This is a new application for a K24 award for Carolyn S. Calfee, MD, Associate Professor of Medicine and Anesthesia at the University of California, San Francisco. Dr. Calfee is a physician specializing in pulmonary and critical care medicine who is strongly committed to a career in patient-oriented research (POR) and to mentoring the next generation of translational scientists. In the 8 years since completing her fellowship, she has developed a well-funded independent research program focused on improving our understanding of the pathogenesis of the acute respiratory distress syndrome (ARDS), 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%. This K24 award will allow Dr. Calfee to achieve two principal goals: (1) to use the tools of molecular epidemiology to improve our understanding of the pathogenesis of human ARDS, with a focus on ARDS risk factors and subphenotypes; and (2) to further develop her skills in mentoring trainees in POR in ARDS while expanding her time devoted to mentoring. Dr. Calfee is at an ideal stage in her career for a K24 award, since providing dedicated protected time for mentoring in POR would allow her to expand her current research program, expand and protect her time dedicated to mentoring, and obtain further training in mentoring skills. Obtaining a K24 award at this critical mid-career stage is vital to supporting Dr. Calfee's career in POR and protecting her ability to continue mentoring trainees in this challenging funding climate. New research to be supported by this award will build on Dr. Calfee's extensive track record in pathogenesis-oriented studies of molecular phenotypes of ARDS, providing tangible support for a promising new direction in her research as well as a wealth of opportunities for trainees. Specifically, this award will support investigation of the novel hypothesis that ARDS contains two distinct subphenotypes (also known as ?endotypes?).42 Dr. Calfee recently identified and validated the presence of two distinct endotypes of ARDS in three large randomized controlled trials.16 These endotypes had strikingly different clinical characteristics, biomarker profiles, and clinical outcomes, and significant endotype-specific treatment responses were identified within a clinical trial previously thought to be ?negative.? However, because these endotypes were identified in the setting of randomized controlled trials, using a narrow set of clinical and biological data, it remains unknown whether an expanded set of clinical characteristics and biomarkers would contribute significantly to ARDS endotype identification. Likewise, it remains unknown whether patients can transition between ARDS endotypes over the course of their illness and how the biology of each endotype evolves over the first several days of ARDS. The research proposed for this award will directly address these gaps in knowledge about ARDS endotypes, so as to improve our ability to design personalized therapies tailored to the biology of disease for critically ill patients with ARDS.

Public Health Relevance

The acute respiratory distress syndrome (ARDS) remains a common and frequently fatal cause of acute respiratory failure in critically ill patients, with no specific preventative strategies or therapies available. The goal of this project is to study the clinical and biological features of ARDS subtypes in a broad sample of patients with ARDS and to determine how these subtypes change over time, in order to tailor therapy to individual ARDS patients and thereby improve clinical outcomes from ARDS.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
1K24HL133390-01
Application #
9161405
Study Section
Special Emphasis Panel (MPOR (MA))
Program Officer
Reineck, Lora A
Project Start
2016-07-15
Project End
2021-06-30
Budget Start
2016-07-15
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$120,269
Indirect Cost
$8,909
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Delucchi, Kevin; Famous, Katie R; Ware, Lorraine B et al. (2018) Stability of ARDS subphenotypes over time in two randomised controlled trials. Thorax 73:439-445
Panzer, Ariane R; Lynch, Susan V; Langelier, Chaz et al. (2018) Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients. Am J Respir Crit Care Med 197:621-631
Sinha, Pratik; Delucchi, Kevin L; Thompson, B Taylor et al. (2018) Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med 44:1859-1869
Robles, Anamaria J; Kornblith, Lucy Z; Hendrickson, Carolyn M et al. (2018) Health Care Utilization and the Cost of Post-Traumatic ARDS Care. J Trauma Acute Care Surg :
Robles, Anamaria J; Kornblith, Lucy Z; Hendrickson, Carolyn M et al. (2018) Health care utilization and the cost of posttraumatic acute respiratory distress syndrome care. J Trauma Acute Care Surg 85:148-154
Famous, Katie R; Delucchi, Kevin; Ware, Lorraine B et al. (2017) Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med 195:331-338
Bos, L D; Schouten, L R; van Vught, L A et al. (2017) Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis. Thorax 72:876-883
Chun, Lauren F; Moazed, Farzad; Calfee, Carolyn S et al. (2017) Pulmonary toxicity of e-cigarettes. Am J Physiol Lung Cell Mol Physiol 313:L193-L206
Chun, Lauren F; Moazed, Farzad; Calfee, Carolyn S et al. (2017) Reply to ""Letter to the Editor: Pulmonary toxicity of electronic cigarettes: more doubts than certainties"". Am J Physiol Lung Cell Mol Physiol 313:L966-L967
Moazed, Farzad; Calfee, Carolyn S (2017) The Canary in the Coal Mine Is Coughing: Electronic Cigarettes and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med 195:974-976

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