Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis.

BACKGROUND: The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. METHODS: The Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. RESULTS: Thirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates-including smoking, body mass index, and individual and area-level socioeconomic status-and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter-pollutants with more than 10 studies-were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure-response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. CONCLUSIONS: The overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high.

Long-term exposure to traffic-related air pollution and stroke: A systematic review and meta-analysis.

BACKGROUND: Stroke remains the second cause of death worldwide. The mechanisms underlying the adverse association of exposure to traffic-related air pollution (TRAP) with overall cardiovascular disease may also apply to stroke. Our objective was to systematically evaluate the epidemiological evidence regarding the associations of long-term exposure to TRAP with stroke. METHODS: PubMed and LUDOK electronic databases were searched systematically for observational epidemiological studies from 1980 through 2019 on long-term exposure to TRAP and stroke with an update in January 2022. TRAP was defined according to a comprehensive protocol based on pollutant and exposure assessment methods or proximity metrics. Study selection, data extraction, risk of bias (RoB) and confidence assessments were conducted according to standardized protocols. We performed meta-analyses using random effects models; sensitivity analyses were assessed by geographic area, RoB, fatality, traffic specificity and new studies. RESULTS: Nineteen studies were included. The meta-analytic relative risks (and 95% confidence intervals) were: 1.03 (0.98-1.09) per 1 µg/m3 EC, 1.09 (0.96-1.23) per 10 µg/m3 PM10, 1.08 (0.89-1.32) per 5 µg/m3 PM2.5, 0.98 (0.92; 1.05) per 10 µg/m3 NO2 and 0.99 (0.94; 1.04) per 20 µg/m3 NOx with little to moderate heterogeneity based on 6, 5, 4, 7 and 8 studies, respectively. The confidence assessments regarding the quality of the body of evidence and separately regarding the presence of an association of TRAP with stroke considering all available evidence were rated low and moderate, respectively. CONCLUSION: The available literature provides low to moderate evidence for an association of TRAP with stroke.

Long-term exposure to traffic-related air pollution and selected health outcomes: A systematic review and meta-analysis.

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP - both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.

Transport-related measures to mitigate climate change in Basel, Switzerland: A health-effectiveness comparison study.

BACKGROUND: Local strategies to reduce green-house gases (GHG) imply changes of non-climatic exposure patterns. OBJECTIVE: To assess the health impacts of locally relevant transport-related climate change policies in Basel, Switzerland. METHODS: We modelled change in mortality and morbidity for the year 2020 based on several locally relevant transport scenarios including all decided transport policies up to 2020, additional realistic and hypothesized traffic reductions, as well as ambitious diffusion levels of electric cars. The scenarios were compared to the reference condition in 2010 assumed as status quo. The changes in non-climatic population exposure included ambient air pollution, physical activity, and noise. As secondary outcome, changes in Disability-Adjusted Life Years (DALYs) were put into perspective with predicted changes of CO2 emissions and fuel consumption. RESULTS: Under the scenario that assumed a strict particle emissions standard in diesel cars and all planned transport measures, 3% of premature deaths could be prevented from projected PM2.5 exposure reduction. A traffic reduction scenario assuming more active trips provided only minor added health benefits for any of the changes in exposure considered. A hypothetical strong support to electric vehicles diffusion would have the largest health effectiveness given that the energy production in Basel comes from renewable sources. CONCLUSION: The planned local transport related GHG emission reduction policies in Basel are sensible for mitigating climate change and improving public health. In this context, the most effective policy remains increasing zero-emission vehicles.

Air pollution and childhood leukaemia: a nationwide case-control study in Italy.

OBJECTIVES: Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. METHODS: The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. RESULTS: Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. CONCLUSIONS: Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

A GIS-based method for modelling air pollution exposures across Europe.

A GIS-based moving window approach was developed as a means for generating high resolution air pollution maps over large geographic areas. The approach is demonstrated by modelling annual mean NO(2) pollution for the EU-15 (excluding Sweden) at the 1 km level on the basis of emissions and meteorological data. Models were developed using monitoring data from 714 background NO(2) sites for 2001 and validated by comparing predicted with observed NO(2) concentrations for a reserved set of 228 background sites. First the emission map (NO(x)) was derived by disaggregating national emissions estimates, categorised by source, to a 1 km grid, using proxies including population and road density, traffic statistics and land cover. A set of annuli was then constructed, of varying radii, and these passed over the emissions grid to derive a calibration between measured annual average concentrations at each monitoring site and distance-weighted emissions in the surrounding area, using a focalsum function. The resulting model was then used to predict concentrations at the reserved set of validation sites, and measures of performance (R(2), RMSE and fractional bias) obtained. Validation gave R(2)=0.61, RMSE=6.59 and FB=-0.01, and indicated performance equivalent to universal kriging and better than ordinary kriging and land use regression.

