Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
Pediatr Pulmonol. 2020 Mar;55(3):809-817. doi: 10.1002/ppul.24600. Epub 2020 Jan 8.
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.
儿童肥胖会导致许多疾病，包括哮喘。有文献表明，肥胖导致的哮喘具有非过敏性或非 T2 表型。在这篇综述中，将肥胖相关性哮喘作为儿童非 T2 哮喘的原型，讨论了几种潜在的儿童哮喘非过敏性机制。肥胖相关性哮喘与单核细胞激活时发生的全身辅助性 T 细胞（Th）1 极化有关。这些免疫反应是由胰岛素抵抗和血脂异常介导的，肥胖相关的代谢异常与肥胖哮喘患者的肺功能缺陷有关。与其他多因素疾病一样，儿童肥胖相关性哮喘既有遗传因素，也有环境因素。除了遗传易感性外，儿童肥胖相关性哮喘中非 T2 免疫反应还与 DNA 甲基化差异有关。对非 T2 免疫反应的生物学的初步研究已经确定了 CDC42 通路中基因的上调。CDC42 是一种 RhoGTPase，在 Th 细胞生理学中起着关键作用，包括优先将幼稚 Th 细胞分化为 Th1 细胞，以及细胞因子的产生和胞吐作用。尽管这些新的途径是有前途的发现，可以指导针对肥胖相关性哮喘的靶向治疗开发，以解决疾病负担问题，但有证据表明，饮食干预，包括饮食改变而不仅仅是热量限制，可以减轻疾病负担。采用富含微量营养素的饮食，包括类胡萝卜素和维生素 D 代谢物 25-OH 胆钙化醇，可能是有益的，因为这些物质与肺功能指数呈正相关，同时对与肥胖哮喘表型相关的代谢异常具有保护作用。
