New Pharmacologic Approaches to Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary Dysplasia is the most common long-term respiratory morbidity of preterm infants, with the risk of development proportional to the degree of prematurity. While its pathophysiologic and histologic features have changed over time as neonatal demographics and respiratory therapies have evolved, it is now thought to be characterized by impaired distal lung growth and abnormal pulmonary microvascular development. Though the exact sequence of events leading to the development of BPD has not been fully elucidated and likely varies among patients, it is thought to result from inflammatory and mechanical/oxidative injury from chronic ventilatory support in fragile, premature lungs susceptible to injury from surfactant deficiency, structural abnormalities, inadequate antioxidant defenses, and a chest wall that is more compliant than the lung. In addition, non-pulmonary issues may adversely affect lung development, including systemic infections and insufficient nutrition. Once BPD has developed, its management focuses on providing adequate gas exchange while promoting optimal lung growth. Pharmacologic strategies to ameliorate or prevent BPD continue to be investigated. A variety of agents, to be reviewed henceforth, have been developed or re-purposed to target different points in the pathways that lead to BPD, including anti-inflammatories, diuretics, steroids, pulmonary vasodilators, antioxidants, and a number of molecules involved in the cell signaling cascade thought to be involved in the pathogenesis of BPD.

Keywords: bronchopulmonary dysplasia; chronic lung disease; pharmacologic management; prematurity; pulmonary hypertension; respiratory distress.

Figure 1

The pulmonary injury sequence representing the stages of lung development and factors contributing to BPD which should be the focus of prevention of the disease. Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. All rights reserved. McEvoy CT, Jain L, Schmidt B, Abman S, Bancalari E, Aschner JL. NHLBI Workshop on the primary prevention of chronic lung disease: Bronchopulmonary dysplasia. Ann Am Thorac Soc. 2014;11: S146–S153. Annals of the American Thoracic Society is an official journal of the American Thoracic Society.

Figure 2

The various pathways to focus therapeutics for treatment of pulmonary hypertension which is a common complication in infants with BPD. Adapted from Semin Perinatol, 40(3), Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide, 160–73, Copyright (2016), with permission from Elsevier.