are the most potent anti-inflammatory (0.164 mg/kg) improved the airway function of horses
drugs currently available for the treatment of RAO. They with RAO for up to 30 h (Cornelisse et al 2004). In the
improve airway function by decreasing smooth muscle same study, fasting the horses before drug administra-
contraction by inhibiting the effects of inflammatory tion improved drug efficacy. However, oral administration
cells and their mediators, potentiating the bronchodilatory of lower dosages of dexamethasone (0.02–0.05 mg/kg,
effects of catecholamines, and by reducing mucus pro- q24h for 7 days) produced inconsistent improvement
duction. Interestingly, horses that fail to improve with (Cesarini et al 2004). Administration of dexamethasone
bronchodilators alone may have a marked improvement in (0.05–0.1 mg/kg q24h IV) for 10–14 days attenuated
airway function when treated with corticosteroids and airway obstruction but pulmonary neutrophilia per-
environmental dust control. Corticosteroids may be admin- sisted (Rush et al 1998a, Lavoie et al 2002b, Robinson
istered orally, systemically or by inhalation. A number of et al 2002). Thus the control of airway neutrophilia
with dexamethasone appears to be dose related, and advantageous because they are easy to use and the amount
while compared in different studies, IV administration of of drug delivered is constant. MDIs are administered
dexamethasone at 0.1 mg/kg, but not at 0.05 mg/kg, to horses using a mask and a spacer, or other specially
resulted in a significant decrease in BALF neutrophilia developed devices to maximize drug delivery to the lower
(Lavoie et al 2002b, Robinson et al 2002). airways. Administration of drugs by positioning the MDI
directly into a nostril is not recommended because it is
ISOFLUPREDONE ACETATE Isoflupredone acetate admin- unlikely to result in delivery of therapeutic dosages of drug.
istered by the intramuscular route (0.03 mg/kg q24h) Efficacy varies according to drug potency, the inhalation
is as effective as dexamethasone (0.04 mg/kg IV q24h) device, and the propellant. Until recently, chlorofluoro-
in improving the airway function of horses with RAO carbons (CFCs) were the most commonly used propellant
(Picandet et al 2003). Isoflupredone has a greater min- for MDIs. However, because of their detrimental effect
eralocorticoid effect than dexamethasone but the hypo- on the ozone layer, they are being replaced with newer
kalemic myopathy reported in cattle and in people treated environmentally friendly gas propellants. As these alterna-
with this drug has not been reported in horses. tive propellants are delivered in a manner that does not
mimic CFCs, the potency of some drugs is greatly affected.
PREDNISOLONE Prednisolone is considered to be less potent As these propellants become available, marked variations in
and toxic than the aforementioned corticosteroids and has drug efficacies and potential toxicities might be expected
been used for the treatment of mildly affected horses or for if they are not evaluated in horses. For these reasons, the
maintenance therapy (Beech 1991). Prednisolone adminis- dosages recommended here are indicative only and are
tration [0.4 mg/kg intramuscular (IM) q24h] for 3 days likely to change with various combinations of devices
failed to improve the airway function of RAO horses, but and propellants. Masks used in combination with an MDI
improved airway hyperreactivity to inhaled histamine in or a DPI will increase airflow resistance and therefore may
seven of eight horses. The clinical significance of these not be suitable for the initial treatment of horses in respi-
findings remains to be ascertained. Oral prednisolone ratory distress.
(1 mg/kg q48h) controlled clinical signs in a horse with
RAO that was only partially responsive to strict environ- BECLOMETHASONE DIPROPIONATE Beclomethasone dipropi-
mental control and bronchodilators (Mair 1996a). However, onate administered via an MDI improves respiratory
after 4 months of prednisolone administration, the horse mechanics in RAO affected horses within 3–4 treat-
developed a severe bacterial pneumonia. ment days (Table 41.3). The maximal beneficial effects
are usually observed during the first week of therapy.
PREDNISONE Prednisone, orally administered, is poorly Beclomethasone also significantly decreased neutrophil
absorbed in horses and appears to be of little benefit, if any, percentages in BAL and prevented the increase of CD4+ T
in the treatment of RAO (Traub-Dargatz et al 1992, Peroni cells associated with exposure to moldy hay (Rush et al
et al 2002, Robinson et al 2002). 1998a). However, the magnitude of response to aerosolized
beclomethasone was less than that to dexamethasone
TRIAMCINOLONE ACETONIDE Triamcinolone acetonide at a (0.1 mg/kg IV q24h) (Rush et al 1998b). There is a three-
dosage of 20–40 mg/500 kg IM is a potent corticosteroid fold range in the dosages of beclomethasone that have
that improved the airway function of RAO-affected horses been reported to be effective for the treatment of RAO
for up to 5 weeks, even in severely affected cases (Lapointe (Ammann et al 1998, Rush et al 1998a,b). The lowest
et al 1993). Because long-acting corticosteroids are more dosage was effective when using a hydrofluoroalkane
likely to induce adverse effects such as laminitis, triamcin- propellant attached to a device that has been shown to
olone is not recommended for the routine control of RAO. increase drug delivery to the distal airways of horses, but
which is not currently commercially available (Rush
Inhaled corticosteroids et al 1998a,b).
Inhalation therapy is well suited for corticosteroid admin-
istration because of the large number of glucocorticoid FLUTICASONE PROPIONATE Fluticasone propionate (Table
receptors present on bronchial epithelial cells and vascular 41.3) is a newer, potent corticosteroid that relieves airway
endothelial cells. Inhalation therapy provides the maximal obstruction and decreases neutrophil percentages in BAL
concentration of drug at the effector sites and minimizes when administered by an MDI and mask to RAO affected
side effects. Inhaled corticosteroids are therefore preferable horses (Giguere et al 2002). Fluticasone also decreases
over systemic administration when prolonged therapy is the expression of IL-4 mRNA in BAL and increases the
required. Inhaled drugs are delivered to a horse using a IFN-γ : IL-4 ratio, suggesting that a modulation towards
mechanical nebulizer, a metered dose inhaler (MDI), and, a Th1 response may contribute to the benefit of corti-
less commonly, with dry powder inhalers (DPI). MDIs are costeroids in RAO (Giguere et al 2002). Interestingly, there
was no reduction in IL-8 in BAL with this therapy, failed to improve the pulmonary function of horses with
indicating that other mediators are also important con- RAO (Thomson & McPherson 1983).
tributors in the persistence of airway neutrophilia. Pentoxifylline, a non-specific PDE inhibitor, is currently
The information available to date in horses suggests that approved in some countries for the treatment of navicular
the short-term administration of inhaled corticosteroids is disease in horses. It is also a bronchodilator, inhibits neu-
efficacious and well tolerated but unfortunately these drugs trophil recruitment to inflammatory sites, and at high
have short residual effects when therapy is discontinued. concentrations is a potent inhibitor of TNF-α production.
Since a delay in response is expected with inhaled cor- High doses of pentoxifylline (16 g/horse, q12h) were as
ticosteroids, when used to treat horses in respiratory beneficial as atropine for the relief of airway obstruction
distress they should be combined with faster acting drugs, in RAO horses, but failed to reduce BAL neutrophilia
such as bronchodilators or systemic corticosteroids in this (Leguillette et al 2002). However, the oral absorption of
situation. Horses may become reluctant to inhale the pentoxifylline is limited and the efficacy of more practical
medication after a while, although replacing the poorly lower dosages needs to be assessed.
tolerated drug with another of the same class will often
overcome this problem. Selective PDE inhibitors
Selective PDE inhibitors, particularly of the PDE4 subtype,
have been studied for the treatment of lower inflamma-
Phosphodiesterase inhibitors
tory airway diseases in people owing to the expression of
Methylxanthine derivatives
PDE4 in airway smooth muscle, pulmonary nerves, and
Aminophylline and pentoxifylline are methylxanthine almost all inflammatory and immune cells relevant to the
derivatives with non-specific phosphodiesterase (PDE) pathogenesis of asthma. A selective PDE4 inhibitor effec-
inhibitory properties. The PDEs are a family of enzymes tive at inhibiting the ex vivo production of inflammatory
that catalyze the hydrolysis of cAMP and cGMP and mediators by equine leukocytes was ineffective for the
thereby terminate their role as secondary messengers treatment of heaves-affected horses (Lavoie et al 2002a).
in mediating cellular responses to various hormones and
neurotransmitters. Activation of cAMP by PDE may be a
common mechanism to facilitate pro-inflammatory effects Anti-leukotrienes
of cytokines and other proliferative agents. Aminophylline Of the various mediators that are known to be involved in
is used primarily as a bronchodilator in horses but it also pulmonary inflammatory diseases, leukotrienes are con-
enhances mucociliary clearance, respiratory drive, and sidered to be amongst the most important. Leukotrienes
contractility of the diaphragm and modulates immune are metabolites of the arachidonic acid produced via
function. Adverse effects, such as excitability, tachycardia, the 5-lipoxygenase enzyme and its essential cofactor, the
muscular tremors, and sweating, are commonly observed. 5-lipoxygenase-activating proteins (FLAP). Cysteinyl leuko-
Theophylline administered intravenously at 12 mg/kg trienes (LTC4, LTD4, LTE4) are potent bronchoconstrictors
over a 15-min period improved airway function in seven that also increase airway vascular permeability and mucus
of 14 horses within 45 min of administration (Pearson production. Furthermore, the main receptor for cysteinyl
& Riebold 1989); however, horses became excitable and leukotrienes, CystLT1, is present on the bronchi of horses
hyperesthetic and some developed muscle tremor. Theo- (Lavoie et al 2002b). However, administration of the LTD4
phylline plasma concentrations of 10 μg/ml or more result receptor antagonist, a 5-lipoxygenase inhibitor and a FLAP
in bronchodilation in ponies with RAO, but adverse effects antagonist was ineffective in treating RAO (Marr et al
are noted when the concentration exceeds 16 μg/ml 1998a, Robinson et al 1998, Lavoie et al 2002b, Kolm
(McKiernan & Koritz 1990). Because of their low thera- et al 2003). These results are consistent with the finding
peutic index, aminophylline and other salts of theophylline that BALF from RAO horses contains only low concentra-
are not routinely used for the management of RAO. Recent tions of cysteinyl leukotrienes (Watson et al 1992).
findings in humans indicate that low-dose theophylline has
anti-inflammatory and immunomodulatory effects and Cromones
potentiates the effects of corticosteroids in patients with The mechanism of action of cromones in heaves is
asthma (Barnes 2003). However, administration of theo- unknown but may include stabilization of inflammatory
phylline [5 mg/kg q12h per os (PO)] for 7 days failed to cells and a local effect on nerve endings. They have been
improve airway obstruction of RAO-affected horses or used primarily prophylactically, to prevent clinical exacer-
to increase the efficacy of low-dose dexamethasone bation, but data regarding their efficacy in RAO are
(Cesarini et al 2004). The potential synergetic effects of conflicting. In one study the preventative effect of sodium
more prolonged administration of theophylline and cor- cromoglycate (80 mg q24h for 4 days using a mechanical
ticosteroids in horses remain to be evaluated. Oral admin- nebulizer) persisted up to 3 weeks (Thomson & McPherson
istration of etamiphylline, a theophylline derivative, also 1981), while in another report that used 520 mg, q24h for
2 days, it failed to prevent clinical exacerbation, although it can be prevented or reversed by dexamethasone admin-
did attenuate pulmonary resistance in a dose-dependent istration, the therapeutic benefits of combined use of
manner (Soma et al 1987). Sodium cromoglycate can also glucocorticoids and β2-agonists should be investigated
be administered using an MDI (10–12 mg/horse, once a (Abraham et al 2002). In SPAOPD, a dosage of 0.8 mg/kg
day). A similar mast cell blocker is nedocromil sodium, which IV improved lung function from 30 min to 2 h post
can be administered at a dose of 10–20 puffs (1 mg/puff) administration (Beadle 1985).
three times per day. Terbutaline sulfate, another β2-adrenergic agonist, is
rapidly cleared from the blood following intravenous
Non-steroidal anti-inflammatory drugs administration to horses, and has low bioavailability when
Although various metabolites of the cyclooxygenase path- administered orally (Torneke et al 2000). However, terbu-
way have been detected in airway secretions of horses with taline (0.02 mg/kg in saline, total volume 4 ml) admin-
chronic airway diseases, non-steroidal anti-inflammatory istered using a mechanical nebulizer resulted in bron-
drugs are not of therapeutic benefit in RAO. The admin- chodilation that lasted up to 4 h (Murphy et al 1980).
istration of antihistamines is also of limited value for the Fenoterol, albuterol, pirbuterol and salmeterol are also
treatment of RAO. β2-agonists with potent bronchodilator effects that can be
administered by inhalation (Table 41.3). With the except-
Bronchodilators ion of salmeterol and pirbuterol, bronchodilation induced
Bronchodilators are used to relieve obstruction caused by by inhaled β2-agonists occurs rapidly and adverse effects
airway smooth muscle contraction and to aid clearance of are minimal. However, the beneficial effects are short-lived
airway secretions. Unlike corticosteroids, their action is (duration <1 h) thus requiring frequent drug adminis-
rapid in onset but short-lived. Bronchodilator administration. Salmeterol has an onset of action of 30–60 min
tration should be combined with strict environmental but its effect lasts up to 6 h (Henrikson & Rush 2001).
dust control and/or corticosteroid administration because Pirbuterol administration improves lung function within
inflammation of the lower airways may progress despite 5 min of drug administration and its effect lasts up to 7 h
the transient improvement in clinical signs observed with (Derksen et al 1996). The use of sympathomimetic agents
these drugs. As a result of their rapid onset of action, such as ephedrine which stimulate both α- and β-receptors
bronchodilators are particularly helpful when immediate has decreased because they are less efficacious than more
relief of clinical signs is required. Administration of bron- specific β2-adrenergic agonists, and are more likely to be
chodilators in RAO may cause a transient worsening of associated with adverse effects.
hypoxemia, possibly as the result of an increase in
physiological dead space (Gallivan & McDonell 1989). Anticholinergics
Although this rarely appears to lead to clinical problems, it As a result of their potentially severe adverse effects, anti-
may be advisable to combine inhaled bronchodilators cholinergic drugs are generally not administered system-
with intranasal oxygen insufflation in horses with severe ically for the treatment of heaves. Atropine (0.01–0.02 mg/kg
respiratory distress and profound hypoxemia. The agents IV) provides rapid bronchodilation of short duration (less
most commonly used for bronchodilation in horses are than 2 h) but is associated with tachycardia, mydriasis,
β2-adrenergic agonists, antimuscarinic agents, and methyl- increased viscosity of respiratory secretions, ileus, and
xathine derivatives. occasionally severe abdominal pain (Beadle 1983, Thomson
& McPherson 1983). Adverse effects are also observed
␤2-adrenergic agonists (Table 41.3) when atropine (0.02 mg/kg in saline, total volume 4 ml)
Clenbuterol has bronchodilating effects and increases is administered using a mechanical nebulizer (Murphy
mucociliary transport. Side effects such as tachycardia and et al 1980). Ipratropium bromide has an onset of action of
sweating are rarely seen with lower oral doses but are more approximately 15–30 min and bronchodilation in RAO
frequent with intravenous administration and may persist may last up to 4–6 h. It is well tolerated when administered
for up to 3 h (Thomson & McPherson 1983). The clinical by inhalation (Robinson et al 1993, Duvivier et al 1999).
efficacy of clenbuterol, at the lower recommended dosage
(0.8 μg/kg q12h), in horses with RAO is inconsistent Antioxidants
if exposure to dusty hay and bedding is maintained There is evidence that oxidative stress may contribute to
(Thomson & McPherson 1983, Erichsen et al 1994). With airway inflammation in RAO (Deaton et al 2004). A
higher dosages (up to 3.2 μg/kg) its efficacy improves, but placebo-controlled study demonstrated that administra-
so do the frequency and severity of the adverse effects tion of dietary antioxidant supplements for 4 weeks to
(Erichsen et al 1994). This poor response may in part result horses with RAO that were in clinical remission improved
from the rapid desensitization and down-regulation of exercise tolerance but did not improve BAL cytology or
β2-adrenoreceptors following administration of therapeutic other pulmonary markers of oxidative stress (Kirschvink
doses of clenbuterol (Abraham et al 2002). As this effect et al 2002).
Expectorant, mucolytic, and Immunological intervention

mucokinetic agents The use of allergen hyposensitization or immunotherapy
Expectorants are drugs that increase pulmonary secre- to treat RAO has increased because of the commercial
tion while mucolytic agents loosen secretions. The term availability of in vitro serum allergy tests. Although uncon-
“mucokinetic agent” may be preferred as it indicates that trolled reports suggest efficacy, to the author’s knowledge,
the agent aids clearance of the respiratory tract secretions. there is no critical scientific evidence to support their use
Although the administration of mucokinetic agents may for the treatment of RAO at present.
help loosen the secretions in the large airways, evidence
of their efficacy in improving the clinical signs of RAO
is sparse. Clenbuterol, because of its bronchodilator and
Case Outcome
mucokinetic properties, is currently the drug of choice for RAO and SPAOPD are considered to be reversible conditions
aiding clearance of mucus from the airways. Oral iodides because marked improvement in airway function is seen in
and nebulized acetylcysteine may facilitate expecto- almost all horses that are properly managed. Presently,
ration but their efficacies have not been determined however, there are no good prognostic indicators and
(Genetzky & Loparco 1985). Iodide should be administered published information on the long-term outcome is sparse
with caution as it is an irritant and can induce or (Ainsworth et al 1998, Nuytten et al 1988). Follow-up
exacerbate bronchospasm. information from horses diagnosed with RAO and treated
Overhydration by administration of extremely high with environmental changes and oral steroid therapy
volumes of isotonic saline solution (30 liters at 10 liters/h, indicate that even with therapy, 78% of horses periodically
q24h, for 1–3 days) combined with bronchodilators or experience episodes of heaves and 41% of owners believe
mucokinetic agents has been used to treat airway obstruc- that their horses have compromised athletic capacity
tion of horses with heaves (Deegen 1981). The proposed (Ainsworth et al 1998). This suggests that the RAO may
beneficial effects of this treatment are improved mucus not be fully reversible and that lung remodeling may even
transport and removal of mucus plugs related to the progress despite appropriate therapy.
liquefaction of excessively viscous mucus. Under controlled While the condition will rapidly deteriorate in some
conditions, however, no improvement in lung function was horses that do not receive appropriate therapy, the clinical
observed in heaves-affected horses when isotonic saline signs may wane and wax, alternating between periods of
(10 liters/h, for 3 h) was administered as sole therapy clinical exacerbations and remission, even when horses are
(Jean et al 2004). This treatment should be administered maintained in the same environment. Anecdotal findings
with caution as a number of side effects, including labored from our and other laboratories indicate that horses that
breathing and colic, were observed with its use. Antitussive have repeatedly developed severe airway obstruction when
agents are not indicated in the treatment of equine heaves, exposed to moldy hay may occasionally remain asymp-
as coughing is a beneficial mechanism essential for the tomatic when exposed to moldy hay, even for prolonged
clearance of respiratory secretions. periods of time.
Death rarely occurs because of RAO per se; however,
Antibiotics severely affected horses may be euthanized because owners
Since bacterial colonization of airways is not uncommon are unable or unwilling to change the environment
in RAO, antimicrobials have been used before the admin- of horses or, rarely, because the horse fails to respond to
istration of corticosteroids, in an attempt to reduce the therapy. While poorly documented, some horses with
risk of secondary bacterial infection. However, this practice bronchiectasis or severe mucus plugging of airways have
is probably not warranted unless there is clinical evidence failed to respond or have responded poorly to environ-
of infection, such as fever, pyrexia, depression, and mental control, and to corticosteroid and bronchodilator
leukocytosis. therapy (Lavoie et al 2004). Glucocorticoid resistance,
defined as a failure to respond to systemic corticosteroids
Alternative therapies but continued response to bronchodilators, has been
Currently, there is an increased interest from horse owners reported in one horse with RAO (Stamper et al 2002).
in the use of alternative therapies, such as acupuncture
and herbal medicines, for the treatment of equine diseases.
REFERENCES
However, there is only very limited information concerning
their efficacy and toxicity. Film-coated extracts of Thymus Abraham G, Brodde OE, Ungemach FR 2002 Regulation
vulgaris and Primula veris administered orally for 1 month of equine lymphocyte beta-adrenoceptors under the
influence of clenbuterol and dexamethasone. Equine
to RAO-affected horses failed to improve the clinical signs, Veterinary Journal 34: 587–593
PAO2 and BAL neutrophilia, but significantly improved lung Aggarwal N, Holmes MA 1999 Characterisation of equine
mechanics (van den Hoven et al 2003). T helper cells: demonstration of Th1- and Th2-like
cells in long-term equine T-cell cultures. Research in Cordeau ME, Joubert P, Dewachi O et al 2004 IL-4, IL-5
Veterinary Science 66: 277–279 and IFN-gamma mRNA expression in pulmonary lym-
Ainsworth DM, Eicker SW, Bennett BJ 1998 Outcome of phocytes in equine heaves. Veterinary Immunology and
horses diagnosed with and treated for heaves. World Immunopathology 97: 87–96
Equine Airway Symposium, Guelph, Canada Cornelisse CJ, Robinson NE, Berney CE et al 2004 Efficacy of
Ainsworth DM, Grunig G, Matychak MB et al 2003 oral and intravenous dexamethasone in horses with
Recurrent airway obstruction (RAO) in horses is recurrent airway obstruction. Equine Veterinary Journal
characterized by IFN-gamma and IL-8 production in 36: 426–430
bronchoalveolar lavage cells. Veterinary Immunology Costa LR, Seahorn TL, Moore RM et al 2000 Correlation of
and Immunopathology 96: 83–89 clinical score, intrapleural pressure, cytological findings
Al-Dewachi O, Joubert P, Taha R et al 2002 Expression of IL-5 of bronchoalveolar fluid, and histopathological lesions of
and IL-9 receptors on neutrophils in horses with heaves. pulmonary tissue in horses with summer pasture-
98th International Conference, American Thoracic associated obstructive pulmonary disease. American
Society, Atlanta, GA Journal of Veterinary Research 61: 167–173
Ammann VJ, Vrins AA, Lavoie JP 1998 Effects of inhaled Costa LR, Seahorn TL, Moore RM et al 2001 Plasma and
beclomethasone dipropionate on respiratory function in bronchoalveolar fluid concentrations of nitric oxide and
horses with chronic obstructive pulmonary disease localization of nitric oxide synthesis in the lungs of
(COPD). Equine Veterinary Journal 30: 152–157 horses with summer pasture-associated obstructive
Barnes PJ 2003 Theophylline: new perspectives for an old pulmonary disease. American Journal of Veterinary
drug. American Journal of Respiratory and Critical Care Research 62: 1381–1386
Medicine 167: 813–818 Couetil LL, Ward MP 2003 Analysis of risk factors for
Beadle RE 1983 Summer pasture-associated obstructive recurrent airway obstruction in North American horses:
pulmonary disease. In: Robinson NE (editor) Current 1,444 cases (1990–1999). Journal of the American
Therapy in Equine Medicine. WB Saunders, Philadelphia, Veterinary Medical Association 223: 1645–1650
pp.512–516 Couetil LL, Rosenthal FS, Simpson CM 2000 Forced expiration:
Beadle RE 1985 Experiences with whole-body plethysmography a test for airflow obstruction in horses. Journal of Applied
in horses with obstructive pulmonary disease. Lung Physiology 88: 1870–1879
Function and Respiratory Diseases in the Horse, Deaton CM, Marlin DJ, Smith NC et al 2004 Pulmonary
International Symposium in Hannover, Germany epithelial lining fluid and plasma ascorbic acid con-
Beadle RE, Horohov DW, Gaunt SD 2002 Interleukin-4 and centrations in horses affected by recurrent airway
interferon-gamma gene expression in summer pasture- obstruction. American Journal of Veterinary Research
associated obstructive pulmonary disease affected horses. 65: 80–87
Equine Veterinary Journal 34: 389–394 Debrue M, Lajoie-Kadoch S, Joubert P et al 2004 Stabling
Beech J 1991 Chronic obstructive pulmonary disease. Veterinary is associated with increased expression of IL-17 mRNA
Clinics of North America; Equine Practice 7: 79–91 in bronchoalveolar cells of horses with heaves. 100th
Bober LA, Waters TA, Pugliese-Sivo CC et al 1995 IL-4 induces International Conference, American Thoracic Society,
neutrophilic maturation of HL-60 cells and activation Orlando, FL
of human peripheral blood neutrophils. Clinical and Deegen E 1981 Massive intravenous infusions: a novel
Experimental Immunology 99: 129–136 secretolytic therapy for horses with chronic obstructive
Boey H, Rosenbaum R, Castracane J et al 1989 Interleukin-4 pulmonary disease (COPD). Proceedings of the American
is a neutrophil activator. Journal of Allergy and Clinical Association of Equine Practitioners 27: 27–33
Immunology 83: 978–984 Derksen FJ, Robinson NE, Armstrong PJ et al 1985 Airway
Bowles KS, Beadle RE, Mouch S et al 2002 A novel model for reactivity in ponies with recurrent airway obstruction
equine recurrent airway obstruction. Veterinary Immu- (heaves). Journal of Applied Physiology 58: 598–604
nology and Immunopathology 87: 385–389 Derksen FJ, Robinson NE, Scott JS et al 1988 Aerosolized
Bureau F, Bonizzi G, Kirschvink N et al 2000a Correlation Micropolyspora faeni antigen as a cause of pulmonary
between nuclear factor-kappaB activity in bronchial dysfunction in ponies with recurrent airway obstruc-
brushing samples and lung dysfunction in an animal tion (heaves). American Journal of Veterinary Research
model of asthma. American Journal of Respiratory and 49: 933–938
Critical Care Medicine 161: 1314–1321 Derksen FJ, Brown CM, Sonea I et al 1989 Comparison of
Bureau F, Delhalle S, Bonizzi G et al 2000b Mechanisms transtracheal aspirate and bronchoalveolar lavage
of persistent NF-kappa B activity in the bronchi of cytology in 50 horses with chronic lung disease. Equine
an animal model of asthma. Journal of Immunology Veterinary Journal 21: 23–26
165: 5822–5830 Derksen FJ, Olszewski M, Robinson NE et al 1996 Use of a
Cesarini C, Hamilton E, Picandet V et al 2004 Efficacy of hand-held, metered-dose aerosol delivery device to
theophylline associated with a low dose of dexametha- administer pirbuterol acetate to horses with “heaves”.
sone in the treatment of horses with heaves. 22th Equine Veterinary Journal 28: 306–310
Symposium of the Veterinary Comparative Respiratory Dixon PM, Nicholls JR, McPherson EA et al 1982 Chronic
Society, Montreal, Canada obstructive pulmonary disease anatomical cardiac
Clarke AF, Madelin TM, Allpress RG 1987 The relationship studies. Equine Veterinary Journal 14: 80–82
of air hygiene in stables to lower airway disease Dixon PM, Railton DI, McGorum BC et al 1995 Equine
and pharyngeal lymphoid hyperplasia in two groups pulmonary disease: a case control study of 300 referred
of Thoroughbred horses. Equine Veterinary Journal cases. Part 4: Treatments and re-examination findings.
Dun F 1859 Veterinary Medicines: Their Actions and Uses. inhaled fluticasone propionate. 18th Annual Veterinary
Sutherland and Knox, Edinburgh Medical Forum, ACVIM, Seattle, WA
Duvivier DH, Bayly WM, Votion D et al 1999 Effects of inhaled Giguere S, Viel L, Lee E et al 2002 Cytokine induction in
dry powder ipratropium bromide on recovery from pulmonary airways of horses with heaves and effect of
exercise of horses with COPD. Equine Veterinary Journal therapy with inhaled fluticasone propionate. Veterinary
31: 20–24 Immunology and Immunopathology 85: 147–158
Eder C, Crameri R, Mayer C et al 2000 Allergen-specific IgE Gilleece MH, Scarffe JH, Ghosh A et al 1992 Recombinant
levels against crude mould and storage mite extracts and human interleukin 4 (IL-4) given as daily subcutaneous
recombinant mould allergens in sera from horses affected injections – a phase I dose toxicity trial. British Journal of
with chronic bronchitis. Veterinary Immunology and Cancer 66: 204–210
Immunopathology 73: 241–253 Girard D, Paquin R, Beaulieu AD 1997 Responsiveness of
Eder C, Curik I, Brem G et al 2001 Influence of environmental human neutrophils to interleukin-4: induction of cyto-
and genetic factors on allergen-specific immunoglobulin- skeletal rearrangements, de novo protein synthesis and
E levels in sera from Lipizzan horses. Equine Veterinary delay of apoptosis. Biochemical Journal 325: 147–153
Journal 33: 714–720 Grünig G, Herman M, Howald B et al 1989 Partial divergence
Erichsen DF, Aviad AD, Schultz RH et al 1994 Clinical efficacy between airway inflammation and clinical signs in equine
and safety of clenbuterol HCl when administered to effect chronic pulmonary disease. Equine Veterinary Journal
in horses with chronic obstructive pulmonary disease 21: 145–148
(COPD). Equine Veterinary Journal 26: 331–336 Halliwell RE, Fleischman JB, Mackay-Smith M et al 1979 The
Eyre P 1972 Equine pulmonary emphysema: a bronchopul- role of allergy in chronic pulmonary disease of horses.
monary mould allergy. Veterinary Record 91: 134–140 Journal of the American Veterinary Medical Association
Fairbairn SM, Lees P, Page CP et al 1993a Duration of antigen- 174: 277–281
induced hyperresponsiveness in horses with allergic Halliwell REW, McGorum BC, Irving P et al 1993 Local
respiratory disease and possible links with early airway and systemic antibody production in horses affected
obstruction. Journal of Veterinary Pharmacology and with chronic obstructive pulmonary disease. Veterinary
Therapeutics 16: 469–476 Immunology and Immunopathology 38: 201–215
Fairbairn SM, Page CP, Lees P et al 1993b Early neutrophil but Hare JE, Viel L, Conlon PD et al 1999 In vitro allergen-induced
not eosinophil or platelet recruitment to the lungs of degranulation of pulmonary mast cells from horses with
allergic horses following antigen exposure. Clinical and recurrent airway obstruction (heaves). American Journal
Experimental Allergy 23: 821–828 of Veterinary Research 60: 841–847
Franchini M, Gilli U, Akens MK et al 1998 The role of neu- Henrikson SL, Rush BR 2001 Efficacy of salmeterol xinafoate
trophil chemotactic cytokines in the pathogenesis of in horses with recurrent airway obstruction. Journal
equine chronic obstructive pulmonary disease (COPD). of the American Veterinary Medical Association
Veterinary Immunology and Immunopathology 66: 53–65 218: 1961–1965
Franchini M, Gill U, von Fellenberg R et al 2000 Interleukin-8 Herszberg B, Ramos-Barbon D, Martin JG et al 2004 Airway
concentration and neutrophil chemotactic activity in smooth muscle remodeling in an equine model of chronic
bronchoalveolar lavage fluid of horses with chronic asthma. 100th International Conference, American
obstructive pulmonary disease following exposure to hay. Thoracic Society, Orlando, FL
American Journal of Veterinary Research 61: 1369–1374 Hoffman A, Kuehn H, Riedelberger K et al 2001 Flowmetric
Gallivan GJ, McDonell WN 1989 An evaluation of the multi- comparison of respiratory inductance plethysmography
breath nitrogen washout as pulmonary function test in and pneumotachography in horses. Journal of Applied
dairy cattle. Canadian Journal of Veterinary Research Physiology 91: 2767–2775
53: 133–142 Holcombe SJ, Jackson C, Gerber V et al 2001 Stabling is
Genetzky RM, Loparco FV 1985 Chronic obstructive pul- associated with airway inflammation in young Arabian
monary disease in horses: Part 1. Compendium on horses. Equine Veterinary Journal 33: 244–249
Continuing Education for the Practicing Veterinarian Jean D 1996 Etude de la variabilité des valeurs de mécanique
7: S407–S414 respiratoire et de la cytologie du lavage bronchoalveolaire
George LW, Tanner ML, Roberson EL et al 1981 Chronic chez les chevaux atteints de maladie pulmonaire
respiratory disease in a horse infected with Dictyocaulus obstructive chronique (MPOC) et de chevaux exempts de
arnfieldi. Journal of the American Veterinary Medical cette maladie. MSc thesis, Faculté des Études Supérieures,
Association 179: 820–822 St-Hyacinthe, Université de Montréal
Gerber H 1973 Chronic pulmonary disease in the horse. Jean D, Vrins A, Lavoie JP 2004 Respiratory and metabolic
Equine Veterinary Journal 5: 26–31 effects of massive administration of isotonic saline
Gerber V, King M, Schneider DA et al 2000 Tracheobronchial solution in heaves-affected and control horses. Equine
mucus viscoelasticity during environmental challenge Veterinary Journal 36: 628–633
in horses with recurrent airway obstruction. Equine Jefcoat AM, Hotchkiss JA, Gerber V et al 2001 Persistent
Veterinary Journal 32: 411–417 mucin glycoprotein alterations in equine recurrent
Gerber V, Robinson NE, Venta RJ et al 2003 Mucin genes in airway obstruction. American Journal of Physiology. Cell
horse airways: MUC5AC, but not MUC2, may play a role Physiology 281: C704–712
in recurrent airway obstruction. Equine Veterinary Joubert P, Silversides DW, Lavoie JP 2001 Equine neutrophils
Journal 35: 252–257 express mRNA for tumour necrosis factor-alpha, inter-
Giguere S, Viel L, Lee E 2000 Cytokine messenger RNA leukin (IL)-1beta, IL-6, IL-8, macrophage-inflammatory-
(mRNA) expression in bronchoalveolar cells from normal protein-2 but not for IL-4, IL-5 and interferon-gamma.
horses and horses with heaves, and effect of therapy with Equine Veterinary Journal 33: 730–733
Joubert P, Cordeau ME, Boyer A et al 2002 Quantification of of the American Veterinary Medical Association 218:
cytokine mRNA expression by pulmonary macrophages 1314–1322
in horses affected by heaves. 20th Symposium of the Lowell F 1964 Observations on heaves: an asthma-like
Veterinary Comparative Respiratory Society, Boston, MA syndrome in the horse. Journal of Allergy 35: 322–330
Kaup F-J, Drommer W, Damsch S et al 1990 Ultrastructural Mair TS 1996a Bacterial pneumonia associated with cor-
findings in horses with chronic obstructive pulmonary ticosteroid therapy in three horses. Veterinary Record
disease (COPD). 2: Pathological changes of the terminal 138: 205–207
airways and the alveolar region. Equine Veterinary Mair TS 1996b Obstructive pulmonary disease in 18 horses at
Journal 22: 349–355 summer pasture. Veterinary Record 138: 89–91
Kirschvink N, Fievez L, Bougnet V et al 2002 Effect of Malikides N 2004 The epidemiology of inflammatory airway
nutritional antioxidant supplementation on systemic and disease in young thoroughbred racehorses in Australia.
pulmonary antioxidant status, airway inflammation and PhD thesis, University of Sydney, Australia
lung function in heaves-affected horses. Equine Veterinary Mansmann RA, Osburn BI, Wheat JD et al 1975 Chicken
Journal 34: 705–712 hypersensitivity pneumonitis in horses. Journal of the
Kolm G, Zappe H, Schmid R et al 2003 Efficacy of montelukast American Veterinary Medical Association 166: 673–677
in the treatment of chronic obstructive pulmonary disease Marr KA, Foster AP, Lees P et al 1997 Effect of antigen
in five horses. Veterinary Record 152: 804–806 challenge on the activation of peripheral blood neu-
Kvart C, Carlsen J, Dahl L et al 1986 Changes in arterial trophils from horses with chronic obstructive pulmonary
oxygen tension in COPD horses after reduction of disease. Research in Veterinary Science 62: 253–260
exposure to dust in the feed and environment. Second Marr KA, Lees P, Page CP et al 1998a Effect of the
International Conference on Equine Exercise Physiology, 5-lipoxygenase inhibitor, fenleuton, on antigen-induced
San Diego, LA. ICEEP Publications neutrophil accumulation and lung function changes in
Lapointe JM, Lavoie JP, Vrins AA 1993 Effects of triamcinolone horses with chronic obstructive pulmonary disease.
acetonide on pulmonary function and bronchoalveolar Journal of Veterinary Pharmacology and Therapeutics
lavage cytologic features in horses with chronic obstruc- 21: 241–246
tive pulmonary disease. American Journal of Veterinary Marr KA, Lees P, Page CP et al 1998b Inhaled leuko-
Research 54: 1310–1316 trienes cause bronchoconstriction and neutrophil accu-
Larson VL, Busch RH 1985 Equine tracheobronchial lavage: mulation in horses. Research in Veterinary Science
comparison of lavage cytologic and pulmonary histopatho- 64: 219–224
logic findings. American Journal of Veterinary Research Marti E, Gerber H, Essich G et al 1991 The genetic basis
46: 144–146 of equine allergic diseases. 1. Chronic hypersensitivity
Lasky JA, Brody AR 1997 Interleukins involved in the bronchitis. Equine Veterinary Journal 23: 457–460
pathogenesis of chronic airway inflammation. Research Mazan MR, Hoffman AM, Manjerovic N 1999 Comparison of
in Immunology 148: 39–47 forced oscillation with the conventional method for
Lavoie JP, Maghni K, Desnoyers M et al 2001 Neutrophilic histamine bronchoprovocation testing in horses. American
airway inflammation in horses with heaves is charac- Journal of Veterinary Research 60: 174–180
terized by a Th2-type cytokine profile. American Journal of Mazan MR, Deveney EF, DeWitt S et al 2004 Energetic cost of
Respiratory and Critical Care Medicine 164: 1410–1413 breathing, body composition, and pulmonary function in
Lavoie JP, Pasloske K, Joubert P et al 2002a Comparison of horses with recurrent airway obstruction. Journal of
dexamethasone and the PDE IV enzyme inhibitor Applied Physiology 97: 91–97
L826-141 in an animal model of chronic asthma. 98th McGorum BC, Dixon PM, Halliwell RE et al 1993a Comparison
International Conference, American Thoracic Society, of cellular and molecular components of bronchoalveolar
Atlanta, GA lavage fluid harvested from different segments of the
Lavoie JP, Leguillette R, Pasloske K et al 2002b Comparison of equine lung. Research in Veterinary Science 55: 57–59
dexamethasone and the LTD4 receptor antagonist McGorum BC, Dixon PM, Halliwell REW 1993b Quantification
L-708,738 on lung function and airway cytology in of histamine in plasma and pulmonary fluids from horses
heaves. American Journal of Veterinary Research with chronic obstructive pulmonary disease, before and
63: 579–585 after natural (hay and straw) challenges. Veterinary
Lavoie JP, Dalle S, Breton L et al 2004 Bronchiectasis in three Immunology and Immunopathology 36: 223–237
adult horses with heaves. Journal of Veterinary Internal McKiernan BC, Koritz GD 1990 Plasma theophylline concen-
Medicine 18: 757–760 tration and lung function in ponies with recurrent
Lawson GHK, McPherson EA, Murphy JR et al 1979 The obstructive lung disease. Equine Veterinary Journal
presence of precipitating antibodies in the sera of horses 22: 194–197
with chronic obstructive pulmonary disease (COPD). McPherson EA, Lawson GHK, Murphy JR et al 1978 Chronic
Equine Veterinary Journal 11: 172–176 obstructive pulmonary disease (COPD): identification of
Leguillette R, Désévaux C, Lavoie JP 2002 Effects of pen- affected horses. Equine Veterinary Journal 10: 47–53
toxifylline on pulmonary function and results of cytologic McPherson EA, Lawson GH, Murphy JR et al 1979a Chronic
examination of bronchoalveolar lavage fluid in horses obstructive pulmonary disease (COPD): factors influencing
with recurrent airway obstruction. American Journal of the occurrence. Equine Veterinary Journal 11: 167–171
Veterinary Research 63: 459–463 McPherson EA, Lawson GHK, Murphy JR et al 1979b
Lorch G, Hillier A, Kwochka RW et al 2001 Comparison of Chronic obstructive pulmonary disease (COPD) in horses:
immediate intradermal test reactivity with serum IgE aetiological studies: responses to intradermal and inha-
quantitation by use of a radioallergosorbent test and lation antigenic challenge. Equine Veterinary Journal
two ELISA in horses with and without atopy. Journal 11: 159–166
Murphy JR, McPherson EA, Dixon PM 1980 Chronic in horses with recurrent airway obstruction (heaves)
obstructive pulmonary disease (COPD): Effects of bron- during a bronchodilator trial. Equine Veterinary Journal
chodilator drugs on normal and affected horses. Equine 32: 393–400
Veterinary Journal 12: 10–14 Robinson NE, Jackson C, Jefcoat A et al 2002 Efficacy of three
Naylor JM, Clark EG, Clayton HM 1992 Chronic obstructive corticosteroids for the treatment of heaves. Equine
pulmonary disease: usefulness of clinical signs, bron- Veterinary Journal 34: 17–22
choalveolar lavage, and lung biopsy as diagnostic and Robinson NE, Berney C, Eberhart S et al 2003 Cough, mucus,
prognostic aids. Canadian Veterinary Journal 33: 591–598 airway obstruction, and inflammation in heaves-affected
Nuytten J, Deprez P, Picavet T et al 1988 Comparison of and control horses. American Journal of Veterinary
different pulmonary function tests and their prognostic Research 64: 550–557
value in horses affected with COPD. Equine Veterinary Rush BR, Flaminio MJ, Matson C et al 1997 Inhaled
Science 8: 361–364 beclomethasone dipropionate for the treatment of
Nyman G, Linderg R, Weckner D et al 1991 Pulmonary gas heaves. 15th Symposium of the Veterinary Comparative
exchange correlate to clinical signs and lung pathology Respiratory Society, University of Liege, Belgium
in horses with chronic bronchiolitis. Equine Veterinary Rush BR, Flaminio MJ, Matson CJ et al 1998a Cytologic
Journal 23: 253–260 evaluation of bronchoalveolar lavage fluid from horses
Obel N, Schmiterlöw C 1948 The action of histamine and with recurrent airway obstruction after aerosol and
other drugs on the bronchial tone of horses suffering parenteral administration of beclomethasone dipropionate
from alveolar emphysema (heaves). Acta Pharmacologica and dexamethasone, respectively. American Journal of
Sinica 4: 71–80 Veterinary Research 59: 1033–1038
Olszewski MA, Robinson NE, Zhu FX et al 1999 Mediators of Rush BR, Raub ES, Rhoads WS et al 1998b Pulmonary
anaphylaxis but not activated neutrophils augment function in horses with recurrent airway obstruc-
cholinergic responses of equine small airways. American tion after aerosol and parenteral administration of
Journal of Physiology 276: L522–L529 beclomethasone dipropionate and dexamethasone,
Pearson EG, Riebold TW 1989 Comparison of bronchodilators respectively. American Journal of Veterinary Research
in alleviating clinical signs in horses with chronic 59: 1039–1043
obstructive pulmonary disease. Journal of the American Schmallenbach KH, Rahman I, Sasse HHL et al 1998 Studies
Veterinary Medical Association 194: 1287–1291 on pulmonary and systemic Aspergillus fumigatus-specific
Pellegrini A, Kalkinc M, Hermann M et al 1998 Equinins in IgE and IgG antibodies in horses affected with chronic
equine neutrophils: quantification in tracheobronchial obstructive pulmonary disease (COPD). Veterinary Immu-
secretions as an aid in the diagnosis of chronic pul- nology and Immunopathology 66: 245–256
monary disease. Veterinary Journal 155: 257–262 Seahorn TL, Beadle RE 1993 Summer pasture-associated
Peroni DL, Stanley S, Kollias-Baker C et al 2002 Prednisone obstructive pulmonary disease in horses – 21 cases
per os is likely to have limited efficacy in horses. Equine (1983–1991). Journal of the American Veterinary
Veterinary Journal 34: 283–287 Medical Association 202: 779–782
Picandet V, Leguillette R, Lavoie JP 2003 Comparison of Seahorn TL, Groves MG, Harrington KS et al 1996 Chronic
efficacy and tolerability of isoflupredone and dexametha- obstructive pulmonary disease in horses in Louisiana.
sone in the treatment of horses affected with recurrent Journal of the American Veterinary Medical Association
airway obstruction (“heaves”). Equine Veterinary Journal 208: 248–251
35: 419–424 Seahorn TL, Beadle RE, McGorum BC et al 1997 Quanti-
Picandet V, Jean D, Lavoie JP 2004 Acid base balance in fication of antigen-specific antibody concentrations in
arterial blood of horses with heaves. 22nd Veterinary tracheal lavage fluid of horses with summer pasture-
and Comparative Respiratory Symposium, Montreal, associated obstructive pulmonary disease. American
Canada Journal of Veterinary Research 58: 1408–1411
Pirie RS, Dixon PM, Collie DD et al 2001 Pulmonary and Soma LR, Beech J, Gerber NH 1987 Effects of cromolyn in
systemic effects of inhaled endotoxin in control and horses with chronic obstructive pulmonary disease.
heaves horses. Equine Veterinary Journal 33: 311–318 Veterinary Research Communications 11: 339–351
Pirie RS, Collie DD, Dixon PM et al 2002 Evaluation of Stamper AJ, Rush BR, Wilkerson MJ et al 2002 Glucocorticoid
nebulised hay dust suspensions (HDS) for the diagnosis resistance in a horse with heaves. 20th Symposium of the
and investigation of heaves. 2: Effects of inhaled HDS Veterinary Comparative Respiratory Society, Boston, MA
on control and heaves horses. Equine Veterinary Journal Thomson JR, McPherson EA 1981 Prophylactic effects
34: 337–342 of sodium cromoglycate on chronic obstructive pul-
Robinson NE 2001 International Workshop on Equine monary disease in the horse. Equine Veterinary Journal
Chronic Airway Disease. Michigan State University 13: 243–246
16–18 June 2000. Equine Veterinary Journal 33: 5–19 Thomson JR, McPherson EA 1983 Chronic obstructive
Robinson NE, Derksen FJ, Berney C et al 1993 The airway pulmonary disease in the horse 2: Therapy. Equine
response of horses with recurrent airway obstruction Veterinary Journal 15: 207–210
(heaves) to aerosol administration of ipratropium bromide. Thomson JR, McPherson EA 1984 Effects of environmental
Equine Veterinary Journal 25: 299–303 control on pulmonary function of horses affected with
Robinson NE, Boehler D, Berney C et al 1998 Failure of a chronic obstructive pulmonary disease. Equine Veterinary
FLAP antagonist to prevent airway obstruction in heaves- Journal 16: 35–38
susceptible horses. World Equine Airways Symposium, Thurlbeck WM, Lowell FC 1964 Heaves in horses. American
Guelph, Canada Journal of Respiratory Diseases 89: 82–88
Robinson NE, Olszewski MA, Boehler D et al 2000 Torneke MK, Ingvast-Larsson JC, Johansson JM et al 2000
Relationship between clinical signs and lung function Pharmacokinetics and pharmacodynamics of terbutaline
in healthy horses. American Journal of Veterinary Viel L 1983 Structural–functional correlations of the lung in
Research 61: 761–765 horses with small airway disease. PhD thesis, University
Traub-Dargatz JL, McKinnon AO, Thrall MA et al 1992 of Guelph
Evaluation of clinical signs of disease, bronchoalveolar Votion DM, Vandenput SN, Duvivier DH et al 1999 Alveolar
and tracheal wash analysis, and arterial blood gas ten- clearance in horses with chronic obstructive pulmonary
sions in 13 horses with chronic obstructive pulmonary disease. American Journal of Veterinary Research
disease treated with prednisone, methyl sulfonmethane, 60: 495–500
and clenbuterol hydrochloride. American Journal of Vrins A, Doucet M, Nunez-Ochoa L 1991 A retrospective
Veterinary Research 53: 1908–1916 study of bronchoalveolar lavage cytology in horses with
Tremblay GM, Ferland C, Lapointe J-M et al 1993 Effect of clinical findings of small airway disease. Zentralblatt fur
stabling on bronchoalveolar cells obtained from normal Veterinarmedizin A 38: 472–479
and COPD horses. Equine Veterinary Journal 25: 194–197 Watson ED, Sweeney CR, Steensma KA 1992 Arachidonate
Turlej RK, Fievez L, Sandersen CF et al 2001 Enhanced metabolites in bronchoalveolar lavage fluid from horses
survival of lung granulocytes in an animal model of with and without COPD. Equine Veterinary Journal
asthma: evidence for a role of GM-CSF activated STAT5 24: 379–381
signalling pathway. Thorax 56: 696–702 Willoughby RA, McDonnel WN 1979 Pulmonary function
van den Hoven R, Zappe H, Zitterl-Eglseer K et al 2003 Study testing in horses. Veterinary Clinics of North America;
of the effect of Bronchipret on the lung function of five Large Animal Practice 1: 171–196
Austrian saddle horses suffering recurrent airway obstruc- Winder NC, von Fellenberg R 1987 Chronic small airway
tion (heaves). Veterinary Record 152: 555–557 disease in horses slaughtered in Switzerland. Schweizer
Vandenput S, Istasse L, Nicks B et al 1997 Airborne dust Archiv fur Tierheilkunde 129: 585–593
and aeroallergen concentrations in different sources of Winder NC, Hermann M, Grünig G et al 1990 Comparison
feed and bedding for horses. Veterinary Quarterly 19: of bronchoalveolar lavage and respiratory secretion
154–158 cytology in horses with clinically diagnosed chronic
Vandenput S, Votion D, Duvivier DH et al 1998a Effect of a set pulmonary disease. Schweizer Archiv fur Tierheilkunde
stabled environmental control on pulmonary function 132: 505–510
and airway reactivity of COPD affected horses. Veterinary Woods PS, Robinson NE, Swanson MC et al 1993 Airborne
Journal 155: 189–195 dust and aeroallergen concentration in a horse stable
Vandenput S, Duvivier DH, Votion D et al 1998b Environ- under two different management systems. Equine
mental control to maintain stabled COPD horses in Veterinary Journal 25: 208–213
clinical remission: effects on pulmonary function. Equine Yang L, Cohn L, Zhang DH et al 1998 Essential role of nuclear
Veterinary Journal 30: 93–96 factor kappaB in the induction of eosinophilia in allergic
van Erck E, Votion DM, Kirschvink N et al 2003 Use airway inflammation. Journal of Experimental Medicine
of the impulse oscillometry system for testing pul- 188: 1739–1750
monary function during methacholine bronchoprovoca- Yu MF, Wang ZW, Robinson NE et al 1994 Modulation of
tion in horses. American Journal of Veterinary Research bronchial smooth muscle function in horses with heaves.
64: 1414–1420 Journal of Applied Physiology 77: 2149–2154
Inflammatory Airway Disease
42 Robert Christley and Bonnie R Rush
Epidemiology
The terms “inflammatory airway disease” (IAD) and “small-
airway inflammatory disease” (SAID) have been used to Until a formal definition of IAD is agreed and adhered to,
describe a syndrome of respiratory tract inflammation understanding this condition will be complicated by the use
in racehorses. Typically, diagnosis of IAD is made on the of varying case definitions. Despite this, useful information
basis of clinical signs (poor performance and cough) and regarding the basic epidemiology of IAD-related condi-
endoscopic findings (nasopharyngeal exudate, pharyngeal tions is available, and should be considered in the light of
lymphoid hyperplasia, and tracheal exudate). This condi- the differences in case definitions, target populations, and
tion has been reported to occur in 11–50% of racehorses methodologies. Amongst young racehorses, the prevalence
in training. of IAD is undoubtedly high, with estimates in different
populations ranging from 11 to 50%. The incidence of IAD
is also high, with one study identifying IAD 2 weeks after
Definition of the Syndrome entering training in 41% of horses that had been free of
Any discussion of IAD is complicated by the lack of a evidence of respiratory disease when they entered the
consistent and precise definition of the syndrome. In 2002 racing yard (Malikides 2003).
the International Workshop on Inflammatory Airway Numerous risk factors for IAD in racehorses have been
Disease summarized much of what is known about IAD identified. These include animal, environmental and manage-
and attempted to define the syndrome (Anon 2003). ment factors. Studies in Australia and the UK have found
Broadly, IAD is a clinical syndrome typified by some or all that, among young racehorses, the risk of IAD (or signs
of the following: related to IAD) decreases with age (Burrell et al 1996,
Chapman et al 2000, Christley et al 2001b). It is well recog-
● cough
nized that allergens and aerotoxins are important in the
● accumulation of secretions in the trachea
development of recurrent airway obstruction (RAO), but
● cytological evidence of airway inflammation
recent epidemiological studies have found that poor ventila-
● nasal discharge
tion and bedding type also influence the risk of IAD in
● poor exercise performance
young racehorses (Clarke et al 1987, Burrell et al 1996,
● delayed recovery following exercise
Malikides 2003). Furthermore, the percentage of neutrophils
● absence of changes in the pattern, rate or depth of
in airway fluid samples is significantly associated with the
respiration
concentration of airborne endotoxin in the environment,
● absence of clinical signs of systemic illness (such as
suggesting a role for poor air hygiene (Malikides et al 2003).
depression, inappetance or pyrexia)
Interestingly, the risk of IAD decreases with the length of
● absence of hematological or serum biochemical evidence
time spent in the stable environment (Christley et al 2001b),
of illness.
perhaps because of the development of tolerance to aero-
Given this broad definition and the plethora of potential toxins (including endotoxin; Schwartz et al 1994) or to
causes for such changes, it seems likely that IAD repre- infectious agents. However, the risk of IAD subsequently
sents the common manifestation of a range of etiological increases following the commencement of racing.
pathways. As such, causes of IAD include non-infectious
causes (such as airborne allergens, aerotoxins, and parti-
Relationship Between IAD and RAO
culates) and infectious causes (including viruses, bacteria,
and mycoplasma). Eventually, IAD may be divided into a The relationship between IAD and RAO is unclear. Some
number of subcategories reflecting these different etiologies. authors suggest that IAD represents a milder or earlier
Such subcategories likely have different prevalences in phase of RAO while others contest that the etiopatho-
different horse populations, and this may account for some genesis of IAD differs fundamentally from that of RAO.
of the current confusion regarding IAD in the literature. Inflammatory airway disease occurs in racehorses, and so
591
592 42 Inflammatory Airway Disease
Table 42.1. Comparison of recurrent airway obstruction (RAO) and inflammatory airway disease (IAD), based on
criteria determined by the International Workshop on Inflammatory Airway Disease (2002) and Davis & Rush (2002)
RAO (symptomatic) IAD
Signalment Older (> 5 years old) Any age, including young racehorses
Clinical signs Increased rate and depth of breathing Absence of change in rate, depth or pattern of breathing
Radiographic features Variable bronchointerstitial pattern Less severe bronchointerstitial changes, less air trapping
BAL and tracheal cytology Marked neutrophilia Fewer inflammatory cells in BAL fluid. Mild neutrophilia,
lymphocytosis and monocytosis
Response to environmental Good Variable to poor

control
Predominant BAL T-lymphocyte CD4+ CD8+

phenotype
BAL, bronchoalveolar lavage.
affects animals at an earlier age than is characteristic for underlying causes are elucidated. However, based on the
RAO (Table 42.1). In addition, IAD differs from RAO in contrasting plausible explanations of the etiology of this
terms of the clinical signs (milder, subclinical or only syndrome, and the variability of research findings, it is
evident at maximal exercise, lack of dyspnea), radiographic likely that several, or all, of the postulated etiologies are
changes (less severe bronchointerstitial changes, less air involved, independently or in combination.
trapping), and cytology [fewer inflammatory cells in bron-
choalveolar lavage (BAL) fluid]. Inflammatory airway Infection with bacteria and mycoplasmas
disease results in cytological changes in the BAL fluid (mild
neutrophilia, lymphocytosis, and monocytosis) that are There is growing evidence that bacteria and mycoplasma
reported to be distinguishable from those seen with RAO may play a role in the etiology of IAD. Tracheal inflam-
(marked neutrophilia, lymphopenia, monocytopenia, and matory changes are positively correlated with the number
normal total cell counts). Furthermore, IAD-affected horses of bacterial colony-forming units in tracheal washes (Wood
have increased numbers of CD8-positive lymphocytes in et al 1993, Burrell et al 1996). In particular, the aerobic
their airways, in contrast to RAO-affected horses, which bacteria Streptococcus zooepidemicus, S. pneumoniae and
are characterized by the presence of CD4-positive cells. For Pasteurella spp., and the mycoplasmas Mycoplasma felis and
this reason, Moore et al (1995) concluded that IAD does M. equirhinis, are significantly associated with lower airway
not have an allergic etiology, is not an early stage of RAO inflammation. However, other workers suggest caution
and is probably a response to infection or environmental when interpreting these results, because inflammation of
factors. However, airway cytological findings in horses with the tracheobronchial tree for any reason may leave it more
RAO are labile and reflect the variable levels of exposure to susceptible to colonization by oropharyngeal bacteria
allergens. Also, when relative cell counts (rather than abso- (Robinson 1997, Viel 1997). These bacteria may, therefore,
lute counts) are used, the presence of a marked relative be a consequence of lower airway inflammation, rather
neutrophilia in acute bouts of RAO necessitates a relative than its cause. Nonetheless, because they are potential
reduction in other cell types and this may account, at least pathogens, it is likely that they may contribute to the
in part, for the relative lymphopenia and monocytopenia worsening and prolongation of IAD.
which occur in RAO. In addition, whilst relative eosinophil
counts are usually reported to be within normal limits in
RAO, four of 32 standardbred racehorses with putative IAD Table 42.2. Putative causes of IAD
had markedly elevated relative eosinophil counts in BAL
Infection with bacteria and/or mycoplasma
fluid, suggesting that the clinical signs of IAD can result from A sequel to exercise-induced pulmonary hemorrhage
a range of etiopathogenic responses (Moore et al 1995). Inhalation of airborne pro-inflammatory agents, such as
endotoxin in stables with suboptimal air hygiene
Exposure to noxious gases such as H2S, NH3, ozone, SO2, NO2,
Etiology and CO
Deep inhalation of particulate matter associated with training
The etiology of IAD likely varies between horses and and racing
among horse populations. The numerous potential causes Recurrent or persistent viral infection
of IAD are listed in Table 42.2. Effective prevention and A type-I hypersensitivity reaction to environmental molds
treatment of this syndrome will be impossible until the
42 Inflammatory Airway Disease 593
Inhalation of particulate matter and airborne monoxide. Furthermore, housed animals may be exposed
pro-inflammatory agents to a range of accumulated noxious gases, including
ammonia, hydrogen sulfide, and methane. Such gases may
In horse stables, the concentration of airborne particles act as respiratory irritants, provoking acute inflammatory
may be up to ten times that of outdoor air and 30–40% of responses with injury to the epithelial cells of the lungs
the total mass of these particles are sufficiently small to and alterations in respiratory function. Many studies in
reach the pulmonary alveoli. Furthermore, activities such humans and animals have demonstrated an association
as cleaning stable bedding and feeding can greatly increase between these air pollutants and impaired lung function,
the levels of airborne dust. However, the movements coughing, and infections of the lower respiratory tract.
and feeding behavior of horses may be more important However, the precise role of these gases in the etiology of
in increasing the concentrations of airborne particulate IAD is currently unknown.
matter in the horse’s breathing zone, which may be 30–40
times higher than in other parts of the stall. Recurrent or persistent viral infection
Stabling can result in an increase in the number of
neutrophils in the BAL fluid of otherwise healthy horses A number of studies suggest a role for viruses in the
that have no overt signs of pulmonary dysfunction, sug- etiology of IAD. Oral administration of interferon-α (IFN-α),
gesting a non-specific response to exposure to stable an endogenous immunostimulant with antiviral activity,
dust. Furthermore, the association between bedding type reduces lower respiratory tract inflammation in race-
and poor ventilation and the occurrence of IAD suggests a horses with chronic IAD. Also, equine herpesviruses (EHV)
role for noxious gases or particulate matter in the etiology 1 and 4 have been isolated from nasal swabs from a small
of IAD. proportion of racehorses with signs of IAD. Similarly,
Recent studies have suggested that the major pro- antibodies to EHV-1 and EHV-4 and to equine influenza
inflammatory component of particulate matter is adherent virus have been detected in the tracheal secretions of
endotoxin. Airborne endotoxin concentrations in some horses with chronic pulmonary inflammation. However, a
horse stables have been reported to exceed those that can number of reports indicate that viruses do not have a
induce pulmonary inflammation in humans. Inhaled major role in the etiology of IAD. For example, Burrell et al
endotoxin can induce pulmonary inflammation in other- (1996) and Christley et al (2001a) found no association
wise normal horses (Pirie et al 2001) and the concentration between IAD and viral seroconversion. In addition, if
of endotoxin in the breathing space is associated with the persistent equine influenza virus infection or postinfection
development of IAD in young racehorses (Malikides 2003). damage to the airways is an important cause of IAD, one
might expect a lower incidence of this syndrome in areas
Exercise that are free of equine influenza, such as Australia.
Unfortunately, there is little information available on the
The prevalence of IAD is higher in horses undergoing incidence of these conditions in different countries, and
exercise training, compared to non-exercised stablemates. any comparison would be difficult because of potential
The cause of this effect is not known but exercise may confounding by management and housing effects.
result in deep inhalation of particulate matter, exposure of
the small airways to cold unconditioned air, and exercise- Type I hypersensitivity reaction
induced pulmonary hemorrhage (EIPH). Increased minute
ventilation and straightening of the airways during exer- The etiopathology of eosinophilic pulmonary inflammation
cise decrease deposition of particles in the upper airways may differ from that of neutrophilic pulmonary inflam-
and large lower airways, leading to greater deposition in mation, and could represent an immune-mediated response
the small airways. As instillation of blood into the airways consistent with a type I hypersensitivity reaction. Studies
is known to induce airway neutrophilia, it is likely that from North America have found that horses affected with
EIPH, a common and repetitive problem in racehorses, eosinophilic pulmonary inflammation typically have a
plays a role in the development of IAD in some horses. The moderate to prominent interstitial pattern on thoracic
increased risk of IAD with commencement of racing that is radiography, and eosinophilic pulmonary granulomas can
reported in some studies supports a role for deep inhalation be identified at post-mortem examination of some horses
of particulate matter during exercise and/or EIPH in the with pulmonary eosinophilia.
etiology of IAD.
Diagnosis
Exposure to noxious gases
The diagnostic approach to horses with suspected IAD
Horses may be exposed to common airborne pollutants, should aim to confirm this diagnosis and to provide
such as sulfur dioxide, nitrogen dioxide, ozone, and carbon information regarding likely etiological factors so as to
guide therapy. In most cases, this should include a full transportation. Provided this restriction is not prolonged,
general physical examination (with or without hematology the tracheal mucus volume rapidly returns to normal.
and serum biochemistry) to rule out concomitant diseases. Hence, information regarding the immediate history of the
A thorough examination of the respiratory tract, including horse before examination should be considered when
auscultation, endoscopy, and cytology and bacteriology of evaluating endoscopic findings.
the airway lining fluids should also be performed. Further
tests, such as thoracic radiographs and pulmonary func- Airway cytology
tion testing, are performed under specific circumstances.
An increased proportion of inflammatory cells in airway
History and clinical signs secretions is one of the principal diagnostic criteria for
IAD. Typically, neutrophils predominate, although, less
A detailed history and physical examination should be frequently, there may also be increases in the numbers
performed on all suspected cases of IAD. Together these of mast cells and/or eosinophils. As the proportion of
help to rule out alternative diagnoses and may identify neutrophils, and other cells, in the airway secretions of
potential etiological factors. Coughing during exercise apparently normal horses depends on numerous factors
and/or eating is the most common presenting complaint. (including type of housing and bedding and methods of
Information regarding the clinical history, effects on sample collection), it is difficult to be too prescriptive about
performance, management and presence of disease in cut-off values for disease. The cut-off values suggested here
the in-contact horses should be determined. Evidence of are for guidance, and clinicians should assess the results for
systemic disease, such as depression, pyrexia or inap- each case in light of other findings. Particular care should
petance, will rule out IAD, or indicate the presence of con- be taken when considering results near the cut-off values.
comitant disease. If the presenting complaint includes a It is believed that horses with different cytological
history of poor performance, an exhaustive examination profiles develop a similar range of clinical signs. Some
should rule out alternative causes such as musculoskeletal studies have associated eosinophilic IAD with poor exercise
disease, upper airway dysfunction, and cardiovascular dis- performance and airway hyperresponsiveness. However,
ease before the poor performance is ascribed to IAD. BAL eosinophilia can also be observed in subclinical or mild
The respiratory examination should evaluate both the disease, indistinguishable from the typical signs of IAD.
upper and lower respiratory tracts. The presence and If BAL eosinophilia is identified, the clinician should
character of nasal discharge should be assessed. Careful investigate parasitic pulmonary disease, including ascarid
thoracic auscultation using a rebreathing bag in a quiet migration and lungworm infection, in addition to hyper-
environment is recommended. Abnormalities on thoracic sensitivity pneumonitis. Aerosolized corticosteroid adminis-
auscultation are rarely present in IAD and identification of tration is recommended for horses with BAL eosinophilia;
these should prompt consideration of other pulmonary however, this treatment has not yet been investigated under
pathological disorders. conditions of a controlled, randomized clinical trial. In the
experience of one author (B.R.R.), eosinophilic pneumonitis
Endoscopy responds slowly and incompletely to immunosuppressive
therapy. However, the other author (R.M.C.) observed cases
Endoscopy of the lower airways is a fundamental compo- of marked eosinophilic IAD that presented as neutrophilic
nent of the diagnostic work-up of horses with suspected IAD within days to weeks, before resolving, as have other
IAD. In many cases, a presumptive diagnosis of IAD can be clinicians (Bruce McGorum, personal communication).
made on the basis of endoscopic findings. In addition, Diagnosis of metachromatic cell inflammation requires
endoscopy can facilitate the collection of tracheal fluid identification of > 2% of the total BAL cell count as mast
samples for cytology and bacteriology and bronchial cells. Clinical signs of metachromatic cell inflammation
samples for cytology. Increased amounts of mucus are a include poor race performance, chronic cough, and airway
common finding in cases of IAD; however, the quantity hyperreactivity. Identification of mast cells in BAL fluid
that constitutes an abnormality is not clear. Grading scores cytology preparations is facilitated by the use of cationic
exist to help reduce the subjectivity of the assessment dyes such as toluidine blue stain, because mast cells are
of mucus quantity (see Chapter 5). Generally, healthy not evident on preparations stained with many of the con-
horses will have no mucus, or only a few mucus droplets, ventional stains. Mast cells are thought to play an impor-
evident. Increased volumes, however, are consistent with tant role in the pathophysiology of early-stage allergic lung
airway inflammation. Caution is required, however, because disease in humans through release of inflammatory
the range of scores observed for normal horses overlaps mediators following antigen exposure. Metachromatic cell
with those of horses with IAD. Furthermore, pooling of inflammation likely represents a local pulmonary hyper-
mucus in the trachea may occur whenever a horse is sensitivity response and may represent an early form of
prevented from lowering its head, such as occurs during RAO. Horses with clinically relevant metachromatic cell
inflammation demonstrated marked bronchoconstriction Airway bacteriology

