Inman M D, Watson R M, Rerecich T, Gauvreau G M, Lutsky B N, Stryszak P, O'Byrne P M
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 2001 Aug 15;164(4):569-74. doi: 10.1164/ajrccm.164.4.2007063.
Comparisons of the potency of different inhaled corticosteroids, delivery devices, and treatment regimens in the management of asthma can only be made when outcome measurements display a dose-dependent effect. These outcomes have been difficult to identify. In this study, we compared in a randomized, double-blind, crossover design, the effects of 6 d treatment with placebo and three doses (50, 100, and 400 microg, twice daily) of mometasone furoate delivered by dry powder inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild asthmatic subjects with dual responses after allergen inhalation were studied. Outcome measurements included early and late asthmatic responses, the change in methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated similar attenuation of early responses and allergen-induced airway hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in FEV(1) after placebo treatment was 23.5% and was significantly reduced in a dose-dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400-microg twice-daily treatments (p = 0.007). The allergen-induced increase in sputum eosinophilia (x10(4) cells/ml) 24 h after challenge during placebo treatment was 60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and 400-microg twice-daily treatments. MF-DPI is effective at attenuating allergen-induced early and late responses, airway hyperresponsiveness, and sputum eosinophilia, and dose-response effects exist for the attenuation of the late response.
只有当疗效测量显示出剂量依赖性效应时,才能对不同吸入性糖皮质激素、给药装置和治疗方案在哮喘管理中的效能进行比较。然而,这些疗效一直难以确定。在本研究中,我们采用随机、双盲、交叉设计,比较了安慰剂治疗6天以及通过干粉吸入器(MF-DPI)给予三剂(50、100和400微克,每日两次)糠酸莫米松对变应原吸入激发后反应的影响。研究了12名变应原吸入后出现双重反应的轻度哮喘患者。疗效测量包括早期和晚期哮喘反应、激发后24小时乙酰甲胆碱气道反应性的变化,以及激发后7小时和24小时痰液嗜酸性粒细胞增多情况。相对于安慰剂,所有三剂MF-DPI均显示出对早期反应和变应原诱导的气道高反应性有相似程度的减轻(p < 0.05)。安慰剂治疗后FEV(1)的晚期最大下降百分比为23.5%,对于每日两次50微克、100微克和400微克的治疗,该百分比以剂量依赖性方式显著降低至12.3%、11.0%和5.9%(p = 0.007)。安慰剂治疗期间,激发后24小时变应原诱导的痰液嗜酸性粒细胞增多(×10(4)细胞/毫升)为60.2,对于每日两次50微克、100微克和400微克的治疗,该数值显著降低至24.0、15.3和6.2。MF-DPI在减轻变应原诱导的早期和晚期反应、气道高反应性以及痰液嗜酸性粒细胞增多方面有效,并且在减轻晚期反应方面存在剂量反应效应。