Role of Mitochondria in Non Severe Asthma

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.