Cumulative neonatal oxygen exposure predicts response of adult mice infected with influenza A virus.
An acceptable level of oxygen exposure in preterm infants that maximizes efficacy and minimizes harm has yet to be determined. Quantifying oxygen exposure as an area-under-the curve (OAUC) has been predictive of later respiratory symptoms among former low birth weight infants. Here, we test the hypothesis that quantifying OAUCin newborn mice can predict their risk for altered lung development and respiratory viral infections as adults. Newborn mice were exposed to room air or a FiO2of 100% oxygen for 4 days, 60% oxygen for 8 days, or 40% oxygen for 16 days (same cumulative dose of excess oxygen). At 8 weeks of age, mice were infected intranasally with a non-lethal dose of influenza A virus. Adult mice exposed to 100% oxygen for 4 days or 60% oxygen for 8 days exhibited alveolar simplification and altered elastin deposition compared to siblings birthed into room air, as well as increased inflammation and fibrotic lung disease following viral infection. These changes were not observed in mice exposed to 40% oxygen for 16 days. Our findings in mice support the concept that quantifying OAUCover a currently unspecified threshold can predict human risk for respiratory morbidity later in life. Pediatr Pulmonol. 2015; 50:222-230. © 2014 Wiley Periodicals, Inc.
Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Echezona T
ET
Maduekwe
Department of Environmental Medicine, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Bradley W
BW
Buczynski
Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Min
M
Yee
Department of Medicine, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Tiruamalai
T
Rangasamy
Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Timothy P
TP
Stevens
Department of Environmental Medicine, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
B Paige
BP
Lawrence
Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, Rochester, New York.
Michael A
MA
O'Reilly
TB; bronchopulmonary dysplasia; chronic lung disease; hyperoxia; infections: pneumonia; prematurity; viral