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Evaluation of wheezing in infants and children

AUTHOR: Khoulood Fakhoury, MD
SECTION EDITOR: Gregory Redding, MD
DEPUTY EDITOR: Elizabeth TePas, MD, MS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2023.

This topic last updated: Feb 15, 2022.

INTRODUCTION

Wheezing is a common presenting symptom of respiratory disease in infants and children. One
in three children experience at least one acute wheezing illness before the age of three years
[1,2]. A nationwide survey performed in the United States between 1988 and 1994 showed that
the prevalence for wheezing amongst 2 to 3 year olds was 26 percent and amongst 9 to 11 year
olds was 13 percent [3-5]. Subsequent reports continue to show similar prevalence. In a 2007
survey in the US and Europe, a total of 9490 children aged one to five years were screened for
respiratory symptoms [5]. Overall, 3077 (32 percent) reported recurrent cough, wheeze, or
breathlessness in the preceding six winter months. The prevalence of these symptoms varied
from 29 percent in Northern Europe to 48 percent in Southern Europe. The overall prevalence in
the US was 27 percent. A large worldwide study looking at older children showed a global
prevalence of wheezing of 11.6 percent in children aged 6 to 7 years and 13.7 percent in
children between 13 to 14 years of age [4].

Wheezing may be either a benign, self-limited process or the presenting symptom of a

significant respiratory disease. The role of the treating clinician is to try to reach the most likely
diagnosis as quickly and efficiently as possible so that therapy, if necessary, can be instituted
and caregiver concerns can be addressed.

A diagnostic approach to wheezing in childhood is presented in this topic review. Other topics
that cover related areas include:
 ● An overview of recurrent wheezing phenotypes in children (see "Wheezing phenotypes
and prediction of asthma in young children")

● The diagnosis and management of childhood asthma (see "Asthma in children younger
than 12 years: Initial evaluation and diagnosis" and "Asthma in children younger than 12
years: Management of persistent asthma with controller therapies")

● Virus-induced wheezing (see "Role of viruses in wheezing and asthma: An overview" and
"Treatment of recurrent virus-induced wheezing in young children")

● The emergent evaluation of children with acute respiratory distress (see "Acute respiratory
distress in children: Emergency evaluation and initial stabilization")

DEFINITION AND PHYSIOLOGY OF WHEEZING

Wheezing is probably the most easily recognized adventitious sound [6]. Its long duration,
typically more than 100 msec, allows its musical quality to be discerned by the human ear. In
sound analysis, the wheeze appears as sinusoidal oscillations with sound energy in the range of
100 to 1000 Hz and with harmonics that exceed 1000 Hz on occasion ( figure 1) [7]. A wheeze
is produced by the oscillation of opposing walls of an airway narrowed almost to the point of
closure [6]. It can be high pitched or low pitched. The pitch of an individual wheeze is
determined not by the diameter of the airway but by the thickness of the airway wall, bending
stiffness, and longitudinal tension [8]. A wheeze can consist of single or multiple notes and
occur during inspiration or expiration or can be biphasic. Some experts distinguish between
wheezes and rhonchi based upon the dominant frequency, or pitch, of the sound. Wheezes
have a dominant frequency greater than 400 Hz, whereas rhonchi are of lower frequency,
approximately 150 Hz, and lower pitch, which is responsible for its resemblance to the sound of
snoring on auscultation [6,9,10]. However, the clinical significance of this distinction, if any, is
not well defined [9].

Wheezes can originate from airways of any size throughout the proximal conducting airways.
Wheezing requires sufficient airflow to generate airway oscillation and produce sound in
addition to narrowing or compression of the airway. Thus, the absence of wheezing in a patient
who presents with acute asthma may be an ominous finding, suggesting impending respiratory
failure.

Wheezing caused by a fixed large or central airway obstruction or tracheomalacia tends to be

low in pitch and has a constant acoustic character throughout the lung (homophonous
wheezing) but varies in loudness depending upon the distance from the site of obstruction. In
contrast, the degree of narrowing varies from place to place within the lung in the setting of
small airway obstruction. As a result, the sounds generated also vary in quality and acoustic
character and are described as heterophonous wheezes [11].

Stridor refers to a monophonic sound that is loudest over the anterior neck. Stridor can be
heard during inspiration, expiration, or throughout the respiratory cycle, depending on the
location and severity of air flow limitation. In general, inspiratory stridor is prominent in the
setting of extrathoracic obstruction, whereas expiratory stridor suggests intrathoracic
obstruction, and, if the obstruction is fixed and severe, then stridor can be biphasic regardless
of its location. (See "Assessment of stridor in children".)

CAUSES

The most likely diagnosis in children with recurrent wheezing is asthma, regardless of the age
of onset, evidence of atopic disease, precipitating causes, or frequency of wheezing [12].
However, other diseases can present with wheezing in infancy and childhood, and patients with
asthma may not wheeze. The differential diagnosis of wheezing includes a variety of congenital
and acquired conditions ( table 1).

Wheezing can be divided clinically according to the acuity of its onset and the mechanism of
airway narrowing. In addition to asthma, new-onset acute wheezing suggests infection or
sudden airway narrowing, whereas chronic or recurrent wheezing may be caused by congenital
abnormalities, cardiac disease, aspiration syndromes, impaired immunologic defenses, or
underlying pulmonary disease. The age of onset of wheezing can also help determine the
etiology. Certain diseases most commonly present in infancy, while other are seen more often
in older children ( table 1).

Acute wheezing (hours to days) — In addition to acute exacerbations of asthma, acute onset
of wheezing in a child is most often caused by an infectious process or foreign body aspiration
(FBA).

Infection — The most common cause of acute wheezing in infants under two years of age is
viral bronchiolitis, usually due to infection with respiratory syncytial virus (RSV). Rhinovirus and
paramyxoviruses, including parainfluenza virus and metapneumovirus, can also result in
wheezing. A typical history is a prodrome of rhinorrhea, cough, and intermittent fever followed
by wheezing and tachypnea. Physical examination usually reveals nasal congestion, tachypnea,
increased work of breathing, and polyphonic wheezes throughout the lungs. (See "Bronchiolitis
in infants and children: Clinical features and diagnosis" and "Human metapneumovirus
infections" and "Parainfluenza viruses in children", section on 'Clinical presentation' and
"Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Clinical
manifestations'.)

Wheezing can also occur with laryngotracheobronchitis. Less commonly, acute wheezing is
associated with atypical pneumonia such as Mycoplasma pneumonia, especially in older
children. Patients with bacterial tracheitis can also have wheezing, but other symptoms such as
toxic looking, high fever, and severe distress will typically guide the diagnosis. (See "Mycoplasma
pneumoniae infection in children", section on 'Pneumonia'.)

