DEFENSE FUNCTIONS IN THE DEVELOPING RESPIRATORY SYSTEM

流行病学和临床研究表明，急性呼吸道损伤在 出生后肺生长可导致慢性支气管炎、哮喘或复发 呼吸道感染一直延伸到成年。然而，潜在的 机制尚未确定。这样做的总体目标是 因此，建议在呼吸道损伤之间建立联系 早期生命和慢性呼吸道疾病的动物模型 与人类相似的解剖学，侧重于粘液纤毛的作用 这一系列事件中的功能障碍。具体目标为1) 建立呼吸道形态和粘液纤毛功能之间的关系 在鼻后肺生长期间，2)调查 出生后不久就会产生机械性和化学性粘膜损伤 永久性粘液纤毛功能障碍，以及3)确定这种缺陷是否会导致 损害细菌在体内的清除，从而影响细菌定植和 可能是呼吸道反复感染。将对羊羔进行研究 纵向上从出生到六个月大(完全成熟)。 出生后不久，臭氧或呼吸道会造成粘膜损伤 模拟呼吸机支持呼吸功能不全的手法。 将对呼吸系统的三个方面进行研究：粘液纤毛 功能、气道功能和气道形态。第一次是在活体内 气管粘液转运速率和肺粘液纤毛清除 通过使用放射照相技术和吸入的不溶性物质进行测量 分别为放射性气溶胶。此外，吸入性气体的清除 细菌气溶胶也将被测定。的组件功能 粘液的测定将在体外测量粘液纤毛清除量 分泌、离子和水的运输以及纤毛搏动频率。 将通过测量肺阻力来评估呼吸道功能 气体分布采用单次氮气测试。常规灯光 显微镜将用于组织学研究。这些观察结果是 有望为慢性阻塞性肺疾病的发病机制提供有价值的新信息 新生儿急性呼吸道损伤后发生的呼吸道疾病。

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.