Westby M, Benson M, Gibson P
UK Cochrane Centre, Summertown Pavilion, Middle Way, Oxford, Oxfordshire, UK, OX2 7LG.
Cochrane Database Syst Rev. 2004;2004(3):CD003269. doi: 10.1002/14651858.CD003269.pub2.
Anticholinergic agents such as ipratropium bromide are sometimes used in the treatment of chronic asthma. They effect bronchodilation and have also been used in combination with beta2-agonists in the management of chronic asthma.
To examine the effectiveness of anticholinergic agents versus placebo and in comparison with beta2-agonists or as adjunctive therapy to beta2-agonists.
The Cochrane Airways Group asthma and wheeze database was searched with a pre-defined search strategy. Searches were current as of August 2003. Reference lists of articles were also examined.
Randomised trials or quasi-randomised trials were considered for inclusion. Studies assessing an anticholinergic agent versus placebo or in combination/comparison with beta2-agonists were included. In practice, all beta2-agonists were short acting. Short-term (less than 24 hours duration) and longer-term studies were separated; the latter are reported in this review and the former in the review, "Anticholinergic agents for chronic asthma in adults short term".
Two reviewers independently assessed abstracts for retrieval of full text articles. Papers were then assessed for suitability for inclusion in the review. Data from included studies were extracted by two reviewers and entered into the software package (RevMan 4.2). We contacted authors for missing data and some responded. Adverse effect data were analysed if reported in the included studies.
The studies analysed were in two groups: those comparing anticholinergics with placebo and those comparing the combination of anticholinergics with short acting beta2-agonists versus short acting beta2-agonists alone. The former group had 13 studies involving 205 participants included in this review, and the latter 9 studies involving 440 patients. Generally methodological quality was poorly reported, and there were some reservations with respect to the quality of the studies. Despite the limited number of studies that could be combined, anticholinergic agents in comparison with placebo resulted in more favourable symptom scores particularly in respect of daytime dyspnoea (WMD -0.09 (95%CI -0.14, -0.04, 3 studies, 59 patients). Daily peak flow measurements also showed a statistically significant improvement for the anticholinergic (e.g. morning PEF: WMD =14.38 litres/min (95%CI 7.69, 21.08; 3 studies, 59 patients). However the clinical significance is small and in terms of peak flow measurements equates to approximately a 7% increase over placebo. The more clinically relevant comparison of a combination of anticholinergic plus short acting beta2-agonist versus short acting beta2-agonist alone gave no evidence in respect of symptom scores or peak flow rates of any significant differences between the two regimes. Again there are reservations with respect to the quality of the information from which these conclusions are drawn.
REVIEWERS' CONCLUSIONS: Overall this review provides no justification for routinely introducing anticholinergics as part of add-on treatment for patients whose asthma is not well controlled on standard therapies. This does not exclude the possibility that there may be a sub-group of patients who derive some benefit and a trial of treatment in individual patients may still be justified. The role of long term anticholinergics such as tiotropium bromide has yet to be established in patients with asthma and any future trials might draw on the messages derived from this review.
抗胆碱能药物如异丙托溴铵有时用于治疗慢性哮喘。它们可引起支气管扩张,也已与β2激动剂联合用于慢性哮喘的治疗。
考察抗胆碱能药物与安慰剂相比的有效性,以及与β2激动剂相比或作为β2激动剂辅助治疗的有效性。
采用预定义的检索策略检索Cochrane气道组哮喘与喘息数据库。检索截至2003年8月的文献。同时也查阅了文章的参考文献列表。
纳入随机试验或半随机试验。纳入评估抗胆碱能药物与安慰剂相比,或与β2激动剂联合/比较的研究。实际上,所有β2激动剂均为短效。短期(持续时间少于24小时)和长期研究分开;本综述报道后者,前者在“抗胆碱能药物用于成人慢性哮喘短期治疗”综述中报道。
两名评价者独立评估摘要以检索全文文章。然后评估论文是否适合纳入本综述。两名评价者提取纳入研究的数据并录入软件包(RevMan 4.2)。我们与作者联系索要缺失数据,部分作者给予了回复。若纳入研究报告了不良反应数据,则进行分析。
分析的研究分为两组:一组是比较抗胆碱能药物与安慰剂,另一组是比较抗胆碱能药物与短效β2激动剂联合用药与单独使用短效β2激动剂。前一组有13项研究,本综述纳入205名参与者,后一组有9项研究,涉及440名患者。总体而言,方法学质量报告不佳,对研究质量存在一些保留意见。尽管可合并的研究数量有限,但与安慰剂相比,抗胆碱能药物可使症状评分更有利。尤其是在日间呼吸困难方面(加权均数差 -0.0 [95%置信区间 -0.14, -0.04];3项研究,59名患者)。每日峰值呼气流速测量也显示抗胆碱能药物有统计学显著改善(例如早晨呼气峰流速:加权均数差 =14.38升/分钟 [95%置信区间 7.69, 21.08];3项研究,59名患者)。然而,临床意义较小,就峰值呼气流速测量而言,比安慰剂组约增加7%。抗胆碱能药物加短效β2激动剂联合用药与单独使用短效β2激动剂这一更具临床相关性的比较,在症状评分或峰值流速方面未显示两种治疗方案之间有任何显著差异。同样,对于得出这些结论所依据的信息质量也存在保留意见。
总体而言,本综述没有理由将抗胆碱能药物作为常规添加治疗用于哮喘在标准治疗下控制不佳的患者。这并不排除可能有一部分患者会从中获益,对个别患者进行治疗试验可能仍然合理。长效抗胆碱能药物如噻托溴铵在哮喘患者中的作用尚未确立,未来的任何试验可能会借鉴本综述得到的信息。