Bronchoalveolar bile acid and inflammatory markers to identify high-risk lung transplant recipients with reflux and microaspiration.

BACKGROUND Gastroesophageal reflux disease (GERD) is a risk factor for chronic lung allograft dysfunction (CLAD). The presence of bile acids—putative markers of gastric microaspiration—and inflammatory proteins in the bronchoalveolar lavage (BAL) has been associated with CLAD, but their relationship with GERD remains unclear. While GERD is thought to drive chronic microaspiration, selection of patients for anti-reflux surgery lacks precision. This multicenter study aimed to test the association of BAL bile acids with GERD, lung inflammation, allograft function, and anti-reflux surgery. METHODS We analyzed BAL obtained during the first post-transplant year from a retrospective cohort of patients with and without GERD, as well as BAL obtained before and after Nissen Fundoplication anti-reflux surgery from a separate cohort. Levels of taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid were measured using mass spectrometry. Protein markers of inflammation and injury were measured using multiplex assay and ELISA. RESULTS At 3 months post-transplant, TCA, IL-1s, IL-12p70, and CCL5 were higher in the BAL of patients with GERD, compared to no-GERD controls. Elevated TCA and GCA were associated with concurrent acute lung allograft dysfunction and inflammatory proteins. Importantly, BAL obtained after anti-reflux surgery contained reduced TCA and inflammatory proteins compared to BAL obtained before anti-reflux surgery. CONCLUSIONS Targeted monitoring of TCA and select inflammatory proteins may be useful in lung transplant recipients with suspected reflux and microaspiration to support diagnosis and guide therapy. Patients with elevated biomarker levels may benefit most from anti-reflux surgery to reduce microaspiration and allograft inflammation.