Caffeine prevents airway hyperreactivity in a neonatal mouse model of continuous positive airway pressure

Abstract Background Continuous positive airway pressure (CPAP) is a primary non-invasive respiratory support modality for preterm infants. While there are benefits to CPAP, evidence suggests it may contribute to long-term wheezing and airway hyperreactivity (AHR) in preterm infants. Most preterm neonates also receive caffeine in addition to CPAP, which is associated with decreased rates of BPD. In a mouse model, we investigated whether caffeine administration during neonatal CPAP prevents long-term AHR. Methods Neonatal mice were fitted with a custom-made mask and received CPAP (6 cmH 2 0) for 3 h/day for the first 7 postnatal days. Mice also received a subcutaneous injection of caffeine (10 mg/kg/day) or saline (control mice) immediately prior to each CPAP session. Two weeks after treatment, mice were assessed for AHR and parameters of lung remodeling. Results CPAP resulted in long-term AHR (vs control mice), which was associated with increased airway αSM-actin expression, epithelial and alveolar septal wall thickening, and decreased radial alveolar counts. Co-administration of caffeine prevented CPAP effects. Conclusion Early caffeine administration protected against the long-term effects of CPAP on AHR and lung remodeling. These data demonstrate that neonatal caffeine benefits long-term respiratory function after CPAP administration by a direct effect on lung and airway development. Impact Neonatal CPAP may have long-term adverse consequences to the immature lung. This study demonstrates that caffeine attenuates the adverse effects of CPAP on lung development and airway remodeling. The results enhance our understanding of the complex effects that caffeine can have on lung development. CPAP may be a contributor to wheezing disorders of former preterm infants, but can be prevented by caffeine therapy. This study raises the clinical significance of CPAP effects on lung development and how caffeine could be optimized to help mitigate its adverse consequences.