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

Award Number: R01ES035421
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/14/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Impact of Macrophage Carbon Load and Epigenetic Aging on Lung Function Decline and Mortality - 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. Findings from this study will inform future research, facilitating the development of novel air quality metrics based on BC to mitigate health risks and address climate change.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $691,990 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	3	3/5/2026	NON-COMPETING CONTINUATION	$691,990
														Subtotal = $691,990

Issue Date FY: 2025 ( Subtotal = $712,649 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	2	3/10/2025	NON-COMPETING CONTINUATION	$712,649
														Subtotal = $712,649

Issue Date FY: 2024 ( Subtotal = $747,121 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	1	3/14/2024	NEW	$747,121
														Subtotal = $747,121

Grand Total All Awards = $2,151,760

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

Award Number: R01ES035421

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/14/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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