Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation.

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.