Long-term exposure to transportation noise and diabetes mellitus mortality: a national cohort study and updated meta-analysis.

BACKGROUND: Long-term exposure to transportation noise is related to cardio-metabolic diseases, with more recent evidence also showing associations with diabetes mellitus (DM) incidence. This study aimed to evaluate the association between transportation noise and DM mortality within the Swiss National Cohort. METHODS: During 15 years of follow-up (2001-2015; 4.14 million adults), over 72,000 DM deaths were accrued. Source-specific noise was calculated at residential locations, considering moving history. Multi-exposure, time-varying Cox regression was used to derive hazard ratios (HR, and 95%-confidence intervals). Models included road traffic, railway and aircraft noise, air pollution, and individual and area-level covariates including socio-economic position. Analyses included exposure-response modelling, effect modification, and a subset analysis around airports. The main findings were integrated into meta-analyses with published studies on mortality and incidence (separately and combined). RESULTS: HRs were 1.06 (1.05, 1.07), 1.02 (1.01, 1.03) and 1.01 (0.99, 1.02) per 10 dB day evening-night level (Lden) road traffic, railway and aircraft noise, respectively (adjusted model, including NO2). Splines suggested a threshold for road traffic noise (~ 46 dB Lden, well below the 53 dB Lden WHO guideline level), but not railway noise. Substituting for PM2.5, or including deaths with type 1 DM hardly changed the associations. HRs were higher for males compared to females, and in younger compared to older adults. Focusing only on type 1 DM showed an independent association with road traffic noise. Meta-analysis was only possible for road traffic noise in relation to mortality (1.08 [0.99, 1.18] per 10 dB, n = 4), with the point estimate broadly similar to that for incidence (1.07 [1.05, 1.09] per 10 dB, n = 10). Combining incidence and mortality studies indicated positive associations for each source, strongest for road traffic noise (1.07 [1.05, 1.08], 1.02 [1.01, 1.03], and 1.02 [1.00, 1.03] per 10 dB road traffic [n = 14], railway [n = 5] and aircraft noise [n = 5], respectively). CONCLUSIONS: This study provides new evidence that transportation noise is associated with diabetes mortality. With the growing evidence and large disease burden, DM should be viewed as an important outcome in the noise and health discussion.

Acute effects of military aircraft noise on sedative and analgesic drug administrations in psychiatric patients: A case-time series analysis.

BACKGROUND: Existing evidence suggests that psychiatric patients are highly noise sensitive, and that noise exposure increases the risk for adverse mental health outcomes, such as psychiatric hospitalizations and even suicide. To investigate acute effects of noise in this vulnerable population, we assessed short-term associations between fighter jet noise and on-demand sedative and analgesic drug administrations in a psychiatric clinic located close to a military airfield in Switzerland. METHODS: We applied a case time series analysis with an hourly time resolution using distributed-lag models. Analysis was adjusted for long-term and seasonal trends, day of week, time of day, time-varying weather conditions and the week of stay. Noise exposure (hourly A-weighted equivalent continuous sound pressure levels (LAeq)) was modelled using detailed flight plans and noise footprints for different fighter jet and route combinations. Outcome data were available from the clinic's records. OUTCOMES: During the study period (06/2016-12/2021), 23,486 flights occurred. 5,968 clinical stays with a median length of 41 days (IQR: 28d, 50d) were recorded. The odds ratio (OR) for medication administration over the lag period of 3 hours after exposure was 1.016 (95 %CI: 1.006, 1.026) per 10 dB LAeq for sedatives and 1.032 (95 %CI: 1.016, 1.048) per 10 dB for analgesics. Effects were larger in multimorbid patients. INTERPRETATION: Case time series analysis is a novel method to investigate transient associations in observational data while minimizing risk of bias. Using an objectively recorded outcome measure, our results demonstrate that psychiatric patients are a vulnerable population, in which noise exposure can lead to symptom exacerbations and adverse events.

