Human Exposure Studies Research Articles

Effect of Traffic-Related Air Pollution on Spontaneous Baroreceptor Sensitivity: A Trial of In-Vehicle Filtration

Human controlled exposure studies suggest that diesel exhaust causes acute changes in blood pressure that are mediated by sympathetic activation, but it is unknown whether this sympathetic response might also cause imbalance directly affecting cardiac autonomic control. Baroreceptor sensitivity (BRS) measures rapid compensatory regulation of heart rate in response to acute changes in blood pressure. Using a crossover trial of real-world in-vehicle commutes, we tested whether exposure to traffic-related air pollutants (TRAP) affects spontaneous BRS in healthy subjects.Young healthy participants were driven through heavy Seattle, WA traffic for two hours on three different days, each separated by several weeks. On two days, on-road air was entrained into the cabin through the vehicle’s factory air vents and sham filters. On another day, the vehicle was equipped with effective filtration. Exposure was double-blinded and participants were randomized to order of exposure. Three minute intervals of continuous blood pressure and pulse intervals were recorded before, during, and up to 24 hours after drive using a Finapres finger pulse waveform device. BRS was calculated as the reduced major axis slope for change in pulse interval per change in blood pressure for rolling 10 second intervals.On filtered days in-vehicle average particle count was reduced by 85%. We used a mixed effects model on the outcome of change from pre-drive BRS measurements, comparing filtered versus unfiltered day at all thirteen time points in nine subjects with measurable BRS, after excluding a single subject with very large changes in BRS. A likelihood ratio test for the effect of filtration on BRS at all time points was not significant (p=0.95). At 7 hours after drive start, BRS, relative to pre-drive levels, was on average 1.01 ms/mmHg higher (95% CI:-7.4, 9.4) in unfiltered drives compared to filtered drives. In conclusion, we did not find evidence that TRAP inhalation causes acute change in BRS.

Global Evidence of Adverse Health Effects Associated with Residential Wood-Burning

Evidence supporting an association between short-term and long-term exposure to several air pollutants, including fine particulate matter, ozone, nitrogen dioxide, and carbon monoxide matter, and multiple health effects is robust. However, evidence regarding exposure to air pollutants emitted from specific sources is more limited. Residential wood-burning emits various components of air pollution and is an important source of ambient, household, and indoor air pollution in many locations throughout the world. In many lower- and middle-income countries, wood, and more broadly biomass, is used by a large proportion of the population for cooking and heating needs and contributes to both household and ambient air pollution. In high-income countries, residential wood-burning is primarily for heating purposes and varies substantially by region and by economic drivers; however, even in high-income countries residential wood-burning can be an important source for both indoor and ambient air pollution. Globally, there have been efforts to reduce exposures resulting from residential wood-burning through the use of improved technology, alternative fuels, regulations, and other approaches, with varying degrees of success. Here, we will review evidence of adverse health effects associated with residential wood-burning from various fields, including ambient air pollution, household air pollution, indoor air pollution, and controlled human exposure studies; we will draw from related evidence, such as wildfire smoke. Synthesizing evidence from across these fields allows for a broader picture of the current evidence, including areas of inconsistent evidence and research needs.

Redefining environmental exposure for disease etiology

Etiological studies of human exposures to environmental factors typically rely on low-throughput methods that target only a few hundred chemicals or mixtures. In this Perspectives article, I outline how environmental exposure can be defined by the blood exposome—the totality of chemicals circulating in blood. The blood exposome consists of chemicals derived from both endogenous and exogenous sources. Endogenous chemicals are represented by the human proteome and metabolome, which establish homeostatic networks of functional molecules. Exogenous chemicals arise from diet, vitamins, drugs, pathogens, microbiota, pollution, and lifestyle factors, and can be measured in blood as subsets of the proteome, metabolome, metals, macromolecular adducts, and foreign DNA and RNA. To conduct ‘exposome-wide association studies’, blood samples should be obtained prospectively from subjects—preferably at critical stages of life—and then analyzed in incident disease cases and matched controls to find discriminating exposures. Results from recent metabolomic investigations of archived blood illustrate our ability to discover potentially causal exposures with current technologies.

