PROJECT SUMMARY/ABSTRACT Chronic respiratory diseases (CRD), such as asthma and chronic obstructive pulmonary disease, impact over 554 million people worldwide and are major contributors to the non-communicable disease burden in the United States. Individuals with CRD show pronounced disparities in disease risk by factors such as age, sex, community type, and environment. Air pollution is one environmental risk factor of concern with nearly 135 million people in the U.S. residing in counties experiencing poor air quality. Evidence suggests that air pollution regulatory standards, despite their design to protect public health, may be inadequate for CRD populations who exhibit elevated sensitivity to even low levels of air pollution exposure. It is critical to estimate air pollution health effects, specifically for vulnerable populations, and identify the underlying and unexplored factors that elevate risk, including the intersection between personal and community-level disadvantage. Minimizing vulnerabilities across groups and by environment is a core principle of environmental justice. Our central hypothesis is that individuals with diagnosed CRD represent a high vulnerability population who display increased mortality risk from acute exposure to fine particulate matter (PM2.5) and ozone air pollution. An additional emphasis is to identify which individual and neighborhood characteristics increase air pollution inequities among CRD patients and unpack their joint contribution to poor health outcomes. To test our hypothesis, we will utilize 20 years of records from the Veterans Health Administration (VHA) and spatiotemporally align individual patient data with state-of-the-art high-resolution air pollution models, environmental metrics, and community sociodemographic and social vulnerability characteristics. Detailed VHA records provides data innovations absent from many large cohorts, including diagnosis of comorbidities, geocoded home addresses to reduce exposure misclassification, and individual characteristics and behavior, such as smoking status and body mass index. In Aim 1, we will estimate the mortality risk in CRD populations attributed to daily PM2.5 and ozone exposure and identify individual characteristics that exacerbate susceptibility. In Aim 2, we will evaluate the intersection between individual vulnerabilities and neighborhood inequities for air pollution associated mortality risk in CRD populations and estimate the differential risk of these contributing causes. In Aim 3, we will estimate the association between air pollution exposure and underlying mortality cause, and quantify non-linear exposure-response relationships, including low-dose exposures. Our research will have a meaningful public health impact by informing air quality regulations as they pertain to individuals with CRD and provide evidence for behavioral interventions and treatment of CRD populations to reduce mortality risk. As a modifiable risk factor, reductions ...