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INTRODUCTION

Lung transplantation is the ultimate treatment for patients with advanced and end-stage lung diseases. The number of lung transplants performed annually has grown consistently over the past 30 years worldwide.1 Indeed, more than 4500 lung transplants have been reported annually to the International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation (ISHLT).1 Although donor organ availability is the primary barrier to increasing the volume of procedures performed, advances in donor selection, management, and the use of donation after circulatory death (DCD) donors and ex vivo lung perfusion (EVLP) have expanded the donor pool and allowed growth in transplant volumes worldwide.2–7 Similarly, growing experience with lung transplantation has resulted in expansion in candidate selection. Today, lung transplant recipients are generally older, have more severe lung disease, have more comorbidities, and are more likely to be hospitalized or require life support before transplantation than 10 years ago.2 Nonetheless, long-term survival after transplantation continues to improve compared with previous eras although the magnitude of this improvement is small on a year-to-year basis.1,2 Indeed, long-term survival after lung transplantation remains significantly worse than after other solid organ transplants including kidney, liver, and heart transplantation.2,8–10 Chronic lung allograft dysfunction (CLAD) has emerged as the leading obstacle to better long-term survival and the most common cause of death beyond the first year after transplantation.1 The incidence of CLAD approaches 30% 3 years after transplantation, and the clinical course is characterized by a progressive decline in lung function culminating in severe clinical and physiologic impairment, respiratory failure, and death.11–13 Other important complications after lung transplantation include infections, cardiovascular disease, chronic kidney disease (CKD), and malignancy.1 Combined with episodes of rejection and the development of CLAD, these comorbidities adversely impact both quality of life and survival after lung transplantation. Better strategies and immunosuppressive regimens to prevent the development of CLAD and minimize the development of other complications are needed to improve long-term outcomes after lung transplantation. These have been the focus of basic, translational, and clinical studies, and ongoing research is critical to this mission.

HISTORY

The first human lung transplant was performed in 1963 by Dr. James Hardy at the University of Mississippi.14 The recipient was a debilitated man with emphysema and lung cancer obstructing the left mainstem bronchus; other comorbidities included malnutrition and CKD. It was thought that a patient with a “terminal” condition was most appropriate for the first human lung transplant, which was considered an experimental treatment at the time. The patient underwent a left single lung transplant from a DCD donor. Immunosuppression consisted of mediastinal irradiation and azathioprine. The allograft functioned well with improvement in gas exchange; however, the recipient developed progressive kidney failure and ultimately died on day 18 after transplantation. In spite of the poor outcome, this early experience demonstrated that lung transplantation was technically ...

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