HIPTox-Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology: A Single-Centre Double-Blind Human Exposure Trial Protocol.

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre and post exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks.

Exposure risks of lead and other metals to humans: A consideration of specific size fraction and methodology.

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 (%GSFload), 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 %GSFload 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 (CaCO3, Fe3O4, Fe2O3, CaHPO4, Pb5(PO4)3Cl) 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.

Lead exposure in Chinese children: Urbanization lowers children's blood lead levels (BLLs).

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 < Igeo ≤ 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.

Long-term air pollution exposure and risk of SARS-CoV-2 infection: A UK-wide cohort study.

BACKGROUND: The association between air quality and risk of SARS-CoV-2 infection is poorly understood. We investigated this association using serological individual-level data adjusting for a wide range of confounders, in a large population-based cohort (COVIDENCE UK). METHODS: We assessed the associations between long-term (2015-19) nitrogen dioxide (NO2) and fine particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), exposures with SARS-CoV-2 infection, level of antibody response among those infected, and COVID-19 disease severity. We used serological data from 10,489 participants in the COVIDENCE UK cohort, and estimated annual average air pollution exposure at each participant's home postcode. RESULTS: After controlling for potential confounders, we found a positive association between 5-year NO2 and PM2.5 exposures and the risk of seropositivity: 10 unit increase in NO2 (µg/m3) was associated with an increasing risk of seropositivity by 1.092 (95% CI 1.02 to 1.17; p-for-trend 0.012). For PM2.5, 10 unit increase (µg/m3) was associated with an increasing risk of seropositivity by 1.65 (95% CI 1.015-2.68; p-for-trend 0·049). In addition, we found that NO2 was positively associated with higher antibody titres (p-for-trend 0·013) among seropositive participants, with no evidence of an association for PM2.5. CONCLUSION: Our findings suggest that the long-term burden of air pollution increased the risks of SARS-CoV-2 infection and has important implications for future pandemic preparedness. This evidence strengthens the case for reducing long-term air pollution exposures to reduce the vulnerability of individuals to respiratory viruses.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

Vitamin D3 regulates PM-driven primary human neutrophil inflammatory responses.

Recent evidence has demonstrated that both acute and chronic exposure to particulate air pollution are risk factors for respiratory tract infections and increased mortality from sepsis. There is therefore an urgent need to establish the impact of ambient particulate matter (PM) on innate immune cells and to establish potential strategies to mitigate against adverse effects. PM has previously been reported to have potential adverse effects on neutrophil function. In the present study, we investigated the impact of standard urban PM (SRM1648a, NIST) and PM2.5 collected from Chiang Mai, Thailand, on human peripheral blood neutrophil functions, including LPS-induced migration, IL-8 production, and bacterial killing. Both NIST and the PM2.5, being collected in Chiang Mai, Thailand, increased IL-8 production, but reduced CXCR2 expression and migration of human primary neutrophils stimulated with Escherichia coli LPS. Moreover, PM-pretreated neutrophils from vitamin D-insufficient participants showed reduced E. coli-killing activity. Furthermore, in vitro vitamin D3 supplementation attenuated IL-8 production and improved bacterial killing by cells from vitamin D-insufficient participants. Our findings suggest that provision of vitamin D to individuals with insufficiency may attenuate adverse acute neutrophilic responses to ambient PM.

Brownfield land and health: A systematic review of the literature.

