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哮喘与慢性阻塞性肺疾病治疗进展:吸入性糖皮质激素与长效β2受体激动剂联合治疗

Advances in asthma and COPD treatment: combination therapy with inhaled corticosteroids and long-acting beta 2-agonists.

作者信息

Miller-Larsson A, Selroos O

机构信息

Medical Science, AstraZeneca R &D, 221 87 Lund, Sweden.

出版信息

Curr Pharm Des. 2006;12(25):3261-79. doi: 10.2174/138161206778194187.

Abstract

Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone, thereby addressing two processes fundamental to asthma: bronchoconstriction and inflammation. Superior control--including a reduction in severe exacerbations--of asthma and COPD by ICS/LABA combination therapy has been demonstrated. Results from clinical studies suggest additive and potentially synergistic effects when the two agents are used in combination. No new safety-related issues have been identified with ICS/LABA compared with the monocomponents. The exact mechanisms for the enhanced efficacy of ICS/LABA combinations are under investigation but likely include drug interactions at the receptor level and interwoven signalling pathways, which may result in improved function of 2- adrenoceptors and steroid receptors. Data from preclinical studies provide evidence of additive, compensatory, complementary and synergistic effects of ICS and LABA in the control of inflammation and airway and lung remodelling. These effects may contribute to the improved efficacy seen when treating asthma and COPD with ICS/LABA combinations in clinical studies. Two ICS/LABA combination products are available: budesonide/formoterol (Symbicort) and salmeterol/fluticasone propionate (SeretideTM). An ICS/LABA combination in a single inhaler represent safe, effective and convenient treatment options for the management of patients with asthma and COPD. Clinical results also suggest that adjustable dosing with budesonide/formoterol provides better asthma control than fixed dosing. Further elucidation of the underlying mechanisms responsible for this superior disease control is needed.

摘要

哮喘治疗指南提倡,对于仅使用吸入性糖皮质激素(ICS)无法控制哮喘的患者,除使用ICS外还应加用长效β2受体激动剂(LABA),从而解决哮喘的两个基本病理过程:支气管收缩和炎症。已证实,ICS/LABA联合治疗能更好地控制哮喘和慢性阻塞性肺疾病(COPD),包括减少严重急性加重发作。临床研究结果表明,两种药物联合使用具有相加作用,且可能有协同效应。与单一成分相比,未发现ICS/LABA有新的安全相关问题。ICS/LABA联合使用疗效增强的确切机制正在研究中,但可能包括受体水平的药物相互作用和相互交织的信号通路,这可能导致β2肾上腺素能受体和类固醇受体功能改善。临床前研究数据证明了ICS和LABA在控制炎症、气道及肺重塑方面具有相加、代偿、互补和协同效应。这些效应可能有助于解释临床研究中使用ICS/LABA联合治疗哮喘和COPD时疗效改善的原因。有两种ICS/LABA联合制剂可供使用:布地奈德/福莫特罗(信必可)和沙美特罗/丙酸氟替卡松(舒利迭)。单一吸入器中的ICS/LABA联合制剂是治疗哮喘和COPD患者安全、有效且便捷的选择。临床结果还表明,布地奈德/福莫特罗的可调节剂量比固定剂量能更好地控制哮喘。需要进一步阐明导致这种更好疾病控制效果的潜在机制。

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