Reactive Oxygen Species in Respiratory Failure, Delirium, and Post-ICU Cognitive Impairment

呼吸衰竭、谵妄和 ICU 术后认知障碍中的活性氧

• 批准号: 10512894
• 负责人: Sikandar Hayat Khan
• 金额: $ 24.29万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10512894
• 关键词: Acute; Acute respiratory failure; Address; Admission activity; Adult; Aging; Alveolar; Alzheimer' s Disease; Alzheimer' s disease related dementia; Astrocytes; Award; Biological; Biological Markers; Blood Circulation; Blood specimen; Clinical Research; Clinical Sciences; Cognition; Cognitive; Cognitive aging; Critical Illness; Delirium; Development Plans; Elderly; Endothelium; Enrollment; Environment; Extravasation; Faculty; Functional disorder; Funding; Geroscience; Goals; Health; Impaired cognition; Impairment; Indiana; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Institutes; Institutionalization; Intensive Care Units; Interleukin-6; Interleukins; K-Series Research Career Programs; Knowledge; Lead; Leadership; Learning; Lipids; Lung; Measures; Mechanical ventilation; Mentors; Mentorship; Neurodegenerative Disorders; Neuroglia; Neurologic Dysfunctions; Neuronal Injury; Outcome; Outcome Study; Outcomes Research; Oxidative Stress; Pathway interactions; Patients; Peripheral; Pharmacological Treatment; Physical Function; Plasma; Play; Prevalence; Production; Prospective Studies; Prospective cohort study; Proteins; Quality of life; Reactive Oxygen Species; Recovery; Research; Research Personnel; Resources; Respiratory Failure; Risk; Role; Sampling; Severities; Survivors; TNF gene; Testing; Time; Training; Translational Research; United States; United States National Institutes of Health; Universities; career; career development; cognitive function; cohort; cytokine; effective therapy; experience; improved; leukocyte activation; medical schools; meetings; mild cognitive impairment; mortality; multidisciplinary; neuroinflammation; oxidative damage; patient oriented; patient population; postoperative delirium; preclinical study; prospective; skills; success

PROJECT SUMMARY One million adults in the United States receive mechanical ventilation for acute respiratory failure (ARF) annually and up to 80% of them develop delirium during their intensive care unit (ICU) stay. Delirium is associated with post-ICU cognitive and physical impairments. Delirium has no effective treatment due to our limited understanding of the pathophysiology connecting ARF and delirium which share a proinflammatory cytokine state. The systemic release of cytokines, ongoing alveolar injury, and production of reactive oxygen species (ROS) may connect ARF and delirium. We hypothesize that increased biomarkers of ROS are associated with increased cognitive and physical function impairments in critically ill older adults. To test our hypothesis, we propose a preliminary, prospective study titled Reactive Oxygen Species in Respiratory Failure, Delirium and Post-ICU Cognitive Impairment. We will measure levels of ROS using samples obtained from 80 critically ill, mechanically ventilated older adults, and follow these patients for 24 months. Blood samples and cognition and physical function assessments will be conducted at multiple time-points to accomplish our study aims. The primary aim is to measure the relationship between biomarkers of ROS and post-ICU mild cognitive impairment (MCI) and Alzheimer’s Disease and Related Dementias (ADRD) in critically ill older adults with acute respiratory failure. The secondary aims are to measure the relationship among biomarkers of oxidative injury and delirium duration and severity in critically ill older adults with ARF; and to measure the relationship among post- ICU biomarkers of inflammation and oxidative stress and post-ICU MCI and ADRD. The proposed career development plan integrates coursework, experiential training and mentorship in aging, and the conduct of prospective clinical research. The candidate will also learn leadership skills, participate in national meetings, and benefit from a well-established and highly successful multidisciplinary mentorship panel with a track record of success in training junior investigators. The candidate’s academic environment includes the highly acclaimed resources and faculty of Indiana University School of Medicine, the distinguished Indiana University Center for Aging Research, Regenstrief Institute, and the NIH-funded Indiana Clinical and Translational Sciences Institute (CTSI). This career development award will guarantee protected time that will be necessary to advance the candidate’s career in studying outcomes for older adults. Knowledge gained during the award will improve scientific understanding of the nexus between ARF, delirium, and ICU-acquired cognitive and physical impairment, and prepare for R01 submissions to further study oxidative stress in aging.

项目概要 美国有 100 万成年人因急性呼吸衰竭 (ARF) 接受机械通气 每年，高达 80% 的患者在重症监护病房 (ICU) 期间出现谵妄。 与 ICU 后认知和身体损伤相关的谵妄目前尚无有效的治疗方法。 我们对 ARF 和谵妄之间的病理生理学了解有限，两者有共同点 促炎细胞因子状态。细胞因子的全身释放、持续的肺泡损伤和 活性氧 (ROS) 的产生可能与 ARF 和谵妄有关。 ROS 生物标志物的增加与认知和身体功能损伤的增加有关 为了检验我们的假设，我们提出了一项初步的前瞻性研究，标题为： 呼吸衰竭、谵妄和 ICU 后认知障碍中的活性氧 我们将。 使用从 80 名重症、机械通气老年人身上获取的样本测量 ROS 水平， 并跟踪这些患者 24 个月的血液样本以及认知和身体功能评估。 将在多个时间点进行以实现我们的研究目标。 ROS 生物标志物与 ICU 后轻度认知障碍 (MCI) 和阿尔茨海默病之间的关系 患有急性呼吸衰竭的危重老年人的疾病和相关痴呆（ADRD）。 次要目标是测量氧化损伤和谵妄的生物标志物之间的关系 患有 ARF 的危重老年人的持续时间和严重程度；并衡量治疗后之间的关系； ICU 炎症和氧化应激生物标志物以及 ICU 后 MCI 和 ADRD。 拟议的职业发展计划将课程作业、体验式培训和指导结合在一起 老化，以及进行前瞻性临床研究，候选人还将学习领导技能， 参加国家会议，并从完善且非常成功的会议中受益 多学科指导小组在培训初级研究者方面拥有成功的记录。 候选人的学术环境包括印第安纳州广受好评的资源和师资 大学医学院、杰出的印第安纳大学衰老研究中心、 Regenstrief 研究所和 NIH 资助的印第安纳临床与转化科学研究所 (CTSI)。 该职业发展奖将保证受保护的时间，这是推进职业发展所必需的 候选人在研究老年人成果方面的职业生涯将在获奖期间获得的知识。 提高对 ARF、谵妄与 ICU 获得性认知和认知能力之间关系的科学认识 身体损伤，并为 R01 提交做准备，以进一步研究衰老中的氧化应激。