Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Controlled Clinical Trial to Evaluate the Efficacy of Supplementation With L. Reuteri + Vit. D3 in Asthmatic Children
Brief Summary: The purpose of this project is to evaluate in a randomized clinical trial, double-blind, controlled, the effects of a dietary supplement containing Lactobacillus reuteri DSM 17938 and vitamin D3 in reducing bronchial inflammation and improve asthma control in patients in children with mild / moderate persistent asthma .


Options:
A: Inclusion Criteria:

* Patients aged between 6 and 14 years old, of both sexes
* Diagnosis of mild / moderate persistent asthma (GINA step 2/3)
* Allergy mite (Dermatophagoides farinae and pteronyssinus + + + / + + + +)
* Levels of vitamin 25 (OH) D \<30 ng / ml
* Signature of the informed consent of one parent or a legal representative

Exclusion Criteria:

* Cardiovascular disease or systemic
* anatomical abnormalities
* Other respiratory diseases
* Taking probiotics and / or prebiotics in the previous 2 weeks
* Taking vitamin D or systemic corticosteroids within 4 weeks
* Participation in other clinical trials
B: Inclusion Criteria:

* Men and women 18 years of age and older
* Physician-diagnosed asthma for at least previous 12 months
* Asthma confirmed by: (a) β-agonist reversibility of forced expiratory volume in 1 second (FEV1) ≥12 % following 180 mcg (4 puffs) levalbuterol at visit 1 OR (b) methacholine provocative concentration causing a 20% fall in FEV1 (PC20) ≤ 8 mg/ml if not receiving an inhaled corticosteroid or ≤ 16 mg/ml if receiving an inhaled corticosteroid at visit 2. Source documentation for PC20 from an AsthmaNet methacholine challenge completed within 6 months of visit 2 will be accepted.
* Stable asthma controller therapy (inhaled corticosteroid or leukotriene modifier only) dose for past 2 weeks
* FEV1 ≥ 50% of predicted at visit 1
* Vitamin D level of less than 30 ng/ml at visit 0
* Experienced no more than one treatment failure in the VIDA run-in or oral corticosteroid (OCS) response periods on previous enrollments
* For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method for the duration of the study

Exclusion Criteria:

* Taking vitamin D supplements containing \> 1000 IU/day of vitamin D
* Taking \>2500 mg/day calcium supplements
* Chronic oral corticosteroid therapy
* Chronic inhaled corticosteroid therapy \> 1,000 mcg of fluticasone daily or the equivalent
* History of physician-diagnosed nephrolithiasis
* Use of concomitant medications that alter vitamin D metabolism - phenytoin, phenobarbital, cardiac glycosides; or absorption - orlistat, cholestyramine, colestipol; or those that interfere with study endpoints
* Impaired renal function (GFR \< 30 ml/min)
* Asthma exacerbation within past 4 weeks requiring systemic corticosteroids
* Respiratory tract infection within past 4 weeks
* Chronic diseases (other than asthma)
* History of cigarette smoking within the past 1 year or \> 10 pack years total
* Serum calcium greater than 10.2 mg/dl on entry
* Urine calcium/creatinine ratio greater than 0.37 (urinary Ca and Creat in mg)
C: 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
D: 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.

Answer: A