ArticlePublisher preview available

Low-Acid Diet for Recalcitrant Laryngopharyngeal Reflux: Therapeutic Benefits and Their Implications

SAGE Publications Inc
Annals of Otology, Rhinology, and Laryngology
Authors:
Jamie A. Koufman
Jamie A. Koufman
Jamie A. Koufman
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Read publisher preview
Download citation
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Objectives Laryngopharyngeal reflux (LPR) is an expensive, high-prevalence disease with a high rate of medical treatment failure. In the past, it was mistakenly believed that pepsin was inactive above pH 4; however, human pepsin has been reported to be active up to pH 6.5. In addition, it has been shown by Western blot analysis that laryngeal biopsy samples from patients with symptomatic LPR have tissue-bound pepsin. The clinical impact of a low-acid diet on the therapeutic outcome in LPR has not been previously reported. To provide data on the therapeutic benefit of a strict, virtually acid-free diet on patients with recalcitrant, proton pump inhibitor (PPI)–resistant LPR, I performed a prospective study of 20 patients who had persistent LPR symptoms despite use of twice-daily PPIs and an H2-receptor antagonist at bedtime. Methods The reflux symptom index (RSI) score and the reflux finding score (RFS) were determined before and after implementation of the low-acid diet, in which all foods and beverages at less than pH 5 were eliminated for a minimum 2-week period. The subjects were individually counseled, and a printed list of acceptable foods and beverages was provided. Results There were 12 male and 8 female study subjects with a mean age of 54.3 years (range, 24 to 72 years). The symptoms in 19 of the 20 subjects (95%) improved, and 3 subjects became completely asymptomatic. The mean pre-diet RSI score was 14.9, and the mean post-diet RSI score was 8.6 (p = 0.020). The mean pre-diet RFS was 12.0, and the mean post-diet RFS was 8.3 (p < 0.001). Conclusions A strict low-acid diet appears to have beneficial effects on the symptoms and findings of recalcitrant (PPI-resistant) LPR. Further study is needed to assess the optimal duration of dietary acid restriction and to assess the potential role of a low-acid diet as a primary treatment for LPR. This study has implications for understanding the pathogenesis, cell biology, and epidemiology of reflux disease.
A preview of this full-text is provided by SAGE Publications Inc.
Learn more
Content available from Annals of Otology, Rhinology, and Laryngology 
This content is subject to copyright.
Low-Acid Diet for Recalcitrant Laryngopharyngeal Reflux:
Therapeutic Benefits and Their Implications
Jamie A. Koufman, MD
Objectives: Laryngopharyngeal reflux (LPR) is an expensive, high-prevalence disease with a high rate of medical treat-
ment failure. In the past, it was mistakenly believed that pepsin was inactive above pH 4; however, human pepsin has
been reported to be active up to pH 6.5. In addition, it has been shown by Western blot analysis that laryngeal biopsy sam-
ples from patients with symptomatic LPR have tissue-bound pepsin. The clinical impact of a low-acid diet on the thera-
peutic outcome in LPR has not been previously reported. To provide data on the therapeutic benefit of a strict, virtually
acid-free diet on patients with recalcitrant, proton pump inhibitor (PPI)–resistant LPR, I performed a prospective study of
20 patients who had persistent LPR symptoms despite use of twice-daily PPIs and an H2-receptor antagonist at bedtime.
Methods: The reflux symptom index (RSI) score and the reflux finding score (RFS) were determined before and after
implementation of the low-acid diet, in which all foods and beverages at less than pH 5 were eliminated for a minimum
2-
week period. The subjects were individually counseled, and a printed list of acceptable foods and beverages was pro-
vided.
Results: There were 12 male and 8 female study subjects with a mean age of 54.3 years (range, 24 to 72 years). The
symptoms in 19 of the 20 subjects (95%) improved, and 3 subjects became completely asymptomatic. The mean pre-diet
RSI score was 14.9, and the mean post-diet RSI score was 8.6 (p = 0.020). The mean pre-diet RFS was 12.0, and the mean
post-diet RFS was 8.3 (p < 0.001).
