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

项目摘要/摘要 在这份申请为期5年的K23职业发展奖的申请书中，我建议进行有指导的研究和职业 发展成为间质肺的独立临床和翻译研究人员 疾病(ILD)。这个项目的目标是确定身体成分在患有以下疾病的受试者中的作用 特发性肺纤维化(IPF)。IPF的患病率正在上升，目前每200名老年人中就有一人受到影响。那里 不是治疗IPF的良方。唯一可用的药物延缓了疾病的发展，但不能逆转疾病。脆弱 影响多达50%的IPF患者，其特点是生理储备减少和增加 对严重的急性侮辱表现的敏感性。IPF中最常见的死亡原因是急性 侮辱。因此，脆弱是IPF发病率和死亡率的一个潜在的可改变的危险因素。 这项建议建立在我的初步工作表明：(1)较大的内脏脂肪组织(VAT)与 随着虚弱程度的增加，(2)同时患有骨质疏松症和内脏肥胖症的受试者比 那些单独患有骨质疏松症的人，(3)可能有不同的运动限制内型，由高 单纯炎症或低炎症伴高VAT；(4)生长激素(GH)轴下调 可能会将增值税和脆弱性联系起来。在R·格雷厄姆·巴尔博士的指导下，我建议评估身体的角色 生物电阻抗分析的成分(共同导师加拉格尔)、炎症和神经内分泌 使用机器学习方法与脆弱风险相关的监管失调(共同导师瓦莱里)。我也会 在严格的过夜试验中评估生长激素轴失调在内脏肥胖症中的作用 礼仪(共同导师Freda)。我建议在两个由NHLBI资助的预期队列中进行这项研究：加西亚博士的 ILD高危家庭(R01HL103676)和Singer博士的晚期肺部疾病肺移植研究 (R01HL134851)。 在导师的指导下，我制定了一个为期5年的职业发展计划，其中包括身体训练 成分分析(加拉格尔博士)、复杂内分泌系统测量(弗雷达博士)、临床试验(Dr。 (Freda)、生物统计学(Valeri博士)、间质性肺疾病中的衰老(Garcia博士)和流行病学(Barr博士)。在 在这个奖项的最后两年，我将申请R01资金并过渡到独立。拟开展的活动 将使我做好准备，进行以病人为导向的研究，以评估身体成分在预后中的作用 ILD。我还将获得设计和进行针对新药的临床试验所需的技能和培训 预防和治疗ILD虚弱的途径。

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.