COPD is a leading cause of death in the US and worldwide and patients suffer high morbidity. A better understanding of contributing factors to the progression and burden of this pervasive disease is critical. Despite population-based epidemiological evidence suggesting exposure to ambient air pollutants causes increased hospitalizations and mortality from COPD, there is very little known about the impact of exposure to air pollutants on the progression of disease. For example, the extent to which exposure to air pollution accelerates lung function loss and contributes to patient-reported outcomes, such as quality of life and dyspnea in COPD remains largely unknown. SPIROMICS is a unique NHLBI-funded prospective cohort study of COPD phenotypes and markers of disease which plans to enroll 3,200 subjects at seven sites across the US. A subgroup of participants will also record daily symptoms over one year. We propose to add state-of-the art air pollution exposure assessment to determine individual-level outdoor and indoor air pollution exposure for all SPIROMICS participants, providing an extraordinary opportunity to understand effects of air pollutants on COPD morbidity and progression.
For Specific Aim 1 a, we aim to determine the impact of long-term outdoor air pollution exposure on COPD morbidity, including lung function decline, patient reported outcomes, and exacerbations by employing sophisticated spatio-temporal air pollution prediction models, supplemented with cohort-specific outdoor monitoring data, to precisely predict participants'ambient exposure to fine particulate matter (PM2.5), light absorbing or """"""""black"""""""" carbon (BC), nitrogen dioxide (NO2), nitrogen oxides (NOx), ozone (O3), sulfur dioxide (SO2)) and link with existing health outcomes collected as part of the SPIROMICS study.
For Specific Aim 1 b, we aim to determine the effect of indoor air pollutants (PM2.5, NO2, NOx, SO2, O3, BC and secondhand smoke) on COPD morbidity by conducting indoor air monitoring in a subset of participants'residences. These data will be combined with validated questionnaire data collected on the entire cohort to model indoor exposure for all participants. Personal monitoring will be used to assess measurement error.
For Specific Aim 2, we will determine whether short-term changes in outdoor air pollution are associated with day-to-day changes in symptoms and exacerbation risk in 300 subjects recording daily symptoms over a one- year period.
For Specific Aim 3 we will examine airway macrophage black carbon content from induced sputum as a biomarker of air pollution (PM2.5 and BC) and determine its association with clinical and subclinical measures of disease severity and prognosis. Our study builds on an established network of investigators with complementary areas of expertise. Findings from this study can provide information to guide public policy and clinical management for individuals with COPD.

Public Health Relevance

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by lung injury due to the total burden of toxic gases and particles that individuals inhale during their lifetime, and is the third leading cause of death inthe United States with substantial economic costs, suggesting a large public health burden. We propose to add state-of-the art air pollution exposure assessment to determine individual-level outdoor and indoor air pollution exposure to an ongoing NHLBI-funded study (SPIROMICS), providing an extraordinary opportunity to understand effects of air pollutants on COPD morbidity and progression. Findings from this study can provide specific information for setting public policy and guide clinical management to improve care of individuals with COPD.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
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Dilworth, Caroline H
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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