during bronchoprovocation challenge with histamine.
Some clinicians use a bronchoprovocation challenge to The lower respiratory tract of the horse is normally sterile,
determine the clinical relevance of cytological findings and although it may transiently contain small numbers of
to monitor the response to treatment. bacteria. The bacterial population of the lower respiratory
tract of normal horses reflects the balance between the
ingress of bacteria from the nasopharynx and environ-
Comparison of tracheal aspirate ment, and the clearance of these bacteria via the
and BAL cytology pulmonary defense mechanisms. In normal horses the
small numbers of bacteria are effectively transient, being
The cytological results of simultaneously collected tracheal
efficiently cleared by normal pulmonary defenses. The
aspirate (TA) and BAL samples are often poorly correlated.
frequency of isolation of bacteria from the lower respira-
In one study in which both TA and BAL were performed
tory tract can increase under some circumstances, such as
following exercise, the diagnosis (IAD or normal) was the
following coughing during sampling, or following exercise
same in approximately 60% of cases. In almost three-
or prolonged head elevation. Therefore, the lower respira-
quarters of cases where discrepancy occurred, IAD was
tory tract is frequently exposed to potentially pathogenic
diagnosed by TA but not by BAL. Unfortunately, there is
bacteria. Whether or not disease occurs as a result of this
still controversy as to whether IAD is a localized or
contamination depends on the efficacy of the pulmonary
generalized respiratory condition; most likely it may be
defense mechanisms.
both. The aforementioned studies comparing the results of
TA and BAL suggest that in some cases the cytological
changes associated with IAD may be localized. Hence, Nasopharyngeal contamination of samples
absence of evidence of inflammation on a single BAL result
should be treated with caution if the index of suspicion for Many organisms isolated from the lower respiratory tract
IAD is high. following nasopharyngeal contamination are similar to
The potential occurrence of localized and generalized those thought to be involved in IAD. Therefore, the types of
changes in IAD has clinical implications. Clinicians may bacteria isolated do not give an indication of the likelihood
consider performing cytology on both TA and BAL samples. of contamination. The presence of squamous epithelial
Collection of one type of sample only should be considered cells (SECs) and food material on microscopic examination
an incomplete clinical database, and the conclusion of of samples has been used as evidence of nasopharyngeal
freedom from IAD should be made with caution. contamination. Several protocols for the quantification of
SECs have been suggested, including the relative percentage
of SECs in the sample and the number of SECs per low-
The effect of exercise on tracheal power field. While estimating the number of SECs/ml
and bronchoalveolar secretions appears to provide useful information as to the likelihood of
contamination, no strict guidelines or cut-off values have
Recent exercise (within 30–60 min) may affect the volume
been established. Furthermore, such information should
of airway secretions and the proportion of cell types
always be interpreted in the light of clinical, cytological,
recovered by tracheal washes or BAL. Post-exercise TA
and bacteriological findings.
samples contain more airway secretions than pre-exercise
washes and specimens obtained after exercise differ in
cytological variables in a proportion of horses. In one Classification of IAD on the basis of airway
study, the proportion of neutrophils in BAL samples from cytology and microbiology
apparently normal horses almost doubled following intense
(race speed) exercise. The reasons for the effect of exercise Although subcategories of IAD are not well defined,
are uncertain. Increased lung movement and airflow differentiation of cases into a number of groups may facili-
during exercise may mechanically force redistribution of tate a rational approach to therapy. We currently recom-
existing secretions, in which case sampling post exercise mend the following classifications:
may maximize the chance of detecting an abnormality.
However, exercise may also expose the lower airways to ● Bacterial IAD – identification of known pathogenic
inhaled environmental agents that are normally removed bacteria (or Mycoplasma spp.), in numbers greater than
in the upper airways, and to blood arising from EIPH, and 102 colony-forming units/ml of tracheal aspirate, in the
hence the cytological changes may represent a new insult presence of neutrophilic inflammation and the absence
rather than a pre-existing pathology. The potential effect of of evidence of upper airway contamination warrants
recent exercise should be considered when results are administration of antimicrobial therapy, preferably
evaluated. based on the results of culture and sensitivity tests.
● Non-bacterial IAD – if bacteria are not considered to 3,000 gases have been identified in exhaled breath. Ethane
be part of the etiology of the airway inflammation, and pentane, markers of oxidative stress, have been
cytological evaluation of BAL or TA may be used to detected in the exhaled breath of horses and other species
categorize cases into one of the following inflammatory with pulmonary inflammatory disease. However, these
profiles: markers are non-specific and will be elevated in any
– Mixed inflammation with high total nucleated cell oxidative disorder. Exhaled breath condensate can be easily
count, neutrophilia (> 5% of total BAL cells, > 20% of collected from unsedated horses. Markers that show some
total TA cells), lymphocytosis, and monocytosis promise as disease indicators include hydrogen peroxide,
– Increased metachromatic cells (mast cells > 2% of carbon monoxide, thiobarbituric acid-reactive substances,
total cells) nitrate, 8-isoprostane, and cytokines and leukotrienes. The
– Eosinophilic inflammation (> 5% of total cells). physical properties of the condensate, including its pH,
may also provide information about respiratory inflam-
mation. As an adjunct to other diagnostic tests, such
Hematology and biochemistry methods may provide objective measures of inflammation
By definition, horses with IAD are free from systemic and may permit frequent monitoring of the respiratory
illness; consequently hematological and serum biochemical tract, which may aid tailoring of treatment protocols and
parameters are usually within normal limits. Identification facilitate future field-based studies.
of abnormalities may suggest alternative or coexisting
diagnoses. Treatment and Prevention
Choice of treatment options for horses with IAD will
Radiography depend on the definitive or putative diagnosis of the
inciting cause. In reality, choice of therapy is often deter-
Generally, radiographic examination of horses with sus-
mined by the previous (perceived) success of particular
pected IAD is unrewarding. Radiographic findings are often
regimens. However, bacterial, neutrophilic IAD appears to
within normal limits and are of little use for grading the
have a relatively short duration (days or a few weeks) in the
degree of pathological change or lung dysfunction. The
absence of therapy and resolution may occur naturally
exception is eosinophilic pulmonary inflammation, because
rather than as a result of veterinary intervention. There-
thoracic radiographs are indicated to identify the severity
fore, in the absence of randomized trials, the appropriate-
of interstitial infiltration and to monitor the response to
ness of treatment protocols remains largely speculative.
therapy and/or disease progression.
Given what is currently known regarding the potential
causes of IAD, rational therapeutic protocols address some
Pulmonary function tests or all of the following:
Conventional measures of pulmonary function, such as ● provision of an environment with low levels of airborne
maximal changes in pleural pressure, pulmonary resist- pro-inflammatory agents
ance, and dynamic compliance, are not altered in horses ● removal of potential inciting causes
with IAD. Some horses with IAD demonstrate airway ● treatment of pathological sequelae, such as airway
hyperreactivity in response to histamine challenge and inflammation and bronchoconstriction.
lower forced expiratory airflows, compared to control Categorization of cases, based on airway bacteriological
horses (Viel 2003). However, to date, these changes have and cytological findings, may help guide therapy. Treat-
only been assessed in non-random populations, such as ment of metachromatic cell and eosinophilic pulmonary
those investigated in referral centers. The prevalence of inflammation in the older (> 6 years) sport horse often
functional abnormalities in the general population of requires long-term therapy, and clinical signs frequently
horses with IAD is unknown, and it is possible that such recur after discontinuation of therapy.
horses represent a subgroup of IAD. In general, pulmonary
function tests are not required to diagnose IAD, although
they may help differentiate this syndrome from RAO, which
Environmental management
is associated with more severe lung dysfunction. Environmental management has long been a mainstay of
treatment of RAO. However, as increased levels of dust,
Breath and breath condensate analysis endotoxin, ammonia and other airborne pollutants can
induce inflammatory changes in otherwise normal horses,
Although not widely available at present, the analysis of management of cases of IAD should incorporate the pro-
breath and breath condensate may offer useful diagnostic vision of a low-irritant environment, regardless of whether
possibilities in the future (Wyse et al 2004). More than environmental pollutants are considered an inciting cause.
Unfortunately, provision of an ideal environment may and triamcinolone acetonide, although only beclometha-
require considerable effort and expense to the horse owner sone dipropionate and fluticasone propionate have been
and hence may be difficult to achieve. widely used in horses. Treatment protocols for these agents
The pollutants considered most likely to be involved in are currently based on data from horses with RAO,
the development of IAD originate from bedding and feed although these should be appropriate for horses with IAD.
and from the excreta of the horse itself, and may reach The dose rate varies with methods of administration. The
high concentrations in poorly ventilated stables. Where recommended dose rate for beclomethasone dipropionate
practical, keeping horses with IAD outdoors or in stables is 500–1,500 μg q12h using the 3M Equine Inhaler®
with open designs may be beneficial. Frequently, however, or 3,750 μg q12h using the Aeromask®. Administration
such modifications are not possible but ensuring that of the lower dose (500 μg) results in similar clinical
windows and doors are open and that vents are unob- efficacy but less adrenal suppression in horses with RAO.
structed may be helpful. Ideally, ventilation should be Fluticasone propionate, at a dose rate of 2,000 μg q12h
sufficient to provide at least eight air changes per hour. via an Aeromask®, has been recommended for horses with
Evidence suggests that modification of a horse’s imme- RAO. At this dose, adrenal suppression is not observed.
diate breathing zone should be the main goal of environ- The most appropriate corticosteroid for intramuscular
mental management. Hence provision of low-dust bedding (IM) or intravenous (IV) administration is dexamethasone
and feed is important. Bedding materials with lower (0.05–0.1 mg/kg q24h). Dexamethasone (at the same
concentrations of respirable dust and other pollutants dose) and prednisolone (1–2 mg/kg q12h to q24h) may be
include shredded paper and cardboard, wood chips and administered orally. Typically, these agents are admin-
large wood shavings, peat moss, and rubber. Where istered at the higher end of the recommended dose rate for
possible, these should be used in place of straw or deep 24–48 h, followed by a reduction in the amount and
litter shavings. Regular removal of fecal material and frequency of administration over several days to weeks.
urine-soaked bedding is essential. Low-dust forage sources, However, whether this dose reduction is required for short-
including soaked hay or preferably haylage, should be used term administration (as is appropriate for most cases of
instead of dry hay. Complete, pelleted diets constitute a IAD) remains uncertain. As noted previously, prednisone is
low-dust source of concentrated feed. poorly absorbed following oral administration and should
not be used.
Corticosteroids
Bronchodilators
The efficacy of corticosteroids in cases of IAD is poorly
documented. However, given the underlying inflammatory By definition, respiratory dysfunction is not a feature of
process involved, administration of corticosteroids may be IAD, and affected horses do not have detectable bron-
beneficial in cases of IAD that are considered not to have choconstriction. However, it is possible that judicious use of
an infectious etiology. The most logical indications for bronchodilators may be appropriate to reduce minor
corticosteroid administration to horses with IAD are those degrees of small airway obstruction, reduce exercise-
cases with eosinophilic and metachromatic cell inflamma- induced cough, aid the removal of mucus, and improve the
tion. Reduction in airway reactivity has been reported delivery of other agents via the inhalation route. The most
following 30-day oral administration of prednisone to commonly used agents are the anticholinergics and
horses with IAD (Viel 2003). However, no control group β2-agonists which may be formulated for inhalation or
was included, and as prednisone remains largely unab- systemic administration. While bronchodilators may
sorbed from the equine gut, other factors were likely to provide temporary beneficial effects, they will not address
have been responsible for the improvement. the underlying inflammatory process or airway hyper-
Corticosteroids may be administered orally, intravenously, reactivity. Furthermore, repeated use of β2-agonists (without
intramuscularly or via inhalation. Recent advances in the corticosteroids) may result in receptor down-regulation,
delivery of inhaled agents to horses should make this route reducing their efficacy.
more popular in the future. In almost all circumstances, Currently, the most common approach to bronchodi-
short-acting corticosteroids are preferred to better tailor lation is the systemic administration of clenbuterol, a
the dose and to reduce the risk of adverse side effects. The β2-agonist. There is a risk of adverse reactions so the
use of corticosteroids should be accompanied by efforts to recommended dosing regimen is 0.8 μg/kg q12h per os,
reduce exposure to potential pro-inflammatory mediators, followed, if necessary, by incremental increases of about
generally through environmental modification; otherwise 0.8 μg/kg every 2 or 3 days. Although doses up to
any beneficial effects may be short-lived. 3.2 μg/kg q12h have been administered in horses with
A range of corticosteroids is available for inhalation RAO, such doses should not be needed in horses with IAD,
therapy (see Chapter 7). It includes beclomethasone dipro- which have no clinically detectable bronchoconstriction.
pionate, budesonide, flunisolide, fluticasone propionate, The presence of clinically detectable airway obstruction,
such as respiratory distress at rest, should prompt con- profile. In contrast, horses with eosinophilic IAD do not
sideration of an alternative diagnosis and the initiation of respond favorably to IFN-α therapy. IFN-α is a proximal
alternative diagnostic testing. mediator of immunomodulation and has antiviral activity.
A number of β2-agonists are available for inhala- The specific mechanism of therapeutic benefit of IFN-α
tion administration. These include albuterol, fenoterol, in horses with IAD is unknown. The pathway for dis-
pirbuterol, formoterol, and salmeterol. The first three of semination of its biological effects following oral admin-
these have rapid onset of action (5 min) and short dura- istration may be the activation of natural defense systems
tion of activity (approximately 1–3 h). Formoterol and originating in oropharyngeal-associated lymphoid tissue
salmeterol have a slower onset of action, but can provide that involves cellular communication and amplification of
up to 8–12 h relief in horses with RAO. As such, salmeterol the immune response. Lymphocytes exposed to IFN-α can
has been recommended for maintenance therapy for transfer enhanced biological effects to naive lymphocytes in
RAO. As salmeterol has much greater β2 selectivity than the absence of IFN-α. It is hypothesized that lymphocytes
albuterol, this agent has reduced risk of adverse (β1) effects recruited to antiviral activity by IFN-α in the oral cavity
at therapeutic dosages. Occasionally in human asthma can enter the circulation and rapidly confer antiviral
patients, the administration of β2-agonists, particularly capability to cells at distant sites. The process would not
albuterol and salmeterol, may be followed by bronchocon- require the continued presence of IFN-α and may represent
striction. This effect has not yet been noted in horses. a major amplification mechanism. This mechanism allows
The anticholinergic agent ipratropium bromide induces the biological effects of IFN-α to reach tissues that are
bronchodilation, attenuates cough, and protects against accessible to mobile lymphocytes, in which penetration of
bronchoconstrictive stimuli. Like atropine, ipratropium IFN-α might be poor, such as the surface of the respiratory
bromide is a non-selective muscarinic antagonist, but is tract, gastrointestinal tract, and the eye. The current high
poorly absorbed following inhalation (approximately 6%) cost and limited availability of IFN-α is likely to restrict the
because of its quaternary ammonium structure. Therefore, use of this drug in horses in the near future.
ipratropium bromide has few systemic adverse effects
and does not inhibit gastrointestinal motility. In RAO- Antibiotics
affected horses, the onset of action following inhalation is
15–30 min, and the duration of action is between 4 and Up to 50% of horses with IAD may have evidence
6 h. The dose rate is dependent on the method of adminis- of bacterial infection. Despite evidence of spontaneous
tration, ranging from 180 to 360 μg/horse (or 0.5–1 μg/kg) resolution of IAD in many cases, antimicrobial therapy
for the Aeromask®, 2 to 3 μg/kg for ultrasonic nebulizers may be rationally used in selected cases of IAD. The bac-
and 200 μg/100 kg (or 2,400 μg/horse) for dry powder teria most commonly involved include Streptococcus spp.,
inhalers. The effects of anticholinergic agents are addi- Pasteurella spp., and Actinobacillus spp. Other organisms,
tive to those of the β2-agonists, with the former acting such as Bordetella bronchiseptica, are also occasionally
principally on the more central airways and the latter isolated and Mycoplasma spp. have been isolated in out-
on the smaller peripheral airways. Hence, combination breaks of IAD. Anaerobic bacteria are rarely, if ever, involved.
therapy has been recommended. Penicillin G has good efficacy against the most common
isolates. Penicillin may be administered as procaine
penicillin (22 mg/kg q12h IM) or sodium or potassium
Sodium cromoglycate penicillin (22 mg/kg q6h IV). Procaine penicillin is often
avoided with race or competition horses because of the
In IAD-affected horses with elevated numbers of meta-
restrictions on the detection of procaine in these horses. In
chromatic cells in BAL fluid, aerosol administration of
addition, intramuscular administration, particularly over
sodium cromolyn (200 mg q12h to q24h) or nedocromil
long periods, may result in muscle pain. Whilst aqueous
sodium may improve the clinical signs of respiratory
preparations of penicillin avoid these problems, the require-
disease. Sodium cromolyn can be administered via a
ment for frequent administration makes its use incon-
nebulizer or metered dose inhaler using a facemask (e.g.
venient in non-hospitalized horses.
Aeromask® or EquineHaler®).
Ceftiofur sodium, a third-generation cephalosporin, is a
popular alternative to penicillin. The recommended dose
Interferon-␣ rate is 2.2–5.0 mg/kg q12h to q24h. Although only licensed
for IM use in the horse, some clinicians have recommended
In horses with a mixed inflammatory cytological profile, IV administration. At North American racetracks, peracute
the administration of low-dose natural human IFN-α clostridial colitis has been anecdotally associated with
reduces the volume of exudate in the respiratory tract, intravenous administration of ceftiofur sodium. The spec-
lowers the total cell counts in BAL fluid, and converts the trum of activity of ceftiofur sodium encompasses the bac-
differential cell count to a non-inflammatory cytological teria commonly isolated from horses with IAD, and muscle
soreness following IM administration tends to be less of a REFERENCES

problem than following procaine penicillin.
Anon 2003 Workshop summary. In: Hoffman A, Robinson NE,
Trimethoprim and sulfonamide combinations have a Wade JF (editors) Havemeyer Foundation Monograph
broad spectrum of activity and the added convenience of Series No. 9, Workshop on Inflammatory Airway Disease:
oral and, in some countries, intravenous administration. Defining the Syndrome. R & W Publications, Newmarket,
However, in North America, a considerable proportion of pp.89–91
Streptococcus spp. isolated from horses are resistant to Burrell MH, Wood JLN, Whitwell KE et al 1996 Respiratory
disease in thoroughbred horses in training: the relation-
trimethoprim–sulfonamide combinations. This does not ship between disease and viruses, bacteria and environ-
yet appear to be such a problem in other areas. The ment. Veterinary Record 139: 308–313
recommended oral dose rate for trimethoprim–sulfonamide Chapman PS, Green C, Main JPM et al 2000 Retrospective
combinations is 15 mg/kg q12h per os; however, some study of the relationships between age, inflammation and
clinicians recommend double this dosage at the same the isolation of bacteria from the lower respiratory tract
of thoroughbred horses. Veterinary Record 146: 91–95
dose interval. Christley RM, Hodgson DR, Rose RJ et al 2001a A case–
In some areas, the use of oxytetracycline is popular for control study of respiratory disease in Thoroughbred
the treatment of IAD, particularly in racehorses. Although racehorses in Sydney, Australia. Equine Veterinary
only bacteriostatic at normal dose rates (5–10 mg/kg q12h Journal 33: 256–264
IV), some clinicians report good results, even with a 24-h Christley RM, Wood JLN, Reid SWJ et al 2001b Coughing in
thoroughbred racehorses: risk factors and tracheal
dosing interval. Benefits of oxytetracyclines include endoscopic and cytological findings. Veterinary Record
their intravenous administration and short or absent with- 148: 99–104
drawal times. Additionally, tetracyclines have direct anti- Clarke AF, Madelin T, Allpress RG 1987 The relationship of air
inflammatory effects, although the efficacy of this action in hygiene in stables to lower airway disease and pharyngeal
cases of IAD is unknown. lymphoid hyperplasia in two groups of Thoroughbred
horses. Equine Veterinary Journal 19: 524–530
Couëtil LL, DeNicola BD 1999 Blood gas, plasma lactate and
Effects on Performance bronchoalveolar lavage cytology analysis in racehorses
with respiratory disease. Equine Veterinary Journal
Anecdotally, IAD is frequently diagnosed as a cause of poor Supplement 30: 77–82
exercise performance. However, the true effect of IAD on Davis E, Rush BR 2002 Equine recurrent airway obstruc-
tion: pathogenesis, diagnosis, and patient management.
performance is incompletely documented. Many horses Veterinary Clinics of North America; Equine Practice
undergoing investigation for poor performance have signs 18: 453–468
of IAD. However, given the high prevalence of IAD, the Hoffman AM 1999 Programme of lung function testing
clinical relevance of this finding is uncertain. Few studies horses with suspected small airway disease. Equine
have investigated the physiological effects of IAD. In one Veterinary Education 11: 322–328
Hoffman AM, Mazan M 2003 Airway obstruction and hyper-
study, submaximal exercise in standardbred trotters failed reactivity in horses with signs of inflammatory airway
to identify an obvious difference in IAD-affected horses, disease. In: Hoffman A, Robinson NE, Wade JF (editors)
compared to healthy horses, in regard to arterial blood gas Havemeyer Foundation Monograph Series No. 9, Workshop
changes (Nyman 2003). In contrast, others have found on Inflammatory Airway Disease: Defining the Syndrome.
that IAD-affected horses develop greater exercise-induced R & W Publications, Newmarket, pp.9–12
Malikides N 2003 Epidemiological studies on inflammatory
hypoxemia than healthy controls during submaximal airway disease (IAD) in young Thoroughbred racehorses.
exercise (Couëtil & DeNicola 1999). In another study, PhD Thesis, University of Sydney
horses with IAD had increased airway reactivity (Hoffman Malikides N, Christley RM, Pirie RS et al 2003 Effect of
& Mazan 2003). Furthermore, although only approaching respirable and total endotoxin on neutrophilic inflam-
significance (P = 0.055), airway resistance was increased mation of lower airways in young Thoroughbred
racehorses in Sydney, Australia. CD-ROM Proceedings of
in horses with IAD, similar to previous studies (Hoffman International Society for Veterinary Epidemiology and
1999), suggesting a degree of airway obstruction in some Economics, Vina Del Mar, Chile
horses with IAD, although not to the same degree as horses Moore BR, Krakowka S, Robertson JT et al 1995 Cytologic
with RAO. Post exercise, horses with IAD have higher blood evaluation of bronchoalveolar lavage fluid obtained
lactate concentrations, lower bicarbonate concentrations, from Standardbred racehorses with inflammatory air-
way disease. American Journal of Veterinary Research
and lower pH than control horses (Couëtil & DeNicola 56: 562–567
1999). Hence there is experimental evidence that IAD Nyman G 2003 Inflammatory airway disease and gas
induces physiological changes in exercising horses that exchange. In: Hoffman A, Robinson NE, Wade JF (editors)
may result in alterations in performance. It is likely that the Havemeyer Foundation Monograph Series No. 9, Work-
clinical impact of IAD on exercise performance is shop on Inflammatory Airway Disease: Defining the
Syndrome. R & W Publications, Newmarket, pp.75–80
dependent upon the nature, duration, and magnitude of Pirie RS, Dixon PM, Collie DD, McGorum BC 2001 Pulmonary
pulmonary inflammation, as well as the nature of the and systemic effects of inhaled endotoxin in horses with
athletic activity of the patient. heaves. Equine Veterinary Journal 33: 311–318
Robinson NE 1997 Pathogenesis and management of airway Hoffman A, Robinson NE, Wade JF (editors) Havemeyer
disease. In: Norwood G (editor) Proceedings of the 43rd Foundation Monograph Series No. 9, Workshop on
Annual Convention of the American Association of Inflammatory Airway Disease: Defining the Syndrome.
Equine Practitioners. American Association of Equine R & W Publications, Newmarket, pp.71–74
Practitioners, Lexington, Kentucky, pp.106–115 Wood JLN, Burrell MH, Roberts CA et al 1993 Streptococci
Schwartz DA, Thorne PS, Jagielo PJ et al 1994 Endotoxin and Pasteurella spp. associated with disease of the equine
responsiveness and grain dust-induced inflammation in lower respiratory. Equine Veterinary Journal 25: 314–318
the lower respiratory tract. American Journal of Hoffman A, Robinson NE, Wade JF (editors) 2003 Havemeyer
Physiology 267: L609–L617 Foundation Monograph Series No. 9, Workshop on Inflam-
Viel L 1997 Small airway disease as a vanguard for chronic matory Airway Disease: Defining the Syndrome. R & W
obstructive pulmonary disease. Veterinary Clinics of Publications, Newmarket.
North America; Equine Practice 13: 549–560 Wyse CA, Yam PS, Sutton DGM et al 2004 Current and future
Viel L 2003 Airway obstruction and hyper-reactivity in uses of breath analysis as a diagnostic tool. Veterinary
horses with signs of inflammatory airway disease. In: Record 154: 353–360
Miscellaneous Pulmonary Disorders
43 Tim Mair
and neurogenic theories have been proposed. Intrathoracic

Pulmonary Neoplasia
disease is present in the majority of cases of hypertrophic
Tumors in the thoracic cavity may occur as primary osteopathy and should be investigated in horses displaying
thoracic neoplasms or tumors that metastasize to the chest these unusual clinical signs.
from a primary site elsewhere in the body. The lungs,
mediastinum and lymph nodes, and pleural cavity may be Lymphoma (lymphosarcoma)
affected. Thoracic neoplasia is uncommon in the horse,
and surveys of necropsy examinations indicate a very Lymphoma involving the mediastinum is the commonest
low incidence. Cotchin and Baker-Smith (1975) reviewed type of thoracic neoplasia identified in horses (Mair et al
1,308 equine post-mortem examinations in an abattoir 1985). In most cases, the lymphoma is multicentric, but
survey, and recorded only two cases of thoracic neoplasia tends to be present in either mediastinal, alimentary,
(one granular cell myoblastoma and one bronchiolar cutaneous or generalized forms (or combinations of these
adenoma). Two other surveys of necropsy examinations forms) (Mair and Hillyer 1992). In addition to the non-
failed to record any cases of thoracic neoplasia in a total of specific clinical signs of inappetence, including weight loss,
931 horses (Baker & Leyland 1975, Sundberg et al 1977). most horses with mediastinal lymphosarcoma develop
Despite the fact that they are rare, thoracic tumors need to a large-volume pleural effusion that results in dyspnea
be considered in the differential diagnosis of any horse and tachypnea. Ventral thoracic and pectoral edema often
presenting with signs of chronic pulmonary disease. occurs in these cases (Fig. 43.1). Auscultation of the chest
The clinical manifestations of thoracic neoplasia are will reveal muffling of the lung sounds in the ventral
variable, but generally include many non-specific signs thorax (usually bilaterally), and the cardiac sounds may
such as depression, inappetence, weight loss, and pyrexia. be audible over a larger than normal area. Confirmation
The identification of such systemic signs in horses pre- of a pleural effusion can be achieved by thoracic ultra-
senting with chronic pulmonary disease should raise the sonography, radiography, and thoracocentesis.
index of suspicion of thoracic neoplasia. Specific respira- The mass, and any associated pleural effusion, acts as a
tory signs such as cough, dyspnea, and pulmonary hemor- space-occupying lesion that results in compression of other
rhage vary, depending on the location of the tumor(s) and organs in the chest, and may cause jugular venous dis-
the extent of the pathology. Coughing is most pronounced tension and pulsation, and dysphagia. The neoplastic mass
in cases where a tumor mass compresses an airway, and sometimes protrudes through the thoracic inlet and can be
dyspnea is particularly marked in cases that have a pleural seen or palpated as a unilateral or bilateral mass at the base
effusion. Mediastinal tumors often present with clinical of the jugular furrow (Fig. 43.1). These masses may
signs that reflect a large-volume pleural effusion such as be amenable to surgical biopsy, although a deep surgical
rapid, shallow breathing and pectoral edema. Intrapul- cut-down may be necessary to reach neoplastic tissue.
monary tumors, on the other hand, tend to present with Generalized enlargement of the peripheral lymph nodes is
exercise intolerance, weight loss, cough, and occasionally rarely present in cases of mediastinal lymphoma.
epistaxis. Lameness, as a result of either bone infiltration or The diagnosis of thoracic lymphoma is based on the
hypertrophic osteopathy (Marie’s disease), is occasionally clinical signs, identification of pleural effusion, pleural fluid
observed in horses with metastatic pulmonary neoplasia. cytology and biopsy of any accessible tumor masses. A
Hypertrophic osteopathy is a rare syndrome characterized mediastinal mass may also be identifiable by ultrasonography
by symmetrical proliferation of subperiosteal bone along (Garber et al 1994). Non-specific hematological changes
the diaphyses and metaphyses of the long bones of the include leukocytosis, neutrophilia and hyperfibrinogenemia.
appendicular skeleton. Affected horses have symmetrical, In a minority of cases, there may be lymphocytosis in the
firm swelling of all four limbs and shifting leg lameness peripheral blood, possibly with the presence of abnormal
(Mair et al 1996). The exact pathophysiology of this bony circulating lymphoblastic cells; however, true leukemias are
proliferation is unclear; however, hormonal, hemodynamic, very rare in the horse. The effusion in cases of lymphoma
601
602 43 Miscellaneous Pulmonary Disorders
primary equine lung tumors include pulmonary and bron-

chial carcinomas and adenocarcinomas (Dill et al 1986,
Uphoff & Lyncoln 1987, Van Rensburg et al 1989, Mair &
Brown 1993); bronchogenic squamous cell carcinoma
(Schultze et al 1988); pulmonary granular cell tumor
(Alexander et al 1965, Misdorp & van Gelder 1968, Parker
et al 1979, Nickels et al 1980, Turk & Breeze 1981, Sutton
& Coleman 1995, Facemire et al 2000, Pusterla et al 2003a);
bronchial myxoma (Murphy et al 1978); and pulmonary
chondrosarcoma (Sullivan 1960, Clem et al 1986).
Pulmonary granular cell tumor

Pulmonary granular cell tumor (also known as granular
cell myoblastoma or putative Schwann cell tumor) appears
to be the most common primary equine intrapulmonary
tumor. This tumor is of mesenchymal origin, probably
derived from myoblasts. The mean age of reported cases is
13 years (Pusterla et al 2003a), and there appears to be no
breed predisposition. The majority of reported cases have
involved mares. Presenting clinical signs generally include
paroxysmal cough, exercise intolerance, and weight loss.
Hypertrophic osteopathy has been recorded in a small
number of affected horses (Alexander et al 1965, Sutton &
Coleman 1995). Some affected horses may survive for
several years with this tumor, although progressive
respiratory distress and weight loss are likely to ensue. The
chronic nature of the clinical presentation can lead to an
incorrect initial diagnosis of recurrent airway obstruction
(Pusterla et al 2003a).
Fig. 43.1. Ventral pectoral edema and mass at the base of the jugular Diagnosis of pulmonary granular cell tumor is achieved
groove in a 7-year-old mare affected by mediastinal lymphoma. by a combination of the clinical history, physical exami-
nation, endoscopy, thoracic radiography and diagnostic
ultrasonography, and possibly biopsy. Hematological exami-
nation often reveals non-specific changes including hyper-
is typically a modified transudate or non-septic exudate, fibrinogenemia and leukocytosis with neutrophilia. Pul-
and neoplastic cells are frequently, but not always, present monary auscultation is frequently unremarkable, although
in the fluid. A large number of the cells in such effusions reduced breath sounds may be identified over one hemi-
will be mononuclear, mainly lymphocytic. Lymphoblasts thorax because of the occlusion of one main-stem bronchus
with mitoses may be present. by the tumor. The tumor usually consists of multiple, well-
Thoracoscopy can be used to examine the pleural cavity defined nodules associated with a major bronchus, and a
and cranial mediastinum in horses with suspected portion of the mass is often seen on endoscopic exami-
mediastinal lymphoma (Vachon & Fischer 1998), as well as nation of the carina or bronchi (this examination requires
other forms of thoracic neoplasia (Ford et al 1987, Rossier the use of an endoscope longer than 1 m). The majority of
et al 1990, Mueller et al 1992). Biopsy of suspect lesions the mass is intrapulmonary and often involves the cranial
can be undertaken during this procedure (see Chapter 20). lung lobes. Thoracic radiographs may reveal cranioventral
opacity, or single or multiple pulmonary nodules. Usually
Primary pulmonary and pleural tumors only one lung is affected. Ultrasonography may show
reduced movement of the pleural surface on the affected
Primary pulmonary neoplasia is very rare. In one review side of the thorax; pleural thickening and “comet-tail”
of 38 cases of thoracic neoplasia in horses, only 7.9% irregularities may also be apparent. Confirmation of the
involved primary neoplasms (Mair & Brown 1993), diagnosis may be achieved by transendoscopic biopsy of a
whereas another review of 35 cases revealed no primary bronchial mass; however neoplastic tissue may not be
lung tumors (Sweeney & Gillette 1989). Examples of present in small mucosal pinch biopsies obtained in this
43 Miscellaneous Pulmonary Disorders 603
way. An alternative way to obtain larger tissue biopsies veins. Thoracic auscultation reveals muffled heart and lung
(with a greater chance of achieving a positive diagnosis) is sounds in the ventral lung fields, and ultrasonographic
to pass a biopsy instrument (such as uterine biopsy forceps) examination reveals a large volume of hypoechoic fluid
through a small tracheotomy incision performed at the with minimal cellularity and few fibrin tags. Pleural
level of the thoracic inlet (Facemire et al 2000). Although fluid recovered from horses with mediastinal neoplasia
the prognosis for this disease is generally very poor, will appear straw-colored and translucent to slightly
granular cell tumors may be amenable to surgical treat- serosanguineous, with the exception of hemangiosarcoma,
ment by lung lobe resection (Facemire et al 2000). Laser in which the pleural fluid is often hemorrhagic. Neoplastic
ablation of the intrabronchial mass may be possible, and effusions typically have low to moderate cellularity (total
may result in temporary clinical improvement. nucleated cell count from 5 × 109/liter to 40 × 109/liter)
characterized by reactive mesothelial cells, lymphocytes
Mesothelioma and macrophages, and a high total protein (3.5–6.5 mg/dl;
35–65 g/liter). Some mediastinal tumors may be exfoliative,
Mesotheliomas are rare malignant tumors that arise from and neoplastic cells can be identified on cytological evalua-
the mesothelial lining of the pleura, pericardium, and tion (melanoma, squamous cell carcinoma, hemangiosar-
peritoneum. There have been a limited number of reports coma); however, the absence of neoplastic cells in malignant
of pleural mesothelioma in the horse (Straub et al 1974, effusions is not uncommon.
Kramer et al 1976, Wallace et al 1987, Colbourne et al The commonest tumors that metastasize to the lungs
1992, Mair et al 1992, Fry et al 2003). In humans, many include adenocarcinoma (renal, ovarian, thyroid), squamous
cases of mesothelioma have been associated with prior cell carcinoma (Fig. 43.2), malignant melanoma, heman-
exposure to asbestos dust, but this association has not been giosarcoma, or undifferentiated sarcoma (Sweeney &
recognized in the small number of documented equine Gillette 1989, Mair & Brown 1993, Jean et al 1994,
cases. The tumor is invariably associated with a pleural Scarrat & Crissman 1998). The clinical features of these
effusion, and clinical signs include weight loss and pro- tumors are generally non-specific and often relate more to
gressive respiratory distress. The presence of a pleural the primary site of tumor formation than to thoracic
effusion can be confirmed by careful thoracic auscultation involvement. Examination of other body systems may
and diagnostic ultrasonography. Thoracocentesis yields a therefore reveal evidence of multisystemic infiltration or
modified transudate, and neoplastic cells may be identified may identify the primary neoplastic mass. Radiography,
in fluid samples (Mair et al 1992); however, distinguishing ultrasonography, thoracocentesis, and pleuroscopy can all
mesothelioma from mesothelial reactivity on the basis of be helpful in the diagnosis of these conditions. Definitive
cytology can be difficult. Thoracoscopy and pleural biopsy diagnosis of intrapulmonary neoplasia may be determined
may provide a positive diagnosis (Fry et al 2003). The by cytological evaluation of bronchoalveolar lavage (BAL)
malignant nature of the tumor and its rapid spread pre- fluid or histopathological evaluation of endoscopic or per-
clude any effective treatment, and affected horses invariably cutaneous lung biopsy. In many cases, however, thoracic
require euthanasia. involvement by tumor is not confirmed in life, and the
diagnosis is made at post-mortem.
Metastatic thoracic neoplasia
The lungs, mediastinal/thoracic lymph nodes, and pleural
cavity may be affected by neoplasia caused by metastatic
spread from a primary site elsewhere in the body. There are
many single case studies reporting a wide variety of
metastatic thoracic neoplasms; however, renal carcinoma,
squamous cell carcinoma (Fig. 43.2), melanoma, fibrosar-
coma, and hemangiosarcoma appear to be the most
common (Prater et al 1989, Sweeney & Gillette 1989, Mair
& Brown 1993, Basher et al 1997, Jorgenson et al 1997,
Murray et al 1997, Duncan 1998, East et al 1998, Scarratt
& Crissman 1998, McConkey et al 2000).
Pleural and mediastinal neoplasms usually produce a
significant volume of malignant pleural effusion. There-
fore, presenting clinical signs are likely to reflect this large-
volume effusion, such as rapid shallow respiration, tachy- Fig. 43.2. Metastatic tumor deposit in the lung as a result of squamous
cardia, weight loss, pectoral edema, and distended jugular cell carcinoma.
● Hydrostatic edema – this results when there is a net

Inhaled Tracheobronchial Foreign Bodies
increase in the difference between the hydrostatic pres-
The commonest forms of foreign body that can lodge in the sure in the microvessels and the hydrostatic pressure in
distal trachea and bronchial tree are thorned twigs or the interstitium.
brambles (Urquhart & Gerring 1981, Brown & Collier ● Permeability edema – this results when endothelial
1983, Duckett et al 1983). The thorns act as barbs that injury increases fluid conductivity across the membrane
allow the foreign body to progress distally but prevent it and decreases the osmotic reflection coefficient and
from being coughed up. Clinical signs include a chronic osmotic gradient.
cough and malodorous breath. A mucopurulent or blood-
stained nasal discharge may be present. The terms cardiogenic and non-cardiogenic are com-
Diagnosis is confirmed by endoscopic examination. monly used to describe these two forms of edema forma-
Treatment involves removal of the foreign body, which can tion (Table 43.1).
often be accomplished using a snare passed through the Fluid flux is sensitive to small intravascular or perivas-
endoscope. Alternatively a distal cervical tracheotomy may cular pressure changes. Intravascular pressure rises may
be made to allow insertion of grasping forceps or a snare. originate downstream (left heart failure) or may follow
The foreign body may break up as it is being removed, and overall vascular volume increases (overhydration) or
several separate procedures may be necessary to remove all redistribution of blood from the systemic to the pulmonary
of the foreign material. Broad-spectrum antibiotic therapy vessels. Normally, a net outflow of fluid from the upstream
should be administered postoperatively. Tracheal foreign capillaries is reabsorbed into the downstream capillaries,
bodies are further discussed in Chapter 40. where the intravascular pressure is lower. When capillary
endothelium is injured, locally or through the effect of
circulating mediators, the vascular permeability to fluids
and solutes is increased resulting in fluid leakage. The
Pulmonary Edema
ability to retain large molecules is lost, protein-rich plasma
The fluid fluxes across the pulmonary vascular endothelium leaks out, and the osmotic pressure in the tissues
are influenced by the same pressure relationships as in the approaches that in the vessels, so that the osmotic force
systemic capillaries. The movement of fluid across the cap- opposing intravascular hydrostatic pressure is lost. This
illary membrane is defined by the Starling–Landis equation: high-permeability or “leaky capillary” state leads to inter-
stitial edema, which can be a fulminant process leading to
J v = K f [(P c – P i ) – σ(π p – π i )]
severe abnormalities of gas exchange.
where: The epithelial cells that line the alveoli have tight
junctions along their apical surface, so this membrane is
Jv = net capillary (microvascular) filtration rate
normally much less permeable than the endothelial
Kf = capillary filtration coefficient
Pc = capillary hydrostatic pressure
Pi = interstitial hydrostatic pressure
Table 43.1. Causes of pulmonary edema
σ = osmotic reflection coefficient
πp = plasma colloid osmotic pressure Cardiogenic edema
πi = interstitial colloid osmotic pressure. Mitral valve rupture
Chordae tendineae rupture
Thus, fluid flux across the capillary is dependent on the Myocarditis
capillary hydrostatic pressure being higher than the Ventricular tachycardia
interstitial hydrostatic pressure, which drives fluid out of Non-cardiogenic edema
the vessel, and oncotic pressure within the capillary lumen Acute upper respiratory tract obstruction
being higher than that in the interstitial fluid, which Acute pulmonary injury
counteracts the hydrostatic pressure. Colloid osmotic – acute alveolitis and interstitial disease
– aspiration – near drowning, inadvertent administration
pressure, therefore, opposes the drive of fluid out of the
of medications into the lungs
capillary (Magdesian 2003). – smoke inhalation
The hydrostatic pressure in the pulmonary microvessels – oxygen toxicity
exceeds the interstitial hydrostatic pressure. This effect – infectious agents
favors microfiltration. The interstitial fluid protein osmotic – anaphylaxis
– idiosyncratic drug reactions
pressure is approximately two-thirds that in the vessel; thus
– endotoxemia and systemic inflammatory response
the net osmotic force is absorptive and inward. The syndrome
components of this equation make it convenient to – embolism
categorize abnormal fluid flux into the lung into two broad – hypertransfusion
types (Culver et al 2004):
membrane, protecting the alveolar spaces as interstitial many different insults may lead to ARDS, a final common
edema increases. However, as interstitial edema increases, pathway leads to alveolar damage.
so a structural failure of the epithelial cells occurs, allow- Acute life-threatening pulmonary edema, with or
ing edema to appear within the alveolar spaces (“alveolar without concomitant pulmonary hemorrhage, may also
edema”). As fluid accumulates, the alveoli can rapidly develop as a consequence of severe upper respiratory
become completely filled because of surface tension effects. tract (URT) obstruction. This complication may further
As a result of these effects, alveoli tend to fill with fluid in compromise gas exchange, and must be addressed when
an “all-or-none” fashion. treating URT obstructions. This complication has multi-
The term “acute respiratory distress syndrome” (ARDS) factorial pathogenesis (Fig. 43.3), including:
was introduced into human medicine over 25 years ago
● The excessively subatmospheric pressures which develop
(Gattinoni et al 2004). The syndrome consists of acute
within the thorax as the horse attempts to inspire
severe alteration in lung structure and function, charac-
against the URT obstruction alter the capillary trans-
terized by hypoxemia, low respiratory compliance, low
mural pressure favoring extravasation of fluid from the
functional residual capacity, and diffuse radiographic
pulmonary capillaries into the pulmonary interstitium
infiltrates, along with increased lung endothelial and
and air spaces.
alveolar epithelial permeability. Two interrelated pathways
● The excessively subatmospheric inspiratory intrathoracic
can lead to the development of ARDS, namely direct lung
pressure also increases venous return while impairing
injury and indirect injury (resulting from an acute systemic
left ventricular function, resulting in pulmonary
inflammatory response). Similar mechanisms can lead to
hypertension and cardiogenic pulmonary edema.
pulmonary injury in horses (Table 43.1), with pulmonary
● The hypoxemia resulting from URT obstruction may
edema being an important consequence. Thus, primary
cause hypoxic pulmonary vasoconstriction which leads
lung injury can result from aspiration (including near
to pulmonary hypertension.
drowning and iatrogenic administration of fluids or
● Sympathetic overstimulation and release of vasoactive
medication into the lungs), inhalation of toxic gases (smoke
substances may increase pulmonary capillary permeability.
inhalation), oxygen toxicity or infectious agents. Secondary
lung injury may be a sequel to anaphylaxis, endotoxemia Pulmonary edema (Fig. 43.4) results in respiratory
and systemic inflammatory response syndrome, embolism, failure that clinically presents as respiratory distress.
and hypertransfusion (Ainsworth & Hackett 2004). Although Radiography, ultrasonography, endoscopy, tracheal aspirates
Excessive subatmospheric pressures
Hypoxemia
Decreased Increased Reduced

extravascular venous return LV function
pressure
Vasoactive
mediators
Transudation Pulmonary hypertension
Increased capillary
permeability
Pulmonary edema
Fig. 43.3. Pathogenesis of pulmonary edema secondary to URT obstruction.

Fig. 43.4. Post-mortem appearance of the

lung of a 15-year-old gelding affected by
acute respiratory distress syndrome sec-
ondary to endotoxemia and gram-negative
sepsis. The lungs are diffusely congested and
edematous.
or BAL, and arterial blood gas analysis are all helpful in interstitial pneumonia experimentally in ponies (Breeze
diagnosing and monitoring the disease process. Where et al 1984), and croton weed (Eupatorium adenophorum)
possible, differentiation between cardiogenic and non- causes chronic interstitial pneumonia in horses in Australia
cardiogenic forms, and diagnosis of the underlying cause and Hawaii (O’Sullivan 1979).
should be made. Non-cardiogenic edema should be treated The pathogenesis of interstitial pneumonia involves four
with furosemide, oxygen, and corticosteroids and non- phases: acute alveolitis; proliferation of cellular and con-
steroidal anti-inflammatory agents (if the pulmonary nective tissue compartments; irreversible interstitial fibrosis;
edema is inflammatory) (Chevalier & Divers 2003). Any and irreparable generalized pulmonary fibrosis (Bruce
underlying systemic inflammatory disease will also need 1995). The clinical signs include weight loss, exercise
to be treated (including by antibiotics, fluid therapy, and intolerance, fever, and progressive respiratory distress.
colloid support). URT obstruction should be corrected, such Cyanosis may be apparent in the terminal stages. Depend-
as by temporary tracheostomy. Cardiogenic pulmonary ing on the stage of disease, most horses with interstitial
edema is most commonly the result of mitral valve rup- pneumonia have leukocytosis characterized by mature
ture, chordae tendineae rupture, myocarditis or ventricu- neutrophilia and hyperfibrinogenemia (Turk et al 1981,
lar tachycardia, and should be treated with furosemide Derksen et al 1982, Kelly et al 1995). Pulmonary ausculta-
[1 mg/kg intravenous (IV)]. Hydralazine (0.5–1.5 mg/kg tion reveals crackles and wheezes, although breath sounds
orally or 0.5 mg/kg IV) can be administered when there is may be inaudible in severely affected horses. Interstitial
severe mitral regurgitation. Lidocaine (0.25–0.5 mg/kg pneumonia is a restrictive pulmonary disease, and affected
slowly IV) or MgSO4 (1–2.5 g/450 kg horse/min IV up to horses tend to have a prolonged inspiratory phase of respira-
25 g total dose) can be used to treat ventricular tachy- tion and an abbreviated expiratory phase, and they breathe
cardia. Myocarditis should be treated with dexamethasone rapidly at low lung volumes. Pulmonary compliance is
(0.05–0.22 mg/kg IV). reduced as a result of pulmonary fibrosis and interstitial
inflammation (“stiff lungs”). Pulmonary hypertension and
cor pulmonale may occur with end-stage disease.
Cytological evaluation of BAL fluid from most horses
Alveolitis and Interstitial Pneumonias with interstitial pneumonia is non-specific and includes
The interstitial pneumonias are a poorly defined, high cellularity and chronic, non-septic mixed inflam-
heterogeneous group of sporadic respiratory diseases in mation (neutrophilia, lymphocytosis, monocytosis) (Derksen
adult horses. Interstitial disorders of foals are discussed et al 1982). Occasional horses may have BAL fluid
in Chapter 45. The etiology is undetermined in the majority eosinophilia. Nonetheless, cytological evaluation of BAL
of cases; however, infectious agents, hypersensitivity pneu- fluid may be indicated to rule out potential differential
monitis, plant toxicity, inhaled chemicals, silicosis, and diagnoses including infectious and neoplastic disorders.
drug reaction have been confirmed to cause interstitial Bacterial culture of transtracheal aspirates and BAL gener-
disease in horses (Bruce 1995). Perilla frutescens causes ally reveals no significant growth (Buergelt et al 1986).
Fig. 43.5. Lateral thoracic radiograph of

8-year-old gelding with chronic progressive
respiratory distress. The radiograph demon-
strates a nodular/miliary interstitial infiltrate
throughout the lungs. Lung biopsy confirmed
chronic interstitial pneumonia and fibrosis.
Fig. 43.6. Lung biopsy of an 11-year-old

Hackney stallion with a 4-month history
of weight loss and progressive respiratory
distress. An interstitial infiltrate (similar
to that in Fig. 43.5) was found on thoracic
radiography. There is fibrosis and thickening
of the alveolar walls, with a mixed macro-
phage and neutrophil infiltrate within the
alveolar spaces and interstitium. Hematoxylin
and eosin stain.
Thoracic radiography is the most valuable non-invasive there is alveolar septal necrosis, fibrin exudation, and
tool for diagnosis and monitoring of disease in most instances hyaline membrane formation within alveolar spaces. With
of interstitial pneumonia. Characteristic radiographic chronicity, the alveolar walls and supporting stroma
findings include diffuse interstitial infiltration with discrete become affected, and type II pneumocytes proliferate,
and diffuse nodularity (Buergelt et al 1986, Berry et al producing loss of the functional alveolar–capillary unit
1991) (Fig. 43.5). The degree of radiographic abnormali- (Fig. 43.6). Interstitial inflammation is often granuloma-
ties may not correlate with the severity of respiratory tous in the subacute stages of disease and eventually
compromise, and prognosis should ultimately be deter- progresses (irreversibly) to pulmonary fibrosis.
mined via histopathological evaluation of a lung biopsy. Horses with interstitial pneumonia are generally
Lung biopsy is very helpful to diagnose interstitial unresponsive to antimicrobial and non-steroidal anti-
pneumonia and determine the extent of pulmonary inflammatory therapy. Treatment with corticosteroids,
fibrosis. A percutaneous lung biopsy is recommended dimethyl sulfoxide, and furosemide is also ineffective unless
(Raphel & Gunson 1981). In the acute phase of disease, instituted early in the disease process (Bruce 1995).
Treatment with corticosteroids and non-steroidal anti- locations, and this can be helpful in reaching a diagnosis
inflammatory therapy should be attempted in horses with (e.g. silicosis and coccidioidomycosis) (Schwartz et al 1981,
acute or subacute interstitial pneumonia based on lung Ziemer et al 1992). Otherwise, the diagnosis is based on
biopsy. The prognosis for return to athletic function is very the results of specific tests including the cytological
poor, regardless of the etiology or stage of disease. The evaluation and culture of tracheal aspirates or BAL fluid,
prognosis for survival is poor in horses with cyanosis, cor serology, and lung biopsy.
pulmonale, and/or pulmonary fibrosis. Although tuberculosis is rare in horses, mycobacterial
infection should be considered as a potential cause of
granulomatous pneumonia. Currently, Mycobacterium avium
Silicosis is the commonest form identified in horses. Mycobacterial
Silicosis is a form of interstitial pneumonia in horses that is infections in horses are generally multisystemic, affecting
caused by inhalation of particulate inorganic silicon predominantly the lung, cervical vertebrae, and gastroin-
dioxide or quartz particles. Human silicosis is a major occu- testinal tract (Mair et al 1986, Buergelt et al 1988). Tissues
pational hazard for those involved in mining, quarrying, obtained by lung biopsy should be submitted for specific
metal casting, sandblasting, and the pottery industry. The mycobacterial culture in suspected cases.
majority of horses with documented pulmonary silicosis Chronic fungal infections, including coccidioidomycosis,
originate from the Monterey-Carmel Peninsula of mid- histoplasmosis, cryptococcosis, and aspergillosis may
coastal California (Schwartz et al 1981). Silicon dioxides be rare causes of chronic granulomatous pneumonia.
are cytotoxic to macrophages as well as being fibrogenic. Coccidioidomycosis appears to be the most commonly
When inhaled, the particles are ingested by alveolar reported of these diseases in the USA. This condition is
macrophages, causing lysis of the cells, alveolitis, granu- seen in the desert areas of southwestern USA and also in
lomatous change, and subsequent fibrosis. Definitive areas of South America. In addition to chronic weight loss
diagnosis is determined by identification of intracyto- and chronic respiratory signs, affected horses may demon-
plasmic silicate crystals in alveolar macrophages on strate musculoskeletal pain, superficial abscessation, inter-
cytological evaluation of respiratory secretions. Transtra- mittent fever, and abdominal pain (Ziemer et al 1992).
cheal aspiration has been used more frequently than BAL Granulomatous pneumonia may occur as part of the
to diagnose silicosis in horses; however, serial transtracheal generalized equine granulomatous disease syndrome
aspirates may be required to identify the characteristic (Pusterla et al 2003b). This is an idiopathic, systemic
intracellular crystals. Cytological evaluation of BAL fluid condition that resembles sarcoidosis in humans. A similar
has been used for identification of silicate crystals, and is a condition has also been reported in horses after the
more sensitive procedure for the diagnosis of pulmonary ingestion of hairy vetch (Anderson & Divers 1983). The
silicosis. Thoracic radiographic examination reveals a principal clinical sign in most reported cases of equine
marked interstitial pattern with miliary, reticulonodular, or idiopathic systemic granulomatous disease is skin lesions
linear patterns (Berry et al 1991). Lung biopsy or necropsy (Stannard 1987), but most cases also have lung lesions,
evaluation is characterized by multifocal, granulomatous as identified by thoracic radiography or post-mortem
pneumonia with areas of pulmonary fibrosis. The prog- examination. Typical clinical signs in addition to skin
nosis for survival is poor. lesions include chronic weight loss, depression, anorexia,
tachycardia, tachypnea, and abnormal lung sounds.
Thoracic radiographs reveal an interstitial pattern with an
Granulomatous Pneumonia underlying miliary or nodular pattern. Hematological data
Granulomatous pneumonia is a rare and sporadic disease usually reveal anemia, neutrophilia, hyperfibrinogenemia,
in horses. Known causes include fungal, bacterial or and hyperglobulinemia (Pusterla et al 2003b). Diagnosis is
parasitic agents, silicate pneumoconiosis, disseminated confirmed by biopsy (skin and lung). Response to systemic
neoplasia, and idiopathic causes (Pusterla et al 2003b). corticosteroid therapy is often poor, although some cases
Horses with granulomatous pneumonia usually have a can be brought into remission with prolonged treatment.
history of weight loss, exercise intolerance, depression, Development of interstitial pneumonia after intravenous
anorexia, fever, tachypnea, cough, nasal discharge, and administration of purified mycobacterial cell wall extract
abnormal lung sounds. Thoracic radiography is particu- (non-specific immunostimulant) has been reported in four
larly useful in helping to differentiate granulomatous horses (Viel & Kenney 1993). The clinical signs included
pneumonia from other chronic pulmonary diseases. cough, fever, tachypnea, lethargy, and leukocytosis. The
Confirmation of granulomatous change requires evalua- pulmonary lesions included progressive, multifocal, granu-
tion of a lung biopsy. lomatous pneumonitis, bronchiolitis, and pulmonary fibrosis.
Some of the underlying diseases that can cause granu- Thoracic radiographic examination revealed diffuse inter-
lomatous pneumonia occur in specific geographical stitial infiltrate and cytological examination of BAL fluid
revealed lymphocytic inflammation. A marked local reaction Idiopathic pulmonary fibrosis appears to be commoner
can be elicited by intradermal injection of mycobacterial in the donkey than the horse. Chronic fibrosis of the sub-
cell wall extract in affected horses. pleural and interstitial lung tissues is commonly found at
post-mortem examination of donkeys, often as an inci-
dental finding. The etiology is unknown. Most affected
Pulmonary Fibrosis donkeys remain bright and alert, with a normal appetite.
Pulmonary fibrosis represents the end stage of a number The sedentary nature of most donkeys means that
of different interstitial lung diseases (Fig. 43.7). It is likely pulmonary fibrosis may be advanced before clinical signs
that all of the various forms of alveolitis, interstitial are obvious. Early clinical signs may include tachypnea and
pneumonia, and granulomatous pneumonia could progress occasional coughing. An episode of acute, severe respira-
eventually to pulmonary fibrosis. In humans, the term tory distress with dyspnea and tachypnea may also be
“idiopathic pulmonary fibrosis” (also known as cryptogenic recognized. Following resolution of this acute respira-
fibrosing alveolitis) is used to describe all patients with tory distress, chronic and progressive dyspnea develops.
pulmonary fibrosis of unknown cause, regardless of differ- Occasional coughing is sometimes observed, and a nasal
ences in histological patterns (Costabel & Britton 2004). On discharge may be present in some cases. Stertor may arise
occasion, horses with similar clinical and pathological if there is concomitant tracheal collapse. There is no
signs are identified. known effective treatment.
The term “idiopathic pulmonary fibrosis” should only be
used in horses with chronic interstitial fibrosis (confirmed
by lung biopsy or post-mortem examination) where the
Smoke Inhalation
disease is limited to the lung, and where other known Smoke inhalation produces edema, congestion, and
causes of interstitial lung disease have been excluded. necrosis of both the upper and lower respiratory tract as a
The clinical features generally include chronic and result of both thermal and chemical injury (Trunkey
progressive respiratory failure, often of insidious onset. 1978). Upper respiratory tract injury primarily results from
Tachypnea and inspiratory dyspnea are present, with or thermal injury as a result of inhalation of hot air and
without a mild cough. Since the disease causes a restrictive particles. Thermal damage to the lower respiratory tract is
defect, affected horses tend to have a prolonged inspiratory less common but can occur with the inhalation of super-
phase of respiration and an abbreviated expiratory phase, heated particles (<5 μm). The majority of lower respiratory
and they breathe rapidly at low lung volumes. Chronic tract damage results from the inhalation of toxic
weight loss and general depression are present. Thoracic chemicals. Highly water-soluble gases, such as aldehydes,
radiographs reveal a diffuse interstitial pattern, and lung ammonia, chlorine, hydrogen chloride, and sulfur dioxide,
biopsy confirms interstitial fibrosis. Treatment with cor- produce rapid pulmonary injury, whereas insoluble gases,
ticosteroids may be attempted but the prognosis is gener- such as nitrogen and phosgene oxide, cause delayed pul-
ally hopeless. monary injury. Carbon monoxide and cyanide toxicities,
Fig. 43.7. Post-mortem appearance of the

lung of a 9-year-old thoroughbred mare with
pulmonary fibrosis. The normal lung tissue is
largely replaced by firm, pale fibrous tissue.
common with smoke inhalation, do not cause direct airway primary predisposing factor is impaired pulmonary defense
damage, but exacerbate tissue hypoxia by impairing oxygen mechanisms including loss of mucociliary clearance,
delivery and utilization. Carbon monoxide toxicity is a impaired alveolar macrophage function, and denuded
common cause of mortality associated with fire (Cahalane respiratory epithelium. Clinical signs include continued
& Demling 1984). Carbon monoxide has a greater affinity cough and nasal discharge and development of fever and
than oxygen for hemoglobin, causing the formation of depression.
carboxyhemoglobin, tissue hypoxia, and death. Cyanide is Endoscopic examination of the upper and lower
inhaled in the form of hydrogen cyanide, commonly in the respiratory tract is the most sensitive indicator of smoke
fumes from burning plastic. The clinical features of cyanide inhalation injury. Thoracic radiography may be useful to
toxicity are those related to severe hypoxia and metabolic monitor the progression of pulmonary edema and con-
acidosis, causing cardiovascular collapse, respiratory solidation, detect the development of bronchopneumo-
arrest, and coma. nia, and identify pneumothorax or pneumomediastinum.
Clinical signs of respiratory injury are often immediate; Thoracic radiography may also identify pulmonary fibrosis
however, some horses may not exhibit signs for 2 to 3 days in patients that have suffered progressive, severe inhalation
and should remain under close observation for at least 72 h injury several months after recovery. Serial blood gas
(Geor & Ames 1991). analysis can be performed to monitor respiratory function
There are three stages of smoke inhalation injury, and carboxyhemoglobin concentrations should be deter-
namely: mined to detect carbon monoxide toxicity. Transtracheal
wash may be performed during the bronchopneumonia
● acute pulmonary insufficiency
stage of smoke inhalation injury to identify opportunistic
● pulmonary edema
pathogens.
● bronchopneumonia.
Oxygen therapy is indicated in horses with smoke
Acute pulmonary insufficiency occurs during the first inhalation injury to facilitate the removal of carbon
36 h, and is attributed to thermal injury to the upper monoxide and improve pulmonary gas exchange (Kemper
respiratory tract (6–18 h after exposure), carbon monoxide et al 1993). Fractional concentrations of 40% oxygen can
and cyanide toxicities (immediate), and chemical injury to be achieved with flow rates of 50–100 ml/kg. Administra-
the tracheobronchial tree and lung parenchyma. Thermal tion of > 50% oxygen for more than 24 h may exacerbate
injury to the upper respiratory tract peaks at 18–24 h pulmonary damage. Tracheostomy may be necessary in
after exposure, and may result in upper airway edema horses with severe injury/edema of the upper airway.
to the point of obstruction necessitating an emergency Indication for tracheostomy is determined by the presence
tracheotomy. Carbon monoxide toxicity is difficult to detect of a loud inspiratory stridor. In addition to providing a
clinically because the presence of carboxyhemoglobin in patent airway, tracheostomy may facilitate the removal of
the blood gives it a bright red color; therefore, the clinician fibrinous casts from the lower respiratory tract.
must anticipate carbon monoxide toxicity in smoke Bronchodilator therapy should be administered as early
inhalation patients. Irritation from soluble gases causes as possible (stage 1 bronchoconstriction) to horses with
bronchoconstriction, mucosal edema of central airways, smoke inhalation injury. Aerosolized albuterol is the
and degradation of pulmonary surfactant. most powerful, rapid-acting bronchodilator and should be
The second stage of inhalation injury begins at paired with a long-acting aerosolized (salmeterol) or oral
approximately 24 h, and is characterized by pulmonary (clenbuterol) β2-agonist. The majority of bronchocon-
edema, which develops as a result of the inflammatory striction associated with smoke inhalation injury is vagally
response initiated by chemical injury. Clinical signs include mediated, so addition of a parasympatholytic agent is
tachypnea, dyspnea, paroxysmal coughing, and nasal valuable. Atropine can be administered on an emergency,
discharge. In instances of severe mucosal injury, a pseudo- single-dose basis and aerosolized ipratropium can be used
membranous cast, consisting of cellular debris, fibrin, and for subsequent maintenance therapy.
proteinaceous exudate, may form in large to medium-sized Furosemide (1–2 mg/kg) will reduce pulmonary edema
airways at 24–72 h. Necrotizing bronchiolitis, intra- via diuretic and non-diuretic mechanisms and is indicated
alveolar hemorrhage, thrombus formation, pneumothorax, upon the development of clinical signs of pulmonary
and massive pulmonary edema are potential sequelae. The edema. Fluid, electrolyte, and acid–base balance should be
presence of subcutaneous emphysema indicates pneu- monitored when furosemide is administered repeatedly.
mothorax and/or pneumomediastinum as the result of Corticosteroid therapy has been used successfully in
ruptured pulmonary bullae. horses with smoke inhalation injury to combat pulmonary
The third stage of smoke inhalation injury is bron- edema and maintain surfactant production. However, the
chopneumonia, which may develop as early as 5–7 days immunosuppressive effects of corticosteroids may unnec-
after exposure. However the development of bacterial essarily predispose patients to bacterial bronchopneu-
infection may occur up to 2 weeks after exposure. The monia and studies in humans and animals with smoke
Fig. 43.8. Endoscopic appearance of the

distal trachea and main-stem bronchi of
an 8-year-old pony gelding with aspiration
bronchopneumonia following an episode
of esophageal obstruction (choke). The air-
ways are inflamed with exudate and food
material.
inhalation have failed to identify the therapeutic benefit of impairment, whereas other horses suffer from chronic
corticosteroid administration. Corticosteroids appear to be exercise intolerance because of pulmonary fibrosis and
particularly detrimental in patients with surface burns, and bronchoconstriction.
therefore their use should be limited to patients with
smoke inhalation injury alone. Dimethyl sulfoxide has
demonstrated therapeutic benefit in some smoke inhalation
Aspiration Pneumonia
patients and is thought to reduce inflammation and edema Horses are unusual in that they tolerate the entry of
via free-radical scavenging. Non-steroidal anti-inflammatory foreign material into the trachea without it inducing the
drugs may be an alternative to corticosteroids for the severe cough response seen in most other species. This
reduction of pulmonary inflammation. poorly developed protective response to aspiration may
The use of intravenous fluid therapy in patients with predispose the horse to aspiration pneumonia.
smoke inhalation is controversial. Clinicians must strike a Many diseases that result in pharyngeal and esophageal
careful balance between maintaining adequate plasma dysphagia can result in the aspiration of food and saliva
volume for the shocked patient and exacerbating pul- into the trachea and lower respiratory tract (Fig. 43.8).
monary edema, during phases 1 and 2 of injury. Intra- Examples of such conditions include esophageal obstruc-
venous fluid therapy is now considered an essential tion (choke) and pharyngeal paralysis/paresis secondary to
component of treatment in human patients with severe guttural pouch mycosis. In addition, aspiration of food and
pulmonary injury and cardiovascular shock, and intra- saliva can arise following treatment of recurrent laryngeal
venous fluid therapy has been successfully used in horses neuropathy by laryngeal prosthesis surgery.
with severe smoke inhalation injury. The nature of the pulmonary injury occurring after
Prophylactic antibiotic therapy is particularly contro- aspiration of foreign material depends on the nature of the
versial. Indiscriminate prophylactic use of antibiotics in material. Thus the aspiration of gastric contents causes
human patients leads to the selection of resistant strains of severe injury resulting in pulmonary edema and hemor-
bacteria and has not reduced mortality in burn patients. rhagic pneumonia (Epstein 1980). Inadvertent deposition
Nonetheless, most equine clinicians consider administra- of mineral oil into the lungs can occur when a nasogastric
tion of prophylactic antibiotics to be standard care in tube is misplaced, or if the oil is administered as an oral
equine patients with severe pulmonary injury, and par- drench. Mineral oil induces a chronic and progressive
ticularly in cases requiring tracheostomy. granulomatous pneumonia that has a poor long-term
The long-term prognosis for horses with smoke inhala- prognosis (Scarratt et al 1998, Bos et al 2002).
tion injury is uncertain. Some horses appear to recover In most cases, aspiration into the lungs causes pul-
uneventfully without detectable evidence of pulmonary monary infection and the development of pneumonia
and/or lung abscesses. The bacterial flora of the oropharynx and/or infectious agents are aspirated, the general health
is mixed, and a variety of organisms can be responsible for and immune status of the horse, and how soon appropriate
the pulmonary infection. Anaerobic infections are common. treatment is instituted (Beech 1991).
The cranioventral portions of the lungs are predominantly
affected by aspiration pneumonia. Clinical signs are similar
to those seen in other forms of bacterial pneumonia (fever,
tachypnea, dyspnea, nasal discharge, coughing, inappe-
Eosinophilic Pneumonia
tence, weight loss, exercise intolerance, etc.). Malodorous Eosinophilic pneumonia (eosinophilic pneumonitis) is an
breath is common in cases of anaerobic infection, abscess uncommon syndrome characterized by (a typically inter-
formation or lung necrosis. Diagnosis is achieved by a stitial) eosinophilic infiltrate into the lungs. The term
combination of the history, clinical signs, endoscopy probably encompasses a group of diverse pulmonary
(identification of mucopurulent exudate with or without diseases that all result in eosinophilia in BAL fluid and
traces of blood in the lower airways), clinical pathology eosinophil infiltrates in the lung tissues. There may or may
(leukocytosis, neutrophilia, hyperfibrinogenemia, hyper- not be peripheral blood eosinophilia.
globulinemia), thoracic radiography (radiodensity in the The clinical signs associated with eosinophilic pneumonia
cranioventral lung fields), ultrasonography (consolidation are similar to many other pulmonary diseases, including
of ventral lung lobes with possible pleural effusion), and chronic coughing, purulent nasal discharge, and dyspnea.
cytology of tracheobronchial aspirates. Culture of aspirates The cause of eosinophilic pneumonia is frequently
should include incubation under both aerobic and difficult to establish, although allergic, fungal, and parasitic
anaerobic conditions. causes must all be considered.
Treatment of aspiration pneumonia depends on pre-
venting further aspiration, and treating the pneumonia as Parasitic diseases
for the more common forms of pneumonia and pleuro-
pneumonia in the adult horse (see Chapter 46). Infection by the lungworm Dictyocaulus arnfieldi can result
in eosinophilic bronchopneumonia. Lungworm infestation
should be suspected in cases of a “herd outbreak” of heaves
in horses with historical exposure to donkeys and/or
Drowning and Near Drowning donkey crosses (Klei 1986). Mules, asses, and donkeys are
Drowning and near drowning are very rare in horses, the natural hosts of D. arnfieldi, but they rarely develop
although several cases have been reported (Austin et al clinical evidence of infestation. Coughing is a prominent
1988, Humber 1988). Submersion in water can lead to feature of the disease and clinical evidence of lower airway
asphyxiation caused by laryngeal obstruction from glottal obstruction (expiratory difficulty) is common. Clinical signs
spasm. Aspiration of water into the lower airways leads to of disease are typically observed in late summer and
dilution of the surfactant levels and resultant atelectasis early fall in geographic areas with cold winter weather.
and hypoxemia. If salt water is aspirated, the hypertonic Horses with lungworm infestation may have peripheral
fluid draws fluid from the pulmonary interstitium and eosinophilia, and eosinophils are the predominant inflam-
circulation, leading to alveolar edema. Aspiration pneu- matory cell type in BAL fluid or transtracheal aspirates
monia may be a sequel to near drowning, and can be (MacKay & Urquhart 1979). Eosinophilic BAL fluid is
detected by auscultation, thoracic radiography, and cyto- not pathognomonic for lungworm infections; however,
logical evaluation of tracheal aspirates. identification of eosinophilia should prompt the clinician to
The immediate treatment of near drowning should determine exposure to donkeys and mules and perform a
include oxygen therapy (if practical). Arterial blood gas Baermann fecal examination on the patient and potential
analysis is helpful in determining the need for oxygen and reservoir hosts. Larvae may be observed in respiratory
in monitoring the course of the condition. Bronchodilators secretions from horses with lungworms and provide
may be helpful to counteract bronchospasm. The use of definitive evidence of infestation. Adult horses rarely
diuretics such as furosemide is controversial, but may develop a patent infection (2%), so negative findings
be helpful to reduce pulmonary edema. Broad-spectrum on Baermann fecal examination do not preclude a diag-
antimicrobials (such as penicillin, gentamicin, and nosis of lungworms. Foals may develop a patent lungworm
metronidazole) are indicated if aspiration pneumonia is infection, in the absence of clinical signs. Ivermectin
diagnosed, and should be considered for prophylaxis (200 μg/kg per os) is effective against both mature and
against infection even if the infection is not established. immature stages of the parasite and is the drug of choice
Pulmonary surfactant therapy might also be considered. for treatment of donkeys and horses with lungworm
The prognosis for near drowning depends on the infection (Britt & Preston 1985).
duration of immersion, the water temperature, the amount Several nematode parasites can infect the lung. These
and type of fluid aspirated, whether foreign material include the migrating larval stages of Parascaris equorum
and Strongyloides westeri. Aberrant migration of other tration is recommended for horses with eosinophilic BAL
parasites, such as Strongylus vulgaris and Habronema sp., fluid; however, this treatment has not yet been investigated
can also occur. Although such parasitic migration is often in a controlled, randomized clinical trial in racehorses.
asymptomatic or is associated with very mild signs of Eosinophilic pneumonitis tends to respond slowly and
respiratory disease (intermittent cough, mild nasal dis- incompletely to immunosuppressive therapy.
charge), it may play an important role in the develop-
ment of secondary bacterial pneumonia in foals and
yearlings. Pulmonary migration of Parascaris equorum
Hemorrhagic Pneumonia (Acute
occurs 7–14 days after larval ingestion, and can induce
Hemorrhagic Pulmonary Infarction
inflammatory changes characterized by eosinophilic and
and Necrotizing Pneumonia)
lymphoid infiltrates. These inflammatory reactions may Acute hemorrhagic pneumonia represents a form/type of
represent an allergic response to parasitic antigens. bacterial pleuropneumonia in which there is evidence
Between 10 and 12 weeks are required for detection of a of hemorrhagic pulmonary infarction, necrotizing pneu-
patent Parascaris equorum infection via fecal flotation tests. monia, and pulmonary thromboembolism (Carr et al
Peripheral blood eosinophilia may be noted in foals with 1997). These horses respond poorly to treatment compared
heavy parasite loads and may reflect parasitic migration. to horses with other forms of bacterial pleuropneumonia.
Hydatid cysts represent a stage of the metacestode Affected horses present with an acute or peracute onset
Echinococcus granulosus, the tapeworm of domestic carni- of severe respiratory distress with a bilateral serosan-
vores. Horses and donkeys can become infected when guineous or hemorrhagic nasal discharge. Thoracic radio-
grazing on pastures that are contaminated by the feces of graphy and ultrasonography reveal evidence of severe
dogs and foxes. The horse acts as an intermediate host in pulmonary consolidation and pleural effusion. A serosan-
which hydatid cysts containing fertile protoscolices develop, guineous suppurative pleural effusion is identified by
usually in the liver and lungs. The cysts can reach 6–7 cm thoracocentesis. Treatment should include the same thera-
in diameter, but are usually asymptomatic (identified at pies as for other cases of bacterial pleuropneumonia, but
post-mortem examination). However, in large numbers, the prognosis for recovery is poor.
cysts can affect lung and liver function, and rupture of the At post-mortem examination, there is a sharp line of
pulmonary or pleural hydatid cyst may result in pleural demarcation between grossly normal and grossly abnormal
effusion. Ante-mortem diagnosis can be achieved by lung, which is palpably firm and dark red to black on
diagnostic ultrasonography and laparoscopy, or by thoracic the cut surface. Thrombosis of large vessels supplying the
radiography. affected areas is frequently found. Necrotic areas sur-
rounded by a fibrous capsule or pulmonary abscesses are
Other causes of eosinophilic pneumonia characteristic of more chronic lesions.
Eosinophilic pneumonia can be one manifestation of the

