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

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.


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


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.


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.


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.

Keywords: Ineffective esophageal motility, Esophageal hypomotility, Esophageal manometry, Gastroesophageal reflux disease, Lung transplantation, Acute rejection

Core Tip: While gastroesophageal reflux (GER) has been associated with poorer outcomes after lung transplant, the impact of esophageal dysmotility remains unclear. Our study found that ineffective esophageal motility identified on pre-transplant esophageal manometry was independently associated with increased acute allograft rejection, even after adjusting for GER. This suggests that esophageal hypomotility may increase the risk of poor lung transplant outcome independent of GER. Routine esophageal function assessment should be considered in the peri-transplant evaluation of lung transplant patients to identify, risk stratify, and more effectively manage esophageal dysfunction in such patients at risk of poorer outcomes.