Asthma and PM10

PM(10) (the mass of particles present in the air having a 50% cutoff for particles with an aerodynamic diameter of 10 μm) is the standard measure of particulate air pollution used worldwide. Epidemiological studies suggest that asthma symptoms can be worsened by increases in the levels of PM(10). Epidemiological evidence at present indicates that PM(10) increases do not raise the chances of initial sensitisation and induction of disease, although further research is warranted. PM(10) is a complex mixture of particle types and has many components and there is no general agreement regarding which component(s) could lead to exacerbations of asthma. However pro-inflammatory effects of transition metals, hydrocarbons, ultrafine particles and endotoxin, all present to varying degrees in PM(10), could be important. An understanding of the role of the different components of PM(10) in exacerbating asthma is essential before proper risk assessment can be undertaken leading to advice on risk management for the many asthmatics who are exposed to air pollution particles

Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.

Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease

Differential pulmonary retention of diesel exhaust particles in Wistar Kyoto and spontaneously hypertensive rats

Spontaneously hypertensive (SH) and normotensive Wistar Kyoto (WKY) rats have been used for understanding the mechanisms of variations in susceptibility to airborne pollutants. We examined the lung burden of diesel exhaust particles (DEP) following inhalation of diesel engine exhaust (DEE) in both strains. The kinetics of clearance was also examined after single intratracheal (IT) instillation of DEP. Lungs were analyzed for DEP elemental carbon (EC) after exposure to DEE (0, 500, or 2000 μ g/m3 4 h/day, 5 days/week×4 weeks). SH rats had 16% less DEP-EC at 500 and 32% less at 2000 μ g/m3 in the lungs, despite having 50% higher than the average minute volume. No strain-related differences were noted in number of alveolar macrophages or their average DEP load as evident from examining cells in bronchoalveolar lavage fluid (BALF). The kinetics of DEP clearance from lungs of male WKY and SH rats was studied following a single instillation at 0.0 or 8.33 mg/kg of DEP standard reference material (SRM 2975) from the National Institute of Standards Technology. SH rats cleared 60% DEP over 112 days while minimal clearance occurred from the lungs of WKY. The pattern of DEP-induced inflammatory response assessed by BALF analysis was similar in both strains, although the overall protein leak was slightly greater in SH rats. A time-dependent accumulation of DEP occurred in tracheal lymph nodes of both strains (SH &gt; WKY). Thus, SH rats may clear DEP more efficiently from their lungs than normotensive WKY rats, with a small contribution of more effective lymphatic drainage

Role of oxidative stress on diesel-enhanced influenza infection in mice

Numerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed to air or 0.5 mg/m3 DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8 and 14 post-infection and lungs were assessed for virus titers, lung inflammation, immune cytokine expression and pulmonary responsiveness (PR) to inhaled methacholine. Exposure to DE during the course of infection caused an increase in viral titers at days 4 and 8 post-infection, which was associated with increased neutrophils and protein in the BAL, and an early increase in PR. Increased virus load was not caused by decreased interferon levels, since IFN-β levels were enhanced in these mice. Expression and production of IL-4 was significantly increased on day 1 and 4 p.i. while expression of the Th1 cytokines, IFN-γ and IL-12p40 was decreased. Treatment with the antioxidant N-acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE-induced changes in cytokine profiles and lung inflammation. We conclude that exposure to DE during an influenza infection polarizes the local immune responses to an IL-4 dominated profile in association with increased viral disease, and some aspects of this effect can be reversed with antioxidants

Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975

Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches

BackgroundAlthough engineered nanomaterials (ENM) are currently regulated either in the context of a new chemical, or as a new use of an existing chemical, hazard assessment is still to a large extent reliant on information from historical toxicity studies of the parent compound, and may not take into account special properties related to the small size and high surface area of ENM. While it is important to properly screen and predict the potential toxicity of ENM, there is also concern that current toxicity tests will require even heavier use of experimental animals, and reliable alternatives should be developed and validated. Here we assessed the comparative respiratory toxicity of ENM in three different methods which employed in vivo, in vitro and ex vivo toxicity testing approaches.MethodsToxicity of five ENM (SiO2 (10), CeO2 (23), CeO2 (88), TiO2 (10), and TiO2 (200); parentheses indicate average ENM diameter in nm) were tested in this study. CD-1 mice were exposed to the ENM by oropharyngeal aspiration at a dose of 100μg. Mouse lung tissue slices and alveolar macrophages were also exposed to the ENM at concentrations of 22–132 and 3.1-100μg/mL, respectively. Biomarkers of lung injury and inflammation were assessed at 4 and/or 24hr post-exposure.ResultsSmall-sized ENM (SiO2 (10), CeO2 (23), but not TiO2 (10)) significantly elicited pro-inflammatory responses in mice (in vivo), suggesting that the observed toxicity in the lungs was dependent on size and chemical composition. Similarly, SiO2 (10) and/or CeO2 (23) were also more toxic in the lung tissue slices (ex vivo) and alveolar macrophages (in vitro) compared to other ENM. A similar pattern of inflammatory response (e.g., interleukin-6) was observed in both ex vivo and in vitro when a dose metric based on cell surface area (μg/cm2), but not culture medium volume (μg/mL) was employed.ConclusionExposure to ENM induced acute lung inflammatory effects in a size- and chemical composition-dependent manner. The cell culture and lung slice techniques provided similar profiles of effect and help bridge the gap in our understanding of in vivo, ex vivo, and in vitro toxicity outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-014-0047-3) contains supplementary material, which is available to authorized users

