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Principal Investigator: Sadiya Sana Khan
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $707,865
Funding agency: National Heart Lung and Blood Institute
ABSTRACT
Chronic lung disease and heart failure (HF) are highly prevalent, commonly co-occur, and are associated with
significant morbidity and mortality. Work from our group and others has demonstrated an independent
relationship between chronic lung disease and incident HF that may be driven in part by inflammation. We have
also documented that even in the absence of symptomatic lung disease, impaired lung function defined by
spirometry is associated with adverse cardiac remodeling on echocardiography and incident HF events. While
symptomatic lung disease and HF often occur in the elderly, many younger adults have relatively asymptomatic
impairment in lung health and cardiac structure and function. These subclinical cardiopulmonary abnormalities
develop during the key modifiable period from young adulthood to midlife. However, data are sparse on the
timing and associated mechanisms of the transition from health to disease spanning young adulthood to midlife,
and related race-sex differences. Without identifying these unique patterns of change, it will not be possible to
screen for subclinical changes and employ prevention strategies prior to irreversible damage in the lung and
heart. This requires upstream identification at the earliest detectable change. While spirometry is the gold
standard for lung disease detection, it is a relatively crude and insensitive measure of impaired lung health. In
contrast, lung injury (quantified using a novel local histogram analysis developed and validated by our group)
from computed tomography (CT) scans is a more sensitive and earlier indicator of impaired lung health (e.g. due
to tobacco, air pollution, and respiratory viral infection). Therefore, we now propose to take advantage of the
Coronary Artery Risk Development in Young Adults (CARDIA) study’s unique platform to study the temporal
relationship of and mechanisms underlying the transition from lung and heart health to disease. To-date, our
group has investigated the predictors and consequences of impaired lung health and HF, separately, in CARDIA.
In this project, we will build upon our prior work by analyzing CT scans to determine the concurrent evolution of
lung injury and adverse cardiac remodeling and identify mechanisms by assaying a multitude of blood-based
biomarkers (using a multiplexed array) and performing 4-dimensional flow cardiovascular magnetic resonance
imaging (cMRI). We will test the hypothesis that detailed imaging and blood-based markers can inform clinically
relevant endotypes reflecting dynamic changes in lung injury and adverse cardiac remodeling during a key
vulnerable period of life through the following specific aims: (1) Determine the longitudinal association between
lung injury and left ventricular end-diastolic volume (LVEDV); (2) Determine the risk of subclinical and clinical HF
among joint lung injury and LVEDV trajectory groups; and (3) Determine the hemodynamic mediators of the
association between lung injury and adverse cardiac remodeling. This study will investigate factors associated
with transitions from cardiopulmonary health to disease and associated mechanisms, and in doing so, will identify
screening strategies and contribute novel pathways for targeted disease interception of lung and heart disease.
Terms: <21+ years old><4-dimensional><Adult><Adult Human><Affect><Age><Age of Onset><Air Pollution><Airway infections><Ancillary Study><Assay><Bioassay><Biological Assay><Biological Function><Biological Markers><Biological Process><Black><Black race><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Cardiac><Cardiac Diseases><Cardiac Disorders><Cardiac health><Cardiopulmonary><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cause of Death><Chronic lung disease><Clinical><Computed Tomography><Cor pulmonale><Coronary Artery Risk Development in Young Adults><Coronary Artery Risk Development in Young Adults Study><Data><Detection><Differences between sexes><Differs between sexes><Disease><Disorder><Dysfunction><EFRAC><Echocardiogram><Echocardiography><Ejection Fraction><Elderly><Emphysema><Epidemiology><Event><Evolution><Four-dimensional><Functional disorder><Goals><Health><Health Care Utilization><Health Transition><Heart><Heart Diseases><Heart Vascular><Heart failure><Heart health><Image><Impairment><Individual><Inflammation><Inflammatory><Intervention><Intervention Strategies><Joints><Left><Left Ventricles><Left ventricular structure><Life><Life Cycle><Life Cycle Stages><Link><Lung><Lung Diseases><Lung Respiratory System><Lung damage><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Mechanics><Mediating><Mediator><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Morbidity><Morbidity - disease rate><Multimodal Imaging><NHLBI><NMR Imaging><NMR Tomography><National Heart, Lung, and Blood Institute><Nuclear Magnetic Resonance Imaging><Outcome Study><Participant><Pathway interactions><Pattern><Phenotype><Physiopathology><Predisposition><Preventative strategy><Prevention><Prevention strategy><Preventive strategy><Proteomics><Public Health><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Emphysema><Pulmonary Heart Disease><Pulmonary Heart Disorder><Pulmonary Hypertension><Race><Races><Research><Respiratory Infections><Respiratory Tract Infections><Risk><Risk Factors><Risk Marker><Scanning><Sex Differences><Sexual differences><Spirometry><Strategic vision><Structure><Susceptibility><Symptoms><Systems Biology><Testing><Time><Tobacco><Tobacco Consumption><Tobacco use><Tomodensitometry><Transthoracic Echocardiography><United States><Ventricular><Ventricular End-Diastolic Volumes><Viral Respiratory Tract Infection><Work><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><Zeugmatography><adult youth><adulthood><advanced age><advanced disease><advanced illness><ages><bio-markers><biologic marker><biomarker><blood-based biomarker><blood-based marker><cardiac MRI><cardiac failure><cardiac magnetic resonance imaging><cardiopulmonary disease><cardiopulmonary disorder><catscan><chronic pulmonary disease><circulatory system><clinical relevance><clinically relevant><co-morbid><co-morbidity><comorbidity><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><critical period><design><designing><disease of the lung><disease prevention><disorder of the lung><disorder prevention><emphysematous><epidemiologic><epidemiological><exposure to tobacco><geriatric><health care service use><health care service utilization><healthcare service use><healthcare service utilization><healthcare utilization><heart disorder><heart sonography><hemodynamics><imaging><imaging study><interventional strategy><life course><lung disorder><lung function><lung health><lung injury><mechanic><mechanical><mid life><mid-life><middle age><middle aged><midlife><mortality><multi-modal imaging><multi-modality imaging><multidisciplinary><multimodality imaging><non-contrast CT><noncontrast CT><noncontrast computed tomography><novel><older adult><older adulthood><pathophysiology><pathway><phenotypic data><pulmonary><pulmonary damage><pulmonary function><pulmonary health><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><racial><racial background><racial origin><resilience><resilient><risk predictor><risk predictors><risk sharing><screening><screenings><senior citizen><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><theories><tobacco exposure><tobacco product use><viral respiratory infection><young adult><young adulthood>