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Particle size is a critical influencing factor in assessing human exposure risk as fine particles are generally more hazardous than larger coarse particles. However, how particle composition influences human health risk is only poorly understood as different studies have different utilised different definitions and as a consequence there is no consensus. Here, with a new methodology taking insights of each size fraction load (%GSF load ), metal bioaccessibility, we classify which specific particle size can reliably estimate the human exposure risk of lead and other metals. We then validate these by correlating the metals in each size fraction with those in human blood, hair, crop grain and different anthropogenic sources. Although increasing health risks are linked to metal concentration these increase as particle size decrease, the adjusted-risk for each size fraction differs when %GSF load is introduced to the risk assessment program. When using a single size fraction (250-50 µm, 50-5 µm, 5-1 µm, and < 1 µm) for comparison, the risk may be either over- or under-estimated. However, by considering bulk and adjusting the risk, it would be possible to obtain results that are closer to the real scenarios, which have been validated through human responses and evidence from crops. Fine particle size fractions (< 5 µm) bearing the mineral crystalline or aggregates (CaCO 3 , Fe 3 O 4 , Fe 2 O 3 , CaHPO 4 , Pb 5 (PO 4 ) 3 Cl) alter the accumulation, chemical speciation, and fate of metals in soil/dust/sediment from the different sources. Loaded lead in the size fraction of < 50 µm has a significantly higher positive association with the risk-receptor biomarkers (BLLs, Hair Pb, Corn Pb, and Crop Pb) than other size fractions (bulk and 50-250 µm). Thus, we conclude that the < 50 µm fraction would be likely to be recommended as a reliable fraction to include in a risk assessment program. This methodology acts as a valuable instrument for future research undertakings, highlighting the importance of choosing suitable size fractions and attaining improved accuracy in risk assessment results that can be effectively compared., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lead is a toxic metal that can pose a huge threat to children's health. China has experienced rapid urbanization since the reform in 1978; however, there has been no examination of the potential influence of this urbanization on children's blood lead levels (BLLs). This study is the initial investigation to explore the correlation between urbanization and BLLs in Chinese children. Five windows of time are considered: pre-2000, 2001-2005, 2006-2010, 2011-2015 and 2016-2021. The results show that urbanization affected lead distribution in urban soil and agricultural soil during the above periods, especially in northern China. The higher non-carcinogenic risk of lead for children is consistent with the lead pollution in soil (3 < I geo  ≤ 4). Urban children's BLLs are slightly higher than those of rural children in 2001-2010, but rural children's BLLs in 2011-2021 are higher than those of urban children during China's urbanization. The areas of rural decline and the areas of urban growth increased across all the window periods. However, the BLLs decrease in all rural and urban areas during all window periods, especially in urban areas. Children's BLLs have a significantly negative correlation with urban areas (p < 0.01). Therefore, China's urbanization has a significant effect on the decrease in children's BLLs. The significance of this study is to provide a fresh perspective and innovative strategy for policymaking in order to reduce children's BLLs and prevent lead exposure. This can be achieved by transforming their external living environment from a rural lifestyle to an urban one, while also ensuring access to well education and maintaining a balanced nutrient intake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We systematically reviewed the association of ambient air pollution with blood pressure (BP) as a primary outcome in adolescents (10-19 years). Five databases (Ovid Medline, Ovid Embase, Web of Science, The Cochrane Library, and LILACS) were searched for relevant articles published up to August 2022. Meta-analyses were conducted using STATA v17 (Protocol - OSF Registries https://doi.org/10.17605/OSF.IO/96G5Q). Eight studies (5 cohort, 3 cross-sectional) with approximately 15,000 adolescents were included. Data from 6 studies were suitable for inclusion in the meta-analyses. In sub-group analyses, non-significant positive associations were observed for cohort studies assessing long-term exposure to PM 10 , PM 2.5 , and NO 2 on systolic and diastolic BP. At age 12 years old (3702 adolescents), we found significant positive associations for long-term exposure to PM 2.5 (β=5.33 (1.56, 9.09) mmHg) and PM 10 (β=2.47 (0.10, 4.85) mmHg) on diastolic BP. Significant positive associations were observed (3,592 adolescents) for long-term exposure to PM 10 (β=0.34 (0.19, 0.50) mmHg) and NO 2 on diastolic BP (β=0.40 (0.09, 0.71) mmHg), and PM 10 on systolic BP (β=0.48 (0.19, 0.77) mmHg). The overall quality of evidence analysed was graded as "low/very low." Insufficient data for short-term exposures to PM 2 . 5 , PM 10 , NO 2 , CO on BP led to their exclusion from the meta-analysis. Inconsistent associations were reported for gender-stratified results. The evidence, though of low-quality and limited, indicated that ambient air pollution was positively associated with adolescent BP. Future studies need improved measures of air pollutant exposures, consideration of gender and socio-economic circumstances on the observed pollution effects, as well as adjustment for other potential confounding factors., (Copyright © 2022. Published by Elsevier Inc.)

