Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice.

Background Exposure to fine airborne particulate matter ( PM 2.5) induces quantitative and qualitative defects in bone marrow-derived endothelial progenitor cells of mice, and similar outcomes in humans may contribute to vascular dysfunction and the cardiovascular morbidity and mortality associated with PM 2.5 exposure. Nevertheless, mechanisms underlying the pervasive effects of PM 2.5 are unclear and effective interventional strategies to mitigate against PM 2.5 toxicity are lacking. Furthermore, whether PM 2.5 exposure affects other types of bone marrow stem cells leading to additional hematological or immunological dysfunction is not clear. Methods and Results Mice given normal drinking water or that supplemented with carnosine, a naturally occurring, nucleophilic di-peptide that binds reactive aldehydes, were exposed to filtered air or concentrated ambient particles. Mice drinking normal water and exposed to concentrated ambient particles demonstrated a depletion of bone marrow hematopoietic stem cells but no change in mesenchymal stem cells. However, HSC depletion was significantly attenuated when the mice were placed on drinking water containing carnosine. Carnosine supplementation also increased the levels of carnosine-propanal conjugates in the urine of CAPs-exposed mice and prevented the concentrated ambient particles-induced dysfunction of endothelial progenitor cells as assessed by in vitro and in vivo assays. Conclusions These results suggest that exposure to PM 2.5 has pervasive effects on different bone marrow stem cell populations and that PM 2.5-induced hematopoietic stem cells depletion, endothelial progenitor cell dysfunction, and defects in vascular repair can be mitigated by excess carnosine. Carnosine supplementation may be a viable approach for preventing PM 2.5-induced immune dysfunction and cardiovascular injury in humans.

[Lung cancer deaths attributable to ambient PM(2.5) exposure in 2016 in China].

Objective: To analyze the lung cancer deaths attributable to ambient PM(2.5) exposure in China in 2016. Methods: All data were from the Global Burden of Disease Study 2016 (GBD 2016). Multiple-source data, including satellite observation, ground measurement, chemical migration model simulation, etc., and the data integration model for air quality (DIMAQ) were used to estimate the grid-level exposure to ambient PM(2.5). Data from the vital registry and cancer registry were used to establish statistical model to estimate the lung cancer deaths by province, age and gender. The lung cancer deaths attributable to PM(2.5) were calculated based on the calculation of population attributable fraction (PAF). The GBD world population age structure was adopted to calculate age-standardized rates for comparison among provinces (including 31 provinces, autonomous regions and municipalities directly under the central government, as well as Hong Kong and Macao special administrative regions, excluding Taiwan of China). Results: In 2016, the lung cancer deaths attributable to ambient PM(2.5) exposure in China were 14.56×10(4) (95% uncertainty interval (UI): 9.63×10(4)-19.55×10(4)), accounting for 24.66% (95%UI: 16.38%-33.12%) of total lung cancer deaths. The lung cancer death rate attributable to PM(2.5) increased with age, with the lowest among 25-29 age group (0.25/10(5), 95%UI: 0.17/10(5)-0.34/10(5)), the highest among ≥80 age group (90.70/10(5), 95%UI: 59.85/10(5)-122.20/10(5)). The lung cancer death rate attributable to PM(2.5) among males (14.84/10(5), 95%UI: 9.78/10(5)-19.93/10(5)) was higher than that in females (6.21/10(5), 95%UI: 4.07/10(5)-8.40/10(5)). The age-standardized death rates (ASDR) of lung cancer attributable to PM(2.5) among males and females in China were higher than the global average level. The attributable ASDR of lung cancer varied among provinces, highest in Shandong (13.51/10(5), 95%UI: 9.14/10(5)-18.20/10(5)) and lowest in Tibet (0.85/10(5), 95%UI: 0.44/10(5)-1.51/10(5)). Conclusion: In 2016, the lung cancer deaths attributable to ambient PM(2.5) exposure in China was heavy, and varied in different age groups, genders and provinces.

Occupational exposure to inorganic particles during pregnancy and birth outcomes: a nationwide cohort study in Sweden.

