TRIAL OF LATE SURFACTANT TO PREVENT BRONCHOPULMONARY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在美国，早产儿支气管肺发育不良（BPD）已成为最常见、最致命和最昂贵的新生儿肺部疾病。BPD的发病机制是多因素的，具有遗传贡献，并且涉及与氧毒性和未发育成熟的肺中的机械通气相关的损伤和炎症。 估计流行率为30 000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、出生时表面活性物质替代、出生后皮质类固醇、维生素A、利尿剂、咖啡因和支气管扩张剂给药，对BPD的总体发生率没有显著影响。 最近的吸入性一氧化氮（iNO）临床试验表明，对BPD的发病率和严重程度以及短期和长期安全性（包括2年神经发育结局）具有有益影响。 极低出生体重儿（ELBW，在本研究中定义为<1000 g且<30 wk妊娠）在7 d龄时继续需要机械通气的婴儿，其BPD的发生率和严重程度最高，与慢性肺部疾病和异常神经发育结局相关。 在最近的研究中，我们发现这组婴儿经常出现呼吸恶化，这与肺表面活性物质功能障碍和表面活性蛋白（SP）B和C含量降低有关，这对维持肺泡和末端气道通畅的正常表面活性物质功能至关重要。基于这些观察结果，我们对含SP-B的市售表面活性剂（Infasurf？）的晚期给药进行了初步研究。我们的初步数据证实，大多数婴儿仍然需要通气后7天的年龄有异常的表面张力测量和后期剂量的表面活性剂耐受性良好，并短暂改善呼吸状态。在接受iNO的婴儿中也会发生表面活性剂功能障碍。 此外，iNO治疗婴儿的表面活性物质功能障碍与不良结局相关。 在这项初步研究中，我们计划研究在接受iNO治疗的BPD高危婴儿中增加晚期表面活性剂给药。 我们假设，在7 - 14天龄之间继续需要机械通气的ELBW婴儿中，除了iNO外，晚期加强剂量的表面活性剂将显著降低这些婴儿表面活性剂功能障碍发作的频率。我们进一步假设，表面活性剂治疗对短期结局（包括死亡或经后36周的BPD）没有不良影响。

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.