Hyperoxia in the Pathogenesis of Bronchopulmonary Dysplasia

  • Anantha K. HarijithEmail author
  • Vineet Bhandari
Part of the Respiratory Medicine book series (RM)


The significant role of hyperoxia in the pathogenesis of bronchopulmonary dysplasia (BPD) is well established, although it is a disease of multifactorial origin. Advances in the management of extreme preterm newborns have increased their survival, though with significant resource utilization and increased costs. Improved survival accompanied a change in the morphology of BPD characterized by alveolar hypoplasia and abnormal vascular organization known as the “new BPD.” Clinical studies have shown that supplemental oxygen is one of the prominent inciting agents for the development of BPD. Exposure of newborn animals to 85–100 % O2 following birth serves as good models of BPD with alveolar simplification. Hyperoxia initially induces focal endothelial cell injury, but, with continued exposure, necrosis of epithelial cells also occurs resulting in impaired lung development. Disruption of lung septation leading to poor development of alveoli results in alveolar simplification leading to BPD. Exposure of premature lungs to hyperoxia results in alteration in angiogenic agents leading to interruption of pulmonary vascular development. Disrupted vascularization adversely impacts alveolar formation. Reactive oxygen species (ROS) is generated upon exposure to hyperoxia. ROS such as the superoxide anion (O2−) reacts with nitric oxide (NO) generated in the vascular endothelium forming peroxynitrite. Hyperoxia triggers increased production of ROS and reactive nitrogen species activating cytotoxic pathways, along with activation of protective pathways such as that of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2). Activation of cytotoxic pathways triggers release of caspases, matrix metalloproteins, interleukins, and interferon apart from transforming growth factor-β. Activation of sphingolipid pathways under hyperoxia has been shown in animal models to contribute to enhanced production of ROS contributing to neonatal lung injury. Knowledge of mechanisms of ROS production could lead to better understanding of therapeutic targets for BPD.


Oxygen Lung injury Newborn Cytokines Antioxidants 



Supported, in part, by grants HL-085103 from the NIH/NHLBI and The Hartwell Foundation to VB.

Conflict of interest None.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of PediatricsChildren’s Hospital at University of Illinois ChicagoChicagoUSA
  2. 2.Department of Neonatology (Pediatrics)Drexel University College of Medicine, St. Christopher’s Hospital for ChildrenPhiladelphiaUSA
  3. 3.Hahnemann University HospitalPhiladelphiaUSA
  4. 4.Temple University HospitalPhiladelphiaUSA

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