Lung Transplantation: Controversies and Evolving Concepts

John A. Belperio, MD

Allan R. Glanville, MB, BS, MD, FRACP

Lung transplantation is now a therapeutic option for patients with end-stage lung and pulmonary vascular disorders. Since the inception of the first lung transplant, there has been substantial progress made in both the clinical and basic science realms. More specifically, we have expanded the donor pool by using after circulatory death lungs and through the use of ex vivo lung perfusion. We have also expanded the recipient pool via the use of extracorporeal membrane oxygenation. In parallel, advances have been made in candidate selection via our ability to prognosticate outcomes of various lung diseases and though the implementation of the lung allocation scoring (LAS) system. This system has resulted in a decreased mortality for patients on the lung transplant waiting list. In addition, risk factors have been identified for poor outcomes postlung transplant with a better understanding of the physiological, cellular, and molecular mechanisms responsible for primary graft dysfunction (PGD), infectious diseases, acute rejection, antibody-mediated rejection, lymphocytic bronchiolitis, organizing pneumonia, obliterative bronchiolitis, restrictive allograft syndrome, and other forms of chronic lung allograft dysfunction (CLAD).

Although early posttransplant survival has improved due to better surgical techniques and perioperative care, the problems of severe PGD, infectious diseases (e.g., bacterial, viral, fungal, and mycobacterial), and allograft rejection continue to be common causes of morbidity and mortality. Thus, there is a need to extend our current understanding of how PGD, infection, and acute and chronic rejection interrelate and lead to the demise of the lung allograft.

This issue of Seminars in Respiratory and Critical Care Medicine is dedicated to lung transplantation and integrates both basic and clinical science, providing a comprehensive perspective on determining which patients need a lung transplant, how the LAS improves waiting times, factors contributing to PGD, the contribution of PGD to morbidity and mortality, diagnosis and treatment of acute rejection, lymphocytic bronchitis, infectious diseases, and CLAD. Dr. Orens goes over the current controversies and new developments in the selection criteria for lung transplantation. With the waiting list for lung transplants far out numbering the availability of donors, Dr. Snell reviews the literature on expanding the donor pool by using after circulatory death lungs. Dr. Egan reviews the role of the LAS system and its impact on pre- and postlung transplantation outcomes. Dr. Shah and colleagues tackle the first insult the lung allograft absorbs, PGD with regard to its new criteria, pathobiology, and treatment. Other insults the lung allograft has to face include acute rejection and infections. These topics are extensively covered. More specifically, Dr. Benzimra evaluates the relevance of surveillance bronchoscopy to pick up infections and/or rejection and its impact on the transplant recipient. Dr. Hachem describes the best immunosuppressive regimens to limit rejection and infection, while Dr. Martinu appraises acute rejection with regard to diagnosis and treatment. Posttransplant infections are also covered. Dr. Gottlieb takes us through community acquired respiratory viruses, Dr. Clark describes fungal infections posttransplant, and Dr. Mitchell evaluates the human respiratory microbiome as it influences long-term outcomes after transplantation. Dr. Derhovanessian weighs in on the risk factors, pathobiology, and treatment of CLAD. Dr. Kolaitis evaluates the quality outcomes as a way to measuring success of lung transplant.

We would like to thank all the contributors for their hard work in preparing this issue of Seminars in Respiratory and Critical Care Medicine dedicated to lung transplantation.