DEFENSE FUNCTIONS IN THE DEVELOPING RESPIRATORY SYSTEM

流行病学和临床研究表明，急性气道损伤， 出生后肺部生长可能导致慢性支气管炎，哮喘或复发 呼吸道感染延续到成年期。 然而，底层 机制尚未确定。 本报告的总体目标 因此，建议建立气道损伤之间的联系， 通过使用具有肺的动物模型的早期生命和慢性气道疾病 解剖学类似于人，并侧重于粘液纤毛的作用， 在这一系列事件中的功能障碍。 具体目标是：（1） 建立气道形态和粘膜纤毛功能之间关系 在鼻后肺生长期间，2）研究 出生后不久的机械和化学粘膜损伤产生 永久性粘膜纤毛功能障碍，和3）确定这种缺陷是否导致 受损的细菌清除，从而细菌定植， 可能是呼吸道复发性感染 羔羊将被研究 在出生到六个月大之间纵向地发育（完全成熟）。 出生后不久的粘膜损伤将由O3或气道产生 手法模拟呼吸功能不全的辅助治疗。 将研究呼吸系统的三个方面： 功能、气道功能和气道形态。 首先，在体内 气管粘液转运率和肺粘液纤毛清除率将 通过使用射线照相技术和吸入的不溶性 放射性气溶胶。 此外，吸入的清除 还将测定细菌气溶胶。 的组件功能 将通过测定粘液的浓度在体外测量粘液纤毛清除率 分泌、离子和水的运输以及纤毛搏动频率。 将通过测量肺阻力评估气道功能 和气体分布通过单次呼吸氮气测试。 常规光学 将使用显微镜进行组织学研究。 这些观察结果 有望提供有价值的新信息的发病机制，慢性 新生儿急性气道损伤后发生的气道疾病。

Epidemiologic and clinical studies suggest that acute airway injury during postnatal lung growth can lead to chronic bronchitis, asthma or recurrent respiratory infections extending into adulthood. However, the underlying mechanisms have not been identified. The overall objective of this proposal is therefore to establish a link between airway damage during early life and chronic airway disease by using an animal model with lung anatomy resembling that of man, and focusing on the role of mucociliary dysfunction in this sequence of events. The specific aims are to 1) establish a relationship between airway morphology and mucociliary function during postnasal lung growth, 2) investigate the possibility that mechanical and chemical mucosal damage shortly after birth produce permanent mucociliary dysfunction, and 3) determine if this defect leads to impaired bacterial clearance in, and thus bacterial colonization and possible recurrent infection of the airways. Lambs will be studied longitudinally between birth and six months of age (full maturation). Mucosal injury shortly after birth will be produced by O3, or airway manipulation simulating ventilatory support for respiratory insufficiency. Three aspects of the respiratory system will be investigated: Mucociliary function, airway function and airway morphology. For the first, in vivo tracheal mucous transport rates and lung mucociliary clearance will be measured by using a radiographic technique and an inhaled insoluble radioaerosol, respectively. In addition, the clearance of an inhaled bacterial aerosol will also be determined. The component functions of mucociliary clearance will be measured in vitro by determination of mucus secretion, ion and water transport as well as ciliary beat frequency. Airway function will be assessed by the measurement of pulmonary resistance and gas distribution by the single-breath nitrogen test. Routine light microscopy will be used for the histologic studies. These observations are expected to provide valuable new information on the pathogenesis of chronic airway disease occurring following acute airway injury in newborns.