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

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