Oxygen Toxicity to the Immature Lung-Part I: Pathomechanistic Understanding and Preclinical Perspectives.

In utero, the fetus and its lungs develop in a hypoxic environment, where HIF-1α and VEGFA signaling constitute major determinants of further development. Disruption of this homeostasis after preterm delivery and extrauterine exposure to high fractions of oxygen are among the key events leading to bronchopulmonary dysplasia (BPD). Reactive oxygen species (ROS) production constitutes the initial driver of pulmonary inflammation and cell death, altered gene expression, and vasoconstriction, leading to the distortion of further lung development.

Oxygen Toxicity to the Immature Lung-Part II: The Unmet Clinical Need for Causal Therapy.

Oxygen toxicity continues to be one of the inevitable injuries to the immature lung. Reactive oxygen species (ROS) production is the initial step leading to lung injury and, subsequently, the development of bronchopulmonary dysplasia (BPD). Today, BPD remains the most important disease burden following preterm delivery and results in life-long restrictions in lung function and further important health sequelae.