Respiratory Medical Franchise, GSK, Brentford, UK William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK
Respiratory Medical Franchise, GSK, Brentford, UK.
Eur Respir J. 2016 May;47(5):1374-82. doi: 10.1183/13993003.01370-2015. Epub 2016 Feb 25.
Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 μg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted.
鉴定一种可预测对吸入性皮质类固醇(ICS)反应的生物标志物将有助于评估 ICS 在慢性阻塞性肺疾病(COPD)中的风险/效益比,并指导治疗。ISOLDE 研究将 751 例患者(平均支气管扩张剂后 1 秒用力呼气量(FEV1)1.4 L:预计正常的 50%)随机分为丙酸氟替卡松 500 μg 每日两次或安慰剂,治疗 3 年,发现两种治疗方法的 FEV1 下降率无差异(p=0.16),丙酸氟替卡松组与安慰剂组相比,中重度加重率显著降低(p=0.026)。我们通过基线血嗜酸性粒细胞计数重新分析 ISOLDE 结果,以探讨嗜酸性粒细胞水平是否可预测 ICS 获益。嗜酸性粒细胞<2%(n=456)的患者接受丙酸氟替卡松治疗与安慰剂治疗后支气管扩张剂后 FEV1 下降率相似(-2.9 mL·年(-1);p=0.688)。嗜酸性粒细胞≥2%(n=214)的患者,接受丙酸氟替卡松治疗与安慰剂治疗相比,下降率降低了 33.9 mL·年(-1)(p=0.003)。与嗜酸性粒细胞<2%组相比,丙酸氟替卡松治疗组与安慰剂治疗组相比,中重度加重率降低更为明显;在两组中,两种治疗方法的首次中重度加重时间均无差异。基线血嗜酸性粒细胞计数≥2%可识别出一组接受 ICS 治疗时 FEV1 下降率较慢的 COPD 患者:目前有必要对此假说进行前瞻性检验。