Article

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

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

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. 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. 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). 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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... If shown to be highly sensitive and specific, new less invasive diagnostic techniques, such as pepsin and trypsin detection in airway mucosa, could enable new epidemiological studies determining real incidence and prevalence. Given the major impact of diet on the development of reflux [20][21][22], such studies will have to take account of specific population characteristics and will be difficult to extrapolate to the worldwide general population. GERD, which is better documented, affects 20-30% of the US population [23,24]. ...
... Pathophysiologically, several factors account for onset of LPR: esophageal dysfunction (transient or permanent sphincter relaxation, dysmotility), unhealthy lifestyle (stress, late meals, aerophagy, smoking, etc.) and low-protein high-fat diet [4,20,22,80]. Fatty foods are associated with longer gastric digestion and onset of reflux episodes [20]. Acid foods and some amino acids contribute to acidic reflux and hence to pepsin enzymatic activity in airway mucosa. ...
... A recent study classified the main foods consumed in Europe in 5 categories according to refluxogenic potential (Tables 2 and 3) [82], enabling authors to develop clinical scores assessing the refluxogenic potential of meals and overall diet [82]. The importance of diet was shown in a recent meta-analysis [1] and in several clinical studies, whether proton-pump inhibitors were associated [20], or not [21], and also in resistant patients [22]. In a recent retrospective study, Zalvan et al. [21] reported that an alkaline "Mediterranean" diet based on plant proteins, cooked vegetables, and low levels of animal fat was quite as effective as proton-pump inhibitors. ...
Article
This review was conducted according to the Patient/problem Intervention Comparison Outcome (PICO) Statements. Some studies reported that 10–30% of patients consulting in ENT come with presenting symptoms of laryngopharyngeal reflux (LPR), but the exact prevalence of LPR is still unknown. Management has not changed in 20 years despite a significant increase in the number of publications on epidemiology, clinical presentation, diagnosis and treatment. The development of hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring (HEMII-pH) and saliva pepsin detection now allow a new multidimensional diagnostic approach associating clinical scores to HEMII-pH and saliva pepsin detection. This new approach may enable personalized treatment according to LPR profile on HEMII-pH (acid, non-acid, mixed; upright, recumbent reflux episodes). Updated treatment of LPR could consist in a 3-month association of dietary measures, proton pump inhibitors, alginate and magaldrate, followed by treatment adaptation.
... Pepsin is a digestive enzyme with maximal activity at pH 1.5-2.5; however, proteolytic activity has been demonstrated at pH levels as high at 6.5, and the enzyme remains stable up to a pH of 8 [9][10][11]. Tissue-bound pepsin within the larynx may be activated by acidic refluxate, leading to tissue damage and inflammation, while another study has demonstrated evidence of receptor-mediated endocytosis [8][9][10]. ...
... however, proteolytic activity has been demonstrated at pH levels as high at 6.5, and the enzyme remains stable up to a pH of 8 [9][10][11]. Tissue-bound pepsin within the larynx may be activated by acidic refluxate, leading to tissue damage and inflammation, while another study has demonstrated evidence of receptor-mediated endocytosis [8][9][10]. Interestingly and counterintuitively, proton pump inhibitors (PPIs) have been shown to exacerbate the pathogenic properties of pepsin, bile salts, and other gastroduodenal enzymes by creating a more alkaline milieu. ...
... Modifications to diet and lifestyle have often been recommended as either first-line or adjunctive therapies for alleviating the symptoms associated with LPR. Common foods that exacerbate LPR are foods with high acidic content; foods containing citrus components, which also tend to be acidic; fatty foods; and foods high in certain spices (pepper) [9]. Lifestyle habits that seem to contribute to LPR symptoms include consuming large meals late in the day and lying flat or sleeping within a few hours after consuming a large meal. ...
Article
Full-text available
The purpose of this article is to review the cornerstone and most recent literature regarding laryngopharynoesophageal reflux (LPR) including epidemiological characteristics, pathophysiology, symptoms, diagnosis, and management. The role of pepsin in the pathophysiology of LPR is highlighted in addition to new diagnostic modalities and pharmacologic therapies that target pepsin.
... Une fois qu'elles seront démontrées comme hautement sensibles et spécifiques, certains nouvelles approches diagnostiques moins invasives, détectant par exemple la pepsine et la trypsine dans le mucus des VADS, pourront permettre l'élaboration de nouvelles études épidémiologiques qui préciseront l'incidence et la prévalence réelle de la maladie. À la vue de l'impact majeur de l'alimentation dans le développement du reflux [20][21][22], ces études devront impérativement tenir compte des caractéristiques des populations étudiées et seront difficilement généralisables à l'ensemble de la population mondiale. Le reflux gastro-oesophagien, mieux documenté, toucherait quant à lui 20 à 30 % de la population Nord-américaine [23,24]. ...
... D'un point de vue physiopathologique, plusieurs facteurs expliquent la survenue de LPR tels que des dysfonctionnements oesophagiens (relaxation transitoire ou permanente des sphincters oesophagiens, dysmotilité oesophagienne), une mauvaise hygiène de vie (stress, repas tardifs, aérophagie, tabac, etc.) et un régime pauvre en protéine et riche en graisse [4,20,22,80]. Les aliments riches en graisses sont associés à un temps de digestion gastrique plus long, et à la survenue d'épisodes de reflux [20]. Les aliments acides et certains acides aminés contribuent à l'acidification des épisodes de reflux et de facto à l'activité enzymatique de la pepsine au niveau des muqueuses des VADS. ...
... Cette classification a permis aux auteurs d'élaborer des scores cliniques évaluant le potentiel refluxogène des repas et du régime global du patient [82]. L'importance du régime a été démontrée dans une récente méta-analyse [1] ainsi que dans plusieurs études cliniques qu'il soit en association avec un IPP [20], soit seul [21], ou prescrit chez des patients résistants [22]. Dans une récente étude rétrospective, Zalvan et al. [21] ont noté que le respect d'un régime alcalin, méditerranéen (basé sur la prise de protéines végétales, de légumes cuits, réduisant l'apport de graisses animales) était tout aussi efficace que la prise d'un IPP. ...
Article
Résumé Cette revue systématique de la littérature a été réalisée à l’aide des critères Patient/problem Intervention Comparison Outcomes. La prévalence reflux laryngopharyngé reste méconnue même si diverses études suggèrent que 10 à 30 % des patients consultant en oto-rhino-laryngologie présentent des plaintes de reflux. Depuis plus de 20 ans, le nombre de publications s’intéressant à l’épidémiologie, la présentation clinique, au diagnostic, et au traitement du reflux laryngopharyngé a fortement augmenté sans toutefois fournir une évolution de la prise en charge. En regard du développement de la pH-impédancemétrie et des techniques de détection de la pepsine dans les sécrétions des voies aérodigestives supérieures, nous sommes en mesure de proposer une nouvelle approche diagnostique basée sur l’association de scores cliniques, des résultats de la pH-impédancemétrie, et de la détection de pepsine salivaire. Sur le plan thérapeutique, cette approche permet de personnaliser le traitement en regard du profil de reflux du patient (acide, non-acide, mixte ; position debout ou allongée) orienté par la pH-impédancemétrie. Ainsi, le traitement actualisé du reflux laryngopharyngé pourrait associer des mesures hygiénodiététiques, la prise d’inhibiteurs de la pompe à protons, d’alginate et de malgaldrate durant trois mois au terme desquels une adaptation du traitement serait réalisée.
... Overall, acid, fat, and low-protein foods, caffeine, alcohol and high-sugar beverages are suspected to be associated with impairments of the tonicity of LES (transient relaxation) or esophageal dysmotility, leading to abnormal acid exposure in the esophagus and GERDrelated symptoms [11]. In otolaryngology, studies found that following a low-fat, high-protein and alkaline diet is associated with higher symptom resolution in patients with LPR symptoms or with recalcitrant symptoms to proton pump inhibitors (PPIs) [6,12]. ...
... A total of 708 relevant studies were identified. From them, 9 described the impact of diet on LPR disease (Table 1) [4,5,12,[15][16][17][18][19][20] and 63 focused on the relationship between the consumption of specific F&B and the development of esophageal dysmotility or sphincter dysfunctions or GERD-related symptoms or findings (i.e., esophagitis, hiatal hernia, etc.). ...
... Note that the effect of diet was assessed in association with some lifestyle changes, i.e., elevation of the head of the bed; avoidance of meal before sleep; and non-fasting eat in the majority of studies. The evidence level of studies is low and there is an important heterogeneity in the LPR diagnostic, content of diet and the outcomes used to assess the diet treatment efficacy [12]. The LPR diagnostic was based in pH monitoring in one study [12]. ...
Article
Full-text available
Objective To develop clinical tools assessing the refluxogenic potential of foods and beverages (F&B) consumed by patients with laryngopharyngeal reflux (LPR). Methods European experts of the LPR Study group of the Young-Otolaryngologists of the International Federation of Oto-rhino-laryngological societies were invited to identify the components of Western European F&B that would be associated with the development of LPR. Based on the list generated by experts, four authors conducted a systematic review to identify the F&B involved in the development of esophageal sphincter and motility dysfunctions, both mechanisms involved in the development of gastroesophageal reflux disease and LPR. Regarding the F&B components and the characteristics identified as important in the development of reflux, experts developed three rational scores for the assessment of the refluxogenic potential of F&B, a dish, or the overall diet of the patient. Results Twenty-six European experts participated to the study and identified the following components of F&B as important in the development of LPR: pH; lipid, carbohydrate, protein composition; fiber composition of vegetables; alcohol degree; caffeine/theine composition; and high osmolality of beverage. A total of 72 relevant studies have contributed to identifying the Western European F&B that are highly susceptible to be involved in the development of reflux. The F&B characteristics were considered for developing a Refluxogenic Diet Score (REDS), allowing a categorization of F&B into five categories ranging from 1 (low refluxogenic F&B) to 5 (high refluxogenic F&B). From REDS, experts developed the Refluxogenic Score of a Dish (RESDI) and the Global Refluxogenic Diet Score (GRES), which allow the assessment of the refluxogenic potential of dish and the overall diet of the LPR patient, respectively. Conclusion REDS, RESDI and GRES are proposed as objective scores for assessing the refluxogenic potential of F&B composing a dish or the overall diet of LPR patients. Future studies are needed to study the correlation between these scores and the development of LPR according to impedance–pH study.
... Over the past few decades, the empirical therapeutic trial based on proton pump inhibitors (PPIs) was proposed as the main cost-effective approach to treat and support the LPR diagnosis [71][72][73][74][75][76][77][78][79][80][81][82][83][84]. Nowadays, this approach is increasingly challenged for many reasons [64,75]. ...
... In that way, the physician could have a critical role in strengthening the relevance of diet in both the suspected and confirmed LPR disease. Because LPR is often due to diet habits [80,81] and stress [82], the primary care physician has a key role in alerting the patient about these favoring factors and preventing recurrence or chronicity of the disease. Some scores assessing the refluxogenic potential of diet were developed [83,84] and, through a mobile phone app, could be useful for patients in the choice of their favorite foods. ...
Article
Full-text available
Laryngopharyngeal reflux (LPR) is a common disease in the general population with acute or chronic symptoms. LPR is often misdiagnosed in primary care because of the lack of typical gastroesophageal reflux disease (GERD) symptoms and findings on endoscopy. Depending on the physician's specialty and experience, LPR may be over-or under-diagnosed. Management of LPR is potentially entirely feasible in primary care as long as General Practitioners (GPs) are aware of certain "red flags" that will prompt referral to a Gastroenterologist or an Otolaryngologist. The use of patient-reported outcome questionnaires and the consideration of some easy ways to diagnose LPR without special instrumentation oropharyngeal findings may help the GP to diagnose and often manage LPR. In this review, we provide a practical algorithm for LPR management for GPs and other specialists that cannot perform fiberoptic examination. In this algorithm, physicians have to exclude some confounding conditions such as allergy or other causes of pharyngolaryngitis and "red flags". They may prescribe an empirical treatment based on diet and behavioral changes with or without medication, depending on the symptom severity. Proton pump inhibitors and alginates remain a popular choice in order to protect the upper aerodigestive tract mucosa from acid, weakly acid and alkaline pharyngeal reflux events.
... According to Ossakow, only 6% of LPR patients present with heartburn as compared to 89% of GERD patients [47]. As reported by Koufman, the incidence of LPR symptoms is distributed as follows: dysphonia or hoarseness in 71% of patients, coughing in 51% of patients, sensation of a foreign body within the throat in 47% of patients, throat clearing in 42% of patients, and hypercalcemia in 35% of patients [16,17]. ...
... Currently, reflux disease is suggested to be the most common cause of laryngitis. Koufman et al. reporter that concomitant reflux was present in as many as 50% of patients reporting with voice disorders [15][16][17]. been measured within the gastrointestinal and respiratory tract mucous membranes. With age, the body levels of hyaluronic acid are depleted [22]. ...
