# Impact of Macrophage Carbon Load and Epigenetic Aging on Lung Function Decline and Mortality

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $747,121

## Abstract

Combustion-emitted particulate matter (CE-PM) is emitted through incomplete combustion of fossil fuels and
biomass and is a critical public health and climate change issue in the United States (US) and worldwide. A key
feature of CE-PM is the presence of black carbon (BC) cores as universal carriers of a wide variety of
combustion-derived chemical constituents. Due to different temporality and spatiality for major CE-PM emissions
and a large intra- and inter-individual variation in respiratory physiology, significant knowledge gaps remain
regarding the dose of BC particles in human lungs as well as the dose-response relationship of lung deposition
dose with lung aging and mortality. Accelerated lung aging is a risk factor for the development of chronic
obstructive pulmonary disease (COPD) and lung cancer, two leading causes of disability and death in the US
and globally. Epigenetic alteration is a hallmark of lung aging and implicates key biological pathways underlying
COPD development. Our overarching goals are 1) to evaluate the impact of lung deposition dose of BC and
sputum methylation change on lung function decline (LFD) and mortality, and 2) to explore the lung dose of BC
– epigenetics interactions. This project will be conducted in 1071 members from the Lovelace Smokers Cohort
and 500 members from the Pittsburgh Lung Screening Study who have ≥4 spirometry and longitudinal sputum
collections. Macrophage carbon load assay is a novel sputum cytology-based method that quantifies BC particles
in macrophages and reflects lung dose of total CE-PM exposure at an individual level over the past several
months. An innovative machine-learning algorithm for engulfed carbon particles has been developed that
automates the scoring process with high accuracy. Aim 1 will evaluate the dose-response relationships between
lung dose of BC, LFD, and mortality. Our recent studies showed that promoter methylation of a 12-gene panel
measured in baseline sputum is capable of quantifying the extent of airway remodeling and predicts LFD and
mortality. Aim 2 will characterize the sputum methylation index (MI) trajectory in longitudinal samples in a subset
(n=200) and then quantify the change of sputum MI between baseline and 5-year follow-up in all study subjects
(n=1571). The endotype (sputum methylation) – phenotype (LFD) correlation will be assessed. Identifying
determinants of sputum MI change is a key component for characterizing its full validity as a lung aging
biomarker. Aim 3 will assess whether total CE-PM exposure, baseline MI, and established risk factors affecting
baseline MI are associated with sputum MI change. Aim 4 will explore the moderation effect of epigenetic lung
aging on the associations between total CE-PM exposure, LFD, and mortality. This study represents a novel and
significant advance for air pollution epidemiology through characterizing the dose of BC in human lungs as well
as its dose-response relationships with lung aging and mortality. ...

## Key facts

- **NIH application ID:** 10882848
- **Project number:** 1R01ES035421-01A1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Steven A Belinsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,121
- **Award type:** 1
- **Project period:** 2024-03-14 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882848

## Citation

> US National Institutes of Health, RePORTER application 10882848, Impact of Macrophage Carbon Load and Epigenetic Aging on Lung Function Decline and Mortality (1R01ES035421-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10882848. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*