Emerging interface between metabolic syndrome and asthma

Abstract

There is growing epidemiological evidence that obesity increases the risk of developing asthma. In some studies, insulin resistance or metabolic syndrome is a stronger risk factor than body mass. The obese-asthma subphenotype is marked by a paucity of inflammation but also by marked symptoms, poor response to glucocorticoids, and peripheral airway dysfunction. Although obesity may predispose to increased Th2 inflammation or atopic tendencies, other mechanisms that are independent of inflammatory cells need to be considered. There is growing evidence of the influence of hyperglycemia, hyperinsulinemia, and insulin-like growth factors on airway structure and function. Also, studies from mouse models of asthma have highlighted the importance of nitric oxide-arginine metabolism abnormalities and oxonitrosative stress in lungs. Such changes are well established features of the metabolic syndrome and may represent an interface between these diseases that can be therapeutically targeted. Such therapies, including administration of L-arginine or statins, increasing endothelial nitric oxide synthase, or the use of arginase inhibitors, have been successful in experimental models but have not yet translated to the clinical arena. We review the current understanding of the potential mechanistic links between obesity and asthma, emphasizing the potential influence of metabolic abnormalities on asthmatic processes, therapeutic implications, and expected challenges.