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RATIONALE: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. OBJECTIVE: To determine whether vitamin D metabolism is altered in asthma or COPD. METHODS: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation in 93 adults with asthma, COPD or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls. MEASUREMENTS AND MAIN RESULTS: The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where statistically significant. CONCLUSIONS: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.

Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed.To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status.A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks.The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01-0.25; p=0.03) but did not affect antigen-stimulated IFN-gamma secretion.A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066).