Mitigating the risk of inflammatory type primary graft dysfunction by applying an integrated approach to assess, modify and match risk factors in lung transplantation.

ABSTRACT

Long-term outcome following lung transplantation remains one of the poorest of all solid organ transplants with a 1- and 5-year survival of 85% and 59% respectively for adult lung transplant recipients and with 50% of patients developing chronic lung allograft dysfunction (CLAD) in the first 5 years following transplant. Reducing the risk of inflammatory type primary graft dysfunction (PGD) is vital for improving both short-term survival following lung transplantation and long-term outcome due to the association of early inflammatory-mediated damage to the allograft and the risk of CLAD. PGD has a multifactorial aetiology and high-grade inflammatory-type PGD is the result of cumulative insults that may be incurred in one or more of the three variables of the transplantation continuum the donor lungs, the recipient and intraoperative process. We set out a conceptual framework which uses a fully integrated approach to this transplant continuum to attempt to identify and, where possible, modify specific donor, recipient and intraoperative PGD risk with the goal of reducing inflammatory-type PGD risk for an individual recipient. We also consider the concept and risk-benefit of matching lung allografts and recipients on the basis of donor and recipient PGD-risk compatibility. The use of ex vivo lung perfusion (EVLP) and the extended preservation of lung allografts on EVLP will be explored as safe, non-injurious EVLP may enable extensive inflammatory testing of specific donor lungs and has the potential to provide a platform for targeted therapeutic interventions on lung allografts.