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Asthma is a chronic inflammatory respiratory disease affecting 6 to 7% of the French adult population and responsible of 1000 deaths in France every year. Many anti-inflammatory treatments are available but few had been developed to target hyperresponsiveness.Investigators and searchers of the Institut du thorax have recently demonstrated the main involvement of Rac1 monomeric G protein in the contraction of airway smooth muscle cells. They show that Rac1 is expressed in the airway smooth muscle cells in mice and its activity is increased in the bronchi of asthma induced mice sensitized to House-Dust Mite. They further demonstrate that Rac1 inhibition in mice by nebulisation reduces airway hyperresponsiveness and pulmonary inflammation. Investigators and searchers of the Institut du thorax would like to seek whether targeting Rac1 would be interesting in asthmatic patients. Primary objective of this study is to determine if Rac1 expression and activity in airway smooth muscle cells are increased in asthmatic patients compare to controlled samples (deceased donor samples). Secondary objective is to determine whether there is a correlation between Rac1 activity and asthma severity.
If Rac1 activity in airway smooth muscles is indeed increased in asthmatic patients depending on asthma severity, Rac1 could be a potential target to treat airway hyperresponsiveness.
Patients will be openly labeled in one of the following group
- 21 patients with severe asthma, without oral corticosteroids treatment.,
- 21 patients with mild to moderate asthma without treatment,
- 21 controlled samples from smooth muscle cells of non-asthmatic deceased donor Bronchial endoscopy with bronchial biopsies will be assessed in all asthmatic patients, Control samples will be obtained from tracheobronchial rings of cadaveric donor. Expression and activity of Rac1 in airway smooth muscle will be determined by immuno-staining on paraffinised biopsies.
Patients will undergo two study visits (D0: inclusion visit, D15: exploratory visit) and one phone call at D21.
Inclusion Visit (D0):
- Signature of the Informed consent,
- Medical History,
- Clinical examination,
- Pulmonary Function Test,
- Blood samples for fibroscopy safety,
- ACT (Asthma Control Test), ACQ (Asthma Control Questionnaire), AQLQ (Asthma Quality of Life Questionnaire), Morisky questionnaire
Exploratory visit (D15)
- Clinical examination,
- Bronchial endoscopy with biopsies Adverse event
Phone Call (D21)
- Adverse event
Recruitment will last 2 years.
Bronchial endoscopy, Bronchial biopsies, Bronchial alveolar enema
Not yet recruiting
Nantes University Hospital
Published on BioPortfolio: 2017-11-05T23:53:10-0500
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