Conclusions: A strict low-acid diet appears to have beneficial effects on the symptoms and findings of recalcitrant (PPI-
resistant) LPR. Further study is needed to assess the optimal duration of dietary acid restriction and to assess the potential
role of a low-acid diet as a primary treatment for LPR. This study has implications for understanding the pathogenesis,
cell biology, and epidemiology of reflux disease.
Key Words: acid reflux, adenocarcinoma, antireflux, Barrett’s esophagus, chronic cough, diet, esophageal cancer, gas-
troesophageal reflux disease, heartburn, hoarseness, laryngopharyngeal reflux, low acid, low fat, pepsin, proton pump
inhibitor.
Annals of Otology, Rhinology & Laryngology 120(5):281-287.
© 2011 Annals Publishing Company. All rights reserved.
281
From the Voice Institute of New York, New York, NY.
Presented at the meeting of the American Broncho-Esophagological Association, Las Vegas, Nevada, April 28-29, 2010.
Correspondence: Jamie A. Koufman, MD, Voice Institute of New York, 200 W 57th St, Suite 1203, New York, NY 10019.
INTRODUCTION
Laryngopharyngeal reflux (LPR) is a controver-
sial, high-prevalence disease, and it differs from
classic gastroesophageal reflux disease (GERD) in
many ways.1-10 Typically, patients with LPR have
daytime (upright) reflux without having heartburn
or esophagitis.1-3 In addition, one of the most im-
portant differences between LPR and GERD is that
the threshold for laryngeal tissue damage is much
lower than that for the esophagus.1,5,8 As many as
50 reflux episodes (less than pH 4) per day are con-
sidered normal for the esophagus, whereas as few
as 3 reflux episodes per week are too many for the
larynx.1
THERAPEUTIC IMPLICATIONS OF CELL BIOLOGY
OF LPR
The cell biology of LPR holds the key to under-
standing the susceptibility of the larynx to peptic in-
jury — and it is peptic (not acid) injury.1,5,8,9,11-17
(Pepsin does, however, require some acid for activa-
tion.) We previously showed that 19 of 20 patients
(95%) with clinical and pH-documented LPR had
tissue-bound pepsin identifiable by Western blot
analysis, as opposed to only 1 of 20 control subjects
(5%).9 In addition, peptic injury is associated with
depletion of key protective proteins, including car-
bonic anhydrase, E-cadherin, and most of the stress
proteins.5,8,9,11-15
Equally important in understanding the biology
of LPR is consideration for the stability and spec-
trum of activity of human pepsin.14 In the past, it
was mistakenly believed that pepsin was inactive
above pH 4.1 The early experiments on which that
result was based were performed with porcine pep-
sin, and not human pepsin. Indeed, pig pepsin is in-
active at greater than pH 4; however, human pepsin
retains some of its proteolytic activity up to pH 6.5,
... The number of studies dedicated to the relationship between LPRD, foods, and beverages has significantly increased in the past few years [48][49][50][51][52][53][54][55]. The first studies conducted by Koufman et al [53,55]. ...
... The number of studies dedicated to the relationship between LPRD, foods, and beverages has significantly increased in the past few years [48][49][50][51][52][53][54][55]. The first studies conducted by Koufman et al [53,55]. proposed a low-acid, low-fat, alkaline water, and high-protein diet to treat patients with primary or recalcitrant LPRD. ...
... proposed a low-acid, low-fat, alkaline water, and high-protein diet to treat patients with primary or recalcitrant LPRD. The anti-acid diet of Jamie Koufman aimed to primarily act on the acidity of gastric content to neutralize the pepsin activity in the upper aerodigestive tract mucosa [11,53,55]. Recently, two studies reported that patients consuming acid, high-fat, and low-protein diets had higher pharyngeal reflux events at the 24-hour HEMII-pH [52], or higher saliva pepsin concentration [53]. ...
