35 research outputs found
Potential Metabolic Biomarkers in Adult Asthmatics
No full textAsthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. In particular, the systematic analysis of all metabolites in a biological system, such as carbohydrates, amino acids, and lipids, has helped identify a novel pathway related to complex diseases. These metabolites are involved in the regulation of hypermethylation, response to hypoxia, and immune reactions in the pathogenesis of asthma. Among them, lipid metabolism has been suggested to be related to lung dysfunction in mild-to-moderate asthma. Sphingolipid metabolites are an important mediator contributing to airway inflammation in obese asthma and aspirin-exacerbated respiratory disease. Although how these molecular variants impact the disease has not been completely determined, identification of new causative factors may possibly lead to more-personalized and precise pathway-specific approaches for better diagnosis and treatment of asthma. In this review, perspectives of metabolites related to asthma and clinical implications have been highlighted according to various phenotypes
Distinct functions of eosinophils in severe asthma with type 2 phenotype: clinical implications
No full textAsthma is commonly recognized as a heterogeneous condition with a complex pathophysiology. With advances in the development of multiple medications for patients with asthma, most asthma symptoms are well managed. Nevertheless, 5% to 10% of adult asthmatic patients (called severe asthma) are in uncontrolled or partially controlled status despite intensive treatment. Especially, severe eosinophilic asthma is one of the severe asthma phenotypes characterized by eosinophilia in sputum/blood driven by type 2 immune responses. Eosinophils have been widely accepted as a central effector cell in the lungs. Some evidence has demonstrated that persistent eosinophilia in upper and lower airway mucosa contributes to asthma severity by producing various mediators including cytokines, chemokines and granule proteins. Moreover, extracellular traps released from eosinophils have been revealed to enhance type 2 inflammation in patients with severe asthma. These novel molecules have the ability to induce airway inf lammation and hyperresponsiveness through enhancing innate and type 2 immune responses. In this review, we highlight recent insight into the function of eosinophil extracellular traps in patients with severe asthma. In addition, the role of eosinophil extracellular vesicles in severe asthma is also proposed. Finally, current biologics are suggested as a potential strategy for effective management of severe eosinophilic asthma
A Dimensional Themes’ Matrix for Identifying Design Problem Structure
No full textDesigners use various design methods and tools to understand user needs, identify using process and context, and set a design direction in the design process. Generally, Human-Centered Design (HCD) process requires the process of classifying and interpreting a vast amount of raw user data into meaningful information. Designers frequently use affinity diagrams to transform the data into meaningful information. However, it is difficult to get rational insights only within the affinity diagram, since it is challenging to synthetically analyze the derived keywords. This paper presents a new method of analyzing user data called ???dimensional themes??? matrix???. The matrix enables designers to understand the design problem structure by positioning user data on the intersections of two keyword dimensions. It provides rationales to insights by enhancing the connectivity of the keyword themes, which is difficult to capture with the original affinity diagram. ?? 2020, The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG
Lactobacillus paracasei-derived extracellular vesicles alleviate neutrophilic asthma by inhibiting the JNK pathway in airway epithelium
No full textBackground: Lactobacillus paracasei has been known to reduce airway resistance and inflammation in asthma. However, the therapeutic effect of its extracellular vesicles (EVs) in patients with asthma remains unclear. Methods: To validate the clinical relevance of L. paracasei-derived EVs (LpEV) in asthma, the composition of gut microbial EVs was verified by metagenomics in LPS-induced C57BL/6 mice. The components of proteins and metabolites in LpEV were identified by peptide mass fingerprinting and metabolomic analysis. The serum levels of specific IgG1 or IgG4 antibodies to LpEV were compared by ELISA between patients with eosinophilic asthma (EA, n = 10) and those with neutrophilic asthma (NA, n = 10) as well as with healthy controls (HCs, n = 10). Finally, therapeutic effects of LpEV and their metabolites in asthma were validated in vivo/in vitro. Results: Significantly lower proportions of EVs derived