Primary graft dysfunction: pathophysiology to guide new preventive therapies

Primary graft dysfunction (PGD) is a common complication of lung transplantation characterized by acute pulmonary edema associated with bilateral pulmonary infiltrates and hypoxemia in the first 3 post-operative days. Development of PGD is a predictor of poor short- and long-term outcomes after lung transplantation, but there are currently limited tools to prevent its occurrence. Areas covered: Several potentially modifiable donor, recipient, and operative risk factors for PGD have been identified. In addition, basic and translational studies in animals and ex vivo lung perfusion systems have identified several biomarkers and mechanisms of injury in PGD. In this review, we outline the clinical and genetic risk factors for PGD and summarize experimental data exploring PGD mechanisms, with a focus on strategies to reduce PGD risk and on potential novel molecular targets for PGD prevention. Expert commentary: Because of the clinical importance of PGD, development of new therapies for prevention and treatment is critically important. Improved understanding of the pathophysiology of clinical PGD provides a framework to explore novel agents to prevent or reverse PGD. Ex vivo lung perfusion provides a new opportunity for rapid development of therapeutics that target this devastating complication of lung transplantation.