BACKGROUND: Patients with gastroesophageal reflux disease (GERD) are commonly instructed to reduce coffee intake. However, prior studies evaluating the effects of coffee on GERD yielded conflicting results. We aimed to perform a comprehensive systematic review and meta-analysis to assess the association between coffee use and risk of GERD and its complications.

METHODS: A protocolized search strategy was developed for PubMed, EMBASE, and Web of Science databases in accordance with PRISMA and MOOSE guidelines. Measured outcomes for GERD were compared between coffee drinkers and non-drinkers. Dichotomous events between unmatched groups were used to calculate pooled proportions with rates estimated using random effects models and effect size. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot asymmetry and Egger regression.

RESULTS: A total of 40 studies encompassing 122,074 patients were included (85,400 coffee drinkers vs 36,674 non-drinkers). GERD was more common among coffee users than non-users [34.9% (CI:28.5-41.8) vs 30.7% (CI:25.2-36.7); OR:1.18 (CI:1.03-1.36; I2=89.38)]. There was no significant association between coffee intake and Barrett's esophagus [22.1% (CI:12.8-35.4) users vs 17.6% (CI:5.5-43.8) non-users; OR:1.13 (CI:0.79-1.61; I2=55.5)]. There was no evidence of publication bias based on funnel plot and Egger regression testing (p>0.05 for all analyses).

CONCLUSION: Coffee use was associated with a small, statistically significant increased rate of GERD, but not Barrett's. The magnitude of this effect, however, is of unclear clinical significance. The role of routine avoidance/reduction of coffee intake as universal lifestyle modification for GERD needs further evaluation.

BACKGROUND: The value of esophageal baseline impedance (BI) in assessing proximal reflux and laryngopharyngeal symptoms (LPS) is unclear.

METHODS: 208 patients with LPS underwent 24-hour combined hypopharyngeal-esophageal impedance-pH monitoring. Proximal/distal BI were obtained and a slope-and-intercept model of proximal BI contour was constructed.

RESULTS: Proximal BI correlated with proximal/pharyngeal reflux (r=-0.21, p<0.01) and reflux symptom index (r=-0.14, p=0.08). Proximal BI contour model incorporating both BI change (slope) and BI just below upper esophageal sphincter (intercept) outperformed models using individual BI measures in predicting proximal (AIC: 110 vs 251-253) or pharyngeal (AIC: 32 vs 141-148) reflux.

CONCLUSION: Proximal esophageal impedance contour predicts proximal reflux n patients with LPS.

BACKGROUND & AIMS: The impact of the esophageal eosinophilic distribution pattern on treatment outcomes in eosinophilic esophagitis (EoE) is unclear. We aimed to determine if the eosinophil distribution at index endoscopy predicts proton pump inhibitor (PPI) response in EoE.

METHODS: This was a cohort study of newly diagnosed adult patients with EoE from 3 hospitals. All included patients received ≥8-week PPI trial and underwent repeat biopsies to assess response. Primary analyses compared PPI response between isolated distal disease (≥15 eosinophils/hpf on distal but not proximal biopsies) and proximal/diffuse eosinophilia (≥15 eosinophils/hpf on proximal ± distal biopsies). Secondary analyses categorized patients as distal-predominant (distal >proximal eosinophils by ≥10/hpf), proximal predominant (proximal >distal eosinophils by ≥10/hpf), or even distribution pattern. Multivariable analyses were performed using logistic regression, adjusting for potential confounders.

