Rebound airway obstruction and responsiveness after cessation of terbutaline: effects of budesonide.
Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.
de Jong
J W
JW
Department of Pulmonology, University Hospital Groningen, The Netherlands.
van der Mark
T W
TW
Koëter
G H
GH
Postma
D S
DS
D000280:Administration, Inhalation; D000287:Administration, Topical; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000336:Aerosols; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D010919:Placebos; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*; D013726:Terbutaline / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D010919:Placebos; D011282:Pregnenediones; D016210:Methacholine Chloride; D019819:Budesonide; D009241:Ipratropium; D013726:Terbutaline