Pediatric obesity-related asthma: A prototype of pediatric severe non-T2 asthma.

Abstract

Childhood obesity contributes to many diseases, including asthma. There is literature to suggest that asthma developing as a consequence of obesity has a nonallergic or non-T2 phenotype. In this review, obesity-related asthma is utilized as a prototype of non-T2 asthma in children to discuss several nonallergic mechanisms that underlie childhood asthma. Obesity-related asthma is associated with systemic T helper (Th)1 polarization occurring with monocyte activation. These immune responses are mediated by insulin resistance and dyslipidemia, metabolic abnormalities associated with obesity, that are themselves associated with pulmonary function deficits in obese asthmatics. As in other multifactorial diseases, there is both a genetic and an environmental contribution to pediatric obesity-related asthma. In addition to genetic susceptibility, differential DNA methylation is associated with non-T2 immune responses in pediatric obesity-related asthma. Initial investigations into the biology of non-T2 immune responses have identified the upregulation of genes in the CDC42 pathway. CDC42 is a RhoGTPase that plays a key role in Th cell physiology, including preferential naïve Th cell differentiation to Th1 cells, and cytokine production and exocytosis. Although these novel pathways are promising findings to direct targeted therapy development for obesity-related asthma to address the disease burden, there is evidence to suggest that dietary interventions, including diet modification, rather than caloric restriction alone, decrease disease burden. Adoption of a diet rich in micronutrients, including carotenoids and 25-OH cholecalciferol, a vitamin D metabolite, may be beneficial since these are positively correlated with pulmonary function indices, while being protective against metabolic abnormalities associated with the obese asthma phenotype.