Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 18, 2025; 15(3): 100111
Published online Sep 18, 2025. doi: 10.5500/wjt.v15.i3.100111
Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation
Wai-Kit Lo, Annel M Fernandez, Natan Feldman, Nirmal Sharma, Hilary J Goldberg, Walter W Chan
Wai-Kit Lo, Natan Feldman, Nirmal Sharma, Walter W Chan, Department of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, United States
Annel M Fernandez, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
Hilary J Goldberg, Department of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
Author contributions: Lo WK and Chan WW initiated study concepts and design and performed statistical analyses; Lo WK, Feldman N, Sharma N, Goldberg HJ, and Chan WW contributed to acquisition of data; Lo WK, Sharma N, Goldberg HJ, and Chan WW performed analysis and interpretation of data; Lo WK, Fernandez AM, and Chan WW drafted the manuscript; Lo WK, Fernandez AM, Feldman N, Sharma N, Goldberg HJ, and Chan WW contributed to critical revision of manuscript for important intellectual content; Chan WW provided administrative support and overall study supervision; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Mass General Brigham Institutional Review Board, approval No. 2011P001563.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available upon reasonable request and approval by the Institutional Review Borad from the corresponding author at wwchan@bwh.harvard.edu.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Walter W Chan, AGAF, FACG, MD, Associate Professor, Department of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, United States. wwchan@bwh.harvard.edu
Received: August 7, 2024
Revised: January 8, 2025
Accepted: February 26, 2025
Published online: September 18, 2025
Processing time: 253 Days and 23.1 Hours
Abstract
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.

Keywords: Gastroesophageal reflux disease; Lung transplant; Multichannel intraluminal impedance; pH-monitoring; Bronchiolitis obliterans syndrome; Chronic rejection

Core Tip: Gastroesophageal reflux has been associated with increased morbidity and mortality after lung transplantation. Abnormal objective measures of reflux on pre-transplant multichannel intraluminal impedance and pH have also been associated with early allograft injury, early rehospitalization and development of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction. However, the relationship between pre-transplant reflux severity and pulmonary function decline after lung transplant remains unclear. Out study demonstrated that abnormal acid exposure time on pre-transplant reflux testing was associated with significant pulmonary function decline defined as ≥ 20% decrease in post-transplant baseline forced expiratory volume in one second. Patients with acid reflux and forced expiratory volume in one second decline are at high risk of poor lung transplant outcomes and should be aggressively managed.