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Differences in Airway Cytokine Profile in Severe Asthma Compared to Moderate Asthma^*

^* From Montreal Chest Institute (Drs. Shannon, Ernst, and Olivenstein), Respiratory Division of the McGill University Health Centre; Meakins-Christie Laboratories (Drs. Yamauchi, Foley, Ludwig, Hamid, Martin, and Mr. Cicora), McGill University; and Respiratory Division (Dr. Lemiere), Hôpital Sacré-Coeur, Montreal, QC, Canada.

Correspondence to: James G. Martin, MD, DSc, Meakins Christie Laboratories, McGill University, 3626 St. Urbain, Montreal, QC, Canada H2X 2P2; e-mail: James.martin{at}mcgill.ca

Abstract

Background: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma.

Methods: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry.

Results: Subjects with severe asthma were more symptomatic, had a lower FEV₁, and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN- expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups.

Conclusion: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.

Key Words: cytokines • immunology • inflammation