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PJMS- Volume 2 Number 1: January-June 2012 Review Article
Laryngo-pharyngeal reflux- A review
Laryngo-pharyngeal reflux or atypical gastro-esophageal reflux disease (GERD) syndrome commonly known as
extra-esophageal reflux is a controversial subject. The available literature remains non-conclusive regarding the
patho-physiology, investigations and management of patients presenting with symptoms of extra-esophageal
disease. It remains unknown whether symptoms are caused by direct exposure to refluxate or are via a referred
sensation or cough reflex or both. Mucosal changes are not specific to laryngo-pharyngeal reflux although laryngeal
pseudo-sulcus has a positive predictive value of 67- 90 % for laryngo-pharyngeal reflux. The symptoms of laryngo-
pharyngeal reflux include hoarseness of voice, throat clearing, dysphagia, increased phlegm and globus sensation;
patients may also have asthma like symptoms. Physical findings which may be secondary to associated smoking,
alcohol, allergic, asthma, viral illness and vocal abuse, include laryngeal edema, erythema, leukoplakia, granulation
or even malignancy. The aims of the treatment include decreasing reflux, improving esophageal clearance and
protecting esophageal and laryngo-pharyngeal mucosa. Lifestyle modification like weight loss, avoiding sweets,
tomatoes, onions, alcohol and caffeine and finishing dinner 3 hours before going to bed may help. Antacids, H2 receptor antagonists, proton pump inhibitors, prokinetic drugs and anti-reflux surgery like fundoplication and injection of biopolymers in lower esophageal sphincter are used. Key words : Laryngopharygeal reflux, laryngeal pseudosulcus, H2 receptor antagonists, prokinetic drugs.
Laryngo-pharyngeal reflux
research work shows the possibility of cellular mechanisms, Laryngo-pharyngeal reflux (LPR), also extra- whereby reflux might affect the upper airway. Acidified pepsin esophageal reflux disease (EERD) refers to retrograde flow of damages inter cellular spaces and pepsin is taken by human gastric contents to the upper aero-digestive tract, which laryngeal ephithelial cells by receptor mediated endocytosis causes a variety of symptoms, such as cough, hoarseness, and Pathogenesis
Although heartburn is a primary symptom among people with gastro-esophageal reflux disease (GERD), Laryngo-pharyngeal reflux differs from gastro- heartburn is present in fewer than 50% of the patients with esophageal reflux disease (GERD) in that it is often not LPR. Other terms used to describe this condition include associated with heartburn and regurgitation symptoms. The atypical reflux, and supra-esophageal reflux (2).
larynx is vulnerable to gastric reflux, so patients often present with laryngo-pharyngeal symptoms in the absence of Gastro-esophageal reflux disease (GERD) was heartburn and regurgitation (6). There are 4 physiological recognized as a clinical entity in the mid-1930s and now is the barriers protecting the upper aero-digestive tract from reflux most prevalent upper gastrointestinal (GI) disorder in clinical injury: the lower esophageal sphincter, esophageal motor practice. Acid-related laryngeal ulcerations and granulomas function with acid clearance, esophageal mucosal tissue were first reported by Chery in 1968 (3). Subsequent studies resistance, and the upper esophageal sphincter. The delicate suggested that acid reflux might be a contributory factor in ciliated respiratory epithelium of the posterior larynx that other laryngeal and respiratory conditions. In 1979, Pellegrini normally functions to clear mucus from the tracheo-bronchial and DeMeester (4) were the first to document the link tree is altered when these barriers fail, and the resultant ciliary between these airway symptoms and reflux of gastric dysfunction causes mucus stasis (7). The subsequent contents. They also proved that treatment of reflux disease accumulation of mucus produces postnasal drip sensation and results