The role of aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use: results of a pooled-analysis from seven European countries.

BACKGROUND: Few studies have considered aircraft noise annoyance and noise sensitivity in analyses of the health effects of aircraft noise, especially in relation to medication use. This study aims to investigate the moderating and mediating role of these two factors in the relationship between aircraft noise levels and medication use among 5860 residents of ten European airports included in the HYENA and DEBATS studies. METHODS: Information on aircraft noise annoyance, noise sensitivity, medication use, and demographic, socio-economic and lifestyle factors was collected during a face-to-face interview at home. Medication was coded according to the Anatomical Therapeutic Chemical (ATC) classification. Outdoor aircraft noise exposure was estimated by linking the participant's home address to noise contours using Geographical Information Systems (GIS) methods. Logistic regressions with adjustment for potential confounding factors were used. In addition, Baron and Kenny's recommendations were followed to investigate the moderating and mediating effects of aircraft noise annoyance and noise sensitivity. RESULTS: A significant association was found between aircraft noise levels at night and antihypertensive medication only in the UK (OR = 1.43, 95%CI 1.19-1.73 for a 10 dB(A)-increase in Lnight). No association was found with other medications. Aircraft noise annoyance was significantly associated with the use of antihypertensive medication (OR = 1.33, 95%CI 1.14-1.56), anxiolytics (OR = 1.48, 95%CI 1.08-2.05), hypnotics and sedatives (OR = 1.60, 95%CI 1.07-2.39), and antasthmatics (OR = 1.44, 95%CI 1.07-1.96), with no difference between countries. Noise sensitivity was significantly associated with almost all medications, with the exception of the use of antasthmatics, showing an increase in ORs with the level of noise sensitivity, with differences in ORs among countries only for the use of antihypertensive medication. The results also suggested a mediating role of aircraft noise annoyance and a modifying role of both aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use. CONCLUSIONS: The present study is consistent with the results of the small number of studies available to date suggesting that both aircraft noise annoyance and noise sensitivity should be taken into account in analyses of the health effects of exposure to aircraft noise.

Mortality and Morbidity Effects of Long-Term Exposure to Low-Level PM2.5, BC, NO2, and O3: An Analysis of European Cohorts in the ELAPSE Project.