Foreign body aspiration — FBA should be suspected in any patient who presents with
wheezing of sudden onset, even in the absence of a clear history of a choking episode. In
addition, FBA should be suspected in any child with a unilateral wheeze or unequal breath
sounds. In children, unlike adults, the foreign body can lodge in any bronchus, without
predilection for the right side. Patients can also present with chronic symptoms if FBA is not
recognized in the acute setting. (See "Airway foreign bodies in children" and 'Structural causes'
below.)

Esophageal foreign body also can present with acute wheezing secondary to compression of
the airways. A history of feeding and swallowing difficulties and the presence of dysphagia are
important clues to the diagnosis. (See "Foreign bodies of the esophagus and gastrointestinal
tract in children".)

Chronic or recurrent wheezing — The differential diagnosis of wheezing that is chronic or

episodic is broad and includes structural abnormalities of the tracheobronchial tree or other
thoracic structures. Nonstructural causes of chronic wheezing include asthma, aspiration
syndromes, bronchopulmonary dysplasia, vocal cord dysfunction, and other disorders
( table 1).

Structural causes — Structural abnormalities, including anomalies of the tracheobronchial

tree and vascular rings or slings, are among the most common etiologies for persistent
wheezing that presents early in life (typically in the first few months) and are not responsive to
asthma therapies.

● Anomalies of the tracheobronchial tree – Congenital tracheomalacia and

bronchomalacia can present with noisy breathing early in life. Wheezing can present at
birth but more commonly becomes apparent in the first two to three months after birth.
The wheezing usually has a constant acoustic character throughout the lung but varies in
loudness depending upon the distance from the site of obstruction and becomes more
pronounced with activity or in the setting of upper respiratory tract infections. Other
 symptoms can include a croup-like cough or stridor, depending upon the location of the
lesion. The severity can range from a thriving child with noisy breathing to a child with
severe respiratory distress.

In a study of 124 children ages 7 to 14 months with poor response to asthma therapy, 46
percent of those children were found to have malacia of the central airways [13]. (See
"Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula" and
"Acute events in infancy including brief resolved unexplained event (BRUE)".)

Vascular rings or slings can cause compression and narrowing of large airways and may
result in wheezing or stridor [14-17]. These include complete rings (eg, double and right
aortic arches) and incomplete rings, also called slings (eg, pulmonary artery sling). (See
"Vascular rings and slings".)

Signs and symptoms of vascular compression of the airways commonly appear early in
life. Biphasic stridor is the most common sign in these patients, but wheezing, respiratory
distress, recurrent respiratory infections, and apnea also may be presenting findings.
Patients may also have symptoms related to esophageal compression by vascular
structures, including feeding difficulty and vomiting.

Fistulas between the tracheobronchial tree and other anatomical structures can cause
wheezing. Tracheoesophageal fistulae, including laryngotracheobronchial clefts, are the
most common of these conditions. Some infants with rare H-type fistulas are not
diagnosed in the immediate postnatal period. These infants can present with chronic
cough and recurrent pneumonia as well as wheezing. Symptoms such as coughing and
choking are increased with feeding. (See "Congenital anomalies of the intrathoracic
airways and tracheoesophageal fistula" and "Approach to chronic cough in children".)

● Mediastinal masses – Mediastinal masses, including tumors, thymic lesions,

bronchogenic cysts, angiomatous lesions, and enlarged lymph nodes, can cause
compression of the trachea or bronchi, resulting in chronic cough and persistent or
progressive wheeze. The anatomic location of the mass within the mediastinum provides
some clues to the underlying diagnosis ( figure 2). (See "Overview of common
presenting signs and symptoms of childhood cancer", section on 'Mediastinal masses' and
"Approach to chronic cough in children".)

● Foreign body aspiration – FBA typically presents with the abrupt onset of wheezing.
However, patients may present with chronic cough, wheezing, or postobstructive
pneumonia if the diagnosis is not recognized initially and the foreign body is retained
 ( algorithm 1). (See 'Foreign body aspiration' above and "Airway foreign bodies in
children".)

● Cardiovascular disease – A range of cardiovascular diseases can present with wheezing:

• Cardiac conditions that result in pulmonary artery dilation, such as large left-to-right
shunts (eg, ventricular septal defect [VSD], atrial septal defect [ASD], pulmonary artery
stenosis, pulmonary hypertension, absent pulmonary valve) and/or left atrial
enlargement (eg, mitral valve stenosis), can compress large airways and cause
wheezing. In addition to compression of the mainstem bronchi by markedly enlarged
central pulmonary arteries, compression of intrapulmonary bronchi by abnormally
branching pulmonary arteries has been reported in patients with absent pulmonic
valves [14,18]. (See "Pathophysiology of left-to-right shunts", section on 'Clinical
manifestations'.)

• However, overcirculation and pulmonary venous congestion are probably the most
common cardiac causes of wheezing. This can occur due to poor left ventricular
function and, less commonly, due to pulmonary venous outflow obstruction. These
conditions can result in distension of the pulmonary vascular bed, bronchiolar wall
edema, increased airway resistance, and wheezing [12]. Inflammatory mediators such
as transforming growth factor (TGF) beta may also play a part in airway remodeling. In
addition, airway hyperactivity has been reported in patients with congestive heart
failure [19]. Cardiac findings including cardiomegaly and murmurs may be absent in
some infants with obstructed venous return; therefore, a high index of suspicion is
required to make the diagnosis. As an example, wheezing was reported as the only
presenting symptom in cases of isolated cor triatriatum [20]. (See "Epidemiology,
pathogenesis, clinical evaluation, and diagnosis of pulmonary veno-occlusive
disease/pulmonary capillary hemangiomatosis in adults".)

Functional (nonstructural) causes — Functional causes of chronic or intermittent wheezing

aside from asthma include aspiration syndromes, paradoxical vocal folds movement (PVFM),
bronchopulmonary dysplasia, and rare disorders such as primary ciliary dyskinesia and
bronchiolitis obliterans.

Common causes of functional wheezing in children include:

● Aspiration syndromes – Aspiration syndromes are important and often unrecognized

causes of recurrent wheezing in young children. In many cases, these patients are
misdiagnosed with difficult-to-control asthma. Aspiration syndromes are associated with a
variety of anatomic and functional disorders. FBA and aspiration associated with fistulas
 are reviewed above (see 'Foreign body aspiration' above and 'Structural causes' above).
The two most common categories of functional disorders leading to aspiration are
gastroesophageal reflux (GER) and swallowing disorders:

• GER seldom involves aspiration of large amounts of gastric contents. However, chronic
microaspiration can cause significant mucosal edema and inflammation and may result
in chronic cough and wheezing. Infants who take a bottle to bed are at increased risk
of both wheezing and asthma during the first five years of life, probably because of
recurrent microaspiration [21]. Children with GER do not always report symptoms of
reflux, such as heartburn or vomiting, but may present with more subtle findings,
including nocturnal symptoms, hoarseness, or recurrent croup. (See "Clinical
manifestations and diagnosis of gastroesophageal reflux disease in children and
adolescents".)

