Optimal asthma control, starting with high doses sf 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 mu g or 1,600 mu g budesonide daily by Turbuhaler(R) for 8 weeks (double-blind), then 1,600 mu g.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-mu g.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 mu g.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 greater than or equal to 3.92 mu mol by week 16 (p=0.3), During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 mu g.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), beta(2)-agonist use 0.2 occasions.day(-1), and PD20 2.4 mu mol). In subjects with poorly controlled asthma, a starting dose of 1,600 mu g.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.