Role of visceral adipose tissue in frailty among patients with Idiopathic Pulmonary Fibrosis

内脏脂肪组织在特发性肺纤维化患者虚弱中的作用

• 批准号: 10686173
• 负责人: Michaela Restivo Anderson
• 金额: $ 17.09万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686173
• 关键词: Acute; Adipose tissue; Adrenal Cortex Hormones; Adult; Affect; Aging; American; Arrhythmia; Award; Biolectric Impedance; Biological Assay; Biology; Biometry; Body Composition; Body mass index; Cause of Death; Central obesity; Cessation of life; Chronic lung disease; Clinical Investigator; Clinical Trials; Communities; Complex; Conduct Clinical Trials; Data; Deposition; Development; Development Plans; Disease; Disease Progression; Down-Regulation; Elderly; Endocrine system; Epidemiology; Etiology; Evaluation; Exercise; FDA approved; Family; Functional disorder; Funding; Future; Goals; Grant; HIV; High Prevalence; Hormone secretion; Hospitalization; Inflammation; Infrastructure; Injury; Insulin-Like Growth Factor I; Interleukin-1 Receptors; Interleukin-1 beta; Interleukin-6; Interstitial Lung Diseases; Intramuscular; Investigation; K-Series Research Career Programs; Knowledge; Lead; Life; Link; Lung Transplantation; Lung diseases; Machine Learning; Measurement; Mediator; Mentors; Mentorship; Morbidity - disease rate; Myocardial Ischemia; National Heart, Lung, and Blood Institute; Neurosecretory Systems; Obesity; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Pilot Projects; Pneumonia; Predisposition; Prevalence; Prevention; Prospective cohort; Prospective, cohort study; Protocols documentation; Pulmonary Fibrosis; Research; Research Priority; Risk; Risk Factors; Role; Selection Criteria; Series; Serum; Severity of illness; Skeletal Muscle; Societies; Somatotropin; Somatotropin-Releasing Hormone; Steroids; Structure of parenchyma of lung; Subgroup; Syndrome; TNF gene; Testing; Testosterone; Therapeutic; Training; Transplantation; Tumor Necrosis Factor Receptor; Variant; Visceral; Work; androgenic; antagonist; career; career development; circulating biomarkers; cohort; design; fibrotic interstitial lung disease; frailty; growth hormone deficiency; health related quality of life; hormone analog; human old age (65+); idiopathic pulmonary fibrosis; modifiable risk; mortality; muscle form; novel; novel therapeutics; participant enrollment; patient oriented; patient oriented research; patient population; prevent; prospective; pulmonary rehabilitation; reduced muscle mass; research and development; respiratory; response; sarcopenia; sarcopenic obesity; skill acquisition; systemic inflammatory response; targeted treatment; therapeutic target; translational approach; translational scientist

PROJECT SUMMARY/ABSTRACT In this application for a 5-year K23 Career Development Award, I propose mentored research and career development leading to a career as an independent clinical and translational investigator in interstitial lung disease (ILD). The goal of this project is to identify the role of body composition in frailty among subjects with idiopathic pulmonary fibrosis (IPF). The prevalence of IPF is rising, currently affecting 1 in 200 older adults. There is no cure for IPF. The only available medications slow disease progression but do not reverse disease. Frailty affects up to 50% of IPF patients, and is characterized by decreased physiologic reserve and increased susceptibility to severe manifestations of acute insults. The most common causes of death in IPF are acute insults. Frailty is thus a potentially modifiable risk factor for morbidity and mortality in IPF. This proposal builds on my preliminary work showing that (1) greater visceral adipose tissue (VAT) is associated with increased frailty, (2) subjects with both sarcopenia and visceral obesity are at greater risk of frailty than those with sarcopenia alone, (3) there may be distinct endotypes of exercise limitation defined by high inflammation alone or low inflammation with high VAT, and (4) down-regulation of the growth hormone (GH) axis may link VAT and frailty. Under the mentorship of Dr. R Graham Barr, I propose to evaluate the roles of body composition by bioelectrical impedance assay (co-mentor Gallagher), inflammation, and neuroendocrine dysregulation associated with frailty risk using a machine-learning approach (co-mentor Valeri). I will also evaluate the role of growth hormone axis dysregulation in sarcopenia with visceral obesity in a rigorous overnight protocol (co-mentor Freda). I propose to perform this in two NHLBI-funded prospective cohorts: Dr. Garcia’s Families-At-Risk for ILD (R01HL103676) and Dr. Singer’s Advanced Lung Disease Lung Transplantation Study (R01HL134851). With guidance from my mentors, I have crafted a 5-year career development plan that includes training in body composition analysis (Dr. Gallagher), measurement of complex endocrine systems (Dr. Freda), clinical trials (Dr. Freda), biostatistics (Dr. Valeri), aging in interstitial lung disease (Dr. Garcia), and epidemiology (Dr. Barr). In the last two years of this award, I will apply for R01 funding and transition to independence. The proposed activities will prepare me to conduct patient-oriented research to evaluate the role of body composition in outcomes in ILD. I will also acquire the skills and training required to design and conduct clinical trials targeting novel pathways to prevent and treat frailty in ILD.

