The Division of Pulmonary, Critical Care, and Sleep Medicine of the Warren Alpert Medical School at Brown University is strongly committed to the academic mission of the Department of Medicine. We have many ongoing funded research projects in a wide variety of fields from clinical research to bench research both within our own department and through collaboration with the other departments in the Brown research community. Each faculty member, whether full-time basic science, clinical research or clinical practice oriented, is encouraged to pursue independent research efforts. The success of these efforts is measured by the fact that, over the past 2 years, there are over 100 publications in the peer-review literature by division faculty. The strong point in the current research is the diversity of these efforts. Research in our division encompasses a diverse mix of basic science biology, clinical studies, therapeutic trials, health services, and ethics research, which substantiates the division’s commitment to encouraging a broad array of research. The funding of research in our division also comes from a wide area of sources, including the NIH, professional societies, dependent foundations, hospital-based, and industry. The Pulmonary/Critical Care Fellows have participated in many of the research projects and have been lead authors on several publications in peer-reviewed journals as a result of their research efforts. An NIH T32 institutional training grant is available.
Active Areas of Research Include:
- Sepsis (mechanisms and treatment)
- Knowledge translation
- Acute lung injury
- Pulmonary Vascular Disease (mechanisms and treatment)
- Mechanisms of Right Ventricular Failure
- Sleep disordered breathing associated with behavior disorders and treatments
- Systemic vascular co-morbidities of COPD
- Tuberculosis in rural Africa
- End-of-life care in the ICU
- Ethical and Practical aspects of rationing medical care
- Role of Stem Cells in lung injury and repair
- Pulmonary Rehabilitation
- Pulmonary Physiology utilizing CPET
Specific Research Group Information
Laboratory of Dean Jack Elias and the Warren Alpert Medical School
Laboratory of Dean Jack Elias
Dr. Elias in the Dean of Medicine and Biological Sciences at Brown University. At Brown, Dr. Elias is leading an ambitious $300 million effort to increase translational research, create new opportunities for students at all levels of training, and to train the next generation of physician-scientists.
Warren Alpert Medical School of Brown University
The medical school of Brown has a broad array of research programs that also work alongside other schools at Brown, including the School of Public Health
The Anti-Inflammatory Response in Severe Sepsis
In collaboration with the lab of Dean Jack Elias, Dr. Mitchell Levy, Dr. Alfred Ayala (Division of Surgical Research), Dr. Sean Moynihan, Dr. Deb Bannerjee, Dr. Bing Ma and Dr. Chun Lee and Dr. Steven Opal have a project looking at both in vivo and in vitro elements of the anti-inflammatory response in severe sepsis and correlating the results with clinical outcomes. Tracking septic patients over the first 7 days of admission to the ICU, this project is evaluating levels of PD-1, IL-7 and Chitenase 3 like-1, along with other inflammatory markers, with outcomes and immune suppression.
A Sepsis bio-bank study is also underway with Dr. Levy, Dr. Ventetuolo, Dr. Moynihan and Dr. Elias (Dean of the Medical School) evaluating the timing and identification of several key cytokines during the immunosuppressive phase of sepsis and the development of ARDS.
Knowledge Translation in Sepsis
Mitchell Levy, MD (Division Chief) is conducting work on performance improvement techniques and has been working with The Surviving Sepsis Campaign to improve the survival of sepsis. The Surviving Sepsis Campaign guidelines were developed and published first in 2004 and then revised and published in 2008, 2012 and 2016. He has conducted several trials, testing the impact of these “sepsis bundles” and a multiple-faceted intervention in facilitating knowledge transfer. In partnership with the Institute for Healthcare Improvement (IHI), two sepsis bundles were developed in 2004 and revised in 2015 and 2018. A multi-faceted performance improvement project (Phase 3) was launched in North American, Europe, Asia and Latin America, the results of which were co-published in Critical Care Medicine and Intensive Care Medicine in January, 2015. The final analysis of 30,000 patients in the sepsis database, demonstrating a clear association with higher compliance with the measures and lower hospitals mortality was also co-published in Critical Care Medicine and Intensive Care Medicine in January, 2015.
Through funding from a Moore Foundation grant, an initiative, “Early identification and management of Sepsis on the medical floors” began in early 2014 and completed in August 2015, demonstrating a significant improvement in compliance with the sepsis measures and an associated decline in mortality from severe sepsis. These initiative have led to a significant change in the global approach to sepsis management. In 2014, New York State introduced the Sepsis Initiative, which demonstrated improved survival associated with compliance with the sepsis bundles. In addition, these data informed the release of the national sepsis program, SEP-1, which has mandated the reporting of compliance with the bundles developed by the Surviving Sepsis Campaigns.
Rhode Island Pulmonary Hypertension Center
The Pulmonary Hypertension Center
James Klinger, MD
Corey Ventetuolo, MD
Christopher Mullin, MD
The Rhode Island Hospital Pulmonary Hypertension Center (RIPHC) was established in 1991, and has been under the leadership of Dr. James Klinger since 2001. Dr. Corey Ventetuolo was recruited in 2012 for her expertise in right heart function and extracorporeal life support (ECMO). Mary Whittenhall, MSN, APRN, AGACNP is the Center’s nurse practitioner in charge an active support group. The RIPHC was the first Pulmonary Hypertension Center in New England to be accredited as a Center of Comprehensive Care by the Pulmonary Hypertension Association. The Center participates in numerous clinical trials of new and approved therapies for the treatment of pulmonary arterial hypertension (PAH) and is currently enrolling patients in several national registry and bio-banking studies. Clinical trials run through the RIH PHC are supported by the NIH, American Heart Association (AHA), PHA, industry sources and the Brown University Department of Medicine.
