Laryngopharyngeal Reflux

D i s e a s e i n C h i l d re n
Naren N. Venkatesan, MD, Harold S. Pine, MD,
Michael Underbrink, MD*

KEYWORDS
 Laryngopharyngeal reflux disease  Extraesophageal reflux disease  Diagnosis

KEY POINTS
 Extraesophageal symptoms of gastroesophageal reflux disease (GERD) have long been
recognized and referred to as laryngopharyngeal reflux disease (LPRD).
 Despite its similarities with GERD, LPRD has been more difficult to diagnose accurately
and consistently.
 This variability has made creating comprehensive treatment guidelines difficult.
 Currently, the treatment of LPRD seems to provide symptomatic benefits as well as im-
provements in these concomitant diseases.
 LPRD should be considered as a chronic disease with a variety of presentations.

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a complex problem in the pediatric popu-

lation and has received significant attention in the literature. Extraesophageal reflux
disease, commonly called laryngopharyngeal reflux disease (LPRD), continues to be
an entity with more questions than answers. Although the role of LPRD has been impli-
cated in various pediatric diseases, it has been inadequately studied in others. LPRD
is believed to contribute to failure to thrive, laryngomalacia, recurrent respiratory pap-
illomatosis (RRP), chronic cough, hoarseness, esophagitis, and aspiration among
other pathologies.
Although the exact prevalence is unknown, it is estimated that nearly 1 in 5 children
likely suffers from reflux disease.1 Currently, given that childhood obesity is on the
increase, and with the association between obesity and reflux, it is likely that the inci-
dence is increasing. As our understanding of various diseases of the aerodigestive
tract increases, the role of reflux as a contributing factor continues to gain attention.
Although the definitions have not changed dramatically, knowledge regarding the

Department of Otolaryngology—Head and Neck Surgery, University of Texas Medical Branch,

301 University Boulevard, Route 0521, Galveston, TX 77555, USA
* Corresponding author.
E-mail address: [email protected]

Pediatr Clin N Am 60 (2013) 865–878

http://dx.doi.org/10.1016/j.pcl.2013.04.011 pediatric.theclinics.com
0031-3955/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
866 Venkatesan et al

benefits of treating LPRD as a contributing factor in many afflictions of the upper aero-
digestive tract has certainly increased.
LPRD is defined by the reflux of either gastric acid or refluxate (containing pepsin)
into the larynx, oropharynx, and/or nasopharynx.2 Although once believed to be an
extension of gastroesophageal reflux disease, the differences in symptoms, findings,
and treatments has led to the evolution of LPRD as a unique and distinct disease pro-
cess.3 It is a disease classically diagnosed by symptomatology in the patient. Although
confirmation of the disease requires objective findings on various tests, including
endoscopy, pH probes, and radiographic studies, a high index of suspicion must be
maintained to diagnose the child.
Although LPRD is present in both infants and younger children, it usually presents
with a different set of symptoms depending on age (Box 1). Infants typically present
with regurgitation, vomiting, dysphagia, anorexia, failure to thrive, apnea, recurrent
croup, laryngomalacia, subglottic stenosis, or chronic respiratory issues. School-
age children tend to demonstrate chronic cough, dyspnea, dysphonia, persistent
sore throat, halitosis, and globus sensation. Older children may also complain of
regurgitation, heartburn, vomiting, nausea, or have chronic respiratory issues. The
symptoms in these children tend to bridge the gap between those seen in infants
and those in teenagers/adults.2 Certain complaints, including dysphagia, vomiting,

Box 1
Various extraesophageal manifestations of GERD

Infants
Failure to thrive
Wheezing
Stridor
Persistent cough
Apnea
Feeding difficulties
Aspiration
Regurgitation
Recurrent croup
Children
Cough
Hoarseness
Stridor
Sore throat
Asthma
Vomiting
Globus sensation
Wheezing
Aspiration
Recurrent pneumonia
 Laryngopharyngeal Reflux Disease in Children 867

regurgitation, dyspnea, and globus sensation, are more broad. The role and manifes-
tations of LPRD in specific disease processes requires further attention (Box 2).

IMPAIRED SWALLOWING AND ASPIRATION

In infants, swallowing is a highly coordinated function requiring the infant to perform

