Asthma Control during and after Cessation of Regular Beta2-Agonist Treatment

Abstract It has been suggested that regular treatment with high doses of β2-agonists might result in poorer control of asthma and increased bronchial responsiveness. We have examined change in FEV1 (Δ FEV1), 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 β2-agonist. Eleven subjects 18 to 50 yr of age with mild asthma inhaled albuterol (200 µg), broxaterol (400 µg), 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% CI, 4.5-15.5; p < 0.01) and by 5.6% after broxaterol (95% CI, 0.15-11.1; p < 0.05) compared with change after placebo; the greatest difference in ΔPD20 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 β2-agonist. Thus, regular treatment with albuterol 200 µg 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 β2-agonists.