Bellia V, Foresi A, Bianco S, Grassi V, Olivieri D, Bensi G, Volonté M
Istituto Clinica delle Malattie Apparato Respiration, Palermo, Italy.
Respir Med. 2002 Nov;96(11):881-9. doi: 10.1053/rmed.2002.1380.
We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone.
我们比较了吸入氧托溴铵、茶碱或二者联合用药对轻至重度慢性阻塞性肺疾病（COPD）患者进行8周治疗的疗效（包括肺量计、呼气峰值流速（PEFR））、生活质量及安全性。我们在29家意大利门诊诊所开展了一项多中心、双盲、双模拟随机平行组研究。招募了一组236例轻至重度COPD患者（基线第1秒用力呼气容积（FEV1）≤预测值的70%）。治疗方案如下：吸入200微克溴化氧托溴铵（N = 75）、口服300毫克缓释茶碱（N = 81）或二者联合（N = 80），均每日服用两次。每4周评估一次肺量计（FEV1和用力肺活量（FVC）），并每日测量早晚的PEFR（服药前及服药后2 - 4小时）。每日记录症状、咳嗽和呼吸困难情况。在基线期和第8周使用疾病特异性圣乔治呼吸问卷（SGRQ）评估健康状况。治疗期间发生的任何不良事件均记录在日记卡上。所有组在4周和8周时FEV1和FVC均有所改善，但治疗组之间的差异未达到统计学显著水平。给药前早晚PEFR的组间差异不显著。给药后早晚PEFR均升高，且在两种药物联合治疗的患者中升高幅度最大。然而，组间差异仅在晚间值时有统计学意义（P = 0.008）。所有组中症状减轻的患者比例都很高，但未观察到组间差异。所有治疗组在8周后SGRQ总分均下降，尤其是氧托溴铵组和联合用药组。仅在使用溴化氧托溴铵治疗的患者中观察到具有临床意义的变化（≥4分），无论是否联用茶碱。单独使用茶碱治疗组的治疗相关不良事件发生率更高（P < 0.02）。我们得出结论，单独吸入溴化氧托溴铵可使COPD患者的FEV1、PEFR和症状得到改善，与单独口服茶碱或二者联合用药相比，差异无统计学意义。溴化氧托溴铵与茶碱联合用药使给药后晚间PEFR有更大改善。单独使用溴化氧托溴铵或与茶碱联合使用比单独使用茶碱能更好地改善生活质量。