Limited number of projects have attempted to partition and quantify indoor- and outdoor-generated PM 2.5 (PM 2.5 ig and PM 2.5 og ) where strong indoor sources (e.g., solid fuel, tobacco smoke, or kerosene) exist. This study aimed to apply and refine a previous recursive model used to derive infiltration efficiency (F inf ) to additionally partition pollution concentrations into indoor and outdoor origins within residences challenged by elevated ambient and indoor combustion-related sources. During the winter of 2016 and summer of 2017 we collected residential measurements in 72 homes in urban and peri-urban Beijing, 12 of which had additional paired residential outdoor measurements during the summer season. Local ambient measurements were collected throughout. We then compared the calculated PM 2.5 ig and using (i) outdoor and (ii) ambient measurements as model inputs. The results from outdoor and ambient measurements were not significantly different, which suggests that ambient measurements can be used as a model input for pollution origin partitioning when paired outdoor measurements are not available. From the results calculated using ambient measurements, the mean percentage contribution of indoor-generated PM 2.5 was 19 % (σ = 22 %), and 7 % (11 %) of the total indoor PM 2.5 for peri-urban and urban homes respectively during the winter; and 18 % (18 %) and 6 % (10 %) of the total indoor PM 2.5 during the summer. Partitioning pollution into PM 2.5 ig and PM 2.5 og is important to allow investigation of distinct associations between health outcomes and particulate mixes, often with different physiochemical composition and toxicity. It will also inform targeted interventions that impact indoor and outdoor sources of pollution (e.g., domestic fuel switching vs. power generation), which are typically radically different in design and implementation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Microplastics (MPs) in freshwater environments have been recognized as one of the important sources of plastic contamination in marine ecosystems. Reducing the amount and spatial distribution of MPs reaching the sea through accumulation behind dams remains unclear. In this study we analyzed the spatial distribution of sediment and surface water MPs in the Aras Dam and from nineteen upstream and downstream locations of the Dam in the Aras River. The MPs abundance ranged from 32 to 528 items/kg dry weight (mean 217.8 ± 132.6) and 1 to 43 items/m 3 (mean 12.8 ± 10.5) in the sediment and surface water stations, respectively. MPs abundance in surface waters collected within the Dam reservoir was significantly higher than those found either upstream or downstream (P < 0.05). For sediments, reservoir MPs concentration was generally higher than upstream and downstream, although their differences were not significant. High MPs concentration was observed in the vicinity of urban areas. Moreover, MPs abundance was positively correlated with total organic carbon (TOC) and clay content (P < 0.01). GAM analysis revealed that clay is the most important variable with lowest Akaike information criterion (AIC) and explained 61.3 % of deviance (R-sq.(adj) = 0.344) in MPs abundance. MP particles ranged from 0.1 to 5 mm in size and were dominated by fibers (53.5 %), black color (24 %) and PE polymer (36.6 %). Our results highlight the high MPs distribution in the Aras River and demonstrate that they accumulate in the surface waters behind the Dam. Consequently, the fate and effects of MPs in international rivers is one of the most politicized issues between countries with a common boundary and therefore needs joint management policies that help mitigate this insidious problem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Due to the adverse health effects of air pollution, researchers have advocated for personal exposure measurements whereby individuals carry portable monitors in order to better characterise and understand the sources of people's pollution exposure., Objectives: The aim of this systematic review is to assess the differences in the magnitude and sources of personal PM 2.5 exposures experienced between countries at contrasting levels of income., Methods: This review summarised studies that measured participants personal exposure by carrying a PM 2.5 monitor throughout their typical day. Personal PM 2.5 exposures were summarised to indicate the distribution of exposures measured within each country income category (based on low (LIC), lower-middle (LMIC), upper-middle (UMIC), and high (HIC) income countries) and between different groups (i.e. gender, age, urban or rural residents)., Results: From the 2259 search results, there were 140 studies that met our criteria. Overall, personal PM 2.5 exposures in HICs were lower compared to other countries, with UMICs exposures being slightly lower than exposures measured in LMICs or LICs. 34% of measured groups in HICs reported below the ambient World Health Organisation 24-h PM 2.5 guideline of 15 μg/m 3 , compared to only 1% of UMICs and 0% of LMICs and LICs. There was no difference between rural and urban participant exposures in HICs, but there were noticeably higher exposures recorded in rural areas compared to urban areas in non-HICs, due to significant household sources of PM 2.5 in rural locations. In HICs, studies reported that secondhand smoke, ambient pollution infiltrating indoors, and traffic emissions were the dominant contributors to personal exposures. While, in non-HICs, household cooking and heating with biomass and coal were reported as the most important sources., Conclusion: This review revealed a growing literature of personal PM 2.5 exposure studies, which highlighted a large variability in exposures recorded and severe inequalities in geographical and social population subgroups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This study examines for the first time the characteristics and human exposure of microplastics (MPs) in settled indoor dust in schools. An average of 195 MPs·g -1 of dust were detected in settled indoor composite dust samples from 28 schools in Shiraz. White-transparent microfibres with lengths 500-1000 μm were the most abundant type of MP found among the samples examined. Polyethylene terephthalate and polypropylene MPs were dominant across all types of MP found including microfibres. MPs had generally smooth morphology with sharp or regular edges which could have been released to the environment as primary MPs. Among all sampling sites, higher concentrations of MPs were found in the south and centre of the city. These were areas affected by high population density, high traffic load and high presence of industrial units and workshops. Principal Component Analysis (PCA) showed a positive strong correlation between sampling sites and MP physical characteristics. The PCA plots revealed that MP sheets and fragments were prevalent in sites in the North of Shiraz, whereas microfibres were mainly associated with sites in the South. The levels of MPs in the South of Shiraz were greater than in the rest of the country and the wind direction and topography were found to be important factors affecting the MP distribution observed. Compared to other population groups, elementary school students had relatively high exposure risk to MPs. This study reveals that microfibres are widespread in Shiraz' schools and pose a high exposure risk to MPs for young students., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of plastics is common across all aspects of human life owing to its durable and versatile nature. The generation and utilization of plastics are directly related to the anthropogenic activities. The extensive use of plastics and adoption of inappropriate waste-management frameworks has resulted in their release into the environment, where they may persist. Different environmental factors, such as, photochemical, thermo-oxidation, and biological degradation, can lead to the degradation of plastics into micro- (MPs) and nano-plastics (NPs). The behaviour and concentration of MPs in the terrestrial environment can depend on their size, density, and local atmospheric conditions. Microplastics and nanoplastics may enter the food web, carrying various organic pollutants, which bio-accumulate at different trophic levels, prompting organism health concerns. Microplastics being airborne identifies as new exposure route. Dietary and airborne exposure to MPs has led researchers to stress the importance of evaluating their toxicological potential. The primary goal of this paper is to explore the environmental fate of MPs from sources to sink in the terrestrial environment, as well as detail their potential impacts on human health. Additionally, this review article focuses on the presence of airborne microplastics, detailed sample pre-processing methods, and outlines analytical methods for their characterization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study investigates the mineralogy, micro-morphology, chemical characteristics and oxidation toxicity of respirable dusts generated in underground coal mines. The active sampling was applied to collect airborne particulates with aerodynamic diameter <4 µm (PM 4 ) at depth greater than 500 m from earth surface. The average mass concentration of PM 4 was extremely higher than recommended values. QXRD and FESEM-EDS analyses were applied to study the micro-mineralogy and micro-morphology of respirable dusts. The chemical analysis by ICP-MS revealed an enrichment of V, Cr, Cu, Zn, As, Ag, Cd and Sb in respirable dust compared with the background environment and world coals. The EPA's health risk model showed that the health risk posed by Cr and Co in all workplaces exceeded the acceptable risk value for human health. The synthetic respiratory tract lining fluid (RTLF) model was utilized to achieve a novel insight into the toxicity of respirable coal dust. The result showed an overall depletion of lung surface antioxidants with the decreasing trend of ascorbic acid > reduced glutathione >> urate, implying low- to medium level of oxidative stress. The result of this study can be applied globally by decision-makers to decrease hazardous exposure of mine workers to respirable dust., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the