Lung transplantation: recent developments and future challenges.

The first successful lung transplantation was not an isolated procedure, but part of combined heart–lung transplantation. Reports of the first series were published in the early 1980s.1 Not until the end of that decade was there large-scale success with isolated lung transplantation: intensive investigation led to the first series of patients who underwent successful double-lung transplantation.2 From the outset, there has been interplay between technical developments in lung transplantation procedures, the cohort of patients being served, and long-term surgical and functional outcomes. If the most optimal benefits are to be achieved, this interplay will remain necessary in the complex arena of lung transplantation. One major development in lung transplantation during the 21st century has been the implementation of the Lung Allocation Score (LAS) in the allocation of available donor lungs.3 The impact of this implementation on the outcomes of lung transplantation is being intensively investigated. The LAS system of organ allocation was devised for 2 reasons: to decrease waiting-list mortality rates by identifying candidates at higher risk of dying before transplantation, and to increase the net benefits of transplantation. A patient's expected survival time while on the waiting list and expected survival time after transplantation are determined, and a weighted score from 0 to 100 yields a balance between transplantation urgency and transplantation benefit. This method of organ allocation differs greatly from the time-accrual method that was used before. The result of implementing the LAS system has been a net decrease in waiting-list survival time, but also a net decrease in one-year post-transplantation survival time—because sicker patients are now receiving transplants in a timely manner. The implementation of the LAS system has resulted in a shift toward lung transplantation in patients who have pulmonary fibrotic disease, instead of in patients who have primarily chronic obstructive pulmonary disease. The transplantation rate in patients with pulmonary hypertension, cystic fibrosis, and other diseases has not changed dramatically. However, patients who have a disease other than pulmonary fibrosis appear to be undergoing transplantation at a stage much later in their disease course than before. This is a natural consequence of the LAS system.4 As another consequence, patients previously deemed unsuitable as transplantation candidates because of extremely high waiting-list mortality rates are now more frequently being considered for transplantation. The increased availability of organs for the sickest patients has led to the development of techniques to temporarily support acutely decompensating patients. The chief development has been the more frequent use of extracorporeal membrane oxygenation (ECMO) to bridge patients to lung transplantation. In ECMO, a cannula is inserted into the patient's venous system, and blood is removed, pumped across a membrane oxygenator, and returned to the patient. The return can be into the patient's venous system or arterial system. The chief technological development has been the miniaturization of the circuit used for venovenous ECMO. Patients with primary pulmonary failure can now be sustained with only partial support. Small, portable circuits, which provide ECMO through a single cannula in the jugular vein, enable patients to remain ambulatory while they await a new lung. The shortage of donor organs is a chronic problem. Implementing the LAS system has increased the allocation of available organs to the sickest patients—those most likely to benefit from transplantation. However, the LAS system has not expanded the donor-organ pool. Despite an increase in donor-lung numbers during the past decade and the greater liberality of many centers in their organ-selection criteria, there remains a substantial shortfall in available organs to meet the demand. The lung is highly sensitive to acute injury, and concerns about pulmonary function after actual or suspected injury have caused many donor lungs to be considered unsuitable for transplantation. However, it appears that a large number of these donor lungs are actually usable, having been subjected only to transient pulmonary dysfunction. Systems are being developed to enable ex vivo evaluation and rehabilitation of potential donor lungs. Success in this investigational area could greatly expand the pool of available lungs.5 In the early 21st century, more lung transplantation procedures than ever are being performed, the mortality rate for wait-listed patients has declined, and the long-term survival rates of high-risk patients have improved. Nonetheless, the success of lung transplantation depends upon further refining the allocation of available donor organs, improving our abilities to keep dying patients alive until lungs become available, expanding the donor pool, and improving postoperative management. Because of active investigation in all of these areas, the future of lung transplantation as a viable treatment for end-stage lung disease seems to be secure.