REFERENCES
group of conditions generally referred to as inflammatory
airway diseases (IAD) (Rush et al 1995, Hoffman et al Ainsworth DM, Hackett RP 2004 Disorders of the respiratory
1998). Diagnosis is achieved by cytological examination of system. In: Reed SM, Bayly WM, Sellon DC (editors)
Equine Internal Medicine, 2nd edn. Saunders, St Louis,
BAL samples. Clinical signs observed in horses with pp.289–353
eosinophilic BAL fluid are indistinguishable from those Alexander JE, Keown GH, Palotay JL 1965 Granular cell
in other IAD-affected horses. Eosinophilic BAL fluid is myoblastoma with hypertrophic pulmonary osteoarthro-
associated with poor exercise performance, high total pathy in a mare. Journal of the American Veterinary
nucleated BAL fluid cell counts, airway hyperrespon- Medical Association 146: 703–708
Anderson CA, Divers TJ 1983 Systemic granuloma-
siveness, and may or may not be accompanied by systemic tous inflammation in a horse grazing hairy vetch.
eosinophilia (Hare & Viel 1998). Journal of the American Veterinary Medical Association
The pathophysiology of pulmonary eosinophilic inflam- 183: 569–570
mation likely represents an immune-mediated pulmonary Austin SM, Foreman JH, Goetz TE 1988 Aspiration pneumonia
response consistent with a type I hypersensitivity reaction. following near drowning in a mare: a case report. Equine
Veterinary Science 8: 313–316
Affected horses typically have a moderate to strong inter- Baker JR, Leyland A 1975 Histological survey of tumours of
stitial pattern on thoracic radiography, and eosinophilic the horse with particular reference to those of the skin.
pulmonary granulomas are often identified at post-mortem Veterinary Record 96: 419–422
examination of horses with pulmonary eosinophilia. If Basher AWP, Severin GA, Chavkin MJ et al 1997 Orbital
eosinophilic BAL fluid is identified, the clinician should neuroendocrine tumours in three horses. Journal of the
investigate parasitic pulmonary disease, including ascarid Beech J 1991 Miscellaneous lung and pleural injuries. In:
migration and lungworm infection, in addition to hyper- Beech J (editor) Equine Respiratory Disorders. Lea &
sensitivity pneumonitis. Aerosolized corticosteroid adminis- Febiger, Philadelphia, pp.213–222
Berry CR, O’Brien TR, Madigan JE et al 1991 Thoracic Epstein PE 1980 Aspiration diseases of the lungs. In Fishman
radiographic features of silicosis in 19 horses. Journal of AP (editor) Pleural Diseases and Disorders. McGraw-Hill,
Veterinary Internal Medicine 5: 248–256 New York pp.1327–1340
Bos M, De Bosschere H, Deprez P et al 2002 Chemical iden- Facemire PR, Chilcoat CD, Sojka J et al 2000 Treatment of
tification of the (causative) lipids in a case of exogenous granular cell tumor via complete right lung resection in a
lipoid pneumonia in a horse. Equine Veterinary Journal horse. Journal of the American Veterinary Medical
34: 744–747 Association 217: 1522–1525
Breeze R G, Laegreid W W, Bayly W M et al 1984 Perilla Ford TS, Vaala WE, Sweeney CR et al 1987 Pleuroscopic
ketone toxicity: a chemical model for the study of equine diagnosis of gastroesophageal squamous cell carcinoma
restrictive lung disease Equine Veterinary Journal 16: in a horse. Journal of the American Veterinary Medical
180–184 Association 190: 1556–1558
Britt DP, Preston JM 1985 Efficacy of ivermectin against Fry MM, Magdesian KG, Judy CE et al 2003 Antemortem
Dictyocaulus arnfieldi in ponies. Veterinary Record 116: diagnosis of equine mesothelioma by pleural biopsy.
343–345 Equine Veterinary Journal 35: 723–727
Brown CM, Collier MA 1983 Tracheobronchial foreign body Garber JL, Reef VB, Reimer JM 1994 Sonographic findings
in a horse. Journal of the American Veterinary Medical in horses with mediastinal lymphosarcoma: 13 cases
Association 182: 280–281 (1985–1992). Journal of the American Veterinary Medical
Bruce EH 1995 Interstitial pneumonia in horses. Compendium Association 205: 1432–1436
on Continuing Education for the Practicing Veterinarian Gattinoni L, Pelosi P, Brazzi L, Valenza F 2004 Acute
17: 1145–1153 respiratory distress syndrome. In Albert RK, Spiro SG,
Buergelt CD, Hines SA, Cantor G et al 1986 A retrospective Jett JR (editors) Clinical Respiratory Medicine, 2nd edn.
study of proliferative interstitial lung disease of horses in Mosby, Philadelphia, pp.743–758
Florida. Veterinary Pathology 23: 750–756 Geor RJ, Ames TR 1991 Smoke inhalation injury in horses.
Buergelt CD, Green SL, Mayhew IG et al 1988 Avian mycobac- Compendium on Continuing Education for the Practicing
teriosis in three horses. Cornell Veterinarian 78: 365–380 Veterinarian 13: 1162–1169.
Cahalane M, Demling RH 1984 Early respiratory abnor- Hare JE, Viel L 1998 Pulmonary eosinophilia associated with
malities from smoke inhalation. Journal of the American increased airway responsiveness in young racing horses.
Veterinary Medical Association 251: 771–773 Journal of Veterinary Internal Medicine 12: 163–170
Carr EA, Carlson GP, Wilson WD et al 1997 Acute hemor- Hoffman AM, Mazan RM, Ellenberg BS 1998 Association
rhagic pulmonary infarction and necrotizing pneumonia between bronchoalveolar lavage cytologic features and
in horses: 21 cases (1967–1993). Journal of the American airway reactivity in horses with a history of exercise
Veterinary Medical Association 210: 1774–1778 intolerance. American Journal of Veterinary Research
Chevalier H, Divers TJ 2003 Pulmonary dysfunction in adult 59: 176–181
horses in the intensive care unit. Clinical Techniques in Humber KA 1988 Near drowning of a gelding. Journal of the
Equine Practice 2: 165–177 American Veterinary Medical Association 192: 377–378
Clem MF, O’Brien TD, Christopher MM et al 1986 Pulmonary Jean D, Lavoie JP, Nunez L, Legace A et al 1994 Cutaneous
chondrosarcoma in a horse. Compendium on Continuing hemangiosarcoma with pulmonary metastasis in a horse.
Education for the Practicing Veterinarian 8: S964–969 Journal of the American Veterinary Medical Association
Colbourne CM, Bolton JR, Mills JN et al 1992 Mesothelioma in 60: 776–777
horses. Veterinary Pathology 14: 513–515 Jorgensen JS, Geoly FJ, Berry CR et al 1997 Lameness and
Costabel U, Britton JR 2004 Idiopathic pulmonary fibrosis and pleural effusion associated with an aggressive fibrosar-
other idiopathic interstitial pneumonias. In Albert RK, coma in a horse. Journal of the American Veterinary
Spiro SG, Jett JR (editors) Clinical Respiratory Medicine, Medical Association 210: 1328–1331
2nd edn. Mosby, Philadelphia, pp.551–558 Kelly DF, Newsholme SJ, Baker JR et al 1995 Diffuse alveo-
Cotchin E, Baker-Smith J 1975 Tumours in horses encountered lar damage in the horse. Equine Veterinary Journal
in an abattoir survey. Veterinary Record 97: 339 27: 76–78
Culver, BH, Sevransky J, Brower R 2004 Pulmonary circula- Kemper T, Spier S, Barratt-Boyes DM et al 1993 Treatment of
tion. In Albert RK, Spiro SG, Jett JR (editors) Clinical smoke inhalation in five horses. Journal of the American
Respiratory Medicine, 2nd edn. Mosby, Philadelphia, Veterinary Medical Association 202: 91–94
pp.85–98 Klei TR 1986 Other parasites. Recent advances. Veterinary
Derksen FJ, Slocombe RF, Brown CM et al 1982 Chronic Clinics of North America; Equine Practice 2: 329–336
restrictive pulmonary disease in a horse. Journal of the Kramer JW, Nickels FA, Bell T 1976 Cytology of diffuse meso-
American Veterinary Medical Association 181: 887–889 thelioma in the thorax in the horse. Equine Veterinary
Dill S, Moise NS, Meschter CL 1986 Cardiac failure in a stallion Journal 8: 81–83
secondary to metastasis of an anaplastic pulmonary MacKay RJ, Urquhart KA 1979 An outbreak of eosinophilic
carcinoma. Equine Veterinary Journal 18: 414–417 bronchitis in horses possibly associated with Dictyocaulus
Duckett WM, Baum JL, Cook W 1983 Bronchial foreign body arnfieldi infection. Equine Veterinary Journal 11: 110–112
in a horse. Equine Practice 5: 8 Magdesian KG 2003 Colloid replacement in the ICU. Clinical
Duncan RB 1998 Malignant sertoli cell tumour in a horse. Techniques in Equine Practice 2: 130–137
Equine Veterinary Journal 30: 355–357 Mair TS, Hillyer MH 1992 Clinical features of lymphosarcoma
East LM, Steyn PE, Dickinson CE, Frank AA 1998 Occult in the horse: 77 cases. Equine Veterinary Education
osseous metastasis of a colonic adenocarcinoma visual- 4: 108–113
ized with technetium Tc99m hydroxymethylene diphos- Mair TS, Brown PJ 1993 Clinical and pathological features of
phate scintigraphy in a horse. Journal of the American thoracic neoplasia in the horse. Equine Veterinary
Veterinary Medical Association 213: 1167–1170 Journal 25: 220–223
Mair TS, Lane JG, Lucke VM 1985 Clinicopathological features Scarratt WK, Moon ML, Sponenberg DP et al 1998
of lymphosarcoma involving the thoracic cavity in the Inappropriate administration of mineral oil resulting in
horse. Equine Veterinary Journal 17: 428–433 lipoid pneumonia in three horses. Equine Veterinary
Mair TS, Taylor FGR, Gibbs C et al 1986 Generalized avian Journal 30: 85–88
tuberculosis in a horse. Equine Veterinary Journal Schultze AE, Sonea I, Bell TG 1988 Primary malignant
18: 226–230 pulmonary neoplasia in two horses. Journal of the
Mair TS, Hillyer, MH, Brown PJ 1992 Mesothelioma of the American Veterinary Medical Association 193: 477–480
pleural cavity in a horse: diagnostic features. Equine Schwartz LW, Knight HD, Whittig LD et al 1981 Silicate
Veterinary Education 4: 59–61 pneumoconiosis and pulmonary fibrosis in horses from
Mair TS, Dyson SJ, Fraser JA et al 1996 Hypertrophic the Monterey-Carmel peninsula. Chest 80: 82S–85S
osteopathy (Marie’s disease) in Equidae: a review of Stannard AA 1987 Generalised granulomatous disease. In:
twenty-four cases. Equine Veterinary Journal 28: 256–262 Robinson NE (editor) Current Therapy in Equine Medicine,
McConkey S, Lopez A, Pringle J 2000 Extramedullary plasma- 2nd edn. WB Saunders, Philadelphia, pp.645–646
cytoma in a horse with ptyalism and dysphagia. Journal Straub R, von Tscharner C, Pauli B et al 1974 Pleural meso-
of Veterinary Diagnostic Investigation 12: 282–284 thelioma in a horse. Schweizer Archiv fur Tierheilkunde
Misdorp W, van Gelder NHL 1968 Granular cell myoblastoma 116: 207–211
in the horse. A report of 4 cases. Pathologia Veterinaria Sullivan DJ 1960 Cartilaginous tumors (chondroma and
5: 385–394 chondrosarcoma) in animals. American Journal of
Mueller POE, Morris DD, Carmichael P et al 1992 Ante- Veterinary Research 21: 531–535
mortem diagnosis of cholangiocellular carcinoma in a Sundberg JP, Burnstein T, Page EH et al 1977 Neoplasms of
horse. Journal of the American Veterinary Medical equidae. Journal of the American Veterinary Medical
Association 201: 899–901 Association 170: 150–152
Murphy JR, Breeze RG, McPherson EA 1978 Myxoma of the Sutton RH, Coleman GT 1995 A pulmonary granular cell
equine respiratory tract. Modern Veterinary Practice tumour with associated hypertrophic osteopathy in a
59: 529–532 horse. New Zealand Veterinary Journal 43: 123
Murray MJ, Cavey DM, Feldman BF et al 1997 Signs of Sweeney CR, Gillette DM 1989 Thoracic neoplasia in equids:
sympathetic denervation associated with a thoracic 35 cases (1967–1987). Journal of the American Veterinary
melanoma in a horse. Journal of Veterinary Internal Medical Association 195: 374–377
Medicine 11: 199–203 Trunkey DD 1978 Inhalation injury. Surgical Clinics of North
Nickels FA, Brown CM, Breeze RG 1980 Equine granular cell America 58: 1133–1140
tumour. Modern Veterinary Practice 61: 593–596 Turk JR, Brown CM, Johnson GC 1981 Diffuse alveolar
O’Sullivan BM 1979 Croton weed (Eupatorium adenophorum) damage with fibrosing alveolitis in a horse. Veterinary
toxicity in horses. Australian Veterinary Journal 55: 19–21 Pathology 18: 560–561
Parker GA, Novilla MN, Brown AC et al 1979 Granular cell Turk MA, Breeze RG 1981 Histochemical and ultrastruc-
tumour (myoblastoma) in the lung of a horse. Journal of tural features of an equine pulmonary granular cell
Comparative Pathology 89: 421–430 tumour (myoblastoma). Journal of Comparative Pathology
Prater PE, Patton CS, Held JP 1989 Pleural effusion resulting 91: 471–481
from malignant hepatoblastoma in a horse. Journal of the Uphoff CS, Lyncoln JA 1987 A primary pulmonary tumour in
American Veterinary Medical Association 194: 383–385 a horse. Equine Practice 9: 19–20
Pusterla N, Norris AJ, Stacy BA et al 2003a Granular cell Urquhart KA, Gerring EL 1981 Tracheobronchial foreign body
tumours in the lungs of three horses. Veterinary Record in a pony. Equine Veterinary Journal 13: 262–264
153: 530–532 Vachon AM, Fischer AT 1998 Thoracoscopy in the horse:
Pusterla N, Pesavento PA, Smith P et al 2003b Idiopathic diagnostic and therapeutic indications in 28 cases.
granulomatous pneumonia in seven horses. Veterinary Equine Veterinary Journal 30: 467–475
Record 153: 653–655 Van Rensburg IBJ, Stadler P, Soley J 1989 Bronchiolo-alveolar
Raphel CF, Gunson DE 1981 Percutaneous lung biopsy in the adenocarcinoma in a horse. Journal of the South African
horse. Cornell Veterinarian 71: 439–448 Veterinary Association 60: 212–214
Rossier Y, Sweeney CR, Heyer G et al 1990 Pleuroscopic Viel L, Kenney D 1993 Suspected adverse pulmonary reac-
diagnosis of hemangiosarcoma in a horse. Journal of the tions to Equimune I.V. in four horses presented to the
American Veterinary Medical Association 196: 1639–1640 Ontario Veterinary College. 12th Veterinary Respiratory
Rush BR, Krakowka S, Robertson JT 1995 Cytologic evalua- Symposium. Kennett Square, PA.
tion of bronchoalveolar lavage fluid obtained from Wallace SS, Jayo MJ, Maddux JM et al 1987 Mesothelioma
Standardbred racehorses with inflammatory airway in a horse. Compendium on Continuing Education for
disease. American Journal of Veterinary Research 56: Practicing Veterinarians 9: 210–216
562–568 Ziemer EL, Pappagianis D, Madigan JE et al 1992 Coccid-
Scarratt WK, Crissman MV 1998 Neoplasia of the respiratory ioidomycosis in horses: 15 cases (1975–1984). Journal
tract. Veterinary Clinics of North America; Equine Practice of the American Veterinary Medical Association 201:
14: 451–474 910–916
Exercise-induced Pulmonary
Hemorrhage
44 Kenneth W Hinchcliff
Exercise-induced pulmonary hemorrhage (EIPH) occurs Age is considered an important risk factor for EIPH with
in horses throughout the world and does not appear to the prevalence of the disorder being higher in older horses
have any geographic distribution. It is a disorder of horses (Pascoe 1981, Raphel & Soma 1982, Mason et al 1983).
that run at high speed, such as thoroughbred or standard- There is no consistent association of sex with prevalence of
bred racehorses. The disorder is uncommon in endurance EIPH (Pascoe et al 1981a, Raphel & Soma 1982, Speirs
horses or draft breeds, although it does occur in horses 1982, Mason et al 1983).
used for these activities. As a general rule, the more intense Among thoroughbred racehorses the prevalence of
the exercise or higher the speed attained, the greater the EIPH increases with increasing speed (Raphel & Soma
proportion of horses with EIPH. 1982, Oikawa 1999), being greater in thoroughbreds after
The prevalence of EIPH varies with the method used to racing than after breezing (galloping). Lesions of EIPH
detect it and the frequency with which horses are exam- are not detected in young thoroughbred racehorses that
ined, as discussed later in this section. Almost all thorough- have trained at speeds less than 7 m/second (Raphel &
bred racehorses in active training have hemosiderophages Soma 1982, Oikawa 1999).
in bronchoalveolar lavage fluid, indicating that all have Epistaxis associated with exercise is almost always
some degree of EIPH (McKane et al 1993). The prevalence attributable to EIPH and occurs only in a small proportion
of EIPH decreases when diagnosis is based on endoscopic of racehorses (Takahashi et al 2001, Williams et al 2001,
examination of horses after exercise or racing. Weideman et al 2003). The prevalence of epistaxis in race-
EIPH is very common in thoroughbred racehorses; horses varies between 0.1 and 9.0%, with the frequency
estimates of prevalence based on a single endoscopic depending on the breed, age and sex of horses selected for
examination of the trachea and bronchi are 43–75% study, the type of racing, and the timing and frequency of
(Pascoe et al 1981a, Raphel & Soma 1982, Mason et al observation of horses after racing. Epistaxis is more com-
1983). The prevalence increases with the frequency of mon in older horses (Takahashi et al 2001, Weideman et al
examination, with over 80% of horses having evidence of 2003). There are conflicting reports of a sex predisposi-
EIPH on at least one occasion following examination after tion although epistaxis may be more common in female
each of three consecutive races (Sweeney et al 1990). thoroughbreds (Takahashi et al 2001, Weideman et al
The prevalence of EIPH in standardbred racehorses is 2003). Epistaxis is more common after races of < 1600 m
assumed to be lower, with 26–34% of horses reported to than after longer races (Takahashi et al 2001), although
have blood in the trachea after racing (Speirs 1982, not all sources agree on this point (Weideman et al 2003).
MacNamara et al 1990). However, these studies were based However, horses in steeplechase races, which are typically
on a single examination and one study (MacNamara et al longer than 2000 m, are at greater risk of epistaxis than
1990) only reported as positive those horses with blood are horses in flat races (Takahashi et al 2001).
covering more than one half of the tracheobronchial tree. Horses that have experienced one episode of epistaxis
When examined after each of three races, 87% of stan- are more likely to have a second episode. For this reason
dardbred racehorses have evidence of EIPH on at least one some racing jurisdictions do not permit horses with epi-
occasion (Lapointe et al 1994), suggesting that EIPH is as staxis to race for a period of weeks to months after the
common in standardbred racehorses as it is in thorough- initial episode, with more prolonged enforced rest after a
bred racehorses. subsequent episode of epistaxis and retirement from racing
EIPH occurs in approximately 62% of racing Quarter after a third bout. The recurrence rate after one episode of
horses, and has been observed in Quarter horses used for epistaxis in thoroughbred horses is approximately 13.5%,
barrel racing (Hillidge et al 1984). The disorder also occurs despite affected horses not being permitted to race for
in racing Appaloosa horses (Hillidge et al 1986) and 1 month after the initial episode of epistaxis (Takahashi
approximately 11% of polo ponies are affected with EIPH et al 2001). This high rate of recurrence suggests that the
(Voynick & Sweeney 1986). inciting pulmonary lesions have not resolved.
617
618 44 Exercise-induced Pulmonary Hemorrhage
Table 44.1. Causes of hemorrhage into

airways of horses or epistaxis
Hemorrhage into trachea or bronchi
Exercise-induced pulmonary hemorrhage Pulmonary
Pulmonary abscess capillary
Trauma
Pneumonia
Pulmonary foreign body Interstitium
Pulmonary neoplasia
Alveolus
Epistaxis
All of the above
Guttural pouch mycosis
Progressive ethmoidal hematoma
Thrombocytopenia
Trauma
Neoplasia
B
Ruptured endothelium
Pathophysiology and Etiology
Epistaxis and hemorrhage into airways can occur as a
result of a number of diseases (Table 44.1). However, Red blood cell Interstitium
the likely proximate cause of EIPH is rupture of alveo-
lar capillary membranes with subsequent extravasation
of blood into interstitial and alveolar spaces (Fig. 44.1) Capillary
endothelium
(West et al 1993). The source of blood in such instances is
the pulmonary circulation. Bleeding from the bronchial
circulation during exercise has been suggested, based on Pulmonary
capillary
histological evidence of bronchial angiogenesis in horses
that have experienced previous episodes of EIPH (Pascoe
1996), but contribution of the bronchial circulation to
Alveolus Alveolar
EIPH has not been demonstrated. Regardless of the con-
epithelium
tribution of bronchial circulation to blood in the airways,
the likely initial lesion is in capillaries associated with the
pulmonary circulation. Hemorrhage into the interstitial
space and alveoli, with subsequent rostral movement of blood
in the airways, results in blood in the trachea and bronchi.
Rupture of alveolar capillaries occurs secondary to an Fig. 44.1. Diagrammatic representation of the proximate cause of
exercise-induced increase in transmural pressure (pressure exercise-induced pulmonary hemorrhage. (A) A normal pulmonary
difference between the inside of the capillary and the capillary–alveolar unit; (B) rupture of the capillary endothelium with
alveolar lumen). If the transmural stress exceeds the tensile subsequent extravasation of red blood cells and plasma into the
interstitial space, rupture of alveolar epithelium and leakage of red
strength of the capillary wall, the capillary ruptures (West
blood cells into the alveolus and air spaces.
& Mathieu-Costello 1994). The proximate cause of alveolar
capillary rupture is the high transmural pressure generated
by positive intracapillary pressures that are largely
attributable to capillary blood pressure, and the lower
intra-alveolar pressure generated by the subatmospheric increase to > 90 mmHg during intense exercise because of
pleural pressures associated with inspiration. the large cardiac output achieved by exercising horses. The
During exercise, the absolute magnitudes of both pul- increases in pulmonary artery pressure, combined with an
monary capillary pressure and alveolar pressure increase, increase in left atrial pressure during exercise, likely result
with a consequent increase in transmural pressure. in an increase in pulmonary capillary pressure. Combined
Strenuous exercise is associated with marked increases in with the increase in pulmonary capillary pressure is a
pulmonary artery pressure in horses (Manohar et al 1993, marked decrease (more negative) in pleural, and there-
Birks et al 1997, Langsetmo et al 2000). Values for mean fore alveolar, pressures during exercise. Pleural pres-
pulmonary arterial pressure at rest of 20–25 mmHg sures of normal horses during inspiration decrease from
44 Exercise-induced Pulmonary Hemorrhage 619
Horses with moderate to severe EIPH have histological

Table 44.2. Potential factors inducing or
contributing to the severity of exercise-induced evidence of inflammation of the small airways (O’Callaghan
pulmonary hemorrhage et al 1987d, Oikawa 1999), and there is a clear association
between presence of EIPH and inflammatory changes in
Pulmonary capillary hypertension
bronchoalveolar or tracheal aspirate fluid (Newton &
Rheologic properties of blood
Subatmospheric intrapleural (alveolar) pressures Wood 2002). However, instillation of autologous blood
Extrathoracic airway obstruction (e.g. laryngeal hemiplegia) into the airways induces a marked inflammatory response
Intrathoracic airway obstruction (e.g. bronchoconstriction) in normal horses (McKane & Slocombe 1999), and it is
Small airway inflammatory disease therefore unclear if inflammation alone induces or pre-
viral or bacterial infections
disposes to EIPH or if the inflammation is a result of EIPH.
allergy
air pollution (dust, ozone) Theoretically, small airway inflammation and bronchocon-
Coagulopathy striction have the potential to produce intrathoracic air-
abnormal platelet function way obstruction and, therefore, a more negative alveolar
capillary fragility pressure. Given that small airway disease is common in
Bronchial neovascularization
horses, there is the potential for an important effect of
Pulmonary fibrosis and altered compliance
Locomotory forces factors such as viral infections, air pollution and allergic
foot strike airway disease to contribute to the initiation or propaga-
abdominal piston tion of EIPH (Deaton & Marlin 2004).
Exercise is accompanied by marked changes in blood
flow characteristics attributable to an increase in hematocrit
and a decrease in red cell deformability (Fedde & Erickson
1998, Weiss & Smith 1998). These changes cause an
approximately – 0.7 kPa (– 5.3 mmHg) at rest to as low as increase in microvascular shear stress and thus could,
– 8.5 kPa (–64 mmHg) during strenuous exercise (Art et al conceivably, contribute to capillary rupture. However, there
1990). Together, the increases in pulmonary capillary is at present no direct evidence that indicates that this is an
pressure and the decrease (more negative) in intrapleural important feature of EIPH development.
(alveolar) pressure contribute to a marked increase in The characteristic location of lesions of EIPH in the
stress in the alveolar wall. Although the alveolar wall and caudodorsal lung fields has led to the proposal that
pulmonary capillary of horses are stronger than those of hemorrhage is a result of tissue damage occurring when
other species, rupture may occur because the wall stress in waves of stress, generated by forelimb foot strike, are
the alveolus exceeds the mechanical strength of the capil- focused and amplified into the narrowing cross-sectional
lary (Birks et al 1994). area of the caudal lung lobes (Schroter et al 1998).
Other factors that could contribute to the pathogenesis According to this theory, the locomotory impact of the
of EIPH are listed in Table 44.2 and include small airway forelimbs results in transmission of forces through the
disease, upper airway obstruction, hemostatic abnormali- scapula to the body wall, from where they pass into the
ties, changes in blood viscosity and erythrocyte shape, lungs caudally and dorsally. As the wave of pressure passes
intrathoracic shear forces associated with gait, and bron- into the narrower caudodorsal regions of the lungs it
chial artery angiogenesis (Pascoe 1996, Schroter et al 1998). generates progressively greater shearing forces that disrupt
It is likely that the pathogenesis of EIPH involves several tissue and cause EIPH. However, studies of intrapleural
processes, including pulmonary hypertension, lower alveolar pressures have not demonstrated the presence of a systemic
pressure, and changes in lung structure, that summate to pressure wave passing through the lung and do not provide
induce stress failure of pulmonary capillaries. support for this hypothesis (Jones et al 2002).
Obstruction of either the upper or lower airways has Horses with EIPH have been suspected of having defects
been proposed as a cause of EIPH (Cook 1988). Inspiratory in either hemostasis or fibrinolysis. However, while exercise
airway obstruction results in more negative intrapleural, induces substantial changes in blood coagulation and
and therefore alveolar, pressures. This effect is exacer- fibrinolysis (McKeever et al 1990), there is no evidence that
bated by exercise with the result that alveolar transmural horses with EIPH have defective coagulation or increased
pressure is greater in horses with airway obstructions fibrinolysis (Bayly et al 1983, Johnstone et al 1991).
during racing (Ducharme et al 1999, Hackett et al 1999). Regardless of the cause, rupture of pulmonary capil-
The higher transmural pressure in such horses may laries and subsequent hemorrhage into airways and
increase the severity of EIPH, although this has not been interstitium causes inflammation of both airways and
demonstrated. Moreover, while inspiratory airway obstruc- interstitium with subsequent development of fibrosis and
tion may predispose to EIPH, the prevalence of this con- alteration of tissue compliance (Fig. 44.2). Heterogeneity
dition is much less than that of EIPH, indicating that it is of compliance within the lungs, and particularly at
not the sole factor inducing EIPH in most horses. the junction of normal and diseased tissue, results in
Pulmonary
Exercise capillary Hemorrhage
rupture
Inflammation
and fibrosis
Exercise
Reduced lung
compliance Angiogenesis
Increased
susceptibility
to capillary
rupture
Fig. 44.2. Schematic of proposed mechanism of perpetuation and

exacerbation of EIPH with continued exercise. See text for details.
development of abnormal shear stress with subsequent

tissue damage. These changes are exacerbated by inflam-
mation and obstruction of small airways with resulting
uneven inflation of the lungs (Robinson & Derksen 1980).
The structural abnormalities, combined with pulmonary
hypertension and the large intrathoracic forces asso-
ciated with respiration during strenuous exercise, cause Fig. 44.3. Horse with exercised-induced pulmonary hemorrhage and
repetitive damage at the boundary of normal and diseased epistaxis.
tissue with further hemorrhage and inflammation. The
process, once started, is lifelong and continues for as long
as the horse continues to perform strenuous exercise
(Pascoe 1996). have blood evident on endoscopic examination of the
tracheobronchial tree performed 30–90 min after strenuous
exercise or racing (McKane et al 1993, Martin et al 1999).
Clinical Signs However, it is important to recognize that EIPH is very
History and presenting complaint common in racehorses and it should be considered the
cause of poor performance only after other causes have
Poor athletic performance or epistaxis are the most com- been eliminated. Severe EIPH undoubtedly results in poor
mon presenting complaints for horses with EIPH. While performance and, on rare occasions, death of thorough-
poor performance may be attributable to any of a large bred racehorses (Gunson et al 1988). However, the effect
number of causes, epistaxis associated with exercise is of less severe EIPH on the race performance of thorough-
almost always secondary to EIPH (Fig. 44.3). bred or standardbred horses has not been conclusively
Epistaxis as the result of EIPH occurs during or shortly determined. A relationship between finishing position and
after exercise and is usually first noticed at the end of a incidence of EIPH, diagnosed by bronchoscopic examina-
race, particularly when the horse is returned to the tion, was not detected for 191 thoroughbred racehorses
paddock or winner’s circle and is allowed to lower its that finished in first, second, or third place (Pascoe et al
head. It is usually bilateral and resolves within hours of the 1981b). Furthermore, there was no relationship between
end of the race. Epistaxis may occur on more than one the proportion of horses with EIPH and placing (first,
occasion, especially when horses are raced or exercised at second or third versus other) in another 98 horses (Pascoe
high speed soon after an initial episode. et al 1981b). Similarly, there was no relationship between
finishing position and proportion of horses with EIPH
in 191 thoroughbreds examined after racing (Raphel &
EIPH and performance Soma 1982). There was no relationship between severity
Failure of racehorses to perform to the expected standard of EIPH, assessed on tracheobronchoscopic examina-
(poor performance) is often, accurately or not, attributed to tion, and race performance in 258 thoroughbreds or 296
EIPH. Many horses with poor performance have cytological standardbred racehorses (Birks et al 2002). Together, these
evidence of EIPH on microscopic examination of tracheo- studies do not demonstrate a clear relationship between the
bronchial aspirates or bronchoalveolar lavage fluid or presence of EIPH, or its severity, and race performance.
In contrast to the studies discussed above, among 452

Diagnostic Tests
thoroughbred horses examined after racing in Hong Kong,
those finishing in the first three positions had less severe There are a variety of techniques available for determining
EIPH than did horses finishing in lower positions (Mason the presence and severity of EIPH including direct exami-
et al 1983). Of horses finishing in the first three places, nation of the airways through a flexible endoscope or
43.9% had evidence of EIPH on tracheobronchoscopic examination of bronchial lavage fluid or tracheal aspirates
examination after racing whereas 55.9% of horses finish- for evidence of hemorrhage. The utility of these diagnostic
ing in fourth to 14th place had evidence of EIPH. Thorough- tests varies and choice of examination technique depends
bred horses with EIPH racing in Victoria, Australia have on the time between the horse racing and the examination
impaired performance compared to unaffected horses. and the desired sensitivity of the test. For instance,
Affected horses have lower likelihood of finishing in the tracheobronchoscopic examination is most appropriate if
first three places, are less likely to be elite money earners a horse is examined within 1–2 h of exercise whereas
and finish further behind the winner than do unaffected examination of airway washings is most appropriate if the
horses (Hinchcliff et al 2004). examination is days to a week after strenuous exercise.
Results of studies in standardbred racehorses indicate Radiography, pulmonary scintigraphic examination, and
either a lack of effect of EIPH on performance or an lung function tests are useful in eliminating other respira-
association between EIPH and superior performance. There tory diseases as a cause of poor performance, but are
was no relationship between presence of EIPH and minimally useful in confirming a diagnosis of EIPH or in
finishing position in 29 standardbred racehorses with determining the severity of hemorrhage.
intermittent EIPH examined on at least two occasions
(Lapointe et al 1994), nor in 92 standardbred racehorses Tracheobronchoscopy
examined on one occasion (Speirs 1982). However, of 965
standardbred racehorses examined after racing, those Observation of blood in the trachea or large bronchi of
finishing first or second were 1.4 times more likely (95% CI horses 30–120 min after racing or strenuous exercise
0.9–2.2) to have evidence of EIPH on tracheobroncho- provides a definitive diagnosis of EIPH. The amount of
scopic examination than were horses that finished in blood in the large airways varies from a few small specks on
seventh or eighth position (Rohrbach 1990). the airway walls to a stream of blood occupying the ventral
one-third of the trachea (Fig. 44.4). Blood may also be
present in the larynx and nasopharynx. If there is a strong
Physical Examination suspicion of EIPH and blood is not present on a single
Apart from epistaxis in a small proportion of affected examination conducted soon after exercise, the exam-
horses, there are few abnormalities detectable on routine ination should be repeated 60–90 min later. Some horses
physical examination of horses with EIPH. Rectal tem- with EIPH do not have blood present in the rostral
perature and heart and breathing rates may be elevated as airways immediately after exercise, but do have blood
a consequence of exercise in horses examined soon after present when examined 1–2 h later. Blood is detectable
exercise, but values of these variables in horses with EIPH by tracheobronchoscopic examination for 1–3 days in
at rest are not noticeably different from those in horses most horses, with some horses having blood detectable
with no evidence of EIPH. Affected horses may swallow for up to 7 days.
more frequently during recovery from exercise than do Bronchoscopic examination can be used to estimate the
unaffected horses, probably as a result of blood in the severity of EIPH through a grading system (Pascoe et al
larynx and pharynx. Coughing is common in horses 1981b, Hinchcliff et al 2005). The interobserver repeata-
recovering from strenuous exercise; after recovery from bility of tracheobronchoscopic assessment of severity of
exercise, horses with EIPH are no more likely to cough EIPH using a 0–4 grading scale has been demonstrated
than are unaffected horses (Christley et al 2001). Other (Hinchcliff et al 2004b) (Fig. 44.4).
clinical signs related to respiratory abnormalities are
uncommon in horses with EIPH. Respiratory distress is ● grade 0 – no blood detected in the pharynx, larynx,
rare in horses with EIPH and when present indicates trachea or main-stem bronchi
severe hemorrhage or other serious lung disease such as ● grade 1 – presence of one or more flecks of blood or ≤ 2
pneumonia, pneumothorax or rupture of a pulmonary short (less than one-quarter the length of the trachea)
abscess. Lung sounds are abnormal in a small number of narrow (< 10% of the tracheal surface area) streams of
EIPH-affected horses and when present are charac- blood in the trachea or main-stem bronchi visible from
terized by increased intensity of normal breath sounds the tracheal bifurcation
during rebreathing examination (O’Callaghan et al 1987a). ● grade 2 – one long stream of blood (more than half the
Tracheal crackles may be present in horses with EIPH but length of the trachea) or >2 short streams occupying
are also heard in unaffected horses (Cook 1974). less than one-third of the tracheal circumference
A B
C D
Fig. 44.4. Tracheobronchoscopic findings in horses with EIPH. (A) A hemorrhage. Reproduced from Hinchcliff et al, 2005, Fig. 1, with
horse with Grade 1 hemorrhage; (B) a horse with Grade 2 hemor- permission.
rhage; (C) a horse with Grade 3 hemorrhage; (D) a horse with Grade 4
● grade 3 – multiple, distinct streams of blood covering It is assumed that a higher score represents more severe
more than one-third of the tracheal circumference; no hemorrhage, but while the repeatability of this scoring
blood pooling at the thoracic inlet system has been established, the relationship between
● grade 4 – multiple, coalescing streams of blood covering the amount of blood in the large airways and the actual
> 90% of the tracheal surface with pooling of blood at amount of hemorrhage has not been established.
the thoracic inlet.
Examination of airway secretions another disease process, such as a pulmonary abscess,

or lavage fluid contributing to the horse’s pulmonary hemorrhage or poor
athletic performance.
The presence of red cells or macrophages containing either
effete red cells or the breakdown products of hemoglobin
Necropsy Examination
(hemosiderophages) in tracheal aspirates or broncho-
alveolar lavage fluid provides evidence of EIPH. Detection of Exercise-induced pulmonary hemorrhage is a rare cause
red cells or hemosiderophages in tracheal aspirates or of death of racehorses. Necropsy examination of affected
bronchoalveolar lavage fluid is believed to be both sensitive horses is usually incidental to examination for another
and specific in the diagnosis of EIPH (Fogarty & Buckley cause of death. Pertinent abnormalities in horses with
1991, McKane et al 1993). Examination of airway fluids EIPH are restricted to the respiratory tract. Grossly, horses
indicates the presence of EIPH in a greater proportion of examined within hours of strenuous exercise, such as
horses than does tracheobronchoscopic examination after horses examined because of catastrophic musculoskeletal
strenuous exercise or racing. The greater sensitivity of injuries incurred during racing, may have severe petechia-
examination of airway fluid is likely attributable to the tion in the caudodorsal lung fields. Horses with chronic
ability of this examination to detect the presence of small disease have blue/gray or blue/brown discoloration of the
amounts of blood or its residual products and the longevity visceral pleural surfaces of the caudodorsal lung fields that
of these products, particularly the latter, in the airways. is often sharply demarcated, especially on the diaphrag-
While endoscopic examination may detect blood in occa- matic surface (Fig. 44.5) (O’Callaghan et al 1987b). The
sional horses up to 7 days after an episode of EIPH, cellular discoloration affects both lungs equally, with 30–50% of
evidence of pulmonary hemorrhage persists for weeks after
a single episode (Fogarty & Buckley 1991, Step et al 1991,
McKane et al 1993). Red blood cells and macrophages
containing red cells are present in bronchoalveolar lavage
fluid or tracheal aspirates for at least 1 week after strenuous
exercise or instillation of autologous blood into airways and
hemosiderophages are present for at least 21 days and pos-
sibly longer (Step et al 1991, McKane et al 1993).
Recent studies have reported the use of red cell numbers
in bronchoalveolar lavage fluid as a quantitative indicator
of EIPH (Meyer et al 1998, Langsetmo et al 2000, Geor
et al 2001, Kindig et al 2001). However, this indicator of
EIPH severity has not been validated nor demonstrated to
be more reliable or repeatable than tracheobronchoscopic
examination and visual scoring. Furthermore, considerable
concern exists over the suitability of red cell counts in
bronchoalveolar lavage fluid for the assessment of EIPH
severity given that an unknown area, although presumably
small, of the lung is examined by lavage and there is a risk
that this area of lung may not be representative of the lung
as a whole, similar to the situation for examination of
bronchoalveolar lavage fluid of horses with pneumonia
(Rossier et al 1991). Bronchoalveolar lavage of selected
segments of both lungs, achieved using an endoscope, may
obviate some of these concerns.
Radiography
Thoracic radiography is of limited use in detecting horses
with EIPH. Radiographs may demonstrate the presence of
densities in the caudodorsal lung fields of some horses
but many affected horses have minimal to undetectable
Fig. 44.5. Lungs of a thoroughbred racehorse with exercise-induced
radiographic abnormalities (Pascoe et al 1983) (Figure pulmonary hemorrhage. The lesions are restricted to the caudodorsal
10.19). Examination of thoracic radiographs of horses lung fields and cause a blue–gray discoloration of the visceral pleural
with EIPH may be useful in ruling out the presence of surface.
the lung fields being discolored in severe cases. Affected of furosemide before racing. The vast majority (> 90%) of
areas do not collapse to the same extent as unaffected areas thoroughbred horses racing in the USA receive furosemide
and, in the deflated lung, have a spleen-like consistency. On before racing at an estimated annual cost of between
cut surface, the discolored areas of lung are predominantly $6,000,000 and $20,000,000 (Heller 2002). Although
contiguous with the dorsal pleural surface and extend accurate numbers are not available, it appears that a
ventrally into the lung parenchyma. Areas of affected lung smaller proportion of standardbred and Quarter horse
may be separated by normal lung. There is proliferation of racehorses receive furosemide before racing. Furosemide is
bronchial vessels, predominantly arteries and arterioles, in administered to 22–32% of standardbred racehorses and
affected areas (O’Callaghan et al 1987c). Histologically, 19% of racing Quarter horses in two racing jurisdictions
affected areas exhibit bronchiolitis, hemosiderophages in (Sime et al 1994, Soma et al 1996, 2000).
the alveolar lumen and interstitial spaces, and fibrosis of The efficacy of furosemide in treatment of EIPH is
interlobular septa, pleura and around vessels and bron- uncertain. While field studies of large numbers of horses
chioles (O’Callaghan et al 1987d). do not demonstrate an effect of furosemide on the preva-
lence of EIPH (Sweeney et al 1990, Birks et al 2002),
studies of thoroughbred horses running on a treadmill
Treatment provide evidence that furosemide reduces the severity of
EIPH (Geor et al 2001, Kindig et al 2001, McDonough et al
Therapy of EIPH is usually a combination of attempts to
2004). Under field conditions, based on tracheobroncho-
reduce the severity of subsequent hemorrhage and efforts
scopic evaluation of the severity of bleeding, furosemide
to minimize the effect of recent hemorrhage. Treatment of
has been reported to reduce or have no influence on
EIPH is problematic for a number of reasons. Firstly, the
the severity of bleeding (Pascoe et al 1985, Birks et al
pathogenesis of EIPH has not been determined although
2002). This apparent inconsistency may be attributable to
the available evidence supports a role for stress failure of
measurement of red blood cell counts in bronchoalveolar
pulmonary capillaries secondary to exercise-induced pul-
lavage fluid of horses that have run on a treadmill not
monary hypertension (see above). Secondly, there is a lack
being representative of effects of furosemide under field
of information using large numbers of horses under field
conditions. The weight of evidence, albeit unconvincing,
conditions that demonstrates an effect of any medication
from field studies does not support a role for furosemide in
or management practice (with the exception of bedding) on
preventing or reducing the severity of EIPH.
EIPH. There are numerous studies of small numbers of
The mechanism by which furosemide may reduce the
horses (< 40) under experimental conditions, but these
severity of EIPH is unknown although it is speculated that
studies often lacked the statistical power to detect treatment
furosemide, by attenuating the exercise-induced increase in
effects and, furthermore, the relevance of studies con-
pulmonary artery and pulmonary capillary pressure of
ducted on a treadmill to horses racing competitively is
horses, reduces the frequency or severity of pulmonary
questionable. Treatments for EIPH are usually intended to
capillary rupture (Manohar 1993, Manohar et al 1993,
address a specific aspect of the pathogenesis of the disease
Gleed et al 1999).
and will be discussed in that context.
Furosemide administration is associated with superior
performance in both thoroughbred and standardbred
Prevention of stress failure of the racehorses (Gross et al 1999, Soma et al 2000). Thorough-
pulmonary capillaries bred horses treated with furosemide are 1.4 times as likely
to win the race, earn more money and have a standardized
There is interest in reducing the pressure difference across
6-furlong race time 0.56–1.09 seconds less than untreated
the pulmonary capillary membrane in an effort to reduce
horses (Gross et al 1999). Similarly, furosemide reduces
EIPH. Theoretically, this can be achieved by reducing the
the 1-mile race times of standardbred pacers by 0.31–0.74
pressure within the capillary or increasing (making less
seconds (Soma et al 2000).
subatmospheric) the pressure within the intrathoracic
Enalapril inhibits angiotensin-converting enzyme activity
airways and alveolus.
in horses, but does not affect the pulmonary artery pres-
sure of exercising horses (Muir et al 2001). Similarly, the
Reducing pulmonary capillary pressure efficacy of enalapril in preventing EIPH has not been
Furosemide administration as prophylaxis of EIPH is demonstrated.
permitted in a number of racing jurisdictions world- Nitric oxide is a potent vasodilator in many vascular
wide, most notably Canada, USA, Mexico, and most South beds. Administration of nitroglycerin (a nitric oxide donor)
American countries (Anonymous 2002). Within the USA reduces pulmonary artery pressure of standing horses but
and Canada, almost all thoroughbred, standardbred and does not affect pulmonary artery pressure of horses during
Quarter horse racing jurisdictions permit administration intense exercise (Manohar & Goetz 1999). The nitric oxide
donor L-arginine has no demonstrated efficacy in reducing attention of some investigators. Application of nasal dilator
pulmonary capillary pressure or EIPH in horses. The effect bands (Flair® strips) reduces nasal resistance by dilating
of L-NAME, an inhibitor of nitric oxide synthetase, on the nasal valve (Holcombe et al 2002), and reduces red cell
pulmonary artery pressure during maximal exercise is count of bronchoalveolar lavage fluid collected from horses
controversial with either no effect or a decrease in pul- after intense exercise on a treadmill (Geor et al 2001,
monary artery pressure reported (Manohar & Goetz 1998, Kindig et al 2001). Furthermore, application of the nasal
Kindig et al 2000). Interestingly, L-NAME administration dilator strips to horses in simulated races reduces red cell
caused an increase in severity of EIPH (Kindig et al 2000). count in bronchoalveolar lavage fluid of some, but not all,
Sildenafil, a phosphodiesterase inhibitor that accentuates horses (Valdez et al 2004).
the effect of nitric oxide and is used in the treatment of The role of small airway inflammation and bron-
erectile dysfunction in men, has been administered to choconstriction in the pathogenesis of EIPH is unclear.
horses in an apparent attempt to reduce EIPH. However, However, horses with EIPH are often treated with drugs
its efficacy in preventing EIPH or reducing pulmonary intended to decrease lower airway inflammation and
capillary pressure has not been demonstrated. relieve bronchoconstriction. The β-adrenergic broncho-
An increase in pulmonary capillary pressure secondary dilatory drugs such as clenbuterol and albuterol are
to altered rheological properties of blood during exercise effective in inducing bronchodilation in horses with bron-
has been suggested as a possible contributing factor to choconstriction but their efficacy in preventing EIPH is
EIPH (Fedde & Erickson 1998). Furosemide increases blood either unknown or, in very small studies, is not evident.
viscosity whereas pentoxifylline increases red blood cell Clenbuterol does not alter the hemodynamic responses
deformability and may attenuate the increase in blood of horses to exertion nor attenuate exercise-induced
viscosity that occurs during exercise (Weiss et al 1994, arterial hypoxemia in normal horses (Slocombe et al 1992,
1996a,b) However, pentoxifylline does not affect the Manohar et al 2000b). A very small study (two horses)
pulmonary capillary pressure of exercising horses and did of ipratropium, a parasympatholytic drug administered
not affect the prevalence of EIPH in a small experimental by inhalation, indicated promise in preventing EIPH
study (Manohar et al 2000a). (Sweeney et al 1984). Corticosteroids, including dexa-
methasone, fluticasone and beclomethasone adminis-
Increasing alveolar inspiratory pressure tered by inhalation, parenterally or enterally, reduce
Airway obstruction, either intrathoracic or extrathoracic, airway inflammation and obstruction but have no demon-
increases airway resistance and results in a more sub- strated efficacy in preventing EIPH. Cromolyn sodium
atmospheric intrathoracic (pleural) pressure during inspi- (sodium cromoglycate) has no efficacy in preventing EIPH
ration to maintain tidal volume and alveolar ventilation. (Hillidge et al 1987).
Causes of extrathoracic airway obstruction include laryn- Water vapor treatment (inhalation of water-saturated
geal hemiplegia and other abnormalities of the upper air) has been proposed as a treatment for EIPH because
airway, whereas intrathoracic obstruction is usually a of its putative effect on small airway disease. However,
result of bronchoconstriction and inflammatory airway water vapor treatment has no effect on EIPH (Sweeney
disease. Horses with partial extrathoracic inspiratory et al 1988).
obstruction or bronchoconstriction and airway inflamma- The use of bedding with low allergenic potential
tion associated with recurrent airway obstruction (heaves) (shredded paper) to prevent EIPH has no apparent effect
have pleural (and hence alveolar) pressures that are lower on prevalence of the condition (Mason et al 1984). While
(more negative) than those in unaffected horses or in it is suggested that preventing or minimizing small air-
horses after effective treatment. way disease may reduce the severity of EIPH, studies to
Partial inspiratory obstruction, such as that produced by demonstrate such an effect have not been reported.
laryngeal hemiplegia, exacerbates the exercise-induced However, optimizing the air quality in barns and stables
decrease in intrapleural pressures with a consequent and preventing infectious respiratory disease appear
increase in transmural capillary pressures (Jackson et al sensible precautions.
1997, Ducharme et al 1999, Hackett et al 1999). These
changes may exacerbate the severity of EIPH although an Interstitial inflammation and
association between upper airway obstructive disease and bronchial angiogenesis
EIPH has not been demonstrated. Surgical correction of
airway obstruction is expected to resolve the more negative Hemorrhage into interstitial tissues induces inflammation
intrapleural pressure but its effect on EIPH is unknown. with subsequent development of fibrosis and bronchial
Recently, the role of the nares in contributing to upper artery angiogenesis (O’Callaghan et al 1987c, McKane
airway resistance, and hence lowering inspiratory intra- & Slocombe 1999, 2002). The role of these changes in
pleural pressure during intense exercise, has attracted the perpetuating EIPH in horses is unclear, but likely is of
some importance. Treatments to reduce interstitial inflam- Summary of treatment options

mation and promote healing with minimal fibrosis have
been proposed. Rest is an obvious recommendation and Selection of therapy for horses with EIPH is problematic.
many racing jurisdictions have rules regarding enforced Given that most horses have some degree of pulmonary
rest for horses with epistaxis. While the recommendation hemorrhage during most bouts of intense exercise, the
for rest is intuitive, there is no information that rest reduces decision must be made not only as to the type of treat-
the severity or incidence of EIPH in horses with prior ment and its timing but also to which horses to treat.
evidence of this disorder. Moreover, the apparent progressive nature of the disease
Similarly, corticosteroids are often administered, by with continued work highlights the importance of early
inhalation, enterally or parenterally, in an attempt to and effective prophylaxis and emphasizes the need for
reduce pulmonary inflammation and minimize fibrosis. studies of possible factors such as air quality and respira-
Again, the efficacy of this intervention in preventing or tory infections in inciting the disorder.
minimizing severity of EIPH has not been documented. The currently favored treatment for EIPH is adminis-
tration of furosemide before intense exercise. Its use
is permitted in racehorses in a number of countries.
Excessive bleeding Increasingly persuasive laboratory evidence of an effect of
furosemide to reduce red cell count in bronchoalveolar
Coagulopathy and fibrinolysis
lavage fluid collected from horses soon after intense
Exercise induces substantial changes in blood coagulation exercise supports the contention that furosemide is effective
and fibrinolysis (McKeever et al 1990). However, there is no in reducing the severity of EIPH in racehorses. However, it
evidence that horses with EIPH have defective coagulation should be borne in mind that neither the relationship
or increased fibrinolysis (Bayly et al 1983, Johnstone et al between severity of EIPH and red cell count in bron-
1991). Regardless of this, aminocaproic acid, a potent choalveolar lavage fluid, nor the efficacy of furosemide in
inhibitor of fibrin degradation, has been administered to reducing severity of EIPH in racehorses in the field
horses to prevent EIPH but its efficacy in preventing EIPH has been demonstrated. In fact, there is evidence that
has not been demonstrated. Similarly, estrogens are given furosemide does not reduce the prevalence of EIPH and
to horses with the expectation of improving hemostasis other evidence that it does not reduce the severity of EIPH
although the effect of estrogens on coagulation in any under field conditions. The association between furosemide
species is unclear. There is no evidence that estrogens administration and superior performance in standardbred
prevent EIPH in horses. and thoroughbred racehorses should be borne in mind
Vitamin K is administered to horses with EIPH presum- when recommending use of this drug.
ably with the expectation that it will decrease coagulation Rest is an obvious recommendation for horses with
times. However, as EIPH is not associated with prolonged EIPH, but the hemorrhage is likely to recur when the horse
bleeding times, it is unlikely that this intervention will is next strenuously exercised. The duration of rest and the
affect the prevalence or severity of EIPH. optimal exercise program for the return of horses to racing
after EIPH is unknown, although some jurisdictions require
Platelet function exercise no more intense than trotting for 2 months. Firm
Aspirin inhibits platelet aggregation in horses and recommendations cannot be made on duration of rest
increases bleeding time (Kopp et al 1985). Seemingly because of a lack of objective information.
paradoxically, aspirin is sometimes administered to horses Although a role for lower airway disease (either
with EIPH because of concerns that increased platelet infectious or allergic) in the genesis of EIPH has not
aggregation contributes to EIPH (Mahony et al 1992). been demonstrated, control of infectious diseases and
There is no evidence that aspirin either exacerbates or minimization of non-infectious lower airway inflammation
prevents EIPH. appears prudent.
Capillary integrity Prognosis

