Effect of disease duration on dose-response of inhaled budesonide in asthma

Background: Inhaled corticosteroids (ICS) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early. Whether treatment should be started with a high or tow dose remains controversial. We investigated the importance of disease duration on the response to the starting dose of the ICS, budesonide, in asthma patients not previously treated with ICS. Methods: Forty patients with newly detected asthma (symptoms for < 12 months) and 41 patients with established asthma (mean duration 5.2 years, range 2-11) were randomized (double-blind, parallel-group) to treatment with budesonide Turbuhaler (R) 100 or 400 mu g twice daily or placebo for 12 weeks. Results: For morning peak expiratory flow (mPEF), all four budesonide treatments resulted in statistically significant improvements from baseline and, after 12 weeks, the changes in all four groups were statistically significantly greater than placebo. In patients receiving early treatment, no significant differences were seen between budesonide doses. In patients with established symptoms, 800 mu g/day improved mPEF significantly more than 200 mu g/day. The 800 mu g/day dose in the early treatment group improved mPEF significantly more than in the delayed treatment group. Changes in forced expiratory volume in 1 s (FEV1), the concentration of inhaled histamine causing a 20% drop in FEV1, and use of as-needed medication behaved in very similar ways to mPEF. Asthma symptoms were reduced in all budesonide groups without a difference between doses. Conclusion: In patients with newly detected asthma treated early the initial ICS dose is not important. In contrast, in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a tow dose. (c) 2008 Elsevier Ltd. All rights reserved.