title: Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction.
abstract: BACKGROUND
  The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown.
  
  
  OBJECTIVE
  We sought to characterize subjects with severe asthma with and without chronic persistent airflow obstruction with respect to airway wall remodeling (histopathologic and radiologic) and specific sputum biomarkers.
  
  
  METHODS
  Subjects with severe asthma with chronic persistent (n = 16) or intermittent (n = 18) obstruction were studied. Endobronchial biopsy specimens were analyzed for airway smooth muscle area, epithelial detachment, basement membrane thickness, and submucosal fibrosis. Levels of eosinophil cationic protein, myeloperoxidase, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 1 (ELISA), and 27 cytokines (multiplex assay) and differential cell counts were measured in induced sputum. Airway thickness was measured by means of high-resolution computed tomographic scanning.
  
  
  RESULTS
  Chronic persistent obstruction was associated with earlier age of onset, longer disease duration, more inflammatory cells in the sputum, and greater smooth muscle area (15.65% +/- 2.69% [n = 10] vs 8.96% +/- 1.99% [n = 14], P = .0325). No differences between groups were found for any of the biomarker molecules measured in sputum individually. However, principal component analysis revealed that the dominant variables in the chronic persistent obstruction group were IL-12, IL-13, and IFN-gamma, whereas IL-9, IL-17, monocyte chemotactic protein 1, and RANTES were dominant in the other group. Airway imaging revealed no differences between groups.
  
  
  CONCLUSIONS
  Subjects with severe asthma with chronic persistent obstruction have increased airway smooth muscle with ongoing T(H)1 and T(H)2 inflammatory responses. Neither airway measurements on high-resolution computed tomographic scans nor sputum analysis seem able to identify such patients.
authors.affiliation: Meakins-Christie Laboratories, Montreal, Quebec H2X 2P2, Canada.
authors.forename: Marta
authors.initials: M
authors.lastname: Kaminska
authors.forename: Susan
authors.initials: S
authors.lastname: Foley
authors.forename: Karim
authors.initials: K
authors.lastname: Maghni
authors.forename: Claudine
authors.initials: C
authors.lastname: Storness-Bliss
authors.forename: Harvey
authors.initials: H
authors.lastname: Coxson
authors.forename: Heberto
authors.initials: H
authors.lastname: Ghezzo
authors.forename: Catherine
authors.initials: C
authors.lastname: Lemière
authors.forename: Ronald
authors.initials: R
authors.lastname: Olivenstein
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: James
authors.initials: J
authors.lastname: Martin
mesh_terms: D000328:Adult; D001249:Asthma / Q000473:pathology*; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D012137:Respiratory System / Q000000981:diagnostic imaging / Q000473:pathology*; D013183:Sputum / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9