Late Breaking Abstract - Comparison of Ex Vivo Airway Epithelium of Transplant Recipients

Bronchiolitis obliterans syndrome (BOS) is a severe complication affecting about 50% of hematopoietic stem cell transplantation (HSCT) and 5-10% of lung transplantation (LT) recipients, often triggered by respiratory viral infections (RVIs). This study examines the impact of transplantation on respiratory epithelium integrity and regenerative capacity, hypothesizing that compromised epithelium poorly responds to RVIs, contributing to BOS occurrence. Using <italic>ex vivo</italic> human airway epithelia (HAE) reconstituted from patient bronchial biopsies, we compared tissues from HSCT and LT donors with controls, both in steady-state and upon infection with SARS-CoV-2 and human parainfluenza virus type 3 (HPIV3). Findings were validated in formalin-fixed paraffin-embedded (FFPE) biopsies from the same donors. HAE differentiation was analyzed under transplant-related drug exposure, and airway epithelial chimerism was assessed using FISH analysis and SNP-based sequencing. HSCT epithelium had fewer ciliated cells and impaired barrier integrity, confirmed in FFPE biopsies. Basal cells treated with HSCT drugs fludarabine and busulfan failed to differentiate properly. HAE from LT patients showed more mucous cells, with LT recipients having significantly higher viral loads. Epithelial chimerism was evident in both FFPE biopsies and <italic>ex vivo</italic> HAE from HSCT and LT recipients. Respiratory function monitoring linked tissue morphology defects to functional decline in HSCT settings. Long-term follow-up aims to correlate these findings with BOS development. This study highlights the pathophysiological defects in the airway post-transplantation and the associated increased viral replication, both potentially contributing to BOS development