INTRODUCTION: Epidemiological cohort studies have consistently found associations between long-term exposure to outdoor air pollution and a range of morbidity and mortality endpoints. Recent evaluations by the World Health Organization and the Global Burden of Disease study have suggested that these associations may be nonlinear and may persist at very low concentrations. Studies conducted in North America in particular have suggested that associations with mortality persisted at concentrations of particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) well below current air quality standards and guidelines. The uncertainty about the shape of the concentration-response function at the low end of the concentration distribution, related to the scarcity of observations in the lowest range, was the basis of the current project. Previous studies have focused on PM2.5, but increasingly associations with nitrogen dioxide (NO2) are being reported, particularly in studies that accounted for the fine spatial scale variation of NO2. Very few studies have evaluated the effects of long-term exposure to low concentrations of ozone (O3). Health effects of black carbon (BC), representing primary combustion particles, have not been studied in most large cohort studies of PM2.5. Cohort studies assessing health effects of particle composition, including elements from nontailpipe traffic emissions (iron, copper, and zinc) and secondary aerosol (sulfur) have been few in number and reported inconsistent results. The overall objective of our study was to investigate the shape of the relationship between long-term exposure to four pollutants (PM2.5, NO2, BC, and O3) and four broad health effect categories using a number of different methods to characterize the concentration-response function (i.e., linear, nonlinear, or threshold). The four health effect categories were (1) natural- and cause-specific mortality including cardiovascular and nonmalignant as well as malignant respiratory and diabetes mortality; and morbidity measured as (2) coronary and cerebrovascular events; (3) lung cancer incidence; and (4) asthma and chronic obstructive pulmonary disease (COPD) incidence. We additionally assessed health effects of PM2.5 composition, specifically the copper, iron, zinc, and sulfur content of PM2,5. METHODS: We focused on analyses of health effects of air pollutants at low concentrations, defined as less than current European Union (EU) Limit Values, U.S. Environmental Protection Agency (U.S. EPA), National Ambient Air Quality Standards (NAAQS), and/or World Health Organization (WHO) Air Quality Guideline values for PM2.5, NO2, and O3. We address the health effects at low air pollution levels by performing new analyses within selected cohorts of the ESCAPE study (European Study of Cohorts for Air Pollution Effects; Beelen et al. 2014a) and within seven very large European administrative cohorts. By combining well-characterized ESCAPE cohorts and large administrative cohorts in one study the strengths and weaknesses of each approach can be addressed. The large administrative cohorts are more representative of national or citywide populations, have higher statistical power, and can efficiently control for area-level confounders, but have fewer possibilities to control for individual-level confounders. The ESCAPE cohorts have detailed information on individual confounders, as well as country-specific information on area-level confounding. The data from the seven included ESCAPE cohorts and one additional non-ESCAPE cohort have been pooled and analyzed centrally. More than 300,000 adults were included in the pooled cohort from existing cohorts in Sweden, Denmark, Germany, the Netherlands, Austria, France, and Italy. Data from the administrative cohorts have been analyzed locally, without transfer to a central database. Privacy regulations prevented transfer of data from administrative cohorts to a central database. More than 28 million adults were included from national administrative cohorts in Belgium, Denmark, England, the Netherlands, Norway, and Switzerland as well as an administrative cohort in Rome, Italy. We developed central exposure assessment using Europewide hybrid land use regression (LUR) models, which incorporated European routine monitoring data for PM2.5, NO2, and O3, and ESCAPE monitoring data for BC and PM2.5 composition, land use, and traffic data supplemented with satellite observations and chemical transport model estimates. For all pollutants, we assessed exposure at a fine spatial scale, 100 × 100 m grids. These models have been applied to individual addresses of all cohorts including the administrative cohorts. In sensitivity analyses, we applied the PM2.5 models developed within the companion HEI-funded Canadian MAPLE study (Brauer et al. 2019) and O3 exposures on a larger spatial scale for comparison with previous studies. Identification of outcomes included linkage with mortality, cancer incidence, hospital discharge registries, and physician-based adjudication of cases. We analyzed natural-cause, cardiovascular, ischemic heart disease, stroke, diabetes, cardiometabolic, respiratory, and COPD mortality. We also analyzed lung cancer incidence, incidence of coronary and cerebrovascular events, and incidence of asthma and COPD (pooled cohort only). We applied the Cox proportional hazard model with increasing control for individual- and area-level covariates to analyze the associations between air pollution and mortality and/or morbidity for both the pooled cohort and the individual administrative cohorts. Age was used as the timescale because of evidence that this results in better adjustment for potential confounding by age. Censoring occurred at the time of the event of interest, death from other causes, emigration, loss to follow-up for other reasons, or at the end of follow-up, whichever came first. A priori we specified three confounder models, following the modeling methods of the ESCAPE study. Model 1 included only age (time axis), sex (as strata), and calendar year of enrollment. Model 2 added individual-level variables that were consistently available in the cohorts contributing to the pooled cohort or all variables available in the administrative cohorts, respectively. Model 3 further added area-level socioeconomic status (SES) variables. A priori model 3 was selected as the main model. All analyses in the pooled cohort were stratified by subcohort. All analyses in the administrative cohorts accounted for clustering of the data in neighborhoods by adjusting the variance of the effect estimates. The main exposure variable we analyzed was derived from the Europewide hybrid models based on 2010 monitoring data. Sensitivity analyses were conducted using earlier time periods, time-varying exposure analyses, local exposure models, and the PM2.5 models from the Canadian MAPLE project. We first specified linear single-pollutant models. Two-pollutant models were specified for all combinations of the four main pollutants. Two-pollutant models for particle composition were analyzed with PM2.5 and NO2 as the second pollutant. We then investigated the shape of the concentration-response function using natural splines with two, three, and four degrees of freedom; penalized