Socio-environmental modifiers of heat-related mortality in eight Swiss cities: A case time series analysis.

In the light of growing urbanization and projected temperature increases due to climate change, heat-related mortality in urban areas is a pressing public health concern. Heat exposure and vulnerability to heat may vary within cities depending on structural features and socioeconomic factors. This study examined the effect modification of the temperature-mortality association of three socio-environmental factors in eight Swiss cities and population subgroups (<75 and ≥ 75 years, males, females): urban heat islands (UHI) based on within-city temperature contrasts, residential greenness measured as normalized difference vegetation index (NDVI) and neighborhood socioeconomic position (SEP). We used individual death records from the Swiss National Cohort occurring during the warm season (May to September) in the years 2003-2016. We performed a case time series analysis using conditional quasi-Poisson and distributed lag non-linear models with a lag of 0-3 days. As exposure variables, we used daily maximum temperatures (Tmax) and a binary indicator for warm nights (Tmin ≥20 °C). In total, 53,593 deaths occurred during the study period. Overall across the eight cities, the mortality risk increased by 31% (1.31 relative risk (95% confidence interval: 1.20-1.42)) between 22.5 °C (the minimum mortality temperature) and 35 °C (the 99th percentile) for warm-season Tmax. Stratified analysis suggested that the heat-related risk at 35 °C is 26% (95%CI: -4%, 67%) higher in UHI compared to non-UHI areas. Indications of smaller risk differences were observed between the low vs. high greenness strata (Relative risk difference = 13% (95%CI: -11%; 44%)). Living in low SEP neighborhoods was associated with an increased heat related risk in the non-elderly population (<75 years). Our results indicate that UHI are associated with increased heat-related mortality risk within Swiss cities, and that features beyond greenness are responsible for such spatial risk differences.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

Health position paper and redox perspectives - Disease burden by transportation noise.

Transportation noise is a ubiquitous urban exposure. In 2018, the World Health Organization concluded that chronic exposure to road traffic noise is a risk factor for ischemic heart disease. In contrast, they concluded that the quality of evidence for a link to other diseases was very low to moderate. Since then, several studies on the impact of noise on various diseases have been published. Also, studies investigating the mechanistic pathways underlying noise-induced health effects are emerging. We review the current evidence regarding effects of noise on health and the related disease-mechanisms. Several high-quality cohort studies consistently found road traffic noise to be associated with a higher risk of ischemic heart disease, heart failure, diabetes, and all-cause mortality. Furthermore, recent studies have indicated that road traffic and railway noise may increase the risk of diseases not commonly investigated in an environmental noise context, including breast cancer, dementia, and tinnitus. The harmful effects of noise are related to activation of a physiological stress response and nighttime sleep disturbance. Oxidative stress and inflammation downstream of stress hormone signaling and dysregulated circadian rhythms are identified as major disease-relevant pathomechanistic drivers. We discuss the role of reactive oxygen species and present results from antioxidant interventions. Lastly, we provide an overview of oxidative stress markers and adverse redox processes reported for noise-exposed animals and humans. This position paper summarizes all available epidemiological, clinical, and preclinical evidence of transportation noise as an important environmental risk factor for public health and discusses its implications on the population level.

Long-Term Exposure to Low-Level PM2.5 and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-µg/m3 increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Evidence Synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution.

