Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

Riverin, Bruno; Maguire, Jonathon L.; Li, Patricia

doi:10.1371/journal.pone.0136841

Cited by 91 publications

(82 citation statements)

References 52 publications

(131 reference statements)

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“…Our results are in accordance with two recent meta-analyses of RCTs [15,16], which conclude that evidence is lacking to support regular use of vitamin D supplements for prevention of asthma exacerbations, but are in contrast with the findings of a recent Cochrane meta-analysis of RCTs [14]. Our findings for atopic dermatitis and IgE agree with recent observational studies and RCTs [3,4,9].…”

Section: Discussionsupporting

confidence: 91%

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

et al. 2017

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BackgroundLow circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable.Methods and findingsWe aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90–1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69–1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92–1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was −0.40 (95% CI −1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia.ConclusionsIn this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.

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Section: Discussionsupporting

confidence: 91%

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

et al. 2017

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“…A Cochrane review of placebo-controlled trials, including 435 children and 658 adults, concluded that vitamin D is likely to reduce the risk of severe asthma exacerbation and healthcare use due to asthma, though children and those with severe asthma were underrepresented in the included studies [111**]. These findings are in accordance with other systematic reviews [112,113]. …”

Section: Vitamin D Supplementationsupporting

confidence: 73%

Strategies to alter the natural history of childhood asthma

Lee-Sarwar

Bacharier

Litonjua

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short- and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation.

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“…Recent meta‐analyses suggest that vitamin D supplementation may reduce the likelihood of asthma exacerbation (Riverin et al. ; Martineau et al. ), and it will be important to determine whether treatment is more effective in individuals that are vitamin D deficient prior to commencing vitamin D supplementation.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

et al. 2017

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In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset. Female BALB/c dams were fed a vitamin D3‐supplemented (2280 IU/kg, VitD+) or nonsupplemented (0 IU/kg, VitD−) diet from 3 weeks of age, and mated at 8 weeks of age. Male offspring were fed the same diet as their mother. Some offspring initially fed the VitD− diet were switched to a VitD+ diet from 8 weeks of age (VitD−/+). At 12 weeks of age, signs of low‐level inflammation were observed in the bronchoalveolar lavage fluid (BALF) of VitD− mice (more macrophages and neutrophils), which were suppressed by subsequent supplementation with vitamin D3. There was no difference in the level of expression of the tight junction proteins occludin or claudin‐1 in lung epithelial cells of VitD+ mice compared to VitD− mice; however, claudin‐1 levels were reduced when initially vitamin D‐deficient mice were fed the vitamin D3‐containing diet (VitD−/+). Reduced total IgM levels were detected in BALF and serum of VitD−/+ mice compared to VitD+ mice. Lung mRNA levels of the vitamin D receptor (VDR) were greatest in VitD−/+ mice. Total IgG levels in BALF were greater in mice fed the vitamin D3‐containing diet, which may be explained by increased activation of B cells in airway‐draining lymph nodes. These findings suggest that supplementation of initially vitamin D‐deficient mice with vitamin D3 suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs.

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Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

Cited by 91 publications

References 52 publications

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

Strategies to alter the natural history of childhood asthma

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

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