This study of vitamin D is designed to assess both the safety and efficacy of potential doses (2,000 IU/day and 4,000 IU/day) in raising a vitamin D level to a normal range in a short period of time (e.g. 4 weeks or less) compared to 200 IU/day.

In children with vitamin D insufficiency or deficiency who are at risk for severe asthma exacerbations, we hypothesize that both vitamin D supplementation with 4,000 IU/day and 2,000 IU/day will safely achieve normal vitamin D levels, but that the higher dose (4,000 IU/day) will result in a larger proportion of subjects achieving this level at 4 and 8 weeks.

Asthma is a major public health problem in the United States and worldwide. Severe disease exacerbations account for the majority of costs attributable to asthma in the United States. Vitamin D is an essential nutrient with significant immuno-modulatory effects. The observation that vitamin D insufficiency and asthma share risk factors such as urban residence, obesity, and African American ethnicity has generated significant interest in exploring a link between these two conditions.

This is an 8-week randomized, double-masked, controlled trial of vitamin D3 (2,000 IU/day and 4,000 IU/day) to achieve vitamin D sufficiency (a serum 25(OH)D ≥30 ng/ml in 60 school-aged children (ages 6 to 14 years) who have vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) and are at risk for severe asthma exacerbations, but whose asthma that is well-controlled on medium-dose inhaled corticosteroid (ICS) at the end of a 4-week run-in period.

Inclusion Criteria:

• Be at least 6 years of age and younger than 15 years of age
• Have physician-diagnosed asthma
• Taking a medium dose of ICS (e.g. fluticasone 220mcg BID) for daily asthma control for at least 6 months in the prior year.
• Have had a severe asthma exacerbation in the previous year, defined as an Emergency Department (ED) visit, hospitalization, or unscheduled clinic visit for asthma resulting in intramuscular, intravenous, or oral steroids.
• Have bronchodilator responsiveness (BDR, an increase in FEV1 ≥12% from baseline after administration of inhaled albuterol) or (if no BDR) increased airway responsiveness to methacholine challenge
• Have vitamin D insufficiency (a serum vitamin D (25(OH)D) level <30 ng/ml)
• Have his/her parents give voluntary written consent to participate in the study

Exclusion Criteria:

• Chronic respiratory disorder other than asthma (e.g., bronchiectasis).
• Severe asthma, as evidenced by any of the following: a) chronic need for medication other than single controller therapy and inhaled β2-agonist, b) intubation for asthma at any time, and c) ≥2 hospitalizations or ≥6 severe asthma exacerbations in the previous year
• History of cigarette smoking in the prior year or former smoking if ≥5 pack-years
• Hepatic or renal disease, metabolic rickets, malabsorptive disorders, or other chronic diseases that would affect vitamin D metabolism
• Immune deficiency, cleft palate or Down's syndrome, which might increase the child's likelihood of respiratory infections
• Treatment with anticonvulsants or pharmacological doses of vitamin D (≥1,000 IU/day of vitamin D2 or D3)
• Chronic oral corticosteroid therapy
• Inability to perform acceptable spirometry
• Use of investigational therapies or participation in clinical trials 30 days before or during the duration of the study
• Serum calcium >10.8 mg/dl
• Serum 25(OH) D <10 ng/ml (severe vitamin D deficiency)