Serum micronutrient concentrations and childhood asthma: the PIAMA birth cohort study. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children. Supplementation with vitamin A early in life and subsequent risk of asthma DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial The effect of vitamin D on airway reactivity and inflammation in asthmatic children: A double-blind placebo-controlled trial.
BACKGROUND Research suggests an influence of micronutrients on  childhood asthma .  So far , evidence mainly originates from cross-sectional studies using nutrient intake data , which is not an accurate measure of nutrient status . This study aim ed to investigate the cross-sectional and prospect i ve associations between serum concentrations of magnesium , vitamin D , selenium , and zinc and prevalence of ( severe ) asthma , atopy , and bronchial hyperresponsiveness ( BHR ) in childhood . METHODS In the Prevention and Incidence of Asthma and Mite Allergy birth cohort study , serum nutrient concentrations were available for a 4-yr-old subgroup ( n = 372 ) and for a different 8-yr-old subgroup ( n = 328 ) . Yearly question naires inquired about asthma prevalence until 8 yr of age . Allergic sensitization was measured at 4 and 8 yr of age ; BHR was measured at 8 yr of age . Data were analyzed with logistic regression and generalized estimating equations models . RESULTS There was a consistent ( non-significant ) inverse association between serum magnesium concentrations and asthma prevalence . Serum vitamin D concentrations measured at age 4 were inversely associated with asthma at ages 4 - 8 [ e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : odds ratio ( OR ) : 0.49 , 95 % confidence interval ( CI ) : 0.25 - 0.95 ] , whereas vitamin D measured at age 8 was positively associated with asthma at age 8 ( e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : OR : 2.14 , 95 % CI : 0.67 - 6.82 ) . CONCLUSIONS Our study contributes to the evidence that children with higher serum magnesium concentrations are less likely to have asthma . The associations between serum vitamin D concentrations and asthma were age-dependent Rationale Asthma exacerbations are commonly precipitated by viral upper respiratory infections ( URIs ) . Vitamin D insufficiency associates with susceptibility to URI in patients with asthma . Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking . Objective To conduct a r and omised controlled trial of vitamin D3 supplementation for the prevention of asthma exacerbation and URI ( co primary outcomes ) . Measurements and methods 250 adults with asthma in London , UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 ( n=125 ) or placebo ( n=125 ) over 1 year . Secondary outcomes included asthma control test and St George 's Respiratory Question naire scores , fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum . Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes . Main results 206/250 participants ( 82 % ) were vitamin D insufficient at baseline . Vitamin D3 did not influence time to first severe exacerbation ( adjusted HR 1.02 , 95 % CI 0.69 to 1.53 , p=0.91 ) or first URI ( adjusted HR 0.87 , 95 % CI 0.64 to 1.16 , p=0.34 ) . No clinical ly important effect of vitamin D3 was seen on any of the secondary outcomes listed above . The influence of vitamin D3 on co primary outcomes was not modified by baseline vitamin D status or genotype . Conclusions Bolus-dose vitamin D3 supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency . Trial registration number NCT00978315 ( Clinical Trials.gov ) BACKGROUND Asthma exacerbations , most often caused by respiratory tract infections , are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs . Vitamin D status might play a role in preventing asthma exacerbations . OBJECTIVES We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations . METHODS We measured  25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children r and omized to receive budesonide , nedocromil , or placebo ( as-needed beta-agonists ) : the Childhood Asthma Management Program . Using multivariable modeling , we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial . RESULTS Thirty-five percent of all subjects were  vitamin D insufficient , as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects . After adjusting for age , sex , body mass index , income , and treatment group , insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit ( odds ratio , 1.5 ; 95 % CI , 1.1 - 1.9 ; P = .01 ) . CONCLUSION Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period BACKGROUND Recent evidence about the various effects of vitamin D ( vit D ) on innate and adaptive immunity has led to a search for the role of vit D in asthma . It is postulated that a decrease in cathelicidin , a multifunctional host defense molecule , production due to low vit D status may predispose to infectious complications in children with asthma . OBJECTIVE The aim of this study was to determine the association of vit D , vit D-binding protein ( VDBP ) and cathelicidin with acute asthma attacks among children with allergic asthma . METHODS This prospect i ve study included 35 patients with acute asthma attack and 32 children with controlled asthma , and all were matched by sampling season , sensitization to mites , and previous severity of asthma . A comprehensive question naire about risk factors , blood sampling for 25-hydroxyvitamin D vit D , VDBP , and cathelicidin levels ; spirometric indices were used . Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis . RESULTS The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group ( p < 0.001 ) . The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma ( p = 0.002 ) . There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels . Risk factors that may influence vit D levels revealed that body mass index ( BMI ) ( p = 0.038 ) , duration of sun exposure ( p < 0.001 ) , and amount of dietary vit D ( p < 0.001 ) independently affected serum vit D levels . Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks ( p < 0.001 , adjusted odds ratio 16.11 ) . Cathelicidin levels showed a significant positive association with asthma attacks and BMI . CONCLUSIONS Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness , and may predispose to an increased risk of asthma .  We examined the long-term effects of vitamin A supplementation early in life on later  asthma risk . In 2006–2008 , we revisited participants from two cohorts in rural Nepal who were enrolled in r and omised trials of vitamin A supplementation . The first cohort received  vitamin A or placebo  for < 16 months during their pre-school years ( 1989–1991 ) . The second cohort was born to mothers who received vitamin A , & bgr;-carotene or placebo before , during and after pregnancy ( 1994–1997 ) . At follow-up , we asked about asthma symptoms and performed spirometry .  Out of 6,421 subjects eligible to participate , 5,430 ( 85 % ) responded to our respiratory survey . Wheezing prevalence during the previous year was 4.8 % in participants aged 9–13 yrs and 6.6 % in participants aged 14–23 yrs . We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction ( p≥0.12 for all comparisons ) . Vitamin A supplementation early in life was not associated with a decreased risk of asthma  in an area with chronic vitamin A deficiency Background Vitamin D levels are alarmingly low ( < 75 nmol/L ) in 65 - 70 % of North American children older than 1 year . An increased risk of viral upper respiratory tract infections ( URTI ) , asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations , two of the most common and costly illnesses of early childhood . The objectives of this study are : 1 ) to compare the effect of ‘ high dose ’ ( 2000 IU/day ) vs. ‘ st and ard dose ’ ( 400 IU/day ) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children ; and 2 ) to assess the effect of ‘ high dose ’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI . Methods / Design This study is a pragmatic r and omized controlled trial . Over 4 successive winters we will recruit 750 healthy children 1–5 years of age . Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be r and omized to the ‘ st and ard dose ’ or ‘ high dose ’ oral supplemental vitamin D for a minimum of 4 months ( 200 children per group ) . Parents will obtain a nasal swab from their child with each URTI , report the number of asthma exacerbations and complete symptom checklists . Unscheduled physician visits for URTIs and asthma exacerbations will be recorded . By May , a blood sample will be drawn to determine vitamin D serum levels . The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model . Secondary analyses will compare  vitamin D serum levels , asthma exacerbations and the frequency of specific viral agents between groups . Discussion Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs . This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers BACKGROUND Cross-sectional studies have reported an association of vitamin D deficiency with increased asthma prevalence and severity , and with allergies . The effect of vitamin D as sole therapy on airway hyper-reactivity ( AHR ) and airway inflammation has not been reported . AIM To evaluate the effect of vitamin D therapy on AHR as assessed by methacholine concentration , causing a 20 % reduction in FEV1 ( PC20 -FEV1 ) and fractional exhaled nitric oxide ( FeNO ) , systemic markers of allergy and inflammation , and exhaled breath condensate cytokines . PATIENTS AND METHODS Children aged 6 - 18 years with a clinical diagnosis of mild asthma currently not receiving anti-inflammatory therapy and with low vitamin D levels were included in this r and omized , double-blind , placebo-controlled study assessing the effect of 6 weeks of treatment with oral vitamin D 14,000 units once weekly or placebo . RESULTS Of the 39 patients included , 20 received vitamin D treatment and 19 received a placebo . Vitamin D replacement result ed in a significant increase in vitamin levels , which remained unchanged in the placebo group ( P < 0.0001 ) . There was no change in IgE , eosinophil count , high sensitivity C-reactive protein , FeNO levels or PC20 -FEV1 following treatment . Similar values of exhaled breath condensate cytokines ( IL4 , IL5 , IL10 , IL17 , and γ interferon ) were observed in both groups . CONCLUSIONS In our small group of children with mild asthma , no difference could be demonstrated between the effect of vitamin D and placebo , despite significant increases in vitamin D blood levels . Larger interventional studies are needed to fully explore the possible effect of vitamin D in asthma
Collectively , the evidence suggests that higher serum levels of 25(OH)D are associated with a reduced risk of asthma exacerbations , but there was little evidence to suggest an association with asthma incidence , prevalence or severity .
Asthma is a major public health issue .
The co-occurrence of the high prevalence of asthma and vitamin D deficiency documented globally in recent decades has prompted several investigations into a possible association between the two conditions .
The objective of this paper was to synthesize the evidence from studies that have measured the association between serum vitamin D  and asthma incidence , prevalence , severity and exacerbations .