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Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes

Award Number: R01HL155522
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes - PROJECT SUMMARY / ABSTRACT Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.5 million people in the United States. Although parenchymal lung disease, which encompasses interstitial lung disease (ILD) and emphysema, is a common lung complication of RA with increasing prevalence and mortality, no strategies currently exist for early detection or risk stratification of progressive disease. This is an area of unmet need that could lead to improved opportunities for intervention and a decrease in the considerable morbidity and mortality of RA-associated parenchymal lung disease. In this proposal, we aim to fully characterize early parenchymal lung disease in RA and establish risk factors for progressive disease. We hypothesize that clinical and molecular risk factors can predict the development and progression of RA-associated parenchymal lung disease, including preclinical ILD (preILD) and emphysema, and that the molecular profile of progressive RA-preILD will overlap with fibrotic RA-ILD. To test this hypothesis, we will propose the following: In Specific Aim 1, we will determine the prevalence and progression of RA-associated preILD and emphysema using visual and objective radiologic approaches and correlate these measurements with functional capacity, respiratory symptoms, and health-related quality of life assessments. In Specific Aim 2, we will define clinical and molecular determinants that predict the development and progression of RA emphysema and compare the molecular profile of emphysema with preILD to provide mechanistic insight into the divergent patterns of parenchymal lung injury caused by RA. In Specific Aim 3, we will demonstrate that progressive RA-preILD and fibrotic RA-ILD have similar molecular signatures, suggesting phenotypic and mechanistic overlap. To achieve the aims of this proposal, a longitudinal cohort of 200 RA patients without a history of ILD will be followed for up to 6 years with detailed clinical, functional, radiologic, and molecular phenotyping. The successful completion of this research will provide us with a better understanding of the early characteristics and natural history of RA-associated ILD and emphysema and establish novel non-invasive ways to identify those at risk for progressive disease. This will enable closer monitoring and earlier opportunities for intervention, potentially leading to decreased morbidity and mortality in individuals afflicted with RA-associated parenchymal lung disease.


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 = $596,610 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	5	4/3/2026	NON-COMPETING CONTINUATION	$596,610
														Subtotal = $596,610

Issue Date FY: 2025 ( Subtotal = $736,799 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	4	5/28/2025	NON-COMPETING CONTINUATION	$73,679
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	4	4/29/2025	NON-COMPETING CONTINUATION	$663,120
														Subtotal = $736,799

Issue Date FY: 2024 ( Subtotal = $732,797 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	002	3	7/27/2024	NON-COMPETING CONTINUATION	$0
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	3	6/20/2024	NON-COMPETING CONTINUATION	$59,818
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	3	4/19/2024	NON-COMPETING CONTINUATION	$672,979
														Subtotal = $732,797

Issue Date FY: 2023 ( Subtotal = $759,661 )
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	2	4/1/2023	NON-COMPETING CONTINUATION	$759,661
2023	2022	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	1	3/28/2023	NEW	$0
														Subtotal = $759,661

Issue Date FY: 2022 ( Subtotal = $708,294 )
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	1	4/15/2022	NEW	$708,294
														Subtotal = $708,294

Grand Total All Awards = $3,534,161

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Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes

Award Number: R01HL155522

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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