Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
J Allergy Clin Immunol. 2014 Aug;134(2):287-94. doi: 10.1016/j.jaci.2014.04.005. Epub 2014 Jun 11.
Eosinophilic airway inflammation measured by using induced sputum is an important treatment stratification tool in patients with severe asthma. In addition, sputum eosinophilia has been shown to be associated with severe exacerbations and airflow limitation.
We sought to identify whether eosinophilic inflammation in sputum is associated with FEV₁ decrease in patients with severe asthma and whether we could identify subgroups of decrease behavior based on the variation of eosinophilic airway inflammation over time.
Ninety-seven patients with severe asthma from the Glenfield Asthma Cohort were followed up with scheduled 3-month visits; the median duration of follow-up and number of visits was 6 years (interquartile range, 5.6-7.6 years) and 2.7 visits per year. Induced sputum was analyzed for eosinophilic inflammation at scheduled visits. Linear mixed-effects models were used to identify variables associated with lung function and overall decrease. In addition, using individual patients' mean and SD sputum eosinophil percentages over time, a 2-step cluster analysis was performed to identify patient clusters with different rates of decrease.
FEV₁ decrease was -25.7 mL/y in the overall population. Postbronchodilator FEV₁ was also dependent on exacerbations, age of onset, height, age, sex, and log10 sputum eosinophil percentages (P < .001). Three decrease patient clusters were identified: (1) noneosinophilic with low variation (mean decrease, -14.0 mL/y), (2) eosinophilic with high variation (mean decrease, -40.9 mL/y), and (3) hypereosinophilic with low variation (mean decrease in lung function, -19.2 mL/y).
The amplitude of sputum eosinophilia was associated with postbronchodilator FEV₁ in asthmatic patients. In contrast, high variability rather than the amplitude at baseline or over time of sputum eosinophils was associated with accelerated FEV₁ decrease.
通过诱导痰测量嗜酸性气道炎症是严重哮喘患者的重要治疗分层工具。此外，痰嗜酸性粒细胞增多与严重加重和气流受限有关。
我们试图确定痰中嗜酸性粒细胞炎症是否与严重哮喘患者的 FEV₁下降有关，以及我们是否可以根据嗜酸性气道炎症随时间的变化来识别下降行为的亚组。
从 Glenfield 哮喘队列中招募了 97 名严重哮喘患者进行定期 3 个月的随访；中位随访时间和随访次数为 6 年（四分位间距，5.6-7.6 年）和每年 2.7 次。在预定就诊时分析诱导痰中的嗜酸性粒细胞炎症。使用线性混合效应模型确定与肺功能和总体下降相关的变量。此外，使用患者个体随时间的平均和 SD 痰嗜酸性粒细胞百分比，进行了 2 步聚类分析，以识别具有不同下降率的患者聚类。
总体人群的 FEV₁下降为 -25.7 mL/y。支气管扩张后 FEV₁也依赖于加重、发病年龄、身高、年龄、性别和对数 10 痰嗜酸性粒细胞百分比（P <.001）。确定了 3 个下降患者聚类：（1）无嗜酸性粒细胞低变异性（平均下降 -14.0 mL/y），（2）嗜酸性粒细胞高变异性（平均下降 -40.9 mL/y），（3）高嗜酸性粒细胞低变异性（肺功能平均下降 -19.2 mL/y）。
哮喘患者支气管扩张后 FEV₁与痰嗜酸性粒细胞的幅度相关。相比之下，高变异性而不是基线或随时间变化的痰嗜酸性粒细胞幅度与 FEV₁下降加速相关。
