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Effects of Early Life Exposure to Household Air Pollution on DNA Methylation and Respiratory Disease in Guatemalan Children from the Household Air Pollution Intervention Network (HAPIN) Trial

Award Number: R01HL163256
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Effects of Early Life Exposure to Household Air Pollution on DNA Methylation and Respiratory Disease in Guatemalan Children from the Household Air Pollution Intervention Network (HAPIN) Trial - PROJECT SUMMARY Household air pollution (HAP) from solid fuel use causes an estimated 400,000 chronic obstructive pulmonary (COPD) deaths each year. Although lung function and lower respiratory disease in childhood are determinants of COPD risk later in life, there are few studies of the influence of early life HAP exposure on respiratory health later in childhood. We propose a HAP study design that is sensitive to emerging chronic respiratory effects by incorporating three key features: 1) assessment of exposure during early life windows of susceptibility, 2) a strong exposure contrast introduced by a randomized intervention, and 3) sensitive endpoints that predict chronic disease later in life. Gestation and infancy are critical windows of susceptibility due to the rapid lung development. Previous HAP intervention trials had only low to moderate effectiveness for reducing HAP exposure. The Household Air Pollution Intervention Network (HAPIN) trial (2017-2021) offers a time-sensitive, unique research opportunity because the liquefied petroleum gas (LPG) stove and fuel intervention lowered median gestational fine particulate matter (PM2.5) exposure in Guatemalan participants by 77%, from 98 to 23 µg/m3. The intervention continued until age 1 year and extensive health data were collected, including pneumonia incidence and severity. We have maintained follow-up of the cohort post-intervention, assessing HAP exposure and child growth at age 2 years plus lung function at age 3 years. We posit that childhood lung function and lower respiratory disease episodes are sensitive indicators of HAP health effects that relate to adulthood COPD. DNA methylation (DNAm) and pneumonia during infancy may influence these respiratory endpoints later in childhood. We propose to leverage our successful LPG cooking intervention in Guatemala to investigate effects of early life HAP exposure on longer-term respiratory health and explore DNAm as a biomarker. We hypothesize that the randomized LPG cooking intervention and lower PM2.5 and black carbon (BC) exposure will be associated with DNAm at age 1 year and greater lung function and fewer lower respiratory disease episodes at age 4-7 years. Aim 1. Estimate effects of a randomized LPG cooking intervention during gestation and infancy (age <1 year) (Aim 1.A) and HAP exposure (PM2.5 and BC) during and after the intervention (Aim1.B) on lung function trajectories (age 3-7 years) and lower respiratory disease incidence (ages of 4 to 7 years). Aim 2. Estimate effects of a randomized LPG cooking intervention (Aim 2.A) and HAP exposure (Aim 2.B) during gestation and early infancy (age <1 year) on DNAm biomarkers at the end of the intervention period (age 1 year). Aim 3. Determine whether DNAm at age 1 year (Aim3.A) and pneumonia episodes until age 1 year (Aim 3.B) are associated with lung function trajectories and lower respiratory disease incidence between ages of 3 to 7 years. Effects of early life HAP on lung function and lower respiratory disease later in childhood would have important implications for the early life origins of COPD in populations exposed to HAP, and identifying epigenetic changes that might underpin this relationship could lead to improved research and interventions.


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: 2024 ( Subtotal = $612,961 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Lung Diseases Research	000	2	5/27/2024	NON-COMPETING CONTINUATION	$612,961
														Subtotal = $612,961

Issue Date FY: 2023 ( Subtotal = $676,427 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Lung Diseases Research	000	1	5/15/2023	NEW	$676,427
														Subtotal = $676,427

Grand Total All Awards = $1,289,388

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Effects of Early Life Exposure to Household Air Pollution on DNA Methylation and Respiratory Disease in Guatemalan Children from the Household Air Pollution Intervention Network (HAPIN) Trial

Award Number: R01HL163256

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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