BACKGROUND: Brownfield land is vacant or derelict land that was previously used for industrial or commercial purposes. Brownfield land is increasingly being targeted for housing development, however, depending on the previous use and remediation activity, it might pose potential risks to the health of residents on or in the vicinity of redeveloped sites. This systematic review of the literature synthesises the empirical evidence on the associations between brownfield land and health. METHODS: We systematically searched EMBASE, MEDLINE, Global Health, Web of Science, Scopus and GreenFile using a study protocol registered on PROSPERO (CRD42022286826). The search strategy combined the keywords "brownfield" and its interchangeable terms such as "previously developed land", and any health outcomes such as "respiratory diseases" and "mortality". Publications identified from the search were screened for eligibility by two authors, and data were extracted from the selected articles. Study quality was assessed based on the Newcastle-Ottawa Scale. RESULTS: Of the 1,987 records retrieved, 6 studies met the inclusion criteria; 3 ecological studies, 2 cross-sectional studies, and 1 longitudinal study. There was considerable heterogeneity in the exposure metrics and health outcomes assessed. All studies found significant positive associations between brownfield land proximity or density with at least one health relevant outcome, including poorer self-reported general health, increased mortality rates, increased birth defects, increased serum metal levels, and accelerated immune ageing. CONCLUSIONS: Brownfield land may negatively affect the health of nearby residents. The epidemiological evidence on health effects associated with brownfield land in local communities, however, remains inconclusive and limited. Further studies are required to build the evidence base to inform future housing policies and urban planning.

Associations between air pollution and mental health service use in dementia: a retrospective cohort study.

BACKGROUND: Little is known about the role of air pollution in how people with dementia use mental health services. OBJECTIVE: We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia. METHODS: In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models. FINDINGS: In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO2: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM2.5 and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO2 levels were linked with poor functional status, but not cognitive function. CONCLUSIONS: Residential air pollution exposure is associated with increased CMHT usage among people with dementia. CLINICAL IMPLICATIONS: Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.

Device-Measured Change in Physical Activity in Primary School Children During the UK COVID-19 Pandemic Lockdown: A Longitudinal Study.

BACKGROUND: Lockdown measures, including school closures, due to the COVID-19 pandemic have caused widespread disruption to children's lives. The aim of this study was to explore the impact of a national lockdown on children's physical activity using seasonally matched accelerometry data. METHODS: Using a pre/post observational design, 179 children aged 8 to 11 years provided physical activity data measured using hip-worn triaxial accelerometers worn for 5 consecutive days prepandemic and during the January to March 2021 lockdown. Multilevel regression analyses adjusted for covariates were used to assess the impact of lockdown on time spent in sedentary and moderate to vigorous physical activity. RESULTS: A 10.8-minute reduction in daily time spent in moderate to vigorous physical activity (standard error: 2.3 min/d, P < .001) and a 33.2-minute increase in daily sedentary activity (standard error: 5.5 min/d, P < .001) were observed during lockdown. This reflected a reduction in daily moderate to vigorous physical activity for those unable to attend school (-13.1 [2.3] min/d, P < .001) during lockdown, with no significant change for those who continued to attend school (0.4 [4.0] min/d, P < .925). CONCLUSION: These findings suggest that the loss of in-person schooling was the single largest impact on physical activity in this cohort of primary school children in London, Luton, and Dunstable, United Kingdom.

The Contribution of Environmental Science to Mental Health Research: A Scoping Review.

Mental health is influenced by multiple complex and interacting genetic, psychological, social, and environmental factors. As such, developing state-of-the-art mental health knowledge requires collaboration across academic disciplines, including environmental science. To assess the current contribution of environmental science to this field, a scoping review of the literature on environmental influences on mental health (including conditions of cognitive development and decline) was conducted. The review protocol was developed in consultation with experts working across mental health and environmental science. The scoping review included 202 English-language papers, published between 2010 and 2020 (prior to the COVID-19 pandemic), on environmental themes that had not already been the subject of recent systematic reviews; 26 reviews on climate change, flooding, air pollution, and urban green space were additionally considered. Studies largely focused on populations in the USA, China, or Europe and involved limited environmental science input. Environmental science research methods are primarily focused on quantitative approaches utilising secondary datasets or field data. Mental health measurement was dominated by the use of self-report psychometric scales. Measures of environmental states or exposures were often lacking in specificity (e.g., limited to the presence or absence of an environmental state). Based on the scoping review findings and our synthesis of the recent reviews, a research agenda for environmental science's future contribution to mental health scholarship is set out. This includes recommendations to expand the geographical scope and broaden the representation of different environmental science areas, improve measurement of environmental exposure, prioritise experimental and longitudinal research designs, and giving greater consideration to variation between and within communities and the mediating pathways by which environment influences mental health. There is also considerable opportunity to increase interdisciplinarity within the field via the integration of conceptual models, the inclusion of mixed methods and qualitative approaches, as well as further consideration of the socio-political context and the environmental states that can help support good mental health. The findings were used to propose a conceptual model to parse contributions and connections between environmental science and mental health to inform future studies.

Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models.

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.

The relationship between air pollution and multimorbidity: Can two birds be killed with the same stone?

Air pollution and multimorbidity are two of the most important challenges for Public Health worldwide. Although there is a large body of evidence linking air pollution with the development of different single chronic conditions, the evidence about the relationship between air pollution and multimorbidity (the co-occurrence of multiple long-term conditions) is sparse. To obtain evidence about this relationship could be challenging and different aspects should be considered, such as its multifaceted and complex nature, the specific pollutants and their potential influence on health, their levels of exposure over time, or the data that could be used for its study. This evidence could be instrumental to inform the development of new recommendations and measures to reduce harmful levels of air pollutants, as means to prevent the development of multimorbidity and reduce its burden.

Characteristics of fine and ultrafine aerosols in the London underground.

Underground railway systems are recognised spaces of increased personal pollution exposure. We studied the number-size distribution and physico-chemical characteristics of ultrafine (PM0.1), fine (PM0.1-2.5) and coarse (PM2.5-10) particles collected on a London underground platform. Particle number concentrations gradually increased throughout the day, with a maximum concentration between 18:00 h and 21:00 h (local time). There was a maximum decrease in mass for the PM2.5, PM2.5-10 and black carbon of 3.9, 4.5 and ~ 21-times, respectively, between operable (OpHrs) and non-operable (N-OpHrs) hours. Average PM10 (52 µg m-3) and PM2.5 (34 µg m-3) concentrations over the full data showed levels above the World Health Organization Air Quality Guidelines. Respiratory deposition doses of particle number and mass concentrations were calculated and found to be two- and four-times higher during OpHrs compared with N-OpHrs, reflecting events such as train arrival/departure during OpHrs. Organic compounds were composed of aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs) which are known to be harmful to health. Specific ratios of PAHs were identified for underground transport that may reflect an interaction between PAHs and fine particles. Scanning transmission electron microscopy (STEM) chemical maps of fine and ultrafine fractions show they are composed of Fe and O in the form of magnetite and nanosized mixtures of metals including Cr, Al, Ni and Mn. These findings, and the low air change rate (0.17 to 0.46 h-1), highlight the need to improve the ventilation conditions.

Association of Ambient Air Pollution with Blood Pressure in Adolescence: A Systematic-review and Meta-analysis.

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 PM10, PM2.5, and NO2 on systolic and diastolic BP. At age 12 years old (3702 adolescents), we found significant positive associations for long-term exposure to PM2.5(ß=5.33 (1.56, 9.09) mmHg) and PM10 (ß=2.47 (0.10, 4.85) mmHg) on diastolic BP. Significant positive associations were observed (3,592 adolescents) for long-term exposure to PM10(ß=0.34 (0.19, 0.50) mmHg) and NO2 on diastolic BP (ß=0.40 (0.09, 0.71) mmHg), and PM10 on systolic BP (ß=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 PM2.5, PM10, NO2, 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.

Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.

Background: Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort. Methods: Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (µg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators. Results: Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)]. Conclusions: This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.

A Review of Road Traffic-Derived Non-Exhaust Particles: Emissions, Physicochemical Characteristics, Health Risks, and Mitigation Measures.

Implementation of regulatory standards has reduced exhaust emissions of particulate matter from road traffic substantially in the developed world. However, nonexhaust particle emissions arising from the wear of brakes, tires, and the road surface, together with the resuspension of road dust, are unregulated and exceed exhaust emissions in many jurisdictions. While knowledge of the sources of nonexhaust particles is fairly good, source-specific measurements of airborne concentrations are few, and studies of the toxicology and epidemiology do not give a clear picture of the health risk posed. This paper reviews the current state of knowledge, with a strong focus on health-related research, highlighting areas where further research is an essential prerequisite for developing focused policy responses to nonexhaust particles.

