Article Text

Download PDFPDF
Original article
Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials
  1. David A Jolliffe1,
  2. Lauren Greenberg1,
  3. Richard L Hooper1,
  4. Carolien Mathyssen2,
  5. Rachida Rafiq3,
  6. Renate T de Jongh3,
  7. Carlos A Camargo4,
  8. Christopher J Griffiths1,5,
  9. Wim Janssens2,
  10. Adrian R Martineau1,5
  1. 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. 2 Department of Respiratory Medicine, Katholieke Universiteit, Leuven, Belgium
  3. 3 Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
  4. 4 Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, UK
  5. 5 Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK
  1. Correspondence to Professor Adrian R Martineau, The Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK ; a.martineau{at}


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.

  • copd exacerbations
View Full Text

Statistics from


  • WJ and ARM contributed equally.

  • Contributors ARM led the funding application, with input from RLH, CAC and CJG who were coapplicants. ARM, DAJ and WJ assessed eligibility of studies for inclusion. ARM, DAJ, CM, RR, RTdJ and WJ were all directly involved in the acquisition of data for the work. RLH designed statistical analyses in consultation with authors contributing individual patient data. Statistical analyses were done by DAJ, LG and RLH. ARM wrote the first draft of the report. All authors revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

  • Funding This research was supported by a grant from National Institute for Health Research (NIHR) under its Health Technology Assessment (HTA) Programme (Reference Number 13/03/25 to ARM).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement A partial dataset, incorporating patient level data from RCTs for which the relevant permission for data sharing have been obtained, is available from the corresponding author at

  • Patient consent for publication Not required.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Airwaves
    The Triumvirate