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Gastroesophageal Reflux–Related Chronic Laryngitis: Con

Gastroesophageal Reflux–Related Chronic Laryngitis: Con Hypothesis:Increasingly, gastroesophageal reflux disease (GERD) is suggested to cause laryngeal signs and symptoms,1often referred to as laryngopharyngeal reflux(LPR). But can LPR still be said to exist in a patient who is unresponsive to aggressive therapy? What should we tell the group of patients whose symptoms or laryngeal signs do not improve under acid-suppressive therapy? Here are a few selected answers from my “learned” colleagues: (1) Patients' symptoms are most definitively still caused by LPR, and lack of response to acid suppression does not rule out reflux as the cause. (2) Intermittent acid reflux may still occur in this group causing patients' findings. (3) Acid is truly not the culprit, and pepsin is the main agent responsible. And (4) Surgical fundoplication should be attempted in the patients who do not respond to therapy. All of these suggestions assume that reflux is the symptoms' cause and never question whether the LPR diagnosis was incorrect in the first place. Should we continue to insist on reflux as the diagnosis just because we may not know what else might be the cause of patients' persistent symptom complex? I would argue that this is not good clinical care. View LargeDownload Michael F. Vaezi, MD, PhD,  MSc (Epi) Herein, I discuss the role of acid-suppressive therapy, review the current lack of evidence on effectiveness of these agents in LPR treatment, and address why patients might not respond to treatment. I ask the critical reader to draw his or her own conclusions about the data and not blindly accept what the “experts” think. Expert opinions over the years have not been based on rigorous scientific evaluation of objective data. Ineffective acid suppression in lpr In treating patients suspected of having LPR, many so-called experts recommend twice-daily administration of proton pump inhibitors (PPIs) for up to 6 months.2This practice is based solely on observational, uncontrolled data suggesting response rates ranging from 50% to 75%.1For example, Park et al3prospectively studied 85 patients with suspected LPR and reported 72% treatment response to twice-daily PPIs at 4 months. Similarly, Belafsky et al2found nearly 50% improvement in patients' symptoms and laryngeal signs 6 months after initiation of aggressive acid suppression. For a more detailed outline of these observational studies, I refer the reader to a review article on this topic.1An additional rationale for the unapproved indication and dosing with PPIs for LPR comes mainly from pH monitoring data demonstrating that the likelihood of normalizing esophageal acid exposure with twice-daily PPI treatment in patients with GERD is 93%, and in those with laryngeal symptoms it is 99%.4Finally, there are no head-to-head controlled studies on the efficacy of twice-daily vs once-daily dosing with PPIs. Two uncontrolled open-label studies, one in suspected reflux laryngitis3and the other in asthma,5form the basis for this questionable practice. Despite widespread treatment with twice-daily PPIs, high-level evidence supporting treatment efficacy in these syndromes is still scant.1,6No controlled studies have investigated the optimal dosage or duration of PPI therapy in LPR. To complicate the matter, nearly all placebo-controlled studies have shown no benefit to PPI therapy in patients suspected of having LPR.7The most recent multicenter study of 145 patients did not show a benefit in those treated for 4 months with esomeprazole, 40 mg twice daily, compared with placebo.8In this practice-based study, patients were eligible if they had a history of 1 or more chronic laryngeal symptoms (throat clearing, globus, sore throat, or hoarseness) as well as laryngoscopic signs indicating reflux laryngitis identified by an otolaryngologist. This study is the largest placebo-controlled study that I am aware of on LPR and showed that esomeprazole and placebo therapy resulted in similar symptom resolution (15% and 16%) and symptom improvement (42% and 46%). The fact that the largest blinded, randomized, multicenter, placebo-controlled study to date in this field resulted in negative findings may initially be disturbing to the zealots in the field. However, this is often the case when science unravels and corrects widely embraced clinical myths. The most recent meta-analysis of over 340 patients examined the study outcomes of 7 randomized controlled trials and found no significant symptom reduction with PPI therapy compared with placebo.7Thus, current evidence based on placebo-controlled studies, the gold standard by which we justify a rational approach to patient therapy, does not suggest a benefit to PPIs in LPR. Some may criticize the design of any of these studies to argue against the findings, but at some point we must step back and allow science, and not our biases, to guide our practice. Why do patients diagnosed as having LPR show no improvement when treated with therapies known to be effective in treating reflux? The disappointing negative findings from placebo-controlled studies in LPR are likely explained by the current diagnostic criteria based on laryngoscopy and