Dr. Mary Rice is a pulmonologist whose long-term career goal is to become an independent translational investigator focused on understanding how environmental exposures affect the development and progression of chronic lung disease. Her research efforts have focused on the study of short- and long-term exposure to ambient air pollution and lung function in the Framingham Heart Study. In this population-based study of adults, she has found that previous-day air pollution exposure within current standards is associated with lower lung function, and long-term pollution exposure is associated with accelerated lung function decline. Her research has resulted in a first place award in a national pulmonary fellows' research competition and two first author publications in the American Journal of Respiratory and Critical Care Medicine. Dr. Rice proposes new research that will move the field forward, and build on these findings and the skills she acquired during her Master's in Public Health training, to understand how pollution at these concentrations may affect the development and progression of chronic lung disease. Her immediate career objectives are (1) to obtain formal and applied training in environmental epidemiology, biostatistics, and the use of quantitative chest CT analysis in research, and (2) to gain practical skills in building a cohort with chronic obstructive pulmonary disease (COPD), and assessing pollution exposure, respiratory symptoms and lung function in this population. Environment: With the guidance of her co-mentors, Drs. Murray Mittleman and George Washko, Dr. Rice has formulated a comprehensive career development plan to accomplish these goals. Dr. Mittleman MD DrPH, Harvard Professor of Epidemiology at Beth Israel Deaconess Medical Center (BIDMC) and the Harvard School of Public Health (HSPH), will serve as Dr. Rice's primary mentor, as he has for nearly 3 years during her research fellowship. Dr. Mittleman is a renowned physician epidemiologist with expertise in the study of acute and chronic effects of pollution exposure. He has a long track record of mentoring trainees to independence and has won awards for his mentorship role. Dr. Washko, the proposed co-mentor, is a pulmonologist and Director of the Chest Imaging Lab at Brigham and Women's Hospital, and Associate Director of the Framingham Heart Study Pulmonary Research Center. He is a pioneer in the use of quantitative imaging analysis in the study of chronic obstructive pulmonary disease (COPD). Dr. Rice will be based within the Division of Pulmonary and Critical Care at BIDMC, which is deeply committed to promoting her as a future leader in translational research focused on understanding the environmental origins of chronic lung disease, and COPD in particular. Dr. Rice will be supported by the Harvard Catalyst Clinical and Translational Science Award, which will provide research space and resources at the BIDMC Clinical Research Center for her new study of the respiratory effects of pollution exposure in people with COPD. This study will provide data for a future R01 proposal. Additionally, the proposed career development plan will take advantage of advanced classes and seminars at HSPH and Harvard Medical School, and a multidisciplinary advisory board with world-class expertise in air pollution exposure assessment, respiratory epidemiology and environmental biostatistics. Research: In her first two aims, Dr. Rice proposes analyses of long-term exposure to traffic and fine particulate matter, estimated by a sophisticated model using satellite-based estimates of particle abundance in the atmospheric column, and (1) measures of emphysema, airway thickness, lung volumes and interstitial lung abnormalities, and (2) measures of pulmonary vascular morphology on chest CT in the Framingham Heart Study. This work builds on her prior work in this cohort to determine if long-term pollution exposure contributes to obstructive lung disease (with alveolar destruction and airway thickening), restrictive lung disease (with parenchymal scarring that stiffens and shrinks the lung), and/or pulmonary vascular disease (with constriction or pruning of the peripheral vasculature). Prior studies of lung function indicate that long-term air pollution exposure may cause obstructive and restrictive effects, and limited evidence suggests pollution may increase right ventricular afterload and mass, possibly a result of pulmonary vascular change. Dr. Rice hypothesizes that years of exposure to traffic-related pollution, like tobacco smoke, contributes to emphysema, airway thickening, interstitial abnormalities, and a lower volume of small caliber peripheral pulmonary vessels. In her third aim, Dr. Rice proposes a new prospective study of people with COPD (n=30) to test associations between daily exposure to ambient air pollutants measured by central site in Boston and also by a novel, light-weight personal monitor, and daily measurements of respiratory symptoms and lung function at home, using state-of-the art spirometry tools. Although studies using administrative data have found that day-to-day increases in outdoor pollution levels are associated with increased risk of COPD admissions and respiratory mortality, little is known about how air pollution at today's levels affects lung function and symptoms in people with COPD, for whom even modest changes in lung function may have clinical importance. This research will advance understanding of how exposure to pollution at relatively low levels affects lung structure in the general population, and lung function and symptoms in people with COPD. Findings may inform air quality standards to protect the public and susceptible populations. Data on personal pollution exposure in COPD may ultimately translate to behavioral interventions to prevent COPD exacerbations.

Public Health Relevance

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive, and debilitating disease that results in millions of acute exacerbations in the U.S. annually. Nonsmoking risk factors, including air pollution exposure, likely play a role in the development and progression of COPD and other chronic lung disease, and may be preventable. This study will examine how exposure to air pollution at relatively low levels in the Northeastern U.S. may contribute to the development of chronic lung disease as determined by computed tomography (CT scan) and will examine how daily exposure to pollution affects the disease course in people with COPD, who may be more susceptible to the effects of air pollution exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23ES026204-04
Application #
9645083
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Joubert, Bonnie
Project Start
2016-03-01
Project End
2021-02-28
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H et al. (2018) Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study. Environ Int 111:14-22
Rice, Mary B; Rifas-Shiman, Sheryl L; Litonjua, Augusto A et al. (2018) Lifetime air pollution exposure and asthma in a pediatric birth cohort. J Allergy Clin Immunol 141:1932-1934.e7
Rice, Mary B; Li, Wenyuan; Dorans, Kirsten S et al. (2018) Exposure to Traffic Emissions and Fine Particulate Matter and Computed Tomography Measures of the Lung and Airways. Epidemiology 29:333-341
Dorans, Kirsten S; Wilker, Elissa H; Li, Wenyuan et al. (2017) Residential proximity to major roads, exposure to fine particulate matter and aortic calcium: the Framingham Heart Study, a cohort study. BMJ Open 7:e013455
Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H et al. (2017) Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study. Arterioscler Thromb Vasc Biol 37:1793-1800
Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H et al. (2017) Residential Proximity to Major Roadways, Fine Particulate Matter, and Hepatic Steatosis: The Framingham Heart Study. Am J Epidemiol 186:857-865
Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H et al. (2016) Residential proximity to major roadways, fine particulate matter, and adiposity: The framingham heart study. Obesity (Silver Spring) 24:2593-2599
Dorans, Kirsten S; Wilker, Elissa H; Li, Wenyuan et al. (2016) Residential Proximity to Major Roads, Exposure to Fine Particulate Matter, and Coronary Artery Calcium: The Framingham Heart Study. Arterioscler Thromb Vasc Biol 36:1679-85