Particulate air pollution from different sources and mortality in 7.5 million adults - The Dutch Environmental Longitudinal Study (DUELS).

BACKGROUND: Long-term exposure to particulate air pollution has been associated with mortality in urban cohort studies. Few studies have investigated the association between emission contributions from different particle sources and mortality in large-scale population registries, including non-urban populations. OBJECTIVES: The aim of the study was to evaluate the associations between long-term exposure to particulate air pollution from different source categories and non-accidental mortality in the Netherlands based on existing national databases. METHODS: We used existing Dutch national databases on mortality, individual characteristics, residence history, neighbourhood characteristics and modelled air pollution concentrations from different sources and air pollution components: particulate matter PM10, primary particulate matter PM10 (PPM10), particulate matter PM2.5, primary particulate matter PM2.5 (PPM2.5), elemental carbon (EC), nitrogen dioxide (NO2) and secondary inorganic aerosol (SIA) in PM10 (SIA10) or in PM2.5 (SIA2.5). We established a cohort of 7.5 million individuals 30 years or older. We followed the cohort for eight years (2008-2015). We applied Cox proportional hazard regression models adjusting for potential individual and area-specific confounders. RESULTS: We found statistically significant associations between total and primary particulate matter (PM10 and PM2.5), elemental carbon and mortality. Adjustment for nitrogen dioxide did not change the associations. Secondary inorganic aerosol showed less consistent associations. All primary PM sources were associated with mortality, except agricultural emissions and, depending on the statistical model, industrial PM emissions. CONCLUSIONS: We could not identify one or more specific source categories of particulate air pollution as main determinants of the mortality effects found in this and in a previous study. This suggests that present policy measures should be focussed on the wider spectrum of air pollution sources instead of on specific sources.

Air pollution in perspective: Health risks of air pollution expressed in equivalent numbers of passively smoked cigarettes.

BACKGROUND: Although the health effects of long term exposure to air pollution are well established, it is difficult to effectively communicate the health risks of this (largely invisible) risk factor to the public and policy makers. The purpose of this study is to develop a method that expresses the health effects of air pollution in an equivalent number of daily passively smoked cigarettes. METHODS: Defined changes in PM2.5, nitrogen dioxide (NO2) and Black Carbon (BC) concentration were expressed into number of passively smoked cigarettes, based on equivalent health risks for four outcome measures: Low Birth Weight (<2500g at term), decreased lung function (FEV1), cardiovascular mortality and lung cancer. To describe the strength of the relationship with ETS and air pollutants, we summarized the epidemiological literature using published or new meta-analyses. RESULTS: Realistic increments of 10µg/m(3) in PM2.5 and NO2 concentration and a 1µg/m(3) increment in BC concentration correspond to on average (standard error in parentheses) 5.5 (1.6), 2.5 (0.6) and 4.0 (1.2) passively smoked cigarettes per day across the four health endpoints, respectively. The uncertainty reflects differences in equivalence between the health endpoints and uncertainty in the concentration response functions. The health risk of living along a major freeway in Amsterdam is, compared to a counterfactual situation with 'clean' air, equivalent to 10 daily passively smoked cigarettes.. CONCLUSIONS: We developed a method that expresses the health risks of air pollution and the health benefits of better air quality in a simple, appealing manner. The method can be used both at the national/regional and the local level. Evaluation of the usefulness of the method as a communication tool is needed.

Air Pollution and Mortality in Seven Million Adults: The Dutch Environmental Longitudinal Study (DUELS).

