Primary Graft Dysfunction (PGD) Following Lung Transplantation

Abstract

Primary graft dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung allograft dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics. Risk factor identification has led to the development of PGD predictive algorithms, although their clinical utility remains limited. Ongoing areas of controversy and discussion include further refinements to the PGD grading scheme to account for technologic advances such as extracorporeal membrane oxygenation and the increased utilization of high flow nasal cannula, the use of PGD as an outcome measure in clinical trials of ex vivo lung perfusion, enhancement of predictive algorithms incorporating biochemical risk factors, and the need for development of therapies targeted at improving PGD outcomes.

Enhanced Mitochondrial DNA Repair Resuscitates Transplantable Lungs Donated After Circulatory Death

“…Only 10%-15% of lungs procured are judged clinically suitable for transplantation because of a subjective but rigorous selection process based on physician experience and physiological parameters. 1 Despite efforts to optimize clinical outcomes, recipients continue to be at risk because of posttransplantation complications such as primary graft dysfunction (PGD), 2 which occurs in up to 20% of lung transplant patients. Persuasive evidence suggests that oxidant stress from ischemiareperfusion (IR) injury contributes to the evolution of PGD.…”

“…Persuasive evidence suggests that oxidant stress from ischemiareperfusion (IR) injury contributes to the evolution of PGD. [2][3][4] The target molecule(s) linking IR-related oxidant stress to PGD and associated activation of inflammatory cascades has not been thoroughly elucidated. Multiple observations, however, suggest that the mitochondrial genome may serve such a sentinel function.…”

Extracellular histones play a pathogenic role in primary graft dysfunction after human lung transplantation

“…2 However, because of the special anatomical structure and physiological functions of the lung, several complications such as primary gra dysfunction (PGD) are commonly seen aer lung transplantation, which may be the reason that survival aer lung transplantation is relatively low compared with other organ transplants. 3,4 PGD is a form of acute lung injury (ALI) that develops within the rst 72 hours aer lung transplantation. 5 It is dened by the presence of hypoxemia and radiographic inltrates, and is a major cause of early mortality and morbidity aer transplant.…”

“…6 The incidence of PGD aer lung transplantation is estimated to be 10 to 30%. 3 PGD is also associated with the development of bronchiolitis obliterans syndrome (BOS), a form of chronic lung allogra dysfunction. 7 Patients with PGD usually had prolonged hospitalization, and increased short-and long-term mortality when compared to non-PGD patients.…”

Primary graft dysfunction and beyond after lung transplantation in the current era

“…Whereas many series of clinical studies have shown that the PGD incidences at all time points and all PGD grade have positive correlation with BOS development , given these recent studies demonstrating that such correlation is not always the case in the current era, the drivers of both short‐ and long‐term survival may remain to be fully understood . While we should continue to prioritize research to understand the drivers underlying PGD and new therapeutic strategies to minimize its occurrence, it also should be reminded that improvements to the surgical techniques used for lung transplant including lung preservation/protection as well as utilization of cardiopulmonary support during the procedure may reduce PGD and/or BOS; however, the standard surgical techniques for lung transplant have basically remained unchanged for the last two decades, and only a few modifications to these techniques have improved long‐term outcomes .…”