• Swallowing disorders related to neurologic or muscular dysfunction of the pharynx

and/or larynx can result in weakness and impaired swallowing, incomplete closure of
the glottis, depressed cough reflex, and recurrent episodes of aspiration. Anatomic
abnormalities, such as laryngeal clefts and vocal cord paralysis, can also cause
swallowing dysfunction leading to aspiration, which may be "silent" (ie, not associated
with coughing or choking events). These infants may present with difficulty sucking or
swallowing, drooling, fatigue, loss of interest in oral feeding, tachypnea, or apnea
during feeding. The classic finding of coughing with feeding may be absent because of
depression of the cough reflex caused by repeated stimulation of the receptors in the
larynx and trachea. (See "Neonatal oral feeding difficulties due to sucking and
swallowing disorders" and "Aspiration due to swallowing dysfunction in children".)

● Bronchopulmonary dysplasia – Bronchopulmonary dysplasia (BPD), also known as

neonatal chronic lung disease or chronic lung disease of prematurity, is an important
cause of respiratory illness in preterm newborns, particularly those with a birth weight
less than 1250 grams. The etiology of BPD is multifactorial. Most patients have a history of
neonatal respiratory distress syndrome. (See "Bronchopulmonary dysplasia (BPD): Clinical
features and diagnosis".)

● Inducible laryngeal obstruction – Inducible laryngeal obstruction (ILO) was historically

known as paradoxical vocal fold motion (PVFM) or vocal cord dysfunction. However, while
inappropriate upper-airway obstruction can be caused by adduction of the true vocal folds
during inspiration, false vocal folds and supraglottic tissue may also dynamically constrict
the airway. ILO can be triggered by a variety of stimuli including exercise, stress, and
others. Exercise-induced laryngeal obstruction (EILO) is ILO restricted to exercise. Most
 studies note a female predominance, but it is also documented in males. This condition is
typically seen in older children, usually teenagers, and adults. The clinical presentation can
range from signs mimicking asthma or croup to total upper airway occlusion [22]. The
stridor resolves completely when the patient is asleep or immediately after endotracheal
intubation or tracheotomy. Patients may complain of dyspnea, throat tightness, a choking
sensation, dysphonia, and cough. (See "Inducible laryngeal obstruction (paradoxical vocal
fold motion)" and "Exercise-induced laryngeal obstruction".)

Less common causes of wheezing in children include disorders leading to recurrent

infection/bronchiectasis:

● Cystic fibrosis – Cystic fibrosis (CF) is the most common autosomal-recessive disease
among White populations, with a frequency of 1 in 2000 to 3000 livebirths. The usual
presenting symptoms and signs include persistent pulmonary infection, pancreatic
insufficiency, and elevated sweat chloride levels. Airway hyperreactivity is a common
finding in CF patients. In one study of young children with CF (mean age 16 months), 50
percent had wheezing [23]. (See "Cystic fibrosis: Clinical manifestations and diagnosis",
section on 'Respiratory tract involvement' and "Cystic fibrosis: Clinical manifestations of
pulmonary disease".)

● Primary ciliary dyskinesia – Primary ciliary dyskinesia is a rare disease (prevalence 1 in

10,000 to 30,000 individuals) that typically presents with wet cough. However, some
children may have associated wheezing. This diagnosis should be considered in patients
who present with recurrent severe upper respiratory tract infections, suppurative otitis,
and chronic sinusitis. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)".)

● Primary immunodeficiencies – Recurrent viral infections of the lower respiratory tract

can present with intermittent episodes of wheezing. In addition, chronic and/or recurrent
pyogenic lung infections in patients with primary immunodeficiencies can result in
bronchiectasis, permanent tissue destruction, and chronic pulmonary disease if
unrecognized or inadequately treated. Wheezing is due to damaged airways in these
patients. Immunodeficiency syndromes, especially those involving immunoglobulin G
(IgG) and/or immunoglobulin A (IgA) deficiency, are among the most common
abnormalities that can cause recurrent bacterial respiratory infections. Both the upper and
the lower respiratory tract can be involved and may result in recurrent otitis, pharyngitis,
or pneumonia. Complement deficiency, T cell abnormalities, and defects in leukocyte
phagocytic and chemotactic activity can result in recurrent upper and lower respiratory
tract infection but are less common. (See "Pulmonary complications of primary
 immunodeficiencies" and "Approach to the child with recurrent infections" and
"Laboratory evaluation of the immune system".)

● Bronchiolitis obliterans – Bronchiolitis obliterans (BO) is a rare disease caused by

epithelial injury to the lower respiratory tract that results in obstruction and obliteration of
the distal airways [24]. BO may occur after chemical, infectious, or immunologic injury but
can be idiopathic. Postviral bronchiolar damage is the most common cause of BO in the
nontransplant population. Adenovirus is the most likely virus to cause BO, but other
pathogens, including influenza, measles, and Mycoplasma, have also been identified in
association with BO [25].

BO is a prominent manifestation of chronic lung transplant rejection and can occur in

children following hematopoietic cell transplantation [26-28]. Patients with BO usually
present with tachypnea, dyspnea, persistent cough, and wheezing that is unresponsive to
bronchodilator therapy. Hypoxemia is present in more severe cases, either at rest or only
with exercise and/or during sleep. (See "Chronic lung allograft dysfunction: Bronchiolitis
obliterans syndrome" and "Pulmonary complications of primary immunodeficiencies",
section on 'Bronchiolitis obliterans' and "Approach to the infant and child with diffuse lung
disease (interstitial lung disease)".)

EVALUATION

Clinical history and physical examination often allow accurate diagnosis. A therapeutic trial of
bronchodilators is appropriate to evaluate for reversible airway obstruction. Most patients who
respond will have asthma. However, a bronchodilator response can also be seen with other
conditions that may lead to inflammation and bronchoconstriction, such as bronchopulmonary
dysplasia (BPD), cystic fibrosis (CF), and aspiration. Radiographic examination, pulmonary
function testing (PFT), bronchoscopy, sweat chloride concentration, and selective laboratory
studies are helpful tools in establishing the underlying etiology of wheezing when used
appropriately [12,29].

Criteria for the diagnosis of asthma and initiation of treatment are discussed in detail
separately ( table 2 and table 3). Prompt institution of timely and appropriate
pharmacotherapy, education, and prevention strategies are appropriate in children who meet
these criteria. (See 'Response to treatment' below and "Asthma in children younger than 12
years: Management of persistent asthma with controller therapies".)
Clinical history — Key parts of the clinical history include determining whether the symptom
really is wheezing and inquiring about details of the onset, course over time, and whether it is
persistent or intermittent. Also, it is important to inquire about other associated symptoms.

