Microaspiration, primarily driven by gastroesophageal reflux, is deleterious to the lung allograft and contributes to poor clinical outcomes in lung transplant (LTx) recipients. Although recent studies have identified bile acids as promising biomarkers, early detection and mitigation of microaspiration remain a clinical challenge. Compared to bronchoalveolar lavage (BAL), bronchial wash (BW) has not gained widespread use at LTx centers but likely better samples the proximal airways, where gastric refluxate first enters the lung allograft. We hypothesized that BW is more useful than BAL to diagnose microaspiration and prognosticate poor clinical outcome in LTx recipients.
BW and BAL (as defined per ISHLT consensus statement, Nov 2020) were concurrently collected during surveillance bronchoscopies at 3 months post-LTx from 61 patients. Three bile acids, taurocholic acid (TCA), glycocholic acid (GCA) and cholic acid, were measured by mass spectrometry. Eleven protein biomarkers of inflammation or epithelial injury were measured by immunoassays.
TCA and GCA levels were higher in BW than in BAL (Figure A). BW TCA and GCA were associated with concurrent decline in lung function (TCA OR=2.2; p=0.03; GCA OR=2.1; p=0.02). TCA, GCA, and most inflammatory proteins in BW, but not in BAL, were associated with decreased overall survival in multivariate Cox proportional hazard models adjusted for recipient age at transplant, sex, primary disease, days post-LTx to bronchoscopy, and concurrent acute rejection (Figure B). Exploratory derivation of BW-based biomarker signatures identified both bile acids and proteins as key parameters in predicting CLAD-free survival and overall survival.
BW may be more useful than BAL as a source of biomarkers to aid in the diagnosis and prognosis of clinically-significant microaspiration after LTx. The potential utility of BW needs to be tested in a larger, independent, prospective validation cohort.