Social Determinants of Health, Asthma-Related Morbidity and Therapeutic Optimization for Black and Latinx Adults with Asthma - Summary: Asthma is a common chronic airway disease that affects 21 million adults in the US with substantial morbidity and healthcare costs. Black and Latinx adults bear a disproportionate share of that burden of disease, partly due to an inequitable distribution of social determinants of health (SDOH). SDOH have 5 components: 1. economic stability, 2. education access and quality, 3. health care access and quality, 4. neighborhood and built environment and 5. social and community context. Attempts to improve asthma outcomes in these populations have mostly been unsuccessful partially because the relationship between SDOH and in Black and Latinx adults with asthma is insufficiently understood. These groups have been vastly underrepresented in research intended to mitigate health disparities, limiting the ability to disentangle the complex relationship that these racial and ethnic groups have with SDOH in the US. The few studies that did so were conducted in children, had limited, retrospective, or cross-sectional asthma outcomes data, or unidimensional SDOH data. Addressing this knowledge gap is critical to the implementation of high-yield policy and interventions that will reduce the burden of disease for these vulnerable populations. In a large pragmatic randomized controlled trial (the PREPARE study), our group collected extensive demographic, clinical, and phenotypic data in addition to prospective asthma morbidity outcome data through monthly surveys. We successfully showed that a ‘Patient-Activated, Reliever-Triggered Inhaled CorticoSteroid’ (‘PARTICS’) strategy plus usual care reduced asthma exacerbations in 1,201 Black and Latinx adults with moderate-severe asthma vs. usual care alone. We also showed that low socioeconomic status (SES) associates with worse asthma morbidity using a multidimensional SES latent variable (defined by poverty, low educational attainment, and unemployment), structural equation modeling and mediation analysis on retrospective baseline data among Black and Latinx PREPARE participants. We also found that Caribbean Latinx adults experience greater asthma morbidity vs. other Latinx subgroups, supporting our overall hypothesis that a distinct set of SDOH exposures (an SDOH exposome) within racial or ethnic groups may impact asthma outcomes. The richness of our PREPARE dataset, enhanced with our ability to analyze geocoded data on all 5 SDOH components, uniquely enables us to address these Specific Aims: Aim 1a: To determine whether Black vs. Latinx adults with moderate-severe asthma have unique SDOH exposomes that distinctly associate with worse asthma morbidity. Aim 1b: To determine whether African American vs. non-African American Black adults experience greater asthma morbidity. Aim 2: To determine baseline SDOH exposomes and clinical characteristics that predict optimal PARTICS responders. Results from this R21 award may identify unique SDOH exposomes for Black and Latinx adults that lead to high-yield interventions, plus facilitate our work implementing the PARTICS strategy, both of which may reduce morbidity in these highly impacted populations.