ABSTRACT
In recent decades, Mongolia has experienced major economic and environmental changes, and suffered
from severe air pollution. Ulaanbaatar (UB) and Darkhan City (DC) have some of the highest ambient particulate
matter (PM) concentrations in the world and frequently suffer epidemics of viral respiratory diseases. The
associations between PM exposure and cardiorespiratory mortality and morbidity have been well documented,
with an established 6.67 million premature deaths globally attributed to air pollution in 2019. Recently, attention
has increased regarding the association of PM pollution and respiratory viral infection. Hence, this U01 proposal,
as part of the Mongolian GEOHealth Hub program, focuses on studying the relationships and interactions
between PM exposure and respiratory viral infections. The U01 project consists of a main study and two pilot
studies to begin Center activities. The main project is designed to test the hypothesis that PM exposure weakens
the immune defense against respiratory viral infection. It has three interconnected specific aims. Aim 1 is to
characterize the relationship between PM exposure and respiratory viral infection through a time-series analysis
of weekly influenza-like illness (ILI) rates in association with PM levels within and across UB and DC, adjusting
for potential confounders and co-pollutants. As an air pollution control measure, UB started the implementation
of processed coal use in May, 2019, whereas DC continues to use raw coal. Nesting this policy intervention into
the time-series analysis strengthens the causal inference of the PM-ILI association derived from natural
variabilities over time. Aim 2 is to examine immunologic and viral responses to personal PM exposure through
two parallel panel studies in residents of UB and DC, respectively. Each panel consists of 100-120 nonsmoking
adults who will be measured semiannually during a 3-year follow-up period. ILI counts and immunologic
biomarkers will be associated with personal PM exposures. Aim 3 is to define the direct effects of PM exposure
on epithelial integrity and immune signaling and the subsequent impact on anti-viral responses. This will be
achieved through cell culture studies that are directly linked to Aim 2 subjects (as cell donors). The two pilot
studies, built upon the Aim 2 main study, aim to explore the effects of PM on pulmonary tuberculosis and bone
mineral loss, respectively. These studies are motivated by high prevalence of both tuberculosis and osteoporosis
in Mongolia and by emerging evidence suggesting PM or heavy metals in PM as risk factors. This U01 proposal
is an interdisciplinary research project involving researchers in epidemiology, toxicology, environmental and
occupational health, exposure science, biostatistics, virology, immunology, environmental engineering,
respiratory medicine, and infectious disease from multiple institutions in Mongolia, Duke University, and Duke
Kunshan University. The U01 research is designed to be the initial main platform for engaging U2R Fellows
(trainees) and Faculty (mentors) in research and training.
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