More and Better Lungs: Ex-Vivo Perfusion of Lungs from Non-Heart-Beating Donors

描述（由申请人提供）：肺部疾病是美国第三大死亡原因。肺移植可以改善许多肺部疾病患者的生活质量，提高生存率。然而，肺移植受到严重限制，因为从传统器官供体——那些遭受致命脑损伤但在脑死亡前进行孵育和通风的个体——移植的合适肺数量不足。由于大多数来自传统器官捐献者的肺不适合移植，美国每年只有1700例肺移植手术。然而，肺组织在循环停止后仍能存活。在动物模型中，该项目的PI表明肺在移植后可以正常工作，即使在死亡后数小时内恢复。每年，美国有超过75万人成为猝死的受害者；如果可以从这些人——非心脏供体（NHBDs）——身上提取肺进行移植，就可以消除肺供体短缺的问题。PI进行了体外肺灌注（EVLP），以确定最初拒绝从传统器官供体移植的人肺的适用性。EVLP后移植这些肺的安全性最近得到了证实。这项拟议的2期临床试验将通过EVLP评估死亡后从NHBDs中取出的肺移植的安全性和有效性，我们将实现这一特定目标：与传统脑死亡器官供体的肺移植相比，使用EVLP评估的NHBDs中取出的肺进行肺移植的非劣效性。我们将从人口众多的北卡罗莱纳郡（威克）的马斯特里赫特1类和2类非hbds以及目标急诊室获取肺。我们将采用EVLP和离体CT扫描的既定方法来评估移植的适宜性。可接受的肺将在北卡罗来纳大学和杜克大学按照irb批准的方案进行移植。结果将与同时移植来自传统器官供体的肺的患者进行比较。

DESCRIPTION (provided by applicant): Lung disease is the third leading cause of death in the United States. Lung transplant could improve quality of life and enhance survival in many lung disease patients. However, lung transplantation is severely limited by an inadequate number of suitable lungs for transplant from conventional organ donors - individuals who sustain a lethal brain injury, but who are incubated and ventilated before brain death occurs. Because most lungs from conventional organ donors are not suitable for transplant, only 1,700 lung transplants are performed annually in the U.S. However, lung tissue remains viable after circulatory arrest. In animal models, the PI of this project showed that lungs can function well after transplant, even if retrieved hours after death. Each year, more than 750,000 people in the U.S. are victims of sudden death; if lungs could be retrieved for transplant from some of these people - non-heart-beating donors (NHBDs) - the lung donor shortage could be eliminated. The PI has performed ex-vivo lung perfusion (EVLP) to determine suitability of human lungs initially turned down for transplant from conventional organ donors. Safety of transplanting these lungs after EVLP has recently been demonstrated. This proposed Phase 2 clinical trial will demonstrate safety and efficacy of transplant of lungs retrieved from NHBDs after death, assessed by EVLP, We will accomplish this Specific Aim: To demonstrate non-inferiority of lung transplant using lungs retrieved from NHBDs assessed by EVLP compared to lung transplant from conventional brain dead organ donors. We will obtain lungs from Maastricht Category 1 and 2 NHBDs in a large-population North Carolina county (Wake) and from targeted emergency rooms. We will apply established methods of EVLP and ex-vivo CT scan to evaluate suitability for transplant. Acceptable lungs will be transplanted at UNC and Duke under IRB-approved protocols. Outcomes will be compared to patients contemporaneously transplanted with lungs from conventional organ donors. Because lungs from NHBDs have not been injured by a prolonged interval of brain death, lungs retrieved from NHBDs may not only be much more plentiful; they may be superior to lungs currently being transplanted from conventional brain-dead donors. Timely retrieval of lungs from NHBDs requires coordination of EMS, law enforcement, medical examiners, and OPO personnel. Through the Office of the N.C. Secretary of Health and Human Services, we commenced a dialogue with leadership of state agencies to facilitate timely lung retrieval from NHBDs. We will use experts at Lung Banks of America, a not-for-profit corporation, to analyze time flow metrics from declaration of death to lung retrieval. With N.C. state government agencies, we will develop practices and policies to improve the yield of successful lung retrieval from NHBDs that can be implemented in N.C. and across the U.S. An ancillary project will determine metabolomic biomarkers for suitability of NHBD lungs for EVLP assessment, and biomarkers associated with poor function after lung transplant. Successful study completion will revolutionize lung transplant and the care of patients with end-stage lung disease.