Molecular biopsy features associated with BLAD in lung transplant recipients

An analysis of the multicenter, international, prospective INTERLUNG study (NCT02812290), evaluating transbronchial biopsy (TBB) gene expression changes associated with baseline lung allograft dysfunction (BLAD) in double lung transplant recipients, were published in The Journal of Heart and Lung Transplantation by Mackova et al. The analysis included 252 TBBs obtained from 214 adult double lung transplant recipients. Biopsies were collected within the first year following transplantation, and BLAD status was assessed 1 year post-transplant.

Key data: Histologic T cell-mediated rejection (TCMR) rates were comparable between biopsies from patients with BLAD and those with normal lung function (23% vs 24%; p = 0.92). However, molecular rejection archetypes were more frequent with BLAD biopsies (12% vs 5%; p = 0.03), as were low surfactant archetypes (10% vs 3%; p = 0.03), whereas no-rejection archetype was less common (47% vs 62%; p = 0.02). A molecular classifier developed using the 1,000 transcripts most strongly associated with BLAD demonstrated modest predictive performance (area under the curve [AUC], 0.58), improving to 0.64 with the addition of clinical variables.

Key learning: TBBs obtained within the first year after lung transplantation from patients with BLAD exhibited molecular features consistent with TCMR that were not detected by histology, suggesting molecular biopsy may identify rejection-associated inflammation not captured by conventional pathology.