Combustion products of burn pit constituents induce more changes in asthmatic than non-asthmatic murine lungs
Background: Burn pits, a military method for waste disposal outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma is found among military personnel. We investigated whether burn pit combustion products (CPs) are more detrimental to the airways of asthmatic than non-asthmatic mice. Mice were exposed to house dust mite antigen (HDM) or phosphate-buffered saline (PBS) 5 times over 2 weeks to initiate asthma-like airway injury. Condensates of CPs or saline were generated by flaming combustion of military cardboard, plastic and military plywood. CPs were instilled oropharyngeally at 24 hours after the final HDM or PBS instillation. The lungs were studied 24 hours later. Results: HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, HDM mice had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than PBS mice. CPs had no effect on HDM-induced eosinophil recruitment. CPs had no effect on mucus production in PBS or HDM mice. However, CPs increased intraluminal mucus, as revealed by AB-PAS staining, only in HDM mice, suggesting that CPs impaired mucociliary clearance (MCC), the lung's primary defense system, only in asthmatic airways. Lung RNA sequencing revealed that CPs increased genes and gene pathways describing inflammatory processes and impaired structure and function of cilia to a greater degree in HDM mice. Conclusions: These data indicate that asthmatic mice are more susceptible to CP-induced lung remodeling and dysfunction than non-asthmatic mice. A likely mechanism is that inhalation of CPs amplifies the changes in cilia and MCC caused by asthma and triggers a positive feedback loop of enhanced inflammation induced by the accumulating mucus.