Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy of Calcifediol Supplementation in Asthma Control in Asthmatic Patients With Vitamin D Deficiency (ACViD)
Brief Summary: Introduction: There are many cross-sectional studies in children and adults indicating that low vitamin D levels in asthmatic patients are correlated with poorer asthma control, poorer lung function, decreased response to glucocorticoids and more frequent exacerbations. Moreover, as there is a significant group of asthmatic patients having insufficient control of their disease, despite high doses of inhaled corticosteroids, we have investigated new treatment alternatives, which include vitamin

Objective: To determine the efficacy of vitamin D supplementation in asthmatic patients with vitamin D deficiency in degree of asthma control.

Materials and methods: A prospective, controlled, randomised, triple-blind study was conducted with a follow-up of 6 months. The patients recruited were over 18 years of age with a medical diagnosis of bronchial asthma and serum 25(OH)D3 levels \< 30 ng/ml. Patients were excluded if they had a smoking habit ≥ 10 pack-years, taking vitamin D supplements, kidney disease (creat. \> 2 mg/dl), hypercalcaemia (corrected with proteins \> 10.5 mg/dl), a repeat episodes of renal colic, any gastrointestinal disease that might interfere with vitamin D absorption, or severe psychosocial problems, or were pregnant or breast-feeding. The randomisation process assigned patients to one of two groups: a group that received vitamin D (in the form of calcifediol (Hidroferol®) in 16,000-IU ampoules taken weekly by the oral route) and another group that received placebo in a presentation with an identical appearance and the same administration regimen. Demographic, clinical, spirometry and laboratory endpoints were collected. The primary endpoint was degree of asthma control as determined by the internationally validated Asthma Control Test (ACT). The secondary endpoints were asthma exacerbations, dose of inhaled corticosteroids and quality of life as measured using the Mini-AQLQ (Asthma Quality of Life Questionnaire).


Options:
A: Inclusion Criteria:

* Medical diagnosis of bronchial asthma
* serum 25(OH)D3 levels \< 30 ng/ml.

Exclusion Criteria:

* smoking habit ≥ 10 pack-years,
* taking vitamin D supplements,
* kidney disease (creat. \> 2 mg/dl),
* hypercalcaemia (corrected with proteins \> 10.5 mg/dl),
* repeat episodes of renal colic,
* any gastrointestinal disease that might interfere with vitamin D absorption,
* severe psychosocial problems,
* pregnant
* breast-feeding
B: 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.
C: Inclusion Criteria:

* Age 1-5 years
* Physician-diagnosed asthma (as per the 2015 Canadian Position Paper on the diagnosis of preschool asthma)
* ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months (as documented by pharmacy/medical records)
* ≥4 upper respiratory tract infections (URTIs) in the past 12 months (as per parental report)
* URTIs as the main asthma trigger (as per parental report)

Exclusion Criteria:

* Intake \> 400 IU/day of vitamin D3 supplements or fish oil in the past 3 months
* Intention to use \> 400 IU/day of vitamin D3 supplements or fish oil in the fall and winter
* Extreme prematurity (\< 28 week gestation)
* No vitamin D supplementation (if breast-fed in the last 6 months)
* Vitamin D restrictive diets, that is, minimal intake of vitamin D fortified milk (\<250 mL/day for 1-3 years or \<375 mL/day for 4-6 years AND no other (or \<200 IU/day) vitamin D supplement
* Recent immigrants from regions at high risk of rickets (in the past 12 months)
* Recent refugees (in the past 12 months)
* Undernourished children
* Other chronic respiratory disease (e.g. Cystic fibrosis, Bronchopulmonary dysplasia) or chronic kidney, gastrointestinal, endocrinological or cardiac diseases, or sickle cell anemia?
* History of bone disorder disease (e.g. rickets, osteomalacia)
* Intake of oral anti-epileptic, diuretic or anti-fungal medications
* Anticipated difficulty with follow-up or with adherence to the intervention or the procedures
D: Inclusion Criteria:

* 6 to 16 years old
* Physician-diagnosed asthma for at least one year
* At least one severe asthma exacerbation in the previous year
* Use of asthma medications (daily controller medication \[ICS or leukotriene inhibitor\] or inhaled β2-agonist \[at least three days per week\]) for at least six months in the previous year
* Vitamin D insufficiency (i.e., serum vitamin D (25(OH)D level \<30 ng/ml (75 nmol/L))
* FEV1 ≥70 % of predicted
* Positive bronchodilator response (i.e., increase in FEV1 ≥8% from baseline after inhaled short acting beta agonist or increased airway responsiveness to methacholine (PC20 ≤8 mg/ml if not on ICS or PC20 ≤16 mg/ml if on ICS)
* Study protocol (i.e., age-appropriate dose of Fluticasone and no other asthma controller medications) approved by the child's regular doctor
* Parental consent and child's assent to participate in the study.

Additional inclusion criteria applied after the run-in period, to be eligible for randomization:

* Adherence with ICS and study medication (≥75% use \[at least 21 of 28 days\]) during the run-in period
* Willingness to be randomized and complete study

Exclusion Criteria:

* Serum calcium \>10.8 mg/dl
* Serum 25(OH) D \<14 ng/ml (35 nmol/L)
* Chronic respiratory disorder other than asthma
* Severe asthma (intubation for asthma at any time OR ≥3 hospitalizations for asthma in previous year OR ≥6 severe asthma exacerbations in previous year)
* Hepatic/renal disease, rickets, malabsorption, or other diseases that would affect vitamin D metabolism
* Current smoking, or former smoking if ≥5 pack-years
* Immune deficiency, cleft palate or Down's syndrome
* Treatment with anticonvulsants or ≥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 trials 30 days before or during the study
* Participant is currently breast feeding an infant
* Pregnancy
* Weight less than 10 kg
* Plans to move out of the study site area in the next year

Additional exclusion criteria applied after the run-in period:

* Any severe asthma exacerbation during the run-in period
* Need for asthma medications other than ICS and p.r.n. rescue inhalers during the run-in period

Answer: A