Long Term Follow up of the Lung Transplant Outcomes Group Cohort

肺移植对于终末期肺部疾病患者是一种潜在的延长生命的治疗方法； 然而，肺移植是一个相对较新的领域，长期结果令人失望，中位数 存活约6年2此外，在幸存的人中，有一半患有慢性肺功能受损 同种异体肺移植功能障碍(CLAD)--这会导致痛苦的症状和残疾。 对肺损伤后发生的临床和生物学过程的理解仍然存在知识空白。 移植；促进这方面的知识对于改善长期结果至关重要。 肺移植结果组(LTOG)是第一个也是最大规模的多中心流行病学研究 肺移植旨在解决围绕移植后早期并发症的问题。LTOG开始 作为一项成立于2007年的11个中心前瞻性队列研究。最初，LTOG侧重于临床机制 和移植后早期并发症的生物标志物(PGD)，严重的 通常会导致早期移植物衰竭和死亡的情况。已有3000多名受试者参加了LTOG 在过去的十年里。在此应用程序中，我们的目标是扩大LTOG的后续行动，并利用这一丰富的 临床数据、生物样本和基础设施的资源，以解决以前无法回答的基本问题 关于肺移植的长期结果的问题。我们将有两个目标聚焦于主要的长期- 肺移植患者预后的关键问题：在目标1中，我们将进行长期包膜表型分析 在LTOG中登记的所有受试者，直到死亡或研究结束，使用当前最先进的定义；以及在目标2中 我们将确定接受者的长期功能状态，包括有针对性的脆弱域措施 以及与功能、残疾和健康相关的生活质量。 我们的建议意义重大，因为它将创造一种独特的资源，能够产生大量新的 在不断增长的领域中的知识，这既是手头数据的直接结果，也是通过促进关于 NHLBI相关的肺部疾病。它在低成本生成新数据源方面具有创新性 一个独特的已建立的队列，并在有效的数据实践中。它对发展新的知识是有影响的 可能通过将长期移植物和患者表型数据与丰富的 通过定义相关肺移植的新机制，早期移植数据和生物样本资源 通过为新一代研究人员提供辅助研究应用的平台。

Lung transplantation is a potentially life extending treatment for patients with end stage lung diseases; however, lung transplant is a relatively new field, and long-term outcomes are disappointing with a median survival of ~6 years.2 Furthermore, among those who survive, half suffer from impaired lung function - chronic lung allograft dysfunction (CLAD) – which causes distressing symptoms and disability.3 Yet, fundamental knowledge gaps persist in the understanding of the clinical and biological processes that occur after lung transplantation; advancing such knowledge is critical to improve long-term outcomes. The Lung Transplant Outcomes Group (LTOG) is the first and largest multicentered epidemiologic study in lung transplantation designed to address issues surrounding early post-transplant complications. LTOG began as an 11-center prospective cohort study formed in 2007. Initially, LTOG focused on the clinical mechanisms and biomarkers for the early post-transplant complication of primary graft dysfunction (PGD), a serious condition that often leads to early graft failure and death. Over 3000 subjects have been enrolled in the LTOG during the past ten years. In this application, we aim to extend follow up of the LTOG and capitalize on this rich resource of clinical data, biosamples, and infrastructure to address fundamental but previously unanswerable questions about the long term outcomes of lung transplantation. We will have two aims focused on major long- term issues key to lung transplant patient outcomes: in Aim 1 we will perform long-term CLAD phenotyping of all subjects enrolled in the LTOG until death or study end using current state-of-the-art definitions; and in Aim 2 we will determine the long term functional status of the recipient including targeted measures of frailty domains and functioning, disability, and health-related quality of life. Our proposal is significant in that it will create a unique resource capable of generating tremendous new knowledge in a growing field, both directly as a result of data in hand and by facilitating new research on NHLBI-relevant lung diseases. It is innovative in generation of a novel data source at a low cost by leveraging a unique established cohort, and in efficient data practices. It is impactful in developing new knowledge that may change transplant practices worldwide by merging long-term graft and patient phenotype data with a rich early-transplant data and biosample resource, by defining new mechanisms of relevant lung transplant syndromes, and by providing a platform for ancillary research applications for a generation of investigators.