BACKGROUND: Long-term exposure to air pollution has been associated with mortality in urban cohort studies. Few studies have investigated this association in large-scale population registries, including non-urban populations. OBJECTIVES: The aim of the study was to evaluate the associations between long-term exposure to air pollution and nonaccidental and cause-specific mortality in the Netherlands based on existing national databases. METHODS: We used existing Dutch national databases on mortality, individual characteristics, residence history, neighborhood characteristics, and national air pollution maps based on land use regression (LUR) techniques for particulates with an aerodynamic diameter ≤ 10 µm (PM10) and nitrogen dioxide (NO2). Using these databases, we established a cohort of 7.1 million individuals ≥ 30 years of age. We followed the cohort for 7 years (2004-2011). We applied Cox proportional hazard models adjusting for potential individual and area-specific confounders. RESULTS: After adjustment for individual and area-specific confounders, for each 10-µg/m3 increase, PM10 and NO2 were associated with nonaccidental mortality [hazard ratio (HR) = 1.08; 95% CI: 1.07, 1.09 and HR = 1.03; 95% CI: 1.02, 1.03, respectively], respiratory mortality (HR = 1.13; 95% CI: 1.10, 1.17 and HR = 1.02; 95% CI: 1.01, 1.03, respectively), and lung cancer mortality (HR = 1.26; 95% CI: 1.21, 1.30 and HR = 1.10 95% CI: 1.09, 1.11, respectively). Furthermore, PM10 was associated with circulatory disease mortality (HR = 1.06; 95% CI: 1.04, 1.08), but NO2 was not (HR = 1.00; 95% CI: 0.99, 1.01). PM10 associations were robust to adjustment for NO2; NO2 associations remained for nonaccidental mortality and lung cancer mortality after adjustment for PM10. CONCLUSIONS: Long-term exposure to PM10 and NO2 was associated with nonaccidental and cause-specific mortality in the Dutch population of ≥ 30 years of age.

Natural-cause mortality and long-term exposure to particle components: an analysis of 19 European cohorts within the multi-center ESCAPE project.

BACKGROUND: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. OBJECTIVES: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. METHODS: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 2.5 µm (PM2.5) and ≤ 10 µm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. RESULTS: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. CONCLUSIONS: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.

Respiratory effects of a reduction in outdoor air pollution concentrations.

BACKGROUND: Air pollution has been associated with respiratory health effects. There is little direct evidence that reductions in air pollution related to abatement policies lead to actual improvement in respiratory health. We assessed whether a reduction in (traffic policy-related) air pollution concentrations was associated with changes in respiratory health. METHODS: Air pollution concentrations and respiratory health were measured in 2008 and 2010 at eight busy urban streets and at four suburban background control locations. Respiratory function was assessed twice in 661 residents by spirometry and measurements of airway resistance. Nitric oxide (NO) in exhaled air was measured as a marker for airway inflammation. RESULTS: Air pollution concentrations were lower in 2010 than in 2008. The declines in pollutants varied among locations, with the largest decline observed in a street with a large reduction in traffic intensity. In regression analyses adjusted for important covariates, reductions in concentrations of soot, NO2, NOx, Cu, and Fe were associated with increases in forced vital capacity (FVC) (∼1% increase per interquartile range [IQR] decline). Airway resistance decreased with a decline in particulate matter (PM10) and PM2.5 (9% per IQR), although these associations were somewhat less consistent. No associations were found with exhaled NO. Results were driven largely by one street where traffic-related air pollution showed the largest reduction. Forced expiratory volume and FVC improved by 3% to 6% in residents of this street compared with suburban background residents. This was accompanied by a suggestive reduction in airway resistance. CONCLUSIONS: Reductions in air pollution may lead to small improvements in respiratory function.

Traffic-related air pollution is related to interrupter resistance in 4-year-old children.

Outdoor air pollution has been associated with decrements in lung function and growth of lung function in school-age children. Lung function effects have not been examined in preschoolers, with the exception of one study on minute ventilation in newborns. Our goal was to assess the relationship between long- and short-term exposure to traffic-related air pollution and interrupter resistance in 4-year-old children. Lung function was measured using the interrupter resistance method in children participating in a Dutch birth cohort study. Long-term average air pollution concentrations of fine particulate matter, nitrogen dioxide and soot at the residential address at birth were assessed using land-use regression models. Daily average air pollution concentrations on the day of clinical examination were obtained from the Dutch National Air Quality Monitoring Network. Significant associations were found between long-term average air pollution concentrations and interrupter resistance. Interrupter resistance increased by 0.04 kPa·s·L(-1) (95% CI 0.01-0.07) per interquartile range increase (3.3 µg·m(-3)) in fine particle concentration. Short-term exposure was not associated with interrupter resistance. Long-term exposure to traffic-related air pollution was associated with increased interrupter resistance in 4-year-old children, supporting previous birth cohort studies reporting effects of air pollution on subjectively reported respiratory symptoms in preschool children.

Impact of low emission zones and local traffic policies on ambient air pollution concentrations.

