Tracheobronchitis in the Critically Ill

危重病人的气管支气管炎

• 批准号: 10666447
• 负责人: Anna Christine Zemke
• 金额: $ 40.4万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666447
• 关键词: Acute; Admission activity; American; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Biology; Blood; Carbon; Chronic; Clinical; Cluster Analysis; Critical Illness; Data; Data Set; Development; Diagnosis; Diagnostic; Elements; Environment; Event; Excision; Financial cost; Functional disorder; Future; Goals; Growth; Healthcare Systems; Host Defense; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Intervention; Intervention Studies; Invaded; Kinetics; Knowledge; Longitudinal cohort; Measurement; Measures; Metagenomics; Metals; Micronutrients; Modeling; Mucosal Immunity; Mucous Membrane; Mutation; Natural History; Nested Case-Control Study; Nutrient; Nutritional; Organism; Outcome; Participant; Pathogenicity; Patients; Persons; Phase; Phenotype; Pneumonia; Population; Predisposition; Public Health; Quality of life; Recovery; Registries; Research Infrastructure; Respiratory Tract Infections; Risk; Shotgun Sequencing; Source; Sputum; Symptoms; Testing; Time; Trachea; Tracheostomy procedure; Ventilator; Ventilator Weaning; Virus Diseases; acute care; airway inflammation; aspirate; clinical predictors; cohort; cytokine; emerging pathogen; experience; health care service utilization; hospital care; improved; microbiome; mortality; pathogen; pathogenic bacteria; personalized medicine; primary outcome; radiological imaging; respiratory; respiratory virus; secondary outcome; systemic inflammatory response

Nearly 30% of people recovering from critical illness requiring tracheostomy placement experience respiratory infections - termed tracheostomy associated tracheobronchitis (TATB) for this proposal. Our understanding of TATB comes from those with acute critical illness, and does not extend to the recovery phase of critical illness. Poor understanding of TATB may contribute to antibiotic overuse and limits testing of interventions. Our objective is to define the natural history and outcomes of TATB, as well as to identify changes in the airway bacterial populations and host innate immune response that predispose to TATB. To accomplish this goal, we will assemble a longitudinal cohort of participants with tracheostomies within a Long-Term Acute Care Hospital (LTACH). In Aim 1 we will assemble a longitudinal registry cohort of people admitted with a tracheostomy to test the hypothesis that tracheobronchitis episodes in the LTACH have clinical impact on long term outcomes. Within the cohort, we will determine the event rate of TATB, measure the effect of diagnosis of TATB on outcomes, including respiratory recovery rate, mortality and healthcare utilization, and determine clinical predictors of being diagnosed with TATB. Although TATB is treated with antibiotics, we do not know how often episodes are caused by active bacterial infections. Alternative causes include viral infections and other reasons for increased respiratory secretions in a population that is colonized with at least one pathogenic organism. In Aim 2 we hypothesize that infectious TATB episodes are caused by a bloom of an existing pathogen with an acute inflammatory response. We will use shallow metagenomics (shotgun sequencing) to determine the bacterial kinetics of infection down to the strain level during episodes. Shallow metagenomics will allow us to distinguish episodes of new pathogen invasion vs a bloom or genetic change in the existing pathogens within the microbiome. We will determine which episodes of TATB are associated with either a local airway inflammatory response or a systemic inflammatory response. Alternatively, viral infections may trigger TATB or trigger pathogenic bacterial growth. We will conduct a nested case-control study to determine if infection with respiratory viruses is associated with TATB. Together, these data will determine clinical endotypes. In Aim 3, we will examine how inflammation promotes the growth of pathogenic bacteria through the release of micronutrients needed for bacteria growth. We will test the hypotheses that breaches in local mucosal immunity or local inflammatory response increase the odds of TATB diagnosis. The nutritional environment in the sputum will be assessed through measurement of bacterial nutrients such as metals and carbon sources, the nutritional environment will be correlated with odds of TATB diagnosis, and the local inflammatory state prior to diagnosis of TATB will be assessed through cytokine profiling. The results from these studies will allow us to target specific phenotypes of TATB in future intervention or scientific studies.

近30％的人从重病中恢复需要气管切开术经验呼吸道 感染 - 该提议称为气管切开术相关的气管造成气管炎（TATB）。我们对 TATB来自患有急性危重疾病的人，并没有扩展到重症疾病的恢复阶段。 对TATB的了解不足可能有助于抗生素过度使用和限制干预措施的测试。我们的目标 是定义TATB的自然历史和结果，并确定气道细菌的变化 种群和宿主先天免疫反应，使TATB容易产生。为了实现这一目标，我们将 在一家长期急诊医院内组装与气管的纵向队列 （ltach）。在AIM 1中，我们将组装一个纵向注册中心的人群，这些人接受气管切开术进行测试 LTACH中气管炎发作的假设对长期有临床影响 结果。在队列中，我们将确定TATB的事件率，测量TATB诊断的影响 关于结果，包括呼吸恢复率，死亡率和医疗保健利用，并确定临床 被诊断为TATB的预测因素。尽管TATB接受了抗生素治疗，但我们不知道多久 发作是由活跃的细菌感染引起的。替代原因包括病毒感染和其他原因 对于用至少一种致病生物定殖的人群中呼吸道分泌的增加。在 AIM 2我们假设感染性TATB发作是由现有病原体的花朵引起的 急性炎症反应。我们将使用浅元基因组学（shot弹枪测序）来确定 发作过程中感染的细菌动力学降至应变水平。浅宏基因组学将使我们能够 区分新病原体入侵的发作与现有病原体中的花朵或遗传变化 微生物组。我们将确定TATB的哪些发作与本地气道有关 炎症反应或全身性炎症反应。或者，病毒感染可能触发tatb或 触发致病细菌生长。我们将进行嵌套的病例对照研究，以确定是否感染 呼吸道病毒与TATB有关。这些数据将共同确定临床内型。在AIM 3中，我们 将检查炎症如何通过释放微量营养素促进致病细菌的生长 细菌生长所需。我们将测试违反局部粘膜免疫或局部违反的假设 炎症反应增加了TATB诊断的几率。痰液中的营养环境将 可以通过测量细菌营养物质（例如金属和碳源）来评估营养 环境将与TATB诊断的几率以及诊断之前的局部炎症状态相关 TATB将通过细胞因子分析评估。这些研究的结果将使我们能够针对特定 TATB在将来的干预或科学研究中的表型。