Serum <scp>IL</scp>‐5 and <scp>IL</scp>‐13 consistently serve as the best predictors for the blood eosinophilia phenotype in adult asthmatics

Agache, Ioana; Strasser, Daniel S.; Klenk, Axel; Agache, Costel; Farine, Hervé; Ciobanu, Cristina; Groenen, Peter M.A.; Akdiş, Cezmi A.

doi:10.1111/all.12906

Cited by 62 publications

(23 citation statements)

References 53 publications

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“…1 Longitudinal follow-up of clinical and molecular profiles is essential to confirm the validity of an endotype. 21 Participants in the Childhood Asthma Management Program (CAMP) study were evaluated 9 and 14 years after they ended the trial. Differences in clinical characteristics observed between subjects assigned to different phenotypic clusters persisted into young adulthood and were associated with differences in molecular signatures for atopy and asthma control.…”

Section: Biomarkers Precision Medicine and Endotypesmentioning

confidence: 99%

“…The next important variables were EDN and eNO. 21 The application of LCA integrating sputum supernatant eicosanoids with quantitative assessment of sputum cells revealed four distinct asthma classes differing in eicosanoid pathways. 32 In severe asthma, TDA identified six novel clinicpatho-biological clusters of underlying disease mechanisms, with elevated mast cell mediators tryptase, chymase, and carboxypeptidase A3.…”

Section: Biomarkers Precision Medicine and Endotypesmentioning

confidence: 99%

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

Agache

Akdiş

2016

Allergology International

161

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: Biomarkers Precision Medicine and Endotypesmentioning

confidence: 99%

Section: Biomarkers Precision Medicine and Endotypesmentioning

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

161

140

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“…Further, peripheral blood characterization was obtained at baseline, which allows consideration for validation of this method to be used as a predictive model for assessing asthma control in a clinical setting. Additionally, blood samples are more likely to reflect systemic inflammation than bronchial biopsies or washings and have been previously reported to be associated with airway inflammation, asthma phenotype, and asthma severity[39, 40]. …”

Section: Discussionmentioning

confidence: 99%

Endotypes of difficult-to-control asthma in inner-city African American children

et al. 2017

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African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

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“…The eosinophilic endotype is present in between 30 and 50% of people with stable asthma, and between 15 and 30% of stable COPD patients 15,35 . Eosinophilic airway inflammation has a clearly identified molecular pathway 36 and has been linked to both prognosis (increased exacerbation rate 37,38 ) and response to treatment with corticosteroids and anti-interleukin (IL)-5 monoclonal antibodies 39,40 . This makes the eosinophilic endotype one of the best-characterized endotypes.…”

Section: Inflammatory Endotypes Of Asthma and Copdmentioning

confidence: 99%

Phenotyping Asthma and COPD

Gibson¹,

McDonald²

2016

BRN

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Clinical management of asthma and COPD is complex, largely because of the marked heterogeneity observed in these conditions. Phenotyping is a new approach that can assist clinicians. This review seeks to describe an approach to clinical and inflammatory/molecular phenotyping of asthma and COPD. Clinical phenotypes can be considered in the key domain areas of comorbidity, airway, and risk factors. Evidence-based therapy can be linked to each of the components of these airway disease phenotypes. The concept can be extended to identify disease endotypes, where a pathogenic mechanism is linked to a specific treatment, and biomarkers are used to identify endotypes. Eosinophilic inflammation is perhaps the best characterized endotype of airway disease. Molecular endotypes are now also being identified using transcriptomic approaches. Phenotyping asthma and COPD represents a new and potentially effective approach to the management of these heterogeneous airway diseases. (BRN Rev. 2016;2:239-52)

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Serum IL‐5 and IL‐13 consistently serve as the best predictors for the blood eosinophilia phenotype in adult asthmatics

Abstract: Serum IL-5 and IL-13 are reliable biomarkers for the blood eosinophilia asthma phenotype. High or low expression of MCP-1, eotaxin, and IL-8 discriminates between eosinophilic asthma severity clusters.

Cited by 62 publications

References 53 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

Endotypes of difficult-to-control asthma in inner-city African American children

Phenotyping Asthma and COPD

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