and coordinate the actions of suck-swallow-breathe, in that order, to avoid aspira-
tion.4 Performing this sequence requires an intact laryngeal sensation, which explains
why children with neurologic deficits tend to have greater feeding difficulties and
increased episodes of microaspirations.
Understanding the effects of reflux on the larynx is the key to better treatment of the
neonate and infant. The supraglottic mucosa must be able to sense the upcoming
food bolus. This sensation leads to appropriate vocal fold closure, while also stimu-
lating the opening of the hypopharynx and upper esophageal sphincter. This highly
sensitive mechanism is important at all ages, but more so in newborns as they begin
to learn cognitive functioning. Edema from chronic irritation by gastric aspirate causes
decreased sensation in these tissues, and thereby increases the risk of aspiration in
these patients.5–7
Testing of the laryngeal adductor reflex can be checked by endoscopy combined
with a pulse of air to the aryepiglottic folds to simulate a food bolus. This testing begins
with a pressure of 2.5 mm Hg and gradually increases in increments of 0.5 mm Hg to
10 mm Hg. The goal is to identify at what pressure the reflex is triggered, with a pos-
itive response being a cough or break in respiration. The need for greater than 4.5 mm
Hg of pressure to obtain a positive response is suggestive of microaspiration and poor
laryngeal adductor reflex in children.
Suskind and colleagues4 showed significant improvement in videofluoroscopic
swallow evaluations and pharyngeal impairment scores when infants with swallowing
issues were treated for GERD. Aviv and colleagues5 demonstrated that just 3 months
of GERD treatment was sufficient time to demonstrate normalization of laryngophar-
yngeal sensation. This improvement in turn led to improved swallowing function and
decreased posterior laryngeal edema. In addition to antireflux medication, thickening
of feeds has always been a traditional method of preventing microaspiration. Thick-
ening helps by improving overall laryngopharyngeal sensing of the bolus and thus
improves the coordination of swallowing.8,9

Box 2
Diseases affected by reflux

Subglottic stenosis
Laryngomalacia
Asthma
Recurrent otitis media
Vocal cord nodules
Vocal cord granuloma
Eosinophilic esophagitis
Allergic rhinitis
Recurrent respiratory papillomatosis
868 Venkatesan et al

Although swallowing is a highly coordinated activity, laryngopharyngeal reflux likely

plays a role in dysfunction of the swallow reflex and therefore requires treatment.
Currently, there are no universally accepted methods for evaluating the role of LPRD
in these patients, although fiber-optic endoscopy can provide visual clues of changes
in the larynx. Empirical trials of a proton pump inhibitor and thickening of feeds can
delineate the role of LPRD and therefore benefit the child in most cases.

LARYNGOMALACIA

In the pediatric population, laryngomalacia is one of the most common causes of

airway distress.10 It typically presents as inspiratory stridor, coughing, choking, or
regurgitation. The lack of inherent strength in the larynx leads to collapse of tissues
and subsequent upper airway obstruction. A recent meta-analysis11 showed that
65% of patients with severe laryngomalacia had reflux. Further analysis revealed
that those children with moderate to severe laryngomalacia were nearly 10 times
more likely to suffer from reflux than those with only mild laryngomalacia. The pro-
posed mechanism is that aerophagia during feedings causes gastric distention lead-
ing to vagal reflexes followed by postprandial vomiting and regurgitation.
The increased association between laryngomalacia and reflux has led to the ques-
tion of whether reflux causes laryngomalacia or is simply present concurrently. Al-
though supraglottic biopsies did show mild intraepithelial infiltrate, pathognomonic
for reflux, the gross morphologic changes did not seem to correspond to laryngoma-
lacia.12,13 These findings only seem to confuse the issue regarding the role of reflux in
laryngomalacia. On the other hand, 2 studies using 24-hour dual-probe pH manometry
showed 100% correlation between laryngomalacia and reflux, where reflux is defined
as at least 1 episode of pH less than 4 for at least 4 seconds.14,15 Unfortunately, there
is still some uncertainty regarding the role of pharyngeal pH monitoring in these pa-
tients. Little and colleagues16 demonstrated that nearly half of patients with extraeso-
phageal reflux were only accurately diagnosed after pharyngeal monitoring and a
negative esophageal study. Rabinowitz and colleagues17 stated that

Beyond its value in clinical practice, upper esophageal reflux testing should be
employed in research studies that evaluate the impact of GER [gastroesophageal
reflux] therapy on ENT [ear, nose, and throat] symptoms.

Although several retrospective studies have reported an improvement in laryngo-

malacia symptoms (cough, stridor, choking) with antireflux treatment, a prospective
trial done by Thompson15 indicates a strong correlation between reflux treatment
and decreased laryngomalacia symptoms. Three levels of laryngomalacia severity
were categorized, ranging from mild (inconsequential stridor during feeding) to mod-
erate (inspiratory stridor, no failure to thrive, and inconsequential dyspnea, cyanosis,
or brief apneas) to severe (inspiratory stridor and life-threatening complications).
Nearly 89% of patients in the moderate and severe groups showed improvement in
coughing and choking after 7.3 months of GERD therapy. Improvements in regurgita-
tion were reported in nearly 70% of patients.
These findings seem to encourage the treatment of laryngomalacia with LPRD.
However, resolution of symptoms may simply be attributed to the natural course of
the disease. Thompson18 commented on the natural history of laryngomalacia in
infants, noting, ‘‘Symptoms worsen at 4–8 months, improve between 8 and 12 months,
and usually resolve by 12–18 months of age.’’ The mean age at diagnosis for patients
in the 2007 study was older than 3 months (102.8 days). Therefore, it seems possible
that many of the symptom improvements reported in this study reflect the natural
 Laryngopharyngeal Reflux Disease in Children 869

history of the disease. No studies have compared the outcome of patients with laryng-
omalacia treated for LPRD with those who receive no treatment. In summary, although
further studies are needed, treatment of laryngomalacia with antireflux therapy may be
beneficial. Each patient should be evaluated independently by an otolaryngologist to
determine disease severity and decide on therapy.

