Insights into early life lung injury from human and murine studies

Extremely preterm infants are highly vulnerable to lung injury and long-term respiratory morbidity, but the biological mechanisms underlying this vulnerability remain unclear. In this thesis, we analysed blood cell and plasma protein profiles from extremely preterm infants and identified two antenatal pathways associated with lung injury: one linked to inflammation before birth and another to low birthweight. Using a mouse model of bronchopulmonary dysplasia (BPD), we found that sustained blockade of the inflammatory molecule IL-1 protected against hyperoxia-induced alveolar damage. In contrast, deficiency of the type I interferon receptor did not alter alveolar injury. Mice with established BPD also showed altered responses to influenza A virus infection.