in elimination of these airway symptoms. provokes throat clearing. Direct refluxate irritation can cause coughing and choking (laryngospasm) because sensitivity in Laryngo-pharyngeal reflux or a typical GERD laryngeal sensory endings is up-regulated by local syndrome or commonly known as extra esophageal reflux is a inflammation (8). This combination of factors can lead to vocal controversial subject. The available literature remains fold edema, contact ulcers, and granulomas that cause other controversial regarding the pathophysiology, investigations LPR-associated symptoms: hoarseness, globus pharyngeus, and management of patients presenting with symptoms of extra-esophageal disease. The terms acid laryngitis was coined 40 years ago as most of the extra-esophageal reflux Recent investigations suggest that vulnerable manifestations affect the laryngopharynx (1). The recent laryngeal tissues are protected from reflux damage by the pH- PJMS- Volume 2 Number 1: January-June 2012 Review Article
regulating effect of carbonic anhydrase in the mucosa of the Diagnosis of Laryngopharyngeal Reflux
posterior larynx (10). Carbonic anhydrase catalyzes hydration of carbon dioxide to produce bicarbonate; this protects tissues History- It is important for physicians to appreciate from acid refluxate. In the esophagus, there is active the potential significance of hoarseness and the relative non- production of bicarbonate in the extracellular space that specificity of laryngitis. Laryngitis is a nonspecific designation functions to neutralize refluxed gastric acid. There is no active of laryngeal inflammation. Often, it is mild and resolves pumping of bicarbonate in laryngeal epithelium and carbonic spontaneously. When persistent, laryngitis must be further anhydrase isoenzyme III, expressed at high levels in normal defined based on probable etiologic factors: viral or bacterial laryngeal epithelium, was absent in 64% (47/75) of biopsy infection, allergy, vocal trauma, postnasal discharge or LPR. specimens from laryngeal tissues of LPR patients (11). Persistent or progressive hoarseness lasting beyond 2 to 3 weeks requires examination of the laryngopharynx to rule out Measurement of exposure to refluxate- It remains
cancer and other serious conditions. This is generally unknown whether symptoms are caused by direct exposure to considered good practice; however, laryngeal examination is refluxate or are via referred sensation or cough reflex or both. particularly important in suspected LPR because of the Upto 50% controls have measurable pH drop to < pH 4, 2cm apparent known association of LPR and upper aerodigestive above the upper esophageal sphincter. Techniques of measuring refluxate exit are varied and yet not standardized across specialties (10).
Laryngopharyngeal reflux should be suspected when clinical history and initial findings are suggestive. Failure to Mucosal Changes- Mucosal changes are not specific
appreciate LPR as different from GERD has been a major to laryngo-pharyngeal reflux although laryngeal pseudo- source of skepticism about the diagnosis in the past. Koufman sulcus has a positive predictive value of 67 -90% for laryngo- was the first to clearly distinguish LPR from GERD, noting that pharyngeal reflux. Exposure of laryngeal mucosa to biliary in a combined reported series of 899 patients, throat clearing secretions for many years post gastrectomy appears to be was a complaint of 87% of LPR patients vs 3% of those with carcinogenic. The role of Helicobacter pylori is not clear. GERD, while only 20% of LPR patients complained of heartburn Treating reflux may reduce the risk of recurrence of laryngeal vs 83% in the GERD group(6). An international survey of cancer, but there is no prospective evidence (12). American Broncho-esophagological Association members revealed that the most common LPR symptoms were throat Clinical Features
clearing (98%), persistent cough (97%), globus pharyngeus (95%), and hoarseness (95%) (11).
