OBJECTIVE: There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs.
METHODS: Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science.
METHODS: We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used.
RESULTS: Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2  = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke\'s edema, nodules, and polyps (P for subgroup difference = .09).
CONCLUSIONS: Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

OBJECTIVE: Non-erosive reflux disease (NERD) accounts for over half of all gastroesophageal reflux cases and is characterized by reflux symptoms with pathologic acid exposure on pH monitoring but no evidence of erosions on upper endoscopy. Ambulatory pH monitoring is limited by availability and patient tolerance. The utility of performing esophageal mucosal biopsies in diagnosing NERD is unclear. We conducted a systematic review and meta-analysis to determine the sensitivity of esophageal mucosal biopsies in diagnosing NERD.
METHODS: Data were obtained from Embase and Ovid MEDLINE from inception to April 2021. Studies were included if esophageal mucosal biopsies were taken and analyzed using conventional histopathologic analysis in symptomatic NERD patients. Relevant data was including histologic abnormalities and location of the biopsy. Sensitivity and specificity were calculated against healthy controls or those with functional heartburn.
RESULTS: The search yielded 2871 studies, of which 10 studies met our inclusion criteria and contained raw data. Histological abnormalities included histologic sum scores, papillary elongation, basal cell hyperplasia, and dilated intraepithelial spaces. When assessing for the presence of any abnormality, biopsies taken <3 cm from the lower esophageal sphincter (LES) had a pooled sensitivity of 0.71 (95% CI 0.64-0.77) and specificity of 0.64 (95% 0.54-0.73); however, analysis of individual histologic features such as the presence of eosinophils improved the sensitivity.
CONCLUSIONS: Although esophageal mucosal biopsies had poor sensitivity at diagnosing NERD, biopsies taken within 3 cm of the LES had higher sensitivity when pathologists reported upon eosinophils and dilated intraepithelial spaces.

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts\' consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

The purpose of this study was to assess the variation in resource utilization for the diagnosis and treatment of dysphonia or hoarseness in patients with suspected laryngopharyngeal reflux (LPRD) and/or gastroesophageal reflux (GERD). Secondary data was collected from a single-institution database of charts from patients evaluated between October 1, 2011 and March 31, 2020. This study was conducted as a retrospective chart review. Key outcome variables included demographic data, initial specialty visit, date of first symptom evaluation to final follow-up visit, additional procedural evaluation, and final diagnosis as attributed by the diagnosing physician. Inclusion criteria included patients ≥18 older referred to providers for suspected LPRD/GERD with a primary complaint of voice changes or hoarseness and appeared for follow-up. A total of 134 subjects were included for analysis. Data analysis included descriptive and univariate analysis, chi-square test of independence, independent means t test, and 1-way analysis of variance. Most patients (88) received some form of procedural evaluation in addition to clinical evaluation. The most frequent was videostroboscopy (59). Patients who first visited a gastroenterologist were more likely to undergo esophageal pH-monitoring (n = 14, P < .001) and manometry (n = 10, P < .001). Patients referred to speech-language pathology were very likely to undergo videostroboscopic evaluation (n = 7, P < .001). The prevailing final diagnosis as attributed by the diagnosing physician was confirmed to be of non-reflux etiology (49) or due to GERD alone (34). LPRD only was the least frequent diagnosis (10). Our results demonstrate that there is significant variation in the number and type of diagnostic tests based on the type of practitioner initially seen by the patient. Additionally, of patients thought to have voice change or hoarseness because of LPRD and/or GERD, more than a third had a non-reflux cause of their symptoms. Further research should identify beneficial patterns in resource utilization and further diagnostic utility of diagnostic procedures for more accurate diagnosis.

OBJECTIVE: Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children.
METHODS: A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021.
RESULTS: A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation.
CONCLUSIONS: Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.

Patients with achalasia frequently develop gastroesophageal reflux (GER)-related symptoms and complications after per-oral endoscopic myotomy (POEM). Reflux symptoms are thought to be due to GER and the current treatment of post-POEM GER focuses on acid suppression with proton pump inhibitors (PPI). However, reflux symptoms in achalasia patients post-POEM can be due to true reflux, nonreflux esophageal acidification due to stasis or acid fermentation, or esophageal hypersensitivity to chemical or mechanical stimuli. True acidic reflux is not always the cause of reflux symptoms. Twenty-four-hour pH monitoring with impedance is essential to differentiate causes of esophageal acidification. PPI is useful only in true acidic reflux. Detection of acid fermentation requires manual review of a 24-h pH study, as automated review often overestimates acid exposure time due to its inability to differentiate true reflux from fermentation. Stasis of ingested acidic food warrants evaluation of esophageal emptying by timed barium esophagogram. In cases of inadequate emptying, esophagogastric junction (EGJ) distensibility can be evaluated by a functional lumen imaging probe. Impaired distensibility with inadequate esophageal emptying suggests treatment failure and may require retreatment. In treatment-refractory patients, esophageal hypersensitivity should be considered and treated with neuromodulators. Thus, the diagnostic approach to post-POEM reflux symptoms should evolve to identify various patterns of esophageal acidification, esophageal emptying patterns, EGJ distensibility, and hypersensitivity. Consequently, the treatment of GER post-POEM should not be limited to treating esophageal acidification by reflux, but should encompass other causes of acidification and esophageal hypersensitivity.