Pulmonary Embolism and Deep Vein Thrombosis
Drs. James Klinger and Corey Ventetuolo have been investigating the role of DVT prophylaxis in the ICU and treatment and follow up of acute submassive pulmonary embolism. The RIHPHC also manages an active population of patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Pulmonary Vascular Research
Dr. Klinger’s research is concentrated on the natriuretic peptides, nitric oxide and downstream signaling mechanisms that are regulated by cGMP and cGMP-dependent protein kinase. His interest in these pathways is related to their role in modulating pulmonary hypertensive and right ventricular hypertrophic responses, as well as pulmonary endothelial barrier function. Presently, Drs. Klinger and Harrington are co-PIs on an RO1 that examines the role of natriuretic peptide C in ameliorating acute lung injury.
In collaboration with Dr. Aliotta (see STEM CELL RESEARCH below), Dr. Klinger also investigates the role of mesenchymal stem cells, extracellular vesicles and micoRNA in pathogenesis and treatment of pulmonary hypertension.
Dr. Ventetuolo’s research focuses on genetic and molecular markers in sex hormone pathways and their influence on sex-based phenotypes in pulmonary vascular and right ventricular health and disease. Her work has focused on the influence of estradiol and other hormones on circulating hematopoietic precursors and markers of angiogenesis in pre- and post-menopausal women and men with PAH. Dr. Ventetuolo’s research is funded by the NIH and the AHA.
Interstitial Lung Disease
Interstitial Lung Disease Program
Barry Shea, MD
Dr. Shea’s laboratory uses a translational approach to better understand the biological mechanisms which drive the development and progression of lung fibrosis, with a focus on the role of ongoing, repetitive lung injury in idiopathic pulmonary fibrosis (IPF). The Shea lab seeks to integrate information obtained from bench research studies using animal models and cell culture systems with the results of clinical investigations of human disease. Towards this end, Dr. Shea has established a longitudinal clinical database and a biorepository of blood, bronchoalveolar lavage (BAL) fluid, and DNA specimens from patients with IPF and other ILDs, and he collaborates closely with the Elias and Chun labs at The Alpert Medical School of Brown University.
Providence VA Clinical Research
Brown University Vascular Research Laboratory
This lab is home to VA and Brown University investigators that share a common interest in mechansism of pathobiology of pulmonary vascular and cardiovascular diseases. As a community of basic science researchers and clinician-scientists, we share the collective vision of translating our research from bench to bedside and beyond. This includes the NIGMS-funded CardioPulmonary Vascular Biology Center of Biomedical Research Excellence, which is led by Brown Pulmonary/Critical Care faculty (Drs. Rounds and Harrington) and is based in the Vascular Research Laboratory at the Providence VAMC. This $10M center provides support for faculty doing research in pulmonary vascular and cardiovascular diseases.
Clinical Research Program at the Providence Veterans Affairs Medical Center
Linda Nici MD (Section Chief) is conducting work on interventions to improve patient-centered outcomes in COPD. Through the Pulmonary Rehabilitation Program as well as the Pulmonary Risk Reduction Initiative, COPD patients at risk for hospital admission or readmission are receiving additional health provider support through education initiatives, promotion of exercise, and identification of risk factors that can be modified to prevent hospitalizations. Current studies include: 1) Rates and predictors of hospital readmission among patients with COPD in the Department of Veterans Affairs using the national VINCI database; 2) The trajectory of physical activity following pulmonary rehabilitation; 3) A brief physician-led education intervention designed to prevent readmission after COPD exacerbation
Matthew Jankowich MD (Co-Director, Providence VAMC Pulmonary Hypertension Clinic) has research interests in pulmonary hypertension and cardiovascular co-morbidities of chronic lung diseases. He has been conducting epidemiologic research with cardiologists Gaurav Choudhary, M.D. and Wen-Chih Wu, M.D. using data from the Jackson Heart Study (JHS), the largest prospective observational study of cardiovascular disease in African-Americans. Brown University is a Vanguard data center for the JHS. Current JHS-approved analyses for which Dr. Jankowich is a lead or co-author include: 1) Neurohormonal markers and pulmonary hypertension in African-Americans in the Jackson Heart Study; 2) The restrictive spirometry phenotype, cardiac structure and function, and heart failure hospitalizations: The Jackson Heart Study; and 3) Iron deficiency in pulmonary hypertension in African-Americans: The Jackson Heart Study. Dr. Jankowich is also site investigator for the Tadalafil for Pulmonary Hypertension Associated with Chronic Lung Disease (TADA-PHiLD) multicenter randomized double-blind placebo-controlled clinical trial (co-PI Dr. Sharon Rounds).
Eric Gartman MD (Director, PFT and CPET laboratories) has research interests in airway disease, diaphragmatic dysfunction and exercise limitation. He is currently the principle investigator for a study evaluating the use of Cardiopulmonary Exercise Testing (CPET) in predicting outcomes after cancer diagnosis and treatment.
In addition to the studies mentioned above, the Providence VAMC implemented lung cancer screening using LDCT starting in December 2013. We are currently evaluating the utility of lung cancer screening in the first two years of implementation in terms of rates of nodule detection, percentage of nodules found to be malignant, and stage at diagnosis compared to the pre-screening population.