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Risk Stratification for COPD Exacerbations with CT Analysis and Multidimensional Trajectory Subtyping

Award Number: R01HL164380
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Risk Stratification for COPD Exacerbations with CT Analysis and Multidimensional Trajectory Subtyping - Project Summary The natural disease course of chronic obstructive pulmonary disease (COPD) is punctuated by events, termed exacerbations, when symptoms are acutely worse. Exacerbations are costly and burdensome – they are associated with accelerated lung function decline, impaired health status, increased hospitalization, and increased mortality. Evidence suggests that some individuals are particularly susceptible to exacerbations, but heterogeneity remains poorly understood. There is thus an urgent need to better delineate COPD heterogeneity and improve identification of groups at risk for these adverse outcomes as early as possible. Our long-term goal is to use quantitative imaging and trajectory-based subtype analysis to delineate COPD subpopulations, enabling early identification of subpopulations at risk for adverse, long-term outcomes. We have developed CT biomarkers of pulmonary vascular pruning, cardiac morphology, emphysema subtypes, airway thickening, and skeletal muscle wasting in CT imaging. However, we have not performed an integrative analysis of these biomarkers that could better delineate homogeneous subgroups. We have also developed a Bayesian trajectory algorithm that incorporates longitudinal data to identify distinct population subgroups with similar biomarker patterns while accounting for factors such as age and smoke exposure. Our overall objective in this proposal is to use multidimensional trajectory analysis to evaluate novel CT biomarkers in terms of exacerbation risk-stratification. Our central hypothesis is that multidimensional trajectory analysis of pulmonary and extra-pulmonary CT biomarkers can identify subgroups with latent susceptibility to exacerbations. The rationale for this work is that by identifying distinct trajectory subgroups using multiple CT biomarkers, we will better delineate COPD heterogeneity, leading to earlier, more precise risk-stratification – especially amongst those patients for whom CT imaging is the most reliably available data source, such as those who have undergone lung cancer CT screening. Aim 1 focuses on the methodical assessment of our novel CT biomarkers in terms of COPD exacerbation risk stratification using trajectory analysis. Aim 2 focuses on using CT biomarkers and trajectory analysis to identify subgroups within a lung cancer screening cohort that are at risk for hospitalizations due to COPD exacerbations. The approach is innovative, in our opinion, because it shifts focus from disease staging to identifying mechanistically similar subgroups (endotypes). The significance of these contributions will be an improved understanding of CT-assessed patterns of abnormality in cardio- pulmonary and extra-pulmonary systems and how these patterns present in trajectory subgroups at risk for adverse events. In turn, we expect this to better enable detection of early disease manifestations and subtype characterization. We expect these contributions to enable further studies of the mechanistic differences between subgroups as well approaches to preempt costly acute events by identifying the early-stage manifestations of at-risk groups.


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 = $771,698 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	4	3/3/2026	NON-COMPETING CONTINUATION	$771,698
														Subtotal = $771,698

Issue Date FY: 2025 ( Subtotal = $819,313 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	3	6/4/2025	NON-COMPETING CONTINUATION	$81,931
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	3	4/23/2025	NON-COMPETING CONTINUATION	$737,382
														Subtotal = $819,313

Issue Date FY: 2024 ( Subtotal = $802,927 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	2	3/8/2024	NON-COMPETING CONTINUATION	$737,382
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	2	6/21/2024	NON-COMPETING CONTINUATION	$65,545
														Subtotal = $802,927

Issue Date FY: 2023 ( Subtotal = $826,313 )
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	1	4/6/2023	NEW	$826,313
														Subtotal = $826,313

Grand Total All Awards = $3,220,251

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Risk Stratification for COPD Exacerbations with CT Analysis and Multidimensional Trajectory Subtyping

Award Number: R01HL164380

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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