most important environmental issues in arid and semi-arid regions is deposition of dust particles. In this study, airborne, passive, and street dust samples were collected in Asaluyeh County, in August 2017, September 2017, and February 2018. The PM 2.5 and PM 10 concentrations for the sampling period ranged between 19.7 and 76.0 μg/m 3 and 47.16-348 μg/m 3 with an average of 46.4 μg/m 3 and 143 μg/m 3 , respectively. Monthly dust deposition rates ranged from 5.2 to 26.1 g/m 2 with an average of 17.85 g/m 2 . Positive Matrix Factorization (PMF) applied to the dust compositional data indicated that Sb, Zn, Pb, Mo, Cu, and As come from anthropogenic sources while Al, Fe, Ti, Mn, Ni, Cr, and Co originate mostly from geogenic sources. The PMF results indicated that the geogenic material was the major source of passive and airborne dust samples. Elemental compositions were similar for passive dust and local surface soil. Frequency-dependent magnetic susceptibility (χ If and χ fd% ) showed that the local soil is entisol. Isothermal remanent magnetization (IRM -100mT /IRM 1T ) versus saturation IRM (SIRM) demonstrated that the background sample contains ferrimagnetic minerals, but with increasing SIRM, the concentration of soft magnetic magnetite-like phases increases and the magnetic particles are larger. Mrs./Ms. versus Bcr/Bc indicated that the magnetic particles sizes were probably between 120 and 1000 nm. Eu values and the mean Eu/Eu* and La/Al values clearly show that the airborne dust is most affected by oil industries, while passive dust samples primarily originated from local surface soils. These assumptions were confirmed by Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model results. The samples display a moderate level of oxidation towards ascorbic acid (OP AA ) and glutathione (OP GSH ). Regarding the passive and airborne dust samples, backward Generalized Estimating Equations (GEE) modeling results display a significant positive relationship between geogenic material and oxidative potential (OP). It includes many redox-active transition metals. Alternatively, the street dust OP is strongly related to geogenic and industrial sources and OP AA is marginally related to urban sources. It was shown that measured magnetic parameters can be used for OP estimation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults., Methods: In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO 2 ) concentrations were measured., Findings: Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO 2 , PM 10 , PM 2.5 , and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV 1 ] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV 1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO 2 , ultrafine particles and PM 2.5 , and an increase in PWV and augmentation index with NO 2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles., Interpretation: Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects., Funding: British Heart Foundation., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Oxidative potential (OP) of particulate matter (PM) is proposed as a biologically-relevant exposure metric for studies of air pollution and health. We aimed to evaluate the spatial variability of the OP of measured PM 2.5 using ascorbate (AA) and (reduced) glutathione (GSH), and develop land use regression (LUR) models to explain this spatial variability. We estimated annual average values (m -3 ) of OP AA and OP GSH for five areas (Basel, CH; Catalonia, ES; London-Oxford, UK (no OP GSH ); the Netherlands; and Turin, IT) using PM 2.5 filters. OP AA and OP GSH LUR models were developed using all monitoring sites, separately for each area and combined-areas. The same variables were then used in repeated sub-sampling of monitoring sites to test sensitivity of variable selection; new variables were offered where variables were excluded (p > .1). On average, measurements of OP AA and OP GSH were moderately correlated (maximum Pearson's maximum Pearson's R = = .7) with PM 2.5 and other metrics (PM 2.5 absorbance, NO 2 , Cu, Fe). HOV (hold-out validation) R 2 for OP AA models was .21, .58, .45, .53, and .13 for Basel, Catalonia, London-Oxford, the Netherlands and Turin respectively. For OP GSH , the only model achieving at least moderate performance was for the Netherlands (R 2 = .31). Combined models for OP AA and OP GSH were largely explained by study area with weak local predictors of intra-area contrasts; we therefore do not endorse them for use in epidemiologic studies. Given the moderate correlation of OP AA with other pollutants, the three reasonably performing LUR models for OP AA could be used independently of other pollutant metrics in epidemiological studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the frame of the OFFICAIR project, office buildings were investigated across Europe to assess how the office workers are exposed to different particulate matter (PM) characteristics (i.e. PM 2.5 mass concentration, particulate oxidative potential (OP) based on ascorbate and reduced glutathione depletion, trace element concentration and total particle number concentration (PNC)) within the buildings. Two offices per building were investigated during the working hours (5 consecutive days; 8h per day) in two campaigns. Differences were observed for all parameters across the office buildings. Our results indicate that the monitoring of the PM 2.5 mass concentration in different offices within a building might not reflect the spatial variation of the health relevant PM characteristics such as particulate OP or the concentration of certain trace elements (e.g., Cu, Fe), since larger differences were apparent within a building for these parameters compared to that obtained for the PM 2.5 mass concentration in many cases. The temporal variation was larger for almost all PM characteristics (except for the concentration of Mn) than the spatial differences within the office buildings. These findings indicate that repeated or long-term monitoring campaigns are necessary to have information about the temporal variation of the PM characteristics. However, spatial variation in exposure levels within an office building may cause substantial differences in total exposure in the long term. We did not find strong associations between the investigated indoor activities such as printing or windows opening and the PNC values. This might be caused by the large number of factors affecting PNC indoors and outdoors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Airborne particulate matter (PM) consists of particles from diverse sources, including vehicle exhausts. Associations between short-term PM changes and stroke incidence have been shown. Cumulative exposures over several months, or years, are less well studied; few studies examined ischaemic subtypes or PM source., Aims: This study combines a high resolution urban air quality model with a population-based stroke register to explore associations between long-term exposure to PM and stroke incidence., Method: Data from the South London Stroke Register from 2005-2012 were included. Poisson regression explored association between stroke incidence and long-term (averaged across the study period) exposure to PM2.5(PM<2.5μm diameter) and PM10(PM<10μm), nitric oxide, nitrogen dioxide, nitrogen oxides and ozone, at the output area level (average population=309). Estimates were standardised for age and sex and adjusted for socio-economic deprivation. Models were stratified for ischaemic and haemorrhagic strokes and further broken down by Oxford Community Stroke Project classification and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification., Results: 1800 strokes were recorded (incidence=42.6/100,000 person-years). No associations were observed between PM and overall ischaemic or haemorrhagic incidence. For an interquartile range increase in PM2.5, there was a 23% increase in incidence (Incidence rate ratio=1.23 (95%CI: 1.03-1.44)) of total anterior circulation infarcts (TACI) and 20% increase for PM2.5 from exhausts (1.20(1.01-1.41)). There were similar associations with PM10, overall (1.21(1.01-1.44)) and from exhausts (1.20(1.01-1.41)). TACI incidence was not associated with non-exhaust sources. There were no associations with other stroke subtypes or pollutants., Conclusion: Outdoor air pollution, particularly that arising from vehicle exhausts, may increase risk of TACI but not other stroke subtypes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A comprehensive chemical characterization and oxidative potential (OP) assessment of PM2.5 was carried out at an urban site of Budapest between June 2010 and May 2013 to investigate the seasonal variability of particulate phase air pollutants and their oxidative activity. Chemical analyses included the determination of the concentration of trace elements, major water-soluble inorganic ions and carbonaceous fractions (total carbon, water-soluble organic carbon, organic carbon, elemental carbon). The OP of PM2.5 was assessed by antioxidant depletion using a synthetic respiratory tract lining fluid containing ascorbate, reduced glutathione and urate. The mean PM2.5 mass concentration (21.0 μg m(-3)) was just below the 25 μg m(-3) annual mean PM2.5 limit value set by the European Commission and showed a seasonal pattern with higher levels during winter. On average, 84% of the gravimetric mass could be reconstructed by the chemical measurements. Organic matter and secondary inorganic ions were the most dominant PM2.5 constituents contributing 40 and 29% of its mass, respectively. Changes in the yearly concentrations were not identified for the investigated compounds between 2010 and 2013. Temporal differences in both ascorbate and glutathione oxidation could be observed during the 3-year long sampling period; however, no clear seasonal trend was apparent. OP metrics were associated mainly with traffic-related trace elements; however, other PM sources (i.e., long-range transport, secondary aerosol formation) could also contribute to particulate OP in Budapest. The weak correlation between OP metrics and PM2.5 mass concentration suggests the possibility of using OP as an additional metric in epidemiology., (Copyright © 2015 Elsevier B.V. All rights reserved.)

