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Background: Supragastric belching (SGB) and rumination are behavioral disorders associated with proton pump inhibitor (PPI) non-response and can be diagnosed using multichannel intraluminal impedance-pH (MII-pH) and post-prandial high-resolution impedance manometry (PPHRIM). This pilot study compared diagnostic yield and inter-rater agreement for SGB and rumination using MII-pH and PPHRIM., Methods: Three esophageal physiologists performed blinded interpretations of MII-pH and PPHRIM in 22 PPI non-responders. Raters selected from 4 diagnostic impressions (normal, GERD, behavioral disorders, GERD+behavioral disorders) without clinical context. Primary outcomes were diagnostic impressions compared against clinical gold standard impression, between raters, and between test modalities. Following a 28-month wash-out period, raters re-interpreted MII-pH with clinical context and under consensus definition of diagnostic criteria., Key Results: Compared to gold standard, rater accuracy for presence of behavioral disorders ranged from 45 to 77% on MII-pH and 45-59% on PPHRIM. On MII-pH, inter-rater agreement was fair for diagnosis (ĸ0.32, p < 0.01) and suboptimal for presence of behavioral disorders (ĸ0.13, p = 0.14). On PPHRIM, inter-rater agreement was suboptimal for both diagnosis (ĸ0.03, p = 0.34) and presence of a behavioral disorder (ĸ-0.22, p = 0.96). Inter-rater agreement improved in post hoc MII-pH interpretations. Rumination was more frequently identified on PPHRIM (23, 35%) compared to MII-pH (7, 11%)., Conclusions and Inferences: Diagnostic accuracy and inter-rater agreement are higher for MII-pH than PPHRIM, and behavioral disorders are more frequently identified on PPHRIM. Identifying behavioral disorders on MII-pH and PPHRIM has implications for clinical evaluation of PPI non-response; clinical context is essential for accurate study interpretation. Further work is needed to standardize definitions and interpretations., (© 2021 John Wiley & Sons Ltd.)

Background: There is a need to identify factors outside of abnormal reflux that contribute to gastroesophageal reflux disease (GERD). Esophageal hypervigilance is a psychological process impacting symptom experience in esophageal disease. However, little is known about the presence of hypervigilance in GERD phenotypes, especially in those with abnormal acid exposure or symptom index scores. The primary aim was to assess differences in self-reported esophageal hypervigilance across different GERD presentations. The secondary aim was to evaluate esophageal hypervigilance as a predictor of symptom severity., Methods: We conducted retrospective data analyses on a cohort of adult patients with reflux symptoms that underwent 96-hour wireless pH monitoring from 9/2015 to 9/2017. Patients were stratified into groups based on the number of days they exhibited positive acid exposure time (AET; 0 days, 1-2 days, 3+ days), and symptom index scores (SI; 0 days, 1-day, 2+ days). Esophageal hypervigilance and anxiety, and symptom frequency and severity were assessed between groups., Key Results: A total of 123 AET cases and 116 SI cases were included for analysis. Esophageal hypervigilance and anxiety scores did not significantly differ based on the number of days of positive AET (p = 0.311) or SI (p = 0.118). Symptom severity and perceived symptom frequency differed between groups. Hypervigilance significantly predicted symptom severity, when controlling for symptom-specific anxiety., Conclusions: Esophageal hypervigilance is persistent across patients with reflux, irrespective of acid burden and symptom index, and significantly predicts symptom severity. Hypervigilance should be considered as an independent factor contributing to esophageal symptom perception., (© 2021 John Wiley & Sons Ltd.)

Background: Increased esophagogastric junction (EGJ) distensibility is thought to contribute to gastroesophageal reflux disease (GERD). Using the functional lumen imaging probe (FLIP), we aimed to assess the esophageal response to distension among patients undergoing esophageal pH monitoring., Methods: 25 patients (ages 22-73; 13 females) who underwent ambulatory wireless esophageal pH testing while off proton-pump inhibitors were evaluated with FLIP during sedated upper endoscopy. Esophageal reflux was quantified by total percent acid exposure time (AET; <6% was considered normal). FLIP studies were analyzed using a customized program generate FLIP topography plots to identify esophageal contractility patterns and to calculate the EGJ-distensibility index (DI). Reflux symptoms were assessed with the GERDQ. Values reflect median (interquartile range)., Results: Among all patients, the AET was 7.2% (3.7-11.1) and EGJ-DI was 4.2 (2.5-7.6) mm 2 /mm Hg. Repetitive antegrade contractions (RACs) were induced in 19/25 (76%) of patients; AET was lower among patients with (6.1%, 3-7.8) than without (14.9, 8.5-22.3) RACs (P = .009). Correlation was weak and insignificant between AET and EGJ-DI, GERDQ and AET, and GERDQ and EGJ-DI. Patients with abnormal AET (n = 16) and normal AET (n = 9) had similar EGJ-DI, 4.6 mm 2 /mm Hg (2.9-9.2) vs 3.2 (2.2-5.1), P = .207 and GERDQ, P = .138., Conclusions: Abnormal esophageal acid exposure was associated with an impaired contractile response to volume distention of the esophagus. This supports that acid exposure is dependent on acid clearance mechanisms., (© 2017 John Wiley & Sons Ltd.)

