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/摘要 对于患有末期肺部疾病的成年人，肺移植旨在扩大生存，营救 残疾并改善与健康相关的生活质量（HRQL）。 2005年的器官分配政策大修 优先针对病人和老年人的肺移植而不会影响一年生存 - 主要测量 移植效率。但是，这项大修的成本为巨大的成本，包括最近的趋势 残疾增加，HRQL较差，长期死亡率增加。迫切需要歧视 候选人可能会在手术后能够改善残疾和HRQL生存，并确定新的信息预期 移植因素有助于候选决策。最近，我们发现脆弱很普遍， 与残疾有关。与其他固体器官移植种群相反，只有两个良好的人物之一 脆弱的措施预测了在肺移植候选者中候补死亡/降落的风险。另外，我们的早期 数据表明，建立的脆弱措施可能会被肺部疾病混淆，从而导致 错误分类。我们还表明，代表脆弱的推定途径的蛋白质生物标志物（即系统性 在肺移植候选者中，炎症，衰老和恶病质）很重要。是否造成路径 脆弱是在异质性肺部疾病中普遍存在的，或者是脆弱的子表型（所谓 具有不同病理学，结果风险和治疗反应的“内型”）尚不清楚。这里，我们 提议在美国三个大型肺移植中心进行的一项前瞻性队列研究，以解决三个基本和 脆弱的新领域可以告知肺部移植领域。在624个肺移植候选者中，我们将 评估现有的脆弱措施以及绩效，生物标志物和拟人措施（包括 肌肉减少症）与肺部疾病有关。在这些候选人中，480最终将接受移植 我们将在移植后一年评估生存，残疾和HRQL。在AIM 1中，我们将使用运营 与肺部疾病相关的脆弱域的测量，以设计新型肺部移植的新型脆弱指数。我们 假设该指数将更好地量化对压力源的脆弱脆弱性，而不是现有措施 在社区居住的老年人人群中发展。在AIM 2中，我们将利用潜在类别分析（LCA） 识别脆弱的内型。我们假设LCA考虑了临床和生物标志物测量的LCA 驾驶脆弱的机制将确定肺部疾病中不同的内型。在AIM 3中，我们将开发临床 预测模型以识别有残疾风险，较差HRQL和肺移植后死亡的模型。我们假设 包括脆弱的模型将更好地预测与没有模型的模型相比，可以更好地预测残疾和HRQL的生存。 总而言之，该提案将产生与接受肺移植的成年人相关的脆弱的新测量。 可能患有肺部疾病的人接受其他主要手术；将向 肺部疾病中脆弱的病理学；最后，通过考虑生存和以患者为中心的结果，将 产生一个预测模型，该模型将立即以无法呈现的方式帮助知情决策。

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.

• 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