European clinical practice guideline: managing and treating laryngopharyngeal reflux disease
Article
Full-text available
  • Dec 2024
  • Eur Arch Oto Rhino Laryngol
Objective To propose a European consensus for managing and treating laryngopharyngeal reflux disease (LPRD) to guide primary care and specialist physicians. Methods Twenty-three European experts (otolaryngologists, gastroenterologists, surgeons) participated in a modified Delphi process to revise 38 statements about the definition, clinical management, and treatment of LPRD. Three voting rounds were conducted on a 5-point scale and a consensus was defined a priori as agreement by 80% of the experts. Results After the third round, 36 statements composed the first European Consensus Report on the definition, diagnosis, and treatment of LPRD. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring is the gold standard for diagnosing LPRD (> 1 pharyngeal reflux event) and treating the LPRD with personalized therapy. The empirical treatment needs to be based on diet, stress reduction, and alginates or antiacids to address the acidic and alkaline reflux events. Proton pump inhibitors are kept for patients with acidic LPRD and gastroesophageal reflux disease (GERD) findings. The treatment needs to be as short as possible (minimum two months). The medication can be progressively reduced for patients with relief of symptoms. Changing medication class can be considered for refractory LPRD rather than an increase in drug doses. Conclusion A consensus endorsed by the Confederation of European Otorhinolaryngology-Head and Neck Surgery Societies is presented to improve the management and treatment of LPRD. The approved statements could improve collaborative research through the adoption of common management approaches to LPRD.
View
... Recent studies have suggested that although pepsin is reactivated by an acidic environment, a neutral pH environment in the laryngopharynx does not completely protect the mucosa from the inflammatory effects of pepsin, as the latter enzyme can reactivate within the lower pH intracellular enviroments (15,16). Moreover, since pepsin survives for hours in the laryngopharynx after a LPR event, it can be reactivated by dietary acids (17). ...
... The same result was found for the secondary outcome, as all groups showed a statistically significant reduction in RFS scores. These data are in line with current literature, since dietary modifications and the use of alginates or magaldrates had already been shown to be able to reduce LPR-related symptoms as well as to improve endoscopic findings (17). ...
Efficacy of dietary modifications and mucosal protectors in the treatment of laryngopharyngeal reflux: a multicenter study
Article
Full-text available
  • Jan 2025
Background Laryngopharyngeal reflux (LPR) is defined as an extraesophageal reflux of gastroduodenal contents to the laryngopharynx, affecting the upper aerodigestive tract. There is currently no standardized treatment protocol for LPR. The use of proton pump inhibitors (PPIs) is widely established in common practice and derives from the standard approach of using PPIs to treat patients with gastroesophageal reflux disease (GERD). However, as PPIs may not be effective on all types of reflux, the aim of our study was to evaluate the effectiveness of dietary changes and mucosal protectants, alone or in combination, in LPR treatment. Methods This multicenter randomized controlled trial included 48 patients divided into three groups: dietary modifications only, mucosal protectors only, and a combination of both. The patients’ responses were assessed over 1 month using the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), along with measurements of salivary and nasal pepsin concentration and rhinomanometry. Results Significant improvements were observed in RSI and RFS scores across all groups. The group receiving combined dietary modifications and mucosal protectors showed the most substantial benefits. Additionally, a notable reduction in salivary and nasal pepsin concentrations and nasal resistances was observed, particularly in patients combining dietary modifications and mucosal protectors. Conclusion The study showed that combined dietary modifications and mucosal protects strategies effectively manage LPR symptoms, offering a potential therapeutic approach.
View
... Also, it is essential to limit the intake of alcoholic beverages, caffeine, chocolate, fatty and spicy foods, juices and carbonated drinks. An anti-reflux diet is the primary treatment approach for the majority of patients (48). In study conducted by Smith et al. was demonstrated that there is a strong correlation between high calorie and fat intake and the severity of cough symptoms (49 ...