Professor Gopal Kanji\u27s Retirement as Editor of Journal of Applied Statistics

(First paragraph) This. issue of Journal of Applied Statistics marks the first in its history which does not fall under the editorship of its founder Professor Gopal Kanji. Following his retirement from the role we would like to use this editorial to outline the history and development of the Journal and pay tribute to the many achievements of Gopal’s career

Complex burial histories of Apollo 12 basaltic soil grains derived from cosmogenic noble gases: implications for local regolith evolution and future in situ investigations

We report the concentrations and isotope ratios of light noble gases (He, Ne, Ar) in ten small basalt fragments derived from lunar regolith soils at the Apollo 12 landing site. We use cosmic ray exposure and shielding condition histories to consider their geological context. We have devised a method of using cosmogenic Ne isotopes to partition the cosmic ray exposure history of each sample into two stages: a duration of ‘deep’ burial (shielding of 5-500 g/cm2) and a duration of near-surface exposure (shielding of 0 g/cm2). Three samples show evidence of measurable exposure at the lunar surface (durations of between 6 ± 2 to 7 ± 2 Myr). The remaining seven samples show evidence of a surface residence duration of less than a few hundred thousand years prior to collection. One sample records a single stage cosmic ray exposure age range of between 516 ± 36 and 1139 ± 121 Myr, within 0-5 g/cm2 of the lunar surface. This is consistent with derivation from ballistic sedimentation (i.e., local regolith reworking) during the Copernicus crater formation impact at ~ 800 Myr. The remaining samples show cosmic ray exposure age cluster around 124 ± 11 Myr, and 188 ± 15 Myr. We infer that local impacts, including Surveyor crater (180-240 Ma) and Head crater (144 Ma), may have brought these samples to depths where the cosmic ray flux was intense enough to produce measurable cosmogenic Ne isotopes. More recent small impacts that formed un-named craters may have exhumed these samples from their deep shielding conditions to the surface (i.e., ~0-5 g/cm2) prior to collection from the lunar surface during the Apollo 12 mission

Mutagenicity and Pollutant Emission Factors of Solid-Fuel Cookstoves: Comparison with Other Combustion Sources

BACKGROUND: Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. OBJECTIVE: We evaluated two categories of solid-fuel cookstoves for eight pollutant and four mutagenicity emission factors, correlated the mutagenicity emission factors, and compared them to those of other combustion emissions. METHODS: We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS), and we combusted propane as a liquified petroleum gas control fuel. We determined emission factors based on useful energy (megajoules delivered, MJd) for carbon monoxide, nitrogen oxides (NOx), black carbon, methane, total hydrocarbons, 32 polycyclic aromatic hydrocarbons, PM2.5, levoglucosan (a wood-smoke marker), and mutagenicity in Salmonella. RESULTS: With the exception of NOx, the emission factors per MJd were highly correlated (r ≥ 0.97); the correlation for NOx with the other emission factors was 0.58-0.76. Excluding NOx, the NDS and FDS reduced the emission factors an average of 68 and 92%, respectively, relative to the TSF. Nevertheless, the mutagenicity emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was between those of a large diesel bus engine and a small diesel generator. CONCLUSIONS: Both mutagenicity and pollutant emission factors may be informative for characterizing cookstove performance. However, mutagenicity emission factors may be especially useful for characterizing potential health effects and should be evaluated in relation to health outcomes in future research. An FDS operated as intended by the manufacturer is safer than a TSF, but without adequate ventilation, it will still result in poor indoor air quality. CITATION: Mutlu E, Warren SH, Ebersviller SM, Kooter IM, Schmid JE, Dye JA, Linak WP, Gilmour MI, Jetter JJ, Higuchi M, DeMarini DM. 2016. Mutagenicity and pollutant emission factors of solid-fuel cookstoves: comparison with other combustion sources. Environ Health Perspect 124:974-982; http://dx.doi.org/10.1289/ehp.1509852