Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma

Abstract

Six patients with asthma (American Thoracic Society (ATS) criteria), maintained on inhaled beta2-agonists alone, were treated with inhaled corticosteroid (budesonide 400 μg b.d.) for a period of three months. Prior to steroid therapy, baseline spirometry, bronchodilator response and bronchial hyperresponsiveness were documented and endobronchial biopsies were obtained for immunopathological analysis. Frozen sections of the biopsies were investigated using immunoperoxidase methods, with a panel of monoclonal antibodies selected to reveal the presence and distribution of lymphocyte and macrophage subsets and HLA-DR expression. After three months the studies were repeated. Studies before steroid therapy revealed a T-cell-dominated inflammation in the bronchial wall of all subjects. Baseline airway obstruction, median (range) forced expiratory volume in one second (FEV1) 78.5 (61-109)% of predicted, with a significant bronchodilator response 20.8 (14-33)% and bronchial hyperresponsiveness to histamine geo-metric mean (SD) PC20 FEV1 0.69 (2.5) mg was documented. Steroid therapy caused a significant reduction in bronchial hyperresponsiveness to histamine, with an increase in geometric mean PC20FEV1 to 2.22 (3.2) mg post steroid (p < 0.03). Concurrent with a reduction in bronchodilator response and an increase in spirometric variables (improved forced mid-expiratory flow (FEF25-75) p < 0.03), there were marked reductions observed in the overall numbers of T-lymphocytes (CD 2, 5, 8), the numbers of CD45RO+ T-cells, and the numbers of macrophages (RFD1+) with the phenotype of antigen presenting cells. In all six subjects, reductions in the quantitative expression of HLA-DR molecules were also seen. These preliminary results demonstrate that inhaled steroid therapy in asthmatics significantly reduces both the underlying T-cell-dominated inflammation in the bronchial wall and the bronchial hyperresponsiveness in these patients. These data go some way to explaining the efficacy of corticosteroids in this condition.