splines with the degrees of freedom determined by the algorithm and shape-constrained health impact functions (SCHIF) using confounder model 3. Additionally, we specified linear models in subsets of the concentration range, defined by removing concentrations above a certain value from the analysis, such as for PM2.5 25 µg/m3 (EU limit value), 20, 15, 12 µg/m3 (U.S. EPA National Ambient Air Quality Standard), and 10 µg/m3 (WHO Air Quality Guideline value). Finally, threshold models were evaluated to investigate whether the associations persisted below specific concentration values. For PM2.5, we evaluated 10, 7.5, and 5 µg/m3 as potential thresholds. Performance of threshold models versus the corresponding no-threshold linear model were evaluated using the Akaike information criterion (AIC). RESULTS: In the pooled cohort, virtually all subjects in 2010 had PM2.5 and NO2 annual average exposures below the EU limit values (25 µg/m3 and 40 µg/m3, respectively). More than 50,000 had a residential PM2.5 exposure below the U.S. EPA NAAQS (12 µg/m3). More than 25,000 subjects had a residential PM2.5 exposure below the WHO guideline (10 µg/m3). We found significant positive associations between PM2.5, NO2, and BC and natural-cause, respiratory, cardiovascular, and diabetes mortality. In our main model, the hazard ratios (HRs) (95% [confidence interval] CI) were 1.13 (CI = 1.11, 1.16) for an increase of 5 µg/m3 PM2.5, 1.09 (CI = 1.07, 1.10) for an increase of 10 µg/m3 NO2, and 1.08 (CI = 1.06, 1.10) for an increase of 0.5 × 10-5/m BC for natural-cause mortality. The highest HRs were found for diabetes mortality. Associations with O3 were negative, both in the fine spatial scale of the main ELAPSE model and in large spatial scale exposure models. For PM2.5, NO2, and BC, we generally observed a supralinear association with steeper slopes at low exposures and no evidence of a concentration below which no association was found. Subset analyses further confirmed that these associations remained at low levels: below 10 µg/m3 for PM2.5 and 20 µg/m3 for NO2. HRs were similar to the full cohort HRs for subjects with exposures below the EU limit values for PM2.5 and NO2, the U.S. NAAQS values for PM2.5, and the WHO guidelines for PM2.5 and NO2. The mortality associations were robust to alternative specifications of exposure, including different time periods, PM2.5 from the MAPLE project, and estimates from the local ESCAPE model. Time-varying exposure natural spline analyses confirmed associations at low pollution levels. HRs in two-pollutant models were attenuated but remained elevated and statistically significant for PM2.5 and NO2. In two-pollutant models of PM2.5 and NO2 HRs for natural-cause mortality were 1.08 (CI = 1.05, 1.11) for PM2.5 and 1.05 (CI = 1.03, 1.07) for NO2. Associations with O3 were attenuated but remained negative in two-pollutant models with NO2, BC, and PM2.5. We found significant positive associations between PM2.5, NO2, and BC and incidence of stroke and asthma and COPD hospital admissions. Furthermore, NO2 was significantly related to acute coronary heart disease and PM2.5 was significantly related to lung cancer incidence. We generally observed linear to supralinear associations with no evidence of a threshold, with the exception of the association between NO2 and acute coronary heart disease, which was sublinear. Subset analyses documented that associations remained even with PM2.5 below 20 µg/m3 and possibly 12 µg/m3. Associations remained even when NO2 was below 30 µg/m3 and in some cases 20 µg/m3. In two-pollutant models, NO2 was most consistently associated with acute coronary heart disease, stroke, asthma, and COPD hospital admissions. PM2.5 was not associated with these outcomes in two-pollutant models with NO2. PM2.5 was the only pollutant that was associated with lung cancer incidence in two-pollutant models. Associations with O3 were negative though generally not statistically significant. In the administrative cohorts, virtually all subjects in 2010 had PM2.5 and NO2 annual average exposures below the EU limit values. More than 3.9 million subjects had a residential PM2.5 exposure below the U.S. EPA NAAQS (12 µg/m3) and more than 1.9 million had residential PM2.5 exposures below the WHO guideline (10 µg/m3). We found significant positive associations between PM2.5, NO2, and BC and natural-cause, respiratory, cardiovascular, and lung cancer mortality, with moderate to high heterogeneity between cohorts. We found positive but statistically nonsignificant associations with diabetes mortality. In our main model meta-analysis, the HRs (95% CI) for natural-cause mortality were 1.05 (CI = 1.02, 1.09) for an increase of 5 µg/m3 PM2.5, 1.04 (CI = 1.02, 1.07) for an increase of 10 µg/m3 NO2, and 1.04 (CI = 1.02, 1.06) for an increase of 0.5 × 10-5/m BC, and 0.95 (CI = 0.93, 0.98) for an increase of 10 µg/m3 O3. The shape of the concentration-response functions differed between cohorts, though the associations were generally linear to supralinear, with no indication of a level below which no associations were found. Subset analyses documented that these associations remained at low levels: below 10 µg/m3 for PM2.5 and 20 µg/m3 for NO2. BC and NO2 remained significantly associated with mortality in two-pollutant models with PM2.5 and O3. The PM2.5 HR attenuated to unity in a two-pollutant model with NO2. The negative O3 association was attenuated to unity and became nonsignificant. The mortality associations were robust to alternative specifications of exposure, including time-varying exposure analyses. Time-varying exposure natural spline analyses confirmed associations at low pollution levels. Effect estimates in the youngest participants (<65 years at baseline) were much larger than in the elderly (>65 years at baseline). Effect estimates obtained with the ELAPSE PM2.5 model did not differ from the MAPLE PM2.5 model on average, but in individual cohorts, substantial differences were found. CONCLUSIONS: Long-term exposure to PM2.5, NO2, and BC was positively associated with natural-cause and cause-specific mortality in the pooled cohort and the administrative cohorts. Associations were found well below current limit values and guidelines for PM2.5 and NO2. Associations tended to be supralinear, with steeper slopes at low exposures with no indication of a threshold. Two-pollutant models documented the importance of characterizing the ambient mixture with both NO2 and PM2.5. We mostly found negative associations with O3. In two-pollutant models with NO2, the negative associations with O3 were attenuated to essentially unity in the mortality analysis of the administrative cohorts and the incidence analyses in the pooled cohort. In the mortality analysis of the pooled cohort, significant negative associations with O3 remained in two-pollutant models. Long-term exposure to PM2.5, NO2, and BC was also positively associated with morbidity outcomes in the pooled cohort. For stroke, asthma, and COPD, positive associations were found for PM2.5, NO2, and BC. For acute coronary heart disease, an increased HR was observed for NO2. For lung cancer, an increased HR was found only for PM2.5. Associations mostly showed steeper slopes at low exposures with no indication of a threshold.

