Ng Choo Y, Madsen Joren C, Rosengard Bruce R, Allan James S
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Front Biosci (Landmark Ed). 2009 Jan 1;14(5):1627-41. doi: 10.2741/3330.
As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients.
由于手术技术、免疫抑制治疗及术后管理的进步,肺移植已成为各种终末期肺病患者公认的治疗选择。目前肺移植术后1年的精算生存率接近80%。然而,在过去15年中,由于急性和慢性肺移植排斥反应,5年精算生存率实际上一直保持在约50%不变(1)。临床医生仍然依赖大量免疫抑制剂来抑制移植排斥反应,但发现自己受到一个无法避免的治疗悖论的限制。免疫抑制不足会因排斥反应导致移植失败,而过度免疫抑制会因机会性感染和恶性肿瘤导致发病率和死亡率增加。事实上,移植排斥、感染和恶性肿瘤是肺移植受者死亡的三个主要原因。还应记住,肺移植受者的移植失败通常是致命事件,因为没有长期机械支持的实际手段,而且鉴于可接受的供体移植物短缺,再次移植的前景也很低。本章回顾了肺移植免疫抑制治疗的现状,并提出了未来肺移植受者管理的替代模式。