Fan Vincent S, Bryson Chris L, Curtis J Randall, Fihn Stephan D, Bridevaux Pierre-Olivier, McDonell Mary B, Au David H
Department of Medicine, University of Washington, Seattle, WA 98108.
Am J Respir Crit Care Med. 2003 Dec 15;168(12):1488-94. doi: 10.1164/rccm.200301-019OC. Epub 2003 Oct 2.
Observational studies of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD) have shown improved survival whereas randomized trials have not. It has been suggested that this difference may be due to immortal time bias. To investigate this further, we performed a prospective cohort study of patients with COPD, using time-dependent methods to determine whether use of inhaled corticosteroids more than 80% of the time reduced the risk of all-cause mortality and COPD exacerbations. Of 8,033 patients, 2,686 (33%) received inhaled corticosteroids. We did not find a significant reduction in mortality for average inhaled steroid use at either low (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.69-1.33) or medium/high dose (HR, 0.86; 95% CI, 0.67-1.10). Similarly, recent inhaled corticosteroid use was not associated with a reduction in mortality at low (HR, 0.80; 95% CI, 0.60-1.07) or medium/high doses (HR, 0.88; 95% CI, 0.71-1.09). There was no association between inhaled corticosteroid use and hospitalizations or exacerbations due to COPD. Patients using medium/high-dose inhaled corticosteroids did not have a significantly lower risk of COPD hospitalizations (HR, 0.85; 95% CI, 0.64-1.13) or COPD exacerbations (HR, 1.13; 95% CI, 0.94-1.36). In a time-dependent study of outpatients with COPD, adherence to inhaled corticosteroid use was not associated with a decreased risk of mortality or exacerbations.
对慢性阻塞性肺疾病（COPD）患者吸入皮质类固醇的观察性研究显示生存率有所提高，而随机试验则未显示出这一结果。有人认为这种差异可能是由于不朽时间偏倚所致。为了进一步研究这一问题，我们对COPD患者进行了一项前瞻性队列研究，采用时间依赖性方法来确定80%以上时间使用吸入皮质类固醇是否能降低全因死亡率和COPD急性加重的风险。在8033名患者中，2686名（33%）接受了吸入皮质类固醇治疗。我们发现，无论是低剂量（风险比[HR]，0.96；95%置信区间[CI]，0.69 - 1.33）还是中/高剂量（HR，0.86；95% CI，0.67 - 1.10）的平均吸入类固醇使用，死亡率均未显著降低。同样，近期低剂量（HR，0.80；95% CI，0.60 - 1.07）或中/高剂量（HR，0.88；95% CI，0.71 - 1.09）吸入皮质类固醇的使用与死亡率降低无关。吸入皮质类固醇的使用与因COPD导致的住院或急性加重之间没有关联。使用中/高剂量吸入皮质类固醇的患者，COPD住院（HR，0.85；95% CI，0.64 - 1.13）或COPD急性加重（HR，1.13；95% CI，0.94 - 1.36）的风险并没有显著降低。在一项对COPD门诊患者的时间依赖性研究中，坚持使用吸入皮质类固醇与死亡率或急性加重风险降低无关。
