Patel K R, Pavia D, Lowe L, Spiteri M
Department of Respiratory Medicine, Western Infirmary, Glasgow, UK.
Respiration. 2006;73(4):434-40. doi: 10.1159/000089426. Epub 2005 Oct 30.
Respimat Soft Mist Inhaler (SMI) is a new-generation inhaler offering improved lung deposition compared with other devices. Bronchodilators administered via Respimat SMI are preserved and stabilized with benzalkonium chloride (BAC) and ethylene diamine tetra-acetic acid (EDTA); both have been reported to cause paradoxical bronchoconstriction if a threshold dose is exceeded.
The aim of this randomized, double-blind, three-period, crossover study was to establish that the safety of inhaled ethanolic and aqueous placebo solutions (containing BAC and EDTA) is equivalent to that of inhaled normal saline solution when administered to asthma patients via Respimat SMI.
Thirty-seven asthma patients with airway hyper-reactivity were randomized to receive four actuations of each of the following three treatments via Respimat SMI, one on each of 3 study days: ethanolic placebo (12 microl 96% ethanol + 0.13 mug EDTA/actuation), aqueous placebo (12 microl water + 5.5 microg EDTA + 1.1 mug BAC/actuation), and normal saline (12 microl 0.9% sodium chloride/actuation). Pulmonary function tests were performed at baseline and at 5, 15, 30, 60, 120 and 180 min after inhalation; the primary endpoint was the lowest FEV(1) recorded between 0 and 30 min.
The mean lowest FEV(1) recorded between 0 and 30 min after inhalation minus the study day baseline was -0.090 litres for ethanolic placebo, -0.121 litres for aqueous placebo and -0.094 litres for normal saline (SEM 0.034 litres for all). The mean treatment differences were: ethanolic placebo versus normal saline 0.004 litres (90% CI -0.075-0.083 litres, p = 0.002), and aqueous placebo versus normal saline -0.028 litres (90% CI -0.107-0.052 litres, p = 0.006). Since both 90% CIs fell within the pre-determined equivalence region of +/-0.15 litres, both treatments were considered equivalent to normal saline.
Ethanolic and aqueous solutions administered via Respimat SMI are safe with regard to paradoxical bronchoconstriction in asthma patients with airway hyper-reactivity.
Respimat软雾吸入器（SMI）是新一代吸入器，与其他设备相比，其肺部沉积效果更佳。通过Respimat SMI给药的支气管扩张剂用苯扎氯铵（BAC）和乙二胺四乙酸（EDTA）进行保存和稳定；如果超过阈值剂量，据报道二者都会引起矛盾性支气管收缩。
这项随机、双盲、三阶段、交叉研究的目的是确定，当通过Respimat SMI给哮喘患者使用时，吸入乙醇安慰剂溶液和水性安慰剂溶液（含有BAC和EDTA）的安全性与吸入生理盐水溶液的安全性相当。
37名气道高反应性哮喘患者被随机分组，通过Respimat SMI接受以下三种治疗，每种治疗各进行4次喷雾，在3个研究日中的每一天各进行1次：乙醇安慰剂（每次喷雾12微升96%乙醇 + 0.13微克EDTA）、水性安慰剂（每次喷雾12微升水 + 5.5微克EDTA + 1.1微克BAC）和生理盐水（每次喷雾12微升0.9%氯化钠）。在基线以及吸入后5、15、30、60、120和180分钟进行肺功能测试；主要终点是吸入后0至30分钟记录的最低第一秒用力呼气容积（FEV₁）。
吸入后0至30分钟记录的平均最低FEV₁减去研究日基线，乙醇安慰剂为-0.090升，水性安慰剂为-0.121升，生理盐水为-0.094升（所有组的标准误均为0.034升）。平均治疗差异为：乙醇安慰剂与生理盐水相比为0.004升（90%置信区间为-0.075至0.083升，p = 0.002），水性安慰剂与生理盐水相比为-0.028升（90%置信区间为-0.107至0.052升，p = 0.006）。由于两个90%置信区间均落在预先确定的±0.15升等效范围内，因此两种治疗均被认为与生理盐水等效。
对于气道高反应性哮喘患者，通过Respimat SMI给药的乙醇溶液和水性溶液在矛盾性支气管收缩方面是安全的。
