The critical role of bronchial smooth muscle remodeling in non-severe asthma

Rationale: Proliferation of bronchial smooth muscle (BSM) cells involves a specific mitochondria-dependent pathway in severe asthmatic patients. However, BSM remodeling and mitochondrial biogenesis have not been assessed in non-severe asthma. We aimed to assess whether a high BSM mass is implicated in non-severe asthma. Methods: We enrolled 30 never smokers subjects, with non-severe asthma. A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide and blood collection. Bronchial-biopsy specimens obtained by fiberoptic bronchoscopy were processed for optic microscopy, immunohistochemistry and electron microscopy analysis. Following BSM remodeling assessment, participants were monitored over a 12 months period. Results: We identified characteristic features of BSM remodeling and mitochondrial biogenesis in non-severe asthmatics. Baseline characteristics were similar in patients with BSM remodeling (“high BSM group”) and subjects without remodeling (“low BSM group”). However, 12 months follow-up showed that Juniper asthma control score and the number of exacerbations were increased in asthmatics with high BSM as compared to low BSM patients. Furthermore, the number of BSM mitochondria was positively correlated to BSM area in non-severe asthma (r = 0.78; P Conclusions: This study reveals that BSM remodeling and mitochondrial biogenesis may play a key role in natural history of non-severe asthma (“Mitasthme” study; ClinicalTrials.gov number, NCT00808730).