The past decades have seen markedly improved survival of increasingly immature preterm infants, yet major health complications persist. This is particularly true for bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, which has become the most common sequelae of prematurity and a significant predictor of respiratory morbidity throughout childhood as well as adult life, neurodevelopmental disability, cardiovascular disease, and even death. The need for novel approaches to reduce BPD and related complications of prematurity has never been more critical. Thus, despite major advances in the use of antenatal steroids, surfactant therapy, and improvements in respiratory support, there is a persistent need for developing therapeutic strategies that more specifically reflect our growing understanding of BPD in the post-surfactant age, or the “new BPD.” In contrast with the severe lung injury leading to marked fibroproliferative disease from the past, the “new BPD” is primarily characterized by an arrest of lung development as related to more extreme prematurity. This distinction and the continued high incidence of BPD and related sequelae suggest the need to identify therapies that target critical mechanisms that support lung growth and maturation in conjunction with treatments to improve respiratory outcomes across the lifespan. As the prevention of BPD and its severity remains a primary goal, we highlight the concept from preclinical and early clinical observations that insulin-like growth factor 1 (IGF-1) can potentially support the natural sequence of lung growth as a replacement therapy after preterm birth. Data supporting this hypothesis are robust and include observations that low IGF-1 levels persist after extremely preterm birth in human infants and strong preclinical data from experimental models of BPD highlight the therapeutic benefit of IGF-1 in reducing disease. Importantly, phase 2a clinical data in extremely premature infants where replacement of IGF-1 with a human recombinant human IGF-1 complexed with its main IGF-1 binding protein 3, significantly reduced the most severe form of BPD, which is strongly associated with multiple morbidities that have lifelong consequences. As physiologic replacement therapy of surfactant heralded the success of reducing acute respiratory distress syndrome in preterm infants, the paradigm has the potential to become the platform for discovering the next generation of therapies like IGF-1, which becomes deficient after extremely premature birth where endogenous production by the infant is not sufficient to maintain the physiologic levels adequate to support normal organ development and maturation.

在过去的几十年里，日益不成熟的早产儿的生存率显着提高，但主要的健康并发症仍然存在。对于支气管肺发育不良 (BPD) 来说尤其如此，这种早产儿的慢性肺部疾病已成为早产儿最常见的后遗症，也是整个儿童期和成年期呼吸系统疾病、神经发育障碍、心血管疾病甚至是儿童时期呼吸系统疾病的重要预测因素。死亡。对减少 BPD 和相关早产并发症的新方法的需求从未如此迫切。因此，尽管在使用产前类固醇、表面活性剂疗法和呼吸支持方面取得了重大进展，但仍然需要开发更具体地反映我们对后表面活性剂时代 BPD 的日益增长的理解的治疗策略，或“新的 BPD”。边缘性人格障碍。” 与过去导致明显纤维增生性疾病的严重肺损伤相比，“新BPD”的主要特征是肺部发育停滞，与更极端的早产有关。这种区别以及 BPD 和相关后遗症的持续高发病率表明，需要确定针对支持肺部生长和成熟的关键机制的治疗方法，并结合改善整个生命周期呼吸结果的治疗方法。由于预防 BPD 及其严重程度仍然是首要目标，我们强调临床前和早期临床观察中的概念，即胰岛素样生长因子 1 (IGF-1) 作为早产后的替代疗法有可能支持肺部生长的自然顺序出生。支持这一假设的数据十分有力，包括人类婴儿在极度早产后持续存在低 IGF-1 水平的观察结果，以及来自 BPD 实验模型的强有力的临床前数据，强调了 IGF-1 在减少疾病方面的治疗益处。重要的是，极早产儿的 2a 期临床数据显示，用与其主要 IGF-1 结合蛋白 3复合的人类重组人 IGF-1 替代 IGF-1，显着减少了最严重的 BPD，而 BPD 与多种疾病密切相关。具有终生后果的疾病。由于表面活性剂的生理替代疗法预示着减少早产儿急性呼吸窘迫综合征的成功，该范式有可能成为发现下一代疗法的平台，如 IGF-1，IGF-1 在极度早产后内源性产生后会变得缺乏。婴儿的营养不足以维持足以支持正常器官发育和成熟的生理水平。