Capillary fragility increases the risk of hemorrhage in The prognosis for racing for horses with clinically signifi-
many species. Various bioflavonoids have been suggested cant EIPH is guarded because of the progressive nature of
to increase capillary integrity and prevent bleeding. How- the disease. Horses that have experienced severe EIPH on
ever, hesperidin and citrus bioflavonoids have no efficacy one occasion are likely to do so again regardless of treat-
in preventing EIPH in horses (Sweeney & Soma 1984). ment. However, the risk of horses experiencing a repeated
Similarly, vitamin C is administered to horses with EIPH bout of severe hemorrhage and the effect of EIPH on career
without scientific evidence of any beneficial effect. longevity are unknown.
REFERENCES pressure and pulmonary artery pressure in exercis-

ing horses. American Journal of Veterinary Research
Anonymous 2002 International agreement on breeding and 60: 485–494
racing and appendices, International Federation of Horse Heller B 2002 Run, Baby, Run: What Every Owner, Breeder,
Racing Authorities and Handicapper Should Know About Lasix in Racehorses.
Art T, Anderson L, Woakes A J et al 1990 Mechanics of The Russell Meerdink Company, Neenah, WI, p.180
breathing during strenuous exercise in Thoroughbred Hillidge CJ, Lane TJ, Johnson E 1984 Preliminary investiga-
horses. Respiration Physiology 82: 279–294 tions of exercise-induced pulmonary hemorrhage in
Bayly WM, Meyers KM, Keck MT 1983 Effects of furosemide racing Quarter Horses. Journal of Equine Veterinary
on exercise-induced alterations in haemostasis in Science 4: 21–23
Thoroughbred horses exhibiting post-exercise epistaxis. Hillidge CJ, Lane TJ, Whitlock TW 1986 Exercise-induced
In: Snow DH, Persson SGB, Rose RJ (editors) Equine pulmonary hemorrhage in the racing Appaloosa horse.
Exercise Physiology. Granta Editions, Cambridge, pp.64–70 Journal of Equine Veterinary Science 5: 351–353
Birks EK, Mathieu-Costello O, Fu Z et al 1994 Comparative Hillidge CJ, Whitlock TW, Lane TJ 1987 Failure of inhaled
aspects of the strength of pulmonary capillaries in rabbit, disodium cromoglycate aerosol to prevent exercise-
dog, and horse. Respiratory Physiology 97: 235–246 induced pulmonary hemorrhage in racing quarter
Birks EK, Mathieu-Costello O, Fu Z et al 1997 Very high horses. Journal of Veterinary Pharmacology and
pressures are required to cause stress failure of pulmonary Therapeutics 10: 257–260
capillaries in thoroughbred racehorses. Journal of Applied Hinchcliff KW, Jackson M, Morley PS et al 2004 Association
Physiology 82: 1584–1592 of exercise-induced pulmonary hemorrhage and per-
Birks EK, Shuler KM, Soma LR et al 2002 EIPH: postrace formance in racing Thoroughbred horses. Proceedings
endoscopic evaluation of Standardbreds and Thorough- of the American Association of Equine Practitioners,
breds. Equine Veterinary Journal Supplement 34: 375–378 Denver 50: 276–277
Christley RM, Hodgson DR, Rose RJ et al 2001 Coughing in Hinchcliff KW, Jackson M, Morley PS et al (2005) Tracheo-
thoroughbred racehorses: risk factors and tracheal bronchoscopic assessment of the severity of exercise-
endoscopic and cytological findings. Veterinary Record induced pulmonary hemorrhage in Thoroughbred race-
148: 99–104 horses. American Journal of Veterinary Research 66:
Cook WR 1974 Epistaxis in the racehorse. Equine Veterinary 596–598
Journal 6: 45–58 Holcombe SJ, Berney C, Cornelisse C J et al 2002 Effect of
Cook WR 1988 Hypotheses on exercise-induced pulmonary commercially available nasal strips on airway resistance
hemorrhage in horses. Journal of the American in exercising horses. American Journal of Veterinary
Veterinary Medical Association 193: 8–10 Research 63: 1101–1105
Deaton C, Marlin D 2004 A review of the effects of envi- Jackson JA, Ducharme NG, Hackett RP et al 1997 Effects of
ronmental pollution on the equine respiratory tract: airway obstruction on transmural pulmonary artery
considerations for the 2004 Athens Olympic Games. pressure in exercising horses. American Journal of
Journal of Equine Comparative Exercise Physiology Veterinary Research 58: 897–903
1: 171–176 Johnstone IB, Viel L, Crane S et al 1991 Hemostatic studies
Ducharme NG, Hackett RP, Gleed RD et al 1999 Pulmonary in racing standardbred horses with exercise-induced
capillary pressure in horses undergoing alteration of pulmonary hemorrhage. Hemostatic parameters at rest
pleural pressure by imposition of various airway resistive and after moderate exercise. Canadian Journal of
loads. Equine Veterinary Journal Supplement 30: 27–33 Veterinary Research 55: 101–106
Fedde MR, Erickson HH 1998 Increase in blood-viscosity Jones JH, Cox TS, Takahashi T et al 2002 Heterogeneity of
in the sprinting horse – can it account for the high intrapleural pressures during exercise. Equine Veterinary
pulmonary arterial-pressure? Equine Veterinary Journal Journal Supplement 34: 391–396
30: 329–334 Kindig CA, Erickson BK, Poole DC 2000 Dissociation of
Fogarty U, Buckley T 1991 Bronchoalveolar lavage findings in exercise-induced pulmonary hemorrhage and pulmonary
horses with exercise intolerance. Equine Veterinary artery pressure via nitric oxide synthase inhibition.
Journal 23: 434–437 Journal of Equine Veterinary Science 20: 715–721
Geor RJ, Ommundson L, Fenton G et al 2001 Effects of Kindig CA, McDonough P, Fenton G et al 2001 Efficacy of
an external nasal strip and frusemide on pulmonary nasal strip and furosemide in mitigating EIPH in
haemorrhage in Thoroughbreds following high-intensity Thoroughbred horses. Journal of Applied Physiology
exercise. Equine Veterinary Journal 33: 577–584 91: 1396–1400
Gleed RD, Ducharme NG, Hackett R 1999 Effects of frusemide Kopp K, Moore J, Byars T et al 1985 Template bleeding time
on pulmonary capillary pressure in horses exercising and thromboxane generation in the horse: effects of
on a treadmill. Equine Veterinary Journal Supplement three non-steroidal anti-inflammatory drugs. Equine
30: 102–106 Veterinary Journal 17: 322–324
Gross DK, Morley PS, Hinchcliff KW et al 1999 Effect of Langsetmo I, Meyer MR, Erickson HH 2000 Relationship
furosemide on performance of Thoroughbreds racing in of pulmonary arterial pressure to pulmonary haemor-
the United States and Canada. Journal of the American rhage in exercising horses. Equine Veterinary Journal
Veterinary Medical Association 215: 670–675 32: 379–384
Gunson DE, Sweeney CR, Soma LR 1988 Sudden death Lapointe JM, Vrins A, McCarvill E 1994 A survey of exercise-
attributable to exercise-induced pulmonary hemorrhage induced pulmonary haemorrhage in Quebec standardbred
in racehorses: nine cases (1981–1983). Journal of the racehorses. Equine Veterinary Journal 26: 482–485
American Veterinary Medical Association 193: 102–106 MacNamara B, Bauer S, Iafe J 1990 Endoscopic evaluation of
Hackett RP, Ducharme NG, Ainsworth DM et al 1999 Effects exercise-induced pulmonary hemorrhage and chronic
of extrathoracic airway obstruction on intrathoracic obstructive pulmonary disease in association with poor
performance in racing Standardbreds. Journal of the Muir WW, Sams RA, Hubbell JAE et al 2001 Effects of
American Veterinary Medical Association 196: 443–445 enalaprilat on cardiorespiratory, hemodynamic, and
Mahony C, Rantanen NW, DeMichael JA et al 1992 Spon- hematologic variables in exercising horses. American
taneous echocardiographic contrast in the thorough- Journal of Veterinary Research 62: 1008–1013
bred: high prevalence in racehorses and a characteristic Newton JR, Wood JLN 2002 Evidence of an association
abnormality in bleeders. Equine Veterinary Journal between inflammatory airway disease and EIPH in young
24: 129–133 Thoroughbreds in training. Equine Veterinary Journal
Manohar M 1993 Furosemide attenuates the exercise-induced Supplement 34: 417–424
increase in pulmonary artery wedge pressure in horses. O’Callaghan MW, Pascoe JR, Tyler WS et al 1987a Exercise-
American Journal of Veterinary Research 54: 952–958 induced pulmonary haemorrhage in the horse: results
Manohar M, Goetz TE 1999 Pulmonary vascular pressures of of a detailed clinical, post mortem and imaging study.
strenuously exercising Thoroughbreds during intravenous I. Clinical profile of horses. Equine Veterinary Journal
infusion of nitroglycerin. American Journal of Veterinary 19: 384–388
Research 60: 1436–1440 O’Callaghan MW, Pascoe JR, Tyler WS et al 1987b Exercise-
Manohar M, Hutchens E, Coney E 1993 Pulmonary haemo- induced pulmonary haemorrhage in the horse: results
dynamics in the exercising horse and their relationship of a detailed clinical, post mortem and imaging study.
to exercise-induced pulmonary haemorrhage. British II. Gross lung pathology. Equine Veterinary Journal
Veterinary Journal 149: 419–428 19: 389–393
Manohar M, Goetz TE 1998 L-Name does not affect exercise- O’Callaghan MW, Pascoe JR, Tyler WS et al 1987c Exercise-
induced pulmonary hypertension in thoroughbred horses. induced pulmonary haemorrhage in the horse: results of
Journal of Applied Physiology 84: 1902–1908 a detailed clinical, post mortem and imaging study. III.
Manohar M, Goetz T, Rothenbaum P et al 2000a Intravenous Subgross findings in lungs subjected to latex perfusions of
pentoxifylline does not affect the exercise-induced pul- the bronchial and pulmonary arteries. Equine Veterinary
monary arterial, capillary or venous hypertension in Journal 19: 394–404
Thoroughbred horses. Journal of Veterinary Pharmacology O’Callaghan MW, Pascoe JR, Tyler WS et al 1987d Exercise-
and Therapeutics 23: 317–322 induced pulmonary haemorrhage in the horse: results
Manohar M, Goetz TE, Rothenbaum P et al 2000b Clenbuterol of a detailed clinical, post mortem and imaging study.
administration does not attenuate the exercise-induced V. Microscopic observations. Equine Veterinary Journal
pulmonary arterial, capillary or venous hypertension in 19: 411–418
strenuously exercising Thoroughbred horses. Equine Oikawa M 1999 Exercise-induced haemorrhagic lesions in the
Veterinary Journal 32: 546–550 dorsocaudal extremities of the caudal lobes of the lungs
Martin BB, Beech J, Parente EJ 1999 Cytologic examination of of young thoroughbred horses. Journal of Comparative
specimens obtained by means of tracheal washes per- Pathology 121: 339–347
formed before and after high-speed treadmill exercise in Pascoe JR 1996 Exercise-induced pulmonary hemorrhage: a
horses with a history of poor performance. Journal of the unifying concept. Proceedings of the American Association
American Veterinary Medical Association 214: 673–677 of Equine Practitioners 42: 220–226
Mason DK, Collins EA, Watkins KL 1983 Exercise-induced Pascoe JR, Ferraro G, Cannon J et al 1981a Exercise-induced
pulmonary haemorrhage in horses. In: Snow DH, pulmonary hemorrhage in racing thoroughbreds: a
Persson SGB, Rose RJ (editors) Equine Exercise Physiology. preliminary study. American Journal of Veterinary
Granta Editions, Cambridge, pp.57–63 Research 42: 703–707
Mason DK, Collins EA, Watkins KL 1984 Effect of bedding on Pascoe JR, Ferraro GL, Cannon JH et al 1981b Exercise-
the incidence of exercise induced pulmonary haemor- induced pulmonary hemorrhage in racing thorough-
rhage in racehorses in Hong Kong. Veterinary Record breds: a preliminary study. American Journal of Veterinary
115: 268–269 Research 42: 703–707
McDonough P, Kindig C, Hildreth T et al 2004 Effect of Pascoe JR, O’Brien TR, Wheat JD et al 1983 Radiographic
furosemide and the equine nasal strip on exercise- aspects of exercise-induced pulmonary hemorrhage in
induced pulmonary hemorrhage and time-to-fatigue racing horses. Veterinary Radiology 24: 85–92
in maximally exercising horses. Journal of Equine Pascoe JR, McCabe AE, Franti CE et al 1985 Efficacy of
Comparative Exercise Physiology 1: 177–184 furosemide in the treatment of exercise-induced pulmonary
McKane SA, Slocombe R 1999 Sequential changes in bron- hemorrhage in Thoroughbred racehorses. American
choalveolar cytology after autologous blood inoculation. Journal of Veterinary Research 46: 2000–2003
Equine Veterinary Journal Supplement 30: 126–130 Raphel CF, Soma LR 1982 Exercise-induced pulmonary
McKane SA, Slocombe RF 2002 Alveolar fibrosis and changes hemorrhage in Thoroughbreds after racing and breezing.
in lung morphometry in response to intrapulmonary American Journal of Veterinary Research 43: 1123–1127
blood. Equine Veterinary Journal Supplement 34: 451–458 Robinson NE, Derksen FJ 1980 Small airway obstruction
McKane SA, Canfield PJ, Rose RJ 1993 Equine bronchoalveolar as a cause of exercise-associated pulmonary hemorrhage.
lavage cytology: survey of thoroughbred racehorses in Proceedings of the American Association of Equine
training. Australian Veterinary Journal 70: 401–404 Practitioners 26: 421–430
McKeever KH, Hinchcliff KW, Kociba GJ et al 1990 Exercise- Rohrbach BW 1990 Exercise-induced pulmonary hemor-
induced changes in clotting time and fibrinolytic activity rhage, chronic obstructive pulmonary disease, and racing
in horses. American Journal of Veterinary Research performance. Journal of the American Veterinary Medical
51: 1335–1339 Association 196: 1563–1564
Meyer TS, Fedde MR, Gaughan EM et al 1998 Quantifica- Rossier Y, Sweeney CR, Ziemer EL 1991 Bronchoalveolar
tion of exercise-induced pulmonary haemorrhage with lavage fluid cytologic findings in horses with pneumonia
bronchoalveolar lavage. Equine Veterinary Journal or pleuropneumonia. Journal of the American Veterinary
30: 284–288 Medical Association 198: 1001–1004
Schroter RC, Marlin DJ, Denny E 1998 Exercise-induced Valdez S, Nieto J, Spier S et al 2004 Effect of an external
pulmonary haemorrhage (EIPH) in horses results from nasal dilator strip on cytologic characteristics of bron-
locomotory impact induced trauma: a novel, unifying choalveolar lavage fluid in Thoroughbred racehorses.
concept. Equine Veterinary Journal 30: 186–192 Journal of the American Veterinary Medical Association
Sime D, Engen R, Miller-Graber P 1994 Frequency and use of 224: 558–561
medications in horses racing in Prairie Meadows. Iowa Voynick BT, Sweeney CR 1986 Exercised-induced pul-
State University Vet 54. monary hemorrhage in polo and racing horses. Journal
Slocombe R, Covelli G, Bayly W 1992 Respiratory mechanics of the American Veterinary Medical Association 188:
of horses during stepwise treadmill exercise tests, and the 301–302
effect of clenbuterol pretreatment on them. Australian Weideman H, Schoeman S, Jordaan G et al 2003 Epistaxis
Veterinary Journal 69: 221–225 related to exercise-induced pulmonary haemorrhage
Soma LR, Uboh CE, Nann L 1996 Prerace venous blood in South African Thoroughbreds. Journal of the South
acid–base values in Standardbred horses. Equine Veterinary African Veterinary Association 74: 127–131
Journal 28: 390–396 Weiss DJ, Smith CM 2nd 1998 Haemorheological alterations
Soma LR, Birks EK, Uboh CE et al 2000 The effects of associated with competitive racing activity in horses:
frusemide on racing times of Standardbred pacers. implications for exercise-induced pulmonary haemor-
Equine Veterinary Journal 32: 334–340 rhage (EIPH). Equine Veterinary Journal 30: 7–12
Speirs VC 1982 Pulmonary hemorrhage in Standardbred race Weiss DJ, Evanson OA, Geor RJ 1994 The effects of furosemide
horses. Australian Veterinary Journal 59: 38–40 and pentoxifylline on the flow properties of equine
Step DL, Freeman KP, Gleed RD et al 1991 Cytologic and endo- erythrocytes: in vitro studies. Veterinary Research
scopic findings after intrapulmonary blood inoculations in Communications 18: 373–381
horses. Journal of Equine Veterinary Science 11: 340–345 Weiss DJ, Geor RJ, Burger K 1996a Effects of furosemide on
Sweeney CR, Soma LR 1984 Exercise-induced pulmonary hemorheologic alterations induced by incremental
hemorrhage in thoroughbred horses: response to furo- treadmill exercise in thoroughbreds. American Journal of
semide or hesperidin-citrus bioflavonoids. Journal of the Veterinary Research 57: 891–895
American Veterinary Medical Association 185: 195–197 Weiss DJ, Geor RJ, Burger K 1996b Effects of pentoxifylline on
Sweeney CR, Soma LR, Bucan CA et al 1984 Exercise-induced hemorheologic alterations induced by incremental
pulmonary hemorrhage in exercising Thoroughbreds: treadmill exercise in thoroughbreds. American Journal of
preliminary results with pre-exercise medication. Cornell Veterinary Research 57: 1364–1368
Veterinarian 74: 263–268 West JB, Mathieu-Costello O 1994 Stress failure of pulmonary
Sweeney CR, Hall J, Fisher JR et al 1988 Efficacy of water capillaries as a mechanism for exercise induced pul-
vapor-saturated air in the treatment of exercise-induced monary haemorrhage in the horse. Equine Veterinary
pulmonary hemorrhage in Thoroughbred racehorses. Journal 26: 441–447
American Journal of Veterinary Research 49: 1705–1707 West JB, Mathieu-Costello O, Jones JH et al 1993 Stress failure
Sweeney CR, Soma LR, Maxson AD et al 1990 Effects of of pulmonary capillaries in racehorses with exercise-
furosemide on the racing times of Thoroughbreds. induced pulmonary hemorrhage. Journal of Applied
American Journal of Veterinary Research 51: 772–778 Physiology 75: 1097–1109
Takahashi T, Hiraga A, Ohmura H et al 2001 Frequency of Williams R, Harkins L, Hammond C et al 2001 Racehorse
and risk factors for epistaxis associated with exercise- injuries, clinical problems and fatalities recorded on
induced pulmonary hemorrhage in horses: 251,609 race British racecourses from flat racing and National Hunt
starts (1992–1997). Journal of the American Veterinary racing during 1996, 1997 and 1998. Equine Veterinary
Medical Association 218: 1462–1464 Journal 33: 478–486
Respiratory Diseases of the Foal
45 Elizabeth A Carr
Respiratory disease is one of the leading causes of and general health, as well as information regarding the
morbidity and mortality in neonatal foals. Many factors farm’s management and overall herd health, is critical in
unique to the neonate make them more susceptible to assessing the potential for illness in the neonate.
respiratory disorders. Prematurity, inadequate colostral
transfer, meconium aspiration, and neonatal sepsis are Prepartum maternal signs
just a few of the syndromes that can result in respira-
tory failure. This chapter reviews the common respiratory Although the majority of mares have an uneventful
syndromes recognized in equine neonatology. Diagnostic gestation and foal with little, if any, intervention, in other
evaluation, clinical assessment, treatment, and potential mares, premonitory signs, either present as a clinical
complications will be discussed. The chapter focuses finding during physical examination or as a component of
primarily on respiratory disorders of the neonatal period. the history, warrant additional scrutiny for potential
In addition, lower respiratory tract syndromes seen prin- problems. Mares that have a history of pregnancy com-
cipally in foals are also discussed. Respiratory disorders plications such as endometritis, dystocia or abortion should
common to weanlings and adult horses are discussed be monitored carefully, and their foals warrant a high
elsewhere in this book. degree of surveillance postpartum. Severe maternal illness
The diagnosis of respiratory disease in the foal can be such as endotoxemia, fever, cardiovascular disease, renal
difficult. Neonatal foals with respiratory disease rarely failure of advanced pregnancy, prepartum uterine artery
cough or exhibit nasal discharge. Clinical signs may be hemorrhage, or conditions requiring general anesthesia
non-specific including increased restlessness, agitation, and and surgical intervention may compromise the fetus and
an elevated respiratory rate. Auscultation is frequently lead to delivery of a weak, sick or premature foal at greater
unrewarding because foals often have little to no abnormal risk for illness.
lung sounds even with significant pulmonary disease.
Consequently, the diagnosis of pulmonary disease can be Parturition
difficult without additional diagnostic testing and a strong
index of suspicion. The decision to perform additional Normal parturition occurs in three stages. Stage 1 can
diagnostic testing (including blood gas analysis, thoracic persist for a variable duration and is associated with
radiography, thoracic ultrasound, and tracheal wash and uterine contractions as the foal moves into position for
culture) needs to be made using historical information on birth. Stage 2 begins with the rupture of the chorioal-
the pregnancy, foaling and early postpartum period, lantoic membrane and ends with delivery of the foal.
coupled with physical examination findings. Stage 3 is expulsion of the placenta. Stage 2 should be
relatively short, lasting approximately 20 min. Because
placental attachments begin to separate and oxygen
History delivery to the foal is compromised during stage 2, delay
The goal in obtaining a history is to identify risk factors or in delivery of the foal can result in asphyxia. If parturi-
events that suggest that the foal may be ill or at risk for tion is prolonged, fetal stress may result in expulsion and
illness. Any foal with identifiable risk factors or evidence of aspiration of meconium. Compression of the thorax as
underlying illness warrants a higher degree of surveillance, it passes through the mare’s pelvic canal assists in removal
and may require additional diagnostic testing to detect of fluid from the lungs. A foal delivered by Caesarean
illness and institute treatment at the earliest possible stage. section does not experience this thoracic compression and
Neonatal foal survival rates are correlated with early needs assistance to remove excess fluid from the lungs.
detection of illness and therapeutic intervention (Gayle Foals with evidence of placentitis, a history of premature
et al 1998). Consequently, when evaluating a foal, it is placental separation, dystocia, premature delivery or
imperative to obtain a detailed history regarding the delivery by Caesarean section are all at greater risk of
pregnancy, parturition, and immediate postpartum period. neonatal illness, sepsis and respiratory failure and should
Information regarding the mare’s previous pregnancies be monitored closely.
633
SECTION 6 : Respiratory Diseases of the Foal
634 45 Respiratory Diseases of the Foal
Postpartum Auscultation of the thorax of the foal should be

performed in a quiet place with the foal standing or in
The normal foal should achieve sternal recumbency within sternal recumbency. Because of the relatively compliant
minutes of birth. Respiratory and heart rates should chest wall of the neonate, foals will experience some
be 60/min or more during the first few minutes and collapse of dependent alveoli when they lie on their sides.
nasal stimulation should result in a sneeze or cough and Consequently, abnormal lung sounds (crackles and wheezes)
obvious avoidance behavior. The foal that cannot achieve may be heard on the dependent side after a period of
sternal recumbency, or that has a respiratory or heart rate prolonged lateral recumbency. Use of a rebreathing bag to
< 60/min at birth is abnormal and warrants continued increase ventilation is generally not necessary when
surveillance and potential intervention. Meconium staining auscultating the neonate given their relatively small size
of the skin is associated with intrauterine stress and is a and thin chest wall and may be contraindicated in hypoxic
concern because of the potential for meconium aspiration. or hypercapnic individuals. While careful auscultation of
The foal should be standing by 2 h of age and nursing soon the thorax is recommended, it can be an insensitive tool for
afterwards. The goal is to ensure colostrum ingestion before assessing lung disease. Lung auscultatory changes are
exposure to potential pathogens in the immediate environ- often subtle, with minimal adventitial sounds even in
ment. A foal that has delayed suckling and spends several the face of severe pneumonia. With larger areas of lung
hours udder seeking and licking the walls and the mare’s consolidation auscultation may reveal a “tubular” or
perineal area is at greater risk for subsequent infection and hollow sound as air is heard moving principally through
illness. Any foal that deviates from normal parameters large airways.
should be carefully monitored and intervention should be
provided as necessary.
Thoracic ultrasound
While the auscultation of abnormal or diminished lung
Examination of the Foal sounds is a clear indication for further diagnostic test-
Respiratory System ing including thoracic ultrasound, radiography, and
Normal vital parameters and behavior patterns have been arterial blood gas analysis, many foals with respiratory
published for foals from birth to several months of age disease may have relatively normal lung sounds. Conse-
(Koterba 1990). Deviation from normal, particularly in the quently, most foals admitted to the clinic will need
early neonatal period, should warrant a careful physical additional diagnostic tests.
examination. A respiratory rate of 60–80 breaths/min is Abdominal ultrasound is routinely performed in all
typical immediately after birth. This rate should decline to neonates admitted to the clinic at Michigan State University
30–40 breaths/min over the first 2 h. Normal foals may and it is easy to include the thorax as well. Ideally the foal
have an elevated respiratory rate when lying in lateral is evaluated standing or in sternal recumbency and the
recumbency. Persistent tachypnea, although a relatively pleural surface is imaged through the intercostal spaces
non-specific clinical finding, warrants a close examination using a 5- to 7.5-MHz probe. Either a sector or linear probe
of the respiratory system particularly if the foal appears can be used, depending on the ultrasonographer’s prefer-
agitated, restless or unwilling to lie down and sleep. A ence. Normal thoracic ultrasound should reveal a sharp
mildly exaggerated inspiratory and expiratory effort may be line at the pleural surface with reverberation artifacts
the only clinical sign of respiratory disease during the early at regularly spaced intervals in the deeper image. These
stages of illness. During nursing, the foal is required to artifactual lines are a repeated reception of the original
breath-hold, and thus in cases with severe respiratory echo from the visceral surface as it “bounces” between
compromise and hypoxemia the foal may be reluctant to the transducer and the receiver. The pleural surface should
nurse for more than a few seconds at a time. appear to glide dorsally and ventrally with breathing so
Neonatal foals have a monophasic breath cycle, unlike that the diaphragm and abdominal viscera are uncovered
adult horses that exhibit a biphasic cycle with both pas- during exhalation. Little to no pleural fluid should be
sive and active components to inspiration and expiration evident. Early signs of respiratory disease include the
(Koterba et al 1995a). In young foals both inspiration generation of pleural “comet tails” that are the result of
and expiration are active but as the foal matures, expiration irregularities in the normally smooth pleural membrane
and then later inspiration become biphasic (Koterba et al (Fig. 45.1). These irregularities can be temporarily seen
1995b). Long apneustic pauses in breathing, i.e. breath- in the normal lung after prolonged recumbency or can
holds during inhalation, are abnormal and suggest central signify early inflammatory changes. Moderate to severe
nervous system derangements such as might be seen with alveolar consolidation results in deeper penetration of the
periparturient asphyxia syndrome. ultrasound waves, allowing observation of parenchymal
45 Respiratory Diseases of the Foal 635
LUNG TIP
FLUID
DIAP
ABSCESS
Fig. 45.1. Ultrasound picture of multiple pleural irregularities, “comet Fig. 45.2. Ultrasound picture of a pulmonary abscess in the right
tails” (arrows). The finding of these pleural irregularities is consistent hemithorax at the level of the eighth intercostal space.
with mild or early pneumonia or prolonged lateral recumbency and
should alert the clinician to pursue further diagnostic evaluation.
carefully. Continued injury as evidenced by pulmonary

contusion or pleural hemorrhage would be an indication
for fracture stabilization (Fig. 45.4) (Bellezzo et al 2004).
changes (Fig. 45.2). Because the ability of ultrasound to
image the deeper lung is limited by air in the abaxial lung Thoracic radiography
fields, it is not accurate in assessing solitary, deep pul-
monary abscesses. When evaluating a case of foal pneu- Although thoracic radiographs are a useful diagnostic tool
monia, both radiographic and ultrasonographic examina- to evaluate the severity of respiratory disease and response
tions of the thorax are recommended to obtain the most to treatment, radiographic changes frequently lag behind
accurate information. clinical findings, necessitating careful interpretation of
Unlike the situation in adult horses, pleural effusion is a the radiographs. For example, in human infants with
relatively uncommon finding in neonatal pneumonia. acute persistent pulmonary hypertension, patients may
Pleural effusion occurs secondary to rib fractures (hemo- exhibit severe hypoxemia and respiratory distress with
thorax) and uroabdomen. In the latter case, the urothorax few radiographic changes. Over time, pulmonary infiltrates
is the result of transudation across the diaphragm from become apparent as edema and inflammation progress;
the uroabdomen. however, the early evaluation may be unremarkable. Con-
In addition to evaluation of the lungs, individual ribs sequently, pulmonary radiographs should be interpreted
should be imaged to assess the presence of rib fractures. carefully and repeat radiographs are indicated in a patient
The simplest way to image the ribs is to place the index with persistent or deteriorating respiratory function.
finger and thumb of one hand into the intercostal spaces The location of pulmonary densities may be helpful in
immediately before and after the rib being imaged, while determining the underlying cause of respiratory disease.
the other hand holds and moves the transducer longitu- Alveolar infiltrates and consolidation in the ventral
dinally down the rib. The most common sites of rib lung fields are frequently associated with pneumonia as a
fractures are just dorsal to the costochondral junction. The result of milk aspiration (Fig. 45.5). However, meconium
ventral fragment frequently displaces inward and can cause aspiration in utero frequently results in a more diffuse
injury to the lung or heart (Fig. 45.3). While rib fractures alveolar infiltrate. Viral infections or hematogenous bac-
have been reported in clinically normal foals with no terial pneumonias typically cause more diffuse alveolar
history of previous trauma, they are a cause of concern infiltrates with varying severity of interstitial and bronchial
particularly in recumbent foals requiring assistance to rise changes. Pulmonary radiographs of foals with primary
(Jean et al 1999, Sprayberry et al 2001). While a normal surfactant deficiency may appear normal immediately after
healthy foal may guard the area of a rib fracture and birth; later radiographic evaluation often reveals diffuse,
minimize further injury, a recumbent foal being assisted to severe alveolar infiltrates and consolidation (Fig. 45.6). In a
stand or restrained for evaluation is at a greater risk of study of 128 foals, an attempt was made to correlate
further injury. Foals with rib fractures should be restrained pulmonary radiographic findings to survival (Bedenice et al
PROX
HEM-
RIB FX
DISTAL FRAG
Fig. 45.3. Ultrasound picture of a fractured rib (RIB FX) just proximal (PROX) to the costochondral junction.
The distal fragment (FRAG) is displaced medially and has caused contusions to the lung directly beneath it
(arrow). Hemorrhage (HEM) can be seen surrounding the fracture site.
HEMORRHAGE
Fig. 45.4. Ultrasound picture of hemorrhage and pulmonary contusions just cranial to a rib fracture. The
detection of this hemorrhage and contusion alerted the clinician to the possibility of a rib fracture. Further
evaluation revealed the fracture of the rib just caudal to this image (see Fig. 45.3).
Table 45.1. Blood gas pH and bicarbonate

values in foals
Position PaCO2 PAO2 HCO3–
Age sampled pH (mmHg) (mmHg) (mEq/l) No.
Birth lateral 7.413 45.7 39.7 26.3 8

± 0.019 ± 1.1 ± 2.1 ± 1.1
2 min lateral 7.312 54.1 56.4 24.0 10

± 0.016 ± 2.0 ± 2.3 ± 1.2
15 min lateral 7.322 50.4 57.5 24.4 9

± 0.025 ± 2.7 ± 3.6 ± 1.6
30 min lateral 7.354 51.5 57.0 25.3 10

± 0.010 ± 1.5 ± 1.8 ± 6.7
60 min lateral 7.362 47.3 60.9 25.3 9

± 0.013 ± 2.2 ± 2.7 ± 1.0
Fig. 45.5. Thoracic radiograph of foal presented with history of
dysphagia. The cardiac silhouette is no longer visible because of the 2h lateral 7.362 47.7 66.5 25.0 8
severe ventral consolidation that is consistent with aspiration ± 0.012 ± 1.7 ± 2.3 ± 0.9
pneumonia.
4h lateral 7.355 45.0 75.7 23.6 10
± 0.017 ± 1.9 ± 4.9 ± 1.1
12 h lateral 7.357 44.3 73.5 23.2 10

± 0.024 ± 1.2 ± 3.0 ± 1.3
24 h lateral 7.393 45.5 67.6 26.2 9

± 0.012 ± 1.5 ± 4.4 ± 1.1
48 h lateral 7.396 46.1 74.9 25.7 8

± 0.008 ± 1.1 ± 3.3 ± 0.6
4 days lateral 7.396 45.8 81.2 23.2 8

± 0.012 ± 1.1 ± 2.1 ± 2.1
Reproduced from Stewart et al 1984, with permission.
Blood gas analysis

At birth the foal’s arterial oxygen tension (PAO2) is much
lower (43 ± 3.9 mmHg) than the adult horse (Table 45.1)
(Rose et al 1982). Within the first hour of life, PAO2 should
increase to 65–75 mmHg, and by 24 h of age it should
approximate adult values. Arterial oxygen tension also
varies with recumbency. When the foal is in lateral
Fig. 45.6. One-day-old neonatal foal with acute onset of respiratory
distress. Radiographs reveal severe, diffuse, alveolar pattern in all lung
recumbency PAO2 can be up to 14 mmHg lower than when
fields. Air bronchograms can be seen particularly clearly in the the foal is standing or sternally recumbent (Stewart et al
dorsocaudal lung field. 1984). Consequently the clinician needs to take into
account the age and posture of the foal when interpreting
arterial blood gas results. Because of this variation and the
relatively low arterial oxygen tension on the first day of life,
2003). Foals with radiographic findings of diffuse pul- the PAO2 threshold indicated for institution of oxygen
monary disease and foals with severe alveolar changes supplementation may vary. A PAO2 of ≥ 60 mmHg gen-
were more likely to die than others. While the results of erally correlates with 90% saturation of hemoglobin or
this study are interesting, radiographic findings remain a greater and for this reason the majority of clinicians
single piece of the puzzle and should be interpreted in the institute oxygen therapy when PAO2 or oxygen saturation is
light of other diagnostic results. < 60 mmHg or < 90%, respectively.
An arterial blood gas analysis is indicated in any foal bodies, and the maturation of type I cells and the closely
with an elevated respiratory rate, dyspnea, cyanosis associated capillaries also occurs during this final develop-
or other evidence of pulmonary disease to determine mental stage.
the severity of compromise, and to assess the need of Once the foal’s placenta detaches during parturition,
adjunctive therapy. If arterial blood gas analysis facili- hypoxia, hypercapnia, and acidosis drive the respiratory
ties are not readily available, or a sample cannot be effort to breathe. The first extrauterine breath requires
obtained, pulse oximetry can be utilized. Pulse oximetry is generation of a large subatmospheric pressure to open
less accurate than arterial blood gas analysis in quantifying airways and alveoli for the first time. During this first
the severity of hypoxemia, particularly in hypovolemic, inhalation, as the alveoli open, surfactant present in the
poorly perfused individuals, but can be useful to evaluate mature fetal lungs is released from the type II alveolar
trends and response to therapy (Chaffin et al 1996). epithelial cells and spreads out along the alveolar sur-
face. As surfactant spreads along the air–fluid interface, it
decreases the surface tension, helping to stabilize the alveoli
Lung Development and the and preventing alveolar collapse during exhalation. The
Fetal–Neonatal Transition large increase in lung volume (resulting in mechanical
Understanding neonatal respiratory diseases, their com- stretch of the pulmonary vasculature) and the increased
plications and treatment is facilitated by knowledge of the oxygen tension in the alveoli cause passive and active
development of the lung and the changes in the lung and vasodilatation. This results in a decrease in pulmonary
circulation that occur at birth (Fig. 45.7). In utero, oxygen vascular resistance and an increase in pulmonary blood
is delivered to the fetus via the placental circulation. flow (Raj & Shimoda 2002). As resistance falls, the pres-
Oxygenated blood enters the fetus via the umbilical vein, sure across the pulmonary circulation falls below that of
through the caudal vena cava to the right atrium. After the systemic circulation. The increased capacitance of the
entering the right chamber of the heart, blood is shunted pulmonary circulation that is associated with pulmonary
to the left chamber of the heart, the aorta, and the sys- vasodilatation accommodates the increase in cardiac out-
temic circulation through the foramen ovale and ductus put directed through the lungs. In addition, the removal of
arteriosus. Before birth, the fetal lung is collapsed and the large placental vasculature results in a decrease
fluid-filled, pulmonary vascular resistance is high as the in systemic vascular area and systemic resistance rises
result of low oxygen tension and there is minimal blood accordingly. The foramen ovale is a one-way valve that
flow through the pulmonary circulatory system (Raj & closes when the pressure in the left atrium exceeds the
Shimoda 2002). Pressures in the right heart and pul- pressure in the right atrium. Similarly, when aortic pres-
monary artery are greater than in the left heart and aorta, sure exceeds pulmonary arterial pressure, blood flow across
respectively, because of this high resistance. The majority the ductus arteriosus reverses. The ductus arteriosus
of oxygenated blood entering the right atrium is directly physically closes during the ensuing first days of life.
shunted across the foramen ovale to the left atrium, thence Physiological stimuli for closure include increased oxygen
to the left ventricle, carotid arteries, and brain. The tension and decreased levels of circulating prostaglandins.
remaining blood entering the right atrium flows via the Persistent flow of a small volume of blood through the
right ventricle and pulmonary artery to be shunted across ductus arteriosus can be auscultated as a systolic murmur
the ductus arteriosus to the descending aorta. The two for the first few days of life.
sides of the fetal heart act in parallel and the right ventricle To allow functional gas exchange, the neonatal lung
is dominant in both size and load. must remain inflated and the foal must establish a func-
Development of the fetal lung begins with the glandular tional residual capacity that provides a reservoir of air for
stage when branching and budding of the bronchial tree is gas exchange. Pulmonary surfactant is essential for this
occurring. Progression to the canalicular stage occurs at because it reduces the surface tension of the air–liquid
approximately 190–210 days in the equine fetus. During interface that lines the alveoli. Surfactant is a mixture
the canalicular stage, the development of acinar structures of dipalmitoyl phosphatidylcholine and proteins that is
consisting of respiratory bronchioles, alveolar ducts, and produced by the type II alveolar cells. Surfactant is pro-
rudimentary alveoli occurs. Surfactant-containing lamellar duced in the equine fetal lung by 100 days of gestation and
bodies are visible in type II pneumocytes and differentia- pulmonary development is considered complete by approxi-
tion from type II into type I cells occurs. Further differen- mately 300 days’ gestation; however, this maturation can
tiation of terminal airways and acinar tubules resulting vary depending on external factors (Arvidson et al 1975,
in a large expansion of the gas exchange surface area Pattle et al 1975) (see Prematurity in the following section).
occurs during this final phase of development. There is an Surfactant is continually being turned over within the lung
increase in the number of surfactant-containing lamellar and its concentration on the alveolar surface depends on
Stage 2 labor begins
Compression of thorax Separation of placenta
Fluid expelled from lungs Hypoxia/hypercapnia/acidosis
Birth (cold/bright environment) Loss of placental vasculature
First breath
Aveoli expand Surfactant released

Oxygen tension increases
Mechanical stretch of capillaries Surface tension decreases
Alveoli remain open
Pulmonary vasodilation
Pulmonary blood flow increases Systemic resistance increases
Pulmonary pressure decreases Systemic pressure increases
Pulmonary Artery Pressure < Aortic Pressure

Right Atrial Pressure < Left Atrial Pressure
Closure of Foramen Ovale Closure of Ductus Arteriosus
Fig. 45.7. Diagram of cardiopulmonary changes occurring at birth.

its rate of production and breakdown. Many factors that mature than a foal born prematurely in a mare with no
accompany neonatal lung disease facilitate the destruc- previous history of illness or problems. Chronic placentitis
tion of surfactant or reduce its production. Meconium is or other maternal factors may retard fetal development
toxic to the type II epithelial cells in which surfactant is resulting in a dysmature foal with inadequately developed
produced, whilst inflammatory mediators, reactive oxygen pulmonary anatomy and insufficient surfactant. Regardless
species, and meconium directly destroy or inactivate sur- of the history, any foal with a gestational age of less than
factant (Oelberg et al 1990, Moses et al 1991, Sun 1993b, 320 days, or physical characteristics of prematurity, should
Holopainen 1999, Dargaville & McDougall 2001, Tollofsrud be monitored carefully for signs of respiratory disease
et al 2003, Fuhrman 2004). and dysfunction.
Unlike the adult horse, in which a stiff chest wall pre- Without surfactant, alveoli tend to collapse at end
vents collapse of the lung in the face of airway obstruction, expiration. The highly compliant chest wall of the equine
the neonate has a compliant chest wall that cannot prevent neonate permits this by failing to prevent lung collapse to
lung collapse. For this reason, the neonate is prone to below normal functional residual capacity. Weak or
develop atelectasis when there is a lack of surfactant or hypoglycemic foals are unable to adequately re-expand
when an intrapulmonary airway becomes obstructed. The these alveoli, further exacerbating the problem.
compliant chest also tends to facilitate collapse of the Exposure to the postnatal environment before complete
dependent lung when foals are laterally recumbent for a lung maturation has several consequences. Inadequate gas
prolonged period of time. exchange surface area results in decreased oxygen uptake
Because the neonatal lung retains some of its fetal and hypoxemia. Insufficient quantity of surfactant results
characteristics, it is prone to some complications that in increased alveolar surface tension and alveolar collapse
do not occur in adults. The fetal pulmonary circulation at lower lung volumes. Incomplete maturation of type I
constricts in response to pulmonary hypoxia. When the alveolar cells exacerbates gas exchange difficulties resulting
fetus becomes hypoxic, constriction of the pulmonary in further hypoxemia. Repetitive collapse and re-expansion
circulation diverts blood away from the non-essential fetal of distal airways and alveoli results in shearing trauma,
lung to more vital organs via the ductus arteriosus. This disrupting the gas exchange membrane further and caus-
high reactivity of the fetal circulation to pulmonary ing protein and edema leakage into the alveolar spaces.
hypoxia is retained in the neonate. As a consequence, lung In addition to the direct consequences of being born
disease and its accompanying alveolar hypoxia can lead to before complete lung maturation, exposure of the prema-
constriction of pulmonary arteries and consequently ture lung to the postnatal environment can negatively
pulmonary hypertension. If pressure in the pulmonary affect further lung maturation and result in acute lung
artery rises high enough, blood flow can reverse through injury and ultimately chronic lung disease. Both hypoxia
the ductus arteriosus thus returning the foal to a fetal and hyperoxia have been shown to disrupt lung maturation
circulation. (Randell et al 1989, Thibeault et al 1990, Kotecha 2000),
probably as a result of the action of pro-inflammatory
cytokines and reactive oxygen species (Warner et al 1998).
Specific Respiratory Disorders of the Foal Antioxidant enzyme concentrations are deficient in the
Prematurity and primary surfactant deficiency developing lung at a time when production of reactive
oxygen species is accelerated (Kotecha 2000). Lipid peroxi-
Most equine clinicians define prematurity in foals as a dation appears to be the main oxidative stress on the
gestation of 320 days or less. However, gestational age neonatal lungs. Major causes of increased production of
alone does not appear to correlate completely with the risk reactive oxygen species include increased inspired oxy-
of prematurity or primary surfactant deficiency. Many foals gen concentrations, ischemia–reperfusion injury, activa-
considered premature by gestational duration have normal tion of the arachidonic acid cascade and inflammatory
respiratory function and physical characteristics, while cell activation.
some term foals have respiratory dysfunction and/or Many of the interventions performed to improve pul-
physical evidence of prematurity (short, silky hair coat, monary function can further exacerbate lung injury
domed head, floppy ears, tendon laxity, and small body and inflammation. Mechanical ventilation that is used to
size). As noted, pulmonary development is considered improve ventilation and gas exchange also results in
complete by approximately 300 days gestation, however, further injury as a result of regional overinflation (volu-
this maturation can vary depending on external factors trauma) and positive-pressure ventilation (barotrauma).
(Arvidson et al 1975, Pattle et al 1975). Chronic in utero The premature lung is particularly susceptible to the
stress hastens maturation of both the lung and hema- trauma associated with mechanical ventilation because
tological systems, although the underlying mechanism is surfactant may be deficient, the lung matrix is not fully
unclear. Consequently, a foal born prematurely to a mare developed, and residual fetal fluids may remain. Excess free
with a chronic illness may be developmentally more radical generation as a result of oxygen toxicity results in
further inflammation in the lung. Consequently, it is easy tion after successful transition. Causes of PPH can be
to see why neonatal respiratory distress syndrome develops divided into three categories.
and why it can be so difficult to treat. Reactive PPH is secondary to underlying pulmonary
parenchymal disease such as meconium aspiration or
Clinical signs infectious pneumonia. Reactive PPH is triggered by inflam-
At birth, premature foals may show few if any signs of matory and obstructive effects of pulmonary diseases,
respiratory disease. A slight increase or exaggeration in rib ventilation–perfusion mismatching, and hypoxemia. The
movement may be the first clinical sign of surfactant most common cause of reactive PPH in human neonates is
deficiency. Over time, an increasingly exaggerated respira- meconium aspiration (Findlay et al 1996). Depending on
tory effort, with abdominal breathing and paradoxical the severity of the underlying pathology, the resulting
chest wall movement, becomes apparent. In an effort to pulmonary hypertension and hypoxemia may result in
maintain functional residual capacity, the foal may have a reversion to fetal circulation with reopening of the foramen
prolonged expiratory phase and an end-expiratory grunt ovale and ductus arteriosus. A similar pathogenesis occurs
may be heard. The foal may be weak and have a poor with bacterial and viral pneumonias, whether the exposure
suckle as hypoxia progresses. The severity of clinical signs is hematogenous or by inhalation (Hintz et al 2000).
in the premature foal depends on many factors, including The second category of PPH is the result of structural or
the extent of prematurity and the severity of the hypoxia, functional cardiac or pulmonary abnormalities. Congenital
as well as complicating factors including bacterial sepsis, diaphragmatic hernia is associated with underdevelop-
and meconium or milk aspiration. Reversion to fetal ment of the pulmonary vascular bed, increased pulmonary
circulation and the development of pulmonary hyperten- vascular smooth muscle, and PPH in human infants.
sion can occur if hypoxia is severe. Congenital hypoplasia or dysplasia of the lungs can also
result in pulmonary hypertension; however, these con-
Treatment ditions have not been reported in the equine neonate.
Premature foals suspected of having surfactant deficiency Tetralogy of Fallot or pulmonary artery atresia can result
should be treated with surfactant replacement therapy. in pulmonary hypertension and is associated with a poor
Synthetic and animal-derived surfactant products are outcome (Vitums et al 1973, Reimer et al 1993, Meurs
available. Because of continued degradation of surfactant et al 1997). Cardiac-disease-associated PPH will not be
by inflammatory enzymes and inactivation by surfactant discussed in this chapter.
inhibitors, re-treatment may be required to maintain res- PPH is caused by structural or biochemical derange-
piratory function (see Surfactant therapy p. 651). ments of pulmonary circulation and pulmonary vasomotor
In addition to surfactant replacement therapy, affected systems. At birth, increased oxygen concentration stimu-
foals require oxygen supplementation and mechanical lates synthesis of vasodilators including nitric oxide,
ventilation (see Intensive management of the foal respira- prostacyclin, and prostaglandin E2. The mechanical effects
tory system p. 649). Broad-spectrum antimicrobial therapy of lung expansion coupled with the increase in local
is recommended because of the increased risk of complicat- vasodilators results in pulmonary vascular dilation. Vaso-
ing pneumonia and sepsis in these neonates. Foals should dilator effects are mediated by increased intracellular
be kept in sternal recumbency or standing as much as production of cyclic GMP (Raj & Shimoda 2002). Patients
• •
possible to improve ventilation–perfusion (V/Q ) matching. with PPH have a reduced production or decreased response
The prognosis for foals with prematurity and surfactant to these vasodilators, particularly if hypoxemia persists
deficiency depends on the degree of prematurity and (Fike & Kaplowitz 1996, Fike et al 1998, Berkenbosch et al
potential complications (bacterial pneumonia, systemic 2000). In addition, chronic in utero hypoxemia can result
inflammatory response syndrome). In general, foals born in pulmonary vascular remodeling and increased amounts
at a gestational length of ≤ 300 days have a relatively of arteriolar smooth muscle making resolution of PPH
poor prognosis. For foals born after 300 days’ gestation, after birth difficult (Rabinovitch et al 1979, Steudel et al
the prognosis depends on additional factors including 1998). In humans, increased pulmonary vascular resist-
prepartum illness in the mare, speed of recognition and ance may develop in fetuses from mothers treated with
institution of treatment, and development of secondary non-steroidal anti-inflammatory drugs such as indomethacin,
complications. but this has not been described in the horse (Tyler et al
1975, Leffler & Cassin 1978).
Persistent pulmonary hypertension
Persistent pulmonary hypertension (PPH), also referred Definitive diagnosis of PPH requires documentation of
to as reversion to fetal circulation, occurs when the elevated pulmonary artery pressure. This requires passing
cardiopulmonary transition from fetus to foal fails or a catheter via the jugular vein through the right heart
when disturbance causes reversion back to fetal func- into the pulmonary artery to measure pressures. This is
rarely performed in equine neonatology and a tentative Although there are currently no published reports of
diagnosis is generally made using arterial blood gas the efficacy of inhaled NO in the management of PPH in
measurements, response to oxygen supplementation as well the equine neonate, inhaled NO was effective in an
as radiographic and ultrasonographic findings. A diagnosis experimental model of PPH in neonatal foals (Lester et al
of PPH should be suspected in any foal with severe 1999). Inhaled NO attenuated the pulmonary hyper-
hypoxemia that is poorly responsive to supplemental tension induced by both hypoxia and the thromboxane
oxygen therapy. In cases of PPH, hypoxemia is severe and mimetic, U46619. The response was dose-dependent
non-responsive to oxygen therapy as a result of the right to between 20 and 160 ppm; however, the equipment used
left shunting of a large percentage of the cardiac output in to measure NO flow rates was imprecise. Whether
the lungs, and through the foramen ovale and ductus doses of this magnitude are truly needed to effec-
arteriosus. Arterial oxygen content remains low because tively resolve PPH in foals remains to be determined
the blood is never exposed to the oxygen-rich alveolar as there are anecdotal reports of successful resolution of
gases. In contrast, hypoxemia because of ventilation– PPH in equine neonates using concentrations as low
perfusion mismatching (as may be seen with aspiration as 5 ppm (Wilkins 2003). In human infants, concentra-
pneumonia) without pulmonary hypertension is generally tions of > 22 ppm are associated with higher methemo-
responsive to oxygen supplementation though the response globin concentrations without any clear benefit on sur-
depends on the severity of the underlying disease. vival or length of hospitalization when compared to lower
In primary PPH, thoracic radiographs may show dosage regimens (Guthrie et al 2004). As many as 30% of
evidence of decreased pulmonary vascular markings human infants fail to respond to inhaled NO therapy and
(Cottrill et al 1987). Physical examination findings of a non-responders commonly have underlying pulmonary
persistent cardiac murmur, coupled with echocardio- parenchymal disease (Goldman et al 1996). Rebound PPH
graphic findings of normal heart structure with right to left has been reported during attempts to wean patients from
shunting through the foramen ovale and ductus arteriosus, inhaled NO therapy (Davidson et al 1999).
are further evidence to support the presence of PPH Magnesium sulfate infusions decrease pulmonary hyper-
(Southwood et al 1996). tension in human neonates. Because magnesium is
relatively inexpensive and easily obtained, it is particularly
useful in developing countries (and possibly veterinary
Treatment clinics) where more expensive therapies may not be readily
Treatment of PPH should include treatment of any under- available or affordable. In a clinical trial in 12 human
lying disease process as well as the pulmonary hyperten- infants with severe PPH, infusions of magnesium sulfate
sion. Hypoxemia and acidosis trigger pulmonary vasocon- resulted in improved oxygenation and improved DA–aO2
striction; consequently, correcting these abnormalities is (Chandran et al 2004). In this report, magnesium sulfate
vital to the resolution of PPH. Nasal oxygen insufflation was infused continuously to achieve serum levels of
should be instituted immediately upon hospitalization. If 3.5–5.5 mmol/liter (8.5–13.4 mg/dl). Dopamine infusions
nasal insufflation fails to significantly improve hypoxemia, were necessary to maintain systemic vascular pressures
mechanical ventilation with supplemental oxygen is indi- during treatment. Magnesium sulfate given by bolus
cated. In acute or mild cases, correction of hypoxemia and injection also causes a significant decrease in pulmonary
acidosis may be enough to trigger pulmonary vasodilata- artery pressure (Haas et al 2002). While magnesium
tion and resolution of pulmonary hypertension. sulfate therapy may be beneficial in PPH, hypermagne-
In refractory cases, inhaled nitric oxide (NO) is recom- semia can result in central nervous system depression
mended to induce relaxation of the pulmonary vascula- and hypoventilation requiring mechanical ventilation to
ture. Inhaled NO disperses across the alveolar capillary maintain adequate gas exchange.
membrane causing increased cGMP in vascular smooth Several phosphodiesterase inhibitors effectively resolve
muscle, so inducing vasodilation. NO is rapidly degraded; pulmonary hypertension. Sildenafil is a specific inhibitor
consequently the effects of inhaled NO are confined to the of phosphodiesterase-5, an enzyme that occurs in high
local pulmonary circulation without affecting systemic concentrations in the smooth muscle cells of the pul-
vascular resistance. Inhaled NO has been shown to improve monary vasculature. Inhibition of phosphodiesterase-5
oxygenation, decrease the need for ventilatory support leads to local increase in cGMP that relaxes pulmonary
and extracorporeal membrane oxygenation and improve vascular smooth muscle (Rabe et al 1993). In both
survival in human infants with PPH (Smyth 2000, Finer & human and animal experimental models, sildenafil dose-
Barrington 2001, Goh et al 2001, Sadiq et al 2003). dependently attenuates PPH, in some cases more effec-
Methemoglobin levels should be monitored during NO tively than inhaled NO (Weimann et al 2000, Ichinose et al
treatment, because NO combines with oxyhemoglobin to 2001, Zhao et al 2001, Lepore et al 2002, Keller et al
produce methemoglobin. 2004). It has been used successfully to ameliorate rebound
PPH during weaning from inhaled NO (Lepore et al 2002, leaks, pneumothorax or interstitial emphysema. Meconium
Keller et al 2004). While case reports of successful is approximately 75% water with the solid fraction con-
resolution of PPH using sildenafil exist, there are currently taining lipids (including free fatty acids, triglycerides, and
no published randomized clinical trials evaluating the cholesterol) and water-soluble components (including
efficacy of sildenafil in treatment of neonatal PPH (Atz & bilirubin, bile acids, and fiber). Bile salts are directly toxic to
Wessel 1999, Michelakis et al 2002, Watanabe et al 2002, pneumocytes resulting in epithelial cell injury, apoptosis,
Carroll & Dhillon 2003, Mehta 2003). Although used and inflammation (Oelberg et al 1990). Both the water-
acutely sildenafil has minimal effects on systemic arterial soluble and lipid-soluble fractions of meconium induce
pressures (Weimann et al 2000), but chronic therapy can inflammatory cell influx, cytokine production and enzyme
be associated with systemic hypotension (Ghofrani et al activation (de Beufort et al 1998, Holopainen et al 1999,
2003). In a porcine meconium aspiration model of pul- Castellheim et al 2004). The inflammatory response and
monary hypertension, sildenafil, in combination with damage to the respiratory membrane results in leakage of
inhaled NO, lowered systemic blood pressure and systemic proteinaceous edema fluid and alveolar flooding. Alveolar
resistance, resulting in profound arterial hypoxemia atelectasis, edema accumulation, and airway plugging
despite increases in inspired oxygen (Shekerdemian exacerbate ventilation–perfusion mismatching, hypoxemia,
et al 2004). More information is needed regarding the and hypercapnia. In severe cases, profound hypoxemia and
efficacy and potential contraindications of sildenafil use in acidosis result in pulmonary vascular constriction, pul-
neonates, particularly those with underlying parenchymal monary hypertension, right to left shunting, and further
disease or sepsis. deterioration of ventilation–perfusion mismatching. Sur-
Surfactant supplementation improves hypoxemia and factant deficiency results from increased degradation
lung function by maintaining alveolar volumes at lower of surfactant by enzymes and inflammatory mediators,
inspiratory pressures and aids in the resolution of PPH decreased production as the result of toxic effects on type II
(see Surfactant therapy, p. 651, for further discussion). pneumocytes, and inhibition of surfactant function by
The prognosis for foals with PPH is fair to good if the surfactant inhibitors present in meconium (Oelberg et al
condition is recognized early. If recognition and treatment 1990, Moses et al 1991, Sun 1993b, Holopainen et al
are not instituted quickly, subsequent inflammatory injury 1999, Dargaville & McDougall 2001, Tollofsrud et al 2003,
and bacterial invasion may result in a poorer prognosis. Fuhrman 2004). These inhibitors affect the ability of sur-
factant to form a monolayer and may inhibit the phos-
pholipid enrichment process that is thought to stabilize the
Meconium aspiration monolayer during compression (Holm & Notter 1999).
Meconium is composed of the remains of glandular

secretions, swallowed amniotic fluid, and cellular debris. It Clinical signs
is moved along the gastrointestinal tract and stored in the Meconium aspiration syndrome is characterized by evi-
distal colon and rectum. Meconium is a dark brown to dence of airway obstruction, alveolar atelectasis, pul-
black pellet or paste and is usually expelled shortly after monary inflammation, and respiratory failure. Meconium
birth. In utero, hypoxemic fetal stress can result in fetal aspiration should be suspected in any difficult or delayed
peristalsis and early expulsion of meconium into the foaling and in foals born with meconium present in
amniotic fluid. Asphyxia triggers fetal gasping, resulting the amniotic fluid or with evidence of meconium stain-
in meconium aspiration into the lungs. The pulmonary ing (yellow-brown discoloration) of the coat. However,
effects of meconium aspiration are induced by direct toxic although meconium-stained amniotic fluid is seen in
injury to cells, mechanical obstruction as the result 10–15% of human births, only approximately 5% of these
of accumulation of debris and secretions, inflammatory infants develop meconium aspiration syndrome. The find-
cellular influx and activation, and reduced activity of ing of meconium in fluid suctioned from the trachea is
surfactant. further confirmation of aspiration and potential respira-
Depending on the severity of aspiration, pathophysio- tory compromise.
logical effects vary from mild ventilation–perfusion mis-
matching, hypoxemia, and airway obstruction to res-
piratory failure and pulmonary hypertension. Because Treatment
meconium is a thick viscous substance it can completely Foals suspected of having meconium aspiration should
obstruct the airway and cause alveolar collapse or cause receive supplemental oxygen and have attempts made to
intermittent obstruction with air trapping and pulmonary remove meconium by suction as soon as possible. Further
overinflation. The abnormally high lung volumes that treatment will be dictated by the severity of clinical signs.
develop with intermittent air trapping can result in air Mild cases of meconium aspiration syndrome are treated
with supportive care and oxygen therapy. Ventilatory white muscle disease, peripartum asphyxia syndrome,
support is instituted in individuals with evidence of septicemia, or during bottle or syringe feeding.
respiratory failure but positive pressure ventilation can Foals are at higher risk for bacteremia and sepsis than
result in further air trapping (volutrauma) and baro- adults. Foals are born with a functional but naive immune
trauma. In severe cases of meconium aspiration syndrome system. The neonatal foal’s neutrophils are deficient in
the use of extracorporeal membrane oxygenation has phagocytic ability and hydrogen peroxide release making
improved survival in human infants (Hansell 2003). the foals more susceptible to early infection (Demmers et al
Surfactant therapy improves respiratory function and 2001, McTaggart et al 2001). While functional T cells are
decreases the duration of mechanical ventilation, oxygen present at birth, in vitro tests suggest that cell-mediated
therapy and hospitalization (Sun 1993a,b, Findlay et al immunity is still deficient. Foals are capable of producing
1996, Cochrane et al 1998, Lotze et al 1998). Depending antibody by 200 days’ gestation, but B-cell numbers may
on the severity of the ongoing inflammatory response, as not reach adult levels until several weeks of age.
well as the volume of inhaled meconium, multiple doses Because of the diffuse epitheliochorial placentation of
of surfactant may be required to maintain respiratory the mare, foals are born without protective passive
function because of ongoing degradation and continued immunity and must ingest colostrum during the immediate
inhibition. Recent data suggest that the addition of post-foaling period to receive passive antibody from the
polymers such as dextrans to surfactant solutions may mare. Colostrum ingestion not only results in antibody
reduce surfactant inhibition in cases of meconium aspira- absorption, but also provides local non-specific immunity
tion syndrome (Tashiro & Robertson 2000). in the gastrointestinal tract. If a foal does not ingest
The use of serial, dilute surfactant lavages to remove colostrum during the immediate post-foaling period, the
residual meconium has been reported to improve outcome gastrointestinal tract is open to invasion by pathogens.
in human infants with meconium aspiration syndrome; During udder seeking, the foal may suckle dirty environ-
however, a significant portion of infants had to have the mental surfaces or the contaminated perineal area of the
procedure halted after developing severe hypoxemia during mare resulting in ingestion of potentially pathogenic
lavage (Wiswell et al 2002). While the idea of removing bacteria. If ingestion of pathogens occurs before ingestion
residual particulate meconium is attractive, the ensuing of colostrum, invasion is enhanced and bacteremia is likely.
inflammatory response appears to be the major factor in The suckle reflex is one of the first behaviors to deteriorate
the development of acute injury in the lungs. Thus the with illness; consequently the septicemic foal is at greater
cost–benefit of these lavages presently is unclear. Smaller risk for aspiration of milk when attempting to nurse.
volume lavage may offer similar benefits with less potential Aspiration of milk can also occur when well-intentioned
for complications (Cochrane et al 1998). owners attempt to bottle-feed an inappetant foal, result-
Inhaled NO is used in patients with clinical or cardio- ing in further contamination of the lower respiratory
vascular evidence of pulmonary hypertension. Inhaled NO tract. Meconium aspiration during a difficult or delayed
has been less successful in resolving hypertension in parturition can also result in pneumonia and bacterial
infants with meconium aspiration syndrome than in those contamination of the lungs.
with primary PPH (The Neonatal Inhaled Nitric Oxide
Study Group 1997). This may be the result of the inability
of NO to diffuse down meconium-plugged airways. The use Clinical signs
of inhaled NO is discussed in more detail under PPH. Because the lungs are the most commonly affected organ
The prognosis for foals with meconium aspiration depends system in septicemic foals, routine evaluation including
on the severity of aspiration and development of secondary thoracic radiography, arterial blood gas, and thoracic
bacterial infection. Uncomplicated cases of mild aspiration ultrasound should be performed in any foal suspected
may be unrecognized. In more severe cases the prognosis of being septic. An elevated respiratory rate, presence of
depends on early recognition and aggressive treatment. abnormal lung sounds on auscultation, and evidence
of alveolar disease on radiographic or ultrasonographic
examinations are strong evidence of pneumonia. In sick or
Bacterial pneumonia weak neonates with a poor suckle reflex, the likelihood of
aspiration can be detected by auscultating over the trachea
Bacterial infection is the most common causes of pneu- as the foal nurses. As discussed previously, the finding of
monia in the equine neonate, with bacteremia and aspira- normal lung sounds on auscultation of the thorax should
tion pneumonia the most common routes of exposure. The not be overly interpreted because many foals with pneu-
lungs are the most frequently affected organs in cases of monia have few if any abnormal adventitial sounds.
neonatal septicemia. Aspiration can result from congenital Radiographs are useful to assess the severity and type of
anomalies such as a cleft palate, dysphagia secondary to pneumonia. Foals with aspiration pneumonia typically
have ventral consolidation whereas the distribution of susceptibility of foals to their toxic effects, including
lung disease is often more diffuse in septicemic foals. The gastrointestinal ulceration and nephrotoxicity. Because
latter is the result of the hematogenous origin of the the neonatal chest wall is more compliant than the adult,
bacteria. Ultrasound evaluation is particularly sensitive in the dependent lung frequently becomes atelectatic, worsen-
detecting abnormalities in acute pneumonia when clinical ing ventilation–perfusion mismatching. Consequently, foals
and radiographic abnormalities may be minimal. Because should be turned frequently or kept in sternal recumbency
of the reflection of the majority of ultrasound waves at an whenever possible. Oxygen supplementation should be
air–tissue interface, ultrasound is not accurate in deter- provided in any hypoxemic foal (see Chapter 14) or foal
mining the severity of deeper pathology. For this reason, it exhibiting respiratory distress or cyanosis.
is recommended that both thoracic radiography and ultra- Because of the potential for false-negative culture
sound be performed to completely evaluate the pulmonary results, the response to treatment should be monitored
parenchyma. closely and re-evaluation performed if a patient fails to
Bacterial infection is the most common cause of lower show improvement within 24–48 h. Clinical response
respiratory disease and for this reason antimicrobial should include a resolution of fever, improved attitude
treatment should be instituted in any foal presented with and appetite, decrease in respiratory rate or effort, and
lower respiratory disease until bacterial involvement is improved arterial oxygenation. Improvement in lung
disproved. Definitive diagnosis of bacterial pneumonia is sounds is not always useful in assessing progress as these
made by culture and cytology of transtracheal aspirates or frequently worsen during disease resolution. This is
bronchoalveolar lavage fluid. If respiratory samples are because air begins to flow into regions of diseased lung that
not available for culture, blood culture results (in com- previously received no airflow. Normalization of white
bination with clinical evidence of pneumonia) can be used blood cell parameters and serum fibrinogen measurements
as presumptive evidence of bacterial pneumonia. While are also useful in assessing the response to treatment.
helpful, blood culture results should be interpreted The prognosis for foals with bacterial pneumonia
cautiously. In one study of neonatal septicemia, approxi- varies depending on many factors including the route of
mately 20% of foals that were negative on blood culture infection, underlying disorders, and other sites of infection.
had bacteria cultured from tissues at the time of post- In general the prognosis is considered fair to good in
mortem examination (Wilson & Madigan 1989). In addi- uncomplicated cases.
tion, blood cultures frequently do not detect multiple
bacterial pathogens. The organisms most commonly missed
on blood cultures are Gram-negative aerobes. Approxi- Viral pneumonia
mately 50% of bacterial pneumonias have mixed infections
including both Gram-negative and Gram-positive pathogens In young foals, viral pneumonia is a relatively rare
(Wilson & Madigan 1989). Common pathogens in septicemia occurrence but is almost universally fatal. The vast
and bacterial pneumonia include Escherichia coli, Klebsiella majority of viral respiratory infections in horses result in
pneumoniae, Actinobacillus spp., Streptococcus spp., Staphylo- upper respiratory tract signs rather than pneumonia,
coccus spp., Enterobacter spp., Serratia spp., Proteus spp., and, particularly in naive weanlings and young adults. Viral
less commonly, anaerobes including Clostridium spp., pathogens associated with neonatal pneumonia include
Bacteroides spp., and Fusobacterium spp. (Wilson & Madigan equine herpes virus-1 (EHV-1), EHV-2, and less commonly
1989, Brewer & Koterba 1990, Marsh & Palmer 2001). EHV-4, equine influenza virus (EIV), equine adenovirus,
and equine arteritis virus (EAV).
EHV-1 infection in horses can result in multiple
Treatment syndromes including late-term abortions, weak or stillborn
The cornerstone for treatment of bacterial pneumonia is term foals, upper respiratory infection in weanlings and
broad-spectrum antimicrobial therapy that can be adjusted adult horses and neurological disease (McCartan et al
once culture and sensitivity results are available. In weak 1995). In neonatal foals, EHV-1 is the most common viral
foals that are unable or unwilling to nurse, supplemental pathogen and almost without exception results in fatal
nutrition should be provided by nasogastric intubation or, pneumonia and sepsis. Clinical signs in neonates infected
if unable to utilize the gastrointestinal tract, via par- with EHV-1 include icterus, petechial hemorrhages, and
enteral nutrition. Because of their high metabolic rate respiratory distress (Perkins et al 1999). The finding of
and minimal body fat, nutritional support needs to be an dilated retinal vessels with retinal hemorrhages has
integral part of the treatment of foals. Non-steroidal anti- been reported to be a common clinical finding in affected
inflammatory drugs are useful in controlling inflam- foals. Complete blood counts frequently reveal a toxic,
mation and minimizing systemic signs (fever, malaise) neutropenic, lymphopenic leukopenia; however, these
but should be used cautiously because of the increased findings are also common in neonatal septicemia making
them unreliable as diagnostic criteria without additional Adenoviral pneumonia has been recognized in immuno-
information or a history of a herd outbreak. Post-mortem deficient foals including Arabian foals with combined
findings include severe diffuse interstitial pneumonia, immunodeficiency (CID) (Dutta 1975, Whitlock & Shively
hepatitis with viral inclusion bodies and bone marrow 1975, Henry 1976, Thompson et al 1976, Perryman et al
depletion. The virus is likely spread from mare and foal 1978, Webb & Walker 1981). Equine adenovirus was
reservoirs to other foals and weanlings; consequently the isolated from 43 of 66 CID-affected foals with evidence of
separation of pregnant mares from other horses and foals pneumonia (Perryman et al 1978). Only one of these foals
is an important mechanism for controlling spread and infec- had uncomplicated adenoviral pneumonia, the majority
tion of mares in late-term gestation (Gilkerson et al 1999). of the remainder having concomitant bacterial or fungal
EHV-2 also has been reported as a cause of respiratory infections. Affected foals received hyperimmunized plasma
disease and pneumonia in young foals. EHV-2 is ubiqui- on a weekly basis in an attempt to protect against adeno-
tous in the equine population and is rarely the cause viral pneumonia. In immunocompetent foals, adenoviral
of significant clinical disease in adult animals (Borchers infection rarely results in significant illness.
et al 1997, Kershaw et al 2001). In one abbatoir study, EIV infection has been reported in association with
EHV-2 was isolated from tissues in 39 of 40 horses severe, acute, fatal interstitial pneumonia in two neonatal
(Edington et al 1994). The majority of infected foals exhibit foals (Britton & Robinson 2002, Peek et al 2004). One case
mild upper respiratory signs but pneumonia, immuno- was associated with an upper respiratory tract disease
suppression, and death are reported. Epidemiological outbreak in horses housed in close proximity (the neonatal
studies suggest that the majority of foals become exposed intensive care unit) to the affected foal. EIV was isolated
to EHV-2 within the first few months of life and subse- from both cases. Post-mortem findings were consistent
quently shed the virus for several months (Fu et al 1986, with a viral pneumonia including a diffuse bronchiolitis,
Murray et al 1996). alveolar necrosis, hemorrhage, and fibrin exudation.
EHV-4 is primarily associated with respiratory disease Immunohistochemical staining for EIV was positive on
outbreaks in young adult horses, particularly those housed lung tissue samples.
in large, transient groups. Exposure to EHV-4 appears to
occur early in life with the vast majority of foals becoming
seropositive by 2 months of age (Gilkerson et al 1991, Acute interstitial pneumonias
Foote et al 2004). Clinical illness is principally an upper
respiratory tract disease with high morbidity in naive Acute interstitial pneumonia is a relatively infrequent
groups and low mortality. cause of acute, severe, respiratory distress and failure in
EAV is a non-arthropod-borne RNA virus in the family foals from several days to several months of age. The
Arteritiviridae. Infection of adult individuals with EAV underlying etiology is likely multifactorial with heat stress
typically results in fever, leukopenia, limb and ventral a common predisposing factor. Prognosis is poor with the
edema, conjunctivitis, epiphora, and rhinitis (Del Piero et al majority of foals succumbing to respiratory failure.
1997). Infected foals may present with acute onset of Clinical signs include an acute onset of tachypnea,
respiratory distress and sudden death (Szeredi et al 2003). dyspnea, and respiratory distress. Affected foals are fre-
Epidemic abortions have also been reported. Affected quently cyanotic and the onset of signs is often rapid and
stallions can become long-term carriers and shed virus in severe. In one retrospective study of 23 cases, three foals
their semen, thus acting as a viral reservoir in the equine were found dead on the farm, five died shortly after
population (Gilbert et al 1997). Affected foals present identification or during transit and two died shortly after
with severe respiratory distress of acute onset. Radio- arrival at the clinic (Lakritz et al 1993). A 39% (nine of
graphic findings are consistent with an interstitial pneu- 23) survival rate was reported.
monia. Cytological abnormalities of a bronchoalveolar Affected individuals have an elevated rectal temperature,
lavage sample in an affected foal included mucus, fibrin, severe respiratory distress, are often cyanotic, depressed,
macrophages, epithelial necrosis, and squamous meta- and unwilling to eat. Many individuals have a marked
plasia (Wilkins et al 1995). The disease is almost uniformly abdominal component to their expiratory effort. Ausculta-
fatal in neonatal foals. Post-mortem findings include tion reveals increased bronchial sounds (hollow tubular
interstitial pneumonia with edema and hemorrhage characteristics) over the larger airways with diminished
and hyaline membranes in the alveoli. The inflamma- sounds in the periphery, supporting decreased ventilation of
tory infiltrate is predominantly macrophages with rare small airways and terminal alveoli. In individuals that
neutrophils. Vascular changes include vasculitis, swollen survive, as the lung disease resolves adventitial sounds
endothelial cells, and fibrinoid necrosis. Viral agents in the (crackles and polyphonic wheezes) become increasingly
endothelial cells and macrophages can be detected using audible in the peripheral lung fields likely as a result of
immunohistochemical staining for EAV. improved ventilation of peripheral airways.
Clinicopathologic findings include hyperfibrinogenemia the thorax is opened. Histopathological examination

