LARYNGOPHARYNGEAL REFLUX

VOICE DISORDERS AND PHONOSURGERY I

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LARYNGOPHARYNGEAL REFLUX State of the Art Diagnosis and Treatment Seckin 0. Ulualp, MD, and Robert J. Toohill, MD

Gastroesophageal reflux (GER) has been implicated in the pathogenesis of several otolaryngologic disorders, such as chronic/posterior laryngitis: laryngeal contact ulcer12,130 or g r a n ~ l o r n a , 3 ~ ,paroxysmal ~,%,~~~ laryngospasm,”J30 vocal cord nodule,68,129J39 Reinke’s edema,129 subglottic ~tenosis,5~,~ laryngotracheal stenosis,3,64,131 globus pharyngeus,””@Jm laryngea131,64,92J45 and hyp~pharyngeal’~~ carcinoma, chronic sinusitis,423337,139 and sudden infant death syndrome.70The incidence of GER related otolaryngologic symptoms and findings in otolaryngology pracRecently luryngophuryngeul reflux tice has been estimated as 4%I3O to (LPR)66has been suggested as a term for the association of laryngeal disorders and GER. Other terms, such as extraesophageal manifestationsof GER and supraesophageal complications of GER, have also been used to indicate this relationship. Gastroesophagealreflux is defined as the entry of the gastric contents into the esophagus without associated belching or vomiting? The term luryngophuryngeul reflux denotes the GER that reaches the structures above the upper esophageal sphincter (UES).Several factors, such as the esophagogastric junction,% esophageal acid clearance,25,41,43,47 esophageal mucosal resistan~e?~ and UES34,3shave been shown to be important in the pathophysiology of GER events. In addition to these structures, functional interactions among pharynx, larynx, lung, and esophagus have been involved in the pathogenesis of GER.t *References 14, 17,40,50,60,61,64,83,111, 116, 122,136, 140, 144, 148, and 151. tReferences 6,39,77, 80, 106, 110,115,118, 120,138, and 152.

From the Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA VOLUME 33 NUMBER 4 * AUGUST 2000

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Anatomy of the esophagogastricjunction involves the lower esophageal sphincter (LES) consisting of the intrinsic muscles of the distal esophagus along with the sling fibers of the stomach and the crural diaphragm.%The LES maintains a high-pressure zone between the esophagus and stomach. LES pressure can be altered because of foods (fat, ethanol, chocolate, cola), drugs (calcium channel blockers, diazepam), hormones (glucagon, gastrin, vasoactive intestinal polypeptide), and tobacco.64LES pressures have been measured in patients with gastroesophageal reflux disease (GERD)124,71,116 posterior laryngitis,50,116 and normal v o l ~ n t e e r s . In 2 ~GERD ~ ~ ~patients ~ ~ ~ ~some ~ ~ studies reported a low LES pressurS4; however, others found either high LES pressurea or normal LES pressure? One study indicated that the LES pressure was similar among normal controls, posterior laryngitis patients, and GERD patienfs.'l6 LES relaxes on swallowing or can be independent from swallowing. During swallowing, LES relaxes and allows the food passage to the stomach. Relaxation of LES independent from swallowing is named as transient LES relaxations.20,90 Transient LES relaxations last longer than LES relaxations induced by swall0w.48,~~ Transient LES relaxations have been suggested as the most important mechanism of GER in normal volu n t e e r ~and ' ~ in patients with GERD." The crural diaphragm is another component of the esophagogastric junction that affects the GER events. GER occurred only during the transient inhibition of the crural diaphragm when the LES pressure was reduced to zero by pharmacologic agentss9or by stimulation of pharyngeal receptor^.'^ The neuronal control of the transient LES relaxation is mediated through the midbrain; however, the mechanism of relaxation of the crural diaphragm is not known.%In normal volunteers, stimulation of the mechanoreceptors of larynx and pharynx resulted in the relaxation of LES.95,134 The amplitude and incidence of the LES relaxation with stimulation of epiglottis and the arytenoids were reported to be greater than that of the mucosa of posterior third of t0ngue.9~Sensory field testing indicated a relationship between laryngopharyngeal structures and LES relaxation and was noted to encompass the majority of laryngeal and pharyngeal regions, excluding the proximal pharynx.134 Esophageal acid clearance is an important factor to reduce the duration that the esophageal mucosa is exposed to the refluxate. Esophageal peristalsis promotes the esophageal acid clearance by removing the refluxate back to the ~ t o m a c hand ~ ~ transporting ,~ the swallowed saliva to neutralize the residual a ~ i d .Esophageal ~,~~ peristalsis includes primary and secondary esophageal peristalsis?1,82Primary esophageal peristalsis is initiated in response to swallowing.81Secondary esophageal peristalsis is produced by local esophageal stimuli.82Although primary esophageal secondary peristalsis is the major mechanism of acid ~learance,"~,'~J~ esophageal peristalsis also contributes to the esophageal volume clearancej2 Primary esophageal peristalsis and secondary esophageal peristalsis have been studied in GERD patient^,"^,'^^ normal volunteers,26,43,107J41 and posterior laryngitis Characteristics of the primary esophageal peristalsis in GERD patients1I2and posterior laryn-

