Long Term Follow up of the Lung Transplant Outcomes Group Cohort

肺移植结果组队列的长期随访

• 批准号: 10407618
• 负责人: Jason D Christie
• 金额: $ 140.45万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10407618
• 关键词: Acute Lung Injury; Address; Ancillary Study; Biological; Biological Assay; Biological Process; Blood specimen; Cessation of life; Chronic; Clinical; Clinical Data; Cohort Studies; Complication; Data; Data Sources; Development; Distress; Enrollment; Event; Focus Groups; Functional disorder; Funding; Future; Generations; Genomics; Grant; Hand; Image; Impairment; Incidence; Infrastructure; Injury to Kidney; Intensive Care; Knowledge; Laboratories; Life; Link; Longterm Follow-up; Lung Transplantation; Lung diseases; Measures; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Outcome; Parents; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Personal Satisfaction; Phenotype; Physical Function; Physical assessment; Physiological; Population; Prognosis; Prospective cohort study; Public Health; Research; Research Personnel; Resources; Risk; Risk Factors; Source; Survivors; Symptoms; Syndrome; Time; Transplant Recipients; Transplantation; Work; clinical biomarkers; clinical risk; cohort; cost; design; disability; early detection biomarkers; epidemiology study; experience; follow-up; frailty; functional status; graft dysfunction; graft failure; graft function; health knowledge; health related quality of life; immune function; improved; innovation; lung allograft; lung injury; microbiome; mortality; novel; phenotypic data; post-transplant; prospective; pulmonary function; success; translational study

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.

肺移植对于终末期肺病患者来说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，长期结果中位数令人失望 生存期约为 6 年。2 此外，在幸存者中，有一半患有肺功能受损 - 慢性 同种异体肺移植功能障碍 (CLAD) – 导致令人痛苦的症状和残疾。3 然而，根本性的 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差距 移植；推进此类知识对于改善长期结果至关重要。 肺移植结果小组 (LTOG) 是全球第一个也是规模最大的多中心流行病学研究 肺移植旨在解决早期移植后并发症的问题。 作为 2007 年成立的 11 中心前瞻性队列研究。最初，LTOG 侧重于临床机制 以及原发性移植物功能障碍 (PGD) 移植后早期并发症的生物标志物，这是一种严重的移植物功能障碍。 LTOG 已招募了超过 3000 名受试者。 在过去的十年中，我们的目标是扩展 LTOG 的后续工作并充分利用这一丰富的成果。 临床数据、生物样本和基础设施资源，用于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集中于主要的长期结果。 长期问题对肺移植患者的结果至关重要：在目标 1 中，我们将进行长期 CLAD 表型分析 使用当前最先进的定义和目标 2 纳入 LTOG 的所有受试者，直至死亡或研究结束； 我们将确定接收者的长期功能状态，包括针对脆弱领域的针对性措施 以及功能、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，能够产生巨大的新资源 不断增长的领域中的知识，既直接来自于现有数据，也通过促进新的研究 NHLBI 相关肺部疾病通过利用低成本生成新颖的数据源。 一个独特的既定群体，以及有效的数据实践，对于开发新知识具有影响力。 通过将长期移植物和患者表型数据与丰富的数据相结合，可能会改变全世界的移植实践 通过定义相关肺移植的新机制，提供早期移植数据和生物样本资源 综合症，并为一代研究人员提供辅助研究应用平台。