(599) - Bile Acid Aspiration Associates with CLAD and Affects the Bronchial District Lipid Profile: Targeted Bile Acid Metabolomics and Lipidomics in Bronchial Washing

Abstract

Lung transplant is the ultimate option for end stage lung disease pts. Overall survival is halted by rejection and chronic lung allograft dysfunction (CLAD). Gastro-esophageal reflux and aspiration has been considered a risk factor for CLAD. Bile acid aspiration was investigated by targeted metabolomics in the bronchial washings from lung transplant patients. Given the detergent properties of bile acids, their effect of the bronchial district lipids was studied using a lipidomics approach. Bronchial washings (BW) (56 samples) were prospectively collected from 51 patients at routine surveillance post-transplant bronchoscopies. Liquid chromatography-mass spectrometry retrospectively assayed BW for 13 bile acids and 25 lipid families inclusive of 250 lipids. Patients were monitored for CLAD and transbronchial biopsies for rejection and inflammation. Bile acids were detected in all BW. BW from pts with CLAD (22/51) had overall greater levels of bile acids (Mann Whitney p=0.03). Different levels (Kruscal Wallis p<0.05) were noted in BW from pts with early (onset <24 mo) CLAD (19.4 nM/L, IQR 15.2 - 35.8), late CLAD (26, 19.3-55.9), and no-CLAD (17.1, 13.5-26.4). Late CLAD vrs no-CLAD group (p=0.02); late CLAD vrs early CLAD (p=0.05); no difference for early CLAD vrs. no CLAD. Total Bile acids correlated (p<0.0005) with: cholesteryl-esters (CE) (Spearman r=0.6); Sphingomyelin (SM) (r=0.5); dihydrosphingomyelin (dhSM) (r=0.55); lactosyl-ceramide (Lac-Cer) (r=0.6); Lysophosphatidylcholine ether (LPCe) (r=0.5). Bile acids levels, high (upper quartile >27.5 nM/L) vrs. low, showed greater levels (p<0.05) of: CE, SM, dhSM, hexosyl-Cer, Lac-Cer, ganglioside GM3, phosphatidic acid, dipalmitoylphosphatidylcholine phosphatidylcholin ether, lysophosphatidylcholine, LPCe, lysophosphatidylinositol, phosphatidylethanolamine-p, lysophosphatidylethanolamine, lysophosphatidylethanolamine-p, phosphatidylinositol, and acylphosphatidylglycerol. Bile acids assayed by mass spec are detected in all lung transplant bronchial washings. High level of bile acids associate with late CLAD onset and have a significant dose related effect on the bronchial district lipidomic profile.