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gitis patients141were similar to that of normal controls. Secondary esophageal peristalsis has been produced by intraesophageal air or water stimul a t i ~ n . ~ In ~ ~GERD J ~ ~patients J ~ ~ the frequency of secondary esophageal peristalsis was smaller than in normal volunteers.112In posterior laryngitis patients secondary esophageal peristalsis was studied by intraesophageal rapid air inje~ti0n.I~' The threshold volume of air required to stimulate secondary esophageal peristalsis in patients with posterior laryngitis was similar to that of normal volunteers.141The parameters of secondary esophageal peristalsis, such as amplitude, duration, and velocity were not significantly different between posterior laryngitis patients and normal volunteers.141Findings from the posterior laryngitis patients showed that secondary esophageal peristalsis was preserved in these patients.14' Esophageal epithelial resistance contributes to the prevention of esophageal injury? Esophageal epithelial resistance is determined by a complex of layers that forms a ba1~ier.9~ Mucus, unstirred water layer, cell membrane and intracellular bridges at the epithelial level, and buffering capacity of the postepithelial defenses interact to prevent the esophageal injury?7Once the esophageal mucosal injury occurs, further prevention is provided by additional buffering caused by increased blood flow in the esophageal ~ a l l . 9 ~ The upper esophageal sphincter is a high-pressure zone that maintains a closed pharyngoesophagealjunction.%The UES provides a barrier against the entry of air into esophagus and regurgitation of materials corning from the During swallowing, UES relaxes and allows the antegrade flow of food.%The UES pressure shows minute by minute vari a t i o n ~ . ~During ~ , ' ~ sleep, the resting pressure of UES decreases significantly? This decrease may provide a favorable condition for esophagopharyngeal re flu^^^; however, the UES resting pressure was not significantly different among normal ~ o l u n t e e r s , ~posterior ~~~~~ laryn~~~" g i t i ~ , " ~and , ' ~ ~GERD patients.116,143 UES response to esophageal stimulation has been studied during esophageal di~tention,5~,l~~,'~~ intraesophageal acid perfusion,34J43 or spontaneous GER event^.^^,'^^,^^ UES response to esophageal distention was partia111gJ41 or complete relaxationllg;however, c ~ n t r a c t i o n ~or~no , ~r~e ~ Jp~o ~n s e ~also ~ ~occurred. , ' ~ ~ Intraesophageal acid perfusion increased the UES pressure depending on the volume and rate of the infusion and the pH of the acid stimuli.35Changes in the UES pressure during spontaneous gastroesophageal reflux events vary across studies. Some studies reported no change in UES pressure during spontaneous GER events in GERD patients'" and in normal control^.^^,'^^ 0thers documented an increase in UES pressure with GER events.132 The UES response to laryngeal stimulation was studied in normal volunteers.121 Stimulation of the larynx with air does increase the UES pressure (i.e., the laryngo-UES contractile reflex).l2I Laryngo-UEScontractile reflex may prevent further esophagopharyngeal reflux by increasing the UES pressure when the esophagopharyngeal refluxate comes in contact with the posterior commissure or the posterior aspects of the arytenoid. Close functional connections of esophagus with the a i r ~ a p ~ ~ t 77,110 and the larynx6,115,118 and the pharynx with the larynx'% and the