Narrative review of relationship between chronic cough and laryngopharyngeal reflux
Article
Full-text available
  • Apr 2024
Gastroesophageal reflux disease (GERD) as a possible cause of chronic cough is known for decades. However, more than 75% of patients with extraoesophageal symptoms do not suffer from typical symptoms of GERD like pyrosis and regurgitations and have negative upper gastrointestinal endoscopy. For such a condition term laryngopharyngeal reflux (LPR) was introduced and is used for more than two decades. Since the comprehensive information on relationship between chronic cough and LPR is missing the aim of this paper is to summarize current knowledge based on review of published information during last 13 years. Laryngopharyngeal reflux is found in 20% of patients with chronic cough. The main and recognized diagnostic method for LPR is 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, revealing reflux episodes irritating the upper and lower respiratory tract mucosa. The treatment of LPR should be initiated with dietary and lifestyle measures, followed by proton pump inhibitor (PPI) therapy and other measures. Despite progress, more research is needed for accurate diagnosis and targeted therapies. Key areas for exploration include biomarkers for diagnosis, the impact of non-acid reflux on symptom development, and the efficacy of new drugs. Further studies with a focused population, excluding other causes like asthma, and using new diagnostic criteria for LPR are essential. It’s crucial to consider LPR as a potential cause of unexplained chronic cough and to approach diagnosis and treatment with a multidisciplinary perspective.
View
... [11][12][13][14] These symptoms are alleviated by anti-reflux surgery [15][16][17][18][19][20][21] and may be ameliorated by less invasive strategies that limit reflux occurrence or neutralize reflux constituents beyond acid (e.g., dietary and lifestyle modification and over-the-counter alginate products). [22][23][24][25] It is therefore reasonable to assume that one or more nonacid constituents of refluxate are responsible for LPR symptoms. Among nonacid components of refluxate, the digestive enzyme pepsin is considered a predominant damaging agent, biomarker, and therapeutic target for reflux-attributed diseases. ...
Inhaled fosamprenavir for laryngopharyngeal reflux: Toxicology and fluid dynamics modeling
Article
Full-text available
  • Jan 2024
Objectives Approximately 25% of Americans suffer from laryngopharyngeal reflux (LPR), a disease for which no effective medical therapy exists. Pepsin is a predominant source of damage during LPR and a key therapeutic target. Fosamprenavir (FOS) inhibits pepsin and prevents damage in an LPR mouse model. Inhaled FOS protects at a lower dose than oral; however, the safety of inhaled FOS is unknown and there are no inhalers for laryngopharyngeal delivery. A pre‐Good Lab Practice (GLP) study of inhaled FOS was performed to assess safety and computational fluid dynamics (CFD) modeling used to predict the optimal particle size for a laryngopharyngeal dry powder inhaler (DPI). Methods Aerosolized FOS, amprenavir (APR), or air (control) were provided 5 days/week for 4 weeks (n = 6) in an LPR mouse model. Organs (nasal cavity, larynx, esophagus, trachea, lung, liver, heart, and kidney) were assessed by a pathologist and bronchoalveolar lavage cytokines and plasma cardiotoxicity markers were assessed by Luminex assay. CFD simulations were conducted in a model of a healthy 49‐year‐old female. Results No significant increase was observed in histologic lesions, cytokines, or cardiotoxicity markers in FOS or APR groups relative to the control. CFD predicted that laryngopharyngeal deposition was maximized with aerodynamic diameters of 8.1–11.5 μm for inhalation rates of 30–60 L/min. Conclusions A 4‐week pre‐GLP study supports the safety of inhaled FOS. A formal GLP assessment is underway to support a phase I clinical trial of an FOS DPI for LPR. Level of Evidence NA.
View
View
View
Association Between Gastroesophageal Reflux Disease and Laryngeal Disorders: Real-World Evidence
Article
  • Sep 2024
  • OTOLARYNG HEAD NECK
Objective The association between gastroesophageal reflux disease (GERD) and laryngeal disorders remains debatable, although it has been the focus of extensive clinical and laboratory research. We conducted this study to obtain evidence on the association. Study Design Population‐based cohort study. Setting Taiwan National Health Insurance Research Database (NHIRD). Methods Using data from Taiwan's NHIRD (January 2000 to December 2018), we performed a population‐based analysis to estimate the risk of laryngeal disorders in patients with GERD and those without GERD. Results The GERD and non‐GERD cohorts comprised 176,319 and 705,276 patients, respectively. The cohorts were matched at a ratio of 1:4 based on sex, age, urbanization level, and income level. The risk of laryngeal disorders was higher in the GERD cohort than in the non‐GERD cohort (adjusted hazard ratio: 1.64; 95% confidence interval: 1.61‐1.67). Conclusion This study is the first to use population data for identifying the association between GERD and laryngeal disorders for real‐world findings. Our population‐based analysis indicates that patients with GERD have an elevated risk of laryngeal disorders.
