High body mass index and risk of exacerbations and pneumonias in individuals with chronic obstructive pulmonary disease: observational and genetic risk estimates from the Copenhagen General Population Study.
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.



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.



For each increase in allele score, BMI was 0.28 kg/m2[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/m2) BMI increase were 0.98 (0.95-1.01), 0.99 (0.96-1.03) and 0.99 (0.96-1.01), respectively.



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.
Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark.|Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Yunus
Y
Çolak
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Shoaib
S
Afzal
Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark.|Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Medical Unit, Respiratory Section, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark.
Peter
P
Lange
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark Boerge.Nordestgaard@regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Børge G
BG
Nordestgaard
D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D011014:Pneumonia / Q000150:complications*; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000235:genetics*; D012307:Risk Factors; D013147:Spirometry
Body mass index; disease exacerbations; genetic polymorphism; obesity; overweight; pneumonia