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: 10704090
• 负责人: Sikandar Hayat Khan
• 金额: $ 23.52万
• 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/10704090
• 关键词: Acceleration; Acute; Acute respiratory failure; Address; Admission activity; Adult; Aging; Alveolar; Alzheimer' s Disease; Alzheimer' s disease related dementia; Astrocytes; Award; Biological; Biological Markers; Blood specimen; Circulation; 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; Institutionalization; Intensive Care Units; Interleukin-6; Interleukins; K-Series Research Career Programs; Knowledge; 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; Patient-Focused Outcomes; 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 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.

项目摘要 美国一百万成年人接受急性呼吸衰竭（ARF）的机械通气 在重症监护室（ICU）住宿期间，其中一对一和多达80％的人会发展ir妄。 del妄为 与ICU后认知和身体障碍有关。由于 我们对连接ARF和Delirum的病理生理学的有限​​理解 促炎性细胞因子状态。细胞因子的全身释放，持续的肺泡损伤和 活性氧（ROS）的产生可能会连接ARF和del妄。我们假设这一点 ROS的生物标志物增加与认知和身体功能障碍增加有关 在重病的老年人中。为了检验我们的假设，我们提出了一项标题为初步的前瞻性研究 呼吸衰竭，del妄和ICU后认知障碍中的活性氧。我们将 使用从80个重病，机械通风的老年人获得的样品测量ROS的水平， 并跟随这些患者24个月。血液样本，认知和身体机能评估 将以多个时间点进行实现我们的研究目标。主要目的是测量 ROS的生物标志物与ICU后轻度认知障碍（MCI）与阿尔茨海默氏症之间的关系 急性呼吸衰竭的重症老年人中疾病和相关痴呆症（ADRD）。这 次要目的是衡量氧化损伤和ir妄的生物标志物之间的关系 患有ARF的重症老年人的持续时间和严重程度；并衡量后的关系 ICU炎症和氧化应激的生物标志物以及ICU后MCI和ADRD。 拟议的职业发展计划将课程工作，专家培训和指导职位整合到 衰老和前瞻性临床研究的进行。候选人还将学习领导能力， 参加全国会议，并受益于建立良好且非常成功的 多学科心态小组具有培训初级调查人员成功的往绩。这 候选人的学术环境包括备受赞誉的印第安纳州资源和学院 杰出的印第安纳大学老龄化研究中心大学医学院， Regenstrief Institute以及NIH资助的印第安纳州临床和转化科学研究所（CTSI）。 该职业发展奖将保证受保护的时间 候选人在研究老年人的成果方面的职业。奖励期间获得的知识将 提高对ARF，del妄和ICU获得认知和ICU的认知和ICU的科学理解 身体障碍，并为R01提交准备进一步研究衰老中的氧化应激。

项目成果

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

• DOI: 10.1001/jamanetworkopen.2023.53158
• 发表时间: 2024-01-02
• 期刊: JAMA network open
• 影响因子: 13.8
• 作者: Khan BA;Perkins AJ;Khan SH;Unverzagt FW;Lasiter S;Gao S;Wang S;Zarzaur BL;Rahman O;Eltarras A;Qureshi H;Boustani MA
• 通讯作者: Boustani MA