Division of Neonatology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.
Division of Pediatric Cardiology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.
Pediatr Res. 2022 Mar;91(4):804-815. doi: 10.1038/s41390-021-01413-w. Epub 2021 Mar 5.
Pulmonary hypertension has emerged as a life-threatening disease in preterm infants suffering from bronchopulmonary dysplasia (BPD). Its development is closely linked to respiratory disease, as vasculogenesis and alveologenesis are closely interconnected. Once clinically significant, BPD-associated pulmonary hypertension (BPD-PH) can be challenging to manage, due to poor reversibility and multiple comorbidities frequently associated. The pulmonary vascular disease process underlying BPD-PH is the result of multiple innate and acquired factors, and emerging evidence suggests that it progressively develops since birth and, in certain instances, may begin as early as fetal life. Therefore, early recognition and intervention are of great importance in order to improve long-term outcomes. Based on the most recent knowledge of BPD-PH pathophysiology, we review state-of-the-art screening and diagnostic imaging techniques currently available, their utility for clinicians, and their applicability and limitations in this specific population. We also discuss some biochemical markers studied in humans as a possible complement to imaging for the detection of pulmonary vascular disease at its early stages and the monitoring of its progression. In the second part, we review pharmacological agents currently available for BPD-PH treatment or under preclinical investigation, and discuss their applicability, as well as possible approaches for early-stage interventions in fetuses and neonates. IMPACT: BPD-associated PH is a complex disease involving genetic and epigenetic factors, as well as environmental exposures starting from fetal life. The value of combining multiple imaging and biochemical biomarkers is emerging, but requires larger, multicenter studies for validation and diffusion. Since "single-bullet" approaches have proven elusive so far, combined pharmacological regimen and cell-based therapies may represent important avenues for research leading to future cure and prevention.
肺高血压已成为患有支气管肺发育不良 (BPD) 的早产儿的一种危及生命的疾病。其发展与呼吸疾病密切相关，因为血管生成和肺泡发生是相互关联的。一旦出现临床意义上的 BPD 相关肺高血压 (BPD-PH)，由于其可逆性差且常伴有多种合并症，管理起来颇具挑战性。BPD-PH 所涉及的肺血管疾病是多种先天和后天因素共同作用的结果，新出现的证据表明，它从出生时就开始逐渐发展，在某些情况下，甚至可能早在胎儿期就开始了。因此，早期识别和干预对于改善长期预后非常重要。基于对 BPD-PH 病理生理学的最新认识，我们回顾了目前可用的最先进的筛查和诊断成像技术，以及它们对临床医生的实用性，以及它们在该特定人群中的适用性和局限性。我们还讨论了一些在人类中研究的生化标志物，作为影像学检测早期肺血管疾病和监测其进展的一种可能补充。在第二部分中，我们回顾了目前用于 BPD-PH 治疗或处于临床前研究阶段的药物，并讨论了它们的适用性，以及在胎儿和新生儿中进行早期干预的可能方法。 影响：BPD 相关 PH 是一种复杂的疾病，涉及遗传和表观遗传因素，以及从胎儿期开始的环境暴露。结合多种成像和生化生物标志物的价值正在显现，但需要更大的、多中心研究来验证和推广。由于迄今为止“单一方法”的效果并不理想，联合药物治疗和基于细胞的治疗可能是未来治愈和预防的重要研究途径。
