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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.


Related in: MedlinePlus

Pairwise comparisons of serum cytokine concentrations between endotypes. Data were analyzed with 1-way analysis of variance with the least significant difference post hoc test. E = endotype, EGF = epidermal growth factor, GM-CSF = Granulocyte-macroprhage colony-stimulating factor, IFN = interferon, IL = interleukin, sRAGE = soluble receptor for advanced glycation end products, TGF-β1 = transforming growth factor-beta 1, TNF = tumor necrosis factor, VEGF = vascular endothelial growth factor.
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Figure 3: Pairwise comparisons of serum cytokine concentrations between endotypes. Data were analyzed with 1-way analysis of variance with the least significant difference post hoc test. E = endotype, EGF = epidermal growth factor, GM-CSF = Granulocyte-macroprhage colony-stimulating factor, IFN = interferon, IL = interleukin, sRAGE = soluble receptor for advanced glycation end products, TGF-β1 = transforming growth factor-beta 1, TNF = tumor necrosis factor, VEGF = vascular endothelial growth factor.

Mentions: Post-hoc analyses of between-group differences were performed. Compared with endotypes 2 and 3, endotype 1 showed relatively high levels of proinflammatory cytokines (IFN-γ, IL-4, IL-5, IL-6, IL-9, IL-17, IL-23, EGF, GM-CSF, and TNF-α) and relatively high levels of anti-inflammatory cytokines (IL-10, TGF-β, and sRAGE). Compared with endotypes 1 and 3, endotype 2 showed relatively low levels of proinflammatory cytokines (INF-γ, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, IL-23, EGF, GM-CSF, TNF-α, and VEGF), and relatively low levels of anti-inflammatory cytokines (IL-10 and sRAGE). Compared with endotypes 1 and 2, endotype 3 displayed relatively high levels of leptin and VFGF, but low sRAGE levels (Table 2 and Figure 3). These results suggest distinct patterns of cytokines among there 3 endotypes.


A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile
Pairwise comparisons of serum cytokine concentrations between endotypes. Data were analyzed with 1-way analysis of variance with the least significant difference post hoc test. E = endotype, EGF = epidermal growth factor, GM-CSF = Granulocyte-macroprhage colony-stimulating factor, IFN = interferon, IL = interleukin, sRAGE = soluble receptor for advanced glycation end products, TGF-β1 = transforming growth factor-beta 1, TNF = tumor necrosis factor, VEGF = vascular endothelial growth factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Pairwise comparisons of serum cytokine concentrations between endotypes. Data were analyzed with 1-way analysis of variance with the least significant difference post hoc test. E = endotype, EGF = epidermal growth factor, GM-CSF = Granulocyte-macroprhage colony-stimulating factor, IFN = interferon, IL = interleukin, sRAGE = soluble receptor for advanced glycation end products, TGF-β1 = transforming growth factor-beta 1, TNF = tumor necrosis factor, VEGF = vascular endothelial growth factor.
Mentions: Post-hoc analyses of between-group differences were performed. Compared with endotypes 2 and 3, endotype 1 showed relatively high levels of proinflammatory cytokines (IFN-γ, IL-4, IL-5, IL-6, IL-9, IL-17, IL-23, EGF, GM-CSF, and TNF-α) and relatively high levels of anti-inflammatory cytokines (IL-10, TGF-β, and sRAGE). Compared with endotypes 1 and 3, endotype 2 showed relatively low levels of proinflammatory cytokines (INF-γ, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, IL-23, EGF, GM-CSF, TNF-α, and VEGF), and relatively low levels of anti-inflammatory cytokines (IL-10 and sRAGE). Compared with endotypes 1 and 2, endotype 3 displayed relatively high levels of leptin and VFGF, but low sRAGE levels (Table 2 and Figure 3). These results suggest distinct patterns of cytokines among there 3 endotypes.

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.


Related in: MedlinePlus