title: Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices.
abstract: BACKGROUND
  Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.
  
  
  METHODS
  Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.
  
  
  RESULTS
  On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB.
  
  
  CONCLUSIONS
  The findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations.
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tong
authors.forename: Mary
authors.initials: M
authors.lastname: Daniels
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Boykin
authors.forename: Q Todd
authors.initials: QT
authors.lastname: Krantz
authors.forename: John
authors.initials: J
authors.lastname: McGee
authors.forename: Michael
authors.initials: M
authors.lastname: Hays
authors.forename: Kasey
authors.initials: K
authors.lastname: Kovalcik
authors.forename: Janice A
authors.initials: JA
authors.lastname: Dye
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U,S, Environmental Protection Agency, Research Triangle Park, NC, USA. gilmour.ian@epa.gov.
authors.forename: M Ian
authors.initials: MI
authors.lastname: Gilmour
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity; D004784:Environmental Monitoring; D005260:Female; D005390:Fires; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008867:Microtomy / Q000379:methods*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009657:North Carolina; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D011112:Polymyxin B / Q000494:pharmacology; D011237:Predictive Value of Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D012987:Soil / Q000737:chemistry*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D004731:Endotoxins; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D012987:Soil; D011112:Polymyxin B