Mullen M, Mullen B, Carey M
American Lung Association of Central New York, Syracuse 13217-6409.
JAMA. 1993 Oct 20;270(15):1842-5.
The purpose of this investigation was to provide an empirical summary of the evidence regarding the association between beta-agonist use and death from asthma. This effort integrated the results of case-control studies that examined the use of beta-agonists among asthmatic patients who died and the use of beta-agonists among asthmatic patients who did not die. The possible moderating effects of patient sample age and mode of delivery (oral, metered-dose inhaler, and nebulizer) were also examined.
An on-line computer search (using MEDLINE) was conducted using the key words beta-agonist and asthma. This search was supplemented by ancestry and descendency approach searches. Studies that were available as of April 1992 were eligible for inclusion in this integration.
Studies were included if they reported the precise numbers of cases and controls who did and did not use a beta-agonist. A total of six case-control studies comprising 15 separate tests of the relation between beta-agonist use and death from asthma and data for 364 cases and 1388 controls were included.
The 2 (case vs control) x 2 (did vs did not use beta-agonist) designs allowed for direct derivation of a chi 2 statistic that tested the association between beta-agonist use and death from asthma. Mode of delivery and average age of sample were also coded.
Statistical integration revealed a significant, although extremely weak, relation between beta-agonist use and death from asthma (z = 3.996; P = .000075; mean r = .055). This relation emerged only when beta-agonists were administered with a nebulizer (z = 4.481; P = .0000038; mean r = .103). There was no association between beta-agonist use and death when beta-agonists were administered by metered-dose inhaler (z = 1.194; P = .11; mean r = .031) or orally (z = 1.247; P = .1; mean r = .031). Adults were more likely than adolescents to evidence the association between beta-agonist use and death.
These results document the extremely small magnitude of the relation between beta-agonist use and death from asthma. Furthermore, these results specify that the weak relation between beta-agonist use and death from asthma may really be restricted to the delivery of beta-agonists with a nebulizer. These findings suggest that the headlines that followed the report by Spitzer et al (1992) were misleading.
本调查旨在对β受体激动剂使用与哮喘死亡之间关联的证据进行实证总结。这项工作整合了病例对照研究的结果，这些研究考察了哮喘死亡患者中β受体激动剂的使用情况以及未死亡哮喘患者中β受体激动剂的使用情况。还研究了患者样本年龄和给药方式（口服、定量吸入器、雾化器）可能产生的调节作用。
使用关键词β受体激动剂和哮喘进行在线计算机检索（使用MEDLINE）。通过追溯和延伸检索方法对该检索进行补充。截至1992年4月可获取的研究有资格纳入本整合研究。
若研究报告了使用和未使用β受体激动剂的病例与对照的确切数量，则纳入该研究。总共纳入了六项病例对照研究，包括对β受体激动剂使用与哮喘死亡之间关系的15项独立测试，以及364例病例和1388例对照的数据。
2（病例与对照）×2（使用与未使用β受体激动剂）设计允许直接得出检验β受体激动剂使用与哮喘死亡之间关联的卡方统计量。给药方式和样本平均年龄也进行编码处理。
统计整合显示，β受体激动剂使用与哮喘死亡之间存在显著关联，尽管极其微弱（z = 3.996；P = 0.000075；平均r = 0.055）。仅当使用雾化器给药β受体激动剂时，这种关联才显现出来（z = 4.481；P = 0.0000038；平均r = 0.10）。当通过定量吸入器给药β受体激动剂时（z = 1.194；P = 0.11；平均r = 0.031）或口服给药时（z = 1.247；P = 0.1；平均r = 0.031），β受体激动剂使用与死亡之间无关联。成年人比青少年更有可能证明β受体激动剂使用与死亡之间的关联。
这些结果证明了β受体激动剂使用与哮喘死亡之间的关联极其微小。此外，这些结果表明，β受体激动剂使用与哮喘死亡之间的微弱关联可能实际上仅限于通过雾化器给药的情况。这些发现表明，斯皮策等人（1992年）报告后出现的头条新闻具有误导性。