Air pollution and resistance to inhaled glucocorticoids: Evidence, mechanisms and gaps to fill.

Substantial evidence indicates that cigarette smoke exposure induces resistance to glucocorticoids, the primary maintenance medication in asthma treatment. Modest evidence also suggests that air pollution may reduce the effectiveness of these critical medications. Cigarette smoke, which has clear parallels with air pollution, has been shown to induce glucocorticoid resistance in asthma and it has been speculated that air pollution may have similar effects. However, the literature on an association of air pollution with glucocorticoid resistance is modest to date. In this review, we detail the evidence for, and against, the effects of air pollution on glucocorticoid effectiveness, focusing on results from epidemiology and controlled human exposure studies. Epidemiological studies indicate a correlation between increased air pollution exposure and worse asthma symptoms. But these studies also show a mix of beneficial and harmful effects of glucocorticoids on spirometry and asthma symptoms, perhaps due to confounding influences, or the induction of glucocorticoid resistance. We describe mechanisms that may contribute to reductions in glucocorticoid responsiveness following air pollution exposure, including changes to phosphorylation or oxidation of the glucocorticoid receptor, repression by cytokines, or inflammatory pathways, and epigenetic effects. Possible interactions between air pollution and respiratory infections are also briefly discussed. Finally, we detail a number of therapies that may boost glucocorticoid effectiveness or reverse resistance in the presence of air pollution, and comment on the beneficial effects of engineering controls, such as air filtration and asthma action plans. We also call attention to the benefits of improved clean air policy on asthma. This review highlights numerous gaps in our knowledge of the interactions between air pollution and glucocorticoids to encourage further research in this area with a view to reducing the harm caused to those with airways disease.

Aflatoxin exposure assessed by aflatoxin albumin adduct biomarker in populations from six African countries: REVIEW ARTICLE.

Aflatoxins are a group of carcinogenic mycotoxins that have been implicated to have other adverse health impacts, including child growth impairment and immune function suppression. Aflatoxin B1 is the most toxic and most common of the aflatoxins. Contamination of various food crops is common in sub-Saharan Africa, particularly in staple crops such as maize and groundnuts, leading to chronic dietary exposure in many populations. For many years we have used the aflatoxin albumin adduct as a biomarker of aflatoxin exposure, assessed using a competitive inhibition enzyme linked immunosorbent assay (ELISA). Here, we review our recent studies of human exposure in six African countries; Gambia, Guinea, Kenya, Senegal, Tanzania and Uganda. This data shows the widespread exposure of vulnerable populations to aflatoxin. Geometric mean (95% confidence interval) levels of the biomarker ranged from 9.7 pg/mg (8.2, 11.5) in Ugandan children to 578.5 pg/mg (461.4, 717.6) in Kenyan adolescents during an acute aflatoxicosis outbreak year. We describe how various factors may have influenced the variation in aflatoxin exposure in our studies. Together, these studies highlight the urgent need for measures to reduce the burden of aflatoxin exposure in sub-Saharan Africa.

PM2.5 and its ionic components at a roadside site in Wuhan, China

PM2.5 samples were collected at a roadside site in Wuhan, China, for one year period. Ion chromatography was used to determine the water soluble ions in PM2.5 samples. Results showed that the overall average of PM2.5 mass was 118.1 ± 70.3 μg m−3, being slightly higher than those measured in urban sites in Wuhan, China. The major water soluble ions were NH4+ (8.7 ± 4.0 μg m−3), NO3− (12.1 ± 9.5 μg m−3), SO42− (15.2 ± 8.2 μg m−3), accounting for 21%、29%、37% of quantified total ions, respectively. NH4+, NO3−, and SO42− were closely correlated, and (NH4)2SO4 and NH4NO3 were possibly their main existing forms. Ion concentrations differed greatly in different seasons, with inconsistent variation pattern for individual ions. Values of NOR (nitrogen oxidation ratio) and SOR (sulfur oxidation ratio) peaked in winter and in summer, respectively. NO3−/SO42− ratio revealed that emission from stationary sources was still remarkable. Significant correlation was observed between Mg2+ and Ca2+, possibly due to their common source of soil dust. On the other hand, Cl− linked with K+, NO3−, NH4+, and SO42−. The data reported here will provide inputs for human exposure and air pollution control studies in Wuhan, China.