Background & Aims: Recognition of rumination and supragastric belching is often delayed as symptoms may be mistakenly attributed to gastroesophageal reflux disease. However, distinct from gastroesophageal reflux disease, rumination and supragastric belching are more responsive to behavioral interventions than to acid-suppressive and antireflux therapies. Postprandial high-resolution impedance manometry (PP-HRIM) is an efficient method to identify rumination and belches. We investigated the distribution of postprandial profiles determined by PP-HRIM, and identified patient features associated with postprandial profiles among patients with nonresponse to proton pump inhibitors (PPIs)., Methods: We performed a retrospective analysis of PP-HRIM studies performed on 94 adults (mean age, 50.6 y; 62% female) evaluated for PPI nonresponsiveness at an esophageal referral center, from January 2010 through May 2016. Following a standard esophageal manometry protocol, patients ingested a solid refluxogenic test meal (identified by patients as one that induces symptoms) with postprandial monitoring up to 90 minutes (median, 50 min). Patients were assigned to 1 of 4 postprandial profiles: normal; reflux only (>6 transient lower esophageal sphincter relaxations (TLESRs)/h); supragastric belch (>2 supragastric belches/h), with or without TLESR; or rumination (≥1 rumination episode/h) with or without TLESR and supragastric belching. The primary outcome was postprandial profile., Results: Of the study participants, 24% had a normal postprandial profile, 14% had a reflux-only profile, 42% had a supragastric belch profile, and 20% had a rumination profile. In multinomial regression analysis, the rumination group most frequently presented with regurgitation, the supragastric belch and rumination groups were younger in age, and the reflux-only group had a lower esophagogastric junction contractile integral. The number of weakly acidic reflux events measured by impedance-pH monitoring in patients receiving PPI therapy was significantly associated with frequency of rumination episodes and supragastric belches., Conclusions: In a retrospective analysis of 94 nonresponders to PPI therapy evaluated by PP-HRIM, we detected an abnormal postprandial pattern in 76% of cases: 42% of these were characterized as supragastric belching, 20% as rumination, and 14% as reflux only. Age, esophagogastric junction contractility, impedance-pH profiles, and symptom presentation differed significantly among groups. PP-HRIM can be used in the clinic to evaluate mechanisms of PPI nonresponse., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Up to 50% of patients with reflux symptoms do not manifest a satisfactory symptom response to proton pump inhibitor (PPI) therapy. Our primary aim in this study was to identify factors associated with symptom perception among PPI non-responder phenotypes., Methods: This prospective observational cohort study was performed from September 2014 to January 2017 at a single academic medical center and included PPI non-responders who underwent 24-h impedance-pH monitoring and completed a questionnaire set measuring patient-reported symptom severity, quality of life (QOL), and psychosocial distress. Participants were separated into cohorts based on impedance-pH results: on PPI: -acid exposure time (AET)/-symptom-reflux association (SRA), +AET, and -AET/+SRA; off PPI: functional (-AET/-SRA), gastroesophageal reflux disease (GERD) (+AET), and reflux hypersensitivity (RHS) (-AET/+SRA). The primary outcome was abnormal GERD symptom severity defined by GerdQ≥8., Results: One hundred and ninety-two participants were included. Impedance-pH on PPI was performed on 125: 72 (58%) -AET/-SRA, 42 (34%) +AET, and 11 (9%) -AET/+SRA. Among the -AET/-SRA group, younger age, higher dysphagia scores, QOL impairment, and higher brief symptom index were associated with GerdQ≥8. Among the +AET group, higher number of reflux-associated symptoms and lower distal contractile integral was associated with GerdQ≥8. Impedance-pH off PPI was performed on 67 participants: 39 (58%) functional, 16 (24%) GERD, and 12 (18%) RHS. Among the functional group, higher QOL impairment and dysphagia scores were seen with GerdQ≥8., Conclusions: Perceptions of reflux symptoms are associated with psychosocial distress, reduced QOL, and sensation of dysphagia among PPI non-responders with normal impedance-pH. Among PPI refractory GERD patients, patient-reported symptom severity is associated with physiological differences, as opposed to psychosocial factors.