from Lactobacillus at the genus level were noted in mice with NA than in control mice. Moreover, the serum levels of LpEV-specific IgG4, but not IgG1, were lower in patients with NA than in those with EA or in HCs and positively correlated with FEV1 (%) values. In addition, oral administration of LpEV reduced airway resistance and inflammation in mice with NA. Finally, LpEV and their 3 metabolites (dodecanoic acid, palmitoleic acid, and D-(−)-tagatose) significantly inhibited JNK phosphorylation/IL-8 production in airway epithelium in vitro. Conclusions: These findings suggest that LpEV may have a therapeutic potential targeting NA by suppressing the JNK pathway and proinflammatory cytokine production in airway epithelium
Epithelial Autoantigen-Specific IgG Antibody Enhances Eosinophil Extracellular Trap Formation in Severe Asthma
No full textPURPOSE: There have been autoimmune mechanisms for the pathogenesis of severe asthma (SA) involving epithelial autoantigen-specific antibodies. This study aimed to find the function of these antibodies in the formation of eosinophil extracellular traps (EETs), contributing to the development of SA. METHODS: Patients with SA (n = 11), those with patients with nonsevere asthma (NSA, n = 41), and healthy controls (HCs, n = 26) were recruited to evaluate levels of epithelial antigens and autoantigen-specific antibodies. Moreover, the significance of epithelial autoantigen-specific antibodies in association with EET production was investigated ex vivo and in vivo. RESULTS: Significantly higher levels of serum cytokeratin (CK) 18 and CK18-specific IgG were observed in patients with SA than in those with NSA (P = 0.001 and P = 0.031, respectively), while no differences were found in serum CK19 or CK19-specific immunoglobulin G (IgG). Moreover, levels of serum CK18 were positively correlated with total eosinophil counts (r = 0.276, P = 0.048) in asthmatics, while a negative correlation was noted between levels of serum CK18 and forced expiratory volume in 1 second (FEV1) %. In the presence of CK18-specific IgG, peripheral eosinophils from asthmatics released EETs, which further increased CK18 production from airway epithelial cells. In severe asthmatic mice, CK18 expression and CK18-specific IgG production were enhanced in the lungs, where EET treatment enhanced CK18 expression and CK18-specific IgG production, either of which was not suppressed by dexamethasone. CONCLUSIONS: These suggest that EETs could enhance epithelial autoantigen (CK18)-induced autoimmune responses, further stimulating EET production and type 2 airway responses, which is a new therapeutic target for SA
Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma
No full textBackground Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs. Methods Peripheral counts of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti-IL-33/TSLP antibody were tested. Results The numbers of EET+ eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these two cells (r = .539, P < .001). When mice were injected with EETs, we observed significant increases in epithelium-derived cytokines (IL-1 alpha, IL-1 beta, CXCL-1, CCL24, IL-33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL-5- or IL-13-producing ILC2s in the lungs. When Rag1(-/-) mice receiving ILC2s were treated with EETs, increased AHR and IL-5/IL-13 levels in BALF were noted, which were effectively suppressed by anti-IL-33 or anti-TSLP antibody. Conclusion EETs could enhance innate and type 2 immune responses in SA, in which epithelium-targeting biologics (anti-IL-33/TSLP antibody) may have a potential benefit.11Nsciescopu
Association between levels of serum TGF-β1 and urinary LTE<sub>4</sub> in the study subjects.
No full textData are represented as Spearman correlation coefficient r (P value).</p
Effect of TGF-β1 on LTC<sub>4</sub>S expression in human peripheral eosinophils.
No full textEffect of TGF-β1 on (A) LTC4S expression and (B) LTC4S levels in peripheral eosinophils in a time- or dose-dependent manner (samples from 3 asthmatic patients were pooled). (C) Function of dexamethasone against TGF-β1 treatment (samples from 3 asthmatic patients were pooled). (D) Comparison of LTC4S levels between ARED and ATA patients (n = 3 asthmatic patients per group).</p
Characteristics of asthmatic patients with high (≥48.1 ng/mL) and low TGF-β1 (<48.1 ng/mL) levels in the first cohort.
No full textCharacteristics of asthmatic patients with high (≥48.1 ng/mL) and low TGF-β1 (<48.1 ng/mL) levels in the first cohort.</p
Relation between levels of urinary LTE<sub>4</sub> and serum EDN.
No full text(A) Levels of serum EDN in the study subjects. Data are presented as mean. P values were obtained by Student’s t test. (B) A correlation between the levels of serum EDN and urinary LTE4. Data are represented as Spearman correlation coefficient r (P value).</p
