TY - JOUR

T1 - High body mass index and risk of exacerbations and pneumonias in individuals with chronic obstructive pulmonary disease

T2 - observational and genetic risk estimates from the Copenhagen General Population Study

AU - Çolak, Yunus

AU - Afzal, Shoaib

AU - Lange, Peter

AU - Nordestgaard, Børge G.

N1 - © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2016/10

Y1 - 2016/10

N2 - BACKGROUND: In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the causal role of high BMI in exacerbations and pneumonias in individuals with COPD. We tested the hypothesis that high BMI is associated with an increased risk of exacerbations and pneumonias in individuals with COPD, both observationally and genetically.METHODS: We genotyped 93 894 individuals of Danish descent, aged 20-100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10 883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up.RESULTS: For each increase in allele score, BMI was 0.28 kg/m(2) [95% confidence interval (CI): 0.25-0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele score increase in individuals with COPD were 1.13 (1.01-1.27) for exacerbations, 1.10 (1.03-1.19) for pneumonias and 1.12 (1.04-1.21) for exacerbations and/or pneumonias. Corresponding multivariable adjusted observational HRs per unit (kg/m(2)) BMI increase were 0.98 (0.95-1.01), 0.99 (0.96-1.03) and 0.99 (0.96-1.01), respectively.CONCLUSIONS: Genetically determined high BMI was associated with an increased risk of recurrent exacerbations and pneumonias in individuals with COPD, whereas this was not the case for observationally determined high BMI. The genetic data are compatible with the notion that high BMI leads to increased risk of exacerbations and pneumonias in individuals with COPD.

AB - BACKGROUND: In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the causal role of high BMI in exacerbations and pneumonias in individuals with COPD. We tested the hypothesis that high BMI is associated with an increased risk of exacerbations and pneumonias in individuals with COPD, both observationally and genetically.METHODS: We genotyped 93 894 individuals of Danish descent, aged 20-100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10 883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up.RESULTS: For each increase in allele score, BMI was 0.28 kg/m(2) [95% confidence interval (CI): 0.25-0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele score increase in individuals with COPD were 1.13 (1.01-1.27) for exacerbations, 1.10 (1.03-1.19) for pneumonias and 1.12 (1.04-1.21) for exacerbations and/or pneumonias. Corresponding multivariable adjusted observational HRs per unit (kg/m(2)) BMI increase were 0.98 (0.95-1.01), 0.99 (0.96-1.03) and 0.99 (0.96-1.01), respectively.CONCLUSIONS: Genetically determined high BMI was associated with an increased risk of recurrent exacerbations and pneumonias in individuals with COPD, whereas this was not the case for observationally determined high BMI. The genetic data are compatible with the notion that high BMI leads to increased risk of exacerbations and pneumonias in individuals with COPD.

U2 - 10.1093/ije/dyw051

DO - 10.1093/ije/dyw051

M3 - Journal article

C2 - 27118560

VL - 45

SP - 1551

EP - 1559

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 5

ER -