BACKGROUND Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined. METHODS We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators. RESULTS Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies. CONCLUSION This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

中文翻译：

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事后RCT和观察性研究中的嗜酸性粒细胞计数是吸入糖皮质激素预防COPD恶化的有效指标：系统评价和荟萃分析。

背景技术已经提出血液嗜酸性粒细胞计数作为预防COPD急性加重时对吸入皮质类固醇（ICS）反应的预测因子。处方ICS的最佳嗜酸性粒细胞计数阈值尚未达成共识。观察性研究对这种作用产生了怀疑。尚未研究吸入糖皮质激素在这种关系中的作用，而与长效支气管扩张药无关。方法我们对随机对照试验（RCT）的事后分析和观察性研究进行了系统的回顾，研究了三个血液嗜酸性粒细胞阈值和ICS的独立作用。所包括的研究按嗜酸性粒细胞阈值的形式（相对计数或绝对计数）和切点进行分类。评估的阈值为嗜酸性粒细胞相对计数为2％，绝对计数为150细胞/μL和300细胞/μL。基于这些计数，对RCT的事后分析进行了ICS使用效果的三项荟萃分析。初步分析包括所有ICS与非ICS方案的研究。进一步的分析检查了ICS的作用，而与长效支气管扩张药的作用无关。结果在COPD患者中，有十六项研究检查了血液嗜酸性粒细胞计数与ICS加重危险反应之间的关系。11项研究（25,881例患者）是RCT的事后分析。五项研究（109,704例患者）为回顾性观察研究。在≥2％血液嗜酸性粒细胞阈值（RR，0.80; 95％CI，0.74-0.85）时，ICS对加重风险降低的独立作用为20％，在≥150细胞/μL血液嗜酸性粒细胞阈值（RR，0.65）下为35％ ; 0.52-0.79），≥300细胞/μL嗜酸性粒细胞阈值时为39％（RR，0.61; 0.44-0.78）。五项观测研究中有四项没有发现关联。结论这是在RCT的事后分析中评估ICS在降低一系列嗜酸性粒细胞阈值的COPD恶化风险中的独立作用的首次系统评价。在这些阈值下，ICS处方与加重发作风险降低之间存在关联。在观察研究中发现缺乏关联性质疑了这些观察与“现实世界” COPD人群的相关性。为了阐明该生物标记物的临床效用，应在前瞻性有效性研究中测试该关联。结论这是在RCT的事后分析中评估ICS在降低一系列嗜酸性粒细胞阈值的COPD恶化风险中的独立作用的首次系统评价。在这些阈值下，ICS处方与加重发作风险降低之间存在关联。在观察研究中发现缺乏关联性质疑了这些观察与“现实世界” COPD人群的相关性。为了阐明该生物标记物的临床效用，应在前瞻性有效性研究中测试该关联。结论这是在RCT的事后分析中评估ICS在降低一系列嗜酸性粒细胞阈值的COPD恶化风险中的独立作用的首次系统评价。在这些阈值下，ICS处方与加重发作风险降低之间存在关联。在观察研究中发现缺乏关联性质疑了这些观察与“现实世界” COPD人群的相关性。为了阐明该生物标记物的临床效用，应在前瞻性有效性研究中测试该关联。在这些阈值下，ICS处方与加重发作风险降低之间存在关联。在观察研究中发现缺乏关联性质疑了这些观察与“现实世界” COPD人群的相关性。为了阐明该生物标记物的临床效用，应在前瞻性有效性研究中测试该关联。在这些阈值下，ICS处方与加重发作风险降低之间存在关联。在观察研究中发现缺乏关联性质疑了这些观察与“现实世界” COPD人群的相关性。为了阐明该生物标记物的临床效用，应在前瞻性有效性研究中测试该关联。