Steven M. Kawut, MD, MS is a Professor of Medicine and Epidemiology at the University of Pennsylvania School of Medicine (Penn) who has committed his career to the research and care of patients with pulmonary vascular disease (PVD). He heads a federally-funded research program based on the epidemiology and treatment of PVD and right ventricular dysfunction. He has also mentored more than fifty trainees to success in patient-oriented research (POR), resulting in publications and funding and in many cases their own independent academic careers. The candidate's immediate- and long-term career goals during this competitive renewal center on acquiring skills in performing comparative effectiveness research (CER) in rare PVDs and developing his mentorship abilities, specifically in transitioning his funded mentees to independence and in becoming mentors of their own trainees. The environment at Penn is ideal to develop the applicant as a mentor and to foster the academic growth of mentees in these areas. Pulmonary arterial hypertension (PAH) is a rare disease which affects people of all ages, leading to significant morbidity and a high risk of mortality. However, many questions about the study and therapeutic approach to PAH remain unanswered. The minimally important difference (MID) for the six-minute walk distance (6MWD) has not been clearly established in PAH. The use of the 6MWD in early phase studies and as a component of clinical outcomes makes this an important area of research even in the era of long-term studies in PAH. With the proliferation of new therapies for PAH, CER of different treatments in PAH in terms of health-related quality of life and clinical worsening is a major area of interest. Dr. Kawut is involved in two new initiatives which can address these critical questions in PAH and serve as training vehicles for himself and his mentees. First, the FDA has provided Dr. Kawut with individual patient-level data (IPD) from all submitted randomized clinical trials (RCTs) in PAH. Second, Dr. Kawut chairs the Steering Committee of the Pulmonary Hypertension Association Registry (PHAR), which is a prospective registry of newly-diagnosed patients with PAH at Pulmonary Hypertension Care Centers.
We aim to derive and validate the MID in the change in 6MWD in PAH and to determine the comparative effectiveness of different drug classes on health-related quality of life and time to clinical worsening in patients with PAH. The long-term goal of this proposal is to refine the conduct of RCTs and clinical care in PAH by validating the MID of the 6MWD and studying the comparative effectiveness of different treatment approaches.
These aims provide not only training opportunities for the mentor, but also valuable training and research experiences for mentees at all levels. The opportunities for direct patient involvement in the CER being proposed and direct patient contact make this project ideal for this K24 renewal.

Public Health Relevance

Pulmonary arterial hypertension (high blood pressure in the lungs) carries significant morbidity and mortality. We will study the comparative effectiveness of different treatment approaches to this disease. Training for the applicant and his mentees will be an important component of this grant.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL103844-07
Application #
9336344
Study Section
NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
Program Officer
Colombini-Hatch, Sandra
Project Start
2011-05-01
Project End
2021-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lagatta, Joanne M; Hysinger, Erik B; Zaniletti, Isabella et al. (2018) The Impact of Pulmonary Hypertension in Preterm Infants with Severe Bronchopulmonary Dysplasia through 1 Year. J Pediatr 203:218-224.e3
Oelsner, Elizabeth C; Smith, Benjamin M; Hoffman, Eric A et al. (2018) Associations between emphysema-like lung on CT and incident airflow limitation: a general population-based cohort study. Thorax 73:486-488
Zamanian, Roham T; Hedlin, Haley; Greuenwald, Paul et al. (2018) Features and Outcomes of Methamphetamine-associated Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 197:788-800
Liu, Chia-Ying; Parikh, Megha; Bluemke, David A et al. (2018) Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study. J Magn Reson Imaging 47:262-271
Hong, Gina; Psoter, Kevin J; Jennings, Mark T et al. (2018) Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis. J Cyst Fibros 17:624-630
Forde, Kimberly A; Fallon, Michael B; Krowka, Michael J et al. (2018) Pulse Oximetry Is Insensitive for Detection of Hepatopulmonary Syndrome in Patients Evaluated for Liver Transplantation. Hepatology :
DuBrock, Hilary M; Krowka, Michael J; Forde, Kimberly A et al. (2018) Clinical Impact of Intrapulmonary Vascular Dilatation in Candidates for Liver Transplant. Chest 153:414-426
Podolanczuk, Anna J; Oelsner, Elizabeth C; Barr, R Graham et al. (2017) High-Attenuation Areas on Chest Computed Tomography and Clinical Respiratory Outcomes in Community-Dwelling Adults. Am J Respir Crit Care Med 196:1434-1442
Porteous, Mary K; Lee, James C; Lederer, David J et al. (2017) Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension. Ann Am Thorac Soc 14:1514-1522
Aaron, Carrie P; Hoffman, Eric A; Lima, Joao A C et al. (2017) Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study. PLoS One 12:e0176180

Showing the most recent 10 out of 88 publications