SUBGLOTTIC STENOSIS

Subglottic stenosis typically presents in the neonate/infant with recurrent crouplike

episodes and chronic cough. Often, these patients may not demonstrate any difficulty
breathing at rest; however, episodes of dyspnea and stridor can quickly develop,
caused by the limited airway circumference in young children, which cannot handle
even minimal inflammatory insults. Three major causes of subglottic stenosis are
trauma, infection, and LPRD.19
The role of LPRD in causing subglottic stenosis has been studied in canine models,
giving it significant credence; however, the effect of acid and pepsin on the human sub-
glottic mucosa has not been as thoroughly studied. The formation of vocal cord gran-
ulomas has long been known as a sequela of reflux, and these same histologic
changes were noted in early subglottic stenosis lesions.20 Although irritation and
mucosal damage begin the stenosis process, the role of reflux in preventing reepithe-
lialization should not be understated.21 Further studies have demonstrated the effect of
reflux at the cellular level, including downregulation of epidermal growth factor recep-
tor, which reduces mucosal turnover, increased transforming growth factor b1, which
causes fibroblast differentiation, and excessive connective tissue deposition.22,23
Although the correlation between reflux and subglottic mucosal changes has been
evaluated, no prospective data are available to better correlate the clinical relation-
ship. Reports of children whose stridor and degree of stenosis decreases with reflux
management advocate for LPRD treatment in this patient population.24 Reviews
show that nearly two-thirds of children with subglottic stenosis have reflux disease
to some extent.24–31 Furthermore, subglottic stenosis correlates with reflux disease
with a relative risk of 2.5.26–28,32 In 1 study, nearly one-third of patients with subglottic
stenosis who were treated for reflux were able to avoid surgical intervention.24 With
these findings and correlations in mind, early evaluation for and treatment of LPRD
may lead to prevention of disease progression and should be encouraged in patients
with subglottic stenosis.

RRP

RRP is a complex, often prolonged, infection of the upper airway by the human pap-
illoma virus. The complexity of this disease is beyond the scope of this article; how-
ever, LPRD treatment provides benefit to these patients. There has been increased
anecdotal evidence in the literature of cases where children with mild to moderate
LPRD have shown improvement or even resolution of disease with antireflux ther-
apy.33,34 The ciliated respiratory epithelium of the larynx has increased sensitivity
when chronically exposed to pepsin and gastric refluxate. This increased sensitivity
may contribute to more advanced presentations of the disease or a more frequent
need for surgical debridement. Some of the concerning findings in disease progres-
sion of RRP, such as laryngeal webs, may be diminished or even prevented if these
children receive antireflux therapy.35 Although treatment of RRP with LPRD therapy
alone is not recommended, ensuring that these patients are placed on adjuvant anti-
reflux therapy may help to minimize the consequences or progression of their disease
and in some cases may even lead to resolution.
870 Venkatesan et al

ASTHMA

Because of concerns about the airway often noted in children with LPRD, asthma and
the role of treatment of LPRD to improve asthma has been postulated. It has been esti-
mated that gastroesophageal reflux may be present in 40% to 80% of children with
asthma.36 There is a growing belief that rhinitis and asthma are often present together,
and that rhinitis can cause laryngeal changes that may mimic LPRD changes. There-
fore, when evaluating asthmatics for LPRD with laryngoscopy, strict criteria should be
used, such as limiting positive findings to vocal cord nodules and granulomas.37
Among asthmatic adults and children, LPRD changes in the larynx have been identi-
fied on laryngoscopy in nearly 70% of cases.37,38 Thus, any patient with suspected
LPRD in addition to asthma and/or allergic rhinitis should undergo pH probe testing
to confirm the diagnosis.
The use of b-agonists has also been studied as a possible trigger for reflux by
reducing the tone of the lower esophageal sphincter.39 However, a recent study
seems to prove that no such correlation exists.37 Another belief was that uncontrolled
asthma may worsen LPRD, but it seems that children with asthma, whether controlled
or uncontrolled, have similar rates of LPRD.16 From the literature to date, the main
concept to note is that these 2 conditions, LPRD and asthma, are often present
together, and they both require treatment. The effect of treatment of one on the status
of the other unfortunately requires further research.

