P033 Predictive biomarkers, and therapeutic targets, from the donor graft associated with the development of primary graft dysfunction after lung transplantation in cystic fibrosis patients

Background: Lung transplantation is the only therapeutic option for patients with terminal lung disease, including cystic fibrosis (CF). Unfortunately, primary graft dysfunction (PGD), first cause of death in perioperative period, associated lower survival rates. We hypothesized that alveolar donor graft, after cold ischemia and inflammation, a critical component PGD pathophysiology recipients. Objective: The goal this study was 1) to impact inflammation on integrity 2) identify markers damage within grafts before development Methods: used cellular animal models inflammation. also collected samples data from 172 donors their recipients (including 67 CF patients). grade determined according ISHLT guidelines. levels inflammatory, damage/integrity, functionality were then determined. Results: Analyses cell cultures porcine tissues, ischemia, revealed reduction tight junction (ZO-1) protein, ENaC CFTR expression. Among recipients, we found duration although below recommended threshold, increased scores. Histological analysis immunostainings biopsies showed epithelial as well reduced ZO-1, expression, among Importantly, observed relationship between ENaC/CFTR channel higher duration, Conclusion: This provides novel insights into damage/dysfunction recipient paves way identification predictive biomarkers targets transplants.