Turner M O, Johnston P R, Pizzichini E, Pizzichini M M, Hussack P A, Hargreave F E
University of British Columbia, Vancouver, Canada.
Can Respir J. 1998 Jul-Aug;5(4):261-8. doi: 10.1155/1998/868379.
Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma.
To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property.
Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 mg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 mg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis.
Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters.
These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist.
沙美特罗是一种强效长效β受体激动剂，可有效缓解哮喘症状并改善气流受限情况。
确定沙美特罗对哮喘轻度嗜酸性粒细胞加重期临床参数的影响是否与二丙酸倍氯米松（BDP）相似，从而判断其是否具有抗炎特性。
34例哮喘患者，症状持续加重至少两周，痰液嗜酸性粒细胞增加4%或更多，采用双盲法随机分为三组，分别使用相同的压力定量吸入器，每日分剂量给予100mg沙美特罗、1mg BDP或安慰剂治疗。患者接受研究药物治疗三周，随后接受一周的开放标签BDP治疗（500mg，每日两次）。每周对患者进行一次检查，每次检查时采集痰液和血液样本。主要观察指标为痰液嗜酸性粒细胞的变化，次要观察指标为血液嗜酸性粒细胞、嗜酸性粒细胞阳离子蛋白（ECP）和临床参数的变化。随机分组后，有3例患者（每组各1例）无法咳出任何痰液，被排除在分析之外。
12例患者接受沙美特罗治疗，10例接受BDP治疗，9例接受安慰剂治疗。沙美特罗治疗对痰液嗜酸性粒细胞几何平均值（从35.5[24.9]降至26.9%[25.8]）、血液嗜酸性粒细胞（从7.6[4.8]降至7.2%[3.9]）或ECP（从33.1[18.1]降至27.8[16.3]mg/L）均无影响，但改善了早晨呼气峰值流速（PEF）和PEF的日变化，且与安慰剂相比，减少了急救药物的使用（所有比较P<0.05）。相比之下，BDP改善了炎症指标（痰液嗜酸性粒细胞从22.5[17.9]降至5.7%[6.8]，血液嗜酸性粒细胞从9.0[5.5]降至2.1%[1.0]，血清ECP从36.5[22.0]降至16.1[10.1]mg/L）以及临床参数。
这些结果表明，沙美特罗可改善哮喘患者的症状和气道功能，但对嗜酸性粒细胞气道浸润无影响。这些发现支持当前的哮喘指南，即建议初始使用吸入性糖皮质激素以最大程度地改善临床症状。虽然沙美特罗也能改善临床症状，但它不能抑制痰液嗜酸性粒细胞增多。对诱导痰或自发痰进行炎症指标分析可能是指导吸入性糖皮质激素和/或长效β受体激动剂使用的一项有价值的临床检测方法。
