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Interactions between Corticosteroids and ß₂-Agonists in Asthma and Chronic Obstructive Pulmonary Disease

GlaxoSmithKline Research and Development, Middlesex, United Kingdom

Correspondence and requests for reprints should be addressed to Malcolm Johnson, Ph.D., GlaxoSmithKline Research & Development, Greenford Road, Middlesex UB6 OHE, UK. Email: malcolm.w.johnson{at}gsk.com

The combination of a long-acting ß₂-agonist (LABA) and an inhaled corticosteroid is more efficacious in asthma and chronic obstructive pulmonary disease (COPD) than other combination therapies or than either alone. Corticosteroids may regulate ß₂-receptor function by increasing expression of the receptor, restoring G-protein/ß₂-receptor coupling, and inhibiting ß₂-receptor downregulation. LABAs may prime the glucocorticoid receptor and affect its nuclear localization by modulating glucocorticoid receptor phosphorylation. These mechanisms suggest the possibility of interactions between the two classes of drugs at the molecular and receptor levels. Indeed, there is evidence that corticosteroid/ß₂-agonist combination therapy has complementary, additive, and synergistic inhibitory effects on proinflammatory signaling pathways, inflammatory mediator release, and recruitment and survival of inflammatory cells. In the asthmatic patient, this is reflected in enhanced anti-inflammatory activity with combination therapy beyond that which can be achieved by either drug alone, or the potential for LABAs to provide a steroid-sparing effect. Corticosteroid/ß₂-agonist combined activity may also overcome the reduced sensitivity to inhaled corticosteroids that has been reported in some patients with COPD.

Key Words: combination therapy • inhaled corticosteroids • long-acting ß₂-agonists • mechanisms

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