The symptoms of laryngo-pharyngeal reflux includes hoarseness of voice, throat clearing, dysphagia, increased Since there is no pathognomonic LPR finding, phlegm and globus sensation. Many patients may have asthma Belafsky et al (13) developed an 8-item clinical severity scale like symptoms. Laryngo-pharyngeal reflux may be suspected if for judging laryngoscopic findings, the Reflux Finding Score, the onset of asthma comes in adults without any family history which appears to be useful for assessment and follow-up of and heart burn precedes onset of asthma. LPR patients. They rated 8 LPR-associated findings on a variably weighted scale from 0 to 4: subglottic edema, Physical finding which may be secondary to ventricular obliteration, erythema/hyperemia, vocal fold associated smoking, alcohol, allergic asthma, viral illness and edema, diffuse laryngeal edema, posterior commissure vocal abuse, include laryngeal edema, erythema, leukoplakia, hypertrophy, granuloma, and thick endolaryngeal edema. The granulation or even malignancy. Laryngoscopic findings such results could range from 0 (normal) to 26 (worst possible as erythema, edema, laryngeal granulomas, and inter- score). Based on their analysis, one can be 95% certain that a arytenoid hypertrophy have been used to establish the patient with a Reflux Finding Score of 7 or more will have LPR diagnosis, but these findings are very nonspecific, and have been described in the majority of asymptomatic subjects undergoing laryngoscopy (9,11). Management
Response to acid suppression therapy has been Patient Education and Lifestyle Changes-
suggested as a diagnostic tool to confirm diagnosis of LPR, but Patients with LPR should be educated as to the nature of the studies have shown that the response to empirical trials of problem and counseled on helpful behavioral and dietary such therapy (as with proton-pump inhibitors) in these changes (15). Important behavioral changes include weight patients is often disappointing. Several studies have loss, smoking cessation, and alcohol avoidance. Ideal dietary emphasized the importance of measuring proximal changes would restrict chocolate, fats, citrus fruits, esophageal, or, ideally, pharyngeal acid exposure in patients carbonated beverages, spicy tomato-based products, red with clinical symptoms of LPR, to document reflux as the cause wines, caffeine, and late-night meals. Such behavioral changes appear to be an independently significant variable in PJMS- Volume 2 Number 1: January-June 2012 Review Article
determining response to medical therapy. Education should laparoscopic Nissen fundoplication surgery (21). In Nissen's include the optimal schedule for taking PPI medications fundoplication, fundus of stomach is wrapped around LES. (omeprazole, esomeprazole, rabeprazole, lansoprazole, and Fundoplication appears superior to medical management in pantoprazole), which work best when taken 30 to 60 minutes Recent developments
Medical Management- There are 4 categories of
drugs used in treating LPR: PPIs, H2-receptor antagonists, A l t h o u g h t h e r e i s i n t e r e s t i n r e c e n t prokinetic agents, and mucosal cytoprotectants. Proton pump nonfundoplication endoscopic techniques like Bard inhibitors are considered the mainstay of medical treatment, EndoCinch System for endoluminal plication, System for although there is some controversy regarding their efficacy. A radiofrequency-induced thermal injury and Enteryx liquid 3-month empirical trial is a cost-effective approach for initial polymer injection, to improve lower esophageal sphincteric assessment and management. Responders can be weaned, function, there are no controlled studies and there is no long- while non-responders should undergo studies to confirm LPR term follow-up evidence to support their use.
Other drugs have been used to treat LPR. Ranitidine has proved to be a more potent inhibitor of gastric secretion Delahunty J E. Acid laryngitis. J. Laryngol. 1972; Otol. 86: 335- than cimetidine and is the H2-receptor antagonist of choice, although it has been found to be of limited value in treating Chheda N N, Seybt M W, Schade R R et al. Normal values for LPR (18). Prokinetic agents that accelerate esophageal pharyngeal pH monitoring. Ann. Otol. Rhinol. Laryngol. 2009; clearance and increase lower esophageal sphincter pressure have fallen out of favor because of reported adverse effects of Cherry J, Margulies S I. ‘Contact ulcer of the larynx.’ ventricular arrhythmias and diarrhea (19). Cisapride has been Laryngoscope. 1968; 78 (11): 122-125.
