Ikeda A, Nishimura K, Koyama H, Izumi T
Chest Disease Research Institute, Kyoto University, Japan.
Chest. 1995 Feb;107(2):401-5. doi: 10.1378/chest.107.2.401.
Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.
多项研究表明，在稳定期慢性阻塞性肺疾病（COPD）的治疗中，抗胆碱能药物至少与β受体激动剂效果相当，甚至可能更优。然而，由于此前大多数研究是在相对高剂量下评估这两种药物的支气管舒张作用，这两种药物联合使用的临床价值仍存在争议。本研究的目的是确定异丙托溴铵和沙丁胺醇按临床可用剂量联合治疗在支气管舒张方面是否优于单独使用异丙托溴铵。26例稳定期COPD男性患者（平均年龄67.5±5.9岁；第一秒用力呼气容积[FEV1]为0.87±0.32L）参与了随机、双盲、安慰剂对照试验。在五个不同的日子里，所有患者分别接受以下一种治疗：（1）40微克异丙托溴铵；（2）80微克异丙托溴铵；（3）40微克异丙托溴铵加200微克沙丁胺醇；（4）80微克异丙托溴铵加400微克沙丁胺醇；或（5）安慰剂，均使用定量吸入器（MDIs）。在吸入前以及吸入后15、30、60、90和120分钟进行肺功能测定。80微克异丙托溴铵和400微克沙丁胺醇联合剂量的FEV1阳性反应显著大于其他任何治疗方案。与单独使用40微克异丙托溴铵相比，200微克沙丁胺醇与40微克异丙托溴铵联合使用时的反应也显著更大。200微克沙丁胺醇与40微克异丙托溴铵联合治疗对用力肺活量的影响明显大于单独使用80微克异丙托溴铵治疗。80微克和40微克异丙托溴铵治疗引起的反应之间未发现显著差异。在整个研究过程中，未观察到任何治疗方案有不良反应。总之，对于COPD患者，异丙托溴铵和沙丁胺醇标准剂量联合使用可能比将异丙托溴铵标准剂量加倍提供更大的支气管舒张作用。
