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 AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

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.

Short-term effects of air pollution and temperature on cattle mortality in the Netherlands.

BACKGROUND: Extreme temperatures and air pollution are both associated with increased mortality risk in humans. However, the effects of temperature and air pollution on cattle have not been investigated much before. OBJECTIVES: Short-term effects of temperature (heat and cold) and air pollution on cattle mortality were investigated and quantified in the Netherlands during 2012-2017. METHODS: Daily data on cattle mortality, weather conditions and mean levels of particulate matter (PM10), ozone (O3), ammonia (NH3) and nitrogen dioxide (NO2) of the Netherlands during 2012-2017 were collected. Associations were investigated with time-series regression using distributed lag non-linear models including lags of up to 25 days. Effects of temperature were expressed as those associated with extreme and moderate heat or cold, defined as Temperature Humidity Index (THI) values below the 1st and 5th percentile, and above the 95th and 99th percentile of the national THI distribution. Effects of air pollutants were expressed per 10 µg/m3 change in daily mean concentrations. RESULTS: Both high and low temperatures were associated with increased mortality amongst different age groups. For instance, the newborn calves of at most 14 days showed a cumulative relative risk (RR) of 2.13 (95%CI: 1.99-2.28) for extreme heat and the pre-weaned calves (15-55 days) showed a cumulative RR of 1.50 (95%CI: 1.37-1.64) for extreme cold. Associations of air pollution with mortality were not consistent, except for the effect of ozone of lag 0-7 and lag 0-25. Exposure to O3 in the newborn calves resulted in a cumulative RR of 1.09 (95%CI: 1.04-1.4) for lag 0-7 and 1.09 (95%CI: 1.03-1.16) for lag 0-25. CONCLUSIONS: Both high and low temperatures were associated with increased mortality amongst pre-weaned calves of 15-55 days, whereas associations in weaned calves (56 days - 1 year) were only observed for low temperatures and in newborn calves of at most 14 days and lactating cattle >2 years only for high temperatures. Associations of air pollution with mortality in all age groups were not consistent, except for the effect of ozone of lag 0-7 and lag 0-25.

Outlier Detection in Urban Air Quality Sensor Networks.

Low-cost urban air quality sensor networks are increasingly used to study the spatio-temporal variability in air pollutant concentrations. Recently installed low-cost urban sensors, however, are more prone to result in erroneous data than conventional monitors, e.g., leading to outliers. Commonly applied outlier detection methods are unsuitable for air pollutant measurements that have large spatial and temporal variations as occur in urban areas. We present a novel outlier detection method based upon a spatio-temporal classification, focusing on hourly NO2 concentrations. We divide a full year's observations into 16 spatio-temporal classes, reflecting urban background vs. urban traffic stations, weekdays vs. weekends, and four periods per day. For each spatio-temporal class, we detect outliers using the mean and standard deviation of the normal distribution underlying the truncated normal distribution of the NO2 observations. Applying this method to a low-cost air quality sensor network in the city of Eindhoven, the Netherlands, we found 0.1-0.5% of outliers. Outliers could reflect measurement errors or unusual high air pollution events. Additional evaluation using expert knowledge is needed to decide on treatment of the identified outliers. We conclude that our method is able to detect outliers while maintaining the spatio-temporal variability of air pollutant concentrations in urban areas.

The impact of ambient air pollution on the human blood metabolome.

BACKGROUND: Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. METHODS: We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. RESULTS: We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. CONCLUSIONS: This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

The effect of high indoor temperatures on self-perceived health of elderly persons.

INTRODUCTION: Exposure to high ambient temperatures leads to an increase in mortality and morbidity, especially in the elderly. This relationship is usually assessed with outdoor temperature, even though the elderly spend most of their time indoors. Our study investigated the relationship between indoor temperature and heat-related health problems of elderly individuals. MATERIAL AND METHODS: The study was conducted in the Netherlands between April and August 2012. Temperature and relative humidity were measured continuously in the living rooms and bedrooms of 113 elderly individuals. Respondents were asked to fill out an hourly diary during three weeks with high temperature and one cold reference week, and a questionnaire at the end of these weeks, on health problems that they experienced due to heat. RESULTS: During the warmest week of the study period (14-20 August), average living room and bedroom temperatures were approximately 5°C higher than during the reference week. More than half of the respondents perceived their indoor climate as too warm during this week. The most reported symptoms were thirst (42.7%), sleep disturbance (40.6%) and excessive sweating (39.6%). There was a significant relationship between both indoor and outdoor temperatures with the number of hours that heat-related health problems were reported per day. For an increase of 1°C of indoor temperature, annoyance due to heat and sleep disturbance increased with 33% and 24% respectively. Outdoor temperature was associated with smaller increases: 13% and 11% for annoyance due to heat and sleep disturbance, respectively. The relationship between outdoor temperature and heat-related health problems disappeared when indoor and outdoor temperatures were included in one model. CONCLUSIONS: The relationship with heat-related health problems in the elderly is stronger with indoor (living room and bedroom) temperature than with outdoor temperature. This should be taken into account when looking for measures to reduce heat exposure in this vulnerable group.