BACKGROUND: Evaluations of the effectiveness of air pollution policy interventions are scarce. This study investigated air pollution at street level before and after implementation of local traffic policies including low emission zones (LEZ) directed at heavy duty vehicles (trucks) in five Dutch cities. METHODS: Measurements of PM(10), PM(2.5), 'soot', NO(2), NO(x), and elemental composition of PM(10) and PM(2.5) were conducted simultaneously at eight streets, six urban background locations and four suburban background locations before (2008) and two years after implementation of the policies (2010). The four suburban locations were selected as control locations to account for generic air pollution trends and weather differences. RESULTS: All pollutant concentrations were lower in 2010 than in 2008. For traffic-related pollutants including 'soot' and NO(x) and elemental composition (Cr, Cu, Fe) the decrease did not differ significantly between the intervention locations and the suburban control locations. Only for PM(2.5) reductions were considerably larger at urban streets (30%) and urban background locations (27%) than at the matching suburban control locations (20%). In one urban street where traffic intensity was reduced with 50%, 'soot', NO(x) and NO(2) concentrations were reduced substantially more (41, 36 and 25%) than at the corresponding suburban control location (22, 14 and 7%). CONCLUSION: With the exception of one urban street where traffic flows were drastically reduced, the local traffic policies including LEZ were too modest to produce significant decreases in traffic-related air pollution concentrations.

Contrasts in oxidative potential and other particulate matter characteristics collected near major streets and background locations.

BACKGROUND: Measuring the oxidative potential of airborne particulate matter (PM) may provide a more health-based exposure measure by integrating various biologically relevant properties of PM into a single predictor of biological activity. OBJECTIVES: We aimed to assess the contrast in oxidative potential of PM collected at major urban streets and background locations, the associaton of oxidative potential with other PM characteristics, and the oxidative potential in different PM size fractions. METHODS: Measurements of PM with aerodynamic diameter ≤ 10 µm (PM10), PM with aerodynamic diameter ≤ 2.5 µm (PM2.5), soot, elemental composition, and oxidative potential of PM were conducted simultaneously in samples from 8 major streets and 10 urban and suburban background locations in the Netherlands. Six 1-week measurements were performed at each location over a 6-month period in 2008. Oxidative potential was measured as the ability to generate hydroxyl radicals in the presence of hydrogen peroxide in all PM10 samples and a subset of PM2.5 samples. RESULTS: The PM10 oxidative potential of samples from major streets was 3.6 times higher than at urban background locations, exceeding the contrast for PM mass, soot, and all measured chemical PM characteristics. The contrast between major streets and suburban background locations was even higher (factor of 6.5). Oxidative potential was highly correlated with soot, barium, chromium, copper, iron, and manganese. Oxidative potential of PM10 was 4.6 times higher than the oxidative potential of PM2.5 when expressed per volume unit and 3.1 times higher when expressed per mass unit. CONCLUSIONS: The oxidative potential of PM near major urban roads was highly elevated compared with urban and suburban background locations, and the contrast was greater than that for any other measured PM characteristic.

Long-term exposure to traffic-related air pollution and type 2 diabetes prevalence in a cross-sectional screening-study in the Netherlands.

BACKGROUND: Air pollution may promote type 2 diabetes by increasing adipose inflammation and insulin resistance. This study examined the relation between long-term exposure to traffic-related air pollution and type 2 diabetes prevalence among 50- to 75-year-old subjects living in Westfriesland, the Netherlands. METHODS: Participants were recruited in a cross-sectional diabetes screening-study conducted between 1998 and 2000. Exposure to traffic-related air pollution was characterized at the participants' home-address. Indicators of exposure were land use regression modeled nitrogen dioxide (NO2) concentration, distance to the nearest main road, traffic flow at the nearest main road and traffic in a 250 m circular buffer. Crude and age-, gender- and neighborhood income adjusted associations were examined by logistic regression. RESULTS: 8,018 participants were included, of whom 619 (8%) subjects had type 2 diabetes. Smoothed plots of exposure versus type 2 diabetes supported some association with traffic in a 250 m buffer (the highest three quartiles compared to the lowest also showed increased prevalence, though non-significant and not increasing with increasing quartile), but not with the other exposure metrics. Modeled NO2-concentration, distance to the nearest main road and traffic flow at the nearest main road were not associated with diabetes. Exposure-response relations seemed somewhat more pronounced for women than for men (non-significant). CONCLUSIONS: We did not find consistent associations between type 2 diabetes prevalence and exposure to traffic-related air pollution, though there were some indications for a relation with traffic in a 250 m buffer.

