Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-Blind, Placebo-Controlled, Crossover Efficacy and Safety Evaluation of 8-Week Treatment Periods of Two Doses [5 Mcg (2 Actuations of 2.5 Mcg) and 10 Mcg (2 Actuations of 5 Mcg)] of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler® as Add-on Therapy in Patients With Severe Persistent Asthma
Brief Summary: The primary objective of this study is to examine efficacy and safety of tiotropium compared to plac ebo as add-on therapy in severe asthmatics according to GINA step 4 classification


Options:
A: Inclusion Criteria:

* Signed Informed Consent Form and an informed assent, if applicable
* Be between the ages of 12 to 75 years
* Have had a history of moderate to severe asthma for at least one year prior to screening
* Have had treatment with a stable regimen of of salmeterol 50 µg twice a day (BID) or formoterol 12 µg BID for at least 8 weeks prior to screening
* Have had treatment with a stable regimen of high-dose inhaled corticosteroids (ICS) for at least 8 weeks prior to screening
* Have inadequately controlled asthma
* Have had at least one asthma exacerbation requiring systemic corticosteroid rescue in the 12 months prior to the screening visit while receiving treatment with high-dose ICS
* Have less than 10 pack-years smoking history
* Have a positive skin test for or a positive, in vitro response to one relevant perennial aeroallergen documented within the 12 months prior to screening
* If a subject has not had a positive skin test or in vitro reactivity in the 12 months prior to screening, the subject must demonstrate a positive response to at least one relevant perennial aeroallergen in a skin or in vitro test prior to randomization
* Female subjects of childbearing potential must use an effective method of contraception from screening through their duration of participation in the study
* For the collection of additional blood samples for future research (optional), provide signed consent and an informed assent, if applicable.

Exclusion Criteria:

* Have had an asthma exacerbation requiring intubation within 12 months prior to screening
* Have active lung disease other than asthma
* Have had an asthma exacerbation requiring treatment with the addition of systemic (oral or intravenous) corticosteroids or an increase in systemic corticosteroids within 30 days prior to screening
* Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc.
* Have significant medical illness other than asthma
* Have taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics, within 3 months prior to screening
* Have taken other investigational drugs within 30 days prior to screening
* Have been treated with Xolair within the 12 months prior to screening
* Have a history of drug or alcohol abuse that, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study
* Have elevated serum IgE levels for reasons other than allergy
* Are pregnant or lactating
B: Inclusion Criteria:

* Have asthma for at least 3 months prior to the study.
* Have been using an allowed pre-study asthma therapy for at least 3 months prior to study.
* Currently have seasonal allergic rhinitis and have had seasonal onset of allergic rhinitis for at least the two previous allergy seasons.
* Have a positive allergy skin test.

Exclusion Criteria:

* Have a history of life-threatening asthma.
* Been hospitalized for asthma within the 6 months prior to the study.
* Have certain conditions that would make study participation unsafe.

The study doctor will evaluate other inclusion and exclusion criteria.
C: Inclusion Criteria:

* Adults aged \>= 18 years.
* Patients with severe persistent allergic asthma with the following characteristics:
* FEV1 (Forced Expiratory Volume in One Second) \<80% of predicted.
* Frequent daily symptoms (\>=4 days/week on average) or nocturnal awakening (\>=1/week on average).
* Multiple severe asthma exacerbations: either \>=2 severe asthma exacerbations having required an unscheduled medical intervention with systemic corticosteroid in the past year, or hospitalization (including emergency room treatment) for an asthma exacerbation in the past year.
* Despite a high dose inhaled corticosteroid \>1000 mg beclomethasone dipropionate or equivalent and a inhaled long-acting B2-agonist.
* With an allergy to a perennial allergen demonstrated with convincing criteria, i.e. positive prick skin test or in vitro reactivity to a perennial aeroallergen (RAST).
* Total serum IgE level \>= 30 to \<=700 IU/ml and suitable serum total IgE level and weight according to Xolair dosing tablets.

Exclusion Criteria:

* Age \< 18 years.
* Smoking history \> 20 pack years.
* Patients who have had an asthma exacerbation during the 4 weeks prior to randomization
* History of food or drug related severe anaphylactoid or anaphylactic reaction
* Elevated serum IgE levels for reasons other than allergy (e.g. parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis).
* Patients with active cancer, suspicion of cancer or any history of cancer.
* Pregnant women.
* Known hypersensitivity to omalizumab or to one of its components.
* Patients already treated with omalizumab (indeed a previous treatment with omalizumab could have modified the FceRI expression).
* Patients who had participated in a clinical trial in the past 3 months.
D: Inclusion Criteria:

Outpatients of either sex, age 18 - 75 years, with at least a documented 5 year history of asthma, and a current diagnosis of severe, persistent asthma (GINA step 4), smoking history \< 10 pack years and \>= 1 year smoking cessation; Patients must be symptomatic

Exclusion Criteria:

Patients

* with a recent history (i.e., six months or less) of myocardial infarction,
* who have been hospitalized for heart failure (NYHA class III or IV) within the past year,
* with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year,
* with malignancy for which the patient has undergone resection, radiation ther apy or chemotherapy within the last five years,
* who have undergone thoracotomy with pulmonary resection,
* with moderate to severe renal impairment (creatinine clearance = 50 mL/min)

Answer: D