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毒蕈碱拮抗剂在哮喘治疗中的作用。

Role of muscarinic antagonists in asthma therapy.

作者信息

Cazzola Mario, Ora Josuel, Rogliani Paola, Matera Maria Gabriella

机构信息

a Chair of Respiratory Medicine, Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.

b Division of Respiratory Medicine, Department of Internal Medicine , University Hospital Tor Vergata , Rome , Italy.

出版信息

Expert Rev Respir Med. 2017 Mar;11(3):239-253. doi: 10.1080/17476348.2017.1289844. Epub 2017 Feb 9.

DOI:10.1080/17476348.2017.1289844
PMID:28140686
Abstract

Higher parasympathetic tone has been reported in asthmatics. In general, cholinergic contractile tone is increased by airway inflammation associated with asthma. Nevertheless, the role of muscarinic antagonists for the treatment of asthma has not yet been clearly defined. Areas covered: The use of SAMAs and LAMAs in asthma has been examined and discussed according with the published evidence. Particular attention has been given to the large Phase III clinical trial program designed to evaluate the efficacy and safety of tiotropium respimat added to standard treatment in adults, adolescents and children with persistent asthma across the spectrum of asthma severity. Expert commentary: The current evidence is that in patients with poorly controlled severe asthma despite the use of ICS and LABA, the addition of tiotropium significantly increases the time to the first severe exacerbation and provides a modest but sustained bronchodilation. Identical results should be produced using other LAMAs. In any case, the documentation that, at least in animal or in vitro models, LAMAs show significant anti-inflammatory and anti-proliferative capacities and are able to inhibit airway remodeling induced by allergens makes a strong presumption that the use of LAMAs in asthma may go beyond the simple bronchodilator effect.

摘要

据报道,哮喘患者的副交感神经张力较高。一般来说,与哮喘相关的气道炎症会增加胆碱能收缩张力。然而,毒蕈碱拮抗剂在哮喘治疗中的作用尚未明确界定。涵盖领域:根据已发表的证据,对短效抗胆碱能药物(SAMAs)和长效抗胆碱能药物(LAMAs)在哮喘中的应用进行了研究和讨论。特别关注了一项大型III期临床试验项目,该项目旨在评估噻托溴铵软雾吸入剂添加到标准治疗方案中,对不同哮喘严重程度的成人、青少年和儿童持续性哮喘患者的疗效和安全性。专家评论:目前的证据表明,在尽管使用了吸入性糖皮质激素(ICS)和长效β2受体激动剂(LABA)但控制不佳的重度哮喘患者中,添加噻托溴铵可显著延长首次严重加重的时间,并提供适度但持续的支气管扩张作用。使用其他长效抗胆碱能药物也应产生相同的结果。无论如何,至少在动物或体外模型中,长效抗胆碱能药物显示出显著的抗炎和抗增殖能力,并能够抑制变应原诱导的气道重塑,这一证据有力地推测,长效抗胆碱能药物在哮喘中的应用可能不仅仅局限于单纯的支气管扩张作用。

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