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Supraesophageal manifestations of GERD. Symptoms and signs. Symptoms and signs of LPR. Hoarseness 71% Chronic cough 51% Globus pharyngeus 47% Heart burn/regurgitation 43%
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Symptoms and signs 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
Treatment of Chronic Throat Symptoms with PPIs Should Be Preceded by pH MonitringAm 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
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.
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
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
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 PharmacolTher. 2003Jaspersen 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. Symptoms • Heartburn • Regurgitation • Dysphagia • Cough • Pulmonary infection • Hoarseness • Throat irritation (soreness, clearing) Typical (%) 83 23 40 47 16 12 3 Atypical (%) 20 - 12 26 - 44 87 Pediatric (%) 16 68 30 - 36 - - 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% 25% 144±121 68% 5% 10% 60% 78% 89% 0% 100% 0% 0% 71±40 100% 89% 8% 10% 80% Koufman JA, Laryngoscope 1991