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.

项目摘要/摘要在此申请5年的K23职业发展奖中，我预示着研究和职业发展导致职业作为间质肺的独立临床和转化调查员疾病（ILD）。特发性肺部FIPFROSIS（IPF）唯一可用的药物可以治愈疾病。影响多达50％的IPF患者，其特征是生理储量减少和增加急性侮辱的表现敏感。因此，侮辱是IPF的病态和死亡率的可修改风险因素。该提议建立在我的初步工作的基础上，表明（1）更大的内脏洛糖组织（增值税）是相关的随着脆弱的脆弱性，（2）患有肌肉减少症和viscopenia and visceral ofessiony的受试者面周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。单独使用炎症或高炎症，高增值税，（4）生长激素（GH）轴的下调可以在R Graham Barr博士的指导下链接增值税和脆弱生物电阻抗测定法（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Frainty风险相关的失调评估生长激素轴失调在肌肉减少症中的作用，并在严格的过夜中内脏观察协议（Co-Centor Freda）。 ILD的家庭风险（R01HL103676）和DR。（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（Dr.）弗雷达（Freda），生物统计学（瓦莱里（Valeri）博士），间质性肺部疾病（Garcia博士）的老化，而流行病学（Barr Dr. Barr）该奖项的最后两年，我将申请R01的资金和过渡到独立我会做好准备进行以患者为导向的研究，以评估身体组成身体身体在结局中的作用 ILD。在ILD中预防和信任的途径。