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UES80,120,133,'38 warrant consideration of the pathophysiology of gastroesophageal and esophagopharyngeal reflux. Airway response to esophageal stimulation has been investigated in human^^,'^^ and a11imals.6,~~ In humans, intraesophageal acid infusion increases the airflow resist a n ~ e . ~In, ' guinea ~~ pigs, esophageal stimulation by hydrochloric acid causes neurogenic inflammation of the airways suggesting the presence of neural pathways communicatingbetween the esophagus and airwa~s.3~ Esophagoglottal closure reflex is an example of a reflex connection between the esophagusand the larynx.115,118 Esophagoglottal closure reflex was reported to be the adduction of the vocal cords in response to abrupt This reflex has been documented in hudistention of the e~ophagus."~ m a n ~ "and ~ felines.'I8In normal volunteers, spontaneousGER events have triggered the esophagoglottalclosure Pharyngoglottal closure reflex'" is an example of the interactionbetween the pharynx and the larynx. Stimulation of the pharynx with injection of water also results in adduction of vocal cords (i.e., the pharyngoglottal closure reflex).'" The esophagoglottal closure reflex and pharyngoglottal closure reflex are postulated as a part of the airway protective mechanism against a~piration."~ Injection of minute amounts of water to the pharynx in humans increases the UES pressure (i.e., the pharyngo-UES contractile r e f l e ~ ) . ' ~ ~ , ' ~ ~ This reflex has been speculated to reduce the chance of further entry of the esophagopharyngealrefluxate into the pharynx by increasing the UES tone when the small amounts of refluxate enter into the p h a r y n ~ . ~ In '~,'~ patients with posterior laryngitis, the threshold volume of water required to trigger the pharyngo-UES contractile reflex was significantly greater than in normal volunteers.'% These findings suggest an altered afferent sensory limb of pharyngo-UES contractile reflex in posterior laryngitis patients.'% The role of GER in the pathogenesis of several disorders has been of interest to otolaryngologists, pulmonologists, and gastroenterologists.The association between the otolaryngologic disorders and GER has been increasingly well recognized since GER was suggested in the pathogenesis of contact ulcer and granuloma of the larynx.I2The pathophysiology of GER-associatedinjury has been studied in a n i r n a l ~ " ~ ~and ,~~ humans.& ~,'~~ Results of these studies suggest the possible injurious role of gastric pepsin in addition to gastric acid. In animals, presence of pepsin delayed the healing of pre-existing submucosal injury in the larynx."' In humans, pepsin has been shown in the sputum samples of patients with laryngopharyngeal reflux suggesting the possible damaging effect of the retained pepsin in the laryngopharynx.65 Patients with laryngopharyngeal reflux are most commonly presented with chronic intermittent symptoms. Therefore, a meticulous synthesis of the information obtained from a complete otolaryngologic examination, diagnostic tests, and response to treatment is essential for the efficient management of patients with laryngopharyngeal reflux associated otolaryngologicdisorders.

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DIAGNOSIS

Otolaryngologic Evaluation A careful history is an important part of the evaluation of patients with laryngopharyngeal manifestations of GER.lZ9Various factors, such as tobacco, ethanol, dietary factors, occupation, and particular medications that may predispose to GER should be identified in each patient. Classic symptoms of GER include heartburn and regurgitation. Only ZO%lZ9 to 43%“ of patients with suspected otolaryngologic manifestations of GER had classic symptoms of GER. Patients usually complain of chronic or intermittent hoarseness? voice fatigue or break,60,1z9,130 chronic excessive throat m u c u ~ , ” ~ J ~ ~ or frequent throat clearing,40,61,64,66,122,136,140 chronic postnatal drip,” sore dysphan . ~ of~ the~ larynx, ~ ~ ~ ~ ~ gia,44,45,96,122 or globus ~ e n ~ a t i oNeoplasms pharynx, and esophagus may also produce similar symptoms; therefore, the presence of an underlying carcinoma must be excluded.%Presence of the laryngopharyngeal complaints without a history of obvious pharyngeal or laryngeal disease leads to a suspicion of GER.lZ9 Laryngeal examination can be performed using indirect laryngoscopy technique, fiberoptic laryngoscopy, rigid angulated laryngoscopy, videostroboscopy,or microlaryngoscopy.1z9 Indirect laryngoscopy is an inexpensive and invaluable technique to evaluate the hypopharynx and the larynx. A carefully performed indirect laryngoscopy provides clues for the diagnosis and should be done in every patient with laryngeal symptoms. Fiberoptic laryngoscopy is used to visualize the larynx under topical anesthesia of either nasal or oral cavities. The visual field, however, is relatively small. Rigid angulated laryngoscopy mostly does not require any topical anesthesia and magnifies the view providing an excellent visualization and documentation of laryngeal disease. All of the previously mentioned methods examine the gross appearance of the larynx and the vocal-cord movements. Laryngeal videostroboscopy provides the detailed information on the vibratory pattern of vocal cords and the detection of small scars, lesions, excessive mucus, and erythema that might escape other visual examining techniques. Microlaryngoscopyis another method that provides a superb visualization along with the ability to obtain biopsy. Microlaryngoscopy is performed commonly under general anesthesia. In the last 3 decades various terms have been used to represent the GER-associatedlaryngeal injury. In the 1970s, posterior laryngitis and acid laryngitis were used to describe the hyperplastic heaping of interarytenoid mucosa with redness or edema of the posterior third of the vocal cords.17Histologically, the mucosa shows epithelial proliferation and papillary down growth areas of keratosis and parakeratosis that are indistinTherefore, a sigguishable from the histology of pachyderma laryngi~.’~ *References13,40,61,62,64,79,116,136,140,144, and 148.

