哮喘亚组特征与循环血中YKL-40水平有关
2017/12/29
摘要
几丁质酶蛋白YKL-40参与调节气道炎症，其在血清中的含量与哮喘的严重程度相关。然而，目前还没有研究探讨YKL-40含量与哮喘表型的相关性。
我们选取了耶鲁大学哮喘和呼吸道疾病中心的（n=156）患者进行聚类分析，根据YKL-40水平来分成不同亚组。将其结果在严重哮喘研究计划(n = 167)和纽约大学/贝尔维尤哮喘储存库(n = 341)队列研究中进行交叉验证。痰标本的转录组分析揭示了哮喘的严重程度与ykl - 40亚群相关的分子途径。
根据YKL-40水平，我们发现了C1-C4四组人群。C3、C4组血清YKL-40水平高于C1、C2组。C3组与哮喘的早期发病、较长的持续时间、严重气道阻塞以及几乎致命的哮喘急性发作有关。C3组血清水平最高，其发病时间最早，气道阻塞较少，但是存在频繁的急性加重。C3和C4组患者的气道转录组分析提示存在非2型炎症途径的激活。
升高的血清YKL-40水平与两种不同的哮喘临床表型有关:一种是不可逆的气道阻塞，另一种是严重的急性加重。血清YKL-40水平对于识别严重或急性加重倾向哮喘的患者具有潜在的价值。
Characterisation of asthma subgroups associated with circulating YKL-40 levels
Jose L. Gomez, Xiting Yan, Carole T. Holm, Nicole Grant, Qing Liu, Lauren Cohn, Vera Nezgovorova, Deborah A. Meyers, Eugene R. Bleecker, Gina M. Crisafi, Nizar N. Jarjour, Linda Rogers, Joan Reibman, Geoffrey L. Chupp
European Respiratory Journal 2017 50: 1700800; DOI: 10.1183/13993003.00800-2017
Abstract
The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.
We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.
Four YKL-40 clusters (C1–C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.
Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.
几丁质酶蛋白YKL-40参与调节气道炎症，其在血清中的含量与哮喘的严重程度相关。然而，目前还没有研究探讨YKL-40含量与哮喘表型的相关性。
我们选取了耶鲁大学哮喘和呼吸道疾病中心的（n=156）患者进行聚类分析，根据YKL-40水平来分成不同亚组。将其结果在严重哮喘研究计划(n = 167)和纽约大学/贝尔维尤哮喘储存库(n = 341)队列研究中进行交叉验证。痰标本的转录组分析揭示了哮喘的严重程度与ykl - 40亚群相关的分子途径。
根据YKL-40水平，我们发现了C1-C4四组人群。C3、C4组血清YKL-40水平高于C1、C2组。C3组与哮喘的早期发病、较长的持续时间、严重气道阻塞以及几乎致命的哮喘急性发作有关。C3组血清水平最高，其发病时间最早，气道阻塞较少，但是存在频繁的急性加重。C3和C4组患者的气道转录组分析提示存在非2型炎症途径的激活。
升高的血清YKL-40水平与两种不同的哮喘临床表型有关:一种是不可逆的气道阻塞，另一种是严重的急性加重。血清YKL-40水平对于识别严重或急性加重倾向哮喘的患者具有潜在的价值。
(复旦大学附属中山医院 呼吸科 包晨 摘译 杨冬 审校)
(European Respiratory Journal 2017 50: 1700800; DOI: 10.1183/13993003.00800-2017)
(European Respiratory Journal 2017 50: 1700800; DOI: 10.1183/13993003.00800-2017)
Characterisation of asthma subgroups associated with circulating YKL-40 levels
Jose L. Gomez, Xiting Yan, Carole T. Holm, Nicole Grant, Qing Liu, Lauren Cohn, Vera Nezgovorova, Deborah A. Meyers, Eugene R. Bleecker, Gina M. Crisafi, Nizar N. Jarjour, Linda Rogers, Joan Reibman, Geoffrey L. Chupp
European Respiratory Journal 2017 50: 1700800; DOI: 10.1183/13993003.00800-2017
Abstract
The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.
We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.
Four YKL-40 clusters (C1–C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.
Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.
