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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

      39,063 Monthly downloads/views I 2.893 Impact Factor I 5.2 CiteScore I 1.16 Source Normalized Impact per Paper (SNIP) I 0.804 Scimago Journal & Country Rank (SJR)

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      Ectopic fat accumulation in patients with COPD: an ECLIPSE substudy

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          Abstract

          Background

          Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities.

          Methods

          Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2–L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT. A dose–response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV 1] decline) was addressed with the Cochran–Armitage trend test. Regression models were used to investigate possible relationships between CT body composition indices and comorbidities.

          Results

          From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2–L3 to assess body composition. CSA of VAT was increased ( P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD ( P<0.002). Progressively increasing CSA of VAT was not associated with adverse clinical outcomes. The probability of exhibiting low 6MWD and accelerated FEV 1 decline increased with progressively decreasing MT attenuation and CSA of MT. In COPD, the probability of having diabetes ( P=0.024) and gastroesophageal reflux ( P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities ( P=0.042). Body composition parameters did not correlate with coronary artery scores or with survival.

          Conclusion

          Ectopic fat accumulation is increased in COPD, and this was associated with relevant clinical outcomes and comorbidities.

          Most cited references21

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          Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old.

          Kenneth F Adams, Arthur Schatzkin, Tamara Harris … (2006)
          Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health-AARP cohort who were 50 to 71 years old at enrollment in 1995-1996. BMI was calculated from self-reported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status. During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated. Excess body weight during midlife, including overweight, is associated with an increased risk of death. Copyright 2006 Massachusetts Medical Society.
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            Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.

            B Goodpaster, F. Leland Thaete, J.-A. Simoneau … (1997)
            Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men (n = 26) and women (n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU.m-2.min-1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (VO2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal (Rd) ranged from 3.03 to 16.83 mg.min-1.kg-1 FFM. Rd was negatively correlated with FM (r = -0.58), visceral fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh fat (r = -0.38) and positively correlated with muscle attenuation (r = 0.48) and VO2max (r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.
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              The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study.

              Harvey O Coxson, Asger Dirksen, Lisa Edwards … (2013)
              Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density. We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552. Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline -1·13 g/L [SE 0·06] per year). The annual decline in lung density was more rapid in women (additional -0·41 [SE 0·14] g/L per year, p=0·003) than men and in current smokers (additional -0·29 [SE 0·14] g/L per year, p=0·047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time. This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema. GlaxoSmithKline. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis
                Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis
                Journal ID (publisher-id): International Journal of COPD
                Title: International Journal of Chronic Obstructive Pulmonary Disease
                Publisher: Dove Medical Press
                ISSN (Print): 1176-9106
                ISSN (Electronic): 1178-2005
                Publication date Collection: 2017
                Publication date (Electronic): 31 January 2017
                Volume: 12
                Pages: 451-460
                Affiliations
                [1 ]Research Centre, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC
                [2 ]Department of Radiology, University of British Columbia, Vancouver, BC, Canada
                [3 ]Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
                [4 ]Hypoxia Pathophysiology Laboratory, Grenoble University Hospital, Grenoble, France
                [5 ]Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht
                [6 ]Research and Development, CIRO, Horn, the Netherlands
                [7 ]Department of Respiratory Medicine, University of Edinburgh
                [8 ]Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK
                Author notes
                Correspondence: François Maltais, Centre de Pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec, QC, Canada G1V 4G5, Fax +1 418 656 4762, Email francois.maltais@ 123456fmed.ulaval.ca
                Article
                Publisher ID: copd-12-451
                DOI: 10.2147/COPD.S124750
                PMC ID: 5293362
                PubMed ID: 28203068
                SO-VID: fa59643d-f9a5-4c48-beff-3603c14ccfcd
                Copyright © © 2017 Martin et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Respiratory medicine
                Keywords: metabolic syndrome,obesity,abdominal adiposity,muscle
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: metabolic syndrome, obesity, abdominal adiposity, muscle

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