SELECTED ARTICLES FROM THE RECENT LITERATURE 2006

12/13/06

Biomarkers of severe asthma

Summary
Background – In about 10% of those with persistent asthma, the disease is severe, and not controlled by inhaled corticosteroids (ICS) even when such drugs are used in high dosage. The mechanisms underlying such ICS-resistant severe asthma (SA) are still not well defined.

Findings – Possible pathogenic mechanisms and biomarkers in SA were discussed in an editorial by Holgate of the Univ of Southampton in the UK. He pointed out that the bronchial inflammatory reaction is frequently different in SA with a predominance of neutrophils, TNF-alpha and IL-8 rather than the eosinophil predominant inflammation seen in those with less severe asthma. The neutrophil predominance in the airways in SA is partially due to the greater inhibition of eosinophil than of neutrophil accumulation by the systemic corticosteroid therapy generally used (often with only modest benefit) in those with SA.

However, there is evidence that increased local secretion of TNF-alpha (in part from local mast cells) may be a major trigger in SA. TNF-alpha is a potent stimulus of IL-8 production. IL-8, in turn, is a major chemoattractant for neutrophils. In several studies the levels of TNF-alpha expressed in inflammatory cells were inversely correlated with expiratory airflow (FEV-1) in individual asthmatics.

Therefore, several pilot trials of anti-TNF-alpha therapy (etanercept or infliximab) in SA have been undertaken with promising results to date. A large controlled trial is underway.

Reference
Clinical and Exper Allergy 2006;36:1355-56

Editor's Comments
The minority (about 10%) of asthmatics with severe, relatively corticosteroid- resistant disease may be a pathogenically heterogeneous group. Some, but not all, improve with omalizumab (monoclonal anti-IgE) therapy. The neutrophil- predominant bronchial inflammatory response in SA has been known for some time. Anti-TNF-alpha therapy does look like a viable option for such SA patients although patients have to be monitored closely for adverse effects of such anti-TNF alpha therapy.

 

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