Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with preterm birth, results from the disruption of normal pulmonary vascular and alveolar growth. Though BPD was once described as primarily due to postnatal injury from mechanical ventilation and oxygen therapy after preterm birth, it is increasingly appreciated that BPD results from antenatal and perinatal factors that interrupt lung development in infants born at the extremes of prematurity. The lung in BPD consists of a simplified parenchymal architecture that limits gas exchange and leads to increased cardiopulmonary morbidity and mortality. This review outlines recent advances in the understanding of pulmonary vascular development and describes how the disruption of these mechanisms results in BPD. We point to future therapies that may augment postnatal vascular growth to prevent and treat this severe chronic lung disease.

A single nucleotide polymorphism in the dimethylarginine dimethylaminohydrolase gene is associated with lower risk of pulmonary hypertension in bronchopulmonary dysplasia

“…The lungs in patients with BPD are characterized by areas of emphysema surrounded by atelectasis with widespread bronchial and bronchiolar mucosal hyperplasia and metaplasia (2, 3). Pulmonary hypertension (PH) is a relatively common complication of BPD, estimated to develop in 25–40% of patients with BPD (3,5–7) and the development of PH is associated with a marked increase in morbidity and mortality in BPD patients (1, 4, 5). The PH in BPD patients is characterized by decreased vascular surface area and vasoconstriction, which contribute to increased vascular resistance leading to the higher pulmonary arterial pressures found in BPD patients with PH (6, 7).…”

Plasma Proendothelin-1 as an Early Marker of Bronchopulmonary Dysplasia

“…In preterm newborns, raised plasma ET-1 levels have been related to the development of respiratory distress syndrome [3] whereas an early increase of ET-1 in the tracheal aspirate has been shown to correlate with subsequent progression to BPD [4]. In addition, the antiangiogenic effect of ET-1 has been linked to the pathogenesis of BPD [5] and evidence from human ex vivo models suggests that ET-1 signaling may play a critical role in the development of a BPD-like fibrotic process in the immature lung [6]. Although ET-1 is unstable in the peripheral blood and therefore less suited for diagnostic use, the more stable C-terminal fragment of the ET-1 precursor (CT-proET-1) can be used to estimate ET-1 release [7].…”

Cardiac Mechanics in Children with Bronchopulmonary Dysplasia

“…Given the vasculopathic changes described in the new form of BPD [1,5,6], RV performance in children born preterm with this complication is a legitimate concern. Using tissue Doppler imaging, Yates et al [12] reported an increased tricuspid E/e ratio suggestive of increased RV end-diastolic pressure, while Koroglu et al [13] reported on reduced tricuspid systolic diastolic annular velocities and increased RV myocardial performance consistent with impaired global systolic and diastolic RV function in children with BPD.…”

“…The new form of BPD is characterized by simplified alveolar structures, alteration of vascular development with abnormal capillary configuration, and variable degrees of interstitial fibroproliferation [1,5,6]. Impairment of alveolar and vascular development is believed to play a role in the development of cardiopulmonary disease and pulmonary hypertension [7].…”