Novel Strategies to Reduce Pulmonary Hypertension in Infants With Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a developmental lung disorder of preterm infants primarily caused by the failure of host defense mechanisms to prevent tissue injury and facilitate repair. This disorder is the most common complication of premature birth, and its incidence remains unchanged over the past few decades. Additionally, BPD increases long-term cardiopulmonary and neurodevelopmental morbidities of preterm infants. Pulmonary hypertension (PH) is a common morbidity of BPD. Importantly, the presence of PH increases both the short-and long-term morbidities and mortality in BPD infants. Further, there are no curative therapies for this complex disease. Besides providing an overview of the pathogenesis and diagnosis of PH associated with BPD, we have attempted to comprehensively review and summarize the current literature on the interventions to prevent and/or mitigate BPD and PH in preclinical studies. Our goal was to provide insight into the therapies that have a high translational potential to meaningfully manage BPD patients with PH.

Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

“…Pulmonary vascular and right ventricular remodeling are common pathological features for BPD-associated pulmonary hypertension. There are no curative therapies, and current management of this disease is limited to pulmonary vasodilators, minimizing further insults to the pulmonary vasculature, and optimizing respiratory status [ 108 , [115] , [116] , [117] ].…”

Focused Update on Pulmonary Hypertension in Children—Selected Topics of Interest for the Adult Cardiologist

“…The decreased vessel density throughout the pulmonary microcapillary network leads to decreased cross sectional area for pulmonary blood flow and increased pulmonary vascular resistance [ 169 , 171 ]. Risk factors for BPD-PH are low birth weight, maternal abnormalities such as oligohydramnion, pre-eclampsia and postnatal injuries, including hyperoxia, hypoxia and infection, all of which lead to endothelial injury, disruption of growth factor expression and the activation of signalling pathways promoting vascular remodelling [ 169 , 172 , 173 , 174 , 175 ]. Genetic susceptibility appears to play a further role in this process.…”

“…The prevalence of PH based on RHC is between 6 and 10.5% [ 224 , 227 , 228 ]. The use of tricuspid regurgitation velocity (TRV) ≥ 2.5 m/s as a non-invasive surrogate marker for elevated PA pressure reveals a 30% prevalence of PH in adults, with 8–10% of them having more severe PH suggested by a TRV > 3 m/s [ 174 , 178 ]. A similar prevalence of PH is reported in children with an average of 30% (8–66%) with TRV > 2.5 m/s and 8% (4–14%) with a TRV > 3 m/s [ 229 , 230 , 231 ].…”

Long Non-coding RNA TUG1 Modulates Expression of Elastin to Relieve Bronchopulmonary Dysplasia via Sponging miR-29a-3p

“…Apart from postnatal determinants of lung injury and low gestational age, adverse antenatal factors, such as gestational hypertensive disorders, maternal obesity, and gestational diabetes, also lead to the pathological and clinical features of BPD (2)(3)(4). Currently, there are many studies to support several therapeutic strategies, including antenatal glucocorticoids, surfactant therapy, interleukin-1 receptor antagonist, and microbiome (5,6). Despite intensifying efforts to manage BPD, BPD incidence and mortality of preterm neonates still pose a great challenge for us (7).…”