# Environmental Cadmium and COPD

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $486,082

## Abstract

The lung is a major portal for respirable environmental toxicants including heavy metals such as cadmium
(Cd), which is recognized to cause chronic obstructive pulmonary disease (COPD). COPD is the third
largest cause of mortality in the US. Airway remodeling with loss of the lumen of small airways and airflow
obstruction precede airspace enlargement and emphysema. Airway remodeling is associated with a profusion
of airway fibroblasts and an increase in extracellular matrix proteins. Vimentin is an intracellular type 3 filament
that can trigger peribronchial fibrosis. The prevalence of COPD is twice as high in a zip code where a
Superfund site is located in Birmingham, Alabama when compared to a control zip code with similar
demographics and smoking prevalence. We postulate that chronic low dose cadmium (Cd) exposure induces
alterations in vimentin-mitochondrial dynamics that results in mitochondrial dysfunction and aberrant activation
of peribronchiolar fibroblasts leading to bronchiolar luminal narrowing and subsequent COPD. We will examine
this hypothesis in the following specific aims: (1) Determine whether exposure to Cd in a cohort of smokers
and never-smokers from a Birmingham community predicts susceptibility to airway remodeling and COPD. (2)
Determine the mechanisms by which Cd mediates alterations in vimentin-mitochondrial dynamics to regulate
fibroblast activation. (3) Determine whether low dose Cd, or pSer39Vim induced airway remodeling and
airspace enlargement in a mouse model of COPD is associated with fibroblast invasion, ECM deposition and
apoptosis resistance. These studies will directly address a significant gap in our understanding of how
cadmium contributes to the pathogenesis of COPD and the role of vimentin filaments in mitochondrial
homeostasis. Early biomarkers of COPD in exhaled breath condensate may help us recognize disease
susceptibility. Importantly, these studies may provide novel therapeutic strategies in patients with COPD.

## Key facts

- **NIH application ID:** 10430125
- **Project number:** 5R01ES029981-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Veena B. Antony
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $486,082
- **Award type:** 5
- **Project period:** 2018-09-21 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430125

## Citation

> US National Institutes of Health, RePORTER application 10430125, Environmental Cadmium and COPD (5R01ES029981-05). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10430125. Licensed CC0.

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