and a neutrophilic leukocytosis. All but one individual was reveals various levels of necrosis of epithelial cells of the
in respiratory failure at the time of examination; arterial distal airways and alveoli. Proteinaceous edema, fibrin, and
blood gas analysis consistently reveals severe hypoxia cellular debris are found within the distal airways and
and hypercapnia with acidosis less commonly reported. alveoli. Inflammatory cellular infiltrate is generally mild
Affected foals are poorly responsive to intranasal oxygen compared to bacterial pneumonia and principally consists
therapy suggesting left to right shunting and/or severe of lymphocytes, plasma cells, and alveolar macrophages.
ventilation–perfusion mismatching. Type II pneumocyte proliferation is a common finding.
The predominant radiographic lesions in foals with
interstitial pneumonia are a diffuse interstitial or broncho-
interstitial infiltrate. Lesions range from a diffuse intersti- Pneumocystis pneumonia
tial infiltrate to a heavier, reticulonodular, bronchointer-
stitial pattern and coalescing alveolar infiltrates. In one Pneumocystis pneumonia is an infrequent cause of
retrospective study, multifocal alveolar infiltrates and respiratory disease in foals but should be suspected in
pulmonary abscessation were also reported in 25% of cases any foal with non-responsive pneumonia, foals that are
examined radiographically (Lakritz et al 1993). suspected of being immunocompromised, and foals with
In the majority of cases the underlying etiology is radiographic findings of interstitial or reticulonodular
unknown. Many agents have been proposed including patterns in the lung fields. The finding of pneumocystis
bacterial, viral, fungal, and toxic agents (Buergelt et al pneumonia is associated with a poor prognosis for survival.
1986, Prescott et al 1991, Ainsworth et al 1993, Lakritz Pneumocystis carinii is a fungal pathogen of the respiratory
et al 1993, Perron Lepage & Suter 1999, Peek et al 2004). tract of mammalian species. In humans, the vast majority
It is unlikely that interstitial pneumonia in foals is the of cases of pneumocystis pneumonia occur in immuno-
result of one etiological agent; rather it is more likely to be compromised individuals (Al Soub et al 2004). In domestic
the result of a common response of the lung to injury. animals pneumocystis pneumonia has been reported in
Multiple bacterial pathogens have been isolated from debilitated or immunocompromised dogs, foals, pigs, and
transtracheal aspirates and post-mortem tissue specimens goats (McConnell et al 1971, Farrow et al 1972, Seibold
including Rhodococcus equi, E. coli, Streptococcus spp., Actino- & Munnell 1977, Furuta et al 1994, Cabanes et al 2000).
bacillus equuli, Klebsiella pneumoniae, Bordetella bronchiseptica, The complete life cycle of P. carinii is unknown. There are
and Pseudomonas spp. (Prescott et al 1991, Ainsworth et al currently three identified forms of the organism, all of
1993, Lakritz et al 1993, Ewing et al 1994, Perron Lepage which exist within the mammalian lung: a trophic form
& Suter 1999, Nout et al 2002, Peek et al 2004). that is the primary proliferative stage, a precyst, and a
Hyperthermia has been proposed to be the common mature cystic form (Cushion 2004). An environmental
factor triggering the onset of severe respiratory dis- reservoir or infectious form has yet to be identified.
tress. The average environmental temperature was in While the exact mode and source of transmission
excess of 32°C (90°F) in one case series and all foals were are unclear, asymptomatic carriers are found in both
hyperthermic on admission (Lakritz et al 1993). Penta- humans and rats and airborne transmission from asympto-
chlorophenol was found in one farm with two affected foals matic carriers to immunosuppressed individuals has
(Lakritz et al 1993). Pentachlorophenol uncouples oxida- been reported (Hong et al 1992, Helweg-Larsen et al 1998,
tive phosphorylation and may have played a role in hyper- 2002, Dumoulin et al 2000). Subsequent immunosup-
thermia and heat stress resulting in acute respiratory pression of carrier rats resulted in clinical pneumocystis
distress. In other reports, viral and fungal agents have been pneumonia. While transmission between individuals in
isolated from affected foals. Therapy with erythromycin has close contact has been reported, it does not seem to be the
been associated with hyperthermia and was a historical primary route of transmission (Helweg-Larsen et al 1998,
finding in some reported cases (Ainsworth et al 1993, Beard et al 2000, Manoloff et al 2003). Early neonatal
Lakritz et al 1993). exposure may play a role in infection and transmission
Treatment of acute interstitial pneumonia should (Pifer et al 1978, Miller et al 2002). In a retrospective
include broad-spectrum antibiotics, anti-inflammatory analysis of respiratory samples from 367 people with
drugs, and oxygen therapy. Bronchodilators and non- bacterial pneumonia, the presence of pneumocystis
steroidal anti-inflammatories have also been utilized with DNA was associated with old age, glucocorticoid therapy,
mixed results. In one case series, clinical improvement and and concurrent disease (Helweg-Larsen et al 2002).
survival appeared to be associated with glucocorticoid Human and animal models suggest that low numbers
therapy (Lakritz et al 1993). of pneumocystis organisms are necessary for transmis-
Post-mortem examination reveals lungs that are sion and the organism can survive for a period of time
diffusely red, wet, and firm and that fail to collapse when in a healthy individual without causing clinical illness
(Dumoulin et al 2000, Gigliotti et al 2003). Whether 1993, Ewing et al 1994, Peters et al 1994, Perron Lepage
immunocompromise of a latently infected individual, or a & Suter 1999, Jensen et al 2001).
new exposure and infection results in clinical disease is Folic acid synthesis inhibitors are the treatment
unclear (Hughes 1998). of choice for pneumocystis pneumonia. Trimethoprim–
Pneumocystis pneumonia has been reported in foals sulfamethoxazole (TMS-SMZ) has been used in all reported
with the vast majority of cases occurring in immuno- cases that have a successful outcome (Ewing et al 1994,
compromised individuals (Shively et al 1973, Perryman Flaminio et al 1998, Clark-Price et al 2004). In one
et al 1978, Whitwell 1992, Ainsworth et al 1993, Ewing case, after the foal developed salmonellosis, treatment
et al 1994, Tanaka et al 1994, Perron Lepage & Suter was switched to dapsone, a sulfone antimicrobial used
1999, Clark-Price et al 2004). Pneumocystis carinii is a for treatment of pneumocystis pneumonia in humans
common cause of pneumonia and mortality in Arabian (Clark-Price et al 2004). Interferon-α and Propionibacterium
foals with CID (Perryman et al 1978). In a three-case acnes were used in two cases for non-specific immuno-
series, two foals had a history of receiving glucocorticoids stimulation. The prognosis for affected foals is guarded to
before the onset of respiratory disease. Hypogamma- poor with the majority of foals dying or being euthanized
globulinemia has been reported in association with because of the poor response and severe hypoxemia.
pneumocystis pneumonia (Whitwell 1992, Flaminio et al At post-mortem the lungs are often enlarged, fail to
1998). The significance of this finding is difficult to deter- collapse and are firm to palpation. A proliferative, inter-
mine given the high prevalence of hypogammaglobu- stitial pneumonia with foamy macrophages and occasional
linemia in 2- to 3-month-old foals. In one case series foals multinucleated giant cells with intracellular organisms is
also had Rhodococcus equi pneumonia that may have present. Type II pneumocyte hyperplasia, edema, and
made them more susceptible to subsequent infection proteinaceous fibrinoid material is frequently found within
with pneumocystis. Rhodococcus equi inhibits macrophage the alveoli. Depending on the chronicity of illness, inter-
phagosome–lysosome fusion and may have affected cellular stitial fibrosis may be present.
immunity to P. carinii. A transient T-cell deficiency was
reported in two foals; both foals responded to treatment Idiopathic transient tachypnea
for pneumocystis pneumonia and their T-cell function
normalized (Flaminio et al 1998, Clark-Price et al 2004). Idiopathic transient tachypnea and hyperthermia has been
Whether this deficiency in functional T cells was the cause observed in neonatal foals most commonly in draft,
or the result of pneumocystis infection is unclear. Arabian and thoroughbred breeds. The syndrome is most
Foals with pneumocystis pneumonia typically present commonly seen in warm and humid climates. Affected
with an acute onset of severe respiratory distress and foals develop an elevated respiratory rate and body tem-
cyanosis. Many cases have a previous history of milder, perature. Clinical signs typically develop in the first few
chronic bacterial pneumonia that subsequently worsened days of life and may persist for several weeks. Treatment
despite antimicrobial treatment. Radiographic findings includes body clipping, environmental temperature control,
vary; the majority of cases have evidence of a diffuse, and cool water or alcohol baths. Treatment with broad-
miliary, reticulonodular or diffuse, bronchointerstitial spectrum antimicrobials is generally recommended until
pattern on thoracic radiographs. Complete blood counts underlying bacterial pneumonia can be ruled out. The
and serum chemistry findings are relatively non-specific. presence of rib fractures should be determined as they
Arterial blood gas results vary with most cases having can result in an elevated respiratory rate without overt
evidence of hypoxemia. Cough, mucopurulent nasal dis- evidence of pulmonary disease.
charge and lymphadenopathy are reported in approxi-
mately half of cases. Many foals with pneumocystis pneu- Neonatal acute respiratory distress syndrome
monia have evidence of mixed bacterial infections in
their lungs. While the insult leading to neonatal acute respiratory
Because pneumocystis proliferates in the alveolus, cyto- distress syndrome (ARDS) may be different in neonates
logical examination of bronchoalveolar lavage samples and adults, the definition remains the same. The syndrome
appears to be a more sensitive diagnostic test than exami- of ARDS is the end result of an inflammatory process
nation of transtracheal wash fluid (Golden 1986, Perron that results in destruction of the alveolar–capillary unit.
Lepage & Suter 1999, Clark-Price et al 2004). Silver stains Diagnosis of ARDS includes a history of sudden onset
are helpful in evaluating histopathological specimens for of respiratory distress, radiographic or ultrasonographic
the presence of pneumocystis organisms. Immunohisto- findings of diffuse bilateral pulmonary infiltrates, and
chemistry and DNA amplification have also been used to respiratory failure (severe unresponsive hypoxemia and
diagnose pneumocystosis (Whitwell 1992, Ainsworth et al respiratory acidosis: see Chapter 43). There are many
causes of ARDS in the neonatal foal including prematurity If an arterial blood gas sample cannot be obtained, pulse
and primary surfactant deficiency, meconium aspiration, oximetry can be used to assess oxygen saturation. Pulse
asphyxia (as a result of dystocia, peripartum asphyxia oximetry is less accurate than arterial gas analysis and
syndrome, placentitis or premature placental separation), is affected by perfusion deficits, location of the device,
persistent pulmonary hypertension (cardiogenic or pul- pigmented skin, and type of transducer, but it has value as
monary), viral and bacterial respiratory infections, systemic a crude assessment of respiratory function and of response
inflammatory response syndrome, and septic shock. In to therapy (Chaffin et al 1996).
human infants the majority of neonatal ARDS develops
in premature infants with primary surfactant deficiency.
While primary surfactant deficiency in foals is sometimes Carbon dioxide measurements
suspected, the deficiency is rarely confirmed (Rossdale et al The carbon dioxide tension in the blood can be directly
1967). Bacterial and viral infections are the most common measured by arterial blood gas sampling or indirectly
cause of ARDS in the equine neonate. via capnography. Capnography uses an infrared sensor
to measure end-tidal PCO2, which correlates with PaCO2.
Capnography is less accurate in assessing PaCO2 in patients
with increased physiological dead space (obstructive lung
Management of the Foal’s disease, pulmonary embolism, poor cardiac output) or
Respiratory System anatomic dead space (shallow breathing).
Monitoring
Arterial blood gases and lactate Cardiac output
The primary goal of therapy in the patient with respira- Ensuring adequate cardiac output and tissue perfusion is
tory failure is maintenance of oxygen delivery for aerobic vital in maximizing survival in critically ill neonates. While
metabolism and removal of carbon dioxide. Oxygen delivery assessment of a patient’s mentation, heart rate, pulse
is affected by both the oxygen content of the blood (con- pressure, and the warmth of the distal extremities are all
centration of hemoglobin and saturation of hemoglobin useful techniques to assess cardiac output and perfusion
with oxygen) and the delivery to the tissues (cardiac output they are not always accurate. In the ideal setting, cardiac
and perfusion). The arterial blood gas and blood lactate are output is measured by placement of a pulmonary artery
the most useful assessments of respiratory function and catheter and measured using thermodilution techniques.
perfusion. Arterial blood gas samples are most commonly This is rarely done in the equine neonatal intensive
collected from the lateral metatarsal artery. In poorly care unit. Instead the clinician must rely on several
perfused or hypothermic patients the femoral or brachial indirect measurements as well as serial physical exami-
artery can be used. In critically ill foals, an arterial catheter nation parameters to assess cardiac output, perfusion and,
can be useful for repetitive sampling; however, in the ultimately, oxygen delivery and uptake by the cells.
author’s experience, they are difficult to maintain. Arterial
and venous hemoglobin saturation, blood lactate, and
carbon dioxide are all important in the assessment of Systemic blood pressure
oxygen delivery and the response to treatment. Unfor- While mean arterial pressure alone does not directly assess
tunately, no one measurement alone is enough. For perfusion or cardiac output, in combination with other
example, an arterial oxygen saturation of 98% is excellent; measurements already discussed it is useful in evaluation of
however, hypoxia may still be present if the foal is these parameters and in assessing response to treatment.
hypovolemic and not perfusing its tissues adequately. Indirect monitoring by use of a tail cuff is most commonly
Consequently, in addition to oxygen content of the blood used in our hospital. It is important to utilize the correct
(assessed by hemoglobin concentration and hemoglobin size cuff and to maintain consistent technique so that the
saturation in the blood), cardiac output and perfusion results are comparable (Marino 1997). Indirect assessment
[evaluated by central venous pressure (CVP), blood lactate, of blood pressure is less accurate than direct measurement
systemic blood pressure, and urine output] need to be but is useful in monitoring patient trends.
maintained. The goal should be to maintain perfusion
(normal blood lactate, CVP ≥ 5 mmH2O, normal mean
systolic blood pressure), provide adequate arterial oxy- Urine output
gen content (oxygen saturation ≥ 90% and adequate Urine output is an indirect assessment of cardiac output
hemoglobin) and ensure adequate ventilation (removal of and renal perfusion. Urine output of 1–2 ml·kg–1·h–1 is
carbon dioxide). adequate although a healthy foal nursing from its dam will
produce significantly greater volumes of urine. Because more normally. Alternatively, central nervous system
a healthy foal nurses significantly more milk (to meet stimulants such as caffeine (loading dose of 10 mg/kg then
nutritional needs) than is needed to meet fluid require- 2.5 mg/kg once a day per os) may aid in maintaining a
ments, urine output is high to excrete the excess fluid. more normal respiratory pattern.
While adequate urine output needs to be determined in
relationship to fluid input, urine output values below
1 ml·kg–1·day–1 should alert the clinician to the possibility Oxygen supplementation
of a problem. Supplemental oxygen is provided via a facemask to all foals
during their initial work-up at our clinic. If hypoxemia is
present, an intranasal cannula is placed and supplemental
Central venous pressure humidified oxygen is provided via insufflation. If this fails
Central venous pressure is an assessment of venous return, to bring arterial oxygen saturation within an acceptable
blood volume and, indirectly, of cardiac output. Normal range, a second cannula is placed in the opposite nostril.
CVP is between 0 and 8 cmH2O (1–6 mmHg). In a hypo- The exact inspired oxygen concentration is difficult to
volemic foal, CVP is often 0 cmH2O or less. Evaluating a determine, and generally flow rates are titrated to deliver
response to fluid therapy (a progressive increase in CVP) is enough oxygen to maintain PAO2 above 60 mmHg (oxygen
helpful in determining if fluid replacement is adequate. saturation ≥ 90%). The use of a percutaneous transtra-
Care must be taken not to overload the foal with fluids, cheal oxygen cannula to deliver higher fractional inspired
particularly with septic patients or patients with already oxygen (FI O2) has been reported (Hoffman 1992). In cases
compromised lung function, because pulmonary edema of refractory hypoxemia mechanical ventilation with 100%
will cause further respiratory compromise. oxygen is indicated.
Blood glucose Ventilatory support

Frequent monitoring of blood glucose is recommended to There are no exact criteria for when to ventilate a foal.
try to maintain normoglycemia. Both hypoglycemia and Ventilatory support is indicated in foals with moderate
hyperglycemia can have negative effects on respiratory to severe hypercapnia, foals with persistent hypoxemia
function. The weak, hypoglycemic foal is often unable to despite oxygen therapy and foals exhibiting a tremendous
generate adequate respiratory muscle activity to maintain respiratory effort to achieve “acceptable” oxygen and
tidal volume or functional residual volume. In humans, carbon dioxide levels. Foals requiring ventilation gener-
hyperglycemia and insulin resistance are common com- ally fall into one of three categories: (1) foals with
plications in patients with sepsis or systemic inflammatory CNS depression (potential causes include periparturient
response syndrome, with improved survival seen when asphyxia syndrome and sepsis) that do not increase their
glucose is closely regulated (van den Berghe et al 2001). In ventilation in response to abnormal arterial levels of CO2
septicemic neonatal foals insulin therapy may be needed to or oxygen; (2) foals that are weak as a result of sepsis,
maintain blood glucose within a normal range. botulism or other disease processes, and while capable of
trying to respond to hypercapnia and hypoxia, are unable
to ventilate adequately because of respiratory muscle
Treatment failure; and (3) foals that have primary pulmonary disease
(examples include aspiration pneumonia, interstitial
Maximizing respiratory function pneumonia) leading to gas exchange deficits and decreased
The neonatal foal with lower respiratory tract disease lung compliance. Of the three categories, foals with severe
requires constant monitoring and care. These foals can be underlying pulmonary disease are the most difficult to
extremely unstable and deteriorate relatively rapidly. ventilate and have the worst prognosis for survival.
Physical care includes keeping the foal in sternal recum- Ventilation should be considered in any foal with a PaCO2
bency to minimize further alveolar collapse and improve that is consistently > 60 mmHg. In foals with central
gas exchange. Foals that cannot be maintained on their depression of ventilation (such as foals with perinatal
sternum should be turned frequently. Many sick foals will asphyxia syndrome), administration of stimulants such
have abnormal respiratory patterns and may breath-hold as caffeine may result in correction of hypoventilation
or have long apneic pauses between breaths. These and hypercapnia. Foals that fail to respond to stimulants
abnormal patterns can result in significant changes in require mechanical ventilation to correct hypercapnia and
blood gas parameters and may be an indication of central respiratory acidosis. While foals can tolerate high blood
nervous system derangement or muscular weakness. levels of carbon dioxide, there are negative consequences
Physical stimulation may help trigger the foal to breathe to persistent, severe hypercapnia. Ventilatory support
should also be strongly considered in any foal that can- twice daily) and the β2-adrenergic agonist clenbuterol
not maintain a PAO2 of 60 mmHg or better despite sternal (0.8 μg/kg per os twice daily). Side effects of aminophylline
positioning and oxygen supplementation. Ventilatory include tachycardia and agitation so it should be avoided
support should also be considered in foals unable to main- in foals receiving caffeine. Oral absorption of amino-
tain a PAO2 of ≥ 60 mmHg without extreme respiratory phylline is variable in the horse. The use of inhaled and
efforts. These foals are working at maximum effort and nebulized bronchodilator therapy also has been reported
would clearly benefit from ventilatory support. (Clarke 1991).
In general, mechanical ventilation of a foal with
significant respiratory compromise is best started earlier Antioxidants
than later. Early institution of ventilation is clearly
Many equine clinicians use antioxidant therapy routinely
associated with a better outcome in human infants. A
in patients with evidence of systemic inflammation;
detailed discussion of mechanical ventilation is beyond the
however, few data exist regarding the benefit of such
scope of this chapter. The readers are referred to an
therapy. A recent report showed a decrease in markers of
excellent, concise review of mechanical ventilation of the
acute lung injury in preterm infants with respiratory
foal (Palmer 2005).
distress syndrome treated with a recombinant human
superoxide dismutase (Davis et al 1997). Clinical outcome
Surfactant therapy was the same in both controls and treatment patients.
Surfactant therapy improves survival and shortens ventila- Further research needs to be performed to evaluate the
tor therapy in human infants (Finer 2004). While primary benefit of antioxidant therapy in treatment of neonatal
surfactant deficiency may be rare in equine neonates, respiratory disease.
secondary deficiency is likely under-recognized (see above).
Surfactant products are very expensive and this limits Antimicrobial therapy
their use in veterinary medicine. Consequently, there are
Treatment of bacterial pneumonia or respiratory disease
few published reports of surfactant use in equine medicine
complicated by bacterial colonization should, whenever
(Perry 1993). Both animal-derived and synthetic surfac-
possible, be based on the results of culture and sensitivity.
tants are commercially available. Synthetic surfactants
However, until these results are available, the clinician
containing surfactant proteins SP-B and SP-C are more
must treat empirically rather than withholding therapy
resistant to inhibitors than those that do not contain these
and compromising care (Table 45.2). To aid in determining
proteins (Mbagwu et al 1999). Doses of 50–200 mg/kg are
the most appropriate therapy in a particular referral
typically used in human infants. The dose of surfactant is
area, the results of bacterial culture and sensitivity from
divided and each portion is instilled down the endotracheal
foals treated the previous year are helpful in assessing
tube with the patient in a variety of postures (right lateral,
changes in resistance patterns and determining empirical
left lateral, dorsal, and ventral recumbency). Manual
antimicrobial therapy. Because multiple bacteria are
ventilation should be performed immediately after each
frequently cultured from foals with pneumonia, a com-
bolus dose to maximize distribution to the distal airways
bination, broad-spectrum therapy is recommended. Initial
and alveoli. Alternatively, surfactant can be given by
broad-spectrum antimicrobial therapy in our hospital
nebulizer, although the effectiveness of this method is not
consists of a penicillin derivative and an aminoglycoside.
known. The use of surfactant lavage therapy to remove
It is important to evaluate renal function and hydration
aspirated debris has been reported (Wiswell et al 2002).
status of the foal before using aminoglycosides. Based on
Recent data suggest that the addition of polymers such
the previous year’s analysis, this combination is effective in
as dextrans to surfactant solutions may also help reduce
the majority of neonatal foal pneumonia cases seen at our
surfactant inhibition in inflammatory or obstructive con-
facility. In addition, response to therapy is important in
ditions (Tashiro & Robertson 2000).
assessing the effectiveness of treatment. Because culture of
blood and tracheal aspirate samples does not always
Bronchodilators identify the offending pathogens, careful evaluation of
The use of bronchodilators is controversial in the foal response is indicated on a daily basis. Favorable response to
with acute respiratory distress and respiratory failure. treatment would include resolution of fever, improved
Dilation of airways in consolidated regions of the lung attitude and appetite, improvement in blood gas values,
may actually worsen ventilation–perfusion mismatching. normalization of white blood cell parameters and reso-
In less severely affected foals and those with chronic or lution of hyperfibrinogenemia. Improvement in all values is
resolving pneumonia, the use of bronchodilators may desirable, while the persistence of abnormalities such as
be beneficial. Commonly used bronchodilators include the hyperfibrinogenemia or a low-grade fever are signs of
methylxanthine derivative aminophylline (5 mg/kg per os inadequate or inappropriate treatment.
Table 45.2. Antibiotic treatment of bacterial pneumonia

Antimicrobial Dosage Frequency Route Comments Spectrum of activity
Amikacin1,6,7,9 22–30 mg/kg SID IV Therapeutic drug monitoring Broad Gram –ve activity
recommended
Concentration-dependent activity
Azithromycin2,3 10 mg/kg SID for 5 days PO Concentrates in pulmonary Some Gram +ve and broad
then every alveolar macrophages Gram –ve aerobes, some
other day anaerobes
Ampicillin1,3–6,8 20 mg/kg QID IV Semisynthetic penicillin Good Gram +ve and some
Gram –ve activity
Amoxicillin1,3–6,8 30 mg/kg TID–QID PO Poorly absorbed in foals Gram +ve activity
> 2 weeks of age
Cephalexin1,5,8 25 mg/kg QID PO Good Gram +ve activity, E.coli,
Klebsiella and Proteus at
high doses
Cephalothin1,5,8 25 mg/kg QID PO Good Gram +ve activity, E.coli,
Klebsiella and Proteus at
high doses
Cefotaxime1,5,8 20–40 mg/kg TID–QID IV Antipseudomonal activity,
Gram –ve aerobes, streptococci
Ceftazidime1,5,8 20–50 mg/kg BID–QID IV Synergism with aminoglycosides Antipseudomonal activity,
Gram –ve aerobes, streptococci
Ceftriaxone1,5,8 25 mg/kg BID IV Good Gram +ve and Gram –ve
activity, some anaerobes
Ceftiofur1,5,8 5 mg/kg SID–BID IV/IM Good Gram +ve and Gram –ve
activity, some anaerobes
Chloramphenicol2,3 Public health concerns* Bactericidal
Enrofloxacin1,6,7,9 2.5 mg/kg SID IV/PO Quinolone-induced arthropathies Good Gram –ve spectrum
seen in foals Some Gram +ve activity
Concentration-dependent activity Poor anaerobic activity
Post-antibiotic effect
Erythromycin 20–30 mg/kg Q4–6 h PO May induce hyperthermia and Some Gram +ve, Gram –ve and
stearate2,3 diarrhea anaerobes
Gentamicin 6.6–8.8 mg/kg SID IV Therapeutic drug monitoring Good Gram –ve activity
sulfate1,6,7,9 recommended
Concentration-dependent activity
Imipenem1,3,4,7,8,10 5–10 mg/kg TID IV Very irritating to tissues Good Gram +ve and
Synthetic penicillin Gram –ve activity, some
Goal is time over MIC anaerobes
Metronidazole1,3 15–25 mg/kg TID–QID IV/PO Most anaerobes and some
protozoa
Penicillin 20,000– QID IV Goal is time over MIC Good Gram +ve, some
(K+ or Na+ )1,3–5,8 50,000 IU anaerobes
Rifampin1,3 5 mg/kg BID PO Used in combination with Gram +ve and anaerobes
macrolides
Ticarcillin1,3,8 50–100 mg/kg TID–QID IV Synthetic penicillin Good activity against Klebsiella
Post-antibiotic effect and Pseudomonas
Goal is time over MIC
Ticarcillin/ 50–100 mg/kg TID–QID IV Synthetic penicillin Addition of clavulanate
clavulanic acid1,3,8 Post-antibiotic effect improves activity against
Goal is time over MIC β-lactamase-producing bacteria
(both Gram –ve and Gram +ve)
Trimethoprim– 30 mg/kg BID–TID PO Gram +ve/Gram –ve spectrum
sulfamethoxazole1,3
SID, once a day; BID, twice a day; TID, thrice a day; QID, four times a day; IV, intravenous; PO, per os; IM, intramuscular; MIC, minimum inhibitory
concentration.
1
Bacteriocidal; 2bacteriostatic; 3good soft tissue penetration; 4synergism with aminoglycosides; 5low potential for toxicity; 6penicillinase resistant; 7high
risk of toxicity; 8time above MIC; 9concentration-dependent killing; 10resistant to β-lactamases.
REFERENCES Clarke A 1991 Practicalities of nebulisation. Equine Veterinary

Education 3: 45–49
Ainsworth DM, Weldon AD, Beck KA 1993 Recognition of Clark-Price SC, Cox JH, Bartoe JT et al 2004 Use of dapsone
Pneumocystis carinii in foals with respiratory distress. in the treatment of Pneumocystis carinii pneumonia in
Equine Veterinary Journal 25: 103–108 a foal. Journal of the American Veterinary Medical
Al Soub H, Taha RY, El Deeb Y et al 2004 Pneumocystis carinii Association 224: 407
pneumonia in a patient without a predisposing illness: Cochrane CG, Revak SD, Merritt TA et al 1998 Bron-
case report and review. Scandinavian Journal of Infectious choalveolar lavage with KL4-surfactant in models of
Diseases 36: 618–621 meconium aspiration syndrome. Pediatric Research
Arvidson GAB, Ekelund L, Rossdale PD 1975 Surfactant 44: 705–715
studies in the fetal and neonatal foal. Journal of Repro- Cottrill CM, O’Connor WN, Cudd T et al 1987 Persistence of
duction and Fertility Supplement 23: 663–665 foetal circulatory pathways in a newborn foal. Equine
Atz AM, Wessel DL 1999 Sildenafil ameliorates the effects Veterinary Journal 19: 252–255
of inhaled nitric oxide withdrawal. Anesthesiology 91: Cushion MT 2004 Pneumocystis: unraveling the cloak of
307–310 obscurity. Trends in Microbiology 12: 243–249
Beard CB, Carter JL, Keely SP et al. 2000 Genetic variation in Dargaville SM, McDougall PN 2001 Surfactant and surfactant
Pneumocystis carinii isolates from different geographic inhibitors in meconium aspiration syndrome. Journal of
regions: implications for transmission. Emerging Infectious Pediatrics 138: 113–115
Diseases 6: 265–272 Davidson D, Kattwinkel J, Dudell G et al 1999 Safety of
Bedenice D, Heuwieser W, Brawer R et al 2003 Clinical and withdrawing inhaled nitric oxide therapy in persistent
prognostic significance of radiographic pattern, distribu- pulmonary hypertension of the newborn. Pediatrics
tion, and severity of thoracic radiographic changes in 104: 231–236
neonatal foals. Journal of Veterinary Internal Medicine Davis JM, Rosenfeld WN, Richter SE et al 1997 Safety
17: 876–886 and pharmacokinetics of multiple doses of recombinant
Bellezzo F, Hunt RJ, Provost R et al 2004 Surgical repair of human CuZn superoxide dismutase administered intra-
rib fractures in 14 neonatal foals: case selection, surgical tracheally to premature neonates with respiratory dis-
technique and results. Equine Veterinary Journal 36: tress syndrome. Pediatrics 100: 24–30
557–562 de Beufort AJ, Elferink JGR, Berger HM 1998 Effect of inter-
Berkenbosch J W, Baribeau J, Perreault T 2000 Decreased leukin 8 in meconium on in-vitro neutrophil chemotaxis.
synthesis and vasodilation to nitric oxide in piglets with Lancet 352: 102–105
hypoxia-induced pulmonary hypertension. American Del Piero F, Wilkins PA, Lopez JW et al 1997 Equine
Journal of Physiology: Lung Cellular and Molecular viral arteritis in newborn foals: clinical, pathological,
Physiology 278: L276–L283 serological, microbiological and immunohistochemical
Borchers K, Wolfinger U, Goltz M et al 1997 Distribution and observations. Equine Veterinary Journal 29: 178–185
relevance of equine herpesvirus type 2 (EHV-2) infections. Demmers SJA, Grondahl G, Jensen-Waern M 2001 Neutrophil
Archives of Virology 142: 917–928 functions and serum IgG in growing foals. Equine
Brewer BD, Koterba, AM 1990 Bacterial isolates and sus- Veterinary Journal 33: 676–680
ceptibility patterns in foals in a neonatal intensive care Dumoulin A, Mazars E, Seguy N et al 2000 Transmission of
unit. Compendium on Continuing Education for the Pneumocystis carinii disease from immunocompetent
Practicing Veterinarian 12: 1773–1781 contacts of infected hosts to susceptible hosts. European
Britton AP, Robinson JH 2002 Isolation of influenza A virus Journal of Clinical Microbiology and Infectious Diseases
from a 7-day-old foal with bronchointerstitial pneumonia. 19: 671–678
Canadian Veterinary Journal 43: 55–56 Dutta S 1975 Isolation and characterization of an adeno-
Buergelt CD, Hines SA, Cantor G et al 1986 A retrospective virus and isolation of its adenovirus-associated virus in
study of proliferative interstitial lung disease of horses in cell culture from foals with respiratory tract disease.
Florida. Veterinary Pathology 23: 750–756 American Journal of Veterinary Research 36: 247–250
Cabanes FJ, Roura X, Majo N 2000 Pneumocystis carinii Edington N, Welch HM, Griffiths L 1994 The prevalence of
pneumonia in a Yorkshire terrier dog. Medical Mycology latent Equid herpesviruses in the tissues of 40 abattoir
38: 451–453 horses. Equine Veterinary Journal 26: 140–142
Carroll WD, Dhillon R 2003 Sildenafil as a treatment for pul- Ewing PJ, Cowell RL, Tyler RD et al 1994 Pneumocystis carinii
monary hypertension. Archives of Diseases of Childhood pneumonia in foals. Journal of the American Veterinary
88: 827–828 Medical Association 204: 929–933
Castellheim A, Lindenskov PH, Pharo A et al 2004 Meconium Farrow BR, Watson AD, Hartley WJ 1972 Pneumocystis
is a potent activator of complement in human serum and pneumonia in the dog. Journal of Comparative Pathology
in piglets. Pediatric Research 55: 310–318 82: 447–453
Chaffin MK, Matthews NS, Cohen ND et al 1996 Evaluation of Fike CD, Kaplowitz MR 1996 Chronic hypoxia alters nitric
pulse oximetry in anaesthetised foals using multiple oxide-dependent pulmonary vascular responses in lungs
combinations of transducer type and transducer attach- of newborn pigs. Journal of Applied Physiology 81:
ment site. Equine Veterinary Journal 28: 437–445 2078–2087
Chandran S, Haqueb ME, Wickramasinghe HT et al 2004 Use Fike CD, Kaplowitz MR, Thomas CJ et al 1998 Chronic hypoxia
of magnesium sulphate in severe persistent pulmonary decreases nitric oxide production and endothelial nitric
hypertension of the newborn. Journal of Tropical Pediatrics oxide synthase in newborn pig lungs. American Journal
50: 219–223 of Physiology 274: L517–L526
Findlay RD, Taeusch HW, Walther FJ 1996 Surfactant Haas KM, Suzuki S, Yamaguchi N et al 2002 Nitric oxide
replacement therapy for meconium aspiration syndrome. further attenuates pulmonary hypertension in magnesium-
Pediatrics 97: 48–52 treated piglets. Pediatric International 44: 670–674
Finer NN 2004 Surfactant use for neonatal lung injury: Hansell D. 2003 Extracorporeal membrane oxygenation
beyond respiratory distress syndrome. Pediatric Respiratory for perinatal and pediatric patients. Respiratory Care
Review 5 (Suppl A): S289–S297 48: 352–362; discussion pp.63–66
Finer NN, Barrington KJ 2001 Nitric oxide for respira- Helweg-Larsen J, Tsolaki AG, Miller RF et al 1998 Clusters of
tory failure in infants born at or near term. Cochrane Pneumocystis carinii pneumonia: analysis of person-to-
Database Syst Rev 2: CD000399 person transmission by genotyping. Quarterly Journal of
Flaminio MJ, Rush BR, Cox JH et al 1998 CD4+ and CD8+ Medicine 91: 813–820
T-lymphocytopenia in a filly with Pneumocystis carinii Helweg-Larsen J, Jensen JS, Dohn B et al 2002 Detection of
pneumonia. Australian Veterinary Journal 76: 399–402 Pneumocystis DNA in samples from patients suspected
Foote CE, Gilkerson JR, Whalley JM 2004 Detection of EHV-1 of bacterial pneumonia – a case–control study. BMC
and EHV-4 DNA in unweaned Thoroughbred foals from Infectious Disease 2: article number 28
vaccinated mares on a large stud farm. Equine Veterinary Henry JN 1976 Adenovirus pneumonia in an Arabian foal.
Journal 36: 341–345 Canadian Veterinary Journal 17: 220–221
Fu ZF, Robinson AJ, Horner GW et al 1986 Respiratory Hintz SR, Halamek LP, Van Meurs KP et al 2000 Secondary
disease in foals and the epizootiology of equine herpes- infection presenting as recurrent pulmonary hyperten-
virus type 2 infection. New Zealand Veterinary Journal sion. Journal of Perinatology 20: 262–264
34: 152–155 Hoffman AM 1992 A percutaneous transtracheal catheter
Fuhrman BP 2004 Surface properties and the meconium system for improved oxygenation in foals with respiratory
aspiration syndrome. Pediatric Critical Care Medicine distress. Equine Veterinary Journal 24: 239–241
5: 200–201 Holm BA, Notter RH 1999 Multiple mechanisms of lung
Furuta T, Nogami S, Kojima S et al 1994 Spontaneous surfactant inhibition. Pediatric Research 46: 85–93
Pneumocystis carinii infection in the dog with naturally Holopainen RAH, Laine J, Peuravuori H et al 1999 Human
acquired generalised demodicosis. Veterinary Record meconium has high phospholipase A2 activity and
134: 423–424 induces cellular injury and apoptosis in piglet lungs.
Gayle JM, Gayle CN, Chaffin MK 1998 Factors associated Pediatric Research 46: 626–632
with survival in septicemic foals: 65 cases (1988–1995). Hong ST, Ryu JS, Chai JY et al 1992 Transmission modes of
Journal of Veterinary Internal Medicine 12: 140–146 Pneumocystis carinii among rats observed by karyotype
Ghofrani HA, Rose F, Schermuly RT et al 2003 Oral sildenafil analysis. Kisaengchunghak Chapchi 30: 283–288
as long-term adjunct therapy to inhaled iloprost in severe Hughes WT 1998 Current issues in the epidemiology, trans-
pulmonary arterial hypertension. Journal of the American mission, and reactivation of Pneumocystis carinii. Seminars
College of Cardiology 42: 158–164 in Respiratory Infections 13: 283–288
Gigliotti F, Harmsen AG, Wright TW 2003 Characterization of Ichinose F, Erana-Garcia J, Hromi J et al 2001 Nebulized
transmission of Pneumocystis carinii f. sp. muris through sildenafil is a selective pulmonary vasodilator in lambs
immunocompetent BALB/c mice. Infection and Immunity with acute pulmonary hypertension. Critical Care Medicine
71: 3852–3856 29: 1000–1005
Gilbert SA, Timoney PJ, McCollum WH et al 1997 Detection of Jean D, Laverty S, Halley J et al 1999 Thoracic trauma in
equine arteritis virus in the semen of carrier stallions by newborn foals. Equine Veterinary Journal 31: 149–152
using a sensitive nested PCR assay. Journal of Clinical Jensen TK, Boye M, Bille-Hansen V 2001 Application of
Microbiology 35: 2181–2183 fluorescent in situ hybridization for specific diagnosis
Gilkerson JR, Drummer HE, Studdert MJ et al 1991 of Pneumocystis carinii pneumonia in foals and pigs.
Epidemiology of EHV-1 and EHV-4 in the mare and Veterinary Pathology 38: 269–274
foal populations on a Hunter Valley stud farm: are mares Keller RL, Hamrick SE, Kitterman JA et al 2004 Treatment of
the source of EHV-1 for unweaned foals? Veterinary rebound and chronic pulmonary hypertension with oral
Microbiology 68: 27–34 sildenafil in an infant with congenital diaphragmatic
Gilkerson JR, Drummer HE, Studdert MJ et al 1999 hernia. Pediatric Critical Care Medicine 5: 184–187
Epidemiological studies of equine herpesvirus 1 (EHV-1) Kershaw O, von Oppen T, Glitz F et al 2001 Detection of
in Thoroughbred foals: a review of studies conducted in equine herpesvirus type 2 (EHV-2) in horses with kerato-
the Hunter Valley of New South Wales between 1995 conjunctivitis. Virus Research 80: 93–99
and 1997. Veterinary Microbiology 68: 15–25 Kotecha S 2000 Lung growth: implications for the newborn
Goh AY, Lum LC, Roziah M 2001 Low-dose inhaled nitric infant. Archives of Diseases in Childhood 82: F69–F74
oxide in term and near-term infants with hypoxic Koterba AM 1990 Physical Examination, 1st edn. Lea & Febiger,
respiratory failure: a Malaysian experience. Medical Philadelphia
Journal of Malaysia 56: 336–340 Koterba AM, Wozniak JA, Kosch PC 1995a Ventilatory and
Golden J, Hollander H, Stulbarg MS et al 1986 Broncho- timing parameters in normal horses at rest up to age one
alveolar lavage as the exclusive diagnostic modality for year. Equine Veterinary Journal 27: 257–264
Pneumocystis carinii pneumonia. Chest 90: 18–22 Koterba AM, Wozniak JA, Kosch PC 1995b Changes in
Goldman AP, Haworth SG, Sigston PE et al 1996 Four breathing pattern in the normal horse at rest up to age
patterns of response to inhaled nitric oxide for persistent one year. Equine Veterinary Journal 27: 265–274
pulmonary hypertension of the newborn. Pediatrics Lakritz J, Wilson WD, Berry CR et al 1993 Bronchointerstitial
98: 706–713 pneumonia and respiratory distress in young horses:
Guthrie SO, Walsh WF, Auten K et al 2004 Initial dosing of clinical, clinicopathologic, radiographic, and pathological
inhaled nitric oxide in infants with hypoxic respiratory findings in 23 cases (1984–1989). Journal of Veterinary
failure. Journal of Perinatology 24: 290–294 Internal Medicine 7: 277–288
Leffler CW, Cassin S 1978 Effect of indomethacin on pul- Palmer J 2005 Ventilatory support of the neonatal foal.
monary vascular response to ventilation of fetal goats. Veterinary Clinics of North American; Equine Practice
American Journal of Physiology 234: H346–H351 21: 457–486
Lepore JJ, Maroo A, Pereira NL et al 2002 Effect of sildenafil on Pattle RP, Schock C, Creasey JM 1975 The development of the
the acute pulmonary vasodilator response to inhaled lung and its surfactant in the foal and in other species.
nitric oxide in adults with primary pulmonary hyper- Journal of Reproduction and Fertility Supplement 23:
tension. American Journal of Cardiology 90: 677–680 651–657
Lester GD, DeMarco VG, Norman WM 1999 Effect of inhaled Peek SF, Landolt G, Karasin AI et al 2004 Acute respiratory
nitric oxide on experimentally induced pulmonary hyper- distress syndrome and fatal interstitial pneumonia
tension in neonatal foals. American Journal of Veterinary associated with equine influenza in a neonatal foal.
Research 60: 1207–1212 Journal of Veterinary Internal Medicine 18: 132–134
Lotze A, Mitchell BR, Bulas DI et al 1998 Multicenter study of Perkins G, Ainsworth DM, Erb HN et al 1999 Clinical,
surfactant (beractant) use in the treatment of term haematological and biochemical findings in foals with
infants with severe respiratory failure. Survanta in Term neonatal Equine herpesvirus-1 infection compared with
Infants Study Group. Journal of Pediatrics 132: 40–47 septic and premature foals. Equine Veterinary Journal
Manoloff ES, Francioli P, Taffe P et al 2003 Risk for Pneumo- 31: 422–426
cystis carinii transmission among patients with pneu- Perron Lepage MF, Suter MM 1999 A case of interstitial
monia: a molecular epidemiology study. Emerging pneumonia associated with Pneumocystis carinii in a foal.
Infectious Diseases 9: 132–134 Veterinary Pathology 36: 621–624
Marino P 1997 Arterial Blood Pressure, 2nd edn. Lippincott, Perry B 1993 The use of bovine derived surfactant in foals
Williams and Wilkins, Philadelphia with respiratory distress. In: 11th Annual Veterinary
Marsh PS, Palmer JE 2001 Bacterial isolates from blood and Medical Forum; 1993 May 20–23; Washington, DC,
their susceptibility patterns in critically ill foals: 543 pp.189–192
cases (1991–1998). Journal of the American Veterinary Perryman LE, McGuire TC, Crawford TB 1978 Maintenance of
Medical Association 218: 1608–1610 foals with combined immunodeficiency: causes and
Mbagwu N, Bruni R, Hernandez-Juviel JM et al 1999 control of secondary infections. American Journal of
Sensitivity of synthetic surfactants to albumin inhibition Veterinary Research 39: 1043–1047
in preterm rabbits. Molecular Genetics and Metabolism Peters SE, Wakefield AE, Whitwell KE 1994 Pneumocystis
66: 40–48 carinii pneumonia in thoroughbred foals: identification of
McCartan CG, Wood JL, Mumford JA 1995 Clinical, serological a genetically distinct organism by DNA amplification.
and virological characteristics of an outbreak of paresis Journal of Clinical Microbiology 32: 213–216
and neonatal foal disease due to equine herpesvirus-1 on Pifer LL, Stagno S, Woods D 1978 Pneumocystis carinii
a stud farm. Veterinary Record 136: 7–12 infection: evidence for high prevalence in normal and
McConnell E E, Basson P A, Pienaar J G 1971 Pneumocystosis immunosuppressed children. Pediatrics 61: 35–41
in a domestic goat. Onderstepoort Journal of Veterinary Prescott JF, Wilcock BP, Carman S et al 1991 Sporadic, severe
Research 38: 117–124 bronchointerstitial pneumonia of foals. Canadian
McTaggart CYJ, Penhale J, Raidal SL 2001 A comparison of Veterinary Journal 32: 421–425
foal and adult horse neutrophil function using flow Rabe KF, Tenor H, Dent G et al 1993 Phosphodiesterase
cytometric techniques. Research in Veterinary Science isozymes modulating inherent tone in human airways:
71: 73–79 identification and characterization. American Journal of
Mehta S 2003 Sildenafil for pulmonary arterial hypertension: Physiology 264: L458–L464
exciting, but protection required. Chest 123: 989–992 Rabinovitch M, Gamble W, Nadas AS et al 1979 Rat
Meurs KM, Hanson C, Honnas C 1997 Tricuspid valve atresia pulmonary circulation after chronic hypoxia: hemo-
with main pulmonary artery atresia in an Arabian foal. dynamic and structural features. American Journal of
Equine Veterinary Journal 29: 160–162 Physiology 236: H818–H827
Michelakis E, Tymchak W, Lien D et al 2002 Oral sildenafil is Raj U, Shimoda L 2002 Oxygen-dependent signaling in
an effective and specific pulmonary vasodilator in patients pulmonary vascular smooth muscle. American Journal
with pulmonary arterial hypertension: comparison with of Physiology: Lung Cellular and Molecular Physiology
inhaled nitric oxide. Circulation 105: 2398–2403 283: L671–L677
Miller RF, Ambrose HE, Novelli V et al 2002 Probable Randell SH, Mercer RR, Young SL 1989 Postnatal growth of
mother-to-infant transmission of Pneumocystis carinii f. pulmonary acini and alveoli in normal and oxygen-
sp. hominis infection. Journal of Clinical Microbiology exposed rats studied by serial section reconstructions.
40: 1555–1557 American Journal of Anatomy 186: 55–68
Moses D, Holm BA, Spitale P et al 1991 Inhibition of Reimer JM, Reef VB, Saik JE 1993 Aortic origin of the right
pulmonary surfactant function by meconium. American pulmonary artery and patent ductus arteriosus in a pony
Journal of Obstetrics and Gynecology 164: 477–481 foal with pulmonary hypertension and right-sided heart
Murray MJ, Eichorn ES, Dubovi EJ et al 1996 Equine failure. Equine Veterinary Journal 25: 466–468
herpesvirus type 2: prevalence and seroepidemiology in Rose RJ, Rossdale PD, Leadon DP 1982 Blood gas and
foals. Equine Veterinary Journal 28: 432–436 acid–base status in spontaneously delivered, term-induced
Nout YS, Hinchcliff KW, Samii VF et al 2002 Chronic pul- and induced premature foals. Journal of Reproduction
monary disease with radiographic interstitial opacity and Fertility Supplement 32: 521–528
(interstitial pneumonia) in foals. Equine Veterinary Rossdale P, Pattle RE, Mahaffey LW 1967 Respiratory distress
Journal 34: 542–548 in a newborn foal with failure to form lung lining film.
Oelberg DG, Downey SA, Flynn MM 1990 Bile salt-induced Nature 215: 1498–1499
intracellular Ca++ accumulation in type II pneumocytes. Sadiq HF, Mantych G, Benawra RS et al 2003 Inhaled nitric
Lung 168: 297–308 oxide in the treatment of moderate persistent pulmonary
hypertension of the newborn: a randomized controlled, Thompson DB, Spradborw PB, Studdert M 1976 Isolation of
multicenter trial. Journal of Perinatology 23: 98–103 an adenovirus from an Arab foal with a combined
Seibold HR, Munnell JF 1977 Pneumocystis carinii in a pig. immunodeficiency disease. Australian Veterinary Journal
Veterinary Pathology 14: 89–91 52: 435–437
Shekerdemian LS, Ravn HB, Penny DJ 2004 Interaction Tollofsrud PA, Lindenskov PH, Drevon CA et al 2003
between inhaled nitric oxide and intravenous sildenafil in Comparison of pulmonary and inflammatory effects of
a porcine model of meconium aspiration syndrome. lipid- and water-soluble components in meconium in
Pediatric Research 55: 413–418 newborn piglets. Biologia Neonatorum 84: 330–337
Shively JN, Dellers RW, Buergelt CD et al 1973 Pneumocystis Tyler TWR, Leffler C, Cassin S 1975 The effects of indome-
carinii pneumonia in two foals. Journal of the American thacin on the pulmonary vascular response to hypoxia
Veterinary Medical Association 162: 648–652 in the premature and mature newborn goat. Proceedings
Smyth RL 2000 Inhaled nitric oxide treatment for pre- of the Society of Experimental Biology and Medicine
term infants with hypoxic respiratory failure. Thorax 150: 695–698
55: S51–S55 van den Berghe GW, Weekers F, Verwaest C et al 2001
Southwood LL, Tobias AH, Schott HC et al 1996 Cyanosis Intensive insulin therapy in the critically ill patients. New
and intense murmur in a neonatal foal. Journal of the England Journal of Medicine 345: 1359–1367
American Veterinary Medical Association 208: 835–837; Vitums AGB, Stone EC, Spencer GR 1973 Transposition of the
discussion 838–839 aorta and atresia of the pulmonary trunk in a horse.
Sprayberry K, Bain FT, Seahorn TL et al 2001 56 cases of rib Cornell Veterinarian 63: 41–57
fractures in neonatal foals hospitalized in a referral center Warner BB, Stuart LA, Papes RA et al 1998 Functional and
intensive care unit from 1997–2001. In: 47th Annual pathological effects of prolonged hyperoxia in neonatal
American Association of Equine Practitioners Conven- mice. American Journal of Physiology 275: L110–L117
tion; 2001 Nov 24–28; San Diego, CA, pp.395–399 Watanabe H, Ohashi K, Takeuchi K et al 2002 Sildenafil for
Steudel W, Scherrer-Crosbie M, Bloch KD et al 1998 Sustained primary and secondary pulmonary hypertension. Clinical
pulmonary hypertension and right ventricular hyper- Pharmacology and Therapeutics 71: 398–402
trophy after chronic hypoxia in mice with congenital Webb RF, Walker KH 1981 Involvement of adenovirus in
deficiency of nitric oxide synthase 3. Journal of Clinical pneumonia in a thoroughbred foal. Australian Veterinary
Investigation 101: 2468–2477 Journal 57: 142–143
Stewart JH, Rose RJ, Barko AM 1984 Respiratory studies in Weimann J, Ullrich R, Hromi J et al 2000 Sildenafil is a
foals from birth to seven days old. Equine Veterinary pulmonary vasodilator in awake lambs with acute
Journal 16: 323–328 pulmonary hypertension. Anesthesiology 92: 1702–1712
Sun B 1993a Exogenous surfactant improves lung compliance Whitlock RH, Shively JN 1975 Adenoviral pneumonia in a
and oxygenation in rats with meconium aspiration. foal. Cornell Veterinarian 65: 393–401
Journal of Applied Physiology 77: 1961–1971 Whitwell K 1992 Pneumocystis carinii infection in foals in the
Sun B 1993b Surfactant inhibition in experimental meconium UK. Veterinary Record 131: 19
aspiration. Acta Paediatrica 82: 182–189 Wilkins PA 2003 Acute respiratory failure: diagnosis, monitor-
Szeredi L, Denes B, Rusvai M 2003 Equine viral arteritis ing techniques, and therapeutics. Clinical Techniques in
in a newborn foal: parallel detection of the virus by Equine Practice 2: 56–66
immunohistochemistry, polymerase chain reaction and Wilkins PA, Lopez J, Cline M 1995 Immunohistochemical
virus isolation. Journal of Veterinary Medicine Series B: diagnosis of equine arteritis infection in a foal. Equine
Infectious Diseases and Veterinary Public Health 50: Veterinary Journal 27: 398
270–274 Wilson WD, Madigan JE 1989 Comparison of bacteriologic
Tanaka S, Kaji Y, Taniyama H et al 1994 Pneumocystis carinii culture of blood and necropsy specimens for determin-
pneumonia in a thoroughbred foal. Journal of Veterinary ing the cause of foal septicemia: 47 cases (1978–1987).
Medical Science 56: 135–137 Journal of the American Veterinary Medical Association
Tashiro K, Robertson B 2000 Dextran reduces surfactant 195: 1759–1763
inhibition by meconium. Acta Paediatrica 89: 1439–1445 Wiswell TE, Finer NN, Donn SM et al 2002 A multicenter,
The Neonatal Inhaled Nitric Oxide Study Group 1997 Inhaled randomized, controlled trial comparing Surfaxin
nitric oxide in full-term and nearly full-term infants with (Lucinactant) lavage with standard care for treat-
hypoxic respiratory failure. New England Journal of ment of meconium aspiration syndrome. Pediatrics
Medicine 336: 597–604 109: 1081–1087
Thibeault DW, Mabry S, Rezaiekhaligh M 1990 Neonatal Zhao L, Mason NA, Morrell NW et al 2001 Sildenafil inhibits
pulmonary oxygen toxicity in the rat and lung changes hypoxia-induced pulmonary hypertension. Circulation
with aging. Pediatric Pulmonology 9: 96–108 104: 424–428
Disorders of the Thoracic Wall, Pleura,
Mediastinum, and Diaphragm
46 T Douglas Byars and Bruce C McGorum
are not witnessed. Furthermore, the horse’s hair coat and

Introduction
dark skin color usually prevent recognition of skin
The thoracic wall and diaphragm function to generate the bruising, which is a useful indicator of chest wall trauma
intrathoracic pressure changes that drive breathing (see in humans.
Chapter 2) and to protect the vital internal thoracic and The sequelae of thoracic trauma are listed in Table 46.1.
abdominal organs. These roles may be compromised by a When assessing horses with thoracic trauma, the clinician
diverse variety of disorders including thoracic trauma, rib should not be blinkered by obvious chest wall injuries, but
fractures, pneumothorax, pleuropneumonia, neoplasia and should perform a thorough evaluation of all body systems.
botulism, thereby leading to abnormalities in breathing This will ensure early recognition and prompt management
and ultimately even to cardiopulmonary failure. of potentially fatal extrathoracic sequelae, such as rupture
The anatomy of the thoracic wall, pleura, mediastinum, or perforation of abdominal viscera and vertebral fracture
and diaphragm is detailed in Chapter 1. (Laverty et al 1996).
Thoracic Wall Trauma Rib Fractures

The thoracic wall may be injured by blunt or penetrating Rib fractures are uncommon in adult horses but occur
trauma. Blunt trauma includes collisions with objects such in around 3–5% of neonates, and were considered to be
as automobiles, fences, and other horses, and compres- the cause of death in 2.5% of neonatal foals in a post-
sion of the neonatal foal’s thorax by forceful uterine mortem study (Jean et al 1999, Schambourg et al 2003).
contractions during parturition. Penetrating injuries In neonates, fractures most commonly occur at or near the
include staking injuries and gunshot wounds. As the right costochondral junctions of ribs 3 to 8 (Schambourg et al
pleural sac may extend up the neck, to 2- to 3-cm rostral to 2003) (Fig. 46.1). They probably result from thoracic
the first rib, it is potentially vulnerable to deep puncture compression by forceful uterine contractions during par-
wounds in this region. The possibility of trauma should not turition, compounded by focal compression of the cranio-
be eliminated on the basis that a traumatic incident was ventral thorax by the foal’s elbow when the forelimb fails
not observed because the horse has a propensity for to extend fully during delivery. Difficult and primiparous
developing a variety of traumatic injuries, many of which foalings are the only known predisposing factors to
thoracic trauma in neonates (Jean et al 1999). While
larger birth weights and dystocia are frequently cited as
predisposing factors, rib fractures also occur in small-birth-
Table 46.1. Sequelae of thoracic trauma
weight foals with uncomplicated deliveries.
Superficial soft tissue injury
Subcutaneous emphysema
Fractures of the ribs, sternum, and vertebrae
Clinical signs
Pneumothorax
Pneumomediastinum
Most foals with uncomplicated rib fractures have no overt
Pleural effusion clinical signs. Because the chest wall and parietal pleura,
Hemothorax but not the visceral pleura, are well endowed with sensory
Infections (pleural infection, pleuropneumonia, pulmonary nerve fibers from the intercostal nerves, foals with rib
abscess)
injuries may have variable pleurodynia (thoracic pain), as
Pulmonary contusion or laceration
Diaphragmatic herniation or laceration
evidenced by stiffness, expiratory grunting, and reluctance
Involvement of other systems (pericardial puncture, intestinal to rise, lie down, circle or nurse. There may be asym-
puncture, vertebral fractures) metrical subcutaneous edema or a hematoma over the
ipsilateral ventral thorax and olecranon. A flail chest
659
SECTION 7 : Disorders of the Thoracic Wall, Pleura, Mediastinum, and Diaphragm
660 46 Disorders of the Thoracic Wall, Pleura, Mediastinum, and Diaphragm
Fig. 46.1. (A) A foal with pulmonary origin

epistaxis caused by laceration of the lung by
sharp ends of fractured ribs. (B) Ultrasound
image of the rib fragments. (C) Post-mortem
view of the inside of the thoracic wall from a
foal showing medial displacement of sharp
ends of two fractured ribs (arrows) and asso-
ciated soft tissue damage. (D) Post-mortem
view of the lungs from an adult horse that
died as a result of pulmonary laceration fol-
lowing thoracic trauma sustained during a
fall while racing. Two lacerations are evident on
the dorsal surface of the left lung (arrows).
C D
46 Disorders of the Thoracic Wall, Pleura, Mediastinum, and Diaphragm 661
occurs when three or more consecutive ribs are fractured

Table 46.2. Sequelae to rib fractures
in at least two places, or are separated from the costo-
chondral junction or sternum. The flail segment is unstable Pneumothorax
and exhibits paradoxical movement, such that it collapses Hemothorax and hemopericardium
Pleural effusion
inwards on inspiration, and moves outward on expira-
Pleural infection
tion. The inspiratory collapse leads to deviation of the Pulmonary contusion
mediastinum towards the contralateral side. The resultant Laceration of lung, pericardium, myocardium, diaphragm,
inability to generate adequate intrapleural pressure swings abdominal viscera
causes generalized hypoventilation and respiratory failure. Diaphragmatic hernia
Sudden death
Foals with fractured ribs may develop a variety of
potentially life-threatening sequelae (Table 46.2), that may
lead to additional clinical signs, including:
● dyspnea (pneumothorax, pulmonary contusion, diaphrag- to risk displacement of unstable fractures may benefit
matic herniation) from judicious administration of sedatives (Sprayberry
● hypovolemic shock and anemia (hemothorax; laceration et al 2001). Foals should be assisted to rise and nurse,
of intercostal artery, lung, myocardium, coronary artery, taking care to avoid direct pressure on the fracture site.
diaphragm, and abdominal viscera) Supplemental oxygen is indicated for foals with hypoxemia.
● bilateral epistaxis (pulmonary laceration; Fig. 46.1A) Pain control is an important aspect of the management of
● cardiac failure (pericardial and myocardial laceration) chest wall injuries to reduce chest splinting and improve
● sudden death. regional lung ventilation. This may minimize retention of
respiratory secretions and prevent regional atelectasis,
Diagnosis which predispose to secondary pneumonia. Intercostal
nerve block using a long-acting anesthetic agent such
Rib fractures may be diagnosed by careful simultaneous as bupivacaine may provide prolonged analgesia. Where
palpation of both hemithoraces, especially over the costo- practical, all of the intercostal nerves supplying the
chondral junctions. This examination is best done with the region of the thoracic injury, and also the intercostal
foal standing, because casting the foal to dorsal recum- nerves immediately cranial and caudal to this region,
bency may displace unstable fragments, leading to lacera- should be blocked. Intercostal nerve block is preferable
tion of internal organs. The clinician should examine for to narcotic analgesia because it does not result in respira-
asymmetry of the thoracic wall, pain, swelling, crepitation tory depression.
or the presence of unstable fragments that produce Surgical repair of rib fractures in neonatal foals has
a pathognomonic “click or pop”. Ultrasonography and been described (Bellazo et al 2004), with internal and
thoracic radiography may aid detection of rib fractures external fixation indicated for foals with fractures of
(Fig. 46.1B), with the former technique being more the ribs in close proximity to the heart and in foals that
useful for detection of greenstick fractures (Sprayberry develop diaphragmatic laceration secondary to rib
et al 2001). Detection and thorough investigation of fractures. Fixation entails using (1) reconstruction plates
the sequelae listed in Table 46.2 may require a combi- with cortical screws and cerclage wires, (2) plates with
nation of ultrasonography, radiography, and ultimately screws and optional wire, or (3) Steinman pins with
exploratory surgery. stainless steel wire. Closed fixations have also been pro-
vided using cerclage wire over external plates or tongue
Treatment depressors. Surgical complications include hemorrhage,
seroma formation, postoperative pneumothorax, and
Uncomplicated rib fractures are treated conservatively, implant failure (R.J. Hunt, personal communication 2004).
simply by stall rest for 2–3 weeks. Hematoma formation Stabilization of rib fractures and associated flail chest in an
during the course of a few days may provide a cushion over adult horse using a plastic stent as an external fixator
sharp rib fragments, thereby minimizing the risk of further secured with orthopedic wire to the ribs under local
damage. Premature turn-out or exercise of foals with anesthesia was reported by Laverty et al (1996).
unstable fractures may cause potentially fatal displacement
of fragments. Ultrasound evaluation and palpation can be Prognosis
used to assess the stability of callus formation. Foals that
spend extended periods of time in recumbency should be Mortality is significant in patients that have sequelae
placed on a cushion pad with the fracture side down to such as pulmonary contusions, pulmonary lacerations,
minimize paradoxical breathing and maximize ventilation. hemothorax, hemopericardium, and pneumothorax, unless
Foals that struggle excessively or that are sufficiently active given appropriate prompt medical or surgical treatment
(Sprayberry et al 2001). Foals with significant hemothorax of abdominal viscera within the pleural cavity using
causing pulmonary tamponade and hemorrhagic shock thoracic ultrasonography or radiography. Ultrasonography
may require pleural drainage and blood replacement. is more useful because displaced intestine, spleen, or liver
are readily identified within the pleural cavity. Ultra-
sonography may also reveal discontinuity of the diaphragm,
Diaphragmatic Hernia and sequelae including hemothorax and pleural effusion.
Pathogenesis While thoracic radiography may identify abdominal viscera
within the pleural cavity and secondary pleural effusions,
Diaphragmatic herniation is an uncommon problem that unlike ultrasonography, radiographic evaluation of the
may be congenital or acquired, with the latter resulting ventral thorax is limited by the cardiac silhouette. Oral
from blunt trauma to the thorax or abdomen, such as from barium contrast radiography may aid identification of
falls, kicks or collisions. Herniation may also result from intestines within the thorax.
laceration of the diaphragm in animals with caudal rib frac-
tures, as a breeding injury in stallions, and as a complication Management
of parturition in mares. Acquired diaphragmatic hernias have
Surgical repair is considered by some to be optional for
ragged edges with associated hemorrhage and more com-
those horses which have relatively asymptomatic chronic
monly occur on the left side of the diaphragm. Congenital
hernias, and which have either a small defect in the
hernias, occurring in neonates as the result of incomplete
diaphragm or a large tear that does not incarcerate bowel.
closure of the crura, generally involve the dorsal diaphrag-
Emergency surgical repair is clearly indicated for horses
matic quadrant and have smooth edges. Horses may have a
with significant clinical compromise, such as intestinal
diaphragmatic hernia for prolonged periods of time without
obstruction and strangulation or hemorrhage, or for horses
exhibiting clinical signs and then have a sudden onset of
with concomitant fractured ribs. Diaphragmatic hernias
clinical signs as a result of further tearing of the diaphragm,
can be treated successfully by primary closure of the
sudden passage of viscera into the pleural cavity or incar-
defect or insertion of a mesh implant via laparotomy
ceration or strangulation of abdominal viscera.
(Steenhaut et al 1992, Santschi et al 1997). Postopera-
tive care includes medical treatment of any associated
Clinical signs
clinical sequelae, stall confinement, and antibiotic therapy.
Diaphragmatic herniation is diagnostically challenging The long-term prognosis is favorable in horses which
because of its varied presentations. The most common are asymptomatic postoperatively and which have a
clinical presentation is abdominal pain as the result of healed surgical site. Horses that are treated successfully
intestinal obstruction and strangulation or involvement can achieve race records similar to their siblings and can
of other abdominal viscera. Only a minority of horses produce foals without recurrence of the herniation
presents solely with signs of respiratory dysfunction, such (Santschi et al 1997).
as tachypnea, dyspnea, exercise intolerance, and coughing.
These horses are likely to have large diaphragmatic Pneumothorax
defects that allow herniation of considerable amounts of
abdominal viscera but without intestinal obstruction or Pathogenesis
ischemia (Perdrizet et al 1989). The presence of abdominal
The pleural cavity is normally at subatmospheric pressure
viscera and secondary effusion in the pleural cavity leads to
because of the net effect of the outward elastic recoil of the
pulmonary atelectasis and reduced tidal volume. Other
thoracic wall and the inward elastic recoil of the lungs.
signs of diaphragmatic herniation include endotoxemic
The subatmospheric intrapleural pressure prevents lung
and hemorrhagic shock and a variety of non-specific
collapse. Pneumothorax is the accumulation of gas, usually
complaints. Occasionally, diaphragmatic hernias are
air, within the pleural cavity. The pathophysiology of pneu-
identified as apparently incidental findings at post-mortem
mothorax is described in Chapter 2, Fig. 2.8. Pneumo-
examinations, suggesting that they may be benign in some
thorax may be classified by etiology (spontaneous, trau-
horses. Auscultation and percussion of the ventral chest
matic, iatrogenic), pathophysiology (open or closed), site
may reveal absence of breath sounds and dullness, respec-
(unilateral or bilateral) or mechanism (simple or tension).
tively. Examination per rectum may reveal a relative paucity
In the horse pneumothorax is commonly bilateral, because
of viscera within the abdominal cavity.
the two pleural cavities often communicate through
small fenestrations in the caudal mediastinum. Unilateral
Diagnosis
pneumothorax occurs in horses that do not have fenes-
Diaphragmatic herniation is frequently confirmed only trations, and in horses with pleural effusions, because of
during exploratory celiotomy or at post-mortem examina- occlusion of the fenestrations by fluid or inflammatory
tion. Definitive pre-mortem diagnosis requires identification debris (Boy & Sweeney 2000).
rioration in cardiopulmonary function. Tension pneu-

Table 46.3. Causes of pneumothorax and
pneumomediastinum mothorax results from a defect in the visceral pleura
(closed tension pneumothorax) or parietal pleura (open
Penetration of the thoracic wall, trachea, esophagus or tension pneumothorax) that acts as a one-way valve. This
diaphragm
permits increasing volumes of air to enter the pleural
Fractured ribs
Blunt external trauma causing tearing of the visceral pleura cavity from the lungs during inspiration, but prevents
Bronchopleural fistula an equal egress of air from the pleural cavity during
Pleuropneumonia and pneumonia exhalation. The intrapleural pressure increases progres-
Wounds of the axilla and ventral neck sively with successive attempts to inhale, until it exceeds
Leaking thoracic drains
that of the atmospheric pressure, and the thorax becomes
Complication of tracheostomy, percutaneous transtracheal
aspiration, lung biopsy, thoracostomy fixed in maximal expansion and effective breathing ceases.
Excessive positive-pressure ventilation in foals (barotrauma) Ventilation–perfusion mismatching and intrapulmonary
Idiopathic (right to left) shunting of blood through the rapidly
collapsing lung cause the PAO2 to decline rapidly. In severely
affected horses, alveolar hypoventilation may lead to
Open versus closed pneumothorax hypercapnia and exacerbate hypoxemia. The increasing
intrapleural pressure displaces the mediastinum towards
Open pneumothorax results from penetrating injuries to the the contralateral side, compromising the function of the
thoracic wall and parietal pleura. Injuries may be accidental contralateral lung and decreasing venous return to
(staking injuries, automobile collisions), malicious (gun- the heart by compressing the large intrathoracic veins.
shots) or iatrogenic (leakage of air through thoracic drains) Rapid cardiopulmonary collapse may ensue.
(Table 46.3). Air is sucked into the pleural cavity through
the defect in the thoracic wall during inhalation, as a result Clinical signs and diagnosis
of the subatmospheric intrapleural pressure. Accumula-
tion of air within the cavity results in loss of the normal Pneumothorax causes variable degrees of respiratory
subatmospheric intrapleural pressure that helps maintains distress, anxiety, sweating, pleurodynia, and thoracic expan-
lung inflation, leading to collapse of the ipsilateral lung. sion. Horses with open pneumothorax usually have an
Thoracic wall defects that are larger than the cross- obvious external wound, especially if a “sucking” sound is
sectional area of the trachea also result in displacement of audible as air enters the thorax during inspiration. Thoracic
the mediastinum towards the contralateral hemithorax. auscultation and percussion may reveal absence of breath
Closed pneumothorax occurs when air enters the pleural sounds and hyperresonance, respectively, over the dorsal
cavity via a route other than a defect in the external thorax. Thoracic radiography and ultrasonography may
thorax. Air may leak through tears in the visceral pleura, help confirm a clinical suspicion of pneumothorax. Thoracic
caused by laceration of the lung by sharp edges of frac- radiographs are best taken during expiration. The dorsal
tured ribs, blunt thoracic trauma such as occurs during margin of the collapsed lung is seen as a horizontal linear
collisions and falls, or barotrauma as the result of excessive opacity lying ventral to the thoracic vertebrae (see Chap-
mechanical ventilation. Air may also enter the pleural ter 10, Fig. 10.22). Radiographs may also reveal under-
cavity via a bronchopleural fistula, which is an abnormal lying causes of pneumothorax including rib fractures or
communication between any part of the bronchial tree and penetrating radiodense foreign bodies. Ultrasonography
the pleural cavity. Bronchopleural fistulae most commonly reveals a static gas reverberation artifact that does not move
result from necrosis and sloughing of subpleural lung with breathing (see Chapter 11, Fig. 11.16). Ancillary diag-
tissue in horses with gangrenous pleuropneumonia, but nostic procedures may not be possible in cases that present
also may occur when lung abscesses or neoplasms erode as acute onset, life-threatening emergencies. In such cases,
through the visceral pleura. Fistulae from terminal airways aspiration of air from the pleural cavity, and the conse-
often heal spontaneously by formation of interpleural quent rapid clinical improvement, confirms the diagnosis.
adhesions, while those involving larger bronchi rarely Once the patient is stabilized, further diagnostic procedures
do so. Closed pneumothorax may also occur as a sequel to can then be performed.
pneumomediastinum (see below).
Management
Simple versus tension pneumothorax
Simple uncomplicated closed pneumothorax without
Simple pneumothorax is self-limiting and non-progressive. dyspnea may be treated conservatively, with stall rest and
Tension pneumothorax, in contrast, leads to progressive, close observation. Air is absorbed from the pleural space,
rapid accumulation of large volumes of air within the albeit slowly, because the venous blood within the pleural
pleural cavity, with resultant rapid life-threatening dete- vessels contains a lower total pressure of dissolved gases
than does the alveolar air or atmospheric air. In humans Antibiotic therapy is indicated for horses with thoracic
with pneumothorax, approximately 1.25% of the air wounds. Pleural lavage (see below) may be indicated in
volume is absorbed daily when patients breathe atmos- horse with penetrating thoracic wounds to minimize
pheric air (Chadha & Cohn 1983). secondary bacterial pleuritis.
Open external wounds should be closed, ideally by
primary closure following local intercostal nerve blocks Pneumomediastinum
and aseptic preparation. In emergency situations, further
ingress of air may be prevented by manual compression Pathogenesis
with a gloved hand or application of a non-porous pressure Pneumomediastinum is the accumulation of gas, usually
pad. Large and complex thoracic defects may require air, within the mediastinum. It often occurs in conjunction
surgical repair under general anesthesia. In these circum- with pneumothorax because of movement of gas between
stances, care must be taken to stabilize patients and remove the two spaces. Pneumomediastinum can occur in horses
air from the pleural cavity before inducing anesthesia. which have tension subcutaneous emphysema as a result
Positive-pressure ventilation of horses with tension pneu- of wounds to the trachea or axilla, or as a rare complica-
mothorax must be performed with care because exacer- tion of transtracheal puncture and tracheostomy (Farrow
bation of the pneumothorax may not be apparent until 1976, Hance & Robertson 1992, Kelly et al 2003). Tension
cardiac arrest occurs. subcutaneous emphysema occurs when air enters through
Air is aspirated from the pleural cavity via a 10-cm a wound that acts as a one-way valve, preventing egress of
blunt teat cannula or 8–10 French catheter inserted in the an equal volume of air. Air then dissects along the subcuta-
dorsal lung field at the level of 13th intercostal space, using neous fascial planes of the neck and into the mediastinum;
a suction apparatus or a large syringe with a three-way thereafter air may pass through the mediastinal pleura into
stopcock. Drainage may be performed intermittently, or the pleural cavity to cause concomitant pneumothorax.
employing a continuous aspiration system with a Heimlich Pneumomediastinum may also result from blunt thoracic
valve (Fig. 46.2) or an underwater seal device, with or trauma. Pneumomediastinum, and concomitant acute bac-
without suction. Bilateral pneumothorax is usually resolved terial mediastinitis, bacterial pleuropneumonia, and pneu-
by aspiration from only one hemithorax. However, in mothorax, may result from perforation of the esophagus.
severe bilateral pneumothorax, and tension pneumothorax, Pneumomediastinum may also result from rupture of alveoli
bilateral tube thoracostomy should be performed. If in horses with pulmonary disorders that lead to air trap-
pneumothorax is the result of leaking thoracostomy tubes ping or emphysema. Air tracks from the ruptured alveoli
or valves, the apparatus should be replaced and suction through the bronchovascular sheaths to the lung hilus and
applied to the new indwelling chest tube and to a drain mediastinum and thereafter into the subcutaneous tissues
inserted into the dorsal pleural cavity. In humans, when a of the dorsum and neck. If the rate of egress of air from the
large volume pneumothorax has persisted for over 24 h, mediastinum into the subcutaneous tissues is insufficient,
rapid evacuation of air from the pleural cavity may occa- the mediastinal pleura may rupture, resulting in con-
sionally induce severe, life-threatening interstitial edema, comitant pneumothorax.
termed “re-expansion pulmonary edema” (Rozenman et al
1996). Consequently slow evacuation using not more than Diagnosis
20 cm water suction pressure is recommended. Ultra-
sonography and radiography can be used to assess restora- Pneumomediastinum per se is rarely life-threatening, but it
tion of lung inflation. Failure of thoracostomy to alleviate may occasionally result in severe respiratory distress and
the respiratory distress should prompt examination for death as the result of acute cardiopulmonary decompen-
concomitant injuries such as fractured ribs or diaphrag- sation. On thoracic radiographs, air in the mediastinum
matic hernia, or continued leakage of air into the pleural outlines structures that are not normally visible, including
cavity. The latter may result from (1) a defect in the visceral the mediastinal blood vessels and esophagus. In contrast,
pleura, (2) iatrogenic lung puncture during insertion of free air surrounding the trachea makes it more difficult to
chest drain, which is rare, (3) leakage around the thora- identify on radiographs. Localized or generalized subcu-
costomy tube or one-way valve, or (4) failure to adequately taneous emphysema is usually readily palpable in horses
close external thoracic wounds. with tension subcutaneous emphysema.
Ancillary treatment is important. Supplemental intra-
nasal oxygen (10–20 ml·kg–1·min–1 or 5–10 liters/min) Management
should be provided if available as it helps reduce hypox- The treatment of pneumomediastinum is largely deter-
emia and aids absorption of air from the pleural cavity, mined by the primary cause. External wounds, such as
by washing out nitrogen from the blood (Chadha & Cohn tracheal perforations, should be closed. Concomitant pneu-
1983). Horses with pleurodynia should receive analgesia mothorax should be managed with a tube thoracostomy.
to minimize chest splinting and its detrimental sequelae. Stall rest should be provided.
Fig. 46.2. (A) Various indwelling chest tubes;