Article
Full-text available
Introduction: Proton pump inhibitors (PPI) are an important breakthrough in the treatment of gastroesphageal reflux disease (GERD). However, in patients with laryngopharyngeal reflux (LPR), one of the extraoesophageal syndromes of this disease, the effectiveness of PPI therapy is partial or limited, and additional treatment is required to alleviate the symptoms. Currently, the important role of hyaluronic acid (HA) and chondroitin sulfate (CS) and their important role in the healing of mucosal damage, primarily the larynx, is emphasized. The aim of the study was to evaluate the results of treatment of patients with LPR by the oral combination preparation of hyaluronic acid and chondroitin sulfate (HA + CS) on a bioadhesive carrier. Material and methods: The study included 51 patients (18 men and 33 women) aged 25–75 years reporting symptoms of LPR, confirmed in the laryngovideoscope study. Patients were qualified for the study on the basis of reflux symptom index (RSI) above 13 points and the scale of reflux morphological symptoms of LPR in laryngofiberoscopic examination (reflux finding score; RFS) above 7 points. They were recommended to use the HA + CS combination for 14 days with subsequent evaluation. Results: Symptoms indicating a serious or severe problem (4 or 5 points on the RSI scale) before treatment are: grunting (48 patients; 90.19%), hoarseness (29 people; 56.86%) and coughing after eating/lying down (37 people; 72.50%). After treatment, the patients indicated that the above conditions limit their daily functioning to a moderate extent (p < 0.001). Symptoms such as the presence of mucus in the throat, a nagging cough, a feeling of obstruction in the throat, defined initially as moderate (3 points), after the supportive treatment decreased to a low level (1 point) (p < 0.001). The total RSI value after treatment was assessed as borderline for LPR diagnosis (median 13, range 12–15). The patient was not free of GERD symptoms, however, a significant reduction of discomfort was achieved in the whole study group. Morphological changes of the larynx before treatment most often included: redness/hyperemia, swelling of the vocal folds and hypertrophy of the posterior commissure. They were found in all patients. After treatment, the total RFS value below the LPR diagnosis limit (median 6, range 5–7) was observed, which compared to RFS (median 9, range 8–10) before treatment indicated a significant reduction of larynx changes in almost the entire study group (N = 50; 98.04%) (p < 0.001). Conclusions: A combined preparation of hyaluronic acid and chondroitin sulfate on a bioadhesive carrier, acting locally, significantly reduces the symptoms of laryngopharyngeal reflux, mainly in patients with: chronic cough, grunting and hoarseness. In addition, by covering the laryngeal mucosa with a protective layer, it allows better hydration and accelerates the healing process and regeneration of the mucosa, which in turn causes a reduction or withdrawal of morphological changes in the larynx.
... Over the past few decades, the empirical therapeutic trial based on proton pump inhibitors (PPIs) was proposed as the main cost-effective approach to treat and support the LPR diagnosis [71][72][73][74][75][76][77][78][79][80][81][82][83][84]. Nowadays, this approach is increasingly challenged for many reasons [64,75]. ...
... In that way, the physician could have a critical role in strengthening the relevance of diet in both the suspected and confirmed LPR disease. Because LPR is often due to diet habits [80,81] and stress [82], the primary care physician has a key role in alerting the patient about these favoring factors and preventing recurrence or chronicity of the disease. Some scores assessing the refluxogenic potential of diet were developed [83,84] and, through a mobile phone app, could be useful for patients in the choice of their favorite foods. ...
Preprint
Full-text available
Laryngopharyngeal reflux (LPR) is a prevalent disease in the general population and may have acute or chronic clinical presentation. LPR may be misdiagnosed in primary care medicine regarding the lack of gastroesophageal reflux disease symptoms and the lack of findings at the gastrointestinal endoscopy. Depending on the physician field of expertise and experience, LPR may be clinically over- or under-diagnosed. The management of LPR is possible in primary care medicine but primary care physician has to consider some red flags that requires to address the patient to otolaryngologist or gastroenterologist. The use of patient-reported outcome questionnaire such as reflux symptom score-12 and the consideration of some oral and pharyngeal findings visualized through the mouth opening may help the primary care physician to evaluate the LPR findings at the diagnosis time and throughout treatment. In this review, we provide a practical algorithm of management of LPR for primary care physician or other specialists that cannot perform fiberoptic examination. In this algorithm, physician has to exclude some confounding conditions such as allergy or other causes of pharyngolaryngitis and red flags. Physician may prescribe an empirical treatment based on diet and behavioral changes with or without medication, depending on the complaint severity of the patient. In case of prescription of medication, proton pump inhibitors and alginate have to be considered in association to protect the upper aerodigestive tract mucosa from acid, weakly acid and alkaline pharyngeal reflux events.
... In 2011, Jamie Koufman described therapeutic benefits of low-acid, alkaline diet in a cohort of 20 LPR patients with recalcitrant symptoms. 18 In this study, resistant LPR patients to PPI-therapy reported significant improvements of reflux symptom index after 2 weeks of low-acid (alkaline) diet, supporting the importance of alkaline diet in the reduction of LPR symptoms. Many physiological mechanisms support the effectiveness of low-fat, low-quickrelease sugar, high-protein, alkaline and plant-based diet. ...
... 37 Protein (plant-based) foods were recommended to patients because proteins increase the LES tonicity. 18,38 In a general way, it is important to keep in mind that the majority of these studies investigated the role of foods and beverages on gastroesophageal physiology and authors mainly focused on GERD and LES functioning. This point is particularly important because the occurrence of pharyngeal reflux events involves the relaxation of both LES and UES. ...
Article
Objectives/hypothesis: To investigate the efficacy of low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet as single treatment for patients with laryngopharyngeal reflux (LPR). Study design: Cross-over observational study. Methods: Patients with LPR diagnosis at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH-monitoring were prospectively recruited from the reflux clinic of three University Hospitals. Patients were instructed to follow low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet for 6 to 12 weeks. Pre- to post-treatment symptom and finding changes were evaluated with reflux symptom score (RSS) and reflux sign assessment. Findings were compared to those of a control period where patients did not receive any treatment or diet. Diet was evaluated with refluxogenic diet score (REDS). Results: Fifty patients completed the study (19 males). Otolaryngological, digestive, and total RSS scores significantly improved from baseline to 6-week post-diet, while there were no significant changes during the control period. At 6-week post-diet, 37 (74%) patients reported significant symptom improvement or relief. Among them, symptoms continued to improve from 6 to 12 weeks in 27 cases, corresponding to a diet success rate of 54%. The REDS was predictive of the baseline RSS (P = .031). Conclusion: Low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet is an alternative cost-effective therapeutic approach for patients with LPR. Patients with higher REDS reported higher baseline symptom score. Level of evidence: 3 Laryngoscope, 2021.
... A diet composed of acid, high-fat, low-protein foods, and acid, alcoholic or high-sugar beverages leads to gastroesophageal dysfunction, including transient relaxations of lower (LES) and upper (UES) esophageal sphincters, which increase both acid esophageal and laryngopharyngeal exposure [8,9]. The authors interested in diet and behavioral changes have mainly studied the impact of an alkaline, low-fat and high-protein diet in patients with LPR symptoms, but not demonstrated LPR [3] or with recalcitrant symptoms to proton pump inhibitors (PPIs), corresponding to potential resistant patients [4,10]. The realization of researches investigating the involvement of diet in the development of LPR was limited by the lack of clinical tool providing rigorous rating to the refluxogenic potential of diet. ...
... The role of diet in the development of reflux has long been recognized and well-studied in patients with GERD. In LPR, there are only a few conducted studies; all of them investigating the impact of low-fat, high-protein, and alkaline diet on the clinical evolution of LPR patients treated by PPIs or with recalcitrant symptoms [2,3,10,[16][17][18][19][20]. Nowadays, there is no study that specifically investigates the refluxogenic potential of foods and beverages on the development of LPR, regarding MII-pH. ...
Article
Full-text available
Objective To assess the impact of diet on the occurrence of proximal reflux episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) in patients with laryngopharyngeal reflux (LPR). Methods Patients with LPR symptoms and findings were recruited from three European hospitals. The LPR diagnostic was confirmed through MII-pH and patients were benefited from gastrointestinal (GI) endoscopy. Regarding the types of reflux at the MII-pH (acid, nonacid, mixed), patients received a 3 month-therapy based on the association of alkaline, low-fat and high-protein diet, proton pump inhibitors, alginate or magaldrate. Reflux symptom score (RSS) and reflux sign assessment (RSA) were used to evaluate laryngeal and extra-laryngeal symptoms and findings from pretreatment to posttreatment. The Global Refluxogenic Score (GRES) was used to assess the refluxogenic potential of the diet of the patients at baseline and posttreatment. The relationship between GRES severity; the MII-pH findings; GI endoscopy; and the therapeutic response was explored through multiple linear regression. Results Eighty-five LPR patients were included. The mean GRES significantly improved from pretreatment (50.7 ± 23.8) to posttreatment (27.3 ± 23.2; P = 0.001). Similarly, RSS and RSA significantly improved from baseline to posttreatment. The baseline GRES was significantly associated with the occurrence of proximal reflux episodes at the MII-pH (P = 0.001). Trends were found regarding the association between GRES and the occurrence of esophagitis (P = 0.06) and between hiatal hernia and DeMeester score (P = 0.06). There was a significant and strong association between the concomitant respect of diet and medication and the improvement of RSS (P = 0.001). Conclusion The consumption of high-fat, low-protein, high-sugar, acid foods, and beverages is associated with a higher number of proximal reflux episodes at the MII-pH, according to the global refluxogenic score of LPR patients.
... Despite the fact that some foods such as fats, fried foods, tomatoes, onions, spices, coffee and beverages, have been identified as refluxogenic, objective evidence is still lacking in determining the influence of such foods on the clinical manifestations of GERD [43,49,50]. However, studies have shown that the elimination or the reduction of gastric irritants decreased the reflux symptoms [51]. ...
... In our study, we found that the consumption of tomatoes aggravated GERD symptoms and was more frequent among them. Limiting the consumption of tomatoes and its products is highly recommended to reduce GERD symptoms [51,52]. ...
Article
Background The prevalence of gastroesophageal reflux disease (GERD) is increasing worldwide and the related chronic symptoms can be associated with morbidity and poor quality of life. Objective: The objective of this study was to identify foods and beverages consumed by the Lebanese population, dietary habits, socio-demographic and lifestyle factors, health parameters and perceived stress, implicated in increasing GERD symptoms. Methods This observational cross-sectional study was carried among Lebanese adults in 2016. A convenient sample of 264 participants was equally divided into a GERD group and a control group. Data on socio-demographic characteristics, lifestyle, health status and dietary habits including Lebanese traditional dishes were collected. The perceived stress scale (PSS) was also used to assess the participants’ perception of stress. Logistic regression analyses were conducted with GERD symptoms (presence or absence) being the dependent variable. Results The GERD symptoms were significantly associated with age (-p-value=0.017), family history of GERD symptoms (-pvalue<0.001), smoking (-p-value=0.003) and chronic medical conditions (-p-value<0.001). Regarding the dietary factors, participants who ate three meals or less/day, between meals and outside home were 2.5, 2.9 and 2.4 times at a higher risk of experiencing GERD symptoms than others respectively. Moreover, the logistic regression model showed that the GERD symptoms were significantly associated with the consumption of coffee (-p-value=0.037), Lebanese sweets (-p-value=0.027), fried foods (-p-value=0.031), ‘Labneh’ with garlic (-p-value<0.001), pomegranate molasses (-p-value=0.011), and tomatoes (-pvalue=0.007). Conclusion Some specific lifestyle factors and components of the Lebanese Mediterranean diet could be associated with GERD symptoms.
... 14,[22][23][24] Treatment options include lifestyle modifications and the use of proton pump inhibitors, alginate or other antireflux medications. 1,14,[25][26][27][28][29][30] Regarding the non-specificity of symptoms and findings associated with LPR, the use of clinical tools is recommended for precisely assessing the treatment efficacy. Another challenge is the lack of specificity of LPR symptoms, which yields the diagnosis difficult. ...
Article
Full-text available
To investigate the psychometric properties of the reflux symptom index (RSI) as short screening approach for the diagnostic of laryngopharyngeal reflux (LPR) in patients with confirmed diagnosed regarding the 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH).
... 14,[22][23][24] Treatment options include lifestyle modifications and the use of proton pump inhibitors, alginate or other antireflux medications. 1,14,[25][26][27][28][29][30] Regarding the non-specificity of symptoms and findings associated with LPR, the use of clinical tools is recommended for precisely assessing the treatment efficacy. Another challenge is the lack of specificity of LPR symptoms, which yields the diagnosis difficult. ...
Article
Full-text available
Objectives To investigate the psychometric properties of the reflux symptom index (RSI) as short screening approach for the diagnostic of laryngopharyngeal reflux (LPR) in patients with confirmed diagnosed regarding the 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). Methods From January 2017 to December 2018, 56 patients with LPR symptoms and 71 healthy individuals (control group) were prospectively enrolled. The LPR diagnosis was confirmed through MII-pH results. All subjects (n = 127) fulfilled RSI and the Reflux Finding Score (RFS) was performed through flexible fiberoptic endoscopy. The sensitivity and the specificity of RSI was assessed by ROC (Receiver Operating Characteristic) analysis. Results A total of 15 LPR patients (26.8%) of the clinical group met MII-pH diagnostic criteria. Among subjects classified as positive for MII- pH diagnoses, RSI and RFS mean scores were respectively 20 (SD ± 10.5) and 7.1 (SD ± 2.5), values not significantly different compared to the negative MII-pH group. The metric analysis of the items led to the realization of a binary recoding of the score. Both versions had similar psychometric properties, α was 0.840 for RSI original version and 0.836 for RSI binary version. High and comparable area under curve (AUC) values indicate a good ability of both scales to discriminate between individuals with and without LPR pathology diagnosis. Based on balanced sensitivity and specificity, the optimal cut-off scores for LPR pathology were ≥ 5 for RSI binary version and ≥ 15 for RSI original version. Both version overestimated LPR prevalence. The original version had more sensitivity and the RSI Binary version had more specificity. Conclusions It would be necessary to think about modifying the original RSI in order to improve its sensitivity and specificity (RSI binary version, adding or changing some items), or to introduce new scores in order to better frame the probably affected of LPR patient.
