Project Summary Responders to the World Trade Center (WTC) site in the aftermath of the 9/11 attacks were exposed to toxic dust, which has been linked to an increased risk of respiratory and cardiovascular disease. Many of these diseases, such as lung cancer, mesothelioma, interstitial lung disease, and asbestosis, have long latency periods of upwards of twenty years, which we are now approaching. While published studies have linked WTC dust exposure to increased risk of various diseases, few have examined the relationship of the amount of exposure to the extent and progression of disease. The respiratory and cardiovascular effects of WTC dust exposure have been studied using pulmonary function tests and the number of cardiovascular events, but computed tomography (CT) scans provide an opportunity to see the early structural changes in the lungs and cardiovascular system before clinical symptoms appear. CT scans are used in the screening and evaluation of respiratory diseases such as lung cancer, interstitial lung disease, and chronic obstructive pulmonary disease, and to visualize coronary arteries and quantify the amount of coronary artery calcifications; in fact, it is possible to detect multiple diseases from a single chest CT scan. While manual evaluation by a radiologist is often the gold standard, automated image analysis tools are able to quickly and accurately quantify these diseases. We propose to apply automated image analysis tools to quantify four respiratory and cardiovascular diseases thought to be related to toxic dust exposure: emphysema, pleural thickening, interstitial lung disease, and coronary artery calcifications. We will apply these tools retrospectively to all available chest CT scans of members of the WTC general responders cohort (GRC) and a propensity-matched cohort of participants enrolled in a lung screening program. The comparison of the extent and progression of diseases in these two cohorts will provide information on the long-term effects of WTC dust exposure. We hypothesize that a higher frequency of these diseases can be found in WTC members and that they will also have a more rapid disease course compared to non-WTC members. We can further analyze the results of the WTC GRC to assess the relationship between WTC dust exposure, which we will estimate using the arrival time to the WTC site, and the extent and progression of these diseases. The results of this research will potentially improve the care of WTC GRC members through the early identification of diseases and updating of screening guidelines.