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

基本信息

批准号：
10482403
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
项目类别：
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/10482403
关键词：
Acute Adipose tissue Adrenal Cortex Hormones Adult Affect Aging American Arrhythmia Award Biolectric Impedance Biological 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 Enrollment 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 of activation protein 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 Therapy Clinical Trials 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 patient oriented patient oriented research patient population prevent prospective pulmonary rehabilitation reduced muscle mass research and development respiratory response sarcopenia sarcopenic obesity skills training systemic inflammatory response targeted treatment therapeutic target translational approach translational scientist

项目摘要

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.

项目概要/摘要在这份为期 5 年的 K23 职业发展奖申请中，我建议指导研究和职业发展成为间质性肺的独立临床和转化研究者该项目的目标是确定身体成分在患有疾病（ILD）的受试者中的虚弱作用。特发性肺纤维化 (IPF) 的患病率正在上升，目前影响每 200 名老年人中就有 1 人。唯一可用的药物无法治愈 IPF，但不能逆转疾病。影响高达 50% 的 IPF 患者，其特点是生理储备减少和增加易受急性损伤的严重影响 IPF 最常见的死亡原因是急性。因此，虚弱是 IPF 发病率和死亡率的一个潜在的可改变的危险因素。该提议建立在我的初步工作的基础上，该工作表明（1）更大的内脏脂肪组织（VAT）与随着虚弱程度的增加，（2）同时患有肌肉减少症和内脏肥胖的受试者比患有肌肉减少症和内脏肥胖的受试者面临更大的虚弱风险那些仅患有肌肉减少症的人，（3）可能存在由高水平定义的运动限制的独特内型仅炎症或低炎症伴高 VAT，以及 (4) 生长激素 (GH) 轴下调在 R Graham Barr 博士的指导下，我建议评估身体的作用。生物电阻抗测定（共同导师 Gallagher）、炎症和神经内分泌的成分我还将使用机器学习方法来调节与虚弱风险相关的失调（共同导师瓦莱里）。在严格的过夜中评估生长激素轴失调在肌肉减少症伴内脏肥胖中的作用我建议在两个 NHLBI 资助的前瞻性队列中执行此操作：Garcia 博士的队列。有 ILD 风险的家庭 (R01HL103676) 和辛格博士的晚期肺病肺移植研究（R01HL134851）。在导师的指导下，我制定了五年职业发展计划，其中包括身体训练成分分析（Gallagher 博士）、复杂内分泌系统测量（Freda 博士）、临床试验（Dr. Freda） Freda）、生物统计学（Valeri 博士）、间质性肺疾病的衰老（Garcia 博士）和流行病学（Barr 博士）。在这个奖项的最后两年，我将申请 R01 资助并过渡到独立提议的活动。将使我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 ILD 还将获得设计和开展针对新型药物的临床试验所需的技能和培训。预防和治疗 ILD 虚弱的途径。