Towards Targeting the ORigin of the Inflammatory Cascade in Allergic Asthma

Inclusion Criteria: Inclusion criteria for all subjects:

• Age between 18 and 45 years old.

• Smoking history ≤2 packyears. Specific inclusion criteria for the two groups:

• Group 1. Patients with ongoing asthma

• Age of onset of asthmatic symptoms: 0 - 18 years.

• Documented history of asthma diagnosed according to latest GINA guidelines, i.e.respiratory symptoms and either bronchodilator reversibility (improvement in FEV1of more than 12% of baseline (and at least 200 mL) after inhalation of 800 µgsalbutamol).

• Use of inhaled corticosteroids or either persistent symptoms of wheeze, cough, ordyspnea or regular use of β2 agonists at least once a week during the last 2months.

• PC20 methacholine < 8 mg/ml.

• Group 2. Non-asthmatic controls

• No history of asthma.

• No use of inhaled corticosteroids or β2-agonists for a period longer than 1month.

• No symptoms of wheeze, nocturnal dyspnea, or bronchial hyperresponsiveness.

• PC20 methacholine > 8 mg/ml, FEV1/FVC > 70% and FEV1 > 80% predicted.

Exclusion Criteria:

• FEV1 <1.2 L,

• Subjects must be able to adhere to the study visit schedule and other protocolrequirements.

• A subject is not eligible to enter and participate if he has not signed and dated awritten informed consent form prior to participation in the study.

• A subjects is not eligible to enter and participate if he does not agree that weinform his general practitioner.

• Upper respiratory tract infection (e.g. colds), within 6 weeks.

• Serious acute infections (such as hepatitis, pneumonia or pyelonephritis) in theprevious 3 months.

• Signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic,endocrine, pulmonary, cardiac, neurologic or cerebral disease.

• Malignancy within the past 5 years (except for squamous or basal cell carcinoma of theskin that has been treated with no evidence of recurrence).

• Known recent substance abuse (drug or alcohol).

• Females of childbearing potential without an efficient contraception unless they meetthe following definition of post-menopausal: 12 months of natural (spontaneous)amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL or the useof one or more of the following acceptable methods of contraception:

1. Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).

2. Hormonal contraception (implantable, patch, oral, injectable).

3. Barrier methods of contraception: condom or occlusive cap (diaphragm orcervical/vault caps) with spermicidal foam/gel/cream/suppository.

4. Continuous abstinence.