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Original Research: COPD |

No Association of 25-Hydroxyvitamin D With Exacerbations in Primary Care Patients With COPDVitamin D and COPD Exacerbations

Milo A. Puhan, MD, PhD; Lara Siebeling, MD; Anja Frei, PhD; Marco Zoller, MD; Heike Bischoff-Ferrari, MD, DrPH; Gerben ter Riet, MD, PhD
Author and Funding Information

From the Institute for Social and Preventive Medicine (Dr Puhan), Horten-Centre for patient oriented research and knowledge transfer (Dr Frei), Institute of General Practice (Drs Frei and Zoller), and Department of Geriatrics (Dr Bischoff-Ferrari), University of Zurich, Zurich, Switzerland; Department of Epidemiology (Dr Puhan), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of General Practice (Drs Siebeling and ter Riet), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and Centre on Aging and Mobility (Dr Bischoff-Ferrari), University of Zurich and Waid City Hospital, Zurich, Switzerland.

Correspondence to: Milo A. Puhan, MD, PhD, Institute for Social and Preventive Medicine, University of Zurich, Hirschengraben 84, Room HRS G29, CH-8001 Zurich, Switzerland; e-mail: milo.puhan@ifspm.uzh.ch


For editorial comment see page 5

Funding/Support: This study was supported by the Swiss National Science Foundation [Grant 3233B0/115216/1], Dutch Asthma Foundation [Grant 3.4.07.045], and Zurich Lung League (unrestricted grant).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(1):37-43. doi:10.1378/chest.13-1296
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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.

Trial registry:  ClinicalTrials.gov; No.: NCT00706602; URL: www.clinicaltrials.gov.

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