The Laboratory of Neonatal Diseases of National Commission of Health; National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.
Neonatology and Pulmonary Rare Disease Unit, Pharmacology & Toxicology Department, Corporate Preclinical R&D, CHIESI, Parma, Italy.
Pediatr Res. 2023 Feb;93(3):541-550. doi: 10.1038/s41390-022-02152-2. Epub 2022 Jun 14.
The pathogenesis of neonatal meconium aspiration syndrome (MAS) involves meconium-induced lung inflammation and surfactant inactivation. Bronchoalveolar lavage (BAL) with diluted surfactant facilitates the removal of meconium. CHF5633, one of the most promising synthetic surfactants, is effective in neonatal respiratory distress syndrome. Here we investigated its efficacy via BAL in an experimental MAS model.
Experimental MAS was induced at birth in near-term newborn rabbits by intratracheal instillation of reconstituted human meconium. First, undiluted CHF5633 was compared with a porcine-derived surfactant (Poractant alfa) via intratracheal bolus (200 mg/kg). Second, the efficacy of BAL with diluted CHF5633 (5 mg/mL, 20 ml/kg) alone, or followed by undiluted boluses (100 or 300 mg/kg), was investigated.
Meconium instillation caused severe lung injury, reduced endogenous surfactant pool, and poor survival. CHF5633 had similar benefits in improving survival and alleviating lung injury as Poractant alfa. CHF5633 BAL plus higher boluses exerted better effects than BAL or bolus alone in lung injury alleviation by reversing phospholipid pools and mitigating proinflammatory cytokine mRNA expression, without fluid retention and function deterioration.
CHF5633 improved survival and alleviated meconium-induced lung injury, the same as Poractant alfa. CHF5633 BAL plus boluses was the optimal modality, which warrants further clinical investigation.
To explore the efficacy of a synthetic surfactant, CHF5633, in neonatal lung protection comparing with Poractant alfa in a near-term newborn rabbit model with meconium-induced lung injury. Similar effects on improving survival and alleviating lung injury were found between CHF5633 and Poractant alfa. Optimal therapeutic effects were identified from the diluted CHF5633 bronchoalveolar lavage followed by its undiluted bolus instillation compared to the lavage or bolus alone regimens. Animals with CHF5633 lavage plus bolus regimen exerted neither substantial lung fluid retention nor lung mechanics deterioration but a trend of higher pulmonary surfactant-associated phospholipid pools.
新生儿胎粪吸入综合征（MAS）的发病机制涉及胎粪诱导的肺炎症和表面活性剂失活。支气管肺泡灌洗（BAL）用稀释的表面活性剂有助于清除胎粪。CHF5633 是最有前途的合成表面活性剂之一，对新生儿呼吸窘迫综合征有效。在这里，我们通过支气管肺泡灌洗（BAL）在实验性 MAS 模型中研究了其疗效。
足月新生兔通过气管内注入重组人胎粪诱导实验性 MAS。首先，通过气管内推注（200mg/kg）比较未稀释的 CHF5633 与猪源表面活性剂（Poractant alfa）。其次，单独用稀释的 CHF5633（5mg/ml，20ml/kg）BAL 或随后用未稀释的推注（100 或 300mg/kg）进行研究。
胎粪注入导致严重的肺损伤、内源性表面活性剂池减少和存活率低。CHF5633 改善生存和缓解肺损伤的效果与 Poractant alfa 相似。CHF5633 BAL 加高剂量推注在减轻肺损伤方面的效果优于 BAL 或单独推注，通过逆转磷脂池和减轻促炎细胞因子 mRNA 表达，而不伴有液体潴留和功能恶化。
CHF5633 改善了生存并减轻了胎粪引起的肺损伤，与 Poractant alfa 相同。CHF5633 BAL 加推注是最佳治疗方案，值得进一步临床研究。
探索一种合成表面活性剂 CHF5633 在足月新生兔胎粪诱导肺损伤模型中的疗效，与 Poractant alfa 进行比较。CHF5633 和 Poractant alfa 在提高生存率和缓解肺损伤方面有相似的效果。与单独的灌洗或推注方案相比，从稀释的 CHF5633 支气管肺泡灌洗后进行未稀释的推注可以获得最佳的治疗效果。用 CHF5633 灌洗加推注方案的动物既没有明显的肺液潴留，也没有肺力学恶化，但有更高的肺表面活性剂相关磷脂池的趋势。
