AbstractIt is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection suggesting neonatal oxygen may have induced hidden molecular changes that may prime to the lung for disease. We discovered that thrombospondin-1 (TSP-1) is elevated in adult mice exposed to high-dose neonatal hyperoxia that is known to cause alveolar simplification and fibrotic lung disease following IAV infection. TSP-1 was also elevated in a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that we recently reported causes a transient change in lung function that resolves by 8 weeks of age. Elevated TSP-1 was also identified in human autopsy samples of BPD-affected former preterm infants. Consistent with TSP-1 being a master TGFβ regulator, an early transient activation of TGFβ signaling, increased airway hyperreactivity, and peribronchial inflammation and fibrosis were seen when 40×8 mice were infected with IAV, which was not seen in infected room air controls. These findings reveal low dose of neonatal hyperoxia that does not affect lung function or structure may still change expression of genes, such as TSP-1, that may prime the lung for disease following respiratory viral infections, and may help explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.
Accelerated Weaning after Early Low Dose Dexamethasone Therapy in Very Preterm Infants