Abstract
Activated pepsin (pepA) in bronchoalveolar lavage (BAL) fluid may be a biomarker of gastric aspiration. We sought to <em>i</em>) evaluate the association of pepA in BAL fluid with acute cellular rejection (ACR) in a cohort of lung transplant recipients (LTRs), <em>ii)</em> assess the association between pepA and isolation of typical gastrointestinal microorganisms from BAL fluid, and <em>iii)</em> explore the accuracy of using pepA concentration as a biomarker of ACR. After IRB approval, we conducted a retrospective observational study analyzing posttransplant BAL fluid samples and concomitant transbronchial biopsies (TBBs) obtained from LTRs who underwent at least two routine surveillance bronchoscopies between March 2020 and August 2022. A total of 349 BAL samples and paired TBBs from 120 LTRs were analyzed. Thirty-five LTRs (29.2%) had at least one episode of ACR during the study period. Most recipients (83.3%) had detectable pepA in at least one BAL sample. LTRs with detection of pepA any time after LTx had a higher likelihood of ACR (OR 9.79 [CI95: 1.26-79.26], P = 0.009). The pepA concentration trended higher as the histological grade of ACR increased, and a cut-off of >2.45 ng/mL provided a sensitivity of 63.3% and specificity of 57.3% to detect ACR. In conclusion, detectable pepA in BAL samples is common among LTRs and was associated with the occurrence of ACR. Furthermore, the BAL pepA concentration trended higher as the histological ACR grade increased; however, this biomarker has several drawbacks if used alone for the detection of ACR, and cautious interpretation is recommended.