Oxidative Stress in Neonatal Lung Diseases

Abstract

Neonates experience abrupt surge in oxygen (O2) tension immediately after birth when their antioxidant defense system is not yet fully established. The more than fivefold increase in O2 tension causes immediate oxidative stress, and the change can be more exaggerated when neonates are born with respiratory distress that requires supplemental O2 to maintain tissue metabolism. This perinatal transition-induced oxidative stress is apparently very different from those experienced by other age groups. There are more than 1 in every 100 neonates who suffer from respiratory distress at birth. When mechanical ventilation is used for respiratory distress, which sometimes can be complicated with infection secondary to the invasive treatments, more oxidative stress will be generated. Mechanical ventilation, oxygen use, and infection are the three major contributors to neonatal chronic lung disease (CLD) – bronchopulmonary dysplasia – and all of them are associated with the generation of reactive oxidants. Persistent pulmonary hypertension of the newborn (PPHN) which occurs 1 in every 500 live births is another common neonatal lung disease mainly due to the persistence of high pulmonary vascular resistance. Increased endogenous oxidative stress has been shown to play a mechanistic role in the decreased vasodilation in PPHN. Inhaled nitric oxide and high concentration oxygen are used to reduce the pulmonary vascular resistance in PPHN. Since the lung is the first organ to confront this dramatic perinatal change, the cells within the lung need to cope with the oxidative stress. Cells respond to the oxidative stress with unfolded protein response, autophagy, and other adaptive mechanisms to survive this challenge by sacrificing their normal functions. When the oxidative stress persists too long, or is too overwhelming, then cell growth will be impaired with the development of chronic lung disease as a complication. The first 2–6 years of life is the most important period for lung growth, so any injury during this critical period can have major long-term impact to adult lung function. Neonates who survive chronic lung disease usually need months or even years of O2 support; this obviously will further prolong the oxidative stress of their lungs. Pulmonary hypertension can complicate the CLD which significantly increases the mortality rate. The CLD survivors are also prone to develop chronic obstructive pulmonary disease which is the major leading cause of death worldwide. Although oxidative stress plays a vital role in causing lung injury, the antioxidant treatment, however, has never shown clinical efficacy indicating that more complicated mechanisms are involved. Roughly 20,000 neonates suffer from chronic lung diseases each year in the USA. New therapeutic strategies are apparently in need to help these neonates with a better lung growth.