title: No association of 25-hydroxyvitamin D with exacerbations in primary care patients with COPD.
abstract: BACKGROUND
  Cross-sectional studies suggest an association of 25-hydroxyvitamin D with exacerbations in patients with COPD, but longitudinal evidence from cohort studies is scarce. The aim of this study was to assess the association of serum 25-hydroxyvitamin D with exacerbations and mortality in primary care patients with COPD.
  
  
  METHODS
  In the main analysis, we included 356 patients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages II-IV, free from exacerbations for ≥ 4 weeks) from a prospective cohort study in Dutch and Swiss primary care settings. We used negative binomial and Cox regression to assess the association of 25-hydroxyvitamin D with (centrally adjudicated) exacerbations and mortality, respectively.
  
  
  RESULTS
  Baseline mean ± SD serum 25-hydroxyvitamin D concentration was 15.5 ± 8.9 ng/dL, and 274 patients (77.0%) had 25-hydroxyvitamin D deficiency (< 20 ng/dL). Compared with patients with severe 25-hydroxyvitamin D deficiency (< 10 ng/dL, n = 106 [29.8%]), patients with moderately deficient (10-19.99 ng/dL, n = 168 [47.2%]) and insufficient (20-29.99 ng/dL, n = 58 [16.3%]) concentrations had the same risk for exacerbations (incidence rate ratio, 1.01 [95% CI, 0.77-1.57] vs 1.00 [95% CI, 0.62-1.61], respectively). In patients with desirable concentrations (> 30 ng/dL, n = 24 [6.7%]), the risk was lower, although not significantly (incidence rate ratio, 0.72 [95% CI, 0.37-1.42]). In patients taking vitamin D supplements, using different cutoffs for 25-hydroxyvitamin D or competing risk models did not materially change the results. We did not find a statistically significant association of 25-hydroxyvitamin D concentration with mortality.
  
  
  CONCLUSIONS
  This longitudinal study in a real-world COPD population that carefully minimized misclassification of exacerbations and the influence of confounding did not show an association of 25-hydroxyvitamin D with exacerbations and mortality.
authors.affiliation: Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: milo.puhan@ifspm.uzh.ch.
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.affiliation: Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lara
authors.initials: L
authors.lastname: Siebeling
authors.affiliation: Horten-Centre for patient oriented research and knowledge transfer, University of Zurich, Zurich, Switzerland; Institute of General Practice, University of Zurich, Zurich, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Frei
authors.affiliation: Institute of General Practice, University of Zurich, Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Zoller
authors.affiliation: Department of Geriatrics, University of Zurich, Zurich, Switzerland; Centre on Aging and Mobility, University of Zurich and Waid City Hospital, Zurich, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Bischoff-Ferrari
authors.affiliation: Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ter Riet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011320:Primary Health Care; D016016:Proportional Hazards Models; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000401:mortality; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D