Chronic lung allograft dysfunction (CLAD) remains the principal limitation to long-term survival after lung transplantation (LT). Early molecular alterations within the graft may precede clinically overt functional decline, but their biological significance remains incompletely defined. In this single-center exploratory pilot study, 16 bilateral lung transplant recipients underwent bronchoalveolar lavage (BAL) sampling at 7 days, 15 days, and 3 months post-transplantation. BAL-derived microRNA (miRNA) profiles were analyzed longitudinally and correlated with long-term clinical outcomes, including CLAD development and phenotypic classification into bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), over extended follow-up (mean 98 months). Distinct early miRNA signatures were detectable within the first weeks after transplantation and were associated with divergent long-term clinical trajectories. Specific miRNAs, namely let-7e-5p and miR-30d-3p, were associated with subsequent CLAD, whereas differential expression patterns distinguished trajectories toward BOS or RAS. Enrichment analyses highlighted networks related to innate immune activation, hypoxia, tissue remodeling, and PI3K–mTOR signaling. Notably, the occurrence of acute rejection did not differ significantly between patients who developed CLAD and those who remained stable. These findings, although preliminary, suggest that early BAL-derived miRNA profiles may reflect biologically distinct graft states associated with long-term CLAD phenotypes.
Gaudioso et al. (Mon,) studied this question.