Ozone augments interleukin-8 production induced by ambient particulate matter

BackgroundExperimental and controlled human exposure studies have demonstrated additive effects of ambient particulate matter and ozone on health. A few epidemiological studies have suggested that ambient particulate matter components are important for the combined effects of ambient particulate matter and ozone on health. However, few studies have examined whether ozone changes the effects of ambient particulate matter on pro-inflammatory cytokine production. In this study, the influence of ozone on pro-inflammatory cytokine production in response to ambient particulate matter was evaluated.ResultsAmbient particulate matter smaller than 1 μm was collected and the suspension of this particulate matter was bubbled through 0.12 ppm and 0.24 ppm ozone. THP1 cells were stimulated by the solution containing the particulate matter with and without bubbling through ozone at 1 μg/mL. The interleukin-8 concentrations in the supernatants of THP1 cells stimulated by collected particulate matter dissolved in solution were 108.3 ± 24.7 pg/mL without ozone exposure, 165.0 ± 26.1 pg/mL for 0.12 ppm ozone bubbling for 1 min, 175.1 ± 33.1 pg/mL for 0.12 ppm for 5 min, 183.3 ± 17.8 pg/mL for 0.12 ppm for 15 min, 167.8 ± 35.9 pg/mL for 0.24 ppm for 1 min, 209.2 ± 8.4 pg/mL for 0.24 ppm for 5 min, and 209.3 ± 14.3 pg/mL for 0.24 ppm for 15 min. Ozone significantly increased interleukin-8 concentrations compared to those for particulate matter dissolved in solution without ozone exposure and the solvent only (8.2 ± 0.9 pg/mL) in an ozone concentration-dependent manner. Collected particulate matter in solutions with or without bubbling through ozone had no effect on interleukin-6 production. The antioxidant N-acetyl-L-cysteine significantly inhibited the increases in interleukin-8 induced by solutions with particulate matter, regardless of ozone exposure. The reactive oxygen species concentration in solutions with collected particulate matter was not associated with ozone bubbling.ConclusionOzone may augment the production of interleukin-8 in response to ambient particulate matter by a mechanism unrelated to reactive oxygen species. These results support the epidemiological evidence for combined effects of ambient particulate matter and ozone on human health.

Ultraviolet Radiation Albedo and Reflectance in Review: The Influence to Ultraviolet Exposure in Occupational Settings.

Ultraviolet (UV) albedo and UV reflectance are defined, compared and contrasted, to explain their roles and place in studies focusing on UV radiation and exposure measurements, in the context of localised albedo measurement and human UV exposure studies. This review recommends that the term UV albedo be used when investigating natural horizontal surfaces when the albedo is not known to change significantly over time. The term UV reflectance should be mostly used for non-natural surfaces and non-horizontal measurements and will change with respect to the geometry of the irradiances reflected and received, and due to the intrinsic nature of the surface itself. UV albedo measurements made in the literature have been compiled, in both broadband and spectral UV albedo measurements. Broadband measurements have been tabulated and spectral UV measurements have been displayed visually. The methodology of measurements is briefly discussed. Finally, studies that consider how high albedo or reflectance sites influence UV exposure are reviewed. It was concluded that there is currently no known relationship between the albedo or reflectance of a surface and the resulting influence it has on individual UV exposure. This presents an opportunity for researchers to continue exploring the influence of reflective UV surfaces.

High-throughput and sensitive determination of urinary zearalenone and metabolites by UPLC-MS/MS and its application to a human exposure study.

