The SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) is a clinical observational study intended to identify different subpopulations of individuals with COPD and ultimately define endotypes within this heterogeneous disease that are responsive to mechanism-specific interventions. The ongoing study is performing intensive longitudinal phenotyping of a cohort that consists of individuals with smoking history with and without COPD, and control participants without smoking history. A cohort of approximately 600 younger individuals is also being enrolled and studied in a similar companion study, named SOURCE that is partially supported by a grant from NHLBI. The purpose of this acquisition is to fund follow-up clinic visits of a combined cohort of SPIROMICS and SOURCE participants (“SPIROMICS III participants”), collecting and analyzing data, CT images, and biospecimens from the combined cohort to answer specific scientific questions related to the natural history and pathobiology of COPD and related lung diseases. The acquisition will also support maintenance of previously collected data and biospecimens, monitoring and oversight of the study, analysis of study data and biospecimens, publication and dissemination of results, and sharing of data and biospecimens as required by NHLBI/NIH policies. In this seven-year contract period investigators will obtain additional longitudinal data from SPIROMICS III participants to address three critical topics that have been prompted by recent findings. These include 1) identify the forms and origins of pathological mucus in COPD and non-obstructive airway disease (NCAD), and test how pathological mucus is related to symptoms and disease progression; 2) explore the use of novel x-ray CT measures to identify emphysema subtypes, vascular abnormalities, and dysanapsis (disproportionate scaling of airway dimensions to lung volume) in COPD, and use imaging methods to track longitudinal progression of these abnormalities; and 3) better characterize environmental exposures and social determinants of health in the COPD population to more precisely relate environmental risk factors to particular COPD subtypes and specific pathobiological mechanisms. This research will exploit the unique characteristics of the SPIROMICS and SOURCE cohorts to extend the findings of those studies in ways that will clarify the early development of COPD, the heterogeneity of COPD and NCAD, and the influence of environmental factors other than smoking on lung disease. To accomplish these goals, offerors will implement a research protocol that includes a clinic visit for approximately 1,800 SPIROMICS III participants (including approximately 1,200 SPIROMICS participants and 600 SOURCE participants), with CT imaging, pulmonary function testing, and sputum collection; continued electronic/telephone follow-up; extensive characterizations of the atmospheric and social environments of the participants; and integrated statistical ana...