Skeletal muscle, subcutaneous fat, and clinical outcomes in smokers

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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