The role of aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and hypertension risk: Results of a pooled analysis from seven European countries.

INTRODUCTION: Many studies, including the HYENA and the DEBATS studies, showed a significant association between aircraft noise exposure and the risk of hypertension. Few studies have considered aircraft noise annoyance and noise sensitivity as factors of interest, especially in relation to hypertension risk, or as mediating or modifying factors. The present study aims 1) to investigate the risk of hypertension in relation to aircraft noise annoyance or noise sensitivity; and 2) to examine the role of modifier or mediator of these two factors in the association between aircraft noise levels and the risk of hypertension. METHODS: This study included 6,105 residents of ten European airports from the HYENA and DEBATS studies. Information on aircraft noise annoyance, noise sensitivity, and demographic, socioeconomic and lifestyle factors was collected during an interview performed at home. Participants were classified as hypertensive if they had either blood pressure levels above the WHO cut-off points or physician-diagnosed hypertension in conjunction with the use of antihypertensive medication. Outdoor aircraft noise exposure was estimated for each participant's home address. Poisson regression models with adjustment for potential confounders were used. Interactions between noise exposure and country were tested to consider possible differences between countries. RESULTS: An increase in aircraft noise levels at night was weekly but significantly associated with an increased risk of hypertension (RR = 1.03, 95% CI 1.01-1.06 for a 10-dB(A) increase in Lnight). A significant association was found between aircraft noise annoyance and hypertension risk (RR = 1.06, 95%CI 1.00-1.13 for highly annoyed people compared to those who were not highly annoyed). The risk of hypertension was slightly higher for people highly sensitive to noise compared to people with low sensitivity in the UK (RR = 1.29, 95%CI 1.05-1.59) and in France (RR = 1.11, 95%CI 0.68-1.82), but not in the other countries. The association between aircraft noise levels and the risk of hypertension was higher among highly sensitive participants (RR = 1.00, 95%CI 0.96-1.04; RR = 1.03, 95%CI 0.90-1.11; RR = 1.12, 95%CI 1.01-1.24, with a 10-dB(A) increase in Lnight for low, medium, and high sensitive people respectively) or, to a lesser extent, among highly annoyed participants (RR = 1.06, 95%CI 0.95-1.18 for a 10-dB(A) increase in Lnight among highly annoyed participants, and RR = 1.02, 95%CI 0.99-1.06 among those not highly annoyed). CONCLUSIONS: The present study confirms findings in the small number of available studies to date suggesting adverse health effects associated with aircraft noise annoyance and noise sensitivity. The findings also indicate possible modifier effects of aircraft noise annoyance and noise sensitivity in the relationship between aircraft noise levels and the risk of hypertension. However, further investigations are needed to better understand this role using specific methodology and tools related to mediation analysis and causal inference.

Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE).

Aims: We investigated whether traffic-related air pollution and noise are associated with incident hypertension in European cohorts. Methods and results: We included seven cohorts of the European study of cohorts for air pollution effects (ESCAPE). We modelled concentrations of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10), >2.5, and ≤10 µm (PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of participants with land use regression. Residential exposure to traffic noise was modelled at the facade according to the EU Directive 2002/49/EC. We assessed hypertension as (i) self-reported and (ii) measured (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or intake of BP lowering medication (BPLM). We used Poisson regression with robust variance estimation to analyse associations of traffic-related exposures with incidence of hypertension, controlling for relevant confounders, and combined the results from individual studies with random-effects meta-analysis. Among 41 072 participants free of self-reported hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years of follow-up. Incidence of self-reported hypertension was positively associated with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI):1.08; 1.37] per 5 µg/m³) and PM2.5 absorbance (RR 1.13 [95% CI:1.02; 1.24] per 10 - 5m - 1). These estimates decreased slightly upon adjustment for road traffic noise. Road traffic noise was weakly positively associated with the incidence of self-reported hypertension. Among 10 896 participants at risk, 3549 new cases of measured hypertension occurred. We found no clear associations with measured hypertension. Conclusion: Long-term residential exposures to air pollution and noise are associated with increased incidence of self-reported hypertension.

Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens, Greece.

BACKGROUND: We followed up, in 2013, the subjects who lived near the Athens International Airport and had participated in the cross-sectional multicountry HYENA study in 2004-2006. OBJECTIVE: To evaluate the association of exposure to aircraft and road traffic noise with the incidence of hypertension and other cardiovascular outcomes. METHODS: From the 780 individuals who participated in the cross-sectional study, 537 were still living in the same area and 420 accepted to participate in the follow-up. Aircraft and road traffic noise exposure was based on the estimations conducted in 2004-2006, linking geocoded residential addresses of the participants to noise levels. We applied multiple logistic regression and Cox proportional hazards models, adjusting for potential confounders. RESULTS: The incidence of hypertension was significantly associated with higher aircraft noise exposure during the night. Specifically, the OR for hypertension per 10 dB increase in Lnight aircraft noise exposure was 2.63 (95% CI 1.21 to 5.71). Doctor-diagnosed cardiac arrhythmia was significantly associated with Lnight aircraft noise exposure, when prevalent and incident cases were considered with an OR of 2.09 (95% CI 1.07 to 4.08). Stroke risk was also increased with increasing noise exposure but the association was not significant. Twenty-four-hour road traffic noise associations with the outcomes considered were weaker and less consistent. CONCLUSIONS: In conclusion, our cohort study suggests that long-term exposure to aircraft noise, particularly during the night, is associated with incident hypertension and possibly, also, cardiovascular effects.