BACKGROUND: There is a long tradition in environmental health of using frameworks for evidence synthesis, such as those of the U.S. Environmental Protection Agency for its Integrated Science Assessments and the International Agency for Research on Cancer Monographs. The framework, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), was developed for evidence synthesis in clinical medicine. The U.S. Office of Health Assessment and Translation (OHAT) elaborated an approach for evidence synthesis in environmental health building on GRADE. METHODS: We applied a modified OHAT approach and a broader "narrative" assessment to assess the level of confidence in a large systematic review on traffic-related air pollution and health outcomes. DISCUSSION: We discuss several challenges with the OHAT approach and its implementation and suggest improvements for synthesizing evidence from observational studies in environmental health. We consider the determination of confidence using a formal rating scheme of up- and downgrading of certain factors, the treatment of every factor as equally important, and the lower initial confidence rating of observational studies to be fundamental issues in the OHAT approach. We argue that some observational studies can offer high-confidence evidence in environmental health. We note that heterogeneity in magnitude of effect estimates should generally not weaken the confidence in the evidence, and consistency of associations across study designs, populations, and exposure assessment methods may strengthen confidence in the evidence. We mention that publication bias should be explored beyond statistical methods and is likely limited when large and collaborative studies comprise most of the evidence and when accrued over several decades. We propose to identify possible key biases, their most likely direction, and their potential impacts on the results. We think that the OHAT approach and other GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them. We emphasize that a broader, "narrative" evidence assessment based on the systematic review may complement a formal GRADE-type evaluation. https://doi.org/10.1289/EHP11532.

Ambient Air Pollution Exposure and Cerebral White Matter Hyperintensities in Older Adults: A Cross-Sectional Analysis in the Three-City Montpellier Study.

BACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on vascular health. OBJECTIVE: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH). METHODS: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes. RESULTS: Participants' (n=582) median age at MRI was 70.7 years [interquartile range (IQR): 6.1], and 52% (n=300) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) µg/m3 for PM2.5, 48.9 (14.6) µg/m3 for NO2, and 2.66 (0.60) 10-5/m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden [odds ratio (OR) for an IQR increase=1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile]. Associations for other regional WMH volumes were inconsistent. CONCLUSION: In this population-based study in older adults, PM2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution. https://doi.org/10.1289/EHP12231.

Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults.

Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 µg/m³. A one interquartile range increase of 7 µg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective Alienor study.

Chronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter ≤2.5 µm (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) was estimated at the participants' geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements). The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 µm (SD:14.4) at baseline. Exposure to higher levels of PM2.5 and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (-0.28 µm/year (95% confidence interval (CI) [-0.44;-0.13]) and -0.26 µm/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (-0.36 µm/year). No statistically significant associations were found with NO2 in the main models. This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe.

Long-term exposure to airborne metals and risk of cancer in the French cohort Gazel.

BACKGROUND: The specific compounds that make ambient fine particulate matter (PM2.5) carcinogen remain poorly identified. Some metals contribute to ambient PM2.5 and possibly to its adverse effects. But the challenge of assessing exposure to airborne metals limits epidemiological studies. OBJECTIVE: To analyze the relationships between several airborne metals and risk of cancer in a large population. METHODS: We estimated the individual exposure to 12 airborne metals of âˆ¼ 12,000 semi-urban and rural participants of the French population-based Gazel cohort using moss biomonitoring data from a 20-year national program. We used principal component analyses (PCA) to derive groups of metals, and focused on six single carcinogenic or toxic metals (arsenic, cadmium, chromium, lead, nickel, and vanadium). We used extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, to analyze the association between each exposure and all-site combined, bladder, lung, breast, and prostate cancer incidence. RESULTS: We identified 2,401 cases of all-site cancer between 2001 and 2015. Over the follow-up, median exposures varied from 0.22 (interquartile range (IQR): 0.18-0.28) to 8.68 (IQR: 6.62-11.79) µg.g-1 of dried moss for cadmium and lead, respectively. The PCA yielded three groups identified as "anthropogenic", "crustal", and "marine". Models yielded positive associations between most single and groups of metal and all-site cancer, with e.g. hazard ratios of 1.08 (95% CI: 1.03, 1.13) for cadmium or 1.06 (95% CI: 1.02,1.10) for lead, per interquartile range increase. These findings were consistent across supplementary analyses, albeit attenuated when accounting for total PM2.5. Regarding specific site cancers, we estimated positive associations mostly for bladder, and generally with large confidence intervals. CONCLUSION: Most single and groups of airborne metals, except vanadium, were associated with risk of cancer. These findings may help identify sources or components of PM2.5 that may be involved in its carcinogenicity.

Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study.

BACKGROUND: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. OBJECTIVE: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. METHODS: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. RESULTS: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval: -2.18 to -0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. CONCLUSIONS: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Long-Term Exposure to Traffic-Related Air Pollution and Diabetes: A Systematic Review and Meta-Analysis.

Objectives: We report results of a systematic review on the health effects of long-term traffic-related air pollution (TRAP) and diabetes in the adult population. Methods: An expert Panel appointed by the Health Effects Institute conducted this systematic review. We searched the PubMed and LUDOK databases for epidemiological studies from 1980 to July 2019. TRAP was defined based on a comprehensive protocol. Random-effects meta-analyses were performed. Confidence assessments were based on a modified Office for Health Assessment and Translation (OHAT) approach, complemented with a broader narrative synthesis. We extended our interpretation to include evidence published up to May 2022. Results: We considered 21 studies on diabetes. All meta-analytic estimates indicated higher diabetes risks with higher exposure. Exposure to NO2 was associated with higher diabetes prevalence (RR 1.09; 95% CI: 1.02; 1.17 per 10 µg/m3), but less pronounced for diabetes incidence (RR 1.04; 95% CI: 0.96; 1.13 per 10 µg/m3). The overall confidence in the evidence was rated moderate, strengthened by the addition of 5 recently published studies. Conclusion: There was moderate evidence for an association of long-term TRAP exposure with diabetes.

Impacts of weather and air pollution on Legionnaires' disease in Switzerland: A national case-crossover study.

BACKGROUND: The number of reported cases of Legionnaires' disease (LD) has risen markedly in Switzerland (6.5/100,000 inhabitants in 2021) and abroad over the last decade. Legionella, the causative agent of LD, are ubiquitous in the environment. Therefore, environmental changes can affect the incidence of LD, for example by increasing bacterial concentrations in the environment or by facilitating transmission. OBJECTIVES: The aim of this study is to understand the environmental determinants, in particular weather conditions, for the regional and seasonal distribution of LD in Switzerland. METHODS: We conducted a series of analyses based on the Swiss LD notification data from 2017 to 2021. First, we used a descriptive and hotspot analysis to map LD cases and identify regional clusters. Second, we applied an ecological model to identify environmental determinants on case frequency at the district level. Third, we applied a case-crossover design using distributed lag non-linear models to identify short-term associations between seven weather variables and LD occurrence. Lastly, we performed a sensitivity analysis for the case-crossover design including NO2 levels available for the year 2019. RESULTS: Canton Ticino in southern Switzerland was identified as a hotspot in the cluster analysis, with a standardised notification rate of 14.3 cases/100,000 inhabitants (CI: 12.6, 16.0). The strongest association with LD frequency in the ecological model was found for large-scale factors such as weather and air pollution. The case-crossover study confirmed the strong association of elevated daily mean temperature (OR 2.83; CI: 1.70, 4.70) and mean daily vapour pressure (OR: 1.52, CI: 1.15, 2.01) 6-14 days before LD occurrence. DISCUSSION: Our analyses showed an influence of weather with a specific temporal pattern before the onset of LD, which may provide insights into the effect mechanism. The relationship between air pollution and LD and the interplay with weather should be further investigated.

Mortality attributable to ambient fine particulate matter and nitrogen dioxide in Switzerland in 2019: Use of two-pollutant effect estimates.

