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. Ratio of Omega‐6 to Omega‐3 Fatty Acids and Childhood Asthma Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Does vitamin D intake during infancy promote the development of atopic allergy? Asthma and pregnancy: a review of two decades Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand? Antioxidants and asthma: will the patient benefit? [Editorial]. The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease A Randomized Trial of Citalopram versus Placebo in Outpatients with Asthma and Major Depressive Disorder: A Proof of Concept Study Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Effects of Vitamin A Supplementation on Iron Status Indices and Iron Deficiency Anaemia: A Randomized 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 Asthma is a leading cause of morbidity for children and is a major public health problem in Australia . Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma . Aim : The aim of conducting this study was to investigate whether  childhood asthma was associated with the ratio of omega 6 ( n‐6 ) to omega 3 ( n‐3 ) fatty acids in the diet ( n‐6:n‐3 ) . Method : The Western Australian Pregnancy Cohort Study is a prospect i ve birth cohort of 2602 children . Using a nested case‐control cross‐sectional study design within this cohort , a group of children were identified as cases with current asthma at 6 or at 8 years of age or as controls with no asthma at 6 or at 8 years .  Dietary details including n‐6 and n‐3 fatty acid intake data were collected by parent response to a question naire when the children were 8 years old . Logistical regression was used to compare quartiles of n‐6:n‐3 intake in cases and controls . Adjustment was made for covariates : gender , gestational age , breastfeeding , older siblings , maternal smoking during pregnancy , maternal age , maternal asthma , child 's current age in months , body mass index , total energy intake , and antioxidant intake  ( vitamins A , C , E , and zinc ) . Results : A response rate of 83 % was achieved by providing complete data from 335 children [ 49 % cases with current asthma ( n = 166 ) , 51 % controls ( n = 169 ) ] . Following adjustment for covariates the association between the ratio of n‐6:n‐3 fatty acids and risk for current asthma was statistically significant ( p = 0.022 ) . Conclusion : We found evidence for a modulatory effect of the dietary n‐6:n‐3 fatty acid ratio on the presence of asthma in children . Our results provide evidence that promotion of a diet with increased n‐3 fatty acids and reduced n‐6 fatty acids to protect children against symptoms of asthma is warranted Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of  vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed RATIONALE Low vitamin D levels are associated with asthma and decreased airway responsiveness . Treatment with inhaled corticosteroids improves airway responsiveness and asthma control . OBJECTIVES To assess the effect of vitamin D levels on prebronchodilator FEV(1 ) , bronchodilator response , and responsiveness to methacholine ( PC(20 ) , provocative concentration of methacholine producing a 20 % decline in FEV(1 ) ) in patients with asthma treated with inhaled corticosteroids . METHODS We measured  25-hydroxyvitamin D levels  in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program . We divided subjects into the vitamin D sufficiency ( > 30 ng/ml ) , insufficiency ( 20 - 30 ng/ml ) , and deficiency ( < 20 ng/ml ) groups . Covariates included age , treatment , sex , body mass index , race , history of emergency department visits , hospitalizations , and season that vitamin D specimen was drawn . Our main outcome measures were change in prebronchodilator FEV(1 ) , bronchodilator response , and PC(20 ) from enrollment to 8 - 12 months . MEASUREMENTS AND MAIN RESULTS Of the 1,024 subjects , 663 ( 65 % ) were vitamin D sufficient , 260 ( 25 % ) were insufficient , and 101 ( 10 % ) were deficient . Vitamin D-deficient subjects were more likely to be older , African American , and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects . In the inhaled corticosteroid treatment group , prebronchodilator FEV(1 ) increased from r and omization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1 ) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group ( P = 0.0072 ) , in adjusted models . CONCLUSIONS In children with asthma treated with inhaled corticosteroids , vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency The active metabolite of vitamin D , 1,25-(OH)2D3 , has immunomodulatory properties in addition to its more established action on bone and calcium metabolism . Recently vitamin D has been proposed as one of several environmental factors responsible for the increase in atopic diseases during the last decades . The