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Thorax. 2019 Apr;74(4):337-345. doi: 10.1136/thoraxjnl-2018-212092. Epub 2019 Jan 10.

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

Author information

1
Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
2
Department of Respiratory Medicine, Katholieke Universiteit, Leuven, Belgium.
3
Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
4
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, UK.
5
Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
#
Contributed equally

Abstract

BACKGROUND:

Randomised 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.

METHODS:

PubMed, 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.

RESULTS:

Four 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).

CONCLUSIONS:

Vitamin 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 NUMBER:

CRD42014013953.

KEYWORDS:

copd exacerbations

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