HOARSENESS

Although laryngopharyngeal reflux is often described as a significant contributor to

adult hoarseness, its role in children has not been as well established. Vocal cord nod-
ules are widely considered to be the most common cause of pediatric hoarseness.40
Various studies have begun to question whether LPRD should be given greater
consideration as a cause of this problem. Gumpert and colleagues41 counted interar-
ytenoid edema or chronic inflammation as a sign of LPRD and found these findings in
90% of children with hoarseness. Although this was a retrospective study, it does
consider the prevalence of at least some LPRD changes in children with hoarseness.
A possible explanation as to why LPRD can often be underdiagnosed is that find-
ings on endoscopy may mimic vocal cord nodules. There is a subtle difference
between nodules seen at the junction between the anterior one-third and posterior
two-thirds of the vocal folds and the pseudonodules of LPRD noted as edema in
the anterior one-third of the vocal folds.42 Although direct laryngoscopy under general
anesthesia may easily highlight these differences, it is significantly more challenging to
note these subtle changes on flexible fiber-optic laryngoscopy in an awake child. This
difficulty may be a key reason why the prevalence of LPRD in children may be
underappreciated.
Early recognition of the role of LPRD and appropriate treatment are key to the most
effective management of the hoarse patient. In adults, the finding of vocal cord nod-
ules43 is managed with a combination of speech therapy and antireflux medication,
typically a proton pump inhibitor. Block and Brodsky42 found similar such benefits
in children. Children with only LPRD findings showed some improvement with phar-
macotherapy and speech therapy compared with pharmacotherapy alone. Perhaps
more remarkable was the improvement seen in children with nodules who were
treated with a combination of pharmacotherapy and speech therapy compared with
those treated with only 1 modality.
These findings, in addition to the treatment of LPRD and nodules in the adult pop-
ulation, seem to imply that appropriate treatment of a child with hoarseness would be
 Laryngopharyngeal Reflux Disease in Children 871

to combine pharmacotherapy with speech therapy.44 Unfortunately, there has been

limited objective evidence in children with hoarseness, specifically with respect to
pH probe findings and pepsin immunoassays. Although further studies are necessary,
it seems prudent that the treatment of children with hoarseness attributed to LPRD
and/or nodules should include pharmacotherapy as well as speech therapy.

COUGH

Cough is a typical complaint in children seen by a pediatrician; it is seen in the clinic in

nearly 35% of preschool children.45 The cough mechanism itself is a complex process
generated in the cerebral cortex. It can be generated spontaneously or occur involun-
tarily as a protective mechanism. Rapidly adapting receptors as well as nocireceptors
are the primary sensory receptors involved in chronic cough.46 Rapidly adapting re-
ceptors are typically involved in response to physical stimuli such as smoke, ingested
solutions, and pulmonary congestion.47 On the other hand, nocireceptors respond to
chemical stimuli (histamines, bradykinins, prostaglandins, and substance P).48
Although nocireceptors tend to maintain their sensitivity, rapidly adapting receptors
respond and transform based on frequency of involvement. Children with chronic al-
lergies, postnasal drainage, asthma, or GERD may demonstrate changes in the
severity and frequency of their cough over time. Thus, some of these diseases may
silently worsen despite no overt symptoms. Recognizing the role of reflux as a cause
of a cough is imperative and should be high in the differential diagnosis once infection
has been ruled out. Specifically, in the setting of a chronic cough (cough for more than
4 weeks), LPRD, allergy, and asthma should be strongly suspected.49
As described in other sections, irritation of the larynx by reflux is best categorized by
the frequency and severity of reflux events. Although it may seem that these acute
events should trigger a spell of coughing, this relationship is not so direct. A recent
study50 evaluating 20 children with reflux evaluated their coughing spells while being
monitored with a pH probe. Findings showed that most coughs, nearly 90%, did not
correspond with a reflux event. The chronic irritation of laryngeal tissues from reflux is
the predominant culprit, rather than acute events, thereby stressing the importance of
long-term treatment to reverse the process.
In the evaluation of chronic cough, it is always possible for 2 pathologies to be pre-
sent simultaneously. In 1 study,25 children with chronic cough underwent esophageal
biopsies for evaluation of GERD. Of those children with positive biopsies, 75% also
had a history of asthma. In a unique study51 involving multiple disciplines, several spe-
cialists evaluated 40 children with cough for longer than 8 weeks. They found that
reflux and asthma were present in nearly half the patients and another quarter of
the patients had multiple causes.
Thus, the evaluation of chronic cough should be extensive with the idea that multiple
factors may be playing a role. LPRD can often be considered as a possible primary
cause. Furthermore, the possibility of a second contributory cause such as LPRD, al-
lergies, or asthma should always be evaluated in patients who are unresponsive to
therapy (Fig. 1).