pH monitoring, which should be reexamined and better defined. The arguments that patients still have reflux as the cause for their complaints based on laryngeal irritation alone is short-sighted and does not critically embrace the likelihood of other nonreflux causes for such irritations. How specific is laryngoscopy in diagnosing LPR? The short answer is not specific at all. Most signs identified in patients suspected to have “LPR” are present in healthy subjects without any symptoms.9Members of the “pH mafia,” as the name suggests, think that ambulatory pH monitoring is somehow going to help when aggressive acid suppression did not,10an approach that makes no sense physiologically. If you believe in acid as the cause of laryngeal irritation, then you should believe in the sea of data showing acid suppression as the most effective form for acid reflux therapy, which is why the current guidelines suggest empirical therapy as the initial approach to treating patients suspected of having reflux.6 The overall pretherapy prevalence of abnormal pH findings in patients with LPR is reported to be 53%.1The abnormality prevalences measured by distal, proximal, and hypopharyngeal pH monitoring are 42%, 44% and 38%, respectively. While these findings suggest that abnormal reflux events may be present in this group of patients, it does not establish a causal relationship, possibly owing to the poor sensitivity of pH monitoring. In a recent study by Bilgen et al,11no significant difference was found in hypopharyngeal acid exposure between 36 patients with laryngeal signs and symptoms and 23 healthy individuals. Given this uncertainty about pH monitoring in this group of patients, can we rely on this test for assured diagnosis? I think NOT! Assuming causality based on prevalent data is too simplistic. Bottom line The current rationale for the use of acid-suppressive therapy for LPR is based solely on observational data. Controlled studies do not support such practice. One important reason for the lack of response in many patients diagnosed as having LPR initially is the overdiagnosis of this condition and too much reliance on laryngoscopic signs for LPR diagnosis. Monitoring pH does not predict response to PPI therapy, and so performing this test before treatment does not help. What should we do at this point? Should we say that there is no such thing as LPR and give up? My answer is yes in some cases and no in others. While our investigators in the field are exploring how best to diagnose this condition, let us retain the flexibility to consider a diagnosis other then LPR once our patients do not respond to therapy. The continued emphasis on GERD as the cause of throat symptoms even in those patients undergoing twice-daily PPI therapy suggests that we do not know what other causes might be involved. We should focus our efforts on searching for these other causes; reflux might be the easy answer, but we must look for the difficult answers when logic points us in that direction. Correspondence:Michael F. Vaezi, MD, PhD, MSc (Epi), Division of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, C2104-MCN, Nashville, TN 37232 (michael.vaezi@vanderbilt.edu). Submitted for Publication: December 3, 2008; final revision received November 16, 2009; accepted May 29, 2010. Financial Disclosure: None reported. References 1. Vaezi MFHicks DMAbelson TIRichter JE Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 2003;1 (5) 333- 344PubMedGoogle ScholarCrossref 2. Belafsky PCPostma GNKoufman JA Laryngopharyngeal reflux symptoms improve before changes in physical findings. Laryngoscope 2001;111 (6) 979- 981PubMedGoogle ScholarCrossref 3. Park WHicks DMKhandwala F et al. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope 2005;1151230- 1238PubMedGoogle ScholarCrossref 4. Charbel SKhandwala FVaezi MF The role of esophageal pH monitoring in symptomatic patients on PPI therapy. Am J Gastroenterol 2005;100 (2) 283- 289PubMedGoogle ScholarCrossref 5. Harding SMRichter JEGuzzo MRSchan CAAlexander RWBradley LA Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med 1996;100 (4) 395- 405PubMedGoogle ScholarCrossref 6. Kahrilas PJShaheen NJVaezi MF et al. American Gastroenterological Association, American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 2008;135 (4) 1383- 1391PubMedGoogle ScholarCrossref 7. Qadeer MAPhillips COLopez AR et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006;101 (11) 2646- 2654PubMedGoogle ScholarCrossref 8. Vaezi MFRichter JEStasney CR et al. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope 2006;116 (2) 254- 260PubMedGoogle ScholarCrossref 9. Hicks DMOurs TMAbelson TIVaezi MFRichter JE The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice 2002;16564- 579PubMedGoogle ScholarCrossref 10. Vaezi MF Con: treatment with PPIs should not be preceded by pH monitoring in patients suspected of laryngeal reflux. Am J Gastroenterol 2006;1018- 10PubMedGoogle ScholarCrossref 11. Bilgen COgüt FKesimli-Dinç HKirazli TBor S The comparison of an empiric proton pump inhibitor trial vs 24-hour double-probe Ph monitoring in laryngopharyngeal reflux. J Laryngol Otol 2003;117 (5) 386- 390PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Otolaryngology - Head & Neck Surgery American Medical Association

