[K23] Applying digital phenotypes and epigenetics to understand clinical outcomes in acute hypoxemic respiratory failure without acute respiratory distress syndrome (NAHRF)
Ente: National Heart Lung and Blood Institute
Scadenza: 2030-07-31
Importo max: 190.944 EUR
Paese: US
Descrizione
PROJECT SUMMARY
Each year approximately 1 million adults receive invasive mechanical ventilation in the United States for acute
hypoxemic respiratory failure (AHRF), and 30-40% of these patients die in the hospital. Most research has
focused on acute respiratory distress syndrome (ARDS), a severe form of AHRF that affects one quarter of
mechanically ventilated adults. Despite over 50 years of research, few pharmacotherapies for ARDS have
shown benefit in clinical trials and, although more common than ARDS with comparable mortality rates, there
are no targeted therapies for non-ARDS AHRF (NAHRF). These failures result, at least in part, from a “one-
size-fits-all” approach to treatment. This K23 proposal aims to advance management of critically ill adults with
NAHRF toward a phenotype-driven, individualized approach that will 1) Improve clinical outcomes through
more precise application of existing and future therapies and 2) Inform future research by enabling phenotype-
based clinical trial screening and enrollment strategies. The Specific Aims are: 1) Develop clinical prediction
models for mortality in adults with NAHRF; 2) Apply machine learning to detect subphenotypes of NAHRF
associated with differential clinical outcomes; and 3) Use sequencing-based whole methylome data to better
understand the biological mechanisms contributing to these outcomes. With these Specific Aims and a career
development plan designed to fill gaps in her training, Dr. Arnold will become an independent clinical
investigator. The career development plan includes didactics, applied learning, and training with her mentors
to: 1) Learn advanced modeling methods for risk stratification and digital phenotyping; 2) Acquire expertise in
the discovery and application of novel biological markers; and 3) Obtain the experience and leadership skills
needed to conduct prospective clinical studies in the acute care setting. Dr. Arnold has assembled a
multidisciplinary team of mentors and advisors with extensive track records of research success, mentorship,
and collaboration in clinical and translational research. Supportive and well-resourced with internationally
recognized leaders in clinical prediction model derivation and validation, clinical trials, emergency care
research, and bioinformatics, UC Davis has a track record of excellence in patient-oriented research and
provides an ideal environment to support Dr. Arnold’s development into a national leader in precision-guided
approaches to NAHRF.
Istituzione: UNIVERSITY OF CALIFORNIA AT DAVIS
PI: Cosby Arnold
Progetto: 5K23HL177334-02
Settori: National Heart Lung and Blood Institute
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