Zimmerman Barry, D'Urzo Anthony, Bérubé Denis
Gage Occupational and Environmental Health Unit, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Pediatr Pulmonol. 2004 Feb;37(2):122-7. doi: 10.1002/ppul.10404.
This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.
这项双盲、安慰剂对照、随机、平行组、多中心研究纳入了302名6至11岁的哮喘儿童，这些儿童单独使用吸入性糖皮质激素治疗效果不佳。患者继续使用现有的吸入性糖皮质激素剂量，此外还接受安慰剂、4.5微克福莫特罗或9微克福莫特罗，每日两次，为期12周（均通过都保装置给药）。特布他林作为缓解药物备用。主要疗效变量为早晨呼气峰流速（PEF）较基线的变化；次要疗效变量包括第1秒用力呼气容积（FEV(1)）、12小时内连续测量的PEF、晚上PEF、哮喘症状评分和生活质量。与安慰剂相比，4.5微克和9微克福莫特罗分别使早晨PEF提高了8升/分钟（P = 0.035）和11升/分钟（P = 0.0045）。与安慰剂相比，晚上PEF和FEV(1)也显著增加，福莫特罗不同剂量之间无统计学显著差异。与安慰剂相比，中午时肺功能改善更大。3个月后，9微克福莫特罗组12小时平均连续PEF增加了24升/分钟（95%可信区间，9，39升/分钟），4.5微克福莫特罗组增加了14升/分钟（95%可信区间，0，29升/分钟）。两个福莫特罗组中严重加重事件的发生率在数值上低于安慰剂组，表示福莫特罗可能有改善儿童加重控制的潜力。两种福莫特罗剂量耐受性良好，未观察到对药物支气管扩张作用的耐受性。福莫特罗使肺功能持续改善，在单独使用吸入性糖皮质激素治疗效果不佳的哮喘儿童中耐受性良好。
