Vitamin D to Reduce Colds and Asthma Attacks in Young Children (DIVA-pilot)

Vitamin D vs. Placebo in the Prevention of Viral-induced Exacerbations in Preschoolers With Asthma: a Pilot RCT

Viral infections are the main cause of asthma attacks in preschoolers, an age group with the highest rate of emergency visits due to asthma. While high doses of inhaled or oral corticosteroids provide benefits, these have been associated with adverse outcomes. Most asthmatic children have lower blood levels of vitamin D compared to non-asthmatic children. Low vitamin D level has been linked to more frequent and more severe asthma attacks as well as with higher dose requirement of inhaled corticosteroid. Recent studies show that vitamin D supplements can reduce the number of asthma attacks triggered by viral infections in children. Unfortunately, most people forget to take vitamin D every day during the fall and winter season as recommended in Canada. A solution is to give a vitamin D bolus by mouth. This has been shown to safely and effectively increase vitamin D levels in children. The investigators hypothesise that a vitamin D bolus given in clinic will sufficiently increase the blood level of vitamin D to prevent the expected winter decline in vitamin D, compared with placebo in preschool-aged children with asthma. This six-month pilot randomized controlled trial aims to: (1) show that a vitamin D bolus is superior to placebo in raising vitamin D levels; (2) record the number of asthma attacks and viral infections in enrolled participants; and (3) identify problems that may call for protocol changes.

bolus placebo given in a 2ml dose by mouth at baseline. This group receives daily vitamin D supplement by mouth for the 6 month study (400IU cholecalciferol per day).

Vitamin D (100,000IU) bolus in a 2ml dose by mouth given at baseline. This group receives a daily vitamin D supplement by mouth for 6 months (400IU cholecalciferol per day).

number of patients with one or more exacerbations requiring oral steroids, as documented by pharmacy dispensation records and medical records

number of patients/person-month of observation documented two days parent-reported on the Canadian Acute Respiratory Illness and Flu Scale and Positive viral presence, determined by polymerase chain reaction on nasal sample

number of days with respiratory tract symptoms as reported on the parent completed Canadian Acute Respiratory Illness & Flu Scale

area under the curve for β-agonist use as documented by parent of the 'Asthma Flare-Up Diary for Young Children'; need for hospital admission

Number of days with asthma symptoms as reported on the parent-reported 'Asthma Flare-Up Diary for Young Children'

participant attendance to all 4 home and clinic visits percentage of patients with all 4 blood and urine tests collected percentage of analyzable viral nasal swabs returned.

Inclusion Criteria: children aged 1-5 years physician-diagnosed asthma as per GINA guidelines upper respiratory tract infections as the main asthma exacerbation trigger ≥4 respiratory infections in the past 12 months ≥1 exacerbation requiring rescue oral steroids in the past 6 months or ≥2 in the previous 12 months. Exclusion Criteria: extreme prematurity (<28 weeks gestation) infants <12 months of age breastfed infants with no vitamin D supplementation recent (<1 year) immigrants from countries where rickets and malnutrition prevalent other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis) endocrine disorder of calcium/ vitamin D metabolism disorder/ disease with associated malabsorption (inflammatory bowel disease) kidney/ liver disease sickle cell anemia medications known to interfere with bone metabolism/ vitamin D levels vitamin D supplementation >1000 IU/ day in past 3 months unable to attend medical visit in 3-4 months plan to leave the province during the next 6 months.

Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.

Jensen ME, Mailhot G, Alos N, Rousseau E, White JH, Khamessan A, Ducharme FM. Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial. Trials. 2016 Jul 26;17(1):353. doi: 10.1186/s13063-016-1483-1.