Booth H, Richmond I, Ward C, Gardiner P V, Harkawat R, Walters E H
Respiratory Immunology Group, Alfred Hospital, Victoria, Australia.
Am J Respir Crit Care Med. 1995 Jul;152(1):45-52. doi: 10.1164/ajrccm.152.1.7599861.
Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids 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, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.
吸入性糖皮质激素目前是大多数哮喘患者的一线治疗药物。然而，已有研究表明，即使在使用低剂量吸入性糖皮质激素的情况下，气道炎症和气道高反应性仍持续存在。为了确保最大的治疗潜力，我们研究了一种新型吸入性糖皮质激素丙酸氟替卡松（FP）（相当于每日4000微克二丙酸倍氯米松[BDP]）3个月的疗效。20名轻度至中度哮喘患者被纳入这项单盲研究。将基线数据与26名正常受试者的数据进行比较。在支气管肺泡灌洗（BAL）和支气管活检中均检测到哮喘患者与正常受试者之间炎症指标的差异。在FP治疗期后，症状评分、肺功能和气道反应性有显著改善，乙酰甲胆碱的平均加倍稀释倍数为2.8。气道淋巴细胞负荷和淋巴细胞活化减少，这可能是吸入性糖皮质激素发挥作用的重要机制。特应性哮喘中肥大细胞数量和活性降低表明糖皮质激素在不同类型哮喘中可能有其他作用靶点。即使在研究前接受低剂量维持BDP治疗的患者中，高剂量FP也能降低淋巴细胞和肥大细胞活性，提示吸入性糖皮质激素对气道炎症有剂量反应效应。FP治疗后BAL嗜酸性粒细胞增多仍然存在，这表明哮喘气道炎症的一部分对糖皮质激素治疗相对耐药。
