Pediatric laryngopharyngeal reflux.
Laryngopharyngeal reflux (LPR) is common in children. It often affects the airway, and it has been associated with life-threatening disease. The diagnosis and treatment of LPR in children is somewhat different from that in adults.
Pediatric laryngopharyngeal reflux (LPR) has gained increasing recognition over the past few years, and it has been identified as a common pediatric disorder. Its symptoms include benign postprandial vomiting during the first year of life, failure to thrive, esophagitis, and airway disturbances. Vandenpias and Sacre-Smits estimated that the incidence of reflux in all infants is 18%. (1) In some conditions--such as tracheoesophageal fistula, neurologic impairment, or oral motor dysphagia--the incidence might be as high as 70%. (2,3)
As early as 1884, Osler postulated an association between reflux and asthma. (4) In 1993, Kaufman wrote that reflux-related life-threatening airway complications of LPR were more common in children than in adults, but that children rarely complained of heartburn and regurgitation. (5)
Classification of pediatric LPR
Gastroesophageal reflux (GER) in the child is classified as physiologic, functional, pathologic, and secondary. (6) Physiologic reflux entails infrequent entails in children who have no abnormalities on diagnostic studies. It is typically asymptomatic, rarely occurs during sleep, and often occurs in the upright position postprandially. Functional GER is defined as silent or asymptomatic reflux and is identified by esophageal pH monitoring (pH-metry). Pathologic GER (gastroesophageal reflux disease [GERD]) is symptomatic and can cause complications in the gastrointestinal and respiratory tract. It can be quantified clinically and pathologically. Finally, secondary GER is a product of another disorder, such as neurologic disease or esophageal dysmotility. (7)
LPR is usually a self-limited disease, and children generally improve by the end of the first year of life upon their transition to a solid diet. Most symptomatic children require positional treatment. Almost all newborns can be shown to have brief postprandial episodes of reflux on esophageal-probe pH monitoring. (8-10) However, children with persistent LPR who are older than 3 years have a higher rate of complications, and they frequently require medical and/or surgical intervention. (11) Identification and treatment of these children can prevent later morbidity.
Infants are physiologically predisposed to GERD because they have a short intra-abdominal esophagus and an immature lower esophageal sphincter (LES). Children are also prone to excessive exposure to esophageal acid at night because their rate of nocturnal swallowing--and thus their esophageal acid clearance--is less than that of adults.
Pediatric manifestations of LPR
During the past two decades, reports of pediatric LPR have appeared more frequently. (12-16) In the 1970s, Fearon and Brama recognized reflux as a cause of various upper respiratory symptoms in children. (17) Other authors subsequently reported respiratory complications of LPR, including recurrent bronchitis, croup, pneumonia, and chronic asthma. (18-24) LPR has also been reported to be associated with contact ulcers and granuloma. (25,26) Although many of these reports suggest an association between reflux and the development of these conditions, it remains difficult to demonstrate a direct causal role. The effect of LPR in the pediatric airway might be mediated by one or all of three mechanisms: (1) microaspiration with stimulation of the laryngeal adductor reflux, (2) micro-aspiration with chemical pneumonitis, and (3) stimulation of an esophageal-vagal and/or autonomic reflex that results in or potentiates bronchial constriction.
Chronic cough and asthma. A subset of children with asthma or chronic cough refractory to standard medical treatment have been found to have LPR. (18-20,27,28) Coughing can also lead to an increase in intra-abdominal pressure, which can promote reflux. Unfortunately, many patients with chronic cough or asthma have other coexisting medical problems that can complicate the diagnosis and management of reflux. In 1991, Andze et al reported that 76% of 131 children with severe asthma had reflux according to single-probe esophageal pH monitoring. (27) Of those with reflux, 69% experienced clinical improvement in their asthma with medical therapy alone, and 88% had good to excellent results following antireflux surgery.
Only a limited number of investigators and clinicians have measured the extent of pharyngeal reflux in children with respiratory disease. (29,30) With the exception of infection, LPR is the most common cause of chronic cough in the 0- to 18-month age group, and it is the third most common cause in pediatric patients overall. (31)
Dysphonia. The child with reflux laryngitis can exhibit dysphonia, chronic cough, globus pharyngeus, or a "wet-sounding" voice or cough. (32-34) There is some evidence that reflux treatment might be beneficial in treating persistent nodules in older children in whom speech therapy or surgical excision has failed. Both Burton et al (20) and Walner and Holinger (35) reported an association between GERD and supraglottic stenosis and granulomas.
