Spitzer W O, Suissa S, Ernst P, Horwitz R I, Habbick B, Cockcroft D, Boivin J F, McNutt M, Buist A S, Rebuck A S
Department of Epidemiology and Biostatistics, Montreal General Hospital, Canada.
N Engl J Med. 1992 Feb 20;326(8):501-6. doi: 10.1056/NEJM199202203260801.
Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators.
Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma.
The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol.
An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.
哮喘的发病率和死亡率似乎在上升，有人认为用于治疗哮喘的药物促成了这一趋势。我们调查了哮喘死亡或濒死与常规使用β2受体激动剂支气管扩张剂之间可能存在的关联。
利用加拿大萨斯喀彻温省的联合医疗保险数据库，我们对从1978年至1987年间开具哮喘药物处方的12301名患者队列中抽取的受试者进行了匹配病例对照研究。我们将129例有致命或濒死哮喘的病例患者与655名对照者（接受过哮喘药物治疗但未发生致命或濒死事件）在居住地区、年龄、接受社会救助情况以及既往因哮喘住院情况方面进行了匹配。
使用定量吸入器给予β受体激动剂与哮喘死亡风险增加相关（比值比，每月每罐2.6；95%置信区间，1.7至3.9），以及与哮喘死亡或濒死综合情况相关（比值比，1.9；95%置信区间，1.6至2.4）。对于哮喘死亡，使用β受体激动剂非诺特罗的比值比为每罐5.4，而β受体激动剂沙丁胺醇为2.4。以微克当量为基础，非诺特罗此结果的比值比为2.3，而沙丁胺醇为2.4。
哮喘死亡或濒死风险增加与常规使用吸入性β2受体激动剂支气管扩张剂相关，尤其是非诺特罗。无论β受体激动剂是否直接导致这些不良反应，或者仅仅是更严重哮喘的一个标志，大量使用这些药物都应提醒临床医生有必要重新评估患者的病情。
