Publications by Year: 2025

2025

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 J Transplant. 2025;15(3):100111. doi:http://dx.doi.org/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.
 

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

INTRODUCTION: Sleeve gastrectomy is associated with an increased incidence of gastroesophageal reflux disease (GERD). In 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 post-procedure.

RESULTS: Fifty patients were included. At 12 months post-EGR, both GERD-Q and Reflux Symptom Index scores significantly improved. Proton pump inhibitor (PPI) 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 PPI dependence. It may represent a preferable treatment option for patients with obesity and concomitant GERD.

Yadlapati R, Chan WW. Evaluation of Patients With Laryngopharyngeal Symptoms: The Role and Strategy for Reflux Testing. Foregut. 2025;5(2):166-173. doi:10.1177/26345161251339980
Gastroenterologists and otolaryngologists commonly care for patients with laryngopharyngeal symptoms such as voice hoarseness, sore throat, throat clearing and cough. Often symptoms are reflexively attributed to gastro-esophageal reflux disease, although poorly response to traditional anti-reflux management strategies. The current paradigm to evaluate for laryngopharyngeal reflux disease highlights the role of reflux monitoring performed off acid suppression. This review discusses the indications for reflux monitoring and reviews considerations for selection and interpretation of the different modalities of reflux monitoring for diagnosis of laryngopharyngeal reflux disease: prolonged wireless pH monitoring as well as impedance-pH monitoring.
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.

Shah ED, Gyawali P, Chan WW. Optimizing the cost-effective evaluation of gastroesophageal reflux by typical symptom phenotypes after failure of empiric acid suppression trial.. The American journal of gastroenterology. Published online 2025. doi:10.14309/ajg.0000000000003576

INTRODUCTION: Concern for gastroesophageal reflux disease (GERD) is the most common reason to consult gastroenterology. We aimed to optimize routine GERD evaluation on cost-effectiveness according to the dominant typical symptom among patients with persistent symptoms failing empiric proton pump inhibitors (PPI).

METHODS: We developed a decision analytic model evaluating all permutations of GERD diagnostics including empiric trials of PPI optimization or discontinuation, upper endoscopy, wireless pH-monitoring, and pH-impedance monitoring. The model was applied to patients with heartburn, regurgitation, and chest pain in general gastroenterology to identify the appropriate combination and order of testing from insurer and patient perspectives. Health outcomes were informed by systematic reviews of clinical trials. Cost outcomes were informed by Centers for Medicare and Medicaid Services and commercial datasets and national observational studies. The time horizon was one year and willingness-to-pay threshold was $100,000/quality-adjusted-life-year (QALY) gained.

RESULTS: For patients with typical persistent GERD symptoms failing empiric PPI, routine up-front ambulatory reflux testing saved $2,500-$4,500 compared to endoscopy alone when no erosive esophagitis is found. The most cost-effective initial ambulatory reflux test was 96-hour wireless pH-monitoring for patients with heartburn and chest pain and 24-hour pH-impedance monitoring for patients with regurgitation, both performed OFF-PPI. Adding ON-PPI pH-impedance monitoring optimized cost-effectiveness for patients with documented evidence of GERD and PPI-refractory symptoms. Patient and insurer perspectives aligned on these optimal diagnostic strategies.

DISCUSSION: Compared to a one-size-fits-all strategy, a tailored approach based on Lyon 2.0 optimizes cost-effective evaluation and management of GERD by phenotyping the appropriate diagnostics to dominant symptom.

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. Published online 2025. 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.

Yadlapati R, Weissbrod P, Walsh E, et al. The San Diego Consensus for Laryngopharyngeal Symptoms and Laryngopharyngeal Reflux Disease.. The American journal of gastroenterology. Published online 2025. doi:10.14309/ajg.0000000000003482

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.

Gyawali P, Marchetti L, Rogers BD, et al. The Lyon Score: A Novel Reflux Scoring System Based on the Lyon Consensus 2.0 That Associates With Treatment Outcome From Antireflux Therapy.. The American journal of gastroenterology. 2025;120(5):1009-1018. doi:10.14309/ajg.0000000000003083

INTRODUCTION: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome.

METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to antireflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from 2 centers (Europe and the United States) constituted the developmental cohort, while 2 separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics analysis determined performance of the Lyon score in predicting treatment response.

RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an area under the curve (AUC) of 0.819 in predicting 50% symptom improvement ( P < 0.001) on receiver operating characteristics, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, P < 0.001), mean nocturnal baseline impedance (AUC 0.785, P < 0.001), and reflux episodes (AUC 0.764, P < 0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, P < 0.001) and Asian validation cohorts (AUC 0.637, P < 0.001) and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts.

DISCUSSION: The novel Lyon score segregates reflux phenotypes and identifies likelihood of symptom response from antireflux therapy.