Laryngomalacia. Attendant to most respiratory diseases is an increased respiratory effort, which creates greater negative intrathoracic pressures and greater intraabdominal pressures. These pressures have been shown to exert a significant potentiating effect on reflux. (33) These pressure increases might be significant in patients with laryngomalacia, and the association between laryngomalacia and reflux has been well documented (figure). (21,22) There is also strong anecdotal evidence that the treatment of severe laryngomalacia can be improved with aggressive reflux management. Children who are being considered for supraglottoplasty should always have their reflux addressed and corrected prior to surgical intervention.
In 1983, the first direct cause-and-effect relationship between stridor and LPR was documented by Orenstein et al. (36) Contencin and Narcy were able to predict the presence of pH-documented LPR in children with stridor with a specificity of 83% and sensitivity of 100%. (29) These results have been supported by the work of Little et al. (30)
Subglottic stenosis. The damaging effects of gastric acid and pepsin on the subglottis have been demonstrated in animal models. (25,37) Reflux increases the risk of stenosis in animal models and is assumed to account for a significant number of patients in whom laryngotracheal reconstruction fails. Antireflux therapy has been recommended for all patients who undergo open laryngotracheal reconstruction. (38,39) Halstead also suggested that antireflux therapy might increase the success of endoscopic repair of subglottic stenosis. (40) However, in 1996, Zalzal et al found no direct correlation between reflux treatment and outcomes following laryngotracheal reconstruction. (41) To date, studies have been limited by a lack of controls. A prospective study examining the effect of reflux treatment on laryngotracheal reconstruction is currently under way at the University of Cincinnati.
Apparent life-threatening events. The evaluation of a child suspected of having apnea or an apparent life-threatening event (ALTE) begins by excluding anatomic laryngeal or tracheal anomalies. Apnea can also arise as a result of both esophageal and laryngotracheal reflux events, which can be caused by direct aspiration, altered gas exchange, or stimulation of the laryngeal chemoreceptor reflex. (42) Apnea can be a significant problem in preterm infants, and there appears to be a 14-fold increase in its frequency in the presence of significant GER. (43) Evidence supports the idea that the normal stimulation of respiration following an apneic episode might not occur in the presence of hypoxia. (44) This hypothesis was supported by a finding in eight infants that direct distal esophageal acid profusion resulted in bradycardia and apnea. (45) The reported incidence of pH-probe-documented reflux in children evaluated for ALTE varies greatly--from 42 to 95%. (46,47) The incidence of both daytime and nocturnal reflu x exceeded that of controls in each of these two reports.
Jolley et al followed 499 children with reflux for 1 year and reported a 9% incidence of sudden infant death syndrome among infants who had a high frequency of GER on pH-metry. (48) Although a direct causal relationship has not been established, it is strongly recommended that any child who has had an ALTE be evaluated for reflux. Animal models have supported these clinical impressions. Wetmore demonstrated that laryngeal instillation of acid causes obstructive apnea secondary to laryngospasm. (49) Duke et al confirmed these data in an immature canine model, and they found evidence that a vagal response from a chemoreceptor probably induced laryngospasm and diaphragmatic arrest in immature canine larynges. (50)
Other considerations. The relationships of LPR to both otitis media and sinusitis are under investigation, but anecdotal reports suggest that reflux might be pathogenic in some cases. (51-54)
A complete history and physical examination should be undertaken, including an evaluation of the child's growth curve. Attention should be paid to the child's birth and perinatal history, feeding, and airway symptoms. The history should elicit the frequency of emesis or regurgitation, the temporal relationship of symptoms to meals, and information on associated respiratory symptoms, associated neurologic or mental disorders, and weight gain. Orenstein et al developed a questionnaire to aid in this task. (55) The presence of signs of neurologic impairment -- such as generalized pharyngeal hypotonia, uncoordinated swallowing, pooling of secretions in the hypopharynx, and signs suggestive of laryngeal irritation (e.g., laryngeal edema and erythema) -- should be investigated by fiberoptic laryngoscopy. Rigid laryngoscopy and bronchoscopy might be indicated to rule out abnormalities, such as the presence of a foreign body, an infection, a subglottic stenosis, a laryngotracheal esophageal cleft, and other anomalies .
Although there are many diagnostic options in the evaluation of LPR, few are critical. An initial assessment should be followed by carefully selected diagnostic studies in those patients with presumed or documented sequelae of reflux. The sensitivity and specificity of a symptom-based diagnosis alone is low, (56) and the sensitivity and specificity of testing is improved with the use of multiple tests. (57)
Barium esophagography and radionucleotide reflux scanning. Barium esophagography has the advantage of demonstrating anatomic abnormalities. However, its sensitivity (20 to 60%) and specificity (64 to 90%) for GER/LPR are limited. (33)
Esophageal radionucleotide reflux scanning can be beneficial in identifying reflux in the postprandial child because he or she typically has a neutral or alkaline pH reading, neither of which is identified by standard pH-metry. In certain cases, this reflux might be responsible for the patient's respiratory symptoms. A scintiscan can also determine the rate of gastric emptying. Delayed scintigraphy can be used to identify patients who have pulmonary microaspiration. (58)
Endoscopy with biopsy. Esophagoscopy allows for direct visualization of the mucosal lining. Combined with biopsy, it can show evidence of mucosal inflammation or esophagitis. Direct examination of the larynx also allows for the detection of increased supraglottic vascularity, laryngeal or subglottic edema, interarytenoid pachydermia, and small lymphoid aggregates in the wall of the trachea; all of these findings are suggestive of GERD. A bronchoalveolar lavage can also be performed. The presence of lipid-laden macrophages is approximately 85% sensitive for GERD, according to Nussbaum et al. (59) There is a poor correlation between pH monitoring and esophageal and laryngeal biopsy findings. (60,61)
pH monitoring. Double-probe 24-hour pH studies combined with symptom-based observation andlor respiratory monitoring are believed to be the current diagnostic gold standard. This combination allows the clinician to correlate reflux with cardiac, respiratory, and observational events. During pH-metry, reflux events are measured for 18 to 24 hours and a diary is maintained to record symptoms, activity, and food consumption. In several studies, the reproducibility of pH monitoring was poor. (62,63) The probe test should be repeated if results do not correlate with the clinical picture. The distal probe should be placed approximately 3 cm above the LES in infants and children, and 5 cm above the LES in adolescents. (30) The proximal probe must be placed just above the upper esophageal sphincter in the hypopharynx.
When screening children for ALTE, values are abnormal when the reflux index is greater than 5% in noninfants and greater than 10% in infants. (1) Normative data for pharyngeal reflux events in controls are unavailable, which makes the establishment of pathologic parameters somewhat controversial. Little et al observed reflux in 76% of 222 children on double pH monitoring. (30) It is notable that 46% of these patients had documented acid exposure with normal esophageal probes; these patients tended to experience more respiratory abnormalities. Little et al suggested that the pharyngeal probe allowed for the identification of an additional 46% of patients with LPR in whom esophageal reflux would have been considered physiologic and in whom test results would have been normal if only an esophageal probe had been employed. The exact definition of pathologic LPR continues to be debated. Contencin and Narcy reported a significant incidence of recurrent laryngotracheitis in patients who experienced more than six pha ryngeal episodes, (29) and Halstead suggested that more than 10 pharyngeal episodes within 24 hours are associated with respiratory difficulties. (64)
In light of the pharyngeal probe's poor reproducibility of results and the lack of established normal values, we believe that empiric antireflux therapy might be indicated in those children in whom LPR is strongly suspected. We use pH probe testing to assess the efficacy of therapy and to evaluate those patients in whom the clinical picture is unclear. It is also possible that a child would have alkaline reflux, which is not identified by pH testing. Alkaline refluxate can potentiate acidic damage, and it can cause its own damage to the esophagus and airway. This type of nonacidic reflux could be measured by impedance testing, but such testing is not yet readily available. (65,66)
There are three phases in the treatment of LPR: lifestyle modification (phase 1), pharmacologic treatment (phase 2), and antireflux surgery (phase 3). (67) The level of treatment is based on the severity of the reflux. It is important to realize that many infants respond to lifestyle and positional therapy alone. Also, many of the drugs used for LPR are not approved by the U.S. Food and Drug Administration (FDA) for infants, despite their widespread use; therefore, establishing a diagnosis prior to pharmaco-therapy is important in these patients. Generally, reflux treatment begins with conservative measures, including elevation of the head of the bed, milk thickening, avoidance of substances that can decrease LES tone, and fasting before bedtime.
If behavior modification fails, the clinician can turn to pharmacologic treatment with either a cytoprotective agent, an [H.sub.2] receptor antagonist, a prokinetic agent, or a proton-pump inhibitor. Pharmacologic therapy for reflux is successful in 80% of cases. Mild reflux can be treated with a combination of conservative measures, an antacid, and an [H.sub.2] blocker. Because proton-pump inhibitors have not been approved by the FDA for use in infants, their use is controversial. It is our belief that proton-pump inhibitors are warranted for severe or life-threatening symptoms.
Surgical intervention is reserved for patients in whom aggressive medical therapy fails and who continue to have life-threatening complications of reflux. The most common surgical procedure is Nissen fundoplication, which carries a 90% success rate and a 1% mortality rate. (68,69) Pennell et al reported improved surgical outcomes in children who did not have respiratory symptoms. (3,70)
A significant percentage of children with reflux also have respiratory disorders. Treatment of these respiratory disorders might be unsuccessful until the reflux is successfully managed. Close monitoring and follow-up of these patients is essential to optimize outcomes.
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|Author:||Postma, Gregory N.|
|Publication:||Ear, Nose and Throat Journal|
|Date:||Sep 1, 2002|
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