Di Marco Fabiano, Verga Massimo, Santus Pierachille, Morelli Nicoletta, Cazzola Mario, Centanni Stefano
Respiratory Medicine Unit, University of Milan, Ospedale San Paolo, Milano, Italy.
Respir Med. 2006 Nov;100(11):1925-32. doi: 10.1016/j.rmed.2006.03.007. Epub 2006 Apr 19.
The aim of our study was to evaluate the pharmacodynamic effects of 1-day treatment with formoterol, tiotropium and their combination in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Twenty-one (19 males, mean age 72+/-8 years, mean FEV1 38+/-14% of predicted values) patients with mild to moderate AECOPD were enrolled. Patients received formoterol (12 microg deliver via Modulite b.i.d.), tiotropium (18 microg dry powder capsules delivered via HandiHaler once daily), and their combination, in randomized sequence. Serial measurements of FEV1, FVC, IC, SpO2 and HR were performed over 24h. Formoterol, tiotropium, and their combination significantly improved the area under curves (AUCs) for FEV1, FVC and IC over 12 and 24h. The mean FEV1, FVC and IC AUC(0-12h) and AUC(0-24h) after formoterol and tiotropium combination were significantly higher than formoterol and tiotropium alone, whereas the differences between the two single drugs were not statistically significant. Formoterol, either alone or in combination with tiotropium, elicited a significantly faster onset of action, and combination elicited a greater maximum bronchodilation than both single drugs in terms of FEV1 and FVC. After 24h the bronchodilating effect of the three treatments disappeared, with the exception of the combination on FEV1. The results of this study have documented that, although the time course of the effects of evaluated drugs differs significantly from that in stable COPD, with a shorter bronchodilation both for tiotropium and formoterol, these two long-acting bronchodilators appear to also be complementary in mild to moderate AECOPD.
我们研究的目的是评估福莫特罗、噻托溴铵及其联合用药1天治疗对慢性阻塞性肺疾病急性加重期（AECOPD）患者的药效学作用。纳入了21例（19例男性，平均年龄72±8岁，平均FEV1为预测值的38±14%）轻度至中度AECOPD患者。患者按随机顺序接受福莫特罗（通过Modulite吸入，每次12μg，每日两次）、噻托溴铵（通过HandiHaler吸入18μg干粉胶囊，每日一次）及其联合用药。在24小时内对FEV1、FVC、IC、SpO2和HR进行连续测量。福莫特罗、噻托溴铵及其联合用药在12小时和24小时内均显著改善了FEV1、FVC和IC的曲线下面积（AUC）。福莫特罗和噻托溴铵联合用药后FEV1、FVC和IC的平均AUC（0 - 12小时）和AUC（0 - 24小时）显著高于单用福莫特罗和噻托溴铵，而两种单药之间的差异无统计学意义。福莫特罗单用或与噻托溴铵联合使用起效明显更快，联合用药在FEV1和FVC方面引起的最大支气管扩张程度大于两种单药。24小时后，除联合用药对FEV1的支气管扩张作用外，三种治疗的支气管扩张作用均消失。本研究结果表明，尽管所评估药物的作用时间过程与稳定期慢性阻塞性肺疾病有显著差异，噻托溴铵和福莫特罗的支气管扩张时间均较短，但这两种长效支气管扩张剂在轻度至中度AECOPD中似乎也具有互补性。