... Jalur ini mempengaruhi kerja kelenjar adrenal yang menghasilkan hormon kortison dan adrenal yang merangsang sel parietal dan kelenjar peptik untuk menghasilkan HCl dan pepsin. [12][13][14] Keluhan utama terbanyak yang membawa subjek datang berobat adalah throat clearing. Hasil penelitian ini sesuai dengan penelitian Kornel yang mendapatkan throat clearing merupakan keluhan pada hampir semua subjek yang didiagnosis LPR. ...
... Many studies have uncovered that certain dietary habits are related to LPR, such as fermented foods [20] and excessive drinking [22]. In addition, some studies have suggested that certain diets, such as low-acid, and plant protein diets have positive effects in the treatments of LPR [15,40]. Studies have also found that low-fat diets are helpful in the treatment of esophageal reflux disease [41]. ...
Article
Full-text available
This study aims to explore associations between emotional eating, depression and laryngopharyngeal reflux among college students in Hunan Province. Methods: This cross-sectional study was conducted among 1301 students at two universities in Hunan. Electronic questionnaires were used to collect information about the students' emotional eating, depressive symptoms, laryngopharyngeal reflux and sociodemographic characteristics. Anthropometric measurements were collected to obtain body mass index (BMI). Results: High emotional eating was reported by 52.7% of students. The prevalence of depressive symptoms was 18.6% and that of laryngopharyngeal reflux symptoms 8.1%. Both emotional eating and depressive symptoms were associated with laryngopharyngeal reflux symptoms (AOR = 3.822, 95% CI 2.126-6.871 vs. AOR = 4.093, 95% CI 2.516-6.661). Conclusion: The prevalence of emotional eating and depressive symptoms among Chinese college students should be pay more attention in the future. Emotional eating and depressive symptoms were positively associated with laryngopharyngeal symptoms. The characteristics of emotional eating require further study so that effective interventions to promote laryngopharyngeal health among college students may be formulated.
... Acid reflux diseases are highly prevalent and GERD and LPR are epidemic. [1][2][3][4][5] The difference between the two entities was highlighted by James in 1991. James emphasized the otolaryngological importance of reflux and described reflux as an underlying etiology in (40-60) % of patients with various voice disorders. ...
Article
Full-text available
p class="abstract"> Background: We sought to evaluate the combination of high-dose prebreakfast proton pump inhibitors (PPIs) (40 mg pantoprazole) and a bedtime high-dose ranitidine (300 mg) dosing as a surrogate and rational regimen for LPR. Methods: 60 subjects that presented to ENT and HNS OPD with symptoms of laryngopharyngeal reflux (LPR) were prospectively evaluated and underwent a comprehensive otolaryngological examination. All subjects were treated sequentially and outcomes recorded using reflux finding score (RFS) and reflux symptom index (RSI). Results: The mean age of the cohort was 35±06.51 (age range, 8-55). Mean RSI of all patients was 24.8 before treatment with combination of PPIs and H2 receptor antagonists. Significant change in RSI were observed after the first 8 weeks of therapy and no further significant changes were observed over the next 16 weeks. Mean RFS of the patients was 12 before starting the treatment and there was a significant response in mean RFS at 16 weeks of therapy. Conclusions: A surrogate high-dose prebreakfast PPI (40 mg pantoprazole) and a bedtime high-dose ranitidine (300 mg) dosing regimen is effective in improving RSI and RFS in majority of cases who present with LPR. </p
... Among non-pharmacological treatments of LPR, diet modification appeared to be effective: patients following a low-fat, high-protein, and alkaline diet had higher rates of symptom resolution [52]. However, a recent systematic review concludes that there is insufficient evidence to recommend diet modifications for LPR [53]. ...
Article
Full-text available
Gastroesophageal reflux disease (GERD) is defined by the presence of symptoms induced by the reflux of the stomach contents into the esophagus. Although clinical manifestations of GERD typically involve the esophagus, extra-esophageal manifestations are widespread and less known. In this review, we discuss extra-esophageal manifestations of GERD, focusing on clinical presentations, diagnosis, and treatment. Common extra-esophageal manifestations of GERD include chronic cough, asthma, laryngitis, dental erosions, and gingivitis. Extra-esophageal involvement can be present also when classic GERD symptoms are absent, making the diagnosis more challenging. Although available clinical studies are heterogeneous and frequently of low quality, a trial with proton pump inhibitors can be suggested as a first-line diagnostic strategy in case of suspected extra-esophageal manifestations of GERD.
... [32][33][34][35][36][37] Patients were additionally educated on dietary and behavioral modification methods. [38][39][40][41][42] These therapy approaches were applied to all patients regardless of the presence of concomitant laryngeal disorders. ...
Article
Objective To determine factors contributing to disease etiology and treatment efficacy. Study Design Original Report. Setting Tertiary academic center. Methods IRB approved prospective study of 20 patients with reported dysphagia who exhibited normal oropharyngeal and esophageal swallowing function as evidenced by videofluoroscopic swallow study, esophagogastroduodenoscopy, high-resolution esophageal manometry with stationary impedance, and Bravo pH probe off proton pump inhibitor. Patients underwent speech-language pathology intervention. Results Atypical laryngeal muscle tension was present in 100% of patients. Forty percent of patients had diagnosed positive gastroesophageal reflux disease. Sixty-five percent of patients showed signs of non-specific laryngeal inflammation and laryngeal hyperresponsiveness during strobolaryngoscopy. All patients reported a mean of 90% recovery by the completion of voice therapy directed toward unloading muscle tension. Conclusion The study results suggest an association between laryngeal muscle tension and these patients’ dysphagia symptoms regardless of associated conditions. Speech-language pathology intervention showed high treatment efficacy. Level of Evidence 2c- Outcomes research.
... In a recent meta-analysis, dietary and behavioral changes were found to be important factors that modulated the therapeutic effectiveness of PPIs [1]. In addition, alkaline and low-fat diets showed positive effects in the treatment of suspected LPR and recalcitrant LPR [35][36][37]. ...
Article
Full-text available
Objectives: This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR). Methods: An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies. Results: Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR. Conclusion: Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.
... Interest is growing in weakly acidic, or nonacidic, reflux, which would intuitively seem less likely to respond to PPIs yet contains the other important elements of gastric contents. Little evidence exists for the role of other factors that might reduce reflux related persistent throat symptoms, such as diet, 33 lifestyle, 34 and alginates. 23 Our trial does not refute reflux as a cause or contributing factor for some patients' symptoms, and although reflux of gastric contents containing pepsin might be implicated in some patients, defining such individuals and appropriate management needs further research. ...
Article
Full-text available
Objective To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. Design Pragmatic, double blind, placebo controlled, randomised trial. Setting Eight ear, nose, and throat outpatient clinics, United Kingdom. Participants 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. Intervention Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. Main outcome measures Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. Results Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups—score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval −0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (−0.6 to 5.4 points). Conclusions No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up. Trial registration ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.
... In practice, 50.5% of both laryngologists and non-laryngologists recognize to just advise diet and behavioral changes for patients with mild LPR. This trend makes particular sense regarding the studies reporting a significant improvement of LPR symptoms or findings in patients treated by low-fat, high-protein, and alkaline diet [42][43][44] but, nowadays, there is no clear definition of "mild" LPR, and no clinical criteria for considering a diet versus a medical treatment for LPR patients. These two points require further clinical studies for developing cost-effective therapeutic approach for the management of LPR. ...
Article
Full-text available
Objective: To investigate current practices of laryngologists and non-laryngologists in management of Laryngopharyngeal Reflux (LPR). Methods: An online survey was sent to members of otolaryngology societies about LPR, and subgroup analysis was performed between laryngologists and non-laryngologists. This survey was conducted by the LPR Study Group of Young Otolaryngologists of the International Federation of Otolaryngological Societies. Results: A total of 535 otolaryngologists completed the survey. Among them, 127 were laryngologists and 408 were non-laryngologists. Collectively, symptoms most commonly attributed to LPR are cough after lying down/meal, throat clearing, and acid brash; most common findings are thought to be arytenoid erythema and posterior commissure hypertrophy. Respectively, 12.5% and 5% of non-laryngologists and laryngologists believe that ≥50% of LPR patients suffer from heartburn (P = .010). Non-laryngologists are more aware about some extra-laryngeal findings associated with LPR (eg, pharyngeal erythema) than laryngologists. Neither laryngologists nor non-laryngologists associated development of benign lesions of the vocal folds with reflux. The management of LPR substantially differs between groups, with laryngologists indicating increased awareness of (impedance)-pH monitoring as well as the prevalence and treatment of nonacid/mixed LPR. Conversely, non-laryngologists are much more likely to include gastroenterology referral in their management of presumed LPR. Respectively, 44.8% and 27.6% of non-laryngologists and laryngologists believe themselves not sufficiently knowledgeable about LPR. Conclusions: Significant differences exist between laryngologists and non-laryngologists in diagnosis and treatment of LPR. Overall only one-third of responders believe themselves to be sufficiently educated about LPR. Level of evidence: 4 Laryngoscope, 2020.
... Studies have shown that pepsin plays a major role in the mechanism by which non-acid substances cause damage to the laryngopharynx [39,40]. Pepsin can be stably present for a long time in an environment with a pH of 6.8 in the laryngopharynx [41,42] and can be activated at a pH of 5.0. Studies have even suggested that the diagnostic criteria should be increased to pH < 5 [43]. ...
Article
Full-text available
Objective: We aimed to analyze the results of 24-h multichannel intraluminal impedance and pH-monitoring (MII-pH) of the laryngopharynx and esophagus in asymptomatic volunteers. Moreover, we also aimed to gain insight into and establish a baseline for laryngopharyngeal reflux in the healthy population by quantitatively and qualitatively comparing the reflux and pH distribution in both the laryngopharynx and the esophagus. Methods: Healthy volunteers were recruited and observed; they underwent 24-h ambulatory combined MII-pH monitoring. The proximal sensor (pH1) was positioned approximately 1 cm above the upper esophageal sphincter with the aid of a solid-state high-resolution esophageal manometer. Laryngopharyngeal reflux events were detected and characterized by the incidence and property of reflux both in the laryngopharynx and the esophagus. Results: Thirty-eight asymptomatic volunteers who completed all the examinations were included in this study. The median pH detected by the proximal sensor was 6.6 (6.2, 7.0), with an average of 6.58 ± 0.74. A total of 814 laryngopharyngeal reflux events were detected, including 722 (89%) in the upright position and 92 (11%) in the supine position with incidence (0%) in the liquid state, 44 (5%) in the mixture, and 769 (95%) in the gaseous state. Furthermore, 5 incidences (1%) of acid reflux and 809 incidences of non-acid reflux (99%) were noted. A total of 5779 esophageal reflux events were detected, including 5020 (87%) in the upright position, 759 (13%) in the supine position, with 2051 (36%) in the liquid state, 2050 (35%) in the mixed condition, and 1678 (29%) in the gaseous state; adding up to 805 incidences (14%) of acid reflux and 4974 incidences (86%) of non-acid reflux. Conclusion: Non-acid reflux in the upright position is characteristic of laryngopharyngeal reflux. Acid reflux is almost undetectable in healthy subjects. Hence, the diagnostic indicators of gastroesophageal reflux disease are not suitable for laryngopharyngeal reflux disease.
... The exact etiology behind the failure of the upper sphincter is uncertain; however, it is also clear that such failure is reversible with effective antireflux treatment [7]. LPR has been associated with vocal cord polyps, vocal cord granulomas, laryngospasm, laryngeal carcinoma, and subglottic stenosis [8]. We report a case of vocal cord polyp diagnosed in a patient with severe GERD. ...
Article
Full-text available
Background: Among the most common benign laryngeal lesions are vocal nodules and polyps. Their etiology is related to vocal abuse. Gastroesophageal reflux disease is a common condition presenting with a broad spectrum of symptoms, among which are extraesophageal manifestations such as laryngeal polyps. Case presentation: A 24-year-old Middle Eastern woman presented to the author's institution with dysphonia and dyspepsia. She underwent endoscopy and was diagnosed with severe reflux disease. In addition, laryngoscopy revealed a polyp at the left vocal cord, and the patient underwent polypectomy. Histopathological examination revealed a laryngeal polyp of telangiectatic type characterized by hyperplastic epithelial covering with reactive atypia, prominent superficial acanthosis with neutrophils, and prominent chronic inflammation and thrombosed vessels in the stroma. Conclusion: This report focuses on the pathological findings associated with a laryngeal polyp in a young patient diagnosed with severe reflux disease. Acknowledging such characteristic changes in a laryngeal polyp could aid in the diagnosis of gastroesophageal reflux disease.
... Patients with stress and anxiety may commonly have autonomic nerve dysfunction that involves esophageal sphincter relaxation and reflux by a disruption of the balance between sympathetic and para-sympathetic nerves [6]. Regarding diet, the consumption of industrial (acidified), acid, low-protein, high-sugar and high-fat diet leads to a higher number of hypopharyngeal reflux events (HREs) and, therefore, LPR symptoms and findings [5,7]. ...
