Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction.
J Allergy Clin Immunol
; 124(1): 45-51.e1-4, 2009 Jul.
Article
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| MEDLINE
| ID: mdl-19481790
ABSTRACT
BACKGROUND:
The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown.OBJECTIVES:
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.CONCLUSION:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sistema Respiratorio
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Asma
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Enfermedad Pulmonar Obstructiva Crónica
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Canadá