Biomarker-based strategies to assess human exposure to mycotoxins have gained increased acceptance in recent years. In this study, an improved method based on UPLC-MS/MS following 96-well μElution solid-phase extraction was developed and validated for the sensitive and high-throughput determination of zearalenone (ZEN) and its five metabolites α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), and zearalanone (ZAN) in human urine samples, using 13C-ZEN as an internal standard for accurate quantification. Two plates of samples (n = 192) could be processed within 2h, and baseline separation of all the analytes was achieved in a total runtime of 6min. The proposed method allowed ZEN and its metabolites to be sensitively determined in a high-throughput way for the first time, and with significantly improved efficiency and accuracy with respect to existing methods. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.02 to 0.06ngmL-1 and from 0.05 to 0.2ngmL-1, respectively. The recoveries for the spiked samples were from 87.9 to 100%, with relative standard deviations (RSDs) of less than 7%. 301 urine samples collected from healthy volunteers aged 0-84years in China were analyzed with and without enzyme hydrolysis to determine total and free ZEN biomarkers, respectively. ZEN, ZAN, α-ZEL, and β-ZEL were detected in 71.4% of the samples at levels of 0.02-3.7ngmL-1 after enzyme hydrolysis. The estimated mean probable daily intake (PDI) was much lower than the tolerable daily intake (TDI). Adolescents had higher exposure than children, adults, and the elderly. Graphical abstract ᅟ.

Verifying community-wide exposure to endocrine disruptors in personal care products – In quest for metabolic biomarkers of exposure via in vitro studies and wastewater-based epidemiology

This study aimed to identify human specific metabolites of selected known or suspected endocrine disruptors (EDCs), mainly UV filters, used in personal care and consumer products whose metabolism has hardly been explored and to select suitable candidate biomarkers for human exposure studies using wastewater based epidemiology (WBE). The analysis of metabolic biomarkers of target chemicals is crucial in order to distinguish between internal and external exposure, since many sources contribute to chemicals being discharged into wastewater. This was achieved through the employment of a new analytical framework for verification of biomarkers of exposure to chemicals combining human biomonitoring and water fingerprinting. Eight EDCs with unknown metabolic pathways (benzophenone-1 (BP-1); benzophenone-2 (BP-2); 4,4′-dihydroxybenzophenone (4,4′-DHBP); 4-benzylphenol (4-BenzPh); homosalate (HO); octocrylene (OC); 3-benzylidene camphor (3-BC), and two EDCs with known metabolism (bisphenol A (BPA) and benzophenone-3 (BP-3)) were tested. The biotransformation observed consisted mainly of phase I processes such as hydrolysis and hydroxylation together with phase II conjugation reactions such as sulphation and glucuronidation. Only two chemicals (BP-1, BP-3) were identified in urine and three chemicals (BPA, BP-1, BP-3) in wastewater. Five newly discovered metabolites (HO-Met1, OC-Met1, 4-BenzPh-Met4, 4-BenzPh-Met5 and 4-BenzPh-Met6) and one previously known metabolite (BPA-Met3) were detected in tested urine/wastewater samples from five WWTPs serving large communities ranging between 17 and 100 thousand inhabitants. The presence of metabolic biotransformation products of OC, 4-BenzPh, BPA and HO in wastewater provides evidence for internal exposure of studied populations to these chemicals.

Insights in particulate matter-induced allergic airway inflammation: Focus on the epithelium.

Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM-induced respiratory responses. We describe the available literature on the topic including invitro studies, findings in humans (ie observations in human cohorts, human controlled exposure and exvivo studies) and invivo animal studies. In brief, it has been shown that exposure to PM modulates the airway epithelium and promotes the production of several cytokines, including IL-1, IL-6, IL-8, IL-25, IL-33, TNF-α, TSLP and GM-CSF. Further, we propose that PM-induced type 2-promoting cytokines are important mediators in the acute and aggravating effects of PM on airway inflammation. Targeting these cytokines could therefore be a new approach in the treatment of asthma.