Article
Full-text available
It is currently well-established that Laryngopharyngeal reflux (LPR) is a prevalent condition in both primary care practice and otolaryngology [1,2]. According to epidemiological studies, the prevalence of LPR-related symptoms ranged from 10 to 30% in European countries [3,4]. The development of LPR may involve diet, lifestyle, stress, and anxiety factors [2,5,6]. Patients with stress and anxiety may commonly have autonomic nerve dysfunction that involves esophageal sphincter relaxation and reflux by a disruption of the balance between sympathetic and para-sympathetic nerves [6]. Regarding diet, the consumption of industrial (acidified), acid, low-protein, high-sugar and high-fat diet leads to a higher number of hypopharyngeal reflux events (HREs) and, therefore, LPR symptoms and findings [5,7]. Celiac disease, lactose intolerance, tobacco, or alcohol consumption are all conditions that may be involved in the development of LPR or in the therapeutic resistance [2,8]. In other words, the modern lifestyle of Western countries may be important in the development of LPR. In this context, we developed a transnational European Reflux Clinic (ERC) dedicated to the management of patient with usual or complicated LPR. The aim of this editorial is to present the proof-of-concept and the practical working of the ERC.
... The positive impact of alkaline and low-fat diet is helpful for singers whose symptoms are refractory to proton-pump inhibitors (PPIs). [16] Dietary changes and changes of habits such as stop smoking (active and passive), reduce weight (in obese), avoid alcohol, and not take meal immediately bedtime. Dietary restrictions such as chocolate, caffeine, fat, tomato sauce, red wine, and gasified beverages. ...
... Patients with stress and anxiety may commonly have autonomic nerve dysfunction that involves esophageal sphincter relaxation and reflux by a disruption of the balance between sympathetic and para-sympathetic nerves [6]. Regarding diet, the consumption of industrial (acidified), acid, low-protein, high-sugar and high-fat diet leads to a higher number of hypopharyngeal reflux events (HREs) and, therefore, LPR symptoms and findings [5,7]. ...
... The positive impact of alkaline and low-fat diet is helpful for singers whose symptoms are refractory to proton-pump inhibitors (PPIs). [16] Dietary changes and changes of habits such as stop smoking (active and passive), reduce weight (in obese), avoid alcohol, and not take meal immediately bedtime. Dietary restrictions such as chocolate, caffeine, fat, tomato sauce, red wine, and gasified beverages. ...
Article
Full-text available
Laryngopharyngeal reflux (LPR) is retrograde flow of gastric content to the larynx and pharynx where these materials come in contact with the upper aerodigestive tract. It is an inflammatory disease associated with voice disorders and lesions in vocal fold. Presence of LPR among professional voice users such as singers can have a dramatic impact on voice quality. Singers are high-risk candidates for LPR because of necessary air support involving higher intra-abdominal pressure, more stress due to professional career, uncomfortable schedules, late meals before going to sleep, and bad food habits such as increased intake of citrus products, fatty, and spicy foods. The objective of this article is to review the current etiopathogenesis, clinical presentations, diagnosis, treatment, and lifestyle modification in cases of singers suffering from LPR and to propose a new patient-related outcome.
... In one study, 28 the authors indicated participants were given individualized dietary recommendations based on Koufman's low acid-diet for laryngopharyngeal reflux but these guidelines were not specified and did not appear to be consistent across participants. 30 Two studies specifically assessed adherence to eating behaviors including avoiding eating or drinking before bed. 20,21 However, the time between eating and bed differed between the two studies with one inquiring about eating two hours before bed 20 and the other inquiring about eating four hours before bed. ...
Article
Full-text available
Gastroesophageal reflux disease (GERD) is a common gastrointestinal illness with symptoms of heartburn, chest pain, and regurgitation. Management of GERD can involve medication use, lifestyle modification (eg, dietary modification), and surgical intervention depending on the individual patient and disease severity. Poor adherence to medication and recommended lifestyle changes may result in increased symptom severity and decreased quality of life. This paper aimed to systematically review the literature on lifestyle modification for the management of GERD. Fourteen articles were included based on search criteria. Following review and analysis, three types of lifestyle modifications were present in the literature and include medication use, dietary recommendations, and sleep recommendations. Despite being a pharmacological treatment, medication adherence was included in the review, as health behavior change can be used to improve adherence. Overall, the factors associated with adherence to modifications varied in terms of impact and directionality, depending on the type of lifestyle modification. Symptom severity emerged as important across all lifestyle modifications, and is associated with increased adherence to medication use, but decreased adherence to dietary guidelines. While patient-provider communication appeared to improve patient knowledge, it is unclear if increased knowledge translates to improved adherence. The review also demonstrated a lack of clear and standardized guidelines across lifestyle modifications, which may have an influence on adherence and adherence reporting. Future research in GERD treatment adherence would benefit from the use of validated measures to assess adherence. Specific recommendations to improving patient adherence are discussed.
... Strict low acid diet seems to be a key component of treatment. 55 The second-line of treatment might include prokinetic drugs, baclofen, or selective serotonin reuptake inhibitors. For voice professionals ...
Article
Full-text available
Objective: To summarize current knowledge about the prevalence, etiology and management of recalcitrant laryngopharyngeal reflux (LPR) patients - those who do not respond to anti-reflux medical treatment. Methods: A literature search was conducted following the PRISMA guidelines to identify studies that reported success of anti-reflux medical treatment with emphasis on studies that attempted to be rigorous in defining a population of LPR patients and which subsequently explored the characteristics of non-responder patients (i.e. etiology of resistance; differential diagnoses; management and treatment). Three investigators screened publications for eligibility from PubMED, Cochrane Library and Scopus and excluded studies based on predetermined criteria. Design, diagnostic method, exclusion criteria, treatment characteristics, follow-up and quality of outcome assessment were evaluated. Results: Of the 139 articles screened, 45 met the inclusion criteria. The definition of non-responder patients varied substantially from one study to another and often did not include laryngopharyngeal signs. The reported success rate of conventional therapeutic trials ranged from 17 to 87% and depended on diagnostic criteria, treatment scheme, definition of treatment failure, and treatment outcomes that varied substantially between studies. The management of non-responders differed between studies with a few differential diagnoses reported. No study considered the profile of reflux (acidic, weakly acid, nonacid, or mixed) or addressed personalized treatment with the addition of alginate or magaldrate, low acid diet, or other interventions that have emerging evidence of efficacy. Conclusion: To date, there is no standardized management of LPR patients who do not respond to traditional treatment approached. A diagnostic and therapeutic algorithm is proposed to improve the management of these patients. Future studies will be necessary to confirm the efficacy of this algorithm through large cohort studies of non-responder LPR patients. This article is protected by copyright. All rights reserved.
... the impact of age, gender, stress (autonomic nerve dysfunction), diet and lifestyle habits on reflux, it is increasingly suggested that the consideration of these outcomes makes sense to improve GERD [22] or LPR [10,17,18,23,24] management. Because the consideration of these outcomes may be time-consuming in a classical consultation, especially the diet evaluation, we developed EPMH to save time. ...
Article
Full-text available
Objectives To investigate usefulness, feasibility, and patient satisfaction of an electronic pre-consultation medical history tool (EPMH) in laryngopharyngeal reflux (LPR) work-up. Methods Seventy-five patients with LPR were invited to complete electronic medical history assessment prior to laryngology consultation. EPMH collected the following parameters: demographic and epidemiological data, medication, medical and surgical histories, diet habits, stress and symptom findings. Stress and symptoms were assessed with perceived stress scale and reflux symptom score. Duration of consultation, acceptance, and satisfaction of patients (feasibility, usefulness, effectiveness, understanding of questions) were evaluated through a 9-item patient-reported outcome questionnaire. Results Seventy patients completed the evaluation (93% participation rate). The mean age of cohort was 51.2 ± 15.6 years old. There were 35 females and 35 males. Patients who refused to participate (N = 5) were > 65 years old. The consultation duration was significantly lower in patients who used the EPMH (11.3 ± 2.7 min) compared with a control group (18.1 ± 5.1 min; p = 0.001). Ninety percent of patients were satisfied about EPMH easiness and usefulness, while 97.1% thought that EPMH may improve the disease management. Patients would recommend similar approach for otolaryngological or other specialty consultations in 98.6% and 92.8% of cases, respectively. Conclusion The use of EPMH is associated with adequate usefulness, feasibility, and satisfaction outcomes in patients with LPR. This software is a preliminary step in the development of an AI-based diagnostic decision support tool to help laryngologists in their daily practice. Future randomized controlled studies are needed to investigate the gain of similar approaches on the traditional consultation format.
Laryngopharyngeal reflux and atypical manifestations of gastroesophageal reflux disease have a high economic and social burden in the United States. There is increasing research supporting the reflex theory and hypersensitivity syndrome underlying this disease pathophysiology. Novel diagnostic biomarkers have gained more traction in the search for a more reliable diagnostic tool, but further research is needed. Current standard-of-care treatment relies on proton pump inhibitor therapy. Antireflux surgery is usually not recommended. Neuromodulators and treatments targeting specific neuronal receptors are discussed. A diagnostic algorithm is proposed for the evaluation of laryngeal symptoms suspected to be related to extraesophageal reflux disease.
Article
Background: At present more attention is paid to the treatment of secretory otitis media in children, but there is also a high incidence of adult patients. The etiology of secretory otitis media in adults is complex and related to many factors. Objectives: The aim of this study was to evaluate the correlation between the Reflux Symptom Index (RSI)/Reflux Finding Score (RFS) and secretory otitis media in adults, and to explore further treatment methods. Material and methods: Taking outpatients in the otology department from January 2017 to May 2019 as the object of study, acoustic immittance tests were performed and the results analyzed. Patients with secretory otitis media received tympanocentesis or tympanotomy and the related components were analyzed.The patients were followed up and the curative effects of different treatment schemes were compared. Results: There were 67 patients with secretory otitis media. The prevalence of secretory otitis media in patients with RSI >13 was significantly higher than that in patients with RSI <13. The prevalence of secretory otitis media in patients with RFS >7 was significantly higher than that in patients with RFS <7 (p < 0 05). The RSI/RFS score of B tympanogram was significantly higher than that of A and C maps (p < 0.05). Among the patients with type B, the serous type was higher in those with an RSI score <13, and the mucus was higher in those with an RSI score >13 (p < 0.05). There was no significant difference in the proportion of glue patients (p > 0.05). In type B patients, the detection rate of pepsin in the experimental group was significantly higher than that in the control group (p < 0.05), and the scores of RSI/RFS in the pepsin-positive group were significantly higher than those in the negative group (p < 0.05). Treatment with acid-suppressive drugs in patients with abnormal RSI/RFS achieved better results (p < 0.05). Conclusions: RSI/RFS may be related to the development of secretory otitis media in adults, and could play a guiding role in its treatment.
Article
Background: Diagnosis and treatment of presumed laryngopharyngeal reflux (LPR) remains controversial. Empiric medication trials remain widespread for suspected LPR despite emerging evidence against proton pump inhibitor (PPI) safety and for pepsin as a mediator of LPR symptoms. Ongoing concerns exist related to inaccurate diagnosis, the cost and morbidity of potentially unnecessary PPI prescriptions, and availability and interpretation of objective reflux testing. Objectives: To review contemporary evidence that does and does not support empiric medication trials for presumed LPR. Methods: PubMed, Scopus and Cochrane Library were searched for literature about benefits, limitations, and alternatives to empiric medication trial for LPR, in order to present both sides of this debate and identify best practices. Results: The majority of physicians perform prolonged empiric medication trial with PPIs for patients with suspected LPR. Because symptoms and signs of LPR are non-specific, empiric medication trials require exclusion of other conditions that can mimic LPR. Following a PPI empiric medication trial, over one-third of patients remain non-responders. The use of hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) has benefits and limitations in objective diagnosis of LPR. Conclusions: Use of PPIs for single-agent empiric medication trial does not account for possible non-responders with nonacid or mixed LPR. If LPR diagnosis remains uncertain, alginates can be added to PPI trials. HEMII-pH testing up front is ideal for patients with suspected LPR, but not always practical; it is indicated when PPI and alginate empiric medication trials have failed or when comorbidities confuse the diagnosis. A more comprehensive, combination therapy empiric medication trial regimen may be needed.
