Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction

Abstract

Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

Keywords: benralizumab; child; dupilumab; mepolizumab; omalizumab; reslizumab.

Figure 1

Eosinophilic asthma inflammatory pathways. There are two aetiologies for eosinophilic inflammation in asthma: an allergic pathway triggered by allergens and a non-allergic mechanism triggered by microbes, pollutants and glycolipids. The key mediators in the pathways are depicted below. Eosinophils release cationic proteins, which lead to bronchial epithelial tissue damage, thus causing airways hyper-responsiveness. Eosinophils also lead to airway smooth muscle cell proliferation through increased eosinophils adhesion caused by the release of cationic proteins and the eosinophilic effect on transforming growth factor-β1 and gene coding of wingless/integrase-1 signaling. IL-13 triggers mucus hyper-secretion. Figure created with BioRender.com.

Figure 2

Licensed mediator cascade of biologics used in eosinophilic asthma. The figure below shows the targets for the licensed biologics. Omalizumab is an IgE-blocker. Mepolizumab, reslizumab and benralizumab are anti IL-5 agents. Dupilumab is an Anti-IL-4/anti-IL-13 agent. Figure created with BioRender.com.