The rhinovirus puzzle: Linking virus and host factors to childhood asthma.

Rhinoviruses (RVs) are the most common respiratory pathogens and a significant cause of asthma exacerbations and wheezing illnesses in children. In addition, RV wheezing illnesses during the preschool years strongly predict asthma development. This review includes updates on RV epidemiology and virus diversity, highlighting species-specific differences and antigenic variability that present significant challenges for vaccine design. Host responses to RV involve canonical antiviral responses originating in airway epithelial cells, followed by activation of adaptive immunity. In patients with asthma and allergic disease, type 2 inflammation, genetic susceptibility, and epithelial remodeling impair these antiviral defenses. These factors, combined with airway dysbiosis, can exacerbate airway injury and lead to more severe illnesses. RV infection disrupts epithelial barrier integrity, promotes pathobiont growth, and induces factors that can drive structural changes associated with airway obstruction and chronic asthma. Therapeutic strategies, including direct antivirals and interferons, show promise but remain limited by adverse effects and modest efficacy, while extreme virus diversity remains an obstacle to vaccine development. Advances in understanding how host factors, such as type 2 inflammation, increase susceptibility to RV infection and illness identify alternative approaches to reducing RV morbidity in high-risk children with allergic diseases and asthma.