Early-Life Viral Lower Respiratory Tract Infections and Their Impact on Childhood Asthma: Molecular Endotypes and Prevention Strategies.

Background

Early-life viral lower respiratory tract infections (LRTIs), particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are major contributors to pediatric morbidity and are strongly linked to asthma. RSV causes about 3.6 million hospitalizations and 100,000 deaths annually in children under 5, mainly in low- and middle-income countries. RSV peaks in infancy, while HRV has more impact later in childhood. Mechanisms include viral epithelial injury, genetic susceptibility (e.g., 17q21 variants), and environmental factors (e.g., allergic sensitization). Together, these raise asthma risk. Diagnosis is difficult due to overlapping presentations and reliance on molecular tests. Preventive strategies include maternal RSV vaccination, long-acting monoclonal antibodies such as nirsevimab and palivizumab, and pediatric vaccine candidates. Strategies to limit allergic sensitization may lower HRV-related asthma risk. Long-term effects include persistent wheeze and asthma, making early life a crucial window for prevention.

Methods

This review summarizes current evidence on the epidemiology, mechanisms, and long-term impact of early viral LRTIs.

Results

It highlights molecular and immunological endotypes of virus-induced asthma and explores the influence of genetic, epigenetic, and microbial factors. Emerging diagnostic tools and preventive strategies-including vaccines, monoclonal antibodies, environmental interventions, and microbiome-targeted therapies-are also discussed as means to reduce the global pediatric asthma burden and improve respiratory health.