# Precision Medicine in the Acute Respiratory Distress Syndrome

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $967,250

## Abstract

ABSTRACT
 The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill
patients, with nearly 200,000 cases per year in the US alone and mortality rates of 30-40%. Clinical trials of
novel pharmacotherapies in ARDS have met with nearly ubiquitous failure, a dismal track record which has
been attributed at least in part to the considerable clinical and biological heterogeneity within this syndrome.
With this strong evidence of significant clinical and biological heterogeneity and a major need for new therapies
to improve poor clinical outcomes, ARDS is a ripe target for the application of precision medicine, yet little has
been done to move from our current one-size-fits-all approach to ARDS clinical care and trials to a more
targeted and personalized approach.
 We recently identified and validated the presence of two distinct subphenotypes (also known as
“endotypes”) of ARDS in four large randomized controlled trials. In an independent analysis of all four
datasets, there was strong evidence for two different endotypes within ARDS: a hyper-inflammatory endotype
and a hypo-inflammatory endotype. These endotypes had strikingly different (1) clinical characteristics, (2)
biomarker profiles, (3) clinical outcomes, and (4) treatment responses. Most notably, significant endotype-
specific treatment responses were identified within three clinical trials previously thought to be “negative.”
While these data are highly promising, we have only a basic understanding of the biology of these endotypes,
of the full range of differential treatment responses they exhibit, of the impact of environmental exposures on
endotypes, and of how best to translate this growing knowledge base into practical tools for application at the
bedside and in clinical trials. In this application, we describe a research program that brings together expertise
in molecular phenotyping of critical illness, environmental exposures assessment, advanced statistical
approaches to analysis of complex multi-dimensional data, an experimental human lung model of ARDS, and
access to clinical trial networks and diverse heterogeneous patient cohorts, in order to determine the optimal
approach to applying precision therapeutics in human ARDS.
 This program has the potential to be paradigm-shifting by developing practical models for personalized
medicine for patients with ARDS, targeted to the biology of an individual patient's disease, with a significant
impact on both clinical trials and ultimately clinical care. In addition, these studies will have a high impact via
identification of endotype-specific therapeutic responses in completed and ongoing ARDS clinical trials and by
improving our understanding of the diverse biology of human ARDS, enhancing the likelihood that successful
new therapeutics will be identified for each endotype. Finally, this program will develop a framework by which
the principles of precision medicine can be applied to the fast-...

## Key facts

- **NIH application ID:** 10331306
- **Project number:** 5R35HL140026-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Carolyn Calfee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $967,250
- **Award type:** 5
- **Project period:** 2018-01-16 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331306

## Citation

> US National Institutes of Health, RePORTER application 10331306, Precision Medicine in the Acute Respiratory Distress Syndrome (5R35HL140026-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10331306. Licensed CC0.

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