Addressing the challenges of phenotyping pediatric pulmonary vascular disease

Abstract

Pediatric pulmonary vascular disease (PVD) and pulmonary hypertension (PH) represent phenotypically and pathophysiologically diverse disease categories, contributing substantial morbidity and mortality to a complex array of pediatric conditions. Here, we review the multifactorial nature of pediatric PVD, with an emphasis on improved recognition, phenotyping, and endotyping strategies for pediatric PH. Novel tailored approaches to diagnosis and treatment in pediatric PVD, as well as the implications for long-term outcomes, are highlighted.

Keywords: childhood; long-term outcomes; pulmonary hypertension; registry studies.

Fig. 1.

Diverse and interactive factors contributing to pulmonary vascular disease in pediatrics.

Fig. 2.

Developmental lung diseases associated with neonatal pulmonary hypertension, including Down syndrome (left panel), bronchopulmonary dysplasia (middle panel), and alveolar capillary dysplasia (right panel). In addition to hypertensive remodeling of small pulmonary arteries (denoted by arrows in each panel), these disorders are further characterized by decreased alveolarization, abnormal lung vascular growth, and prominent intrapulmonary vessels (bronchopulmonary or venous, as noted by V in right panel, alveolar capillary dysplasia).

Fig. 3.

Factors associated with survival in pediatric pulmonary hypertensive vascular disease from the Spanish Registry highlight the importance of large registry studies for uncommon diseases such as pediatric pulmonary hypertension. (Reprinted with permission of the American Thoracic Society. Copyright © 2016 American Thoracic Society. Del Cerro Marin MJ, Sabate Rotes A, Rodriguez Ogando A, et al. 2014. Assessing pulmonary hypertensive vascular disease in childhood. Data from the Spanish registry. Am J Respir Crit Care Med 190: 1421–1429. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.)

Fig. 4.

Chest X-ray (left panel) and CT angiography demonstrating pulmonary vein stenosis in an infant with severe bronchopulmonary dysplasia and pulmonary hypertension.

Fig. 5.

Early life pulmonary vascular development impacts adult pulmonary vascular endowment and risk for pulmonary hypertension.