Extracellular Traps: A Novel Therapeutic Target for Severe Asthma

Choi, Youngwoo; Quoc, Quang Luu; Park, Hae‐Sim

doi:10.2147/jaa.s366014

Cited by 5 publications

(5 citation statements)

References 82 publications

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“… 32 Eosinophil extracellular trap (EET) which is released from activated eosinophils contains a mixture of web‐like DNA fibers and granule proteins. 33 EET‐forming eosinophil counts were positively correlated with serum EDN levels and negatively correlated with FEV 1 % in patients with SA. 34 In this context, EET and EDN have been postulated to be involved in the mechanism of activated eosinophils and potential therapeutic target for AERD.…”

Section: Discussionmentioning

confidence: 92%

“…As AERD is not fully understood by enhanced production of type 2 cytokines or cysteinyl leukotrienes, novel molecules related to activated eosinophils have been proposed to be implicated in AERD pathogenesis 32 . Eosinophil extracellular trap (EET) which is released from activated eosinophils contains a mixture of web‐like DNA fibers and granule proteins 33 . EET‐forming eosinophil counts were positively correlated with serum EDN levels and negatively correlated with FEV 1 % in patients with SA 34 .…”

Section: Discussionmentioning

confidence: 99%

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Association of eosinophil‐derived neurotoxin levels with asthma control status in patients with aspirin‐exacerbated respiratory disease

Ban

Yang

et al. 2023

Clinical & Translational All

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Background The long‐term goals of asthma treatment are to achieve well control of symptoms and to minimize the future risk of asthma exacerbation. Identifying biomarkers for uncontrolled asthma is important for improving the asthma outcome. This study aimed to investigate the association of the levels of eosinophil‐derived neurotoxin (EDN) with asthma control status in specific asthma phenotype, aspirin‐exacerbated respiratory disease (AERD), and aspirin‐tolerant asthma (ATA). Methods A total of 136 adult asthmatics, including 47 asthmatics with AERD and 89 asthmatics with ATA, were enrolled. Plasma, sputum, and urine were collected at enrollment and the levels of EDN were measured by the K‐EDN ELISA kit. Urinary leukotriene E4 (LTE 4 ) level was measured using liquid chromatography–mass spectrometry (LC‐MS)/MS methods. Asthma control status was evaluated according to the GINA guideline, asthma control test and asthma control questionnaire scores. Results In the total study subjects, sputum levels of EDN as well as of urine and plasma EDN showed significantly higher levels in patients with uncontrolled asthma than in those with well‐controlled or partly‐controlled asthma (ANOVA, p < 0.001); in patients with AERD, the sputum EDN levels showed significant correlations with ACT, ACQ, and AQLQ scores ( p = 0.010, r = −0.536, p = 0.001, r = 0.665, and p < 0.001, r = −0.691, respectively), while no differences were noted in patients with ATA. Sputum EDN level was the only significant factor for ACT, ACQ, and AQLQ scores in patients with AERD ( p = 0.001, p < 0.001, and p < 0.001, respectively) in the multivariate analysis adjusting for age, sex, peripheral eosinophil count, and urine LTE 4 . The ROC curve analysis demonstrated that sputum EDN can predict uncontrolled asthma with 80% sensitivity and 88.2% specificity for ACT ≤ 19 (area under the ROC curve [AUC] = 0.824, p = 0.019); 71.4% sensitivity and 86.7% specificity for ACQ ≥ 1.5 (AUC = 0.752, p = 0.049) only in AERD patients. Conclusion The level of sputum EDN may be a potential biomarker for identifying the asthma control status in patients with AERD.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Association of eosinophil‐derived neurotoxin levels with asthma control status in patients with aspirin‐exacerbated respiratory disease

Ban

Yang

et al. 2023

Clinical & Translational All

Self Cite

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“…In vitro studies have shown that IL-5 can stimulate eosinophils to release EETs in a ROS-dependent manner [ 32 ]. Furthermore, in patients with severe eosinophilic asthma, peripheral blood eosinophils exhibit enhanced release of EETs when co-stimulated with IL-5 and LPS [ 93 ], suggesting that elevated levels of IL-5 in vivo may play an important role in the pathogenesis of severe eosinophilic asthma [ 94 ].…”

Section: Therapeutic Targets For Eetsmentioning

confidence: 99%

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy

Shen,

Zhang,

Zhao

et al. 2023

Respir Res

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Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

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“…As such, NETs have been implicated in the pathogenesis of asthma in adults. Indeed, both NETs and eosinophil extracellular traps (EETs) seem to be implicated in persistent asthma [ 27 ]; however, the aspects of these mechanisms remain understudied. In particular, the protein profile of NET structures, which is determined by the disease microenvironment, is not known, and NETosis in severe childhood asthma remains a scientific puzzle.…”

Section: Introductionmentioning

confidence: 99%

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation

et al. 2023

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Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.

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Extracellular Traps: A Novel Therapeutic Target for Severe Asthma

Cited by 5 publications

References 82 publications

Association of eosinophil‐derived neurotoxin levels with asthma control status in patients with aspirin‐exacerbated respiratory disease

Association of eosinophil‐derived neurotoxin levels with asthma control status in patients with aspirin‐exacerbated respiratory disease

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation

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