Precision Medicine for the discovery of treatable mechanisms in severe Asthma.

Precision Medicine for the discovery of treatable mechanisms in severe Asthma.

Publication date: Mar 13, 2019

Although the complex disease of asthma has been defined as being heterogeneous, the extent of its endophenotypes remain unclear. The pharmacological approach to initiating treatment has, until recently, been based on disease control and severity. The introduction of antibody therapies targeting the Type2 inflammation pathway for patients with severe asthma has resulted in the recognition of an allergic and an eosinophilic phenotype, which are not mutually exclusive. Concomitantly, molecular phenotyping based on a transcriptomic analysis of bronchial epithelial and sputum cells has identified a Type-2-high inflammation cluster characterised by eosinophilia and recurrent exacerbations, as well as Type-2-low clusters linked with IL-6 trans-signalling, interferon pathways, inflammasome activation and mitochondrial oxidative phosphorylation pathways. Systems biology approaches are establishing the links between these pathways or mechanisms, and clinical and physiologic features. Validation of these pathways contributes to defining endotypes and treatable mechanisms. Precision medicine approaches are necessary to link treatable mechanisms with treatable traits and biomarkers derived from clinical, physiologic and inflammatory features of clinical phenotypes. The deep molecular phenotyping of airway samples along with non-invasive biomarkers linked to bioinformatic and machine learning techniques will enable the rapid detection of molecular mechanisms that transgresses beyond the concept of treatable traits. This article is protected by copyright. All rights reserved.

Chung, K.F. and Adcock, I.M. Precision Medicine for the discovery of treatable mechanisms in severe Asthma. 04217. 2019 Allergy.

Concepts Keywords
Airway Biomarker
Allergic Asthma
Antibody Respiratory therapy
Asthma Clinical medicine
Bioinformatic Branches of biology
Biomarkers Medicine
Bronchial Eosinophilia
Eosinophilia High inflammation
Eosinophilic
Epithelial
Inflammasome
Inflammation
Interferon
Mitochondrial
Oxidative Phosphorylation
Pharmacological
Phenotype
Phenotypes
Sputum
Transcriptomic

Semantics

Type Source Name
gene UNIPROT EAF2
pathway BSID Oxidative phosphorylation
gene UNIPROT IL6
disease DOID eosinophilia
disease MESH eosinophilia
disease MESH inflammation
pathway BSID Asthma
disease DOID Asthma
disease MESH Asthma

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