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A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Screeplot of principal component analysis. Six components had eigen values ≥1 (dotted line, and because 0.981 is approximately equal to 1, we also captured the sixth component)) and explained 80.113% of the variance.
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Figure 1: Screeplot of principal component analysis. Six components had eigen values ≥1 (dotted line, and because 0.981 is approximately equal to 1, we also captured the sixth component)) and explained 80.113% of the variance.

Mentions: Cytokine profile data were processed with PCA, and the 6 largest principal components extracted explained 80.113% of the information contained in the original data (Figure 1, Tables S3 and S4), suggesting that these 6 components alone explained most of the variability among groups.


A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile
Screeplot of principal component analysis. Six components had eigen values ≥1 (dotted line, and because 0.981 is approximately equal to 1, we also captured the sixth component)) and explained 80.113% of the variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998303&req=5

Figure 1: Screeplot of principal component analysis. Six components had eigen values ≥1 (dotted line, and because 0.981 is approximately equal to 1, we also captured the sixth component)) and explained 80.113% of the variance.
Mentions: Cytokine profile data were processed with PCA, and the 6 largest principal components extracted explained 80.113% of the information contained in the original data (Figure 1, Tables S3 and S4), suggesting that these 6 components alone explained most of the variability among groups.

View Article: PubMed Central - PubMed

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.

No MeSH data available.