BackgroundRandomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial.ResultsFour eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75).ConclusionsVitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels.Trial registration numberCRD42014013953.

BackgroundAlthough vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients.ObjectiveTo assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life.MethodsWe performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms.ResultsAt baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P<0.001). Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months. In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life.ConclusionVitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients.

BackgroundVitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients.Methods/DesignWe will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate.DiscussionThis study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined.Trial registrationThis trial is registered in ClinicalTrials.gov, ID number NCT02122627. Date of Registration April 2014.