Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Neonatology. 2024;121(5):596-607. doi: 10.1159/000540002. Epub 2024 Jul 25.
Bronchopulmonary dysplasia (BPD) is the most common long-term complication of extreme preterm birth. It is associated with lifelong multisystemic consequences. Advances in neonatal care have not reduced the incidence of BPD and no new breakthrough therapy has been successfully translated into the clinic in recent decades.
Current evidence demonstrates benefit of new modalities of first-line noninvasive positive pressure ventilation, selected strategies of postnatal corticosteroid administration, alternative surfactant delivery methods, and caffeine. Promising emerging therapies that are being translated from bench to bedside include mesenchymal stromal cells (MSCs), insulin-like growth factor 1/binding protein-3 (IGF-1/IGFBP-3), and interleukin 1 receptor (IL-1R) antagonist (anakinra). Strong preclinical data support efficacy of MSCs in attenuating neonatal lung injury. Early-phase clinical trials have already demonstrated safety and feasibility in preterm infants. Phase II studies that aimed at demonstrating efficacy are currently underway. Both IGF-1/IGFBP-3 and IL-1R antagonist present with biological plausibility and animal data of efficacy. Phase I/II clinical trials are currently recruiting patients.
Early noninvasive respiratory support, late systemic dexamethasone, less invasive surfactant administration, and caffeine are proven strategies in reducing the risk of BPD. Potentially disruptive therapies - MSCs, IGF-1/IGFBP-3, and anakinra - are being advanced to clinical trials and their efficacy in remains to be demonstrated. Continued research efforts are needed in the growing population of extremely preterm infants at risk of developing BPD.
支气管肺发育不良（BPD）是极早产儿最常见的长期并发症。它与终生多系统后果有关。新生儿护理的进步并没有降低 BPD 的发病率，而且近几十年来，没有新的突破性治疗方法成功转化为临床应用。
目前的证据表明，新型一线无创正压通气模式、选择的产后皮质类固醇给药策略、替代表面活性剂输送方法和咖啡因都有益处。正在从基础研究转化为临床应用的有前途的新兴疗法包括间充质基质细胞（MSCs）、胰岛素样生长因子 1/结合蛋白 3（IGF-1/IGFBP-3）和白细胞介素 1 受体（IL-1R）拮抗剂（anakinra）。强有力的临床前数据支持 MSCs 减轻新生儿肺损伤的疗效。早期临床试验已经证明了早产儿使用的安全性和可行性。目前正在进行旨在证明疗效的 II 期研究。IGF-1/IGFBP-3 和 IL-1R 拮抗剂具有生物学合理性和动物疗效数据。I/II 期临床试验正在招募患者。
早期无创呼吸支持、晚期全身地塞米松、微创表面活性剂给药和咖啡因是降低 BPD 风险的已证实策略。潜在的突破性疗法——MSCs、IGF-1/IGFBP-3 和 anakinra——正在推进临床试验，其疗效仍有待证明。在有发生 BPD 风险的极早产儿不断增加的人群中，需要继续进行研究。
