Detection of Cav1 Calcium Channels in Inflammatory Cells of Asthmatic Children

Study Overview
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Brief Summary
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Asthma affects about 10% of children and 6% of adults in industrialized countries. Lymphocytes (L) Th2, a T cell population (LT) producing interleukin (IL) -4, 5 and 13 are broadly involved in this pathology in experimental models and in humans. Many studies show that the signaling pathways activated by the commitment of T receiver differ depending LT. The identification of specific signaling pathways links to Th2 offer new therapeutic approaches. Precedent study showed that mouse Th2 selectively expressed related to calcium channels sensitive channels Cav1 voltage, normally found in excitable cells where they are defined as receivers dihydropyridine (DHP). The goal of the present study is to show the presence of Cav1 channels in inflammatory cells in allergic asthmatics and show overexpression of these channels in the peripheral blood mononuclear cells from asthmatic subjects before and / or after stimulation with the TCR in comparison with controls.

Official Title
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Detection of Cav1 Calcium Channels in Inflammatory Cells of Asthmatic Children

Conditions
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Asthma

Intervention / Treatment
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* Procedure: Induced sputum method using hypertonic serum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Asthmatic children arm : Girl not in childbearing potential or taking contraceptive treatment Asthma diagnosis in at least 6 months as defined by clinical symptoms (expiratory dyspnea, wheezing, sibilance) and respiratory function (reversibility of VEMS at least 12% after salbutamol administration) Allergologic tests positives to airborne allergens : positive prick test and/or specific IgE > 0,35 kU/L for at least one allergen Asthma severity between mild to moderate based on Global initiative for asthma classification during more than one month with inhaled corticotherapies +/- long term action beta -mimetic long compounds (salmeterol, formoterol) Patient insured with a social security scheme For control children arm : Girl not in childbearing potential or taking contraceptive treatment No medical history of asthma No medical history of allergy or symptoms of allergy on skin (atopic dermatitis), respiratory tract (rhino-conjunctivitis, asthma) or food allergy Exclusion Criteria: For both arms: Chronic respiratory pathology : known occlusive or restrictive respiratory syndrome like interstitial lung disease, neuromuscular disease, mucoviscidoses, respiratory tract abnormalities with cough, dyspnea or digital hippocratism. History of pulmonary or nose and throat infectious disease during last 4 months Parasitic disease non treated during last 3 months Dyspnea during the inclusion Systemic corticotherapy during the last 3 months before inclusion Immunosuppressive therapy during the last 3 months before inclusion Diabeta Disease causing immune disorder Infection during inclusion Participation to another study witch implies medical treatment during last 3 months before inclusion For asthmatic children arm : Chronic pulmonary pathology (excluding asthma) Asthma exacerbation during inclusion VEMS < 70% of normal range or VEMS < 70% of normal range after inhalation of serum (despite salbutamol administration) Patient unable to complete pulmonary function testing

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asthmatic children<br>Induced sputum method using hypertonic serum | Procedure: Induced sputum method using hypertonic serum<br>* Collection of expectoration in sterile vial, conserved in ice all along the examination<br>|
| Sham Comparator: Control children<br>Induced sputum method using hypertonic serum | Procedure: Induced sputum method using hypertonic serum<br>* Collection of expectoration in sterile vial, conserved in ice all along the examination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of sequence coding for Cav1 in cells as assessed by reverse transcription polymerase chain reaction |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Cav1 channels as assessed by correlation between Cav1 expression and eosinophils in expectoration collection |  | Day 1 | 
| Presence of Cav1 channels as assessed by correlation between Cav1 expression and lymphocytes T in expectoration collection |  | Day 1 | 
| Comparison of CRTH2+ cells in total blood between asthmatic and control group |  | Day 1 | 
| Comparison of Cav1 channels and cytokines Th2 expression between asthmatic and control group before T-Cell receptor stimulation |  | Day 1 | 
| Comparison of Cav1 channels and cytokines Th2 expression between asthmatic and control group after T-Cell receptor stimulation |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphocytes Th2, Cav1 channels