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Principal Investigator: Andrea Levine
Organization: UNIVERSITY OF MARYLAND BALTIMORE
Fiscal Year: 2024
Award: $154,500
Funding agency: National Institute on Aging
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.
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trend><Epidemiological trend><Epidemiology trend><Etiology><Future><GCP1><Genetic><Grant><HPGF><Hand><Hepatocyte-Stimulating Factor><Homologous Chemotactic Cytokines><Hybridoma Growth Factor><Hypoxemia><Hypoxia><Hypoxic><IFN-Gamma><IFN-beta 2><IFN-g><IFN-γ><IFNB2><IFNG><IFNγ><IL-6><IL-8><IL6 Protein><IL8><IL8 gene><Immune><Immune Interferon><Immune response><Immunes><Immunological response><Impairment><Infection><Infiltration><Inflammaging><Inflammation><Inflammatory><Inflammatory Response><Intercrines><Interferon Gamma><Interferon Type II><Interleukin-6><Intervention><Intervention Strategies><K60><Knowledge><Length><Leukocytes><Leukocytes Reticuloendothelial System><Life><Link><MGI-2><Marrow leukocyte><Measures><Mediator><Mentors><Modeling><Myeloid Differentiation-Inducing Protein><Outcome><Oxygen Deficiency><Pathway interactions><Patients><Phenotype><Plasma><Plasma Proteins><Plasma Serum><Plasmacytoma Growth Factor><Predisposition><Process><Publishing><Pulmonary Diffusing Capacity><Replicative Senescence><Research><Research Support><Reticuloendothelial System, Serum, Plasma><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 associated ARDS><SARS-CoV-2 associated acute respiratory distress syndrome><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 induced ARDS><SARS-CoV-2 induced acute respiratory distress syndrome><SARS-CoV-2 pandemic><SARS-CoV-2 related ARDS><SARS-CoV-2 related acute respiratory distress syndrome><SARS-CoV-2/ARDS><SARS-CoV-2/acute respiratory distress syndrome><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCYB8><SIS cytokines><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Severities><Shock Lung><Stiff lung><Susceptibility><TSG-1><Telomere Shortening><Testing><Training><Virus><White Blood Cells><White Cell><Work><Wuhan coronavirus><adult youth><advanced age><age associated><age correlated><age dependent><age linked><age related><age specific><age-related inflammation><ages><aging associated><aging related><b-ENAP><bio-markers><biologic><biologic 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syndrome><social role><telomere><telomere attrition><transcriptional differences><wet lung><white blood cell><white blood corpuscle><young adult><young adulthood>