Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials

Abstract

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.

Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential?

“…However, in a subgroup analysis of patients with severe vitamin D deficiency at baseline (25 (OH)D levels < 10 ng/ml), a significant reduction in exacerbations was observed [83]. Similar results were observed by two other studies [84,85] and by a recent meta-analysis, including all individual patient data, confirming that the protective effect of vitamin D supplementation against COPD exacerbations is restricted to those with the lowest baseline 25(OH)D levels [86]. Two large RCTs are still ongoing and might give us more insight into the role of vitamin D in exacerbations: Lung VITAL [87] and PRE-COVID [88].…”

“…The PRECOVID study will be the first RCT examining the effects of vitamin D supplementation on exacerbation rate in vitamin D-deficient COPD patients. As shown in the meta-analysis of prior studies [86], the anticipated effect in this targeted subgroup may be huge.…”

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

“…This mistaken approach rendered dissimilar results; thus, vitD supplements failed to prevent cancer or to reduce cardiovascular events [53][54][55]. However, in patients with baseline vitD levels less than 25 nmol/L (10 ng/mL), supplements were beneficial in respiratory diseases, such as reducing asthma [16] and chronic obstructive pulmonary disease [17] exacerbations.…”

“…However, new randomized controlled trials with moderate or high doses of vitD rendered dissimilar results. For instance, vitD supplements failed to demonstrate systemic antihypertensive effects or to reduce cardiovascular events [13][14][15], but succeeded in reducing asthma [16] and chronic obstructive pulmonary disease (COPD) [17] exacerbations in patients with baseline 25(OH)vitD levels lower than 25 nmol/L (10 ng/mL) About 85% of total 25(OH)vitD is bound to vitD-binding protein (DBP), about 15% is bound to albumin, and only less than 1% is free [18]. Albumin-bound 25(OH)vitD dissociates rapidly and is also biologically available in tissues, and DBP acts as a reservoir for vitD.…”

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases—An Umbrella Review

“…In our search for SRs on vitamin D and COPD risk, we identified six SRs [31,[100][101][102][103][104] (Supplemental Tables S6-S9 and Figure S2) of which three reported MAs on pooled data regarding vitamin D status or vitamin D supplementation and COPD risk [101,102,104]. The study quality assessed by the AMSTAR 2 tool was very heterogeneous (Supplemental Tables S6-S9).…”