Is it wheezing? — When a patient presents with a history of wheezing, it is crucial to ask the
patient or the caregiver(s) to describe what they actually are experiencing or hearing (or
demonstrate it with a home video or audio recording taken on a mobile phone). On many
occasions, the word "wheezing" is used as a general term to describe noisy breathing that is
primarily due to upper airway noises, including snoring, congestion, rattling, gurgling noises, or
stridor [30,31]. It is essential to try to validate the symptom of wheezing if caregiver report is
the only source of information and no wheezing is heard on examination of the child. (See
"Asthma in children younger than 12 years: Initial evaluation and diagnosis".)

Age at onset — Structural abnormalities (such as tracheomalacia/bronchomalacia, vascular

compression/rings, tracheal stenosis/webs), virus-induced wheezing (bronchiolitis and
laryngotracheitis), and foreign body aspiration (FBA) are typically seen during infancy and early
childhood ( table 1). Other disorders, such as paradoxical vocal fold movement (PVFM), tend
to present in later childhood to adolescence.

Speed of onset and persistence — Two important aspects of the medical history include
whether the onset of wheezing was acute or gradual and whether the wheezing is intermittent
or persistent.

Acute onset of wheezing (apart from acute exacerbation of asthma) raises the possibility of FBA,
particularly if there is a history of choking. Persistent wheezing presenting very early in life
suggests a congenital or structural abnormality. In contrast, paroxysmal or intermittent
wheezing is a characteristic finding in patients with asthma. Persistent wheezing with sudden
onset is consistent with FBA, whereas the slowly progressive onset of wheezing may be a sign
of extraluminal bronchial compression by a growing mass or lymph node. Less frequently,
patients with interstitial lung disease (ILD) may occasionally present with persistent wheezing.
(See "Classification of diffuse lung disease (interstitial lung disease) in infants and children" and
"Approach to the infant and child with diffuse lung disease (interstitial lung disease)".)

Association with viral respiratory infections — Virus-induced wheezing is common in the

first few months to years of life. Among children younger than two years of age, the incidence
of wheezing with respiratory illnesses is approximately 30 percent and peaks between two and
six months [32,33]. Typically, these infants present with classic coryzal symptoms that progress
to coughing, wheezing, and, occasionally, respiratory distress over a period of three to five
days. Resolution is gradual over approximately two weeks. These episodes are variably
responsive to bronchodilators and systemic glucocorticoids but not antibiotics, expectorants, or
antihistamines. A symptom-free period typically ensues, followed by recurrent wheezing with
subsequent viral illnesses in up to 50 percent of these infants. While most of these young
children will not have virus-induced wheezing after three years of age, some will go on to
develop asthma. (See "Role of viruses in wheezing and asthma: An overview" and "Treatment of
recurrent virus-induced wheezing in young children".)

Associated cough — Cough is a symptom commonly associated with wheezing [34]. The
nature of the associated cough (wet versus dry) may be helpful in determining the underlying
etiology. Wet cough typically results from excessive mucus production, mostly due to infection
or inflammation (eg, bronchiectasis, CF, primary ciliary dyskinesia, and chronic aspiration). In
contrast, pure bronchoconstriction or structural causes for airway narrowing (eg, airway
malacia or compression, foreign body, vascular ring) are usually associated with a dry cough.
However, the underlying etiology of a dry cough can be complicated by a secondary process,
making this distinction difficult (eg, mechanical obstruction can lead to impaired mucus
clearance resulting in infection and a wet cough). Asthma can present with either a dry or wet
cough depending upon the degree of airway obstruction and the amount of mucus produced
(mucus production can vary from one patient to another and can vary at different times in the
same patient).

Differentiating asthma from other causes of wheezing — Features in the history that favor
the diagnosis of asthma include:

● Intermittent episodes of wheezing that usually are the result of a common trigger (ie,
upper respiratory infections, weather changes, exercise, or allergens)

● Seasonal variation

● Family history of asthma and/or atopy

● Good response to asthma medications (see 'Response to treatment' below)

● Positive asthma predictive index (see "Wheezing phenotypes and prediction of asthma in
young children", section on 'Asthma Predictive Index (API)')

Clinical features that suggest a diagnosis other than asthma include the following ( table 4):

● Poor response to asthma medications, including inhaled bronchodilators, inhaled

glucocorticoids, or systemic glucocorticoids. (See 'Response to treatment' below.)
 ● A history of neonatal or perinatal respiratory problems and wheezing since birth, which
suggests a congenital abnormality. (See "Congenital anomalies of the intrathoracic
airways and tracheoesophageal fistula".)

● Wheezing associated with feeding or vomiting, which can result from gastroesophageal
reflux (GER), impaired swallowing, or laryngeal cleft complicated by aspiration. (See
"Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and
adolescents" and "Neonatal oral feeding difficulties due to sucking and swallowing
disorders".)

● A history of choking, especially with associated coughing or shortness of breath. These

findings suggest FBA, even if it does not immediately precede onset of wheezing
symptoms. (See "Airway foreign bodies in children".)

● Wheezing with little cough. This finding suggests a purely mechanical cause of
obstruction, such as small airways or a vascular ring, rather than asthma, in which cough
is a prominent component in children.

● Symptoms that vary with changes in position, which may be caused by tracheomalacia,
bronchomalacia, or vascular rings. (See "Congenital anomalies of the intrathoracic airways
and tracheoesophageal fistula".)

● Poor weight gain and recurrent ear or sinus infections, which suggest CF,
immunodeficiency, or ciliary dysfunction. (See "Approach to the child with recurrent
infections" and "Cystic fibrosis: Clinical manifestations and diagnosis".)

Physical examination — General examination of a wheezy child should include measurement

of weight and height, vital signs including oxygen saturation, a complete lung and chest
examination, and digital inspection for the presence of cyanosis or clubbing. The last two
findings suggest the presence of a wheezing illness other than asthma ( table 4).

Chest examination should focus on the following features:

● Inspection for the presence of respiratory distress, tachypnea, retractions, or structural

abnormalities. Pertinent findings include an increased anteroposterior (AP) diameter
associated with chronic hyperinflation, pectus excavatum caused by chronic airway
obstruction and exaggerated swings in intrathoracic pressure, or scoliosis complicated by
airway compression. (See "Pectus excavatum: Etiology and evaluation" and "Adolescent
idiopathic scoliosis: Clinical features, evaluation, and diagnosis", section on 'Clinical
presentation'.)
 ● Palpation to detect supratracheal lymphadenopathy or tracheal deviation.

● Percussion to define the position of the diaphragm and detect differences in resonance
among lung regions. Percussion is the most underperformed part of the examination.

● Auscultation to identify the characteristics and location of wheezing, as well as variations

in air entry among different lung regions. A prolonged expiratory phase suggests airway
narrowing. Wheezing caused by a large or central airway obstruction (eg, vascular ring,
subglottic stenosis, tracheomalacia) has a constant acoustic character throughout the lung
but varies in loudness depending upon the distance from the site of obstruction. In
contrast, the degree of narrowing varies from place to place within the lung in the setting
of small airway obstruction (eg, asthma, CF, primary ciliary dyskinesia, aspiration). The
presence of persistent focal wheezing is usually indicative of a localized and mostly
structural airway abnormality, and, therefore, airway evaluation by imaging or
bronchoscopy is warranted. (See 'Radiography' below.)

