Mark J. Nieuwenhuijsen

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

BACKGROUND Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING European Communitys Seventh Framework Programme.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

BACKGROUND Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING European Communitys Seventh Framework Program (FP7/2007-2011).

Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review

OBJECTIVES AND METHODS Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research. RESULTS AND CONCLUSIONS Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects— in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure. RECOMMENDATIONS Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right—for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed.

Development of Land Use Regression Models for PM2.5, PM2.5 Absorbance, PM10 and PMcoarse in 20 European Study Areas; Results of the ESCAPE Project

Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.

Fine particle (PM2.5) personal exposure levels in transport microenvironments, London, UK

In order to investigate a specific area of short-term, non-occupational, human exposure to fine particulate air pollution, measurements of personal exposure to PM2.5 in transport microenvironments were taken in two separate field studies in central London, UK. A high flow gravimetric personal sampling system was used; operating at 16 l min−1; the sampler thus allowed for sufficient sample mass collection for accurate gravimetric analysis of short-term travel exposure levels over typical single commute times. In total, samples were taken on 465 journeys and 61 volunteers participated. In a multi-transport mode study, carried out over 3-week periods in the winter and in the summer, exposure levels were assessed along three fixed routes at peak and off-peak times of the day. Geometric means of personal exposure levels were 34.5 μg m−3 (G.S.D.=1.7, ns=40), 39.0 μg m−3 (G.S.D.=1.8, ns=36), 37.7 μg m−3 (G.S.D.=1.5, ns=42), and 247.2 μg m−3 (G.S.D.=1.3, ns=44) for bicycle, bus, car and Tube (underground rail system) modes, respectively, in the July 1999 (summer) measurement campaign. Corresponding levels in the February 2000 (winter) measurement campaign were 23.5 μg m−3 (G.S.D.=1.8, ns=56), 38.9 μg m−3 (G.S.D.=2.1, ns=32), 33.7 μg m−3 (G.S.D.=2.4, ns=12), and 157.3 μg m−3 (G.S.D.=3.3, ns=12), respectively. In a second study, exposure levels were measured for a group of 24 commuters travelling by bicycle, during August 1999, in order to assess how representative the fixed route studies were to a larger commuter population. The geometric mean exposure level was 34.2 μg m−3 (G.S.D.=1.9, ns=105). In the fixed-route study, the cyclists had the lowest exposure levels, bus and car were slightly higher, while mean exposure levels on the London Underground rail system were 3–8 times higher than the surface transport modes. There was significant between-route variation, most notably between the central route and the other routes. The fixed-route study exposure was similar in level and in variability to the ‘real’ commuters study, suggesting that the routes chosen and the number of samples taken provided a reasonably good estimate of the personal exposure levels in the transport microenvironments of Central London. This first comprehensive PM2.5 multi-mode transport user exposure assessment study in the UK also showed that mean personal exposure levels in road transport modes were approximately double that of the PM2.5 concentration at an urban background fixed site monitor.

Improving health through policies that promote active travel: A review of evidence to support integrated health impact assessment

BACKGROUND Substantial policy changes to control obesity, limit chronic disease, and reduce air pollution emissions, including greenhouse gasses, have been recommended. Transportation and planning policies that promote active travel by walking and cycling can contribute to these goals, potentially yielding further co-benefits. Little is known, however, about the interconnections among effects of policies considered, including potential unintended consequences. OBJECTIVES AND METHODS We review available literature regarding health impacts from policies that encourage active travel in the context of developing health impact assessment (HIA) models to help decision-makers propose better solutions for healthy environments. We identify important components of HIA models of modal shifts in active travel in response to transport policies and interventions. RESULTS AND DISCUSSION Policies that increase active travel are likely to generate large individual health benefits through increases in physical activity for active travelers. Smaller, but population-wide benefits could accrue through reductions in air and noise pollution. Depending on conditions of policy implementations, risk tradeoffs are possible for some individuals who shift to active travel and consequently increase inhalation of air pollutants and exposure to traffic injuries. Well-designed policies may enhance health benefits through indirect outcomes such as improved social capital and diet, but these synergies are not sufficiently well understood to allow quantification at this time. CONCLUSION Evaluating impacts of active travel policies is highly complex; however, many associations can be quantified. Identifying health-maximizing policies and conditions requires integrated HIAs.

The health risks and benefits of cycling in urban environments compared with car use: health impact assessment study

Objective To estimate the risks and benefits to health of travel by bicycle, using a bicycle sharing scheme, compared with travel by car in an urban environment. Design Health impact assessment study. Setting Public bicycle sharing initiative, Bicing, in Barcelona, Spain. Participants 181 982 Bicing subscribers. Main outcomes measures The primary outcome measure was all cause mortality for the three domains of physical activity, air pollution (exposure to particulate matter <2.5 µm), and road traffic incidents. The secondary outcome was change in levels of carbon dioxide emissions. Results Compared with car users the estimated annual change in mortality of the Barcelona residents using Bicing (n=181 982) was 0.03 deaths from road traffic incidents and 0.13 deaths from air pollution. As a result of physical activity, 12.46 deaths were avoided (benefit:risk ratio 77). The annual number of deaths avoided was 12.28. As a result of journeys by Bicing, annual carbon dioxide emissions were reduced by an estimated 9 062 344 kg. Conclusions Public bicycle sharing initiatives such as Bicing in Barcelona have greater benefits than risks to health and reduce carbon dioxide emissions.

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

BACKGROUND Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. METHODS We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. FINDINGS A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. INTERPRETATION Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. FUNDING The European Union.

Maternal exposure to particulate air pollution and term birth weight : a multi-country evaluation of effect and heterogeneity

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent. Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association. Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates. Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations. Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.

Birth weight and prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE): A meta-analysis within 12 European birth cohorts

Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight. Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions. Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20–484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 50–1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): –250, –50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: –18, 4 g). Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.