PUBLICATIONS

2025

Chan WW, Schroeder M, Richardson A, et al. Validation of Esophageal Global Symptom Severity as a Patient-Reported Outcome for Evaluation of Reflux Symptoms.. The American journal of gastroenterology. 2025;120(8):1760-1769. doi:10.14309/ajg.0000000000003499

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.

Shah ED, Yadlapati R, Chan WW, Gyawali P. Optimizing evaluation of gastroesophageal reflux with atypical symptoms: Cost-effectiveness and cost-minimalization analysis.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Published online 2025. doi:10.1016/j.cgh.2025.11.014

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.

Flanagan R, Hurtte E, Muftah M, et al. Functional Lumen Imaging Probe (FLIP) Predictors of Esophageal Clearance in Symptomatic Post-Fundoplication Patients: Opening Diameter Has Greater Value Than Distensibility Index.. Clinical and translational gastroenterology. Published online 2025. doi:10.14309/ctg.0000000000000922

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.

Lo WK, Fernandez AM, Feldman N, Sharma N, Goldberg HJ, Chan WW. Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation.. World journal of transplantation. 2025;15(3):100111. doi:10.5500/wjt.v15.i3.100111

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.

Hartnett DA, Muftah M, Leung R, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Published online 2025. doi:10.1016/j.cgh.2025.06.032

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.

Muftah M, Hartnett DA, Hiramoto B, et al. Yield of esophageal biopsy patterns for the diagnosis of eosinophilic esophagitis.. Gastrointestinal endoscopy. 2025;102(2):194-201.e1. doi:10.1016/j.gie.2025.01.018

BACKGROUND AND AIMS: The pattern of inflammation in eosinophilic esophagitis (EoE) is patchy, necessitating multiple biopsies to optimize diagnostic yield. Current consensus-based guidelines recommend 6 total biopsy samples at 2 sites, distal and either middle or proximal esophagus, although this recommendation is based on limited data. We aimed to determine whether this biopsy protocol sufficiently captures EoE diagnoses by evaluating the distribution of eosinophilia in a large EoE cohort.

METHODS: This was a retrospective study of consecutive patients newly diagnosed with EoE with ≥2 esophageal segments biopsied. Demographic variables, clinical characteristics/history, endoscopic findings, and histologic results were manually reviewed. Distribution (proximal, middle, and/or distal) of eosinophilia (>15 eosinophils/high-power field [HPF]) was assessed. Predictors for non-distal disease (<15 eosinophils/HPF on distal biopsy samples) were evaluated by using multivariable logistic regression.

RESULTS: A total of 511 patients newly diagnosed with EoE with ≥2 segments biopsied were included. All patients underwent distal esophageal biopsy. Overall, 286 (56.0%) had ≥1 site with <15 eosinophils/HPF, including 51 (10%) with non-distal disease. Among patients with 3 segments biopsied (n = 60), 19 (31.7%) had eosinophilia at only 1 site, including 6 (10%) with isolated midesophageal disease and no isolated proximal eosinophilia. Discordant mid and proximal biopsy results were found in 18 (30%) patients, with 17 of 18 (94.4%) having mid esophageal eosinophilia. On multivariable analysis, increasing age (odds ratio, 1.02; 95% CI, 1.002-1.04; P = .03) and male sex (odds ratio, 1.89; 95% CI, 1.002-3.55; P = .049) independently predict non-distal disease.

CONCLUSIONS: Isolated segmental eosinophilia is common in EoE, including up to 10% non-distal disease. Discordant mid and proximal biopsy findings are prevalent, with no isolated proximal eosinophilia. Standard protocol should include routine biopsies of both distal and middle esophagus to maximize diagnostic yield.

Jirapinyo P, Leung D, Chan WW, Thompson CC. The Impact of Endoscopic Gastric Remodeling on Gastroesophageal Reflux Disease.. Clinical and translational gastroenterology. 2025;16(8):e00867. doi:10.14309/ctg.0000000000000867

INTRODUCTION: Sleeve gastrectomy is associated with an increased incidence of gastroesophageal reflux disease (GERD). By contrast, the impact of endoscopic gastric remodeling (EGR) on GERD symptoms remains unclear.

METHODS: This prospective study included patients who underwent EGR and completed validated GERD-related patient-reported outcome questionnaires at baseline and 12 months postprocedure.

RESULTS: Fifty patients were included. At 12 months post-EGR, both GERD questionnaire and Reflux Symptom Index scores significantly improved. Proton-pump inhibitor use decreased from 38% at baseline to 20% at 12 months ( P = 0.047). The presence of a hiatal hernia at baseline was associated with greater symptom improvement.

DISCUSSION: EGR improves both typical and atypical GERD symptoms and reduces proton-pump inhibitor dependence. It may represent a preferable treatment option for patients with obesity and concomitant GERD.

Algara MA, Chan WW. Update on laryngopharyngeal reflux disease.. Current opinion in gastroenterology. 2025;41(4):251-259. doi:10.1097/MOG.0000000000001108

PURPOSE OF REVIEW: Chronic laryngopharyngeal symptoms (LPS) are increasingly prevalent presentations to gastroenterologists' offices, and clinicians often make a presumptive diagnosis of laryngopharyngeal reflux disease (LPRD) based on LPS symptoms or laryngoscopic findings alone. Such presumptive diagnoses of LPRD often are incorrect, and establishing the correct diagnosis poses significant challenges for clinicians. This review addresses the timely need for advances in evaluating and managing LPS/LPRD, given their diagnostic complexity and the healthcare burden of ineffective empiric treatments.

RECENT FINDINGS: Recent evidence emphasizes the diverse etiologies of LPS including LPRD, oropharyngeal or other airway pathologies, allergic conditions, and cognitive-affective processes or altered brain-larynx interaction. The diagnostic approach should be individualized and multimodal, including upfront reflux testing over empiric acid suppression trials for possible LPRD, given the poor correlation between LPS and objective evidence of reflux. Predictive models and risk stratification tools such as the COuGH RefluX score show promise to help guide testing and therapeutic strategies. Reflux testing modalities include wireless pH monitoring and impedance-based testing (traditional impedance-pH or combined hypopharyngeal-esophageal reflux monitoring). Biochemical testing for salivary pepsin may also offer adjunctive value. Management should include antireflux strategies for those with objectively-proven LPRD, alongside treatments targeting nonreflux mechanisms of LPS, such as voice therapy, neuromodulation, and behavioral therapy.

SUMMARY: An individualized, multidisciplinary approach is essential in managing LPS/LPRD. Objective reflux testing improves diagnostic accuracy, avoids unnecessary therapies, and enables tailored treatment. Future research should further refine diagnostic thresholds, validate risk stratification tools, and explore novel therapeutic targets to optimize outcomes.