objective of this study was to determine whether the estimated dose of dietary vitamin D3 during the first year of life is associated with atopic diseases up to the age of 6 years . In a prospect i ve birth cohort study 123 six-year-old children were investigated for the cumulative incidence of atopic dermatitis , allergic rhinitis or asthma by means of a postal question naire . Their vitamin D3 intake during infancy was recorded in a previous study and the relationship between lower or higher vitamin D3 intake and atopic illness later in childhood was assessed . Atopic manifestations were more prevalent in the group with higher intake of vitamin D3 . Although small , this study supports previous investigations suggesting a role of vitamin D intake during infancy in the development of atopic allergy later in childhood . If these findings are confirmed in prospect i ve controlled clinical trials , prevention through modified vitamin D3 supplementation in infancy could be discussed to reduce the burden of atopic illnesses The prevalence of asthma among pregnant women varies among studies from 4 to 8 % , making it by far the most common respiratory disorder complicating pregnancy . Controversy exists among the numerous retrospective and prospect i ve studies regarding pregnancy outcomes of asthmatic patients . Overall , the literature indicates that women with severe asthma are at an increased risk for preterm delivery , low birth weight , preeclampsia and Caesarean delivery , especially in the absence of inhaled corticosteroid therapy . Asthmatic women carrying a female fetus may particularly be at increased risk of these adverse outcomes . On the other h and , mild or moderate , well-controlled asthma is associated with favorable pregnancy and perinatal outcomes . Pregnancy also influences the course of asthma . Recently published data indicate that the real risk for an exacerbation during pregnancy may be underestimated . There is no question , however , that the risk of having an exacerbation correlates closely with the severity of asthma . The mechanisms responsible for these changes are not fully understood . Maternal hypoxia or inflammatory processes have been suggested and could explain reduced fetal growth through alterations in placental function . The goal of asthma therapy is to maintain adequate oxygenation of the fetus by prevention of exacerbations . Optimal management of asthma during pregnancy should include scheduled monitoring of objective lung function tests , avoiding triggers , patient education and tailored pharmacologic therapy . Inhaled corticosteroids are the treatment of choice for all levels of persistent asthma , yet other drug classes , such as β2-agonists and theophylline , are effective and safe for use during pregnancy BACKGROUND Low levels of vitamin D are associated with asthma severity , airway remodeling , and exacerbation rate increase , especially in nonatopic asthma . Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms . OBJECTIVE We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma . METHODS In a double-blind , r and omized , placebo-controlled trial , we investigated the effect of long-acting vitamin D3 ( 400,000 IU ) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic ( ≥53 % ) and /or eosinophilic ( ≥3 % ) airway inflammation . Sputum induction was performed at baseline and after 9 weeks . Other measurements included question naires , blood sample s , and pulmonary function . RESULTS Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group . Regarding sputum eosinophils , the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels ( interaction P = .015 ) . In patients with eosinophil levels  of 26.2 % or more ( median in patients with sputum eosinophilia , > 3 % ) , eosinophils decreased from a median of 41.0 % to 11.8 % after vitamin D treatment as compared with an increase from 51.8 % to 63.3 % in patients receiving placebo ( P = .034 ) . Vitamin D treatment also result ed in slightly better Asthma Control Question naire scores ( P = .08 ) . CONCLUSIONS Vitamin D supplementation  reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation , but did not affect sputum neutrophils . Also , a small effect on asthma control was observed . These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma IMPORTANCE In asthma and other diseases , vitamin D insufficiency is associated with adverse outcomes . It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency . OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS The VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma ) r and omized , double-blind , parallel , placebo-controlled trial study ing adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by January 2014 . After a run-in period that included treatment with an inhaled corticosteroid , 408 patients were r and