Special issues in the management and selection of the donor for lung transplantation

Semin Immunopathol (2011) 33:201–210 DOI 10.1007/s00281-011-0256-x REVIEW Special issues in the management and selection of the donor for lung transplantation Priyumvada M. Naik & Luis F. Angel Received: 28 June 2010 / Accepted: 14 January 2011 / Published online: 15 April 2011 # Springer-Verlag 2011 Abstract Lung transplantation is a viable treatment option for select patients with end-stage lung disease. Two issues hamper progress in transplantation: first, donor shortage is a major limitation to increasing the number of transplants performed. Secondly, recipient outcomes remain disappointing when compared with other solid organ transplant results. Outcomes are limited by primary graft dysfunction (PGD), the posttransplant acute lung injury that increases both short-and long-term mortality. Attempts to overcome donor shortage have included aggressively managing solid organ donors to increase the number of donor lungs suitable for transplantation. Yet, the quality of the lung donor is likely to be related to the probability of the recipient experiencing PGD. PGD is the culmination of a series of insults, hemodynamic, metabolic, and inflammatory, that begin with the brain dead donor and result in poor recipient outcomes. Understanding the mechanism of donor lung This article is published as part of the special issue on Transplantation and Tolerance. P. M. Naik (*) Heart Lung Institute, Center for Thoracic Transplant, St. Joseph’s Hospital, 500 W. Thomas Road, Suite 500, Phoenix, AZ 85013, USA e-mail: L. F. Angel Cardiothoracic Surgery and Pulmonary and Critical Care Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, 7841, San Antonio, TX 78229-3900, USA e-mail: injury resulting from brain death and the possible treatment strategies for its inhibition could help to increase the number of usable lungs and decrease the rate of PGD in the recipient. Here we present a review of the key pathways which result in donor lung injury, and follow this with a brief review of recent biomarkers that are proving to be instrumental to our ability to predict truly unsuitable lungs, and our ability to predict and hopefully prevent or treat recipients with subsequent lung injury. Keywords Organ donation . Lung transplantation . Donor management . Brain death Introduction The first lung transplant was performed in 1963 by Dr. James Hardy at the University of Mississippi [1]. The recipient survived 18 days. Over the next 20 years, another 40 lung transplants were performed, though the longest survival achieved was 10 months [2, 3]. With the introduction of cyclosporine to immunosuppression regimens, as with all solid organ transplants, lung transplant volumes have increased. Unfortunately, survival after lung transplantation continues to lag behind other solid organ transplants. Based on data from the Organ Procurement and Transplant Network (OPTN), 1-, 3-, and 5-year survival in 2006 was 85%, 65%, and 50%, respectively. Short-term outcomes are complicated by primary graft dysfunction (PGD), a form of ischemia–reperfusion injury (IRI) that pathophysiologically is similar to acute lung injury. PGD is seen in 15–50% of cases and results in increased mortality, prolonged ventilator course, intensive care unit (ICU) and 202 hospital length of stay (LOS), and healthcare costs [4, 5]. Even long-term outcomes in recipients with PGD are worse than those who do not develop PGD. PGD is a risk factor for the development of bronchiolitis obliterans syndrome (BOS), the clinical correlate of obliterative bronchiolitis, which is the greatest limitation to graft survival long-term [6, 7]. While many recipient risk factors have been identified, it is now widely known that the risk of allograft dysfunction is the result of the culmination of a series of insults, beginning within donor [8]. Although some of these inflammatory and immunologic changes increase risk of lung injury in the recipient, a portion of these changes may be reversible. For example, brain death itself results in neurogenic pulmonary edema, but evidence shows this dissipates over time [9]. However, the donor may still have clinical and radiographic evidence of edema when the organ procurement organization (OPO) staff becomes involved. Unfortunately, this translates to OPO staff not obtaining consent for lung donation from families, which leads to lower numbers of lungs being offered nationally. Multiple studies of donor management strategies that include OPO referral of all potential donors for lung donation have shown improved rates of lung consent, referral, offer, and ultimately transplantation [10, 11]. This inability to identify acceptable donor lungs that may look poor at the outset partially explains why the number of patients waiting for this potentially lifeextending procedure has steadily increased while the number of donors available nationally has remained between 14% and 17% [12]. This is lower than procurement rates of any other solid organ. In 2007, over 14,000 pairs of kidneys were procured from deceased donors. In contradistinction, 2,500 pairs of lungs were procured [12]. During that period, 4,678 people waited for lung transplants. Only 31% of those people received transplants, due to donor availability. Seven percent of patients died while waiting for lungs, and an additional 8% were removed from the waitlist because of worsening of their lung disease or other complications [12]. Almost 40% of patients on the waitlist in 2007 had been waiting for longer than a year, with 20% of them waiting longer than 2 years [12]. Thus, though the number of patients who wait for transplant continues to increase, the number of available donors remains markedly low, resulting in greater numbers of deaths while on the waitlist. Brain death itself can mask acceptable organs as well as confer risk both to lung suitability pretransplant, and to recipient outcomes. Further understanding of these principles is necessary to form treatment strategies in an effort to increase procurement rates of lungs from brain dead donors, as well as minimize risk conferred by subsequent lung injury and improve recipient outcomes. Semin Immunopathol (2011) 33:201–210 What makes lungs so susceptible? The impact of brain death on donor lung suitability Donor availability is clearly the greatest impediment to increasing lung transplantation rates, more so than any other solid organ or tissue procured for transplant. Factors that predispose lungs to deteriorate prior to organ donation include aspiration, contusion, infection, and the multitude of events that occur as a consequence of brain death. In other solid organ transplants, outcomes from living donors are excellent when compared with brain dead donors, even when taking ischemic times into consideration [13]. In contradistinction, animal studies of kidney, liver, and heart recipients from brain dead donors resulted in poorer outcomes [14–16]. Furthermore, long-term out (...truncated)