title: High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Vitamin D and omega-3 polyunsaturated fatty acid supplementation in athletes with exercise-induced bronchoconstriction: a pilot study Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment Does vitamin D administered to children with asthma treated with inhaled glucocorticoids affect short-term growth or bone turnover? Correlation of vitamin D with Foxp3 induction and steroid-sparing effect of immunotherapy in asthmatic children. Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma Distinct endotypes of steroid-resistant asthma characterized by IL-17Ahigh and IFN-γhigh immunophenotypes: Potential benefits of calcitriol Effectiveness of vitamin D3 in severe persistent asthmatic patients: A double blind, randomized, clinical study Prevention of corticosteroid-induced osteoporosis by alfacalcidol Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) Therapy of steroid-induced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate. The effect of vitamin D on airway reactivity and inflammation in asthmatic children: A double-blind placebo-controlled trial. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. Improved control of childhood asthma with low‐dose, short‐term vitamin D supplementation: a randomized, double‐blind, placebo‐controlled trial Effect of vitamin D3 on mild to moderate persistent asthmatic patients: A randomized controlled pilot study
abstract: 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 ) 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 Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing .  We examined the effect of prenatal vitamin D on childhood wheezing  in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either  no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol  , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze  [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT There is intense interest in the role of vitamin D in the development of asthma and allergies . However , studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies . To address this uncertainty , the Vitamin D Antenatal Asthma Reduction Trial ( VDAART ) was developed . VDAART is a r and omized , double-blind , placebo-controlled trial of vitamin D supplementation  in pregnant women to determine whether prenatal supplementation can prevent the development of  asthma and allergies in women 's offspring . A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications , such as preeclampsia , preterm birth , and gestational diabetes .  Women were r and omized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3 . Women who were between the gestational ages of 10 and 18 weeks were r and omized from three clinical centers across the United States - Boston Medical Center , Washington University in St. Louis , and Kaiser Permanente Southern California Region ( San Diego , CA ) . Supplementation took place throughout pregnancy . Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events . Offspring are being evaluated quarterly through question naires and yearly during in-person visits until the 3rd birthday of the child . Ancillary studies will investigate neonatal T-regulatory cell function , maternal vaginal flora , and maternal and child intestinal flora Objective : The aim of this pilot study was to determine the combined effect of vitamin D and omega-3 polyunsaturated fatty acid ( PUFA ) supplementation on airway function and inflammation in recreational athletes with exercise-induced bronchoconstriction ( EIB ) . Methods : Ten recreational athletes with EIB participated in a single-blind , placebo-controlled trial over six consecutive weeks . All subjects attended the laboratory on three occasions . Each visit was separated by a period of 3 weeks : visit 1 ( usual diet ) , visit 2 ( placebo ) and visit 3 ( SMARTFISH ® NutriFriend 2000 ; 30 µg vitamin D3–3000 mg eicosapentaenoic acid , 3000 mg docosahexaenoic acid ) consumed once daily for a period of 3 weeks . Venous blood was collected at the beginning of each trial to determine  vitamin  D status . Spirometry was performed pre- and post-eucapnic voluntary hyperpnoea ( EVH ) . Results : The Maximum fall in FEV1 ( ΔFEV1max ) post-EVH was not different between visits ( usual diet : −15.9 ± 3.6 % , placebo : −16.1 ± 6.1 % , vitamin D + omega-3 PUFA : −17.8 ± 7.2 % ) . Serum vitamin  D remained unchanged between visits . Conclusion : Vitamin D and omega-3 PUFA supplementation does not attenuate the reduction in lung function post-EVH . This finding should be viewed as preliminary until the results of r and omised controlled trials are made available 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 The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of  seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo  in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 ( 18.6 % ) children in the  placebo  group [ relative risk ( RR ) , 0.58 ; 95 % CI : 0.34 , 0.99 ; P = 0.04 ] . The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements ( RR : 0.36 ; 95 % CI : 0.17 , 0.79 ; P = 0.006 ) and who started nursery school after age 3 y ( RR : 0.36 ; 95 % CI : 0.17 , 0.78 ; P = 0.005 ) . In