SELECTED ARTICLES FROM THE RECENT LITERATURE 2006

10/4/06

Phosphodiesterase inhibition and airways remodeling in asthma

Summary
Background - Airways remodeling (Air Re) occurs commonly in persistent asthma (PA), sometimes resulting in poorly reversible airflow obstruction. Air Re is thought to be due to effects of growth factors and the local deposition in the airway wall of extracellular matrix (ECM) proteins released from airway smooth muscle (ASM) cells. How do current asthma therapies affect such events?

Findings - Burgess et al of the Univ of Sydney in Australia examined the in vitro effects of various therapeutic agents on the release of several ECM components from TGF-beta stimulated ASM. The ASM were obtained from asthmatics and non-asthmatics.

They found that soflumilast, a phosphodiesterase 4 (PDE4) inhibitor, reduced the release of connective tissue growth factor (CTGF), collagen I and fibronectin from the ASM cells. Corticosteroids and long-acting beta 2 agonists were ineffective in this regard.

The authors concluded that corticosteroids and long-acting beta agonists may reduce symptoms and improve quality of life but may not control the release/deposition of ECM components which led to Air Re. Use of an additional therapeutic agent such as a PDE4 inhibitor may help prevent Air Re.

Reference
J Allergy Clin Immunol 2006;118:649-57

Editor's Comments
These findings are of considerable interest and potential therapeutic importance. Recent studies have shown moderate benefit of PDE4 inhibitor therapy in COPD but less consistent benefit in PA.

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