Rumination syndrome is a functional disorder characterized by the involuntary regurgitation of recently swallowed food from the stomach into the mouth, from where it can be re-chewed or expelled. Clinically, it is characterized by repeated episodes of effortless food regurgitation. The most usual complaint is frequent vomiting. The physical mechanism that generates regurgitation events is dependent on an involuntary process that alters abdominal and thoracic pressures accompanied by a permissive oesophageal-gastric junction. The diagnosis of rumination syndrome is clinical, highlighting the importance of performing an exhaustive anamnesis on the characteristics of the symptoms. Complementary tests are used to corroborate the diagnosis or rule out organic pathology. Treatment is focused on behavioural therapies as the first line, reserving pharmacological and surgical therapies for refractory cases.

Esophageal acid exposure time (AET) during 24 h pH monitoring is reproducible and predictive outcomes of treatment for gastroesophageal reflux disease. Several small Asian studies have investigated the normal range of the AET; the range may be different from that in Western populations. We evaluated its normal range in healthy Asian compared to Western subjects.
We searched PubMed, Embase, Cochrane Library, and KoreaMed for studies that reported pH monitoring parameters in healthy subjects. Studies that reported the AET values of healthy subjects were eligible for the analyses. The upper limit of normal of the AET was obtained from the 95th percentile of the available raw data or calculated as the mean value +2 standard deviations.
Nineteen Asian and 49 Western studies were assessed. The estimated AET values were analyzed using a bootstrapping technique, weighted according to the sample size. The mean AET was 1.1% and 2.9% in the Asian and Western populations, respectively. The upper limit of the reference range was 3.2% (95% confidence interval [CI], 2.7-3.9%) and 8.2 (95% CI, 6.7-9.9) in the Asian and Western populations, respectively. The normal AET differed between the Asian and Western populations because the CI of the two groups did not overlap.
The upper limit of normal of the AET in healthy Asian subjects was 3.2% (95% CI, 2.7-3.9%), which was lower than that of healthy Western subjects.

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.

OBJECTIVE: Gastroesophageal reflux disease (GERD) has been associated with head and neck cancer (HNC), including laryngeal and pharyngeal anatomical sites. A systematic review and meta-analysis was performed to examine these associations.
METHODS: Articles were retrieved from the Medline, Web of Science, Scopus, and Embase databases using keywords \"gastroesophageal reflux disease\", \"laryngopharyngeal reflux\", \"head and neck cancer\", and associated variants. Inclusion criteria were English language publications, human subjects, and controlled studies with described development of head and neck cancer among individuals with GERD. 13 studies with a total of 39,824 patients were included.
RESULTS: Overall, presence of GERD was associated with an increased risk of developing HNC (OR = 1.86, 95% Confidence Interval [CI] = 1.27-2.74). This association remained significant with laryngeal cancers (OR = 1.95, 95% CI = 1.33-2.86), but not pharyngeal cancers (OR = 1.56, 95% CI = 0.86-2.83). Subgroup analyses of hypopharyngeal (OR = 2.26, 95% CI = 0.67-7.68) and oropharyngeal subsites (OR = 1.39, 95% CI = 0.51-3.84) were not statistically significant. Meta-analysis of studies that objectively assessed reflux, such as pH monitor placement, showed statistical significance (OR = 2.81, 95% CI = 1.36-5.81), while studies that used subjective reporting or chart review of GERD were not significant (OR = 1.46, 95% CI = 0.89-2.40). Association between H. pylori infection and head and neck cancers was not statistically significant (OR = 2.66, 95% CI = 0.59-11.97).
CONCLUSIONS: A diagnosis of GERD is associated with a later diagnosis of HNC, but this association is not significant for pharyngeal cancers. Associations of GERD with HNC may be specific to laryngeal cancers.
METHODS: Systematic review and meta-analysis of case control studies (3a).