Genome-Wide Association Analysis of Body Mass in Chronic Obstructive Pulmonary Disease

Wan, Emily S.; Cho, Michael H.; Boutaoui, Nadia; Klanderman, Barbara J.; Sylvia, Jody S.; Ziniti, John; Won, Sungho; Lange, Christoph; Pillai, Sreekumar; Anderson, Wayne H.; Kong, Xiangyang; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Regan, Elizabeth A.; Murphy, James R.; Make, Barry J.; Crapo, James D.; Wouters, Emiel; Celli, Bartolomé R.; Silverman, Edwin K.; DeMeo, Dawn L.

doi:10.1165/rcmb.2010-0294oc

Cited by 52 publications

(43 citation statements)

References 49 publications

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“…Nevertheless, our data indicate that there is a small subgroup of patients with disease-specific muscle wasting defined by continuous fat-free mass decline, which might be partly explained by excess exacerbation count, an observation in line with previous reports [11]. Alternatively, our findings are also in line with a genetic predisposition for the development of a thin body habitus in a subgroup of COPD patients [12], but this does not fully explain the high prevalence of low muscle mass in COPD patients. Additional causes seem responsible for this phenotype.…”

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confidence: 92%

Continuous fat-free mass decline in COPD: fact or fiction?

et al. 2015

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Patients with chronic obstructive pulmonary disease (COPD) generally have lower fat-free mass (a surrogate marker of skeletal muscle mass) compared with their healthy peers [1,2], and this is associated with decreased functional capacity [3], the presence of other comorbidities (e.g. osteoporosis and renal impairment) [4] and increased mortality risk [5]. To date, longitudinal observational studies have shown no difference in the mean decline in fat-free mass over time between COPD patients and non-COPD control subjects [6,7]. However, it remains unknown whether and to what extent a subgroup of COPD patients suffer continuous loss of fat-free mass. We hypothesised that COPD patients have 1) a higher prevalence of continuous fat-free mass decline, and 2) that this subgroup has a steeper decline of fat-free mass compared with a non-COPD control group with a continuous fat-free mass decline. We tested this hypothesis in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, which had a 3 year follow-up period.The design, aims and methodology of ECLIPSE have been described elsewhere [8]. Fat-free mass was measured by a trained research nurse using bio-electrical impedance (Bodystat 1500; Bodystat Ltd, Douglas, UK) (each centre had the same device) after at least 4 h fasting and calculated with a COPD specific formula [9]. Only subjects with complete fat-free mass data throughout the study were included in the present analysis. Low attenuation was determined by a chest computed tomography scan. Decline was defined as any fat-free mass measurement during follow-up that was lower than the fat-free mass of the previous year, and the number of years with a fat-free mass decline was summed. The prevalence of 3-year fat-free mass decline was calculated. Severe (hospitalisations) and moderate (use of corticosteroids/ antibiotics) exacerbations during the 3 year follow-up were recorded. Frequent exacerbators were defined as those patients with at least two exacerbations per year in the 3 year follow-up. The Chi-squared test was used to test the prevalence of fat-free mass decline between the COPD patients and the non-COPD control group. The unpaired t-test was used to compare the characteristics and level of decline in the patient group with the control group, and the characteristics in the group with a continuous decline compared with the remaining group. A p-value <0.05 was considered statistically significant.

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confidence: 92%

Continuous fat-free mass decline in COPD: fact or fiction?

et al. 2015

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“…COPD-related cachexia is a phenotype that impacts a subset of COPD individuals and has a significant impact on mortality, and BMI is a clinically relevant COPD phenotype. 61 They performed a meta-analysis of 3 COPD case-control cohorts including ECLIPSE, GenKOLS and NETT, and replicated their top findings in the first 1000 individuals of the COPDGene® cohort. In the meta-analysis, their most significant SNP was located within the fat mass and obesity-associated gene, FTO.…”

Section: Copd-related Phenotype Genomewide Association Studiesmentioning

confidence: 83%

Chronic Obstructive Pulmonary Disease Genetics: A Review of the Past and a Look Into the Future

Hardin

Silverman

2014

J COPD F

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Abbreviations: single nucleotide polymorphism, SNP; genome-wide association studies, GWAS; forced expiratory volume in 1 second, FEV1; early-onset COPD, EOCOPD; National Emphysema Treatment Trial, NETT; Normative Aging Study, NAS; International COPD Genetics Network, ICGN; linkage disequilibrium, LD; Evaluation of COPD Longitudinally to Identify Surrogate Endpoints, ECLIPSE; cigarettes per day, CPD; forced volume capacity, FVC; Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium, CHARGE; messenger RNA, mRNA; body mass index, BMI; C-reactive protein, CRP; tumor necrosis factor-alpha, TNF-alpha; Clara cell secretory protein, CC16; surfactant protein D, SP-D; Funding: K12 HL120004, The Sheila J. Goodnight, MD, FCCP, Clinical Research Grant in Women's Lung Health, R01HL089856; P01HL105339; R01HL075478 Date of Acceptance: February 28, 2014 Citation: Hardin M, Silverman EK. Chronic obstructive pulmonary disease genetics: a review of the past and a look into the future.