Associations between lifestyle and air pollution exposure: Potential for confounding in large administrative data cohorts.

BACKGROUND: Cohorts based on administrative data have size advantages over individual cohorts in investigating air pollution risks, but often lack in-depth information on individual risk factors related to lifestyle. If there is a correlation between lifestyle and air pollution, omitted lifestyle variables may result in biased air pollution risk estimates. Correlations between lifestyle and air pollution can be induced by socio-economic status affecting both lifestyle and air pollution exposure. OBJECTIVES: Our overall aim was to assess potential confounding by missing lifestyle factors on air pollution mortality risk estimates. The first aim was to assess associations between long-term exposure to several air pollutants and lifestyle factors. The second aim was to assess whether these associations were sensitive to adjustment for individual and area-level socioeconomic status (SES), and whether they differed between subgroups of the population. Using the obtained air pollution-lifestyle associations and indirect adjustment methods, our third aim was to investigate the potential bias due to missing lifestyle information on air pollution mortality risk estimates in administrative cohorts. METHODS: We used a recent Dutch national health survey of 387,195 adults to investigate the associations of PM10, PM2.5, PM2.5-10, PM2.5 absorbance, OPDTT, OPESR and NO2 annual average concentrations at the residential address from land use regression models with individual smoking habits, alcohol consumption, physical activity and body mass index. We assessed the associations with and without adjustment for neighborhood and individual SES characteristics typically available in administrative data cohorts. We illustrated the effect of including lifestyle information on the air pollution mortality risk estimates in administrative cohort studies using a published indirect adjustment method. RESULTS: Current smoking and alcohol consumption were generally positively associated with air pollution. Physical activity and overweight were negatively associated with air pollution. The effect estimates were small (mostly <5% of the air pollutant standard deviations). Direction and magnitude of the associations depended on the pollutant, use of continuous vs. categorical scale of the lifestyle variable, and level of adjustment for individual and area-level SES. Associations further differed between subgroups (age, sex) in the population. Despite the small associations between air pollution and smoking intensity, indirect adjustment resulted in considerable changes of air pollution risk estimates for cardiovascular and especially lung cancer mortality. CONCLUSIONS: Individual lifestyle-related risk factors were weakly associated with long-term exposure to air pollution in the Netherlands. Indirect adjustment for missing lifestyle factors in administrative data cohort studies may substantially affect air pollution mortality risk estimates.

Road traffic noise and registry based use of sleep medication.

BACKGROUND: Road traffic noise has been associated with adverse health effects including sleep disturbances. Use of sleep medication as an indicator of sleeping problems has rarely been explored in studies of the effects of traffic noise. Furthermore, using registry data on sleep medications provides an opportunity to study the effects of noise on sleep where attribution of sleep problems to noise is not possible. METHODS: We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-10) (n = 13,019). Individual data on sleep medications was obtained from the Norwegian Prescription Database (NorPD). Noise levels (L night) were modeled for the most exposed façade of the building at each participant's home address. Logistic regression models adjusted for potential confounders were used to analyze the association between traffic noise and sleep medication use both for one whole year and for the summer season. The results were reported as changes in the effect estimate per 5 decibel (dB) increase in noise level. RESULTS: We observed no association between traffic noise and sleep medication use during one year [odds ratio (OR) = 1.00; 95% confidence interval (CI): 0.96, 1.04]. For sleep medication use in the summer season, there was a positive, however non-significant association (OR = 1.04; 95% CI: 0.99, 1.10). Among individuals sleeping with the bedroom window open, the association increased slightly and was borderline statistically significant (OR = 1.06; 95% CI: 1.00, 1.12). CONCLUSIONS: We found no evidence of an association between traffic noise and sleep medication use during one year. However, for the summer season, there was some suggestive evidence of an association. These findings indicate that season may play a role in the association between traffic noise and sleep, possibly because indoor traffic noise levels are likely to be higher during summer due to more frequent window opening. More studies are, however, necessary in order to confirm this.

Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts.

BACKGROUND: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. METHODS: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 µm (PM2.5), less than 10 µm (PM10), and 10 µm to 2.5 µm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. RESULTS: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 µg/m and for PM10, 1.22 (0.91-1.63) per 10 µg/m. CONCLUSION: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.

Multi-country willingness to pay study on road-traffic environmental health effects: are people willing and able to provide a number?