Identifying trends in ultrafine particle infiltration and carbon dioxide ventilation in 92 vehicle models.

There has been ongoing research aimed at reducing pollution concentrations in vehicles due to the high exposure which occurs in this setting. These studies have found using recirculate (RC) settings substantially reduces in-cabin traffic-related pollution concentrations but possibly leads to an adverse accumulation of carbon dioxide (CO2) from driver respiration. The aim of this study was to highlight how vehicle models and ventilation settings affect in-cabin concentrations to ultrafine particles (UFP) and CO2 in real-world conditions. We assessed the ability of different vehicles to balance reductions in UFP against the build-up of in-cabin CO2 concentrations by measuring these pollutants concurrently both inside and outside the vehicle to derive an in/out ratio. When ventilation settings were set to RC, UFP concentrations inside the vehicles (median: 3205 pt./cm3) were 86% lower compared to outside air (OA) (23,496 pt./cm3) across a 30-min real-world driving route. However, CO2 concentrations demonstrated a rapid linear increase under RC settings, at times exceeding 2500 ppm. These concentrations have previously been associated with decreased cognitive performance. Our study did not find an effect of gasoline fuelled vehicles affecting in-cabin UFP levels compared to hybrid or electric vehicles, suggesting that self-pollution was not an issue. We also found that certain vehicle models were better at reducing both in-cabin UFP and CO2 concentrations. The results suggest that under RC settings in/out CO2 ratios are largely determined by the leakiness of the vehicle cabin, whereas in/out UFP ratios are primarily determined by the efficacy of the in-built air filter in the vehicles ventilation system.

Alterations to the urinary metabolome following semi-controlled short exposures to ultrafine particles at a major airport.

BACKGROUND: Inflammation, oxidative stress and reduced cardiopulmonary function following exposure to ultrafine particles (UFP) from airports has been reported but the biological pathways underlying these toxicological endpoints remain to be explored. Urinary metabolomics offers a robust method by which changes in cellular pathway activity can be characterised following environmental exposures. OBJECTIVE: We assessed the impact of short-term exposures to UFP from different sources at a major airport on the human urinary metabolome. METHODS: 21 healthy, non-smoking volunteers (aged 19-27 years) were repeatedly (2-5 visits) exposed for 5h to ambient air at Amsterdam Airport Schiphol, while performing intermittent, moderate exercise. Pre- to-post exposure changes in urinary metabolite concentrations were assessed via 1H NMR spectroscopy and related to total and source-specific particle number concentrations (PNC) using linear mixed effects models. RESULTS: Total PNC at the exposure site was on average, 53,500 particles/cm3 (range 10,500-173,200) and associated with significant reductions in urinary taurine (-0.262 AU, 95% CI: -0.507 to -0.020) and dimethylamine concentrations (-0.021 AU, 95% CI: -0.040 to -0.067). Aviation UFP exposure accounted for these changes, with the reductions in taurine and dimethylamine associating with UFP produced during both aircraft landing and take-off. Significant reductions in pyroglutamate concentration were also associated with aviation UFP specifically, (-0.005 AU, 95% CI: -0.010 - <0.000) again, with contributions from both landing and take-off UFP exposure. While non-aviation UFPs induced small changes to the urinary metabolome, their effects did not significantly impact the overall response to airport UFP exposure. DISCUSSION: Following short-term exposures at a major airport, aviation-related UFP caused the greatest changes to the urinary metabolome. These were consistent with a heightened antioxidant response and altered nitric oxide synthesis. Although some of these responses could be adaptive, they appeared after short-term exposures in healthy adults. Further study is required to determine whether long-term exposures induce injurious effects.