INTRODUCTION: Air pollution health risk assessments have traditionally used single-pollutant effect estimates for one proxy ambient air pollutant such as PM2.5. Two-pollutant effect estimates, i.e. adjusted for another correlated pollutant, theoretically enable the aggregation of pollutant-specific health effects minimizing double-counting. Our study aimed at estimating the adult mortality in Switzerland in 2019 attributable to PM2.5 from a single-pollutant effect estimate and to the sum of PM2.5 and NO2 from two-pollutant estimates; comparing the results with those from alternative global, European and Swiss effect estimates. METHODS: For the single-pollutant approach, we used a PM2.5 summary estimate of European cohorts from the project ELAPSE, recommended by the European Respiratory Society and International Society for Environmental Epidemiology (ERS-ISEE). To derive the two-pollutant effect estimates, we applied ELAPSE-based conversion factors to ERS-ISEE PM2.5 and NO2 single-pollutant effect estimates. Additionally, we used World Health Organization 2021 Air Quality Guidelines as counterfactual scenario, exposure model data from 2019 and Swiss lifetables. RESULTS: The single-pollutant effect estimate for PM2.5 (1.118 [1.060; 1.179] per 10 µg/m3) resulted in 2240 deaths (21,593 years of life lost). Using our derived two-pollutant effect estimates (1.023 [1.012; 1.035] per 10 µg/m3 PM2.5 adjusted for NO2 and 1.040 [1.023; 1.058] per 10 µg/m3 NO2 adjusted for PM2.5), we found 1977 deaths (19,071 years of life lost) attributable to PM2.5 and NO2 together (23% from PM2.5). Deaths using alternative effect estimates ranged from 1042 to 5059. DISCUSSION: Estimated premature mortality attributable to PM2.5 alone was higher than to both PM2.5 and NO2 combined. Furthermore, the proportion of deaths from PM2.5 was lower than from NO2 in the two-pollutant approach. These seemingly paradoxical results, also found in some alternative estimates, are due to statistical imprecisions of underlying correction methods. Therefore, using two-pollutant effect estimates can lead to interpretation challenges in terms of causality.

Association between exposure to multiple air pollutants, transportation noise and cause-specific mortality in adults in Switzerland.

BACKGROUND: Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. METHODS: Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. RESULTS: During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10-5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted < 20 µg/m3 for PM2.5 and NO2, < 1.5 10-5/m BC and < 53 dB Lden total transportation noise. The O3 association was inverse for all outcomes. Including noise attenuated all outcome associations, though many remained significant. Across outcomes, noise was robust to adjustment to air pollutants (e.g. natural mortality 1.037 (1.033, 1.042) per 10 dB Lden total transportation noise, after including BC). CONCLUSION: Long-term exposure to air pollution and transportation noise in Switzerland contribute to premature mortality. Considering co-exposures revealed the importance of local traffic-related pollutants such as NO2, BC and transportation noise.

Suicide and Transportation Noise: A Prospective Cohort Study from Switzerland.

BACKGROUND: Although plausible from a pathophysiological point of view, robust evidence for effects of transportation noise on mental health remains scarce. Meanwhile, psychiatric diseases are among the most prevalent noncommunicable diseases worldwide, and suicide as a mortality outcome highly connected to mental disorders presents a pressing public health issue. The aim of this study was to investigate the association between source-specific transportation noise, particulate matter (PM) air pollution, residential greenness, and suicide by means of a nationwide cohort study. METHODS: Road traffic, railway and aircraft noise exposure as well as exposure to air pollution [PM with aerodynamic diameter ≤2.5µm (PM2.5)] and greenness [normalized difference vegetation index (NDVI)] were linked to 5.1 million adults (age 15 y and older) in the Swiss National Cohort, accounting for their address history. Mean noise exposure in 5-y periods was calculated. Individuals were followed for up to 15 y (2001-2015). Time-varying Cox regression models were applied to deaths by suicide (excluding assisted suicide). Models included all three noise sources, PM2.5, and NDVI plus individual and spatial covariates, including socioeconomic status. Effect modification by sex, age, socioeconomic indicators, and degree of urbanization was explored. RESULTS: During the follow-up, there were 11,265 suicide deaths (10.4% poisoning, 33.3% hanging, 28.7% firearms, 14.7% falls). Road traffic and railway noise were associated with total suicides [hazard ratios: 1.040; 95% confidence interval (CI): 1.015, 1.065; and 1.022 (95% CI: 1.004, 1.041) per 10 dB day-evening-night level (Lden)], whereas for aircraft noise, a risk increase starting from 50 dB was masked by an inverse association in the very low exposure range (30-40 dB). Associations were stronger for females than males. The results were robust to adjustment for residential greenness and air pollution. CONCLUSION: In this longitudinal, nationwide cohort study, we report a robust association between exposure to road traffic and railway noise and risk of death by suicide after adjusting for exposure to air pollution and greenness. These findings add to the growing body of evidence that mental health disorders may be related to chronic transportation noise exposure. https://doi.org/10.1289/EHP11587.

