Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma

Background-It is desirable to prescribe the minimal effective dose of inhal ed steroids to control asthma. To ensure that inflammation is suppressed wh ilst using the lowest possible dose, a sensitive and specific method for as sessing airway inflammation is needed. Methods-The usefulness of exhaled nitric oxide (NO), sputum eosinophils, an d methacholine airway responsiveness (PC20) for monitoring airway inflammat ory changes following four weeks of treatment with an inhaled corticosteroi d (budesonide via Turbohaler) were compared. Mild stable steroid naive asth matic subjects were randomised into two double blind, placebo controlled st udies. The first was a parallel group study involving three groups receivin g either 100 mu g/day budesonide (n = 8), 400 mu g/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 mu g budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhal ed NO, and sputum eosinophilia. Results-There were significant improvements in FEV1 following 400 mu g and 1600 mu g budesonide (11.3% and 6.5%, respectively, p<0.05). This was accom panied by significant reductions in eosinophil numbers in induced sputum (0 .7 and 0.9 fold, p<0.05). However, levels of exhaled NO were reduced follow ing each budesonide dose while PC20, was improved only with 1600 mu g budes onide. These results suggest that exhaled NO and PC20 may not reflect the c ontrol of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophil s, and PC20, to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 mu g daily. Conclusion-Monitoring the number of eosinophils in induced sputum may be th e most accurate guide to establish the minimum dose of inhaled steroids nee ded to control inflammation. This, however, requires further studies involv ing a larger number of patients.