Article
Background: Cough both protects and clears the airway. Cough has three phases: breathing in (inspiration), closure of the glottis, and a forced expiratory effort. Chronic cough has a negative, far-reaching impact on quality of life. Few effective medical treatments for individuals with unexplained (idiopathic/refractory) chronic cough (UCC) are known. For this group, current guidelines advocate the use of gabapentin. Speech and language therapy (SLT) has been considered as a non-pharmacological option for managing UCC without the risks and side effects associated with pharmacological agents, and this review considers the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of SLT in this context. Objectives: To evaluate the effectiveness of speech and language therapy for treatment of people with unexplained (idiopathic/refractory) chronic cough. Search methods: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, trials registries, and reference lists of included studies. Our most recent search was 8 February 2019. Selection criteria: We included RCTs in which participants had a diagnosis of UCC having undergone a full diagnostic workup to exclude an underlying cause, as per published guidelines or local protocols, and where the intervention included speech and language therapy techniques for UCC. Data collection and analysis: Two review authors independently screened the titles and abstracts of 94 records. Two clinical trials, represented in 10 study reports, met our predefined inclusion criteria. Two review authors independently assessed risk of bias for each study and extracted outcome data. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs) or geometric mean differences. We used standard methods recommended by Cochrane. Our primary outcomes were health-related quality of life (HRQoL) and serious adverse events (SAEs). Main results: We found two studies involving 162 adults that met our inclusion criteria. Neither of the two studies included children. The duration of treatment and length of sessions varied between studies from four sessions delivered weekly, to four sessions over two months. Similarly, length of sessions varied slightly from one 60-minute session and three 45-minute sessions to four 30-minute sessions. The control interventions were healthy lifestyle advice in both studies.One study contributed HRQoL data, using the Leicester Cough Questionnaire (LCQ), and we judged the quality of the evidence to be low using the GRADE approach. Data were reported as between-group difference from baseline to four weeks (MD 1.53, 95% confidence interval (CI) 0.21 to 2.85; participants = 71), revealing a statistically significant benefit for people receiving a physiotherapy and speech and language therapy intervention (PSALTI) versus control. However, the difference between PSALTI and control was not observed between week four and three months. The same study provided information on SAEs, and there were no SAEs in either the PSALTI or control arms. Using the GRADE approach we judged the quality of evidence for this outcome to be low.Data were also available for our prespecified secondary outcomes. In each case data were provided by only one study, therefore there were no opportunities for aggregation; we judged the quality of this evidence to be low for each outcome. A significant difference favouring therapy was demonstrated for: objective cough counts (ratio for mean coughs per hour on treatment was 59% (95% CI 37% to 95%) relative to control; participants = 71); symptom score (MD 9.80, 95% CI 4.50 to 15.10; participants = 87); and clinical improvement as defined by trialists (OR 48.13, 95% CI 13.53 to 171.25; participants = 87). There was no significant difference between therapy and control regarding subjective measures of cough (MD on visual analogue scale of cough severity: -9.72, 95% CI -20.80 to 1.36; participants = 71) and cough reflex sensitivity (capsaicin concentration to induce five coughs: 1.11 (95% CI 0.80 to 1.54; participants = 49) times higher on treatment than on control). One study reported data on adverse events, and there were no adverse events reported in either the therapy or control arms of the study. Authors' conclusions: The paucity of data in this review highlights the need for more controlled trial data examining the efficacy of SLT interventions in the management of UCC. Although a large number of studies were found in the initial search as per protocol, we could include only two studies in the review. In addition, this review highlights that endpoints vary between published studies.The improvements in HRQoL (LCQ) and reduction in 24-hour cough frequency seen with the PSALTI intervention were statistically significant but short-lived, with the between-group difference lasting up to four weeks only. Further studies are required to replicate these findings and to investigate the effects of SLT interventions over time. It is clear that SLT interventions vary between studies. Further research is needed to understand which aspects of SLT interventions are most effective in reducing cough (both objective cough frequency and subjective measures of cough) and improving HRQoL. We consider these endpoints to be clinically important. It is also important for future studies to report information on adverse events.Because of the paucity of data, we can draw no robust conclusions regarding the efficacy of SLT interventions for improving outcomes in unexplained chronic cough. Our review identifies the need for further high-quality research, with comparable endpoints to inform robust conclusions.
Article
To investigate the clinical patterns and disease evolution of laryngopharyngeal reflux (LPR) patients. Patients with LPR diagnosed by hypopharyngeal‐esophageal impedance‐pH monitoring were prospectively followed in three medical centers. Symptoms and findings were assessed with reflux symptom score (RSS) and reflux sign assessment (RSA). Patients were treated with 3‐to 9‐month diet and combination of proton pump inhibitors, alginate or magaldrate. Patients were followed for 3 years to determine the clinical evolution of symptoms over time. LPR that did not recur was defined as acute. Recurrent LPR consisted of reflux with one or several recurrences yearly despite successful treatment. Chronic LPR was reflux with a chronic course of symptoms. Predictive indicators of clinical evolution were investigated. One hundred forty patients and 82 healthy individuals completed the evaluations. Among patients, 41 (29.3%), 57 (40.7%), and 42 (30.0%) had acute, recurrent, or chronic LPR respectively. Baseline quality of life‐RSS (QoL‐RSS) and RSS total scores were significantly higher in chronic LPR patients. The post‐treatment decrease of QoL‐RSS and RSS of acute LPR patients were significantly faster as compared to recurrent and chronic patients. QoL‐RSS >5 reported adequate sensitivity (94.2) and specificity (75.3). QoL‐RSS thresholds defined acute (QoL‐RSS = 6–25), recurrent (QoL‐RSS = 26–38), and chronic (QoL‐RSS > 38) LPR. Baseline QoL‐RSS may predict the clinical course of LPR patients: acute, recurrent, or chronic. A novel classification system that groups patients according to the longevity, severity, and therapeutic response of symptoms was proposed: the International Federation of Otorhinolaryngological Societies Classification of LPR. III Laryngoscope, 2022 Reflux may be acute, recurrent, and chronic.
Chapter
Reflux disease, both gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR), has been treated for decades with ever-increasing expensive medication, cost-consuming diagnostic testing, endoscopic procedures, and finally a variety of surgical interventions for those that fail conservative treatment. Although diet and behavioral modifications are sometimes, not always, mentioned, time spent is often limited and barely reinforced. The modern patient typically wants, actually demands, a medication as the culture in modern society is pharmacologically based. Eighty-one percent of Americans take at least one prescription drug. Forty percent over age 65 are on more than five prescription with antidepressants, statins, and proton pump inhibitors (PPI) leading the rest by a far margin [1]. With reflux, typically a PPI is tried, often beyond the recommended time frame. Failure leads to a change in brand name, the addition of a second daily dose, a higher dose, and the addition of a different medication, such as an H2 blocker. Ultimately, billions are spent with this pharmacological approach often prolonging patient discomfort and anxiety for months to years.
Article
Objective Laryngopharyngeal reflux (LPR) and associated symptoms can be refractory to treatment with acid suppressing medication. We investigated the role and evidence for complementary and alternative medicine (CAM) for LPR in this systematic review. Review Methods Complementary and alternative treatment was defined in this systematic review as any non-acid suppressing medication, treatment, or therapy. A literature search was performed by two authors in consultation with a medical librarian using controlled vocabulary for “complementary and alternative medicine” and “laryngopharyngeal reflux” in the databases PubMed and EMBASE, with supplemental searches with Google Scholar. Results Twenty articles were included in this review for the modalities: alginate, diet modification, prokinetics, respiratory retraining, voice therapy, rikkunshito (RKT), hypnotherapy, and sleep positioning. The studies were analyzed for bias based on the Cochrane criteria for RCTs and Methodological Index for non-RCT (MINORS) criteria for all other studies. For each modality a level of evidence was assigned to the current body of evidence using the GRADE approach. Conclusion There is mixed evidence with a high degree of bias and heterogeneity between studies for the modalities presented in the paper. Based on this review, an anti-reflux diet is recommended for all patients and there is some low-quality evidence to support alkaline water. For patients with predominant vocal symptoms there is evidence that supports voice therapy. There is insufficient evidence to recommend prokinetics at this time. For patients with predominant globus symptoms, alginate, RKT, and relaxation strategies may be used in conjunction with acid suppressing medications for symptom relief.
Article
Objectives/Hypothesis To assess the impact of diet on the saliva pepsin concentration of patients with laryngopharyngeal reflux (LPR). Study Design Non‐controlled Prospective Study. Methods Patients with positive LPR regarding hypopharyngeal–esophageal impedance‐pH monitoring (HEMII‐pH) were enrolled from three European Hospitals. Patients collected three saliva samples, respectively, in the morning (fasting), and 1 to 2 hour after lunch and dinner. Patients carefully detailed foods and beverages consumed during meals and before the pepsin samples. The 3‐month treatment was based on the association of diet, proton pump inhibitors, alginate, or magaldrate regarding the HEMII‐pH characteristics. Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were used for assessing the pre‐ to posttreatment clinical evolution. The Refluxogenic Diet Score and the Refluxogenic Score of a Dish (RESDI) were used to assess the refluxogenic potential of foods and beverages. The relationship between saliva pepsin concentration, HEMII‐pH, RESDI, RSS, and RSA was investigated through multiple linear regression. Results Forty‐two patients were included. The saliva pepsin concentration of the 24‐hour period of testing was significantly associated with foods and beverages consumed during the testing period and the evening dinner (r s = 0.973, P < .001). RSS and RSA significantly improved throughout treatment. The level of saliva pepsin in the morning was a negative predictive factor of the therapeutic response regarding RSA and RSS (P < .036). Conclusions Foods and beverages may significantly impact the saliva pepsin concentration of patients with LPR. Patients with high‐level saliva pepsin in the morning had lower therapeutic response compared with those with low‐level saliva pepsin. Level of Evidence 4 Laryngoscope , 2020
Article
Objectives To investigate the prevalence of laryngopharyngeal reflux (LPR) and knowledge of LPR in the Chinese nurse population. Method From October 2021 through December 2021, participants were recruited from the PLA General Hospital's Sixth Medical Center. All included participants completed the Reflux Symptom Index (RSI), and LPR was defined as RSI > 13. In addition, each participant was asked to record whether they had any habits such as preferring to consume high-fat food and carbonated beverages, over-eating at dinner, sedentary after meals and lying down within 2 hour after meals, as well as whether they were aware of LPR. For the participants with RSI >13 points, they were treated using diet and lifestyle behavioral recommendations and were prescribed a twice daily pantoprazole (20 mg, 3 months). Results A total of 828 participants were included. The positivity and awareness rates of LPR were 3.38% and 55.96%, respectively. RSI scores were significantly higher in LPR-positive subjects than in LPR-negative (16.79 ± 4.43 vs. 1.33 ± 2.33). Among the participants with LPR, there were significant positive association between RSI scores and preferring to consume high-fat food and carbonated beverages, over-eating at dinner, lying down within 2 hour after a meal, and sedentary after meals. RSI scores in 63% of participants with LPR significantly decreased from baseline to 1 month posttreatment. From 1 to 3 months posttreatment, 90% of participants had significantly lower RSI scores than pretreatment. Conclusions There are a certain number of LPR patients in the Chinese nurse population, however, knowledge of LPR among nurses is unsatisfactory. Over-eating at dinner, lying down within 2 hour after a meal and sedentary after meals are risk factors for LPR. With combined regular dietary and lifestyle behavioral change and acid-suppressing treatment, most patients with LPR achieve effective remission.
Chapter
Laryngopharyngeal reflux (LPR) is a clinical diagnosis characterized by symptoms due to irritation of extra-esophageal structures including the larynx, pharynx, and lower airway. Although there is not yet a gold-standard diagnostic technique to diagnose LPR, multiple treatment modalities, including lifestyle changes, medical therapies, and surgical therapies, have been proposed. This chapter will evaluate the evidence supporting the different treatment options for LPR.
Chapter
Since the 1960s, laryngopharyngeal reflux (LPR) has been hypothesized as reflux of gastric contents through the upper and lower esophageal sphincter (LES) into the larynx and pharynx (Francis and Vaezi, Clin Gastroenterol Hepatol, 13:1560–1566, 2015). A lax LES or increased pressure through a normal LES has often been considered a factor in LPR, resulting in reflux of acidic or nonacidic nature. Concurrent gastroesophageal reflux disease (GERD) is usually not present. This was first noted by Koufman with 81% of pH-documented LPR patients showing normal esophagoscopy (Koufman, Laryngoscope, 101:1–78, 1991). General symptoms of LPR include hoarseness of the voice, sore throat, chronic cough, globus sensation, dysphagia, sinusitis, and symptoms of asthma. LPR diagnosis via laryngoscopy is subjective and controversial at best with concern for overdiagnosis. Based on its assumed etiology, LPR treatment is based largely on the same standard of care used for GERD with very little in the way of prevention or LPR-specific treatments.
Article
Full-text available
Laryngopharyngeal reflux (LPR) is a prevalent disease associated with non-specific symptoms and findings. Many gray areas persist in the pathogenesis of LPR, the diagnosis and the treatment. Symptoms are poorly correlated with fiberoptic signs or hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring findings. The therapeutic response remains uncertain with some resistant patients to medical or surgical treatment. The development of LPR-symptoms and findings may be related to the refluxate of a myriad of gastroduodenal enzymes, which may modify the laryngopharyngeal and oral microbiome leading to mucosa maintenance and recovery impairments. The diet of patient is important because it may impact the microbiome composition and some foods are known to increase the number of hypopharyngeal reflux events. The number of hypopharyngeal reflux events may be increased by autonomic nerve dysfunction that may have an important role in the persistence of LPR-symptoms.
Article
Full-text available
Objective To assess the evolution of symptoms and findings of laryngopharyngeal reflux (LPR) patients according to the type of reflux (acid, nonacid, mixed and gastroesophageal (GERD)). Design Prospective uncontrolled multi‐center study. Methods One hundred and six patients with LPR have been recruited from three European Hospitals. According to the reflux characteristics at the impedance‐pH monitoring (acid, nonacid, mixed, GERD), patients received a personalized treatment based on the association of diet, pantoprazole, alginate, or magaldrate for 3 months. Reflux Symptom Score (RSS) was assessed at baseline, 6 and 12 weeks posttreatment. Reflux Sign Assessment (RSA) has been used to rate laryngeal and extra‐laryngeal findings at baseline and 12 weeks posttreatment. Overall success rate and the evolution of symptoms and findings were evaluated according to the LPR types. Results 102 LPR patients (42 acid, 33 nonacid, 27 mixed, including 49 with LPR and GERD) completed the study. RSS and RSA total scores significantly improved from baseline to posttreatment time in acid, mixed and nonacid groups. The presence of GERD in addition to LPR did not impact the clinical improvement. The 3‐month success rates of treatment ranged from 62% to 64% and there were no significant differences between groups. The success rate of patients with nonacid LPR was similar to those of patients with mixed and acid LPR. Conclusion MII‐pH is useful to specify the type of LPR and the related most adequate therapeutic regimen. Nonacid or mixed LPR similarly respond to treatment than acid LPR but require a treatment based on alginate or magaldrate covering the nonacid proximal reflux events.
