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Platelet Activation Pathways and Respiratory Morbidity in COPD

Award Number: K23HL151758
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/20/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Platelet Activation Pathways and Respiratory Morbidity in COPD - PROJECT SUMMARY / ABSTRACT Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Currently, the treatment of COPD relies on a stepwise algorithm of inhaler therapies without targeting systemic processes. Mounting evidence suggests that activated platelets may play a role in COPD but the mechanisms and impact of platelet activation on COPD outcomes are not known. Furthermore, it has been difficult to differentiate respiratory events from cardiovascular symptoms since COPD and cardiovascular disease (CVD) are highly comorbid. Understanding the role of platelets and potential for targeted antiplatelet therapy in COPD patients without CVD could lead to novel therapeutic options. Prior studies demonstrating an association between platelet activation and worse respiratory morbidity in COPD have employed non-specific surrogate biomarkers. Likewise, prior studies showing an association of aspirin use with improved COPD morbidity and mortality have been among prevalent users in observational cohorts susceptible to selection bias and confounding by indication. In order to understand the potential role of specific platelet activation pathways on respiratory morbidity in COPD, we propose directly measuring platelet activation and reactivity in a sample of 115 individuals with COPD without overt or subclinical CVD as determined by absence of coronary artery calcification on computed tomography scan. Specifically, we will measure membrane receptors uniquely expressed on activated platelets (CD62P/P-selectin, CD63, CD154/CD4L, and PAC1), platelet-leukocyte conjugates (platelet-monocyte and platelet-neutrophil conjugates), and platelet response (i.e. change in activation) to stimulation with three agonists (adenosine diphosphate, thromboxane, and serotonin). We hypothesize that higher proportion of baseline circulating activated platelets, higher proportion of platelet- leukocyte conjugates, and increased platelet reactivity in response to low doses of agonists will be associated with higher baseline respiratory symptoms, worse quality of life and higher rate of acute exacerbations of COPD over 1 year. Furthermore, we will conduct a randomized double-blinded sequential crossover study of three aspirin doses in 48 individuals with COPD without CVD to determine the most effective aspirin dose for suppression of platelet activation and reactivity in this population. Completion of the proposed aims will elucidate the role of platelet activation and reactivity pathways on respiratory outcomes in COPD and inform the design of a larger randomized controlled trial of antiplatelet therapy in COPD. We will recruit from the large pool of participants in ongoing and completed COPD studies at Johns Hopkins supplemented by leveraging the infrastructure of the Johns Hopkins COPD Precision Medicine Center of Excellence. My ultimate career goal is to be an independent translational researcher focusing on identifying novel targets for individualized therapy in COPD. My career development plan includes expert mentorship, formal coursework, and hands-on experience to develop new skills in COPD endotyping, translational research, platelet biology, and clinical trial design.


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 = $0 )
2026	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	5	12/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $197,031 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	5	1/13/2025	NON-COMPETING CONTINUATION	$197,031
														Subtotal = $197,031

Issue Date FY: 2024 ( Subtotal = $196,475 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	4	1/12/2024	NON-COMPETING CONTINUATION	$196,475
														Subtotal = $196,475

Issue Date FY: 2023 ( Subtotal = $197,055 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	3	2/1/2023	NON-COMPETING CONTINUATION	$197,055
														Subtotal = $197,055

Issue Date FY: 2022 ( Subtotal = $197,623 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	2	2/19/2022	NON-COMPETING CONTINUATION	$197,623
														Subtotal = $197,623

Issue Date FY: 2021 ( Subtotal = $198,179 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	1	2/19/2021	NEW	$198,179
														Subtotal = $198,179

Grand Total All Awards = $986,363

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Platelet Activation Pathways and Respiratory Morbidity in COPD

Award Number: K23HL151758

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/20/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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