title: Bronchial Smooth Muscle Remodeling in Nonsevere Asthma.
abstract: BACKGROUND
  Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from nonsevere asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in individuals with severe asthma. However, BSM remodeling and mitochondrial biogenesis have not been examined in nonsevere asthma.
  
  
  OBJECTIVE
  We aimed to assess whether an increase in BSM mass was also implicated in nonsevere asthma and its relationship with mitochondria and clinical outcomes.
  
  
  METHODS
  We enrolled 34 never-smoker subjects with nonsevere asthma. In addition, we recruited 56 subjects with nonsevere asthma and 19 subjects with severe asthma as comparative groups (COBRA cohort [Cohorte Obstruction Bronchique et Asthme; Bronchial Obstruction and Asthma Cohort; sponsored by the French National Institute of Health and Medical Research, INSERM]). A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide measurement, and blood collection. Bronchial biopsy specimens were processed for immunohistochemistry and electron microscopy analysis. After BSM remodeling assessment, subjects were monitored over a 12-month period.
  
  
  RESULTS
  We identified characteristic features of remodeling (BSM area >26.6%) and increased mitochondrial number within BSM in a subgroup of subjects with nonsevere asthma. The number of BSM mitochondria was positively correlated with BSM area (r = 0.78; P < 0.001). Follow-up analysis showed that subjects with asthma with high BSM had worse asthma control and a higher rate of exacerbations per year compared with subjects with low BSM.
  
  
  CONCLUSIONS
  This study reveals that BSM remodeling and mitochondrial biogenesis may play a critical role in the natural history of nonsevere asthma (Mitasthme study). Clinical trial registered with www.clinicaltrials.gov (NCT00808730).
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.|3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Girodet
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Benoit
authors.initials: B
authors.lastname: Allard
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.|3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Thumerel
authors.affiliation: 3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Begueret
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupin
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Olga
authors.initials: O
authors.lastname: Ousova
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Régis
authors.initials: R
authors.lastname: Lassalle
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Elise
authors.initials: E
authors.lastname: Maurat
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.|3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Annaig
authors.initials: A
authors.lastname: Ozier
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Trian
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.|3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: 1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.|2 INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and.|3 CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC1401, Service d'Anatomopathologie, Pessac, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Berger
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000502:physiology*; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001999:Bronchoscopy; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology
keywords: asthma; exacerbation; mitochondria; remodeling; smooth muscle