Article
Objectives To assess the feasibility of middle-term proton pump inhibitor (PPI) weaning in patients with laryngopharyngeal reflux (LPR) and evaluate patient awareness of PPI adverse events. Methods We conducted a cross-sectional study of 100 LPR patients treated with an association of diet, PPIs, and alginate. Patients were followed from September 2016 to May 2020. At the end of the initial 3-to-6 months therapeutic period, LPR patients were weaned from PPIs and instructed to respect diet and stress management over the long-term. The 3-year symptom recurrence rate, PPI use, and patient awareness of PPI adverse events were assessed. Results Sixty-seven patients completed the evaluation. Twenty-seven patients (40.3%) reported a chronic course of LPR-symptoms, requiring chronic or occasional PPI use. LPR symptom recurrence occurred 1-to-2 or 3-to-5 times yearly in 8.9% and 20.9% of patients, respectively. Recurrences were managed by short-term diet, alginate, or PPI intake. The remaining patients (29.9%) did not report middle-term LPR recurrence. The 3-year weaning rate of occasional or chronic use of PPIs was 64.2%. Among participants, 26.8% were aware of PPI-related adverse events, most frequently through physicians (33%), online sources (17%), and friends or family (17%). Nonresponder patients were significantly more aware of PPI adverse events than responders (P = 0.029). PPI-attributed adverse events occurred in 29.8% of patients. Conclusion Sixty-four percent of LPR patients treated with PPIs were weaned at 3-year posttreatment time. Different forms of LPR may exist regarding symptom relief, recurrences, and chronic course.
Research
Full-text available
The study's purpose was to examine changes (if any) within the participants' voices over six weeks of voice lessons using the Vocal Function Exercises as an adjunct therapy for suspected LPR-related voice disorders.
Article
Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition of the upper aerodigestive tract mucosa induced by reflux content from stomach. Some of vocal cord diseases are associated with laryngopharyngeal reflux. Because of the pathophysiological features, proton pump inhibitor shows therapeutic effect on some vocal cord diseases. As like that, the gastric reflux contents can make macroscopic or microscopic morphological changes in the upper aerodigestive tract mucosa. Although the pathophysiology of LPRD is relatively clear, clinical diagnosis is still difficult. The diagnosis of LPRD includes objective tests such as 24-hours multichannel intraluminal impedance-pH metry and subjective tests such as questionnaire method. However, the objective verification of reflux is difficult due to invasiveness of the method, and the questionnaire methods have limitations because many symptoms are not specific for LPRD. Moreover, most methods are not fully standardized until now. Despite these limitations, many researchers are struggling to standardize diagnosis and treatment of LPRD, and there are several new achievements recently. Therefore, the purpose of this article is to review the recent literature on the clinical presentation, diagnosis, and treatment of LPRD, and to systematize our knowledge.
Article
Laryngopharyngeal reflux (LPR) is frustrating, as symptoms are nonspecific and diagnosis is often unclear. Two main approaches to diagnosis are empiric treatment trials and objective reflux testing. Initial empiric trial of Proton pump inhibitors (PPI) twice daily for 2-3 months is convenient, but risks overtreatment and delayed diagnosis if patient complaints are not from LPR. Dietary modifications, H2-antagonists, alginates, and fundoplication are other possible LPR treatments. If objective diagnosis is desired or patients' symptoms are refractory to empiric treatment, pH testing with/without impedance should be considered. Additionally, evaluation for non-reflux etiologies of complaints should be performed, including laryngoscopy or videostroboscopy.
Article
Laryngopharyngeal reflux (LPR) is a syndrome caused by reflux of gastric contents into the pharynx or larynx, which leads to symptoms of throat clearing, hoarseness, pain, globus sensation, cough, excess mucus production in the throat, and dysphonia. LPR is a challenging condition, as there is currently no gold standard for diagnosis or treatment, and thus this presents a burden to the healthcare system. Strategies for treatment of LPR are numerous. Medical therapies include proton pump inhibitors, which are first line, H2 receptor antagonists, alginates, and baclofen. Other noninvasive treatment options include lifestyle therapy and the external upper esophageal sphincter compression device. Endoscopic and surgical options include antireflux surgery, magnetic sphincter augmentation, and transoral incisionless fundoplication. Functional laryngeal disorders and laryngeal hypersensitivity can present as LPR symptoms with or without gastroesophageal reflux disease. Though there are minimal studies in this area, neuromodulators and behavioral interventions are potential treatment options. Given the complexity of these patients and numerous available treatment options, we propose a treatment algorithm to help clinicians diagnose and triage patients into an appropriate therapy. Laryngopharyngeal reflux (LPR) is a syndrome caused by reflux of gastric contents into the pharynx or larynx. LPR is a challenging condition, as there is currently no gold standard for diagnosis or treatment. Strategies for treatment of LPR are numerous. In this review we aim to outline current LPR treatment in an algorithmic approach and discuss how clinicians can identify patients who may be more responsive to certain therapies.
Article
Objective The role of lifestyle habits in patients with laryngopharyngeal reflux disease (LPRD) is comparatively underexplored. We aim to examine the specific lifestyle habits in patients with LPRD. METHODS Systematic sampling was applied to select respondents aged 18 through 80 years in otorhinolaryngology-head and neck surgery (OHNS) clinics in Nan Fang Hospital during August 2017–July 2018, 1658 eligible participants were included by a systematic sampling method. Subjects with RSI score>13 were considered as LPRD patients. The risk of reflux symptoms was estimated and multivariate calculated as odds ratios in relation to exposure to tobacco smoking, alcohol, coffee, tea, carbonated drinks, chocolate, spicy food, night sleep time, dinner-to-bed time, subjective sleep quality, and physical exercise. Results There was a significant dose-response association between carbonated beverage and LPRD. Among people who had drinking carbonated drinks the odds ratio was 1.76 (OR 1.77, 95% CI 1.24–2.50, P = .002) compared with non-carbonated drinker. A similar positive association was found for poor subjective sleep quality and shorter night sleeping time, the odds ratio for reflux was 1.58 (95% CI 1.14 to 2.18) among those who always have poor subjective sleep quality compared with those whose have good subjective sleep quality. The odds ratio for reflux was 2.29 (95% CI 1.23–4.28, P = .015) among those who always sleep 3–5 hours every night compared with those who sleep more than 8 hours every night. Beyond that, we found high BMI may have a negative correlation with LPRD, the odds ratio for reflux was .61 (95% CI 0.39 to .95, P = .054) among those whose BMI >25 kg/m2 compared with those BMI ≤ 20 kg/m2. Conclusions Patients with LPRD may have certain lifestyle habits, avoid carbonated beverage, poor subjective sleep quality, and lack of sleep should be advised in treatment of LPRD.
Article
Objective: More than 20% of the US population suffers from laryngopharyngeal reflux. Although dietary/lifestyle modifications and alginates provide benefit to some, there is no gold standard medical therapy. Increasing evidence suggests that pepsin is partly, if not wholly, responsible for damage and inflammation caused by laryngopharyngeal reflux. A treatment specifically targeting pepsin would be amenable to local, inhaled delivery, and could prove effective for endoscopic signs and symptoms associated with nonacid reflux. The aim herein was to identify small molecule inhibitors of pepsin and test their efficacy to prevent pepsin-mediated laryngeal damage in vivo. Methods: Drug and pepsin binding and inhibition were screened by high-throughput assays and crystallography. A mouse model of laryngopharyngeal reflux (mechanical laryngeal injury once weekly for 2 weeks and pH 7 solvent/pepsin instillation 3 days/week for 4 weeks) was provided inhibitor by gavage or aerosol (fosamprenavir or darunavir; 5 days/week for 4 weeks; n = 3). Larynges were collected for histopathologic analysis. Results: HIV protease inhibitors amprenavir, ritonavir, saquinavir, and darunavir bound and inhibited pepsin with IC50 in the low micromolar range. Gavage and aerosol fosamprenavir prevented pepsin-mediated laryngeal damage (i.e., reactive epithelia, increased intraepithelial inflammatory cells, and cell apoptosis). Darunavir gavage elicited mild reactivity and no discernable protection; aerosol protected against apoptosis. Conclusions: Fosamprenavir and darunavir, FDA-approved therapies for HIV/AIDS, bind and inhibit pepsin, abrogating pepsin-mediated laryngeal damage in a laryngopharyngeal reflux mouse model. These drugs target a foreign virus, making them ideal to repurpose. Reformulation for local inhaled delivery could further improve outcomes and limit side effects. Level of evidence: NA. Laryngoscope, 2022.
Chapter
This chapter summarizes an integrative East-West medicine approach for the treatment of reflux disease. The conceptual framework of integrative East-West medicine, therapeutic effects of acupuncture based upon mechanistic and clinical studies, nutritional recommendations from a traditional Chinese medicine (TCM) perspective, and implications upon the brain-gut-microbiota axis are all described. The potential for a brain-naso-sinus-pharynx-larynx-microbiota axis is also discussed using TCM pattern diagnosis as a point of reference for translational investigative research.
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.
Article
Full-text available
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.
Article
Full-text available
This is the second annual report of an international collaborative research group that is examining the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The results of clinical and experimental studies are presented. Carbonic anhydrase (CA), E-cadherin, and MUC gene expression were analyzed in patients with LPR, in controls, and in an in vitro model. In patients with LPR, we found decreased levels of CAIII in vocal fold epithelium and increased levels in posterior commissure epithelium. The experimental studies confirm that laryngeal CAIII is depleted in response to reflux. Also, cell damage does occur well above pH 4.0. In addition, E-cadherin (transmembrane cell surface molecules, which have a key function in epithelial cell adhesion) was not present in 37% of the LPR laryngeal specimens. In conclusion, the laryngeal epithelium lacks defenses comparable to those in esophageal epithelium, and these differences may contribute to the increased susceptibility of laryngeal epithelium to reflux-related injury.
Article
Full-text available
Background: The incidence of esophageal adenocarcinoma is rising dramatically. This increase may reflect increased disease burden, reclassification of related cancers, or overdiagnosis resulting from increased diagnostic inten- sity, particularly upper endoscopy for patients with gas- troesophageal reflux disease or Barrett esophagus. Meth- ods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to extract infor- mation on incidence, stage distribution, and disease- specific mortality for esophageal adenocarcinoma as well as information on related cancers. Results: From 1975 to 2001, the incidence of esophageal adenocarcinoma rose approximately sixfold in the United States (from 4 to 23 cases per million), a relative increase greater than that for melanoma, breast, or prostate cancer. Reclassification of squamous cell carcinoma is an unlikely explanation for the rise in incidence, because the anatomic distribution of esophageal cancer in general has changed. The only loca- tion with increased incidence is the lower third of the esophagus—the site where adenocarcinoma typically arises. Reclassification of adjacent gastric cancer is also unlikely because its incidence has also increased. Because there has been little change in the proportion of patients found with in situ or localized disease at diagnosis since 1975 (from 25% to 31%) and because esophageal adeno- carcinoma mortality has increased more than sevenfold (from 2 to 15 deaths per million), overdiagnosis can be excluded as an explanation for the rise in incidence. Con- clusion: The rising incidence of esophageal adenocarci- noma represents a real increase in disease burden. (J Natl Cancer Inst 2005;97:142- 6)
Article
Full-text available
This is the third annual report of an international research network studying the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The objective of this study was to investigate the presence of E-cadherin (epithelial cadherin; the intercellular junctional complex protein) in relation to the presence of (intracellular) pepsin and carbonic anhydrase isoenzyme III (CAIII). Fifty-four laryngeal biopsy specimens from 18 LPR patients were studied by immunohistochemistry and Western blotting for pepsin, E-cadherin, and CAIII. These data were compared to those from normal control subjects analyzed in another research study. Intracellular pepsin was detected in LPR patients, but not in controls. E-cadherin expression was reduced in patients with LPR. Carbonic anhydrase III expression was not found in the vocal fold or in the majority of samples taken from the ventricle of LPR patients and was inversely associated with E-cadherin membranous expression. The findings of depleted E-cadherin and CAIII and the presence of pepsin appear to correlate with LPR. The reduced protective response indicated by the reduced expression of CAIII may play an important role in the disruption of the intercellular barrier associated with the down-regulation of E-cadherin.
