Pediatric obesity and severe asthma: Targeting pathways driving inflammation

Asthma affects more than 300 million people of all ages worldwide, including about 10-15% of school-aged children, and its prevalence is increasing. Severe asthma (SA) is a particular and rare phenotype requiring treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic glucocorticoid courses to achieve symptom control or remaining "uncontrolled" despite this therapy. In SA, other diagnoses have been excluded, and potential exacerbating factors have been addressed. Notably, obese asthmatics are at higher risk of developing SA. Obesity is both a major risk factor and a disease modifier of asthma in children and adults: two main "obese asthma" phenotypes have been described in childhood with high or low levels of Type 2 inflammation biomarkers, respectively, the former characterized by early onset and eosinophilic inflammation and the latter by neutrophilic inflammation and late-onset. Nevertheless, the interplay between obesity and asthma is far more complex and includes obese tissue-driven inflammatory pathways, mechanical factors, comorbidities, and poor response to corticosteroids. This review outlines the most recent findings on SA in obese children, particularly focusing on inflammatory pathways, which are becoming of pivotal importance in order to identify selective targets for specific treatments, such as biological agents.