Lo WK, Flanagan R, Sharma N, Goldberg HJ, Chan WW. Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk. World journal of transplantation. 2023;13(4):138-146. doi:10.5500/wjt.v13.i4.138

BACKGROUND: Gastroesophageal reflux (GER) has been associated with poor outcomes after lung transplantation for chronic lung disease, including increased risk of chronic rejection. GER is common in cystic fibrosis (CF), but factors influencing the likelihood of pre-transplant pH testing, and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.

AIM: To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.

METHODS: This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant. Patients with pre-transplant anti-reflux surgery were excluded. Baseline characteristics (age at transplantation, gender, race, body mass index), self-reported GER symptoms prior to transplantation, and pre-transplant cardiopulmonary testing results, were recorded. Reflux testing consisted of either 24-h pH- or combined multichannel intraluminal impedance and pH monitoring. Post-transplant care included a standard immunosuppressive regimen, and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients. The primary outcome of chronic lung allograft dysfunction (CLAD) was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria. Statistical analysis was performed with Fisher's exact test to assess differences between cohorts, and time-to-event Cox proportional hazards modeling.

RESULTS: After applying inclusion and exclusion criteria, a total of 60 patients were included in the study. Among all CF patients, 41 (68.3%) completed reflux monitoring as part of pre-lung transplant evaluation. Objective evidence of pathologic reflux, defined as acid exposure time > 4%, was found in 24 subjects, representing 58% of the tested group. CF patients with pre-transplant reflux testing were older (35.8 vs 30.1 years, P = 0.01) and more commonly reported typical esophageal reflux symptoms (53.7% vs 26.3%, P = 0.06) compared to those without reflux testing. Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing. Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses (68% vs 85%, P = 0.003). There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not, after controlling for confounders (Cox Hazard Ratio 0.26; 95%CI: 0.08-0.92).

CONCLUSION: Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD. Systematic reflux testing may enhance outcomes in this patient population.

Lo WK, Hiramoto B, Goldberg HJ, Sharma N, Chan WW. Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux. World journal of gastroenterology. 2023;29(21):3292-3301. doi:10.3748/wjg.v29.i21.3292

BACKGROUND: Gastroesophageal reflux is associated with poorer outcomes after lung transplant, likely through recurrent aspiration and allograft injury. Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes, the role of esophageal manometry in the assessment of lung transplant patients remains debated, and the impact of esophageal dysmotility on transplant outcomes is unclear. Of particular interest is ineffective esophageal motility (IEM) and its associated impact on esophageal clearance.

AIM: To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.

METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018. Patients with pre-transplant anti-reflux surgery were excluded. Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing. Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection, defined histologically per International Society of Heart and Lung Transplantation guidelines. Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery, last clinic visit, or death. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between groups.

RESULTS: Of 184 subjects (54% men, mean age: 58, follow-up: 443 person-years) met criteria for inclusion. Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis (41%). During the follow-up period, 60 subjects (33.5%) developed acute rejection. The all-cause mortality was 16.3%. Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection [hazard ratio (HR): 1.984, 95%CI: 1.03-3.30, P = 0.04], confirmed on Kaplan-Meier curve. On multivariable analysis, IEM remained independently associated with acute rejection, even after controlling for potential confounders such as the presence of acid and nonacid reflux (HR: 2.20, 95%CI: 1.18-4.11, P = 0.01). Nonacid reflux was also independently associated with acute rejection on both univariate (HR: 2.16, 95%CI: 1.26-3.72, P = 0.005) and multivariable analyses (HR: 2.10, 95%CI: 1.21-3.64, P = 0.009), adjusting for the presence of IEM.

CONCLUSION: Pre-transplant IEM was associated with acute rejection after transplantation, even after controlling for acid and nonacid reflux. Esophageal motility testing may be considered in lung transplant to predict outcomes.

Flanagan R, Muftah M, Perencevich M, Chan W, Stein DJ. A Nationwide Survey of Gastroenterology Program Leadership Regarding Implementation of the GI Hospitalist Model. Digestive diseases and sciences. 2023;68(5):1714-1717. doi:10.1007/s10620-022-07763-7

BACKGROUND: Academic gastroenterology (GI) hospitalists are increasing, however the impacts on fellowship training and clinical care are unclear. Motivations for implementation of the GI hospitalist model are uninvestigated.

AIMS: We aimed to determine the prevalence of GI hospitalists, explore motivations for and against adoption of a GIH model, and investigate the model's effects on fellowship training.

METHODS: Leadership at current general GI fellowships were surveyed about current staffing models, as well as effects and perceptions of the hospitalist model.

RESULTS: There was a total of 52 (26%) respondents and 12 (23%) reported having a GI hospitalist at their institution. A majority of respondents stated burnout and reduced time on service for other faculty was a primary reason for hiring a GI hospitalist.

DISCUSSION: The largest perceived benefit of a hospitalist is reduced burnout and time on service for outpatient GI faculty. Many respondents also believed a GIH would improve fellowship education and quality of inpatient care.

Flanagan R, Lopes EW, Brown JRG, Tracy MS, Chan WW. Association Between Opioid Use and Outpatient Visits for Dysphagia: An Analysis of the National Ambulatory Medical Care Survey in 2008-2018. Clinical and translational gastroenterology. 2023;14(3):e00552. doi:10.14309/ctg.0000000000000552

INTRODUCTION: Opioid-induced esophageal dysfunction has been described with characteristic manometric patterns, but the population burden of dysphagia attributable to opioid use remains unclear.

METHODS: The National Ambulatory Medical Care Survey from 2008 to 2018 was used to assess the relationship between opioid use and outpatient visits for dysphagia.

RESULTS: After controlling for potential confounders, there were no significant difference in ambulatory visits for dysphagia between opioid users and nonusers (adjusted odds ratio = 0.98, confidence interval: 0.59-1.65).