Quantitative determination of regional contributions to fine and coarse particle mass in urban receptor sites.

In this study, we demonstrate that regression analysis of trajectories residence time estimates the contributions of geographical sectors to fine and coarse particle mass in urban receptor sites. We applied the methodology to coarse and fine particles in Amsterdam, Athens, Birmingham and Helsinki. The sectors with the highest contributions on PM2.5 and PM10-2.5 for Amsterdam and Birmingham were Central/Eastern Europe and the Atlantic Ocean/North Sea, respectively. For Athens, the four sectors within 500 km accounted for the largest fraction of PM2.5. The Mediterranean Sea and North Africa added more than half of PM10-2.5 in Athens. For Helsinki, more than 50% of PM2.5 and PM10-2.5 were from sources outside Finland. This approach may be applied to assess the impact of transport on particle mass levels, identify the spatial patterns of particle sources and generate valuable data to design national and transnational efficient emission control strategies.

Lung function and indicators of exposure to indoor and outdoor particulate matter among asthma and COPD patients.

OBJECTIVES: Misclassification of exposure related to the use of central sites may be larger for ultrafine particles than for particulate matter < or =2.5 microm and < or =10 microm (PM(2.5) and PM(10)) and may result in underestimation of health effects. This paper describes the relative strength of the association between outdoor and indoor exposure to ultrafine particles, PM(2.5) and PM(10) and lung function. METHODS: In four European cities (Helsinki, Athens, Amsterdam and Birmingham), lung function (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)) and peak expiratory flow (PEF)) was measured three times a day for 1 week in 135 patients with asthma or chronic obstructive pulmonary disease (COPD), covering study periods of >1 year. Daily concentrations of particle number, PM(2.5) and PM(10) were measured at a central site in each city and both inside and outside the subjects' homes. RESULTS: Daily average particle number concentrations ranged between 2100 and 66 100 particles/cm(3). We found no association between 24 h average particle number or particle mass concentrations and FVC, FEV(1) and PEF. Substituting home outdoor or home indoor concentrations of particulate air pollution instead of the central site measurements did not change the observed associations. Analyses restricted to asthmatics also showed no associations. CONCLUSIONS: No consistent associations between lung function and 24 h average particle number or particle mass concentrations were found in panels of patients with mild to moderate COPD or asthma. More detailed exposure assessment did not change the observed associations. The lack of association could be due to the high prevalence of medication use, limited ability to assess lagged effects over several days or absence of an effect.

Gas cooking is associated with small reductions in lung function in children.

Inconsistent effects of gas cooking on lung function have been reported. In a previous study from Austria, we demonstrated a significant, though small, reduction of lung function parameters in children living in homes with gas stoves. We used a larger international database to check if this finding can be generalised. To study the relative impact of cooking with gas on lung function parameters of primary school children in a wide range of geographical settings, we analysed flow and volume data of approximately 24,000 children (aged 6-12 yrs) from nine countries in Europe and North America. Exposure information was obtained by comparable questionnaires and spirometry according to an American Thoracic Society/European Respiratory Society protocol. Linear regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytical tools. On average, gas cooking reduced lung function parameters. Overall effects were small (-0.1-0.7%) and only significant for forced vital capacity and forced expiratory volume in 1 s. There was some indication that allergic children were more affected by gas cooking. Under current housing conditions, gas cooking is associated with only small reductions in lung function.

Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.

Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.

An 8.35 Mb overlapping interstitial deletion of 8q24 in two patients with coloboma, congenital heart defect, limb abnormalities, psychomotor retardation and convulsions.

