Clinical and Biological Factors Predicting Lung Transplant Textbook Outcomes (U01)

项目总结/摘要 虽然肺移植是终末期肺病的唯一治疗选择，但术后早期 并发症是常见的，限制了患者的长期生存，同时增加了经济效益。 已经很昂贵的治疗负担。成功的手术结果可以通过理想或“教科书”来定义 结果”（TO），其中患者没有明显的早期术后并发症， 移植可包括原发性移植物功能障碍、急性肺同种异体移植物功能障碍、肾衰竭或感染。我们集团 最近发表了第一个基于单中心数据的肺移植TO定义， 与更差的患者生存率和更高的卫生系统成本密切相关。随后的 对62个美国肺移植中心的登记分析发现，达到TO的比率范围为27%至72%， 强调结果的广泛可变性以及干预和改进的潜力。肺移植 本提案中的临床中心包括杜克大学、路易斯维尔大学、明尼苏达大学和 宾夕法尼亚大学.这些中心是四个最古老和最受尊敬的肺移植中心， 该国家具有地理和规模多样性，包括小型，中型和大型。我们的提案旨在 了解关键的移植前临床特征，以及新的潜在生物老化差异， 导致早期结果更差或无法达到TO。我们假设特定的临床变量和 生物老化测量可以预测早期并发症。移植前患者的生物学年龄可能会导致 器官特异性晚期肺病，因此通过肺移植得到改善。或者，生物年龄 可能是跨器官系统的系统性过程，不会通过移植解决。为了确定 器官特异性老化与系统性老化的比较，我们将评估受体移植前的生物老化， 免疫系统和肺衰竭使用迭代机器学习，我们将开发和验证TO预测 基于所识别的临床变量和生物测量结果来建立模型，以确定个性化的 肺移植的围手术期风险。这不仅仅是一个预测工具， 允许识别潜在的可修改的临床和生物学变量，可以利用这些变量来改善 成果。作为更大的肺移植联盟的一部分，我们将招募参与者并提供数据， 在肺移植联盟的主持下，通过共同的研究方案收集生物标本。 协调中心和指导委员会。

PROJECT SUMMARY/ABSTRACT While lung transplantation is the only treatment option for end-stage lung disease, early post-operative complications are common and limit long-term patient survival while concomitantly increasing the economic burden of an already expensive therapy. Successful surgical outcomes can be defined by an ideal or “textbook outcome” (TO) where the patient does not have significant early post-operative complications, which for lung transplant can include primary graft dysfunction, acute lung allograft dysfunction, renal failure or infection. Our group recently published the first lung transplant TO definition based on single-center data and found failure to achieve TO was strongly associated with worse patient survival and significantly higher cost to the health system. A subsequent registry analysis of 62 US lung transplant centers found the rate of achieving TO ranged from 27% to 72%, emphasizing wide variability in outcomes and potential for intervention and improvement. The Lung Transplant Clinical Center in this proposal include Duke University, University of Louisville, University of Minnesota and University of Pennsylvania. These centers are four of the oldest and most respected lung transplant centers in the country with geographic and size diversity, including small, medium, and large volumes. Our proposal aims to understand the critical pretransplant clinical characteristics, as well as novel underlying biologic aging differences, that contribute to worse early outcomes, or failure to achieve a TO. We hypothesize that specific clinical variables and biological aging measures can predict early complications. Biological age in the pretransplant patient may be driven by organ specific advanced lung disease and therefore ameliorated with lung transplant. Alternatively, biological age may be a systemic process across organs systems and does not resolve with transplant. To determine the significance of organ specific versus systemic aging, we will evaluate pretransplant biological aging in the recipient's pretransplant immune system and explanted lung. Using iterative machine learning we will develop and validate a TO prediction model based on the identified clinical variables and biological measurements to determine a personalized perioperative risk of lung transplantation for individual candidates. More than just a predictive tool, this proposal will allow for identification of potentially modifiable clinical and biologic variables that can be leveraged to improve outcomes. As part of the larger Lung Transplant Consortium, we will enroll participants and contribute data and biospecimens through a common research protocol under the auspices of the Lung Transplant Consortium Data Coordinating Center and Steering Committee.