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%从需要气管切开术的危重病中恢复的人经历呼吸道感染 感染-在本提案中称为气管造口术相关性气管支气管炎（TATB）。我们理解 TATB来自急性危重病患者，并不延伸到危重病的恢复阶段。 对TATB的认识不足可能导致抗生素的过度使用，并限制了干预措施的测试。我们的目标 目的是确定TATB的自然病程和转归，以及确定气道细菌的变化， 人群和宿主先天免疫反应易患TATB。为了实现这一目标，我们将 在一家长期急性护理医院内收集一组接受气管切开术的纵向受试者队列 （LACH）。在目标1中，我们将对接受气管造口术的患者进行纵向登记队列研究， 假设LACH中的气管支气管炎发作对长期 结果。在队列中，我们将确定TATB的事件发生率，衡量TATB诊断的效果， 结果，包括呼吸恢复率，死亡率和医疗保健利用，并确定临床 TATB的预测因子虽然TATB可以用抗生素治疗，但我们不知道多久 发作是由活动性细菌感染引起的。其他原因包括病毒感染和其他原因 在至少有一种病原微生物定殖的人群中增加呼吸道分泌物。在 目的2：我们假设传染性TATB发作是由现有病原体的大量繁殖引起的， 急性炎症反应我们将使用浅层宏基因组学（鸟枪测序）来确定 感染的细菌动力学在发作期间下降到菌株水平。浅层宏基因组学将使我们能够 区分新病原体入侵与现有病原体中的水华或遗传变化的事件， 微生物组我们将确定哪些TATB发作与局部气道 炎症反应或全身性炎症反应。或者，病毒感染可触发TATB或 引发致病细菌生长。我们将进行巢式病例对照研究，以确定是否感染 呼吸道病毒与TATB有关。总之，这些数据将确定临床内型。在目标3中，我们 将研究炎症如何通过释放微量营养素促进致病菌的生长 细菌生长所必需的。我们将检验局部粘膜免疫或局部免疫系统受损的假设， 炎症反应增加TATB诊断的可能性。痰液中的营养环境 通过测量细菌营养物如金属和碳源来评估， 环境将与TATB诊断的几率以及诊断前的局部炎症状态相关 将通过细胞因子分析评估TATB的水平。这些研究的结果将使我们能够针对特定的 TATB的表型在未来的干预或科学研究。