Dysbiotic Infections in Chronic Obstructive Pulmonary Disease

项目摘要 该项目旨在使用生理相关的动物模型来定义细菌的决定因素， 慢性阻塞性肺疾病患者发生机会性感染期间的持续性。 流感嗜血杆菌（Haemophilusinfluenzae，Hi）是COPD患者常见的条件致病菌， 表明这些感染可能涉及生物膜。我们假设：i）生物膜是Hi的决定因素 COPD相关感染期间在肺中的持续存在，ii）具有嗜酸性粒细胞（非生物膜）的细菌感染 细菌引发COPD疾病的炎症加剧和恶化，以及iii）Hi菌株（和其他 细菌的机会）可能在它们引发COPD恶化的能力上不同。为了解决这些 假设，我们将完成以下具体目标： 具体目标1。定义生物膜在烟雾肺内的Hi定殖/持久性中的作用- 暴露的雪貂 具体目标2。细菌感染对COPD炎症加重和严重程度的影响 病理生理学 在我们对细菌在COPD疾病期间持续存在的方式的理解方面仍然存在重大差距， 以及这些感染在宿主反应的周期性变化中的意义，这些变化是病情加重的基础。 完成本提案中概述的工作将为慢性COPD相关细菌的研究提供新的思路。 感染及其对这种疾病的管理的影响，这是主要的公共卫生问题之一， 全世界的问题。

PROJECT SUMMARY This project aims to use a physiologically relevant animal model to define determinants of bacterial persistence during opportunistic infections occurring in patients with chronic obstructive pulmonary disease. Haemophilus influenzae (Hi) is a common opportunistic pathogen in patients with COPD, and much evidence indicates that these infections might involve biofilms. We hypothesize that: i) biofilms are a determinant of Hi persistence in the lung during COPD-related infections, ii) bacterial infection with planktonic (non-biofilm) bacteria initiates inflammatory exacerbation and worsening of COPD disease, and iii) strains of Hi (and other bacterial opportunists) may differ in their capacity to initiate COPD exacerbations. In order to address these hypotheses, we will complete the following Specific Aims: Specific Aim 1. Define role(s) of biofilms in colonization/persistence of Hi within the lungs of smoke- exposed ferrets. Specific Aim 2. Test impact of bacterial infection in inflammatory exacerbation and severity of COPD pathophysiology. Significant gaps remain in our understanding of the means whereby bacteria persist during COPD disease, and the implications for these infections in the periodic changes in host responses that underlie exacerbations. The completion of the work outlined in this proposal will shed new light on chronic COPD-related bacterial infections and their implications for the management of this disease, which is among the leading public health problems worldwide.