BACKGROUND: The health impacts from traffic-related pollutants bring costs to society, which are often not reflected in market prices for transportation. We set out to simultaneously assess the willingness-to-pay (WTP) for traffic-related air pollution and noise effect on health, using a single measurement instrument and approach. We investigated the proportion and determinants of "protest vote/PV responses (people who were against valuing their health in terms of money)" and "don't know"/DK answers, and explored the effect of DK on the WTP distributions. METHODS: Within the framework of the EU-funded project INTARESE, we asked over 5,200 respondents in five European countries to state their WTP to avoid health effects from road traffic-related air pollution and noise in an open-ended web-based questionnaire. Determinants of PV and DK were studied by logistic regression using variables concerning socio-demographics, income, health and environmental concern, and risk perception. RESULTS: About 10% of the respondents indicated a PV response and between 47-56% of respondents gave DK responses. About one-third of PV respondents thought that costs should be included in transportation prices, i.e. the polluter should pay. Logistic regression analyses showed associations of PV and DK with several factors. In addition to social-demographic, economic and health factors known to affect WTP, environmental concern, awareness of health effects, respondent's ability to relax in polluted places, and their view on the government's role to reduce pollution and on policy to improve wellbeing, also affected the PV and DK response. An exploratory weighting and imputation exercise did not show substantial effects of DK on the WTP distribution. CONCLUSIONS: With a proportion of about 50%, DK answers may be a more relevant issue affecting WTP than PV's. The likelihood to give PV and DK response were influenced by socio-demographic, economic and health factors, as well as environmental concerns and appreciation of environmental conditions and policies. In contested policy issues where actual policy may be based on WTP studies, PV and DK answers may indeed affect the outcome of the WTP study. PV and DK answers and their determinants therefore deserve further study in CV studies on environmental health effects.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Exposure to aircraft and road traffic noise and associations with heart disease and stroke in six European countries: a cross-sectional study.

BACKGROUND: Although a number of studies have found an association between aircraft noise and hypertension, there is a lack of evidence on associations with other cardiovascular disease. For road traffic noise, more studies are available but the extent of possible confounding by air pollution has not been established. METHODS: This study used data from the Hypertension and Environmental Noise near Airports (HYENA) study. Cross-sectional associations between self-reported 'heart disease and stroke' and aircraft noise and road traffic noise were examined using data collected between 2004 and 2006 on 4712 participants (276 cases), who lived near airports in six European countries (UK, Germany, Netherlands, Sweden, Greece, Italy). Data were available to assess potential confounding by NO2 air pollution in a subsample of three countries (UK, Netherlands, Sweden). RESULTS: An association between night-time average aircraft noise and 'heart disease and stroke' was found after adjustment for socio-demographic confounders for participants who had lived in the same place for ≥ 20 years (odds ratio (OR): 1.25 (95% confidence interval (CI) 1.03, 1.51) per 10 dB (A)); this association was robust to adjustment for exposure to air pollution in the subsample. 24 hour average road traffic noise exposure was associated with 'heart disease and stroke' (OR: 1.19 (95% CI 1.00, 1.41), but adjustment for air pollution in the subsample suggested this may have been due to confounding by air pollution. Statistical assessment (correlations and variance inflation factor) suggested only modest collinearity between noise and NO2 exposures. CONCLUSIONS: Exposure to aircraft noise over many years may increase risks of heart disease and stroke, although more studies are needed to establish how much the risks associated with road traffic noise may be explained by air pollution.

PM10, and children's respiratory symptoms and lung function in the PATY study.

Studies of the impact of long-term exposure to outdoor air pollution on the prevalence of respiratory symptoms and lung function in children have yielded mixed results, partly related to differences in study design, exposure assessment, confounder selection and data analysis. We assembled respiratory health and exposure data for >45,000 children from comparable cross-sectional studies in 12 countries. 11 respiratory symptoms were selected, for which comparable questions were asked. Spirometry was performed in about half of the children. Exposure to air pollution was mainly characterised by annual average concentrations of particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) measured at fixed sites within the study areas. Positive associations were found between the average PM(10) concentration and the prevalence of phlegm (OR per 10 µg · m(-3) 1.15, 95% CI 1.02-1.30), hay fever (OR 1.20, 95% CI 0.99-1.46), bronchitis (OR 1.08, 95% CI 0.98-1.19), morning cough (OR 1.15, 95% CI 1.02-1.29) and nocturnal cough (OR 1.13, 95% CI 0.98-1.29). There were no associations with diagnosed asthma or asthma symptoms. PM(10) was not associated with lung function across all studies combined. Our study adds to the evidence that long-term exposure to outdoor air pollution, characterised by the concentration of PM(10), is associated with increased respiratory symptoms.

Neurobehavioral effects of exposure to traffic-related air pollution and transportation noise in primary schoolchildren.

BACKGROUND: Children living close to roads are exposed to both traffic noise and traffic-related air pollution. There are indications that both exposures affect cognitive functioning. So far, the effects of both exposures have only been investigated separately. OBJECTIVES: To investigate the relationship between air pollution and transportation noise on the cognitive performance of primary schoolchildren in both the home and school setting. METHODS: Data acquired within RANCH from 553 children (aged 9-11 years) from 24 primary schools were analysed using multilevel modelling with adjustment for a range of socio-economic and life-style factors. RESULTS: Exposure to NO(2) (which is in urban areas an indicator for traffic-related air pollution) at school was statistically significantly associated with a decrease in the memory span length measured during DMST (χ(2)=6.8, df=1, p=0.01). This remained after additional adjustment for transportation noise. Statistically significant associations were observed between road and air traffic noise exposure at school and the number of errors made during the 'arrow' (χ(2)=7.5, df=1, p=0.006) and 'switch' (χ(2)=4.8, df=1, p=0.028) conditions of the SAT. This remained after adjustment for NO(2). No effects of air pollution exposure or transportation noise exposure at home were observed. Combined exposure of air pollution and road traffic noise had a significant effect on the reaction times measured during the SRTT and the 'block' and the 'arrow' conditions of the SAT. CONCLUSIONS: Our results provide some support that prolonged exposure to traffic-related air pollution as well as to noise adversely affects cognitive functioning.

