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).

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.

Association between air pollution exposure and mental health service use among individuals with first presentations of psychotic and mood disorders: retrospective cohort study.

BACKGROUND: Growing evidence suggests that air pollution exposure may adversely affect the brain and increase risk for psychiatric disorders such as schizophrenia and depression. However, little is known about the potential role of air pollution in severity and relapse following illness onset. AIMS: To examine the longitudinal association between residential air pollution exposure and mental health service use (an indicator of illness severity and relapse) among individuals with first presentations of psychotic and mood disorders. METHOD: We identified individuals aged ≥15 years who had first contact with the South London and Maudsley NHS Foundation Trust for psychotic and mood disorders in 2008-2012 (n = 13 887). High-resolution (20 × 20 m) estimates of nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. In-patient days and community mental health service (CMHS) events were recorded over 1-year and 7-year follow-up periods. RESULTS: Following covariate adjustment, interquartile range increases in NO2, NOx and PM2.5 were associated with 18% (95% CI 5-34%), 18% (95% CI 5-34%) and 11% (95% CI 3-19%) increased risk for in-patient days after 1 year. Similarly, interquartile range increases in NO2, NOx, PM2.5 and PM10 were associated with 32% (95% CI 25-38%), 31% (95% CI 24-37%), 7% (95% CI 4-11%) and 9% (95% CI 5-14%) increased risk for CMHS events after 1 year. Associations persisted after 7 years. CONCLUSIONS: Residential air pollution exposure is associated with increased mental health service use among people recently diagnosed with psychotic and mood disorders. Assuming causality, interventions to reduce air pollution exposure could improve mental health prognoses and reduce healthcare costs.

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.

Mental health consequences of urban air pollution: prospective population-based longitudinal survey.

PURPOSE: The World Health Organisation (WHO) recently ranked air pollution as the major environmental cause of premature death. However, the significant potential health and societal costs of poor mental health in relation to air quality are not represented in the WHO report due to limited evidence. We aimed to test the hypothesis that long-term exposure to air pollution is associated with poor mental health. METHODS: A prospective longitudinal population-based mental health survey was conducted of 1698 adults living in 1075 households in South East London, from 2008 to 2013. High-resolution quarterly average air pollution concentrations of nitrogen dioxide (NO2) and oxides (NOx), ozone (O3), particulate matter with an aerodynamic diameter < 10 µm (PM10) and < 2.5 µm (PM2.5) were linked to the home addresses of the study participants. Associations with mental health were analysed with the use of multilevel generalised linear models, after adjusting for large number of confounders, including the individuals' socioeconomic position and exposure to road-traffic noise. RESULTS: We found robust evidence for interquartile range increases in PM2.5, NOx and NO2 to be associated with 18-39% increased odds of common mental disorders, 19-30% increased odds of poor physical symptoms and 33% of psychotic experiences only for PM10. These longitudinal associations were more pronounced in the subset of non-movers for NO2 and NOx. CONCLUSIONS: The findings suggest that traffic-related air pollution is adversely affecting mental health. Whilst causation cannot be proved, this work suggests substantial morbidity from mental disorders could be avoided with improved air quality.

Mechanistic link between diesel exhaust particles and respiratory reflexes.

BACKGROUND: Diesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm. OBJECTIVE: We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs. METHODS: In this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus. RESULTS: We demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers. CONCLUSIONS: This study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.

Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes.

Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPMin vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.

PURPOSE: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. METHODS: The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF. RESULTS: SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution. CONCLUSION: The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.

Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid.

When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. FROM THE CLINICAL EDITOR: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics.

Acute exposure to wood smoke from incomplete combustion--indications of cytotoxicity.

BACKGROUND: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. METHODS: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 µg/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. RESULTS: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. CONCLUSIONS: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure. TRIAL REGISTRATION: NCT01488500.

Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium - an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects.

BACKGROUND: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms. METHODS: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 µg/m(3)) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis. RESULTS: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge. CONCLUSION: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.

Carbon in airway macrophages from children with asthma.

BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. METHODS: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers.

BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects. METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells. RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells. CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Air pollution exposure affects circulating white blood cell counts in healthy subjects: the role of particle composition, oxidative potential and gaseous pollutants - the RAPTES project.

