Role of Mitochondria in Non Severe Asthma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2009-11-30

Brief Summary

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Asthma is a frequent disease characterized by bronchial hyperresponsiveness, inflammation and remodelling. Bronchial remodelling is an abnormal repair process that contributes to the development of poorly reversible airway narrowing. It can appear very early in the evolution of the disease and involves an increased mass of bronchial smooth muscle (BSM). The mechanism of such an increase has been related with an increase in smooth muscle cell proliferation. Recently, we have demonstrated that, BSM increased proliferation is induced by an enhanced mitochondrial biogenesis in severe asthma (T. Trian et al. J Exp Med 2007). The objective of this study is to investigate the role of smooth muscle cell mitochondria in non severe asthma

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Detailed Description

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Bronchial remodelling mainly involves an increased mass of bronchial smooth muscle (BSM), which is related with an increase proliferation of BSM cells. Recently, using BSM cells obtained from severe asthmatics, we have demonstrated that such an increase proliferation was induced by an activation cascade involving an abnormal calcium entry, and the subsequent activation of Calmodulin-kinase IV, PGC-1alpha, NRF-1 and mt-TFA leading to an increase mitochondrial biogenesis (T. Trian et al, J Exp Med 2007). The objective of this study is to investigate the role of BSM cell mitochondria in non severe asthma.

For this purpose, 30 non severe asthmatic adult patients (\>18 yr) will be prospectively recruited from the "CHU de Bordeaux" according to the Global Initiative for Asthma (GINA) guidelines. Inclusion visit will include written informed consent, asthma control questionnaire, clinical examination, lung function testing (i.e. arterial gas, exhaled NO, plethysmography), prick tests, chest X Ray and blood sample for total IgE levels. Bronchial specimens will be obtained from all subjects by fiberoptic bronchoscopy. BSM remodelling will be evaluated by morphological analysis. Patients will be divided into 2 groups according to the presence or the absence of BSM remodelling. Using BSM cell culture, the role of mitochondria will be analyzed by electronic microscopy, confocal microscopy, immunoblotting, RT-PCR and oxygraphy.

Conditions

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Asthma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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1

fiberoptic fibroscopy

Group Type EXPERIMENTAL

fiberoptic fibroscopy

Intervention Type PROCEDURE

Bronchial specimens will be obtained by fiberoptic bronchoscopy within 15 days after the enrolment

Interventions

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fiberoptic fibroscopy

Bronchial specimens will be obtained by fiberoptic bronchoscopy within 15 days after the enrolment

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Male or female aged more than 18 years
* Diagnosis of intermittent asthma, mild persistent asthma or moderate persistent according to ATS criteria
* Forced expiratory volume in one second \> 60% predicted
* Written informed consent

Exclusion Criteria

* Smoker or former smoker (tobacco or cannabis)
* Adults protected by law
* Subjects not affiliated with social security
* Subjects during exclusion relative to another protocol or for which the annual maximum allowance of 3800 euros has been reached
* Subject with any co-morbidity (except chronic rhinitis, chronic sinusitis nasal polyps or gastro-oesophageal reflux)
* Asthma exacerbation within 6 weeks before enrolment
* Infections of the upper airway within 3 months before enrolment
* Chronic viral infections (hepatitis, HIV)
* Pregnancy or breastfeeding
* Contraindications to bronchoscopy

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No