title: Neonatal oxygen exposure alters airway hyper-responsiveness but not the response to allergen challenge in adult mice.
abstract: BACKGROUND
  Infants born prematurely are often treated with supplemental oxygen, which can increase their risk for airway hyper-responsiveness (AHR), asthma, reduced lung function, and altered responses to respiratory viral infections later in childhood. Likewise, exposure of newborn mice to hyperoxia alters baseline pulmonary mechanics and the host response to influenza A virus infection in adult mice. Here, we use this mouse model to test the hypothesis that neonatal hyperoxia also promotes AHR and exacerbated allergen-induced symptoms in adult mice.
  
  
  METHODS
  Baseline lung mechanics and AHR measured by methacholine provocation were assessed in adult male and female mice exposed to room air or 100% oxygen (hyperoxia) between post-natal days 0-4. AHR and lung inflammation were evaluated after adult female mice were sensitized with ovalbumin (OVA) plus alum and challenged with aerosolized OVA.
  
  
  RESULTS
  Baseline lung compliance increased and resistance decreased in adult female, but not male, mice exposed to neonatal hyperoxia compared with siblings exposed to room air. Neonatal hyperoxia significantly enhanced methacholine-induced AHR in female mice, but did not affect allergen-induced AHR to methacholine or lung inflammation.
  
  
  CONCLUSIONS
  Increased incidence of AHR and asthma is reported in children born prematurely and exposed to supplemental oxygen. Our findings in adult female mice exposed to hyperoxia as neonates suggest that this AHR reported in children born prematurely may reflect non-atopic wheezing due to intrinsic structural changes in airway development.
authors: Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA.
authors: Jean F
authors: JF
authors: Regal
authors: B Paige
authors: BP
authors: Lawrence
authors: Alex C
authors: AC
authors: Johnson
authors: Sarah J
authors: SJ
authors: Lojovich
authors: Michael A
authors: MA
authors: O'Reilly
mesh_terms: D000367:Age Factors; D000403:Airway Resistance; D000818:Animals; D000831:Animals, Newborn; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008170:Lung Compliance; D008297:Male; D016210:Methacholine Chloride; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin
keywords: airway hyper-responsiveness; allergen; asthma; eosinophilia; lung inflammation; murine; neonatal hyperoxia