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

Abstract

Background-It is desirable to prescribe the minimal eVective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed. Methods-The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC 20 ) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 µg/day budesonide (n = 8), 400 µg/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 µg budesonide or placebo. The groups were matched with respect to age, PC 20 , baseline FEV 1 (% predicted), exhaled NO, and sputum eosinophilia. Results-There were significant improvements in FEV 1 following 400 µg and 1600 µg budesonide (11.3% and 6.5%, respectively, p<0.05). This was accompanied 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 following each budesonide dose while PC 20 was improved only with 1600 µg budesonide. These results suggest that exhaled NO and PC 20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC 20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 µg daily. Conclusion-Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

“…To date, the dose-dependent effect of ICS on airway eosinophilia has mainly been assessed on induced sputum samples. These studies also indicate that ICS are effective, from low doses onwards, at reducing eosinophil number, and that the dose-response curve is relatively flat [17][18][19][20]. To what extent this is paralleled by changes in mucosal eosinophil number has not been fully established in humans.…”

“…Adopting the latter strategy meant that the subjects were treated with a mean additional dose of 400 mg of ICS over a 2-yr treatment period. Also, JATAKANON et al [17] demonstrated that only a dose of 1,600 mg budesonide was sufficient to decrease methacholine airway responsiveness, whereas 400 mg was sufficient to reduce exhaled nitric oxide levels and sputum eosinophil number. These observations illustrate that the mechanisms underlying AHR are relatively resistant to steroid treatment.…”

Respiratory heat and moisture loss is associated with eosinophilic inflammation in asthma

“…However, all patients in the current stable asthma group were taking regular inhaled corticosteroids, and in steroid-treated patients the relationship between NO and sputum eosinophils is much less pronounced [27,28]. These two markers vary in their response to inhaled steroid treatment [30,31]. EBC pH has previously been reported to correlate with sputum eosinophils in asthma by KOSTIKAS et al [32].…”

Optimal asthma control, starting with high doses of inhaled budesonide

“…AHR is a fundamental component of the definition of asthma, and has been associated with asthma exacerbations [23], airway inflammation [24] and decline in lung function [25]. Previous studies have shown a dose-dependent improvement in AHR with inhaled corticosteroid treatment [26,27], and asthma outcomes and basement membrane thickness improved when AHR was added to a treatment algorithm [7]. A recent study by MEIJER et al [11] showed that high-dose fluticasone was more effective in improving AHR than oral prednisolone.…”