Mechanism and Dynamics of Bronchial Hyper-reactivity to Methacholine in Distal Airway on Obese Patients With Asthma

Study Overview
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Brief Summary
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New insights of small airway contribution to asthma have been gained. Poor levels of control and recurrent exacerbations were shown to have the phenotypic counterpart of asthma with predominant small airway involvement. Very few pathological specificities were identified at this site: mast cells infiltration was suggested as the specific inflammatory change when compared to the proximal airways.Biomarkers in asthma are still complex to validate, especially in the blood, since compartmentalisation is intense in the lung and the airways, a property attributed to the filtering role of the lung to maintain homeostasis. Over the last few years, Fraction exhaled Nitric Oxide (FENO) was developed as a non-invasive and indirect reflection of airway eosinophilic inflammation]. In the blood, peripheral eosinophil counts were shown as a correct T helper 2 (TH2)-phenotype identifier but not perfectly related to airway eosinophilic infiltration. Club cell secretory protein (SCGB1A1) levels have been shown to have some relevance in asthma, chronic obstructive pulmonary disease (COPD), BOS, sarcoidosis, and lung cancer.A biomarker for small airway disease in asthma may improve the management of the disease, identify areas of therapeutic resistance and constitute a therapeutic guidance tool. In this study, investigators aimed to assess small airway involvement in asthmatic women as far as they could. For this purpose, investigators analysed trends in air trapping by acquiring expiratory CT slices at each dose during a bronchoprovocation test with metacholine. Biomarkers were subsequently tested and confronted to clinical and demographical characteristics in their ability to predict the small airway involvement index obtained at CT.

Detailed Description
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Patients will be recruited in the respiratory department of University Hospital in Montpellier (France) from June 2012 to March 2014. All patients are asthmatics, in order to avoid any gender-related biases, investigators decided to include only women. All participants had normal range spirometry, specifically regarding forced expiratory volume. Each patient will undergo a bronchial provocation test coupled with a thoracic CT scan. Bronchial and alveolar Nitric Oxyde will also be measured, a blood sample will be obtained in order to measure biomarker concentrations, and the patients will be asked to answer the validated Asthma Control Questionnaire in order to quantify asthma control.

Official Title
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Mechanism and Dynamics of Bronchial Hyper-reactivity to Methacholine in Distal Airway on Obese Patients With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Other: metacholine provocation test and CT-scan low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female >= 18 yrs Asthma Treated with Inhaled Corticosteroid (ICS) normal range spirometry Exclusion Criteria: Patients with other respiratory disease Patients with myocardial infarction (for 3 month before enrollment) Patients with cerebrovascular accident (for 3 month before enrollment) Patients with arterial aneurysm known Patients in pregnancy Patients nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal weight<br>Included patients with a BMI < 25 will be part of this group. | Other: metacholine provocation test and CT-scan low dose<br>* Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose<br>|
| Overweight<br>Included patients with a BMI >= 25 and <30 will be part of this group. | Other: metacholine provocation test and CT-scan low dose<br>* Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose<br>|
| Obese<br>Included patients with a BMI >= 30 will be part of this group. | Other: metacholine provocation test and CT-scan low dose<br>* Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inspiratory:expiratory mean lung density | Baseline versus post-methacholine challenge | 4 hours (after the enrollment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung fractal dimension | Baseline versus post-methacholine challenge | 4 hours (after the enrollment) | 
| Bronchial morphometry | Analysis of CT imaging | Baseline | 
| CC10 level | Clara cell 10 kD protein levels in blood | Baseline | 
| FeNO | Exhaled nitric oxide level | Baseline | 
| FaNO | Alveolar nitric oxide level | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Airways, asthma, overweight