Asthma risk reduced by 67 percent with Vitamin D supplementation if level was initially low– meta-analysis Nov 2017

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Overview Asthma and Vitamin D

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Meta-analysis Nov 2017

Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data
Lancet Respir Med. 2017 Nov;5(11):881-890. doi: 10.1016/S2213-2600(17)30306-5. Epub 2017 Oct 3.
Jolliffe DA1, Greenberg L1, Hooper RL1, Griffiths CJ2, Camargo CA Jr3, Kerley CP4, Jensen ME5, Mauger D6, Stelmach I7, Urashima M8, Martineau AR9.

BACKGROUND:
A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown.

METHODS:
For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953.

FINDINGS:
Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56-0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation.

Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11-0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58-1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56).

INTERPRETATION:
Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients.

FUNDING:
Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).

Copyright © 2017 Elsevier Ltd. All rights reserved.

PMID: 28986128 PMCID: PMC5693329
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Meta-analysis April 2019

Association between vitamin D status and asthma control: A meta-analysis of randomized trials
Mingming Wanga, Meicen Liub, Cairu Wanga, Yue Xiaoa, Tong Ana, Meijuan Zou c, Gang Chen gc, email the author
DOI: https://doi.org/10.1016/j.rmed.2019.02.016 |
Highlights
•Vitamin D may be an adjunct therapy for a certain group of patients with asthma.
•We evaluated the influence of baseline vitamin D status on asthma-related outcomes.
•Treatment effect was found in patients with air limitation and vitamin D insufficiency.
•More RCTs are required to evaluate the identical dose and duration of vitamin D.

Background
There is a controversy in terms of the efficacy of vitamin D supplementation in improving asthma symptom control. Moreover, whether there is a difference in the treatment effect with respect to baseline vitamin D status remains unknown. This meta-analysis was to assess the correlations of vitamin D status with asthma-related respiratory outcomes.

Methods
PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials of vitamin D supplementation in patients with asthma. Primary outcomes were the rate of asthma exacerbation and predicted percentage of forced expiratory volume in first second (FEV1%). Secondary outcomes were asthma control test (ACT) scores, fractional exhaled nitric oxide (FeNO), interleukin-10 (IL-10) and adverse events.

Results
A total of 14 randomized controlled trials (1421 participants) fulfilled the inclusion. Vitamin D supplementation was associated with a significant reduction in the rate of asthma exacerbation by 27% (RR: 0.73 95%Cl (0.58–0.92)). In subgroup analysis, the protective effect of exacerbation was restricted in patients with vitamin D insufficiency (vitamin D < 30 ng/ml) (RR: 0.76 95%Cl (0.61–0.95)). An improvement of FEV1% was demonstrated in patients with vitamin D insufficiency and air limitation (FEV1% < 80%) (MD: 8.3 95%Cl (5.95–10.64). No significant difference was observed in ACT scores, FeNO, IL-10 and adverse events.

Conclusions
Vitamin D supplementation reduced the rate of asthma exacerbation, especially in patients with vitamin D insufficiency. Additionally, the benefit of vitamin D had a positive effect on pulmonary function in patients with air limitation and vitamin D insufficiency.

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