DIAGNOSIS

Because of its subtlety, LPRD may be difficult to recognize in patients with the chronic
effects of this disease. To the otolaryngologist, many physical examination findings
may suggest LPRD; however, most of these findings can only be seen when viewing
the larynx (Box 3).52 Without the ability to view the larynx, the index of suspicion must
be even higher for the pediatrician. A child with any of the conditions discussed as well
872 Venkatesan et al

Fig. 1. (A) Laryngomalacia with vocal cords open. (B) Laryngomalacia with collapse and
obstruction of airway in same patient. (C) Posterior pharyngeal wall cobblestoning. (D) Sub-
glottic stenosis. (E) Right true vocal fold cyst. (F) Bilateral true vocal fold nodules. (G) Early
formation of right true vocal fold granuloma (Noted posteriorly).
 Laryngopharyngeal Reflux Disease in Children 873

Box 3
Reflux findings seen on laryngoscopy

Lingual tonsil swelling

Postglottic edema
Postglottic erythema
Arytenoid edema
Arytenoid erythema
Laryngeal ventricle obliteration
True vocal fold edema
Laryngomalacia
Tracheomalacia
Vocal fold nodules
Subglottic stenosis
Hypopharyngeal cobblestoning
Narrowed trachea
Increased secretions

as unresponsive or unexplained difficulty with feeding or the airway should suggest

the possibility of reflux as a contributing factor and prompt a referral to a specialist.
Diagnosis of reflux begins with a thorough history paying special attention to feeding
and airway symptoms. With regard to feeding, it is crucial to know if a child has regur-
gitation or emesis and the timing of these events (ie, how long after meals?). Deciding if
the child has adequate weight gain that correlates with oral intake is also important.
Previous airway issues should be identified as well, because diseases such as
subglottic stenosis, laryngomalacia, and RRP may have already been diagnosed.
Knowledge of choking incidents, chronic cough, and recurrent crouplike episodes
may suggest an underlying anatomic airway issue or even microaspiration. If there
is a sufficient index of suspicion, the practitioner should enlist the help of specialists
and obtain objective data for the evaluation of LPRD.
Reflux disease has been evaluated and diagnosed using a variety of objective tests,
including histopathology from esophageal biopsies, barium esophograms, and double
and/or single pH probes. The 24-hour pH probe study is considered the current gold
standard for the diagnosis of LPRD and can be helpful in evaluating the severity of
disease.

TREATMENT

Although diagnostic measures can be used to determine if a child has LPRD, the de-
cision to proceed with work-up and treatment is key. Empirical therapy with either pro-
ton pump inhibitors or histamine (H2) blockers is often the preferred initial approach in
children with presumed GERD. The primary care practitioner must decide when to
initiate diagnostic work-up of LPRD/GERD.
With regard to extraesophageal symptoms and laryngopharyngeal involvement of
reflux, there are certain diseases that can be readily diagnosed by simple endoscopy,
such as subglottic stenosis, laryngomalacia, laryngeal edema, RRP, vocal cord gran-
ulomas, or vocal cord nodules. The diagnosis of 1 of these conditions should prompt
874 Venkatesan et al

a course of medical therapy and a period of observation for symptomatic improve-

ment. In the case of more complex issues (swallowing difficulty, aspiration, cough)
additional diagnostic testing before medical therapy is often warranted. Treatment
options for LPRD include lifestyle modifications, medical therapy, and/or surgical
therapy.1,53
Lifestyle modification for reflux typically centers on 3 actions: altering food compo-
sition, adjusting the diet to eliminate known triggers of reflux, and adjusting postural
positioning. As children grow older, they can begin to follow similar guidelines as for
adults. As stated earlier, thickening of feeds improves laryngeal sensation and overall
swallowing function. Frequent but smaller meals can also help to reduce reflux. Sleep
positioning may provide further benefit to infants by encouraging sleep in the lateral
position as well as elevating the head of the bed if possible.3 Avoidance of known trig-
gers of LPRD is often a key dietary modification that improves symptoms in older chil-
dren. Much like GERD, avoidance of certain foods (ie, juices and spicy foods,
chocolates, and mints) and not eating meals just before sleep can help to decrease
reflux.2 These changes alone (elevating the head of the bed, milk thickening, and fast-
ing before bedtime) may even lead to complete resolution of LPRD.54,55
If lifestyle changes are insufficient in resolving symptoms of LPRD, medical therapy
is the next avenue to explore. As with adults, the recommended first-line therapy is
proton pump inhibitors (PPIs). They bind irreversibly to active proton pumps and pro-
vide greatest efficacy when taken just before a meal.55 In adults, a 30-minute gap
between consumption of medication and commencing a meal is typically recommen-
ded. Among the various PPIs, esomeprazole has been shown to provide the greatest
benefit.56 In children, similar studies have not been performed; however, in neonates
and infants, lansoprazole and omeprazole are the only PPIs approved by the US Food
and Drug Administration.
Histamine-2 receptor antagonists (H2RAs), once a mainstay in treatment, have now
become second-line therapy. They have typically been used to either help wean pa-
tients off PPIs or to supplement PPI therapy. Unlike PPIs, they are typically taken at
night to provide nocturnal suppression of acid as they reduce meal-stimulated gastric
acid production by nearly 70%.57 In children, the use of a H2RA is most helpful for
weaning off PPIs. Ranitidine is available as a syrup, which may help to increase patient
compliance. Although the use of PPIs and H2RAs have been studied in adults, there is
no consensus on their role in the treatment of reflux.58 Although further studies are
needed, the use of a PPI or H2RA in short courses of therapy can often yield beneficial
results. The failure to respond to either a PPI or H2RA in cases of suspected reflux
indicates a lack of significant reflux, insufficient dosage, or the need to consider
surgical intervention.
Surgical therapy for reflux should be reserved for those children whose symptoms
are life threatening or drastically affecting their quality of life despite maximum med-
ical therapy. Although surgery may seem appealing by promising the possibility of
eliminating the need for medication, it carries with it the risk of high failure rates, sig-
nificant morbidity, and even death.59 As some of these situations (coughing, choking,
aspiration, or recurrent pneumonias) compromise a patient’s respiratory status, the
risks of surgery may greatly outweigh the projected benefits. If all factors have
been considered, fundoplication can be entertained as a possibility. Nissen fundopli-
cation is the gold standard procedure performed for the surgical treatment of GERD.
This procedure attempts to restore the integrity of the lower esophageal sphincter.
When performed on appropriate patients, it has a 90% symptom control rate.60,61
Furthermore, when performed on patients without respiratory issues, the success
rate increases even further.62
 Laryngopharyngeal Reflux Disease in Children 875