RESULTS: A total of 266 patients (50.8% male; 89.1% White) met inclusion criteria, including 66 with isolated distal and 200 with proximal/diffuse disease. PPI response was higher among patients with isolated distal disease (histologic remission [<15 eosinophils/hpf post-PPI]: 63.6% vs 44.5%; P = .01; deep remission [<6 eosinophils/hpf]: 54.5% vs 31.0%; P = .001; symptom improvement: 92.4% vs 81.0%; P = .03). On multivariable analyses, isolated distal disease remained independently associated with histologic response (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.10-3.77; P = .02), deep remission (aOR, 2.46; 95% CI, 1.33-4.54; P = .02), and symptom improvement (aOR, 4.1; 95% CI, 1.4-12.01; P = .01). On secondary analyses, proximal-predominant eosinophilia independently predicted PPI histologic nonresponse compared with distal-predominant (aOR, 0.52; 95% CI, 0.28-0.99; P = .04) or any nonproximal (aOR, 0.54; 95% CI, 0.3-0.97; P = .04) pattern.

CONCLUSIONS: Isolated distal eosinophilia at index endoscopy independently predicted PPI response in patients with EoE, whereas proximal-predominant pattern predicted nonresponse. Patterns of esophageal eosinophilic distribution may reflect different disease phenotypes and help guide management.

INTRODUCTION: The term laryngopharyngeal reflux (LPR) is frequently applied to aerodigestive symptoms despite lack of objective reflux evidence. The aim of this initiative was to develop a modern care paradigm for LPR supported by otolaryngology and gastroenterology disciplines.

METHODS: A 28-member international interdisciplinary working group developed practical statements within the following domains: definition/terminology, initial diagnostic evaluation, reflux monitoring, therapeutic trials, behavioral factors and therapy, and risk stratification. Literature reviews guided statement development and were presented at virtual/in-person meetings. Each statement underwent 2 or more rounds of voting per the RAND Appropriateness Method; statements reaching appropriateness with ≥80% agreement are included as recommendations.

RESULTS: The term laryngopharyngeal symptoms (LPS) applies to aerodigestive symptoms with potential to be induced by reflux and include cough, voice change, throat clearing, excess throat phlegm, and throat pain. Laryngopharyngeal reflux disease (LPRD) refers to patients with LPS and objective evidence of reflux. Importantly, the presence of LPS does not equate to LPRD. Laryngoscopy has value in assessing for nonreflux laryngopharyngeal processes, but laryngoscopic findings alone cannot diagnose LPRD. LPS patients should be categorized as with or without concurrent esophageal reflux symptoms. While lifestyle modification and empiric trials of acid suppression ± alginates are appropriate when esophageal reflux symptoms coexist, upper endoscopy and ambulatory reflux monitoring are required for LPRD diagnosis when symptoms persist, when LPS is isolated, or when management needs to be escalated to include invasive antireflux management. The two recommended ambulatory reflux monitoring modalities, 24-hour pH-impedance and 96-hour wireless pH monitoring, are not mutually exclusive with distinct roles for the evaluation of LPS. Laryngeal hyperresponsiveness and hypervigilance commonly contribute to both LPS and LPRD presentations and are responsive to laryngeal recalibration therapy and neuromodulators.

DISCUSSION: The San Diego Consensus represents the formal modern-day interdisciplinary care paradigm to evaluate and manage LPS and LPRD.

INTRODUCTION: Visual Analog Scales (VAS) are simple, easy for patients to comprehend, and require limited translation. We evaluated the value of esophageal global symptom severity (GSS) measured using VAS in assessing initial reflux symptom burden as compared with other validated questionnaires, esophageal symptom burden, and outcome after reflux management.

METHODS: We analyzed pooled data from published historical cohorts of patients undergoing pH-impedance testing for reflux symptoms from 3 continents (North America, Europe, Asia). Univariate (Spearman correlation), multivariable (general linear regression), and receiver operating characteristic analyses were performed to compare GSS with validated symptom instruments including gastroesophageal reflux disease questionnaire (GERDQ), GERD health-related quality of life (GERD-HRQL), Reflux Symptom Index (RSI), and metrics from pH-impedance monitoring per Lyon Consensus 2.0.

