Prevention and treatment of chronic lung disease of the newborn infants

慢性肺部疾病（CLD）的发病率达到极低出生体重儿的20%。本研究旨在了解慢性呼吸窘迫综合征的发病机制，探讨慢性呼吸窘迫综合征的防治策略。1)高频振荡通气条件下肺表面活性物质亚组分制备急性呼吸窘迫综合征兔模型，分别进行常规强制通气（CMV）和高频振荡通气（HFOV）。通气4h后，收集支气管肺泡灌洗液。采用超离心分离法分离表面活性剂亚型，评价各通气模式下表面活性剂亚型转化情况。我们可以证明HFOV在表面活性剂亚型转化方面优于CMV。2)日本先天性肺泡蛋白沉积症和表面活性蛋白B缺乏症先天性肺泡蛋白沉积症（CAP）属于VI型CLD。1998年至2002年间，在日本发现了2例CAP和1例部分表面活性剂蛋白B（SP-B）缺乏。典型的SP-B缺乏症伴有帧移位突变121ins2，导致截断的无功能SP-B，未被发现。我们还分析了3例CAP中SP-B mRNA缺失形式的丰度，即SP-B mRNA的选择性剪接。与正常肺相比，这些患者的“次要”SP-B mRNA含量更高。3) CLD患儿气管支气管吸入物中的抗IL-8自身抗体我们之前报道过III型CLD患者早期气管支气管吸入物中存在大量IL-8。在本研究中，III型CLD婴儿的抗il -8 IgM抗体明显高于I型、II型和V型CLD。抗IL-8自身抗体的存在似乎是限制游离IL-8在肺中的生物利用度的机制。

The incidence of chronic lung disease (CLD) reaches 20% of the very low birth weight infants. In the present study, we tried to understand the pathogenesis of CLD and develop strategy for prevention and treatment of CLD.1)Subfractions of pulmonary surfactant under high frequency oscillatory ventilationWe made a rabbit model of acute respiratory distress syndrome, then performed conventional mandatory ventilation (CMV) or high frequency oscillatory ventilation (HFOV). After 4h ventilation, bronchoalveolar lavage fluid was collected. Surfactant subtype was fractionated using ultracentrifugation and surfactant subtype conversion was evaluated in each ventilatory mode. We could demonstrate that HFOV was superior to CMV in terms of surfactant subtype conversion.2)Congenital alveolar proteinosis and surfactant protein B deficiency in JapanCongenital alveolar proteinosis (CAP) is classified into type VI CLD. Two cases of CAP and one case of partial surfactant protein B(SP-B) deficiency were identified in Japan between 1998 and 2002. Typical SP-B deficiency with a frame shift mutation, 121ins2, leading to a truncated nonfunctional SP-B, was not identified. We also analyzed abundance of the deletion form of SP-B mRNA, i.e., alternatively spliced SP-B mRNA in 3 cases of CAP. The contents of the "minor" SP-B mRNA in those patients were higher as compared to those in normal lungs.3)Anti-IL-8 autoantibody in the tracheobronchial aspirates in infants with CLDWe reported previously a large amount of IL-8 in tracheobronchial aspirates during the early stage of life in type III CLD. In the present study, anti-IL-8 IgM antibody in infants with type III CLD was significantly higher as compared to type I, type II, and type V CLD. The presence of anti-IL-8 autoantibody seems to be the mechanism that limits the bioavailability of free IL-8 in the lung.