Bronchodilatateurs bêta 2-adrénergiques et corticoïdes : complémentarité ou synergie d’action

Abstract

It is accepted that maintenance therapy of asthma must include anti-inflammatory drugs, such as glucocorticosteroids, and bronchodilators, such as β 2-adrenoceptors agonists, to treat acute exacerbations and/or to relieve symptoms. Several studies have demonstrated that a single dose of β 2-adrenoceptors agonists induces a bronchoprotective effect on indirect bronchoconstricting stimuli (allergen, adenosine, exercise). Such a bronchoprotective effect is partly explained by the inhibitory effect of β 2-adrenoceptor agonists on the release of mediators by inflammatory cells. However, short-term regular treatment with β-adrenoceptor agonists leads to tolerance to the bronchoprotective effect of β 2-adrenoceptor agonists. This tolerance is due to the rapid desensitization of inflammatory cells to the β 2-adrenoceptor agonist-induced effects. Inhaled corticosteroids have been proven to prevent or reverse desensitization induced by β 2-adrenoceptor agonists in vitro and recently in asthmatic patients. In addition, different studies have shown that long-acting β 2-adrenergic agonists can be used effectively in combination with low doses of inhaled corticosteroids. Adding long-acting β 2-adrenergic agonists to inhaled glucocorticosteroids (low or high doses) decreased the exacerbation rate in patients with moderate to severe persistent asthma, suggesting that combination of these two drugs improves the control of the bronchial inflammatory process. Recently, long-acting β 2-adrenergic agonists have been shown to prime glucocorticosteroid receptors, facilitating therefore its nuclear translocation and in turn the anti-inflammatory effects of glucocorticosteroids. In conclusion, the positive interactions (synergy) between β 2-adrenergic agonists and glucocorticosteroids can explain the long-term efficiency of the association in the control of asthma.