omized . INTERVENTIONS Oral vitamin D3 ( 100,000 IU once , then 4000 IU/d for 28 weeks ; n = 201 ) or placebo ( n = 207 ) was added to inhaled ciclesonide ( 320 µg/d ) . If asthma control was achieved after 12 weeks , ciclesonide was tapered to 160 µg/d for 8 weeks , then to 80 µg/d for 8 weeks if asthma control was maintained . MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure ( a composite outcome of decline in lung function and increases in use of β-agonists , systemic corticosteroids , and health care ) . RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks ( 28 % [ 95 % CI , 21%-34 % ] with vitamin D3 vs 29 % [ 95 % CI , 23%-35 % ] with placebo ; adjusted hazard ratio , 0.9 [ 95 % CI , 0.6 - 1.3 ] ) . Of 14 prespecified secondary outcomes , 9 were analyzed , including asthma exacerbation ; of those 9 , the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control ( 111.3 µg/d [ 95 % CI , 102.2 - 120.4 µg/d ] in the vitamin D3 group vs 126.2 µg/d [ 95 % CI , 117.2 - 135.3 µg/d ] in the placebo group ; difference of 14.9 µg/d [ 95 % CI , 2.1 - 27.7 µg/d ] ) . CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency . These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01248065 Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases , prompting calls for widespread treatment of individuals with low vitamin D levels . Most of New Zeal and 's population have vitamin D levels for at least part of the year that are considered insufficient ( 25-hydroxyvitamin D < 50 - 80 nmol/L ) . However , evidence for benefits of vitamin D supplementation in such population s is controversial and there is some evidence of harmful effects . Until adequately powered , r and omised , controlled trials of vitamin D supplementation demonstrate safe improvements in health , clinicians should not focus on detecting/treating individuals with vitamin D insufficiency , instead treating those at high risk of vitamin D deficiency ( 25-hydroxyvitamin D < 25 nmol/L ) , such as the frail elderly , and those with specific clinical indications . Treatment for such individuals does not require vitamin D measurements . Requests for vitamin D measurements in Auckl and have nearly quadrupled in the past decade , from 8500 in the year 2000 to 32,800 in 2010 , with substantial increases in cost . Vitamin D measurement is often inaccurate and imprecise , and the vast majority of tests performed currently do not reveal vitamin D deficiency . Therefore , a move away from  routine vitamin D measurements  seems sensible , though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia OVER THE PAST THREE DECADES , many studies have been published of the associations between a variety of different measures of antioxidants and both  asthma and lung function .  While there is always a risk of publication bias , the general trend of these studies has been to suggest an association between higher dietary antioxidant intake with less asthma and better lung function . The study by Yoon et al. in this issue of the Journal adds to this body of literature by identifying 100 patients with relatively stable asthma , and demonstrating that those with a serum total antioxidant capacity ( TAC ) over the mean value have a higher baseline lung function than those with a serum TAC less than the mean value , although there was no signifi ca nt difference in bronchial reactivity.1 However , TAC levels were not signifi cantly correlated with longitudinal changes in pulmonary function , although the higher baseline lung function result ed in greater forced expiratory volume both one and two years after enrolment — as would probably be expected . As serum TAC refl ects a composite of endogenous and exogenous factors , only the latter category can be considered amenable to intervention . These include environmental tobacco exposure ( which was not adjusted for in the article by Yoon et al. ) , ambient pollution and dietary antioxidants.2 Recognition is growing of the importance of societal level interventions to reduce tobacco consumption and hence exposure to this and other forms of ambient pollution . The challenge for epidemiological research ers is to distinguish causality from association ; this is particularly true for nutritional research , where the problems of confounding by lifestyle , pre-natal exposures and possibly even pre-conception exposures ( via epigenetics ) are manifold . The only study design that can deliver these answers is the r and omised controlled trial , and these are better able to consider the secondary treatment of diseases such as asthma , rather than the primary prevention of asthma due to logistical considerations such as cost and recruitment . However , selection of the intervention is diffi cult , as relatively small studies ( compared to pharmaceutical studies ) of individual antioxidants