ASTHMA CONTROL DURING AND AFTER CESSATION OF REGULAR BETA-(2)-AGONIST TREATMENT

It has been suggested that regular treatment with high doses of beta2-agonists might result in poorer control of asthma and increased bronchial responsiveness. We have examined change in FEV1(DELTAFEV1), bronchial reactivity, peak expiratory flow (PEF), and symptoms during and after 3 wk of regular treatment with a relatively low dose of albuterol and broxaterol, a new beta2-agonist. Eleven subjects 18 to 50 yr of age with mild asthma inhaled albuterol (200 mug), broxaterol (400 mug), or placebo three times a day for 3 wk with a 2- to 4-wk run-in/washout period between treatments. Ipratropium bromide was allowed for symptomatic relief. The PD20 (dose of histamine causing a 20% fall in FEV1) was measured before and 11, 35, and 59 h after cessation of treatment and a bronchodilator dose-response study before and 83 h after cessation of treatment. Change from baseline after albuterol and broxaterol are compared with change after placebo. Diurnal change in PEF (amplitude % mean) increased during treatment with albuterol by 6.5% (95% Cl, 1.7-12.3; p < 0.02) mainly because of a fall in morning PEF. Cessation of treatment with both beta2-agonists was associated with a fall in FEV1 and PD20 compared with placebo. After 11 h, mean FEV1 had fallen by 10% after albuterol (95% Cl, 4.5-15.5; p < 0.01) and by 5.6% after broxaterol (95% Cl, 0.15-11.1; p < 0.05) compared with change after placebo; the greatest difference in DELTAPD20 occurred 59 h after stopping treatment and was 1.47 doubling doses for albuterol (95% Cl, 0.6-2.4; p < 0.01) and 0.95 doubling doses for broxaterol (95% Cl, 0.05-1.8; p < 0.05). There was no significant change in the bronchodilator dose-response curves after either beta2-agonist. Thus, regular treatment with albuterol 200 mug three times a day for 3 wk was associated with an increase in PEF variability and, after cessation of treatment, a fall in FEV1 and increased bronchial reactivity that persisted for 59 h. We conclude that adverse effects can occur both during and after cessation of 3 wk of regular treatment with relatively low doses Of beta2-agonists.