About 400,000 premature adult deaths attributable to air pollution occur each year in the European Region. Road transport emissions account for a significant share of this burden. While important technological improvements have been made for reducing particulate matter (PM) emissions from motor exhausts, no actions are currently in place to reduce the non-exhaust part of emissions such as those from brake wear, road wear, tyre wear and road dust resuspension. These "non-exhaust" sources contribute easily as much and often more than the tailpipe exhaust to the ambient air PM concentrations in cities, and their relative contribution to ambient PM is destined to increase in the future, posing obvious research and policy challenges. This review highlights the major and more recent research findings in four complementary fields of research and seeks to identify the current gaps in research and policy with regard to non-exhaust emissions. The objective of this article is to encourage and direct future research towards an improved understanding on the relationship between emissions, concentrations, exposure and health impact and on the effectiveness of potential remediation measures in the urban environment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors., Methods: We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 ., Findings: Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31])., Interpretation: Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.

A robust database shows that dietary supplements of vitamins E and C are safe for the general population. Because these nutrients supply antioxidant and other functions for homeostasis and protection against free radical damage, supplementation has been intensively studied. Because of perceived benefits, many persons consume quantities of vitamins E and C well above the recommended dietary allowances. As safety guidance, tolerable upper intake levels have been established by the Food and Nutrition Board, Institute of Medicine, at 1000 mg for vitamin E and 2000 mg for vitamin C in adults. Many clinical trials with these vitamins have involved subjects with various diseases, and no consistent pattern of adverse effects has occurred at any intake. Numerous studies of vitamin C supplementation have provided no pattern of evidence to support concerns about safety other than occasional gastrointestinal upset or mild diarrhea resulting from the osmotic effects of unabsorbed quantities of vitamin C. Evidence of bleeding effects and other potential adverse effects of high vitamin E intakes in humans is not convincing. Evidence of adverse effects of vitamin C that result from its effects on iron absorption and metabolism has not been confirmed in clinical trials. Thus, we conclude from clinical trial evidence that vitamin E supplements appear safe for most adults in amounts

Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-alpha in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 microg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35-4.88) Md (Q1-Q3) vs. air 0.94 (0.53-1.23); P = 0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.

Breathing high concentrations of diesel exhaust (DE) induces pulmonary inflammation, bronchoconstriction, increased airway reactivity, and oxidative stress in healthy subjects. To examine if these responses occur at environmentally relevant concentrations of DE, we exposed 25 healthy subjects to DE (PM(10) 100 microg/m(3), 0.6 ppm NO(2) for 2-h) and filtered air on separate occasions. Immediately following DE exposure, subjects displayed an increase in subjective symptoms and a mild bronchoconstriction. Six hours following the cessation of DE exposure neither airway inflammation, nor antioxidant depletion (ascorbate, urate, and reduced glutathione), was seen at any level of the respiratory tract. Instead, an increased flux of reduced glutathione into the bronchial (p < 0.01) and nasal airways (p < 0.05) was observed. In separate, in vitro experiments, DE was found to have comparable oxidative activity to the transition metal rich residual oil fly ash (ROFA) particle, significantly depleting lung lining fluid ascorbic acid and reduced glutathione in a transition metal and superoxide-dependent mechanism. Together, these data indicate that even though DE has marked oxidative activity, this effect is not observed to any great extent in the airways of healthy subjects. We interpret these findings as being indicative that the antioxidant network at the air-lung interface in healthy subjects is capable of dealing with the oxidative challenge posed by DE at ambient concentrations.

