Vitamin D supplementation, lung function and asthma control in children with asthma and low vitamin D levels.
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ABSTRACT:
SUBMITTER: Han YY
PROVIDER: S-EPMC8556333 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Vitamin D supplementation, lung function and asthma control in children with asthma and low vitamin D levels.
Han Yueh-Ying YY Forno Erick E Bacharier Leonard B LB Phipatanakul Wanda W Guilbert Theresa W TW Cabana Michael D MD Ross Kristie K Blatter Joshua J Rosser Franziska J FJ Durrani Sandy S Luther James J Wisniewski Stephen R SR Celedón Juan C JC
The European respiratory journal 20211028 4
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Project description:ImportanceSevere asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear.ObjectiveTo determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels.Design, setting, and participantsThe Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019.InterventionsParticipants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old).Main outcomes and measuresThe primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial.ResultsAmong 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, -13.1 days [95% CI, -42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9).Conclusions and relevanceAmong children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients.Trial registrationClinicalTrials.gov Identifier: NCT02687815.
| S-EPMC7448830 | biostudies-literature
Project description:BackgroundObservational studies have yielded inconsistent findings for the relation between vitamin D level and total IgE or allergic sensitization.ObjectiveTo determine whether vitamin D supplementation reduces levels of total IgE and IgE to each of 2 common indoor allergens in children with asthma and low vitamin D levels.MethodsTotal IgE, IgE to Dermatophagoides pteronyssinus, and IgE to Blattella germanica were measured at the randomization and exit visits for 174 participants in the Vitamin D Kids Asthma Study, a multicenter, double-blind, randomized placebo-controlled trial of vitamin D3 supplementation (4000 IU/d) to prevent severe exacerbations in children with persistent asthma and vitamin D levels less than 30 ng/mL. Multivariable linear regression was used for the analysis of the effect of vitamin D supplementation on change in each IgE measure.ResultsParticipants were followed for an average of 316 days. At the exit visit, more subjects in the vitamin D arm achieved a vitamin D level equal to or more than 30 ng/mL compared with those in the placebo arm (87% vs 30%; P < .001). In a multivariable analysis, vitamin D3 supplementation had no significant effect on change in total IgE, IgE to Dermatophagoides pteronyssinus, or IgE to Blattella germanica between the exit and randomization visits (eg, for log10 total IgE, β = 0.007; 95% CI, -0.061 to 0.074; P = .85).ConclusionsVitamin D supplementation, compared with placebo, has no significant effect on serum levels of total IgE, IgE to dust mite, or IgE to cockroach in children with asthma and low vitamin D levels.
| S-EPMC8655021 | biostudies-literature
Project description:RationalePatients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma.ObjectivesTo determine the effect of vitamin D levels on phenotype and GC response in asthma.MethodsNonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells.Measurements and main resultsA total of 54 adults with asthma (FEV(1), 82.9 +/- 15.7% predicted [mean +/- SD], serum vitamin D levels of 28.1 +/- 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (+/-9.3) ml (mean +/- SE) increase in FEV(1) for each nanogram per milliliter increase in vitamin D (P = 0.02). Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV(1) of 1.03 (+/-0.2) mg/ml versus 1.92 (+/-0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (+/-0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression.ConclusionsIn asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response. Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).
| S-EPMC2868500 | biostudies-literature
Project description:BackgroundLung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial.ObjectiveWe examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).MethodsThe 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years.ResultsA total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (β, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P = .003) and positively associated with FEV1 (β, 0.018 L; 95% CI, 0.005-0.031; P = .008) and forced vital capacity (β, 0.022 L; 95% CI, 0.009-0.036; P = .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (β, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P < .001 for R5 and β, -0.063 L; 95% CI, -0.099 to -0.028; P < .001 for FEV1).ConclusionsLow gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood.
| S-EPMC8315297 | biostudies-literature
Project description:BackgroundIt is unclear whether exposure to polycyclic aromatic hydrocarbons (PAH) affects lung function in children with asthma. Whether vitamin D insufficiency enhances any detrimental effects of PAH on lung function in asthmatic children is also unknown.MethodsCross-sectional study of 1,821 children (6-17 years) who participated in the 2007-2012 National Health and Nutrition Examination Survey. Multivariable linear regression was used to analyze the relation between molar mass of urinary PAH metabolites (sum of all PAH (ΣmolPAH), sum of PAH with 2 benzene rings (Σmol2-PAH), or sum of PAH with 3 or 4 benzene rings (Σmol3,4-PAH)) and lung function or exhaled fraction of nitric oxide (FeNO) in children with and without asthma. In this multivariable analysis, we tested whether vitamin D insufficiency (a serum 25(OH)D level <30 ng/mL) interacts with PAH exposure on lung function in children with asthma.ResultsChildren in the highest quartiles of urinary Σmol3,4-PAH had 2.3 times increased odds of asthma than those in the lowest quartile of Σmol3,4-PAH. Urinary PAH were not associated with lung function in children with or without asthma. Given a significant interaction between vitamin D insufficiency and PAH metabolites on lung function in asthmatic children, we stratified the analysis by vitamin D status. In this analysis, urinary PAH metabolites were significantly associated with 2.7-3.9% reduced %predicted FEV1 and %predicted FEV1/FVC in children with asthma and vitamin D insufficiency, but not in those with asthma and vitamin D sufficiency.ConclusionsVitamin D insufficiency and PAH exposure may have synergistic detrimental effects on lung function in asthmatic children.