Trends in relative risk estimates for the association between air pollution and mortality in The Netherlands, 1992-2006.

BACKGROUND: Daily variations in the levels of air pollution are well known to be associated with daily variations in mortality counts. Given the large number of time-series studies, there is little need for simple replication of these results in additional locations. However, additional analyses of time-series data might be useful in elucidating remaining questions on the role of air pollution on mortality. OBJECTIVES: Because of ongoing issues related to causality, changing toxicity, the difficulty in isolating the independent effects of individual pollutants, the availability of new methods to detect effect thresholds, and questions about the extent to which effects are restricted to frail members of the population, additional analyses of time-series data might be helpful in addressing these issues. We show an example where additional time-series analyses can be helpful in elucidating specific questions in the field of air pollution epidemiology. METHODS: We analysed daily mortality and air pollution data using Poisson regression in generalised additive models. Air pollution data for the overall period 1992-2006 and for four different periods were analysed to assess the overall risk estimates for the whole period and to assess variability over time for the different effect estimates. RESULTS AND CONCLUSION: We found some statistically significant upward trends, but this was only the case for a few associations without a consistent pattern over the cause-specific deaths. Whether these findings are consistent over time or whether our findings are merely the result of statistical chance can only be elucidated by continuation of monitoring of the relative risks over time in the future. Although these results may indicate that both photochemical and particulate matter air pollution might have become more toxic, the lack of a clear pattern in the results makes these conclusions speculative.

Land use regression model for ultrafine particles in Amsterdam.

There are currently no epidemiological studies on health effects of long-term exposure to ultrafine particles (UFP), largely because data on spatial exposure contrasts for UFP is lacking. The objective of this study was to develop a land use regression (LUR) model for UFP in the city of Amsterdam. Total particle number concentrations (PNC), PM10, PM2.5, and its soot content were measured directly outside 50 homes spread over the city of Amsterdam. Each home was measured during one week. Continuous measurements at a central urban background site were used to adjust the average concentration for temporal variation. Predictor variables (traffic, address density, land use) were obtained using geographic information systems. A model including the product of traffic intensity and the inverse distance to the nearest road squared, address density, and location near the port explained 67% of the variability in measured PNC. LUR models for PM2.5, soot, and coarse particles (PM10, PM2.5) explained 57%, 76%, and 37% of the variability in measured concentrations. Predictions from the PNC model correlated highly with predictions from LUR models for PM2.5, soot, and coarse particles. A LUR model for PNC has been developed, with similar validity as previous models for more commonly measured pollutants.

Radiation-induced tumour necrosis factor-alpha expression: clinical application of transcriptional and physical targeting of gene therapy.

Promising data are emerging on a new anticancer agent, Ad.EGR-TNF, an adenoviral vector, which contains radio-inducible DNA sequences from the early growth response (EGR1) gene promoter and cDNA for the gene encoding human tumour necrosis factor-alpha. Ad.EGR-TNF combines the well-documented broad-spectrum anticancer activity of TNFalpha with the proven clinical usefulness of radiotherapy. Systemic delivery of the TNFalpha protein has had limited success clinically because of severe dose-limiting toxic effects. This limitation has been overcome by the use of a gene delivery approach, combined with a radiation-inducible promoter to express the TNFalpha protein in the irradiated tumour tissue. Preclinical and early phase I clinical testing indicates that effective concentrations of TNFalpha can be delivered to the tumour site without significant systemic exposure or toxic effects. The combination of radiation and TNFalpha gene delivery has produced striking antitumour effects in model systems in animals. In the clinical setting, potent anticancer activity has been observed with a high rate of complete and partial objective tumour responses. A novel mechanism of destruction of the tumour vasculature seems to be central to this distinct antitumour activity. This review summarises the rationale, mechanistic basis, preclinical data, and preliminary clinical findings for this new treatment model.

Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children.

Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n approximately 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 micro m in aerodynamic diameter, and "soot") at the home of each subject of the cohort. Questionnaire-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before 1 year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed.