Abstract Rationale Veterans deployed to Southeast Asia were exposed to deployment-related airborne particulate matter including air pollutants, dust storms, and burn-pit smoke. Exposure to airborne particulate matter has been associated with immune dysfunction and infections, asthma, and chronic lung diseases. Immune hyperactivation resulting in proinflammatory cytokine production has been associated with respiratory symptoms, prompting the need to fully elucidate systemic immune response in deployed veterans. Methods Participants consisted of veterans with land-based deployment who participated in the VA-Cooperative Study 595 and completed a respiratory health questionnaire. We assessed 40 non-smokers with persistent (N = 16) and without (N = 24) respiratory symptoms. Testing included full pulmonary function tests (PFTs), oscillometry, and peripheral blood mononuclear cell (PBMC) collection. Immune activation was assessed ex vivo using PBMCs stimulated with vehicle (control: cell culture media), lipopolysaccharide (LPS, gram-negative bacterial component), beta-(β)-glucan (fungal cell wall protein), or T-lymphocyte coactivators (α-CD3+CD28 antibodies) for 36 hours to measure cytokine production from supernatants using LegendPlex. Correlation analysis was performed between the cytokines and oscillometry measurements using Pearson’s correlation. Results There were no significant differences between %-predicted TLC, FEV1, FVC, FEV1/FVC ratio, and DLCO for veterans with or without symptoms. Symptomatic veterans had significantly greater values of the frequency dependency (R5-R19), area of reactance (AX), and resonant frequency (Fres). Ex vivo PBMCs stimulation with α-CD3+CD28 antibodies showed significantly increased T-helper (Th)17-associated cytokine IL-17A (P = 0.03) and an increased trend in Th1- (IFN-γ) and Th2-associated cytokines (IL-9 and IL-22) in the symptomatic group than the asymptomatic group. PBMCs’ stimulation with LPS led to a significant decrease in IL-2 (P = 0.04) and IL-9 (P = 0.004) and an increase in IL-22 (P 0.0001) in symptomatic compared to the asymptomatic group. β-glucan stimulation resulted in a significant decrease in IL-13 (P = 0.004) and an increase in IL-22 (P 0.0001) in symptomatic. Interestingly, we found that both IL-9 and IL-17A significantly positively correlated with indicators of small airway dysfunction (R5-R19, AX, Fres, and X5 respiratory system reactance) in all veterans (Table 1). Conclusion In this sample of deployed veterans, those with persistent respiratory symptoms had evidence of small airway dysfunction compared to asymptomatic veterans. PBMC activation studies showed a significant increase in Th17 response over Th1 and Th2. However, stimulation with pathogen-associated proteins led to a significant decrease in T lymphocyte responses, suggesting that deployment-related airborne particulate matter may suppress antimicrobial response to infections. There was also a significant positive correlation between IL-9 and IL-17A, and oscillometry measurements. This abstract is funded by: VA BLR&D I01 BX004619
Marrufo et al. (2026) studied this question.