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

> **NIH NIH R03** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $154,500

## Abstract

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.

## Key facts

- **NIH application ID:** 10906138
- **Project number:** 5R03AG082798-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Andrea Levine
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $154,500
- **Award type:** 5
- **Project period:** 2023-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906138

## Citation

> US National Institutes of Health, RePORTER application 10906138, The Association Between Aging, Inflammation, and Clinical Outcomes in Acute Respiratory Distress Syndrome (5R03AG082798-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10906138. Licensed CC0.

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