Supraesophageal manifestations of GERD

Symptoms and signs of LPR Hoarseness 71% Chronic cough 51% Globus pharyngeus 47% Heart burn/regurgitation 43% Chronic throat clearing 42% Difficulty swallowing 35% Cummings(III) ch.126 Gastroesophageal reflux disease P2426

Chronic Throat Symptoms Treatment of Chronic Throat Symptoms with PPIs Should Be Preceded by pH Monitring Am J Gastroenterol 2006;101:6-11 Chronic Throat Symptoms pH Monitoring Empiric treatment with PPIs

PRO:Empiric treatment with PPIs is not appropriate without testing PPIs are not innocent drugs Side effects: Headache, diarrhea, constipation, flatulence, abdominal pain, dry mouth. Less common: anaphylactic shock, Stevens-Johnson syn., pancreatitis, nephritis, toxic epidermal necrolysis. Predispose treated individuals to pneumonia

PPIs are not innocent drugs PPIs interfere with neutrophil function by increasing intracellular calcium leading to immunoedeficiency. In hospitalized patients more CD enteritis. Mask and delay the diagnosis of esophageal AdenoCa.

PPIs are not innocent drugs Rebound and hypersecretion after PPIs withdrawal. Hypergastrinemia Increased parietal cell mass Increase ECL cells activity Rebound might last more than 2 months ( Fossmark et al. )

A successful empirical trial with PPIs does not necessarily confirm the diagnosis of reflux Meta-analysis by Numans et al: Sensitivity – 78% Specificity -54% Predictive value in LPR should be even lower

PPI trial in LPR has the predictive value of a coin flip PPIs are overused Placebo effect in LPR is high Steward et al: Rabeprazole bid + lifestyle modification 53% response Vs. Placebo bid + lifestyle modification 50% response Noordzij et al: placebo response of 50% PPI trial in LPR has the predictive value of a coin flip We are creating PPI addicts

Ambulatory pH testing complemented by laryngoscopy Dual-probe pH testing is the gold standard for LPR The proximal pH sensor is placed 1cm above the UES in the hypopharyngs Proximal esophageal acid exposure can not be relied upon to diagnose extraesophageal disease!!!

Ambulatory pH testing Merati et al. Meta-analysis of 790 extraesophageal pH reports in 16 studies for LPR Hypopharyngeal pH study does appear to be able to discriminate LPR patients from normal. Sensitivity of 80%

Laryngoscopy as adjunct test Laryngoscopy alone cannot be relied upon to make the diagnosis of LPR Tobacco, environmental pollutants, infections, excessive voice use and allergy can all cause laryngeal inflammation. Combination of laryngoscopy and dual-probe pH testing should be considered the gold standard in the diagnosis of LPR

Treatment with PPIs should not preceded with pH monitoring in suspected LPR Prolonged pH monitoring is considered the gold standard in the diagnosis of GERD However pH monitoring is not likely to help in the diagnosis or treatment of LPR

The important questions: Does the presence of esophageal acid reflux suggest a casual association between throat symptoms and GERD? Does the absence of abnormal acid exposure in the esophagus or even in the hypopharyngs suggest lack of such an association? Should the pH test be performed on or off therapy and does it matter? NO!!!

pH monitoring The overall pre-therapy prevalence of an abnormal pH test us 53% The prevalence of excessive distal, proximal and hypopharyngeal acid exposure is 42%, 44% and 38% No established casual relationship Number and duration of hypopharyngeal reflux events are similar between controls and LPR patients ( Bilgen et al)

pH testing is a poor predictor of response to therapy 28/39 patients with posterior laryngitis were found to have abnormal pharyngeal reflux However, both groups had improvement in symptoms and laryngeal findings with PPIs. (Ulualp et al)

The dichotomy in the literature regarding pH monitoring is a result of: Probe positioning Lack of consensus regarding duration and amount of reflux to denote abnormal acid reflux Poor sensitivity of pH monitoring: 70%, 55% and 40% for distal, proximal and hypopharyngeal probes. Intermittent nature of reflux events

pH testing in patients under treatment Was not found to be clinically helpful Among 115 pts with extraesophageal symptoms while on BID therapy only 2% had abnormal acid exposure. Impedance studies did not reveal a significant role for non-acid reflux.

Posterior laryngitis

Specificity of laryngoscopy The laryngeal signs are nonspecific. In a study o 105 healthy subjects without any symptoms, the majority had abnormal laryngeal findings. 91/105 (87%) had at least one abnormal finding 3 abnormal findings have been identified: Posterior cricoid awall erythema Vocal cord erythema and edema Arytenoid medial wall erythema and edema

The role of empiric therapy Aggressive acid suppression would identify those whose laryngeal signs and symptoms are related to GERD An overall response rate of 50-70% could be expected. The lack of response among the remaining patients is most likely related to an overlap between GERD and other causes The suggestion that PPI therapy is not safe even for a short time period is not based on any solid data.

Medical antireflux treatment of reflux laryngitis: placebo-controlled studies Symptoms Laryngoscopy L: 43%; P: 54% L: 35%; P: 33% Lansoprazole 30 mg b.d. × 3 months 15 Havas et al No a priori predictors of response L: 58% P: 30% L: 50% P: 10%* 20 El-Serag et al. Mild hoarseness and throat clearing better with omeprazole O: NC; P: NC O: 48%; P: 19% Omeprazole 40 mg b.d. × 2 months 30 Noordzij et al. Patients on placebo did as well as pantoprazole Pan: N.S. P: N.S. Pan: 43%; P: 41% Pantoprazole 40 mg b.d. × 3 months 14 Eherer et al. Enrolled patients had either no or minimal classic GERD symptoms Eso: N.S.; P: N.S. Eso: 42%; P: 46% Esomerprazole 40 mg b.d. × 4 months 145 Vaezi et al.