Crackles can be present in conjunction with wheezing in asthma and in a variety of other
conditions, such as those leading to bronchiectasis (eg, CF, primary ciliary dyskinesia,
immunodeficiency). Early inspiratory crackles are often present in patients with asthma
due to air flowing through secretions or slightly closed airways during inspiration. Late
inspiratory crackles are usually associated with ILD and early congestive heart failure.
Thus, the presence of crackles does not exclude the diagnosis of asthma [35].

● Assessment of response to therapy. Marked improvement in wheezing immediately

(within a few minutes) after bronchodilator therapy is suggestive of asthma but does not
rule comorbid conditions if clinically suspected. (See 'Response to treatment' below.)

The exam should also focus on extrapulmonary findings that suggest an etiology for wheezing.
The cardiac examination includes auscultation for murmurs and evaluation for signs of heart
failure. Examination of the skin for eczema (common in atopic patients) or other cutaneous
lesions may assist in diagnosis. Nasal examination may reveal signs of allergic rhinitis, sinusitis,
or nasal polyps. The presence of nasal polyps in children necessitates an evaluation for CF. (See
"Approach to the infant or child with a cardiac murmur" and "Heart failure in children: Etiology,
clinical manifestations, and diagnosis" and "Atopic dermatitis (eczema): Pathogenesis, clinical
manifestations, and diagnosis" and "Allergic rhinitis: Clinical manifestations, epidemiology, and
diagnosis" and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis"
and "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Acute
bacterial rhinosinusitis' and "Cystic fibrosis: Clinical manifestations and diagnosis".)
Radiography — A chest radiograph (AP and lateral films) should be obtained in children with
new-onset wheezing of undetermined etiology or chronic, persistent wheezing not responding
to therapies. It is not necessary to obtain a chest radiograph with every exacerbation in children
with asthma, unless there is a specific indication. (See "Acute asthma exacerbations in children
younger than 12 years: Emergency department management", section on 'Indications for chest
radiograph'.)

In most cases, a plain chest radiograph provides a good image of the large airways, including
the tracheal air column and main stem bronchi. Plain films can also help differentiate between
diffuse and focal disease. The presence of generalized hyperinflation suggests diffuse air
trapping and airway disease, seen in asthma, CF, primary ciliary dyskinesia, bronchiolitis
obliterans (BO), and aspiration. In contrast, localized findings suggest structural abnormalities
or FBA. A chest radiograph can also detect parenchymal lung disease, atelectasis, and, in some
cases, areas of bronchiectasis.

In addition, chest radiographs may reveal cardiomegaly, enlarged pulmonary vessels,

pulmonary edema, or other signs of cardiac failure. Plain radiographs also are helpful in
detecting mediastinal masses or enlarged lymph nodes and may suggest the presence of
vascular rings (eg, right aortic arch). (See "Vascular rings and slings".)

Other radiologic studies may be helpful in selected cases ( table 5):

● Chest computed tomography (CT) can provide detailed anatomy of the mediastinum, large
airways, and lung parenchyma.

● Magnetic resonance imaging (MRI) with contrast (magnetic resonance angiography [MRA])
or multidetector computed tomography (MDCT) [15] is the study of choice when a vascular
ring or sling is suspected.

● Barium swallow may help in identifying vascular rings, swallowing dysfunction, aspiration
syndromes including GER, and some cases of tracheoesophageal fistula and is indicated
only when these conditions are suspected. (See "Vascular rings and slings", section on
'Evaluation' and "Gastroesophageal reflux in infants" and "Clinical manifestations and
diagnosis of gastroesophageal reflux disease in children and adolescents" and "Congenital
anomalies of the intrathoracic airways and tracheoesophageal fistula", section on
'Diagnosis' and "Aspiration due to swallowing dysfunction in children".)

● A videofluoroscopic swallowing study (also called a modified barium swallow) is suggested

in children under two years of age who have recurrent wheezing that is unresponsive to
bronchodilators or inhaled or systemic glucocorticoids to identify possible swallowing
 dysfunction [36]. (See "Aspiration due to swallowing dysfunction in children", section on
'Videofluoroscopic swallow study'.)

Pulmonary function tests — PFTs are an important component of the diagnostic evaluation of
a wheezy child. (See "Overview of pulmonary function testing in children".)

Infant PFT, if available and indicated, is helpful in assessing airway obstruction. Moreover, this
test can be used to quantify the response to bronchodilators [12,37,38]. Airway resistance and
functional residual capacity also can be measured using gas dilution or body plethysmography
and can help quantify airway obstruction and the response to bronchodilators [12]. This test
requires sedation and therefore is reserved for selected patients for whom this information
may help with diagnosis and management.

In older children who are cooperative, PFT with inspiratory and expiratory flow-volume loops is
helpful in determining the presence, degree, and location of airway obstruction, as well as the
response to bronchodilators ( figure 3). Methacholine challenge testing and exercise testing
can confirm airway hyperreactivity in patients for whom the diagnosis of asthma still is in
question. Exercise testing with laryngoscopy is helpful to confirm the diagnosis of PVFM if
suspected. (See "Overview of pulmonary function testing in children" and "Bronchoprovocation
testing" and "Flow-volume loops".)

Response to treatment — For patients with diffuse wheezing, a trial of inhaled

bronchodilators can be used to confirm the presence of reversible airway disease. However, a
partial or negative response may not rule out asthma. Inflammation and airway swelling may
contribute to wheezing in addition to bronchoconstriction, especially in infants and young
children. Thus, if asthma is still suspected in a patient with chronic or persistent symptoms, the
combination of inhaled glucocorticoids and bronchodilators for at least two weeks (or five to
seven days of oral glucocorticoids if the patient has more severe symptoms) may result in
significant improvement in symptoms and help in making the diagnosis of asthma. Further
work-up is indicated if the response to this therapy is inadequate or if a comorbid condition is
still suspected in a patient who had a positive response to bronchodilator. (See "Asthma in
children younger than 12 years: Initial evaluation and diagnosis".)

Laboratory studies — There are few laboratory investigations that are useful in the initial
evaluation of the wheezy child. In most cases, the probable diagnosis is suspected on the basis
of the clinical history and physical examination. The role of laboratory tests, when indicated, is
either to confirm the diagnosis or to rule out other less likely diagnoses [29]. Complete blood
counts are important in patients with chronic or systemic symptoms and may reveal anemia,
leukocytosis, or leukopenia. Eosinophilia in this setting supports an underlying allergic process
or possible parasitic infection. Further studies should be obtained based upon the suspected
diagnosis ( table 5).