View
Laryngopharyngeal Reflux Disease
Chapter
  • Apr 2024
LPRD can be caused by acidic or nonacidic reflux. Treatment failure with empiric PPIs does not rule out nonacidic reflux. Stroboscopic evaluation of the larynx is recommended in dysphonic patients that are unresponsive to LPRD treatment. Because LPR symptoms are often vague and can overlap with other etiologies, objective testing using HEMII-pH and HREM can help rule in or rule out LPRD. Up-front testing using HEMII-pH and HREM appears to be more cost-effective in the diagnosis and treatment of LPR compared to empiric medication trials. Currently, the decision between empiric therapy and objective testing depends on physician and patient preferences. For nonacidic or refractory LPRD, alginate therapy is often recommended as an adjunct to acid suppression for empiric medication trials or alternative therapy before anti-reflux surgery.
View
View
The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus
Article
Full-text available
  • Nov 2023
  • LARYNGOSCOPE
Objective The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. Methods Forty‐eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. Results After the third round, 79.2% of statements ( N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non‐specific laryngeal and extra‐laryngeal symptoms and signs that can be evaluated with validated patient‐reported outcome questionnaires and clinical instruments. The hypopharyngeal–esophageal multichannel intraluminal impedance–pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. Conclusion A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. Level of Evidence 5 Laryngoscope , 2023
View
Pepsin as a Marker of Extraesophageal Reflux
Article
Full-text available
Diagnosis of extraesophageal reflux (EER) currently relies on tools designed for diagnosis of gastroesophageal reflux. Such tools lack the sensitivity and reproducibility to detect the less frequent and mildly acidic reflux associated with upper airway disease. Pepsin has been posited to be a reliable biological marker of EER. Our aim was to present a comprehensive literature review of the use of pepsin as a diagnostic marker of EER. Two methods are typically used for detection of pepsin in the airways: enzymatic and immunologic. The limitations, advantages, and examples of use of each are discussed. Pepsin assay has been used to identify refluxate in trachea, lung, sinus, middle ear, combined sputum and saliva, and breath condensate. An immunologic pepsin assay of combined sputum and saliva was determined to be 100% sensitive and 89% specific for detection of EER (based on pH-metry), and an enzymatic test of nasal lavage fluid (100% sensitivity and 92.5% specificity) demonstrated an increased incidence of EER in patients with chronic rhinosinusitis. Pepsin assay identified tracheal pepsin to be an indicator of bronchopulmonary dysplasia and related mortality risk in ventilated preterm infants. Pepsin assay is a useful tool for correlation of reflux with airway disease and is a reliable diagnostic marker of EER.
View
Low cancer incidence rates in Ohio Amish
Article
Full-text available
  • Sep 2009
  • CANCER CAUSE CONTROL
The Amish have not been previously studied for cancer incidence, yet they have the potential to help in the understanding of its environmental and genetic contributions. The purpose of this study was to estimate the incidence of cancer among the largest Amish population. Adults from randomly selected households were interviewed and a detailed cancer family history was taken. Using both the household interview data and a search of the Ohio cancer registry data, a total of 191 cancer cases were identified between the years 1996 and 2003. The age-adjusted cancer incidence rate for all cancers among the Amish adults was 60% of the age-adjusted adult rate in Ohio (389.5/10(5) vs. 646.9/10(5); p < 0.0001). The incidence rate for tobacco-related cancers in the Amish was 37% of the rate for Ohio adults (p < 0.0001). The incidence rate for non-tobacco-related cancers in the Amish was 72% of the age-adjusted adult rate in Ohio (p = 0.0001). Cancer incidence is low in the Ohio Amish. These data strongly support reduction of cancer incidence by tobacco abstinence but cannot be explained solely on this basis. Understanding these contributions may help to identify additional important factors to target to reduce cancer among the non-Amish.