SUMMARY

Extraesophageal symptoms of GERD have long been recognized and referred to as

LPRD. Despite its similarities with GERD, LPRD has been more difficult to diagnose
accurately and consistently. This variability has made creating comprehensive treat-
ment guidelines difficult. Much of the current information regarding the role of LPRD
has been learned by noting its presence in conjunction with another well-
understood disease (laryngomalacia, subglottic stenosis, vocal cord nodules, and
so forth). Currently, the treatment of LPRD seems to demonstrate symptomatic ben-
efits as well as improvements in these concomitant diseases. Thus, LPRD should be
considered as a chronic disease with a variety of presentations. High clinical suspicion
along with consultation with an otolaryngologist, who can evaluate for laryngeal find-
ings, is necessary to accurately diagnose LPRD. Future studies will work to illuminate
the role of gastric acid and refluxate on the upper aerodigestive tract. However, until
excluded, the role of LPRD should never be underestimated and should always be
treated in symptomatic patients.

REFERENCES

1. Vandenplas Y, Sacre-Smith L. Continuous 24-hour esophageal pH monitoring in

285 asymptomatic infants 0 to 15 months old. J Pediatr Gastroenterol Nutr 1987;
6:220–4.
2. Stavroulaki P. Diagnostic and management problems of laryngopharyngeal
reflux disease in children. Int J Pediatr Otorhinolaryngol 2006;70:579–90.
3. McGuirt WF Jr. Gastroesophageal reflux and the upper airway. Pediatr Clin
North Am 2003;50:487–502.
4. Suskind DL, Thompson DM, Gulati M, et al. Improved infant swallowing after
gastroesophageal reflux disease treatment: a function of improved laryngeal
sensation? Laryngoscope 2006;116:1397–403.
5. Aviv JE, Liu H, Parides M, et al. Laryngopharyngeal sensory deficits in patients
with laryngopharyngeal reflux and dysphagia. Ann Otol Rhinol Laryngol 2000;
109:1000–6.
6. Link DT, Willging JP, Miller CK, et al. Pediatric laryngopharyngeal sensory
testing during flexible endoscopic evaluation of swallowing: feasible and correl-
ative. Ann Otol Rhinol Laryngol 2000;109:899–905.
7. Thompson DM. Laryngopharyngeal sensory testing and assessment of airway
protection in pediatric patients. Am J Med 2003;115(Suppl 3A):166S–8S.
8. Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of
gastroesophageal reflux. J Pediatr 1987;110:181–6.
9. Henry SM. Discerning differences: gastroesophageal reflux and gastroesopha-
geal reflux disease in infants. Adv Neonatal Care 2004;4:235–47.
10. Holinger LD. Etiology of stridor in the neonate, infant, and child. Ann Otol Rhinol
Laryngol 1980;89:397–400.
11. Hartl TT, Chadha NK. A systematic review of laryngomalacia and acid reflux.
Otolaryngol Head Neck Surg 2012;147(4):619–26.
12. Chandra RK, Gerber ME, Holinger LD. Histological insight into the patho-
genesis of severe laryngomalacia. Int J Pediatr Otorhinolaryngol 2001;61:
31–8.
13. Iyer VK, Pearman K, Raafat F. Laryngeal mucosal histology in laryngomalacia:
the evidence for gastro-oesophageal reflux laryngitis. Int J Pediatr Otorhinolar-
yngol 1999;49:225–30.
876 Venkatesan et al

