Nishimura K, Koyama H, Ikeda A, Sugiura N, Kawakatsu K, Izumi T
Chest Disease Research Institute, Kyoto University, Japan.
Chest. 1995 Mar;107(3):718-23. doi: 10.1378/chest.107.3.718.
To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler.
Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks.
The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred).
On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders.
确定口服氨茶碱对稳定期慢性阻塞性肺疾病（COPD）患者的附加作用，这些患者每日4次使用定量吸入器吸入400微克沙丁胺醇和80微克异丙托溴铵。
24例稳定期COPD男性患者（第1秒用力呼气容积[FEV1]为0.96±0.43升；预计值的36.8±17.0%[预计%]）完成了一项为期4周的口服氨茶碱随机、双盲、安慰剂对照交叉试验。
治疗期间平均血清氨茶碱水平为15.0±5.5微克/毫升。总体而言，在未吸入支气管扩张剂的情况下，安慰剂期FEV1为0.93±0.42升，氨茶碱期为1.00±0.43升（与安慰剂有显著差异；p<0.01）。吸入400微克沙丁胺醇和80微克异丙托溴铵后15分钟和60分钟时，安慰剂组的FEV1分别为1.12±0.43升和1.14±0.46升，氨茶碱组的FEV1分别为1.18±0.45升（p<0.01）和1.20±0.47升（p<0.01）。每日呼气峰值流速也有所改善。氨茶碱期和安慰剂期的每日症状评分无显著差异。然而，8例患者在服用氨茶碱期间报告有主观获益，因此被视为主观反应者。在主观反应者中，氨茶碱期吸入后FEV1有显著改善（氨茶碱与安慰剂治疗后15分钟FEV1的变化为预计值的3.1%；60分钟时为3.5%），而在主观无反应者中，支气管扩张剂使用后安慰剂期和氨茶碱期的FEV1无显著差异（15分钟时为预计值的1.7%；60分钟时为1.6%）。
总体而言，氨茶碱有轻微的支气管扩张作用，但不能改善稳定期COPD患者的症状。然而，三分之一的COPD患者可能对氨茶碱有主观反应。氨茶碱的附加支气管扩张作用可能与主观反应者的症状改善有关。