Article
Full-text available
The objectives of this study were to define the conditions that give rise to a stress protein response in laryngeal epithelium and to investigate whether and how stress protein dysfunction contributes to reflux-related laryngeal disease. Western analysis was used to measure stress protein (squamous epithelial proteins Sep70 and Sep53 and heat shock protein Hsp70) and pepsin levels in esophageal and laryngeal tissue specimens taken from both normal control subjects and patients with pH-documented laryngopharyngeal reflux (LPR) who had documented lesions, some of whom had laryngeal cancer. A porcine organ culture model was used to examine the effects of low pH and pepsin (0.1% porcine pepsin A) on stress protein levels. A laryngeal squamous carcinoma (FaDu) cell line was used to examine uptake of human pepsin 3b-tetramethyl-5 and -6 isothiocyanate. Sep70, Sep53, and Hsp70 were found to be expressed at high levels, and pepsin was not detected, in esophageal and laryngeal specimens taken from normal control subjects and in esophageal specimens taken from LPR patients. The patients with LPR were found to have significantly less laryngeal Sep70 (p = .027) and marginally less laryngeal Sep53 (p = .056) than the normal control subjects. Laryngeal Hsp70 was expressed at high levels in the LPR patients. The patients with laryngeal cancer had significantly lower levels of Sep70, Sep53 (p < .01), and Hsp70 (p < .05) than the normal control subjects. A significant association was found between the presence of pepsin in laryngeal epithelium from LPR patients and depletion of laryngeal Sep70 (p < .001). Using the organ culture model, we demonstrated that laryngeal Sep70 and Sep53 proteins are induced after exposure to low pH. However, in the presence of pepsin, Sep70 and Sep53 levels are depleted. Confocal microscopy analysis of cultured cells exposed to labeled pepsin revealed that uptake is by receptor-mediated endocytosis. These findings suggest that receptor-mediated uptake of pepsin by laryngeal epithelial cells, as may occur in LPR, causes a change in the normal acid-mediated stress protein response. This altered stress protein response may lead to cellular injury and thus play a role in the development of disease.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
During 25 years (1960-84) 657 patients were operated on for squamous cell carcinomas (n = 230), adenocarcinomas (n = 399) or anaplastic carcinomas (n = 28) of the thoracic oesophagus or cardia. The male:female ratio was 2.8:1 and the mean age was 66 years (range 22-91 years). Oesophagogastrectomy (n = 514) was performed whenever technically possible. From the first (1960-64) to the last (1980-84) 5-year period the proportion of adenocarcinomas increased from 56 to 78 per cent (P less than 0.001), poorly differentiated cancers increased from 34 to 65 per cent (P less than 0.0001), and stage III-IV tumours increased from 72 to 88 per cent (P less than 0.05). Five-year cumulative rates(s.e.) were 11(3) per cent for operations during 1960-69 (n = 262), 8(2) per cent during 1970-79 (n = 256) and 3(2) per cent during 1980-84 (n = 139; P less than 0.05). Hospital mortality rates (less than or equal to 30 days) and 5-year cumulative survival rates(s.e.) were 6.5 per cent and 36(7) per cent (n = 46) for stage I, 14.0 per cent and 21(4) per cent (n = 114) for stage II, 17.8 per cent and 5(1) per cent (n = 258) for stage III and 23.8 per cent and 3(1) per cent (n = 239) for stage IV tumours (P less than 0.05 and P less than 0.001). Well differentiated (n = 70) cancers, those of medium differentiation (n = 239) and poorly differentiated cancers (n = 348) had 5-year survival rates(s.e.) of 24(5), 10(2) and 5(1) per cent, respectively (P = 0.0007). Squamous cell carcinomas had a better prognosis than adenocarcinomas, even after stratification according to location of primary tumour. The 657 patients who underwent surgery constituted 50 per cent of a total of 1316 cases with cancer of the oesophagus and cardia reported from our catchment area during the study period. Frequency of surgery decreased with age. The annual incidence (number per 100,000 inhabitants aged 20 years or more) of adenocarcinomas of the lower oesophagus and cardia doubled to 5.9 in 1980-84, while that of squamous cell carcinomas tended to decrease (to 2.9). A successive worsening of long-term survival after surgery was explained by significant changes in cancer characteristics having pronounced prognostic significance. Over the 25 years the carcinomas changed towards the present pattern where poorly differentiated adenocarcinomas of the lower third of the oesophagus and cardia in stages III-IV have become predominant.
Article
Esophagitis occurs in patients with excessive acid and/or alkaline gastroesophageal reflux. This observation prompted us to develop a continuously perfused in vivo rabbit esophageal model to examine the potential for different endogenous injurious agents to cause H+ back diffusion and morphologic evidence of esophagitis. We found that HCl at physiologic pH values did not break the mucosal barrier to H+ back diffusion or cause esophagitis. Bile salts at physiologic concentrations in both an acid or alkaline perfusate broke the mucosal barrier and caused H+ back diffusion, but failed to cause a morphologic injury consistent with clinical reflux esophagitis. Instead, proteolytic enzymes, such as pepsin in an acid environment and trypsin in an alkaline environment, caused a severe hemorrhagic erosive esophagitis consistent with that seen clinically. We feel new therapeutic strategies for the treatment of reflux esophagitis should be directed at proteolytic enzymes rather than only HCl or bile salts. Finally, we showed sucralfate to be a mucosal protectant against the acid-pepsin injury.
Article
Esophagitis has been associated with the reflux of acidic gastroduodenal contents. These contents may contain not only HCl but also pepsin, bile, and pancreatic enzymes. This experiment was designed to compare the roles of these components in experimental acid esophagitis. The esophagus of the rabbit was cannulated and perfused continuously via a recirculating system with pH 2 acid test solution. Net flux of H+, K+, glucose, and hemoglobin plus the recovery of tritiated water were determined before and after the addition of pepsin, taurodeoxycholate, or trypsin. Afterward the esophageal segments were graded for gross and microscopic esophagitis. These studies show that pepsin caused significant gross and microscopic esophagitis. Moreover, pepsin also caused significant increases in H+, K+, glucose, and hemoglobin flux as well as decreased recovery of tritiated water. Taurodeoxycholate increased esophageal mucosal permeability to H+, K+, and glucose and decreased the recovery of tritiated water but did not cause significant pathologic change. Trypsin and acid alone did not result in significant esophagitis by either pathologic or ionic permeability criteria. These results show tha disruption of the esophageal mucosal barrier cannot be equated with pathologic injury and that different components of the gastroduodenal contents may have different sites or mechanisms of injury.
Article
The evaluation of medical and surgical outcomes relies on methods of accurately quantifying treatment results. Currently, there is no validated instrument whose purpose is to document the physical findings and severity of laryngopharyngeal reflux (LPR). To evaluate the validity and reliability of the reflux finding score (RFS). Forty patients with LPR confirmed by double-probe pH monitoring were evaluated pretreatment and 2, 4, and 6 months after treatment. The RFS was documented for each patient at each visit. For test-retest intraobserver reliability assessment, a blinded laryngologist determined the RFS on two separate occasions. To evaluate interobserver reliability, the RFS was determined by two different blinded laryngologists. The mean age of the cohort was 50 years (+/- 12 standard deviation [SD]). Seventy-three percent were women. The RFS at entry was 11.5 (+/- 5.2 SD). This score improved to 9.3 (+/- 4.7 SD) at 2 months, 7.3 (+/- 5.5 SD) at 4 months, and 6.1 (+/- 5.2 SD) at 6 months of treatment (P <.001 with trend). The mean RFS for laryngologist no. 1 was 10.8 (+/- 4.1 SD) at the initial screening and 10.8 (+/- 4.0 SD) at the repeat evaluation (r = 0.95, P <.001). The mean RFS for laryngologist no. 2 was 11.1 (+/- 3.8 SD) at the initial screening and 10.9 (+/- 3.7 SD) at the repeat evaluation (r = 0.95, P <.001). The correlation coefficient for interobserver variability was 0.90 (P <.001). The RFS accurately documents treatment efficacy in patients with LPR. It demonstrates excellent inter- and intraobserver reproducibility.
Article
To describe the occurrence of relative proton pump inhibitor (PPI) drug resistance in the treatment of laryngopharyngeal reflux (LPR). A retrospective review was performed for 1053 consecutive adults undergoing double-probe (simultaneous esophageal and pharyngeal) pH testing in our laboratory. Two hundred five patients who had pH studies performed while taking at least a daily dose of PPI therapy were identified; 167 qualified for further analysis. The pH data was reviewed for the presence of abnormalities in either esophageal or pharyngeal acid exposure to evaluate drug efficacy. Forty-four percent (74/167) of the study patients demonstrated abnormal levels of acid exposure. Results were further analyzed to compare failure rates based on different dosage regimens. Patients on once daily doses of PPI failed at a rate of 56%, with lower failure rates for higher-dose regimens. A significant number of LPR patients on PPI therapy demonstrate relative drug resistance.
Article
Laryngopharyngeal reflux (LPR) in otolaryngology patients appears to be different from classic gastroesophageal reflux disease (GERD). In particular, esophagitis and its principal symptom, heartburn, considered the diagnostic sine qua non of GERD, are often absent in LPR. It has therefore been postulated that LPR patients have superior esophageal function. Esophageal acid clearance (EAC) is a measure of the ability of the esophagus to restore neutral pH after reflux events have occurred. It is considered an excellent overall measure of esophageal function. The mean EAC can be calculated from 24-hour pH monitoring data. A comparison of EAC in patients with GERD and LPR has not been previously reported. To compare the EAC of 1) patients with LPR alone, 2) patients with GERD alone, 3) patients with both LPR and GERD, and 4) patients without either LPR or GERD, we studied 200 otolaryngological patients who had undergone 24-hour double-probe (simultaneous pharyngeal and distal esophageal) pH monitoring, 50 in each group. The subgrouping of each patient was determined by previously established pH monitoring criteria. We defined GERD as abnormal esophageal reflux and LPR as abnormal pharyngeal reflux. The patients with GERD had a mean (+/-SD) EAC of 1.44 +/- 1.2 minutes, and those with LPR had a mean EAC of 1.00 +/- 1.00 minutes (p < .05). The patients with both GERD and LPR had a mean EAC of 1.53 +/- 1.01 minutes. The patients without reflux had a mean EAC of 0.53 +/- 0.38 minutes. We conclude that patients with LPR have significantly better EAC than those with GERD. These data suggest that patients with LPR have superior esophageal function. This finding may clarify our understanding of the differences in mechanisms, symptoms, and incidence of esophagitis in patients with LPR and GERD.
Article
Esophageal epithelium has intrinsic antireflux defenses, including carbonic anhydrases (CAs I to IV) that appear to be protective against gastric reflux. This study aimed to investigate the expression and distribution of CA isoenzymes in laryngeal epithelium. Laryngeal biopsy specimens collected from the vocal fold and interarytenoid regions were analyzed by Western blotting and immunofluorescence. Carbonic anhydrases I and II were expressed by the majority of samples analyzed. In contrast, CA III was differentially expressed in the interarytenoid samples and was not detected in any vocal fold samples. The expression of CA III was increased in esophagitis as compared to normal esophageal tissue. Carbonic anhydrase I and III isoenzymes were distributed cytoplasmically in the basal and lower prickle cell layers. The laryngeal epithelium expresses some CA isoenzymes and has the potential to protect itself against laryngopharyngeal reflux. Laryngeal tissue may be more sensitive to injury due to reflux damage than the esophageal mucosa because of different responses of CA isoenzymes.
Article
Laryngopharyngeal reflux (LPR) is present in up to 50% of patients with voice disorders. Currently, there is no validated instrument that documents symptom severity in LPR. We developed the reflux symptom index (RSI), a self-administered nine-item outcomes instrument for LPR. The purpose of this investigation was to evaluate the psychometric properties of the RSI. For validity assessment, 25 patients with LPR were evaluated prospectively before and six months after b.i.d. treatment with proton pump inhibitors (PPI). Each patient completed the RSI as well as the 30-item voice handicap index (VHI). For reliability assessment, the study patients were given the RSI on two separate occasions before the initiation of treatment. Normative RSI data were derived from 25 age-matched and gender-matched controls taken from an existing database of asymptomatic individuals without any evidence of LPR. The mean RSI (+/- standard deviation) of patients with LPR improved from 21.2 (+/- 10.7) to 12.8 (+/- 10.0), and the mean VHI improved from 52.2 (+/- 24.7) to 41.5 (+/- 25.0) after 6 months of therapy (p = 0.001 and 0.065, respectively). Of the three VHI subscales (emotional, physical, functional), only the functional subscale improved significantly (p = 0.037). Patients who experienced a five point or better improvement in RSI were 11 times more likely to experience a five-point improvement in VHI (95% confidence interval = 1.7, 76.8). For reliability assessment, the first and second pretreatment RSIs were 19.9 (+/- 11.1) and 20.9 (+/- 9.6), respectively (correlation coefficient = 0.81, p < 0.001). The single-item correlation coefficients ranged from 0.41 to 0.91 (p < 0.05 for all items). The mean pretreatment RSI in patients with LPR was significantly higher than controls (21.2 versus 11.6; p < 0.001). The mean RSI of patients with LPR after 6 months of PPI therapy approached that of asymptomatic controls (p > 0.05). The RSI is easily administered, highly reproducible, and exhibits excellent construct and criterion-based validity.
Article
To report the prevalence of esophagitis in patients with pH-documented laryngopharyngeal reflux. Prospective study of 58 consecutive patients with documented laryngopharyngeal reflux, all of whom underwent transnasal esophagoscopy as part of their reflux evaluations. All patients with a diagnosis of laryngopharyngeal reflux confirmed by abnormal pharyngeal pH monitoring over a 5-month period were included, and all subjects completed a self-administered reflux symptom index and underwent transnasal esophagoscopy with directed biopsy. Of the 58 study patients with pH-documented laryngopharyngeal reflux, the mean age was 49 years (+/- 13 y), and 53% (31 of 58) were women. Of the study group, 40% (23 of 58) had heartburn and 48% (28 of 58) had abnormal esophageal reflux (by pH monitoring criteria); by transnasal esophagoscopy with biopsy, 12% (7 of 58) had esophagitis and another 7% (4 of 58) had Barrett's metaplasia. Thus, 60% of the study cohort had heartburn, and 81% (47 of 58) had normal esophageal epithelium (i.e., esophagitis or Barrett's metaplasia). In the present series of patients with documented laryngopharyngeal reflux the prevalence of esophagitis and Barrett's metaplasia was only 19%. These data confirm the clinical impression that the patterns, mechanisms, and manifestations of laryngopharyngeal reflux differ from those of classic gastroesophageal reflux disease. Unlike gastroesophageal reflux disease, patients with laryngopharyngeal reflux uncommonly have esophagitis. Thus, although esophagoscopy may be an excellent method for screening the esophagus, it is not the method of choice for diagnosing laryngopharyngeal reflux.
Article
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. A 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. From 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. 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.
