# Project 3 Heavy Metals Exacerbate Lower Respiratory Tract Infections

> **NIH NIH P42** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $209,652

## Abstract

PROJECT SUMMARY / ABSTRACT
 The heavy metals, cadmium, arsenic, and manganese, have been identified at high levels in
the air and soil of the Affected Area (proposed Superfund site). Heavy metals released into the
environment have a significant effect on respiratory health. Although the pathogenesis of
chronic obstructive pulmonary disease (COPD) and asthma are complex, the environmental
exposure to heavy metals is often overlooked in the development of these diseases. Lower
respiratory tract infections (LRTIs) are a main cause of COPD and asthma exacerbations, which
contributes to the morbidity and mortality of these diseases. The residents of the Affected Area
have 30% higher diagnosed LRTIs than residents from the Control Area. Lung macrophages
have a critical role in host defense to respiratory pathogens. Lung macrophages not only initiate
an innate immune response to infection and injury, but they are also involved in repair of injury.
Alveolar epithelial cells (AEC) are injured during infection that results in lung injury by disruption
of the cellular barrier. It is not known if heavy metals regulate the macrophage phenotype to
hinder the repair of the AEC barrier function. We hypothesize that exposure to heavy metals
exacerbates LRTI and lung injury due to the persistence of a classically activated phenotype in
lung macrophages. This persistence impairs the repair of the alveolar epithelium after injury.
The goals of Aim 1 are to determine if heavy metal-exposed mice have increased bacterial or
viral load, lung injury, and mortality compared to vehicle-exposed mice infected with S.
pneumoniae or respiratory syncytial virus (RSV) due to the persistence of classically activated
lung macrophages. In Aim 2 we will utilize genetic approaches to determine the mechanism(s)
by which macrophages maintain persistent classical activation. The goals of Aim 3 are to
determine if macrophage phenotypic switching is impaired in residents from the Affected Area
compared to the Control Area and if BAL fluid from residents in the Affected Area impairs wound
closure and increases permeability of injured AEC. Studies from Project 3 will define the
molecular mechanism(s) by which heavy metal exposure increases LRTIs in residents of the
Affected Area and proposed Superfund site, providing a potential therapeutic target to reduce
the exacerbations seen in these chronic lung diseases.

## Key facts

- **NIH application ID:** 9840807
- **Project number:** 1P42ES027723-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** A BRENT CARTER
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,652
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840807

## Citation

> US National Institutes of Health, RePORTER application 9840807, Project 3 Heavy Metals Exacerbate Lower Respiratory Tract Infections (1P42ES027723-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9840807. Licensed CC0.

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