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Principal Investigator: ALEXA A PRAGMAN
Organization: MINNEAPOLIS VA MEDICAL CENTER
Fiscal Year: 2024
Funding agency: Veterans Affairs
This is an application for a Merit Award to Dr. Alexa A. Pragman, M.D., Ph.D., a Staff Physician in Infectious
Disease at the Minneapolis VA and an Assistant Professor at the University of Minnesota. Dr. Pragman’s
current work on the chronic obstructive pulmonary disease lung microbiota is funded by a 5-year Career
Development Award-2 from the VA Office of Research and Development. Dr. Pragman has established a
record of accomplishments and publications related to her patient-oriented work on the lung microbiota in
chronic inflammatory pulmonary diseases. This Merit Award will provide the resources necessary to study the
effects of fine particle airborne pollution on the lung microbiota of veterans following deployment to southwest
Asia (Iraq, Afghanistan, or neighboring countries).
Following deployment to southwest Asia, veterans are disproportionately affected by chronic lung problems
including coughing, wheezing, and shortness of breath. While deployed, these veterans were exposed to
excessive concentrations of airborne particulate matter of ≤2.5 μm in size (PM2.5) as a result of seasonal dust
storms, burn pit smoke, and industrial pollution. PM2.5 exposure causes acute and chronic respiratory
problems, and may lead to diseases such as asthma and chronic obstructive pulmonary disease. PM2.5
exposure has been linked to airway and gut microbiota dysbiosis in humans and rodent models, suggesting
that dysbiosis is a potential mediator for the inflammation, symptoms, and lung tissue destruction that continue
long after excessive PM2.5 exposure has stopped. Dysbiosis is defined as an imbalance or maladaptation in the
community of micro-organisms inhabiting a particular site.
In this Merit Award application, Dr. Pragman proposes a prospective case-control study to assess the
relationships between PM2.5 exposure, microbiota dysbiosis, and inflammation. This will be accomplished in
collaboration with VA Cooperative Study #595, Service and Health Among Deployed Veterans (SHADE), which
aims to understand the association between PM2.5 exposures during deployment and subsequent respiratory
symptoms. Dr. Pragman’s study will recruit 140 SHADE participants with chronic lung symptoms (coughing,
shortness of breath, or wheezing) and 140 SHADE participants without chronic lung symptoms. All subjects will
provide saliva and stool samples for microbiota analyses on an annual basis for 3 years. Sputum samples for
microbiota analysis will also be obtained from a subset of subjects on the same schedule. We will assess
microbiota dysbiosis and tissue-specific and systemic markers of inflammation. Our analysis will take into
account PM2.5 exposure levels (obtained from the SHADE study), tissue or site-specific effects, and incorporate
other risk factors for microbial dysbiosis. In Aim 1, Dr. Pragman will determine associations between
deployment-related PM2.5 exposure and site-specific dysbiosis. In Aim 2, Dr. Pragman will determine
associations between site-specific dysbiosis and respiratory symptoms. In Aim 3, Dr. Pragman will determine
site-specific associations between dysbiosis and inflammation. Our overall objective is to establish microbial
dysbiosis as a mediator between PM2.5 exposure and respiratory symptoms. Our central hypothesis is that
deployed veterans’ PM2.5 exposures place them at increased risk for dysbiosis, which in turn increases risk of
developing chronic respiratory symptoms and disease. These findings may identify veterans at high risk for
developing lung disease, and may identify a new treatment target—the microbiota—for primary and secondary
prevention of lung disease in this high-risk veteran population.
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