Studies have linked air pollution exposure to cardiovascular health effects, but it is not clear which components drive these effects. We examined the associations between air pollution exposure and circulating white blood cell (WBC) counts in humans. To investigate independent contributions of particulate matter (PM) characteristics, we exposed 31 healthy volunteers at five locations with high contrast and reduced correlations amongst pollutant components: two traffic sites, an underground train station, a farm and an urban background site. Each volunteer visited at least three sites and was exposed for 5 h with intermittent exercise. Exposure measurements on-site included PM mass and number concentration, oxidative potential (OP), elemental- and organic carbon, metals, O3 and NO2. Total and differential WBC counts were performed on blood collected before and 2 and 18 h post-exposure (PE). Changes in total WBC counts (2 and 18 h PE), number of neutrophils (2 h PE) and monocytes (18 h PE) were positively associated with PM characteristics that were high at the underground site. These time-dependent changes reflect an inflammatory response, but the characteristic driving this effect could not be isolated. Negative associations were observed for NO2 with lymphocytes and eosinophils. These associations were robust and did not change after adjustment for a large suite of PM characteristics, suggesting an independent effect of NO2. We conclude that short-term air pollution exposure at real-world locations can induce changes in WBC counts in healthy subjects. Future studies should indicate if air pollution exposure-induced changes in blood cell counts results in adverse cardiovascular effects in susceptible individuals.

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.

Acute nasal pro-inflammatory response to air pollution depends on characteristics other than particle mass concentration or oxidative potential: the RAPTES project.

OBJECTIVES: To investigate which air pollution characteristics are associated with biomarkers for acute nasal airway inflammation in healthy subjects. We hypothesised that associations would be strongest for oxidative potential (OP) of particles. METHODS: 31 volunteers were exposed to ambient air pollution at five sites in The Netherlands: two traffic sites, an underground train station, a farm and an urban background site. Each subject visited at least three sites between March and October 2009 and was exposed for 5 h per visit including exercise for 20 min every hour (h). Air pollution measurements during this 5-h-period included particulate matter (PM) mass concentration, elemental composition, elemental and organic carbon (OC), particle number concentration, OP, endotoxins, O3 and NO2. Pro-inflammatory biomarkers were measured before, 2 and 18 h postexposure, including cytokine IL-6 and IL-8, protein and lactoferrin in nasal lavage (NAL) as well as IL-6 in blood. One- and two-pollutant mixed models were used to analyse associations between exposure and changes in biomarkers. RESULTS: In two-pollutant models, cytokines in NAL were positively associated with OC, endotoxin and NO2; protein was associated with NO2; and lactoferrin was associated with all PM characteristics that were high at the underground site. In blood, associations with OC and endotoxin were negative. CONCLUSIONS: We observed no consistent effects in two-pollutant models for PM mass concentration and OP. Instead, we found consistent associations with nasal inflammatory markers for other PM characteristics, specifically OC, endotoxin and NO2.

Components of ambient air pollution affect thrombin generation in healthy humans: the RAPTES project.

OBJECTIVES: Increases in ambient particulate matter (PM) have been associated with an elevated risk of stroke, myocardial ischaemia and coronary heart disease, with activation of blood coagulation likely playing an important role. PM-mediated activation of two major activation pathways of coagulation provides a potential mechanism for the observed association between PM and cardiovascular disease. However, it remains unclear which specific characteristics and components of air pollution are responsible. METHODS: In order to investigate those characteristics and components, we semiexperimentally exposed healthy adult volunteers at five different locations with increased contrasts and reduced correlations among PM characteristics. Volunteers were exposed for 5 h, exercising intermittently, 3-7 times at different sites from March to October 2009. On site, we measured PM mass and number concentration, its oxidative potential (OP), content of elemental/organic carbon, trace metals, sulphate, nitrate and gaseous pollutants (ozone, nitrogen oxides). Before and 2 and 18 h after exposure we sampled blood from the participants and measured thrombin generation using the calibrated automated thrombogram. RESULTS: We found that thrombin generation increases in the intrinsic (FXII-mediated) blood coagulation pathway in relation to ambient air pollution exposure. The associations with NO2, nitrate and sulphate were consistent and robust, insensitive to adjustment for other pollutants. The associations with tissue factor-mediated thrombogenicity were not very consistent. CONCLUSIONS: Ex vivo thrombin generation was associated with exposure to NO2, nitrate and sulphate, but not PM mass, PM OP or other measured air pollutants.