Rea H H, Garrett J E, Lanes S F, Birmann B M, Kolbe J
Respiratory Services, Green Lane Hospital, Auckland, New Zealand.
Chest. 1996 Dec;110(6):1446-51. doi: 10.1378/chest.110.6.1446.
To measure the association between asthma drugs and death or ICU admission due to asthma (severe life-threatening attack of asthma [SLTA]), and to assess the possibility that these associations may not be causal but due to the prescription of these drugs to patients with more severe disease (confounding).
Retrospective cohort study of 655 asthmatics who attended an emergency department in 1986 to 1987 followed till death or May 1989.
Outcome events were death or ICU admission due to asthma (SLTA). All hospital attendances were identified and patients classified at each according to drug exposure and a wide variety of measures of asthma severity. Incidence rates were computed as total outcome events divided by person-time contributed for each subject classified according to drug use and asthma severity. Rate ratio (RR) estimates for severe asthma outcomes associated with use as compared to nonuse of asthma drugs were calculated. Severity markers were identified and used to adjust the crude RR estimates.
One hundred five SLTAs (15 deaths, 90 ICU admissions) occurred in 66 patients. Like inhaled fenoterol, oral beta-agonists, theophylline, cromolyn, inhaled steroids, and oral steroids were all associated with an increased risk of SLTA. When adjusted progressively for measures of severity, these increased risks became insignificant except for cromolyn.
Unadjusted RR estimates for severe asthma events comparing exposure to a particular drug with nonuse are overestimates due to confounding. Control with two severity markers (hospital admission in the last year, use of oral corticosteroid at the time of previous admission) removes some confounding but control for additional severity markers not available in previous studies reduces the effect estimates further. These results suggest that the problem of confounding is substantial in nonrandomized epidemiologic studies of asthma drugs. Previous studies reporting RR estimates are likely to be confounded.
测定哮喘药物与因哮喘导致的死亡或入住重症监护病房（严重危及生命的哮喘发作[SLTA]）之间的关联，并评估这些关联可能并非因果关系而是由于将这些药物用于病情更严重的患者（混杂因素）的可能性。
对1986年至1987年到急诊科就诊并随访至死亡或1989年5月的655名哮喘患者进行回顾性队列研究。
结局事件为因哮喘（SLTA）导致的死亡或入住重症监护病房。确定所有的医院就诊情况，并根据药物暴露情况以及多种哮喘严重程度指标对每位患者进行分类。发病率计算为总结局事件数除以根据药物使用和哮喘严重程度分类的每个受试者的人时。计算与使用哮喘药物相比未使用哮喘药物时严重哮喘结局的率比（RR）估计值。确定严重程度标志物并用于调整粗RR估计值。
66名患者发生了105次SLTA（15例死亡，90例入住重症监护病房）。与吸入用非诺特罗、口服β受体激动剂、茶碱、色甘酸钠、吸入性糖皮质激素和口服糖皮质激素一样，所有这些药物都与SLTA风险增加有关。在逐步根据严重程度指标进行调整后，除色甘酸钠外，这些增加的风险变得不显著。
由于混杂因素，将接触特定药物与未接触进行比较时，未调整的严重哮喘事件RR估计值会高估。用两个严重程度标志物（去年住院、上次入院时使用口服糖皮质激素）进行对照可消除一些混杂因素，但对先前研究中未有的其他严重程度标志物进行对照可进一步降低效应估计值。这些结果表明，在哮喘药物的非随机流行病学研究中，混杂因素问题很严重。先前报告RR估计值的研究可能存在混杂。
