Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
Department of Paediatrics, Monash University, Melbourne, Victoria, Australia; Monash Newborn, Monash Health, Clayton, Victoria, Australia.
J Reprod Immunol. 2017 Nov;124:21-29. doi: 10.1016/j.jri.2017.09.013. Epub 2017 Oct 2.
Bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (BPD-PH) are chronic inflammatory cardiopulmonary diseases with devastating short- and long-term consequences for infants born prematurely. The immature lungs of preterm infants are ill-prepared to achieve sufficient gas exchange, thus usually necessitating immediate commencement of respiratory support and oxygen supplementation. These therapies are life-saving, but they exacerbate the tissue damage that is inevitably inflicted on a preterm lung forced to perform gas exchange. Together, air-breathing and necessary therapeutic interventions disrupt normal lung development by aggravating pulmonary inflammation and vascular remodelling, thus frequently precipitating BPD and PH via an incompletely understood pathogenic cascade. BPD and BPD-PH share common risk factors, such as low gestational age at birth, fetal growth restriction and perinatal maternal inflammation; however, these risk factors are not unique to BPD or BPD-PH. Occurring in 17-24% of BPD patients, BPD-PH substantially worsens the morbidity and mortality attributable to BPD alone, thus darkening their outlook; for example, BPD-PH entails a mortality of up to 50%. The absence of a safe and effective therapy for BPD and BPD-PH renders neonatal cardiopulmonary disease an area of urgent unmet medical need. Besides the need to develop new therapeutic strategies, a major challenge for clinicians is the lack of a reliable method for identifying babies at risk of developing BPD and BPD-PH. In addition to discussing current knowledge on pathophysiology, diagnosis and treatment of BPD-PH, we highlight emerging biomarkers that could enable clinicians to predict disease-risk and also optimise treatment of BPD-PH in our tiniest patients.
支气管肺发育不良（BPD）和 BPD 相关肺动脉高压（BPD-PH）是慢性炎症性心肺疾病，对早产儿有毁灭性的短期和长期后果。早产儿不成熟的肺部无法充分进行气体交换，因此通常需要立即开始呼吸支持和氧气补充。这些治疗方法是救命的，但它们会加剧对早产儿被迫进行气体交换的肺部造成的组织损伤。呼吸和必要的治疗干预一起通过加重肺部炎症和血管重塑，频繁地引发 BPD 和 PH，从而破坏正常的肺发育，尽管这一过程的发病机制尚不完全清楚。BPD 和 BPD-PH 有共同的危险因素，如出生时的低胎龄、胎儿生长受限和围产期母体炎症；然而，这些危险因素并非 BPD 或 BPD-PH 所特有。在 17-24%的 BPD 患者中，BPD-PH 大大加重了 BPD 本身的发病率和死亡率，从而使情况更加恶化；例如，BPD-PH 的死亡率高达 50%。由于缺乏治疗 BPD 和 BPD-PH 的安全有效方法，新生儿心肺疾病成为急需解决的未满足医疗需求领域。除了需要开发新的治疗策略外，临床医生面临的一个主要挑战是缺乏一种可靠的方法来识别有发生 BPD 和 BPD-PH 风险的婴儿。除了讨论 BPD-PH 的病理生理学、诊断和治疗的现有知识外，我们还强调了新兴的生物标志物，这些标志物可以使临床医生能够预测疾病风险，并优化我们最小的患者的 BPD-PH 治疗。
