Rebound airway obstruction and responsiveness after cessation of terbutaline: effects of budesonide

Am J Respir Crit Care Med. 1996 Jan;153(1):70-5. doi: 10.1164/ajrccm.153.1.8542165.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Topical
  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / therapeutic use*
  • Adult
  • Aerosols
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchial Provocation Tests
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Budesonide
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids
  • Humans
  • Ipratropium / therapeutic use
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Placebos
  • Pregnenediones / administration & dosage
  • Pregnenediones / therapeutic use*
  • Terbutaline / administration & dosage
  • Terbutaline / therapeutic use*
  • Time Factors


  • Adrenergic beta-Agonists
  • Aerosols
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Glucocorticoids
  • Placebos
  • Pregnenediones
  • Methacholine Chloride
  • Budesonide
  • Ipratropium
  • Terbutaline