A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile.
A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile.
复制标题
通过血清细胞因子谱的无偏聚类鉴定具有更严重疾病的哮喘的全身炎症内型
DOI：
10.1097/md.0000000000003774
复制
发表时间：
2016-06
期刊：
影响因子：
1.6
通讯作者：
Cai S
中科院分区：
文献类型：
--
作者：
Liang Z;Liu L;Zhao H;Xia Y;Zhang W;Ye Y;Jiang M;Cai S
哮喘是一种临床和分子异质性疾病。提示全身炎症在一组哮喘患者中起重要作用。我们假设有一个以全身炎症为特征的哮喘患者亚组。在这项研究中，我们的目标是根据循环生物标志物来区分哮喘亚型，并确定是否可以识别哮喘的全身炎症内在型。在本横断面研究中，从一个单一的学术门诊前瞻性招募了50例未经治疗的哮喘患者，并对其临床、功能和炎症参数进行了表征。用抗人细胞因子抗体芯片检测20种血清细胞因子的表达谱。然后，基于主成分分析（PCA）转换后的数据进行层次聚类分析，对临床组进行分类。主成分分析表明，6个独立的成分解释了80.113%的方差，基于PCA的层次聚类确定了3个内型。其中一种内型表现为全身炎症标志物（如瘦素、血管内皮生长因子（VEGF））升高，以及晚期糖基化终产物（sICAM）（一种抗炎分子）可溶性受体水平降低。纳入更多女性患者，循环中性粒细胞计数更高，症状更严重。总之，我们确定了一种以全身炎症和严重症状为特征的内源性哮喘。VEGF、瘦素水平的升高和血清瘦素水平的降低可能导致这种哮喘内源性的全身性炎症。
AbstractAsthma is considered as a clinical and molecularly heterogeneous disorder. Systemic inflammation is suggested to play an important role in a group of asthma patients. We hypothesized that there is a subgroup of patients with asthma characterized by systemic inflammation. In this study, we aimed to discriminate asthma subtypes based on circulating biomarkers and to determine whether a systemic inflammatory endotype of asthma could be identified. In the present cross-sectional study, 50 patients with untreated asthma were prospectively recruited from a single academic outpatient clinic, and characterized with respect to clinical, functional, and inflammatory parameters. The expression profiles of 20 serum cytokines were assessed by anti-human cytokine antibody array. Then, hierarchical clustering analysis was performed based on principal component analysis (PCA)-transformed data to classify the clinical groups. PCA showed that 6 independent components accounted for 80.113% of the variance, and PCA-based hierarchical clustering identified 3 endotypes. One of the endotypes was evidenced by elevated systemic inflammation markers such as leptin, vascular endothelial growth factor (VEGF), and reduced levels of soluble receptor for advanced glycation end products (sRAGE), an anti-inflammatory molecule. More female patients were included, with higher circulating neutrophil counts and more severe symptoms. In conclusion, we identified an endotype of asthma characterized by systemic inflammation and severe symptoms. Increased levels of VEGF, leptin and decreased level of sRAGE may contribute to the systemic inflammation of this asthma endotype.