Organic UV filters in indoor dust and human urine: A study of characteristics, sources, associations and human exposure

Organic ultraviolet (UV) filters are emerging contaminants that may pose health risks to humans. We measured the concentrations of four commonly used organic UV filters (2-hydroxy-4-methoxybenzophenone (BP-3), 4-methylbenzylidene camphor (4-MBC), homosalate (HMS), and octocrylene (OC)) in 203 indoor dust samples and 98 human urine samples from households in eastern China. The total concentrations of the four organic UV filters ranged from 66.6–56,123.0 ng g−1 in indoor dust and 1.17–52.15 μg g−1 (creatinine-adjusted concentration (Cr)) in urine. BP-3 was the most abundant organic UV filter in the urine samples (median concentration: 1.89 μg g−1 Cr), while OC was the most abundant in the indoor dust samples (median concentration: 325.7 ng g−1). No significant correlations were found between organic UV filter concentrations in paired urine and dust samples, but the concentrations of UV filters in the indoor dust samples were positively correlated with family income and sunscreen use. The sources of the organic UV filters in the indoor dust samples differed based on the geographical location of the tested household. The fraction of human exposure to organic UV filters that resulted from ingestion or dermal absorption of indoor dust was close to 8%.

Carboxyhaemoglobin Levels among Traders Exposed to Vehicular Emissions in Three Motor Parks in Ibadan, Nigeria.

Carbon monoxide (CO) remains a leading cause of work-related chemical poisoning. Vehicular emissions are the primary daily ambient source of CO in urban Nigerian motor parks, where there have been few human exposure studies. Using a cross-sectional comparative design, we assessed carboxyhaemoglobin levels (% COHb), a biomarker of CO exposure, among traders at three motor parks (AMP, IMP, and NMP) and other traders (nonmotor park workers) in Ibadan, Nigeria, using a noninvasive pulse CO-dosimeter (Rad 57). Ninety-three traders were proportionally allocated between motor parks; 93 other traders were selected based on specific study inclusion criteria. Mean ages of motor park traders and other traders were comparable, 37.8 ± 11.1 and 38.7 ± 9.6, respectively. Mean % COHb for traders (range 3–22) at AMP, IMP, and NMP was 11.2 ± 3.8, 11.6 ± 3.1, and 12.2 ± 3.3, respectively, while mean % COHb for other traders was about three times lower, 4.1 ± 1.7 (range 2–8). Overall, mean % COHb for motor park traders, 11.7 ± 3.3, was also significantly higher than for other traders (p < 0.05). Nevertheless, mean % COHb for both groups exceeded the current World Health Organization guideline, 2.5%. This study suggested that motor park traders have higher % COHb and thus are highly susceptible to exposure and more vulnerable to known risks of adverse health effects from exposure to CO.

Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A Cl- channels.

Bile acids stimulate a bicarbonate‐rich choleresis, in part, through effects on cholangiocytes. Because Cl− channels in the apical membrane of cholangiocytes provide the driving force for secretion and transmembrane member 16A (TMEM16A) has been identified as the Ca2+‐activated Cl− channel in the apical membrane of cholangiocytes, the aim of the present study was to determine whether TMEM16A is the target of bile‐acid–stimulated Cl− secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to ursodeoxycholic acid (UDCA) or tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+]i, membrane Cl− permeability, and transepithelial secretion. Bile‐acid–stimulated Cl− currents demonstrated biophysical properties consistent with TMEM16A and were inhibited by pharmacological or molecular (small‐interfering RNA; siRNA) inhibition of TMEM16A. Bile acid–stimulated Cl− currents were not observed in the presence of apyrase, suramin, or 2‐aminoethoxydiphenyl borate (2‐APB), demonstrating that current activation requires extracellular ATP, P2Y, and inositol 1,4,5‐trisphosphate (IP3) receptors. TUDCA did not activate Cl− currents during pharmacologic inhibition of the apical Na+‐dependent bile acid transporter (ASBT), but direct intracellular delivery of TUDCA rapidly activated Cl− currents. Conclusion: Bile acids stimulate Cl− secretion in mouse and human biliary cells through activation of membrane TMEM16A channels in a process regulated by extracellular ATP and [Ca2+]i. These studies suggest that TMEM16A channels may be targets to increase bile flow during cholestasis. (Hepatology 2018;68:187‐199).

Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF2α, 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Personal and Occupational Exposure to Traffic-Related Fine Particulate Matter in Accra, Ghana

Background/Aim: Air pollution levels in fast-growing sub-Saharan African cities are among the highest in the world, but human exposure studies are limited, especially, traffic-related exposures. Our aim was to measure personal fine particulate matter (PM2.5) exposure of commercial minibus and taxi drivers (the most popular means of public transportation in Ghana’s capital), and street mobile vendors (hawkers) and street stationary vendors (vendors) in Accra, Ghana. Methods: We measured 24-hour personal PM2.5 exposure of 99 subjects, comprising 29 minibus drivers, 26 taxi drivers, 29 street vendors, and 15 street hawkers in the Accra metropolis. PM2.5 was measured both gravimetrically and continuously, with time-matched global positioning system coordinates. The instruments were placed in backpacks, which were worn by the vendors and hawkers during the 24-hour measurement period. Taxi drivers had the backpacks placed beside them near the front passenger’s seat. For the mini bus drivers, field assistants carried the backpacks on their laps at the front passenger’s seat and rode along the drivers. Results: Across all four occupational groups, average (SD) personal PM2.5 exposure was 56.4 (63.2) μg/m3; group means ranged from 26.0 μg/m3 for hawkers to 83.4 μg/m3 for taxi drivers. Individual exposure was &gt; 100 μg/m3 for some drivers. Exposure was significantly higher among drivers than vendors (78 vs 29 μg/m3; 95% CI: 28, 70; p-value &lt; 0.001). The highest exposure to the drivers occurred on major and secondary roads, although &lt; 20% of their commute time was spent there compared to minor roads and alleys. Conclusions: Our results support the need for urban air quality management plans that will address the role traffic to reduce exposure to the thousands who commute daily by minibuses and taxis or work near roadways in Accra, and when combined with policies to reduce urban biomass use, will greatly reduce urban population exposure in Accra.

Comparison of VOC measurements made by PTR-MS, adsorbent tubes–GC-FID-MS and DNPH derivatization–HPLC during the Sydney Particle Study, 2012: a contribution to the assessment of uncertainty in routine atmospheric VOC measurements

Abstract. Understanding uncertainty is essential for utilizing atmospheric volatile organic compound (VOC) measurements in robust ways to develop atmospheric science. This study describes an inter-comparison of the VOC data, and the derived uncertainty estimates, measured with three independent techniques (PTR-MS, proton-transfer-reaction mass spectrometry; GC-FID-MS, gas chromatography with flame-ionization and mass spectrometric detection; and DNPH–HPLC, 2,4-dinitrophenylhydrazine derivatization followed by analysis by high-performance liquid chromatography) during routine monitoring as part of the Sydney Particle Study (SPS) campaign in 2012. Benzene, toluene, C8 aromatics, isoprene, formaldehyde and acetaldehyde were selected for the comparison, based on objective selection criteria from the available data. Bottom-up uncertainty analyses were undertaken for each compound and each measurement system. Top-down uncertainties were quantified via the inter-comparisons. In all seven comparisons, the correlations between independent measurement techniques were high with R2 values with a median of 0.92 (range 0.75–0.98) and small root mean square of the deviations (RMSD) of the observations from the regression line with a median of 0.11 (range 0.04–0.23 ppbv). These results give a high degree of confidence that for each comparison the response of the two independent techniques is dominated by the same constituents. The slope and intercept as determined by reduced major axis (RMA) regression gives a different story. The slopes varied considerably with a median of 1.25 and a range of 1.16–2.01. The intercepts varied with a median of 0.04 and a range of −0.03 to 0.31 ppbv. An ideal comparison would give a slope of 1.00 and an intercept of 0. Some sources of uncertainty that are poorly quantified by the bottom-up uncertainty analysis method were identified, including: contributions of non-target compounds to the measurement of the target compound for benzene, toluene and isoprene by PTR-MS as well as the under-reporting of formaldehyde, acetaldehyde and acetone by the DNPH technique. As well as these, this study has identified a specific interference of liquid water with acetone measurements by the DNPH technique. These relationships reported for Sydney 2012 were incorporated into a larger analysis with 61 similar published inter-comparison studies for the same compounds. Overall, for the light aromatics, isoprene and the C1–C3 carbonyls, the uncertainty in a set of measurements varies by a factor of between 1.5 and 2. These uncertainties (∼50 %) are significantly higher than uncertainties estimated using standard propagation of error methods, which in this case were ∼22 % or less, and are the result of the presence of poorly understood or neglected processes that affect the measurement and its uncertainty. The uncertainties in VOC measurements identified here should be considered when assessing the reliability of VOC measurements from routine monitoring with individual, stand-alone instruments; when utilizing VOC data to constrain and inform air quality and climate models; when using VOC observations for human exposure studies; and for comparison with satellite retrievals.

