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First published online on December 10, 2007
Chest, doi:10.1378/chest.07-1881
A more recent version of this article appeared on February 1, 2008
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Differences in airway cytokine profile in severe asthma compared to moderate asthma

Joanne Shannon, MD2; Pierre Ernst, MD; Yasuhiro Yamauchi, MD2; Ronald Olivenstein, MD; Catherine Lemiere, MD3; Susan Foley, MD2; Leo Cicora RT2; Mara Ludwig, MD2; Qutayba Hamid, MD, PhD2 and James G. Martin, MD, DSc21 Montreal Chest Institute and the Respiratory Division of the McGill University Health Centre, Montreal Quebec

2Meakins-Christie Laboratories, McGill University, Montreal, Quebec 3Respiratory Division, Hôpital Sacré-Coeur, Montreal, Quebec

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 Th1 (interferon-{gamma}) and Th2 cytokines (interleukin) (IL-4), (IL-5) and the neutrophil and eosinophil associated chemokines (IL-8 and eotaxin) in the airway tissues of severe and moderate asthmatics.

Methods: Subjects with severe asthma (n=24) and a comparison moderate asthma group (n=26) were assessed with spirometry, induced sputum, exhaled nitric oxide and bronchial biopsies were obtained. The expression of proteins of interest in the epithelium and sub-epithelium 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 interferon-{gamma} expression was 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 both 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 • inflammation • immunology






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