OBJECTIVES: The aim of this study was to investigate if occupational exposure to inorganic particles or welding fumes during pregnancy is associated with negative birth outcomes. DESIGN: A prospective national cohort study. SETTING: All single births from 1994 to 2012 in Sweden. Information on birth weight, preterm birth, small for gestational age, smoking habits, nationality, age, occupation, absence from work and education was obtained from nationwide registers. Exposure to inorganic particles (mg/m3) was assessed from a job exposure matrix. PARTICIPANTS: This study included all single births by occupationally active mothers (995 843). OUTCOME MEASURES: Associations between occupational exposures and negative birth outcomes in the form of low birth weight, preterm birth and small for gestational age. RESULTS: Mothers who had high exposure to inorganic particles and had less than 50 days (median) of absence from work during pregnancy showed an increased risk of preterm birth (OR 1.18; 95% CI 1.07 to 1.30), low birth weight (OR 1.32; 95% CI 1.18 to 1.48) as well as small for gestational age (OR 1.20; 95% CI 1.04 to 1.39). The increased risks were driven by exposure to iron particles. No increased risks were found in association with exposure to stone and concrete particles. High exposure to welding fumes was associated with an increased risk of low birth weight (OR 1.22; 95% CI 1.02 to 1.45) and preterm birth (OR 1.24; 95% CI 1.07 to 1.42). CONCLUSIONS: The results indicate that pregnant women should not be exposed to high levels of iron particles or welding fumes.

Afghanistan Particulate Matter Enhances Pro-Inflammatory Responses in IL-13-Exposed Human Airway Epithelium via TLR2 Signaling.

Since the start of Afghanistan combat operations in 2001, there has been an increase in complaints of respiratory illnesses in deployed soldiers with no previous history of lung disorders. It is postulated that deployment-related respiratory illnesses are the result of inhalation of desert particulate matter (PM) potentially acting in combination with exposure to other pro-inflammatory compounds. Why some, but not all, soldiers develop respiratory diseases remains unclear. Our goal was to investigate if human airway epithelial cells primed with IL-13, a type 2 inflammatory cytokine, demonstrate stronger pro-inflammatory responses to Afghanistan desert PM (APM). Primary human brushed bronchial epithelial cells from non-deployed, healthy subjects were exposed to APM, both with and without IL-13 pretreatment. APM exposure in conjunction with IL-13 resulted in significantly increased expression of IL-8, a pro-inflammatory cytokine involved in neutrophil recruitment and activation. Furthermore, expression of TLR2 mRNA was increased after combined IL-13 and APM exposure. siRNA-mediated TLR2 knockdown dampened IL-8 production after exposure to APM with IL-13. APM with IL-13 treatment increased IRAK-1 (a downstream signaling molecule of TLR2 signaling) activation, while IRAK-1 knockdown effectively eliminated the IL-8 response to APM and IL-13. Our data suggest that APM exposure may promote neutrophilic inflammation in airways with a type 2 cytokine milieu.

Short communication: Diagnosis of lung cancer increases during the annual southeast Asian haze periods.

There have been few but timely studies examining the role of air pollution in lung cancer and survival. The Southeast Asia haze is a geopolitical problem that has occurred annually since 1997 in countries such as Malaysia, Singapore and Indonesia. To date, there has been no study examining the impact of the annual haze in the presentation of lung cancer. Data on all lung cancers and respiratory admissions to Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2010 to 31th October 2015 were retrospectively collected and categorized as presentation during the haze and non-haze periods defined by the Department of Environment Malaysia. We report a lung cancer incidence rate per week of 4.5 cases during the haze compared to 1.8 cases during the non-haze period (p<0.01). The median survival for subjects presenting during the haze was 5.2 months compared to 8.1 months for the non-haze period (p<0.05). The majority of subjects diagnosed during the haze period initially presented with acute symptoms. Although this study could not suggest a cause and effect relationship of the annual haze with the incidence of lung cancer, this is the first study reporting a local air pollution-related modifiable determinant contributing to the increase in presentation of lung cancer in Southeast Asia.

Ambient air levels and health risk assessment of benzo(a)pyrene in atmospheric particulate matter samples from low-polluted areas: application of an optimized microwave extraction and HPLC-FL methodology.

A new methodology involving a simple and fast pretreatment of the samples by microwave-assisted extraction and concentration by N2 stream, followed by HPLC with fluorescence detection, was used for determining the concentration of benzo(a)pyrene (BaP) in atmospheric particulate matter (PM10 fraction). Obtained LOD, 1.0 × 10(-3) ng/m(3), was adequate for the analysis of benzo(a)pyrene in the samples, and BaP recovery from PAH in Fine Dust (PM10-like) certified reference material was nearly quantitative (86%). The validated procedure was applied for analyzing 115 PM10 samples collected at different sampling locations in the low-polluted area of Extremadura (Southwest Spain) during a monitoring campaign carried out in 2011-2012. BaP spatial variations and seasonal variability were investigated as well as the influence of meteorological conditions and different air pollutants concentrations. A normalized protocol for health risk assessment was applied to estimate lifetime cancer risk due to BaP inhalation in the sampling areas, finding that around eight inhabitants per million people may develop lung cancer due to the exposition to BaP in atmospheric particulates emitted by the investigated sources.

