Key points

Introduction

Gastroesophageal reflux disease (GERD) is a complex problem in the pediatric population 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 implicated in various pediatric diseases, it has been inadequately studied in others. LPRD is believed to contribute to failure to thrive, laryngomalacia, recurrent respiratory papillomatosis (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. Currently, given that childhood obesity is on the increase, and with the association between obesity and reflux, it is likely that the incidence 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 benefits of treating LPRD as a contributing factor in many afflictions of the upper aerodigestive 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. 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 process. 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. Certain complaints, including dysphagia, vomiting, regurgitation, dyspnea, and globus sensation, are more broad. The role and manifestations of LPRD in specific disease processes requires further attention ( Box 2 ).

Introduction

Gastroesophageal reflux disease (GERD) is a complex problem in the pediatric population 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 implicated in various pediatric diseases, it has been inadequately studied in others. LPRD is believed to contribute to failure to thrive, laryngomalacia, recurrent respiratory papillomatosis (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. Currently, given that childhood obesity is on the increase, and with the association between obesity and reflux, it is likely that the incidence 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 benefits of treating LPRD as a contributing factor in many afflictions of the upper aerodigestive 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. 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 process. 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. Certain complaints, including dysphagia, vomiting, regurgitation, dyspnea, and globus sensation, are more broad. The role and manifestations 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 aspiration. 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 stimulating 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.

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 positive 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 colleagues showed significant improvement in videofluoroscopic swallow evaluations and pharyngeal impairment scores when infants with swallowing issues were treated for GERD. Aviv and colleagues demonstrated that just 3 months of GERD treatment was sufficient time to demonstrate normalization of laryngopharyngeal 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. Thickening helps by improving overall laryngopharyngeal sensing of the bolus and thus improves the coordination of swallowing.

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. 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-analysis 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 proposed mechanism is that aerophagia during feedings causes gastric distention leading to vagal reflexes followed by postprandial vomiting and regurgitation.

The increased association between laryngomalacia and reflux has led to the question of whether reflux causes laryngomalacia or is simply present concurrently. Although supraglottic biopsies did show mild intraepithelial infiltrate, pathognomonic for reflux, the gross morphologic changes did not seem to correspond to laryngomalacia. 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. Unfortunately, there is still some uncertainty regarding the role of pharyngeal pH monitoring in these patients. Little and colleagues demonstrated that nearly half of patients with extraesophageal reflux were only accurately diagnosed after pharyngeal monitoring and a negative esophageal study. Rabinowitz and colleagues 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 laryngomalacia symptoms (cough, stridor, choking) with antireflux treatment, a prospective trial done by Thompson 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 moderate (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 regurgitation 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. Thompson 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 history of the disease. No studies have compared the outcome of patients with laryngomalacia 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.

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 subglottic mucosa has not been as thoroughly studied. The formation of vocal cord granulomas has long been known as a sequela of reflux, and these same histologic changes were noted in early subglottic stenosis lesions. Although irritation and mucosal damage begin the stenosis process, the role of reflux in preventing reepithelialization should not be understated. Further studies have demonstrated the effect of reflux at the cellular level, including downregulation of epidermal growth factor receptor, which reduces mucosal turnover, increased transforming growth factor β1, which causes fibroblast differentiation, and excessive connective tissue deposition.

Although the correlation between reflux and subglottic mucosal changes has been evaluated, no prospective data are available to better correlate the clinical relationship. Reports of children whose stridor and degree of stenosis decreases with reflux management advocate for LPRD treatment in this patient population. Reviews show that nearly two-thirds of children with subglottic stenosis have reflux disease to some extent. Furthermore, subglottic stenosis correlates with reflux disease with a relative risk of 2.5. In 1 study, nearly one-third of patients with subglottic stenosis who were treated for reflux were able to avoid surgical intervention. 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.