Unraveling the mechanisms of virus-induced asthma exacerbation: epithelial injury, immune dysregulation, and novel interventions.

Viral infections account for 60-80 % of asthma exacerbations (AE), representing a major burden in both pediatric and adult populations. The pathogenesis of virus-induced asthma exacerbation (VAE) is mechanistically complex, involving disruption of epithelial integrity, defective interferon responses, and abnormal activation of immune cells such as macrophages and innate lymphoid cells. In addition, the interplay between type 2 (T2) and non-T2 inflammation is dynamically regulated during viral infections, further amplifying airway dysfunction and remodeling. Although inhaled corticosteroids and biologics targeting T2 pathways are widely used, their efficacy in VAE is limited, especially in patients with neutrophilic or steroid-insensitive phenotypes, and virus-specific antiviral therapies for asthma are lacking. Recent advances have highlighted novel approaches targeting host immunity and epithelial-immune interactions, but most of these strategies remain in preclinical or early clinical phases, with few personalized treatment approaches available. This review summarizes insights into VAE pathogenesis and therapeutic advances, and discusses challenges and future directions in the development of targeted therapeutic strategies.