From phenotype to biological treatment of severe asthma

Severe asthma is considered a complex and heterogeneous disease, which includes different phenotypes, defined in terms of both clinical and molecular characteristics and different underlining endotypes. According to different studies, there are several clinical phenotypes of severe asthma in children. Most children are allergic to multiple aeroallergen sensitization (house dust mites, pollen, molds) and have high levels of total and specific IgE, reversible airflow obstruc- tion and early signs of remodelation. A small subgroup of children has persistent airflow limitation (FEV1 <80% predicted). There are two major underlining functional or pathophysiologic mechanisms for different phenotypes of asthma and severe asthma accord- ing to the immune mechanism: Type 2 asthma (Th2-high asthma, eosinophils in serum and sputum, high IgE levels, high FeNO; key cytokines IL-4, IL-5, IL-13) and non-Type 2 asthma (Th2-low asthma, neutrophilic, paucigranulocytic and mixed granulocytic inflam- mation; key cytokines IL-8, IL-17, IL-22). The type 2 asthma endotype is more common in children, while biomarkers involved in the pathogenesis, such as IgE and IL-5 have become targets for biological therapy. The non-type 2 asthma endotype, less frequent in children with severe asthma, has fewer therapeutic options. The effect of azithromycin is still under investigation. Severe asthma, although uncommon, is a complex and high-risk phenotype of childhood asthma. Close monitoring of the patient and precise definition of underlying endotype during evaluation enables identification and use of personalized, endotype-targeted treatment.
Category: Review
Volume: Vol. 66, No 1-2, january-june 2022
Authors: Blaženka Kljaić Bukvić-, Irena Ivković-Jureković, Marta Navratil, Marijana Rogulj, Davor Bandić, Jadranka Kelečić, Silvije Šegulja, Darko Richter
Reference work: Paediatr Croat. 2022;66:23-9

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