DISCUSSION: No correlation between opioid use and ambulatory visits for dysphagia was found in a nationwide sample. Opioid-related manometric changes may be clinically relevant only in a small proportion of patients.

Zhou JC, Gavini S, Chan WW, Lo WK. Relationship Between Esophageal Disease and Pulmonary Fibrosis. Digestive diseases and sciences. 2023;68(4):1096-1105. doi:10.1007/s10620-023-07908-2

Esophageal disorders are prevalent among patients with chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). Gastroesophageal reflux disease (GERD) has been associated with IPF prevalence, severity, and respiratory decline. The pathophysiologic relationship between GERD and IPF is likely bidirectional, with aspiration of refluxate leading to lung inflammation and fibrosis, while the restrictive pulmonary physiology may contribute to altered transdiaphragmatic pressure gradient and increased reflux. Esophageal symptoms are frequently absent and do not predict esophageal dysfunction or pathologic reflux in patients with IPF, and objective diagnostic tools including upper endoscopy, ambulatory reflux monitoring, and high-resolution manometry are often needed. Impedance-based testing that identifies both weakly/non-acidic and acid reflux may provide important additional diagnostic value beyond pH-based acid testing alone. Novel metrics and maneuvers, including advanced impedance measures on impedance-pH study and provocative testing on HRM, may hold promise to future diagnostic advancements. The main treatment options include medical therapy with acid suppressants and anti-reflux surgery, although their potential benefits in pulmonary outcomes of IPF require further validations. Future directions of research include identifying phenotypes of IPF patients who may benefit from esophageal testing and treatment, determining the optimal testing strategy and protocol, and prospectively assessing the value of different esophageal therapies to improve outcomes while minimizing risks. This review will discuss the pathophysiology, evaluation, and management of esophageal diseases, particularly GERD, in patients with IPF, as informed by the most recent publications in the field, in hopes of identifying targets for future study and research.

Kamal AN, Dhar SI, Bock JM, et al. Best Practices in Treatment of Laryngopharyngeal Reflux Disease: A Multidisciplinary Modified Delphi Study. Digestive diseases and sciences. 2023;68(4):1125-1138. doi:10.1007/s10620-022-07672-9

BACKGROUND: Laryngopharyngeal reflux (LPR) is a common otolaryngologic diagnosis. Treatment of presumed LPR remains challenging, and limited frameworks exist to guide treatment.

METHODS: Using RAND/University of California, Los Angeles (UCLA) Appropriateness Methods, a modified Delphi approach identified consensus statements to guide LPR treatment. Experts independently and blindly scored proposed statements on importance, scientific acceptability, usability, and feasibility in a four-round iterative process. Accepted measures reached scores with ≥ 80% agreement in the 7-9 range (on a 9-point Likert scale) across all four categories.

RESULTS: Fifteen experts rated 36 proposed initial statements. In round one, 10 (27.8%) statements were rated as valid. In round two, 8 statements were modified based on panel suggestions, and experts subsequently rated 5 of these statements as valid. Round three's discussion refined statements not yet accepted, and in round four, additional voting identified 2 additional statements as valid. In total, 17 (47.2%) best practice statements reached consensus, touching on topics as varied as role of empiric treatment, medication use, lifestyle modifications, and indications for laryngoscopy.

CONCLUSION: Using a well-tested methodology, best practice statements in the treatment of LPR were identified. The statements serve to guide physicians on LPR treatment considerations.

Lo WK, Goldberg HJ, Sharma N, Wee JO, Chan WW. Routine Reflux Testing Guides Timely Antireflux Treatment to Reduce Acute and Chronic Rejection After Lung Transplantation. Clinical and translational gastroenterology. 2023;14(1):e00538. doi:10.14309/ctg.0000000000000538

INTRODUCTION: Gastroesophageal reflux has been associated with poorer lung transplantation outcomes, although no standard approach to evaluation/management has been adopted. We aimed to evaluate the effect of timely antireflux treatment as guided by routine reflux testing on postlung transplant rejection outcomes.

METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center. All patients underwent pretransplant ambulatory pH monitoring. Timely antireflux treatment was defined as proton pump inhibitor initiation or antireflux surgery within 6 months of transplantation. Patients were separated into 3 groups: normal pH monitoring (-pH), increased reflux (+pH) with timely treatment, and +pH with delayed treatment. Rejection outcomes included acute rejection, bronchiolitis obliterans syndrome, and chronic lung allograft dysfunction per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses using Cox proportional hazard models were applied. Patients not meeting outcomes were censored at death or last clinic visit.

RESULTS: One hundred seventy-five patients (59% men/mean 56.3 yr/follow-up: 496 person-years) were included. On multivariable analyses, +pH/delayed treatment patients had higher risks of acute rejection (adjust hazard ratio [aHR]:3.81 [95% confidence interval [CI]: 1.90-7.64], P = 0.0002), bronchiolitis obliterans syndrome (aHR: 2.22 [95% CI: 1.07-4.58], P = 0.03), and chronic lung allograft dysfunction (aHR: 2.97 [95% CI: 1.40-6.32], P = 0.005) than +pH/timely treatment patients. Similarly, rejection risks were increased among +pH/delayed treatment patients vs -pH patients (all P < 0.05). No significant differences in rejection risks were noted between +pH/timely treatment patients and -pH patients. Failure/complications of antireflux treatment were rare and similar among groups.

DISCUSSION: Timely antireflux treatment, as directed by pretransplant reflux testing, was associated with reduced allograft rejection risks and demonstrated noninferiority to patients without reflux. A standardized peri-transplant test-and-treat algorithm may guide timely reflux management to improve lung transplant outcomes.