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

David A. Jolliffe, Lauren Greenberg, Richard L. Hooper, Carolien Mathyssen, Rachida Rafiq, Renate T. de Jongh, Carlos A. Camargo, Christopher J. Griffiths, Wim Janssens, Adrian R. Martineau

Research output: Contribution to journalArticleAcademicpeer-review

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.
LanguageEnglish
Pages337-345
Number of pages74
JournalThorax
DOIs
Publication statusE-pub ahead of print - 2019

Cite this

Jolliffe, David A. ; Greenberg, Lauren ; Hooper, Richard L. ; Mathyssen, Carolien ; Rafiq, Rachida ; de Jongh, Renate T. ; Camargo, Carlos A. ; Griffiths, Christopher J. ; Janssens, Wim ; Martineau, Adrian R. / Vitamin D to prevent exacerbations of COPD: Systematic review and meta-analysis of individual participant data from randomised controlled trials. In: Thorax. 2019 ; pp. 337-345.
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title = "Vitamin D to prevent exacerbations of COPD: Systematic review and meta-analysis of individual participant data from randomised controlled trials",
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.",
author = "Jolliffe, {David A.} and Lauren Greenberg and Hooper, {Richard L.} and Carolien Mathyssen and Rachida Rafiq and {de Jongh}, {Renate T.} and Camargo, {Carlos A.} and Griffiths, {Christopher J.} and Wim Janssens and Martineau, {Adrian R.}",
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Vitamin D to prevent exacerbations of COPD: Systematic review and meta-analysis of individual participant data from randomised controlled trials. / Jolliffe, David A.; Greenberg, Lauren; Hooper, Richard L.; Mathyssen, Carolien; Rafiq, Rachida; de Jongh, Renate T.; Camargo, Carlos A.; Griffiths, Christopher J.; Janssens, Wim; Martineau, Adrian R.

In: Thorax, 2019, p. 337-345.

Research output: Contribution to journalArticleAcademicpeer-review

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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.

PY - 2019

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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.

AB - 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.

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