Elucidation of the immunoinflammatory mechanisms underlying severe virus-induced respiratory disease in early childhood

Severe lower respiratory infections cause acute viral bronchiolitis (AVB) in infancy and are a major risk factor for the development of persistent asthma in childhood. The underlying cellular/molecular mechanisms operative in infants/pre- school children with AVB and in school-age children with acute exacerbations of asthma in circulating cells/local airways tissues were elucidated. This thesis identified dysregulated expression of interferon-dependent pathways following respiratory viral infections as a defining immunophenotypic feature of A VB-susceptible infants and a subset of children. Personalised transcriptomic profiling unmasked sub-phenotypes that were not apparent by conventional group-wise comparisons offering exciting possibilities for improved prevention/treatment in the respiratory field.