title: Altered small airways in aged mice following neonatal exposure to hyperoxic gas.
abstract: BACKGROUND
  Supplemental oxygen is necessary in the respiratory support of very preterm infants, but it may contribute to bronchopulmonary dysplasia and an increased risk of poor lung function in later life. It is well established that hyperoxia can inhibit alveolarization, but effects on the developing conducting airways, which are important determinants of lung function, are poorly understood. It is possible that prolonged exposure of the immature lung to hyperoxic gas alters the development of small conducting airways (bronchioles), and that these effects may persist throughout life.
  
  
  OBJECTIVE
  To examine the effects of neonatal inhalation of hyperoxic gas on the bronchiolar walls in adulthood.
  
  
  METHODS
  Neonatal mice (C57BL/6J) born at term inhaled 65% O2 from birth until postnatal day 7; thereafter, they were raised in room air until 10 months postnatal age (P10mo), which is advanced adulthood. Age-matched controls inhaled room air from birth. We investigated small conducting airways with a diameter between 105-310 µm.
  
  
  RESULTS
  At P10mo, bronchiolar walls of hyperoxia-exposed mice contained ∼18% more smooth muscle than controls (p < 0.05), although there was no effect on bronchiolar epithelium or collagen. Neonatal hyperoxia resulted in significantly fewer bronchiolar-alveolar attachments at P10mo (p < 0.05); this was accompanied by persistent simplification of the lung parenchyma, as indicated by greater mean linear intercept and less parenchymal tissue (p < 0.05).
  
  
  CONCLUSIONS
  Neonatal exposure to hyperoxia induces remodeling of the bronchiolar walls and loss of bronchiolar-alveolar attachments in adulthood, both of which could contribute to impaired lung function and airway hyper-reactivity.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
authors.forename: Foula
authors.initials: F
authors.lastname: Sozo
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000453:epidemiology / Q000503:physiopathology; D055745:Bronchioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000150:complications* / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D010100:Oxygen