Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol

Rafiq, Rachida; Aleva, Floor; Schrumpf, Jasmijn A.; Heijdra, Yvonne F.; Taube, Christian; Daniëls, Hans; Lips, Paul; Bet, Pierre M; Hiemstra, Pieter S.; Ven, André J. van der; Heijer, Martin den; Jongh, Renate T. de

doi:10.1186/s12890-015-0101-4

Cited by 25 publications

(24 citation statements)

References 66 publications

(81 reference statements)

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“…In this study, Rafiq et al 62 will also reported a significant reduction in the levels of tumor necrosis factor α at week 12.…”

supporting

confidence: 61%

“…The study of Rafiq et al 62 and a subsequent meta--analysis will finally address the issue of whether vitamin D supplementation in deficient patients with COPD should be recommended in a clinical setting to reduce exacerbations and improve physical functioning. increased in the supplemented group compared with placebo, particularly in the group with severe vitamin D deficiency.…”

mentioning

confidence: 99%

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Vitamin D supplementation in respiratory diseases - evidence from RCT

Mathyssen¹,

Gayan‐Ramirez²,

Bouillon³

et al. 2017

Polish Archives of Internal Medicine

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Pulmonary diseases are one of the most important causes of morbidity and mortality. Although vitamin D is best known for its role in calcium, phosphorus, and bone homeostasis, it has gained attention in the recent years because of a wide range of extraskeletal effects, including its immunomodulatory and antibacterial potential. Vitamin D deficiency is highly prevalent in chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, tuberculosis, and asthma, and several clinical studies have been conducted investigating the effect of vitamin D supplementation on disease outcomes. In this review, we searched for positive evidence on vitamin D supplementation from randomized controlled trials and elaborated on the optimal serum vitamin D levels and dosing regimens for an effective intervention. While vitamin D supplementation seems to be beneficial as an add -on treatment for adult patients with asthma and a potent intervention to reduce exacerbations in patients with COPD, there is little evidence for its therapeutic use in cystic fibrosis, pneumonia, and tuberculosis. the debate on the appropriate levels of 25(OH)D is still ongoing, most studies define the levels of less than 20 ng/ml (50 nmol/l) as deficient because they are associated with chronic diseases. 5 This is also the threshold used in most governmental guidelines for vitamin D. 16 The levels below 10 ng/ml (25 nmol/l) are considered as severe deficiency because they are associated with an increased risk of rickets or osteomalacia. It is also assumed that patients with these levels exhibit a true risk for infections and chronic diseases. 17 Other research groups reported that the serum 25(OH)D concentrations of 30 ng/ml (75 nmol/l) or even higher, as found in native populations living around the equator, are needed for optimal health. 5,10 Importance of vitamin D in pulmonary diseases Vitamin D deficiency is associated with multiple diseases such as cancer, hypertension, and autoimmune diseases, but also with several lung diseases. 5 A recent meta -analysis demonstrated that vitamin D levels are significantly lower in patients with tuberculosis (TB) compared with controls (apart from the African population). 18 About 70% to 90% of patients with TB have 25(OH)D levels below 20 ng/ml. 19,20 Janssens et al 6 demonstrated that patients with COPD had significantly lower 25(OH)D levels compared with healthy smokers and that vitamin D deficiency correlated with disease severity. While 31% of the healthy smokers were vitamin D deficient, this percentage increased gradually to 60% in stage 3 of COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) to even 77% in the most severe stage of the disease.Vitamin D deficiency is also highly prevalent in CF. Up to 75% of adults and 95% of pediatric patients with CF are vitamin D deficient, [21][22][23] despite routine oral supplementation. 24 In patients with CF, vitamin D deficiency seems to be associated with a decreased pulmonary function in adult...

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“…In this study, Rafiq et al 62 will also reported a significant reduction in the levels of tumor necrosis factor α at week 12.…”

supporting

confidence: 61%

mentioning

confidence: 99%

Vitamin D supplementation in respiratory diseases - evidence from RCT

Mathyssen¹,

Gayan‐Ramirez²,

Bouillon³

et al. 2017

Polish Archives of Internal Medicine

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“…Since the study was small and it reported a protective effect of vitamin D supplementation against exacerbations, the effect of its omission, if any, may have been to slightly bias results of this meta-analysis towards the null. We are aware of at least one ongoing RCT of vitamin D supplementation for the prevention of COPD exacerbations25 (n=240, scheduled to complete follow-up in 2019). Inclusion of IPD from this study and other eligible studies in a future meta-analysis has potential to increase power for subgroup analyses and generalisability of results.…”

Section: Discussionmentioning

confidence: 99%

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

Jolliffe

Greenberg

Hooper

et al. 2019

Thorax

Self Cite

160

110

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BackgroundRandomised 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.MethodsPubMed, 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.ResultsFour 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).ConclusionsVitamin 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 numberCRD42014013953.

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“…However, the study by Lehouck et al65 held inconsistent results that vitamin D supplementation had no effect on the rate of COPD exacerbations. A study exploring the effect of vitamin D supplementation on the incidence of exacerbations in vitamin D deficiency comorbid COPD patients is in progress 66. Maybe, it can broaden our knowledge of vitamin D and COPD exacerbation.…”

Section: Discussionmentioning

confidence: 99%

The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis

Zhu

Wang

et al. 2016

COPD

107

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BackgroundIn recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases. However, the association between serum vitamin D and COPD is not well studied. This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD.MethodsA systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases. The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency. Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method.ResultsA total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included. Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002). Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326). Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk.ConclusionSerum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation. Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation. It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD.

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Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol

Cited by 25 publications

References 66 publications

Vitamin D supplementation in respiratory diseases - evidence from RCT

Vitamin D supplementation in respiratory diseases - evidence from RCT

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

The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis

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