תודה רבה

אפידמיולוגיה של תופעות על וושטיות ב-GERD בנבדקים עם צרבת קלה ב- 80% נמצאה לפחות תופעה על-ושטית אחת בנבדקים ללא צרבת ב-49% נמצאו תופעות על ושטיות במחקר VA על 101,366 נבדקים ב-17% מהנבדקים עם אזופגיטיס היו תופעות על- ושטיות Lock GR et al. Gastroenterology. 1997

6215 נבדקים עם GERD ס"ה ב-32.8% תופעות ע"ו Prevalence of extra-oesophageal manifestations in GERD: an analysis based on the ProGERD Study. 6215 נבדקים עם GERD ס"ה ב-32.8% תופעות ע"ו עם אזופגיטיס- 34.9% ללא אזופגיטיס – 30.5% % Aliment Pharmacol Ther. 2003 Jaspersen D et al

Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. (2200 individuals) % Lock GR et al. Gastroenterology. 1997

Introduction Comparision of the GERD Symptoms of the Typical Esophagitis Patient, the “Atypical” Otolaryngology Patient, and Pediatric Patient. Typical (%) 83 23 40 47 16 12 3 Atypical (%) 20 - 12 26 44 87 Pediatric (%) 16 68 30 - 36 Symptoms Heartburn Regurgitation Dysphagia Cough Pulmonary infection Hoarseness Throat irritation (soreness, clearing) Koufman JA, Laryngoscope 1991

Introduction Comparision of History, Laryngeal Examination, and Diagnostic Testing in Otolaryngology Patient With Cervical Symptoms(n=63) or Esophagitis(n=36), and in Controls(n=10) A. Symptoms Heartburn and/or regurgitation Hoarseness, dysphagia, globus, throat clearing and cough B. Laryngeal Examination Normal Erythema Contact ulcer or granulation C. Diagnostic Studies Upper esophageal sphincter pressure (mmHg) Positive standard acid reflux test Positive Bernstein acid perfusion test Abnormal esophageal manometry Esophageal dysmotility Abnormal esophageal acid clearance Otolaryngology Pt. Esophagitis Pt. 6% 100% 50% 25% 144±121 68% 5% 10% 60% 78% 89% 0% 100% 71±40 8% 10% 80% Koufman JA, Laryngoscope 1991

Upper GI Endoscopy

Left Vocal Fold Granuloma: Pre and Post anti-acid therapy

54 patients with chronic persistent cough possibly due to reflux GORD in patients with pulmonary symptoms 54 patients with chronic persistent cough possibly due to reflux Normal 22% (n=12) Reflux 78% (n=42) Schnatz et al., Am J Gastroenterol 1996; 91: 1715–18.

Patients with abnormal acid reflux (%) Abnormal acid reflux linked to asthma 100 90 82 80 70 61 60 55 53 Patients with abnormal acid reflux (%) 40 33 20 Ducolone et al. (n=51) Nagel et al. (n=44) Giudicelli et al. (n=140) Sontag et al. (n=104) DeMeester et al. (n=77) Larrain et al. (n=105) Kiljander et al. (n=107) Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

Asthmatics with gastroesophageal reflux Long term results of a randomized trial of medical and surgical antireflux therapies Asthmatics with gastroesophageal reflux Long term results of a randomized trial of medical and surgical antireflux therapies Asthmatics with gastroesophageal reflux Long term results of a randomized trial of medical and surgical antireflux therapies Sontag SJ, O'Connell S, Khandelwal S, et al. Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical anti-reflux therapies. Am J Gastroenterol 2003; 98: 987–99.

Mucosal healing

Poe RH, Kalloy MC. Chronic cough and gastroesophageal reflux disease Poe RH, Kalloy MC. Chronic cough and gastroesophageal reflux disease. Experience with specific therapy for diagnosis and treatment. Chest 2003; 123: 679–84.

Patients Responding, No (%) Weeks of anti-reflux Rx . Cumulative Response to GERD Therapy Patients Responding, No (%) Weeks of anti-reflux Rx 16 (41) 2 38 (86) 4 42 (95) 6 43 (99) 8 (44 (100 12

24hr double probe pH-metry Diagnosis 24hr double probe pH-metry

Management of LPRD dietary & life style modification plus ranitidine 1 tablet(150mg) twice daily After 8weeks improve (-) After 8weeks improve (+) ranitidine 300mg bid or tid persistent medication for 6 months After 6 months improve (-) Consider surgical management Cummings(III) ch.126 Gastroesophageal reflux disease P2419

Cummings(III) ch.126 Gastroesophageal reflux disease P2426

Range of presentations of GERD Typical symptoms (Heartburn/regurgitation) Atypical symptoms Complications With oesophagitis Chest pain (visceral hyperalgesia) Oesophageal erosions and/or ulcers Without oesophagitis Hoarseness (‘reflux laryngitis’) Stricture Barrett’s oesophagus Asthma, chronic cough, wheezing Oesophageal adenocarcinoma Dental erosions Nathoo, Int J Clin Pract 2001; 55: 465–9.

Common signs 70 Interarytenoid bar 29 Arytenoid medial wall edema 21 Table 1. Ear, nose and throat (ENT) signs in normal volunteers Common signs 70  Interarytenoid bar 29  Arytenoid medial wall edema 21  Posterior pharyngeal wall cobblestoning 15 Intererytenoid bar erythema 10  Posterior cricoid wall edema  True vocal cord edema %