Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction.
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.
Kaminska
Marta
M
Meakins-Christie Laboratories, Montreal, Quebec H2X 2P2, Canada.
Foley
Susan
S
Maghni
Karim
K
Storness-Bliss
Claudine
C
Coxson
Harvey
H
Ghezzo
Heberto
H
Lemière
Catherine
C
Olivenstein
Ronald
R
Ernst
Pierre
P
Hamid
Qutayba
Q
Martin
James
J
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
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9