Please select the eligibility criteria that correspond to the clinical trial below.
Title: Steroids In Eosinophil Negative Asthma
Brief Summary: Because approximately half of all mild-moderately-severe asthma is persistently non-eosinophilic, it is important to determine prospectively if patients who are persistently non-eosinophilic differ in their benefit from inhaled corticosteroid treatment compared to patients who are not persistently non-eosinophilic.


Options:
A: Inclusion Criteria:

* Physician-diagnosed asthma for at least previous 12 months.
* Able to perform reproducible spirometry.
* Baseline FEV1≥70% of predicted.
* Asthma confirmed either by:

  * Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR
  * Methacholine PC20 ≤ 16 mg/ml
* At least 1 of the following indications for chronic controller therapy:

  * Asthma Symptoms \> 2 days/week OR
  * Nocturnal Asthma Symptoms \> 2 nights/month OR
  * Short-acting beta-agonist use for symptom control \> 2 days/week
* For participants ≥18 years of age: Ability to provide informed consent. For participants under 18 years of age: Ability to provide verbal or written assent and ability of parent to provide informed consent.
* Willingness, if female and able to conceive, to utilize one medically-acceptable form of contraception.

Exclusion Criteria:

* Chronic inhaled or oral corticosteroid therapy.
* Use of inhaled or oral corticosteroid therapy within 6 weeks.
* New allergen immunotherapy within the past 3 months or anticipated changes to an ongoing immunotherapy regimen.
* Use of omalizumab within 3 months.
* History of:

  * bladder-neck obstruction, urinary retention or benign prostatic hyperplasia
  * narrow angle glaucoma
  * significant cardiovascular disorders and arrhythmias
  * life-threatening asthma requiring treatment with intubation or mechanical ventilation within the past 5 years
* Respiratory tract infection within past 6 weeks.
* History of smoking within the past 1 year, or \> 10 pack-years total if ≥ 18 years of age, or \> 5 pack-years total if \< 18 years of age.
* Chronic diseases or medical conditions (other than asthma) that could put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, endocrine or nervous system, or immunodeficiency.
B: Inclusion Criteria:

* Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
* History of asthma symptoms that are adequately controlled in the 4 weeks prior to study entry, and meets at least one of the following criteria:

  1. History of mild persistent asthma symptoms (on average greater than 2 days per week with symptoms or albuterol use for symptoms or greater than 2 night-time awakenings per month during the year prior to study entry) and has been treated with a single-controller inhaled corticosteroid (ICS) dose less than or equal to 160 mcg per day of a beclomethasone-equivalent or a leukotriene receptor antagonist (LTRA) (in an age-appropriate dose) for the 4 weeks prior to study entry; individuals treated with a combination controller therapy (e.g. ICS+LTRA or ICS+long-acting beta-agonist (LABA)) in the past 8 weeks will not be eligible
  2. Not currently being treated with ICS, a history of mild persistent asthma, and 1 to 2 exacerbations in the year prior to study entry (but none in the 3 months prior to study entry)
* Forced expiratory volume in one second (FEV1) reversibility of greater than or equal to 12% following bronchodilator administration (4 puffs); individuals who do not meet this requirement may qualify for enrollment if their methacholine provocative concentration at 20% (PC20) is less than or equal to 12.5 milligrams per milliliter (mg/ml)
* History of clinical varicella or varicella vaccine; individuals needing the vaccine may receive it from their primary care physician prior to study entry
* Ability of parent to provide informed consent; verbal assent must be obtained from children less than 7 years of age and written assent must be obtained from children between 7 and 18 years of age
* If female, willing to use an effective form of contraception

Participants will be eligible for the 44 weeks of treatment if, after the 4-week screening period, their asthma remains controlled, and they demonstrate at least 80% predicted pre-bronchodilator FEV1. Participants must meet ALL of the criteria stated below during the 8-week screening period to continue in the study:

* Meets the definition of acceptable asthma control, which is NOT having one or more of the following during ANY 2-week period:

