Airway Hyperreactivity Is Delayed after Mild Neonatal Hyperoxic Exposure

Abstract

Background: Wheezing disorders are prominent in former preterm infants beyond the neonatal period.

Objectives: We used a neonatal mouse model to investigate the time course of airway hyperreactivity in response to mild (40% oxygen) or severe (70% oxygen) neonatal hyperoxia.

Methods: After hyperoxic exposure during the first week of postnatal life, we measured changes in airway reactivity using the in vitro living lung slice preparation at the end of exposure [postnatal day 8 (P8)] and 2 weeks later (P21). This was accompanied by measures of smooth muscle actin, myosin light chain (MLC) and alveolar morphology.

Results: Neither mild nor severe hyperoxia exposure affected airway reactivity to methacholine at P8 compared to normoxic controls. In contrast, airway reactivity was enhanced at P21 in mice exposed to mild (but not severe) hyperoxia, 2 weeks after exposure ended. This was associated with increased airway α-smooth muscle actin expression at P21 after 40% oxygen exposure without a significant increase in MLC. Alveolar morphology via radial alveolar counts was comparably diminished by both 40 and 70% oxygen at both P8 and P21.

Conclusions: These data demonstrate that early mild hyperoxia exposure causes a delayed augmentation of airway reactivity, suggesting a long-term alteration in the trajectory of airway smooth muscle development and consistent with resultant symptomatology.