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: 9376992
• 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/9376992
• 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; Muscular Atrophy; Pathway interactions; Patients; Pectoralis Muscles; Phase; Phenotype; Population; Recruitment Activity; Testing; United States; cohort; disease diagnosis; genetic variant; improved; mortality; outcome forecast; public health relevance; 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.

恶病质以体重和肌肉的快速损失为特征，常见于许多复杂疾病，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，恶病质的存在与预后不良。同样重要的是观察到，并不是每个被诊断患有复杂疾病（如COPD和CHF）的患者都会出现恶病质。这些信息促使我假设，在这些不同的复杂的慢性特征中，有共同的基因和途径影响恶病质。COPD是美国第三大死亡原因，据估计，高达20%的COPD病例出现恶病质，但由于定义恶病质的局限性，这一数字可能被高估。恶病质的发展是死亡率的一个强有力的预测因素。本研究有三个具体目的：1）确定与COPD恶病质和相关性状相关的遗传和基因组变异; 2）测试COPD病例中胸肌面积（PMA）、去脂质量（FFM）和基因表达数据之间的显著关系; 3）确定COPD病例中与恶病质和PMA相关的基因表达特征。作为我的K99分析的一部分，我利用了几个特征良好的COPD人群的可用性，以研究肌肉萎缩和恶病质的标志物，如低PMA和BMI的变化。然而，该领域需要集中于针对肌肉消耗和恶病质表型的COPD病例队列的研究。这样一个队列的开发是她申请的R 00阶段（目标2）的一个关键重点，并将为她的第一个R 01申请提供试点数据。