St. Louis College of Pharmacy, St. Louis, MO, USA.
Ann Pharmacother. 2013 May;47(5):704-13. doi: 10.1345/aph.1R641. Epub 2013 Apr 23.
To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma.
A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics.
Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not.
Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified.
Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.
综述长效抗胆碱能药物噻托溴铵在哮喘患者中的临床应用数据。
通过 EMBASE 和 MEDLINE（1966 年-2012 年 11 月）进行文献检索。检索仅限于发表在英文期刊上的人类数据。检索词包括哮喘、噻托溴铵和长效抗胆碱能药物。
对噻托溴铵在哮喘患者中的应用相关信息进行了综述。纳入了随机对照试验和开放标签试验。还对检索到的已发表文章的参考文献进行了检查，以寻找其他适合纳入综述的研究。如果数据来源于人类研究，特别是来源于随机、安慰剂对照试验，则优先考虑。纳入了涉及哮喘患者使用长效抗胆碱能药物噻托溴铵的试验和病例报告；相反，不纳入涉及异丙托溴铵的试验。
两项大型随机对照试验支持了在已接受联合高剂量糖皮质激素/长效β激动剂（LABA）治疗但哮喘控制仍不佳的特定患者中，加用噻托溴铵治疗方案的安全性和有效性。药物基因组学研究表明，β2-肾上腺素能受体（ADRB2；16 Arg/Arg 和 16 Arg/Gly）多态性的患者对噻托溴铵治疗特别敏感。较小的研究表明，该优势在痰液中性粒细胞占优势的患者中更为显著，并且噻托溴铵可以协助减少吸入性皮质激素（ICS）的剂量。未发现心血管事件风险增加。
噻托溴铵应考虑用于接受高剂量 ICS 和 LABA 治疗后仍有症状的哮喘患者。具体而言，痰液中性粒细胞水平较高或 ADRB2 基因 16 Arg/Arg 或 16 Arg/Gly 多态性的患者似乎反应最好。