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans.

Diesel exhaust (DE) is a paradigm for traffic-related air pollution. Human adaptation to DE is poorly understood and currently based on oversimplified models. DE promotes allergic responses, but protein expression changes mediated by this interaction have not been systematically investigated. The aim of this study was to define the effect of inhaled DE on allergen-induced proteins in the lung.We performed a randomised and blinded controlled human crossover exposure study. Participants inhaled filtered air or DE; thereafter, contralateral lung segments were challenged with allergen or saline. Using label-free quantitative proteomics, we comprehensively defined DE-mediated alteration of allergen-driven secreted proteins (secretome) in bronchoalveolar lavage. We further examined expression of proteins selected from the secretome data in independent validation experiments using Western blots, ELISA and immunohistochemistry.We identified protein changes unique to co-exposure (DE+allergen), undetected with mono-exposures (DE or allergen alone). Validation studies confirmed that specific proteins (e.g. the antimicrobial peptide cystatin-SA) were significantly enhanced with DE+allergen compared to either mono-exposure.This study demonstrates that common environmental co-exposures can uniquely alter protein responses in the lungs, illuminating biology that mono-exposures cannot. This study highlights the value of complex human in vivo models in detailing airway responses to inhaled pollution.

Formulae Evaluation for Estimating Body Surface Area of Korean Children.

Body surface area (BSA) is an important parameter in the conduct of human exposure studies and in clinical processes in children. The aim of this paper was to compare seven BSA formulas and to find out which of these formulas is appropriate for use with Korean children. Body surface area was calculated according to age, age-group and BMI-group using the height and weight data of Korean children (n = 4899) ages 1 to 18 from Korea National Health and Nutrition Examination Survey (2012-2014). We used the formulas of Banerjee and Bhattacharya (1961), Fujimoto and Watanabe (1969), US EPA (1985), Gehan and George (1970), Boyd (1935), Haycock et al (1978) and Mosteller (1987). The average values of the seven formulas were calculated and used as norm values for comparison. All predictions showed a strong positive correlation with the overall average BSA values. Overestimations were observed on the calculations of Gehan and George (1970), US EPA (1985) and Boyd (1935) formulas. Banerjee and Bhattacharya (1961) and Fujimoto and Watanabe (1969) values showed underestimations and the largest error size of 0.027 m2 for all ages. BSA estimates of Mosteller (1987) and Haycock et al (1978) were found to be closer to the overall average BSA values with the least error size of 0.004 m2. Mosteller's formula is recommended for use in the conduct of human exposure studies and in clinical practice among Korean children, although Haycock et al formula is appropriate for children from 1 to 2 years old.

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

SummaryEpidemiological 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 UPM in 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.