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nificant portion of patients with pachyderma laryngis was suggested to have acid laryngiti~.'~ In the 1980s, chronic nonspecific laryngitis was shown to be often secondary to the irritation caused by GER.14 Later on, based on the histologic findings from the affected laryngeal mucosa and the history, acid posterior laryngitis was the diagnosism Acid laryngitis was used to represent the posterior laryngitis patients with documented GER.Is0 In the beginning of the 1990s, the term peptic laryngitis was suggested to be a better term than the reflux laryngitis or acid laryngitis because of the documented injurious effect of pepsin on previously injured subglottic mucosa of dogs." In other studies, however, patients with suspected GER were named as either patients with reflux l a r y n g i t i ~ ~ , ~ ~ , ' ~ ' , ~ ~ or patients with posterior l a r y n g i t i ~ . ~ ~ , ~ ~ , ~ ~ , ~ ~ ~ Esophageal Endoscopy

Esophageal endoscopy (esophagoscopy)provides the visualization of the esophageal mucosa and is commonly performed as an initial investigation for the evaluation of traditional reflux symptoms.21Esophagitishas been shown in 30% to 50% of patients with typical symptoms of heartburn.3O Esophagitis was documented in 50% to 67% of patients with laryngeal symptoms with and without objective findings by endoscopy.79,'3s In a recent study, esophagoscopyfindings from 15 patients with objective findings of posterior laryngitis revealed macroscopic esophagitis in two patients and hiatal hernia in three patients.'% Plausible explanation of the different observation rates of esophagitis between studies may be the differgnces in methodology. In patients with esophagitis, however, the incidence of laryngitis and hoarseness was between 0.1% and 0.2% respect i ~ e l y Therefore, .~~ relatively low incidence of esophagitis in posterior laryngitis patients and infrequent findings of laryngitis in patients with esophagitis may be postulated because of the different pathophysiologic mechanisms of reflux between these two patient groups. Radiologic Techniques

Radiographic imaging methods to evaluate patients with GERD include radionuclide scintiscanning and barium e ~ o p h a g r a mRadionu.~~ clide scintiscanning using a gamma camera is a simple and noninvasive method with minimal radiation exposure to the patient.98The fraction of administered radioactive material refluxing into the esophagus is used as GER An abnormal GER index on radionuclide scintiscanningwas shown in only 30% of patients with endoscopically proven reflux esophagitisS2and 11%of patients with head and neck symptoms of re flu^.^^ Compared with the esophageal endoscopy and 24-hour intraesophageal pH monitoring, radionuclide scintigraphy was less sensitive in GERD patients'= and thus has a limited role to demonstrate GER.

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Barium esophagram is a convenient, inexpensive, and noninvasive technique that assesses the GERD by combining various examination techniquesloo,lol: full column, mucosal relief, double-contrast, and motion recording. Presence of GER, evaluation of esophageal motility and clearance, and detection of changes related to reflux esophagitis can be demonstrated by barium es~phagram.~~,~,'"'" In previous studies of patients diagnosed with GERD, GERD symptoms, or posterior laryngitis, barium esophagram was found to be less sensitive than 24-hour pharyngeal pH monitoring.5,15,@, 104,113,128,136 Ambulatory 24-Hour Pharyngoesophageal pH Monitoring