Association between modelled traffic-related air pollution and asthma score in the ECRHS.

The aim of our analysis was to study the association between air pollution and asthma among adults. For this goal, a previously developed "asthma score" was used. Persons aged 25-44 yrs were randomly selected (1991-1993) and followed up (2000-2002) within the European Community Respiratory Health Survey (ECRHS I and II, respectively). The asthma score was defined from 0 to 5, based on the positive answers to the following symptoms reported for the last 12 months: wheeze/breathlessness, chest tightness, dyspnoea at rest, dyspnoea after exercise and woken by dyspnoea. Participants' home addresses were linked to outdoor modelled NO2 estimates for 2001. Negative binomial regression was used to model the asthma score. The score from ECRHS II was positively associated with NO2 (ratio of the mean asthma score (RMS) 1.23, 95% CI 1.09-1.38, for an increase of 10 microg x m(-3)). After excluding participants with asthma and symptoms at baseline, the association remained (RMS 1.25, 95% CI 1.05-1.51), and was particularly high among those reporting a high score in ECRHS II. The latter probably reflects incident cases of asthma. Our results suggest that traffic-related pollution causes asthma symptoms and possibly asthma incidence in adults. The asthma score offers an alternative with which to investigate the course and aetiology of asthma in adults.

Association between annoyance and individuals' values of nitrogen dioxide in a European setting.

INTRODUCTION: Annoyance caused by air pollution has been proposed as an indicator of exposure to air pollution. The aim of this study was to assess the geographical homogeneity of the relationship between annoyance and modelled home-based nitrogen dioxide (NO2) measurements. METHODS: The European Community Respiratory Health Survey II was conducted in 2000-1, in 25 European centres in 12 countries. This analysis included 4753 subjects (from 37 in Tartu, Estonia, to 532 in Antwerp, Belgium) who answered the annoyance question and with available outdoor residential NO2 (4399 modelled and 354 measured) including 20 cities from 10 countries. Annoyance as a result of air pollution was self-reported on an 11-point scale (0, no disturbance at all; 10, intolerable disturbance). Demographic and socioeconomic factors, smoking status and the presence of respiratory symptoms or disease were measured through a standard questionnaire. Negative binomial regression was used. RESULTS: The median NO2 concentration was 27 microg.m(-3) (from 10 in Umeå, Sweden, to 57 in Barcelona, Spain). The mean of annoyance was 2.5 (from 0.7 in Reykjavik, Iceland, to 4.4 in Huelva, Spain). NO2 was associated with annoyance (ratio of the mean score 1.26 per 10 microg.m(-3), 95% CI 1.19 to 1.34). The association between NO2 and annoyance was heterogeneous among cities (p for heterogeneity <0.001). CONCLUSIONS: Annoyance is associated with home outdoor air pollution but with a different strength by city. This indicates that annoyance is not a valid surrogate for air pollution exposure. Nevertheless, it may be a useful measure of perceived ambient air quality and could be considered a complementary tool for health surveillance.

Effects of the herbicide hexazinone on nutrient cycling in a low-pH blueberry soil.

The herbicide hexazinone was applied as the commercial formulation Velpar L at field-rate (FR) concentrations of FR (14.77 microg ai g(-1)), FRx5 (73.85 microg ai g(-1)), FRx10 (147.70 microg ai g(-1)), FRx50 (738.50 microg ai g(-1)), and FRx100 (1477.00 microg ai g(-1)) to acidic soil, pH 4.12, taken from a lowbush blueberry field. Hexazinone was tested for inhibitory effects on various transformations of the nitrogen cycle and soil respiration. Nitrogen fixation was unaffected by hexazinone levels up to FRx100 following a 4-week incubation period. Ammonification was initially inhibited by all levels of hexazinone, but after 4 weeks, ammonification in all treatment systems was equal to or greater than the control. Nitrification was more sensitive to hexazinone; however, application at a field-rate level caused no inhibition. Inhibitory effects were noted above FR after a 2-month endpoint analysis and above FRx5 after a 6-month endpoint analysis. Hexazinone concentrations up to and including FRx100 stimulated denitrification. Soil respiration was also stimulated over a 3-week period when applied at a level up to 100 times the recommended field rate. In general, it was found that when applied at the recommended field application rate, hexazinone does not adversely affect the nitrogen cycle or soil respiration in acidic lowbush blueberry soils.