  1. On average, on more than 2 days per week, experiences one or more of the following:

     1. Diary-reported symptoms
     2. The use of inhaled bronchodilator (not including pre-exercise)
     3. Peak flows in the yellow zone (less than 80% of personal best defined as based on peak expiratory flow (PEF) value obtained at study visit 1
  2. More than 1 night-time awakening due to asthma
* Demonstrates adherence with taking study medications (at least 75% of scheduled doses), rescue medications (using both rescue inhalers for at least 75% of rescue doses), and completing patient diaries (at least 75% of days)
* Pre-bronchodilator FEV1 greater than or equal to 80% predicted at study visits 2 and 3
* Agrees to not use a spacer with beclomethasone/placebo study and rescue medications

NOTE: In January 2008, the Data and Safety Monitoring Board (DSMB) approved changes in the TREXA eligibility criteria, by which neither FEV1 reversibility ≥ 12% nor a participant's methacholine PC20 ≤ 12.5 mg/ml were required for randomization.

Exclusion Criteria:

* Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:

  1. Oral - Use within 2-week period of the screening visit
  2. Injectable - Use within 2-week period of the screening visit
  3. Nasal corticosteroids may be used at any time during the study at the discretion of the study investigator or primary care physician
* Current or prior use of medications known to significantly interact with corticosteroid disposition (within a 2-week period of study visit 1), including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, or ketoconazole
* Pre-bronchodilator FEV1 less than 60% predicted at study visit 1
* Any hospitalization for asthma in the year prior to study entry
* Presence of chronic or active lung disease other than asthma
* Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study
* History of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
* Any asthma exacerbation in the past 3 months or more than 2 in the past year.
* History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure
* History of adverse reactions to ICS preparations or any of its ingredients
* Receiving hyposensitization therapy other than an established maintenance regimen (continuous regimen for at least 3 months)
* Pregnant or breastfeeding
* Cigarette smoking or smokeless tobacco use in the year prior to study entry
* Refusal to consent to a genotype evaluation
* Current participation or participation within 1 month of study entry in another investigational drug trial
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before study completion
C: Inclusion Criteria:

* diagnosis of mild to moderate asthma, FEV1 ³ 60% of predicted normal values pre-bronchodilator, daily use of inhaled GCS during the last 3 months

Exclusion Criteria:

* Regular need of \>4 inhalations of a short-acting b2-agonist/day, known or suspected hypersensitivity to any of the investigational drugs or inhaled lactose, use of any b-blocking agent, having smoked ³10 pack-years
D: Inclusion Criteria:

* Written signed and dated informed consent obtained.
* Male or female patients aged ≥ 18 years.
* A positive reversibility test
* Patients who experienced at least one severe exacerbation in the 12 months before entry (but not in the last month)
* Using inhaled corticosteroids (ICS) in monotherapy or using ICS in a fixed or free combination with long acting beta2 agonists (LABA) at a constant dose for two months before screening visit
* Not fully controlled asthmatics (which means partly controlled or/and uncontrolled patients according to GINA guidelines 2007) in the last month before screening visit
* Forced expiratory volume in the first second (FEV1) ≥ 60% of predicted for the patient normal value.
* Non smokers or ex-smokers

Exclusion Criteria:

* Pregnant or nursing (lactating) women. Women of child-bearing potential UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \>40 mIU/mL or are using one or more of acceptable methods of contraception
* Body Mass Index (BMI) \> 34 kg/m2.
* Patient with lower respiratory tract infections affecting the patient's asthma within 30 days of the screening visit.
* Use of systemic steroids in the last month.
* Patients with other lung diseases such as COPD, cystic fibrosis, interstitial lung diseases or any other clinically or functionally significant lung disorder.
* Patients who have an uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease.
* Clinically relevant laboratory abnormalities
* Patients who have an abnormal QTcF interval value
* Intolerance or contra-indication to treatment with beta2-agonists and/or ICS or allergy to any component of the study treatments.
* Patients treated with slow-release corticosteroids in the 3 months prior to screening visit.
* Patients being treated with anti-IgE antibodies.
* Patients treated with LABA or ICS/LABA fixed combination in the 24h before screening visit
* Severe asthma exacerbation in the last month before screening visit

Answer: A