Arginine and Nitric Oxide Pathways in Obesity-Associated Asthma

Obesity is a comorbidity that adversely affects asthma severity and control by mechanisms that are not fully understood. This review will discuss evidence supporting a role for nitric oxide (NO) as a potential mechanistic link between obesity and late-onset asthma (>12 years). Several studies have shown that there is an inverse association between increasing body mass index (BMI) and reduced exhaled NO. Newer evidence suggests that a potential explanation for this paradoxical relationship is related to nitric oxide synthase (NOS) uncoupling, which occurs due to an imbalance between L-arginine (NOS substrate) and its endogenous inhibitor, asymmetric di-methyl arginine (ADMA). The review will propose a theoretical framework to understand the relevance of this pathway and how it may differ between early and late-onset obese asthmatics. Finally, the paper will discuss potential new therapeutic approaches, based on these paradigms, for improving the respiratory health of obese subjects with asthma.