Obesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches.

Abstract

Though obesity-related asthma associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and glucagon-like-peptide 1 (GLP-1) receptor agonists, have been associated with improved asthma outcomes, though GLP-1R agonist data in asthma is limited to individuals with co-morbid obesity. Monoclonal antibodies approved for treatment of moderate to severe asthma generally appear to be effective in individuals with obesity, though this is based on retrospective or secondary analysis of clinical trials; moreover, while most of these asthma biologics are approved for use in the pediatric population, the impact of obesity on their efficacy has not been well studied in youth. Potential therapeutic targets being investigated include IL-6, arginine metabolites, nitro-fatty acids, and mitochondrial antioxidants, with clinical trials for each currently underway. Potential therapeutic targets include adipose tissue eosinophils and the GLP-1-Arginine-Advanced glycation end products axis, though data in humans is still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of interferon-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, in order to facilitate effective treatment development for this unique asthma phenotype.