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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.

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Pairwise comparisons of clinical parameters between endotypes. Data were analyzed with one-way analysis of variance with the least significant difference post hoc test. ACQ-5 = 5-item Asthma Control Questionnaire, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity
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Figure 4: Pairwise comparisons of clinical parameters between endotypes. Data were analyzed with one-way analysis of variance with the least significant difference post hoc test. ACQ-5 = 5-item Asthma Control Questionnaire, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity

Mentions: To determine whether the patients within these endotypes represented clinically distinct subgroups of asthma, the clinical features of the 3 endotypes were analyzed (Table 3 and Figure 4). Endotype 1 showed a higher proportion of males, low blood basophil levels, high baseline forced vital capacity (FVC), high baseline FEV1, and low ACQ-5. Endotype 2 showed high blood neutrophil levels, high blood basophil levels, high FVC, high FEV1, and low ACQ-5. Finally, endotype 3 showed a high proportion of females, high blood neutrophil levels, low blood basophil levels, low baseline FVC, low baseline FEV1, high datime symptom score, and high ACQ-5 score. Therefore, both endotypes 1 and 2 had a higher frequency of patients with relatively normal lung function and moderate symptoms, although endotype 1 contained significantly more male patients. Endotype 3 had a higher-frequency female patients, and was characterized by decreased lung function and more severe symptoms (Figure 4).


A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile
Pairwise comparisons of clinical parameters between endotypes. Data were analyzed with one-way analysis of variance with the least significant difference post hoc test. ACQ-5 = 5-item Asthma Control Questionnaire, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Pairwise comparisons of clinical parameters between endotypes. Data were analyzed with one-way analysis of variance with the least significant difference post hoc test. ACQ-5 = 5-item Asthma Control Questionnaire, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity
Mentions: To determine whether the patients within these endotypes represented clinically distinct subgroups of asthma, the clinical features of the 3 endotypes were analyzed (Table 3 and Figure 4). Endotype 1 showed a higher proportion of males, low blood basophil levels, high baseline forced vital capacity (FVC), high baseline FEV1, and low ACQ-5. Endotype 2 showed high blood neutrophil levels, high blood basophil levels, high FVC, high FEV1, and low ACQ-5. Finally, endotype 3 showed a high proportion of females, high blood neutrophil levels, low blood basophil levels, low baseline FVC, low baseline FEV1, high datime symptom score, and high ACQ-5 score. Therefore, both endotypes 1 and 2 had a higher frequency of patients with relatively normal lung function and moderate symptoms, although endotype 1 contained significantly more male patients. Endotype 3 had a higher-frequency female patients, and was characterized by decreased lung function and more severe symptoms (Figure 4).

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