Vitamin D and Severe Asthma Exacerbations

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)