Bronchial Smooth Muscle Remodeling in Nonsevere Asthma. 2016

Pierre-Olivier Girodet, and Benoit Allard, and Matthieu Thumerel, and Hugues Begueret, and Isabelle Dupin, and Olga Ousova, and Régis Lassalle, and Elise Maurat, and Annaig Ozier, and Thomas Trian, and Roger Marthan, and Patrick Berger
1 University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France.

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).

UI MeSH Term Description Entries
D008297 Male Males
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D001999 Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Bronchoscopic Surgical Procedures,Surgical Procedures, Bronchoscopic,Bronchoscopic Surgery,Surgery, Bronchoscopic,Bronchoscopic Surgeries,Bronchoscopic Surgical Procedure,Bronchoscopies,Surgeries, Bronchoscopic,Surgical Procedure, Bronchoscopic
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D056151 Airway Remodeling The structural changes in the number, mass, size and/or composition of the airway tissues. Airway Remodelling,Asthmatic Airway Remodeling,Asthmatic Airway Remodelling,Asthmatic Airway Wall Remodeling,Asthmatic Airway Wall Remodelling,Small Airway Remodeling,Small Airway Remodelling,Airway Wall Remodelling,Airway Remodeling, Asthmatic,Airway Remodeling, Small,Airway Remodelings,Airway Remodelings, Asthmatic,Airway Remodelings, Small,Airway Remodelling, Asthmatic,Airway Remodelling, Small,Airway Remodellings,Airway Remodellings, Asthmatic,Airway Remodellings, Small,Airway Wall Remodellings,Asthmatic Airway Remodelings,Asthmatic Airway Remodellings,Remodeling, Airway,Remodeling, Asthmatic Airway,Remodeling, Small Airway,Remodelings, Airway,Remodelings, Asthmatic Airway,Remodelings, Small Airway,Remodelling, Airway,Remodelling, Airway Wall,Remodelling, Asthmatic Airway,Remodelling, Small Airway,Remodellings, Airway,Remodellings, Airway Wall,Remodellings, Asthmatic Airway,Remodellings, Small Airway,Small Airway Remodelings,Small Airway Remodellings,Wall Remodelling, Airway,Wall Remodellings, Airway

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