Background:

Bronchial hyper responsiveness (BHR) assessed by methacholine challenge test (MCT) may aid in the diagnosis of asthma, while negative MCT can help to exclude the diagnosis. Laboratory measures that predict the results of MCT are expected to reduce the number of procedures. The possible capacity of High sensitive C-reactive protein (hs-CRP), a marker of systemic inflammation, to predict negative or positive MCT in children has not been evaluated.

Aim: to evaluate the capacity of hs-CRP to predict positive or negative MCT in school aged children and to compare it with markers of airway inflammation: Fractional exhaled Nitric Oxide (FeNO) and markers of allergic sensitization (IgE and peripheral blood eosinophils).

Design: Prospective study evaluating these parameters in patients with positive and negative MCT.

Participant selection: The study population included subjects (age range 6 to 18 years) referred for Methacholine Challenge Test (MCT)

Sample size: 130 participants in the two groups. Intervention: Each subject will undergo evaluation including a respiratory questionnaire, methacholine challenge test with determination of PC20(the provocative concentration that reduced FEV1 by 20% from baseline), exhaled nitric oxide (eNO). Venous blood will be analyzed for complete blood count + eosinophils, IGE levels, hs-CRP. All measurements will be evaluated in a single 3 hour visit, with no follow up study visits.

Primary end point: hs-CRP levels as add on tool to predict negative or positive MCT in children Secondary outcome parameters: All other parameters are the secondary end points.

Inclusion Criteria:

• Age range 6 to 18 years
• Patient referred for Methacholine Challenge Test (MCT)

Exclusion Criteria:

• Base line FEV1(forced expiratory volume in the first second) < 65%
• The presence of other systemic or lung disease
• Anti-inflammatory drugs
• Upper respiratory tract infection in the last month

subjects (age range 6 to 18 years) referred for Methacholine Challenge Test (MCT)