Departments of Epidemiology and Biostatistics and of Medicine, Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, , Montreal, Québec, Canada.
Thorax. 2013 Nov;68(11):1029-36. doi: 10.1136/thoraxjnl-2012-202872.
BACKGROUND: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use. METHODS: We formed a new-user cohort of patients with COPD treated during 1990-2005. Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia. A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity. RESULTS: The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year). Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75). The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17). The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26). CONCLUSIONS: ICS use by patients with COPD increases the risk of serious pneumonia. The risk is particularly elevated and dose related with fluticasone. While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials.
背景:已知吸入性皮质类固醇(ICS)会增加慢性阻塞性肺疾病(COPD)患者发生肺炎的风险。目前尚不清楚不同的吸入制剂(特别是氟替卡松和布地奈德)的肺炎风险是否存在差异,以及这种风险是否会随着剂量和长期使用时间的增加而增加。
方法:我们组建了一个新的 COPD 患者队列,这些患者在 1990 年至 2005 年期间接受治疗。通过魁北克省健康保险数据库确定了研究对象,并随访至 2007 年或直至发生严重肺炎事件(定义为首次因肺炎住院或因肺炎死亡)。采用巢式病例对照分析,以调整年龄、性别、呼吸疾病严重程度和合并症后,评估当前 ICS 使用者发生严重肺炎的比率比(RR)。
结果:该队列共纳入了 163514 例患者,其中 20344 例患者在 5.4 年的随访期间发生了严重肺炎事件(发生率为 2.4/100/年)。当前使用 ICS 与严重肺炎发生率增加 69%相关(RR 1.69;95%CI 1.63 至 1.75)。长期使用 ICS 与风险持续相关,在停止使用 ICS 后,风险逐渐下降,6 个月后消失(RR 1.08;95%CI 0.99 至 1.17)。氟替卡松的严重肺炎发生率较高(RR 2.01;95%CI 1.93 至 2.10),且与日剂量相关,而布地奈德的严重肺炎发生率较低(RR 1.17;95%CI 1.09 至 1.26)。
结论:COPD 患者使用 ICS 会增加发生严重肺炎的风险。氟替卡松的风险尤其高且与剂量相关。虽然不能排除残余混杂因素的影响,但这些结果与最近的随机试验结果一致。
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