View
Changing impact of gastroesophageal reflux in medical and otolaryngology practice
Article
  • Jul 2005
Objectives/Hypothesis. A major trend in gastroesophageal reflux disease (GERD) is an observed increased prevalence of the problem, with an associated burden on health care resources. There are relatively few objective reports of increasing prevalence of this disease, and there are no epidemiologic reports that discuss changing practice strategies in managing the disease. The clinical problem is of critical importance to practicing otolaryngologists, who manage the impact of GERD on diseases affecting the ear, nose, and throat. The hypothesis of this thesis is that 1) GERD is an increasing problem affecting outpatient office visits over time, and 2) the disease is increasingly managed with prescription pharmacotherapy. Study Design: Retrospective national medical database review using the National Ambulatory Medical Care Survey. Methods. Twelve years of data (1990-2001) were examined with visits weighted to provide U.S. estimates of care. Average annual frequencies and visit rates were calculated for total visits and by age, sex, race, and physician specialty. Selected issues in GERD treatment were also examined, including prescriptions and physician/patient counseling regarding stress management, tobacco abuse, and diet modification. Trends were reported based on changes in care across three time periods to satisfy statistical significance: 1990 to 1993, 1994 to 1997, and 1998 to 2001. Results. Between 1990 and 1993 and 1998 and 2001, there was a significant increase in U.S. ambulatory care visits for GERD, from a rate of 1.7 per 100 to 4.7 per 100. There were no significant changes in race, although there was a small trend toward increased GERD visits in the age group over 44 years old and in the male sex. Office visits to otolaryngologists increased from 89,000 to 421,000 between the time periods of 1990 to 1993 and 1998 to 2001. This also represented a percent increase in office encounters by otolaryngologists compared with visits by all specialties from 2.9% to 4.4%. Over the three time periods, there was a fall in prescriptions for histamine (H2) blockers from 58.1% to 20.7% of total prescriptions. Over the same three time periods, prescriptions of proton pump inhibitors increased from 13.2% to 64.6%. Physician recommendations for over the counter medications fell from 18.8% to 6.6%. Average annual counseling during ambulatory care visits for GERD was assessed for the period from 1998 to 2001 as follows: diet counseling was provided at 27.2% of encounters, tobacco cessation counseling was provided at 3.9%, and stress management was discussed at 3.9% Conclusions: During the 1990s, there was a substantial increase in the use of ambulatory care services for GERD. Although much of this increase was among the primary care community, otolaryngologists appeared to have an increasingly prominent role in the management of this disease. There have also been dramatic changes in physician prescribing patterns for GERD, with the emergence of the - predominant role of proton pump inhibitors. However, the use of physician counseling for lifestyle modification of factors known to affect GERD remains very low. The increasing impact of GERD on physician practice emphasizes the importance of both physician and patient education in the delivery of health care related to this disease.
View
Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: A prospective study
Article
  • Sep 2003
Barrett's esophagus (BE) is a premalignant condition for which regular endoscopic follow-up is usually advised. We evaluated the incidence of esophageal adenocarcinoma (AC) in patients with BE and the impact of endoscopic surveillance on mortality from AC.MethodsA cohort of newly diagnosed BE patients was studied prospectively. Endoscopic and histological surveillance was recommended every 2 yr. Follow-up status was determined from hospital and registry office records and telephone calls to the patients.ResultsFrom 1987 to 1997, BE was diagnosed in 177 patients. We excluded three with high-grade dysplasia (HGD) at the time of enrollment. Follow-up was complete in 166 patients (135 male, 31 female). The mean length of endoscopic follow-up was 5.5 yr (range 0.5–13.3). Low-grade dysplasia (LGD) was present initially in 16 patients (9.6%) and found during follow-up in another 24 patients. However, in 75% of cases, LGD was not confirmed on later biopsies. HGD was found during surveillance in three patients (1.8%), one with simultaneous AC; two with HGD developed AC later. AC was detected in five male patients during surveillance. The incidence of AC was 1/220 (5/1100) patient-years of total follow-up, or 1/183.6 (5/918) patient-years in subjects undergoing endoscopy. Four AC patients died, and one was alive with advanced-stage tumor. The mean number of endoscopies performed for surveillance, rather than for symptoms, was 2.4 (range 1–10) per patient. During the follow-up years the cohort had a total of 528 examinations and more than 4000 biopsies.Conclusions The incidence of AC in BE is low, confirming recent data from the literature reporting an overestimation of cancer risk in these patients. In our patient cohort, surveillance involved a large expenditure of effort but did not prevent any cancer deaths. The benefit of surveillance remains uncertain.
