Peters Stephen P, Prenner Bruce M, Mezzanotte William S, Martin Paula, O'Brien Christopher D
Section on Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Allergy Asthma Proc. 2008 Sep-Oct;29(5):499-516. doi: 10.2500/aap.2008.29.3147. Epub 2008 Aug 8.
Safety concerns have been raised regarding the regular use of long-acting beta(2)-adrenergic agonists (LABAs) alone or with inhaled corticosteroids (ICSs). The purpose of this study was to examine the long-term safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI). This 52-week, double-blind study (SD-039-0728; n=708) included patients >or=12 years of age with moderate to severe persistent asthma previously receiving ICSs. After 2 weeks on budesonide pMDI 320 microg twice daily (b.i.d.), patients were randomized 3:1:1 overall to budesonide/formoterol pMDI 640/18 microg b.i.d., budesonide/formoterol pMDI 320/9 microg b.i.d., or budesonide pMDI 640 microg b.i.d. The incidence of adverse events (AEs) was similar across the groups. Drug-related AEs (>or=2% overall) were oral candidiasis, tremor, and pharyngolaryngeal pain. No clinically meaningful differences in laboratory, electrocardiogram, or Holter monitor variables were observed. The percentage of patients with >or=1 asthma exacerbation was significantly lower (p=0.006) with budesonide/formoterol 640/18 (12.2%) and numerically lower with budesonide/formoterol 320/9 (14.4%) versus budesonide (21.8%). The number of asthma exacerbations per patient-treatment year was lower with budesonide/formoterol 640/18 (0.174; p=0.004) and budesonide/formoterol 320/9 (0.185; p=0.049) versus budesonide (0.315). Improvements in forced expiratory volume in 1 second and diary variables were significantly greater (p<0.001) with both budesonide/formoterol doses versus budesonide. Budesonide/formoterol 640/18 and 320/9 microg b.i.d. showed an acceptable safety profile relative to budesonide, with no significant or unexpected patterns of abnormalities observed by adding a LABA to budesonide for up to 1 year in this patient population. Improvements in asthma control were shown with both doses of budesonide/formoterol versus budesonide.
对于单独或与吸入性糖皮质激素（ICS）联合长期使用长效β₂肾上腺素能激动剂（LABA），人们已提出安全性担忧。本研究的目的是考察布地奈德/福莫特罗压力定量吸入气雾剂（pMDI）的长期安全性。这项为期52周的双盲研究（SD - 039 - 0728；n = 708）纳入了年龄≥12岁、中度至重度持续性哮喘且之前接受ICS治疗的患者。在使用布地奈德pMDI 320μg每日两次（b.i.d.）治疗2周后，患者总体按3:1:1随机分组，分别接受布地奈德/福莫特罗pMDI 640/18μg b.i.d.、布地奈德/福莫特罗pMDI 320/9μg b.i.d.或布地奈德pMDI 640μg b.i.d.治疗。各治疗组不良事件（AE）的发生率相似。与药物相关的AE（总体发生率≥2%）为口腔念珠菌病、震颤和咽喉疼痛。在实验室检查、心电图或动态心电图监测指标方面未观察到具有临床意义的差异。与布地奈德组（21.8%）相比，布地奈德/福莫特罗640/18组（12.2%）发生≥1次哮喘加重的患者百分比显著更低（p = 0.006），布地奈德/福莫特罗320/9组（14.4%）在数值上更低。与布地奈德组（0.315）相比，布地奈德/福莫特罗640/18组（0.174；p = 0.004）和布地奈德/福莫特罗320/9组（0.185；p = 0.049）每位患者每年哮喘加重的次数更低。与布地奈德相比，两种布地奈德/福莫特罗剂量组的第1秒用力呼气量和日记变量方面的改善均显著更大（p < 0.001）。相对于布地奈德，布地奈德/福莫特罗640/18和320/9μg b.i.d.显示出可接受的安全性，在该患者群体中，布地奈德加用LABA长达1年未观察到显著或意外的异常模式。与布地奈德相比，两种剂量的布地奈德/福莫特罗均显示出哮喘控制的改善。
