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茚达特罗:全面综述。

Indacaterol: a comprehensive review.

机构信息

Pulmonary Unit, Cardiovascular and Thoracic Department, University and General Hospital, Verona, Italy.

出版信息

Int J Chron Obstruct Pulmon Dis. 2013;8:353-63. doi: 10.2147/COPD.S21625. Epub 2013 Jul 25.

Abstract

At present there is no cure for chronic obstructive pulmonary disease (COPD). However, some nonpharmacologic treatments, such as rehabilitation and lung volume reduction surgery, as well as pharmacologic intervention, can relieve some of the patient's symptoms and improve quality of life, while also reducing the rate of exacerbations and hospitalizations. There needs to be a paradigm shift away from the unjustified nihilistic approach to COPD towards considering it a preventable and treatable disease. After patients quit smoking and start to lead healthier lifestyles, long-acting bronchodilators, such as long-acting beta-adrenergic agents (LABA) and long-acting antimuscarinic agents (LAMA), are recommended as the cornerstone of treatment for COPD, either as monotherapy or in combination. COPD is characterized by a reduced maximum expiratory flow and slow forced emptying of the lungs, which progress over time and are not completely reversible. In this condition, gas gets trapped in the lungs and pulmonary hyperinflation occurs. LABA and LAMA improve airway patency and deflate the lungs. Indacaterol is the first once-daily LABA approved for treatment of COPD, and is administered by inhalation through the Breezhaler® device. The speed of bronchodilation is similar to that with salbutamol (ie, about five minutes) and longer (ie, 24 hours) than that with traditional LABA, with the same 12-hour effect as salmeterol and formoterol, both of which require twice-daily administration. This is why indacaterol has been called the "ultra-LABA". On the one hand, the fast onset of action provides immediate relief of symptoms, and on the other, its constant 24-hour bronchodilation provides "pharmacologic stenting" which facilitates lung emptying, thereby decreasing trapped gas and pulmonary hyperinflation. Once-daily administration of a fast and long-acting bronchodilator can improve patient adherence with therapy, which is known to be a major problem for many medical treatments. Dose-finding trials have shown that 75 μg is the minimum dose needed to achieve clinically important improvement. However, indacaterol 150 μg and 300 μg achieve an even greater improvement in lung function and patient-oriented outcomes. Further, these two doses of indacaterol significantly reduce pulmonary hyperinflation, thereby improving exercise tolerance and ability to perform day-to-day activities. It is more effective on lung volumes at the 300 μg dose than formoterol, and better than salmeterol and tiotropium at the 150 μg dose, at least in the acute setting. It is noteworthy that few studies document these results in patients with COPD and moderate airflow obstruction. These are exactly the kind of patients our research should be concentrating on, in view of the accelerated decay in forced expiratory volume in one second at this stage of the disease. Finally, all the relevant studies show that indacaterol is consistently well tolerated by patients with COPD at every stage, and that it has a high safety profile.

摘要

目前,慢性阻塞性肺疾病(COPD)还无法治愈。然而,一些非药物治疗,如康复和肺减容手术,以及药物干预,可以缓解患者的一些症状,提高生活质量,同时降低恶化和住院的几率。我们需要从对 COPD 不合理的消极态度转变为认为它是一种可预防和可治疗的疾病。患者戒烟并开始过上更健康的生活方式后,长效支气管扩张剂,如长效β-激动剂(LABA)和长效抗胆碱能药物(LAMA),被推荐作为 COPD 治疗的基石,无论是单独使用还是联合使用。COPD 的特点是最大呼气流量降低和肺部缓慢排空,这些情况会随着时间的推移而进展,且无法完全逆转。在这种情况下,气体会被困在肺部,导致肺部过度充气。LABA 和 LAMA 可以改善气道通畅性并排空肺部。茚达特罗是第一种被批准用于治疗 COPD 的每日一次 LABA,通过 Breezhaler®装置吸入给药。支气管扩张的速度与沙丁胺醇相似(即大约 5 分钟),但持续时间更长(即 24 小时),比传统的 LABA 持续时间更长(即 24 小时),与需要每日两次给药的沙美特罗和福莫特罗的 12 小时作用相同。这就是为什么茚达特罗被称为“超长效 LABA”。一方面,其快速起效可以立即缓解症状,另一方面,其持续 24 小时的支气管扩张作用可以提供“药物支架”,促进肺部排空,从而减少被困气体和肺部过度充气。每日一次给予快速长效支气管扩张剂可以提高患者对治疗的依从性,这是许多医疗治疗的一个主要问题。剂量探索试验表明,75μg 是达到临床重要改善所需的最小剂量。然而,茚达特罗 150μg 和 300μg 可显著改善肺功能和以患者为中心的结局。此外,这两种剂量的茚达特罗可显著减轻肺部过度充气,从而提高运动耐量和日常活动能力。在 300μg 剂量时,它对肺容积的作用优于福莫特罗,在 150μg 剂量时,它优于沙美特罗和噻托溴铵,至少在急性情况下是这样。值得注意的是,很少有研究在 COPD 合并中度气流阻塞患者中记录这些结果。鉴于疾病的这一阶段,第一秒用力呼气量的衰减速度加快,这些正是我们的研究应该关注的患者类型。最后,所有相关研究都表明,茚达特罗在 COPD 患者的各个阶段都能被很好地耐受,且安全性良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c65e/3728154/d86e8d243015/copd-8-353Fig1.jpg

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