This article reviews existing therapeutic strategies and emerging treatment targets for obesity-related asthma, including pathways such as GLP-1R, IL-6, and arginine metabolism. Additionally, the authors identify several areas requiring further investigation, such as IFN signaling, Rho-GTPase pathway, and integrins. These findings offer new insights for precision treatment of obesity-related asthma.
Literature Overview
This article, titled 'Obesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches,' published in the American Journal of Respiratory and Critical Care Medicine, reviews and summarizes current treatment approaches for obesity-related asthma along with their underlying mechanisms. It also proposes several potential therapeutic targets. The article emphasizes the impact of obesity on asthma phenotypes and discusses treatment strategies targeting metabolic and inflammatory pathways.
Background Knowledge
Obesity-related asthma is a complex and difficult-to-treat asthma phenotype, often associated with poor clinical outcomes, including inadequate asthma control, reduced quality of life, and increased frequency of acute exacerbations. Current treatment mainly relies on weight loss, comorbidity management (e.g., gastroesophageal reflux, sleep apnea), and traditional asthma medications, which have limited efficacy. Obesity can lead to non-Type 2 (non-T2) inflammatory responses, and thus the effectiveness of existing biologics in obese populations remains uncertain. Recent advances in understanding the comorbid mechanisms of obesity and asthma have identified several potential therapeutic targets, including IL-6, arginine metabolism, nitro-fatty acids, and mitochondrial antioxidants. Furthermore, genomic and epigenetic studies suggest that pathways such as IFN signaling, Rho-GTPase, and integrins may serve as novel treatment targets. These findings provide a theoretical foundation for developing precision treatment strategies tailored to obesity-related asthma.
Research Methods and Experiments
The article reviews existing pharmacological treatments for obesity-related asthma, such as metformin and GLP-1 receptor (GLP-1R) agonists, summarizing their potential benefits in improving asthma control. The authors also analyzed the efficacy of monoclonal antibodies (e.g., omalizumab, dupilumab, mepolizumab) in obese populations, finding that while most remain effective, obesity may influence treatment response. Several emerging therapeutic targets are discussed, including IL-6, arginine metabolism, nitro-fatty acids, mitochondrial antioxidants, as well as pathways involving adipose tissue eosinophils and the GLP-1–arginine–AGE axis.
Key Conclusions and Perspectives
Research Significance and Prospects
This article provides a comprehensive review of obesity-related asthma and proposes multiple novel therapeutic targets. Future research should focus on understanding how BMI affects the efficacy of biologics and further investigate non-T2 inflammatory pathways. Additionally, precision medicine studies based on gene editing and animal models are required to validate the translational applicability of these targets in humans.
Conclusion
Obesity-related asthma represents a difficult-to-treat phenotype, with current therapeutic strategies primarily relying on weight loss, comorbidity management, and conventional asthma medications, which offer limited effectiveness. Emerging therapeutic targets such as GLP-1R, IL-6, arginine metabolism, nitro-fatty acids, and mitochondrial antioxidants show promising therapeutic potential but require further investigation. Genomic and epigenetic studies suggest that pathways including IFN signaling, Rho-GTPase, and integrins may serve as future therapeutic targets. Further prospective and randomized controlled trials are needed to validate the efficacy of these strategies across diverse populations, particularly in children and adolescents, to enable precision treatment for obesity-related asthma.
