Clinical Trial: Role of Mitochondria in Non Severe Asthma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Role of Mitochondria in Human Bronchial Smooth Muscle Remodeling in Non Severe Asthma

Brief Summary: 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

Detailed Summary:

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.


Sponsor: University Hospital, Bordeaux

Current Primary Outcome: BSM mitochondrial biogenesis assessed by the number of mitochondrial sections using electron microscopy, the porin content using western blot, and mitochondrial oxygen consumption evaluated by oxygraphy. [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • BSM remodelling assessed by optic microscopy and immunohistochemistry (using anti-alpha smooth muscle actin antibody). [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]
  • Transcription factors involved in mitochondrial biogenesis assessed by quantitative RT-PCR and western blot. [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]


Original Secondary Outcome: Same as current

Information By: University Hospital, Bordeaux

Dates:
Date Received: December 15, 2008
Date Started: February 2009
Date Completion:
Last Updated: February 15, 2010
Last Verified: February 2010