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Structural Determinants of Disease Progression in COPD

Award Number: R01HL151421
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/05/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Structural Determinants of Disease Progression in COPD - Project Summary/ Abstract Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lungs that results in airflow limitation; it affects 24 million adults in the United States, and is the third leading cause of death. Recent studies challenge the paradigm that COPD is uniformly progressive, but the mechanisms that underlie distinct trajectories of disease progression are not well understood. A major hurdle in the advancement of therapies that alter the progression of disease is our inability to precisely phenotype individuals with variable disease trajectories; reliable surrogate biomarkers to predict clinical progression in individual subjects are lacking. Furthermore, existing pharmacotherapies have a modest impact on respiratory morbidity and fail to impact the rate of FEV1 decline. These medications target airway tone and inflammation, and none directly target structural changes involving the airways or alveolar remodeling (emphysema) that underlie FEV1 change. Thus, a major gap in understanding is the identification of inter-dependent pathways of structural airway/alveolar remodeling that determine disease progression which would inform more precise diagnostic and therapeutic strategies for COPD. The origins of COPD are believed to be in the small conducting airways less than 2 mm in diameter but these data are mostly cross-sectional. In addition, COPD is characterized by both airway remodeling and alveolar destruction; it is likely that both processes contribute to disease initiation and progression. Our preliminary findings suggest that disease progression occurs due to a complex interplay of structural changes in the lungs, both in the parenchyma and in the airways, including mechanical stretch of normal parenchyma, distribution of emphysema, and airway remodeling. Disease progression is not reflected entirely by FEV1 changes and progression of structural disease is an important determinant of disease trajectory. Based on these findings, we hypothesize that structural anatomic and mechanical factors in both the airway and alveolar compartments contribute to disease progression in COPD. To test these hypotheses, we will analyze data from two large well-characterized cohorts (Genetic Epidemiology of COPD, COPDGene, and Subpopulations and Intermediate Outcome Measures in COPD Study, SPIROMICS) with 5-year follow-up with the following specific aims. Aim 1 of this application will be to determine whether mechanically affected lung leads to initiation and progression of emphysema. In Aim 2, we will determine whether the spatial distribution of emphysema influences disease progression. In Aim 3, we will determine whether longitudinal changes in airway remodeling are associated with lung function decline. The results will identify mechanisms of disease progression, establish novel imaging biomarkers, and help create precise models that will allow development of more targeted therapies to attenuate disease progression.


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 = $526,124 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	5	4/15/2024	NON-COMPETING CONTINUATION	$483,175
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	5	6/22/2024	NON-COMPETING CONTINUATION	$42,949
														Subtotal = $526,124

Issue Date FY: 2023 ( Subtotal = $522,011 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	4	3/15/2023	NON-COMPETING CONTINUATION	$522,011
														Subtotal = $522,011

Issue Date FY: 2022 ( Subtotal = $519,041 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	3	6/14/2022	NON-COMPETING CONTINUATION	$51,906
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	3	3/16/2022	NON-COMPETING CONTINUATION	$467,135
														Subtotal = $519,041

Issue Date FY: 2021 ( Subtotal = $519,019 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	3/16/2021	NON-COMPETING CONTINUATION	$519,019
														Subtotal = $519,019

Issue Date FY: 2020 ( Subtotal = $540,212 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	4/3/2020	NEW	$540,212
														Subtotal = $540,212

Grand Total All Awards = $2,626,407

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Structural Determinants of Disease Progression in COPD

Award Number: R01HL151421

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/05/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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