Levy Liran, Moshkelgosha Sajad, Huszti Ella, Wang Stella, Hunter Sarah, Zhang Chen Yang Kevin, Ghany Rasheed, Keshavjee Shaf, Singer Lianne G, Tikkanen Jussi, Juvet Stephen, Martinu Tereza
Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Netwrok, Toronto, ON, Canada; Institute of Pulmonary Medicine, Sheba Medical Center and School of Medicine, Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, Israel.
Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Netwrok, Toronto, ON, Canada.
J Heart Lung Transplant. 2025 Apr;44(4):634-642. doi: 10.1016/j.healun.2024.11.020. Epub 2024 Nov 19.
Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are primarily used to detect acute cellular rejection (ACR) or infection in lung transplant (LTx) recipients. We previously identified a BAL protein signature associated with chronic lung allograft dysfunction (CLAD) or death/retransplant in patients with stable minimal (grade A1) ACR. This present study aimed to determine whether similar BAL biomarkers predict outcomes in stable patients when ACR grade is undetermined.
The cohort included all adult, first bilateral LTx performed 2010-2017. Clinical status was categorized as unstable or stable based on the presence or absence of a ≥ 10% drop in FEV1. Clinically-stable patients with grade AX TBB (inadequate biopsies) during the first year post-transplant, not preceded by ACR (grade A≥1 or B≥1), were included. IL6, S100A8, IL10, TNF-receptor-1, IL1α, pentraxin3, and CXCL10 were measured in the BAL using a multiplex bead assay. Associations with subsequent CLAD or death/retransplant were assessed using multivariable Cox proportional hazards models, adjusted for relevant clinical covariates.
Among 107 patients with stable AX biopsies at a median of 188 days post-transplant, the median times from biopsy to CLAD and death/retransplant were 972 and 1410 days, respectively. CXCL10 was significantly associated with CLAD, while IL6, S100A8, pentraxin3, TNF-receptor-1, and IL10 were associated with death/retransplant (p < 0.05 for all).
A focused BAL protein signature in stable patients with ungradable TBB early post-transplant may predict worse outcomes. Such select BAL biomarkers may identify patients who require more aggressive management strategies or closer monitoring.
