Increase in failed swallows from pre- to post-lung transplant esophageal function testing is associated with acute rejection

Abstract

BACKGROUND

The pathophysiology behind gastroesophageal reflux disease and its association with poor outcomes after lung transplantation is incompletely understood. The physiologic impact of lung transplantation on pulmonary function, intrathoracic pressures, and vagal innervation may affect esophageal motility, bolus clearance and reflux risk. However, the effect of changes in esophageal function after lung transplantation on the risk of poor post-transplant outcomes remains unclear.

AIM

To evaluate the association between change in esophageal motility pre-/post-lung transplantation and rejection outcome.

METHODS

This was a retrospective cohort study of lung transplant recipients who underwent both pre-and post-transplant esophageal testing including high resolution manometry (HRM) at a tertiary center. Acute cellular rejection (ACR) was defined histologically per International Society for Heart and Lung Transplantation criteria. Univariate analyses were performed using student’s t-test, χ² test, and Spearman’s correlation where appropriate. Multivariable time-to-event analysis using Cox proportional hazards model was applied. Subjects not meeting ACR outcome were censored at death or date of last clinic visit.

RESULTS

55 subjects (65% men, mean age: 61, median follow-up: 840 days) were included, with 17 (31%) experiencing ACR. Increase in failed swallows correlated with lower baseline total lung capacity (TLC) (R = -0.32, P = 0.05) and decreased post-transplant esophageal bolus clearance (R = -0.45, P = 0.004). On multivariable analysis, post-transplant hypomotility independently predicted increased ACR (HR: 3.62, 95%CI: 1.11-11.8; P = 0.03). Kaplan-Meier analysis demonstrated increased ACR for subjects with increased vs unchanged failed swallows post-transplant (P = 0.048). On Cox regression, a 20% elevated risk of ACR was found for every 10% increase in failed swallows, after controlling for confounders including reflux severity

CONCLUSION

Esophageal hypomotility, specifically an increase in failed swallows on HRM, from pre- to post-lung transplantation was independently associated with ACR. Additionally, lower baseline TLC correlated with increase in failed swallows, suggesting restrictive lung disease may be associated with post-transplant esophageal hypomotility. Lung transplantation may affect esophageal function and contribute to rejection outcomes. Routine esophageal function testing may help identify patients at higher risk for poor lung transplantation outcomes.

Keywords: Esophageal dysmotility; High-resolution manometry; Ineffective esophageal motility; Failed swallows; Lung transplantation; Acute rejection

Core Tip: Gastroesophageal reflux has been associated with poor outcomes after lung transplantation, though the pathophysiology remains unclear. Lung transplantation itself may modulate this risk through impacts on pulmonary function and intrathoracic pressures, which alters esophageal motility to affect bolus clearance and reflux severity. Our study demonstrated that increased failed swallows from pre- to post-transplant testing was associated with increased risk of acute rejection after lung transplant, and was inversely correlated with baseline percent-predicted total lung capacity. The physiologic impact of lung transplantation may therefore affect esophageal function and contribute to rejection outcomes, suggesting a need for routine manometric testing in this high-risk patient population.