14. Matthews BL, Little JP, Mcguirt WF Jr, et al. Reflux in infants with laryngomalacia:
results of 24-hour double-probe pH monitoring. Otolaryngol Head Neck Surg
1999;120:860–4.
15. Thompson DM. Abnormal sensorimotor integrative function of the larynx in
congenital laryngomalacia: a new theory of etiology. Laryngoscope 2007;
117(6 Pt 2 Suppl 114):1–33.
16. Little JP, Matthews BL, Glock MS, et al. Extraesophageal pediatric reflux:
24-hour double-probe pH monitoring of 222 children. Ann Otol Rhinol Laryngol
Suppl 1997;169:7.
17. Rabinowitz SS, Piecuch S, Jibaly R, et al. Optimizing the diagnosis of gastro-
esophageal reflux in children with otolaryngologic symptoms. Int J Pediatr Oto-
rhinolaryngol 2003;67:625.
18. Thompson DM. Laryngomalacia: factors that influence disease severity and out-
comes of management. Curr Opin Otolaryngol Head Neck Surg 2010;18:564–70.
19. Karkos PD, Leong SC, Apostolidou MT, et al. Laryngeal manifestations and
pediatric laryngopharyngeal reflux. Am J Otol 2006;27(3):200–3.
20. Delahunty JE, Cherry J. Experimentally produced vocal cord granulomas.
Laryngoscope 1968;78(11):1941–7.
21. Little FB, Koufman JA, Kohut RI, et al. Effect of gastric acid on the pathogenesis
of subglottic stenosis. Ann Otol Rhinol Laryngol 1985;94(5):516–9.
22. Yellon RF, Parameswarran M, Brandom BW. Decreasing morbidity following
laryngotracheal reconstruction in children. Int J Pediatr Otorhinolaryngol 1997;
41(2):145–54.
23. Jarmuz T, Roser S, Rivera H, et al. Transforming growth factor-beta 1, myofibro-
blasts, and tissue remodelling in the pathogenesis of tracheal injury: potential
role of gastroesophageal reflux. Ann Otol Rhinol Laryngol 2004;113(6):488–97.
24. Halstead LA. Gastroesophageal reflux: a critical factor in pediatric subglottic
stenosis. Otolaryngol Head Neck Surg 1999;120:683–8.
25. Yellon RF, Coticchia J, Dixit S. Esophageal biopsy for the diagnosis of gastro-
esophageal reflux-associated otolaryngologic problems in children. Am J Med
2000;108(Suppl 4a):131S–8S.
26. Mitzner R, Brodsky L. Multilevel esophageal biopsy in children with airway man-
ifestations of extraesophageal reflux disease. Ann Otol Rhinol Laryngol 2007;
116:571–5.
27. Halstead LA. Role of gastroesophageal reflux in pediatric upper airway disor-
ders. Otolaryngol Head Neck Surg 1999;120:208–14.
28. Carr MM, Nagy ML, Pizzuto MP, et al. Correlation of findings at direct laryngos-
copy and bronchoscopy with gastroesophageal reflux disease in children: a
prospective study. Arch Otolaryngol Head Neck Surg 2001;127:369–74.
29. Carr MM, Abu-Shamma U, Brodsky LS. Predictive value of laryngeal pseudosul-
cus for gastroesophageal reflux in pediatric patients. Int J Pediatr Otorhinolar-
yngol 2005;69:1109–12.
30. Giannoni C, Sulek M, Friedman EM, et al. Gastroesophageal reflux association
with laryngomalacia: a prospective study. Int J Pediatr Otorhinolaryngol 1998;
43:11–20.
31. Can MM, Nguyen A, Poje C, et al. Correlation of findings on direct laryngoscopy
and bronchoscopy with presence of extraesophageal reflux disease. Laryngo-
scope 2000;110:1560–2.
32. Stroh BC, Faust RA, Rimell FL. Results of esophageal biopsies performed
during triple endoscopy in the pediatric patient. Arch Otolaryngol Head Neck
Surg 1998;124:545–9.
 Laryngopharyngeal Reflux Disease in Children 877