have not been encouraging.3,4 One particular problem observed in these studies is that the individuals who volunteer to participate in these studies are often already eating a healthy diet , have an interest in healthy eating and hence may have little room for nutritional improvement . The most promising nutritional interventions in asthma have tended to involve combinations of antioxidants5 and , more recently , increased fruit and vegetable intake.6  The latter study suggested that those who received fi ve servings of vegetables and two servings of fruit daily were less than half as likely to have an exacerbation during the following 14 weeks . Further r and omised controlled studies of this nature are required to permit an enhanced underst and ing of the role of oxidation with regard to asthma aetiology and severity , and hopefully to permit translation of epidemiological observations into tangible effects from which the individual patient can benefi The Global Asthma Network ( GAN ) , established in 2012 , followed the International Study of Asthma and Allergies in Childhood ( ISAAC ) . ISAAC Phase One involved over 700 000 adolescents and children from 156 centres in 56 countries ; it found marked worldwide variation in symptom prevalence of asthma , rhinitis and eczema that was not explained by the current underst and ing of these diseases ; ISAAC Phase Three involved over 1 187 496 adolescents and children ( 237 centres in 98 countries ) . It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high , and identified several environmental factors that required further investigation . GAN Phase I , described in this article , builds on the ISAAC findings by collecting further information on asthma , rhinitis and eczema prevalence , severity , diagnoses , asthma emergency room visits , hospital admissions , management and use of asthma essential medicines .  The subjects will be the same age groups as ISAAC , and their parents . In this first global monitoring of asthma in children and adults since 2003 , further evidence will be obtained to underst and asthma , management practice s and risk factors , leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden . The Global Asthma Network undertakes global studies of asthma surveillance , management and risk factors RATIONALE Restoration of vitamin D sufficiency may reduce asthma exacerbations , events that are often associated with respiratory tract infections and cold symptoms . OBJECTIVES To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency . METHODS Colds were assessed in the AsthmaNet VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness ) trial , in which 408 adult patients were r and omized to receive placebo or cholecalciferol ( 100,000 IU load plus 4,000 IU/d ) for 28 weeks as add-on therapy . The primary outcome was cold symptom severity , which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey . MEASUREMENTS AND MAIN RESULTS A total of 203 participants experienced at least one cold .  Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml ( 95 % confidence interval [ CI ] , 40.1 - 43.7 ng/ml ) by 12 weeks , vitamin D supplementation had no effect on the primary outcome : the average peak WURSS-21 scores ( 62.0 [ 95 % CI , 55.1 - 68.9 ; placebo ] and 58.7 [ 95 % CI , 52.4 - 65.0 ; vitamin D ] ; P = 0.39 ) . The rate of colds did not differ between groups ( rate ratio [ RR ] , 1.2 ; 95 % CI , 0.9 - 1.5 ) ; however , among African Americans , those receiving vitamin D versus placebo had an increased rate of colds ( RR , 1.7 ; 95 % CI , 1.1 - 2.7 ; P = 0.02 ) . This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency , regardless of treatment assignment ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = 0.009 ) . CONCLUSIONS Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) BACKGROUND The prevalence of asthma has increased in recent years and depression is common in this population . Minimal data are available on the treatment of depressed asthma patients . METHODS Ninety adults with asthma and current major depressive disorder were r and omized to receive citalopram or placebo for 12 weeks . At each visit , the Hamilton Rating Scale for Depression ( HRSD ) , Inventory of Depressive Symptomatology - Self-Report , Asthma Control Question naire , and Asthma Quality of Life Question naire were administered , and oral corticosteroid use assessed . RESULTS In the evaluable sample ( n = 82 ) , the primary outcome , a r and om regression analysis of HRSD scores , revealed no significant between-group differences . Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6 . Changes in asthma symptoms were similar between groups . The groups had similar rates of oral corticosteroid use at baseline , but the citalopram group had less corticosteroid use during the study . Changes in asthma symptom severity correlated with changes in depressive symptom severity . CONCLUSIONS A reduction in depressive symptoms was associated with improvement in asthma .  