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Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials.
Thorax. 2019 04; 74(4):337-345.T

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

30630893

Citation

Jolliffe, David A., et al. "Vitamin D to Prevent Exacerbations of COPD: Systematic Review and Meta-analysis of Individual Participant Data From Randomised Controlled Trials." Thorax, vol. 74, no. 4, 2019, pp. 337-345.
Jolliffe DA, Greenberg L, Hooper RL, et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax. 2019;74(4):337-345.
Jolliffe, D. A., Greenberg, L., Hooper, R. L., Mathyssen, C., Rafiq, R., de Jongh, R. T., Camargo, C. A., Griffiths, C. J., Janssens, W., & Martineau, A. R. (2019). Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax, 74(4), 337-345. https://doi.org/10.1136/thoraxjnl-2018-212092
Jolliffe DA, et al. Vitamin D to Prevent Exacerbations of COPD: Systematic Review and Meta-analysis of Individual Participant Data From Randomised Controlled Trials. Thorax. 2019;74(4):337-345. PubMed PMID: 30630893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. AU - Jolliffe,David A, AU - Greenberg,Lauren, AU - Hooper,Richard L, AU - Mathyssen,Carolien, AU - Rafiq,Rachida, AU - de Jongh,Renate T, AU - Camargo,Carlos A, AU - Griffiths,Christopher J, AU - Janssens,Wim, AU - Martineau,Adrian R, Y1 - 2019/01/10/ PY - 2018/05/19/received PY - 2018/11/20/revised PY - 2018/11/26/accepted PY - 2019/1/12/pubmed PY - 2019/8/31/medline PY - 2019/1/12/entrez KW - copd exacerbations SP - 337 EP - 345 JF - Thorax JO - Thorax VL - 74 IS - 4 N2 - 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. SN - 1468-3296 UR - https://www.unboundmedicine.com/medline/citation/30630893/Vitamin_D_to_prevent_exacerbations_of_COPD:_systematic_review_and_meta_analysis_of_individual_participant_data_from_randomised_controlled_trials_ L2 - http://thorax.bmj.com/cgi/pmidlookup?view=long&amp;pmid=30630893 DB - PRIME DP - Unbound Medicine ER -