Interactions between corticosteroids and beta2-agonists in asthma and chronic obstructive pulmonary disease.
The combination of a long-acting beta(2)-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 beta(2)-receptor function by increasing expression of the receptor, restoring G-protein/beta(2)-receptor coupling, and inhibiting beta(2)-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/beta(2)-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/beta(2)-agonist combined activity may also overcome the reduced sensitivity to inhaled corticosteroids that has been reported in some patients with COPD.
Johnson
Malcolm
M
GlaxoSmithKline Research & Development, Greenford Road, Middlesex UB6 OHE, UK. malcolm.w.johnson@gsk.com
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D003692:Delayed-Action Preparations