Optimal asthma control, starting with high doses of inhaled budesonide

Abstract

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, β2-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.