1. Molecular phenotyping of ARDS:  ARDS is a common and frequently fatal cause of acute respiratory failure, with an estimated U.S. incidence of 190,600 cases/year even prior to COVID-19, which led to an avalanche of ARDS cases.  While advances in supportive care have helped improve outcomes over the past two decades, mortality in ARDS patients has plateaued at 30-40%.  Furthermore, 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 strong evidence of 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 towards a more personalized approach.  Our research group has identified and validated two distinct subphenotypes of ARDS in numerous randomized controlled trials and cohort studies, and we have recently identified these same molecular subphenotypes within sepsis cohorts (Sinha et al, Lancet Resp 2023) suggesting that they may represent treatable traits. These subphenotypes have strikingly different clinical characteristics, biomarker profiles, clinical outcomes, and -- most importantly -- differential treatment responses. This work is supported by an NHLBI R35 Emerging Investigator Award on "Precision Medicine in ARDS".

EARLI Study: The Early Assessment of Renal and Lung Injury (EARLI) study is a long-standing observational cohort that enrolls patients at UCSF Medical Center at Parnassus Moffitt-Long Hospital and Zuckerberg San Francisco General Hospital. The EARLI study recruits patients who are admitted directly from the emergency department into the ICU to identify novel risk factors and biomarkers of early organ injury and to facilitate the development of both prevention and treatment strategies. Dr. Calfee serves as Co-PI of the EARLI study.

APS Consortium: Our group is funded by the NHLBI as part of the ARDS, Pneumonia, and Sepsis Consortium (APS Consortium) as the California Clinical Center Hub Institution. The California Clinical Center will coordinate enrollment across four sites: UCSF Parnassus, Stanford University, UCSF Fresno, and Zuckerberg San Francisco General Hospital. A major goal of the Consortium is to better understand the clinical and biological heterogeneity in critical illness to develop effective therapies. Dr. Calfee is the PI for the UCSF center and serves as co-chair of the Scientific Sub-Committee for the APS Steering Committee.

2. COMET Study (Enrollment concluded April 2023): The COMET study was a UCSF study that collected biological samples of blood, respiratory secretions, and viral shedding in nasal secretions from COVID-19 coronavirus patients in order to identify immunophenotypic features for the development of effective therapeutic interventions. The COMET study was closely aligned with the multi-center IMPACC study funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and many eligible participants from COMET were included in IMPACC. The goal of the study was to better understand how COVID-19 affects the immune system, why it causes difficulty breathing, and why some people become more sick than others. Dr. Calfee served as the Clinical Lead PI for COMET and a member of the Executive Committee. Additional information can be found here: LINK.

3.  Novel Therapies for ARDS and COVID-19:  We are interested in novel therapies for ARDS and have been involved in several federally funded clinical trials, in collaboration with Dr. Michael Matthay’s group. This work included the first Phase I/II trial of mesenchymal stem cells for ARDS, a recently completed Department of Defense phase IIb trial of mesenchymal stem cells for ARDS, and participation in the NHLBI-funded Prevention and Early Treatment of Acute Lung Injury (PETAL) clinical trials Network, the successor to the highly successful NHLBI ARDS Network which conducted the landmark trial of low tidal volume ventilation for ARDS, among many others.

4.   Acute pulmonary effects of tobacco products:  Although progress has been made in understanding the pathophysiology of ARDS, it remains unclear why only some of the many patients with clinical conditions that put them at risk for ARDS progress to develop the syndrome. This unanswered question led to our interest in the role of cigarette smoke exposure in the development of ARDS.  Our group identified a link between both active smoking and secondhand smoke exposure and a nearly 3-fold increase in the odds of developing of ARDS after severe blunt trauma (Calfee et al, AJRCCM 2011); our follow-up work reported a similar association in non-pulmonary sepsis (Calfee et al, CCM 2015).   We have also investigated the mechanisms by which cigarette smoking may promote ARDS, including studies of plasma and bronchoalveolar lavage biomarkers and the lung microbiome (Panzer et al, AJRCCM 2017).  In recent years, we have reported an association between air pollution and ARDS development (Ware et al, AJRCCM 2015; Reilly et al, AJRCCM 2018).  In addition to this independent work, we lead a project in UCSF's Tobacco Center of Regulatory Science (TCORS).  Our project studied the relationship between cigarette smoke exposure and infection-related ARDS in both human subjects and mouse models and are now studying the acute impact of e-cigarette exposure on lung injury using infectious and non-infectious experimental models.