Non-eosinophilic Asthma Endotypes

Agache, Ioana

doi:10.1007/s40521-015-0052-2

Cited by 12 publications

(7 citation statements)

References 68 publications

(61 reference statements)

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“…79 In addition, type 1 immune response, metabolic or epigenetic factors, or the activation of the epithelial-mesenchymal trophic unit that may lead to extensive remodeling without any inflammation have been identified as modulators. The endotyping of the non-type 2 allergic diseases lags well behind type 2 immune response, and until now, no endotypedriven interventions have been proven to be effective.…”

Section: Neutrophilic Inflammationmentioning

confidence: 99%

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Agache

Akdiş

2016

Allergology International

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163

140

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Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

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Section: Neutrophilic Inflammationmentioning

confidence: 99%

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Agache

Akdiş

2016

Allergology International

Self Cite

163

140

View full text Add to dashboard Cite

show abstract

“…Most patients undergo an impairment of quality of life, and pulmonary function tests (PFTs) reveal a significant obstructive impairment of the lung function volume [3]. Although pathogenic mechanisms of these impairments are not well known, recent studies suggest of the involvement of specific endotypes (atopic, non-atopic eosinophilic, neutrophilic, paucigranulocytic, and mixed) and stimulates the research of new and therapeutic approaches [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Personalized Approach of Severe Eosinophilic Asthma Patients Treated with Mepolizumab and Benralizumab

Bergantini

d’Alessandro

Cameli

et al. 2020

Int Arch Allergy Immunol

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Background: New anti-IL-5 antibodies, mepolizumab and benralizumab, have recently been approved for severe asthma, sharing the same inclusion criteria. Objective: To contribute on biomarkers research leading to the personalized choice, we investigated L-selectin, Krebs von den Lungen (KL-6), and lymphocyte subsets as bioindicators of airway hyper-responsiveness and remodeling. Materials and Methods: A cohort of 28 patients affected by severe eosinophilic asthma were treated with anti-IL-5 drugs. According to clinical parameters, patients were subdivided into early and partial responders. Lymphocytes subsets were analyzed through flow cytometry, while KL-6 and sL-selectin were analyzed on serum samples. Clinical, functional, and immunological data at baseline (T0), after 1 month (T1), and 6 months of therapy were collected in a database. Results: All treated patients showed an increase in the percentage of forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity ratio and a decrease of peripheral eosinophils for both drugs after 1 month of treatment. Mepolizumab-treated patients also showed decreased CD8 + and NKT-like cell percentages and a significant increase in sL-selectin concentrations between T0 and T1. Stratifying the cohort of our patients in early and partial responders at T0, they showed a reduction of peripheral eosinophils, sL-selectin and KL-6, while no differences were found at T0 between early and partial responders patients treated with benralizumab. Conclusions: This real-life study provides new insights for the personalized approach to severe asthma therapy. Although preliminary, the results indicate that besides eosinophils, KL-6 and sL-selectin are useful as biomarkers of early response that can also involve in the pathogenesis of severe asthma.

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“…Although the exact mechanisms underlying asthma exacerbations have yet to be defined, studies suggest that RV infection of airway epithelium leads to cytokine interaction with allergic inflammation to overwhelm both innate and antigen-specific Th2 pathways resulting in enhanced Th2-related inflammation (71617). Moreover, both in children and adults, a complex association between RV infection and asthma exacerbation may also induce a non-Th2 immune response, along with increased AHR, mucus hypersecretion, airway remodeling, and respiratory failure (6).…”

Section: Asthma Exacerbationmentioning

confidence: 99%

“…However, in cases of severe and refractory asthma the multidimensional mechanisms and related immune response have yet to be defined. In non-Th2 response, the severity of augmented asthma and increased airway remodeling associated with poor prognosis have been correlated with a complex innate and adaptive immune response (6). Herein, the innate and adaptive immune signatures of asthma exacerbated by respiratory viral infection are discussed.…”

Section: Introductionmentioning

confidence: 99%

The Interplay between Host Immunity and Respiratory Viral Infection in Asthma Exacerbation

et al. 2019

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Asthma is one of the most common and chronic diseases characterized by multidimensional immune responses along with poor prognosis and severity. The heterogeneous nature of asthma may be attributed to a complex interplay between risk factors (either intrinsic or extrinsic) and specific pathogens such as respiratory viruses, and even bacteria. The intrinsic risk factors are highly correlated with asthma exacerbation in host, which may be mediated via genetic polymorphisms, enhanced airway epithelial lysis, apoptosis, and exaggerated viral replication in infected cells, resulting in reduced innate immune response and concomitant reduction of interferon (types I, II, and III) synthesis. The canonical features of allergic asthma include strong Th2-related inflammation, sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), eosinophilia, enhanced levels of Th2 cytokines, goblet cell hyperplasia, airway hyper-responsiveness, and airway remodeling. However, the NSAIDresistant non-Th2 asthma shows a characteristic neutrophilic influx, Th1/Th17 or even mixed (Th17-Th2) immune response and concurrent cytokine streams. Moreover, inhaled corticosteroid-resistant asthma may be associated with multifactorial innate and adaptive responses. In this review, we will discuss the findings of various in vivo and ex vivo models to establish the critical heterogenic asthmatic etiologies, host-pathogen relationships, humoral and cell-mediated immune responses, and subsequent mechanisms underlying asthma exacerbation triggered by respiratory viral infections.

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Non-eosinophilic Asthma Endotypes

Cited by 12 publications

References 68 publications

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Personalized Approach of Severe Eosinophilic Asthma Patients Treated with Mepolizumab and Benralizumab

The Interplay between Host Immunity and Respiratory Viral Infection in Asthma Exacerbation

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