Combustion products of burn pit constituents induce more changes in asthmatic than non-asthmatic murine lungs.

Abstract

Background: Burn pits, a method for disposal of military waste outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma (persistent or intermittent symptoms of asthma but no change in pulmonary function tests) 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.

Methods: 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 aspirated oropharyngeally at 24 h after the final HDM or PBS instillation. The lungs were studied 24 h later.

Results: HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, mice exposed to HDM had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than control mice exposed to PBS. Expression of neutrophil chemokines was enhanced. CPs had no effect on HDM-induced eosinophil recruitment or expression of Th2 cytokines. 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. Enhanced chemokine expression suggests that the CXCL1,2,5/CXCR2 axis may be the mechanism of the increased neutrophil recruitment. A potential mechanism of mucus accumulation 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 this accumulating mucus.