DNA damage in buccal mucosa cells of pre-school children exposed to high levels of urban air pollutants.

Air pollution has been recognized as a human carcinogen. Children living in urban areas are a high-risk group, because genetic damage occurring early in life is considered able to increase the risk of carcinogenesis in adulthood. This study aimed to investigate micronuclei (MN) frequency, as a biomarker of DNA damage, in exfoliated buccal cells of pre-school children living in a town with high levels of air pollution. A sample of healthy 3-6-year-old children living in Brescia, Northern Italy, was investigated. A sample of the children's buccal mucosa cells was collected during the winter months in 2012 and 2013. DNA damage was investigated using the MN test. Children's exposure to urban air pollution was evaluated by means of a questionnaire filled in by their parents that included items on various possible sources of indoor and outdoor pollution, and the concentration of fine particulate matter (PM10, PM2.5) and NO2 in the 1-3 weeks preceding biological sample collection. 181 children (mean age ± SD: 4.3 ± 0.9 years) were investigated. The mean ± SD MN frequency was 0.29 ± 0.13%. A weak, though statistically significant, association of MN with concentration of air pollutants (PM10, PM2.5 and NO2) was found, whereas no association was apparent between MN frequency and the indoor and outdoor exposure variables investigated via the questionnaire. This study showed a high MN frequency in children living in a town with heavy air pollution in winter, higher than usually found among children living in areas with low or medium-high levels of air pollution.

Mutagenic, cytotoxic, and genotoxic properties of tobacco smoke produced by cigarillos available on the Canadian market.

Cigarillos (aka little cigars) have been increasing in popularity unlike cigarettes; but relatively little is known about the toxicology of the mainstream smoke (MSS) from such products. Therefore, the objective of this work was to compare the toxicological properties of the MSS (Health Canada Intensive smoking conditions) from a range of cigarillo products with the toxicological properties of MSS of cigarettes. Three in vitro assays were used to evaluate the toxicities of the MSS total particulate matter (TPM): (1) mutagenicity using Ames assay with Salmonella strains TA98 and TA100 with S9 metabolic activation (+S9); (2) cytotoxicity using the Neutral Red Uptake (NRU) assay with CHO (Chinese Hamster Ovary) cells; and (3) genotoxicity using the micronucleus assay with CHO cells and short-term exposures (3-h ± S9). The Ames assay (TA100+S9) and the NRU assay were also applied to the gas/vapour phase of the MSS that passed through the Cambridge pad. On a per-milligram-nicotine basis, the preferred way of comparing toxicities of different types of tobacco products, the MSS from cigarillos was not less toxic, and in some cases more toxic (TPM fraction TA98+S9, NRU), than the MSS from cigarettes. Thus, our findings support our prior work on smoke mutagenicity that showed MSS from cigarillos was not less toxic than MSS from cigarettes.

Evaluation of exposure to the airborne asbestos in an automobile brake and clutch manufacturing industry in Iran.

About 2000 tons of chrysotile is used annually to produce friction materials in Islamic Republic of Iran. Approximately, 3000 workers are exposed to the asbestos fibers in the different processes of brake and clutch manufacturing. In the current study, asbestos fiber concentrations during brake and clutch manufacture were measured. This study also evaluated the fiber size and morphology distribution according to the Asbestos International Association (AIA) for standardization analytical method for asbestos. The airborne asbestos fiber concentrations and its chemical composition of 92 personal samples were analyzed by phase contrast microscopy (PCM) and scanning electron microscope (SEM) equipped with an energy-dispersive X-ray analyzer (EDX). Personal monitoring of fiber levels demonstrated counts that ranged from 0.31 to 1.3 PCM f/ml (15.5-51.5 SEM f/ml). Geometric means of the asbestos concentrations were 1.3 PCM f/ml (51.5 SEM f/ml) and 0.86 PCM f/ml (42.1 SEM f/ml) according to the brake weighting and mixing and clutch mixing process, respectively. The geometrical mean concentrations were 0.63 PCM f/ml (31 SEM f/ml), which is considerably higher than threshold limit value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) which is 0.1f/ml. The SEM data demonstrate that the fibrous particles consisted, approximately, of chrysotile (50%), tremolite (30%), and actinolite (20%). Based on these findings, the 50% of airborne fibers inhaled by the workers were amphiboles asbestos with fibers equal and greater than 5 microm in length and 0.2 microm in diameter, and thus not included in the PCM-based fiber counts. Therefore, it might be expected that workers who worked in the brake and clutch manufacture will suffer from negative health effects of exposing to the amphibole asbestos fibers.

