Primary Graft Dysfunction (PGD) is severe acute lung injury after lung transplantation. PGD has a major impact on outcomes following lung transplantation, markedly increasing morbidity, mortality, and cost. Thus, reduction in the incidence of PGD would dramatically improve clinical and economic outcomes following lung transplantation. In addition, concern about PGD following lung transplantation is the main reason why potential lung donors are not considered suitable for use. Consequently, reduction of PGD incidence could also increase the number of transplants performed. Despite the clear importance of PGD to lung transplantation, fundamental questions about characteristics of donors and recipients that increase PGD risk remain unanswered. Likewise, investigation of biological mediators in PGD risk and pathogenesis is in the early stages, though recent studies by our group have begun to address these questions.
We aim to study the association of clinical variables in donors and recipients with subsequent development of PGD. Specifically, we hypothesize that inherent clinical risk factors of the donor and recipient influence the risk of PGD. This study takes advantage of our established multicenter cohort study infrastructure to identify an expanded sample of patients to achieve the following specific aims: 1) determine the association of clinical and biological risk factor variables in recipients with development of PGD following lung transplantation;2) determine the association of clinical risk factor variables in donors with development of PGD following lung transplantation;and 3) develop and validate a predictive model for PGD based on donor and recipient clinical and biological variables. The goals of our aims are to both provide insight into the mechanisms of PGD by studying clinical risk factors, as well as aid in prediction of PGD based on donor and recipient characteristics. To achieve these aims, we will perform a multicenter cohort study of 1700 patients undergoing lung transplantation at 9 centers in the U.S. Greater understanding of these risk factor variables will lead to improved recipient selection, donor selection, and donor-recipient matching to reduce the incidence of PGD. Identification of clinical and biological risk factors will also suggest further clinical and bench research into understanding mechanisms of these risk factor associations. In addition, better ability to predict PGD will likewise directly influence lung transplant practice, leading to expansion of available donor organs in lower risk candidates, as well as identification of high risk procedures for clinical trial enrollment.
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