Transcriptomic profiling of the airway epithelium in COPD links airway eosinophilia to type 2 inflammation and corticosteroid response.

To compare the gene expression of type 2 inflammation in airway epithelial brushings of COPD patients with and without airway eosinophilia and to investigate the changes after inhaled corticosteroids (ICS).

比较有无气道嗜酸性粒细胞增多的COPD患者气道上皮刷检样本中2型炎症相关基因表达，并研究吸入性皮质类固醇（ICS）治疗后的变化。

Methods

Post hoc analyses of the DISARM randomised controlled trialinvestigated the expression of airway inflammation (type 1, 2 and 17), interleukin (IL)-13 and mast cell gene signatures at baseline and after 12-week ICS treatment.

对DISARM随机对照试验的事后分析研究了基线和12周吸入性皮质类固醇治疗后气道炎症（1型、2型和17型）、白细胞介素（IL）-13和肥大细胞基因表达谱的表达。

Gene signatures were generated from RNA sequencing of airway epithelial brushings.

基因表达谱是通过气道上皮细胞刷取样本的RNA测序生成的。

Airway eosinophilia was defined as eosinophils >1% of the total leukocyte count in bronchoalveolar lavage.

气道嗜酸性粒细胞增多被定义为支气管肺泡灌洗液中嗜酸性粒细胞占总白细胞计数的>1%。

Gene set enrichment analyses identified upregulated canonical pathways in airway eosinophilia.

基因集富集分析识别出气道嗜酸性粒细胞增多中上调的典型通路。

Results

Among 58 COPD patients, 38% had airway eosinophilia at baseline.

在58名慢性阻塞性肺疾病（COPD）患者中，38%在基线时存在气道嗜酸性粒细胞增多。

Patients with airway eosinophilia had more severe airflow obstruction and more radiographic emphysema than the non-eosinophilia group.

与非嗜酸性粒细胞增多组相比，存在气道嗜酸性粒细胞增多的患者表现出更严重的气流阻塞和更多的放射性肺气肿。

Patients with airway eosinophilia showed a higher epithelial expression of type 2 airway inflammation and IL-13 and mast cell activation at baseline, but the expression of type 1 and type 17 airway inflammation was similar to patients without airway eosinophilia.

具有气道嗜酸性粒细胞增多的患者在基线时表现出更高的2型气道炎症和IL-13以及肥大细胞激活的上皮表达，但1型和17型气道炎症的表达与没有气道嗜酸性粒细胞增多的患者相似。

The airway eosinophilia group showed an upregulation of canonical pathways related to type 2 immune response and asthma.

气道嗜酸性粒细胞增多组显示出与2型免疫反应和哮喘相关的典型途径的上调。

Treatment with ICS for 12 weeks reduced the epithelial expression of type 2 inflammation and mast cell gene signatures in patients with airway eosinophilia, while this change was not significant in patients without airway eosinophilia.

在气道嗜酸性粒细胞增多症患者中，吸入性糖皮质激素（ICS）治疗12周，显著降低了气道上皮细胞中2型炎症和肥大细胞基因特征的表达，而在无气道嗜酸性粒细胞增多症患者中，这种变化并不显著。

Conclusions

Airway eosinophilia marks a subset of COPD patients with increased airway epithelial expression of type 2 inflammation and a response to ICS treatment.

气道嗜酸性粒细胞增多症标志着一组COPD患者，其气道上皮细胞中2型炎症表达增加，并对ICS治疗有反应。