children with a previous diagnosis of asthma , asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3 ) compared with 12 children receiving placebo ( RR : 0.17 ; 95 % CI : 0.04 , 0.73 ; P = 0.006 ) . CONCLUSION This study suggests that vitamin D(3 ) supplementation during the winter may reduce the incidence of influenza A , especially in specific subgroups of schoolchildren . This trial was registered at https://center.umin.ac.jp as UMIN000001373 Background Trials in school-aged children suggest vitamin D supplementation reduces asthma exacerbations . Primary aim : to examine whether vitamin D3 ( 100,000 IU ) rapidly raises serum 25-hydroxyvitamin D ( 25OHD ) ≥75 nmol/L in asthmatic preschoolers . Methods In a double-blind , r and omised , placebo-controlled trial , preschool-aged children with asthma received 100,000 IU vitamin D3 ( intervention ) or placebo ( control ) , followed by 400 IU vitamin D3 daily for 6 months . Serum 25OHD was measured at baseline , 10 days , 3 and 6 months . Outcomes included the group difference in 25OHD change from baseline at 3 months ( Δ25OHD ) ; the proportion of children with 25OHD ≥75 nmol/L at 3 months ; the pattern in serum vitamin D over 6 months ; the proportion of children with hypercalciuria at any time point ( safety ) ; and group rates for oral corticosteroids . Continuous outcomes were analysed using generalised linear mixed models and group rate ratios of events per child were assessed using a Poisson distribution model . Results Twenty-two children were r and omised ( intervention:11 ; control:11 ) during winter . At 3 months , the group difference in Δ25OHD ( 7.2 nmol/L ; 95 % CI : -13.7 , 28.1 ) was not significant ; yet , 100 % versus 54.5 % ( intervention versus control ) had serum 25OHD ≥75 nmol/L. There was a significant group difference in Δ25OHD at 10 days ( 110.3 nmol/L ; 95 % CI : 64.0 , 156.6 ) . One child in each group had transient hypercalciuria at 10 days . Group oral corticosteroids rates were 0.82 and 1.18/child , intervention versus control ( rate ratio = 0.68 ; 95 % CI : 0.30 , 1.62 ; non-significant ) . Conclusions Following 100,000 IU vitamin D3 , all children reached serum 25OHD ≥75 nmol/L , compared with half who received placebo . Daily supplementation , sun exposure and insufficient power may explain the absence of a significant 3-month group difference in Δ25OHD . No clinical ly important alterations in bone metabolism biomarkers occurred . Group oral corticosteroid rates will inform sample size calculations for the larger trial . ( NCT01999907 , 25 November 2013 ) 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 Calcidiol , the major circulating metabolite of vitamin D , supports induction of pleiotropic antimicrobial responses in vitro . Vitamin D supplementation elevates circulating calcidiol concentrations , and thus has a potential role in the prevention and treatment of infection . The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported . To characterize these effects , we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were r and omized to receive adjunctive high-dose vitamin D or placebo in a clinical trial , and who fulfilled criteria for per- protocol analysis . Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia , monocytosis , hypercytokinaemia , and hyperchemokinaemia . Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses , but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4 , CC chemokine lig and 5 , and IFN-α . We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment . Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality Our objective was to assess whether administration of 25-OH-vitamin D to children with asthma treated with inhaled dry-powder budesonide 400 microg daily affects short-term growth or markers of bone turnover . We utilized a r and omized , double-blind , two-period crossover trial with run-in and washout periods of 2 weeks and treatment periods of 4 weeks duration . The setting was an Outpatient clinic in a secondary referral center . Subjects included 14 boys and 3 girls with a mean age of 11.7 ( range , 6.1 - 14.4 ) years . Interventions included 15 microg ( 600 IU ) 25-OH-vitamin D ( cholecalciferol ) in one tablet ABCDin(R ) once daily in the morning . Primary outcome measures were : lower leg growth rate , serum osteocalcin , and serum markers of type I collagen turnover , i.e. , the amino terminal propeptide of type I procollagen ( PINP ) , the carboxy terminal propeptide of type I procollagen ( PICP ) ( formation markers ) , and the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen ( ICTP ) ( degradation markers ) . Secondary outcome measures were parameters of asthma control and serum 25-OH-vitamin D. Lower leg growth rate was 0.22 mm/week during vitamin D and 0.25 mm/week during placebo treatment ( NS ) . Osteocalcin was 59.9 and 57.8 microg/l during vitamin D and placebo treatment , respectively , PINP 574 and 565 microg/l , PICP 381 and 382 microg/l , and ICTP 11.5 and 11.1 microg/l , respectively ( NS ) . Serum 25-OH-vitamin D was 76.3 nmol/l and 48.2 nmol/l , respectively ( P < 0.001 ) . There were no statistically significant differences in measures of pulmonary function . In conclusion , administration of 25-OH-vitamin D does not affect short-term growth or markers of bone turnover in children with asthma treated with inhaled dry-powder budesonide 400 microg daily BACKGROUND Vitamin D promotes different toleragenic processes of the immune system ; however , its role in allergen specific immunotherapy ( SIT ) is still undefined . OBJECTIVE To determine whether the immunologic and clinical effectiveness of allergen SIT depends on the serum level of 25-hydroxyvitamin D ( 25[OH]D ) and its changes during SIT in asthmatic children . METHODS This is a retrospective secondary analysis of pooled data obtained from our 2 recently published prospect i ve , r and omized , placebo-controlled trials on asthmatic children undergoing allergen immunotherapy .  Both trials , which assessed the effect of different pharmacologic modulation of SIT effectiveness , were conducted according to the same study protocol . Children from the placebo arms in these trials were treated with immunotherapy only and were included in the present analysis . The study population consisted of 36 children . Data concerning clinical ( asthma symptoms score and percent change in minimal daily inhaled corticosteroid dose ) and immunologic parameters ( including serum level of 25[OH]D ) were analyzed in all patients . RESULTS Patients with a higher serum level of 25(OH)D experienced more significant reduction in asthma symptoms score and steroid-sparing effect of SIT and had higher transforming growth factor â production and higher Foxp3 induction during SIT . Steroid-sparing effect correlated with 25(OH)D serum level at baseline , after 3 months of SIT , and with the changes in serum level of 25(OH)D during the build-up phase of SIT . Better response to SIT was observed among children with an 25(OH)D serum level higher than 30 ng/mL. CONCLUSION The efficacy of allergen SIT correlates with 25(OH)D serum concentration . It seems that a serum level of 25(OH)D higher than 30 ng/mL facilitates the optimal effect of allergen immunotherapy 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 Background A small population of patients with severe asthma does not respond to glucocorticoids ( steroid resistant [ SR ] ) . They have high morbidity , highlighting an urgent need for strategies to enhance glucocorticoid responsiveness . Objective We investigated the immunologic differences between steroid-sensitive ( SS ) and SR asthmatic patients and the effect on immunophenotype of oral calcitriol treatment because it has been previously shown to beneficially modulate the clinical response to glucocorticoids in patients with SR asthma . Methods CD8-depleted P BMC s were isolated from 12 patients with SS and 23 patients with SR asthma and cultured for 7 days with anti-CD3 and IL-2 with or without dexamethasone . Cytokine production was assessed in supernatants by using the Cytometric Bead Array . Patients with SR asthma were subsequently r and omized to oral calcitriol or placebo therapy , and identical studies were repeated . Results Patients with SR asthma produced significantly increased IL-17A and IFN-γ levels compared with those in patients with SS asthma , although it was evident that cells from individual patients might overproduce one or the other of these cytokines . Production of IL-17A was inversely and production of IL-13 was positively associated with the clinical response to prednisolone . Oral calcitriol , compared with placebo , therapy of the patients with SR asthma significantly improved dexamethasone-induced IL-10 production in vitro while suppressing dexamethasone-induced IL-17A production . This effect mirrored the previously demonstrated improvement in clinical response to  oral glucocorticoids  in calcitriol-treated patients with SR asthma . Conclusions IL-17Ahigh and IFN-γhigh immunophenotypes exist in patients with SR asthma . These data identify immunologic pathways that likely underpin the beneficial clinical effects of calcitriol in patients with SR asthma by directing the SR cytokine profile toward a more SS immune phenotype , suggesting strategies for identifying vitamin D responder immunophenotypes 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 Summary We studied the effect of alphacalcidol ( 1-α-hydroxycholecalciferol ) on bone metabolism in patients who were placed on glucocorticoid therapy .  We selected 41 women ( age : 32–52 yrs ) who were recently diagnosed with systemic lupus erythematodes , multiple sclerosis , rheumatoid arthritis or asthma bronchiale . Patients did not have other disease or take drugs known to influence bone metabolism . Patients were r and omly enrolled into two groups and were given 5–25 mg prednisone daily . After 4 weeks , group A ( n=21 ) received 0.5–1.0μg ( mean=0.54±0.03μg ) alphacalcidol and group B ( control ; n=20 ) was given 500 mg calcium daily for three years . There were no significant differences in age and steroid doses between groups . Serum calcium ( Ca ) , osteocalcin ( OC ) , collagen I C-terminal propeptide ( PICP ) , parathyroid hormone ( PTH ) , and urinary calcium and deoxypyridinoline crosslink excretion ( DPD ) were measured before corticosteroid administration , and before alphacalcidol or calcium treatment as well as 6 weeks , 6 months , and 1 , 2 , and 3 years later . Bone mineral density ( BMD ) was examined before treatment and 6 months , 1 , 2 , and 3 years later by DEXA and SPA . OC and PICP decreased significantly after 4 weeks on steroid in both groups and increased in group A but not in group B after 6 weeks of treatment with alphacalcidol and remained unchanged for 3 years . Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A , but not in group B , after 6 weeks on alphacalcidol . Serum Ca , urinary Ca , and DPD did not change significantly in either group during the study period . Lumbar spine and femoral neck BMD were significantly reduced in group B after 6 months and 1 year , respectively , and continued to decrease during the study , while no significant change in group A was observed . BMD of the radius did not change in either group for 2 years but there was a significant reduction by the third year in group B. Based on these results , alphacalcidol treatment appears to be effective in preventing glucocorticoid-induced bone loss in these patients by reducing secondary hyperparathyroidism and stimulating bone formation 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 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 ) In a prospect i ve , controlled , and r and omized clinical trial , we examined the effects of treatment with vitamin D ( 1,000 IU/d ) , calcium ( 1 g/d ) , and ethane-1-hydroxy-1,1-diphosphonate ( EHDP ; 7.5 mg/kg body weight ) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids .  The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray . Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics .  Bone density increased during the observation period by 5 % in the treated group , compared with a decrease of 4.3 % in the untreated control group ( p < 0.01 ) . Moreover , in the treated group no radiologically visible new fractures occurred ; in the control group new fractures were observed in four patients . There were no serious side effects of the applied drugs during the 6-mo period . Therefore , the combination of EHDP , calcium , and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics 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 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 Introduction Oral glucocorticoid therapy reduces bone mineral density ( BMD ) and increases fracture risk . It is uncertain whether inhaled glucocorticoids , the most commonly used long-term therapy for asthma , have a similar effect . If bone loss does occur , it is unclear whether this is preventable by calcitriol . Patients with asthma receiving inhalational plus intermittent oral glucocorticoids  lose bone , and treatment with 0.5 μg/day of calcitriol will prevent bone loss . Methods A 2-year r and omized double-blind placebo-controlled trial . One hundred eight patients with asthma were stratified by gender , age , and inhaled glucocorticoid dose and treated with calcitriol ( n=55 ) or placebo ( n=53 ) . There were 41 men ( mean age 53.2±1.7 years ) and 67 women ( mean age 49.1±1 years ) with moderate to severe asthma ( requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy ) . BMD values at the lumbar spine ( LS ) and femoral neck ( FN ) were measured at baseline and at 6 , 12 , and 24 months using dual x-ray absorptiometry . Results Changes in LS and FN BMD . Bone loss occurred in both groups at the FN ( both p<0.03 ) and at the LS in the calcitriol ( p<0.001 ) , but not the control , group . Bone loss was not less in the calcitriol group at either site . Conclusion Patients with asthma receiving inhalational plus intermittent short courses of  oral glucocorticoids  lose bone . Calcitriol is unlikely to be appropriate therapy against this bone loss 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 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 CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P < 0.001 ) . The area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P < 0.001 ; and D(3 ) i m , 1361 + /- 492 vs. D(2 ) i m , 728 + /- 195 , P < 0.01 . 25(OH)D significantly influences PTH levels at 3 ( P < 0.03 ) , 7 ( P < 0.01 ) , 30 ( P < 0.01 ) , and 60 d ( P < 0.05 ) . At 60 d , the form of vitamin ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH 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 : 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
target: Meta- analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use .
  Children and people with frequent severe asthma exacerbations were under-represented ; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups
background: BACKGROUND Several clinical trials of vitamin D to prevent  asthma exacerbation  and improve  asthma control  have been conducted in children and adults , but a meta- analysis restricted to double-blind , r and omised , placebo-controlled trials of this intervention is lacking .
  OBJECTIVES To evaluate the efficacy of administration of vitamin D and its hydroxylated metabolites in reducing the risk of severe asthma exacerbations ( defined as those requiring treatment with systemic corticosteroids ) and improving asthma symptom control .