Optimal asthma control, starting with high doses of inhaled budesonide

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel‐group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 µg or 1,600 µg budesonide daily by Turbuhaler® for 8 weeks (double‐blind), then 1,600 µg·day ‐1 for 8 weeks (single‐blind), followed by 14 months of open‐label budesonide dose down‐titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1–16 was change in airway hyperresponsiveness (AHR), and, for the open‐label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200‐ and 1,600‐µg·day ‐1 starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L·min ‐1 , p=0.8). Subjects starting with 3,200 µg·day ‐1 were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of ≥3.92 µmol by week 16 (p=0.3). During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 µg·day ‐1 , p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days·week ‐1 , β 2 ‐agonist use 0.2 occasions·day ‐1 , and PD20 2.4 µmol). In subjects with poorly controlled asthma, a starting dose of 1,600 µg·day ‐1 budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.