Project Summary/Abstract Primary graft dysfunction (PGD) is the most common cause of morbidity and mortality after lung transplantation resulting in significant negative effects on quality of life and cost. PGD has a complex relationship with donor organ use because uncertainty in organ quality and concern that poor donor quality causes susceptibility to PGD results in high discard rates for potentially transplantable organs. With almost 1 in 5 candidates dying awaiting lungs for transplant, calls for new methods to define donor quality and PGD risk have become a major public health challenge. The long-term objective of our line of research is to prevent recipient death and expand the donor pool through better donor selection. Recent evidence suggests innate immune activation is important in PGD pathogenesis based on transcripts from donor lung tissue, bronchial wash and blood. Using these transcripts, we have developed two objective gene expression based risk assessment tools to stratify PGD risk and identify organs which may be suitable for transplant from the pool of unused organs. Utilizing these tools, we will conduct a prospective multicenter cohort study to externally validate our prediction tools for donor pool expansion. Successful completion of our aims will lead to an objective marker of donor organ quality whose application will simplify subjective decision making in donor selection and identification of new organs for donor pool expansion.