Variability and consistency in lung inflammatory responses to particles with a geogenic origin.

BACKGROUND AND OBJECTIVE: Particulate matter <10 µm (PM10 ) is well recognized as being an important driver of respiratory health; however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community sampled geogenic PM10 . METHODS: This was achieved by collecting earth material from two regional communities in Western Australia (Kalgoorlie-Boulder and Newman), extracting the PM10 fraction and exposing mice by intranasal instillation to these particles. The physicochemical characteristics of the particles were assessed and lung inflammatory responses were compared to control particles. The primary outcomes were cellular influx and cytokine production in the lungs of the exposed mice. RESULTS: The physical and chemical characteristics of the PM10 from Kalgoorlie and Newman differed with the latter having a higher concentration of Fe and a larger median diameter. Control particles (2.5 µm polystyrene) caused a significant influx of inflammatory cells (neutrophils) with little production of proinflammatory cytokines. In contrast, the geogenic particles induced the production of MIP-2, IL-6 and a significant influx of neutrophils. Qualitatively, the response following exposure to particles from Kalgoorlie and Newman were consistent; however, the magnitude of the response was substantially higher in the mice exposed to particles from Newman. CONCLUSIONS: The unique physicochemical characteristics of geogenic particles induced a proinflammatory response in the lung. These data suggest that particle composition should be considered when setting community standards for PM exposure, particularly in areas exposed to high geogenic particulate loads.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function.

BACKGROUND: Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre-existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. OBJECTIVES: To assess the physiological consequences of an acute DEP exposure during the peak of influenza-induced illness. METHODS: We exposed adult female BALB/c mice to 100 µg DEP (or control) 3.75 days after infection with 10(4.5) plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. RESULTS: Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. CONCLUSIONS: A single dose of DEP is not sufficient to physiologically exacerbate pre-existing respiratory disease caused by influenza infection in mice.

Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent.

CONTEXT: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse. OBJECTIVE: To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure. MATERIALS AND METHODS: Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 µg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. RESULTS: DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP. CONCLUSIONS: Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies.