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 hy perresponsiveness often demonstrate progressive, unlimited airway narr owing in response to inhaled bronchoconstrictor stimuli, which is like ly to be due to inflammatory changes within the airway wall, It is unk nown whether regular therapy with inhaled steroids can limit this exce ssive response. Objective: We investigated the effect of inhaled budes onide on the development of a plateau on the dose-response curve to me thacholine in patients with asthma who did not show such a plateau bef ore the study. Methods: Thirty-one atopic patients with asthma (age, 1 9 to 31 years; FEV(1) > 70% of predicted value; PC20 < 8 mg/ml) with d ocumented absence of a maximal-response plateau to methacholine on two occasions during the run-in period, participated in a double-blind, p lacebo-controlled, parallel study, Standardized methacholine challenge s were performed at -1, 0, 4, 8, and 12 weeks of treatment with inhale d 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 considere d if three or more consecutive data points fell within a 5% response r ange. Results: Thirty patients completed the study. There was a steady increase in the number of budesonide-treated patients exhibiting a ma ximal-response plateau on the dose-response curve from zero of 15 pati ents at run-in to nine of 14 patients at week 12, as compared with fou r of 16 patients in the placebo group (p = 0.03, chi square test). Thi s was accompanied by a significant improvement in PC20 in the budesoni de group as compared with the placebo group (p < 0.01 at week 12), whe reas the changes in FEV(1) were not significantly different between th e 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 th e absence of a plateau. This indicates that inhaled steroids are likel y to reduce the hazard of unlimited airway narrowing in asthma.