BACKGROUND: In patients with asthma, single doses of inhaled glucocorticosteroids (ICS) have been reported to have antiinflammatory actions that can be detected several hours after drug administration. However, the onset and duration of the effect have not been investigated. We therefore measured airway blood flow ([Formula: see text]aw) as an index of airway inflammation to determine the time course and dose dependence of the antiinflammatory action of an ICS in 20 patients with moderate asthma receiving regular ICS treatment. METHODS: [Formula: see text]aw and spirometry were measured before and serially for 360 minutes after a single inhaled dose of 360 μg, 720 μg, and 1,440 μg budesonide or placebo as well as after four repetitive 720-μg budesonide doses given 30 minutes apart. RESULTS: Baseline mean [Formula: see text]aw was increased and FEV1 was decreased without significant differences among the 5 treatment days. After budesonide inhalation, there was a transient, dose-dependent decrease in mean [Formula: see text]aw from 12 to 21%, with significant differences from baseline at 60 and 90 minutes for the 720-μg and 1,440-μg doses (P < 0.05). Thirty minutes after four repetitive budesonide administrations, mean [Formula: see text]aw was 28% below baseline (P < 0.05) and remained 11% below baseline after 270 minutes. There was no change in mean FEV1 after any of the treatments. CONCLUSIONS: In subjects with moderate asthma who use ICS regularly, inhaledbudesonide caused a transient dose-dependent vasoconstriction in the airway, thereby reversing one manifestation of airway inflammation. These results suggest that a pure controller medication can have immediate beneficial effects not paralleled by changes in airflow. Clinical trial registered with www.clinicaltrials.gov (NCT 01219738).
RCT Entities:
BACKGROUND: In patients with asthma, single doses of inhaled glucocorticosteroids (ICS) have been reported to have antiinflammatory actions that can be detected several hours after drug administration. However, the onset and duration of the effect have not been investigated. We therefore measured airway blood flow ([Formula: see text]aw) as an index of airway inflammation to determine the time course and dose dependence of the antiinflammatory action of an ICS in 20 patients with moderate asthma receiving regular ICS treatment. METHODS: [Formula: see text]aw and spirometry were measured before and serially for 360 minutes after a single inhaled dose of 360 μg, 720 μg, and 1,440 μg budesonide or placebo as well as after four repetitive 720-μg budesonide doses given 30 minutes apart. RESULTS: Baseline mean [Formula: see text]aw was increased and FEV1 was decreased without significant differences among the 5 treatment days. After budesonide inhalation, there was a transient, dose-dependent decrease in mean [Formula: see text]aw from 12 to 21%, with significant differences from baseline at 60 and 90 minutes for the 720-μg and 1,440-μg doses (P < 0.05). Thirty minutes after four repetitive budesonide administrations, mean [Formula: see text]aw was 28% below baseline (P < 0.05) and remained 11% below baseline after 270 minutes. There was no change in mean FEV1 after any of the treatments. CONCLUSIONS: In subjects with moderate asthma who use ICS regularly, inhaled budesonide caused a transient dose-dependent vasoconstriction in the airway, thereby reversing one manifestation of airway inflammation. These results suggest that a pure controller medication can have immediate beneficial effects not paralleled by changes in airflow. Clinical trial registered with www.clinicaltrials.gov (NCT 01219738).
Authors: Tim Harrison; Ian D Pavord; James D Chalmers; Glenn Whelan; Malin Fagerås; Annika Rutgersson; Laura Belton; Shahid Siddiqui; Per Gustafson Journal: ERJ Open Res Date: 2020-06-08