Step-Down Compared to Fixed-Dose Treatment With Inhaled Fluticasone Propionate in Asthma*

Background: Inhaled corticosteroids (ICSs) are an effective treatment of asthma even when administered at a low dose. Once asthma is controlled, current guidelines recommend that the dose of ICS be reduced to the lowest possible and effective dose. Although the most appropriate strategy for the stepping down has not yet been defined, quantification of sputum eosinophils and bronchial hyperresponsiveness (BHR) are indeed measures of asthma control. Objective: To compare the efficacy of step-down and fixed-dose strategies in the control of BHR to methacholine and eosinophilic inflammation patients with mild-to-moderate asthma. Methods: We performed a double-blind, randomized study to compare inhaled fluticasone propionate (FP), 1,000 g/d, then reduced to 200 g/d (group 1; n 18) to a fixed dose of FP, 200 g/d (group 2; n 17) administered for 6 weeks and then 8 weeks in reducing the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and sputum eosinophils in 35 patients. The duration of the efficacy was also followed subsequently after 8 weeks of placebo treatment. Results: PD20 remarkably increased with both treatment strategies, but differences between groups were not significant. Sputum eosinophils (median values, percentage) at baseline and after each treatment period were not different (group 1, 16.4 to 1.0 to 2.7%; group 2, 16.7 to 2.8 to 2.8%, respectively). The percentages of patients in whom sputum eosinophilia was normalized (< 3%) were as follows: group 1, 69% and 60%; group 2, 50% and 57%. After placebo treatment, sputum eosinophils were still “normalized” in approximately one third of patients. Conclusion: Step-down and fixed-dose strategies with FP improved PD20 and sputum eosinophilia to a similar degree. The effect on sputum eosinophils persisted longer than that on methacholine. (CHEST 2005; 127:117–124)