Pulmonary hypertension in bronchopulmonary dysplasia

Abstract

Pulmonary hypertension (PH) is a common complication of neonatal respiratory diseases, including bronchopulmonary dysplasia (BPD), and recent studies have increased awareness that PH worsens the clinical course, morbidity and mortality of BPD. Recent evidence indicates that up to 18% of all extremely low-birth-weight infants will develop some degree of PH during their hospitalization, and the incidence rises to 25-40% of the infants with established BPD. Risk factors are not yet well understood, but new evidence shows that fetal growth restriction is a significant predictor of PH. Echocardiography remains the primary method for evaluation of BPD-associated PH, and the development of standardized screening timelines and techniques for identification of infants with BPD-associated PH remains an important ongoing topic of investigation. The use of pulmonary vasodilator medications, such as nitric oxide, sildenafil, and others, in the BPD population is steadily growing, but additional studies are needed regarding their long-term safety and efficacy.

Figure 1

Lung photomicrograph from a child with severe BPD and PH. Note the dramatically thickened pulmonary arteries (arrow), as well as findings of increased hemosiderin laden macrophages in the alveolar spaces and organizing pneumonia.

Figure 2

The distribution of birth weight (BW) percentiles according to PH status. Bar graphs of five BW subgroups demonstrates that greater than one-half of infants with pulmonary hypertension had birth weights <25^th percentile. PHTN: pulmonary hypertension.

Figure 3

Echocardiographic images depicting the septal flattening as seen in pulmonary hypertension. The upper image shows mild septal flattening, while the bottom image shows worse disease

Figure 4

Nitric oxide (NO), prostacyclin (PGI₂) and endothelin (ET)-1 signaling pathways in the regulation of pulmonary vascular tone. NO produced by endothelial cells stimulates soluble guanylate cyclase to increase intracellular cyclic GMP (cGMP). PGI₂ produced by vascular endothelium stimulates adenylate cyclase to increase intracellular cyclic AMP (cAMP). Both cGMP and cAMP indirectly decrease free cytosolic calcium, resulting in smooth muscle relaxation. Sildenafil enhances vasodilation via inhibition phosphodiesterase 5 (PDE5) and the hydrolysis of cGMP. ET-1 produced by endothelial cells binds endothelin A (ETA) and endothelin B (ETB) receptors on smooth muscle cells. The ET-1 receptor antagonist Bosentan augments smooth muscle vasoconstriction by blocking ET-1 effects.