33. McKenna M, Brodsky L. Extraesophageal acid reflux and recurrent respi-

ratory papillomatosis in children. Int J Pediatr Otorhinolaryngol 2005;69:
597–605.
34. Borkowski G, Sommer P, Stark T, et al. Recurrent respiratory papillomatosis
associated with gastroesophageal reflux disease in children. Eur Arch Otorhino-
laryngol 1999;256(7):370–2.
35. Holland BW, Koufman JA, Postma GN, et al. Laryngopharyngeal reflux and
laryngeal web formation in patients with pediatric recurrent respiratory papil-
lomas. Laryngoscope 2002;112(11):1926–9.
36. Thakkar K, Boatright RO, Gilger MA, et al. Gastroesophageal reflux and asthma
in children: a systematic review. Pediatrics 2010;125:925–30.
37. Kilic M, Ozturk F, Kirmemis O, et al. Impact of laryngopharyngeal and gastro-
esophageal reflux on asthma control in children. Int J Pediatr Otorhinolaryngol
2013;77(3):341–5.
38. Eryuksel E, Dogan M, Golabi P, et al. Treatment of laryngo-pharyngeal reflux im-
proves asthma symptoms in asthmatics. J Asthma 2006;43:539–42.
39. Parsons JP, Mastronarde JG. Gastroesophageal reflux disease and asthma.
Curr Opin Pulm Med 2010;16:60–3.
40. Wohl DL. Nonsurgical management of pediatric vocal fold nodules. Arch Otolar-
yngol Head Neck Surg 2005;131(1):68–70.
41. Gumpert L, Kalach N, Dupont C, et al. Hoarseness and gastroesophageal reflux
in children. J Laryngol Otol 1998;112(1):49–54.
42. Block BB, Brodsky L. Hoarseness in children: the role of laryngopharyngeal re-
flux. Int J Pediatr Otorhinolaryngol 2007;71:1361–9.
43. Kuhn J, Toohill RJ, Ulualp SO, et al. Pharyngeal acid reflux events in patients
with vocal cord nodules. Laryngoscope 1998;108:1146–9.
44. Karkos PD, Wilson JA. Empiric treatment of laryngopharyngeal reflux with proton
pump inhibitors; a systematic review. Laryngoscope 2006;116:144–8.
45. Kogan MD, Pappas G, Yu SM, et al. Over-the-counter medication use among
preschool-age children. JAMA 1994;272:1025–30.
46. Mazzone SB. Sensory regulation of the cough reflex. Pulm Pharmacol Ther
2004;17:361–8.
47. Palmer R, Anon JB, Gallagher P. Pediatric cough: what the otolaryngologist
needs to know. Curr Opin Otolaryngol Head Neck Surg 2011;19:204–9.
48. Millqvist E, Bende M. Role of the upper airways in patients with chronic cough.
Curr Opin Allergy Clin Immunol 2006;6:7–11.
49. Chang AB, Landau LI, van Asperen PP, et al. Cough in children: definitions and
clinical evaluation. Med J Aust 2006;184:398–403.
50. Chang AB, Connor FL, Petsky HL, et al. An objective study of acid reflux and
cough in children using an ambulatory pHmetry-cough logger. Arch Dis Child
2011;96(5):468–72.
51. Khoshoo V, Edell D, Mohnot S, et al. Associated factors in children with chronic
cough. Chest 2009;136:811–5.
52. May JG, Shah P, Lemonnier L, et al. Systematic review of endoscopic airway
findings in children with gastroesophageal reflux disease. Ann Otol Rhinol Lar-
yngol 2011;120(2):116–22.
53. Cezard JP. Managing gastro-oesophageal reflux disease in children. Digestion
2004;69(Suppl):3–8.
54. Bach KK, McGuirt WF Jr, Postma GN. Pediatric laryngopharyngeal reflux. Ear
Nose Throat J 2002;81(9 Suppl 2):27–31.
878 Venkatesan et al

55. Meyer TK, Olsen E, Merati A. Contemporary diagnostic and management tech-
niques for extraoesophageal reflux disease. Curr Opin Otolaryngol Head Neck
Surg 2004;12(6):519–24.
56. Miner P Jr, Katz PO, Chen Y, et al. Gastric acid control with esomeprazole, lan-
soprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover
study. Am J Gastroenterol 2003;98:2616–20.
57. Katz PO. Optimizing medical therapy for gastroesophageal reflux disease: state
of the art. Rev Gastroenterol Disord 2003;3:59–69.
58. Chang A, Lasserson T, Gaffney J, et al. Gastro-oesophageal reflux treatment for
prolonged non-specific cough in children and adults. Cochrane Database Syst
Rev 2005;(2):CD004823.
59. Hassall E. Wrap session: is the Nissen slipping? Can medical treatment replace
surgery for severe gastroesophageal reflux disease in children? Am J Gastroen-
terol 1995;90(8):1212–20.
60. Fung KP, Seagram G, Pasieka J, et al. Investigation and outcome of 121 infants
and children requiring Nissen fundoplication for management of gastroesopha-
geal reflux. Clin Invest Med 1990;13:237–46.
61. Little AG, Ferguson MK, Skinner DB. Reoperation for failed antireflux operations.
J Thorac Cardiovasc Surg 1986;91:511–7.
62. Pennell RC, Lewis JE, Cradock TV, et al. Management of severe gastroesopha-
geal reflux in children. Arch Surg 1984;119:553–7.