Vitamin E is indispensible for reproduction in female rats. In humans, vitamin E deficiency primarily causes neurologic dysfunctions, but the underlying molecular mechanisms are unclear. Because of its antioxidative properties, vitamin E is believed to help prevent diseases associated with oxidative stress, such as cardiovascular disease, cancer, chronic inflammation, and neurologic disorders. However, recent clinical trials undertaken to prove this hypothesis failed to verify a consistent benefit. Given these findings, a group of European scientists met to analyze the most recent knowledge of vitamin E function and metabolism. An overview of their discussions is presented in this article, which includes considerations of the mechanisms of absorption, distribution, and metabolism of different forms of vitamin E, including the alpha-tocopherol transfer protein and alpha-tocopherol-associated proteins; the mechanism of tocopherol side-chain degradation and its putative interaction with drug metabolism; the usefulness of tocopherol metabolites as biomarkers; and the novel mechanisms of the antiatherosclerotic and anticarcinogenic properties of vitamin E, which involve modulation of cellular signaling, transcriptional regulation, and induction of apoptosis. Clinical trials were analyzed on the basis of the selection of subjects, the stage of disease, and the mode of intake, dosage, and chemical form of vitamin E. In addition, the scarce knowledge on the role of vitamin E in reproduction was summarized. In conclusion, the scientists agreed that the functions of vitamin E were underestimated if one considered only its antioxidative properties. Future research on this essential vitamin should focus on what makes it essential for humans, why the body apparently utilizes alpha-tocopherol preferentially, and what functions other forms of vitamin E have.

Objective: We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia., Study Design: Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously., Results: Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased; and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk., Conclusion: Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease.

Objective: The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preeclampsia in the blood of pregnant women in whom preeclampsia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preeclampsia and with women who were at low risk for the development of preeclampsia., Study Design: This was a prospective case control study. The subjects were women at risk of preeclampsia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preeclampsia developed later, in 17 women without preeclampsia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preeclampsia., Results: Ascorbic acid was reduced early in preeclampsia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preeclampsia., Conclusion: Gestational profiles of several markers were abnormal in the group with preeclampsia, and some of the markers that may prove useful in the selective prediction of preeclampsia were identified.

Prolonged low-medium intensity exercise is associated with increased oxidative stress in humans. We hypothesized that competitive equine endurance racing would induce changes in circulatory antioxidants and produce systemic oxidative stress. Forty horses competing in a 140-km endurance race in warm conditions [shade temperature 15-19 degrees C; 62-88% relative humidity (%RH)] were sampled before (Pre), immediately after exercise (End) and at approximately 16 h into recovery (+16 h). Plasma ascorbic acid concentration was not different between Pre [11.1 (median); 4.6-20.3 micromol/L (range)] and End [9.7; 3.0-38.9 (range) micromol/L] but was significantly decreased at +16 h (5.5; 2.8-15.5 micromol/L; P < 0.05). Total red cell hemolysate glutathione (TGSH) concentration was significantly reduced by exercise (Pre 1261; 883-1532 micromol/L; End 1065; 757-1334 micromol/L; P < 0.05) and at +16 h recovery (1032; 752-1362 micromol/L; P < 0.05). Glutathione redox ratio was unchanged by exercise but was significantly decreased at +16 h compared with that at both Pre and End (P < 0.05). The concentration of total barbituric acid reactive substances (TBARS) in plasma was increased compared with that at Pre (309; 66-1048 nmol/L), both at End (408; 170-1196 nmol/L; P < 0.05) and +16 h (380; 99-1161 nmol/L; P < 0.05). alpha-Tocopherol was unchanged by exercise or recovery. Mean race speed was 16.5 +/- 1.6 km/h and ranged from 13.9 to 19.7 km/h. Mean speed during competition in horses that completed the full 140 km (n = 28) was significantly correlated with end of exercise ascorbic acid (r = 0.622; P = 0.0004). Although there were increases in creatine phosphokinase (CK), aspartate aminotransferase (AST) and TBARS and a loss of TGSH, this study failed to demonstrate evidence of classical oxidative stress.

Epidemiological studies suggestthat asthmatics are more affected by ozone than healthy people. This study tested three hypotheses (1) that short-term exposure to ozone induces inflammatory cell increases and up-regulation of vascular adhesion molecules in airway lavages and bronchial tissue 6 h after ozone exposure in healthy subjects; (2) these responses are exaggerated in subjects with mild allergic asthma; (3) ozone exacerbates pre-existent allergic airways inflammation. We exposed 15 mild asthmatic and 15 healthy subjects to 0.2 ppm of ozone or filtered air for 2 h on two separate occasions. Airway lavages and bronchial biopsies were obtained 6 h post-challenge. We found that ozone induced similar increases in bronchial wash neutrophils in both groups, although the neutrophil increase in the asthmatic group was on top of an elevated baseline. In healthy subjects, ozone exposure increased the expression of the vascular endothelial adhesion molecules P-selectin and ICAM- 1, as well as increasing tissue neutrophil and mast cell numbers. The asthmatics showed allergic airways inflammation at baseline but ozone did not aggravate this at the investigated time point. At 6 h post-ozone-exposure, we found no evidence that mild asthmatics were more responsive than healthy to ozone in terms of exaggerated neutrophil recruitment or exacerbation of pre-existing allergic inflammation. Further work is needed to assess the possibility of a difference in time kinetics between healthy and asthmatic subjects in their response to ozone.