discontinued because of such serious adverse effects. Pellegrini C A, DeMeester T R. et al. “ Gastroesophageal reflux Tegaserod is a prokinetic agent that was recently and pulmonary aspiration: incidence, functional abnormality, demonstrated to decrease reflux and lower esophageal and results of surgical therapy.” Surgery. 1979; 86(1): 110 – sphincter relaxation events, and that was found useful in treating some LPR cases with associated esophageal dyskinesia. Sucralfate is a polysulfated salt of sucrose that may Johnston N. Review article: Uptake of pepsin at pH 7- in non- be helpful as an adjunct in protecting injured mucosa from acid reflux – causes inflammatory, and perhaps even harmful effects of pepsin and acid. Antacids (sodium neoplastic, changes in the laryngopharynx, Aliment. bicarbonate–, aluminum-, and magnesium-containing over- the-counter antacids) may relieve GERD symptoms but do not Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of The aims of the treatment include decreasing reflux, improving esophageal clearance and protecting esophageal acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991;101(4 pt 2 suppl 53)1-78 Koufman J, Sataloff RT, Toohill R. Laryngopharyngeal reflux: consensus conference report. J Voice. 1996; 10215-216 Anti reflux surgical management- When medical
Hanson DG, Jiang JJ. Diagnosis and management of chronic management fails, patients with demonstrable high-volume laryngitis associated with reflux. Am J Med. 2000;108(suppl liquid reflux and lower sphincter incompetence are often candidates for surgical intervention. Fundoplication, either Axford SE, Sharp N, Ross PE. et al. Cell biology of laryngeal complete (Nissen or Rossetti) or partial (Toupet or Bore), is the epithelial defenses in health and disease: preliminary studies. most common procedure performed, and the laparoscopic approach is preferred (20). The goal of surgery is to restore Ann Otol Rhinol Laryngol. 2001;1101099-1108.
competence of the lower esophageal sphincter, and the Ylitalo R, Ramel S. Extraesophageal reflux in patients with outcome measures for LPR include demonstration of reduced contact granuloma: a prospective controlled study. Ann Otol pharyngeal reflux episodes. Excellent results have been reported in 85% to 95% of reflux cases, but results with LPR are 10. Postma GN. Ambulatory pH monitoring methodology. Ann not as impressive (21). Focusing on a carefully screened group Otol Rhinol Laryngol Suppl. 2000;18410-14 of patients with demonstrable extraesophageal reflux (LPR), 11. Ford CN, Inagi K, Khidr A, Bless DM, Gilchrist KW. Sulcus Oelschlager et al reported a significant decrease in pharyngeal vocalis:A rational analytical approach to diagnosis and reflux (7.9 to 1.6 episodes per 24 hours; P<.05) and esophageal management. Ann Otol Rhinol Laryngol. 1996;105189-200.
acid exposure (7.5% to 2.1%; P<.05) following basic 12. Morrison MD. Is chronic gastroesophageal reflux a causative factor in glottic carcinoma? Otolaryngol Head Neck Surg. PJMS- Volume 2 Number 1: January-June 2012 Review Article
trial of high-dose omeprazole in laryngitis. Am J Gastroenterol. 13. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the Reflux Finding Score (RFS). Laryngoscope. 18. Fackler WK, Ours TM, Vaezi MF, Richter JE. Long-term effect of H2RA therapy on nocturnalgastric acid breakthrough. 14. Vaezi MF. Extraesophageal manifestations of gastresophageal reflux disease. Clin Cornerstone. 2003;532-38 19. Castell DO. Future medical therapy of reflux esophagitis. J Clin 15. Katz PO, Castell DO. Medical therapy of supraesophageal Gastroenterol. 1986;8(suppl 1) 81-85.
gastresophageal reflux disease. Am J Med. 2000;108(suppl 4a) 20. Fuchs KH, Breithaupt W, Fein M, Maroske J, Hammer I. Laparoscopic Nissen repair: Indications, techniques and long- 16. Steward DL, Wilson KM, Kelly DH. et al. Proton pump inhibitor term benefits. Langenbecks Arch Surg. 2005;390197-202 therapy for chronic laryngo-pharyngitis: a randomized 21. Oelschlager BK, Eubanks TR, Oleynikov D, Pope C, Pellegrini CA. placebo-control trial. Otolaryngol Head Neck Surg. 2004;131, Symptomatic and physiologic outcomes after operative treatment for extraesophageal reflux. Surg Endosc. 2002;16, 17. Williams RB, Szczesniak MM, Maclean JC, Brake HM, Cole IE, Cook IJ. Predictors of outcome in an open label, therapeutic 22. Charles N. Ford, MD. Evaluation and management of laryngopharyngeal reflux. JAMA 2005, 294(12) 1534-1540.

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