Testing for infection — Viral infection is an important cause of wheezing in children and is
mediated through numerous mechanisms. Viruses in the Paramyxoviridae family (eg,
respiratory syncytial virus and parainfluenza virus) and picornavirus family (eg, human
rhinovirus) are important precipitants of wheezing in young children. Metapneumovirus,
another member of the Paramyxoviridae family, can result in upper and lower respiratory tract
infection and may present with wheezing [39,40]. Thus, viral studies can be helpful in
confirming the etiology of wheezing in infants and young children presenting with symptoms
suggestive of bronchiolitis. However, they are not routinely recommended. Testing is reviewed
in greater detail separately. (See "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Virology' and "Human metapneumovirus infections" and "Role of viruses
in wheezing and asthma: An overview" and "Parainfluenza viruses in children", section on
'Diagnosis' and "Respiratory syncytial virus infection: Clinical features and diagnosis", section on
'Diagnosis'.)

Sputum stain and cultures may be useful in a setting suggestive of bacterial infections,
including atypical infections (eg, mycobacterial or fungal infections), that can result in
wheezing. Tuberculin skin testing and specific serologic assays can be helpful if these infections
are suspected. Serologic testing for Mycoplasma may be performed if such an infection is
suspected since Mycoplasma is an increasingly recognized cause of wheezing and may
predispose children to the subsequent development of asthma [41,42]. (See "Overview of
nontuberculous mycobacterial infections" and "Clinical manifestations and diagnosis of allergic
bronchopulmonary aspergillosis" and "Tuberculosis disease in children: Epidemiology, clinical
manifestations, and diagnosis", section on 'Pulmonary tuberculosis' and "Community-acquired
pneumonia in children: Clinical features and diagnosis", section on 'Laboratory evaluation' and
"Mycoplasma pneumoniae infection in children", section on 'Approach to testing'.)

Sweat chloride test — The sweat chloride test is the gold standard for diagnosing CF and is
indicated in children with chronic lung problems, including wheezing. It is expected that the
majority of patients with CF will be diagnosed at birth due to newborn screening for CF.
However, false negatives can occur. Thus, obtaining a sweat test is appropriate if clinical
suspicion of the disease remains. Intermediate sweat testing results should be clarified by DNA
analysis, and sweat chloride testing should be repeated. (See "Cystic fibrosis: Clinical
manifestations and diagnosis".)

The presence of diarrhea, failure to thrive, and/or clubbing should raise the suspicion for CF
and warrants further evaluation. One should also have a low threshold to obtain this test in a
patient with persistent or recurrent pulmonary symptoms that are unresponsive to asthma
therapies, especially when wheezing is associated with a chronic productive cough, since
identifying a patient with CF has major implications for the patient, the family, and future
reproductive decisions. The sweat chloride test should be undertaken at a facility with
substantial experience, and clinicians interpreting the results should be aware of other
conditions that result in elevated sweat chloride concentrations. (See "Cystic fibrosis: Clinical
manifestations and diagnosis".)

Other studies — Immunoglobulin levels can be used to screen for immunodeficiencies. If

there is a high suspicion of immunodeficiency, then a more detailed immunologic work-up is
appropriate ( table 5). Elevated immunoglobulin E (IgE) can be indicative of an allergic
process. Skin prick testing (or in vitro testing) may be helpful in the patient with signs and
symptoms suggestive of environmental allergies. (See "Approach to the child with recurrent
infections" and "Laboratory evaluation of the immune system" and "Allergic rhinitis: Clinical
manifestations, epidemiology, and diagnosis", section on 'Allergen-specific testing'.)

Endoscopy — Endoscopy is a diagnostic tool used in patients with suspected FBA, persistent
symptoms, or inadequate response to therapy. Rigid bronchoscopy is used in patients with
sudden onset of wheezing and suspected FBA. Flexible bronchoscopy can identify structural
airway abnormality, including airway malacia (during spontaneous breathing when performed
under conscious sedation). A structural abnormality was identified in up to 33 percent of infants
with chronic wheezing not responsive to asthma therapies by bronchoscopy [36].
Nasopharyngoscopy, which allows visualization of the vocal cords and larynx without lower
airway endoscopy, is mainly helpful in identifying type of cells in the airways to confirm
diagnosis and phenotype of asthma (eosinophilic versus neutrophilic) and also can be helpful
when infection or aspiration is suspected. However, the recommendation for bronchoscopy and
bronchoalveolar lavage (BAL) in infants with chronic or recurrent wheezing is conditional with
low quality of evidence [36]. (See "Airway foreign bodies in children" and "Approach to the infant
and child with diffuse lung disease (interstitial lung disease)" and "Aspiration due to swallowing
dysfunction in children", section on 'Evaluation of airway anatomy'.)

Twenty-four-hour esophageal pH and impedance monitoring — GER is common among

children under two years of age with recurrent wheezing. Thus, 24-hour esophageal pH
monitoring is suggested in infants and children with recurrent wheezing, particularly in children
under two years of age with recurrent wheezing who are unresponsive to bronchodilators or
inhaled or systemic glucocorticoids, since GER symptoms may be subtle in this age group [36].
Evaluation for GER is also suggested for older children with poor response to asthma therapies,
especially if they have any suggestive symptoms. Presenting symptoms may include excessive
burping or emesis, coughing after meals, and nocturnal cough or wheeze along with
discomfort indicated by crying and/or arching of the back. A positive response to empiric
therapy (acid suppression) may be used to support a presumed diagnosis of GER [29]. (See
"Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and
adolescents".)

Twenty-four-hour esophageal pH monitoring is preferred over an upper gastrointestinal series

or gastroesophageal scintigraphy for the diagnosis of GER. Multichannel intraluminal
impedance (MII) monitoring is a technique that permits measurement of all reflux episodes,
including those that are weakly acidic or alkaline. It is usually used in combination with pH
monitoring. In a trial comparing the two techniques, combined MII-pH monitoring detected
reflux events that caused symptoms twice as often as pH monitoring alone [43].

SUMMARY AND RECOMMENDATIONS

● Definition and physiology of wheezing – A wheeze is a continuous musical sound heard

during chest auscultation that lasts longer than 250 msec. It is produced by the oscillation
of opposing walls of an airway narrowed almost to the point of closure. It can be high
pitched or low pitched, consist of single or multiple notes, occur during inspiration or
expiration or biphasic, and originate from airways of any size. (See 'Definition and
physiology of wheezing' above.)

● Causes – Wheezing is a common presenting symptom of respiratory disease in children. It

may be either a benign, self-limited process or the presenting symptom of a significant
respiratory disease ( table 1). (See 'Causes' above.)

• Acute-onset wheezing – In addition to asthma, acute onset of wheezing in a child is

most often caused by infection or foreign body aspiration (FBA). (See 'Acute wheezing
(hours to days)' above.)

