The immunological landscape of viral infections in asthma: mechanistic insights and therapeutic paradigm shifts

Asthma is a common chronic respiratory disease in which respiratory viral infections—particularly rhinoviruses—are closely intertwined with disease manifestations. Such infections contribute substantially to pediatric asthma episodes and to a notable proportion of adult asthma presentations, reflecting the underlying immune dysregulation characteristic of asthma. Key components of the innate antiviral response—including the airway epithelium, dendritic cells, and natural killer cells—exhibit diminished antiviral activity in asthma, a deficiency that permits greater viral replication and persistence. Concurrently, individuals with asthma frequently exhibit type 2 immunity, an immune profile that drives IgE production, eosinophilic inflammation, and airway hyperresponsiveness. Children are particularly susceptible to the immunological impacts of respiratory viral infections in the context of asthma, potentially due to immune immaturity and less robust early-life antiviral defenses. Crucially, the crosstalk between innate and adaptive immunity dictates the severity of asthma-related clinical manifestations during viral infections: a compromised antiviral innate response, when paired with a type 2-skewed adaptive immune environment, can synergistically promote severe airway inflammation and airflow obstruction. Although inhaled corticosteroids (ICS) remain a cornerstone of maintenance therapy for preventing asthma exacerbations, ICS-based therapy does not fully prevent virus-associated exacerbations, particularly in patients with type 2-low, neutrophil-predominant, or severe uncontrolled asthma. By contrast, oral or systemic corticosteroids remain the first-line treatment for acute exacerbations, highlighting the need to distinguish maintenance ICS therapy from acute systemic corticosteroid use. Future therapeutic strategies should therefore prioritize enhancing antiviral immune responses and modulating virus-induced neutrophilic inflammation to better prevent and mitigate asthma-related clinical challenges associated with viral infections.