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Meta-Analysis: Vitamin D Pills Lower COPD Exacerbation Risk

Vitamin D supplements reduced moderate to severe COPD exacerbations in patients with low circulating levels of its 25-hydroxyvitamin D (25-OH-D) metabolite at baseline, a meta-analysis indicated.

But no such effect was seen for patients with at least normal 25-OH-D levels (at least 25 nmol/L) prior to supplementation, according to Adrian Martineau of Queen Mary University in London, and colleagues writing in Thorax.

Supplementation was associated with a 45% reduction in exacerbations in 25-OH-D deficient patients in the analysis of three small randomized trials conducted in Belgium (n=182), Britain (n=240), and the Netherlands (n=47).

Identifying COPD patients with low vitamin D levels could prove to be an effective strategy for improving outcomes, Martineau said in a press statement. Martineau noted that around 20% of patients with COPD in the U.K. have low levels of vitamin D.

“Reducing risk of attacks in such a large group would have major benefits for patients and for the National Health Service, since many attacks require costly hospital admission,” he said.

The researchers searched major research databases for studies examining vitamin D supplementation in COPD patients through late 2017. Their analysis used fixed-effects models adjusting for age, sex, and Global Initiative for Chronic Obstructive Lung Disease spirometric grade. Individual participant data were obtained for 469 of the 472 (99.4%) participants in the three trials they found that met their inclusion criteria.

Oral vitamin D3 was given in all three studies, with varying doses and schedules; totals ranged from 220,000 IU in six months to 1.2 million IU per year.

Among the main findings from the meta-analysis:

  • Supplementation did not influence the overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio [aIRR] 0.94, 95% CI 0.78-1.13)
  • Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-OH-D levels <25 nmol/L (aIRR, 0.55, 95% CI 0.36-0.84) but not in those with baseline 25-OH-D levels ≥25 nmol/L (aIRR, 1.04, 95% CI 0.85-1.27; P=0.015 for interaction)
  • Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76-1.75)

That supplements’ benefit was limited to patients with low baseline levels matched that of a 2017 meta-analysis by the same researchers examining vitamin D trials for preventing asthma exacerbations.

“Since acute respiratory infections commonly precipitate exacerbations of both asthma and COPD, it may be that protective effects of vitamin D against these outcomes are mediated by a common mechanism, namely induction of antiviral and antimicrobial responses,” the researchers wrote.

They added that the study findings are consistent with the results of some observational studies, but not all. They suggest that the failure in some studies to show a protective effect may be due to the low number of participants with low baseline vitamin D status.

A study limitation cited by the researchers was the limited number of randomized controlled trials examining vitamin D supplementation in COPD available for pooling. Too few trials, the researchers noted, to justify construction of a funnel plot to assess publication bias.

They concluded that their findings should therefore be “interpreted with caution.”

“We are aware of at least one ongoing RCT of vitamin D supplementation for the prevention of COPD exacerbations [PRECOVID, n=240, scheduled to complete follow-up in 2019]. Inclusion of individual patient data from this study and other eligible studies in a future meta-analysis has potential to increase power for subgroup analyses and generalizability of results,” they wrote.

This research was funded by the National Institute for Health Research under its Health Technology Assessment Program.

The researchers declared no relevant relationships with industry related to this study.


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