Frailty and patient centered outcomes in candidates for lung transplantation

肺移植候选人的虚弱和以患者为中心的结果

• 批准号: 10191001
• 负责人: Jonathan Paul Singer
• 金额: $ 69.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10191001
• 关键词: Abdomen; Achievement; Address; Adult; Age; Aging; Allografting; American; Area; Automobile Driving; Benefits and Risks; Biological Markers; Body Composition; Cachexia; Categories; Cessation of life; Clinical; Clinical Trials; Communities; Country; Data; Decision Making; Development; Disease; Elderly; Functional disorder; Future; Geriatrics; Guidelines; Individual; Infrastructure; Knowledge; Lung; Lung Transplantation; Lung diseases; Measurement; Measures; Mediating; Medical; Modeling; Multicenter Studies; NIH Program Announcements; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Diabetes and Digestive and Kidney Diseases; Operative Surgical Procedures; Organ Transplantation; Outcome; Outcome Study; Pathway interactions; Patient-Focused Outcomes; Patients; Pennsylvania; Performance; Perioperative complication; Phenotype; Physical Performance; Physiological; Policies; Population; Prospective Studies; Prospective cohort study; Research; Resources; Risk; Risk Factors; San Francisco; Societies; Solid; Sum; Syndrome; Therapeutic Intervention; Transplant Recipients; Transplantation; Universities; Validity of Results; Waiting Lists; clinical biomarkers; cost; design; disability; disability risk; evidence base; fitness; frailty; graft function; health related quality of life; human old age (65+); improved; indexing; instrument; mortality; mortality risk; novel; organ allocation; post-transplant; predictive modeling; programs; prospective; protein biomarkers; risk stratification; sarcopenia; stressor; survival outcome; survival prediction; systemic inflammatory response; tool; transplant centers; treatment response; trend

PROJECT ABSTRACT/SUMMARY For adults suffering from from end-stage lung disease, lung transplantation aims to extend survival, relieve disability, and improve health-related quality of life (HRQL). An overhaul in organ allocation policy in 2005 prioritized lung transplant for sicker and older adults without impacting one-year survival – the primary measure of transplant efficacy. This overhaul has come at substantial cost, however, including recent trends towards increased disability, poorer HRQL, and increased longer-term mortality. There is an urgent need to discriminate candidates likely to survive after surgery with improved disability and HRQL and to identify new informative pre- transplant factors to aid in candidacy decision-making. Recently, we found that frailty was prevalent and associated with disability. In contrast to other solid organ transplant populations, only one of two well-established measures of frailty predicted risk of waitlist death/delisting in lung transplant candidates. Additionally, our early data suggests that established measures of frailty may be confounded by lung disease, resulting in misclassification. We also showed that protein biomarkers representing putative pathways of frailty (i.e., systemic inflammation, aging, and cachexia) are important in lung transplant candidates. Whether the pathways causing frailty are universal across heterogeneous lung diseases or whether sub-phenotypes of frailty (so called “endotypes”) with distinct pathobiology, outcome risks, and treatment responses exist are unknown. Herein, we propose a prospective cohort study in three large U.S. lung transplant centers to address three fundamental and new areas in which frailty may inform the field of lung transplantation. In 624 lung transplant candidates, we will assess existing frailty measures as well as performance, biomarker, and anthropomorphic measures (including sarcopenia) relevant in lung disease. Of these candidates, 480 will ultimately undergo transplantation in whom we will evaluate survival, disability, and HRQL one year after transplant. In Aim 1, we will use operational measures of frailty domains relevant in lung disease to design a novel frailty index for lung transplantation. We hypothesize that this index will better quantify frailty-attributable vulnerability to stressors than existing measures developed in community-dwelling older adult populations. In Aim 2, we will utilize latent class analysis (LCA) to identify endotypes of frailty. We hypothesize that LCA that considers clinical and biomarker measures of mechanisms driving frailty will identify distinct endotypes in lung disease. In Aim 3, we will develop a clinical prediction model to identify those at risk for disability, poor HRQL, and death after lung transplant. We hypothesize that a model that includes frailty will better predict survival with improved disability and HRQL than a model without. In sum, this proposal will yield a novel measure of frailty relevant for adults undergoing lung transplantation and, possibly, those with lung disease undergoing other major surgeries; will provide new knowledge into the pathobiology of frailty in lung disease; and, finally, by considering survival and patient-centered outcomes, will yield a prediction model that will immediately aid informed decision making in a way that is not presently possible.