View
View
Reflux laryngitis and its sequelae: The diagnostic role of ambulatory 24-hour pH monitoring
Article
  • Dec 1988
  • J Voice
Ambulatory 24-h intraesophageal pH monitoring was performed in 32 patients with hoarseness, documented laryngeal pathologic findings or lesions, globus, and/or chronic cough. The laryngeal lesions included granulomas, stenoses, and carcinomas. Twenty-two (68.8%) of the patients had no symptoms specific for reflux. One-half of the patients underwent pH monitoring with a double probe, one probe being placed in the distal esophagus and the second being placed in the hypopharynx just behind the laryngeal inlet. Twenty-four (75%) of the patients had abnormal studies, i.e., significant reflux. Of those, 17 (70.8%) had upright reflux, 13 (54.2%) had supine nocturnal reflux, and 10 (41.7%) had both types. Seven of the 16 patients undergoing double-probe-type monitoring had reflux into the pharynx (43.8%). These data suggest that occult gastroesophageal reflux may be involved in the pathogenesis of many conditions commonly encountered in otolaryngologic practice.
View
View
Laryngopharyngeal Reflux Symptoms Improve Before Changes in Physical Findings
Article
  • Jun 2001
  • LARYNGOSCOPE
Background: Patients with laryngopharyngeal reflux (LPR) undergoing treatment appear to have improvement in symptoms before the complete resolution of the laryngeal findings. Objective: To determine whether patients with LPR experience an improvement in symptoms before the complete resolution of the laryngeal findings. Methodology: Forty consecutive patients with LPR documented by double-probe pH monitoring were evaluated prospectively. Symptom response to therapy with proton pump inhibitors was assessed at 2, 4, and 6 months of treatment with a self-administered reflux symptom index (RSI). In addition, transnasal fiberoptic laryngoscopy (TFL) was performed and a reflux finding score (RFS) was determined for each patient at each visit. Results: The mean RSI at entry was 19.3 (+/- 8.9 standard deviation) and it improved to 13.9 (+/- 8.8) at 2 months of treatment (P <.05). No further significant improvement was noted at 4 months (13.1 +/- 9.8) or 6 months (12.2 +/- 8.1) of treatment. The RFS at entry was 11.5 (+/- 5.2), and it improved to 9.4 (+/- 4.7) at 2 months, 7.3 (+/- 5.5) at 4 months, and 6.1 (+/- 5.2) after 6 months of treatment (P <.05 with trend). Conclusions: Symptoms of LPR improve over 2 months of therapy. No significant improvement in symptoms occurs after 2 months. This preliminary report demonstrates that the physical findings of LPR resolve more slowly than the symptoms and this continues throughout at least 6 months of treatment. These data imply that the physical findings of LPR are not always associated with patient symptoms, and that treatment should continue for a minimum of 6 months or until complete resolution of the physical findings.
View
Systematic review: Persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies
Article
  • Sep 2010
  • ALIMENT PHARM THER
Persistent gastro-oesophageal reflux disease (GERD) symptoms can occur despite proton pump inhibitor (PPI) therapy. To assess the prevalence and potential determinants of persistent GERD symptoms in primary care and community-based studies. Studies were identified by systematic PubMed and Embase searches; pooled prevalence data are shown as sample-size weighted means and 95% confidence intervals. Nineteen studies in individuals with GERD taking a PPI were included. In interventional, nonrandomized primary care trials, the prevalence of persistent troublesome heartburn and regurgitation was 17% (6-28%) and 28% (26-30%) respectively; in randomized trials, it was 32% (25-39%) and 28% (26-30%), respectively. In observational primary care and community-based studies, 45% (30-60%) of participants reported persistent GERD symptoms. Overall, persistent GERD symptoms despite PPI treatment were more likely in studies with a higher proportion of female participants [>60% vs. <50%, risk ratio (RR): 3.66; P < 0.001], but less likely in studies from Europe than in those from the USA (RR: 0.71; P < 0.001), and were associated with decreased psychological and physical well-being. Persistent GERD symptoms despite PPI treatment are common in the primary care and community setting. Alternative approaches to management are required.