Explorative Assessment of the Temperature-Mortality Association to Support Health-Based Heat-Warning Thresholds: A National Case-Crossover Study in Switzerland.

Defining health-based thresholds for effective heat warnings is crucial for climate change adaptation strategies. Translating the non-linear function between heat and health effects into an effective threshold for heat warnings to protect the population is a challenge. We present a systematic analysis of heat indicators in relation to mortality. We applied distributed lag non-linear models in an individual-level case-crossover design to assess the effects of heat on mortality in Switzerland during the warm season from 2003 to 2016 for three temperature metrics (daily mean, maximum, and minimum temperature), and various threshold temperatures and heatwave definitions. Individual death records with information on residential address from the Swiss National Cohort were linked to high-resolution temperature estimates from 100 m resolution maps. Moderate (90th percentile) to extreme thresholds (99.5th percentile) of the three temperature metrics implied a significant increase in mortality (5 to 38%) in respect of the median warm-season temperature. Effects of the threshold temperatures on mortality were similar across the seven major regions in Switzerland. Heatwave duration did not modify the effect when considering delayed effects up to 7 days. This nationally representative study, accounting for small-scale exposure variability, suggests that the national heat-warning system should focus on heatwave intensity rather than duration. While a different heat-warning indicator may be appropriate in other countries, our evaluation framework is transferable to any country.

Comparison of traditional Cox regression and causal modeling to investigate the association between long-term air pollution exposure and natural-cause mortality within European cohorts.

Most studies investigating the health effects of long-term exposure to air pollution used traditional regression models, although causal inference approaches have been proposed as alternative. However, few studies have applied causal models and comparisons with traditional methods are sparse. We therefore compared the associations between natural-cause mortality and exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using traditional Cox and causal models in a large multicenter cohort setting. We analysed data from eight well-characterized cohorts (pooled cohort) and seven administrative cohorts from eleven European countries. Annual mean PM2.5 and NO2 from Europe-wide models were assigned to baseline residential addresses and dichotomized at selected cut-off values (PM2.5: 10, 12, 15 µg/m³; NO2: 20, 40 µg/m³). For each pollutant, we estimated the propensity score as the conditional likelihood of exposure given available covariates, and derived corresponding inverse-probability weights (IPW). We applied Cox proportional hazards models i) adjusting for all covariates ("traditional Cox") and ii) weighting by IPW ("causal model"). Of 325,367 and 28,063,809 participants in the pooled and administrative cohorts, 47,131 and 3,580,264 died from natural causes, respectively. For PM2.5 above vs. below 12 µg/m³, the hazard ratios (HRs) of natural-cause mortality were 1.17 (95% CI 1.13-1.21) and 1.15 (1.11-1.19) for the traditional and causal models in the pooled cohort, and 1.03 (1.01-1.06) and 1.02 (0.97-1.09) in the administrative cohorts. For NO2 above vs below 20 µg/m³, the HRs were 1.12 (1.09-1.14) and 1.07 (1.05-1.09) for the pooled and 1.06 (95% CI 1.03-1.08) and 1.05 (1.02-1.07) for the administrative cohorts. In conclusion, we observed mostly consistent associations between long-term air pollution exposure and natural-cause mortality with both approaches, though estimates partly differed in individual cohorts with no systematic pattern. The application of multiple modelling methods might help to improve causal inference. 299 of 300 words.