Network Medicine Approaches to Cachexia in COPD

网络医学治疗慢性阻塞性肺病恶病质的方法

• 批准号: 9418079
• 负责人: Merry-Lynn Noelle McDonald Donnelly
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9418079
• 关键词: Area; Body Weight decreased; Cachexia; Cause of Death; Chronic; Chronic Obstructive Airway Disease; Complex; Congestive Heart Failure; Data; Development; Diagnosis; Disease; Etiology; Fatty acid glycerol esters; Gene Expression; Gene Expression Profile; Genes; Investigation; Lead; Malignant Neoplasms; Medicine; Muscle; Muscular Atrophy; Pathway interactions; Patients; Pectoralis Muscles; Phase; Phenotype; Population; Testing; United States; Weight; cohort; disease diagnosis; genetic variant; improved; mortality; outcome forecast; public health relevance; recruit; targeted treatment; trait

Cachexia, featuring rapid loss of weight and muscle, is common to many complex diseases such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and cancer. Regardless of the primary disease diagnosis, the presence of cachexia is associated with poor prognosis. Equally important is the observation that not every patient diagnosed with a complex disease such as COPD and CHF becomes cachectic. This information motivated me to hypothesize that there are common genes and pathways influencing cachexia in these different complex, chronic traits. COPD is the third leading cause of death in the United States and it has been estimated that as high as 20% of COPD cases develop cachexia, however this number may be overestimated due to limitations associated with defining cachexia. The development of cachexia is a strong predictor of mortality. This study has three specific aims: 1) Identify genetic and genomic variants associated with cachexia and related traits in COPD; 2) Test for significant relationships between pectoralis muscle area (PMA), fat-free mass (FFM) and gene expression data in COPD cases; 3) Identify gene expression signatures associated with cachexia and PMA in COPD cases. As part of my K99 analyses, I took advantage of the availability of several well-characterized COPD populations in order to investigate markers of muscle wasting and cachexia such as low PMA and change in BMI. However, the field is in need of investigations focused on cohorts of COPD cases phenotyped for muscle wasting and cachexia. The development of such a cohort is a key focus of the R00 phase of her application (Aim 2) and will lead to pilot data for her first R01 applications.

恶病质的特点是体重和肌肉快速下降，是许多复杂疾病的常见病，如慢性阻塞性肺病 (COPD)、充血性心力衰竭 (CHF) 和癌症。无论原发疾病的诊断如何，恶病质的存在都与不良预后相关。同样重要的是，并非所有被诊断患有慢性阻塞性肺病和慢性心力衰竭等复杂疾病的患者都会出现恶病质。这些信息促使我假设在这些不同的复杂、慢性特征中存在影响恶病质的共同基因和途径。 COPD 是美国第三大死亡原因，据估计，高达 20% 的 COPD 病例会出现恶病质，但由于恶病质定义的局限性，这一数字可能被高估。恶病质的发生是死亡率的有力预测因素。这项研究有三个具体目标：1）识别与慢性阻塞性肺病恶病质和相关特征相关的遗传和基因组变异； 2）测试COPD病例中胸肌面积（PMA）、去脂体重（FFM）和基因表达数据之间的显着关系； 3) 识别 COPD 病例中与恶病质和 PMA 相关的基因表达特征。作为 K99 分析的一部分，我利用了几个特征明确的 COPD 人群的可用性来研究肌肉萎缩和恶病质的标志物，例如低 PMA 和 BMI 变化。然而，该领域需要针对肌肉萎缩和恶病质表型的慢性阻塞性肺病病例队列进行研究。此类群体的开发是她申请的 R00 阶段（目标 2）的重点，并将为她的第一个 R01 申请提供试点数据。