Oshagbemi Olorunfemi A, Odiba Jephthah O, Daniel Abraham, Yunusa Ismaeel
Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Netherlands.
Monash Institute of Pharmaceutical Sciences, Melbourne, Australia.
Curr Drug Targets. 2019;20(16):1670-1679. doi: 10.2174/1389450120666190808141625.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 recommends the use of absolute blood eosinophil count as a guide for the escalation and de-escalation of inhaled corticosteroids (ICS) in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). We evaluated the risk of moderate or severe exacerbations among patients escalating and de-escalating ICS therapy by absolute blood eosinophil thresholds in this systematic review.
Through a comprehensive literature search of Pubmed/MEDLINE, EMBASE, and clinical trial sites up to April 2019, we identified relevant studies. We used generic inverse variance method with fixed-effects estimates to compare the risk of moderate or severe exacerbations among COPD patients with elevated blood eosinophil counts exposed to inhaled corticosteroids (ICS) versus non-ICS treatments groups expressed as risk ratios.
Ten studies (8 randomised control trials and 2 observational studies) were included, with a total of 85,059 COPD patients. In our pooled analysis, we found an overall reduction in risk of moderate or severe exacerbations in patients with absolute blood eosinophil thresholds ranging from ≥ 100 to ≥ 340 cells/µL among patients escalating ICS (RR, 0.77, 95% CI, 0.73-0.81). For studies evaluating the effects of de-escalation of ICS on moderate to severe exacerbations using blood eosinophil thresholds of ≥ 300 to ≥ 340 cells/µL had an increased risk of moderate or severe exacerbations following the de-escalation of ICS (RR, 1.66, 95% CI, 1.31-2.10).
This study confirms the validity of the recommended absolute blood eosinophil count thresholds for the escalation and de-escalation of ICS among COPD patients. However, this recommendation is for COPD patients with prior exacerbations rather than among newly diagnosed COPD patients as observed in this study. COPD patients with current or past history of asthma represent a unique phenotypic group which should be further evaluated.
慢性阻塞性肺疾病全球倡议（GOLD）2019版建议，在慢性阻塞性肺疾病（COPD）患者的药物治疗中，使用绝对嗜酸性粒细胞计数作为吸入性糖皮质激素（ICS）剂量上调和下调的指导依据。在本系统评价中，我们评估了根据绝对血液嗜酸性粒细胞阈值上调和下调ICS治疗的患者中发生中度或重度急性加重的风险。
通过对截至2019年4月的Pubmed/MEDLINE、EMBASE和临床试验网站进行全面的文献检索，我们确定了相关研究。我们使用固定效应估计的通用逆方差方法，以风险比来比较血液嗜酸性粒细胞计数升高的COPD患者中，接受吸入性糖皮质激素（ICS）治疗组与非ICS治疗组发生中度或重度急性加重的风险。
纳入了10项研究（8项随机对照试验和2项观察性研究），共有85059例COPD患者。在我们的汇总分析中，我们发现，在ICS上调的患者中，绝对血液嗜酸性粒细胞阈值在≥100至≥340个细胞/微升之间的患者，中度或重度急性加重的风险总体降低（风险比，0.77；95%置信区间，0.73 - 0.81）。对于使用≥300至≥340个细胞/微升的血液嗜酸性粒细胞阈值评估ICS减量对中度至重度急性加重影响的研究，ICS减量后中度或重度急性加重的风险增加（风险比，1.66；95%置信区间，1.31 - 2.10）。
本研究证实了所推荐的绝对血液嗜酸性粒细胞计数阈值对于COPD患者中ICS上调和下调的有效性。然而，正如本研究中所观察到的，该建议适用于既往有急性加重史的COPD患者，而非新诊断的COPD患者。目前或既往有哮喘病史的COPD患者代表了一个独特的表型组，应进一步评估。