| S-EPMC6345525 | biostudies-literature
Project description:BackgroundAn increasing number of studies have suggested that vitamin D can be used to treat childhood asthma, but its clinical effects are still unclear. We conducted this meta-analysis to examine the latest estimates of the effectiveness and safety of using vitamin D to treat childhood asthma.MethodsThe PubMed, The Cochrane Library, ScienceDirect, Embase, Scopus, Ovid MEDLINE, Web of Science, and Google Scholar databases were searched for randomized controlled trials (RCTs) describing vitamin D supplementation interventions for asthmatic children. Asthma exacerbation, vitamin D levels, the predicted percentage of forced expiratory volume in the first second (FEV1%) and adverse effects (AEs) were analyzed as the main outcome measures.ResultsAfter screening, eight RCTs with 738 children were included. Compared with placebos, vitamin D supplementation had a stronger effect on serum vitamin D levels [mean difference (MD) = 13.51 (4.24, 22.79), p = 0.004]. The pooled results indicated that no significant changes were found between the groups in asthma control, as measured by adopting the following indicators: asthma exacerbation [risk ratio (RR) = 0.92 (0.68, 1.25), p = 0.60]; Childhood Asthma Control Test (CACT) scores [MD = 0.15 (-0.43, 0.74), p = 0.61]; hospitalizations for asthma exacerbation [RR = 1.20 (0.48, 2.96), p = 0.70]; acute care visits [RR = 1.13 (0.77, 1.65), p = 0.63]; steroid use [RR = 1.03 (0.41, 2.57), p = 0.95]; and fractional exhaled nitric oxide (FeNO) [MD =-3.95 (-22.87, 14.97), p = 0.68]. However, vitamin D supplementation might reduce the FEV1% [MD = -4.77 (-9.35, -0.19), p = 0.04] and the percentage of predicted forced vital capacity (FVC%) [MD =-5.01 (-9.99, -0.02), p = 0.05] in patients. Subgroup analysis revealed no difference in AEs between the two groups.ConclusionsVitamin D supplementation significantly increased patients' serum vitamin D levels, but it had no benefit for asthma control. However, vitamin D supplementation might reduce patients' lung function. It is essential to systemically search for more large-scale, rigorous, and well-designed RCTs to fully confirm these conclusions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288838, PROSPERO CRD42021288838.
| S-EPMC9277022 | biostudies-literature
Project description:Rationale: In practice, asthma control is assessed according to symptom burden and office spirometry. However, spirometry poorly tests peripheral lung function, which may be abnormal in asthma. Impluse oscillometry (IOS) and multiple-breath washout (MBW) are novel methods which measure reactance (X5) and ventilation heterogeneity (VH) in the peripheral lung, but how well these tests reflect asthma control is poorly understood. Objective: To compare the diagnostic accuracy of tests of large airways caliber (FEV1, FEV1/FVC, R20), peripheral zone properties (X5, VH), and airways inflammation (FeNO) as predictors of poor control in asthmatic children (44 poorly controlled/10 controlled). Methods: 54 children enriched in severe asthma completed a symptom-based control scale (ACT/cACT) and lung function tests after overnight bronchodilator withhold. The accuracy of each variable to predict poor control was ranked by area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. Results: Among measures of large airways caliber, the FEV1% had the highest ROC curve area, with low sensitivity but perfect specificity. Among measures of peripheral lung function, X5 and VH in the conducting zone had fair curve areas with higher sensitivity but lower specificity compared to the FEV1%. VH in the acinar zone and FeNO both had poor accuracy. Conclusion: Tests of large airway and peripheral zone lung function performed disparately as predictors of poor control in a sample of children enriched in severe asthma. Further studies in a larger sample with more diverse phenotypic features are necessary to validate this preliminary conclusion.
| S-EPMC6642863 | biostudies-literature
Project description:BackgroundThere is conflicting evidence about the association between low vitamin D levels in children and development of asthma in later life. The objective of this study was to systematically review the evidence for an epidemiological association between low serum levels of vitamin D and the diagnosis of asthma in children.MethodsWe used the Cochrane methodology for conducting systematic reviews. The search strategy included an electronic search of MEDLINE and EMBASE in February 2013. Two reviewers completed, in duplicate and independently, study selection, data abstraction, and assessment of risk of bias.ResultsOf 1081 identified citations, three cohort studies met eligibility criteria. Two studies found that low serum vitamin D level is associated with an increased risk of developing asthma late in childhood, while the third study found no association with either vitamin D2 or vitamin D3 levels. All three studies suffer from major methodological shortcomings that limit our confidence in their results.ConclusionsAvailable epidemiological evidence suggests a potential association between low serum levels of vitamin D and the diagnosis of asthma in children. High quality studies are needed to reliably answer the question of interest.
| S-EPMC4064110 | biostudies-literature
Project description:ObjectiveTo determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs.Study designA decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions.ResultAdditional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort.ConclusionVitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma.
| S-EPMC6414472 | biostudies-literature
Project description:BACKGROUND:Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear. OBJECTIVE:We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score. METHODS:We analysed 270 children, 6- to 17-years old, with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels. RESULTS:Of all children, 14.8% (40/270) (and 28% (38/135) of African Americans) carried two non-5-repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 vs. 30 nmol/mol creatinine, P = 0.0134), significantly worse FEV1% predicted (84 vs. 91, P = 0.017) and a trend towards worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = -0.192, P = 0.009). CONCLUSION AND CLINICAL RELEVANCE:Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.
| S-EPMC3633142 | biostudies-literature