Asthme corticorésistant et corticodépendant : quelles solutions ?

Abstract: A small proportion of asthma patients do not obtain full benefit from corticosteroid therapy. Corticoresistant asthmatics do not demonstrate benefit in lung function following a course of oral prednisolone for two weeks, and corticosteroid-dependent asthmatics need chronic oral prednisolone to maintain some degree of control and are often patients with severe asthma. The mechanisms by which the effect of corticosteroids are blunted in some patients with asthma have been evaluated mainly in circulating blood cells. The poor clinical response to corticosteroids is also reflected in the reduced anti-inflammatory effects of steroids on cell activation. The mechanisms of poor response include the production of glucocorticoid receptor (GR)-β receptor that competes with the active natural GRα receptor, binding of GRα with inflammatory transcription factors, defect of translocation of activated GRα into the nucleus, phosphorylation of GRα for diminished binding affinity by IL-2 and IL-4, and defect in recruitment of histone deacetylase-2 to the activated transcriptional complex. A solution to corticosteroid resistance in corticosteroid-resistant or -dependent asthmatics should be possible by using possible drug targets as indicated by these mechanisms. However, much more work is needed. [Copyright &y& Elsevier]