Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction

• Published in: Journal of allergy and clinical immunology Vol. 124; no. 1; pp. 45 - 51.e4
• Main Authors: Kaminska, Marta, Foley, Susan, Maghni, Karim, Storness-Bliss, Claudine, Coxson, Harvey, Ghezzo, Heberto, Lemière, Catherine, Olivenstein, Ronald, Ernst, Pierre, Hamid, Qutayba, Martin, James
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2009; Elsevier; Elsevier Limited
• Subjects: Adult; Airway management; airway smooth muscle; Allergy and Immunology; Asthma; Asthma - pathology; Biological and medical sciences; biopsy; Chemokines; cytokines; Female; fibrosis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocytes - metabolism; high-resolution computed tomographic scan; Humans; Immunopathology; inflammation; Male; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Methods; Middle Aged; Molecular weight; Muscle, Smooth - pathology; Muscular system; Proteins; Pulmonary Disease, Chronic Obstructive - pathology; remodeling; Respiratory System - diagnostic imaging; Respiratory System - pathology; reticular basement membrane; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severe asthma; Smooth muscle; sputum; Sputum - immunology; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tomography, X-Ray Computed; Values; Vascular endothelial growth factor; Canada; Montreal Quebec Canada; reticular basement membrane; ATS; FeNO; remodeling; SMA; airway smooth muscle; sputum; WA; MPO; high-resolution computed tomographic scan; CT; MMP; ECP; inflammation; MIP; biopsy; fibrosis; cytokines; HRCT; Severe asthma; ASM; MCP; RBM; TIMP; Fraction of exhaled nitric oxide; Matrix metalloproteinase; Computed tomography; Smooth muscle area; Myeloperoxidase; Wall area percentage; Monocyte chemotactic protein; High-resolution computed tomography; American Thoracic Society; Tissue inhibitor of matrix metalloproteinase; Eosinophil cationic protein; Macrophage inflammatory protein; High resolution; Smooth muscle; Remodeling; Respiratory system; Obstruction; Respiratory tract; Immunology; Human; Immunopathology; Radiodiagnosis; Cytokine; Inflammation; Basement membrane; Anatomic pathology; Chronic; Biopsy; Sputum; Fibrosis; Medical imagery; Computerized axial tomography
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2009.03.049

The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown. 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. 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. 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-γ, whereas IL-9, IL-17, monocyte chemotactic protein 1, and RANTES were dominant in the other group. Airway imaging revealed no differences between groups. Subjects with severe asthma with chronic persistent obstruction have increased airway smooth muscle with ongoing T H1 and T H2 inflammatory responses. Neither airway measurements on high-resolution computed tomographic scans nor sputum analysis seem able to identify such patients.