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

项目摘要/摘要 虽然肺移植是终末期肺部疾病的唯一治疗选择，但术后早期 并发症很常见，限制了患者的长期生存，同时也增加了经济上的 本已昂贵的治疗负担。成功的手术结果可以用一本理想的或“教科书”来定义 结果“(To)如果患者术后早期没有明显的并发症，对肺 移植可包括原发移植物功能障碍、急性同种异体肺移植功能障碍、肾功能衰竭或感染。我们的团队 最近发表了第一份基于单中心数据的肺移植定义，并发现未能实现 与较差的患者存活率和显著较高的医疗系统成本密切相关。后续的 对62个美国肺移植中心的注册分析发现，达标率从27%到72%不等， 强调结果的广泛差异性以及干预和改进的潜力。肺移植 该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。这些中心是美国历史最悠久、最受尊敬的四个肺移植中心。 地理和大小不同的国家，包括小型、中型和大型。我们的建议旨在 为了了解移植前的关键临床特征，以及新的潜在生物衰老差异， 这会导致较差的早期结果，或者无法实现TO。我们假设特定的临床变量和 生物老化措施可以预测早期并发症。移植前患者的生物学年龄可能是由 由器官特有的晚期肺部疾病引起，因此通过肺移植得到改善。或者，生物年龄 可能是一个跨越器官系统的系统性过程，不能通过移植来解决。以确定其重要性 器官特定老化与系统老化的对比，我们将评估受者移植前的生物老化 免疫系统和移植肺。使用迭代机器学习，我们将开发和验证预测 基于所识别的临床变量和生物测量的模型来确定个性化 个体受者肺移植的围手术期风险。这项提议不仅仅是一种预测工具，它还将 允许识别潜在的可修改的临床和生物变量，这些变量可以用来改善 结果。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和 在肺移植联盟的主持下通过共同研究方案进行的生物检疫数据 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.