Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.
Respiratory Division, National Heart and Lung Institute, Imperial College London, London, UK.
Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.
This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.
Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150-300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150-300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150-300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).
We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.
ClinicalTrials.gov Identifiers: NCT00168844 , NCT00168831 , NCT00387088 , NCT00782210 , NCT00782509 , NCT00793624 , NCT00796653 , NCT01431274 , NCT01431287 , NCT02296138 and NCT00975195 .
慢性阻塞性肺疾病（COPD）的特征是进行性气流受限和慢性炎症。预测 COPD 加重（可导致疾病进展）对指导预防治疗和改善结局很重要。血嗜酸性粒细胞是对吸入性皮质类固醇（ICS）有反应的患者的生物标志物；然而，其作为 COPD 加重的预测生物标志物的有效性尚不清楚。
本事后分析汇集了 Boehringer Ingelheim 赞助的 11 项 III 期和 IV 期 COPD 随机研究的数据，这些研究具有相似的方法学。从这些研究中收集了加重数据，排除了 WISDOM®研究中 ICS 撤药组的患者。根据基线血嗜酸性粒细胞计数、基线 ICS 使用情况以及研究前一年的加重次数对患者进行分组。
共有 22,125 名患者可提供加重率数据和基线嗜酸性粒细胞计数；其中 45.6%患者的基线血嗜酸性粒细胞计数≤150 个/μL，34.3%患者的计数为 150-300 个/μL，20.1%患者的计数>300 个/μL。嗜酸性粒细胞计数最低的患者发生加重的比例最低，随着嗜酸性粒细胞计数的增加，加重率略有增加。按加重史分层时，上一年无加重的患者每年的加重率与嗜酸性粒细胞计数呈正相关（嗜酸性粒细胞计数≤150 个/μL 的患者为 0.38，嗜酸性粒细胞计数为 150-300 个/μL 的患者为 0.39，嗜酸性粒细胞计数>300 个/μL 的患者为 0.44）。上一年有一次加重的患者也观察到类似的趋势，分别为 0.62、0.66 和 0.67。对于上一年有≥2 次加重的患者，加重率在 1.02（嗜酸性粒细胞计数≤150 个/μL）到 1.10（嗜酸性粒细胞计数 150-300 个/μL）和 1.07（嗜酸性粒细胞计数>300 个/μL）之间波动。与未使用 ICS 的患者（范围为 0.45 至 0.49）相比，基线时使用 ICS 的患者（范围为 0.75 至 0.82）的加重率更高。
我们未发现基线血嗜酸性粒细胞计数与加重率之间存在有临床意义的关系。因此，目前的分析不支持使用血嗜酸性粒细胞来预测加重风险；然而，先前的加重史被发现是未来加重的更可靠预测因素。
ClinicalTrials.gov 标识符：NCT00168844、NCT00168831、NCT00387088、NCT00782210、NCT00782509、NCT00793624、NCT00796653、NCT01431274、NCT01431287、NCT02296138 和 NCT00975195。
