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. Our previous studies established valid clinical diagnoses and have demonstrated markedly diverging longitudinal lung function trajectories in the largest and most diverse WTC occupational cohort. Besides our expertise with longitudinal lung function analyses, we were uniquely able to demonstrate associated quantitative chest computer tomography (QCT) metrics that have helped validate and characterize the disease processes that have been associated with WTC occupational exposures. QCT has revolutionized respiratory research, and has contributed important and novel information on interstitial, proximal and distal airway, and vascular changes that underlie the process of inflammatory remodeling and disease progression. Our observations in this cohort have also identified a subgroup who has experienced unexpected and significant lung function gain in adult life, suggesting a process of resolution in need of improved understanding. Our studies have been on the forefront of occupational respiratory research. We propose three specific aims to deploy novel QCT and spirometric markers to investigate early interstitial and airway injury and remodeling in subjects who have experienced accelerated lung function decline or developed chronic obstructive pulmonary disease while on longitudinal and clinical surveillance.