Biomarkers for severe eosinophilic asthma

Yancey, Steven W.; Keene, Oliver N.; Albers, Frank C.; Ortega, Héctor; Bates, Stewart; Bleecker, Eugene R.; Pavord, Ian

doi:10.1016/j.jaci.2017.10.005

Cited by 202 publications

(178 citation statements)

References 70 publications

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“…It is well established that systemic corticosteroids and biologics targeting the IL-5 pathway have a strong impact on blood eosinophil concentrations 6. Our observation that also changes in ICS doses profoundly impact on blood eosinophils has two important clinical implications.…”

Section: To the Editormentioning

confidence: 66%

Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Lommatzsch

Klein

Stoll

et al. 2018

Thorax

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Here, we report that increasing treatment with inhaled corticosteroids (ICS) in patients with not well-controlled asthma from a medium to a high dose results in a profound reduction of blood eosinophils (median fall in blood eosinophil concentrations from 560 to 320 cells/µL). Therefore, ‘normal values’ of blood eosinophils in patients with asthma need to be considered in view of the individual ICS doses of the patients. In addition, increases in the dose of ICS may result in blood eosinophil concentrations which would formally preclude treatment with biologics targeting the interleukin-5 pathway.

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Section: To the Editormentioning

confidence: 66%

Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Lommatzsch

Klein

Stoll

et al. 2018

Thorax

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show abstract

“…Moreover, it is noteworthy that clinical factors such as prognosis and recurrence rate are also essential to appraise the whole concept of eosinophilic CRS. Furthermore, eosinophil‐relevant biomarkers may be clinically used for diagnostic purposes, for classification guidance, or as tools for predicting prognosis and treatment response in CRSwNP . Considering future directions in CRS classification, cluster analysis of not only traditional phenotype information but also endotype features should be used.…”

Section: Resultsmentioning

confidence: 99%

Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement

Lou

Zhang

Bachert

et al. 2018

Int Forum Allergy Rhinol

170

157

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BackgroundTissue eosinophils are characteristic of inflammation in most but not all patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and may be useful for defining subgroups and making treatment choices. However, no consistent diagnostic criteria for CRSwNP with eosinophilic inflammation have been established.MethodsRelated literature review was performed and current developments in the diagnosis of eosinophilic CRSwNP were summarized. Details in histopathology, definition of tissue eosinophilia, eosinophil as an indicator of disease recurrence, eosinophilic shift, and related biomarkers in CRSwNP are included in this review article.ResultsMucosal eosinophilia exhibits significant geographic and ethnic differences and may increase over time. Tissue eosinophilia can be defined using a cutoff value based on reference values from healthy mucosa, but typical disease‐specific values should also be employed to increase sensitivity and specificity for clinical use. Recent developments highlight the diagnostic criteria for eosinophilic CRSwNP based on cluster analysis, which were also associated with clinical outcomes. Additionally, some promising eosinophil‐relevant biomarkers, such as eosinophilic cation protein and interleukin 5 (IL‐5), may be clinically applied as diagnostic or predictive tools for CRSwNP in the future.ConclusionSinonasal tissue eosinophilia is present in a majority of CRSwNP patients but is currently more common in the West than in the East. Cutoff values of eosinophils as the diagnostic criteria of eosinophilic CRSwNP are subject to change with geographic and ethnic differences over time. It will be important to identify validated eosinophil‐related biomarkers in different continents/countries for future research and for the introduction of precision medicine.

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“…Integration of signals from the microenvironment preferentially activates different secretory pathways within eosinophils; discrete activation profiles measurable by image analysis of peripheral blood eosinophils could therefore provide insight into disease phenotype or endotype and response to treatment. Allergic disease, asthma, and parasite infection have been the focus for eosinophil‐related research these past decades, but there is growing appreciation of their contribution to host defense against bacteria and viruses, various hypereosinophilic syndromes, autoimmune disease, cancer, and a range of eosinophilic gastrointestinal disorders that are increasing in prevalence .…”

Section: Discussionmentioning

confidence: 99%

Diffusion Mapping of Eosinophil‐Activation State

et al. 2019

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Eosinophils are granular leukocytes that play a role in mediating inflammatory responses linked to infection and allergic disease. Their activation during an immune response triggers spatial reorganization and eventual cargo release from intracellular granules. Understanding this process is important in diagnosing eosinophilic disorders and in assessing treatment efficacy; however, current protocols are limited to simply quantifying the number of eosinophils within a blood sample. Given that high optical absorption and scattering by the granular structure of these cells lead to marked image features, the physical changes that occur during activation should be trackable using image analysis. Here, we present a study in which imaging flow cytometry is used to quantify eosinophil activation state, based on the extraction of 85 distinct spatial features from dark‐field images formed by light scattered orthogonally to the illuminating beam. We apply diffusion mapping, a time inference method that orders cells on a trajectory based on similar image features. Analysis of exogenous cell activation using eotaxin and endogenous activation in donor samples with elevated eosinophil counts shows that cell position along the diffusion‐path line correlates with activation level (99% confidence level). Thus, the diffusion mapping provides an activation metric for each cell. Assessment of activated and control populations using both this spatial image‐based, activation score and the integrated side‐scatter intensity shows an improved Fisher discriminant ratio rd = 0.7 for the multivariate technique compared with an rd = 0.47 for the traditional whole‐cell scatter metric. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

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Biomarkers for severe eosinophilic asthma

Cited by 202 publications

References 70 publications

Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement

Diffusion Mapping of Eosinophil‐Activation State

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