Aspirated bile acids affect lung immunity and function

Introduction: As bile acids(BAs), molecules affecting motility and immunity in the gut, also promote CLAD when aspirated, we hypothesized their involvement in airway immunity and contractility. BAs and airway infections in post-Tx bronchial washings (BWs) were monitored. We investigated distal airway kinetics (in vitro)to BAs and their role in pulmonary function (in vivo). Methods: BW(238) from 111 lung-Tx pts were tested for BAs (LC-MS) and infections. Murine and human precision-cut lung slices were perfused with 30µM BAs and 300 nM of acetylcholine(ACh): airway lumen area(LA) analyzed with video-phase contrast microscopy. Mice were nebulized with 1mM BA and incremental methacholine(MCh). Lung resistance(Rn) measured on Flexivent. Results: Bacteria were in 29% (71/238) of BW and showed greater: total BAs(p=0.0003); unconjugated(p=0.0002); conjugated(p=0.01); primary(p=0.0015); secondary(p=0.002). Fungi were in 14%(35/238) of BW with greater primary BAs(p=0.045). In-vitro perfusion of BAs in airways pre-contracted with ACh showed ~60% relaxation of LA(p Conclusion: BAs strongly associate to bacterial infections confirming their involvement in allograft dysfunction. Reduced bronchial reactivity suggests that BAs may affect both lung innate defense and function. The effect of BAs on airway reactivity may impair airway clearance and in turn promote infections.