Skeletal muscle, subcutaneous fat, and clinical outcomes in smokers

描述(申请人提供)：在美国估计有2400万慢性阻塞性肺病患者中，大约25%已经或将遭受无意的和病理性的骨骼肌丧失。这600万人的中位生存期将减少约50%。这一过程有几种可能的原因，包括全身炎症、废用性萎缩、激素不足、低氧血症和氧化应激。这些情况的众多共同导致在吸烟者中观察到的恶病质，在一个特定的个体中出现不止一种情况并不意外。由于脱脂体重(FFM)的不同损失和肥胖随年龄增加的交互趋势，简单的测量方法，如身体质量指数(BMI)，可能对这些过程不敏感，直到它处于后期，对治疗干预不太顺从甚至难以接受。临床医生和研究人员面临的挑战不是检测个人的氧化应激程度或全身炎症，而是检测和诊断恶病质本身。这项研究的目的是验证和应用基于计算机断层扫描的吸烟者身体成分测量方法。为此，我们将在两项大型观察性研究(COPDgene和ECLIPSE)中改进和应用我们基于图像的胸肌和竖脊肌肉以及邻近的皮下脂肪和横隔肌厚度的评估。我们将从目标1开始，在第一轮COPD基因研究中探索这些指标与死亡率和其他与疾病严重程度相关的临床指标之间的联系。然后，我们将使用在月食中获得的横截面和纵向数据来复制和扩展这些观测结果。最后，在目标3中，我们将检查身体成分的CT测量的变化以及肺功能和其他临床相关疾病测量的变化。我们将通过完成对所有第二轮COPDgene CT扫描的分析来实现这一点

DESCRIPTION (provided by applicant): Of the estimated 24 million people in the United States with COPD, approximately 25% have or will suffer from the unintentional and pathologic loss of skeletal muscle. These 6 million people will have an approximate 50% reduction in median survival. There are several possible causes of this process including systemic inflammation, disuse atrophy, hormonal insufficiency, hypoxemia, and oxidative stress. The multitude of these conditions collectively results in the cachexia observed in smokers and it is not unexpected for more than one to be present in a given individual. Because of the differential loss of fat free mass (FFM) and the reciprocal tendency for increased adiposity with age, a simple measure such as body mass index (BMI) may be insensitive to these processes until it is at its latter stages when it is less amenable or even refractory to therapeutic intervention. The challenge to clinicians and investigators is not the detection of an individual's degree of oxidative stress or systemic inflammation but rather the detection and diagnosis of cachexia itself. The purpose of this investigation is to validate and apply a computed tomographic based measure of body composition in smokers. We will do this by refining and applying our image based assessment of the pectoralis and erector spine muscles and adjacent subcutaneous fat as well as diaphragm muscle thickness in two large observational studies, COPDGene and ECLIPSE. We will begin in Aim 1 by exploring the association of these measures with mortality and other clinically relevant metrics of disease severity in the Round 1 COPDGene Study. We will then replicate and expand upon these observations using both cross sectional and longitudinal data obtained in ECLIPSE. Finally, in Aim 3 we will examine the change in CT measures of body composition and change in lung function and other clinically relevant measures of disease. We will do this by completing our analysis of all of the Round 2 COPDGene CT scans