Evolving Concepts and Controversies in Lung Transplantation

John A. Belperio, M.D., Jonathan B. Orens, M.D.

Lung transplantation is now considered to be a therapeutic option for patients with end-stage pulmonary and pulmonary vascular disorders. Since the inception of the first lung transplant there has been substantial progress made in both clinical and basic scientific realms. More specifically there have been advances in candidate selection, in identification of risk factors for poor outcomes, and in our understanding of the molecular, cellular, and physiological mechanisms responsible for primary graft dysfunction (PGD), infectious diseases, acute rejection, lymphocytic bronchiolitis, obliterative bronchiolitis, and chronic lung allograft dysfunction. Similar advances in our ability to prognosticate outcomes of various lung diseases have been implemented in the lung allocation scoring system, which has resulted in a decreased mortality for patients on the lung transplant waiting list.

Although early survival has improved due to better surgical techniques, infectious diseases 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 interact leading 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 lung allocation score improves waiting-list times, factors contributing to PGD, the contribution of PGD to mortality as well as long-term outcomes, diagnosis, and treatment of antibody-mediated rejection, acute cellular rejection, lymphocytic bronchitis, infectious diseases, and chronic lung allograft dysfunction.

Drs. Merlo and Orens provide a perspective on the selection criteria for obstructive and restrictive lung diseases, pulmonary hypertension, and bronchiectasis, as well as when to consider single versus double lung transplantation. Drs. Takahashi and Garrity review the role of the lung allocation scoring system and its impact on pre- and post–lung transplantation outcomes. Drs. Diamond and Kotloff provide an overview of the prognosis of obstructive lung diseases and clinical criteria used for determining the most appropriate time to list these patients for a lung transplant. Drs. Hayes and Meyer provide the criteria being used for cystic fibrosis and bronchiectasis patients to undergo lung transplantation. Dr. O'Beirne and colleagues discuss in detail when idiopathic pulmonary fibrosis (IPF) patients need a lung transplant and critique the studies that look at the role of single versus double lung transplantation for these patients. Dr. Saggar and associates discuss idiopathic pulmonary arterial hypertension and disorders associated with secondary pulmonary hypertension, review the role of medical therapies, optimal timing and selection criteria for lung transplantation, results following transplantation, and the rationale for bilateral versus single lung transplantation.

Dr. Lee and colleagues review the risk factors for primary graft dysfunction (PGD) and the effects of PGD on long-term outcomes. Drs. Floreth and Bhorade give a summary of induction and maintenance immune suppression and provide therapies for lung allograft rejection. Dr. Martinu and associates provide an overview of the biology, pathology, diagnostic criteria, and treatment options for acute allograft rejection and antibody-mediated rejection. Dr. Weigt and associates provide an overview of risk factors, pathogenesis, pathology, and treatment of BOS. Dr. Glanville adds insight into the role of bronchoscopy (surveillance versus clinically indicated) and establishes the role for acute cellular rejection and lymphocytic bronchiolitis and the development of bronchiolitis obliterans syndrome (BOS).

Drs. Hosseini-Moghaddam and Husain target fungal infections as a cause of significant morbidity and mortality post–lung transplant. With augmentation of immunosuppressive medication there is increased risk of infection; Drs. Lease and Zaas evaluate the role of pre- and posttransplant infectious diseases on overall outcomes. Drs. Shah and McDyer evaluate the role of viruses and lung allograft dysfunction.

In addition to reviewing the progress made in the field of lung transplantation, this issue of Seminars in Respiratory and Critical Care Medicine highlights the areas where additional knowledge is required to improve the outcomes for lung transplant patients. Novel clinical and basic science studies will be required to understand the role of antibody-mediated rejection, and the interactions of infection and rejection with the pathogenesis of chronic lung allograft dysfunction. 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.