Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2023; 29(21): 3292-3301
Published online Jun 7, 2023. doi: 10.3748/wjg.v29.i21.3292
Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux
Wai-Kit Lo, Brent Hiramoto, Hilary J Goldberg, Nirmal Sharma, Walter W Chan
Wai-Kit Lo, Brent Hiramoto, Walter W Chan, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, MA 02115, United States
Hilary J Goldberg, Nirmal Sharma, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 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, Hiramoto B, Goldberg HJ, and Sharma N performed analysis and interpretation of data; Lo WK, Hiramoto B, and Chan WW drafted the manuscript; Chan WW, Lo WK, Hiramoto B, Goldberg HJ, and Sharma N contributed to critical revision of manuscript for important intellectual content; Chan WW and Lo WK performed statistical analyses; 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, No. 2011P001563.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: Lo WK, Hiramoto B, and Goldberg HJ, Sharma N-no relevant conflicts of interest for this article; Chan WW-Scientific Advisory Board (Takeda Pharmaceuticals, Phathom Pharmaceuticals, Sanofi Pharmaceuticals).
Data sharing statement: No additional data are available.
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.
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:
Corresponding author: Walter W Chan, AGAF, FACG, MD, Associate Professor, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States.
Received: March 5, 2023
Peer-review started: March 5, 2023
First decision: April 3, 2023
Revised: April 14, 2023
Accepted: April 28, 2023
Article in press: April 28, 2023
Published online: June 7, 2023
Research background

Gastroesophageal reflux is associated with poor outcomes after lung transplantation. However, the impact of esophageal dysmotility and role of esophageal manometry remains unclear. Ineffective esophageal motility (IEM) is a disorder of esophageal motility associated with decreased esophageal clearance that may worsen transplant outcomes.

Research motivation

Esophageal evaluation remains poorly standardized in lung transplantation, and this work suggests that routine esophageal motility testing to identify IEM may help identify patients at risk for acute rejection.

Research objectives

To evaluate the relationship between IEM and acute rejection after lung transplantation, controlling for confounders including coexisting pathologic acid and nonacid reflux.

Research methods

This was a retrospective cohort study of lung transplant recipients that underwent pre-transplant esophageal testing including manometry and pH at a tertiary referral center.

Research results

IEM on pre-transplant esophageal manometry was associated with higher risk of acute rejection on time-to-event analysis. On multivariable Cox regression analysis, IEM remains independently associated with increased acute rejection, even after controlling for pathologic reflux. In addition, increased non-acid reflux was also an independent risk factor for acute rejection in the multivariable model.

Research conclusions

Lung transplant candidates with IEM had a greater risk of developing acute rejection, independent of pathologic acid and nonacid reflux. Additionally, nonacid reflux was independently associated with acute rejection. These findings suggest that IEM and other disorders affecting esophageal clearance may contribute to the pathophysiology of allograft injury, independent of a reflux-associated pathway.

Research perspectives

Future research should focus on the implementation of standardized esophageal motility testing in lung transplantation, investigation of the impact of IEM and other disorders of esophageal motility on longer term transplant outcomes including chronic rejection and survival, and assessment of changes in esophageal motility after transplant and its effect on transplant outcomes.