Effect of Monthly Vitamin D Supplementation on Preventing Exacerbations of Asthma or Chronic Obstructive Pulmonary Disease in Older Adults: Post Hoc Analysis of a Randomized Controlled Trial

Abstract

Randomized controlled trials have suggested that vitamin D supplementation can prevent asthma and chronic obstructive pulmonary disease (COPD) exacerbations. For COPD, the benefit appears to be limited to individuals with baseline 25-hydroxyvitamin D (25OHD) levels <25 nmol/L. We performed a post hoc analysis of data from a randomized, double-blinded, placebo-controlled trial to investigate the effect that monthly, high-dose vitamin D supplementation (versus placebo) had on older adults with asthma and/or COPD. Specifically, we investigated whether vitamin D supplementation prevented exacerbations of these conditions. Participants were randomly assigned either to an initial oral dose of 200,000 IU vitamin D3 followed by 100,000 IU monthly or to placebo, with an average follow-up period of 3.3 years. Among the 5110 participants, 775 had asthma or COPD at the beginning of the study, and were eligible for inclusion in this analysis. Exacerbations were defined by the prescription of a short-burst of oral corticosteroids. The mean age of the participants was 67 years old, and 56% were male. The mean baseline blood 25OHD level was 63 nmol/L; 2.3% were <25 nmol/L. Overall, we found that vitamin D supplementation did not affect the exacerbation risk (hazard ratio 1.08; 95%CI 0.84-1.39). Among those with baseline 25OHD <25 nmol/L, however, the hazard ratio was 0.11 (95%CI 0.02-0.51); p for interaction = 0.001. Although monthly vitamin D supplementation had no overall impact on risk of exacerbations of asthma or COPD, we found evidence of a probable benefit among those with severe vitamin D deficiency.

Keywords: asthma; chronic obstructive pulmonary disease; exacerbations; oral corticosteroids; randomized controlled trial; supplement; vitamin D.

Figure 1

Flow diagram for selecting participants with asthma or chronic obstructive pulmonary disease in the ViDA study. COPD = chronic obstructive pulmonary disease; FEV₁ = forced expiratory volume in 1 s; FVC = forced vital capacity; SABA = short-acting β-agonist; LABA = long-acting β-agonist. ^a Dispensed inhaled corticosteroids, SABA or LABA at any time from 12 months before randomisation, to 36 months after. ^b Died by 31 July 2015.

Figure 2

Mean cumulative number of exacerbations of asthma or chronic obstructive pulmonary disease during follow-up to 31 July 2015, by study treatment.

Figure 3

Mean cumulative number of exacerbations of asthma or chronic obstructive pulmonary disease during follow-up to 31 July 2015 for deseasonalized baseline serum 25-hydroxyvitamin D subgroups (panels A–D), by study treatment.