• Chronic or recurrent wheezing – The most likely diagnosis in children with recurrent
wheezing is asthma. However, not all patients with asthma wheeze, and other diseases
can present with chronic or episodic wheezing. The differential diagnosis is broad and
includes structural abnormalities of the tracheobronchial tree or other thoracic
structures (eg, vascular rings and slings, mediastinal masses). Nonstructural
(functional) causes include aspiration syndromes (from gastroesophageal reflux [GER]
and dysphagia), bronchopulmonary dysplasia, vocal cord dysfunction (including
paradoxical vocal fold movement [PVFM] in older children), abnormal immunologic
 defense mechanisms, bronchiolitis obliterans (BO), and interstitial lung disease (ILD).
(See 'Chronic or recurrent wheezing' above.)

● Evaluation – Clinical history and physical examination often allow accurate diagnosis
( table 5). Additional diagnostic tools are helpful in establishing the underlying etiology
of wheezing in select patients. (See 'Evaluation' above.)

• Clinical history – When a patient presents with a history of wheezing, it is crucial to

ask the patient or the caregivers to describe what they actually are experiencing or
hearing (or demonstrate it with a home video or audio recording taken on a mobile
phone). On many occasions, the word "wheezing" is used as a general term to describe
noisy breathing, including snoring, congestion, gurgling noises, or stridor. Two
important aspects of the medical history include the patient's age at the onset of
wheezing and the course of onset (acute versus gradual). Certain clinical features favor
the diagnosis of asthma or suggest another diagnosis ( table 4). (See 'Clinical history'
above.)

• Physical exam – General examination of a wheezy child should include measurement

of weight and height; vital signs including oxygen saturation; digital inspection for the
presence of cyanosis or clubbing; a complete chest examination; and cardiac, skin, and
nasal examinations. (See 'Physical examination' above.)

• Imaging – Anteroposterior (AP) and lateral chest radiographs are suggested in children
with new-onset wheezing of undetermined etiology or chronic persistent wheezing not
responding to therapies. Other radiologic studies may be helpful in selected cases
( table 5). (See 'Radiography' above.)

• Pulmonary function testing – Pulmonary function tests (PFTs) are an important

component of the diagnostic evaluation of a wheezy child. Impulse oscillometry, if
available, is helpful in assessing airway obstruction in infants. In older children who are
cooperative, PFT with inspiratory and expiratory flow-volume loops is helpful in
determining the presence, degree, and location of airway obstruction, as well as the
response to bronchodilators ( figure 3). (See 'Pulmonary function tests' above.)

• Response to treatment – For patients suspected of having asthma, a trial of inhaled

bronchodilators with or without glucocorticoids can be used to confirm the diagnosis
prior to initiating a more extensive work-up. Further work-up is indicated if the
response to therapy is inadequate. (See 'Response to treatment' above.)
 • Laboratory studies – There are few laboratory investigations that are useful in the
initial evaluation of the wheezy child. Any studies obtained beyond chest radiographs
and PFTs should be based upon the suspected diagnosis ( table 5). These studies
include tests to examine for viral, bacterial, or fungal infections; sweat chloride test to
diagnose cystic fibrosis (CF), evaluation for immunodeficiency, or allergy; endoscopy to
examine for FBA, tracheomalacia, or ILD; and work-up for GER if indicated. (See
'Laboratory studies' above and 'Endoscopy' above.)

Use of UpToDate is subject to the Terms of Use.

Topic 5752 Version 24.0

GRAPHICS

Acoustics and waveforms of lung sounds

The first column shows typical values for the frequency (hertz) and duration (milliseconds) of the various sou
show amplitude time plots in unexpanded and time-expanded modes, respectively (amplitude is measured
seconds). The unexpanded plots contain screenshots of the entire sound, with a vertical line showing where
msec) were obtained. All tracings begin with inspiration.

From: Bohadana A, Izbicki G, Kraman SS. Fundamentals of lung auscultation. N Engl J Med 2014; 370:744. Copyright © 2014 Massach
permission from Massachusetts Medical Society.

Graphic 131965 Version 1.0

Causes of wheezing in children

Acute Chronic or recurrent

Asthma Structural abnormalities
Bronchiolitis* Tracheo-bronchomalacia*
Laryngotracheobronchitis ¶ Vascular compression/rings*
Atypical infection (Mycoplasma pneumonia) Δ Tracheal stenosis/webs*
Bacterial tracheitis Cystic lesions/masses
Foreign body aspiration ¶ Tumors/lymphadenopathy

Esophageal foreign body Cardiomegaly

Functional abnormalities

Asthma

Gastroesophageal reflux

Recurrent aspiration

Cystic fibrosis

Immunodeficiency

Primary ciliary dyskinesia

Bronchopulmonary dysplasia

Retained foreign body (trachea or

esophagus)

Bronchiolitis obliterans

Pulmonary edema

Inducible laryngeal obstruction (vocal cord

dysfunction) Δ

Interstitial lung disease

* These disorders tend to present in infancy.

¶ These disorders are more commonly seen in young children (toddlers and preschoolers).

Δ These disorders are more commonly seen in teenagers.

Graphic 67370 Version 6.0

Common diagnostic possibilities of mediastinal masses

The differential diagnosis of a mediastinal mass depends upon the anatomic

compartment in which it arises.

Redrawn from: Baue AE, et al. Glenn's Thoracic and Cardiovascular Surgery. 5th ed. Appleton &
Lange, Norwalk, CT, 1991.

Graphic 56637 Version 6.0

Natural course of foreign body aspiration

Graphic 68288 Version 3.0

Classifying asthma severity in children 0 to 4 years of age

Classification of asthma severity (children 0 to 4 years

of age)
Components of severity
Persistent
Intermittent
Mild Moderate Severe

Impairment Symptoms ≤2 days/week >2 days/week, Daily Throughout

but not daily the day

Nighttime 0 1 to 2 3 to 4 >1 time/week

awakenings times/month times/month

Short-acting ≤2 days/week >2 days/week, Daily Several times

beta2-agonist but not daily per day
use for
symptom
control (not
prevention of
EIB)

Interference None Minor Some Extremely

with normal limitation limitation limited
activity

Risk Exacerbations 0 to 1/year ≥2 exacerbations in 6 months requiring oral

requiring oral steroids, or ≥4 wheezing episodes/1 year
systemic lasting >1 day AND risk factors for persistent
glucocorticoids asthma

Consider severity and interval since last exacerbation

Frequency and severity may fluctuate over time

Exacerbations of any severity may occur in patients in any

severity category

Classifying severity in children who are not currently taking long-term control medication.
Level of severity is determined by both impairment and risk. Assess impairment domain by
caregiver's recall of previous 2 to 4 weeks. Assign severity to the most severe category in which any
feature occurs. At present, there are inadequate data to correspond frequencies of exacerbations
with different levels of asthma severity. For treatment purposes, patients who had ≥2 exacerbations
requiring oral glucocorticoids in the past 6 months, or ≥4 wheezing episodes in the past year, and
who have risk factors for persistent asthma may be considered the same as patients who have
persistent asthma, even in the absence of impairment levels consistent with persistent asthma.

