EFFECT OF HIGH-DOSE INHALED FLUTICASONE PROPIONATE ON AIRWAY INFLAMMATION IN ASTHMA

Inhaled corticosteroids are now first-line therapy for most patients w ith asthma. However, it has been shown that there is ongoing airway in flammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potentia l we investigated the effect of 3 mo of a very high dose of a new inha led corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 m u g daily of beclomethasone dipropionate [BDP]). Twenty asthmatics wit h mild-to-moderate disease were recruited into this single-blind study . Baseline data were compared with those from 26 normal subjects. Diff erences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP tr eatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling diluti ons of methacholine. Reduction in the airway lymphocyte load and lymph ocyte activation was demonstrated and is likely to be an important mec hanism mediating the effects of inhaled corticosteroids. Decreased mas t cell numbers and activity in atopic asthma suggest that corticostero ids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggestin g a dose-response effect of inhaled corticosteroids on airway inflamma tion. BAL eosinophilia was still present after FP, indicative of a com ponent of asthmatic airway inflammation that is relatively resistant t o corticosteroid therapy.