Chromosome analysis in two young patients with multiple congenital anomalies revealed a de novo interstitial deletion of 8q that has not been reported before. The deletions were overlapping by 8.35 Mb (8q24.21q24.23). The clinical features shared by our patients were coloboma, VSD, digital abnormalities, congenital dislocation of a hip, feeding problems, psychomotor delay and convulsions. The deletion included the region for Langer-Giedion syndrome (TRPS1 and EXT1) in the girl only. However, she is too young to present features of this syndrome, apart from dysmorphic features like a bulbous nose and notched alae nasi. Several genes are present in the commonly deleted region, including genes with unknown function, and genes for which haploinsufficiency is known to have no phenotypic effect in mice (Wnt1). A gene that might play a role in the convulsions of our patients is KCNQ3.

The joint association of air pollution and noise from road traffic with cardiovascular mortality in a cohort study.

OBJECTIVES: Associations between cardiovascular mortality and air pollution and noise together were investigated. METHODS: Data from the ongoing Netherlands Cohort Study on Diet and Cancer (120,852 subjects; follow-up 1987-1996) were used. Cox proportional hazard analyses were conducted for the association between cardiovascular mortality and exposure to black smoke, traffic intensity on the nearest road and road traffic noise at the home address. RESULTS: The correlations between traffic noise and background black smoke, and traffic intensity on the nearest road were moderate at 0.24 and 0.30, respectively. Traffic intensity was associated with cardiovascular mortality, with highest relative risk (95% confidence interval) for ischaemic heart disease (IHD) mortality being 1.11 (1.03 to 1.20) (increment 10,000 motor vehicles/24 h). Relative risks for black smoke concentrations were elevated for cerebrovascular (1.39 (0.99 to 1.94)) and heart failure mortality (1.75 (1.00 to 3.05)) (increment 10 microg/m(3)). These associations were insensitive to adjustment for traffic noise. There was an excess of cardiovascular mortality in the highest noise category (>65 dB(A)), with elevated risks for IHD (1.15 (0.86 to 1.53)) and heart failure mortality (1.99 (1.05 to 3.79)). After adjustment for black smoke and traffic intensity, noise risk reduced to unity for IHD mortality and was slightly reduced for heart failure mortality. CONCLUSIONS: Associations between black smoke concentrations and traffic intensity on the nearest road with specific cardiovascular causes of death were not explained by traffic noise in this study.

Hourly variation in fine particle exposure is associated with transiently increased risk of ST segment depression.

OBJECTIVES: To evaluate whether hourly changes in fine particle (PM(2.5), diameter<2.5 microm) exposure or outdoor particle concentrations are associated with rapid ischaemic responses. METHODS: 41 non-smoking elderly people with coronary heart disease were followed up with biweekly clinic visits in Helsinki, Finland. The occurrence of ST segment depressions >0.1 mV was recorded during submaximal exercise tests. Hourly variations in personal PM(2.5) exposure and outdoor levels of PM(2.5) and ultrafine particles (<0.1 microm) were recorded for 24 h before a clinic visit. Associations between particulate air pollution and ST segment depressions were evaluated using logistic regression. RESULTS: Both personal and outdoor PM(2.5) concentrations, but not outdoor ultrafine particle counts, were associated with ST segment depressions. The odds ratio (per 10 microg/m(3)) for personal PM(2.5) concentration during the hour preceding a clinic visit was 3.26 (95% CI 1.07 to 9.99) and for 4 h average outdoor PM(2.5) it was 2.47 (95% CI 1.05 to 5.85). CONCLUSIONS: Even very short-term elevations in fine particle exposure might increase the risk of myocardial ischaemia. The precise mechanism is still unknown but could involve changes in autonomic nervous control of the heart.

Bacteria and mould components in house dust and children's allergic sensitisation.

It has been suggested that early childhood exposure to microbial agents decreases the risk of allergies in children. The current authors studied the association between microbial agents in house dust and allergic sensitisation in children aged 2-4 yrs. Nested case-control studies were performed within ongoing birth cohort studies in Germany, the Netherlands and Sweden and approximately 180 sensitised and 180 nonsensitised children were selected per country. Levels of bacterial endotoxin, beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) were measured in dust samples from the children's mattresses and the living-room floors. Combined across countries, higher amounts of mattress dust and higher mattress dust loads of endotoxin, beta(1,3)-glucans and EPS were associated with a significantly decreased risk of sensitisation to inhalant allergens. After mutual adjustment, only the protective effect of the amount of mattress dust remained significant (odds ratio (95% confidence interval) 0.57(0.39-0.84)). Higher amounts of mattress dust may decrease the risk of allergic sensitisation to inhalant allergens. The effect might be partly attributable to endotoxin, beta(1,3)-glucans and extracellular polysaccharides, but could also reflect (additional) protective effects of (microbial) agents other than the ones measured. It is not possible to distinguish with certainty which component relates to the effect, since their levels are highly correlated.

