TRIAL OF LATE SURFACTANT TO PREVENT BRONCHOPULMONARY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 早产儿的支气管肺发育不良(BPD)已成为美国最常见、最致命、最昂贵的新生儿肺部疾病。BPD的发病机制是多因素的，有遗传因素，涉及与氧中毒和机械通气相关的损伤和炎症，在不发达、未成熟的肺。估计患病率为3万例/年。目前预防和治疗早产儿肺部疾病的治疗方法，包括产前皮质类固醇治疗、出生时替代表面活性物质、出生后给予皮质类固醇、维生素A、利尿剂、咖啡因和支气管扩张剂，对BPD的总体发生没有显著影响。最近的临床试验表明，吸入一氧化氮(INO)对BPD的发生率和严重程度以及短期和长期安全性，包括两年的神经发育结果都有有益的影响。极低出生体重儿(ELBW，在本研究中定义为&lt；1000 g和&lt；30周妊娠)在7天大时继续需要机械通气的婴儿BPD的发生率和严重程度最高，BPD与慢性肺部疾病和异常神经发育结局有关。在最近的研究中，我们发现这组婴儿有频繁的呼吸恶化，这与肺表面活性物质功能障碍和表面活性物质蛋白(SP)B和C含量降低有关，这些蛋白对维持肺泡和终末呼吸道通畅的正常表面活性物质功能至关重要。基于这些观察，我们进行了含有SP-B的商业表面活性物质(INFASURF？)晚期给药的初步研究。我们的初步数据证实，大多数在7天后仍需要呼吸机的婴儿有异常的表面张力测量，晚期使用表面活性物质的耐受性良好，并可短暂改善呼吸状态。接受iNO治疗的婴儿也会出现肺表面活性物质功能障碍。此外，接受iNO治疗的婴儿的表面活性物质功能障碍与不良结局有关。在这项先导性研究中，我们计划研究在接受iNO治疗的BPD高危婴儿中添加晚期表面活性物质。 我们推测，在7至14天内继续需要机械通气的ELBW婴儿，除静脉注射iNO外，晚期加强剂量的表面活性物质将显著减少这些婴儿表面活性物质功能障碍的发生率。我们进一步假设，肺表面活性物质治疗不会对短期结果产生不良影响，包括在月经后36周死亡或BPD。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bronchopulmonary dysplasia (BPD) of prematurity has emerged as the most common, lethal and expensive neonatal pulmonary disorder in the United States. The pathogenesis of BPD is multi-factorial, has a genetic contribution, and involves injury and inflammation associated with oxygen toxicity and mechanical ventilation in an underdeveloped, immature lung. The estimated prevalence is 30,000 cases/year. Current therapeutic approaches to the prevention and treatment of lung disease in premature infants, including antenatal corticosteroid treatment, replacement surfactant at birth, postnatal administration of corticosteroids, vitamin A, diuretics, caffeine, and bronchodilators have not significantly impacted the overall occurrence of BPD. Recent clinical trials of inhaled nitric oxide (iNO) indicate a beneficial impact on the incidence and severity of BPD as well as short- and long-term safety including 2-year neurodevelopmental outcome. Extremely low birth weight infants (ELBW, defined as <1000 g and <30 wk gestation for the purposes of this study) who continue to require mechanical ventilation at 7 d of age have the highest incidence and severity of BPD, which is associated with chronic pulmonary disease and abnormal neurodevelopmental outcome. In recent studies we found that this group of infants has frequent respiratory deteriorations that are associated with dysfunctional pulmonary surfactant and decreased content of surfactant proteins (SP) B and C, which are critical for normal surfactant function to maintain patency of alveoli and terminal airways. Based on these observations, we have performed pilot studies of late administration of SP-B-containing commercial surfactant (Infasurf?). Our preliminary data confirm that the majority of infants still requiring ventilation after 7 d of age have abnormal surface tension measurements and that late doses of surfactant are well tolerated and transiently improve respiratory status. Episodes of surfactant dysfunction also occur among infants receiving iNO. Moreover, surfactant dysfunction in iNO-treated infants is associated with adverse outcome. In this pilot study, we plan to study the addition of late surfactant administration to infants at high risk for BPD who are receiving iNO therapy. We hypothesize that late booster doses of surfactant, in addition to iNO, administered to ELBW infants who continue to require mechanical ventilation between 7 and 14 days of age will significantly decrease the frequency of episodes of surfactant dysfunction in these infants. We further hypothesize that there will be no adverse effects of surfactant treatment on short-term outcomes including death or BPD at 36 weeks postmenstrual age.