Transitions from Impaired Respiratory Health to Lung Disease

Northwestern University At Chicago, Evanston IL

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY / ABSTRACT The greatest driver of respiratory-related morbidity in people with and without chronic lung disease is medically attended respiratory illnesses (MARI) such as respiratory viral infections, pneumonia, and acute exacerbations of chronic lower respiratory disease. While several studies have identified radiologic and molecular factors associated with respiratory exacerbations in older smokers with established lung disease, few studies have identified factors predictive of respiratory morbidity earlier in life in the general population when prevention strategies have their greatest impact. The Coronary Artery Risk Development in Young Adults (CARDIA) study (community-based prospective study, age 18-30 at inception, 40 years follow-up and recent contact in 79.3% of the surviving cohort) represents an ideal cohort to ascertain early factors that predict future respiratory events in a general population. In prior funding periods, our group has defined impaired respiratory health as a precursor to chronic lung disease. We identified radiologic features of subclinical lung injury (quantitative interstitial abnormality on CT scan) and lifecourse lung function trajectories that precede the development of COPD/emphysema and pulmonary fibrosis. We discovered circulating proteins that reflect activation of pathways related to innate immunity, fibrosis, and metabolic dysfunction that are associated with impaired respiratory health manifesting as accelerated loss of lung function and early lung injury on CT scan. We hypothesize that these radiologic and molecular biomarkers of impaired respiratory health measured in middle age are associated with future MARI and inform the mechanistic underpinnings of susceptibility to respiratory morbidity. This renewal of the CARDIA Lung Study proposes to integrate our framework of impaired respiratory health to identify molecular, radiologic, and genetic features relevant to future respiratory morbidity. We will quantify proteins that comprised our predictive panel testing against prospectively adjudicated MARI in CARDIA, a critical step for clinical translation to the general population. We will next integrate existing CT-scan based parenchymal features with novel pulmonary vascular and airway measurements to create a comprehensive atlas of the human lung in middle age. We will identify combinations of features within the CT atlas that influence the risk of MARI in CARDIA. Finally, we will evaluate whether and where proteins in our proteomic signature of impaired respiratory health are expressed in diseased lung tissue and thereby have the potential to be causal therapeutic targets for the prevention of chronic lung disease.