Bronchoalveolar Lavage Markers of Inflammation Early Post Lung-Transplant are Associated with CLAD and Death

PURPOSE Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are used in the evaluation of patients after lung transplant to detect acute cellular rejection (ACR) or infection. We have previously shown that a focused BAL protein signature early post-transplant may predict CLAD or death in a subset of clinically-stable patients with A1 ACR. The aim of the current study was to determine whether similar BAL markers would have similar predictive characteristics irrespective of ACR grade. METHODS The cohort consisted of all adult, first, bilateral lung transplants performed 2010-2017. Clinical status was categorized as unstable or stable based on presence or absence of ≥10% concurrent drop in FEV1. Clinically-stable patients with grade AX TBB (which are not routinely treated at our center, thus avoiding the confounding effect of ACR treatment) during the first-year post-transplant, not preceded by ACR (grade A≥1 or grade B≥1) were included. IL6, S100A8, IL10, TNF-receptor1, IL-1α, pentraxin3 and CXCL10, previously shown to be associated with worse outcomes, were measured in the BAL using a multiplex bead assay. Association with subsequent CLAD or death was assessed using Cox proportional hazards models adjusted for age, sex, native lung disease, and CMV-mismatch. RESULTS 107 patients matched the inclusion criteria with a stable AX occurring at a median time of 188 days (IQR 96-279) post-transplant. Median time from AX TBB to CLAD or death was 462 (IQR 330, 928) and 582 days (IQR 251-1410), respectively. In multivariable models, levels of CXCL10 and IL10 were associated with both CLAD development and death while IL6, S100A8 and pentraxin3 were only associated with death (P<0.05 for all). CONCLUSION A focused BAL protein signature in clinically-stable patients with ungradable TBB, early post-transplant, may be informative in determining a subset of patients who are at increased risk for worse outcome and may benefit from a more aggressive management strategy.