THE EFFECT OF TREATMENT WITH ORAL CORTICOSTEROIDS ON ASTHMA SYMPTOMS AND AIRWAY INFLAMMATION

To improve understanding of the mechanisms of action of oral corticost eroids in asthma, we have conducted a double-blind, placebo-controlled study with prednisolone (20 mg for 2 wk followed by 10 mg for 4 wk) o r placebo in 14 and 13 atopic corticosteroid-naive asthmatic subjects, respectively. Before and after treatment subjects underwent bronchosc opy with bronchoalveolar lavage (BAL) and bronchial biopsy. Treatment with prednisolone, but not placebo, significantly reduced asthma sympt oms (from mean +/- SEM total weekly score of 34 +/- 6.2 to 15.7 +/- 3. 2, p = 0.02) and albuterol usage (from mean +/- SEM number of puffs/wk of 29.7 +/- 6.2 to 18.2 +/- 3.7, p = 0.01) and significantly increase d FEV(1) (from 89.8 +/- 4.4% to 99.3 +/- 4.1% of predicted, p = 0.03). There were no significant changes in inflammatory or epithelial cell counts, levels of T-cell activation or albumin concentration in BAL. H owever, immunohistochemistry of bronchial biopsies showed that in the submucosa prednisolone significantly decreased numbers of mast cells b y 62% (from median 45 to 17/mm(2), p = 0.01), eosinophils by 81% (from median 30.1 to 5.7/mm(2), p = 0.004), and CD4+ T-cells by 68% (from m edian 64.6 to 18.5/mm(2), p = 0.02). In the epithelium only the reduct ion in the numbers of eosinophils was significant (from median 1.1 to O/mm of epithelium, p = 0.02). There were no significant changes in an y cell counts in the subjects receiving placebo, and comparison of the changes between the treatment groups identified a significant prednis olone-related reduction in submucosal eosinophil and mast cell counts (p = 0.003 and 0.03, respectively). The temporal association between t he clinical and physiologic improvement, and the correlation between t he magnitude of change in CD4+ T-cell counts in the submucosa and incr ease in PC20 methacholine (r(s) = 0.60, p = 0.049) suggests that the r eduction in airways inflammatory cell numbers underlies the clinical e fficacy of oral corticosteroids.