human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    