Gastroesophageal Reflux–Related Chronic Laryngitis: Con

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American Medical Association
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Copyright © 2010 American Medical Association. All Rights Reserved.
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0886-4470
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1538-361X
DOI
10.1001/archoto.2010.149
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Abstract

Hypothesis:Increasingly, gastroesophageal reflux disease (GERD) is suggested to cause laryngeal signs and symptoms,1often referred to as laryngopharyngeal reflux(LPR). But can LPR still be said to exist in a patient who is unresponsive to aggressive therapy? What should we tell the group of patients whose symptoms or laryngeal signs do not improve under acid-suppressive therapy? Here are a few selected answers from my “learned” colleagues: (1) Patients' symptoms are most definitively still caused by LPR, and lack of response to acid suppression does not rule out reflux as the cause. (2) Intermittent acid reflux may still occur in this group causing patients' findings. (3) Acid is truly not the culprit, and pepsin is the main agent responsible. And (4) Surgical fundoplication should be attempted in the patients who do not respond to therapy. All of these suggestions assume that reflux is the symptoms' cause and never question whether the LPR diagnosis was incorrect in the first place. Should we continue to insist on reflux as the diagnosis just because we may not know what else might be the cause of patients' persistent symptom complex? I would argue that this is not good clinical care. View LargeDownload Michael F. Vaezi, MD, PhD,  MSc (Epi) Herein, I discuss the role of acid-suppressive therapy, review the current lack of evidence on effectiveness of these agents in LPR treatment, and address why patients might not respond to treatment. I ask the critical reader to draw his or her own conclusions about the data and not blindly accept what the “experts” think. Expert opinions over the years have not been based on rigorous scientific evaluation of objective data. Ineffective acid suppression in lpr In treating patients suspected of having LPR, many so-called experts recommend twice-daily administration of proton pump inhibitors (PPIs) for up to 6 months.2This practice is based solely on observational, uncontrolled data suggesting response rates ranging from 50% to 75%.1For example, Park et al3prospectively studied 85 patients with suspected LPR and reported 72% treatment response to twice-daily PPIs at 4 months. Similarly, Belafsky et al2found nearly 50% improvement in patients' symptoms and laryngeal signs 6 months after initiation of aggressive acid suppression. For a more detailed outline of these observational studies, I refer the reader to a review article on this topic.1An additional rationale for the unapproved indication and dosing with PPIs for LPR comes mainly from pH monitoring data demonstrating that the likelihood of normalizing esophageal acid exposure with twice-daily PPI treatment in patients with GERD is 93%, and in those with laryngeal symptoms it is 99%.4Finally, there are no head-to-head controlled studies on the efficacy of twice-daily vs once-daily dosing with PPIs. Two uncontrolled open-label studies, one in suspected reflux laryngitis3and the other in asthma,5form the basis for this questionable practice. Despite widespread treatment with twice-daily PPIs, high-level evidence supporting treatment efficacy in these syndromes is still scant.1,6No controlled studies have investigated the optimal dosage or duration of PPI therapy in LPR. To complicate the matter, nearly all placebo-controlled studies have shown no benefit to PPI therapy in patients suspected of having LPR.7The most recent multicenter study of 145 patients did not show a benefit in those treated for 4 months with esomeprazole, 40 mg twice daily, compared with placebo.8In this practice-based study, patients were eligible if they had a history of 1 or more chronic laryngeal symptoms (throat clearing, globus, sore throat, or hoarseness) as well as laryngoscopic signs indicating reflux laryngitis identified by an otolaryngologist. This study is the largest placebo-controlled study that I am aware of on LPR and showed that esomeprazole and placebo therapy resulted in similar symptom resolution (15% and 16%) and symptom improvement (42% and 46%). The fact that the largest blinded, randomized, multicenter, placebo-controlled study to date in this field resulted in negative findings may initially be disturbing to the zealots in the field. However, this is often the case when science unravels and corrects widely embraced clinical myths. The most recent meta-analysis of over 340 patients examined the study outcomes of 7 randomized controlled trials and found no significant symptom reduction with PPI therapy compared with placebo.7Thus, current evidence based on placebo-controlled studies, the gold standard by which we justify a rational approach to patient therapy, does not suggest a benefit to PPIs in LPR. Some may criticize the design of any of these studies to argue against the findings, but at some point we must step back and allow science, and not our biases, to guide our practice. Why do patients diagnosed as having LPR show no improvement when treated with therapies known to be effective in treating reflux? The disappointing negative findings from