Does the effect of PM10 on mortality depend on PM nickel and vanadium content? A reanalysis of the NMMAPS data.

BACKGROUND: Lack of knowledge regarding particulate matter (PM) characteristics associated with toxicity is a crucial research gap. Short-term effects of PM can vary by location, possibly reflecting regional differences in mixtures. A report by Lippmann et al. [Lippmann et al., Environ Health Perspect 114:1662-1669 (2006)] analyzed mortality effect estimates from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) for 1987-1994. They found that average concentrations of nickel or vanadium in PM2.5 (PM with aerodynamic diameter < 2.5 microm) positively modified the lag-1 day association between PM10 and all-cause mortality. OBJECTIVE: We reestimated the relationship between county-specific lag-1 PM10 (PM with aerodynamic diameter < 10 microm) effects on mortality and county-specific nickel or vanadium PM2.5 average concentrations using 1987-2000 effect estimates. We explored whether such modification is sensitive to outliers. METHODS: We estimated long-term average county-level nickel and vanadium PM2.5 concentrations for 2000-2005 for 72 U.S. counties representing 69 communities. We fitted Bayesian hierarchical regression models to investigate whether county-specific short-term effects of PM10 on mortality are modified by long-term county-specific nickel or vanadium PM2.5 concentrations. We conducted sensitivity analyses by excluding individual communities and considering log-transformed data. RESULTS: Our results were consistent with those of Lippmann et al. However, we found that when counties included in the NMMAPS New York community were excluded from the sensitivity analysis, the evidence of effect modification of nickel or vanadium on the short-term effects of PM10 mortality was much weaker and no longer statistically significant. CONCLUSIONS: Our analysis does not contradict the hypothesis that nickel or vanadium may increase the risk of PM to human health, but it highlights the sensitivity of findings to particularly influential observations.

Particulate matter in the environment: pulmonary and cardiovascular effects.

PURPOSE OF REVIEW: The mechanisms related to adverse respiratory and cardiovascular effects in populations exposed to particulate matter are under debate and different models have been used to further our understanding of the various aspects of those effects. In this review we present some studies that may give new insights into the cellular and systemic mechanisms related to particulate matter toxicity. RECENT FINDINGS: Strong epidemiological evidence is now available regarding exposure markers and health effects. This is evident in the correlation between carbon content in macrophages and decrease in lung function, an increase in the risk of chronic obstructive pulmonary disease, lung cancer and postnatal mortality. The role of outdoor temperature and a missing allele for GSTM1 and the impact of these factors on cardiovascular effects are also reported. At the experimental level, the effects of particulate matter and the interactions between different cell types, the role of toll-like receptor-2 and 4, the translocation of particles through cell monolayers and the activation of endothelial cells by particulate matter are also discussed. The role of composition is under intense debate, and different statistical analyses have been proposed. SUMMARY: Experimental studies on the effects of particulate matter are giving plausibility to the epidemiological findings, but the possible mechanisms of action are also becoming a hot topic.

Apheis: Health impact assessment of long-term exposure to PM(2.5) in 23 European cities.

INTRODUCTION: Apheis aims to provide European decision makers, environmental-health professionals and the general public with up-to-date and easy-to-use information on air pollution (AP) and public health (PH). In the Apheis-3 phase we quantified the PH impact of long-term exposure to PM(2.5) (particulate matter < 2.5 microm) in terms of attributable number of deaths and the potential gain in life expectancy in 23 European cities. METHODS: We followed the World Health Organization (WHO) methodology for Health Impact Assessment (HIA) and the Apheis guidelines for data collection and analysis. We used the programme created by PSAS-9 for attributable-cases calculations and the WHO software AirQ to estimate the potential gain in life expectancy. For most cities, PM(2.5) levels were calculated from PM10 measurements using a local or European conversion factor. RESULTS: The HIA estimated that 16,926 premature deaths from all causes, including 11,612 cardiopulmonary deaths and 1901 lung-cancer deaths, could be prevented annually if long-term exposure to PM(2.5 )levels were reduced to 15 microg/m3 in each city. Equivalently, this reduction would increase life expectancy at age 30 by a range between one month and more than two years in the Apheis cities. CONCLUSIONS: In addition to the number of attributable cases, our HIA has estimated the potential gain in life expectancy for long-term exposure to fine particles, contributing to a better quantification of the impact of AP on PH in Europe.