High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND

Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis.

OBJECTIVE

To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations.

DESIGN

Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367)

SETTING

University Hospitals Leuven, Leuven, Belgium.

PATIENTS

182 patients with moderate to very severe COPD and a history of recent exacerbations.

INTERVENTION

100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year.

MEASUREMENTS

The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death.

RESULTS

Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042).

LIMITATION

This was a single-center study with a small sample size.

CONCLUSION

High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations.

PRIMARY FUNDING SOURCE

Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).