高T2型重症哮喘与血嗜酸性粒细胞、呼出气一氧化氮和血清骨膜蛋白相关
2019/04/10
摘要
背景：气道上皮细胞(airway epithelial cells, AECs)的2型(T2)免疫反应将轻-中度哮喘归类为高T2型。我们检测了目前可用的临床生物标志物能否预测U-BIOPRED队列中AECs定义的高T2型。
方法：对103例哮喘患者和44例健康对照者的支气管刷样本进行检测，获得AECs的转录组表达谱，并使用基因集变异分析来计算暴露于白细胞介素（IL）-13的AECs的T2哮喘基因表达特征的相对表达分数。
结果：基于AEC基因表达，37%哮喘患者(45%非吸烟重度哮喘，n=49；33%吸烟或戒烟重度哮喘，n=18；28%轻-中度哮喘，n=36)被定义为高T2型。这些患者症状更多，伴随着呼出气一氧化氮(FeNO)与血、痰嗜酸性粒细胞水平更高，但血清IgE与骨膜蛋白无明显差异。痰嗜酸性粒细胞增多与高T2型基因表达最相关。FeNO (≥30ppb)和血液嗜酸性粒细胞 (≥300/µL)可以适度地预测高T2型哮喘。痰IL-4、IL-5、IL-13蛋白水平与基因表达并不相关。
结论：高水平的FeNO、血和痰嗜酸性粒细胞计数可在一定程度上预测高T2型重度哮喘，但血清IgE或骨膜蛋白预测价值较差。目前尚需要更好的床旁生物标志物来预测高T2型哮喘。
“T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin
Pavlidis S; Takahashi K; Ng Kee Kwong F; Xie J; Hoda U; Sun K; Elyasigomari V; Agapow P; Loza M; Baribaud F; Chanez P; Fowler SJ; Shaw DE; Fleming Louise J; Howarth PH; Sousa AR; Corfield J; Auffray C; De Meulder B; Knowles R; Sterk PJ; Guo Y; Adcock IM; Djukanovic R; Fan Chung K.
European Respiratory Journal；2019;53(1):1800938.
Abstract
BACKGROUND: Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.
METHODS: The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.
RESULTS: 37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300 cells·µL−1) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.
CONCLUSIONS: T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.
背景：气道上皮细胞(airway epithelial cells, AECs)的2型(T2)免疫反应将轻-中度哮喘归类为高T2型。我们检测了目前可用的临床生物标志物能否预测U-BIOPRED队列中AECs定义的高T2型。
方法：对103例哮喘患者和44例健康对照者的支气管刷样本进行检测，获得AECs的转录组表达谱，并使用基因集变异分析来计算暴露于白细胞介素（IL）-13的AECs的T2哮喘基因表达特征的相对表达分数。
结果：基于AEC基因表达，37%哮喘患者(45%非吸烟重度哮喘，n=49；33%吸烟或戒烟重度哮喘，n=18；28%轻-中度哮喘，n=36)被定义为高T2型。这些患者症状更多，伴随着呼出气一氧化氮(FeNO)与血、痰嗜酸性粒细胞水平更高，但血清IgE与骨膜蛋白无明显差异。痰嗜酸性粒细胞增多与高T2型基因表达最相关。FeNO (≥30ppb)和血液嗜酸性粒细胞 (≥300/µL)可以适度地预测高T2型哮喘。痰IL-4、IL-5、IL-13蛋白水平与基因表达并不相关。
结论：高水平的FeNO、血和痰嗜酸性粒细胞计数可在一定程度上预测高T2型重度哮喘，但血清IgE或骨膜蛋白预测价值较差。目前尚需要更好的床旁生物标志物来预测高T2型哮喘。
(代思思1 张红萍2 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（European Respiratory Journal；2019;53(1):1800938）
（European Respiratory Journal；2019;53(1):1800938）
“T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin
Pavlidis S; Takahashi K; Ng Kee Kwong F; Xie J; Hoda U; Sun K; Elyasigomari V; Agapow P; Loza M; Baribaud F; Chanez P; Fowler SJ; Shaw DE; Fleming Louise J; Howarth PH; Sousa AR; Corfield J; Auffray C; De Meulder B; Knowles R; Sterk PJ; Guo Y; Adcock IM; Djukanovic R; Fan Chung K.
European Respiratory Journal；2019;53(1):1800938.
Abstract
BACKGROUND: Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.
METHODS: The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.
RESULTS: 37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300 cells·µL−1) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.
CONCLUSIONS: T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.
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探索哮喘小气道功能障碍的相关性和程度(ATLANTIS)：一项前瞻性队列研究的基线数据
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