Project Summary Our long-term goal has been to characterize the heterogeneous group of chronic lower airway diseases (LAD) observed in World Trade Center (WTC) workers and volunteers, uncover their risk factors and comorbidities, identify subgroups with adverse and favorable lung function trajectories and outcomes, and develop and deploy novel imaging approaches to the investigation of the lung injury underlying them. Such goal will in turn translate into better understanding of disease pathophysiology, more targeted, personalized, and perhaps disease modifying treatment approaches, and improved surveillance and prevention strategies. The goal of this project has been to characterize the transitions into chronic obstructive pulmonary disease (COPD) among former workers and volunteers at the WTC disaster site. Following our objective characterization of our COPD cases, our multidisciplinary investigative team proposes to establish the quantitative computed tomography (QCT) characteristics that may differentiate WTC-related from non- WTC-related COPD, investigate characteristics and longitudinal lung function trajectories of WTC patients with pre-COPD, and investigate lung mechanical strain (LMS) as an early QCT marker of lung injury associated with chronic disease and accelerated longitudinal lung function decline. This project will be conducted in the occupational cohort followed at Mount Sinai. To that end, we will utilize the WTC Pulmonary Evaluation Unit Chest CT Imaging Archive, a large repository with more than 3000 chest CT images on 1700 WTC workers, as well as linked datasets with disease symptoms, both pre- WTC and WTC-related occupational exposures, detailed pulmonary function and longitudinal spirometry measurements and body weight trends, visual imaging classification and grading, and quantitative computer tomography (QCT) measurements of airway, body composition, and pulmonary parenchymal and vascular abnormalities.