The Diagnostic and Prognostic Value of Large Airway Bronchial Wash in Evaluating Microaspiration in Lung Transplant Recipients

Abstract

Microaspiration induces lung inflammation which contributes to chronic lung allograft dysfunction (CLAD) and death in lung transplant (LTx) recipients. Early detection and mitigation of microaspiration may therefore improve outcomes. Bronchial wash (BW) has been underused compared to bronchoalveolar lavage (BAL) at most LTx centers. As BW likely better reflects the proximal airways, we hypothesized that the BW is a useful sample to analyze biomarkers of microaspiration and inflammation which may predict CLAD and death. Large airway BW and BAL were collected concurrently during recipient routine bronchoscopies at 3 months post-LTx (n=61, 28% of whom had gastroesophageal reflux). Mass spectrometry was performed to measure 3 bile acids, taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid, as putative biomarkers of microaspiration. Ten inflammatory proteins were measured by multiplex assay. Spearman's correlation was used to assess relationships between biomarkers. Cox proportional hazards models were used for survival analysis, adjusted for age, sex, primary disease, days from LTx to BW, and acute rejection. BW bile acid levels were higher than their BAL equivalents, and correlated with inflammatory markers in both samples (Fig A). BW bile acids showed no association with CLAD, though high IL-1α and IL-6 were predictors of early CLAD (Fig B). Notably, high BW TCA and GCA, as well as IL-1β, IL-6, IL-8, IL-12, CCL2, and CCL5 were all associated with early death (Fig C). In BAL, high IL-6 predicted early CLAD, but no other biomarker was associated with CLAD or death. Bile acid and inflammatory marker levels in BW at 3 months post-LTx are significant prognostic factors for CLAD or death in LTx recipients and may be more useful predictive biomarkers than BAL levels in the context of microaspiration. Collection and analysis of BW for these biomarkers may allow for better evaluation of microaspiration and its inflammatory sequalae.