RESULTS: One thousand two hundred ninety-six patients (mean age 52.0 years, 61.9% female) were included: 937, 197, and 162 from North America, Europe, and Asia, respectively. GSS significantly correlated with GERDQ (R = 0.455), GERD-HRQL (R = 0.440), RSI (R = 0.491), acid exposure time (AET) (R = 0.158), and total reflux episodes (R = 0.161) ( P < 0.0001 for each comparison). The mean GSS was higher with abnormal GERDQ, GERD-HRQL, RSI, pathologic AET, and conclusive GERD per Lyon Consensus ( P < 0.0001 each comparison). On receiver operating characteristic analyses, GSS was noninferior to GERDQ, GERD-HRQL, and RSI in predicting pathologic AET and total reflux episodes, and conclusive GERD. Percentage improvement in GSS after antireflux treatment significantly correlated with change in GERDQ (R = 0.536, P < 0.0001) and treatment satisfaction (R = 0.532 P = 0.0002). On multivariable linear regression analyses, percentage change in GSS remained an independent predictor of both change in GERDQ (β = 0.813, P < 0.0001) and satisfaction with antireflux therapy (β = 1.90, P = 0.0006).

DISCUSSION: GSS correlates with other validated reflux questionnaires and discriminates abnormal from normal reflux burden in patients with reflux symptoms. GSS change also reflects reflux treatment outcome and satisfaction. GSS is a useful addition to patient symptom assessment before and after GERD treatment.

BACKGROUND: The pathophysiology behind gastroesophageal reflux disease and its association with poor outcomes after lung transplantation is incompletely understood. The physiologic impact of lung transplantation on pulmonary function, intrathoracic pressures, and vagal innervation may affect esophageal motility, bolus clearance and reflux risk. However, the effect of changes in esophageal function after lung transplantation on the risk of poor post-transplant outcomes remains unclear.

AIM: To evaluate the association between change in esophageal motility pre-/post-lung transplantation and rejection outcome.

METHODS: This was a retrospective cohort study of lung transplant recipients who underwent both pre-and post-transplant esophageal testing including high resolution manometry (HRM) at a tertiary center. Acute cellular rejection (ACR) was defined histologically per International Society for Heart and Lung Transplantation criteria. Univariate analyses were performed using student's t-test, χ 2 test, and Spearman's correlation where appropriate. Multivariable time-to-event analysis using Cox proportional hazards model was applied. Subjects not meeting ACR outcome were censored at death or date of last clinic visit.

RESULTS: 55 subjects (65% men, mean age: 61, median follow-up: 840 days) were included, with 17 (31%) experiencing ACR. Increase in failed swallows correlated with lower baseline total lung capacity (TLC) (R = -0.32, P = 0.05) and decreased post-transplant esophageal bolus clearance (R = -0.45, P = 0.004). On multivariable analysis, post-transplant hypomotility independently predicted increased ACR (HR: 3.62, 95%CI: 1.11-11.8; P = 0.03). Kaplan-Meier analysis demonstrated increased ACR for subjects with increased vs unchanged failed swallows post-transplant (P = 0.048). On Cox regression, a 20% elevated risk of ACR was found for every 10% increase in failed swallows, after controlling for confounders including reflux severity.

CONCLUSION: Esophageal hypomotility, specifically an increase in failed swallows on HRM, from pre- to post-lung transplantation was independently associated with ACR. Additionally, lower baseline TLC correlated with increase in failed swallows, suggesting restrictive lung disease may be associated with post-transplant esophageal hypomotility. Lung transplantation may affect esophageal function and contribute to rejection outcomes. Routine esophageal function testing may help identify patients at higher risk for poor lung transplantation outcomes.

BACKGROUND AND AIMS: Many patients with laryngopharyngeal symptoms (LPS), chronic cough, or belching are referred to gastroenterologists for evaluation and management of GERD. We aimed to optimize a cost-effective approach to evaluating atypical GERD symptoms.

METHODS: We developed a decision analytic model comparing common strategies: (1) usual care defined by empiric PPI and endoscopy, or (2) comprehensive one-time diagnostics including endoscopy and ambulatory reflux testing to guide therapy. The model was applied to patients with LPS, belching, and chronic cough from patient and insurer perspectives. The time horizon was one year, and the willingness-to-pay threshold was set to $100,000/quality-adjusted life-year (QALY) gained.

