Siddiqui Salman H, Pavord Ian D, Barnes Neil C, Guasconi Alessandro, Lettis Sally, Pascoe Steven, Petruzzelli Stefano
University of Leicester, Leicester, UK,
National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK,
Int J Chron Obstruct Pulmon Dis. 2018 Nov 6;13:3669-3676. doi: 10.2147/COPD.S179425. eCollection 2018.
Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS). We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.
The studies assessed ICS/long-acting β agonist (LABA) combinations vs LABA alone. Using data from each study, we modeled COPD exacerbation rates, predose FEV, and St George's Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).
In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts. In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm. In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm. Change in FEV was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV was observed at higher eosinophil levels in the Dransfield studies. ICS/LABA led to greater improvements in St George's Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.
Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction. Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations.
越来越多的证据表明,血液嗜酸性粒细胞计数与患者对吸入性糖皮质激素(ICS)的反应性相关。我们对FORWARD研究以及德兰斯菲尔德博士进行的两项重复研究的数据进行了事后预测建模,以评估基线嗜酸性粒细胞计数与ICS对慢性阻塞性肺疾病(COPD)患者急性加重和肺功能影响之间的关系。
这些研究评估了ICS/长效β受体激动剂(LABA)联合用药与单独使用LABA的效果。利用每项研究的数据,我们对一系列连续的嗜酸性粒细胞水平(FORWARD研究中为0 - 1000个嗜酸性粒细胞/微升,德兰斯菲尔德研究中为0 - 993个嗜酸性粒细胞/微升)下的COPD急性加重率、用药前第一秒用力呼气容积(FEV)以及圣乔治呼吸问卷评分([仅FORWARD研究有])进行了建模。
在所有研究中,与单独使用LABA相比,ICS/LABA在所有嗜酸性粒细胞水平下均能降低急性加重的发生率,且随着基线血液嗜酸性粒细胞计数的增加,降低幅度逐渐增大。在FORWARD研究中,ICS/LABA组中嗜酸性粒细胞计数在0至1000个/微升之间时,年急性加重率为每年0.78至0.83次,而仅使用LABA组的年急性加重率为每年0.81至1.54次。在德兰斯菲尔德研究中,ICS/LABA组中嗜酸性粒细胞计数在0至993个/微升之间时,年急性加重率为每年0.54至1.02次,仅使用LABA组的年急性加重率为每年0.56至1.75次。在FORWARD研究中,接受ICS治疗的患者中,FEV的变化与嗜酸性粒细胞计数无关,而在德兰斯菲尔德研究中,在较高嗜酸性粒细胞水平下观察到ICS在FEV方面的治疗获益增加。在FORWARD研究中,嗜酸性粒细胞计数≥67个/微升的患者中,与单独使用LABA相比,ICS/LABA使圣乔治呼吸问卷总分有更大改善。
COPD患者血液嗜酸性粒细胞计数较高与ICS在降低急性加重方面的有益效果增加相关。需要进一步的前瞻性数据来评估血液嗜酸性粒细胞作为治疗推荐生物标志物的作用。