# The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $586,903

## Abstract

PROJECT SUMMARY
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death in the United States with high
morbidity, including poor quality of life and respiratory exacerbations leading to hospitalization and increased
mortality. There are no disease modifying drugs for COPD. Low-income individuals are disproportionately
affected by COPD and have significantly worse health outcomes compared to those with higher income. Our
team, and others, found that increased exposure to social environmental stressors is associated with worse
COPD respiratory symptoms and quality of life, independent of chronologic age, education, BMI, and smoking
history. However, strategies to reduce social/behavioral risk factors have, to date, been inefficient. Thus,
complementary strategies to reduce the burden of disease are needed; biologic mechanisms, e.g. epigenetics,
that could be intervened upon, could provide a promising alternative strategy.
 Strong parallel lines of evidence support epigenetic involvement in the biologic response to social stress
exposures and for COPD pathogenesis. Both individual loci and the epigenetic aging pathway are implicated.
Our preliminary results further support DNA methylation (DNAm; a type of epigenetic data) is related to both
worse COPD outcomes and increased social stress exposure, in a low-income population. Despite this
evidence, no studies have rigorously examined DNAm in the context of both social stressors and COPD
outcomes. Therefore, this ESI-led proposal tests the hypothesis that social environment stressors contribute
to worsened COPD respiratory and quality of life outcomes through epigenetic mechanisms, including in the
epigenetic aging pathway and at individual (non-aging) loci. We leverage two existing COPD studies that
collected unified measures of social stressors, from across the lifespan, COPD health outcomes, as well as
blood and induced sputum biosamples with suitable prevalence and variability in exposures and outcomes.
 In Aim 1, we test for accelerated epigenetic aging mechanisms in social stress effects on COPD health
outcomes. In Aim 2, we test for DNA methylation mechanisms at a targeted set of loci (previously associated
with COPD, socioeconomic position, or social stressors). For each aim, blood and induced sputum DNAm will
be tested in parallel, and results compared across specimen types to further inform mechanism/biomarker
utility. Social stress exposures to be tested include past adverse childhood experience and recent violence,
discrimination, and perceived stress as well as a composite index of stress. COPD outcomes to be tested
include impact of COPD on health and life quality (via SGRQ and CAT score) and respiratory symptom
severity (via mMRC and exacerbation frequency). Aim 3 will relate DNAm findings from Aims 1-2 to induced
sputum gene expression levels to identify downstream functional gene expression changes. Our results can
provide new DNA and/or RNA biologic targets tha...

## Key facts

- **NIH application ID:** 10052092
- **Project number:** 1R01MD015407-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christine Ladd-Acosta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $586,903
- **Award type:** 1
- **Project period:** 2021-04-13 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052092

## Citation

> US National Institutes of Health, RePORTER application 10052092, The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes (1R01MD015407-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10052092. Licensed CC0.

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