HEPA Filtration Modifies Pulmonary Responses to Episodic Eucalyptus Smoke Exposure in Male Long-Evans Rats
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Background and purpose: As wildland fires increase in frequency and severity, their threat to both and human and ecosystem health grows. Epidemiological studies have shown associations between wildland fire smoke inhalation and increased hospitalizations for cardiorespiratory-related health effects. Smoke from wildland fires is a complex mixture made up of two distinct chemical phases, gas and particulate. The gas phase is primarily comprised of carbon monoxide, carbon dioxide, nitrogen oxides, and a variety of other volatile organic compounds. The particle phase is made up of suspended carbonaceous particulates, with the primary concern for health effects being fine particulate matter (PM2.5). Understanding the contribution of each phase to pulmonary toxicity provides critical information that can be used to inform effective solutions to better protect human health from wildland fire smoke exposure. As such, the purpose of the current study was to characterize the toxicity of HEPA filtered smoke, in comparison to whole smoke in a rodent model.
Methods: 12-week-old male Long-Evans rats were exposed to filtered air, whole eucalyptus smoke (3.52 mg/m3 PM), or HEPA filtered smoke (0.2mg/m3 PM) for 1 hour per day for 4 consecutive days, followed by a 3-day break, then 3 more consecutive days (7 days total across a ~2-week period). Ventilatory function was assessed using whole body plethysmography (WBP) on exposure days 1, 4, 8, and 10, both 0- and 2-hours post-exposure. Bronchoalveolar lavage fluid (BALF) was collected for analysis of lung injury, immune cell differentials, and cytokines. RNA from lung tissue was sequenced to evaluate changes in response to smoke exposure.
Results: Shortly following exposure, WBP revealed an overall decrease (p < 0.05) in breathing frequency for the whole smoke group, while exposure to filtered smoke had the opposite effect, increasing breathing frequency (p < 0.05) immediately following exposure, compared to air exposed controls. Expiratory time was increased overall due to whole smoke exposure (p < 0.05), while the filtered group experienced an overall decrease (p < 0.05), compared to controls. 2-hours post-exposure, tidal volume was increased due to whole smoke exposure (p < 0.05), while exposure to filtered smoke resulted in an overall decrease (p < 0.05) in tidal volume. A significant reduction in BALF n-acetyl-glycosaminidase, a marker for macrophage activation, was detected following exposure to both whole and filtered smoke (p < 0.01). Furthermore, exposure to filtered smoke reduced neutrophils in the BALF (p < 0.05) for the filtered group only. This was consistent with reductions in some of the inflammatory cytokines measured, namely IL13 (p < 0.01) and KC/GRO (p = 0.05). Such effects were not present in BALF from rats exposed to whole smoke. A limited number of differentially expressed genes were detected between the whole smoke- and air-exposed lung tissue (n = 2). However, 69 differentially expressed genes were detected in the lungs of rats exposed to filtered smoke, compared to air-exposed controls. These included fatty acid binding protein 1 (FABP1), FXYD domain-containing ion transport regulator 5 (FXYD5), as well as high mobility group box 2 (HMGB2), all of which have been associated with lung disease or injury.
Conclusions: This data demonstrates exposure to filtered eucalyptus smoke results in worsened pulmonary outcomes when compared to whole smoke from both a molecular and physiological standpoint. However, further study is needed to understand the dynamic relationship between the gaseous and particle phases that drive adverse health effects. (This abstract does not necessarily reflect US EPA policy.)