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: 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
• 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

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.

项目总结/摘要 在这份为期5年的K23职业发展奖的申请中，我建议指导研究和职业生涯 发展导致职业生涯作为一个独立的临床和翻译研究者在间质性肺 疾病（ILD）。本项目的目标是确定身体成分在受试者中的脆弱性中的作用， 特发性肺纤维化（IPF）。IPF的患病率正在上升，目前影响1/200的老年人。那里 不能治愈IPF。唯一可用的药物减缓疾病进展，但不能逆转疾病。虚弱 影响高达50%的IPF患者，其特征为生理储备降低和 对急性损伤的严重表现的敏感性。IPF中最常见的死亡原因是急性 侮辱。因此，虚弱是IPF发病率和死亡率的潜在可改变风险因素。 这项建议建立在我的初步工作，表明（1）更大的内脏脂肪组织（VAT）是相关的 随着虚弱程度的增加，（2）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虚弱的风险更大 （3）运动受限可能有不同的内型， 炎症单独或低炎症与高增值税，和（4）下调生长激素（GH）轴 可能会把增值税和脆弱联系起来。在格雷厄姆巴尔博士的指导下，我建议评估身体的作用 通过生物电阻抗测定（共同导师Gallagher）、炎症和神经内分泌测定组合物 使用机器学习方法研究与虚弱风险相关的失调（合作导师Valeri）。我也会 在一个严格的通宵研究中， 方案（共同指导者Freda）。我建议在两个NHLBI资助的前瞻性队列中进行这项研究：加西亚博士的 ILD风险家族（R 01 HL 103676）和Dr. Singer的晚期肺病肺移植研究 （R01HL134851）。 在导师的指导下，我制定了一个5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（Gallagher博士） Freda）、生物统计学（Valeri博士）、间质性肺病中的衰老（Garcia博士）和流行病学（巴尔博士）。在 在这个奖项的最后两年，我将申请R 01资助并过渡到独立。拟议活动 我将准备进行以病人为导向的研究，以评估身体成分在结果中的作用， ILD。我还将获得设计和进行针对新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。