# COPD Cachexia: Deciphering the Impact of Antioxidants, Iron and Mitochondrial Function Using 'Omics Approaches

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $111,375

## Abstract

SUMMARY
 Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the United States
with mortality continuing to rise despite advances in medicine. Cachexia, a form of muscle wasting, is a
debilitating co-morbidity whose prevalence increases with severity of COPD. But, cachexia still occurs among
COPD patients with milder disease severity. Cachexia is most often thought of with respect to cancer. However,
by population prevalence there are more COPD patients with cachexia than cancer patients with cachexia. Yet
there have been few studies investigating the etiology of COPD cachexia underscoring the need for
investigations of COPD cachexia and weight-loss. Accumulating data including our own points to a role for iron
toxicity in the etiology of COPD cachexia. Heme is an essential component of mitochondrial cytochromes
providing protection from reactive oxygen species (ROS). Defects in heme biosynthesis cause buildup of free
iron, ROS and mitochondrial dysfunction. Buildup of free iron leads to iron toxicity and production of ROS
particularly in the absence of adequate intake of antioxidants such as Vitamins E. As such, our overarching
hypothesis is iron toxicity in COPD cachexia is driven by impaired antioxidant and mitochondrial function. This
supplement will expand on Aim1 of the parent R01. 1) To determine whether genomic variation associated with
the absorption and regulation of Vitamin E is more common in COPD cachexia we will perform analysis of whole-
genome sequence data from subjects recruited from All of Us and participants in the Trans Omics for Precision
Medicine (TOPMed) Initiative.

## Key facts

- **NIH application ID:** 10659943
- **Project number:** 3R01HL153460-02S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Merry-Lynn Noelle McDonald Donnelly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $111,375
- **Award type:** 3
- **Project period:** 2021-06-10 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10659943

## Citation

> US National Institutes of Health, RePORTER application 10659943, COPD Cachexia: Deciphering the Impact of Antioxidants, Iron and Mitochondrial Function Using 'Omics Approaches (3R01HL153460-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10659943. Licensed CC0.

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