View
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 Acid and Pepsin in the Development of Laryngeal Injury
Article
  • May 1991
Occult (silent) gastroesophageal reflux disease (GER, GERD) is believed to be an important etiologic factor in the development of many inflammatory and neoplastic disorders of the upper aerodigestive tract. In order to test this hypothesis, a human study and an animal study were performed. The human study consisted primarily of applying a new diagnostic technique (double‐probe pH monitoring) to a population of otolaryngology patients with GERD to determine the incidence of overt and occult GERD. The animal study consisted of experiments to evaluate the potential damaging effects of intermittent GER on the larynx. Two hundred twenty‐five consecutive patients with otolaryngologic disorders having suspected GERD evaluated from 1985 through 1988 are reported. Ambulatory 24‐hour intraesophageal pH monitoring was performed in 197; of those, 81% underwent double‐probe pH monitoring, with the second pH probe being placed in the hypopharynx at the laryngeal inlet. Seventy percent of the patients also underwent barium esophagography with videofluoroscopy. The patient population was divided into seven diagnostic subgroups: carcinoma of the larynx (n = 31), laryngeal and tracheal stenosis (n = 33), reflux laryngitis (n = 61), globus pharyngeus (n = 27), dysphagia (n = 25), chronic cough (n = 30), and a group with miscellaneous disorders (n = 18). The most common symptoms were hoarseness (71%), cough (51%), globus (47%), and throat clearing (42%). Only 43% of the patients had gastrointestinal symptoms (heartburn or acid regurgitation). Thus, by traditional symptomatology, GER was occult or silent in the majority of the study population. Twenty‐eight patients (12%) refused or could not tolerate pH monitoring. Of the patients undergoing diagnostic pH monitoring, 62% had abnormal esophageal pH studies, and 30% demonstrated reflux into the pharynx. The results of diagnostic pH monitoring for each of the subgroups were as follows (percentag with abnormal studies): carcinoma (71%), stenosis (78%), reflux laryngitis (60%), globus (58%), dysphagia (45%), chronic cough (52%), and miscellaneous (13%). The highest yield of abnormal pharngeal reflux was in the carcinoma group and the stenosis group (58% and 56%, respectively). By comparison, the diagnostic barium esophagogram with videofluoroscopy was frequently negative. The results were as follows: esophagitis (18%), reflux (9%), esophageal dysmotility (12%), and stricture (3%). All of the study patients were treated with antireflux therapy. Follow‐up was available on 68% of the patients and the mean follow‐up period was 11.6 ± 12.7 months. After 6 months of treatment, symptoms had resolved in 85% and medical therapy had failed in 15%. Subsequently, an additional 20% experienced medical treatment failure. Fifteen percent of patients underwent Nissen fundoplication, and all subsequently had resolution of symptoms. To further investigate the role of gastroesophageal reflux in the development of laryngeal damage, experiments mimicking the effects of intermittent reflux (of acid and pepsin) on the canine larynx were performed. The results of these experiments revealed: 1 . Intermittent reflux (three episodes per week) can result in severe laryngeal damage if there is prior mucosal injury; 2 . pepsin, and not hydrochloric acid, is the principal injurious agent of the refluxate; and, 3 . severe laryngeal damage can occur even when the pH of the refluxate is 4.0. The manuscript describes the limitations and advantages of standard diagnostic procedures and of 24‐hour pH monitoring. The differences between gastroenterology and otolaryngology patients with GERD are emphasized and specific new diagnostic and therapeutic recommendations are made.
View