DE PEDIATRIC COBRE: OXYGEN AND BAROTRAUMA EFFECTS ON HUMAN AIRWAY EPITHELIUM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。尽管在围产期和新生儿重症监护方面取得了显着进展，但慢性肺部疾病仍然是早产或新生儿期或婴儿早期危重病后的常见事件。婴儿慢性肺病（CLDI），因为它现在经常被称为，包括一组异质性的条件源于严重的疾病在新生儿期或生命早期，其中往往包括其他疾病以外的主要影响肺部。治疗急性非肺部疾病，如败血症或先天性心脏病，可能导致CLDI 2。 该提案的总体目标是研究BPD和CLDI发病机制的关键组成部分。为了做到这一点，我们将重点关注两个特定的因素，这两个因素对慢性肺部疾病的发展有重要作用，即氧中毒（高氧）和气压伤。我们将重点关注与BPD和CLDI发展高度相关的成果。这些将包括评估炎症介质，气道中的先天抗菌因子，气道重塑过程和坏死和凋亡细胞损伤的组织学证据。细胞内的调节机制也将集中在炎症中的NF-κ B通路的核心作用进行评估。最后，通过选择性使用重要的临床和临床前治疗，我们将评估这些药物和策略的潜在有用性，并探索它们在细胞水平上的作用机制。

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. Despite remarkable advances in perinatal and neonatal intensive care, chronic lung disease remains a common occurrence after premature birth or critical illness in the neonatal period or early infancy. Chronic lung disease of infancy (CLDI), as it is now frequently referred to, encompasses a heterogeneous group of conditions stemming from severe illness in the neonatal period or early in life, which often includes disorders other than those primarily affecting the lung. The treatment of an acute non-pulmonary illness, such as sepsis or congenital heart disease, may result in CLDI2. The overall thrust of this proposal is to study key components of the pathogenesis of BPD and CLDI. To do this, we will focus on two specific factors that contribute importantly to the development of chronic lung disease, oxygen toxicity (hyperoxia) and barotrauma. We will focus on outcomes that are highly relevant to the development of BPD and CLDI. These will include assessment of mediators of inflammation, innate antibacterial factors in the airway, the airway remodeling process and histological evidence of both necrotic and apoptotic cell injury. Intracellular regulatory mechanisms will also be evaluated focusing on the central role of the NF-kb pathway in inflammation. Finally, through the selective use of important clinical and pre-clinical treatments, we will assess the potential usefulness of these drugs and strategies and explore their mechanisms of action at the cellular level.