David Geffen School of Medicine, Division of Pulmonary and Critical Care Medicine, UCLA, Los Angeles, California, USA.
Respir Res. 2010 Oct 29;11(1):149. doi: 10.1186/1465-9921-11-149.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients.
慢性阻塞性肺疾病（COPD）的特征是进行性气流受限和衰弱症状。对于中重度 COPD 患者，长效支气管扩张剂是治疗的主要手段；随着症状的进展，指南建议将来自不同类别的支气管扩张剂联合使用以提高疗效。吸入长效β2-激动剂（LABA）自 20 世纪 90 年代末以来已被批准用于 COPD 的治疗，包括福莫特罗和沙美特罗。它们改善肺功能、呼吸困难症状和运动受限、健康相关生活质量，并且可能降低恶化的发生率，尽管并非所有患者在症状或健康相关生活质量方面都取得了有临床意义的改善。此外，LABA 具有可接受的安全性，并且与呼吸死亡率增加无关，尽管心悸和震颤等不良反应可能限制可耐受的剂量。福莫特罗和沙美特罗的作用持续时间为 12 小时；然而，在 COPD 中需要持续支气管扩张。作用持续时间为 24 小时的 LABA 与每日两次的 LABA 相比，可能在疗效方面有所改善，而每日一次的给药方案可能有助于提高依从性。新的 LABA 还应具有快速起效的特点，安全性至少与现有的 LABA 相当。目前正在开发具有每日一次作用谱的多种新型 LABA，可能会根据这些标准进行评估。具有 24 小时支气管扩张作用和快速起效的 LABA 茚达特罗是这些药物中最先进的。来自大型临床试验的初步结果表明，茚达特罗可改善肺功能，与安慰剂和其他长效支气管扩张剂相比。具有 24 小时支气管扩张作用的其他 LABA 包括卡莫特罗、维兰特罗三苯乙酸酯和奥达特罗，早期结果表明人类有可能每日一次给药。每日一次 LABA 的引入也为开发两种或更多类别的每日一次长效支气管扩张剂的联合吸入剂提供了机会，通过简化治疗方案以及提高疗效，这可能对 COPD 患者有益。单独使用和与长效抗毒蕈碱拮抗剂联合使用的每日一次 LABA 代表了 COPD 治疗的一个有前途的进展，并且可能会进一步改善患者的结局。
