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: 10618983
• 负责人: Jason D Christie
• 金额: $ 144.58万
• 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/10618983
• 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.

肺移植是一种潜在的延长终末期肺部疾病患者生命的治疗方法; 然而，肺移植是一个相对较新的领域，长期结果令人失望， 存活约6年。2此外，在存活的患者中，一半患有肺功能受损-慢性 肺移植物功能障碍（CLAD）-导致令人痛苦的症状和残疾。3然而， 知识差距持续存在于对肺移植后发生的临床和生物学过程的理解中， 移植;推进这些知识对于改善长期结果至关重要。 肺移植结局组（LTOG）是美国第一个也是最大的多中心流行病学研究。 肺移植旨在解决移植后早期并发症的问题。LTOG开始 2007年形成的一项11中心前瞻性队列研究。最初，LTOG专注于临床机制 和移植后早期并发症原发性移植物功能障碍（PGD）的生物标志物， 这种情况通常会导致早期移植失败和死亡。超过3000例受试者已入组LTOG 在过去的十年里。在这个应用程序中，我们的目标是延长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，以解决基本但以前无法回答的问题 关于肺移植长期效果的问题。我们将有两个目标集中在主要的长期- 肺移植患者结局的关键问题：在目标1中，我们将对以下患者进行长期CLAD表型分析： 入组LTOG直至死亡或研究结束的所有受试者（使用当前最新技术水平定义）;以及目标2 我们将确定接受者的长期功能状态，包括脆弱领域的目标措施 和功能，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 知识在一个不断增长的领域，无论是直接由于数据在手，并通过促进新的研究， NHLBI相关肺部疾病。它是创新的，通过利用低成本生成新的数据源， 一个独特的既定队列，并在有效的数据实践。在发展新知识方面， 通过将长期移植物和患者表型数据与丰富的 早期移植数据和生物样本资源，通过定义相关肺移植的新机制 综合征，并通过提供一个平台，为辅助研究应用一代调查。

项目成果

Early post-lung transplant calcineurin inhibitor management varies widely: An international survey.

肺移植后早期钙调神经磷酸酶抑制剂的管理差异很大：一项国际调查。

• DOI: 10.1111/ctr.14510
• 发表时间: 2022
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Farrell,ChristineL;Miano,ToddA;Griffiths,Stephen;Christie,JasonD;Diamond,JoshuaM;Shashaty,MichaelGS
• 通讯作者: Shashaty,MichaelGS

Body Mass Index and Cause-Specific Mortality after Lung Transplantation in the United States.

美国肺移植后的体重指数和特定原因死亡率。

• DOI: 10.1513/annalsats.202207-613oc
• 发表时间: 2023
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Anderson,MichaelaR;Cantu,Ed;Shashaty,Michael;Benvenuto,Luke;Kalman,Laurel;Palmer,ScottM;Singer,JonathanP;Gallop,Robert;Diamond,JoshuaM;Hsu,Jesse;Localio,ARussell;Christie,JasonD
• 通讯作者: Christie,JasonD

Pro-inflammatory IgG1 N-glycan signature correlates with primary graft dysfunction onset in COPD patients.

促炎性 IgG1 N-聚糖特征与 COPD 患者原发性移植物功能障碍的发生相关。

• DOI: 10.1016/j.trim.2021.101491
• 发表时间: 2022
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: McQuiston,Alexander;Scott,Danielle;Nord,Dianna;Langerude,Logan;Pelaez,Andres;Machuca,Tiago;Mehta,Anand;Drake,RichardR;Christie,JasonD;Angel,Peggi;Atkinson,Carl
• 通讯作者: Atkinson,Carl

Transplanting candidates with stacked risks negatively affects outcomes.

移植具有多重风险的候选人会对结果产生负面影响。

• DOI: 10.1016/j.healun.2023.05.020
• 发表时间: 2023
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: Cantu,Edward;Jin,Dun;McCurry,Madeline;Friskey,Jacqueline;Lisowski,Jessica;Saleh,Aya;Diamond,JoshuaM;Anderson,Michaela;Clausen,Emily;Hsu,Jesse;Gallop,Robert;Christie,JasonD;Schaubel,Douglas
• 通讯作者: Schaubel,Douglas