Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Vitamin D levels, lung function, and steroid response in adult asthma. Vitamin D status has a linear association with seasonal infections and lung function in British adults. The effect of vitamin D on airway reactivity and inflammation in asthmatic children: A double-blind placebo-controlled trial. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma. Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) Effectiveness of vitamin D3 in severe persistent asthmatic patients: A double blind, randomized, clinical study Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Effect of vitamin D3 on mild to moderate persistent asthmatic patients: A randomized controlled pilot study Improved control of childhood asthma with low‐dose, short‐term vitamin D supplementation: a randomized, double‐blind, placebo‐controlled trial DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial Supplementation with vitamin A early in life and subsequent risk of asthma Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers.
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 RATIONALE Patients with asthma exhibit variable response to inhaled corticosteroids ( ICS ) . Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid ( GC ) response in asthma . OBJECTIVES To determine the effect of vitamin D levels on phenotype and GC response in asthma . METHODS Nonsmoking 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 RESULTS A 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 . CONCLUSIONS In 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 . clinical trials.gov ( NCT00495157 , NCT00565266 , and NCT00557180 ) Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with  respiratory infections and lung function .  We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms 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 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 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 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 BACKGROUND Vitamin D is hypothesized to have some roles in innate and adaptive immunity , inflammation reduction , and remodeling ; therefore , it is supposed to affect the asthma phenotype , severity , and response to inhaled corticosteroid ( ICS ) . OBJECTIVE To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers ( ICS or ICS plus long-acting β-agonist ) on airway functions . METHODS A r and omized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period . Data on age , sex , body mass index , stage of asthma , serum total IgE , history of allergic rhinitis , atopic dermatitis , food allergy , and urticaria were collected .  Spirometric parameters ( forced expiratory volume in 1 second [ FEV1 ] and ratio of FEV1 to forced vital capacity ) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention . Patients were divided in 2 groups r and omly . Both groups received asthma controllers ( budesonide or budesonide plus formoterol ) according to their stage , but the intervention group received vitamin D supplementation ( 100,000-U bolus intramuscularly plus 50,000 U orally weekly ) in addition to asthma controllers . RESULTS FEV1 improved significantly in both groups after 8 weeks , but no significant difference was found between the 2 groups at baseline ( P = .20 ) or after 8 weeks ( P = .99 ) ; however , a significant improvement was seen in the intervention group in the last 16 weeks , and FEV1 was significantly better in the intervention group than the other group after 24 weeks ( P < .001 ) . CONCLUSION Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks . TRIAL REGISTRATION i rct .ir Identifier : I RCT 201302079608N1 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 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 ) Objective : To assess the pulmonary function and quality of life in asthma patients receiving vitamin D3 supplementation with inhaled budesonide and formoterol . Material s and Methods : This was a double blinded , r and omized , comparative study . Patients were recruited as per the study criteria and r and omized into two groups :  usual care group ( n = 69 ) patients  received budesonide ( 800 μg ) with formoterol ( 24 μg ) and  intervention care group ( n = 72 ) patients  received vitamin D3 ( 1000 IU ) supplementation along with budesonide ( 800 μg ) plus formoterol ( 24 μg ) for a period of 6 months . Results : A total of 140 patients completed the study . Significant within-group improvement and non-significant between-group improvement is observed with respect to FEV1 . In terms of health-related quality of life , within-group comparison revealed a significant ( P < 0.05 ) improvement in all the domains of SGRQ . However , between-group comparisons showed statistically significant ( P < 0.05 ) improvement in symptom , impact and total scores . Conclusion : On the basis of our findings , we conclude that supplementation of vitamin D3 is effective in improving the quality of life rather than pulmonary function in severe asthmatics . However , further studies are warranted to substantiate the present findings BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research Background : Asthma is a common chronic inflammatory disease of the bronchial airways . Well defined treatment options for asthma are very few . The role of vitamin D3 on asthma is still baffling . Aim : We have examined the effect of vitamin D3 supplementation in mild to moderate persistent asthma patients . Material s and Methods : We conducted an open labeled , r and omized comparative trial in 48 asthma patients . The study duration was about 90 days . The study had a run-in-period of 2 weeks . At the end of run-in-period , patients were divided into two groups : Usual care group ( n = 31 ) patients received budesonide and formoterol and intervention care group ( n = 32 ) patients received vitamin D3 supplementation along with their regular medicine . Results : The primary outcome of the study was to measure the improvement in forced expiratory volume in 1 second ( FEV1 ) . Patients in both groups had a significant improvement in FEV1 at the end of the study . The mean difference in percentage predicted FEV1 in usual care and intervention care group was 4.95 and 7.07 respectively . Conclusion : The study concluded that adjunctive therapy of vitamin D3 is effective in asthma patients . The present study will be an evidence based report ; however , future studies are warranted in longer duration of time to substantiate the present findings In our prior r and omized trial on preventing influenza , asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group . We aim ed to clarify whether low‐dose , short‐term vitamin D supplementation , in addition to st and ard treatments , improves control of childhood asthma 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 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 The relation between vitamin A status and the degree of lung airway obstruction was examined in a cross-sectional study of 36 male subjects aged 43 - 74 y who were assigned to five groups as follows : healthy nonsmokers ( n = 7 ) , healthy smokers ( n = 7 ) , mild chronic obstructive pulmonary disease ( COPD -mild ) patients ( n = 9 ) , COPD -moderate-severe patients ( n = 7 ) , and COPD -moderate-severe patients with exacerbation ( + ex ; n = 6 ) .  Smoking habits , pulmonary function tests , energy-protein status were assessed ; serum concentrations of retinyl esters , retinol , retinol binding protein , and transthyretin and relative dose responses were measured . In addition , 12 male smokers aged 45 - 61 y with mild COPD were r and omly assigned to two groups for a longitudinal study : six subjects consumed vitamin A ( 1000 RE/d ; COPD -vitamin A ) and six subjects received placebo for 30 d. Lowered serum retinol concentrations were found in the COPD -moderate-severe and COPD -moderate-severe+ex groups . Measurements of vitamin A status in healthy smokers and in COPD -mild patients were not different from those in healthy nonsmokers . The improvement of pulmonary function test results after vitamin A supplementation [ mean increase for 1-s forced expiratory volume ( FEV1 ) = 22.9 % in the COPD -vitamin A group ] may support the assumption of a local ( respiratory ) vitamin A deficiency in patients with this disease
Available evidence from this systematic review suggests that high dose vitamin D may prevent  asthma exacerbation .
CONTEXT Observational studies have suggested a relationship between vitamin D status and asthma-related respiratory outcomes .
The benefit of vitamin D supplementation for pulmonary function , symptoms and exacerbations is not well established .
OBJECTIVE To systematic ally review paediatric clinical trials investigating the role of vitamin D on asthma-related respiratory outcomes .