Pedersen S
J Allergy Clin Immunol. 1986 Mar;77(3):505-9. doi: 10.1016/0091-6749(86)90186-7.
In a double-blind crossover study, 16 children with asthma were treated with two puffs of terbutaline (0.25 mg per puff)/placebo from a pressurized aerosol with a tube spacer. The puffs of terbutaline were taken either immediately after each other (TT) or with a pause of 3 minutes (3TT) or 10 minutes (10TT) between the two puffs. All active treatments compared with placebo resulted in a significant bronchodilation, both under normal day-to-day conditions and during acute attacks of bronchoconstriction (p less than 0.01). Under basic conditions there was no statistically significant difference in increase in FEV1 after TT, 3TT, and 10TT treatments (22%, 24%, and 25%, respectively). During attacks of acute wheeze, however, a pause between the two puffs of terbutaline improved bronchodilation significantly from 49% (TT), to 68% (3TT), and 78% (10TT) (p less than 0.01). There was no statistically significant difference between 3TT and 10TT treatments. It is concluded that pauses between the doses of inhaled terbutaline is likely to improve bronchodilation during episodes of wheeze or poor control of symptoms, whereas there appears to be no need to recommend pauses between the puffs in the routine day-to-day management of children with moderate asthma.