Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
StatMind, Lund, Sweden.
Lancet Respir Med. 2018 Feb;6(2):117-126. doi: 10.1016/S2213-2600(18)30006-7. Epub 2018 Jan 10.
BACKGROUND: The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease (COPD) who will experience fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response. We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD. METHODS: We analysed data from three AstraZeneca randomised controlled trials of budesonide-formoterol in patients with COPD with a history of exacerbations and available blood eosinophil counts. Patients with any history of asthma were excluded. Negative binomial regression analysis was done using splines for modelling of continuous variables to study the primary outcome of annual exacerbation rate adjusted for exposure time and study design. The trials are registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744. FINDINGS: 4528 patients were studied. A non-linear increase in exacerbations occurred with increasing eosinophil count in patients who received formoterol alone. At eosinophil counts of 0·10 × 10 cells per L or more, a significant treatment effect was recorded for exacerbation reduction with budesonide-formoterol compared with formoterol alone (rate ratio 0·75, 95% CI 0·57-0·99; p=0·015). Interactions were observed between eosinophil count and the treatment effects of budesonide-formoterol over formoterol on St George's Respiratory Questionnaire (p=0·0043) and pre-bronchodilator FEV (linear effect p<0·0001, p=0·067). Only eosinophil count and smoking history were independent predictors of response to budesonide-formoterol in reducing exacerbations (eosinophil count, p=0·013; smoking history, p=0·015). INTERPRETATION: In patients with COPD treated with formoterol, blood eosinophil count predicts exacerbation risk and the clinical response to ICS. FUNDING: AstraZeneca.
背景：外周血嗜酸性粒细胞计数可能有助于识别那些接受吸入性皮质类固醇（ICS）治疗后，哮喘恶化次数较少的慢性阻塞性肺疾病（COPD）患者。先前的事后分析提出了一些任意的嗜酸性粒细胞截断值，这些截断值在评估治疗反应的复杂相互作用方面存在局限性。我们将嗜酸性粒细胞计数建模为连续变量，以确定决定 COPD 患者哮喘恶化风险和 ICS 临床反应的特征。
方法：我们分析了三项阿斯利康布地奈德福莫特罗治疗 COPD 患者的随机对照试验数据，这些患者有哮喘恶化史和可用的血嗜酸性粒细胞计数。排除有任何哮喘史的患者。使用样条进行非线性回归分析，对连续变量进行建模，以研究调整暴露时间和研究设计后的年度恶化率的主要结局。这些试验在 ClinicalTrials.gov 注册，NCT00206167、NCT00206154 和 NCT00419744。
结果：共研究了 4528 例患者。在接受福莫特罗单药治疗的患者中，嗜酸性粒细胞计数增加与哮喘恶化呈非线性关系。当嗜酸性粒细胞计数达到 0.10×10 个/升或更高时，与福莫特罗单药治疗相比，布地奈德福莫特罗治疗可显著降低哮喘恶化的发生率（比值比 0.75，95%置信区间 0.57-0.99；p=0.015）。在圣乔治呼吸问卷（p=0.0043）和支气管扩张剂前 FEV 方面，观察到嗜酸性粒细胞计数与布地奈德福莫特罗相对于福莫特罗的治疗效果之间存在交互作用（p=0.067）。只有嗜酸性粒细胞计数和吸烟史是预测布地奈德福莫特罗降低哮喘恶化发生率的独立指标（嗜酸性粒细胞计数，p=0.013；吸烟史，p=0.015）。
结论：在接受福莫特罗治疗的 COPD 患者中，血液嗜酸性粒细胞计数可预测哮喘恶化风险和 ICS 的临床反应。
资金来源：阿斯利康。
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