(B) placement of a 24 French blunt catheter
with a condom one-way valve; (C) an indwell-
ing chest catheter with a Heimlich valve.
C
monia. There is no specific treatment. Horses should be

Table 46.4. Causes of hemothorax
rested in a quiet environment. Antibiotics may be adminis-
Trauma (blunt and penetrating) tered to counteract secondary bacterial infection, which is a
Complication of lung biopsy common sequel. Analgesics should be administered to reduce
Coagulopathy
pleurodynia. Bronchodilators may aid clearance of blood
Rupture of a major vessel or aneurysm
Bleeding tumors, especially hemangiosarcoma and exudate from the airways. As contused lung is suscep-
Abscess tible to developing edema and exacerbation of ventilation–
Pulmonary infarction perfusion mismatching following crystalloid infusions, fluid
replacement should be performed cautiously.
Pleural Effusion
Hemothorax
Pathogenesis
Hemothorax is rare in horses, but may be caused by
various disorders (Table 46.4). Horses with acute intra- The pleural cavity is a potential space that normally
pleural hemorrhage are likely to present with hemorrhagic contains only a small volume of clear to slightly turbid
shock rather than with respiratory failure. This is because yellowish, non-clotting pleural fluid. Tight regulation of
the volume of blood loss that causes death as a result of the volume and composition of pleural fluid is essential
acute hemorrhagic shock (approximately 15 liters for for efficient mechanical coupling between the lung and
a 500-kg horse) is insufficient to cause life-threatening chest wall. This mechanical coupling facilitates instan-
pulmonary tamponade. Thus the prime therapeutic con- taneous transmission of forces of breathing, which are
sideration is replacement of blood volume. The underlying applied perpendicularly to the pleural surface, while simul-
cause of the hemothorax should also be sought, because taneously providing lubrication to enable frictionless
this is an important determinant of subsequent case movement between the two pleural surfaces in response
management. Whether it is beneficial to drain free blood to shear stresses. In the normal horse, pleural fluid is pro-
from the pleural cavity is unclear, as there are insufficient duced by a net filtration pressure gradient through the
data in the literature to answer this question. Some case parietal pleura, while it is absorbed by a net absorptive
reports indicate that hemothorax may resolve successfully pressure gradient through the visceral pleura. These pres-
without thoracostomy (Perkins et al 1999). In these cases, sure gradients are, in part defined by the Starling–Landis
rapid autotransfusion of blood from the pleural cavity via equation (see Chapter 43). Pleural fluid is also resorbed by
the pleural lymphatics may have led to rapid resolution electrolyte-coupled liquid absorption through mesothe-
of hemothorax. However, other authors state that free lial cells in both pleurae, and by vesicular transport of
blood should be drained (Laverty et al 1996). Drainage liquid associated with protein transocytosis (Zocchi 2002).
of blood may be beneficial because it facilitates pulmonary Pleural fluid, protein, and cells are also absorbed by lym-
re-expansion, which may arrest hemorrhage arising from phatic drainage through numerous stomata present in the
the low-pressure pulmonary parenchymal vessels. Further- parietal pleura. Pleural effusions occur when fluid is
more, free blood left within the pleural cavity represents an produced at a rate faster than it is removed; there are five
ideal culture medium for bacteria, and, in humans, may general mechanisms by which this may occur:
lead to fibrous pleurisy and permanent impairment of lung
● increased transpleural hydrostatic pressure gradient (e.g.
expansion. To date, there are no reports of fibrous pleurisy
congestive cardiac failure)
as a sequel to hemothorax in the horse. Disadvantages of
● decreased colloid osmotic pressure (e.g. hypopro-
tube thoracotomy include iatrogenic introduction of micro-
teinemia)
organisms into the pleural cavity, injury to the lung or
● impaired lymphatic drainage (e.g. obstruction by
heart, and disruption of blood clots causing recurrence of
neoplasm)
bleeding from a pleural defect (Perkins et al 1999).
● increased vascular permeability (e.g. inflammation)
● excessive volumes of peritoneal fluid may pass via
Pulmonary Contusion diaphragmatic lymphatics or diaphragmatic defects into
the pleural cavity.
Lung contusion results from blunt trauma to the thorax
when the glottis is closed (e.g. automobile collisions and The first two mechanisms produce a bilateral pleural
horses falling at jumps). It may occur in conjunction transudate or modified transudate. If congestive heart
with other traumatic thoracic injuries. If severe, it carries failure is present, there may also be tachycardia, abnormal
a poor prognosis because it causes a rapid ventilation– jugular distension, and ventral edema. The third and
perfusion mismatch and has life-threatening sequelae fourth mechanisms will produce unilateral or bilateral
including hemorrhagic, infarctive, and gangrenous pneu- pleural exudates. The last mechanism will produce either a
Table 46.5. Causes of pleural effusion Table 46.6. Normal constituents of equine
pleural fluid
Pleural infections (pleuropneumonia; bacterial, mycoplasma,
viral or fungal) Appearance clear to slightly turbid, yellowish,
Thoracic neoplasia non-clotting fluid
Penetration of chest wall, esophagus, or diaphragm
Thoracic trauma Cells < 10 × 109/liter, with approximately 32–90%
Extension of peritoneal effusion neutrophils, 5–66% mononuclear/meso-
Liver disease thelial type cells, 0–16% lymphocytes and
Congestive heart failure 0–0.5% eosinophils
Hypoproteinemia
Total protein < 35 g/l
Diaphragmatic hernia
Pulmonary hydatidosis pH similar to blood pH
Pulmonary granulomas
Idiopathic Glucose > 2 mmol/l
Bacteriologically sterile
Adapted from Brobst & Parry 1987, with permission.
transudate or exudate, depending on the nature of the

peritoneal fluid. Some disorders may produce effusion via
several of the aforementioned mechanisms. For example, Treatment
thoracic neoplasia may cause pleural effusion by (1)
obstruction of lymphatics or mediastinal lymph nodes, (2) Treatment of pleural effusions is directed at the under-
increased hydrostatic pressure as a result of venous lying cause, and at drainage of pleural fluid to improve
obstruction, and (3) increased permeability because of ventilation (see below). In human medicine, persistent or
inflammation around neoplasms. recurrent pleural effusions that are caused by primary
Some of the numerous causes of pleural effusion are lesions for which there is no effective treatment may
listed in Table 46.5. Approximately two-thirds of all pleural be managed using chemical pleurodesis. This involves
effusions in North American horses are the result of pleuro- instillation of irritants such as tetracycline or talc to
pneumonia, pneumonia or lung abscesses (Raphel & Beech produce adhesions between the visceral and parietal
1981), while in the UK approximately 60% of pleural effu- pleurae to reduce the dead space. While this procedure may
sions are associated with neoplasia (Mair 1987). be considered for horses (Ainsworth & Hackett 2004),
welfare implications mean that selection of cases is critical.
Clinical signs For example, it is not an appropriate option for horses in
the terminal stages of thoracic neoplasia. Furthermore,
Horses with small volumes of pleural effusion may be in humans it causes significant pleurodynia and may
asymptomatic, while large volumes may cause respiratory initially exacerbate pleural effusion. Clinicians considering
distress. Exudates are associated with pleurodynia. Cough- performing pleurodesis should consult a detailed medical
ing is rarely the result of pleural effusion, and is more likely text (Lee & Light 2004).
to be attributable to underlying pulmonary disease.
Chylothorax
Investigation
Chylothorax, the accumulation of chyle within the pleural
The cause of the pleural effusion should be determined, cavity, is rarely reported in horses (Mair et al 1988,
where possible, by signalment and case history, clinical Schumacher et al 1989, Brink et al 1996, Scarratt et al
examination, pleural fluid analysis, radiography, ultra- 1997). Chylothorax results from a leak in the thoracic
sonography, and pleuroscopy. Thoracocentesis should be duct, which drains lymph from the gastrointestinal tract,
performed in all horses with suspected pleural effusion, liver, abdominal wall, and hind limbs. Chyle has a high
to confirm the presence of pleural effusion, to improve protein content and contains predominantly lymphocytes.
ventilation, to remove inflammatory debris, toxins and Chyle from suckling foals has a high chylomicron content,
bacteria, and to obtain samples for laboratory analysis. which imparts a characteristic milky opacity, while chyle
Thoracocentesis is a relatively simple and safe technique. from adults has a lower chylomicron content and may
Normal horses have small volumes of clear to slightly consequently lack a milky appearance (Brink et al 1996).
turbid, yellowish, non-clotting pleural fluid (Table 46.6). The underlying disorders associated with chylothorax
Detailed information on the collection, processing, and include congenital diaphragmatic hernia, meconium impac-
analysis of pleural fluid is presented in Chapter 9. tion, neoplasia, and idiopathic causes. Differentiation of
chylothorax from pseudochylous effusion that results from range of aerobic and anaerobic bacteria are involved, most
severe chronic inflammatory processes is discussed in of which are commensals of the oropharynx (Sweeney et al
Chapter 9. Management of chylothorax is reported infre- 1985, 1991, Mair & Lane 1989, Byars & Becht 1991,
quently in horses, but may include thoracic drainage, Chaffin & Carter 1993). Common aerobic isolates include
restricted exercise, low-fat diets, and ligation of the thoracic β-hemolytic streptococci, Pasteurella spp., Escherichia coli,
duct. Prognosis is guarded. Klebsiella pneumoniae, Enterobacter spp., and Actinobacillus
spp. Common anaerobic isolates include Clostridium spp.,
Fusobacterium spp., Peptostreptococcus spp., and Bacteroides spp.
Pleuropneumonia Anaerobic bacteria are most commonly associated with
Etiopathogenesis disease of more than 5–7 days’ duration (Sweeney et al
1991), and their presence is associated with a poor prog-
Pleuropneumonia most commonly occurs in conjunction nosis (Sweeney et al 1985), in part because it suggests that
with bacterial pneumonia and lung abscesses (Table 46.7). substantial tissue damage has occurred to convert the
Thus the risk factors for pleuropneumonia are similar to normal aerobic environment of the lung to an anaerobic
those for pneumonia, and include factors that: environment. Polymicrobial infections, and mixed aerobic
and anaerobic infections, are more common than single
● cause aspiration of oropharyngeal bacteria
isolates. Viruses (African horse sickness, equine infectious
● inhibit clearance of secretions from the lower airways
anemia), mycoplasmas (Mycoplasma felis), fungi (Coccidioides
● compromise pulmonary defense mechanisms.
immitis, Cryptococcus neoformans) and hydatid cysts are less
Risk factors include long-distance transportation common causes of pleuropneumonia. Carr et al (1997)
(> 800 km), strenuous exercise, general anesthesia and reported 21 horses which had suppurative hemorrhagic
surgical procedures, respiratory viral infections, corti- pleural effusion associated with hemorrhagic pulmonary
costeroid therapy, disorders of the upper airway, exercise- infarction, necrotizing pneumonia, and, in some cases, pul-
induced pulmonary hemorrhage, systemic diseases, and monary thromboembolism. This etiology of this syndrome
dysphagia (Chaffin & Carter 1993, Austin et al 1995, was not determined, but many cases followed strenuous
Raidal 1995, Raidal et al 1995, Racklyeft et al 2000). exercise and the pathology resembled that of porcine
Long-distance transportation is the single most important Actinobacillus pleuropneumoniae infection. Actinobacillus spp.
risk factor because prolonged head elevation prevents and Streptococcus equi var. zooepidemicus were cultured from
postural drainage of respiratory secretions, and facilitates some affected horses. This syndrome had a poorer prognosis
aspiration of upper respiratory tract bacteria into the than conventional pleuropneumonia.
lower airways. This leads to accumulation of purulent Three phases are recognized in the pathogenesis of
respiratory secretions within the distal airways (Raidal et al equine pleuropneumonia (Chaffin & Carter 1993):
1997a). In addition, long-distance transportation is immu-
nosuppressive. It may also expose horses to environments ● Exudative phase – initially bacteria colonize the periph-
that have poor air hygiene, resulting in inhalation of eral lung, causing localized pneumonia and/or pul-
bacteria and pro-inflammatory agents. Strenuous exercise monary micro-abscessation. There is a predilection for
is also a risk factor because it is immunosuppressive involvement of the ventral aspects of the cranial lung
and because it results in inhalation of particulates from lobes and the cranial aspects of the caudal lung lobes,
the racetrack and aspiration of oropharyngeal secretions especially on the right side, consistent with aspiration
deep into the lung. Consequently, even a single episode of being the major route of infection. Extension of the
strenuous exercise significantly increases the numbers of inflammatory response to the contiguous visceral pleura
aerobic and anaerobic bacteria within the lower airway increases the permeability of the capillaries within
(Raidal et al 1997b). Pleuropneumonia most commonly the visceral pleura, leading to production of a sterile,
affects younger horses, 1–5 years old, associated with active protein-rich inflammatory parapneumonic effusion.
competition and frequent long-distance transport. A wide Parenchymal damage predisposes to secondary coloniza-
tion with anaerobes. Systemic antibiotic therapy alone
may be effective at this early stage.
Table 46.7. Causes of pleuropneumonia
● Fibrinopurulent phase – direct extension of bacterial
infection into the pleural cavity causes production of
Extension of pneumonia or lung abscess large volumes (up to 80 liters) of septic fibrinopurulent
Penetrating and blunt thoracic injury
exudate. Large quantities of fibrin cover the pleural
Penetrating injuries of the esophagus or diaphragm
Systemic spread (bacteremia or septicemia)
surfaces, producing a complex network of fibrin strands
Pulmonary hydatidosis and loculi.
Neoplasia ● Organization phase – organization of fibrin into fibrous
tissue results in a thick “pleural peel” that limits thoracic
expansion and may lead to interpleural adhesions. The sequelae such as fibrin deposition, loculi formation, pleural
residual pleural exudate, containing inflammatory adhesions, and pneumothorax, and select the optimal site
and necrotic debris, may become more viscous to pro- for thoracocentesis (Rantanen et al 1981, Reimer et al
duce a pleural empyema. There may be significant lung 1989, Chaffin et al 1994b). Gas echoes in the pleural
necrosis and bronchopleural fistulae may develop. effusion have been described with anaerobic infections,
gangrenous pneumonia, bronchopleural fistulae, and
Clinical signs iatrogenic leakage or air during thoracocentesis. Ultra-
sound can also detect concurrent cardiopulmonary lesions,
The clinical signs of pleuropneumonia are variable. such as pulmonary consolidation (hepatization), compres-
Affected horses are commonly “sick” (i.e. depressed, sion atelectasis, abscesses, infarction and pericardial
anorexic, febrile), in contrast to horses with recurrent effusions (Fig. 46.3).
airway obstruction. Additional signs include lethargy,
anorexia, pyrexia, tachycardia, tachypnea, various degrees Thoracic radiography
of respiratory distress, elbow abduction, and ventral
Radiography is diagnostic of pleural effusion whenever a
edema. Nasal discharge may be absent, or may be muco-
fluid line is noted that obliterates the normally distinct
purulent, purulent or serosanguineous. Malodorous breath
heart shadow and caudal vena cava (Chapter 10, Fig. 10.20).
and fetid nasal discharge may suggest anaerobic infection
However, radiography does not readily permit identification
or tissue necrosis, and is consequently a poor prognostic
of the affected hemithorax, assessment of the character of
sign. Mucous membranes may appear normal, cyanotic or
the fluid, or evaluation of the ventral lung field deep to the
toxic. Pleurodynia (thoracic pain) is common and often
fluid. Radiography, ideally performed after thoracocentesis,
severe, resulting in an anxious facial expression, a fast
may allow evaluation of the mid and dorsal lung fields
shallow breathing pattern, stilted gait, reluctance to
for the presence of underlying disorders such as abscesses
turn in tight circles and to lie down, a characteristic soft
and neoplasms. Radiography may identify lesions within
suppressed cough, expiratory grunting, especially during
the axial lung fields, which cannot be identified by ultra-
palpation of the chest, and forelimb pointing. Forced
sonography. Thoracic radiography is fully discussed in
rebreathing is contraindicated in horses with pleurodynia.
Chapter 10.
Clinicians must be careful not to mistake pleurodynia
for colic because this is likely to lead to inappropriate
diagnostic evaluation and treatment. The occurrence of Thoracocentesis and transtracheal aspirate
secondary constipation and ileus in horses with pleuro- Thoracocentesis is essential to confirm a diagnosis of
dynia may confound this error. Pleuropneumonia may also pleuropneumonia, and to provide samples for cytological,
be mistaken for laminitis, rhabdomyolysis (Chaffin et al biochemical, and microbiological testing (laboratory evalu-
1994a) or hypocalcemia. ation is discussed in Chapter 9). Diagnostic microbiology
Auscultation reveals absence of lung sounds over the is often pivotal to the case outcome, by providing data to
ventral thorax, and increased lung sounds, with or without guide appropriate antimicrobial selection. Ideally, anti-
adventitious sounds, in the dorsal lung fields. Horses with biotics should be withheld for a minimum of 24 h before
exudates within the large airways commonly have coarse microbiological sampling. Bacterial culture of both pleural
crackles audible over the distal cervical trachea. Cardiac fluid and transtracheal aspirates will optimize detection of
sounds may be transmitted more dorsally than normal. organisms associated with pleuropneumonia.
Pleural friction rubs are rarely present in acute cases but
may be audible in chronic patients. Percussion will reveal Pleuroscopy
dullness over the ventral thorax and may elicit coughing
Pleuroscopy is rarely warranted in cases of acute pleuro-
and evidence of pleurodynia. Patients with cardiovascular
pneumonia. However, it may provide additional informa-
compromise may have tachycardia, jugular distension, and
tion regarding sequelae such as fibrin deposition, loculi
toxic mucous membranes.
formation, pleural adhesions, bronchopleural fistulae, and
lung abscesses. Pleuroscopy is discussed in Chapter 20.
Diagnosis and investigation
of pleuropneumonia
Hematology and biochemistry
Ultrasonographic examination Horses with acute pleuropneumonia commonly have
Ultrasonography is the best diagnostic modality for detect- an inflammatory hematological profile, i.e. leukocytosis,
ing and evaluating suspected pleural disease (Chapter 11). neutrophilia, possibly with a left shift and toxic neutrophils,
Ultrasonography can be used to assess the nature of pleural hyperfibrinogenemia, hyperglobulinemia, and hypoalbu-
fluid (echodense, echolucent, gas echoes), volume of fluid, minemia. Patients with advanced disease may have a toxic
determine whether it is unilateral or bilateral, identify neutropenia, hypoproteinemia, and hemoconcentration.
A C
B D
Fig. 46.3. Ultrasound images from horses with pleuropneumonia: fibrinous pleuropneumonia; (C) hepatized lung – note intrapulmonary
(A) pleural effusion outlining the ventral border of the free-floating lung air trapping and outline of an airway; (D) pleural abscess formation
with diaphragm and spleen to the right of the image; (B) loculated secondary to pleuropneumonia.
Antibiotic therapy
Treatment of pleuropneumonia
Administration of antibiotics to which the causal
A successful case outcome is dependent on early recog- organism(s) are sensitive is essential for patient survival.
nition and prompt initiation of appropriate treatment. Transtracheal aspirates and pleural fluid should be
Ideally treatment should be commenced within 48 h of a cultured to provide retrospective antimicrobial sensitivity
predisposing event to prevent significant bacterial invasion data. Empirical therapy should be commenced immediately,
of pulmonary parenchyma (Raidal 1995). Treatment is while awaiting culture and sensitivity data. Analysis of
usually prolonged and is determined by the degree of car- Gram-stained smears of these samples may provide data to
diopulmonary compromise evident at the time of diagnosis guide selection of an empirical antibiotic regimen. Suitable
and by the development of sequelae during the course of empirical combinations should be effective against many of
treatment. Treatment involves: the bacteria that cause pleuropneumonia and include
penicillin, gentamicin, and metronidazole, or ceftiofur and
● prompt administration of systemic, broad-spectrum, metronidazole. Selection of antimicrobials for long-term
bactericidal antibiotics therapy, such as metronidazole or potentiated sulfonamides,
● drainage of pleural effusion should be based on the sensitivity of the most recent
● ancillary treatments isolates. It is important to recognize that most antibiotics
● prompt recognition and appropriate treatment of are ineffective in the presence of exudates because of
sequelae. inhibitory effects of components of purulent secretions,
changes in pH, or volume dilution of the drug to non- ● hypovolemia and collapse if fluid is removed too rapidly
therapeutic levels. It is therefore essential to drain thoracic ● local cellulitis
fluid in patients with significant volumes of pleural fluid. ● pneumothorax
● cardiac dysrhythmia
● cardiac, pulmonary or diaphragmatic laceration.
Pleural drainage
Pleural drainage should be performed to improve ventila-
tion and remove microorganisms, toxins, inflammatory Pleural lavage
mediators, and inflammatory debris. It may be performed This may be of benefit in selected cases to aid removal of
intermittently or continuously, depending upon the degree tenacious exudate, bacteria, toxins, fibrin, and inflamma-
of patient compromise, and the volume and nature of the tory debris. It should be performed early in the disease
fluid. Continuous drainage, via an indwelling chest tube, course, before the development of fibrin loculi and adhe-
is indicated in most patients with pleuropneumonia, sions, which would otherwise limit its value. Between 5
especially those with suspected anaerobic infections and and 20 liters of warmed sterile saline are instilled via an
those in which intermittent drainage is relatively ineffec- ingress catheter into the dorsal pleural cavity, and the fluid
tive. Intermittent drainage is reserved for horses with small is removed via an egress catheter inserted in the ventral
volumes (< 5 liters) of fluid. A 24 French blunt thoracos- pleural cavity. It is rarely possible to recover the full volume
tomy tube is recommended for most patients including of the instilled fluid. This technique is probably contra-
foals, as smaller diameter tubes such as teat cannulae often indicated in horses with patent bronchopleural fistulae
become occluded by inflammatory debris (Fig. 46.2). The as the lavage fluid will enter the airways, further com-
optimal site is ideally defined by ultrasound evaluation, promising lung function and also inducing coughing.
but the sixth or seventh intercostal space is usually suit-
able. It is not essential to select the most ventral site for
tube insertion because lung expansion usually moves the Thoracotomy
fluid towards the internal tube opening. Standing thoracotomy is indicated for horses with large
The site is surgically prepared and local anesthetic quantities of thickened, organized fibrinopurulent debris
(6–10 ml) is infiltrated from the skin to the sensitive or empyema, especially those with fetid contents that
parietal pleura. A stab incision is made with a no.10 scalpel cannot be removed by conventional pleural drainage
through the skin, and enlarged slightly to accommodate and lavage (Grant 1997). Patient selection is critical for
the chest tube and trocar. The tube is inserted directly a successful outcome (Chaffin et al 1994b). It is of most
between the ribs. Subcutaneous tunneling is not recom- benefit for horses with large, persistent, unilateral local-
mended as this may lead to kinking and occlusion of the ized pockets of thick, inspissated debris following reso-
drain. As the insertion of large-bore chest drains through lution of the disease in the contralateral hemithorax.
the intercostal muscles requires considerable force, care The disease should be confined to one hemithorax or
must be taken to prevent advancing the drain too deeply walled off from the remainder of the ipsilateral hemi-
when the resistance suddenly decreases as the tube thorax. The mediastinum must be complete, or a visceral
enters the pleural cavity. The tube is inserted to a depth of to parietal adhesion must seal off the abscess cavity
approximately 8 cm, and anchored to the skin with a from the surrounding ipsilateral pleural cavity. Prior to
suture attached through “dog-eared” adhesive tape or by thoracotomy the area is fully investigated using ultra-
a pursestring suture to prevent slippage. The external sonography. A large-bore open thoracic drain is inserted
opening of the tube is connected to a one-way valve to into the lesion and the patient is monitored for 2 h; if this
prevent air aspiration when fluid drainage is complete is well tolerated without development of unilateral or
(Fig. 46.2). A Heimlich valve, or a condom or a finger of a bilateral pneumothorax, it indicates that the lesion is
surgical glove with the closed end cut off, will suffice walled off from the remainder of the pleural cavity. The
(Fig. 46.2). For horses with bilateral effusions, bilateral onset of respiratory distress indicates development of
indwelling tubes are placed only if drainage via a unilateral pneumothorax and contraindicates the procedure. The
drain does not effectively drain both hemithoraces. Rapid surgical site is prepared and infiltrated with local anes-
removal of large volumes of pleural fluid should be avoided thetic. A vertical incision, capable of allowing either finger
to prevent hypovolemia. Indwelling tubes should be or hand insertion, is made into the thorax, usually at the
monitored regularly and can be kept in place as long as seventh or eighth intercostal space, from the level of the
they are productive. Tubes should be removed when non- lateral thoracic vein to the ventral border of the latissimus
productive or if a painful local cellulitis ensues. Complica- dorsi. This allows removal of all accessible necrotic tissue
tions of chest drainage are uncommon but include: and fibrin by both lavage and manual extraction using
appropriate forceps. It is not necessary to remove all fibrin Medical treatment of cranial thoracic masses, includ-
at this stage, as residues will be removed by flushing over ing antibiotics, diuretics, digoxin, and anti-inflammatory
the following days (Grant 1997). The pleural cavity is then drugs, is effective for some horses. Surgical drainage may
lavaged with warmed 1% povidone iodine solution. The be required for horses that are unresponsive to medical
contralateral pleural cavity is monitored for pneumo- therapy. Drainage is usually performed on the standing
thorax, which is managed by tube thoracostomy if sedated horse, or less commonly under short-duration
required. The incision is left open and debris is removed general anesthesia. The horse’s right foreleg is held for-
daily both manually and by flushing until granula- ward and a large-bore trocar and catheter are inserted
tion tissue closes the thoracic wound. Alternatively a rib under ultrasound guidance into the mass to permit suc-
resection or large thoracotomy may be performed to pro- tion and lavage. Alternatively a laparoscope may be used
vide even greater access to the pleural cavity. These last to penetrate the abscess; this facilitates visualization
procedures, however, have increased postoperative mor- of each tissue layer as it is penetrated, thereby allow-
bidity and usually preclude return of the horse to athletic ing safe introduction of the trocar (Fischer 2002). The
function (Shearer et al 1986, Chaffin et al 1994b, Grant decrease in volume of the mass postoperatively should
1997). A loss of thoracic compliance compromises future result in rapid resolution of the clinical signs of heart
athletic performance in all cases. failure. Drainage is best performed as a single procedure;
indwelling tubes are not recommended because the
Ancillary treatments triceps musculature causes crimping and occlusion of
the catheter and stimulation of the heart by the catheter
Supplemental oxygen may be administered to horses with
may cause dysrhythmias (Byars et al 1991). Repeated
significant hypoxemia, provided the procedure is well
drainage may be required if the mass recurs.
tolerated. Analgesia is indicated to alleviate pleurodynia.
Fluid and plasma therapy may be required in horses
with acute pleuropneumonia, to counteract significant Extrapulmonary abscesses
losses of fluid and protein into the pleural space. The Extrapulmonary (pleural) abscesses may require surgical
effects of toxemia may be minimized by administration of drainage when antibiotic therapy alone is ineffective
flunixin, hyperimmune plasma, colloids, and pentoxifylline. because of the thick capsule and large volume of exudate
and necrotic debris. They are usually amenable to percu-
taneous drainage via a large-bore (no. 20F to 40F) chest
Complications of pleuropneumonia
tube, inserted under ultrasonographic guidance. The sharp
Byars et al (1991) and Byars & Becht (1991) described tip is thrust through the capsule without pushing the
a variety of serious sequelae in horses with infectious lesion away from the chest wall and causing leakage of
pleuropneumonia, including cranial thoracic masses (7.2% exudate into the thoracic cavity. Both suction and lavage
of horses), bronchopleural fistulae (6.5%), pericarditis are employed while moving the tube in and out to break
(2.6%), and laminitis (1.3%). Resolution of many of these up the debris. As the abscess is walled off from the rest of
complications necessitates invasive intervention. Other the pleural cavity, a one-way valve is usually not required.
sequelae include pleural adhesions (Chapter 11, Fig. 11.8), Antibiotics are administered, based on culture of the exudate.
pleural empyema, pneumothorax, catheter-associated jugu- Anaerobic infections are often present and the necrotic
lar thrombophlebitis, disseminated intravascular coagula- debris is often fetid.
tion, colitis, and colic.
Pleural empyema
Cranial thoracic masses (abscesses) Accumulation of tenacious pus within the pleural cavity
The heart may act as a ball valve to trap effusion and commonly necessitates thoracotomy.
inflammatory debris in the cranial thorax. Organization of
this material may result in cranial thoracic masses Bronchopleural fistula
including encapsulated abscesses and pockets of empyema These develop when gangrenous pneumonia, abscesses or
(Byars et al 1991). Cranial thoracic masses can produce neoplasms cause necrosis of peripheral lung tissue and lead
subtle clinical signs or cause tachycardia, jugular pulsation to direct communication between the pleural cavity and
and ventral edema as a result of heart failure because the airways. Diagnosis is confirmed by pleuroscopy or by
of compression of the great vessels. Forelimb “pointing” instillation of fluorescein dye (from sterile ophthalmic
may occur in the absence of laminitis. The diagnosis strips) into the pleural cavity, followed by observation of
is confirmed by ultrasonographic imaging of the mass in dye at the external nares or within the trachea. During
the cranial thorax. It may be necessary to pull the right pleural lavage patients with bronchopleural fistulae will
forelimb forward to image this region. often cough vigorously because the lavage fluid can pass
from the pleural cavity into the airways. Fistulae com-

Mediastinal Masses
monly spontaneously seal because of adhesion develop-
ment between the adjacent visceral and parietal pleurae, These relatively uncommon lesions include abscesses,
following resolution of the underlying lesion, although this neoplasia, and lymphadenopathy. Mediastinal abscesses are
process may take several months. Partial pneumonectomy relatively uncommon but can result from esophageal rup-
has been used successfully to treat a bronchopleural fistula ture or chronic lymph node infection, particularly with
and pulmonary abscess in a filly (Sanchez et al 2002). Streptococcus equi subsp. equi (bastard strangles). Thoracic
neoplasia is reviewed in Chapter 43. Clinical signs of medi-
Pneumothorax astinal masses reflect compression of the trachea or larger
bronchi (respiratory distress, wheezing), esophagus (regur-
Pneumothorax develops in horses with pleuropneumonia
gitation), airways (cough) or large thoracic veins and
as a result of a bronchopleural fistula or air leaking around
lymphatics (head and neck edema, jugular vein distension).
thoracic drains, or via the site of thoracocentesis, thora-
Horner syndrome may reflect dysfunction of the sympa-
cotomy or transtracheal puncture.
thetic innervation to the head. Diagnosis is made prin-
cipally by thoracic radiography, ultrasonography, and
Laminitis endoscopy. Ultrasonographic examination is restricted to
Laminitis is a relatively infrequent complication of pleuro- the cranial mediastinum, because air-filled lung reflects
pneumonia. The onset may be subtle and the forelimb ultrasound and precludes examination of the central
involvement is frequently asymmetrical; consequently it and caudal mediastinum. Endoscopy of the esophagus or
may be mistaken for pleurodynia. The “sinker syndrome” is trachea may reveal a compressive mass. Treatment will be
often encountered and hoof separation at the coronary dependent on the nature of the mass. Antibiotic therapy
band may eventually result in the patient being subjected and drainage of accessible abscesses may be indicated.
to humane euthanasia.
Colic Neuromuscular Disorders Which

Colic is a common complication of pleuropneumonia. It is Compromise Breathing
most often associated with ileus, and production of scant
Neuromuscular disorders which cause paresis, paralysis or
dry feces. It may result from anorexia, dehydration, pleuro-
spasm of the intercostal muscles and diaphragm can
dynia, and the lack of effective thoracic compression for
compromise the horse’s ability to breathe (Tables 46.8 and
defecation.
46.9). Horses with botulism in particular may die from
respiratory failure as a result of flaccid paralysis of the res-
Prognosis of pleuropneumonia piratory muscles. The clinician should therefore be aware
that horses with botulism are unable to maintain an
The prognosis is generally favorable, with survival rates increased depth and rate of breathing because of flaccid
ranging from 48 to 98% in horses receiving prompt and paralysis of respiratory muscles and diaphragm. Conse-
aggressive treatment (Raphel & Beech 1982, Byars & Becht quently, increased respiratory effort will not herald the
1991, Seltzer & Byars 1996). Complicated sequelae such as
cranial thoracic masses, multiple abscesses, and broncho-
pleural fistula are associated with decreased survival (Byars
& Becht 1991). The prognosis for future athletic perform-
Table 46.8. Neuromuscular disorders which
ance can also be considered fairly good, with the excep-
compromise breathing
tion of those that have complicated sequelae (Reef 1990).
Indeed Seltzer & Byars (1996) reported that 61% of Disorders of the neuromuscular junctions
thoroughbreds raced after recovery from uncomplicated Botulism
infectious pleuropneumonia, with 56% of these horses Disorders which cause myodegeneration of respiratory
muscles
winning at least once.
Atypical myoglobinuria
Nutritional myodegeneration
Ionophore toxicity
Pleural Fibrosis and Neoplasia Disorders which cause tetany of breathing muscles
Tetanus
Pleural fibrosis and neoplasia are described in Chapter 43. Miscellaneous disorders
Pulmonary neoplasia may occasionally cause hypertrophic Diaphragmatic muscle paralysis
osteopathy (Fig. 46.4).
A B
Fig. 46.4. (A) A 14-year-old Appaloosa gelding with hypertrophic osteopathy; (B) post-mortem specimen of proximal phalanx from the
same horse.
onset of respiratory failure, as it does in disorders such as chloride, magnesium, and bicarbonate, make the phrenic
recurrent airway obstruction. Instead, the first sign of nerve sensitive to the depolarizing electrical activity of the
respiratory failure may be cyanosis. Mechanical ventilation adjacent myocardium. The involuntary diaphragmatic
and oxygen supplementation are indicated in horses with contraction and resultant “thump” are thus synchronous
respiratory paralysis caused by botulism. Myodegeneration with the heartbeat and not with the breathing cycle.
of intercostal and diaphragmatic muscles occurring in Synchronous diaphragmatic flutter is most commonly
atypical myoglobinuria, nutritional myodegeneration, and associated with exhaustive exercise including racing and
ionophore toxicity may lead to respiratory dysfunction. endurance rides, and with hypocalcemic syndromes such
Bilateral idiopathic diaphragmatic paralysis can result in as lactational tetany, transport tetany, cantharidin (blister
significant hypoventilation, paradoxical breathing and beetle) toxicity, and idiopathic hypocalcemia. Diagnosis
respiratory failure (Amory et al 1994). is straightforward because of the pathognomonic clinical
signs, with laboratory confirmation being made by elec-
trolyte analysis, including assessment of total and ionized
calcium and magnesium levels.
Synchronous Diaphragmatic Treatment consists of parenteral administration of
Flutter (“Thumps”) calcium and occasionally chloride solutions. The response
“Thumps” produced by unilateral or bilateral contraction to treatment is usually rapid, thus supporting the diag-
of the diaphragm may be heard or palpated over the thorax nosis. The prognosis is considered favorable, although a
and flanks in horses with synchronous diaphragmatic rest period of 7–10 days is often indicated. Supplementa-
flutter. It is probable that acid–base and electrolyte dis- tion of electrolytes either in the feed or in the water may
turbances, and in particular disturbances of calcium, prevent this condition in endurance horses.
Table 46.9. Summary of features that may aid differentiation of neuromuscular

disorders that can compromise breathing
Signalment Clinical signs Diagnostic aids
Botulism Ingestion of contaminated food Diffuse myasthenia. Variable Definitive diagnosis rarely
including silage. Foals grazing autonomic signs including ileus, achieved. Diagnosis supported by
pastures which harbor spores. constipation and megaesophagus detection of toxin in fresh food,
Rarely toxicoinfection from serum and feces, or culture of
wounds. Outbreaks possible organism from feces or food. False
positives and negatives occur.
EMG findings are supportive
Atypical Typically affects horses and Stiff, stilted gait. Variable muscle Markedly elevated muscle
myoglobinuria ponies that are grazing poor pain, distress, sweating, tachycardia, enzymes. Myoglobinuria.
quality pasture, with no tachypnea. Myoglobinuria. Many Histopathology of muscle biopsies
supplementary feeding and horses are alert, responsive and have
no exercise. Outbreaks may normal appetite. Variable ileus,
occur dysphagia and urinary retention
Nutritional Regions with selenium-deficient Stiff, stilted gait. Firm, swollen, Markedly elevated muscle
myodegeneration soils. Mainly foals < 1 year old. painful muscles. Myoglobinuria. enzymes. Myoglobinuria. Low
(subacute skeletal Group outbreaks may occur Variable distress, sweating, erythrocyte glutathione peroxidase
form) dysphagia, tachycardia and activity. Low blood and tissue
tachypnea selenium and possibly low blood
and tissue vitamin E
Acute ionophore Ingestion of ionophores such as Acute toxicity causes muscular Detection of monensin in feed or
toxicity monensin. Outbreaks may occur weakness, hypovolemic shock and stomach contents. Markedly
hemolysis. Possible generalized elevated muscle enzymes.
sweating, ataxia, myoglobinuria, Myoglobinuria
cardiac dysrhythmias, ileus, colic,
diarrhea, dyspnea and sudden death
Tetanus Unvaccinated horses, usually Tetany of skeletal muscles, stiff gait, None
with puncture wound “rocking horse stance”, raised tail
head, anxious facial expression, ileus,
third eyelid flicks across during
menace response. Progresses to
recumbency and opisthotonus
Adapted from McGorum 2003, with permission.

EMG, electromyography.
REFERENCES Brink P, Wilkins LP, Spano JS 1996 Chylothorax due to

primary thoracic haemangiosarcoma in a horse. Equine
Ainsworth DM, Hackett RP 2004 Disorders of the respiratory Veterinary Journal 28: 241–244
system. In: Reed SM, Bayly WM, Sellon DC (editors) Brobst DF, Parry BW 1987 Normal clinical pathology data. In:
Equine Internal Medicine, 2nd edn. WB Saunders, Robinson NE (editor) Current Therapy in Equine
Philadelphia, pp.289–353 Medicine 2. WB Saunders, London, p.729
Amory H, Lomba F, Lekeux PM et al 1994 Bilateral diaphrag- Byars TD, Becht JL 1991 Pleuropneumonia. Veterinary Clinics
matic paralysis in a pony. Journal of the American of North America; Equine Practice 7: 63–78
Veterinary Medical Association 205: 587–591 Byars TD, Dainis CM, Seltzer KL et al 1991 Cranial thoracic
Austin SM, Foreman JH, Hungerford LL 1995 Case–control masses in the horse: a sequel to pleuropneumonia.
study of risk factors for development of pleuropneumonia Equine Veterinary Journal 23: 22–24
in horses. Journal of the American Veterinary Medical Carr EA, Carlson GP, Wilson WD et al 1997 Acute
Association 207: 325–328 haemorrhagic pulmonary infarction and necrotizing
Bellazo F, Hunt RJ, Provost P et al 2004 Surgical repair of rib pneumonia in thoroughbred racehorses: 21 cases
fractures in 14 neonatal foals: case selection, surgical (1967–1993). Journal of the American Veterinary Medical
techniques and results. Equine Veterinary Journal Association 210: 1774–1778
36: 557–562 Chadha TS, Cohn MA 1983 Non-invasive treatment of pneumo-
Boy MG, Sweeney CR 2000 Pneumothorax in horses: 40 cases thorax with oxygen inhalation. Respiration 44: 147–152
(1980–1997). Journal of the American Veterinary Chaffin MK, Carter GK 1993 Equine bacterial pleuro-
Medical Association 216: 1955–1959 pneumonia. Part I. Epidemiology, pathophysiology, and
bacterial isolates. Compendium on Continuing Education Raidal SL, Love DN, Bailey GD 1997b Effect of a single bout of
for the Practicing Veterinarian 15: 1642–1650 high intensity exercise on lower respiratory tract
Chaffin MK, Carter GK, Relford RI 1994a Equine bacterial contamination in the horse. Australian Veterinary
pleuropneumonia. Part II. Clinical signs and diagnostic Journal 75: 293–295
evaluation. Compendium on Continuing Education for Rantanen NW, Gage L, Paradis MR 1981 Ultrasound as a
the Practicing Veterinarian 16: 362–379 diagnostic aid in pleural effusion in horses. Veterinary
Chaffin MK, Carter GK, Byars TD 1994b Equine bacterial Radiology 22: 211–216
pleuropneumonia. Part III. Treatment, sequelae, and Raphel CF, Beech J 1982 Pleuritis secondary to pneumonia or
prognosis. Compendium on Continuing Education for the lung abscessation in 90 horses. Journal of the American
Practicing Veterinarian 16: 1585–1596 Veterinary Medical Association 181: 808–810
Farrow CS 1976 Pneumomediastinum in horse – complication Reef VB 1990 Outcome and return to performance in horses
of transtracheal aspiration. Journal of the American with pleuropneumonia evaluated ultrasonographically.
Veterinary Radiology Society 17: 192–195 Proceedings of the 8th American College of Veterinary
Fischer AT 2002 Management of pleuritis. Equine Veterinary Internal Medicine, pp.573–575
Education 14: 293–294 Reimer JM, Reef VB, Spencer PA 1989 Ultrasonography as a
Grant BD 1997 Thoracotomy. In: Rantanen NW, Hauser ML diagnostic aid in horses with anaerobic bacterial pleuro-
(editors) The Diagnosis and Treatment of Respiratory pneumonia and/or pulmonary abscessation: 27 cases
Disease. Proceedings of the Dubai International Equine (1984–1986). Journal of the American Veterinary
Symposium. Rantanen Design, USA pp.419–424 Medical Association 194: 278–282
Hance SR, Robertson JT 1992 Subcutaneous emphysema Rozenman J, Yellin A, Simansky DA et al 1996 Re-expansion
from an axillary wound that resulted in pneumo- pulmonary oedema following spontaneous pneumothorax.
mediastinum and bilateral pneumothorax in a horse. Respiratory Medicine 90: 235–238
Journal of the American Veterinary Medical Association Sanchez LC, Murphy DJ, Bryant JE et al 2002 Use of diagnostic
200: 1107–1110 thoracoscopy and partial pneumonectomy for the
Jean D, Laverty S, Halley J et al 1999 Thoracic trauma in treatment of a pulmonary abscess and bronchopleural
newborn foals. Equine Veterinary Journal 31: 149–152 fistula in a Thoroughbred filly. Equine Veterinary
Kelly G, Prendergast M, Skelly C et al 2003 Pneumothorax Education 14: 290–293
in a horse as a complication of tracheotomy. Irish Santschi EM, Juzwiak JS, Moll HD et al 1997 Diaphragmatic
Veterinary Journal 56: 153–156 hernia repair in three young horses. Veterinary Surgery
Laverty S, Lavoie JP, Pascoe JR et al 1996 Penetrating wounds 26: 242–245
of the thorax in 15 horses. Equine Veterinary Journal Scarratt WK, Wallace MA, Pleasant RS et al 1997 Chylo-
28: 220–224 thorax and meconium impaction in a neonatal colt.
Lee YCG, Light RW 2004 Management of malignant pleural Equine Veterinary Journal 29: 77–79
effusions. Respirology 9: 148–156 Schambourg MA, Laverty S, Mullim S et al 2003 Thoracic
Mair TS 1987 Pleural effusions in the horse. In: Grunsell CSG, trauma in foals: post mortem findings. Equine Veterinary
Hill FWG, Raw ME (editors) The Veterinary Annual, Journal 35: 78–81
27th edn. Scientechnica, Bristol, pp.139–146 Schumacher J, Brusie R, Spano J 1989 Chylothorax in an
Mair TS, Lane JG 1989 Pneumonia, lung abscesses and Arabian filly. Equine Veterinary Journal 21: 132–134
pleuritis in adult horses: a review of 51 cases. Equine Seltzer KL, Byars TD 1996 Prognosis for return to rac-
Veterinary Journal 21: 175–180 ing after recovery from infectious pleuropneumonia
Mair TS, Pearson H, Waterman AE et al 1988 Chylothorax in thoroughbred racehorses: 70 cases (1984–1989).
associated with a congenital diaphragmatic defect in a Journal of the American Veterinary Medical Association
foal. Equine Veterinary Journal 20: 304–306 208: 1300–1301
McGorum BC 2003 Diffuse skeletal muscle weakness. Shearer DC, Slone DE, Moll DE et al 1986 Rib resection
In: Robinson NE (editor) Current Therapy in Equine and thoracotomy as a treatment for chronic pleuritis.
Medicine 5. WB Saunders, London, pp.740–745 Proceedings of the American Association of Equine
Perdrizet JA, Dill SG, Hackett RP 1989 Diaphragmatic-hernia Practitioners 31: 265–268
as a cause of dyspnea in a draft horse. Equine Veterinary Sprayberry KA, Bain FT, Seahorn TL 2001 56 cases of rib
Journal 21: 302–304 fractures in neonatal foals in a referral center intensive
Perkins G, Ainsworth DM, Yeager A 1999 Hemothorax in care unit from 1997–2001. Proceedings of the American
2 horses. Journal of Veterinary Internal Medicine Association of Equine Practitioners 47: 395–399
13: 375–378 Steenhaut M, Verschooten F, Demoor A et al 1992 Surgical
Racklyeft DJ, Raidal S, Love DN 2000 Towards an under- correction of diaphragmatic-hernia in the horse – a
standing of equine pleuropneumonia: factors relevant for report of 6 cases. Vlaams Diergeneeskundig Tijdschrift
control. Australian Veterinary Journal 78: 334–338 61: 181–186
Raidal SL 1995 Equine pleuropneumonia. British Veterinary Sweeney CR, Divers TJ, Benson CE 1985 Anaerobic bacteria in
Journal 151: 233–262 21 horses with pleuropneumonia. Journal of the American
Raidal SL, Love DN, Bailey GD 1995 Inflammation and Veterinary Medical Association 187: 721–724
increased numbers of bacteria in the lower respiratory Sweeney CR, Holcombe SJ, Barningham SC et al 1991 Aerobic
tract of horses within 6 to 12 h of confinement with the and anaerobic bacterial isolates from horses with pneu-
head elevated. Australian Veterinary Journal 72: 45–50 monia or pleuropneumonia and antimicrobial suscepti-
Raidal SL, Taplin RH, Bailey GD et al 1997a Antibiotic bility patterns of the aerobes. Journal of the American
prophylaxis of lower respiratory tract contamination in Veterinary Medical Association 198: 839–842
horses confined with head elevation for 24 or 48 hours. Zocchi L 2002 Physiology and pathophysiology of pleural fluid
Australian Veterinary Journal 75: 126–131 turnover. European Respiratory Journal 20: 1545–1558
Index
Page numbers followed by “b,” “f,” or “t” adaptive immunity, 71–72, 71t, 77 hyperresponsive see airway hyper-
refer to boxes, figures and tables respectively adduction, laryngeal movement, 487t responsiveness (AHR)
adenocarcinoma inflammation
computed tomography, 268 cytology, 140
A
metastatic, 603 pro-inflammatory agents, 565t
abdominal muscles, exhalation, 23 adenosine triphosphate (ATP), 45 recurrent airway obstruction,
abdominal pain, diaphragmatic hernia, adhesins 568–570
662 Streptococcus equi, 330 summer-pasture-associated
abduction, laryngeal movement, 487t Streptococcus pneumoniae, 347 obstructive pulmonary
abortion Streptococcus zooepidemicus, 345 disease, 568–570
equine arteritis virus, 307 adrenergic agonists, vasomotor rhinitis, obstruction
equine herpesvirus-1, 297, 302, 304 370 breathing abnormalities, 108t
abscess(es) aerophagia, fourth branchial arch defect clinical signs, 25
epiglottic, 524 syndrome, 468 exercise-induced pulmonary hemor-
laryngeal, 527 aerosol delivery devices, 95 rhage, 619
lymph node, 552 African horse sickness (AHS), 316–319 gait–breathing coordination, 22
mediastinal, 673 cardiac/edematous form (Dikkop), 317 recurrent airway obstruction,
metastatic, 333, 335 clinical signs, 317 567–570
pleural, 672 diagnosis, 317–318 remodeling, recurrent airway
pulmonary, 166, 169f, 182, 183f, 338 epidemiology, 318–319 obstruction, 571, 571f
retropharyngeal, 157, 332, 333f, 336, historical context, 316–317 responsiveness measurement, 225,
336f, 503 insect vectors, 316, 318 228–230b
Rhodococcus equi infection, 357, 357f mixed form, 317 equipment, 228–229b, 228f, 229f
submandibular, 332, 333f outbreaks, 316–317, 318 response determination/expression,
absorption pathogenesis, 317 230b
laser light, 534 post-mortem examination, 317, 318 secretions see mucus accumulation
sound, 176 prevention, 318–319 smooth muscle, 26–28
accessory cervical tracheal bronchus, 549 pulmonary form (Dunkop), 317 autonomic control, 27, 27f
acemannan, 88 vaccination, 318–319 functions, 26–27
acepromazine virology, 317 inflammatory mediators, 28
blood gas values, 203, 204t African horse sickness virus (AHSV), 317 recurrent airway obstruction,
epiglottic entrapment axial division, agalactia, strangles, 333 567–568, 570
461 age/aging see also alveoli; bronchi; bronchiole(s)
guttural pouch mycosis, 426 exercise-induced pulmonary hemor- airway casts (Curschmann’s spirals), 131,
acetozolamide, 446 rhage, 617 575, 576f
acetylcysteine, 584 follicular pharyngeal hyperplasia, 442 airway hyperresponsiveness (AHR), 28,
acidemia, 205 fourth branchial arch defect syndrome, 225
acidosis, 205t 467 causes, 28, 225
acid-stable picornavirus (ASPV), 313 frontomaxillary opening, 265 definition, 574
acoustic coupling gel, 177 laryngoplasty, 500 measurement, 228–230b
acoustic impedance, 176, 177 lower respiratory tract bacterial recurrent airway obstruction, 574
acoustic shadow, 176–177, 176f, 177f infections, 338 tests, 225
acquired equine mucosal immunodeficiency, recurrent airway obstruction, 572 alar cartilages, 3
79 recurrent laryngeal neuropathy, 484 alar fold(s), 3, 373, 374f
Actinobacillus, 348b, 349 Rhodococcus equi pneumonia, 357 examination, 103
Actinobacillus equuli, 347, 348–349 summer-pasture-associated obstructive resection, 374–375
Actinobacillus lignerieresii, 348 pulmonary disease, 572 stenosis, 373–375
active medium, lasers, 534 air-bronchograms, 164 clinical signs, 374
acute respiratory distress syndrome (ARDS), air shadow, guttural pouch tympany, 423, diagnosis, 374
605, 605f 423f prognosis, 375
neonatal, 648–649 airway(s), 19 signalment, 374
radiography, 166 frictional resistance, 24–25 treatment, 374–375
acyclovir, 301 functions, 20t temporary retraction, 374, 375f
677
678 Index
albuterol, 93–94 amoxicillin, 652t foals, 645, 651, 652t

exercise-induced pulmonary hemor- amphotericin-B, 85, 384 laser surgery, postoperative, 536
rhage, 625 ampicillin, 652t near drowning, 612
inflammatory airway disease, 598 amplification, lasers, 534 Rhodococcus equi pneumonia, 360–361,
ipratropium bromide and, 94 amyloid AA, 384 361t
recurrent airway obstruction, 93–94, amyloid AL, 384 surfactant deficiency, 641
93f, 578t, 583 amyloidosis, nasal, 384–386 see also individual drugs/drug types
smoke inhalation, 610 clinical signs, 385, 385f antimycotic medication, 429, 429f
stereoisomers, 93–94 anaphylactic reactions, tracheostomy, 554 antioxidants
alkalemia, 205 anatomic dead space, 46 foals, 651
alkalosis, 205t anatomic shunt, 50 recurrent airway obstruction, 584
allergen hyposensitization, recurrent anemia, 117 antitussive agents, 96
airway obstruction, 584 anesthesia antiviral therapy, equine influenza virus,
“allergy theory,” 565 blood gas analysis, 203–204, 204t 297
Alternaria fungi, 138, 138f general see general anesthesia apomucin, 55
alternative therapy, recurrent airway intercostal nerve block, rib fractures, apoptosis, neutrophils, 137
obstruction, 584 661 Arabian foals
altitude thoracocentesis, 127 guttural pouch tympany, 422
alveolar oxygen diffusion, 47 see also sedation pneumocystis pneumonia, 648
hypoxemia, 52, 206 aneurysms, guttural pouch mycosis, 424, L-arginine, exercise-induced pulmonary
alveolar–arterial O2 tension difference 424f hemorrhage, 625
(P(A–a)O2), 207–208 annular ligament, 545 argon laser, 534
calculation, 207 antibiotics arterial and mixed venous oxygen
increased, 207–208 Bordetella bronchoseptica pneumonia, 85 concentration (C(a–V)O2)
alveolar capillary rupture, 618 dorsal displacement of the soft palate, difference, 208–209
alveolar clearance 449 arterial cannulation, blood gas analysis,
recurrent airway obstruction, 575 enterocolitis-induction, 84 203–204
scintigraphy, 193t, 197–198, 230 guttural pouch empyema, 432 arterial carbon dioxide tension (PaCO2),
imaging, 197 inflammatory airway disease, 598–599 206, 225, 227
measurement, 197–198 laryngeal reinnervation, 512 normal values, 206, 206t
radiopharmaceuticals, 197 pleuropneumonia, 670–671 arterial hypoxemia, 117
alveolar consolidation, foal, 634–635, 635f pneumothorax, 664 arterial oxygen tension (PaO2), 207, 225,
alveolar dead space (VDALV), 46 recurrent airway obstruction, 584 227
alveolar ducts, 13, 26 smoke inhalation, 611 foals, 637
alveolar edema, 605 Streptococcus equi infection, 335–336 interpretation, 207
alveolar gas equation, 46 temporary tracheostomy after care, arterioles, pulmonary, 34
alveolar hypoxemia, 52 557 Arthus reaction, recurrent airway obstruc-
alveolar minute ventilation (VA), 46 thoracoscopy, 272 tion, 566–567
alveolar (A) O2 tension (PAO2), 46 see also individual drugs artificial breeding, equine arteritis virus
alveolar patterns, thoracic radiography, antibodies see immunoglobulin(s) control/prevention, 311,
165f, 166 anticholinergics 312–313
alveolar rupture, pneumomediastinum, inflammatory airway disease, 597, 598 aryepiglottic fold(s), 9, 459
664 recurrent airway obstruction, 583 axial deviation see axial deviation of
alveolar septum, 13–14, 14f antifungal drugs the aryepiglottic folds (ADAF)
capillary network, 14, 15f coccidioidomycosis, 384 congenital cysts, 521
alveoli, 13, 14f conidiobolomycosis, 384 radiography, 158
epithelium, 13 mycotic nasal infection, 381 arytenoid cartilage, 7, 8
function, 20t see also individual drugs abduction loss, post laryngoplasty,
recurrent airway obstruction, 571 antigenic shift, viruses, 288–289 503–504
surfactant deficiency, 640 anti-inflammatory therapy chondropathy see arytenoid
see also entries beginning alveolar dorsal displacement of the soft palate, chondropathy
alveolitis, 606–608 449 collapse see arytenoid collapse
ambroxol, 65 epiglottic entrapment, 461 depression maneuver, 106, 486
American College of Veterinary Internal laser surgery, postoperative, 536 erythema, post-tracheoscopy, 525
Medicine (ACVIM), nasal paralysis, 369 fourth branchial arch defect syndrome,
Streptococcus equi infection non-infectious pulmonary disease, 467
prevention guidelines, 89–92 granulomas, 524–527, 525f, 526f
336–337 recurrent airway obstruction, 580–582 endoscopy-induced, 527
amikacin, 85, 652t see also individual drugs/drug types laser surgery, 526
aminocaproic acid, 626 anti-leukotrienes, recurrent airway treatment, 526
aminoglycosides, 85, 339 obstruction, 582 high-speed treadmill endoscopy, 237
aminophylline, 95 antimicrobial therapy, 83–85 muscular process palpation, 486,
adverse effects, 582, 651 arytenoid chondropathy, 516 487f
foals, 651 bacterial pneumonia, 645 arytenoid chondropathy, 515
recurrent airway obstruction, 578t, epiglottic entrapment, post-operative, recurrent laryngeal neuropathy,
582 463 486, 487f
Index 679
arytenoid cartilage (cont’d) attenuation, 175–177 bedding materials

partial removal see partial “atypical” strangles, 333–334, 335, 337 exercise-induced pulmonary hemor-
arytenoidectomy see also Streptococcus equi infection rhage, 625
radiography, 158 auditory tube inflammatory airway disease, 597
“slap test,” reflex adduction, 489–490 computed tomography, 269 recurrent airway obstruction, 579
swellings, 527 diverticuli see guttural pouch(es) summer-pasture-associated obstructive
arytenoid chondropathy, 515–519, 525, auricular artery, blood gas analysis, 203 pulmonary disease, 579
525f, 526f auscultation, foals, 634 Bernouilli effect, 114
acute stage, 515, 516f autolysin, 346 Besnoitia bennetti, 527
diagnosis, 515 axial deviation of the aryepiglottic folds ␤-adrenoceptors, airway smooth muscle,
endoscopic examination, 515, 516f (ADAF) 27
mucosal swelling, 515 concurrent disorders, 242 ␤2-agonists, 93–95
prognosis, 518 grading, 242, 242f, 242t bronchospasm, 27
radiography, 158 high-speed treadmill endoscopy, 242 inflammatory airway disease, 597–598
surgery, 517–518 laser surgery, 536–537, 537f long-acting, 94–95
complications, 518–519 azaperone, 204t mucociliary clearance, 65
treatment, 516–518 azithromycin, 84, 361, 361t, 652t overuse, asthma, 95
improvement, 516, 516f azygos vein, 34 recurrent airway obstruction, 578t,
medical, 516–517 583
arytenoid collapse, 503–504 short acting, 93–94
B
bilateral vocal fold collapse and, 521 indications, 93
causes, 245 bacillus Calmette–Guérin (BCG) vaccine, bighead see osteodystrophia fibrosa
high-speed treadmill endoscopy, 86–87 bile salts, meconium, 643
244f, 245 bacteria, 140, 141f biochemistry
arytenoid depression maneuver, 106 infectious disease see bacterial inflammatory airway disease, 596
recurrent laryngeal neuropathy, 486 infection(s) pleuropneumonia, 669
arytenoidectomy, partial see partial normal flora, 138 recurrent airway obstruction, 575
arytenoidectomy see also bacteriology; individual bacteria summer-pasture-associated obstructive
arytenoideus transversus, 9 bacterial infection(s), 327–353 pulmonary disease, 575
arytenoideus ventralis, 9 inflammatory airway disease, 592–593, bioflavonoids, 626
arytenoideus vocalis, 9 595 biopsy
asinine herpesvirus(es), 297, 298 lower respiratory tract, 338–343 lung see lung biopsy
Aspergillus mucus accumulation, 61 sinoscopy, 259
culture, 145, 146, 146f post-mortem examination, 279 blinkers, scintigraphy, 186
guttural pouch mycosis, 424 fetuses and foals, 281–282 blood culture, bacterial pneumonia, foals,
Aspergillus fumigatus recurrent airway obstruction, 567 645
mycotic sinusitis, 400 respiratory immunity, 77–78 blood gas analysis, 201–209
nasal infection, 380–381 sample evaluation, 139 anesthesia, 203–204, 204t
recurrent airway obstruction, 566 upper respiratory tract, 140t applications, 201
Aspergillus nidulans, 424 see also individual organisms/infections body temperature, 204
asphyxiation, water submersion, 612 bacterial pneumonia, foals, 644–645 equipment, 201–202
aspiration pneumonia, 611–612, 611f treatment, 645, 652t availability, 202
clinical signs, 612 bacteriology operation, 201–202
diagnosis, 612 inflammatory airway disease, 595 foals, 637–638, 637t, 649
near drowning, 612 quantitative, 340, 340b information provided, 205–209
post laryngoplasty, 504 recurrent airway obstruction, 575 interstitial pneumonias, acute, 647
radiography, 166, 168f summer-pasture-associated obstructive laryngoplasty efficacy, 499
treatment, 612 pulmonary disease, 575 near drowning, 612
aspirin, 626 “ball-valve effect,” guttural pouch normal values, 206t
asthma, 569 tympany, 423 recurrent airway obstruction, 575
asymmetry, laryngeal movement, 487t band neutrophils, 137 sample collection, 202–204
asynchrony, laryngeal movement, 487t barometric pressure, 45 puncture technique, 203–204
atelectasis basal cells, 4 sites, 202–203, 202t
neonates, 640 basidiobolomycosis, 382 sample storage/handling, 204, 205t
radiography, 166 Basidiobolus haptosporus, 382 smoke inhalation, 610
ultrasonography, 180–181, 181f basisphenoid bone, avulsion fracture, blood gas syringes, 204, 205t
atheromas, 141 434 blood glucose, foals, 650
atlanto-occipital joints, 188 basophils, 137 blood lactate, foals, 649
atmospheric hypoxemia, 52 “bastard strangles,” 333 blood pH, 205–206
atmospheric pressure (PB), 207 B-cell leukemia-2 (Bcl-2) protein, 62 causes of changes in, 205t
atom, 533 beclomethasone dipropionate definition, 205
atropine endogenous cortisol production, 90–91 “safe values,” 206
adverse effects, 583 inflammatory airway disease, 340, blood pressure monitoring, foals, 649
mucociliary clearance, 65 597 blood transfusion, guttural pouch mycosis,
recurrent airway obstruction, 92, 583 recurrent airway obstruction, 90–91, 426–427
smoke inhalation, 610 90f, 578t, 581 bluetongue virus, 318
680 Index
blunt trauma bronchial pattern, thoracic radiography, smoke inhalation, 610