Background: Ischemic preconditioning, an endogenous protection mechanism, occurs in many organs, including lungs. The efficacies of differing ischemic durations in protecting the lung are unknown. We compared the ability of three preconditioning protocols to protect rat lungs during storage., Methods: Function was measured in five groups of perfused, ventilated rat lungs. Group 1 lungs underwent control perfusion (60 minutes) without storage. Groups 2 through 5 underwent the following prestorage protocols: group 2, 20 minutes of perfusion; group 3, 10 minutes of perfusion, 5 minutes of cessation of ventilation and perfusion (ischemia), and 5 minutes of reperfusion; group 4, 5 minutes of perfusion, 10 minutes of ischemia, and 5 minutes of reperfusion; and group 5, 2 periods of 5 minutes of ischemia and 5 minutes of reperfusion. Lungs were then flushed with, and immersed (6 hours) in modified bicarbonate buffer (4 degrees C). Lung function was reassessed during 40 minutes of reperfusion (37 degrees C). Subsequently we examined preconditioning by stopping ventilation or perfusion separately., Results: After reperfusion, lungs in group 2 had a compliance of 0.015+/-0.002 mL/cm H2O (mean +/- SE, n = 10), significantly lower than lungs in group 1 (0.063+/-0.002 mL/cm H2O). Ischemic preconditioning was protective, with lungs in groups 3, 4, and 5 having compliances greater (p<0.05) than those in group 2. Preconditioning by cessation of ventilation alone was also effective., Conclusions: Preconditioning attenuates deterioration in lung compliance on reperfusion to a degree dependent on the protocol used.

Unlabelled: Hypertension and renal injury in experimental polycystic kidney disease., Background: Hypertension accelerates renal failure in autosomal dominant polycystic kidney disease (ADPKD), and evidence suggests a role for the renin-angiotensin system (RAS) in the functional and structural changes. To explore the hypothesis that RAS adaptations contribute to disease progression, we examined RAS activity and the long-term consequences of antihypertensive drugs, which suppress (enalapril) or stimulate (hydralazine) the RAS, in experimental polycystic kidney disease., Methods: Studies were conducted in male heterozygous cystic Han:SPRD rats (Cy/+) and in unaffected littermates (controls). In protocol 1, either angiotensin II (Ang II), enalaprilat, or saline vehicle was acutely infused into cystic and control rats, which were aged 10 to 12 weeks. The mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured at baseline and after an infusion of test substances. In protocol 2, cystic rats received chronic therapy with either enalapril, hydralazine, or no therapy for 10 to 12 weeks of age and then underwent renal function and RAS studies. In protocol 3, similar cohorts were followed for 40 weeks to assess the effects of therapy on blood pressure, proteinuria, serum creatinine, RAS parameters, and renal morphology., Results: In protocol 1, cystic rats had massive kidneys, slightly elevated blood pressure, and profound renal vasoconstriction and reduced GFR. Ang II induced similar changes in MAP and renal function in control and cystic rats. Enalaprilat induced little effect on MAP but more striking increases in GFR and RPF in cystic rats. In protocol 2, at 10 weeks of age, enalapril was superior in preserving renal function, but neither drug limited the expansion of the tubulointerstitium. In protocol 3, at 40 weeks of age, both drugs ameliorated the increase in serum creatinine, although only enalapril reduced proteinuria and kidney size., Conclusions: In polycystic rats, acute RAS suppression markedly ameliorates renal dysfunction. However, although chronic enalapril and hydralazine protect against the loss of renal function, only enalapril limits renal growth and proteinuria, and neither significantly limits tubulointerstitial fibrosis. The long-term studies give clear support to the importance of blood pressure control, per se, but only partial support to the importance of the particular agent used. As in clinical studies, angiotensin-converting enzyme inhibition may be less beneficial in ADPKD than in renal diseases characterized by predominant glomerular injury.

Background: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia., Methods: 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study., Findings: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002)., Interpretation: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Background: Raising intracellular cyclic adenosine monophosphate levels protects lungs from ischemia-reperfusion injury. We hypothesized that the phosphodiesterase inhibitor theophylline would protect lungs during storage., Methods: Rat lungs were perfused with modified bicarbonate buffer mixed with rat blood (4:1 vol/vol) (37 degrees C) and ventilated (80 breaths/min). After 20 minutes of perfusion during which vascular resistance and airway compliance were measured, lungs were flushed with and then immersed in bicarbonate buffer (4 degrees C) alone or containing theophylline (30 to 1,000 micromol/L). After 6 hours of storage, lung function was reassessed during 40 minutes of reperfusion., Results: Lungs stored in the presence of theophylline had improved lung function on reperfusion. After 40 minutes of reperfusion, pulmonary compliance was 0.008+/-0.004 mL/cm H2O, 0.022+/-0.010, 0.037+/-0.007, 0.044+/-0.006, and 0.073+/-0.003 mL/cm H2O, and vascular resistance was 3.84+/-0.40 cm H2O x min x mL(-1), 3.64+/-0.78, 2.12+/-0.35, 2.22+/-0.25, and 1.90+/-0.38 cm H2O x min x mL(-1) in lungs stored in the presence of 0, 30, 100, 300, or 1,000 micromol/L theophylline, respectively. Similar improvements were obtained for wet to dry weight ratio and gas exchange., Conclusions: Theophylline merits investigation as a potentially beneficial addition to solutions for the flushing and storage of human lungs for transplantation.

