Intervention with vitamin D versus placebo, time to first acute exacerbation
Change in time (days) to first acute exacerbation with asthma-like symptoms requiring OCS and / or hospitalization / treatment at a pediatric ward.
Intervention with vitamin D versus placebo, duration of symptoms
Change of the duration (days) of symptoms / hospitalization.
Intervention with vitamin D versus placebo, need for medical treatment
Change in the need for medical treatment during exacerbations, including SABA, short-acting anticholinergic inhalations (SAMA) and OCS.
Intervention with vitamin D versus placebo, daily symptom burden
Change in the daily symptom burden between exacerbations.
Intervention with vitamin D versus placebo, step-down of preventive treatment
Is the intervention associated with successful step-down of preventive medical asthma treatment.
Safety profile of vitamin D intervention, calcium levels in blood
This study also aims to examine the safety profile of vitamin D intervention. This is done by examining group differences in the proportion of children with clinically significant:
Hypo-calcemia (defined as total β-calcium below 2.20 mmol / l after correction for albumin)
Hyper-calcemia (defined as total β-calcium above 2.55 mmol / l after correction for albumin)
Safety profile of vitamin D intervention, calcium levels in urine
This study also aims to examine the safety profile of vitamin D intervention. This is done by examining group differences in the proportion of children with clinically significant:
● Hyper-calciuri as defined by Ca/creatinine-ratio in urine with a value above 1,0 mmol/mmol
Safety profile of vitamin D intervention, serum 25OHD level
This study also aims to examine the safety profile of vitamin D intervention. This is done by examining group differences in the proportion of children with clinically significant serum 25OHD> 250 nmol / L.
Safety profile of vitamin D intervention, Adverse Events
This study also aims to examine the safety profile of vitamin D intervention. This is done by examining group differences in the proportion of children with clinically significant incidence(s) of Adverse Events.
Exploratory outcomes, baseline 25OHD
Analyzing baseline serum 25OHD (mol / L).
Exploratory outcomes, genetic variation in VDR
Analyzing genetic variation of the Vitamin D Receptor gene (VDR).
Exploratory outcomes, genetic variation in VDBP
Analyzing genetic variation of the Vitamin D Binding Protein gene (VDBP).
Exploratory outcomes, expression levels of genes involved in the vitamin D metabolism
Analyzing expression in vitamin D metabolism related to VDR and Vitamin D binding protein (VDBP) and other relevant candidates in the vitamin D processing pathway.
Exploratory outcomes, expression levels of asthma-related genes
Analyzing expression levels in known asthma-related genes, e.g. 17q21 and other relevant genes.
Exploratory outcomes, genetic variation in asthma-related genes
Analyzing genetic variation in known asthma-related genes, e.g. 17q21 and other relevant genes.
Exploratory outcomes, respiratory microbiome, conventional culture
Alpha- and beta Diversity of gut microbiota using conventional culturing assays.
Exploratory outcomes, respiratory microbiome
Alpha- and beta diversity of gut microbiota using 16S rRNA sequencing and whole genome sequencing.
Exploratory outcomes, respiratory virus detection
Alpha- and beta diversity of vira using targeted q-PCR.
Exploratory outcomes, respiratory immune profile, blood eosinophilocyte counts
Measuring blood eosinophilocyte counts for inhalation allergens.
Exploratory outcomes, respiratory immune profile, total-IgE
The study also aims to examine a wide range of exploratory outcomes to gain insight into the mechanisms of action behind the effects of vitamin D supplementation and possible effect modification, which can help identify children with particularly high effects of treatment, by analyzing the respiratory immune profile at the time of inclusion. Atopic status by measuring total-IgE for inhalation allergens.
Exploratory outcomes, respiratory immune profile, specific-IgE
The study also aims to examine a wide range of exploratory outcomes to gain insight into the mechanisms of action behind the effects of vitamin D supplementation and possible effect modification, which can help identify children with particularly high effects of treatment, by analyzing the respiratory immune profile at the time of inclusion.
● Atopic status by measuring specific-IgE levels for inhalation allergens.
Exploratory outcomes, atopic status, measuring blood eosinophilocyte counts
The study also aims to examine a wide range of exploratory outcomes to gain insight into the mechanisms of action behind the effects of vitamin D supplementation and possible effect modification, which can help identify children with particularly high effects of treatment, by analyzing the atopic status by measuring blood eosinophilocyte counts, for inhalation allergens.
Exploratory outcomes, atopic status, total-IgE and specific-IgE levels
The study also aims to examine a wide range of exploratory outcomes to gain insight into the mechanisms of action behind the effects of vitamin D supplementation and possible effect modification, which can help identify children with particularly high effects of treatment, by analyzing the atopic status by measuring total-IgE and specific-IgE levels for inhalation allergens.
COVID-19 risk and Vitamin-D
Does the vitamin-D intervention decrease the risk of COVID-19 infection, as determined by PCR test.
COVID-19 symptom burden and Vitamin-D
Does D-vitamin supplementation change the symptom burden (in number of days) of COVID-19 infection, as determined by PCR test.
COVID-19 infection length and Vitamin-D
Does D-vitamin supplementation change length (number of days) of COVID-19 infection, as determined by PCR test.
Daycare absence
Does D-vitamin supplementation change number of days absent from daycare.
Health economic benefits
Does D-vitamin supplementation change the number of days parents need to stay home to look after their children when they are absent from daycare.