placebo-controlled studies in LPR are likely explained by the current diagnostic criteria based on laryngoscopy and pH monitoring, which should be reexamined and better defined. The arguments that patients still have reflux as the cause for their complaints based on laryngeal irritation alone is short-sighted and does not critically embrace the likelihood of other nonreflux causes for such irritations. How specific is laryngoscopy in diagnosing LPR? The short answer is not specific at all. Most signs identified in patients suspected to have “LPR” are present in healthy subjects without any symptoms.9Members of the “pH mafia,” as the name suggests, think that ambulatory pH monitoring is somehow going to help when aggressive acid suppression did not,10an approach that makes no sense physiologically. If you believe in acid as the cause of laryngeal irritation, then you should believe in the sea of data showing acid suppression as the most effective form for acid reflux therapy, which is why the current guidelines suggest empirical therapy as the initial approach to treating patients suspected of having reflux.6 The overall pretherapy prevalence of abnormal pH findings in patients with LPR is reported to be 53%.1The abnormality prevalences measured by distal, proximal, and hypopharyngeal pH monitoring are 42%, 44% and 38%, respectively. While these findings suggest that abnormal reflux events may be present in this group of patients, it does not establish a causal relationship, possibly owing to the poor sensitivity of pH monitoring. In a recent study by Bilgen et al,11no significant difference was found in hypopharyngeal acid exposure between 36 patients with laryngeal signs and symptoms and 23 healthy individuals. Given this uncertainty about pH monitoring in this group of patients, can we rely on this test for assured diagnosis? I think NOT! Assuming causality based on prevalent data is too simplistic. Bottom line The current rationale for the use of acid-suppressive therapy for LPR is based solely on observational data. Controlled studies do not support such practice. One important reason for the lack of response in many patients diagnosed as having LPR initially is the overdiagnosis of this condition and too much reliance on laryngoscopic signs for LPR diagnosis. Monitoring pH does not predict response to PPI therapy, and so performing this test before treatment does not help. What should we do at this point? Should we say that there is no such thing as LPR and give up? My answer is yes in some cases and no in others. While our investigators in the field are exploring how best to diagnose this condition, let us retain the flexibility to consider a diagnosis other then LPR once our patients do not respond to therapy. The continued emphasis on GERD as the cause of throat symptoms even in those patients undergoing twice-daily PPI therapy suggests that we do not know what other causes might be involved. We should focus our efforts on searching for these other causes; reflux might be the easy answer, but we must look for the difficult answers when logic points us in that direction. Correspondence:Michael F. Vaezi, MD, PhD, MSc (Epi), Division of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, C2104-MCN, Nashville, TN 37232 (michael.vaezi@vanderbilt.edu). Submitted for Publication: December 3, 2008; final revision received November 16, 2009; accepted May 29, 2010. Financial Disclosure: None reported. References 1. Vaezi MFHicks DMAbelson TIRichter JE Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 2003;1 (5) 333- 344PubMedGoogle ScholarCrossref 2. Belafsky PCPostma GNKoufman JA Laryngopharyngeal reflux symptoms improve before changes in physical findings. Laryngoscope 2001;111 (6) 979- 981PubMedGoogle ScholarCrossref 3. Park WHicks DMKhandwala F et al. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope 2005;1151230- 1238PubMedGoogle ScholarCrossref 4. Charbel SKhandwala FVaezi MF The role of esophageal pH monitoring in symptomatic patients on PPI therapy. Am J Gastroenterol 2005;100 (2) 283- 289PubMedGoogle ScholarCrossref 5. Harding SMRichter JEGuzzo MRSchan CAAlexander RWBradley LA Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med 1996;100 (4) 395- 405PubMedGoogle ScholarCrossref 6. Kahrilas PJShaheen NJVaezi MF et al. American Gastroenterological Association, American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 2008;135 (4) 1383- 1391PubMedGoogle ScholarCrossref 7. Qadeer MAPhillips COLopez AR et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006;101 (11) 2646- 2654PubMedGoogle ScholarCrossref 8. Vaezi MFRichter JEStasney CR et al. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope 2006;116 (2) 254- 260PubMedGoogle ScholarCrossref 9. Hicks DMOurs TMAbelson TIVaezi MFRichter JE The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice 2002;16564- 579PubMedGoogle ScholarCrossref 10. Vaezi MF Con: treatment with PPIs should not be preceded by pH monitoring in patients suspected of laryngeal reflux. Am J Gastroenterol 2006;1018- 10PubMedGoogle ScholarCrossref 11. Bilgen COgüt FKesimli-Dinç HKirazli TBor S The comparison of an empiric proton pump inhibitor trial vs 24-hour double-probe Ph monitoring in laryngopharyngeal reflux. J Laryngol Otol 2003;117 (5) 386- 390PubMedGoogle ScholarCrossref

Journal

Archives of Otolaryngology - Head & Neck SurgeryAmerican Medical Association

Published: Sep 20, 2010

Keywords: gastroesophageal reflux disease,chronic laryngitis

References