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“…53 Although low BMI is a prognostic factor in COPD, and is part of multidimensional prognostic indices, 54 there is limited information on the management of patients with cachexia, including the potential for drug interactions and abnormal metabolism, 55 and the effect on cost and health service utilization. 56,57 Potential interventions including the use of mechanical ventilation (to decrease the energy expenditure of breathing), nutritional supplementation, 58 anabolic steroids and growth hormone releasing factors such as ghrelin (to counterbalance the switch from catabolism to anabolism), have met with mixed results.…”

Section: Cachexia and Muscle Wastingmentioning

confidence: 99%

“…50,51 Biologic plausibility for this association has been strengthened by metabolomic studies showing similar profiles of amino acid metabolism in those with either emphysema or cachexia, 52 and an association between cachexia in COPD individuals and specific genetic polymorphisms within genes related to fat mass and obesity. 53 Although low BMI is a prognostic factor in COPD, and is part of multidimensional prognostic indices, 54 there is limited information on the management of patients with cachexia, including the potential for drug interactions and abnormal metabolism, 55 and the effect on cost and health service utilization. 56,57 Potential interventions including the use of mechanical ventilation (to decrease the energy expenditure of breathing), nutritional supplementation, 58 anabolic steroids and growth hormone releasing factors such as ghrelin (to counterbalance the switch from catabolism to anabolism), have met with mixed results.…”

Section: Cachexia and Muscle Wastingmentioning

confidence: 99%

Defining COPD-Related Comorbidities, 2004-2014

2014

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IntroductionOver the past 60 years we have witnessed radical transformations in population demographics and the burden of diseases that are shaping health care and which have an immediate and future impact within the field of respiratory diseases. Despite improvements in life expectancy and lower death rates in the United States over this period, COPD rose to the third leading cause of death in 2008, a testament to the growing importance of chronic diseases and disability.1 Refinements in the understanding of the pathophysiology and mechanisms responsible for susceptibility and heterogeneity of COPD (reviewed in other articles in the same issue of this journal) have occurred over the past 10 years. The search for additional ways to modify important outcomes has been enriched by two separate but related concepts that, at the turn of the century, were not always part of the mainstream AbstractChronic obstructive pulmonary disease (COPD) is a disease of aging in combination with genetic, environmental, and behavioral risk factors. Aging and many of these risk factors are shared with other diseases, and, as a result, it is not surprising that patients with COPD often have coexistent diseases. This review of COPD comorbidities uses a framework in which coexistent diseases are considered important comorbidities if they are more frequent, have more severe consequences, influence the progression and outcomes of COPD, or are clustered together into proposed phenotypes, supplemented by a framework in which certain comorbidities are expected to share specific pathogenic mechanisms. This review explores classic COPD comorbidities such as cardiovascular disease, cachexia and sleep apnea, but also looks at more recently described comorbidities, such as gastroesophageal reflux, osteoporosis and depression/anxiety. understanding of the disease. The first one is that the degree of obstruction -which defines the disease and its severity -does not fully correlate with COPD outcomes (exacerbations, death, and health-related quality-of-life [HR-QOL]). 2,3 The second is that a bidirectional interplay exists between the persistent inflammatory processes damaging the lungs and other organs. As a result, COPD is a complex disease linked with other comorbidities that influences treatment effectiveness and outcomes. This paper presents a review of the importance of COPD comorbidities in the development, progression, prognosis and therapy of COPD, and identifies the gaps in knowledge and research in this area. Challenges in the Identification and Interpretation of COPD ComorbiditiesIn the United States, COPD patients are usually older adults who have a history of tobacco exposure. These traits are shared with other chronic conditions, including cardiovascular disease and cancer. The typical patient with COPD reports, on average, 4 or more additional diseases 4 and on any given day one-third of COPD patients use 5-10 different medications. 5 There are several different frameworks that can help to decide if the relevance of a coexistent dise...

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Genome-Wide Association Analysis of Body Mass in Chronic Obstructive Pulmonary Disease

Cited by 52 publications

References 49 publications

Continuous fat-free mass decline in COPD: fact or fiction?

Continuous fat-free mass decline in COPD: fact or fiction?

Chronic Obstructive Pulmonary Disease Genetics: A Review of the Past and a Look Into the Future

Defining COPD-Related Comorbidities, 2004-2014

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