应用布地奈德福莫特罗作为缓解药物对哮喘急性加重作用的随机双盲对照研究
2007/06/27
Rabe等为了观察按需吸入激素和长效 β2受体激动剂（LABA）对哮喘控制的影响，在20个国家的289个中心进行了一项为期12个月的随机双盲对照研究。在此研究中比较了应用三种药物进行缓解治疗的有效性：传统的短效 β2受体激动剂（特布他林0.4mg），一种快速起效的LABA（福莫特罗4.5mg），以及LABA和吸入激素的联合制剂（布地奈德福莫特罗剂量分别为160mg，4.5mg ）。共纳入3394名患者（年龄大于等于12岁），受试者已经应用布地奈德福莫特罗（剂量分别为160mg，4.5mg）1喷，Bid维持治疗，但在2周的导入期中仍有哮喘症状，导入期结束后患者仍然规律应用布地奈德福莫特罗，同时随机应用三种药物之一缓解治疗。所有患者主要终点指标为出现第一次严重加重的间隔时间，严重加重定义为导致住院，和／或急诊就诊或口服糖皮质激素超过3天。
结果表明按需应用布地奈德福莫特罗组出现第一次严重发作的间隔时间最长。特布他林组，福莫特罗组，布地奈德福莫特罗组一年内出现严重急性加重的患者比例分别为37％，295，19％。但三组之间哮喘控制天数没有明显差异，按需应用布地奈德福莫特罗并没有改善患者症状。
作者认为在规律应用布地奈德福莫特罗规律治疗的基础上按需应用此联合制剂可减少患者严重急性发作。
但在这一研究中即使是按需应用布地奈德福莫特罗组哮喘未控制天数也在60％，夜间出现症状的次数也大于每周1次，其病情没有得到良好的控制。同时该研究未纳入按需吸入激素组或按照GINA建议加大维持治疗剂量组，因此还不适宜大规模推广。
（马艳良 北京大学人民医院呼吸科 100044 摘译）
( Lancet. 2006;368:744-753 )
Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled,double-blind study.
Rabe KF, Atienza T, Magyar P, Larsson P, Jorup C, Lalloo UG.
Lancet. 2006 Aug 26;368(9537):744-53.
BACKGROUND: The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy.
METHODS: We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or
more.
FINDINGS: Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated.
INTERPRETATION: Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.
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怀孕前3个月的哮喘患者吸入糖皮质激素致胎儿先天畸形的危险度分析
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不同 “降阶梯治疗”战略在轻度持续性哮喘中的应用