Ambulatory pH monitoring studies have been performed to assess the esophageal and pharyngeal acid exposure in patients and normal volunteers. The equipment for ambulatory pH monitoring includes a portable data logger for data storage, a pH electrode, a computer, and a software analysis of pH Portable data loggers are light weight units carried on waist belts or shoulder ~traps.5~ Data from the pH electrodes The pH values are missed beare recorded at 6 to 8 second inter~als.5~ tween the sampling times; however, this has negligible impact on the overall acid exposure time.= Patients can activate the event markers on the data logger to indicate the timing of symptoms, meals, and recumbency as a p p r ~ p r i a t e . ~In~ addition, , ~ , ~ ~ ~ patients keep a diary indicating the same events in order to correlate them with the pH tracing.5n,51,59,116,136,140 On completion of the study, data from the portable data logger are transferred to a computer for subsequent printing and Several types of pH electrodes are available for the ambulatory pH recording; these include antimony monocrystalline electrodes, unipolar glass electrodes, or combined glass electr0des.5~ Each electrode has its own advantages and disadvantages; however, any one electrode can be used satisfactorily for clinical pH monitoring. The pH electrode is positioned transnasally in the vicinity of uES50,62,@,116,131,136,137.140 or LESlL51,55.108,116, 136,140 under the topical anesthesia of the nasal cavity. Conventionally, the esophageal pH electrode has been positioned 5 cm above the manometrically determined upper margin of the LES in GERD patients.50,55,116 The sensitivity of the pH monitoring test is decreased when the pH electrode is positioned high above the LES.' In GER-associated otolaryngologic disorders, additional pH electrodes have been placed to monitor the acid reflux events in the proximal esophagus below the UES,50,142 in the pharynx above the uES,11,62,64*68, 116,131,136,137,140 in proximal esophagus and pharynx,68.116,131.136.137,140 or at the level of UES.'" Manometric localization of the UES has been used commonly to determine the position of the pH electrode; however, fluoros c ~ p i and c ~ ~endoscopic124 positioning are performed also. The technical disadvantage of the probe located in the pharynx is the spurious read-

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that may be attributed to the loss of mucosal contact,1'6,131,136,140,148 electrode movement,1'6,131,136,140,148 pH change caused by oral intake,116,131,136,140 or intermittent drying and moistening of the electrode.6s,108,116,131,136,'40,'48 Some studies advocate the positioning of the pH probe at the level of the UES'" or below the lower limit of the UESWIn both techniques, however, documentation of the acid reflux events does not verify that the acid refluxate reaches the pharynx bypassing the UES. In pH ~ t u d i e ~ ~using , ~ the ~ simultaneous ~ , ~ ~ , ~pH ~ monitoring ~ , ~ ~ from the pharynx, proximal esophagus, and distal esophagus, spurious readings were corrected by the following approach pharyngeal acid reflux event has to be simultaneous or preceded by a decrease in pH of similar or larger magnitude in the proximal and distal esophageal sites. A thorough evaluation of the acid reflux events requires minute by minute analysis with the previous method in addition to the pH analysis provided by the software package. Most software packages analyze the pH data for the following variables: (1) percent total time pH less than 4; (2) percent upright time pH less than 4;(3) percent recumbent time pH less than 4;(4) number of reflux episodes with pH less than 4;(5) number of reflux episodes with pH less than 4 for 5 or more minutes, and the period of the longest single acid exposure episode.59Esophageal acid exposure time (i.e., percentage of the study time that the pH value was 4 or less) is the most useful discriminator between physiologic and pathologic refl~x.5~ There is no threshold value of esophageal acid exposure equated to a diagnosis of GERD.29Interpretation of the ambulatory pH monitoring test results in patients with otolaryngologic disorders can be made in two ways. One method is evaluation of the results based on the values obtained from a group of normal ~ o l u n t e e r s . ~ ,The @ , other ~ ~ method is comparison of results with a group or GERD patients.5°,116,'48 of normal volunteers68~116,131,136,140,150 In patients with LPR disorders, ambulatory pH monitoring studies have revealed abnormal esophageal pH test results based on previously determined limits of normal value^.^,",^^ In between group comparison, however, distal esophageal acid exposure time of posterior laryngitis patients was not significantly different from GERD patientsIW,ll6 normal cont r o l ~ , " ~ , and ' ~ , ~patients ~ with GER-related symptoms and without laryngitis.50,116Proximal esophageal acid exposure time in posterior laryngitis patients has been found to be either greateP or similar to that of GERD patients.'I6 Findings from pharyngeal pH monitoring documented the pharyngeal acid reflux events in patients with otolaryngologic disorders, such as posterior laryngiti~,@,"~,'~~,'~ vocal cord n0dules,6~J~~ laryngeal and tracheal s t e n o ~ i s , @ idiopathic , ~ ~ ~ subglottic sten~sis;~ chronic sinusitis refractory to conventionaltherapy,137 and carcinoma of the larynx.@On the other hand, pharyngeal acid reflux events were uncommon in normal healthy volunteer^^^^,^^,'^^ and GERD patients.'16 In a recent study pharyngoesophageal pH monitoring test results were reported in a group of normal controls and patients with various otolaryngologic disorders; isolated posterior laryngitis, combined posterior laryngitis and chronic sinusitis, coming68,116,131,136,137,140,148