Corticosteroid use , an important measure of severe asthma exacerbations , was lower in the citalopram group . Larger clinical trials in this population are warranted Objective To define the therapeutic role of vitamin D in children with moderate to severe bronchial asthma as an adjunct to st and ard treatment . Methods Hundred asthmatic children of either sex , attending the respiratory and asthma clinic were enroled in the study . Diagnosis was made on the basis of history and clinical examination . R and omization was done using sealed opaque envelop method . In addition to the treatment as per GINA guidelines , one group received oral vitamin D3 ( Cholecalciferol ) 60,000 IU per month for 6 mo and the other group received placebo powder in the form of glucose sachet with a double blinded design . Monthly follow up of every patient was done and during every visit change in severity , level of control , Peak expiratory flow rate ( PEFR ) , steroid dosage , number of exacerbations and number of emergency visits were assessed . Results Monthly doses of 60,000 IU vitamin D significantly reduced the number of exacerbations as compared to placebo ( p = 0.011 ) . PEFR significantly increased in the treatment group ( p = 0.000 ) . Monthly doses of vitamin D significantly reduced the requirement of steroids ( p = 0.013 ) and emergency visits ( p = 0.015 ) . Control of asthma was achieved earlier in patients who received monthly vitamin D. Vitamin D significantly reduced the level of severity of asthma patients over 6 mo of treatment ( p = 0.016 ) . Conclusions Vitamin D has a definite role in the management of moderate to severe persistent bronchial asthma as an adjunct to st and ard treatment INTRODUCTION The objective of this study was to report the impact of exacerbations on health-related quality of life ( HRQL ) and health utility in patients with moderate to severe asthma ( BTS levels 4 & 5 ) in the UK . MATERIAL S AND METHODS Prospect i ve data regarding HRQL were collected ( n=112 ) using the EQ-5D , mini Asthma Quality of Life Question naire ( mAQLQ ) , and Asthma Symptom Utility ( ASUI ) measures . RESULTS The mAQLQ , EQ-5D and ASUI were all significantly worse for patients suffering exacerbations ( p<0.001 ) compared to those without . There was also evidence of a further HRQL decrement in those patients who had been admitted to hospital as a result of an exacerbation during the four-week study . CONCLUSIONS This study documents the impact of asthma exacerbations on HRQL in patients with moderate to severe asthma . There was some evidence of floor effects on the mAQLQ and ASUI in their ability to capture the impact of exacerbations . These study data are suitable for use in economic evaluations Iron deficiency anaemia ( IDA ) is the most common nutritional deficiency in the world including developed and developing countries . Despite intensive efforts to improve the quality of life of rural and aboriginal communities in Malaysia , anaemia and IDA are still major public health problems in these communities particularly among children . A r and omized , double-blind , placebo-controlled trial was conducted on 250 Orang Asli ( aboriginal ) schoolchildren in Malaysia to investigate the effects of a single high-dose of vitamin A supplementation ( 200,000 IU ) on iron status indices , anaemia and IDA status . The effect of the supplement was assessed after 3 months of receiving the supplements ; after a complete 3-day deworming course of 400 mg/day of albendazole tablets . The prevalence of anaemia was found to be high : 48.5 % ( 95 % CI = 42.3 , 54.8 ) . Moreover , 34 % ( 95 % CI = 28.3 , 40.2 ) of the children had IDA , which accounted for 70.1 % of the anaemic cases . The findings showed that the reduction in serum ferritin level and the increments in haemoglobin , serum iron and transferrin saturation were found to be significant among children allocated to the vitamin A group compared to those allocated to the placebo group ( p < 0.01 ) . Moreover , a significant reduction in the prevalence of IDA by almost 22 % than prevalence at baseline was reported among children in the vitamin A group compared with only 2.3 % reduction among children in the placebo group . In conclusion , vitamin A supplementation showed a significant impact on iron status indices and IDA among Orang Asli children . Hence , providing vitamin A supplementation and imparting the knowledge related to nutritious food should be considered in the efforts to improve the nutritional and health status of these children as a part of efforts to improve the quality of life in rural and aboriginal communities
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 .