Article
To determine whether the presence of laryngopharyngeal reflux symptoms is associated with the presence of esophageal adenocarcinoma (EAC). Most patients diagnosed with EAC have incurable disease at the time of detection. The majority of these patients are unaware of the presence of Barrett's esophagus prior to cancer diagnosis and many do not report typical symptoms of gastroesophageal reflux disease (GERD). This suggests that the current GERD symptom-based screening paradigm may be inadequate. Data support a causal relation between complicated GERD and laryngopharyngeal reflux symptoms. We theorize that laryngopharyngeal reflux symptoms are not recognized expeditiously, resulting in chronic esophageal injury and an unrecognized progression of Barrett's esophagus to EAC. This is a case-comparison (control) study. Cases were patients diagnosed with EAC (n = 63) between 1997 and 2002. Three comparison groups were selected: 1) Barrett's esophagus patients without dysplasia (n = 50), 2) GERD patients without Barrett's esophagus (n = 50), and 3) patients with no history of GERD symptoms or antisecretory medication use (n = 56). The risk factors evaluated included demographics, medical history, lifestyle variables, and laryngopharyngeal reflux symptoms. Typical GERD symptoms and antisecretory medication use were recorded. Multivariate analysis of demographics, comorbid risk factors, and symptoms was performed with logistic regression to provide odds ratios for the probability of EAC diagnosis. The prevalence of patients with laryngopharyngeal reflux symptoms was significantly greater in the cases than comparison groups (P = 0.0005). The prevalence of laryngopharyngeal reflux symptoms increased as disease severity progressed from the non-GERD comparison group (19.6%) to GERD (26%), Barrett's esophagus (40%), and EAC patients (54%). Symptoms of GERD were less prevalent in cases (43%) when compared with Barrett's esophagus (66%) and GERD (86%) control groups (P < 0.001). Twenty-seven percent (17 of 63) of EAC patients never had GERD or laryngopharyngeal reflux symptoms. Fifty-seven percent of EAC patients presented without ever having typical GERD symptoms. Chronic cough, diabetes, and age emerged as independent risk factors for the development of EAC. Symptoms of laryngopharyngeal reflux are more prevalent in patients with EAC than typical GERD symptoms and may represent the only sign of disease. Chronic cough is an independent risk factor associated with the presence of EAC. Addition of laryngopharyngeal reflux symptoms to the current Barrett's screening guidelines is warranted.
Article
The objective was to investigate the potential use of pepsin and carbonic anhydrase isoenzyme III (CA-III) as diagnostic markers for laryngopharyngeal reflux disease. Prospective cell biological investigation was conducted of laryngeal biopsy specimens taken from 9 patients with laryngopharyngeal reflux disease and 12 normal control subjects using antibodies specific for human pepsin (produced in the authors' laboratory within the Department of Otolaryngology at Wake Forest University Health Sciences, Winston-Salem, NC) and CA-III. Laryngeal biopsy specimens were frozen in liquid nitrogen for Western blot analysis and fixed in formalin for pepsin immunohistochemical study. Specimens between two groups (patients with laryngopharyngeal reflux disease and control subjects) were compared for the presence of pepsin. Further analyses investigated the correlation between pepsin, CA-III depletion, and pH testing data. Analysis revealed that the level of pepsin was significantly different between the two groups (P < .001). Secondary analyses demonstrated that presence of pepsin correlated with CA-III depletion in the laryngeal vocal fold and ventricle (P < .001) and with pH testing data in individuals with laryngopharyngeal reflux disease. Pepsin was detected in 8 of 9 patients with laryngopharyngeal reflux disease, but not in normal control subjects (0 of 12). The presence of pepsin was associated with CA-III depletion in the laryngeal vocal fold and ventricle. Given the correlation between laryngopharyngeal reflux disease and CA-III depletion, it is highly plausible that CA-III depletion, as a result of pepsin exposure during laryngopharyngeal reflux, predisposes laryngeal mucosa to reflux-related inflammatory damage.
Article
The incidence of esophageal adenocarcinoma is rising dramatically. This increase may reflect increased disease burden, reclassification of related cancers, or overdiagnosis resulting from increased diagnostic intensity, particularly upper endoscopy for patients with gastroesophageal reflux disease or Barrett esophagus. We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to extract information on incidence, stage distribution, and disease-specific mortality for esophageal adenocarcinoma as well as information on related cancers. From 1975 to 2001, the incidence of esophageal adenocarcinoma rose approximately sixfold in the United States (from 4 to 23 cases per million), a relative increase greater than that for melanoma, breast, or prostate cancer. Reclassification of squamous cell carcinoma is an unlikely explanation for the rise in incidence, because the anatomic distribution of esophageal cancer in general has changed. The only location with increased incidence is the lower third of the esophagus-the site where adenocarcinoma typically arises. Reclassification of adjacent gastric cancer is also unlikely because its incidence has also increased. Because there has been little change in the proportion of patients found with in situ or localized disease at diagnosis since 1975 (from 25% to 31%) and because esophageal adenocarcinoma mortality has increased more than sevenfold (from 2 to 15 deaths per million), overdiagnosis can be excluded as an explanation for the rise in incidence. The rising incidence of esophageal adenocarcinoma represents a real increase in disease burden.
Article
The gastroenterology literature suggests that gastroesophageal reflux disease (GERD) is often associated with obesity. The National Institutes of Health uses body mass index (BMI) to identify patients who are overweight (BMI 25-30) or obese (BMI > 30). The aim of this study was to determine whether there is a relationship between laryngopharyngeal reflux (LPR) and elevated BMI. The study involved a retrospective review of 500 pH-probe studies performed consecutively within the department. Studies performed on antireflux medication or after fundoplication were excluded. From the included study reports, age, sex, height, weight, use of tobacco or alcohol, and pharyngeal and esophageal probe findings were recorded. After controlling for other factors, the relationship between LPR and BMI was determined and statistical analysis performed. Two hundred and eighty-five of the 500 pH studies met inclusion criteria. The overall mean BMI was 27.9 +/- 6.42. The mean BMI for patients with normal studies was 25.6 +/- 5.07, for those with isolated LPR 25.9 +/- 6.44, for those with isolated GERD 28.3 +/- 6.81, and for those with globally abnormal studies (LPR and GERD) 28.8 +/- 6.55. Abnormal pharyngeal reflux did not correlate with increasing BMI; however, abnormal esophageal reflux events correlated with increasing BMI (P = .002). The mean number of pharyngeal reflux events was not elevated in obese patients, whereas the mean number of esophageal reflux events was significantly elevated in obese (P = .02) when compared with nonobese patients. This study demonstrates that pharyngeal reflux is not associated with increasing BMI or obesity in LPR patients. In contrast, abnormal esophageal reflux (GERD) is associated with increasing BMI and obesity. Because of the LPR patient selection bias of this study, these findings may not be applicable to the GERD populations routinely seen by gastroenterologists.
Article
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.
Article
To determine whether measurement of pepsin in throat sputum by immunoassay could be used as a sensitive and reliable method for detecting laryngopharyngeal reflux (LPR) compared with 24-hour double-probe (esophageal and pharyngeal) pH monitoring. Patients with clinical LPR undergoing pH monitoring provided throat sputum samples during the reflux-testing period for pepsin measurement using enzyme-linked immunoadsorbent assay. Pepsin assay results from 63 throat sputum samples obtained from 23 study subjects were compared with their pH monitoring data. Twenty-two percent (14/63) of the sputum samples correlated the presence of pepsin with LPR (pH < or = 4 at the pharyngeal probe), of which the median concentration of pepsin was 0.18 microg/mL (range 0.003-22 microg/mL). Seventy-eight percent (49/63) of the samples unassociated with (pharyngeal) reflux contained no detectible pepsin. Mean pH values for pepsin-positive samples were significantly lower than negative samples at both esophageal probe (pH 2.2 vs. pH 5.0) (P < .01) and the pharyngeal probe (pH 4.4 vs. pH 5.8) (P < .01). When the pepsin assay results were compared with the pharyngeal pH data for detecting reflux (events pH < or = 4), the pepsin immunoassay was 100% sensitive and 89% specific for LPR. Detection of pepsin in throat sputum by immunoassay appears to provide a sensitive, noninvasive method to detect LPR.
Article
There is a perception that the prevalence of gastroesophageal reflux disease (GERD) is increasing, but few studies have directly tackled this issue. By using a systematic approach, this review aimed to assess objectively whether the prevalence of GERD is changing with time. First, population-based studies that reported the prevalence of at least weekly heartburn and/or acid regurgitation were subjected to a time-trend analysis with a Poisson regression model. Second, population-based studies reporting the prevalence of GERD symptoms at 2 time points in the same source population were reviewed. Third, longitudinal studies that charted the prevalence of GERD symptoms and esophagitis in primary and secondary care were examined. The Poisson model revealed a significant (P < .0001) trend for an increase in the prevalence of reflux symptoms in the general population over time. Separately, significant increases with time were found for North America (P = .0005) and Europe (P < .0001) but not Asia (P = .49). Studies of the same source population over time indicated an increase in the prevalence of GERD in the U.S., Singapore, and China but not Sweden. An increase in the prevalence of GERD or esophagitis was found in the majority of longitudinal studies. There is evidence that the prevalence of GERD has increased during the past 2 decades. If this trend continues, it could contribute to the rapidly increasing incidence of more serious complications associated with GERD, such as esophageal adenocarcinoma, as well as costs to healthcare systems and employers.
Article
Exposure of laryngeal epithelia to pepsin during extra-esophageal reflux causes depletion of laryngeal protective proteins, carbonic anhydrase isoenzyme III (CAIII), and squamous epithelial stress protein Sep70. The first objective of this study was to determine whether pepsin has to be enzymatically active to deplete these proteins. The second objective was to investigate the effect of pH on the activity and stability of human pepsin 3b under conditions that might be found in the human esophagus and larynx. Prospective translational research study. An established porcine in vitro model was used to examine the effect of active/inactive pepsin on laryngeal CAIII and Sep70 protein levels. The activity and stability of pepsin was determined by kinetic assay, measuring the rate of hydrolysis of a synthetic pepsin-specific substrate after incubation at various pH values for increasing duration. Active pepsin is required to deplete laryngeal CAIII and Sep70. Pepsin has maximum activity at pH 2.0 and is inactive at pH 6.5 or higher. Although pepsin is inactive at pH 6.5 and above, it remains stable until pH 8.0 and can be reactivated when the pH is reduced. Pepsin is stable for at least 24 hours at pH 7.0, 37 degrees C and retains 79% +/- 11% of its original activity after re-acidification at pH 3.0. Detectable levels of pepsin remain in laryngeal epithelia after a reflux event. Pepsin bound there would be enzymatically inactive because the mean pH of the laryngopharynx is pH 6.8. Significantly, pepsin could remain in a form that would be reactivated by a subsequent decrease in pH, such as would occur during an acidic reflux event or possibly after uptake into intracellular compartments of lower pH.
Article
To review and summarize the current literature on transnasal esophagoscopy, and to compare information with conventional esophagoscopy. Medline (Ovid), book chapters. A thorough review of the literature using the Medline database was performed with the following search terms: esophagoscopy, transnasal esophagoscopy, ultrathin endoscopy, and esophagoscope. The literature seems to support the equivalence of transnasal esophagoscopy and conventional esophagoscopy in image quality and diagnostic capability. It also points to some potential advantages of transnasal esophagoscopy. Transnasal esophagoscopy is a useful tool for accurate diagnosis and can be used in a variety of office procedures.
Kouf-man JA. Sensitive pepsin immunoassay for detection of laryn-gopharyngeal reflux
  • J Knight
  • Lively
  • Mo
  • Johnston
  • Dettmar
Knight J, Lively MO, Johnston N, Dettmar PW, Kouf-man JA. Sensitive pepsin immunoassay for detection of laryn-gopharyngeal reflux. Laryngoscope 2005;115:1473-8
Reflux r287 Koufman, Low-Acid Diet for Laryngopharyngeal Reflux 287 laryngitis and its sequelae: the diagnostic role of 24-hour pH monitoring
  • Ja Koufman
  • Gj Wiener
  • Wu
  • Castell
Koufman JA, Wiener GJ, Wu WC, Castell DO. Reflux r287 Koufman, Low-Acid Diet for Laryngopharyngeal Reflux 287 laryngitis and its sequelae: the diagnostic role of 24-hour pH monitoring. J Voice 1988;2:78-9
Validity and reli-ability of the reflux symptom index (RSI)
  • Belafsky Pc
  • Postma Gn
  • Koufman
  • Ja
Belafsky PC, Postma GN, Koufman JA. Validity and reli-ability of the reflux symptom index (RSI). J Voice 2002;16:274-7.
Dropping acid: the reflux diet cookbook and cure
  • Ja Koufman
  • Jc Stern
  • Bauer
Koufman JA, Stern JC, Bauer MM. Dropping acid: the reflux diet cookbook and cure. Minneapolis, Minn: Reflux Cook books, 2010.
Code of Federal Regulations — Title 21 — Food and Drugs Chapter I, Department of Health and Human Services Subchapter B — Food for Human Consumption Part
  • Acidified
Acidified foods. Code of Federal Regulations — Title 21 — Food and Drugs Chapter I, Department of Health and Human Services Subchapter B — Food for Human Consumption Part
Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies
  • Mr Amin
  • Gn Postma
  • P Johnson
  • N Digges
  • Ja Koufman
  • A Becher
  • R Jones
Amin MR, Postma GN, Johnson P, Digges N, Koufman JA. Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux. Otolaryngol Head Neck Surg 2001;125:374- 8. 23. El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther 2010;32:720-37.