项目摘要/摘要 在此申请为5年的K23职业发展奖中，我提出了指导的研究和职业 发展导致职业成为独立临床和翻译的研究人员 疾病（ILD）。该项目的目的是确定身体成分在具有 特发性肺纤维化（IPF）。 IPF的患病率正在上升，目前影响200名老年人中有1个。那里 无法治愈IPF。唯一可用的药物缓慢疾病进展，但不会逆转疾病。脆弱 影响多达50％的IPF患者，其特征是生理储量减少和增加 对严重急性伤害表现的敏感性。 IPF中最常见的死亡原因是急性 侮辱。因此，脆弱是IPF发病率和死亡率的潜在可修改风险因素。 该提议建立在我的初步工作的基础上，表明（1）更大的内脏脂肪组织（VAT）是相关的 随着脆弱性和内脏肥胖症患者的脆弱性，（2）脆弱的风险大于 那些单独患有肌肉减少症的人（3）可能存在不同的运动限制的内部型号。 单独使用炎症或高增值税的低炎症，以及（4）生长马（GH）轴的下调 可能会将增值税和脆弱的人链接起来。在R Graham Barr博士的心态下，我建议评估身体的角色 生物电阻抗测定法（Co-centor Gallagher），炎症和神经内分泌的组成 使用机器学习方法（Co-Centor Valeri）与脆弱风险相关的失调。我也会 评估生长赛轴功能障碍在肌肉减少症中具有内脏肥胖症的作用 协议（Co-Centor Freda）。我建议在两个NHLBI资助的潜在队列中执行此操作：Garcia博士 ILD的家庭风险（R01HL103676）和Singer博士的晚期肺疾病肺移植研究 （R01HL134851）。 在我的导师的指导下，我制定了一项为期5年的职业发展计划，其中包括身体培训 组成分析（Gallagher博士），复杂内分泌系统（Freda博士）的测量，临床试验（博士 弗雷达（Freda），生物统计学（Valeri博士），间质性肺部疾病（Garcia博士）和流行病学（Barr博士）。在 该奖项的最后两年，我将申请R01的资金和过渡到独立。拟议的活动 我会做好准备进行以患者为导向的研究，以评估身体成分在结果中的作用 ill。我还将获得针对新颖的设计和进行临床试验所需的技能和培训 预防和治疗ILD中的脆弱的途径。

项目成果

Provider beliefs and practices regarding the management of obesity in lung transplant recipients.

提供者关于肺移植受者肥胖管理的信念和实践。

• DOI: 10.1016/j.jhlto.2023.100028
• 发表时间: 2024
• 期刊: JHLT open
• 作者: Diamond,JoshuaM;Benvenuto,Luke;Claridge,Tamara;Witek,Stephanie;Christie,JasonD;Singer,JonathanP;Anderson,MichaelaR
• 通讯作者: Anderson,MichaelaR

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

• DOI: 10.1016/j.healun.2021.08.005
• 发表时间: 2021-12
• 期刊: JOURNAL OF HEART AND LUNG TRANSPLANTATION
• 影响因子: 8.9
• 作者: Furfaro, David;Rosenzweig, Erika B.;Shah, Lori;Robbins, Hilary;Anderson, Michaela;Kim, Hanyoung;Abrams, Darryl;Agerstrand, Cara L.;Brodie, Daniel;Feldhaus, Danielle;Costa, Joseph;Lemaitre, Philippe;Stanifer, Bryan P.;D'Ovidio, Frank;Sonett, Joshua R.;Arcasoy, Selim;Benvenuto, Luke
• 通讯作者: Benvenuto, Luke

Right single lung transplantation or double lung transplantation compared with left single lung transplantation in chronic obstructive pulmonary disease.

• DOI: 10.1016/j.healun.2020.06.009
• 发表时间: 2020-09
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: Benvenuto LJ;Costa J;Piloni D;Aversa M;Anderson MR;Shah L;Robbins HY;Stanifer B;Sonett JR;Arcasoy SM;D'Ovidio F
• 通讯作者: D'Ovidio F

Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.

• DOI: 10.1016/j.healun.2021.11.002
• 发表时间: 2022-03
• 期刊: JOURNAL OF HEART AND LUNG TRANSPLANTATION
• 影响因子: 8.9
• 作者: Benvenuto, Luke J.;Anderson, Michaela R.;Aversa, Meghan;Snyder, Mark E.;Robbins, Hilary;Shah, Lori;Grewal, Harpreet Singh;Anderson, David;Costa, Joseph;Stanifer, Brian P.;Lemaitre, Philippe;Sonett, Joshua R.;D'Ovidio, Frank;Arcasoy, Selim M.
• 通讯作者: Arcasoy, Selim M.

Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity.

ABO 血型的肺移植等候名单结果因疾病严重程度而异。

• DOI: 10.1016/j.healun.2022.10.024
• 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: Greissman,Samantha;Anderson,Michaela;Dimango,Angela;Grewal,Harpreet;Magda,Gabriela;Robbins,Hilary;Shah,Lori;Costa,Joseph;Stanifer,Bryan;D'-Ovidio,Frank;Juarez,MiguelLeiva;Lemaitre,Philippe;Sonett,Joshua;Arcasoy,Selim;Benvenuto
• 通讯作者: Benvenuto