pneumomediastinum, 664 164, 165f summer-pasture-associated obstructive
pulmonary contusion, 666 bronchial veins, 34 pulmonary disease, 578t, 583
thoracic wall, 659 bronchiectasis see also individual drugs
tracheal, 549 radiography, 576, 577f bronchoesophageal artery, 34
body temperature, blood gas analysis, recurrent airway obstruction, 571–572 bronchoesophageal grasping forceps, 535,
204 bronchiole(s), 12 535f
body weight, recurrent laryngeal epithelium, 12, 14f bronchopleural fistula, 672–673
neuropathy, 484 frictional resistance, 24, 24f pneumothorax, 663, 673
Bohr’s equation, 46 function, 20t bronchopneumonia
bone remodeling, guttural pouch mycosis, smooth muscle, 26 clinical signs, 578
158 bronchitis, infectious see equine influenza equine herpesvirus-4, 301
Bordetella bronchoseptica pneumonia, virus foals, 338–339, 338t
84–85 bronchoalveolar lavage (BAL) clinical signs, 338
botulism, 673–674, 675t bacterial culture, 139 diagnosis, 338–339
brachial artery, blood gas analysis, 203 contraindications, 121 management, 339
brain eosinophils, 144 pathogens, 338
damage, cryotherapy-induced, 415 epithelial cells, 133, 142–143 pathology, 338
osteodystrophia fibrosa see osteodys- equipment, 125 prevention, 339
trophia fibrosa exercise-induced pulmonary hemor- Streptococcus zooepidemicus, 345
BRDL flowmetrics ultrasonic pneumo- rhage, 623 smoke inhalation, 610
tachograph system, 231 fluid, 125–127, 126f bronchorelaxation, recurrent airway
breath color, 130 obstruction, 567–568
first extrauterine, 638 foamy surfactant, 126f, 129 bronchospasm
malodorous, 104 fungal culture, 146 inflammation, 27
laryngeal foreign bodies, 528 hemosiderophages, 143 muscarinic receptors, 92
pleuropneumonia, 669 indications, 119–120 recurrent airway obstruction, 567
breath and breath condensate analysis, infection vs. contamination, 145 treatment, 27
596 inflammatory airway disease, 592, bronchovascular bundle, 11–12, 12f
inflammatory airway disease, 596 594, 595 bronchus-associated lymphoid tissue
breath cycle, foals, 634 inflammatory cells, 133 (BALT), 74
breathing, 19–31 interpretation, 142–144 “bubbling” sounds see crackles
abnormalities, 108, 108t interstitial pneumonias, 606 buccopharyngeal septum, persistence
audiovisual inspection, 107 lymphocytes, 136, 143 377–378
depth assessment, 107–108 macrophages, 134, 134f, 143 buccotomy, lateral, 400
pattern assessment, 108 recurrent airway obstruction, 570 “bullfrog” see guttural pouch tympany
pleural pressure cyclic changes, 22f, mast cells, 137, 144 Büngner’s bands, 475, 475f
23–24 mucus evaluation, 130–131, 142 bupivacaine, 661
rate assessment, 107 neutrophils, 136, 143–144 butorphanol, 461–462
resting horse, 20–21, 21f normal appearance, 126f, 129
see also ventilation recurrent airway obstruction, 570,
C
breath sounds see respiratory sounds 575, 577t, 592
breed red blood cells, 132, 142 caffeine, foals, 650, 651
recurrent airway obstruction, 572 silicosis, 608 calcium-activated family member 1
recurrent laryngeal neuropathy, 484 summer-pasture-associated obstructive (CLCA 1), 62
summer-pasture-associated obstructive pulmonary disease, 575, 577t callus formation, rib fractures, 661
pulmonary disease, 572 technique, 125–127, 126f campylotthinus lateralis see wry nose
bromhexine, 65 “blind” catheter, 127 Candida, guttural pouch mycosis, 424
bronchi, 10–11, 11f, 12f complications, 127 canter, breathing patterns, 21–22
accessory cervical tracheal, 549 endoscopic, 125–127 carbamino compounds, 52–53
branching pattern, 10–11 total nucleated cell counts, 131, 142 carbon dioxide (CO2)
epithelium, 11, 13f bronchoconstriction alveolar capillary membrane diffusion, 47
“irritation forms,” 142–143, 143f exercise-induced pulmonary hemor- cyanosis, 116–117
function, 20t rhage, 625 elimination, 52
radiography, 163 inflammatory mediators, 568 hypocapnia, 205t, 206, 207
smooth muscle, 11, 26 recurrent airway obstruction, 568 impaired elimination see hypercapnia
see also bronchiole(s); entries beginning bronchodilatation, hypercapnic, 49 measurement, foals, 649
broncho-/bronchial bronchodilator therapy, 92–95 release at the lungs, 53
bronchial arteries, 34 anticholinergic, 92 secondary acid–base effects, 207
exercise-induced pulmonary hemor- foals, 651 solubility coefficient, 45
rhage, 625–626 inflammatory airway disease, 340, transport in blood, 52–53
bronchial circulation, 14–15, 34 597–598 see also hypercapnia
anastomoses, 34 near drowning, 612 carbon dioxide laparoflator, thoracoscopy,
exercise-induced pulmonary hemorrhage, recurrent airway obstruction, 577, 272
618 578t, 579t, 583 carbonic acid, 45, 52–53, 207
venous drainage, 14 Rhodococcus equi pneumonia, 361–362 carbonic anhydrase, 53
Index 681
carbon monoxide diffusing capacity test Cheyne–Stokes breathing, 108t colostrum ingestion, 644
(DLCO), 227 chicken hypersensitivity pneumonitis, 578 combined immunodeficiency (CID)
carbon monoxide inhalation, 609–610 chickpea (Cicer arietinum) ingestion, equine adenoviruses, 646
carbon monoxide transfer factor, 227 laryngeal paralysis, 481 pneumocystis pneumonia, 648
cardiac output chloramphenicol, 652t comet tails, 179, 179f
foals, 649 chloride shift, 53 foals, 634, 635f
oxygen flux, 51 chlorofluorocarbons (CFCs), metered-dose pulmonary granular cell tumor, 602
cardiac sounds, 115 inhaler, 581 common carotid artery temporary
carina, endoscopy, 546 choanal atresia, 377–378 occlusion, 414
carotid arterial puncture, 202 “choke ring,” 448 common mucosal immune system, 74
carotid artery, blood gas analysis, 202 cholera toxin, vaccines, 78 complement fixing (CF) antibody test,
catarrh, infectious see equine influenza chondritis, post-laryngoplasty, 504 equine herpesviruses,
virus chondroids, 281 301–302
catheterization, guttural pouch sampling, guttural pouch empyema, 157, 333, compound inflammation scores, 144
122 431–432, 433f computed tomography (CT), 263–270
catheter-tip mounted strain-gauge pressure removal, 336 acquisition, 263–264
transducers, 218–219b sampling, 122 adenocarcinoma, 268
caudal maxillary osteotomy, 396, 398f chondromas, intratracheal, 559 auditory tube, 269
caudal maxillary sinus (CMS), 6, 154 chromatolysis, recurrent laryngeal cheek teeth, 266
sinoscopy neuropathy, 475 contrast media, 264–265, 265f
structure observed, 256–258, 258f, chromophore, 534 dental
261 chyle, 667 periapical infections, 266, 267f
trephination sites, 255, 255f chylothorax, 148, 667–668 sinusitis, 399, 399f
cavison-mounted microphones, 250–251, chylous effusions, 130, 148 foals, 266
251f cicatrix see laryngeal stenosis frontomaxillary opening, 265–266
cefotaxime, 652t Cicer arietinum (chickpea) ingestion, general anesthesia, 264
ceftazidime, 652t laryngeal paralysis, 481 guttural pouch empyema (GPE), 269,
ceftiofur cilia, 57 269f
bronchopneumonia, foals, 339 ciliated cells, 132, 132f image reconstruction, 263–264
foals, 652t ciliocytophthoria, 142–143 indications, 265
inflammatory airway disease, 340, ciliocytophthoria, parainfluenza-3, 316 larynx, 269
598–599 ciliostasis, Mycoplasma spp., 351 multi-slice, 264
pleuropneumonia, 342 citrus bioflavonoids, 626 nasal, 265
pneumonia, 83, 342 Clara cells, 12 neoplasia, 387
ceftriaxone, 652t clarithromycin, 84, 361, 361t paranasal sinuses, 265
cementoma formation, dental sinusitis, clavulinic acid, 652t patient positioning, 264, 264f
155, 155f cleft palate, 454–455, 454f pharynx, 269
central venous pressure, foals, 650 clenbuterol, 94–95 principles, 263–265
cephalexin, 652t abuse, 94 progressive ethmoid hematoma (PEH),
cephalothin, 652t adverse effects, 95 267–268, 268f
cervical nerve, first exercise-induced pulmonary hemor- sinusitis, 266–267, 267f, 399, 399f
dissection, 510 rhage, 625 spiral, 264
laryngeal reinnervation, 509 foals, 651 squamous cell carcinomas, 268
pathway, 509f, 510 inflammatory airway disease, 340, stylohyoid bones, 269
challenge infection, equine influenza virus 597–598 fractures, 270
vaccine evaluation, 293 mucociliary clearance, 65 upper respiratory tract, 265–270
cheek teeth recurrent airway obstruction, 578t, window level, 263
computed tomography, 266 583, 584 window width, 263
endoscopy, 259f repartitioning properties, 94 conchal bulla, sinoscopy, 261
erupted crowns, 188 summer-pasture-associated obstructive conchal necrosis, 405
maxillary see maxillary cheek teeth pulmonary disease, 578t, 583 conchofrontal sinus, 6, 154
periapical infection, 185 Clostridium difficile, 84 conidiobolomycosis, 382
removal, 400 coagulopathy, exercise-induced pulmonary clinical signs, 383, 383f
rostral see rostral cheek teeth hemorrhage, 626 diagnosis, 383–384
scintigraphy, 187–188, 187f, 187t Coccidioides immitis, 382, 400 pathology, 383
“cold spots,” 187–188 coccidioidomycosis, 382 treatment, 384
chemical ablation clinical signs, 383 Conidiobolus coronatus, 382, 400
epidermal inclusion cysts removal, 373 granulomatous pneumonia, 608 Conidiobolus lamprauges, 400
progressive ethmoid hematoma, pathology, 383 conjunctivitis
415–416 treatment, 384 equine herpesvirus-1, 300–301
chemical pleurodesis, pleural effusion, 667 coefficient for O2 utilization, 51 parainfluenza-3, 316
chemoprophylaxis, Rhodococcus equi cold (therapeutic) lasers, 534 consolidation
pneumonia, 365 colic bronchopneumonia, foals, 338
chest tubes, indwelling, 664, 665f fourth branchial arch defect syndrome, post-mortem testing, 278
insertion technique, 671 468 respiratory sounds, 112f, 113
pleuropneumonia, 665f, 671 pleuropneumonia, 673 ultrasonography, 181–182, 182f, 183f
682 Index
contrast media, computed tomography, fine, 113t, 114f, 115 cytadhesins, Mycoplasma spp., 350
264–265, 265f inflammatory airway disease, 339 cytokines, 72b
renal damage, 265 pleuropneumonia, 669 antiviral action, 77
contrast paranasal sinusography, 153 pneumonia/pleuropneumonia, 341 recurrent airway obstruction, 568
cordectomy see vocal cordectomy cranial thoracic masses (abscesses), 672 see also individual types
Cornell Throat Support Device, 449 drainage, 672 cytology, 131–139
corniculate cartilages, 8 craniopharyngeal duct, 453 airway irritation, 140
post laryngoplasty, 504, 505f crepitus, post temporary tracheostomy, cyst(s), 133f, 141–142
“corona,” mesothelial cells, 135 557 delayed processing, 137–138
corticosteroids cricoarytenoid articulation, diarthrodial, 8 hematoma(s), 142
aerosolized/inhaled, 90–91 cricoarytenoideus dorsalis, 8–9 hemorrhagic effusions, 148
recurrent airway obstruction, atrophy assessment, 106 hypersensitivity reaction, 141
90–91, 581–582 recurrent laryngeal neuropathy, 511 inflammatory airway disease, 594–595
dorsal displacement of the soft palate, reinnervation, 509–511 neoplasia, 142, 149
449 postoperative assessment, 512 parasite infections, 139–140
dorsoventral tracheal collapse, 549 surgical access, 510–511, 511f patterns, 144
epiglottic entrapment, post-operative, cricoarytenoideus lateralis, 9 pneumocystis pneumonia, 648
463 recurrent laryngeal neuropathy, 475, polyps, 142
exercise-induced pulmonary hemor- 475f recurrent airway obstruction, 575
rhage, 625, 626 cricoid cartilage, 8 red blood cells, 131
inflammatory airway disease, 340, fracture, 522 summer-pasture-associated obstructive
594, 597 cricopharyngeal–laryngeal dysplasia see pulmonary disease, 575
mucus accumulation, 65 fourth branchial arch defect cytotoxic T lymphocyte (CTL) precursor
purpura hemorrhagica, 336 syndrome (4-BAD) detection, equine herpesviruses,
recurrent airway obstruction, 578t, cricothyroid membrane, 8 304
579t, 580–582 cricotracheal ligament (membrane), 545 cytotoxins, Mycoplasma spp., 350
smoke inhalation, 610–611 examination, 107
summer-pasture-associated obstructive prolapse, 546
D
pulmonary disease, 578t cromolyn sodium, 625
systemic, 89–90 cromones, 91, 582–583 dapsone, 85, 384, 648
adverse effects, 580 crura, diaphragm, 15 dead space, 21, 21f
recurrent airway obstruction, cryotherapy dead space ventilation (VDANAT), 46, 46f
580–581 complications, 415 deep tracheal fascia, 545
Corynebacterium parvum see Propionibac- progressive ethmoid hematoma, 415 deglutition, fourth branchial arch defect
terium acnes cryptococcosis, 382 syndrome, 470
costal arch, 15 clinical signs, 383 demand hypoxia, 52
costal pleura, 16 diagnosis, 384 dembrexine, 65
costochondral junctions, 15 pathology, 383 dental disorders, scintigraphy, 188–189,
CO transfer factor, 227 treatment, 384 189f
cough/coughing, 29, 109 Cryptococcus neoformans, 145, 382, 400 dental infections, periapical
bronchoalveolar lavage, 125 Culicoides bolitinos, 318 computed tomography, 266, 267f
dorsoventral tracheal collapse, Culicoides imicola, 318 scintigraphy, 188, 189f
547–548 Culicoides midges, African horse sickness, sinusitis, 155
equine herpesviruses, 301 316, 318 dental sinusitis, 399–400
equine influenza virus, 289–290, 292 Culicoides obsoletus, 318 causes, 399
examination techniques, 120t Culicoides pulicaris, 318 computed tomography, 399, 399f
exercise-induced pulmonary hemor- cuneiform cartilages, 8 postoperative care, 400
rhage, 621 Curschmann’s spirals (airway casts), 131, prognosis, 400
inflammatory airway disease, 594 575, 576f radiography, 155–156, 155f, 399
inflammatory sign, 29 cutaneous colli (panniculus) muscle, 543 “haloes,” 155
laryngeal foreign bodies, 528 cyanide toxicity, 609–610 sinoscopy, 261
lungworm infection, 612 cyanosis, 116–117 tooth extraction, 399–400
mechanism, 29 cyst(s) treatment, 399–400
mucus accumulation, 60 aryepiglottic folds, 521 unsuccessful, 400
neoplasia, 601 cytological examination, 133f, dental tissue tumors, 403
percussion, 116t 141–142 dentigerous cysts, 268–269, 269f
post arytenoidectomy, 518 dentigerous, 268–269, 269 deoxyhemoglobin, 53
post laryngoplasty, 502–503 duplication, combined tracheal and desert fever see coccidioidomycosis
recurrent airway obstruction, 29, 29f, esophageal, 549 detomidine, 204t, 272, 461
573 epidermal inclusion, 372–373, 372f “dew drop” appearance, palatopharyngeal
cough suppressants, 96 hydatid, 613 arch, 159
covariance technique, 218b nasal, 103 dexamethasone, 89
CpG oligodeoxynucleotides (CpG motifs), 86 paralaryngeal accessory bronchial, 521 arytenoid chondropathy, 516
crackles, 109, 114–115 pharyngeal see pharyngeal cysts dorsal displacement of the soft palate,
bronchopneumonia, foals, 338 sinus see sinus cysts 449
coarse, 113t, 114–115 temporal, 268–269, 269f follicular pharyngeal hyperplasia, 444
Index 683
dexamethasone (cont’d) dorsal conchal sinus, 3, 4f, 6 expiratory, 109, 109t

inflammatory airway disease, 340, 597 radiography, 154 causes, 109, 110f
laser surgery, postoperative, 536 dorsal cricoarytenoid muscle, 25 expiratory vs. inspiratory, 108–109,
mucus accumulation, 65 atrophy, recurrent laryngeal 109t
recurrent airway obstruction, 578t, neuropathy, 483 guttural pouch empyema, 431
580–581 dorsal displacement of the soft palate inspiratory, 109, 109t
dexamethasone-21-isonicotinate, 89 (DDSP), 446–452 nostril dilation, 103
recurrent airway obstruction, 578t, causes, 447
580 diagnosis
E
diaphragm, 15 during exercise, 448–449
activity with exercise, 22–23, 22f at rest, 448 Echinacea angustifolia extract, 89
disorders, 662, 674 epiglottis, 238–239, 239f, 451, 524 Echinococcus granulosus, 613
inhalation, 22–23 exhalation, 447 echoes, ultrasonography, 175–176
post-mortem examination, 277–278 gait–breathing coordination, 22 Eco-Medics Exhalyzer 5, 231
post-mortem rupture, 277 high-speed treadmill endoscopy, Eco-Medics mask, 214
synchronous flutter, 115, 674 238–239, 447f, 448 edema
ultrasonography, 178 at rest, 238, 238f African horse sickness, 317
diaphragmatic hernia, 662 inhalation, 447 alveolar, 605
acquired, 277, 662 laser surgery, 540 facial see facial swelling
clinical signs, 662 muscle dysfunction, 442, 447–448 guttural pouch tympany, 422, 422f
congenital, 277, 662 palate examination, 448 head, 117, 522–523
diagnosis, 662 radiography, 159, 159f laryngeal, 522, 523, 523f
management, 662 respiratory sounds, 239, 252, 252f lymphoma, 601, 602f
pathogenesis, 662 silent displacers, 447 peripheral subcutaneous, 117
persistent pulmonary hypertension, surgery, 449–452 pulmonary see pulmonary edema
641 evidence of previous attempts, 448 strangles, 333
post-mortem examination, 277, 662 treatment, 449–452 subpleural, Hendra virus, 315
prognosis, 662 ulceration, 238 eicosanoids, 39
radiography, 170, 662 dorsal meatus, nasal turbinates, 3, 4 electrons, 533
surgery, 662 dorsal metatarsal artery, sample collection, embolization microcoils
ultrasonography, 662 203 internal carotid artery ligation,
diaphragmatic pleura, 16 dorsal pharyngeal recess, 7 427–428
diarthrodial cricoarytenoid articulation, 8 dorsal tracheal ligament, 545 neurological damage, 428
diazepam, blood gas values, 204t 30° dorsolateral–lateral oblique radiographs, EMLA (eutectic mixture of local anesthetic),
Dictyocaulus arnfieldi see lungworm 152, 152f blood gas analysis, 203
(Dictyocaulus arnfieldi) dorsoventral radiographs, 152, 152f emphysema
infection doxapram hydrochloride, 96, 490 post temporary tracheostomy,
diet draft breeds, recurrent laryngeal 557–558, 558f
osteodystrophia fibrosa, 389–390 neuropathy, 484–485 recurrent airway obstruction, 571
see also feed “drainage angle,” 393, 393f subcutaneous, 117
99m
Tc-diethylene triamine pentaacetic acid drowning, 612 tracheal rupture, 549–550
(DTPA), 194t, 195 drug testing, clenbuterol, 95 enalapril, 624
alveolar clearance, 197–198 ductus arteriosus, 638 end-expiratory abdominal lift/heave, 108
diffusion, 19 dull tone, percussion, 116 end-expiratory lung volume (EELV), 212,
diffusion rate, 46 Dunkop, 317 225, 225f
digital arteries, blood gas analysis, 203 see also African horse sickness (AHS) calculation, 226b, 227b
Dikkop, 317 duplication cyst, combined tracheal and measurement, 226–227b
see also African horse sickness (AHS) esophageal, 549 endoscopy
dilator naris lateralis, 3 dynamic airway collapse carina, 546
dimethylsulfoxide pathogenesis, 111f cheek teeth, 259f
follicular pharyngeal hyperplasia, 444 wheezes, 111f, 114 cleft palate, 454, 454f
post-operative epiglottic entrapment, dynamic compliance (Cdyn), 214–215 complications
463 calculation, 217–218b, 217f, 218f granuloma induction, 527
smoke inhalation, 611 definition, 212 laryngeal inflammation, 522
diode laser, 534–535 dysphagia direct sinus see sinoscopy
direct sinus endoscopy see sinoscopy esophageal, 104 epiglottic entrapment, 241, 241f, 460,
distemper see equine influenza virus examination techniques, 120t 460f, 461f
distraction osteogenesis, wry nose, fourth branchial arch defect syndrome, epiglottic hypoplasia, 460–461
376–377 468 epiglottitis, 524, 525f
diverticulitis, chronic, 434 guttural pouch mycosis, 425, 430 fourth branchial arch defect syndrome
DNA vaccines, Rhodococcus equi pharyngeal, 104, 106 (4-BAD), 243–244, 243f,
pneumonia, 364 post laryngoplasty, 502–503 468–469, 469f, 470f
donkeys dyspnea frontomaxillary opening, 258f
dorsoventral tracheal collapse, 547 definition, 108 guttural pouch(es), 106, 420
equine influenza virus, 290 dorsoventral tracheal collapse, 547 guttural pouch empyema (GPE), 334,
idiopathic pulmonary fibrosis, 609 examination techniques, 120t 431, 432f, 434
684 Index
endoscopy (cont’d) enzyme-linked immunosorbent assays epiglottitis

guttural pouch mycosis (GPM), 426, (ELISA) acute, 524
430, 430f African horse sickness, 317 endoscopy, 524, 525f
guttural pouch tympany, 423 equine arteritis virus, 308 peracute, 524
hepatopathy, laryngeal paralysis, 480, equine arteritis virus vaccines, 312 epistaxis, 104
480f equine herpesviruses, 302 causes, 411, 618t
high-speed treadmill see high-speed equine influenza virus, 291 examination techniques, 104, 120t
treadmill endoscopy (HSTE) Hendra virus, 315 exercise-induced pulmonary hemor-
hyovertebrotomy, 421 eosinophilic pneumonia, 612–613 rhage, 104, 617, 620, 620f
inflammatory airway disease (IAD), eosinophilic pneumonitis see eosinophilic guttural pouch mycosis, 104, 157,
339, 339f, 594 pneumonia 158f, 425, 426–427, 426f
intraoperative eosinophilic pulmonary inflammation, maxillary fractures, 157
laryngoplasty, 497, 498f 593, 597 nasal amyloidosis, 385
laryngeal foreign bodies, 528, 528f eosinophils, 137, 137f, 144 progressive ethmoid hematoma, 411
laryngoplasty, 497, 498f, 499f parasitic infection, 137f, 139, 144 racing jurisdictions, 617
nasal septum deformity, 378 recurrent airway obstruction, 570 rib fractures, 660f, 661
nasopharyngeal collapse, 242–243, epidermal cysts, 103 sinus fractures, 404
445 epidermal growth factor receptor (EGFR), epithelial atypia, 142–143
neurological damage, 430, 430f 62 epithelial cells, 132–133
pharyngeal cysts, 453–454, 453f epidermal inclusion cysts, nasal diverticu- recurrent airway obstruction, 570
pharynx, 7, 8f lum, 372–373, 372f summer-pasture-associated obstructive
postoperative epidermoid cysts, 372–373, 372f pulmonary disease, 570
guttural pouch empyema (GPE), 434 epiglottic abscess, 524 epizootic cough see equine influenza virus
laryngoplasty, 499f epiglottic chondritis, 448 equine adenovirus infection, 319
partial arytenoidectomy, 517–518 epiglottic entrapment, 459–465, 459f clinical signs, 319
progressive ethmoid hematoma (PEH), axial division, 461 foals, 646
410f, 411 with curved bistoury, 461, 463, 464f equine adenovirus type 1, 319
pulmonary granular cell tumor, 602 with laser, 461–463, 462f, 464f equine adenovirus type 2, 319
recurrent airway obstruction (RAO), clinical signs, 459–460 Equine AeroMask™, 95
576 concurrent upper respiratory tract pulmonary function testing, 213–214,
recurrent laryngeal neuropathy see disorders, 464 215f
recurrent laryngeal diagnosis, 459–461 equine arteritis virus (EAV), 306–313
neuropathy (RLN) dorsal displacement of the soft palate, abortion, 307
rostral displacement of the palatopharyn- 448 clinical signs, 307–308, 307f
geal arch (RDPA), 469, 470f endoscopy, 460, 460f, 461f diagnosis, 308–309
sinusitis, 393, 393f high-speed treadmill, 241, 241f fetal, 308
smoke inhalation, 610 epiglottic inflammation, 523–524 epidemiology, 309–310
summer-pasture-associated obstructive epiglottis length, 459 breed differences, 310
pulmonary disease (SPAOPD), exercise responses, 460 control, 312–313
576 inspiratory upper airway pressure, 460 prevention, 310–313
temporohyoid osteoarthropathy, 434 laser surgery, 461–463, 462f, 536 foals, 307, 646
trachea see tracheoscopy post-operative care, 463 historical context, 306–307
endothelial nitric oxide synthase (eNOS), prognosis, 463–464 immunity, 307
38 radiography, 159 outbreaks, 306, 313
endothelin, 38 surgical complications, 463–464 pathogenesis, 307–308
endothoracic fascia, 545 treatment, 461–463 persistently infected stallions,
endotoxins epiglottic hypoplasia, 521 308–309
inflammatory airway disease, 593 assessment, 460–461 post-mortem findings, 646
recurrent airway obstruction, 567 dorsal displacement of the soft palate, shedding, 308–309, 646
energy fluence, 534 448 structure, 307
enilconazole, 85, 400 endoscopy, 460–461 stud farm infection, 309, 310f
enrofloxacin radiography, 159, 461 transmission, 308, 309–310
foals, 652t epiglottic inflammation, 523–524 vaccination, 311–312
inflammatory airway disease, 340 idiopathic, 524 killed virus vaccine, 312
pleuropneumonia, 342 epiglottic retroversion, 244–245 live vaccines, 312
pneumonia, 83, 342 epiglottis, 7–8, 459 stallions, 312
enterocolitis, antibiotic-induced, 84 axial collapse of lateral margins, 244–245 subunit vaccine, 312
entomorphomycois see conidiobolomycosis concurrent disorders, 243f, 244–245 virology, 307
environmental management high-speed treadmill endoscopy, virulence, 309, 311f
inflammatory airway disease, 596–597 244–245 Equine Haler™, 95
recurrent airway obstruction, deformity, 521 equine herpesvirus-1 (EHV-1), 297–306
579–580, 579t dorsal displacement of the soft palate, abortion, 297, 302
Rhodococcus equi pneumonia, 364–365 238–239, 239f, 524 clinical signs, 300–301, 300f
Streptococcus equi infection, 335 examination, 106 control, 304–306
summer-pasture-associated obstructive radiography, 158 abortion, 304
pulmonary disease, 580 see also entries beginning epiglottic horses-in-training, 305
Index 685
equine herpesvirus-1 (EHV-1) (cont’d) equine idiopathic systemic granulomatous foals, 652t
management of, 304–305 disease, 608 hyperthermia-induction, 647
pregnant mares, 304 equine influenza virus, 287–297 Rhodococcus equi pneumonia, 84,
diagnosis, 301–302 airway hyperresponsiveness, 28 360–361, 361t
economic losses, 301 antigenic drift, 288 side effects, 84, 361
epidemiology, 302–303 vaccine efficacy, 296 erythrophages, 134
host range, 302 basic reproductive rate (R0), 292 erythrophagia, 137
infection distribution, 302 clinical signs, 289–291 esophageal dysphagia, 104
fetuses, 281, 282f complications, secondary, 290 esophageal pressure, 215
foals, 281, 282f, 302, 645–646 control, 293 frequency response, 218b, 219f, 220f
historical context, 297–298 culture, 291 measurement, 218–220b
immune response, 77, 303–304 diagnosis, 291–292 catheter positioning, 219b
cytokines, 304 epidemiology, 292–293 swallowing, 215
mucosal antibody secretion, 304 foals, 290, 645–646 esophagus, 543
recovery, 304 hematological changes, 290 dysphagia, 104
incubation period, 300 historical context, 287 fourth branchial arch defect syndrome,
inflammatory airway disease, 593 immunity, 77, 293, 294 470
latency, 302–303 incubation period, 289 perforation, pneumomediastinum, 664
pathogenesis, 300 international control, 297 pressure see esophageal pressure
post-mortem examination, 279, 302 maternal antibodies, 295–296 radiography, 162f, 163
foals, 646 mortality rates, 290 X-ray beam center point, 152t
pregnant mares, 304 mucociliary clearance, 64, 291, 291f rupture, 550
prevalence, 302 mutations, 288 estrogens, 626
reactivation, 302–303, 303f neurological complications, 290 etamiphylline, 582
route of infection, 302 outbreaks, 287 ethmoidal sinus, 6
shedding, 300 vaccinated vs. unvaccinated ethmoids, 4–6, 5f
strains, 298, 299f animals, 290 ethmoturbinates, 4
structure, 298, 298f pathogenesis, 289–291 progressive ethmoid hematoma, 4, 409,
treatment, 301 phylogenetic relationships, 288, 289f, 410f
vaccination, 305–306 296 scintigraphy, 188
administration route, 306 post-mortem findings, 646 Eupatorium adenophorum, 606
DNA vaccines, 306 prevention, 293 eustachian tube diverticulae see guttural
virology, 298–300 rest, 297 pouch(es)
equine herpesvirus-2 (EHV-2), 297–298 sample collection, 291 euthanasia
foals, 646 shedding, 292 cleft palate, 454
prevalence, 302 structure, 288 cryptococcosis, 384
treatment, 301 surveillance system, 288 nasal neoplasia, 387
equine herpesvirus-4 (EHV-4), 297–306 treatment, 297 exercise
clinical signs, 300–301 types, 288 breathing patterns, 21–22, 22f
control, 304–306 vaccines/vaccination bronchoalveolar secretion, 595
horses-in-training, 305 boosters, 295 inflammatory airway disease, 593
management of, 304–305 Canarypox-vectored, 294 intolerance
diagnosis, 301–302 inactivated, 293–294 nasopharyngeal collapse, 445
epidemiology, 302–303 live, 294 recurrent laryngeal neuropathy, 485
host range, 302 mucus accumulation, 65 pleural pressure changes, 22f, 23–24
infection distribution, 302 outbreaks and, 290 pleuropneumonia, 668
prevalence, 302 potency, 293–294 post laryngoplasty, 499
foals, 646 schedules, 294–296, 295f pulmonary blood distribution, 49
historical context, 297–298 strain selection, 296 pulmonary capillary transit time, 47
immune response, 303–304 updating criteria, 288 pulmonary function measurement, 231
cytokines, 304 virology, 288–289 pulmonary hemodynamics, 39–40, 39f
mucosal antibody secretion, 304 equine morbillivirus see Hendra virus (HeV) pulmonary hemorrhage induction see
recovery, 304 equine mucosal immunodeficiency, exercise-induced pulmonary
inflammatory airway disease, 593 acquired, 79 hemorrhage (EIPH)
latency, 302–303 equine phycomycosis, 382 pulmonary right-to-left shunt, 40
pathogenesis, 300 equine rhinitis A virus (ERAV), 313 tracheal secretion, 595
post-mortem examination, 302 equine rhinitis B2 virus (ERBV2), 313 ventilation changes, 21–22, 21f
reactivation, 302–303 equine rhinitis B virus (ERBV), 313 exercise-induced pulmonary hemorrhage
route of infection, 302 equine rhinitis virus(es), 313–314 (EIPH), 617–629
treatment, 301 equine rhinitis virus-1 (ERV-1), 313 age, 617
vaccination, 305–306 equine rhinitis virus-2 (ERV-2), 313 alveolar wall stress, 619
administration route, 306 equine rhinitis virus-3 (ERV-3), 313 clinical signs, 620–621
DNA vaccines, 306 equine shipping fever, 340–341, 345 diagnostic tests, 621–623
virology, 298–300 equine tonsil, 7 diffusion limitations, 40, 40f
equine herpesvirus-5 (EHV-5), 297, erythromycin dorsoventral tracheal collapse, 547
298 Bordetella bronchoseptica pneumonia, 85 epistaxis, 104, 617, 620, 620f
686 Index
exercise-induced pulmonary hemorrhage facial paralysis flow–volume curve, 223, 224f

(EIPH) (cont’d) nasal collapse, 369 fluconazole, 85, 384
etiology, 618–620, 618t temporohyoid osteoarthropathy, 434 “fluid line,” guttural pouch tympany, 423
grading system, 621–622, 622f facial swelling flunisolide, 91
history, 620–621 progressive ethmoid hematoma, 411 fluorescent optodes, blood gas analysis, 201
hypervolemia, 41 sinus cysts, 401, 401f fluticasone propionate, 90
inflammatory airway disease, 593 sinus neoplasia, 403–404, 403f inflammatory airway disease, 340, 597
inhaled nitric oxide treatment, 41 Faenia rectivirgula (Micropolysporua faeni), recurrent airway obstruction, 90, 578t,
pathophysiology, 618–620, 619t, 620f 566 581–582
performance, 620–621 false nostril, 3, 103 foals, 633–656
physical examination, 621 false nostril flutter (high blowing), 105, abnormal respiratory patterns, 650
post-mortem examination, 279, 280, 369 arterial carbon dioxide tension, 206,
623–624, 624f farmer’s lung, 566 206t
presenting complaint, 620–621 Fc region, 76 blood gas analysis sample collection,
prevalence, 617 fecal culture, Rhodococcus equi, 360 202, 202t, 203
prognosis, 626 fecal floatation, round worn infection, computed tomography, 266
pulmonary capillary stress failure, 139–140 examination, 634
618–619 feed history, 633–634
prevention, 624–625 inflammatory airway disease, 597 lung radiography, 163
radiography, 166, 169f, 623 recurrent airway obstruction, 579 maternal signs, 633
risk factors, 617 summer-pasture-associated obstructive monitoring, 649–650
scintigraphy, 198 pulmonary disease, 579 pleural effusion, 168–169
speed, 617 fenoterol post-mortem examination, 281–282,
treatment, 624–626 inflammatory airway disease, 598 302
exhalation, 108 recurrent airway obstruction, 578t, respiratory disorders, 633–656
abdominal muscle contraction, 23 583 respiratory system management,
epiglottal entrapment, 241 fetal–neonatal transition, 638, 639f 649–652
pleural pressures, 23–24 fetus thoracic radiography, 163, 635–637,
resting horse, 20–21 circulation, 638 637f
exhaled inflammation markers, recurrent pulmonary hypoxia, 640 thoracic ultrasound, 634–635
airway obstruction, 577 reversion to see persistent see also individual diseases/disorders
Exhalyzer, 213, 214f pulmonary hypertension (PPH) folic acid synthesis inhibitors, 648
exophthalmos, sinus cysts, 401 equine arteritis virus (EAV) diagnosis, follicular lymphoid hyperplasia, 7
exotoxins 308 follicular pharyngeal hyperplasia, 442–444
streptococci, 327 post-mortem examination, 281–282 age-related, 442
Streptococcus equi infection, 331 fever see pyrexia diagnosis, 442–443
Streptococcus zooepidemicus, 345 fibrinolysis, exercise-induced pulmonary etiology, 442
expectorant therapy, 96 hemorrhage, 619, 626 grading, 442–443, 443f
recurrent airway obstruction, 584 fibrinous pleurisy, pleuropneumonia, 341 post-mortem examination, 280
expiratory grunts, 113t fibrosis, exercise-induced pulmonary treatment, 443–444
external abdominal oblique muscles, 23 hemorrhage, 626 fomoterol, 598
external carotid artery (ECA), 419 fibrotic strictures, tracheal, 550, 551f foramen ovale, 638
guttural pouch mycosis, 429 fibrous adhesions, thoracoscopy, 273–274 forced expiration, 221–223
ligation, 429–430 Fick’s law, 46 measurement technique, 221–223
external intercostal muscles, 23 figure-of-eight nosebands recurrent airway obstruction, 574
extubation, laryngeal obstruction, 479 dorsal displacement of the soft palate, forced oscillatory mechanics (FOM), 215,
449 220–221, 221f
nasopharyngeal collapse, 445 measurement, 212, 223b
F
fistula systems, 220, 222f, 223b
facemasks bronchopleural, 663, 672–673 recurrent airway obstruction, 574
cast molded, 214, 216f guttural pouch tympany, 424 forced oscillatory (FOT) system, 220f,
microphones, 250 oronasal, 371, 372f 222f, 223b
pulmonary function testing, 213–214, salpingopharyngeal, 539 foreign bodies
214f, 215f sinonasal, 396, 398f, 399 epiglottic inflammation, 524
facial artery, blood gas analysis, 203 tracheal, 554, 559–560, 559f laryngeal see laryngeal foreign bodies
facial bone flaps, choanal atresia surgery, flail chest, 659–661 tracheobronchial see tracheobronchial
378 Flair® strips, exercise-induced pulmonary foreign bodies
facial bones, osteodystrophia fibrosa, 389, hemorrhage, 625 forelimb foot strike, exercise-induced
389f Fleisch pneumotachnograph, 212b, 213f pulmonary hemorrhage, 619
facial “horns,” 405 flexible endoscopes forelimb “pointing,” cranial thoracic
facial lumps, 405 sinoscopy, 256, 257f, 258f masses, 672
facial nerve, 4 thoracoscopy, 272 formaldehyde injections
damage floating rib, 15 epidermal inclusion cysts removal, 373
nasal collapse, 369 flow measuring devices, 212–213, 213f laminitis development, 415
temporohyoid osteoarthropathy, calibration, 213b neurological complications, 415–416
434 recording and analysis, 213b progressive ethmoid hematoma, 415
Index 687
formalin injections, progressive ethmoid inflammatory airway disease-affected

G
hematoma, 415 horses, 62
formants, 251–252 gag reflex, pharyngeal paralysis, 106 normal appearance, 132, 132f
fourth branchial arch defect syndrome gait, breathing patterns, 21–22, 485 recurrent airway obstruction affected
(4-BAD), 467–472 gallium-67 (67Ga), 198–199 horses, 62
age at presentation, 467 galloping, breathing patterns, 21–22 staining, 55, 56f
clinical manifestations, 468 Galt trephine drill bit, 256, 256f granular cell myoblastoma see pulmonary
definition, 467–468 gas(es) granular cell tumor
diagnosis, 468–471 blood, analysis see blood gas analysis granular cell tumor see pulmonary
differential diagnosis, 471 concentration/content in liquid, 45 granular cell tumor
endoscopy, 468–469, 469f, 470f diffusion, 45 granulation tissue
high-speed treadmill, 243–244, alveolar capillary membrane, 46–48 intralaryngeal, 538
243f, 469 movement from blood to tissue, 51–52 laser surgery, 538
exploratory surgery, 470–471 see also individual gases subepiglottic, 538
laryngeal cartilage, 468, 469f gas exchange, 13, 45–54 tracheal, post traumatic, 550–551
laryngeal examination, 106 definitions, 45 tracheostomy, post removal, 559, 560f
palpation, 468, 471 property testing, 225, 227, 230 see also granuloma(s)
prognosis, 471 recurrent airway obstruction, 575 granuloma(s)
racing performance statistics, 471, 472 units, 45 apical, 266, 267f
radiography, 159, 159f, 469–470, gas inclusions, periapical, 266f arytenoid cartilage, 524–527, 525f,
470f gas transfer rate (Vgas), 46 526f
thoroughbreds, 468 gastric content aspiration, 611 dental sinusitis, 155, 155f
thyroid cartilage maldevelopment, 471 gastrointestinal sounds, 115 fungal, 382–384, 383f
treatment, 471 gender intratracheal, 559
fractional inspired concentration of oxygen recurrent airway obstruction, 572 laryngeal, 524–527
(FIO2), 207 recurrent laryngeal neuropathy, 484 foreign bodies, 528, 528f
frictional resistance, airflow, 24–25 summer-pasture-associated obstructive surgery-induced, 524–525
clinical consequences, 25 pulmonary disease, 572 nasal, 371
frontal sinoscopy general anesthesia post-laryngoplasty, 504
structures observed, 256–258, 258f, computed tomography, 264 post-tracheostomy, 559
259 head edema, 522–523 granulomatous pneumonia, 608–609
trephination sites, 255, 255f laser surgery, 535 grass sickness, rhinitis sicca, 103, 104f,
frontal sinus, 6 mucosal inflammation, 545 370, 370f
endoscopy see frontal sinoscopy oxygen flux, 51 gravity
eversion, 405 thoracoscopy, 273 pulmonary blood flow, 37, 37f
fractures, 404 ventilation–perfusion matching, 48, 49 ventilation distribution, 28
radiography, 154 genioglossus, 440–441, 441f greenstick fractures, ribs, 661
trephination, 190 geniohyoideus, 441 groans, 109
frontomaxillary opening gentamicin grunts, 109, 113t
age-related changes in locations, 265 arytenoid chondropathy, 516 “grunt to the stick test,” recurrent
computed tomography, 265–266 Bordetella bronchoseptica pneumonia, laryngeal neuropathy, 485
endoscopy, 258f 85 guanylate cyclase, 38
frusemide, 606, 610 foals, 652t Gulf Stream disease see equine influenza
␣-1,2-fucose, 60, 62 inflammatory airway disease, 340 virus
functional residual capacity (FRC), 225, pleuropneumonia, 84, 342 “gurgles,” dorsal displacement of the soft
225f pneumonia, 83, 342 palate, 239
definition, 20 German warmbloods, recurrent airway guttural pouch(es)
pulmonary vascular resistance, 36, 36f obstruction, 572 anatomy, 7, 8f, 419–420
fungal infection(s) giant cells, 134, 135f clinical examination, 106
granulomas, 382–384 glass syringes, blood gas analysis, 204, compartments, 419
clinical signs, 382–383, 382f, 383f 205t computed tomography, 269
diagnosis, 383–384 glossoepiglottic fold ulceration, 524, 524f disorders, 419–436
pathology, 383 glossopharyngeal nerve, 26 diagnosis, 420
treatment, 384 guttural pouch mycosis, 425, 430 distension, 106, 420
sample evaluation glottis, 7 empyema see guttural pouch empyema
lower respiratory tract, 139, 140t glove powder (corn starch), 139 (GPE)
upper respiratory tract, 139 ␤-D-glucan, 567 endoscopy, 106, 420
see also specific organisms/infections glucose oxidation, 45 epithelium, 132, 419
fungal pneumonia, treatment, 85 glycerin, follicular pharyngeal hyperplasia, fungal infection see guttural pouch
fungal spores, ingested, macrophages, 444 mycosis (GPM)
134, 135f, 138 glycolysis, 45 hemorrhage, 269, 425, 426, 427f, 434
furosemide goblet cell(s), 11, 12, 55 lavage, 336, 336f, 432–433
exercise-induced pulmonary hemor- hyperplasia masses, 158
rhage, 624–625, 626 airway irritation, 140 neoplasia, 158, 435, 435f
mucociliary clearance, 65 recurrent airway obstruction, 570, neurovascular relations, 419, 419f
performance enhancement, 624 570f physical examination, 420
688 Index
guttural pouch(es) (cont’d) antigenic drift, 288 hemorrhagic pneumonia, 613

post-mortem examination, 280–281 pyrexia, 290 imaging, 613
radiography, 153, 157–158, 420 Habronema spp., 613 post-mortem examination, 613
normal appearance, 157, 157f Halicephalobus gingivalis infection, 401 hemorrhagic pulmonary infarction, acute,
X-ray beam center point, 152t halo, mesothelial cells, 135 613
sample collection, 122 hamartoma, guttural pouches, 435 hemorrhagic shock, hemothorax, 666
indications, 119 Hamburger, 53 hemosiderophages, 134, 143
surgical approaches, 420–422 haydust exposure, recurrent airway exercise-induced pulmonary hemor-
patient positioning, 420 obstruction, 78–79 rhage, 143
tympany see guttural pouch tympany head and neck angle, pulmonary function hemostasis, exercise-induced pulmonary
guttural pouch empyema (GPE), 431–434, testing, 211 hemorrhage, 619
431f head collar, fabric, 151 hemothorax, 666
causes, 431 head edema, 117 blood drainage, 666
clinical signs, 431 causes, 522 causes, 666t
computed tomography, 269, 269f laryngeal inflammation, 522–523 cytology, 148
diagnosis, 334, 431–432 head neoplasia, 191 Hendra virus (HeV), 314–316
endoscopy, 334, 431, 432f health and safety, post-mortem clinical signs, 315
post surgery, 434 examination, 283 control, 315–316
laser surgery, 539, 540f “heart failure cells,” 279 diagnosis, 315
nasopharyngeal paralysis, 446 heave, 109 epidemiology, 315
postural changes, 431, 432f heave line, 109, 110f, 573 historical context, 314
radiography, 157, 334, 431, 432f heaves see recurrent airway obstruction pathogenesis, 315
strangles, 332–333 (RAO) prevention, 315–316
Streptococcus equi infection, 334 height, recurrent laryngeal neuropathy, transmission, 315
surgery, 433–434 484 virology, 314
anesthesia induction, 433, 433f Heimlich valve, 665f, 671 wildlife reservoir, 315
treatment, 432–434 helium analyzer, 227b Henry’s law, 45
non-surgical, 432–433 helium dilution, 225 hepatized lung, 181
pouch irrigation, 432–433 helium re-breathing, 226–227b, 226f hepatopathy, laryngeal paralysis, 480–481
ultrasonography, 334 hemagglutination inhibition (HI) tests, endoscopy, 480, 480f
guttural pouch lavage equine influenza virus, 288, herbal medicine, recurrent airway obstruc-
guttural pouch empyema, 432–433 291–292 tion, 584
Streptococcus equi infection, 336, 336f hemangiosarcoma, 603 herpes virus, mucociliary clearance, 64
guttural pouch mycosis (GPM), 424–430 hematology Hertz (Hz), 175
clinical signs, 425 inflammatory airway disease, 596 hesperidin, 626
99m
diagnosis, 426–427 pleuropneumonia, 669 Tc-hexamethylpropyleneamine oxime
diphtheritic membrane formation, 424, pulmonary granular cell tumor, 602 (HMPAO)-radiolabeled
425f recurrent airway obstruction, 575 leukocytes, 186
endoscopy, 426 Streptococcus equi infection, 334 high blowing (false nostril flutter), 105,
neurological damage, 430, 430f summer-pasture-associated obstructive 369
epistaxis, 104, 157, 158f, 425, pulmonary disease, 575 high-speed treadmill endoscopy (HSTE),
426–427, 426f hematoma(s) 235–247
inflammation, 424–425 cytological examination, 142 acclimatization, 236
nasopharyngeal paralysis, 446 laryngeal reinnervation, 513 adjunctive diagnostic tests, 237
neurological damage, 425, 430 progressive ethmoid see progressive endoscopy attachment, 237, 237f
post-mortem findings, 280 ethmoid hematoma (PEH) equipment, 235–236
predisposing factors, 424 rib fractures, 661 exercise test protocol, 236–237, 237t
radiography, 157–158, 157f hemoglobinemic hypoxia, 52 unfit horses, 237
sampling contraindications, 122 hemoglobin, oxygen binding, 50–51 heart rate monitoring, 236, 237t
surgery, 422 ␣-hemolysis, 328 indications, 235
treatment, 427–430 ␤-hemolysis, 328 patient preparation, 236
guttural pouch tympany, 422–424 ␥-hemolysis, 328 resting endoscopic examination, 235
clinical signs, 422–423, 422f hemoptysis, 104 training, 236–237
endoscopy, 423 hemorrhage upper respiratory tract
history, 422–423 guttural pouch(es), 269, 425, 426, dynamic obstructions, 238–247
laser surgery, 423–424, 539 427f, 434 multiple disorders, 239f, 245, 245f
radiography, 158, 423, 423f intrapleural, thoracoscopy-induced, normal appearances, 237–238
treatment, 423–424 273 high-speed treadmill video-endoscopy,
nasal septum excision, 378–379 237
pulmonary, exercise-induced see histamine
H
exercise-induced pulmonary mechanism of action, 225
H3N8 virus, 287 hemorrhage (EIPH) provocation testing, 229b
antigenic drift, 288 submucosal, 522 recurrent airway obstruction, 569–570
outbreaks in other species, 289 see also epistaxis histotoxic hypoxia, 52
pyrexia, 290 hemorrhage scores, 144 histotoxins, recurrent airway obstruction,
H7N7 virus, 287 hemorrhagic diapedesis, 148 568
Index 689
Hoppengarten cough see equine influenza blood gas analysis, 203 immunoglobulin G (IgG), 75–76, 75f
virus drug induced, 490 plasma cell production, 76
hormones, removal by pulmonary circula- psychogenic, 205t Streptococcus equi infection, 330
tion, 38–39 respiratory alkalosis, 205t subclasses, 76–77
Horner syndrome, 25 respiratory sounds, 113 immunoglobulin Ga (IgGa), 76–77
examination techniques, 120t stimulation, 490 immunoglobulin Gb (IgGb), 76–77
mediastinal masses, 673 Hyphomyces destruens, 400 immunoglobulin M (IgM), 75, 76
vasomotor rhinitis, 370 hypocapnia, 205t, 206, 207 immunological testing, recurrent airway
Whitehouse approach, 421–422 hypoepiglotticus muscle, 7, 8 obstruction, 576–577
Horserace and Betting Levy Board (HBLB) hypogammaglobulinemia, pneumocystis immunology, 71–81
Code of Practice pneumonia, 648 immunopathology, 78–79
equine herpesvirus-1 control, 304 hypoglycemia, foals, 650 immunostimulant preparations, 85–88
Streptococcus equi infection prevention, hypopharyngeus muscle, 437 indications, 86
336–337 hypovolemia, foals, 650 mechanism of action, 85–86
horsesickness fever, 317 hypoxemia immunotherapy, recurrent airway obstruc-
Hounsfield units (HU), 263 altitude, 52, 206 tion, 584
hydatid cysts, 613 arterial carbon dioxide tension, 206 imperforate buccopharyngeal septum,
hydralazine, 606 definition, 208 377–378
hydrothorax, African horse sickness, 317 persistent pulmonary hypertension, impulse oscillometry system (IOS), 220,
hyoepiglotticus, 25 642 222f, 223b
dorsal displacement of the soft palate, pneumothorax, 663 inclusion bodies, equine herpesvirus-1,
238–239 recurrent airway obstruction, 575 302
hyoglossus, 441, 441f tidal, 52 Indian vetch (Lathyrus sativus), laryngeal
hyoid muscles, 441–442, 441f upper airway obstruction, 554 paralysis, 481
hyovertebrotomy, 420–421 hypoxia inducible nitric oxide synthase (iNOS),
endoscopy, 421 definition, 208 summer-pasture-associated
vessel identification, 421 fetal circulation, 640 obstructive pulmonary
hypercapnia, 53 lung maturation, 640 disease, 570
arterial carbon dioxide tension, 206 neonates, 640 infection/infectious disease
pneumothorax, 663 hypoxic pulmonary vasoconstriction (HPV), bacterial see bacterial infection(s)
upper airway obstruction, 554 38, 49 fungal see fungal infection(s)
hyperglycemia, foals, 650 pulmonary hypertension, 41 post-laryngoplasty, 503
hyperimmune plasma, Rhodococcus equi respiratory immunity, 77–78
pneumonia, 361, 363–364 viral see viral infection(s)
I
hyperkalemic periodic paralysis (HYPP) see also parasites; specific organisms/
laryngeal paralysis, 481 idiopathic laryngeal hemiplegia see infections
nasopharyngeal collapse, 444, 521 recurrent laryngeal infectious bronchitis see equine influenza
hyperparathyroidism, secondary, 389 neuropathy (RLN) virus
hypersensitivity disorders, 78–79 imipenem, 652t infectious catarrh see equine influenza
hypersensitivity reactions immunity virus
cytology, 141 infectious diseases, 77–78 inflammatory airway disease (IAD), 338t,
inflammatory airway disease, 593 mucosal, 72–75 339–340, 591–600
recurrent airway obstruction, 566–567 vaccine-induced, 78 bacterial, 595
type I immunodeficiency, 79 clinical signs, 339, 594
“early-phase response,” 566 severe combined see severe combined cytology, 594–595
inflammatory airway disease, 593 immunodeficiency (SCID) classification, 595–596
“late-phase response,” 566 immunofluorescence, equine nasopharyngeal sample contamina-
recurrent airway obstruction, 566 herpesviruses, 301 tion, 595
type III, 566–567 immunoglobulin(s), 75–77 definition, 565, 591
hypertension equine herpesvirus antibodies, 304 diagnosis, 340, 593–596
persistent pulmonary see persistent maternal equine influenza virus anti- endoscopy, 339, 339f, 594
pulmonary hypertension (PPH) bodies, 295–296 eosinophilic pneumonia, 613
recurrent airway obstruction, 41, 574 technetium-99m-labeled antigranulo- epidemiology, 591
hyperthermia cyte monoclonals, 186, 199 equine herpesviruses, 301
dorsoventral tracheal collapse, 549 see also specific types etiology, 592, 592t
drug-induced, 647 immunoglobulin A (IgA), 75–76, 75f exercise-induced pulmonary hemor-
respiratory distress, foals, 647 in colostrum, 79 rhage, 593
hypertonic saline, intravenous, guttural deficiency, 79 exercise performance, 599
pouch mycosis, 426 equine influenza virus, 77 history, 594
hypertrophic osteopathy, 674f foals, 79 immunopathology, 78
clinical features, 117, 601 plasma cell production, 76 management, 340
lameness, 601 secretory, 73, 76, 76f metachromatic inflammation,
laryngeal cartilages, 527 Streptococcus equi infection, 330 594–595, 597
radiography, 171, 173f immunoglobulin D (IgD), 76 mucus accumulation, 61
hyperventilation, 206 immunoglobulin E (IgE), 76 non-bacterial, 596
auscultation, 111 type I hypersensitivity reaction, 566 prevalence, 339
690 Index
inflammatory airway disease (IAD) (cont’d) foals, 646–647 lamina propria lymphocytes, isolated, 74
prevention, 340, 596–599 clinical signs, 646 laminar flow, 35
recurrent airway obstruction vs., etiology, 646, 647 laminitis, 673
591–592, 592t post-mortem examination, 647 Lancefield groups, 329
risk factors, 591 radiography, 647 group C, 327–328, 328f
Streptococcus zooepidemicus, 345 treatment, 647 laryngeal abscess, 527
treatment, 596–599 Hendra virus, 315 laryngeal burr, epidermal inclusion cysts
inflammatory disorders, 78–79 pathogenesis, 606 removal, 373, 373f
see also specific disorders prognosis, 608 laryngeal edema
inhalation, 108 radiography, 607, 607f external laryngeal trauma, 522
epiglottal entrapment, 241 treatment, 607–608 head edema induced, 523, 523f
lung expansion, 19–20 interstitium, radiography, 162f, 163 laryngeal foreign bodies, 527–529
muscles, 22–23 intradermal allergen testing, recurrent clinical signs, 528
pleural pressures, 23 airway obstruction, 576–577 diagnosis, 528, 528f
resting horse, 20–21 intralaryngeal round stents, laryngeal endoscopy, 528, 528f
inhalation anesthesia, arterial cannulation, stenosis, 530 radiography, 528–529
203–204 intravenous fluid therapy, smoke removal, 529
inhalation therapy inhalation, 611 treatment, 529
inflammatory airway disease, 597 intubation, laryngeal inflammation, 522, laryngeal granulomas, 524–527
scintigraphy, 193t, 198 525 surgery-induced, 524–525
innate immunity, 71–72, 71t, 77 iodides, recurrent airway obstruction, 584 laryngeal hemiparesis, surgical
in situ hybridization, 283–284 Iohexol, 153 management, 497–508
inspiration see inhalation ionophore toxicity, acute, 675t laryngeal hemiplegia, 23
interannular ligaments, 107 ipratropium bromide, 92 arytenoid chondropathy, 515
intercostal blood vessel perforation, albuterol sulfate and, 94 guttural pouch mycosis, 430
thoracoscopy, 273 exercise-induced pulmonary hemor- idiopathic see recurrent laryngeal
intercostal muscles, 23 rhage, 625 neuropathy (RLN)
intercostal nerve block, rib fractures, 661 inflammatory airway disease, 340, 598 respiratory sounds, at exercise, 251,
interferon-␣ (IFN-␣), 77, 87–88 recurrent airway obstruction, 578t, 251f
follicular pharyngeal hyperplasia, 444 584 surgical management, 497–508
inflammatory airway disease, 593, 598 irradiance, 534 laryngeal inflammation, 522–523
mechanism of action, 88 isocontour function, scintigraphy, 196 external laryngeal trauma, 522
pneumocystis pneumonia, 648 isoflupredone acetate, 578t, 581 parasitic, 527
treatment failure, 88 isotonic saline solution, recurrent airway laryngeal movements
interferon-␤ (IFN-␤), 77 obstruction, 584 abnormal, 490–491
interferon-␥ (IFN-␥), 72b itraconazole, 85, 384 examination, post exercise, 490
recurrent airway obstruction, 569 ivermectin, 401, 612 grading, at rest, 491, 492t
Rhodococcus equi infection, 78 normal, 487–488, 487t, 488f, 489f
interleukin-2 (IL-2), 72b stimulation technique, 488–490
J
interleukin-3 (IL-3), 62 laryngeal mucosal ulceration, idiopathic,
interleukin-4 (IL-4), 72b, 569 J001X scintigraphy, 199 524–527
interleukin-5 (IL-5), 72b, 569 jugular vein “kissing,” 525
interleukin-6 (IL-6), 72b distension, 117 laryngeal nerves, cranial, 9
interleukin-7 (IL-7), 569 O2 tensions, 208 laryngeal obstruction
interleukin-8 (IL-8), 568 extubation, 479
interleukin-9 (IL-9), 569 laryngeal reinnervation, 512–513
K
interleukin-10 (IL-10), 72b laryngeal palpation, external, 515
interleukin-12 (IL-12), 72b karyolysis, neutrophils, 136–137, 137f, laryngeal paralysis
interleukin-13 (IL-13), 72b 148 known/suspected causes, 479–481
internal abdominal oblique muscle, 23 keel stent, laryngeal stenosis, 530 nerve damage, 479, 479t
internal carotid artery, 427, 428f ketamine, 463 non-recurrent laryngeal neuropathy,
internal carotid artery ligation ketoconazole, 85, 384 479–481, 480t
balloon-tipped catheter insertion, 427 “kissing” lesions, arytenoid chondropathy, postanesthesia, 479–480
complications, 428–429 515 surgical management, 497–508
guttural pouch mycosis, 427–430 Krebs cycle, 45 laryngeal reinnervation, 509–514
internal intercostal muscles, 23 krypton-81m (81mKr) gas, 194–195, 194t clinical case results, 513
interstitial pattern, radiography, 164, 165f “kunkers,” 400 standardbreds, 513
generalized, 164 thoroughbreds, 513
nodular, 164 warmblood, 513
L
interstitial pneumonia, 606–608 complications, 512–513
breathing abnormalities, 108t L-708,738, 92 endoscopic assessment, postoperative,
clinical signs, 606 ␤-lactam antibiotics, 85 512
diagnosis, 606–607 lactic acid, 45 future directions, 514
disseminated pulmonary granulomas, lameness historical context, 509–510
87 hypertrophic osteopathy, 117, 601 postoperative management, 512
etiology, 606 Rhodococcus equi infection, 357 prosthetic laryngoplasty vs., 514
Index 691
laryngeal reinnervation (cont’d) innervation, 474–475, 475f long distance transportation

success assessment, 512 intrinsic muscles, 8–9, 9f equine influenza virus, 292
technique, 510–511 lateral ventricle, 9 pleuropneumonia, 342, 668
laryngeal saccules, 9 mucosa, 9 pneumonia, 342
laryngeal stenosis, 521, 529–531, 529f post-mortem examination, 280 longus capitis muscle, 543
causes, 530, 530f radiography, 158–159 lower respiratory tract (LRT)
treatment, 530–531 normal appearance, 157f, 158 auscultation, 111–116
laryngeal tie-forward, 452, 453f X-ray beam center point, 152t hyperventilation, 111
BC distance, 452 see also entries beginning laryngo-/ limitations, 111
BT distance, 452 laryngeal protocol, 111
dorsal displacement of the soft palate, laser fibers, 534 bacterial infections, 140t, 146, 338–343
447, 452 lasers age-related, 338, 338t
postoperative care, 452 colors, 534 opportunist pathogens, 343, 343f
laryngeal trauma, external, 522 components, 534 sample evaluation, 139, 140t
laryngeal tumors, 531 power and safety classification system, clinical examination, 107–109
laryngeal ventricles, 9 533–534 defense mechanisms, 71t
radiography, 158 principles, 533–534 diameter, 26–28
laryngeal webbing see laryngeal stenosis pulsed vs. continuous modes, 534 sampling, 122–128
laryngomalacia, 521 systems, 534–535 collection timing, 122
laryngoplasty tissue interactions, 534 epithelial cells, 132–133
complications, 502–504, 504f wavelength, 533 indications, 119–121
correctional surgery, 502–503, 502f laser surgery, 533–541 smooth muscle contraction, 26–28
efficacy, 499–500 collateral thermal damage, 540 lung(s)
clinical cases, 500–502 complications, 540 air replenishment, 19–20
endoscopy contact technique, 534 anatomy, 11–14, 12f
intraoperative, 497, 498f instrumentation, 535, 535f biopsy see lung biopsy
postoperative, 499f non-contact technique, 534 dead space, 21, 21f
failure, 501 patient safety, 535 defense mechanisms, 71t
laryngeal reinnervation vs., 514 personnel safety issues, 535 development, 638
outcomes postoperative treatment, 536 fetal, 638
non-racing breeds, 501–502 preoperative preparations, 535 hepatized, 181
racehorses, 500–501 procedures, 536–540 lobes, 11
postoperative care, 498–499, 499f progressive ethmoid hematoma, 415 lobules, 11
prothesis infection, 503 lateral radiographs, 151, 151f lymphatics, 15
repeat surgery, 504 center points, 152t post-mortem examination, 278
respiratory noise reduction, 253 lateral tracheal flattening (scabbard fetuses/foals, 281–282
suture penetration into airway, 504, trachea), 543, 546 post-mortem samples, 278–279
504f latex agglutination test radiography, 163
suture prosthesis, 497 cryptococcosis, 384 ultrasonography, 178
suture removal/replacement, 503 streptococci, 329 volume expansion, 19–20
technique, 497–499 Lathyrus sativus (Indian vetch), laryngeal volumes, 20
upper airflow flow mechanics, 499 paralysis, 481 see also entries beginning pulmonary/
variations, 497–498 Lathyrus spp. ingestion, 481 respiratory
ventriculocordectomy vs., 506–507 least squares regression, dynamic com- lung abscess see pulmonary abscess
laryngospasm, 525 pliance calculation, 217b, lung biopsy, 274–275
laryngotomy 218f contraindications, 274
dorsal displacement of the soft palate, leukocytosis, interstitial pneumonias, indications, 274
449, 450f 606 interstitial pneumonias, 607, 607f
epiglottic augmentation, 451 leukotriene receptor antagonists, 91–92 percutaneous, 274
epiglottic entrapment resection, 463 levalbuterol, 93–94 complications, 274
laryngeal foreign bodies, 529 levamisole phosphate, 88–89 pulmonary granular cell tumor,
laryngotracheobronchitis see equine levator nasolabialis, 3 602–603
influenza virus levator veli palatini muscle, 439, 440f silicosis, 608
larynx, 7–9, 25, 473–474 ligamentum arteriosum, 34 thoracoscopically guided wedge
abductor muscles, 23, 491 lidocaine, pulmonary edema, 606 resection, 274–275, 275f
cartilage, 7–8 light source, thoracoscopy, 272 transendoscopic pinch, 274, 274f
fractures, 522 linezolid, 361 lungfish, 474
computed tomography, 269 lingual tonsil, 7, 74f, 75 lungworm (Dictyocaulus arnfieldi) infection,
congenital defects, 521 linguofacial vein ligation, nerve muscle 279, 612
development, 474 pedicle graft, 510 clinical signs, 579
epithelium, 9 Lippizaner horses, recurrent airway diagnosis, 139, 579
examination, 106–107 obstruction, 572 lymphadenopathy
extrinsic muscles, 8 liquid nitrogen cryotherapy, progressive equine herpesvirus-1, 301
function, 7, 20t ethmoid hematoma, 415 submandibular, 105
high-speed treadmill endoscopy, 237, lobeline, 96 lymph node abscess, tracheal compression,
238f lobelinum hydrochloridum, 490 552
692 Index
lymph node enlargement, strangles, 332, meconium staining, skin, 634 Miniature horses
332f meconium, surfactant inhibitors, 643 alar fold stenosis, 374
lymphocytes, 72, 136, 568–569 medetomidine, 204t trachea, 10
aggregated, 74 mediastinal pleura, 16 modified Whitehouse approach, 421
free luminal, 74 mediastinum guttural pouch tympany, 423
immunophenotype, 75t abscesses, 673 molds
intraepithelial, 74 disorders, 664, 673 recurrent airway obstruction, 78–79,
recurrent airway obstruction, 571 laryngeal paralysis, 479t 567
sample interpretation, 143 masses, 673 summer-pasture-associated obstructive
lymphoid hyperplasia, 141 clinical signs, 673 pulmonary disease, 566
lymphoma (lymphosarcoma), 601–602 imaging, 673 mononuclear cells, large, 134–135
clinical signs, 601 radiography, 170 mononuclear phagocytes, 135
diagnosis, 601–602 post-mortem examination, 278 montelukast, 92
tracheal compression, 552 radiography, 163 Mortola–Saetta method, dynamic com-
lymphomegaly, peripheral, 117 tumors pliance measurement, 218b
lytA gene, 346 clinical signs, 601 M proteins
tracheal compression, 545, 552 Streptococcus equi infection, 330–331
ultrasonography, 180, 181f Streptococcus zooepidemicus, 345
M
mediators, pulmonary circulation, 37–38 MUC2, 56, 57f, 62
macrophages, 134, 134f, 143 medications, pharmacology/therapeutics, MUC5AC, 56, 57f, 62, 571
delayed processing, 137 83–99 MUC5B, 56, 62
exercise-induced pulmonary hemor- see also specific drugs/drug types mucins, 55–57, 57f
rhage, 623 melanoma, guttural pouches, 158, 435, genes, 56
reactive, 134 435f hypersecretion, 61–62, 61f
recurrent airway obstruction, 570 memory B cells, 73–74 production, immunology, 62–63
magnesium sulfate infusions, 642 meningoencephalitis, postoperative, 414 recurrent airway obstruction, 63, 571
malodorous breath, 104 mesothelial cells, 16, 135, 136f mucociliary apparatus, 55–58, 56f
laryngeal foreign bodies, 528 mesothelioma, 603 mucociliary clearance, 57–58
pleuropneumonia, 669 post-mortem findings, 278 autonomic control, 58
mandible, scintigraphy, 188 metabolic acidosis, 205t disease, 64
manure, Rhodococcus equi pneumonia, 364 metabolic alkalosis, 205t equine influenza virus, 291, 291f
Marie’s disease see hypertrophic osteopathy metastatic abscess, Streptococcus equi gravity, 57, 65
mast cells, 137, 138f, 144 infection, 333, 335 radiographic markers assessment,
inflammatory airway disease, 594 metered dose inhaler (MDI) 231
recurrent airway obstruction, 569–570 preparation, 95 recurrent airway obstruction, 64
type I hypersensitivity reaction, 566 recurrent airway obstruction, 581 scintigraphy, 193t, 198
mast cell stabilizers, 91 methacholine, 225 therapy, 65
maxillary bone metronidazole trachea, 545
dental sinusitis, 266–267 bronchopneumonia, foals, 339 viral infection, 64
fractures, 157 foals, 652t mucociliary function, 55–69
swelling, reserve tooth crowns, 405 inflammatory airway disease, 340 mucokinetic agents, 584
maxillary cheek teeth pleuropneumonia, 84, 342 mucolytics
apical infection, 399 pneumonia, 342 mucus accumulation, 65–66
dental sinusitis, 155 microbial culture peptide, 66
eruption cysts, 554 follicular pharyngeal hyperplasia, 443 recurrent airway obstruction, 584
radiography, 153–154, 153f interpretation, 144–146 mucosa-associated lymphoid tissue
X-ray beam center point, 152t lower respiratory tract, 146 (MALT), 73
maxillary sinus, 4–6, 6f upper respiratory tract, 145, 146f mucosal immunity, 72–75
fractures, 404, 404f nasal/nasopharyngeal sample collection, response initiation, 73, 73f
X-ray beam center point, 152t 121–122 mucosal lymphoid nodules, 74
maximal change in pleural pressure, 215 Rhodococcus equi pneumonia, 360 mucous glycoproteins see mucins
maximal change in pleural pressure during sample processing, 128 mucous membrane, oral, 439
tidal volume (⌬Ppl max), 24, microbial surface components recognizing mucus
212 adhesive matrix molecules accumulation of see mucus
calculation, 215 (MSCRAMMS), 330 accumulation
lung function indicator, 24 microfold (M) cells, 73 composition, 55
Mead–Whittenberger technique, 217b, microphones disease-induced alterations, 63–64,
217f cavison-mounted, 250–251, 251f 63f, 64f
mechanical ventilation, premature lungs, in facemasks, 250 evaluation, 130–131
640 in nasopharynx, 250 guttural pouch tympany, 423
meconium aspiration, 281, 640, 643–644 recurrent laryngeal neuropathy, 486 inflammatory airway disease, 594
clinical signs, 643 Micropolysporua faeni (Faenia rectivirgula), physical properties, 57
pathophysiological effects, 643 566 recurrent airway obstruction, 63, 63f,
persistent pulmonary hypertension, 641 milk aspiration, 635, 637f 571
prognosis, 644 miller’s disease see osteodystrophia fibrosa viscoelasticity, 57
treatment, 643–644 mineral oil, aspiration pneumonia, 611 viscosity, 57
Index 693
mucus accumulation, 55–69 dilation, 25 pathology, 386

airway thickness, 60 assessment, 103 permanent tracheostomy, 554
associated diseases, 58–60 examination, 103–104, 120t prevalence, 386
causes, 61–64 exercise-induced pulmonary hemor- prognosis, 387
clinical significance, 58–61 rhage, 625 signalment, 386
environment, 65 exhaled air volume assessment, 103 treatment, 387
epidemiology, 58–61 movement, 3, 23 nasal occlusion maneuver, 488–489
exercise-induced pulmonary hemor- paralysis, 103 limitations, 489
rhage, 623 respiratory sound recording, 250–251, recurrent laryngeal neuropathy, 489
mechanisms, 61–64 251f nasal oxygen insufflation, 642
prevention, 64–66 wounds, 375, 375f nasal paralysis, 369
quantification, 58, 58t, 59f nasal cavity nasal polyps, 280, 387, 387f, 388
recurrent airway obstruction, 570–571, anatomy, 3–6, 153–154 nasal prosthesis, nasal paralysis, 369
570f computed tomography, 265 nasal septum, 3, 371f, 374f, 378
therapy, 64–66 diseases, 369–392 deformity, 378–380
mucus cell metaplasia, 62 distortion/deformation surgical complications, 380, 380f
mucus-producing cells, 55 nasal neoplasia, 386 deviation, 378
mucus score, 58, 58t, 59f permanent tracheostomy, 554 displacement, sinusitis, 393
multiple breath nitrogen washout, 225, epithelium, 132 excision, 378–380
226b examination, 103–104 hemorrhage, 378–379
multiple inert gas elimination technique function, 20t post-mortem examination, 280
(MIGET), 227, 230 post-mortem examination, 280 radiography, 154
multiple linear regression (MLR) technique, radiography, 153–154, 153f resection, 379–380, 379f
total pulmonary resistance, sample collection, 121–122 thickening, 378
218b indications, 119 nasal turbinates, 3–4, 4f
multisystemic eosinophilic epitheliotrophic submucosa, 4 post-mortem examination, 280
disease, 279 nasal collapse, 369 nasal valve, 3
muscarinic receptors nasal conchae, 3 nasal washes, 121
airway smooth muscle, 27 nasal dilator bands, exercise-induced nasofrontal bone-flap osteotomy, 394–396,
bronchospasm, 92 pulmonary hemorrhage, 625 395f, 396f, 397f
muscular tremors, 115 nasal discharge, 104, 116 exudate, 397f
mycobacterial cell wall products, 87 bilateral, 104 trephination, 396, 397f
adverse reactions, 87 bronchopneumonia, foals, 338 nasofrontal suture exostoses, 404–405
granulomatous pneumonia development, dental sinusitis, 399 clinical signs, 405
608–609 equine herpesvirus-1, 300 radiography, 405
mycobacterial infections equine influenza virus, 290 nasofrontal suture periostitis, 157
granulomatous pneumonia, 608 examination techniques, 120t nasogastric tubes, wry nose, 376
post-mortem examination, 279 guttural pouch empyema, 431 nasolacrimal duct, 3
mycobacterial preparations, immunostimu- of milk, cleft palate, 454 nasolacrimal orifice, 103
lant activity, 86–87 mycotic sinusitis, 400 nasomaxillary aperture (NMA), 6, 6f
Mycobacterium avium, 608 nasal neoplasia, 386 nasomaxillary opening, 4–6
Mycoplasma, 349–351, 350b oronasal fistula, 371 nasopharyngeal cicatrix, 455, 455f
cell culture, 351 pleuropneumonia, 669 permanent tracheostomy, 554
clinical disease, 349 progressive ethmoid hematoma, 411 nasopharyngeal collapse, 242–243,
diagnosis, 351 purulent secretions, 104 444–446, 444f, 446f
features, 349 sinus cysts, 401 causes, 444
inflammatory airway disease, 592 sinusitis, 393 diagnosis, 445
management, 351 strangles, 332, 332f dorsoventral, 242, 244f
pathogenesis, 350–351 unilateral, 104 endoscopy, 445
virulence factors, 350 nasal diverticulum (false nostril), 3, 103 high-speed treadmill, 242–243
Mycoplasma equirhinis, 146, 350, 592 nasal flutter see alar fold(s), stenosis experimental induction, 243
Mycoplasma felis, 146, 349, 592 nasal granuloma, 371 inflammation, 444
mycoplasma immunodominant protein nasal infection, mycotic, 380–381 lateral, circumferential, 242, 244f
(MIA), 350 clinical signs, 381 models, 444–445
mycotic plaques, 381, 381f diagnosis, 381, 381f treatment, 445–446
myelinopathy, recurrent laryngeal signalment, 381 nasopharyngeal paralysis, 446
neuropathy, 476 treatment, 381 nasopharyngeal scarring, 455, 455f
myoglobinuria, atypical, 675t nasal mucosa examination, 103 nasopharyngeal tonsil, 74f, 75
nasal neoplasia, 385–387 nasopharynx, 7
biopsy, 386 anatomy, 437–442
N
clinical signs, 386 constrictor muscles, 437, 438f
N-acetyl cysteine (NAC), 65–66 computed tomography, 387 dilating muscles, 437, 438f
nacystelyn, 66 diagnosis, 386–387 disorders, 437–457
L-NAME, 38, 625 differential diagnosis, 386, 387f functional, 444–454
nares, 3 grading, 386 inflammatory, 442–444
abductor muscles, 23 metastasis, 386 epithelium, 437
694 Index
nasopharynx (cont’d) muscle dissection, 510