RESULTS: For patients with LPS, up-front testing, including pH-impedance monitoring and wireless pH monitoring, optimized cost-effectiveness by identifying patients who can convincingly stop PPI therapy ($220-301 saved to patients, ∼$3,300 saved to insurers, +0.01 QALY-gained/year). For patients with belching, up-front testing, including pH-impedance monitoring, optimized cost-effectiveness by identifying patients with supragastric belching who would benefit from diaphragmatic breathing ($3,424 saved to patients, $5,847 saved to insurers, +0.10 QALY-gained/year). For patients with cough-predominant LPS, demonstration that GERD is absent with comprehensive testing appears cost-effective from an insurers' perspective, but not necessarily from patients' perspective, and the decision can be left to the patients and providers.

CONCLUSION: Phenotyping the approach to the dominant symptom may optimize evaluating patients with atypical GERD symptoms. These conclusions are consistent with the Lyon 2.0 and San Diego consensus recommendations of treatment avenues distinct from GERD management.

BACKGROUND: Clinically relevant esophagogastric junction metrics on functional lumen imaging probe (FLIP) in post-fundoplication patients remain unclear.

METHODS: 63 symptomatic post-fundoplication patients underwent FLIP, barium esophagram, and high-resolution manometry. Logistic regressions and receiver-operating characteristic curves for distensibility index (DI) at 60 mL and maximal diameter were generated to predict impaired clearance.

RESULTS: Maximal diameter (OR:0.77, CI:0.62-0.96,p=0.02, AUROC=0.73), but not DI, independently predicted impaired clearance. Diameter >16.5 mm achieved >90% sensitivity for normal clearance; DI <2.0 mm2/mmHg and diameter <8 mm were >90% specific for impaired clearance.

CONCLUSIONS: Maximal diameter on post-fundoplication FLIP predicts impaired clearance and discriminates better than DI.

BACKGROUND: Gastroesophageal reflux disease has been shown to contribute to allograft injury and rejection outcomes in lung transplantation through a proposed mechanism of aspiration, inflammation, and allograft injury. The value of pre-transplant reflux testing in predicting reduction in pulmonary function after lung transplantation is unclear. We hypothesized that increased reflux burden on pre-transplant reflux testing is associated with pulmonary function decline following lung transplant.

AIM: To assess the relationship between pre-transplant measures of reflux and pulmonary function decline in lung transplant recipients.

METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant reflux testing with 24-hour pH-impedance off acid suppression at a tertiary center in 2007-2016. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using Cox proportional hazards models to assess associations between reflux measures and reduction in forced expiratory volume in 1 second (FEV1) of ≥ 20% post-transplant. Patients not meeting endpoint were censored at time of post-transplant fundoplication, last clinic visit, or death, whichever was earliest.

RESULTS: Seventy subjects (58% men, mean age: 56 years) met the inclusion criteria. Interstitial lung disease represented the predominant pulmonary diagnosis (40%). Baseline demographics were similar between groups and were not associated with pulmonary decline. The clinical endpoint (≥ 20% FEV1 decline) was reached in 18 subjects (26%). In time-to-event univariate analysis, FEV1 decline was associated with increased acid exposure time (AET) [hazard ratio (HR) = 3.49, P = 0.03] and increased proximal acid reflux (HR = 3.34, P = 0.04) with confirmation on Kaplan-Meier analysis. Multivariate analysis showed persistent association between pulmonary decline and increased AET (HR = 3.37, P = 0.04) when controlling for potential confounders including age, body mass index, and sex. Sub-group analysis including only patients with FEV1 decline showed that all subjects with abnormal AET progressed to bronchiolitis obliterans syndrome.

CONCLUSION: Increased reflux burden on pre-transplant testing was associated with significant pulmonary function decline post-transplant. Pre-transplant reflux assessment may provide clinically relevant information in the prognostication and management of transplant recipients.