Lung lining fluid antioxidants represent a potentially important protective barrier of lung epithelial cells to damaging effects of air pollutants, yet no information is apparently available concerning lung lining fluid antioxidants in broilers. Therefore, goals of this study were to establish uric acid, ascorbic acid, reduced (GSH) and oxidized (GSSG) glutathione, and protein concentrations in lung lining fluid obtained from male broiler chickens maintained for 6 to 7 wk within environmentally controlled rooms (Control) or chronically exposed to high levels of dust and ammonia within a broiler rearing house (House). The entire respiratory tract was carefully removed following an overdose of anesthetic and lavage fluid was collected after flushing the lungs with heparin-saline (10 mL per lung). There was no difference in GSH, but GSSG, uric acid, and protein concentrations were higher in House birds than in Controls. An increase in the GSSG to total glutathione (GSx) ratio, an indicator of oxidative stress, was also observed in birds maintained in the House environment. Ascorbic acid was not detected in House-reared birds and detected in only 4 of 12 Controls. Regression analysis revealed positive correlations between lung lining fluid protein and uric acid (r = 0.71; P < 0.01), protein and GSSG (r = 0.73; P < 0.01), and uric acid and GSSG concentrations (r = 0.69, P < 0.01). Additionally, GSSG was positively correlated (r = 0.66; P < 0.01) with the right ventricular weight ratio, an index commonly used in identifying the development of pulmonary hypertension syndrome in broilers. These data, the first to document lung lining fluid antioxidants in avian species, indicate an oxidative stress can be detected in fluid of broilers exposed to high levels of dust and ammonia in a simulated poultry house environment.

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependent manner.

Leukotriene B4 (LTB4) has been reported to promote the formation of lung oedema when infused into the pulmonary circulation of adult animals. The present study evaluated the hypothesis that LTB4 was responsible, in part, for the oedema that develops during oxidative injury of the immature lung. Significant increases were found in LTB4 concentration in bronchoalveolar lavage fluid obtained from pre-term guinea pig pups maintained in 95% oxygen for 48 h (P < 0.05) and 72 h (P < 0.05) compared to pups maintained in 21% oxygen. Cellular analysis of lavage fluid revealed a concurrent influx of neutrophils into the hyperoxic-injured lung at these times. The protein concentration of lavage fluid was also increased by 48-h hyperoxia exposure indicating elevated pulmonary microvascular permeability. In a second series of experiments, pups exposed to 95% oxygen (and 21% oxygen controls) were treated with a specific LTB4 antagonist (U-75302), at either 0.5, 1.5 or 3.0 mg 100 g body wt to ascertain if LTB4 played a role in either neutrophil recruitment or oedema formation in the immature lung. The number of neutrophils recovered in bronchoalveolar lavage fluid was significantly reduced, compared to vehicle-treated pups, in pups treated with U-75302, at both 1.5 and 3.0 mg/100 g body wt but not 0.5 mg/100 g body wt. Histopathological analysis of pups treated with 1.5 mg U-75302/100 g body wt revealed fewer neutrophils in the pulmonary interstitium (198 vs. 218 mm-2, P < 0.05). The extent of lung microvascular permeability, elevated by hyperoxic exposure, was modulated by increasing concentrations of U-75302. Specifically, treatment with 0.5, 1.5 and 3.0 mg U-75302/100 g body wt reduced microvascular permeability by 17, 67 and 98%, respectively. In conclusion, LTB4 plays an important role in oedema formation in acute oxidative injury of the immature lung and this is mediated, in part, through neutrophils.

Detailed analysis of the pattern of human and rodent lung phosphatidylcholine (PC) species during fetal development revealed a progressive increase in two disaturated species. The rise in the fractional content of dipalmitoyl PC (PC16:0/16:0) and myristoylpalmitoyl PC (PC14:0/16:0) was accompanied at each time point by a fall of similar magnitude in palmitoyloleoyl PC (PC16:0/18:1). Up to 20% of term lung PC was PC14:0/16:0. The temporal increase in rodent lung PC saturation began later in gestation than the human, and in the rat a significant increase in PC saturation only occurred postnatally. In this respect the guinea pig more closely resembled the human. For each mammal, a ratio of whole lung PC16:0/16:0 to PC16:0/18:1 (the P/O ratio) provided a sensitive marker of fetal lung maturity. The PC composition of whole adult lung and its saturation enrichment in bronchoalveolar lavage samples were similar in human, guinea pig and rat. We propose that the guinea pig provides a useful model for human lung prematurity studies.