Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2023; 13(4): 138-146
Published online Jun 18, 2023. doi: 10.5500/wjt.v13.i4.138
Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk
Wai-Kit Lo, Ryan Flanagan, Nirmal Sharma, Hilary J Goldberg, Walter W Chan
Wai-Kit Lo, Ryan Flanagan, Walter W Chan, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
Nirmal Sharma, Hilary J Goldberg, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
Author contributions: Chan WW and Lo WK initiated study concepts and design; Lo WK, Goldberg HJ, and Chan WW contributed to acquisition of data; Chan WW, Lo WK, Flanagan R, Goldberg HJ, and Sharma N performed analysis and interpretation of data; Lo WK, Flanagan R, and Chan WW drafted the manuscript; Chan WW, Lo WK, Flanagan R, Goldberg HJ, and Sharma N contributed to critical revision of manuscript for important intellectual content; Chan WW and Lo WK performed statistical analyses; and Chan WW provided administrative support and overall study supervision.
Institutional review board statement: The study was reviewed and approved by the Mass General Brigham Healthcare Institutional Review Board (2011P001563).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: Guidelines of the STROBE statement have been adopted for this manuscript.
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, MD, MPH, Associate Professor, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, United States. wwchan@bwh.harvard.edu
Received: November 20, 2022
Peer-review started: November 20, 2022
First decision: March 15, 2023
Revised: March 22, 2023
Accepted: March 31, 2023
Article in press: March 31, 2023
Published online: June 18, 2023
Processing time: 207 Days and 22.4 Hours
Abstract
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.

Keywords: Cystic fibrosis; Gastroesophageal reflux; Lung transplantation; pH monitoring

Core Tip: This study found that objective evidence of gastroesophageal reflux disease was present in > 50% of lung transplant candidates with cystic fibrosis (CF). However, CF patients were less likely than those with other pulmonary diagnoses to undergo pre-transplantation reflux testing. CF patients who underwent objective reflux testing were less likely to develop chronic lung allograft dysfunction, as those tested positive were more likely to undergo anti-reflux surgery. Our findings provided evidence for the association of routine peri-transplant reflux testing with improved lung transplant outcomes in CF patients, and the importance of timely identification of reflux to allow early intervention.