Effect of regular terbutaline on the airway response to inhaled budesonide

The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined.

Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment.

Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20.

Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.