Putting Fine Particulate Matter and Dementia in the Wider Context of Noncommunicable Disease: Where are We Now and What Should We Do Next: A Systematic Review.

INTRODUCTION: A significant proportion of the global population regularly experience air quality poorer than that recommended by the World Health Organization. Air pollution, especially fine particulate matter (PM2.5), is a risk factor for various noncommunicable diseases (NCDs) and is emerging as a risk factor for dementia. To begin to understand the full impact of PM2.5, we review the longitudinal epidemiological evidence linking PM2.5 to both dementia and to other leading NCDs and highlight the evidence gaps. Our objective was to systematically review the current epidemiological evidence for PM2.5 as a risk factor for cognitive decline and incident dementia and to put this in context with a systematic overview of PM2.5 as a potential risk factor in other leading NCDs. METHODS: We performed 2 systematic reviews. A high-level review of reviews examining the relationship between PM2.5 and leading NCDs and an in-depth review of the longitudinal epidemiological data examining relationships between PM2.5 incident dementia and cognitive decline. RESULTS: There were robust associations between PM2.5 and NCDs although in some cases the evidence was concentrated on short rather than longer term exposure. For those articles reporting on incident dementia, all reported on longer term exposure and 5 of the 7 eligible articles found PM2.5 to be associated with increased risk. CONCLUSION: The evidence base for PM2.5 as a risk factor for dementia is growing. It is not yet as strong as that for other NCDs. However, varied measurement/methodology hampers clarity across the field. We propose next steps.

Acute cardiovascular effects of controlled exposure to dilute Petrodiesel and biodiesel exhaust in healthy volunteers: a crossover study.

BACKGROUND: Air pollution derived from combustion is associated with considerable cardiorespiratory morbidity and mortality in addition to environmental effects. Replacing petrodiesel with biodiesel may have ecological benefits, but impacts on human health remain unquantified. The objective was to compare acute cardiovascular effects of blended and pure biodiesel exhaust exposure against known adverse effects of petrodiesel exhaust (PDE) exposure in human subjects. In two randomized controlled double-blind crossover studies, healthy volunteers were exposed to PDE or biodiesel exhaust for one hour. In study one, 16 subjects were exposed, on separate occasions, to PDE and 30% rapeseed methyl ester biodiesel blend (RME30) exhaust, aiming at PM10 300 µg/m3. In study two, 19 male subjects were separately exposed to PDE and exhaust from a 100% RME fuel (RME100) using similar engine load and exhaust dilution. Generated exhaust was analyzed for physicochemical composition and oxidative potential. Following exposure, vascular endothelial function was assessed using forearm venous occlusion plethysmography and ex vivo thrombus formation was assessed using a Badimon chamber model of acute arterial injury. Biomarkers of inflammation, platelet activation and fibrinolysis were measured in the blood. RESULTS: In study 1, PDE and RME30 exposures were at comparable PM levels (314 ± 27 µg/m3; (PM10 ± SD) and 309 ± 30 µg/m3 respectively), whereas in study 2, the PDE exposure concentrations remained similar (310 ± 34 µg/m3), but RME100 levels were lower in PM (165 ± 16 µg/m3) and PAHs, but higher in particle number concentration. Compared to PDE, PM from RME had less oxidative potential. Forearm infusion of the vasodilators acetylcholine, bradykinin, sodium nitroprusside and verapamil resulted in dose-dependent increases in blood flow after all exposures. Vasodilatation and ex vivo thrombus formation were similar following exposure to exhaust from petrodiesel and the two biodiesel formulations (RME30 and RME100). There were no significant differences in blood biomarkers or exhaled nitric oxide levels between exposures. CONCLUSIONS: Despite differences in PM composition and particle reactivity, controlled exposure to biodiesel exhaust was associated with similar cardiovascular effects to PDE. We suggest that the potential adverse health effects of biodiesel fuel emissions should be taken into account when evaluating future fuel policies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01337882 /NCT01883466. Date of first enrollment March 11, 2011, registered April 19, 2011, i.e. retrospectively registered.