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bined posterior laryngitis and vocal cord nodule, combined posterior laryngitis and laryngotracheal stenosis, and isolated chronic sinusitis.140In the distal esophagus and proximal esophagus, the number of acid reflux episodes and the percent acid exposure time was not significantly different among the studied groups.140 The prevalence of pharyngeal acid reflux events in patients with isolated posterior laryngitis and those with a combination of posterior laryngitis and other otolaryngologic disorders was significantly higher than that of patients without posterior laryngitis and Thus, prevalence of pharyngeal acid reflux events has normal been suggested to be significantly higher when posterior laryngitis is present along with other otolaryngologic disorders compared with controls and isolated otolaryngologic disorders.lM The reproducibility, sensitivity, specificity, and the optimum pH threshold of ambulatory pharyngeal pH monitoring have been studied in a group of patients with posterior laryngitis and the healthy age-matched Posterior laryngitis patients and controls underwent pharyngoesophageal pH monitoring twice and the data were analyzed for the threshold pH of 4 and 5. Reproducibility of pharyngeal pH monitoring test results was 69% for the posterior laryngitis patients and 79%for the controls with the threshold pH of 4. The relatively low reproducibility of the pH monitoring has been attributed to the heterogeneityof the etiology of posterior laryngitis patients and to the episodic and infrequent nature of pharyngeal acid reflux events. Sensitivity of the pharyngeal pH monitoring with the threshold pH of 4 was similar to that of pH 5; however, the specificity decreased when the threshold pH of 5 was applied. The threshold pH 5 increased the reproducibility of the pharyngeal pH monitoring. Therefore, the use of pharyngeal pH threshold of 5 has been suggested in patients with high suspicion for the GER-associated otolaryngologic disorders. Recently a group of patients with posterior laryngitis underwent pharyngeal pH monitoring, esophageal endoscopy, and barium esophagram.'% Pharyngeal acid reflux events recorded by pH monitoring were more frequently detected in posterior laryngitis patients than the esophageal sequela of reflux disease documented by esophageal endoscopy or occurrence of reflux during barium studies. TREATMENT

The therapeutic approaches against the GER in otolaryngologic disorders associated with GER include life style modifications,40,61,64.111,122, 130,144,151 acid suppressive therapy,40,6L@A% 111,122,129,13Jr151 and surgical therapy.22,40,61,64,111,151 Although life style modifications have not been evaluated in controlled studies,2l several studies reported a decrease in distal esophageal acid exposure with the elevation of the head of the bed,54,126 decreased fat decrease in smoking,146and avoiding recumbency for 3 hours postprandially.'* In a large group of patients with posterior laryngitis,

