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.
 

BACKGROUND: 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 to other validated questionnaires, esophageal symptom burden, and outcome following reflux management.

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

RESULTS: 1296 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). Mean GSS was higher with abnormal GERDQ, GERD-HRQL, and RSI, pathologic AET and conclusive GERD per Lyon Consensus (p<0.0001 each comparison). On ROC analyses, GSS was non-inferior 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 anti-reflux therapy (β=1.90, p=0.0006).

CONCLUSIONS: 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 term 'laryngopharyngeal reflux' ('LPR') is frequently applied to aerodigestive symptoms despite lack of objective reflux evidence. This initiative aimed to develop a modern care paradigm for LPR supported by otolaryngology and gastroenterology disciplines.

METHODS: A 28-member international inter-disciplinary 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 non-reflux 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 anti-reflux management. The two recommended ambulatory reflux monitoring modalities, 24h pH-impedance and 96h 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.

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

Patient-reported outcome (PRO) measures are essential tools for assessing a patient's subjective experience related to disease and health. PROs measure symptom severity and evaluate treatment efficacy across a range of conditions at a particular point in time. While PROs focusing on esophageal symptoms and esophageal hypervigilance exist, disease-specific PROs for commonly encountered benign esophageal disorders such as gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and achalasia are limited. Most GERD-specific PROs fail to address the complete spectrum of GERD presentations, and those that provide daily assessment are more suited for research. Similarly, many EoE-specific PROs were designed for clinical trials. Comprehensive instruments incorporating EoE symptoms, as well as endoscopic and histologic features of active inflammation and fibrostenotic changes are needed. The psychometric properties of the Eckardt Score used for achalasia has significant limitations, stemming primarily from the dominance of dysphagia in scoring. Newer achalasia-specific PROs attempt to overcome this by capturing nuanced patient experiences. Broader symptom PROs are often used assess esophageal symptoms across the spectrum of benign esophageal disorders, including a PRO that assesses esophageal hypervigilance and symptom specific anxiety (EHAS). Future efforts should focus on creating user-friendly PROs that comprehensively evaluate not just clinical presentation but also the disease state, which will enhance clinical symptom follow-up, quality of life assessment and research applications. Assessments of hypervigilance and visceral anxiety will complement these applications as these measures are both a PRO and an important moderator of symptom severity and quality of life.

BACKGROUND AND AIMS: Functional lumen imaging probe (FLIP) Panometry provides assessment of the esophagogastric junction (EGJ) opening and esophageal body contractile activity during an endoscopic procedure and is increasing being incorporated in comprehensive esophageal motility assessments. We aimed to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme.

METHODS: A working group of 19 FLIP Panometry experts convened in a modified Delphi consensus process to produce and assess statements on the FLIP Panometry procedure and interpretation. Three rounds of voting were conducted on an agreement scale of 1-9 for appropriateness followed by face-to-face discussions and opportunity for revisions of statements. The "percent agreement" was proportion of votes with score ≥7 indicating level of agreement on appropriateness.

RESULTS: A total of 40 statements were selected for final inclusion for the Dallas Consensus, including FLIP Panometry protocol, interpretation of EGJ opening and contractile response, and motility classification scheme. Key statements included: "FLIP Panometry should be interpreted in the context of the clinical presentation, the accompanying EGD findings and other relevant complementary testing". (Median response 9.0; 100% agreement). "A major motor disorder is unlikely in the setting of a "Normal" FLIP Panometry classification (Median response 9.0; 94% agreement). "Diminished or absent contractile response with reduced esophageal opening [i.e. "non-spastic obstruction] supports the diagnosis of a disorder of EGJ outflow. (Median response 8.5; 94% agreement).

CONCLUSION: The standardized approach for performance and interpretation of the Dallas Consensus can facilitate use of FLIP Panometry in broad clinical settings.

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment.

METHODS: A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported.

RESULTS: Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts.

DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

INTRODUCTION: There are limited epidemiological studies on eosinophilic esophagitis (EoE) in Asia. We studied the temporal trend of EoE in Asia, the presenting symptoms, and association with atopic diseases.

METHODS: Literature search on PubMed, Embase, MEDLINE, Scopus, and Web of Science was performed to retrieve studies published between 1980 and 2023 that reported the prevalence or incidence of EoE in Asia. We used a random-effects model to estimate the pooled incidence and prevalence. I2 index and Cochran Q test were used to assess heterogeneity. Subgroup analyses were conducted for study types, different regions, years of examination, and age groups. The proportion of atopic diseases among patients with EoE was presented.

RESULTS: Twenty-five studies from Asia were included. The pooled prevalence of EoE was 33.5 cases per 100,000 inhabitants in population-based studies and 11.0 cases per 1,000 patients/visitors in hospital-based studies. The incidence rate among children was 12.3 cases per 1,000 patients/visitors, whereas for adults, it was only 0.2 cases per 1,000 patients/visitors. Among population-based studies, there was an increase in prevalence from 19.8 per 100,000 individuals in 2005-2009 to 73.0 per 100,000 individuals in 2015-2019. A similar upward trend was observed in hospital-based studies conducted during the same period. Patients with EoE commonly presented with dysphagia (36.3%) and nausea and vomiting (34.6%). History of atopy was reported in 57.2% of patients with EoE in Asia.

DISCUSSION: The prevalence and incidence of EoE in Asia have been rising over the past decades. Because of the limited number of Asian studies and variations in patient sources, caution should be exercised when interpreting these results.

BACKGROUND: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

AIMS: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.S.

METHODS: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) in 2005-2008. Adults aged ≥ 20 with TSH, free T4 (fT4), and bowel health data were included. Multivariable logistic regression models were constructed to examine associations between thyroid function and bowel health measures, adjusting for potential confounders.

RESULTS: Among 6,552 participants, 93.6%, 4.3%, 1.7%, and 0.4% had TSH levels of 0.24-5.4, 5.4-10, < 0.24, and ≥ 10 mIU/L, respectively. There were no significant differences in prevalence of thyroid dysfunction between individuals with constipation or diarrhea and those without. In fully adjusted models, TSH was not a significant predictor of constipation, diarrhea, or FI, but higher fT4 was protective against constipation as a continuous variable (OR 0.47, CI: 0.26-0.85, p = 0.014)). Neither hypothyroid nor hyperthyroid status significantly correlated with constipation or diarrhea, although hyperthyroidism was associated with FI (OR 3.58, CI:1.51-8.49, p = 0.005).

CONCLUSION: While bowel disturbances were common in this nationally representative sample, the yield of thyroid function testing was low. Overt hypo- and hyperthyroidism were not significantly associated with constipation or diarrhea. Clinical utility of routine thyroid testing for bowel symptoms may be low in patients without systemic manifestations of severe thyroid disease.