Exposure modifiers of the relationships of transportation noise with high blood pressure and noise annoyance.

In the cross-sectional hypertension and exposure to noise near airports study the relationship between road traffic noise, aircraft noise and hypertension and annoyance was investigated. The data collection comprised a variety of potentially exposure modifying factors, including type of housing, location of rooms, window opening habits, use of noise-reducing remedies, shielding due to obstacles, lengths of exposure. In the present paper the quantitative role of these factors on the relationship between road and aircraft noise exposure and outcomes was analyzed. Multiple logistic and linear regression models were calculated including these co-factors and related interaction terms with noise indicators, as well as stratified analyses. Type of housing, length of residence, location of rooms and the use of noise reducing remedies modified the relationship between noise and hypertension. However, the effects were not always in the direction of a stronger association in higher exposed subjects. Regarding annoyance, type of housing, location of rooms, noise barriers, window opening habits, noise insulation, the use of noise reducing remedies, hours spent at home during daytime were significant effect modifiers. The use of noise-reducing remedies turned out to be indicators of perceived noise disturbance rather than modifiers reducing the annoyance.

Proximity to livestock farms and COVID-19 in the Netherlands, 2020-2021.

OBJECTIVES: In the Netherlands, during the first phase of the COVID-19 epidemic, the hotspot of COVID-19 overlapped with the country's main livestock area, while in subsequent phases this distinct spatial pattern disappeared. Previous studies show that living near livestock farms influence human respiratory health and immunological responses. This study aimed to explore whether proximity to livestock was associated with SARS-CoV-2 infection. METHODS: The study population was the population of the Netherlands excluding the very strongly urbanised areas and border areas, on January 1, 2019 (12, 628, 244 individuals). The cases are the individuals reported with a laboratory-confirmed positive SARS-CoV-2 test with onset before January 1, 2022 (2, 223, 692 individuals). For each individual, we calculated distance to nearest livestock farm (cattle, goat, sheep, pig, poultry, horse, rabbit, mink). The associations between residential (6-digit postal-code) distance to the nearest livestock farm and individuals' SARS-CoV-2 status was studied with multilevel logistic regression models. Models were adjusted for individuals' age categories, the social status of the postal code area, particulate matter (PM10)- and nitrogen dioxide (NO2)-concentrations. We analysed data for the entire period and population as well as separately for eight time periods (Jan-Mar, Apr-Jun, Jul-Sep and Oct-Dec in 2020 and 2021), four geographic areas of the Netherlands (north, east, west and south), and for five age categories (0-14, 15-24, 25-44, 45-64 and > 65 years). RESULTS: Over the period 2020-2021, individuals' SARS-CoV-2 status was associated with living closer to livestock farms. This association increased from an Odds Ratio (OR) of 1.01 (95% Confidence Interval [CI] 1.01-1.02) for patients living at a distance of 751-1000 m to a farm to an OR of 1.04 (95% CI 1.04-1.04), 1.07 (95% CI 1.06-1.07) and 1.11 (95% CI 1.10-1.12) for patients living in the more proximate 501-750 m, 251-500m and 0-250 m zones around farms, all relative to patients living further than 1000 m around farms. This association was observed in three out of four quarters of the year in both 2020 and 2021, and in all studied geographic areas and age groups. CONCLUSIONS: In this exploratory study with individual SARS-CoV-2 notification data and high-resolution spatial data associations were found between living near livestock farms and individuals' SARS-CoV-2 status in the Netherlands. Verification of the results in other countries is warranted, as well as investigations into possible underlying exposures and mechanisms.

Assessment of drinking water safety in the Netherlands using nationwide exposure and mortality data.

