Longitudinal Evaluation of Southwest Asia Asthma Patient Cohort (LEAP2)

About This Grant

Significance to VA: The Promise to Address Comprehensive Toxics (PACT) Act legislation of 2022 has expanded access to care for veterans diagnosed with deployment-related respiratory diseases (DRRDs) such as asthma following Southwest Asia (SWA) deployment during conflicts in Iraq and Afghanistan from 1990- present. Previous studies indicate an increased incidence of asthma in SWA-deployed veterans. Many deployed veterans also report exposure to hazards (e.g. burn pits, diesel, dust/sand) that likely trigger variable but poorly defined inflammatory and immunologic airway responses that are thought to contribute to deployment-related asthma (DRA). In our VA clinical cohort of over 400 veterans with SWA DRA we have observed poor asthma control despite management with asthma guideline-based treatment. SWA DRA has not been well-characterized in terms of endotypes and biological drivers, and little is known about how SWA DRA compares to adult-onset asthma in patients without complex military and occupational exposures. Yet, few efforts exist to monitor and optimize care for this high-risk veteran population. The clinical course and long-term prognosis of veterans with DRA is uncertain. Thus, VA-based clinical cohorts and research programs are needed to understand disease course, pathological mechanisms driving disease, and to optimize future treatment strategies. Innovation and Impact: This is the first comprehensive study that aims to investigate drivers of poor asthma control in the largest cohort of veterans with SWA DRA by integrating occupational and residential exposure-related epidemiology, particulate matter modeling, and mechanistic evaluation characterizing asthma inflammation and immune function using mass cytometry and metabolomics that will be foundational in identifying potential targets for asthma therapies. Furthermore, comparison between the SWA DRA group and an adult-onset asthma group from the general population will yield insights in whether there are important similarities or differences between different adult asthma populations. Specific Aims: Aim 1 - Compare clinical and biological characteristics of SWA DRA to a general adult-onset asthma cohort and identify the clinical predictors of disease severity in SWA DRA. Aim 2 - Determine how air quality/particulate matter impacts disease severity in SWA DRA and adult-onset asthma in a nondeployed population. Aim 3 - Elucidate the immunologic processes impacting disease severity in SWA DRA. Methodology: We will characterize SWA DRA endotypes and determine if post-deployment exposure to air pollution is associated with adverse respiratory health outcomes and also will compare the SWA DRA population to a general adult-onset asthma cohort. This study will utilize comprehensive medical and exposure questionnaires, multiple types of lung function testing, and blood tests to detect asthma inflammation during a baseline and 12-month follow-up visit. Using an air pollution model (particulate matter of 2.5 micrometers, ozone, and nitrogen oxide), we will assess how environmental exposures impact asthma control and exacerbations. Toward identification of specific biomarkers and disease mechanisms, our team will conduct molecular investigations on blood and lung samples using mass cytometry and metabolomics while banking specimens for future -omics and translation work. Path to Translation/Implementation: Our approach addresses the critical need to understand factors that contribute to suboptimal asthma control in the SWA DRA population. If we find that SWA DRA longitudinal outcomes differ and are worse than in general adult-onset asthma, this will inform future prevention efforts and medical surveillance of current and future veterans who may encounter similar hazardous inhalational exposures. Data generated from this study will be used to support future VA collaborative studies that harness team science approaches to identifying drivers of inflammation and immune dysfunction as well as potential targets for therapy of SWA DRA. Future research will include identifying unique SWA DRA endotypes that may benefit from targeted pre-clinical and clinical trials of novel or existing asthma pharmacotherapy and treatment strategies.