EFFECTS OF TREATMENT WITH FORMOTEROL ON BRONCHOPROTECTION AGAINST METHACHOLINE

PURPOSE: In addition to their bronchodilatory effects, beta(2)-agonist s protect against bronchoconstriction, such as that caused by methacho line challenge. However, tachyphylaxis to this beneficial effect devel ops after chronic use of beta(2)-agonists. We studied whether the freq uency or dose of treatment with a long-acting beta(2)-agonist (formote rol) affects the degree of bronchoprotection afforded against methacho line challenge and to compare this with the effects of a short-acting beta(2)-agonist (terbutaline). PATIENTS AND METHODS: In a randomized, parallel group, double-blind study at two centers, patients with stabl e asthma of mild to moderate severity who were treated with inhaled co rticosteroids were treated with formoterol 6 mu g twice daily, 24 mu g twice daily, 12 mu g once daily; terbutaline 500 mu g four times dail y, or placebo. Treatments were given by dry powder inhaler for a perio d of 2 weeks. Of the 72 patients who were enrolled, 67 completed the s tudy. Methacholine challenge was performed to calculate the provocativ e dose that caused a 20% fall in forced expiratory volume in 1 second at baseline (unprotected) after an initial 1-week run-in without beta( 2)-agonists, 1 hour after the first dose of study treatment, and again 1 hour after 7 and 14 days of study treatment. RESULTS: Each of the f our active treatments exhibited significant tachyphylaxis (P < 0.05) t o protection against methacholine challenge when comparing first/last dose las geometric mean protection ratio versus baseline): formoterol 24 mu g twice daily (9.6-fold/1.6-fold), 12 mu g once daily (7.1-fold/ 2.2-fold), 6 mu g twice daily (6.2-fold/2.3-fold), and terbutaline 500 mu g four times daily (2.9-fold/2.0-fold), There were no significant differences among treatments after 2 weeks in bronchoprotection agains t methacholine challenge. For all formoterol regimens, the bronchodila tor response 1 hour after inhalation was maintained over the 2-week tr eatment period. Diurnal control of morning and evening peak flow was s ignificantly better with formoterol 24 mu g twice daily than with terb utaline. CONCLUSIONS: Tachyphylaxis to bronchoprotection against metha choline challenge develops after 2 weeks of therapy with formoterol, a long-acting beta(2)-agonist, at all three dosage regimens mens that w ere tested. In contrast, the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment. (C) 1998 by Excerpta Medi ca, Inc.