The role of hyperoxia in the pathogenesis of experimental BPD

Abstract

Supplemental oxygen is often used as a life-saving therapy in the treatment of preterm infants. However, its protracted use can lead to the development of bronchopulmonary dysplasia (BPD), and more recently, has been associated with adversely affecting the general health of children and adolescents who were born preterm. Efforts to understand how exposure to excess oxygen can disrupt lung development have historically focused on the interplay between oxidative stress and antioxidant defense mechanisms. However, there has been a growing appreciation for how changes in gene-environment interactions occurring during critically important periods of organ development can profoundly affect human health and disease later in life. Here, we review the concept that oxygen is an environmental stressor that may play an important role at birth to control normal lung development via its interactions with genes and cells. Understanding how changes in the oxygen environment have the potential to alter the developmental programing of the lung, such that it now proceeds along a different developmental trajectory, could lead to novel therapies in the prevention and treatment of respiratory diseases, such as BPD.

Figure 1

Lung development is divided into five different stages, including the embryonic (E), pseudoglandular (P), canalicular (C), saccular (S), and alveolar (A) periods. With the exception of the alveolar period, lung development primarily occurs in a relative hypoxic environment in utero until it transitions to a relative hyperoxic environment at birth. Lung development is disrupted when preterm infants, whose lungs are often in the saccular stage (bold) and developing under low oxygen conditions, transition into room air or are exposed to therapeutically elevated levels of oxygen.

Figure 2

The integration of a specific oxygen environment with genes and cells is required for proper development of the lung. Representative genes and cell types that may be affected by exposure to hyperoxia, as described throughout this chapter, are noted in the figure.