Tracheobronchitis in the Critically Ill

危重病人的气管支气管炎

• 批准号: 10410921
• 负责人: Anna Christine Zemke
• 金额: $ 35.31万
• 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/10410921
• 关键词: Acute; American; Antibiotic Resistance; Antibiotics; Aspirate substance; 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; Hospitals; Host Defense; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Intervention; Intervention Studies; 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; Public Health; Quality of life; Recovery; Registries; Research Infrastructure; Respiratory Tract Infections; Risk; Shotgun Sequencing; Source; Sputum; Symptoms; Testing; Time; Tracheostomy procedure; Ventilator; Ventilator Weaning; Virus Diseases; acute care; airway inflammation; clinical predictors; cohort; cytokine; emerging pathogen; experience; health care service utilization; 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%的危重病恢复期需要气管切开的人经历了呼吸道 感染--称为气管切开术相关性气管支气管炎(TATB)。我们对此的理解 TATB来自那些患有急性危重疾病的人，不会延伸到危重疾病的恢复期。 对TATB缺乏了解可能会导致抗生素的过度使用，并限制干预措施的测试。我们的目标 是确定TATB的自然历史和结果，以及确定呼吸道细菌的变化 易患TATB的人群和宿主的先天免疫反应。为了实现这一目标，我们将 在一家长期急性护理医院内召集一组接受气管切开术的纵向队列参与者 (LTACH)在目标1中，我们将对接受气管切开术的患者进行纵向登记队列以进行测试 LTACH中气管支气管炎发作对长期临床影响的假说 结果。在队列内，我们将确定TATB的事件发生率，测量TATB的诊断效果 结果，包括呼吸恢复率、死亡率和医疗保健利用率，并确定临床 被诊断为TATB的预测因素。虽然TATB是用抗生素治疗的，但我们不知道多久治疗一次 发作是由活跃的细菌感染引起的。其他原因包括病毒感染和其他原因 用于在至少有一种病原体的种群中增加呼吸道分泌物。在……里面 目的2我们假设传染性TATB发作是由一种现有的病原体爆发引起的， 急性炎症反应。我们将使用浅元基因组学(鸟枪式测序)来确定 在发病期间，细菌感染的动力学下降到菌株水平。浅层元基因组学将使我们能够 区分新病原体入侵的时期与水华或现有病原体的遗传变化 微生物群。我们将确定哪些TATB发作与局部呼吸道相关 炎症反应或全身炎症反应。或者，病毒感染可能会引发TATB或 引发致病细菌的生长。我们将进行嵌套式病例对照研究，以确定是否感染了 呼吸道病毒与TATB有关。总而言之，这些数据将决定临床内型。在目标3中，我们 将研究炎症如何通过释放微量营养素来促进病原菌的生长 是细菌生长所必需的。我们将检验破坏局部粘膜免疫或局部免疫的假说 炎症反应增加诊断TATB的几率。痰中的营养环境会 通过测量金属和碳源等细菌营养进行评估，营养 环境将与TATB诊断的几率以及诊断前的局部炎症状态相关 将通过细胞因子谱对TATB进行评估。这些研究的结果将使我们能够针对特定的 在未来的干预或科学研究中，TATB的表型。