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Obesity and Childhood Asthma: The Role of Adipose Tissue

Award Number: R01HL149693
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/22/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Obesity and Childhood Asthma: The Role of Adipose Tissue - PROJECT SUMMARY Both childhood asthma and obesity are major public health problems. There is strong evidence of an association between both diseases; obese children with asthma have increased asthma severity, poor control, and reduced medication response. Yet, to date, the underpinning mechanisms are not well understood. Our central hypothesis is that the obese asthma is driven by changes in the epigenetic regulation and transcriptomic activity within adipose tissue. To test this hypothesis, we will recruit a cohort of children with asthma, obesity, both, or controls, in whom we will perform extensive phenotyping, and obtain subcutaneous and intra-abdominal adipose tissue. In addition to BMI, we will assess other indices of adiposity and body composition measured by anthropometry and impedance analysis. In Specific Aim 1, we will assess the transcriptomic and epigenetic changes in adipose tissue (using RNA-seq and genome-wide DNA methylation, respectively) associated with obesity and asthma in this cohort, after adjustment for relevant covariates. Secondary measures will include body composition and adiposity distribution, and atopy and inflammatory biomarkers. We will then integrate genome-wide genotyping, DNA methylation, and RNA-seq data via mQTL, eQTL, and eQTM analyses. In Specific Aim 2, we will use the same approach to evaluate measures of asthma severity and control in children with obesity and asthma. We will focus on acute exacerbations, Asthma Control Test (ACT) scores, and lung function changes. And in Specific Aim 3, we will conduct an initial functional/causal validation by assessing differential gene expression in normal and asthmatic bronchial epithelial and airway smooth muscle cells, in response to treatment with the products of the top genes identified in Aims 1-2, as well as other candidate genes for obese asthma from the literature. This proposal innovates by focusing on the “source” tissue of obese asthma, rather than using blood biomarkers or mediators, and by validating the effect of the top results on the “target” tissues. Elucidating adipose tissue pathways associated with obese asthma will have critical implications for our understanding of this phenotype and may allow us to identify ways to improve the management of these patients.


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 = $625,613 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Lung Diseases Research	006	6	6/25/2024	NON-COMPETING CONTINUATION	$51,071
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Lung Diseases Research	002	6	2/14/2024	NON-COMPETING CONTINUATION	$574,544
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	4	11/20/2023	NON-COMPETING CONTINUATION	-$490,871
2024	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Lung Diseases Research	001	5	11/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$490,869
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	004	4	3/21/2024	NON-COMPETING CONTINUATION	-$191,789
2024	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Lung Diseases Research	005	5	3/21/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$531,305
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	003	3	3/21/2024	NON-COMPETING CONTINUATION	-$339,516
														Subtotal = $625,613

Issue Date FY: 2023 ( Subtotal = $682,660 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	4	3/22/2023	NON-COMPETING CONTINUATION	$682,660
														Subtotal = $682,660

Issue Date FY: 2022 ( Subtotal = $614,070 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	3	6/13/2022	NON-COMPETING CONTINUATION	$614,070
														Subtotal = $614,070

Issue Date FY: 2021 ( Subtotal = $535,421 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	2	3/26/2021	NON-COMPETING CONTINUATION	$535,421
														Subtotal = $535,421

Issue Date FY: 2020 ( Subtotal = $521,524 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	1	2/21/2020	NEW	$521,524
														Subtotal = $521,524

Grand Total All Awards = $2,979,288

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Obesity and Childhood Asthma: The Role of Adipose Tissue

Award Number: R01HL149693

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 11/22/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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