Determinants of house dust endotoxin in three European countries - the AIRALLERG study.

UNLABELLED: The comparison of endotoxin levels between study populations and countries is limited as a result of differences in sampling, extraction, and storage procedures. The objective of this study is to assess the levels and determinants of endotoxin in mattress and living room floor dust samples from three European countries, namely, Germany, the Netherlands, and Sweden, using a standardized sampling, storage, and analysis protocol. The mattress and living room floor dust was collected from the homes of 1065 German, Dutch, and Swedish (pre-)school children. All the samples were collected in the cool season and analyzed for endotoxin in a central laboratory. The determinants were assessed by a standardized questionnaire. The endotoxin concentrations in mattress and living room floor dust were found to be the highest in German homes and lowest in the Swedish ones. Differences between the geometric means were small (factor 1.1-1.7). Most of the associations between endotoxin concentrations and potential determinants were not statistically significant and heterogeneous across countries. However, keeping pets and having more than four persons living in the home were consistently associated with up to 1.7-fold higher endotoxin concentrations in mattress and floor dust. Furthermore, having carpets or rugs, and opening the windows frequently was associated with up to 3.4-fold and 1.3-fold higher endotoxin concentrations in living room floor dust, respectively. The proportion of variance explained by the questionnaire variables was generally low. In conclusion, the data on housing characteristics did not accurately predict the endotoxin concentrations in house dust, and could only partly explain the differences between countries. PRACTICAL IMPLICATIONS: The differences between the endotoxin concentrations in German, Dutch, and Swedish homes are small. House dust endotoxin concentrations are associated with a number of housing factors, such as pet-ownership, floor cover, number of persons living in the home, and ventilation. The variability of the endotoxin levels between homes and countries can only be partly explained by these factors.

Air pollution and development of asthma, allergy and infections in a birth cohort.

Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms and respiratory infections during the first 4 yrs of life in a birth cohort study (n = approximately 4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM(2.5), particles with a 50% cut-off aerodynamic diameter of 2.5 mum and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n = 713). Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0-1.4) for soot), doctor-diagnosed asthma (1.3 (1.0-1.7)), ear/nose/throat infections (1.2 (1.0-1.3)) and flu/serious colds (1.2 (1.0-1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2-2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements. Traffic-related pollution was associated with respiratory infections and some measures of asthma and allergy during the first 4 yrs of life.

NO2 and children's respiratory symptoms in the PATY study.

OBJECTIVES: NO2)is a major urban air pollutant. Previously reported associations between ambient NO2)and children's respiratory health have been inconsistent, and independent effects of correlated pollutants hard to assess. The authors examined effects of NO2 on a spectrum of 11 respiratory symptoms, controlling for PM10 and SO2, using a large pooled dataset. METHODS: Cross sectional studies were conducted in Russia, Austria, Italy, Switzerland, and the Netherlands, during 1993-99, contributing in total 23 955 children. Study-specific odds ratios for associations with ambient NO2 are estimated using logistic regressions with area-level random effects. Heterogeneity between study-specific results, and mean estimates (allowing for heterogeneity) are calculated. RESULTS: Long term average NO2 concentrations were unrelated to prevalences of bronchitis or asthma. Associations were found for sensitivity to inhaled allergens and allergy to pets, with mean odds ratios around 1.14 per 10 microg/m3 NO2. SO2 had little confounding effect, but an initial association between NO2 and morning cough was reduced after controlling for PM10. Associations with reported allergy were not reduced by adjustment for the other pollutants. Odds ratios for allergic symptoms tended to be higher for the 9-12 year old children compared with the 6-8 year old children. CONCLUSIONS: Evidence for associations between NO2 and respiratory symptoms was robust only for inhalation allergies. NO2 most likely is acting as an indicator of traffic related air pollutants, though its direct effect cannot be ruled out. This remains important, as policies to reduce traffic related air pollution will not result in rapid reductions.