苯二氮䓬类药物使用与哮喘患者病情加重及死亡率之间的关联：一项使用英国临床实践研究数据链的配对病例对照和生存分析。

Association between benzodiazepine use and exacerbations and mortality in patients with asthma: a matched case-control and survival analysis using the United Kingdom Clinical Practice Research Datalink.

作者信息

Nakafero Georgina, Sanders Robert D, Nguyen-Van-Tam Jonathan S, Myles Puja R

机构信息

Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.

Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.

出版信息

Pharmacoepidemiol Drug Saf. 2015 Aug;24(8):793-802. doi: 10.1002/pds.3799. Epub 2015 May 27.

DOI:10.1002/pds.3799

PMID:26013409

Abstract

PURPOSE

To investigate the association between the gamma-aminobutyric acid (GABA)ergic drugs, benzodiazepines or zopiclone and the occurrence of asthma exacerbations and subsequent mortality in a cohort of asthma patients.

METHODS

The number of patients that were included were 105,747 for those without asthma exacerbation and 25,895 for those with exacerbated asthma. A nested case-control study probed the association between benzodiazepines or zopiclone and occurrence of asthma exacerbation (primary outcome) using conditional logistic regression. Cox regression was used to determine the association between the drugs and all-cause mortality in patients with recorded asthma exacerbation. Adjusted matched odds ratios (adj mOR) and adjusted hazard ratios (adj HR) with 95% confidence intervals (CI) are presented.

RESULTS

Current benzodiazepine use was associated with increased occurrence of asthma exacerbation (adj mOR 1.49; 95%CI [1.15, 1.93]; P = 0.001) as was current zopiclone use (adj mOR 1.59; 95%CI [1.37, 1.85]; P < 0.001). In patients with an asthma exacerbation, current benzodiazepine use was associated with increased all-cause mortality during a median follow-up of 2 years (adj HR 2.78; 95%CI [1.26, 6.12]; P = 0.011), and the association between zopiclone use and all-cause mortality showed borderline statistical significance (adj HR 1.58; 95%CI [0.98, 2.54]; P = 0.058).

CONCLUSION

Benzodiazepines and zopiclone may increase the likelihood of asthma exacerbation, and benzodiazepines may also increase the likelihood of mortality following exacerbation. These data suggest that caution should be exercised when prescribing benzodiazepines to patients with asthma.

摘要

目的

在一组哮喘患者中，研究γ-氨基丁酸（GABA）能药物、苯二氮䓬类药物或佐匹克隆与哮喘急性加重的发生及随后死亡率之间的关联。

方法

未发生哮喘急性加重的患者有105747例，发生哮喘急性加重的患者有25895例。一项巢式病例对照研究采用条件逻辑回归探究苯二氮䓬类药物或佐匹克隆与哮喘急性加重的发生（主要结局）之间的关联。Cox回归用于确定这些药物与有哮喘急性加重记录患者的全因死亡率之间的关联。给出了调整后的匹配比值比（adj mOR）和调整后的风险比（adj HR）及95%置信区间（CI）。

结果

当前使用苯二氮䓬类药物与哮喘急性加重发生率增加相关（adj mOR 1.49；95%CI [1.15, 1.93]；P = 0.001），当前使用佐匹克隆也是如此（adj mOR 1.59；95%CI [1.37, 1.85]；P < 0.001）。在哮喘急性加重的患者中，在中位随访2年期间，当前使用苯二氮䓬类药物与全因死亡率增加相关（adj HR 2.78；95%CI [1.26, 6.12]；P = 0.011），并且使用佐匹克隆与全因死亡率之间的关联显示出临界统计学意义（adj HR 1.58；95%CI [0.98, 2.54]；P = 0.058）。