Development and validation of a sensitive method for tetracycline in gingival crevicular fluid by HPLC using fluorescence detection.

Increased interest in the clinical use of antibiotics for periodontal therapy required the development of a sensitive assay for the quantitation of tetracycline in gingival crevicular fluid (GCF). An HPLC method was developed and validated for tetracycline which separates and identifies the degradation component epi-tetracycline. The HPLC assay employs a C18 reversed-phase Hypersil column with a mobile phase composed of methanol and sodium acetate buffer containing CaCl2 and EDTA disodium salt. The chromatographic separation was monitored by a fluorescent detector with an excitation wavelength of 375 nm and an emission wavelength of 512 nm. Tetracycline was extracted from GCF collected on Periopapers by addition of a methanol solution containing the internal standard, doxycycline, and the mobile phase buffer (25:75, v/v). The mean percent recovery for the extraction method was 107.8% with all the % R.S.D. below 7.5%. The mean inter- and intra-batch accuracy was 104.1 and 105.3%, respectively with a coefficient of variation of less than 9.5%. The lower limit of detection was 2.5 ng on the Periopapers. The typical GCF volumes collected were 0.1-1 microliter. The method was validated for the linear concentration range 2.5-1000 ng of tetracycline on the Periopaper. This assay for tetracycline was shown to be an accurate, precise and rugged method.

Potential genoprotective role for UDP-glucuronosyltransferases in chemical carcinogenesis: initiation of micronuclei by benzo(a)pyrene and benzo(e)pyrene in UDP-glucuronosyltransferase-deficient cultured rat skin fibroblasts.

UDP-glucuronosyltransferases (UGTs) are cytoprotective and may also be genoprotective. Since over 10% of the population have hereditary deficiencies in UGTs, this family of enzymes could constitute an important determinant of susceptibility to chemical carcinogenesis, teratogenesis, and neurodegeneration. Fibroblasts contain Phase I and II drug-metabolizing enzymes, including UGTs, and undergo mitosis, rendering them susceptible to xenobiotic genotoxicity associated with micronucleus formation, which is thought to reflect carcinogenic initiation. Accordingly, skin fibroblasts may provide an accessible model for elucidating genoprotective mechanisms in both animals and humans and for characterizing the potential role of UGTs as determinants of individual toxicological susceptibility. To test this hypothesis, the carcinogen/teratogen benzo(a)pyrene [B(a)P], or its noncarcinogenic B(e)P isomer, was incubated with cultured skin fibroblasts obtained from male RHA-J/J rats. These rats have a hereditary homozygous deficiency in bilirubin UGT and demonstrate reduced xenobiotic glucuronidation, enhanced cytochrome P-450-catalyzed bioactivation, covalent binding, and toxicity of acetaminophen and B(a)P. Control fibroblasts were cultured from UGT-normal congenic homozygous male RHA-(+/+) rats and male Wistar rats. The cells were incubated with 10 microM B(a)P or B(e)P either for assessment of micronucleus formation or for quantifying the bioactivation and covalent binding of B(a)P and the glucuronidation of its hydroxylated metabolites. Compared to control fibroblasts incubated only with buffer, micronucleus formation was not enhanced by either DMSO vehicle or B(e)P. In contrast, B(a)P significantly enhanced micronucleus formation in all cells, and UGT-deficient cells (RHA-J/J) had a > 2-fold higher B(a)P-initiated micronucleus formation compared to UGT-normal cells (RHA-(+/+)) (P < 0.05). Glucuronidation of total B(a)P metabolites was 10% lower in RHA-J/J UGT-deficient fibroblasts, and the covalent binding of B(a)P to protein, reflective of an electrophilic reactive intermediate and DNA-alkylating agent, was up to 3-fold higher in RHA-J/J UGT-deficient fibroblasts or fibroblast homogenates compared to UGT-normal controls (P < 0.05). In fibroblast homogenates, addition of the UGT cosubstrate UDP-glucuronic acid reduced B(a)P covalent binding, corroborating the cytoprotective importance of UGTs. There was a highly significant correlation between decreasing glucuronidation of B(a)P metabolites and increasing bioactivation and covalent binding of B(a)P (r = -0.889; P = 0.018) in fibroblasts from RHA-J/J and RHA-(+/+) rat strains, indicating an important genoprotective role for UGT. These results provide the first evidence that hereditary UGT deficiencies may enhance susceptibility to chemical carcinogenesis and suggest that skin fibroblasts may provide a useful and highly sensitive model for human risk assessment.