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antireflux precautions consisting of avoidance of oral intake for 3 hours before bed time and elevation of the head of the bed during sleep resulted in the resolution or significant improvement of laryngeal symptoms and inflammation in 93 of 182 (51%)patients." The pharmacologic therapies against GER include antacids, alginic acid, acid suppressive agents, and prokinetic agents. Antacids and alginic acid have been proposed for their acid neutralizing effect and significant decreases in reflux symptoms in patients with reflux d i s e a ~ e . 3 ~AlJ~ though antacids appear to be effective in control of mild to moderate symptoms of reflux disease, a placebo effect needs to be ascertained in patients with laryngopharyngeal reflux. Prokinetic agents include bethanechol, metoclopramide, and cisapride. Bethanechol has been shown to increase LES pressure, to decrease GER, and to improve esophageal acid clearing in patients with r e f l ~ x . ~ , ' ~ ~ Metoclopramide has been reported to increase LES pressure and improve abnormal gastric emptying in patients with r e f l ~ ~Cisapride x.~~ increases the LES pressure and amplitude of esophageal peristalsi~~~ and promotes the gastric emptying.lo,los Cisapride has been suggested as an adjunct therapy in GER-associated otolaryngologic disorders when barium esophagram demonstrates motility, peristaltic, or LES dysfunction.129 Acid suppressivetherapy consists of H2 receptor blocking agents and proton pump inhibitors. Current H2 receptor blocking agents are cimetidine hydrochloride, ranitidine hydrochloride, famotidine, and nizatidine. In chronic laryngitis patients treated with H2 blockers and antireflux precautions, a satisfactory clinical response was achieved in 54% of patients after 6 weeks of therapy." After cessation of H2 blockers, some recurrent symptoms occurred in 92% of chronic laryngitis patients." Agents suppressing the gastric acid by inhibiting the proton pump are omeprazole and lansoprazole. Omeprazole has been recently studied for the treatment of posterior laryngitis.40,61,83 In patients with posterior laryngitis who are unresponsive H2 blockers, treatment with omeprazole has improved the laryngeal The majority of the patients with chronic laryngitis had recurrent symptoms after stopping the omeprazo1e.40,61 Empiric trials of antireflux therapy for 8 weeks in posterior laryngitis patients have been proposed as a reasonable first option with improvement of laryngeal symptoms and signs in two thirds of the patient~.'~' In addition, empiric therapy with omeprazole may be useful in confirming the suspicion of reflux laryngitis after an otolaryngologic evaluation; however, there is a potential for false-positive and false-negative results.'" Nissen fundoplication has been done for the surgical treatment of GER.22,40,61 Patients who did not respond"," or could not tolerate" acidsuppressive therapy had good outcomes with fundoplication. Prompt response of the patients to correction of GER with Nissen fundoplication supports the role of gastroesophageal reflux in the pathophysiology of posterior laryngitis."

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SUMMARY

Gastroesophagopharyngealreflux has been implicated in the pathogenesis of a wide variety of otolaryngologic disorders. Patients with GERassociated otolaryngologic disorders infrequently have the classic symptoms of gastroesophageal reflux, such as heartburn. The clinical presence of laryngopharyngeal reflux most commonly is characterized by chronic intermittent symptoms. All patients should undergo complete otolaryngologic evaluation with the careful investigation of predisposing factors to GER and examination of the larynx. Esophageal endoscopy can be considered in patients with esophageal symptoms; otherwise esophagitis is uncommon in patients with GER-associated otolaryngologic disorders. Barium esophagram is an inexpensive and convenient technique to document the esophageal abnormalities; however, the role of barium esophagram to detect the gastroesophageal reflux in otolaryngologic disorders associated with GER is limited. Ambulatory 24-hour pharyngoesophageal pH monitoring provides the documentation of pharyngeal and esophageal acid exposure. Interpretation of the ambulatory pH monitoring results should consider the technical difficulties of the test and the different characteristics of gastroesophagopharyngeal acid reflux in this patient group. Real pharyngeal acid reflux events need to be identified from the spurious readings with detailed analysis of the data. PharyngealpH monitoring is important in this patient group since the minute amounts of acid may cause laryngeal injury. Because of the intermittent nature of esophagopharyngeal reflux, however, pharyngeal pH monitoring may not document acid reflux in all patients who suffer from the consequences of laryngopharyngeal reflux. Therefore, improvement of the laryngopharyngeal-associated signs and symptoms with the treatment supports the role of gastroesophagopharyngeal reflux. Treatment consists of combination of antireflux precautions and acid suppressive agents. Acid suppressive therapy includes H2 blockers and proton pump inhibitors. Proton pump inhibitors provide relief of symptoms even in cases unresponsive to H2 blockers. Patients who are intolerant to the acid suppressivetherapy may benefit from surgical treatment with Nissen fundoplication.Until the development of more specific methods to document the role of esophagopharyngeal reflux in patients with otolaryngologic disorders, concurrent use of the information obtained from the complete otolaryngologic evaluation, diagnostic tests, and response to treatment are essential for the efficient management of patients with gastroesophagopharyngeal reflux-associated otolaryngologic disorders. References 1. Anggiansah A, SumboonnanondaK, Wang J, et a1 Significantly reduced acid detection at 10 centimeters compared to 5 centimeters above lower esophageal sphincter in patients with acid reflux. Am J Gastroenterol88:842-846,1993

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