项目摘要/总结 对于患有终末期肺部疾病的成年人，肺移植旨在延长生存期，缓解 改善与健康相关的生活质量（HRQL）。2005年对器官分配政策进行了全面改革 在不影响一年生存率的情况下，优先为病情较重和老年人进行肺移植-主要措施 移植的功效。然而，这一改革付出了巨大的代价，包括最近的趋势， 残疾增加，HRQL较差，长期死亡率增加。迫切需要区别对待 候选人可能在手术后生存，残疾和HRQL得到改善，并确定新的信息性预 移植因素以帮助候选人决策。最近，我们发现脆弱是普遍的， 与残疾有关。与其他实体器官移植人群相比，只有两个公认的 虚弱程度的测量可预测肺移植候选人的等待名单死亡/除名风险。此外，我们的早期 数据表明，虚弱的既定措施可能会受到肺部疾病的干扰，导致 分类错误我们还表明，代表假定的脆弱途径的蛋白质生物标志物（即，系统性 炎症、老化和恶病质）在肺移植候选者中是重要的。是否导致 虚弱在异质性肺部疾病中是普遍的，或者虚弱的亚表型（所谓的 具有不同病理生物学、结果风险和治疗反应的内型（endotypes）是未知的。在此我们 我建议在美国三个大型肺移植中心进行一项前瞻性队列研究，以解决三个基本问题， 脆弱性可能为肺移植领域提供信息的新领域。在624名肺移植候选人中，我们将 评估现有的脆弱性指标以及性能、生物标志物和拟人指标（包括 肌肉减少症）与肺部疾病相关。在这些候选人中，480人最终将接受移植， 我们将评估移植后一年的存活率、残疾率和HRQL。在目标1中，我们将使用 肺疾病相关的脆弱领域的措施，以设计一种新的脆弱指数肺移植。我们 假设该指数将比现有措施更好地量化脆弱归因于压力的脆弱性 在社区居住的老年人群体中发展。在目标2中，我们将利用潜在类别分析（LCA） 确定脆弱的内在型。我们假设LCA考虑了临床和生物标志物指标， 驱动虚弱的机制将识别肺病中不同的内型。在目标3中，我们将开发一种临床 预测模型，以确定那些在肺移植后残疾，HRQL差和死亡的风险。我们假设 包括虚弱的模型将比不包括虚弱的模型更好地预测具有改善的残疾和HRQL的存活率。 总之，这一建议将产生一种新的测量接受肺移植的成人相关虚弱的方法， 可能，那些患有肺部疾病的人正在接受其他大手术;将为他们提供新的知识。 最后，通过考虑生存率和以患者为中心的结局， 产生一个预测模型，将立即帮助知情决策的方式，目前是不可能的。

项目成果

Frailty trajectories in adult lung transplantation: A cohort study.

• DOI: 10.1016/j.healun.2019.03.006
• 发表时间: 2019-07
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: A. Venado;C. McCulloch;J. Greenland;P. Katz;A. Soong;Pavan Shrestha;S. Hays;J. Golden;R. Shah;L. Leard;M. Kleinhenz;J. Kukreja;L. Zablotska;I. Allen;K. Covinsky;P. Blanc;J. Singer

A nonlinear relationship between visceral adipose tissue and frailty in adult lung transplant candidates.

成人肺移植候选物中内脏脂肪组织与脆弱的非线性关系。

• DOI: 10.1111/ajt.15525
• 发表时间: 2019-11
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Anderson MR;Kolaitis NA;Gao Y;Kukreja J;Greenland J;Hays S;Wolters P;Golden J;Diamond J;Palmer S;Arcasoy S;Udupa J;Christie JD;Lederer DJ;Singer JP
• 通讯作者: Singer JP

What is Frailty?

• DOI: 10.1164/rccm.207i11p5
• 发表时间: 2023-06-01
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7

Rehabilitation for People with Respiratory Disease and Frailty: An Official American Thoracic Society Workshop Report.

• DOI: 10.1513/annalsats.202302-129st
• 发表时间: 2023-06
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3

Current Beliefs and Practices Regarding the Management of Obesity in Patients with Progressive Interstitial Lung Disease.

当前关于进行性间质性肺病患者肥胖管理的信念和实践。

• DOI: 10.1513/annalsats.202201-019rl
• 发表时间: 2022
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Anderson,MichaelaR;Aronson,KerriI;Diamond,JoshuaM;Christie,JasonD;Singer,JonathanP
• 通讯作者: Singer,JonathanP