BACKGROUND: Although drinking water in the Netherlands is generally accepted as safe, public concern about health risks of long-term intake still exist. OBJECTIVE: The aim was to explore associations between drinking water quality for nitrate, water hardness, calcium and magnesium and causes-of-death as related to cardiovascular diseases amongst which coronary heart disease and colorectal cancer. METHODS: We used national administrative databases on cause-specific mortality, personal characteristics, residential history, social economic indicators, air quality and drinking water quality for parameters specified by the EU Drinking Water Directive. We put together a cohort of 6,998,623 persons who were at least 30 years old on January 1, 2008 and lived for at least five years on the same address. The average drinking water concentration over 2000-2010 at the production stations were used as exposure indicators. We applied age stratified Cox proportional hazards models. RESULTS: Magnesium was associated with a reduced risk for mortality due to coronary heart diseases: HR of 0.95 (95% CI: 0.90, 0.99) per 10 mg/L increase. For mortality due to cardiovascular diseases, a 100 mg/L increase in calcium was associated with a HR of 1.08 (95% CI: 1.03, 1.13) and an increase of 2.5 mmol/L of water hardness with a HR of 1.06 (95% CI: 1.01, 1.10). The results show an elevated risk for coronary heart disease mortality at calcium concentrations below 30 mg/L, but over the whole exposure range no exposure response relation was observed. For other combinations of drinking water quality parameters and cause-specific mortality studied, no statistical significant associations were identified. CONCLUSION: We identified in this explorative study a protective effect of magnesium for the risk of mortality to coronary heart disease. Also we found an increased risk of mortality due to cardiovascular disease associated with the concentration of calcium and the water hardness in drinking water.

Global, regional, and national burden of mortality associated with short-term temperature variability from 2000-19: a three-stage modelling study.

BACKGROUND: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5°â€ˆ× 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19. METHODS: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5°â€ˆ× 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. FINDINGS: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6). INTERPRETATION: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. FUNDING: Australian Research Council, Australian National Health & Medical Research Council.

Fluctuating temperature modifies heat-mortality association around the globe.

Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days' minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: -0.33 to 1.69), 1.34% (95% CI: -0.14 to 2.73), 1.99% (95% CI: 0.29-3.57), and 2.73% (95% CI: 0.76-4.50) of total deaths for Q1-Q4 (first quartile-fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25-9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: -0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health.

Medication use in relation to noise from aircraft and road traffic in six European countries: results of the HYENA study.

OBJECTIVES: Studies on the health effects of aircraft and road traffic noise exposure suggest excess risks of hypertension, cardiovascular disease and the use of sedatives and hypnotics. Our aim was to assess the use of medication in relation to noise from aircraft and road traffic. METHODS: This cross-sectional study measured the use of prescribed antihypertensives, antacids, anxiolytics, hypnotics, antidepressants and antasthmatics in 4,861 persons living near seven airports in six European countries (UK, Germany, the Netherlands, Sweden, Italy, and Greece). Exposure was assessed using models with 1 dB resolution (5 dB for UK road traffic noise) and spatial resolution of 250×250 m for aircraft and 10×10 m for road traffic noise. Data were analysed using multilevel logistic regression, adjusting for potential confounders. RESULTS: We found marked differences between countries in the effect of aircraft noise on antihypertensive use; for night-time aircraft noise, a 10 dB increase in exposure was associated with ORs of 1.34 (95% CI 1.14 to 1.57) for the UK and 1.19 (1.02 to 1.38) for the Netherlands but no significant associations were found for other countries. For day-time aircraft noise, excess risks were found for the UK (OR 1.35; CI: 1.13 to 1.60) but a risk deficit for Italy (OR 0.82; CI: 0.71 to 0.96). There was an excess risk of taking anxiolytic medication in relation to aircraft noise (OR 1.28; CI: 1.04 to 1.57 for daytime and OR 1.27; CI: 1.01 to 1.59 for night-time) which held across countries. We also found an association between exposure to 24hr road traffic noise and the use of antacids by men (OR 1.39; CI 1.11 to 1.74). CONCLUSION: Our results suggest an effect of aircraft noise on the use of antihypertensive medication, but this effect did not hold for all countries. Results were more consistent across countries for the increased use of anxiolytics in relation to aircraft noise.

Maternal smoking during pregnancy and childhood obesity: results from the CESAR Study.

Childhood obesity is a worldwide public health concern. Recent studies from high income countries have demonstrated associations between maternal smoking during pregnancy and children's excess body weight. We examine associations between maternal smoking during pregnancy and children's overweight or obesity, in six countries in the less affluent Central/Eastern European region. Questionnaire data were analysed, for 8,926 singleton children aged 9-12 years. Country-specific odds ratios for effects of maternal smoking during pregnancy on being overweight, and on obesity, were estimated using logistic regression. Heterogeneity between country-specific results, and mean effects (allowing for heterogeneity) were estimated. Positive associations between maternal smoking and overweight were seen in all countries but Romania. While not individually statistically significant, the mean odds ratio was 1.26 (95% CI 1.03-1.55), with no evidence of between-country heterogeneity. Obese children were few (2.7%), and associations between obesity and maternal smoking during pregnancy were more heterogeneous, with odds ratios ranging from 0.71 (0.32-1.57) in Poland to 5.49 (2.11-14.30) in Slovakia. Between-country heterogeneity was strongly related to average persons-per-room, a possible socioeconomic indicator, with stronger associations where households were less crowded. Estimates of dose-response relationships tended to be small and non-significant, even when pooled. Our results provide evidence of a link between maternal smoking in pregnancy and childhood overweight. Associations with obesity, though strong in some countries, were less consistent. Maternal smoking may confer an addition to a child's potential for obesity, which is more likely to be realised in affluent conditions.