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Published on: October 19, 2013
Airway Hyperreactivity Is Delayed after Mild Neonatal Hyperoxic Exposure
Harris Onugha1, Peter M MacFarlane, Catherine A Mayer
1Division of Neonatology, Rainbow Babies and Children's Hospital, and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
Insights
Neonatal exposure to mild hyperoxia delayed airway hyperreactivity in mice, suggesting long-term changes in airway smooth muscle development. This may explain wheezing disorders in infants after premature birth.
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Developmental biology
Background:
- Wheezing disorders are common in infants born prematurely.
- Neonatal hyperoxia is a risk factor for respiratory issues in these infants.
Purpose of the Study:
- To investigate the long-term effects of neonatal hyperoxia on airway hyperreactivity.
- To determine the impact of mild (40% oxygen) versus severe (70% oxygen) hyperoxia.
Main Methods:
- A neonatal mouse model was used to assess airway reactivity.
- In vitro living lung slice preparation was employed at postnatal days 8 and 21.
- Measurements included airway reactivity, smooth muscle actin, myosin light chain (MLC), and alveolar morphology.
Main Results:
- No immediate changes in airway reactivity were observed at postnatal day 8.
- Mild hyperoxia exposure led to enhanced airway reactivity at postnatal day 21, two weeks after exposure cessation.
- Increased airway alpha-smooth muscle actin expression was noted after mild hyperoxia, without significant MLC changes.
- Both mild and severe hyperoxia reduced alveolar counts at both time points.
Conclusions:
- Early, mild neonatal hyperoxia exposure results in a delayed increase in airway reactivity.
- This suggests a long-term alteration in airway smooth muscle development.
- Findings align with the persistent symptomatology observed in former preterm infants.
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.
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