Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants.

Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH); however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signaling pathways with the risk for BPD or PH.

Lung MRI as a Potential Complementary Diagnostic Tool for Early COPD.

Introduction: Many knowledge gaps in the nature of early chronic obstructive pulmonary disease (COPD) still exist, mainly because COPD has always been considered a disease of the elderly. Little attention has been paid to the pathologic changes in the lungs of young adults with risk factors for COPD, such as bronchopulmonary dysplasia. One major limitation is the current lack of noninvasive ways to sensitively measure or image functional declines from subjects who are at risk for COPD but haven't yet developed more significant clinical symptoms of the disease.

Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension.

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR ( = 64) and healthy controls ( = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF).

Bronchopulmonary dysplasia.

In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth.

Heterogeneous response of endothelial cells to insulin-like growth factor 1 treatment is explained by spatially clustered sub-populations.

A common strategy to measure the efficacy of drug treatment is the comparison of ensemble readouts with and without treatment, such as proliferation and cell death. A fundamental assumption underlying this approach is that there exists minimal cell-to-cell variability in the response to a drug. Here, we demonstrate that ensemble and non-spatial single-cell readouts applied to primary cells may lead to incomplete conclusions due to cell-to-cell variability.

Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet.

Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as (PND) . The trajectory of such early vascular changes remains unknown.

Long-term ventilation for children with chronic lung disease of infancy.

Purpose Of Review: Modern medical advances have resulted in an increased survival after extremely preterm birth. However, some infants will develop severe bronchopulmonary dysplasia (BPD) and fail to wean from invasive or noninvasive positive pressure support. It remains unclear which infants will benefit from tracheostomy placement for chronic ventilation.

Drugs for the Prevention and Treatment of Bronchopulmonary Dysplasia.

Rates of bronchopulmonary dysplasia (BPD) are increasing. After preterm birth, there are important developmental periods in which neonates are more vulnerable to stressful events. These periods are opportunities for pharmacologic interventions.

Acute Vasoreactivity Testing during Cardiac Catheterization of Neonates with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

Objectives: To assess whether better baseline pulmonary hemodynamics or positive acute vasoreactivity testing (AVT) during cardiac catheterization are associated with improved outcomes in infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH).

Study Design: This retrospective, single-center study included 26 premature neonates with BPD who underwent catheterization to evaluate PH. AVT was assessed with exposure to 100% fractional inspired oxygen with or without inhaled nitric oxide.

Recent advances in antenatal factors predisposing to bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains a major cause of late morbidities and death after preterm birth. BPD is characterized by an arrest of vascular and alveolar growth and high risk for pulmonary hypertension; yet mechanisms contributing to its pathogenesis and early strategies to prevent BPD are poorly understood. Strong epidemiologic studies have shown that the "new BPD" reflects the long-lasting impact of antenatal factors on lung development, partly due to placental dysfunction, as reflected in recent data from animal models.

Early Pulmonary Vascular Disease in Preterm Infants Is Associated with Late Respiratory Outcomes in Childhood.

Rationale: Early pulmonary vascular disease (PVD) after preterm birth is associated with a high risk for developing bronchopulmonary dysplasia (BPD), but its relationship with late respiratory outcomes during early childhood remains uncertain.

Objectives: To determine whether PVD at 7 days after preterm birth is associated with late respiratory disease (LRD) during early childhood.

Methods: This was a prospective study of preterm infants born before 34 weeks postmenstrual age (PMA).

Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review.

Objectives: To summarize evidence regarding microbial dysbiosis of the airway associated with bronchopulmonary dysplasia (BPD) and to explore heterogeneity among studies.

Study Design: We included studies that evaluated the airway microbiome in preterm infants who developed BPD using culture-independent molecular techniques and reported alpha- and beta-diversity metrics and microbial profiles.

Results: The 6 included studies had substantial clinical and methodological heterogeneity.

Echocardiographic Measurements of Right Ventricular Mechanics in Infants with Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age.

Objective: To test the hypothesis that specific echocardiographic measurements of right ventricular (RV) mechanics at 36 weeks postmenstrual age (PMA) are associated with the severity of bronchopulmonary dysplasia (BPD).

Study Design: A subset of 93 preterm infants (born between 27 and 29 weeks of gestation) was selected retrospectively from a prospectively enrolled cohort. BPD was defined using the National Institutes of Health workshop definition, with modifications for oxygen reduction testing and altitude.

Intrauterine growth restriction decreases NF-κB signaling in fetal pulmonary artery endothelial cells of fetal sheep.

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia, a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis; however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The NF-κB pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NF-κB-regulated proangiogenic targets in fetal PAEC.

Antenatal Vitamin D Preserves Placental Vascular and Fetal Growth in Experimental Chorioamnionitis Due to Intra-amniotic Endotoxin Exposure.

Background: Chorioamnionitis (CA) is associated with a high risk for the development of bronchopulmonary dysplasia (BPD) after preterm birth, but mechanisms that increase susceptibility for BPD and strategies to prevent BPD are uncertain. As a model of CA, antenatal intra-amniotic (IA) endotoxin (ETX) exposure alters placental structure, causes fetal growth restriction, increases perinatal mortality, and causes sustained cardiorespiratory abnormalities throughout infancy. Vitamin D (Vit D) has been shown to have both anti-inflammatory and proangiogenic properties.

An Approach to Children with Pulmonary Edema at High Altitude.

Unlabelled: Liptzin, Deborah R., Steven H. Abman, Ann Giesenhagen, and D.

Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted.

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

Rationale: Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA.

Objectives: Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy.