Please select the eligibility criteria that correspond to the clinical trial below.
Title: Vitamin D to Prevent Severe Asthma Exacerbations
Brief Summary: This study will determine whether vitamin D3 prevents severe asthma attacks in children who have a serum vitamin D (25(OH)D) level \<30 ng/ml and who are being treated with inhaled corticosteroids for asthma. Half the participants will receive vitamin D3 at a dose of 4,000 IU/day, and the other half will receive placebo.


Options:
A: 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
B: Principal Inclusion Criteria:

* Medical record diagnosis of asthma
* Age ≥ 16 years and ≤ 80 years on day of first dose of IMP
* If a woman of child-bearing potential, is sexually abstinent or has negative pregnancy test within 7 days of recruitment and agrees to use reliable form of contraception until she has completed the study
* Able to give written informed consent to participate in the study

Principal Exclusion Criteria:

* Diagnosis of COPD
* Known sarcoidosis, hyperparathyroidism, nephrolithiasis, active tuberculosis, vitamin D intolerance, liver failure, renal failure, terminal illness, lymphoma or other malignancy not in remission for ≥ 3 years
* Any other condition that, in an investigator's judgement, might compromise patient safety or compliance, interfere with evaluation or preclude completion of the study
* Taking benzothiadiazine derivative, cardiac glycoside, carbamazepine, phenobarbital, phenytoin or primidone
* Taking dietary supplement containing vitamin D up to 2 months before first dose of IMP
* Treatment with any investigational medical product or device up to 4 months before first dose of IMP
* Breastfeeding, pregnant or planning a pregnancy
* Baseline corrected serum calcium \> 2.65 mmol/L
* Baseline serum creatinine \> 125 micromol/L
* Smoking history \>15 pack-years
C: Inclusion Criteria:

* age 1-5 years
* physician-diagnosed asthma as per the Global Initiative for Asthma (GINA) guidelines
* URTIs as the main asthma trigger (parental report)
* ≥4 URTIs in the past 12 months (parental report)
* ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months

Exclusion Criteria:

* intake or intention to use more than 400 IU/day of vitamin D supplement
* extreme prematurity (\<28 weeks gestation)
* infants \<12 months of age
* no vitamin D supplementation when breast-fed
* recent (\<1 year) immigrants from a region at high risk of rickets
* children with vitamin D restrictive diets e.g. vegans
* other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis)
* condition(s) that alter calcium or vitamin D metabolism/absorption (hypo/hyperparathyroidism, kidney/liver disease, inflammatory bowel disease)
* medications that interfere with vitamin D metabolism (anti-epileptics, diuretics, antacids, anti-fungal drug)
* vitamin D supplementation \>1000 IU/ day in last 3 months
* anticipated difficult follow-up (unable to attend clinic visits; plan to leave the province).
D: * This study is open to all VITAL participants (NCT 01169259). Population includes men 50 years of age or older and women 55 years of age or older in the United States
* Participants who live in selected metropolitan areas of the U.S. (where we set up the infrastructure for clinic or home visits), are eligible for pulmonary function measurements.

Answer: A