Protective effect of inhaled budesonide against unlimited airway narrowing to methacholine in atopic patients with asthma

Background: Patients with asthma who have moderate to severe airway hyperresponsiveness often demonstrate progressive, unlimited airway narrowing in response to inhaled bronchoconstrictor stimuli, which is likely to be due to inflammatory changes within the airway wall, It is unknown whether regular therapy with inhaled steroids can limit this excessive response. Objective: We investigated the effect of inhaled budesonide on the development of a plateau on the dose-response curve to methacholine in patients with asthma who did not show such a plateau before the study. Methods: Thirty-one atopic patients with asthma (age, 19 to 31 years; FEV(1) > 70% of predicted value; PC20 < 8 mg/ml) with documented absence of a maximal-response plateau to methacholine on two occasions during the run-in period, participated in a double-blind, placebo-controlled, parallel study, Standardized methacholine challenges were performed at -1, 0, 4, 8, and 12 weeks of treatment with inhaled budesonide, 800 mu g two times a day, or corresponding placebo, and after a 2-week washout period, Airway response was measured by FEV(1) (percent fall from baseline), A maximal-response plateau was considered if three or more consecutive data points fell within a 5% response range. Results: Thirty patients completed the study. There was a steady increase in the number of budesonide-treated patients exhibiting a maximal-response plateau on the dose-response curve from zero of 15 patients at run-in to nine of 14 patients at week 12, as compared with four of 16 patients in the placebo group (p = 0.03, chi square test). This was accompanied by a significant improvement in PC20 in the budesonide group as compared with the placebo group (p < 0.01 at week 12), whereas the changes in FEV(1) were not significantly different between the groups (p = 0.77 at week 12). Conclusion: Regular treatment with the inhaled corticosteroid budesonide limits maximal airway narrowing in response to methacholine by introducing a plateau on the dose-response curve in patients with asthma, who were initially characterized by the absence of a plateau. This indicates that inhaled steroids are likely to reduce the hazard of unlimited airway narrowing in asthma.