Abstract
BACKGROUND: Exposure to military burn pit smoke during deployment is associated with different respiratory and non-respiratory diseases. However, information linking smoke exposure to human pulmonary health is lacking. This study examined the effects of simulated burn pit smoke condensates on human airway epithelial cells (HAECs) from twelve donors (smokers/non-smokers, biological female/male) cultured at an air-liquid interface and exposed to condensates from three simulated burn pit waste materials (cardboard, plywood, and plastic) incinerated at two combustion conditions: smoldering and flaming. Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay. RESULTS: Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs. CONCLUSIONS: This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. Future studies are needed to further characterize how sex and smoking status affect deployment-related diseases.