Multi-Dimensional Perspective of the Gene and Environmental Interaction in Asthma.
Asthma is a debilitating disease, and its diagnosis and disease management remain imprecise. It continues to impose a major global burden on public health, medicine, and the economy. Asthma exhibits marked heterogeneity in clinical phenotypes, and environmental and genetic risk factors remain incompletely defined. Moreover, its significant geographical and ethnic variation limits diagnostic precision. They also hinder effective risk stratification and accurate prediction of disease exacerbations. To date, most asthma research and therapeutic development have focused on allergen-mediated immune responses. Conversely, the adverse effects of environmental chemical pollutants have received less attention. This imbalance has limited the development of a comprehensive understanding of asthma pathogenesis. It has also slowed progress toward truly precision-based therapies. Simultaneously, growing experimental and clinical evidence highlights causal links between environmental exposures and disease. The concepts of the exposome and exposomics have also emerged. These provide useful frameworks to study disease development and progression. In this review, we summarize recent multicenter studies on asthma. These studies show that environmental determinants of asthma are not uniform, as different asthma phenotypic clusters have distinct environmental exposure profiles. Moreover, environmentally driven metabolic reprogramming plays an important role, resulting in bioactive metabolites that also deserve careful attention. These factors are crucial for advancing precision environmental medicine.