Late Breaking Abstract - Multicenter study of bronchial wash-bile acid signature for the diagnosis of aspiration and prediction of chronic lung allograft dysfunction

<bold>Purpose</bold>: Bile acids (BA) have been independently validated as a marker of aspiration linked to increased risk of chronic lung allograft dysfunction (CLAD). We aimed to confirm that a large airway bronchial wash (LABW) BA-based aspiration signature will predict CLAD in a large multi-center cohort and will be associated with inflammation. <bold>Methods:</bold> Two-center retrospective (n=313) cohort included consecutive lung transplant recipients with LABW available at 3 months post-transplant. Fifteen BA and 48 inflammatory mediators were measured by tandem mass spectrometry and by 48-multiplex assay, respectively. Cox regression model, logistic regression and non-parametric statistical analyses ware performed. <bold>Results:</bold> The median concentration of total BA was 4.25nM (ir:1.9-14.3). Primary conjugated BA were the most abundant species. 8.6nM and 86% were the upper tertile cut-offs used to define high total BA concentration and percent conjugated BA, respectively. Having both high total BA levels and high percentage of conjugated BA independently predicted CLAD (HR 1.9, 95% CI 1.2-2.9, p=0.005) and mortality (HR 2.6, 95% CI 1.7-4.0, p<0.001). Primary BAs strongly correlated with most cytokines. <bold>Conclusion:</bold> Elevated BA in LABW at 3 months after transplant, particularly conjugated BA, predict mortality and CLAD. Increased levels of primary BA correlate with high cytokines, highlighting their pro-inflammatory role. These findings in a large multi-center cohort support our previous observations that a LABW bile acid-based signature can serve as a diagnostic tool for aspiration and as a predictor of poor long-term outcomes.