血液嗜酸性粒细胞计数、加重情况以及慢性阻塞性肺疾病患者添加吸入氟替卡松维兰特罗后的反应：两项平行随机对照试验数据的二次分析。
Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials.
机构信息
GlaxoSmithKline, Research Triangle Park, NC, USA.
GlaxoSmithKline, Research Triangle Park, NC, USA.
出版信息
Lancet Respir Med. 2015 Jun;3(6):435-42. doi: 10.1016/S2213-2600(15)00106-X. Epub 2015 Apr 12.
BACKGROUND
The short-term benefits of inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are greater in patients with evidence of eosinophilic airway inflammation. We investigated whether blood eosinophil count is a useful biomarker of the long-term effect of the inhaled corticosteroid fluticasone furoate on exacerbation frequency.
METHODS
We did a post-hoc analysis of data from two replicate, randomised, double-blind trials of 12 months' duration (Sept 25, 2009 to Oct 21, 2011 and Oct 17, 2011) in which once a day vilanterol 25 μg was compared with 25 μg vilanterol plus 50 μg, 100 μg, or 200 μg fluticasone furoate in patients with moderate-to-severe COPD and a history of one or more exacerbation in the previous year. We compared exacerbation rates according to two baseline eosinophil cell count strata (<2% and ≥2%), and according to four baseline percentage groupings. We also assessed lung function and incidence of pneumonia per strata in treatment groups.
FINDINGS
We included 3177 patients in the analyses, with 2083 patients (66%) having an eosinophil count of 2% or higher at study entry. Across all doses of inhaled corticosteroids, fluticasone furoate and vilanterol reduced exacerbations by 29% compared with vilanterol alone (mean 0·91 vs 1·28 exacerbations per patient per year; p<0·0001) in patients with eosinophil counts of 2% or higher, and by 10% (0·79 vs 0·89; p=0·2827) in patients with eosinophil counts lower than 2%. Reductions in exacerbations with fluticasone furoate and vilanterol, compared with vilanterol alone, were 24% in patients with baseline eosinophil counts of ≥2-<4%, 32% for those with counts of 4-<6%, and 42% for those with eosinophil counts of ≥6%. In patients treated with vilanterol alone, exacerbation rates increased progressively with increasing eosinophil count percentage category. Improvement in trough forced expiratory volume in 1 s (FEV1) and the increased risk of pneumonia with fluticasone furoate and vilanterol compared with vilanterol alone were not associated with eosinophil count.
INTERPRETATION
Blood eosinophil count is a promising biomarker of response to inhaled corticosteroids in patients with COPD. Blood eosinophil count could potentially be used to stratify patients for different exacerbation rate reduction strategies.
FUNDING
GlaxoSmithKline (study ID 201595).
背景
对于慢性阻塞性肺疾病（COPD）患者，吸入性皮质类固醇的短期益处在于有气道嗜酸性粒细胞炎症证据的患者中更大。我们研究了血液嗜酸性粒细胞计数是否是评估吸入性皮质类固醇糠酸氟替卡松长期影响（频率加重）的有用生物标志物。
方法
我们对两项为期 12 个月的随机、双盲、重复试验的数据进行了事后分析（2009 年 9 月 25 日至 2011 年 10 月 21 日和 2011 年 10 月 17 日），其中每天一次维兰特罗 25μg 与 25μg 维兰特罗加 50μg、100μg 或 200μg 糠酸氟替卡松比较，用于中重度 COPD 患者和前一年有一次或多次加重史的患者。我们根据两个基线嗜酸性粒细胞细胞计数分层（<2%和≥2%）和四个基线百分比分组比较了加重率。我们还评估了治疗组中每个分层的肺功能和肺炎发生率。
结果
我们将 3177 名患者纳入分析，其中 2083 名患者（66%）在研究开始时嗜酸性粒细胞计数为 2%或更高。在所有剂量的吸入性皮质类固醇中，糠酸氟替卡松和维兰特罗与单独使用维兰特罗相比，降低了 29%的加重率（平均每位患者每年发生 0.91 次与 1.28 次加重；p<0.0001），在嗜酸性粒细胞计数为 2%或更高的患者中，降低了 10%（0.79 次与 0.89 次；p=0.2827），在嗜酸性粒细胞计数低于 2%的患者中。与单独使用维兰特罗相比，糠酸氟替卡松和维兰特罗治疗可使嗜酸性粒细胞计数≥2-<4%的患者的加重率降低 24%，使嗜酸性粒细胞计数为 4-<6%的患者降低 32%，使嗜酸性粒细胞计数≥6%的患者降低 42%。在单独使用维兰特罗治疗的患者中，随着嗜酸性粒细胞计数百分比类别的增加，加重率逐渐增加。与单独使用维兰特罗相比，使用糠酸氟替卡松和维兰特罗可改善呼气峰流速（FEV1），增加肺炎风险，但与嗜酸性粒细胞计数无关。
结论
血液嗜酸性粒细胞计数是 COPD 患者对吸入性皮质类固醇反应的一个有前途的生物标志物。血液嗜酸性粒细胞计数可能有助于分层不同的患者，以达到不同的减轻加重率的策略。
资金
葛兰素史克（研究 ID 201595）。
Zotero 插件