EIB: exercise-induced bronchoconstriction.

Reproduced from: National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and
Management of Asthma. NIH Publication no. 08-4051, 2007.

Graphic 61691 Version 5.0

Classifying asthma severity in children 5 to 11 years of age

Classification of asthma severity (children 5 to 11 years

of age)
Components of severity
Persistent
Intermittent
Mild Moderate Severe

Impairment Symptoms ≤2 days/week >2 days/week, Daily Throughout

but not daily the day

Nighttime ≤2 times/month 3 to 4 >1 time/week, Often 7

awakenings times/month but not times/week
nightly

Short-acting ≤2 days/week >2 days/week, Daily Several times

beta2-agonist but not daily per day
use for
symptom
control (not
prevention of
EIB)

Interference None Minor Some Extremely

with normal limitation limitation limited
activity

Lung function Normal FEV1 FEV1 = FEV1 = 60 FEV1 <60%

between >80% to 80% predicted
exacerbations predicted predicted FEV1/FVC
FEV1 >80% FEV1/FVC FEV1/FVC = <75%
predicted >80% 75 to 80%
FEV1/FVC
>85%

Risk Exacerbations 0 to 1/year (see ≥2 in 1 year (see footnote)

requiring oral footnote)
systemic
Consider severity and interval since last exacerbation
glucocorticoids
Frequency and severity may fluctuate over time for patients in
any severity category

Relative annual risk of exacerbations may be related to FEV1

Classifying severity in children who are not currently taking long-term control medication.
Level of severity is determined by both impairment and risk. Assess impairment domain by
patient's/caregiver's recall of the previous 2 to 4 weeks and spirometry. Assign severity to the most
severe category in which any feature occurs. At present, there are inadequate data to correspond
frequencies of exacerbations with different levels of asthma severity. In general, more frequent and
intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or ICU admission)
indicate greater underlying disease severity. For treatment purposes, patients who had ≥2
exacerbations requiring oral systemic glucocorticoids in the past year may be considered the same
as patients who have persistent asthma, even in the absence of impairment levels consistent with
persistent asthma.

EIB: exercise-induced bronchoconstriction; FEV1: forced expiratory volume in 1 second; ICU:

intensive care unit.

Reproduced from: National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and
Management of Asthma. NIH Publication no. 08-4051, 2007.

Graphic 51579 Version 10.0

Features suggestive of a diagnosis other than asthma in children

History
Onset of symptoms in early infancy

Neonatal respiratory distress +/- ventilatory support

Neonatal neurologic dysfunction

Intractable wheezing unresponsive to bronchodilators

Wheezing associated with feeding or vomiting

Difficulty swallowing +/- recurrent vomiting

Diarrhea

Poor weight gain

Stridor

Oxygen requirement >1 week after acute attack

Physical examination
Failure to thrive

Clubbing

Cardiac murmur

Stridor

Focal lung signs

Nasal polyps

Crackles on auscultation

Cyanosis

Laboratory features
Focal or persistent chest radiograph abnormalities

Anemia

Irreversible airflow obstruction

Hypoxemia

Adapted from: Canny GJ, Levison H. Childhood asthma: A rational approach to treatment. Ann Allergy 1990; 64:406.

Graphic 70442 Version 4.0

Approach to evaluation of wheezing in children based upon suspected
diagnosis

Suspected diagnosis Signs and symptoms Diagnostic evaluation

Acute

Asthma History of recurrent wheeze, History, PFT with

cough, at least partial response bronchodilators, empiric trial of
to bronchodilator bronchodilators, exercise or
methacholine challenge testing,
chest radiography only if
atypical, skin (or in vitro) testing
for aeroallergen sensitization if
history suggests inhalant
allergen triggers

Viral bronchiolitis Prodrome with rhinitis, occurs History, age, season

in infancy and early childhood,
In selected cases: Rapid antigen
seasonal pattern
testing (RSV, influenza), viral
cultures, chest radiography

Foreign body Sudden onset of coughing and History, physical examination,

wheezing chest radiography, rigid
bronchoscopy

Chronic

Asthma As above As above

Tracheomalacia Persistent wheeze, starts early History, fluoroscopy, flexible

in life, poor response to bronchoscopy or dynamic CT
bronchodilators, varies with with airway protocol
position and activity

Cystic fibrosis Chronic productive cough, Sweat chloride test, genetic

crackles, with or without testing
clubbing, failure to thrive,
recurrent respiratory infections

Swallowing dysfunction Neurologic abnormality Videofluoroscopic swallowing

(nonuniversal), choking with study (modified barium
eating, symptoms exaggerated swallow)
by feeding

Gastroesophageal reflux Symptoms sometimes related 24-hour esophageal pH

to eating, vomiting, refusal to monitoring, multichannel
eat, failure to thrive intraluminal impedance
monitoring
 Vascular ring or sling Persistent symptoms, starts Chest radiograph, MRI, or CT
early in infancy, may be angiogram
exaggerated by position,
Barium swallow
homophonous wheeze

Tracheal stenosis Persistent symptoms, with or Chest radiograph, CT scan,

without stridor, homophonous bronchoscopy
wheeze

Mediastinal nodes or mass Persistent symptoms, localized Chest radiograph, CT scan

wheezing, no response to
bronchodilator, systemic
symptoms of underlying
disease

Immunodeficiency Recurrent sinopulmonary Immunoglobulins, vaccine

infections, crackles, FTT, responses
clubbing

Primary ciliary dyskinesia Persistent sinusitis and otitis Ciliary biopsy, genetic testing,
media with draining ears, exhaled nasal nitric oxide (ENO)
recurrent respiratory infection,
wet cough with sputum
production, crackles, clubbing,
FTT

Inducible laryngeal Inspiratory stridor, poor Exercise testing, pulmonary

obstruction (vocal cord response to bronchodilators, function tests, laryngoscopy
dysfunction) absent symptoms during sleep, while symptomatic
teenage, exercise related

Bronchiolitis obliterans History of predisposing disease, Chest CT scan

ie, viral infection or
In rare cases: Lung biopsy is
transplantation, dyspnea,
needed
persistent wheezing

PFT: pulmonary function test; RSV: respiratory syncytial virus; CT: computed tomography; MRI:
magnetic resonance imaging; FTT: failure to thrive.

Data from: Dorkin HL. Noisy breathing. In: Respiratory Disease in Children: Diagnosis and Management, Loughlin GM, Eigen
H (Eds), Williams and Wilkins 1994. p.171.

Graphic 62889 Version 11.0

Schematic flow-volume loop configuration in a
spectrum of airway lesions

(A) Normal.

(B) Variable extrathoracic upper airway obstruction.

(C) Variable intrathoracic upper airway lesions.

(D) Fixed upper airway obstruction.

(E) Lower airways obstruction.

Graphic 63544 Version 3.0