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

Public Health Relevance

Computed tomographic assessments of skeletal muscle and subcutaneous fat in subjects enrolled in the COPDGene and ECLIPSE studies may provide insight into the nature, severity, and clinical impact of body composition and change in body composition in smokers. This may in turn lead to new therapies for patients with COPD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL122464-01A1
Application #
8818055
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Punturieri, Antonello
Project Start
2014-12-01
Project End
2018-11-30
Budget Start
2014-12-01
Budget End
2015-11-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
Martinez, Carlos H; Diaz, Alejandro A; Meldrum, Catherine A et al. (2017) Handgrip Strength in Chronic Obstructive Pulmonary Disease. Associations with Acute Exacerbations and Body Composition. Ann Am Thorac Soc 14:1638-1645
McDonald, Merry-Lynn N; Diaz, Alejandro A; Rutten, Erica et al. (2017) Chest computed tomography-derived low fat-free mass index and mortality in COPD. Eur Respir J 50:
Araki, Tetsuro; Yanagawa, Masahiro; Sun, Fangui Jenny et al. (2017) Pleural abnormalities in the Framingham Heart Study: prevalence and CT image features. Occup Environ Med 74:756-761
Kinsey, C Matthew; San José Estépar, Raul; van der Velden, Jos et al. (2017) Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer. Cancer Epidemiol Biomarkers Prev 26:38-43
Putman, Rachel K; Gudmundsson, Gunnar; Araki, Tetsuro et al. (2017) The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes. Eur Respir J 50:
Putman, Rachel K; Hatabu, Hiroto; Araki, Tetsuro et al. (2016) Association Between Interstitial Lung Abnormalities and All-Cause Mortality. JAMA 315:672-81
Araki, Tetsuro; Putman, Rachel K; Hatabu, Hiroto et al. (2016) Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med 194:1514-1522
Araki, Tetsuro; Nishino, Mizuki; Gao, Wei et al. (2016) Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking. Eur Radiol 26:15-24
Diaz, Alejandro A; Zhou, Linfu; Young, Tom P et al. (2014) Chest CT measures of muscle and adipose tissue in COPD: gender-based differences in content and in relationships with blood biomarkers. Acad Radiol 21:1255-61
McDonald, Merry-Lynn N; Diaz, Alejandro A; Ross, James C et al. (2014) Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc 11:326-34