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The Association Between Aging, Inflammation, and Clinical Outcomes in Acute Respiratory Distress Syndrome

衰老、炎症与急性呼吸窘迫综合征临床结果之间的关联

基本信息

批准号：
10722669
负责人：
Andrea Levine
金额：
$ 15.45万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722669
关键词：
2019-nCoV Acute Respiratory Distress Syndrome Age Aging Biological Biological Aging Biological Markers COVID-19 COVID-19 pandemic COVID-19/ARDS Cell Aging Cell Cycle Arrest Cells Cessation of life Chronology Clinical Clinical Data Clinical Trials Coupled Data Development Elderly Epidemiological trend Etiology Future Genetic Grant Hand Hypoxemia Hypoxia IL8 gene Immune Immune response Impairment Infection Infiltration Inflammaging Inflammation Inflammatory Inflammatory Response Interferon Type II Interleukin-6 Intervention Knowledge Length Leukocytes Life Link Measures Mediator Mentors Modeling Outcome Pathway interactions Patients Phenotype Plasma Plasma Proteins Predisposition Process Publishing Pulmonary Diffusing Capacity Research Research Support Risk Factors Role Sampling Severities Telomere Shortening Testing Training Virus Work age related biological heterogeneity chemokine cohort comorbidity cytokine differential expression effective therapy mortality non cardiogenic pulmonary edema novel pathogen peripheral blood prognostic prognostic value protein biomarkers senescence telomere young adult

项目摘要

ABSTRACT Acute Respiratory Distress Syndrome (ARDS) is a highly fatal condition characterized by diffuse pulmonary infiltrates and severe hypoxemia. The outcomes of ARDS are significantly worse in older adults, a finding that has been underscored by the ongoing COVID-19 pandemic. ARDS is known to be more severe with advanced biological age, as demonstrated by the relationship between telomere length and severity of ARDS. Aging is characterized by inflammation and cellular senescence, two processes which may mechanistically explain worse outcomes seen in older adults with ARDS. Recently, two inflammatory subphenotypes have been described in ARDS. The hyperinflammatory subphenotype has a higher mortality, similar to that of older adults. A considerable overlap exists in the protein biomarkers which define the hyperinflammatory subphenotype and those which circumscribe the age defining process of senescence, suggesting that age may play a role in the biological heterogeneity of ARDS. Furthermore, inflammation and cellular senescence are both canonical age- related processes. The proposed research will test the relationships between aging, inflammation, and outcomes in ARDS and determine whether biological age differs between the two previously defined inflammatory subphenotypes of ARDS. Finally, this work will attempt to define novel senescent subphenotypes of ARDS and establish the degree to which these subphenotypes overlap with the already defined inflammatory subphenotypes. This work will be performed in two distinct cohorts, a COVID-19 and non-COVID-19 cohort allowing for additional analysis regarding whether the relationship between age, inflammation, and outcomes is differentially expressed in COVID-19 versus non-COVID-19 ARDS. This work will contribute significantly to a deeper mechanistic understanding of ARDS and will support predictive enrichment in ARDS clinical trials which will contribute to more effective therapies for older adults with ARDS.

摘要急性呼吸窘迫综合征（ARDS）是一种高度致命的疾病，其特征是弥漫性肺动脉高压。浸润和严重低氧血症。老年人的ARDS预后明显更差，这一发现持续的COVID-19疫情凸显了这一点。已知晚期ARDS更严重，生物学年龄，如端粒长度与ARDS严重程度之间的关系所证明的那样。衰老是其特征在于炎症和细胞衰老，这两个过程可能在机械上解释更糟的情况。老年成人ARDS患者的预后。最近，两种炎性亚表型已被描述， ARDS。高炎症亚表型具有较高的死亡率，与老年人相似。一在定义高炎症亚表型的蛋白质生物标志物中存在相当大的重叠，那些限制了衰老的年龄定义过程，这表明年龄可能在衰老过程中发挥作用。 ARDS的生物学异质性。此外，炎症和细胞衰老都是典型的年龄- 相关过程。这项拟议中的研究将测试衰老、炎症和结果之间的关系。并确定生物学年龄是否在先前定义的两种炎症之间存在差异 ARDS的亚型。最后，这项工作将试图定义新的ARDS衰老亚表型，确定这些亚表型与已经定义的炎性表型重叠的程度，亚表型这项工作将在两个不同的队列中进行，即COVID-19队列和非COVID-19队列允许进一步分析年龄、炎症和结果之间的关系，在COVID-19与非COVID-19 ARDS中差异表达。这项工作将大大有助于更深入地了解ARDS的机制，并将支持ARDS临床试验中的预测富集，将有助于更有效地治疗老年人的ARDS。