COPD is a disease with high morbidity and mortality. Environmental exposures are often responsible for disease development and worsening of existing disease. Recent evidence shows that exposure to indoor air pollution (particulate matter (PM) and nitrogen dioxide (NO2)) increases COPD severity, but the mechanisms for this worsening remain unknown. Furthermore, preliminary studies suggest that a subgroup of individuals with chronic bronchitis demonstrate worse symptoms and outcomes following exposure to indoor pollutants, suggesting that the alterations in mucus production and clearance common to chronic bronchitics may play a role in this observation. However, the specifics of the why this group may be more susceptible to the health effects of indoor pollution exposure remain to be fully understood. In this application, the investigators plan to investigate the role of mucociliary clearance (MCC) and mucus properties in predicting response to indoor air pollution exposure in individuals with COPD. They also aim to determine whether MCC and mucus properties change over time following PM and NO2 exposure in a subgroup of individuals with chronic bronchitis. To complete their aims the investigators will leverage resources from an ongoing Baltimore-based cohort study of former smokers with COPD that aims to determine whether home interventions designed to reduce PM and NO2 exposure improve health outcomes. In this current application, to determine whether baseline MCC and mucus properties predict response to PM and NO2 exposure, 60 individuals with COPD will undergo baseline assessment of MCC using gamma camera technology and induced sputum will be analyzed for mucin concentration, DNA concentration, and mucus solids concentration; individuals will be followed longitudinally with assessment of clinical outcomes along with comprehensive indoor environmental assessment at baseline, 3 months, and 6 months of follow up. In a group of 20 individuals with chronic bronchitis, we will assess MCC and mucus properties along with indoor environmental monitoring at baseline, 3 months and 6 months of follow up to determine whether changes in NO2 and PM concentration alter these mucus outcomes. Ultimately, the information gained from this application will contribute to understanding the mechanism behind the adverse health effects observed in COPD in relation to pollution exposures, and to determine whether these exposures can alter critical components of host defense. Additionally, these data will have implications for the management of COPD and utilization of environmental modification strategies for at-risk individuals. The candidate, a physician completing her training in Pulmonary and Critical Care Medicine, has demonstrated a dedication to developing a career in clinical research that is tied closely to her strong background in environmental health. Though she is early in her career, she has shown a great deal of initiative, motivation, and productivity in her ongoing research endeavors. This application is structured to allow the candidate to achieve her long-term career goal of becoming an independent clinical investigator exploring the role of environmental exposures in determining COPD outcomes and the mechanisms by which such exposures impact disease. In the immediate timeframe, this application would allow the candidate dedicated time to conduct the outlined research project, as well as pursue didactic training in design and conduct of clinica trials and further quantitative methods relevant to this project and future research plans. Additionally, the data generated from this research proposal will form the basis for an R01 application. The Career Development Plan for this candidate includes a structured approach to mentoring, didactic coursework focused on a specific research goal, participation in local and national meetings and identification and regular assessment of career milestones. The research environment provided by Johns Hopkins University as well as the mentorship team described in this application will assist in Dr. Paulin's successful completion of her career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful young clinical researchers in a supportive and collaborative environment. The pre-existing structure of the parent study for this application, set within the strong foundation of the Center for Childhood Asthma in the Urban Environment, as well as the applicant's established and ongoing collaboration with her team of mentors, will ensure that the study goals will be completed within the timeframe of this award. We have assembled a mentoring team of established faculty with many years of productive research experience and substantial prior mentoring experience. Each has distinct, complementary strengths in areas of research relevant to this proposal. In addition, each member of the Mentoring Committee serves as an excellent role model for the candidate's career development into an independent investigator.

Public Health Relevance

This project seeks to understand the role of mucociliary clearance and mucus properties in contributing to poor outcomes and disease progression in COPD following indoor air pollution exposures. The investigators will also determine whether exposure to indoor air pollution can result in changes in mucociliary clearance and mucus properties in individuals with COPD. This study will help to identify why individuals with COPD experience poor outcomes following air pollution exposures and why individuals with COPD who have increased sputum production are more susceptible to the health effects of indoor air pollution, and ultimately will allow us to identify future therapeutic targets and environmental modifications with the goal to reduce morbidity of this very common and debilitating disease.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZES1)
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Thompson, Claudia L
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Dartmouth-Hitchcock Clinic
United States
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Paulin, Laura M; Smith, Benjamin M; Koch, Abby et al. (2018) Occupational Exposures and Computed Tomographic Imaging Characteristics in the SPIROMICS Cohort. Ann Am Thorac Soc 15:1411-1419
Raju, Sarath; Keet, Corinne A; Paulin, Laura M et al. (2018) Rural Residence and Poverty are Independent Risk Factors for COPD in the United States. Am J Respir Crit Care Med :
Burkes, Robert M; Gassett, Amanda J; Ceppe, Agathe S et al. (2018) Rural Residence and COPD Exacerbations: Analysis of the SPIROMICS Cohort. Ann Am Thorac Soc :
Fawzy, Ashraf; Putcha, Nirupama; Paulin, Laura M et al. (2018) Association of thrombocytosis with COPD morbidity: the SPIROMICS and COPDGene cohorts. Respir Res 19:20
Putcha, Nirupama; Paul, Gabriel G; Azar, Antoine et al. (2018) Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS. PLoS One 13:e0194924
McCormack, Meredith C; Paulin, Laura M; Gummerson, Christine E et al. (2017) Colder temperature is associated with increased COPD morbidity. Eur Respir J 49:
Hansel, Nadia N; Paulin, Laura M; Gassett, Amanda J et al. (2017) Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study. BMJ Open Respir Res 4:e000186
Nnodum, Benedicta Nneoma; McCormack, Meredith C; Putcha, Nirupama et al. (2017) Impact of Physical Activity on Reporting of Childhood Asthma Symptoms. Lung 195:693-698
Paulin, Laura M; Williams, D 'Ann L; Peng, Roger et al. (2017) 24-h Nitrogen dioxide concentration is associated with cooking behaviors and an increase in rescue medication use in children with asthma. Environ Res 159:118-123
Belli, Andrew J; Bose, Sonali; Aggarwal, Neil et al. (2016) Indoor particulate matter exposure is associated with increased black carbon content in airway macrophages of former smokers with COPD. Environ Res 150:398-402

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