Cazzola M, D'Amato M, Califano C, Di Perna F, Calderaro E, Matera M G, D'Amato G
Department of Respiratory Medicine, A. Cardarelli Hospital, Naples, Italy.
Clin Ther. 2002 Apr;24(4):595-604. doi: 10.1016/s0149-2918(02)85135-9.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking.
The aim of the study was to compare the inhaled beta2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II).
A dose-response curve to formoterol via Turbuhaler or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 microg formoterol via Turbuhaler (48-microg cumulative metered dose); B = 200 + 200 + 400 microg salbutamol via pMDI (800-microg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded.
Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV1, inspiratory capacity (IC), and forced vital ca- pacity (FVC). There was no significant difference between FEV1, IC, and FVC values after 48 microg formoterol and 800 microg salbutamol. There was no significant difference in FEV1 after 24 microg formoterol and 800 microg salbutamol; however, the difference in FEV1 after 24 and 48 microg formoterol was significant. Neither heart rate (mean differences from baseline after 48 microg formoterol, 1.9 beats/min [95% CI, -3.4, 7.2] and 800 microg salbutamol, 3.7 beats/min [95% CI, -1.1, 8.5]) nor SpO2 (mean percentage differences from baseline after 48 microg formoterol, -0.37% [95% CI, -1.22, 0.47] and 800 microg salbutamol, -0.75% [95% CI, -1.73, 0.23]) changed significantly. However, SpO2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol.
In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.
慢性阻塞性肺疾病（COPD）急性加重期的治疗方法是增加患者现有支气管扩张剂治疗的剂量或用药频率。已有研究建议使用福莫特罗治疗COPD轻度急性加重期；然而，目前仍缺乏福莫特罗与沙丁胺醇（治疗该病症的金标准支气管扩张剂）累积剂量的比较。
本研究旨在比较吸入性β2受体激动剂沙丁胺醇（起效迅速、作用时间短）和福莫特罗（起效迅速、作用时间长），二者均按需用于因COPD轻度急性加重期（安东尼森I型或II型加重）而就诊于门诊的患者。
构建了通过都保吸入器吸入福莫特罗或通过压力定量吸入器（pMDI）吸入沙丁胺醇的剂量反应曲线。在连续2天中，患者随机接受以下两种活性剂量方案：A = 通过都保吸入器吸入12 + 12 + 24微克福莫特罗（累积定量剂量48微克）；B = 通过pMDI吸入200 + 200 + 400微克沙丁胺醇（累积定量剂量800微克）。每隔30分钟增加一次剂量，每次给药后25分钟进行测量。将福莫特罗或沙丁胺醇剂量反应曲线期间的最大1秒用力呼气量（FEV1）值作为比较两种治疗方法的主要结局变量。每个评估期还测量了脉搏血氧饱和度（SpO2）和脉搏率。记录患者自发报告或研究人员观察到的每一个不良事件。
16名患者（2名女性，14名男性），年龄51至77岁（大多数年龄超过65岁）参与了本研究。福莫特罗和沙丁胺醇均引起FEV1、吸气容量（IC）和用力肺活量（FVC）显著的、剂量依赖性的大幅增加。48微克福莫特罗和800微克沙丁胺醇后的FEV1、IC和FVC值之间无显著差异。24微克福莫特罗和800微克沙丁胺醇后的FEV1无显著差异；然而，24微克和48微克福莫特罗后的FEV1差异显著。心率（48微克福莫特罗后与基线的平均差异为1.9次/分钟[95%CI，-3.4，7.2]，800微克沙丁胺醇后为3.7次/分钟[95%CI，-1.与基线的平均差异为-0.37%[95%CI，-1.22，0.47]，800微克沙丁胺醇后为-0.75%[95%CI，-1.73，0.23]）均无显著变化。然而，2名患者在接受最高剂量福莫特罗后、1名患者在接受最高剂量沙丁胺醇后SpO2降至90%以下。
在这一小群选定的COPD轻度急性加重期患者中，通过都保吸入器吸入的福莫特罗可引起快速的支气管扩张，且呈剂量依赖性，与沙丁胺醇引起的支气管扩张无显著差异。此外，福莫特罗的耐受性似乎与沙丁胺醇相当。
