Pauwels RA, Pedersen S, Busse WW, et al. Lancet. 2003;361:1071–1076
Purpose of the Study.
To determine whether treatment with low-dose inhaled budesonide would prevent severe asthma-related events and accelerated lung function decline among patients with recent-onset, mild, persistent asthma.
A group of 7241 patients, 5 to 66 years of age, with mild asthma symptoms for 3 months to 2 years, were recruited from 499 sites in 32 countries.
Patients were randomly allocated to receive 400 μg of budesonide (200 μg for patients <11 years of age) or placebo once daily. The primary outcome measure was time to the first severe asthma-related event (admission, emergency treatment, or death), analyzed with an intent-to-treat approach. Follow-up visits, with spirometry and adverse event monitoring, occurred at 6 and 12 weeks after randomization and then every 3 months for 3 years. Patients recorded asthma-related events between visits. Changes in medication regimens, including the addition of inhaled corticosteroids, were allowed if considered clinically necessary.
Budesonide reduced the risk of severe asthma-related events by 44% (hazard ratio: 0.56; 95% confidence interval: 0.45–0.71; P < .0001) and prolonged the time to the first asthma-related event. Budesonide-treated patients experienced significantly fewer severe asthma-related events, life-threatening exacerbations, days with symptoms, and courses of inhaled or systemic corticosteroids. The improvements in postbronchodilator forced expiratory volume in 1 second (FEV1) after 3 years were more striking among adults than among children (P = .004), although the improvements in postbronchodilator FEV1 after 1 year and in prebronchodilator FEV1 were similar. Surprisingly, budesonide did not improve postbronchodilator FEV1 among adolescent patients. Children in the budesonide group exhibited slowed growth (mean height difference: −0.43 cm/year; 95% confidence interval: −0.54 to −0.32 cm/year; P < .0001) to a lesser degree with each successive year.
Long-term, once-daily treatment with low-dose budesonide decreased the risk of severe exacerbations and improved asthma control among patients with mild persistent asthma of recent onset.
Data on asthma-related events, symptoms, and medication use were not reported separately for the 2 pediatric age groups included in the study (5–10 years and 11–17 years). However, the morbidity associated with mild persistent asthma and the improvements in prebronchodilator FEV1 with budesonide treatment observed in this study suggest that children with mild persistent asthma may benefit from budesonide treatment early in the course of their disease. As always, the benefits of inhaled corticosteroids among children must be weighed against the potential side effect of mild growth delay.