O
examination, 105–106 surgical technique, 510–511
high-speed treadmill endoscopy neuromuscular disorders obesity, respiratory sounds, 113
appearance, 237–238 breathing compromise, 673–674, 673t, occipital artery, 427, 428f
inspiration, 437, 438f 675t ocular discharge, equine herpesvirus-1,
lymphocytes, 75 laryngeal paralysis, 480–481, 480t 300
microphone placement, 250 neuron loss, recurrent laryngeal odor receptors, 4
mucous membrane, 439 neuropathy, 475 Office International des Epizooties (OIE),
neoplasia, 454 neutrophil nuclear hyposegmentation Code of Conduct, 297
radiography, 158–159 artifact, 138 olfactory epithelium, 4
normal appearance, 157f, 158 neutrophils, 136–137, 143–144 olfactory nerve (CN I), 4
X-ray beam center point, 152t apoptosis, 137 omohyoideus, 441–442, 543
respiratory sound recording, 250 bacterial infections, 140, 141f laryngeal reinnervation, 510
sample collection, 121–122 inflammatory airway disease, 594 resection, 451
indications, 119 karyolysis, 136–137, 137f, 148 onion bulbs, 475f
natamycin, 400 mucus accumulation, 61, 62 opiate agonists, cough suppression, 96
near drowning, 612 pleuropneumonia, 147 opioids, epiglottic entrapment axial
nebulization recurrent airway obstruction, 568, 575 division, 461–462
airway responsiveness measurement, summer-pasture-associated obstructive opsonophagocytosis, 330
228–229b, 228f pulmonary disease, 568, 575 optical electrodes, blood gas analysis, 201
Rhodococcus equi pneumonia, 361–362 Newmarket cough see equine influenza optical resonator, lasers, 534
neck virus optode-based analyzers, blood gas analysis,
disorders, laryngeal paralysis, 479t Nipah virus, 314 201
neoplasia, head edema, 522, 523f nitric oxide (NO) organic iodide
necropsy examination see post-mortem exercise, 39–40, 40f conidiobolomycosis, 384
examination inhaled mycotic nasal infection, 381
necrotizing pneumonia, 613 meconium aspiration, 644 organophosphate-induced toxicity,
nedocromil sodium, 91, 583 persistent pulmonary hypertension, laryngeal paralysis, 481
nematode parasites, 612–613 642 oronasal fistula, 371, 372f
neodymium:yttrium–aluminum–garnet vascular tone, 37–38 oropharynx, 7
(Nd:YAG) laser, 535 nitrofurazone, 444 osteitis, scintigraphy, 189
neonate(s) nitroglycerin, 624 osteodystrophia fibrosa, 388–390, 405
post-mortem examination, 281–282 nodular lymphoid tissue, 74–75 clinical signs, 389, 389f
rib fractures, 659, 660f noise, 250 diagnosis, 389
see also foals non-adrenergic non-cholinergic excitatory etiopathology, 389
neon re-breathing, 227b nervous system (eNANC), 28 prevalence, 389
neoplasia non-adrenergic non-cholinergic inhibitory prognosis/treatment, 389–390
cytology, 142 nervous system (iNANC), radiography, 389
pleural fluid, 149 27–28 osteoma(s), 388, 388f
guttural pouch, 158, 435, 435f non-steroidal anti-inflammatory drugs paranasal sinuses, 403
metastatic thoracic, 603, 603f (NSAIDs) osteomyelitis, Rhodococcus equi infection,
nasal see nasal neoplasia bacterial pneumonia, 645 357
nasopharynx, 454 epiglottic entrapment, post-operative, osteotomy
neck, 522, 523f 463 caudal maxillary, 396, 398f
paranasal sinuses, 157, 403–404 recurrent airway obstruction, 583 nasofrontal bone-flap see nasofrontal
pleural effusion, 148–149 Rhodococcus equi pneumonia, 361 bone-flap osteotomy
post-mortem examination, 280, 281 tracheal rupture, 550 ostium, 419–420
pulmonary, 601–603 nose surgical enlargement, 422
sinus see sinus neoplasia anatomy, 3 otitis interna, 434
thoracic, 170, 172f, 271, 601 epithelium, 4, 5f otitis media, 434
upper respiratory tract, 268 frictional resistance, 24 output coupler, lasers, 534
see also tumor(s); individual types innervation, 4 ␤-N-oxalylamino-L-alanine, 481
Neoprene exercise boots, high-speed see also entries beginning naso-/nasal oximeters, 207
treadmill endoscopy, 236 nosebleeds see epistaxis oxitropium bromide, 92
nerve anastomosis, laryngeal reinnerva- nostrils see nares oxygen (O2)
tion, 509, 513 notifiable diseases, equine arteritis virus, alveolar capillary membrane diffusion,
nerve blocks, rib fractures, 661 311 47
nerve damage, laryngeal paralysis, 479, noxious gas exposure arteriovenous content differences,
479t inflammatory airway disease, 593 208–209
nerve implantation, 509 recurrent airway obstruction, 567 cascade, 45, 45t
nerve muscle pedicle (NMP) graft Nramp1 gene, 356 exchange, ventilation–perfusion ratios,
technique nuclear factor-␬B, recurrent airway 50
closure, 511 obstruction, 569, 570 flux (DO2), 51
first cervical nerve dissection, 510 nucleus ambiguus, 474 hemoglobin binding, 50–51
graft insertion, 511 nutritional myodegeneration, 675t movement from atmosphere to
historical context, 509–510 nystatin, 400, 430 alveolus, 45–46
Index 695
oxygen (O2) (cont’d) Parascaris equorum (round worm), cleaning, 559

partial pressures (PO2), 19, 19f 139–140, 612–613 indications, 554
alveolar–arterial O2 tension parasites inflammation of site, 558–559
difference (P(A–a)O2), 207–208 cytological diagnosis, 139–140 nasal paralysis, 369
alveolar (A) O2 tension (PAO2), 46 eosinophilic pneumonia, 612–613 procedure, 556–557, 557f
inspired air (PI O2), 45–46 laryngeal inflammation, 527 persistent pulmonary hypertension (PPH),
jugular venous O2 tensions, 208 parathormone, osteodystrophia fibrosa, 641–643
venous oxygen (Pv O2), 208 389 causes, 641–642
pathways for, 19 parietal pleura, 16 clinical signs, 641–642
solubility coefficient, 45 pars costalis, 15 diagnosis, 641–642
therapeutic see oxygen therapy partial arytenoidectomy radiography, 642
transport, 50–51, 51f arytenoid chondropathy, 517–518 reactive, 641
oxygen therapy complications, 518–519 treatment, 642–643
foals, 650 mucosal flap formation, 517 Perspex block and cell sedimentation
intranasal postoperative endoscopy, 517–518, 518f technique, 129
dorsoventral tracheal collapse, 549 prognosis, 518 pharyngeal cysts, 452–454
pneumothorax, 664 partial pressure (P), 45 clinical signs, 453
Rhodococcus equi pneumonia, 361 partial pressure of oxygen in inspired air endoscopy, 453–454, 453f
smoke inhalation, 610 (PI O2), 45–46 laser surgery, 537–538, 537f
oxyhemoglobin (HbO2) dissociation curve, particulate matter inhalation, inflamma- radiography, 159, 454
50–51, 51f tory airway disease, 593 surgical excision, 454
oxytetracycline, 339, 340, 342 Pasteurella, 347–349, 348b, 592 pharyngeal dysphagia, 104, 106
Pasteurella caballi, 347, 348–349 pharyngeal lymphoid hyperplasia, 78
Pasteurellaceae, 347–349, 348b pharyngeal masses, laser surgery,
P
clinical disease, 347 537–538, 537f
pain diagnosis, 349 pharyngeal ostium catheterization, guttural
control, rib fractures, 661 features, 348 pouch tympany, 424
diaphragmatic hernia, 662 management, 349 pharyngeal reflex, pharyngeal paralysis,
thoracic see pleurodynia; pleurodynia pathogenesis, 349 106
(thoracic pain) virulence factors, 348–349 pharyngeal sprays, post-operative epiglottic
palate, development, 454 pathological shunt, 50 entrapment, 463
palatine aponeurosis, 440 penetrating trauma pharyngitis see follicular pharyngeal
palatine artery, guttural pouch mycosis, thoracic wall, 659 hyperplasia
429–430 tracheal, 549 pharynx
palatine tonsils, 74, 74f penetration index (PI), 195–196 anatomy, 6–7
palatinus muscle, 440 penicillin computed tomography, 269
palatopharyngeal arch, “dew drop” arytenoid chondropathy, 516 dilatation, 25
appearance, 159 bronchopneumonia, foals, 339 endoscopy, 7, 8f
palatopharyngeus muscle, 437, 440 foals, 652t epithelium, 7, 132
palatoschisis see cleft palate inflammatory airway disease, 340, 598 examination, 105–106
palmar arteries, blood gas analysis, 203 pleuropneumonia, 83–84, 342 function, 20t
panniculus (cutaneous colli) muscle, 543 pneumonia, 83, 342 muscles, 7, 23, 437
parainfluenza-3 (PI3), 316 Streptococcus equi infection, 336 palpation, 105–106
clinical signs, 316 Streptococcus pneumonia infection, 347 post-mortem examination, 280
diagnosis, 316 Streptococcus zooepidemicus infection, see also entries beginning pharyngeal
epidemiology, 316 345–346 pH, blood see blood pH
paralaryngeal accessory bronchial cyst, pentachlorophenol, 647 phenylbutazone
521 pentamidine, 85 arytenoid chondropathy, 516
paranasal sinuses pentoxifylline, 582, 625 laryngeal reinnervation, 512
anatomy, 6, 7f, 394f peptide mucolytics, 66 laser surgery, postoperative, 536
computed tomography, 265 percussion phosphodiesterase inhibitors, 95
cysts, 268 paranasal sinuses, 105 persistent pulmonary hypertension,
disorders, 393–407 thorax, 115–116, 116f 642–643
drainage, 6 abnormal, 116t recurrent airway obstruction, 582
epithelium, 132 indirect technique, 115–116 phosphorus, osteodystrophia fibrosa, 389
examination, 105 perfusion scintigraphy, 193t, 196–197 photons, 533
fractures, 404, 404f imaging, 196 phrenic nerve, 15
neoplasia, 157, 403–404 radiopharmaceuticals, 196 physiological dead space (VDPHYS), 46
percussion, 105 ventilation–perfusion ratio assessment, piezoelectric-type transducer, 213b, 213f
post-mortem examination, 280 196–197, 197f pink eye, 306
radiography, 153–154, 153f pericardial sac, post-mortem sampling, 278 pirbuterol, 93, 578t, 583, 598
scintigraphy, 188 Perilla frutescens, 606 pixels, 263
sinoscopy, 255–261 peripheral neuropathy, hepatic disease, 481 plasma bicarbonate concentration (HCO3–),
traumatic injury, 404 permanent tracheostomy, 553 201, 207
see also individual sinuses after care, 558–559 plasma cells (reactive lymphocytes), 136
parapoxvirus ovis, inactivated, 87 choanal atresia, 378 plastic syringes, blood gas analysis, 205t
696 Index
platelet function, exercise-induced “pleural peel,” pleuropneumonia, fungal, 85

pulmonary hemorrhage, 626 668–669 hematogenous, 166
pleura(e), 15–16 pleural pressure management, 342
disorders, 662–674 cyclic changes, 22f, 23–24 mycotic, 166
post-mortem examination, 277–278 exercise, 618–619 necrotizing, 613
tumors, 602 pleural tumors, 602 pathogenesis, 341
ultrasonography, 178 pleuritis radiography, 166, 167–168f
see also entries beginning pleuro-/pleural pleural fluid, 148 treatment, 83
pleura adhesions, 179, 180f post-mortem findings, 278 see also specific types
pleural abscess thoracoscopy, 273–274 pneumonitis, chicken hypersensitivity,
drainage, 672 ultrasonography, 179, 179f, 180f 578
pleuropneumonia complication, 672 pleurodynia (thoracic pain), 16, 659 pneumotachographs, ultrasonic, 213b
pleural cavity, 16 breathing abnormalities, 108t pneumothorax, 662–664
sampling indications, 119–121 clinical signs, 116 air aspiration, 664
pleural drainage examination techniques, 120t breathing abnormalities, 108t
complications, 671 percussion, 116t causes, 663t
pleuropneumonia, 342, 342f, 671 pleuropneumonia, 669 classification, 662
pleural effusion, 666–667 pleuropneumonia, 338t, 340–342, clinical signs, 663
breathing abnormalities, 108t 668–674 closed, 663
causes, 667t causative organisms, 83, 668 diagnosis, 663
clinical signs, 667 clinical signs, 341, 669 drainage, 664, 665f
congestive heart failure, 666–667 complications, 672–673 management, 663–664
with fibrinous tags, 180, 180f diagnosis, 341–342, 669 mechanism, 23, 24f
foals, 168–169, 635 etiology, 668–669, 668t open, 663, 664
investigation, 667 exudative phase, 668 pathogenesis, 662
mesothelioma, 603 fibrinopurulent phase, 668 pleuropneumonia, 342, 673
pathogenesis, 666–667 investigations, 669 pneumonia, 342
pleural exudates, 667 management, 342 post-mortem examination, 277, 278
pneumonia/pleuropneumonia, 341 organization phase, 668–669 post temporary tracheostomy, 558
radiography, 167–168, 170f pathogenesis, 341, 668–669 radiography, 169, 171f, 663
respiratory sounds, 112f, 113 peripheral subcutaneous edema, respiratory sounds, 112f
treatment, 667 117 simple, 663
ultrasonography, 178–179, 179f phases, 668–669 tension, 663
pleural empyema, 672 pleural fluid changes, 147–148 thoracocentesis-induced, 128
pleural fluid (PF), 16 post-mortem findings, 278 thoracoscopy-induced, 273
bacterial culture, 139 prognosis, 673 ultrasonography, 182–184, 183f, 663
biochemical evaluation, 130 radiography, 669 Poiseuille equation, 34–35, 35f, 212b
cholesterol concentration, 130 risk factors, 668 Poiseuille flow, 35
collection see thoracocentesis thoracoscopy, 271 Poiseuille’s law, 34–35, 35f
color, 130 treatment, 83–84, 670–672 pollen, summer-pasture-associated
contamination, 148 ancillary, 672 obstructive pulmonary
exudate, 147, 147t ultrasonography, 669, 670f disease, 566
glucose concentration, 130 pleuroscopy, pleuropneumonia, 669 polymerase chain reaction (PCR)
inflammatory cells, 133 ply gene, 346 African horse sickness, 317
interpretation, pathological changes, Pneumabort K, 305 post-mortem examination, 283
147–149 Pneumocystis carinii, 647 Rhodococcus equi pneumonia, 360
lactate concentration, 130 diagnosis, 146 polypropylene, 205t
large mononuclear cells, 134–135 forms, 647 polyps
modified transudate, 147, 147t pneumocystis pneumonia, 647–648 cytological examination, 142
neoplasia, 149 carriers, 647 laryngeal foreign bodies, 528, 529f
neutrophils, 136, 137 clinical signs, 648 nasal, 280, 387, 387f, 388
normal, 127, 129, 130, 666, 667t cytology, 648 tracheal, 561, 561f
pH, 130 post-mortem examination, 648 polysynovitis, Rhodococcus equi, 357, 358f,
pleuropneumonia, 341 radiography, 648 362
post-mortem collection, 278 severe combined immunodeficiency, ponies, dorsoventral tracheal collapse,
production, 666 79 546–547
red blood cells, 132 treatment, 85, 648 poor contact artifacts, ultrasonography,
resorption, 666 pneumolysin, 346 177, 178f
total nucleated cell counts, 131 pneumomediastinum, 664 population inversion, 533
total protein content, 130 causes, 663t positive-pressure ventilation,
transudate, 147, 147t radiography, 169, 664 pneumothorax, 664
triglyceride concentration, 130 pneumonia, 338t, 340–342 postanesthesia laryngeal paralysis,
pleural friction rubs, 113t, 115 aspiration see aspiration pneumonia 479–480
pleuropneumonia, 669 causative organisms, 83 posterior nasal atresia, 377–378
pleural lavage, pleuropneumonia, clinical signs, 341 post-exercise hyperpnea, chest circum-
671–672 diagnosis, 341–342 ference, 23
Index 697
post-mortem examination, 277–284 pro-inflammatory agents, airborne pulmonary eosinophilia, idiopathic, 279
adult horse, 277–281 inflammatory airway disease, 593 pulmonary fibrosis, 609, 609f
euthanased horses, 279 recurrent airway obstruction, 565t breathing abnormalities, 108t
fetuses, 281–282 Propionibacterium acnes, 86, 648 idiopathic, 609
foals, 281–282 protons, 533 pulmonary function testing, 211–233
health and safety, 283 Pseudallescheria boydii facemasks, 213–214, 214f, 215f
method, 277–282 culture, 145 guidelines, 211
molecular pathology, 283–284, 283f mycotic sinusitis, 400 indications, 211
sample collection, 282, 282t nasal infection, 380–381 mechanical property measurements,
sample fixation, 282 pseudochylous effusions, 130, 148 212
selection, 277–282 Pseudomonas aeruginosa, 146 sedation, 211
power source, lasers, 534 pterygopharyngeus muscle, 437 see also individual tests
Prague/56 H7N7 virus see H7N7 virus pulmonary abscess pulmonary granular cell tumor, 280,
prednisolone bronchopneumonia, foals, 338 602–603
dorsal displacement of the soft palate, radiography, 166, 169f pulmonary hemodynamics, 34–37
449 ultrasonography, 182, 183f exercise, 39–40, 39f
follicular pharyngeal hyperplasia, pulmonary arterial wedge pressure, 36 pressure–flow relationship, 35–36, 35f,
443–444 pulmonary arterioles, 34 36f
inflammatory airway disease, 597 pulmonary artery, 33–34 pulmonary hemorrhage, exercise-induced
recurrent airway obstruction, 581 pressure measurement, 36 see exercise-induced pul-
prednisone, 89–90 radiography, 163 monary hemorrhage (EIPH)
recurrent airway obstruction, 581 pulmonary artery catheters, foals, 649 pulmonary infarction, acute hemorrhagic,
pregnancy, ventilation–perfusion match- pulmonary artery pressure (PAP) 613
ing, 49 exercise, 618–619 pulmonary infection
prematurity, 640–641 measurement, 641–642 scintigraphy, 193t, 198–199
premaxilla fractures, 404 persistent pulmonary hypertension, see also specific organisms/infections
presensitization, type III hypersensitivity 641–642 pulmonary inflammation
reaction, 566 pulmonary blood flow, 33–43 eosinophilic, 593, 597
primary sinus empyema see sinusitis anatomy, 33–34 scintigraphy, 193t, 198–199
Primula veris, 584 disease, impact of, 41–42 pulmonary masses
procaine penicillin, 598 distribution in the lungs, 37, 37f respiratory sounds, 113
progressive ethmoid hematoma (PEH), redistribution during exercise, 39–40 ultrasonography, 181, 182, 182f
409–417 pulmonary bullae, 167 pulmonary neoplasia, 601–603
biopsy, 412 pulmonary capillaries, 34 primary, 602
causes, 409 pulmonary capillary transit time, 47–48, pulmonary perfusion, scintigraphy, 193t,
chemical ablation, 415–416 47f 198
clinical signs, 411 pulmonary capillary transmural pressure, pulmonary trunk, 33
computed tomography, 267–268, 41 pulmonary vascular resistance (PVR)
268f pulmonary circulation, 14 calculation, 36
cryotherapy, 415 anastomoses, 34 definition, 35
diagnosis, 402, 403f, 411–412 anatomy, 33–34 exercise, 39
differential diagnosis, 411 blood coagulation control, 38 lung volume, 36, 36f
endoscopy, 410f, 411 innervation, 34 pulmonary veins, 33, 34
fungal infection, secondary, 411 non-respiratory functions, 38–39 radiography, 163
gross appearance, 412–413 radiography, 162f, 163 pulmonary venules, 34
hemorrhage, 409, 410f, 411–412, regulation, 37–38 pulse oximetry, foals, 638, 649
412f pulmonary congestion, post-mortem pumping, 533
intraoperative, 414 findings, 279 purpura hemorrhagica
histology, 412–413 pulmonary contusion, 666 clinical signs, 333, 334f
laser surgery, 415, 539–540 pulmonary disorders, 601–615 diagnosis, 334
char development, 540 see also individual disorders pathogenesis, 330
nasal obstruction, 411 pulmonary edema, 604–606 treatment, 336
post-mortem examination, 280 African horse sickness, 317 putative Schwann cell tumor see pul-
postoperative care, 414 cardiogenic, 604, 604t, 606 monary granular cell
postoperative complications, causes, 604t tumor
414–415 diagnosis, 605–606 pyrexia, 116
prevalence, 409 hydrostatic, 604 equine herpesvirus-1, 300
prognosis, 416 injury-induced, 605 equine influenza virus, 290, 290f
radiography, 156, 156f, 412 non-cardiogenic, 604, 604t, 606 equine rhinitis A virus, 313
recurrence, 416 pathogenesis, 604–605, 605f examination techniques, 120t
scintigraphy, 191 permeability, 604 horsesickness fever, 317
signalment, 409–411 post-mortem findings, 279 parainfluenza-3, 316
sinoscopy, 260f, 261, 412, 412f radiography, 167 strangles, 332
sites, 409, 409f, 410f re-expansion, 664 pyruvate, 45
surgical ablation, 413–415, 413f smoke inhalation, 610 pythiosis, 382
treatment, 413–416 treatment, 606 Pythium insidosum, 382
698 Index
genetics, 572 high-speed treadmill endoscopy

Q
histopathology, 570f, 571–572, examination, 239–241
quarantine 571f history, 484–485
equine influenza virus, 292 history, 577t laryngeal muscle lesions, 475,
Rhodococcus equi pneumonia, 362 hypersensitivity reactions, 566–567 475f
Streptococcus equi, 337 imaging, 576 laryngeal palpation, 486–487
quartz particulate inhalation, 608 immunopathology, 78–79 laser surgery, 538–539
inflammatory airway disease com- muscular lesions, 475, 475f
parison, 591–592, 592t pathological changes, 474–476,
R
intrathoracic airway collapse, 26 474f
racehorses laboratory findings, 575–577 pathology, 483
laryngoplasty lung function assessment, 574–575 post-mortem examination, 280
age at time of surgery, 500 mucus accumulation, 58–60, 60f presenting signs, 484–485
surgical outcomes, 500–501 disease status/environment, 60, prevalence, 483–484
permanent tracheostomy, 554 60f respiratory sounds, 106–107
recurrent laryngeal neuropathy, mucus biophysical properties, 63–64, at exercise, 251–252
485–486 63f, 64f subclinical, 484
radiography, 151–174 natural history, 572 surgery, 241, 252–253
bacterial pneumonia, foals, 644–645 pathogenesis, 565–567, 565t respiratory noise reduction,
cassettes, 151 pathology, 571–572 252–253
choanal atresia, 377 pathophysiology, 567–571 vocalization changes, 485
contrast material, 153 post-mortem examination, 279–280 red blood cells
inflammatory airway disease, 596 prevalence, 572 cytology, 131
pulmonary granular cell tumor, 602 prognosis, 584 exercise-induced pulmonary hemor-
safety, 151 pulmonary hypertension, 41 rhage, 623
silicosis, 608 radiography, 166, 576, 577f, 577t reflection, 175–176, 175f
techniques, 151–153 respiratory manifestations, 572–573 refraction, 176
thoracic see thoracic radiography respiratory mechanics, 574–575 renal compensation, plasma bicarbonate,
see also individual disorders; individual scintigraphy, 197–198, 576 207
structures signalment, 577t Renault bodies, 475
radiolabeled leukocyte scintigraphy, treatment, 90–91, 578–584, 578t, repulsion, cheek teeth removal, 400
199 579t residual volume, 20
radiology, 151–174 ventilation–perfusion mismatching, resistance, tubes, 24
radiopharmaceuticals, 194t 50 resonant tone, percussion, 116
radio-stethoscopes, 250 ventilation–perfusion ratios, 41, 41f respiratory acidosis, 205t, 207
radiotherapy recurrent laryngeal nerve, 9, 474–475, respiratory alkalosis, 205t, 206, 207
nasal neoplasia, 387 475f respiratory distress
sinus neoplasia, 404 compression, 476 acute see acute respiratory distress
“rattling” sounds, 114 distal axonopathy, 475f syndrome (ARDS)
see also crackles laryngeal paralysis, 479 exercise-induced pulmonary hemor-
reactive oxygen species, prematurity, neuropathy see recurrent laryngeal rhage, 621
640 neuropathy (RLN) recurrent airway obstruction, 573,
re-breathing bag, 111, 112f recurrent laryngeal neuropathy (RLN), 573f
re-breathing test, pneumonia/pleuro- 473–477, 483–495 respiratory impedance (Zrs), 220–221,
pneumonia, 341 age of onset, 484 223b
rectus abdominis, 23 airway impedance with exercise, respiratory inductance plethysmography
rectus capitus muscle rupture, 157 25–26, 26f (RIP), 224
recurrent airway obstruction (RAO), arytenoid cartilage movement, 491 recurrent airway obstruction, 575
41–42, 565–589 clinical aspects, 483–484 summer-pasture-associated obstruc-
airflow rates, 26 clinical progression, 493 tive pulmonary disease,
airway hyperresponsiveness, 28 corniculate cartilage, 8 575
arterial oxygen tension, 207 diagnosis, 106–107, 484–493, respiratory muscles, 22–23
clinical manifestations, 572–574, 492–493 control of, 26
577t endoscopic examination, 487–493 respiratory noises see respiratory sounds
clinical scores, 574 appearance at rest, 488, 490f respiratory quotient (RQ), 45
clinicopathological correlations, indications, 487 respiratory reactance (Xrs), 220, 223b,
572 laryngeal movements, 487–493 223f
coughing, 29, 29f, 573 endoscopic grading, 498f respiratory resistance (Rrs), 220–221,
definition, 565 during exercise, 238f, 239–240, 223b, 223f
diagnosis, 577, 577t 240, 240t, 245f, 493, respiratory resonant frequency (Fres),
differential diagnosis, 577–579 493t 223b, 223f
endoscopy, 576 at rest, 239–241, 492–493 respiratory sounds, 105
environmental control, 579–580, etiopathogenesis, 473–477 abnormal, 109
579t exercise intolerance, 485 adventitious, 113–115, 113t
epidemiology, 572 external examination, 486–487 airflow patterns, 24f, 25
etiology, 565–567 gait–breathing coordination, 22 alar fold stenosis, 374
Index 699
respiratory sounds (cont’d) rest risk levels, 356

dorsal displacement of the soft epiglottic entrapment, 461 screening, 362–363
palate, 239, 252, 252f exercise-induced pulmonary hemor- blood counts, 363
epiglottic entrapment, 241, 460 rhage, 626 diagnostic tests vs., 363
exercise-induced pulmonary retinal hemorrhages, equine herpesvirus-1, imaging techniques, 363
hemorrhage, 621 645 visual inspection, 363
exercise-related, 105, 251, 251f retropharyngeal abscesses signalment, 358
fourth branchial arch defect post laryngoplasty, 503 tracheobronchial aspiration, 360
syndrome, 468 strangles, 157, 332, 333f treatment, 84, 360–362
guttural pouch empyema, 431 drainage, 336, 336f duration, 361
guttural pouch tympany, 422 retropharyngeal lymph node, 419 isolation, 362
histories, 249 reverberation artifacts, ultrasonography, ultrasonography, 359, 359f
interstitial pneumonias, 606, 646 176, 176f rib(s), 15
laryngeal function, abnormal, reverse transcription polymerase chain floating, 15
106–107 reaction (RT-PCR), equine fracture see rib fractures
nasopharyngeal collapse, 242, arteritis virus, 308 ultrasonography, 176f, 177f, 178
445 reversion to fetal circulation see persistent rib fractures, 659–662, 660f
normal, 111–113 pulmonary hypertension (PPH) clinical signs, 659–661
body condition, 113 Reynolds ratio/number, 35 diagnosis, 661
decreased audibility, 113 rhinitis life-threatening sequelae, 661, 661t
distal cervical trachea, 112 causes, 280 post-mortem examination, 278
increased audibility, 113 clinical features, 280 prognosis, 661–662
lung fields, 112–113, 112f mycotic, 405 radiography, 170–171, 172f
pleuropneumonia, 669 rhinitis sicca, 103, 104f, 370, 370f surgical repair, 661
pneumothorax, 663 vasomotor, 369–370 complications, 661
post arytenoidectomy, 518–519 rhinitis sicca, 103, 104f, 370, 370f treatment, 661
post-laryngeal reinnervation, 513 rhinophycomycosis see conidiobolomycosis ultrasonography, 635, 636f, 660f, 661
post laryngoplasty, 499–500 rhinoscopy, choanal atresia, 377 rifampin, 84, 360, 361t, 652t
recording methods, 250–251 rhinosporidiosis, 382 rima glottis
recurrent airway obstruction, clinical signs, 382–383, 382f intermittent dorsal displacement of the
572 diagnosis, 383 soft palate, 239, 239f
recurrent laryngeal neuropathy, pathology, 383 recurrent laryngeal neuropathy, 491
483, 484–485 treatment, 384 “roarers/roaring,” recurrent laryngeal
assessment, 485–486 Rhinosporidium seeberi, 145, 382, 400 neuropathy, 107, 473, 483,
surgical effectiveness assessment, Rhodococcus equi, 355 484, 485
249, 253 pneumocystis pneumonia, 648 romifidine, 204t
surgical reduction, 253 Rhodococcus equi pneumonia, 355–366 rostral cheek teeth
“thick winded,” 105 age at onset, 357 apical infection with intranasal
upper airflow obstruction, 105 blood counts, 358 drainage, 370–371
upper respiratory tract, 249–254 clinical signs, 357–358 computed tomography, 266
see also specific sounds control, 362–363 location, 370, 371f
respiratory stimulants, 96 diagnosis, 358–360 rostral displacement of the palatopharyn-
respiratory tract non-specific testing, 358–359 geal arch (RDPA), 243f, 467
anatomy, 3–17 endemic farms, 355 endoscopy, 469, 470f
clinical examination, 103–117 environmental exposure, 356 rostral maxillary sinoscopy, 258–259
function, 3 environmental management, 364–365 structures observed, 258–259
lower see lower respiratory tract (LRT) epidemiology, 355 trephination sites, 255, 255f
lymphoid tissue distribution, 73–75 extrapulmonary disorders, 357–358, rostral maxillary sinus (RMS), 6
sampling see respiratory tract samples 357f, 358f, 358t radiography, 153–154
upper see upper respiratory tract (URT) diagnosis, 360 round worm (Parascaris equorum),
see also airway(s) treatment, 362 139–140, 612–613
respiratory tract samples, 119–150 farm history, 358 RTX toxins, 348–349
collection fecal shedding, 357
indications, 119–121 immune response, 77–78
S
techniques, 121–128 immunity, 356
cytological changes intra-abdominal abscesses, 357, 357f safety harness, high-speed treadmill
delayed processing, 137–138 lung sounds, 358 endoscopy, 236
patterns, 144 mares as infection source, 356–357 salmeterol, 94
evaluation, 129–140 post-mortem examination, 281–282 anti-inflammatory properties, 94
gross examination, 129–130 prevalence, 355–356 inflammatory airway disease, 340,
handling, 128–129 prevention, 363–365 598
interpretation, 140–149 horse densities, 364 recurrent airway obstruction, 578t,
processing, 128–129 ventilation, 364–365 583
slide preparation/staining, 129 prognosis, 362 smoke inhalation, 610
transportation, 128–129 radiography, 166, 168f, 358–359, salpingopharyngeal fistula, guttural pouch
transport medium, 128 359f, 363 tympany, 539
700 Index
salt water aspiration, 612 shedding, infectious agents computed tomography, 266–267,
San Joaquin fever see coccidioidomycosis equine arteritis virus, 308–309, 646 267f
saturated vapor pressure of water (PH2O), equine herpesvirus-1, 300 dental see dental sinusitis
46 equine influenza virus, 292 endoscopy, 393, 393f
scabbard trachea, 543, 546 Rhodococcus equi pneumonia, 357 mycotic, 400
scatter, 176 Streptococcus equi infection, 331 post-mortem findings, 280
Schwann cells, recurrent laryngeal Shetland ponies, trachea, 10 prognosis, 399
neuropathy, 475 shoes, high-speed treadmill endoscopy, radiography, 154–155, 154f,
scintigraphy 236 393–394
disadvantages, 185 “shunt,” 48f, 50 scintigraphy, 189–190, 190f
history of, 185 shunt flow, alveolar–arterial oxygen sinoscopy, 259f, 260f, 261
J001X, 199 tension, 208 Streptococcus equi infection, 333
perfusion see perfusion scintigraphy signalment, 103 treatment, 394
protocol, 186–187 alar fold stenosis, 374 sinus lavage, sinoscopy, 259
pulmonary, 193–199 mycotic nasal infection, 381 sinus mycosis, 260f
applications, 193t, 230 nasal amyloidosis, 385 sinus neoplasia, 403–404
lateral images, 193 nasal neoplasia, 386 clinical signs, 403–404, 403f
radiolabeled leukocyte, 199 osteomas, 388 diagnosis, 404
regional variation assessment, progressive ethmoid hematoma, permanent tracheostomy, 554
194–196, 194t 409–411 prognosis, 404
imaging, 195 recurrent airway obstruction, 577t sinoscopy, 261, 261f
interpretation, 195–196, 196f Rhodococcus equi pneumonia, 358 surgical resection, 404
radiopharmaceuticals, 194 wry nose, 376 tumor types, 403
research applications, 198–199 sildenafil, 625, 642–643 sinus trephination, 190
upper respiratory tract, 185–192 silicon dioxide inhalation, 608 skin lesions, equine idiopathic systemic
age-related variations, 187, 187t silicosis, 608 granulomatous disease, 608
disorders, 188–191 Simonsiella spp., 138, 138f skull fractures
normal anatomy, 187–188 single breath test for carbon dioxide computed tomography, 270
patient positioning, 186, 186f (SBT-CO2) see volumetric scintigraphy, 191, 191f
views, 186–187 capnography slap (thoracolaryngeal) test, 106,
dorsal, 186, 187f, 188, 188f single radial hemolysis (SRH) test, 292, 489–490
lateral, 186, 186f, 187–188, 188f 293 slide agglutination test, Streptococcus
oblique, 186 single radial immunodiffusion (SRD) test, pneumoniae, 347
ventral, 187 293 slides, regional discrepancies, 131
Scopulariopsis spp. pneumonia, 85 sinker syndrome, 673 small airway inflammation, exercise-
secretolytics, 65 sinonasal fistulation, 396 induced pulmonary
secretory immunoglobulin A (sIgA), 73, hemorrhage control, 396, 398f, 399 hemorrhage, 619, 625
76 sinonasal mycoses, sinoscopy, 260f, 261 smears, 129
transport, 76, 76f sinoscopy, 255–261 smoke evacuation system, laser surgery,
sedation applications, 259 535
bronchoalveolar lavage, 125 biopsy, 259 smoke inhalation, 609–611
epiglottic entrapment axial division, complications, 261 acute pulmonary insufficiency, 610
461–462 equipment, 256, 256f, 258f diagnosis/investigation, 610
laser surgery, 535 findings, 259–261 laryngeal inflammation, 522
pulmonary function testing, 211 indications, 259 prognosis, 611
radiography, 151 normal, 259–261 treatment, 610–611
scintigraphy, 186 sinus surgery, 259 smooth muscle, airway see airway(s),
selective phosphodiesterase inhibitors, technique, 255–259 smooth muscle
582 trephination sites, 255, 255f S-nitroso-Hb, 52
semen testing, equine arteritis virus, 309 trephine hole creation, 256, 256f, sodium cromoglycate, 91
septal fenestration, guttural pouch 257f inflammatory airway disease, 340,
tympany, 539, 539f sinus cysts, 401–402 598
serology clinical signs, 401 recurrent airway obstruction, 578t,
interpretation, 146 diagnosis, 401 582–583
Rhodococcus equi pneumonia, etiology, 401 vasomotor rhinitis, 370
359–360 histologic examination, 402 sodium iodide
seroma formation, postoperative radiography, 156, 156f, 401, 402f conidiobolomycosis, 384
laryngeal reinnervation, 512 scintigraphy, 190, 191f mycotic nasal infection, 381
laryngoplasty, 503 sinoscopy, 260f, 261 sodium pertechnetate, radiolabeled
serum neutralization (SNT) test, equine treatment, 401–402, 402f aerosols, 195
arteritis virus, 308 sinus empyema, primary see sinusitis soft palate, 7, 438–440, 439f
severe combined immunodeficiency sinus irrigation, sinusitis, 394, 396, collapse, 444, 444f
(SCID), 79 398f disorders, 437–457
equine adenovirus, 319 sinusitis, 393–399 dorsal displacement see dorsal
Pneumocystis carinii infection, 79 bacterial growth, 393 displacement of the soft
Rhodococcus equi, 79 bony changes, 189 palate (DDSP)
Index 701
soft palate (cont’d) retropharyngeal abscesses, 157, 332, stridor, 109, 113t, 114
examination, 106 333f dorsoventral tracheal collapse, 547
radiography, 158 drainage, 336, 336f fourth branchial arch defect syndrome,
tonsil, 74–75, 74f see also Streptococcus equi infection 468
“vertical billowing,” 239, 239f, 444 strap muscles (sternothyrohyoideus laryngeal foreign bodies, 528
sound, 249–250 muscles), 8, 441, 543 recurrent laryngeal neuropathy, 473
sound–matter interactions, 175–177 streamline flow, 35 “strike-through” scintigraphy, 188
sound spectrum, 250 streptococci, 327–337 Strongyloides westeri, 356, 612–613
sound wave, 249 biochemical properties, 329 Strongylus vulgaris, 613
spectrogram analysis, 250 capsules, 327 styloglossus, 441–442, 441f
exercising horses, 251–253, 251f differentiation, 327–328, 328f stylohyoid bones
recurrent laryngeal neuropathy, 486 features, 327b, 328f computed tomography, 269, 270
sphenopalatine sinus, 6 hemolysis, 328–329 fracture, 158, 270
squamous cell carcinomas patterns, 328 radiography, 153, 158
computed tomography, 268 sugar fermentation patterns, 329, stylopharyngeus, 25, 437, 438f
metastatic, 603, 603f 329b nasopharyngeal collapse, 444f, 445
nasal, 385 see also specific types subepiglottic cysts, 452–453, 454
sinuses, 403 Streptococcus dysgalactiae, 347 laser surgery, 538
tracheal, 560 Streptococcus equi infection, 329–337 radiography, 159
squamous epithelial cells (SECs), bacterial capsules, 330 submandibular abscess, strangles, 332,
nasopharyngeal sample bacterial culture, 334 333f
contamination, 595 sample collection, 334 submandibular lymphadenopathy, 105
stable conditions carrier state, 331, 337 submandibular lymph node, 105
inflammatory airway disease, 593, detection, 335 enlargement, nasal neoplasia, 386
597 clinical signs, 332–334 submucosal glands, 55
recurrent airway obstruction, 568 cultures, 145 submucosal hemorrhage, 522
stagnant hypoxia, 52 diagnosis, 145, 334–335 subpleural edema, Hendra virus, 315
stains, 129 environmental management, 335 suckle reflex, illness, 644
standard breeds features, 329–330, 329f suckling, delayed, 634
exercise-induced pulmonary hemor- fomite transmission, 331 suction units
rhage, 617, 621 guttural pouch empyema, 431, 434 laser surgery, 535
laryngeal reinnervation, 513 immune response, 77 thoracoscopy, 272
staphylectomy management, 335–336 sulfonamides
dorsal displacement of the soft palate, morbidity, 331 inflammatory airway disease, 599
449, 451, 451f pathogenesis, 330–331 Streptococcus equi infection, 336
sternothyroideus tenectomy and, 451 post-mortem examination, 280–281, summer-pasture-associated obstructive
Starling–Landis equation, 604 281f pulmonary disease (SPAOPD),
stents, dorsoventral tracheal collapse, prevention, 336–337, 337b 565–589
549 prognosis, 337 clinical features, 572–574, 577t
sternal fractures, 172, 173f risk groups, 331b clinical scores, 574
sternal recumbency, 634 shedding, 331 clinicopathological correlations, 572
sternohyoideus, 441, 543 transmission, 331–332 definition, 565
sternothyrohyoideus, 8, 441–442, 543 vaccines, 337 diagnosis, 576, 577t
sternothyrohyoid myectomy, DDSP, virulence factors, 330–331, 330b endoscopy, 576
449–451, 450f Streptococcus equi subsp. equi see environmental control, 580
sternothyroidectomy and laser cautery, Streptococcus equi infection epidemiology, 572
452 Streptococcus equi var. zooepidemicus see etiology, 565–567
sternothyroideus, 543 Streptococcus zooepidemicus histopathology, 570f, 571f, 572
sternothyroid tendon transection, 451 Streptococcus pneumoniae, 346–347, history, 577t
sternum, 15 346b laboratory findings, 575–577
steroid drugs see corticosteroids clinical disease, 346 lung function assessment, 574–575
stertor, progressive ethmoid hematoma, diagnosis, 347 natural history, 572
411 equine isolates, 346 pathogenesis, 565–567, 565t
“stiff lungs,” interstitial pneumonias, inflammatory airway disease, 592 pathology, 571–572
606 management, 347 prevalence, 572
“stockinet socks,” sinonasal fistulation, pathogenesis, 346–347 prognosis, 584
396, 399 Streptococcus zooepidemicus, 83, 343–346, respiratory manifestations, 572–573
stoma (permanent tracheal fistula), 554, 344b treatment, 578–584
559–560 clinical disease, 344 medical, 578t, 580–584
strangles diagnosis, 345 surfactant, 13
“atypical,” 333–334, 335, 337 inflammatory airway disease, 592 alveolar lining surface tension, 20
“bastard,” 333 management, 345–346 deficiency, primary, 640–641
clinical signs, 106, 332–333 pathogenesis, 345 clinical signs, 641
lymph node enlargement, 332, 332f structure, 344–345 prognosis, 641
management, 335–336 virulence factors, 344–345, 344b radiography, 635–637, 637f
prognosis, 337 streptolysin, 328 treatment, 641
702 Index
surfactant (cont’d) temporary tracheostomy, 553 thoracic wall

functions, 20, 638 after care, 557–558 disorders, 659–662
lavage, 651 cleaning, 557 neonatal foal, 640
meconium aspiration, 644 guttural pouch empyema, 433 trauma, 659, 659t
meconium, effects of, 640, 643 indications, 554 thoracocentesis
production, 638 laryngeal inflammation, 523, 523f “blind” technique, 127
recurrent airway obstruction, 63–64 partial arytenoidectomy, 517 catheters, 127, 127f
therapy, 641, 651 procedure, 555–556, 556f complications, 128
meconium aspiration, 644 prophylactic, post surgery, 554 contamination, 128
persistent pulmonary hypertension, suture loops, 556, 556f indications, 120t, 121
643 tracheal ring fractures, 550 pleural effusion, 667
surgery tubes, 556, 557 pleuropneumonia, 341, 342f, 669
choanal atresia, 377–378 temporohyoid articulation ossification, technique, 127–128
cleft palate repair, 455 158 thoracolaryngeal (“slap”) test, 106,
dorsoventral tracheal collapse, 549 temporohyoid osteoarthropathy, 434 489–490
epiglottic entrapment, 461–463 endoscopy, 434 thoracoscopy, 271–276
guttural pouches, 420–422 temporohyoid osteopathy, 158 cannulas, 272, 272f
laryngeal hemiparesis, 497–508 temporomandibular joints complications, 273–274
laryngeal hemiplegia, 497–508 radiography, 153 equipment, 272
paranasal sinuses fractures, 404, 404f scintigraphy, 188 guided wedge resection lung biopsy,
progressive ethmoid hematoma, tensor veli palatini, 25, 439–440, 440f 274–275, 275f
413–415, 413f terbutaline, 95 indications, 271
recurrent laryngeal neuropathy, 241, recurrent airway obstruction, 583 local anesthetic, 273
252–253 test matings, equine arteritis virus, 309 lung reinflation, 273
see also specific techniques/indications tetanus, 675t mediastinal lymphoma, 602
sustentacular cells, 4 tetanus antitoxin, 557 pneumothorax induction, 273
swabs tetracycline, 85 pneumothorax-related complications,
handling, 128 T-helper cells, 72b 273
microbiological sample collection, 121 mucin production, 62 portal creation, 273
nasal, 121 recurrent airway obstruction, premedication, 272
nasopharyngeal, 121 568–569 structures visualized, 273
transportation, 128 Th 1 subset, 72b technique, 272–273
swallowing Th 2 subset, 72b thoracotomy
exercise-induced pulmonary hemor- theophylline, 95, 582 patient selection, 672
rhage, 621 therapeutic (cold) lasers, 534 pleuropneumonia, 672
guttural pouches, 7, 8f thermal injury, 609 procedure, 671–672
high-speed treadmill endoscopy Thermoactinomyces vulgaris, 566 thorax
appearance, 238 “thick winded” breath noises, 105 anatomy, 12f, 15–16
induction, 488 thoracic cavity, post-mortem examination, palpation, 116
swelling see edema 277–278 percussion, 115–116, 116f, 116t
synchronous diaphragmatic flutter thoracic inlet, 15 see also entries beginning thora-/thoracic
(thumps), 115, 674 thoracic neoplasia, 170, 172f thoroughbreds
clinical signs, 601 exercise-induced pulmonary hemor-
metastatic, 603, 603f rhage, 617, 620–621
T
thoracoscopy, 271 respiratory noise assessment, recurrent
tachypnea, foals, 634, 648 thoracic radiography, 161–171 laryngeal neuropathy,
tack modification, dorsal displacement of air gap technique, 162 485–486
the soft palate, 449 alveolar patterns, 164, 165f three-day event horses, recurrent
tail cuffs, 649 breathing movement artifact, 162 laryngeal neuropathy, 485
Technegas (99mTc-carbon), 194t, 195 bronchial pattern, 164, 165f thrombi, elimination in lungs, 38
technetium-99m (99mTc), 185 centering points, 161f, 162 thumps (synchronous diaphragmatic
technetium-99m-diphosphonate, 189 chemical restraint, 161–162 flutter), 115, 674
technetium-99m-labeled albumin exposure factors, 162 Thymus vulgaris, 584
microspheres/aggregates, foals, 163 thyroglossal duct, 452–453
194t, 196 grid use, 162 thyrohyoideus, 8, 442
technetium-99m-labeled antigranulocyte horse positioning, 161 prosthesis, 442
monoclonal antibody Fab′ indications, 163 thyroid cartilage, 8
fragment, 199 interpretation, 164–166 thyroid glands, 543
technetium-99m-labeled antigranulocyte interstitial pattern, 164, 165f thyroid lamina, 8
murine antibody Fab′ movement blur, 162 thyroid notch, 8
fragment, 186 normal radiographic anatomy, 163 ticarcillin, 652t
technetium-99m-methylene diphosphonate overexposure, 162 tidal-breathing flow–volume (TBFV) loops,
(99mTc-MDP), 185 radiographic patterns, 164–166 212, 223–225, 224f
technetium-99m-nanocolloid, 194t techniques, 161–163 variables, 224
telescope, thoracoscopy, 272 underexposure, 162 tidal hypoxemia, 52
temporal cysts, 268–269, 269f vascular pattern, 166 tidal volume, 20, 46, 212
Index 703
tiotropium bromide, 92 lymphocytes, 136, 143 endoscopy, 553

tissue hypoxia, 52 macrophages, 134, 143 history, 553
tissue perfusion, 51–52 mast cells, 144 inhaled, 604
tongue, 440–441, 441f mucus evaluation, 130–131, 142 removal, 553, 553f
tongue-ties neutrophils, 136, 143–144 treatment, 604
dorsal displacement of the soft palate, normal appearance, 124f, 129 tracheobronchial tree see lower respira-
449 recurrent airway obstruction, 575 tory tract (LRT)
nasopharyngeal collapse, 445 red blood cells, 132, 142 tracheobronchoscopy, exercise-induced
tonsil(s), 7, 74, 74f, 75 total nucleated cell counts, 131, 142 pulmonary hemorrhage,
total lung capacity, 20 tracheal collapse, dorsoventral, 546–549 621–622, 622f
total nucleated cell counts (TNCC), 131 cartilage ring deformity, 547, 547f, tracheoscopy, 545–546
total pulmonary resistance (RL), 212, 548f tracheal collapse, dorsoventral,
214–215 causes, 547 548–549
calculation, 217–218b, 217f clinical signs, 547–548 tracheal venous congestion, 546
toxic peripheral neuropathy, laryngeal dorsal ligament–tracheal ring separa- tracheobronchial foreign bodies, 553
paralysis, 480t, 481 tion, 547, 548f tracheostomy, 553–560
trachea endoscopy, 548–549 airway obstruction, post removal,
adventitia, 545 grading system, 547 551f, 559, 560f
anatomy, 9–10, 543–545, 544f palpation, 548 emergency
benign lesions, 560 radiography, 160, 160f, 549 arytenoid chondropathy, 516
blood supply, 543 surgery, 549 choanal atresia, 377
cartilage, 10, 160, 543 treatment, 549 laryngeal foreign body removal, 529
dorsoventral flattening, 107 tracheal compression, extramural, 552 permanent see permanent
cartilaginous nodules, 545 tracheoscopy, 545 tracheostomy
congenital defects, 549 tracheal deviation, left-sided intrathoracic, procedure, 555, 555f
disorders, 543–562 546 smoke inhalation, 610
endoscopy, 10, 10f tracheal fistula temporary see temporary tracheostomy
epithelium, 10, 11, 545 permanent (stoma), 554, 559–560 tracheobronchial foreign bodies, 553
examination, 107 post permanent tracheostomy, 559, types, 553–554
frictional resistance, 24, 24f 559f transendoscopic pinch biopsy, 274, 274f
function, 20t tracheal fistulation, permanent, 559–560 transmural pressure, exercise-induced
innervation, 10, 543–545 procedure, 560 pulmonary hemorrhage,
lamina propria, 10 tracheal growths, 560–561 618
lymphatic drainage, 545 trachealis muscle, 10, 545 transtracheal aspirate
mucociliary clearance, 545 tracheal masses pleuropneumonia, 669
mucosa, 545 extraluminal, 160–161 silicosis, 608
palpation, 9 intraluminal, 160, 551 transverse facial artery, blood gas analysis,
post-mortem examination, 278 tracheal mastocytosis, 560–561 202–203
radiography, 160, 163 tracheal mucosa rents, 550 transversus abdominis, 23
X-ray beam center point, 152t tracheal perforation, 160 transversus nasi, 3
rings, 545 tracheal reconstruction, 552 trauma
smooth muscle, 26 tracheal resection, 551–552 blunt see blunt trauma
see also entries beginning tracheo-/tracheal tracheal rings laryngeal, 522
tracheal aspirate (TA) examination, 107 thoracic wall, 659, 659t
bacterial culture, 139 fracture, 550 tracheal see tracheal trauma
bacterial infection, 145 permanent tracheostomy, 556, 557 treadmills, 235, 236f
collection technique, 122–125 tracheal rupture, 107, 160 triamcinolone acetonide, 89
endoscopic, 123–124, 123–124f clinical signs, 549–550 recurrent airway obstruction, 578t,
guarded catheter systems, 124–125 radiography, 550 581
transtracheal aspiration technique, tracheoscopy, 550 tri-iodinated, water-soluble contrast
123 treatment, 550 media, 264–265
color, 130 tracheal stenosis, post tracheostomy, 560f side effects, 265
contamination, 125, 133 tracheal sump, 115 trimethoprim–sulfamethoxazole
prevention, 124 tracheal trauma, 549–551 (TMS-SMZ)
contraindications, 121 blunt, 549 foals, 652t
eosinophils, 144 causes, 549 pneumocystis pneumonia, 85, 648
epithelial cells, 133, 133f, 142–143 chondroma-type swellings, 551, 551f trimethoprim–sulfonamide
exercise-induced pulmonary hemor- clinical signs, 549–550 bronchopneumonia, foals, 339
rhage, 623 penetrating, 549 inflammatory airway disease, 340,
fungal culture, 146 radiography, 160 599
hemosiderophages, 143 tracheal tumors, 560–561, 561f pneumonia, 83
indications, 119–120 tracheal washes, equine herpesviruses, tubal tonsils, 74, 74f
infection vs. contamination, 145 301 tuberculosis, 608
inflammatory airway disease, 595 tracheobronchial foreign bodies, 552–553 tumor(s)
inflammatory cells, 133 clinical signs, 553 dental tissue, 403
interpretation, 142–144 diagnosis, 604 intrapulmonary, 601
704 Index
tumor(s) (cont’d) urea dilution technique, 131 ventriculectomy

laryngeal, 531 urine output, foals, 649–650 efficacy, 506–507
mediastinal, 545, 552, 601 uterine contraction, rib fractures, 659 laryngeal reinnervation, 512
pleural, 602 uvula retractor muscle, 440 technique, 504–506
pulmonary granular cell see pulmonary ventriculocordectomy
granular cell tumor bilateral approach, 505
V
tracheal, 560–561, 561f efficacy, 506–507
see also neoplasia; individual types vaccines/vaccination induced laryngeal hemiplegia, 253,
tumor necrosis factor-␣ (TNF-␣), 77 African horse sickness, 318–319 253f
bacillus Calmette–Guérin, 86–87 laryngoplasty and, 506–507
cholera toxin, 78 laryngoplasty vs., 506
U
equine arteritis virus, 311–312 laser use, 505–506, 506f
ulcer(s) equine herpesvirus-1, 305–306 respiratory noise reduction, 253,
dorsal displacement of the soft palate, equine herpesvirus-4, 305–306 253f
448 equine influenza virus see equine technique, 504–506
glossoepiglottic fold, 524, 524f influenza virus, vestibular disease, 434
laryngeal mucosa, 524–527 vaccines/vaccination Viborg’s triangle, 421
ultrasonic pneumotachographs, 213b immunity induction, 78 viral infection(s), 287–326
ultrasonography, 175–184 Rhodococcus equi pneumonia, 364 diagnosis, 140
atelectasis, 180–181, 181f Streptococcus equi infection, 337 inflammatory airway disease, 593
bacterial pneumonia, foals, 645 Streptococcus pneumonia, 347 mucociliary clearance, 64
consolidation, 181–182, 182f, 183f vagus nerve, 26, 27 outbreaks, 287
definition, 175 guttural pouch mycosis, 425, 430 parapoxvirus ovis, inactivated, 87
diaphragm, 178 Validyne-style transducer, 212–213b, post-mortem examination, 279
herniation, 662 213f fetus/neonate, 281
guttural pouch empyema (GPE), 334 esophageal pressure measurement, recurrent airway obstruction, 567
limitations, 175 218b respiratory immunity, 77
lung(s), 178 valley fever see coccidioidomycosis sample collection, 121–122
mediastinum, 180, 181f vascular impedance, 35 see also individual viruses/diseases
normal anatomy, 178 vascular pattern, thoracic radiography, viral isolation
patient preparation, 177, 177f 166 blood collection, 121–122
physics, 175–177 vasculitis, strangles, 333 interpretation, 146
pleura, 178 vasoconstriction mediators, 37 sample transportation/storage,
pleural effusions, 178–179, 179f vasodilatation mediators, 37 128–129
pleuritis, 179, 179f, 180f vasodilators, persistent pulmonary viral pneumonia
pleuropneumonia, 669, 670f hypertension, 642 foals, 645–646
pneumothorax, 182–184, 183f, 663 vasomotor rhinitis, 369–370 radiography, 166, 167f
probe positioning, 175f, 176 venous admixture, 48f, 50 virus neutralization (VN) test
pulmonary abscess, 182, 183f alveolar hypoxemia, 52 African horse sickness, 317
rib(s), 176f, 177f, 178 venous oxygen (PvO2), 208 equine arteritis virus, 308
fractures, 635, 636f, 660f, 661 ventilation, 19, 46, 46f equine herpesviruses, 301–302
scanning protocol, 178 distribution throughout lungs, visceral pleurae, 15
sound–matter interactions, 175–177 28–29 visible light, 533
technique, 177–178 equipment, 212–213b, 213f vital capacity, 20
thoracic artifacts, 634 exercise, 21–22, 21f vitamin C, exercise-induced pulmonary
transducers, 177–178 measurement, 212 hemorrhage, 626
transesophageal, 175 see also breathing vitamin K, exercise-induced pulmonary
upper respiratory tract (URT) ventilation–perfusion matching, 38, 227 hemorrhage, 626
bacterial infections, 140t ventilation–perfusion mismatching, 48f, vocal cordectomy
sample evaluation, 139 49–50, 227 complications, 539
clinical examination, 103–107 ventilation–perfusion ratios, 48–49, 48f laser, 538–539
computed tomography, 265–270 exercise, 40 laryngeal reinnervation, 512
defense mechanisms, 71t regional compliance difference, recurrent laryngeal neuropathy,
obstruction see upper respiratory tract 48–49, 49f 253, 538–539
obstruction scintigraphy, 196–197, 197f vocal folds, 8
post-mortem examination, 280–281 ventilatory support fourth branchial arch defect
radiography, 151 foals, 650–651 syndrome, 467
resistance, 25 indications, 650–651 vocalization, recurrent laryngeal
resistance regulation, 25–26 meconium aspiration, 644 neuropathy, 485
sample interpretation, 140–142 ventral conchal bulla, 154 vocal ligaments, 8
see also airway(s) ventral conchal sinus (VCS), 3, 4f, 6 vocal process, 8
upper respiratory tract obstruction radiography, 154 volumetric capnography, 230
dynamic, 25–26 ventral meatus, nasal turbinates, 3, 4 foals, 649
pulmonary edema, 605 ventricles recurrent airway obstruction,
respiratory sounds, 105 of heart, 33, 36 574
temporary tracheostomy, 554 of larynx, 9, 158 voxel, 263
Index 705
Whitehouse approach, 421–422 diagnosis, 376

W
Horner syndrome, 421–422 prognosis, 377
water aspiration, 612 patient positioning, 420 signalment, 376
water vapor treatment, exercise-induced temporary tracheostomy, 422 surgery, 376–377
pulmonary hemorrhage, 625 whole body plethysmography, summer- treatment, 376–377
weight loss, 116 pasture-associated obstructive
wheezes, 26, 109, 113t, 114, 114f pulmonary disease, 574–575
X
expiratory, 113t, 114 “wood sawing” noise (“roaring”),
inspiratory, 113t, 114 recurrent laryngeal xylazine, 204t, 211, 461
monophonic, 114 neuropathy, 107, 473, 483, xylometazoline, 370
polyphonic, 114 484, 485
“whistlers/whistling,” recurrent laryngeal wry nose, 375–377
Z
neuropathy, 107, 483, 484, associated conditions, 376
485 clinical signs, 376, 376f zygomatic arch, scintigraphy, 188

Equine Respiratory Medicine and Surgery

Uploaded by

Copyright:

Available Formats

Equine Respiratory Medicine and Surgery

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Equine Respiratory Medicine and Surgery

Uploaded by

Copyright:

Available Formats

For Elsevier:

Commissioning Editor: Joyce Rodenhuis

Bruce C McGorum BSc, BVM&S, PhD, CertEM, DipECEIM, MRCVS

Padraic M Dixon MVB, PhD, MRCVS

N Edward Robinson BVetMed, PhD, MRCVS

Jim Schumacher DVM, MS, Diplomate ACVS

© 2007 Elsevier Limited. All rights reserved.

First published 2007

ISBN 10: 0 7020 2759 6

British Library Cataloguing in Publication Data

Library of Congress Cataloging in Publication Data

Dr Christine M Adreani VMD Dr Frederik J Derksen DVM, PhD

4 1 Anatomy of the Respiratory System

1 Anatomy of the Respiratory System 5

Fig. 1.3A–D. Types of epithelium found in

Fig. 1.4. Lateral radiograph of the caudal

6 1 Anatomy of the Respiratory System

Fig. 1.5. Endoscopic view of the caudal

1 Anatomy of the Respiratory System 7

lingual tonsil has been described at the base of the tongue

8 1 Anatomy of the Respiratory System

thyroid cartilage. The thyroid cartilage has a narrow

1 Anatomy of the Respiratory System 9

10 1 Anatomy of the Respiratory System

dorsally. When this muscle relaxes, the ends of the

1 Anatomy of the Respiratory System 11

corresponding to a middle lobe. The bronchus to the

12 1 Anatomy of the Respiratory System

1 Anatomy of the Respiratory System 13

Alveolar ducts and alveoli

14 1 Anatomy of the Respiratory System

(Fig. 1.16). The capillary network in the septum is so

The Pulmonary Circulation

1 Anatomy of the Respiratory System 15

Endo, BM, Epi

16 1 Anatomy of the Respiratory System

1 Anatomy of the Respiratory System 17

100 Replenishing the Air in the Lungs

some new air is brought in during inhalation.

Volume expansion in the lung occurs in the

20 2 How Horses Breathe: the Respiratory Muscles and the Airways

have been reported after transportation (Hobo et al 1997).

2 How Horses Breathe: the Respiratory Muscles and the Airways 21

contraction of the diaphragm and other inspiratory 2000

respiratory system down to its equilibrium position (inward

Fig. 2.4. Effect of prolonged heavy exercise on minute and alveolar

22 2 How Horses Breathe: the Respiratory Muscles and the Airways

so that contraction pulls the tendinous center of the

2 How Horses Breathe: the Respiratory Muscles and the Airways 23

24 2 How Horses Breathe: the Respiratory Muscles and the Airways

Air To nares To alveoli

2 How Horses Breathe: the Respiratory Muscles and the Airways 25

26 2 How Horses Breathe: the Respiratory Muscles and the Airways

2.5 secretions, exudates and mucosal thickening, which are a

1.5 Clinical consequences of changes in airway

2 How Horses Breathe: the Respiratory Muscles and the Airways 27

28 2 How Horses Breathe: the Respiratory Muscles and the Airways

2 How Horses Breathe: the Respiratory Muscles and the Airways 29

This action increases intrathoracic pressure so that when

Coughing is a sign of inﬂammation