Koopmans J G, Lutter R, Jansen H M, van der Zee J S
Department of Pulmonology, Academic Medical Center, F4-208, P O Box 22700, 1100 DE Amsterdam, The Netherlands.
Thorax. 2006 Apr;61(4):306-12. doi: 10.1136/thx.2005.051292. Epub 2006 Jan 31.
Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.
After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.
Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001).
The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.
与增加吸入性糖皮质激素剂量相比，在吸入性糖皮质激素基础上加用长效β2受体激动剂沙美特罗可更好地控制哮喘症状。然而，对于加用沙美特罗对哮喘炎症过程的长期影响知之甚少，而控制炎症过程被认为对哮喘的长期转归很重要。
在4周的氟替卡松导入期后，54例过敏性哮喘患者被随机分为两组，采用双盲、平行组设计，每日两次接受250微克氟替卡松治疗，其中一组加用50微克沙美特罗，另一组不加用，治疗1年（两组氟替卡松的每日总剂量均为500微克）。主要结局指标为痰液嗜酸性粒细胞数量和嗜酸性粒细胞阳离子蛋白浓度。次要结局指标为与中性粒细胞相关的痰液参数和呼吸膜通透性标志物。在治疗期开始前和结束时测定对变应原诱导变化的影响。
在氟替卡松基础上加用沙美特罗可使呼气峰值流速、症状评分、急救药物使用量及支气管高反应性得到改善（所有指标p<0.05）。在治疗期间，对痰液细胞分类计数和细胞因子浓度以及治疗结束时变应原激发诱导的变化均无持续影响（p>0.05）。然而，在治疗期间，加用沙美特罗可显著降低痰液中α2-巨球蛋白与白蛋白的比值（p = 0.001）。
在氟替卡松基础上加用沙美特罗对变应原诱导的支气管细胞炎症无持续影响，但可使血浆蛋白透过呼吸膜的大小选择性得到显著改善。这可能有助于解释在过敏性哮喘患者中，长效β2受体激动剂与吸入性糖皮质激素联合使用时临床结局得到改善的原因。
