嗜酸粒细胞性重症哮喘和嗜酸粒细胞性COPD患者2型气道炎症的分子标志物相似
2021/02/09
摘要
背景：气道和全身嗜酸性粒细胞增多是重症哮喘和慢性阻塞性肺病的重要可治疗特征。COPD患者嗜酸性粒细胞增多的分子基础尚不清楚，但可能与2型细胞因子（IL5，IL13）和前列腺素D2（PGD2）有关。
方法：本研究包括非阻塞性气道疾病（OAD）对照组（n=19）、慢性阻塞性肺病（COPD）队列组（n=96）和重症哮喘队列组（n=84）。评估人口统计学、急性加重史、疾病影响（SGRQ）和肺功能测定。根据痰中嗜酸粒细胞比例（≥3%）或血中嗜酸粒细胞计数（≥300/μL），将受试者分为嗜酸细胞性哮喘。痰中2型炎症指标包括ELISA法检测PGD2、IL5、IL13基因表达（qPCR）和造血PGD2合酶（HPGDS）。
结果：除HPGDS mRNA在非OAD对照组最高，COPD组最低外，2型标志物在各组间无差异。嗜酸性和非嗜酸性重症哮喘患者的IL5、IL13 mRNA和PGD2水平显著升高，但在嗜酸性COPD与嗜酸性重症哮喘或非嗜酸性COPD之间无差异。HPGDS在嗜酸性重症哮喘中的表达高于嗜酸性COPD。用痰或血嗜酸粒细胞截断值结果相似。痰中IL5和IL13在重度哮喘中高度相关（r=0.907，p<0.001），在COPD中高度相关（r=0.824，p<0.001），在重度哮喘中与痰嗜酸性粒细胞中度相关（IL5 r=0.440，p<0.001；IL13 r=0.428，p<0.001），在COPD中弱相关（IL5 r=0.245，p<0.05；IL13 r=0.317，p<0.05）。
结论：嗜酸粒细胞性哮喘与嗜酸粒细胞性COPD患者2型气道炎症分子标志物无明显差异，COPD患者嗜酸粒细胞与2型气道炎症分子标志物相关性明显弱于重症哮喘患者。
Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic COPD
Michael Fricker, Vanessa M McDonald, Natasha A Winter, Katherine J Baines, Peter A B Wark, Jodie L Simpson, Peter G Gibson
Abstract
Background: Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2 ).
Methods: This study included non-obstructive airways disease (OAD) controls (n=19), a COPD cohort (n=96) and a severe asthma cohort (n=84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS).
Results: Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non-OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non-eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non-eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut-offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r=0.907, p<0.001) and COPD (r=0.824, p<0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r=0.440,p<0.001; IL13 r=0.428,p<0.001) and weakly correlated in COPD (IL5 r=0.245,p<0.05; IL13 r=0.317,p<0.05).
Conclusions: Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD, however the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
背景：气道和全身嗜酸性粒细胞增多是重症哮喘和慢性阻塞性肺病的重要可治疗特征。COPD患者嗜酸性粒细胞增多的分子基础尚不清楚，但可能与2型细胞因子（IL5，IL13）和前列腺素D2（PGD2）有关。
方法：本研究包括非阻塞性气道疾病（OAD）对照组（n=19）、慢性阻塞性肺病（COPD）队列组（n=96）和重症哮喘队列组（n=84）。评估人口统计学、急性加重史、疾病影响（SGRQ）和肺功能测定。根据痰中嗜酸粒细胞比例（≥3%）或血中嗜酸粒细胞计数（≥300/μL），将受试者分为嗜酸细胞性哮喘。痰中2型炎症指标包括ELISA法检测PGD2、IL5、IL13基因表达（qPCR）和造血PGD2合酶（HPGDS）。
结果：除HPGDS mRNA在非OAD对照组最高，COPD组最低外，2型标志物在各组间无差异。嗜酸性和非嗜酸性重症哮喘患者的IL5、IL13 mRNA和PGD2水平显著升高，但在嗜酸性COPD与嗜酸性重症哮喘或非嗜酸性COPD之间无差异。HPGDS在嗜酸性重症哮喘中的表达高于嗜酸性COPD。用痰或血嗜酸粒细胞截断值结果相似。痰中IL5和IL13在重度哮喘中高度相关（r=0.907，p<0.001），在COPD中高度相关（r=0.824，p<0.001），在重度哮喘中与痰嗜酸性粒细胞中度相关（IL5 r=0.440，p<0.001；IL13 r=0.428，p<0.001），在COPD中弱相关（IL5 r=0.245，p<0.05；IL13 r=0.317，p<0.05）。
结论：嗜酸粒细胞性哮喘与嗜酸粒细胞性COPD患者2型气道炎症分子标志物无明显差异，COPD患者嗜酸粒细胞与2型气道炎症分子标志物相关性明显弱于重症哮喘患者。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Allergy. 2021 Jan 20. doi: 10.1111/all.14741. doi: 10.1111/all.14741.)
(Allergy. 2021 Jan 20. doi: 10.1111/all.14741. doi: 10.1111/all.14741.)
Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic COPD
Michael Fricker, Vanessa M McDonald, Natasha A Winter, Katherine J Baines, Peter A B Wark, Jodie L Simpson, Peter G Gibson
Abstract
Background: Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2 ).
Methods: This study included non-obstructive airways disease (OAD) controls (n=19), a COPD cohort (n=96) and a severe asthma cohort (n=84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS).
Results: Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non-OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non-eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non-eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut-offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r=0.907, p<0.001) and COPD (r=0.824, p<0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r=0.440,p<0.001; IL13 r=0.428,p<0.001) and weakly correlated in COPD (IL5 r=0.245,p<0.05; IL13 r=0.317,p<0.05).
Conclusions: Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD, however the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
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一种高强度肺康复计划对肥胖的哮喘患者短期及长期影响：一项随机对照试验
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寡细胞型哮喘的异质性：前瞻性队列研究的层次聚类分析
