title: A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile.
abstract: Asthma 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.
authors.affiliation: From the Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University (ZL, LL, HZ, YX, WZ, YY, SC); and State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (ZL, MJ).
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Liang
authors.forename: Laiyu
authors.initials: L
authors.lastname: Liu
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Ye
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001323:Autoantibodies / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013183:Sputum / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines