Sex-specific associations of environmental exposures with prevalent diabetes and obesity - results from the KORA Fit study.

BACKGROUND: Promising evidence suggests a link between environmental factors, particularly air pollution, and diabetes and obesity. However, it is still unclear whether men and women are equally susceptible to environmental exposures. OBJECTIVES: We aimed to assess sex-specific long-term effects of environmental exposures on metabolic diseases. METHODS: We analyzed cross-sectional data from 3,034 participants (53.7% female, aged 53-74 years) from the KORA Fit study (2018/19), a German population-based cohort. Environmental exposures, including annual averages of air pollutants [nitrogen oxides (NO2, NOx), ozone, particulate matter of different diameters (PM10, PMcoarse, PM2.5), PM2.5abs, particle number concentration], air temperature and surrounding greenness, were assessed at participants' residences. We evaluated sex-specific associations of environmental exposures with prevalent diabetes, obesity, body-mass-index (BMI) and waist circumference using logistic or linear regression models with an interaction term for sex, adjusted for age, lifestyle factors and education. Further effect modification, in particular by urbanization, was assessed in sex-stratified analyses. RESULTS: Higher annual averages of air pollution, air temperature and greenness at residence were associated with diabetes prevalence in men (NO2: Odds Ratio (OR) per interquartile range increase in exposure: 1.49 [95% confidence interval (CI): 1.13, 1.95], air temperature: OR: 1.48 [95%-CI: 1.15, 1.90]; greenness: OR: 0.78 [95%-CI: 0.59, 1.01]) but not in women. Conversely, higher levels of air pollution, temperature and lack of greenness were associated with lower obesity prevalence and BMI in women. After including an interaction term for urbanization, only higher greenness was associated with higher BMI in rural women, whereas higher air pollution was associated with higher BMI in urban men. Discussion We observed sex-specific associations of environmental exposures with metabolic diseases. An additional interaction between environmental exposures and urbanization on obesity suggests a higher susceptibility to air pollution among urban men, and higher susceptibility to greenness among rural women, which needs corroboration in future studies.

Assessing the health burden from air pollution.

A broader approach to assessing the burden of disease from air pollution is required.

Long-term exposure to air pollution and chronic kidney disease-associated mortality - results from the pooled cohort of the European multicentre ELAPSE-study.

Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO2), black carbon (BC), ozone (O3), particulate matter ≤2.5µm (PM2.5) and several elemental constituents of PM2.5. Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289 564 persons died from CKD. Associations were positive for PM2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5µg/m3, BC (1.26 (1.03-1.53) per 0.5×10- 5/m), NO2 (1.13 (0.93-1.38) per 10µg/m3) and inverse for O3 (0.71 (0.54-0.93) per 10µg/m3). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality.

Inter-annual trends of ultrafine particles in urban Europe.

Ultrafine particles (UFP, those with diameters ≤ 100 nm), have been reported to potentially penetrate deeply into the respiratory system, translocate through the alveoli, and affect various organs, potentially correlating with increased mortality. The aim of this study is to assess long-term trends (5-11 years) in mostly urban UFP concentrations based on measurements of particle number size distributions (PNSD). Additionally, concentrations of other pollutants and meteorological variables were evaluated to support the interpretations. PNSD datasets from 12 urban background (UB), 5 traffic (TR), 3 suburban background (SUB) and 1 regional background (RB) sites in 15 European cities and 1 in the USA were evaluated. The non-parametric Theil-Sen's method was used to detect monotonic trends. Meta-analyses were carried out to assess the overall trends and those for different environments. The results showed significant decreases in NO, NO2, BC, CO, and particle concentrations in the Aitken (25-100 nm) and the Accumulation (100-800 nm) modes, suggesting a positive impact of the implementation of EURO 5/V and 6/VI vehicle standards on European air quality. The growing use of Diesel Particle Filters (DPFs) might also have clearly reduced exhaust emissions of BC, PM, and the Aitken and Accumulation mode particles. However, as reported by prior studies, there remains an issue of poor control of Nucleation mode particles (smaller than 25 nm), which are not fully reduced with current DPFs, without emission controls for semi-volatile organic compounds, and might have different origins than road traffic. Thus, contrasting trends for Nucleation mode particles were obtained across the cities studied. This mode also affected the UFP and total PNC trends because of the high proportion of Nucleation mode particles in both concentration ranges. It was also found that the urban temperature increasing trends might have also influenced those of PNC, Nucleation and Aitken modes.

Prospective health care costs and lost work days associated with diabetes-related distress and depression symptoms among 1488 individuals with diabetes.

The aim of this study was to investigating the impact of major depression symptoms and diabetes-related distress on future health care costs and lost workdays in individuals with diabetes. We linked survey data from a random sample of a German statutory health insurance (SHI) with diabetes (n = 1488, 63.0% male, mean age 66.9 years) with their SHI data one year after the survey. Within the survey data we identified major depression symptoms (Patient Health Questionnaire-9) and diabetes-related distress (Problem Areas in Diabetes Scale). We retrieved health care costs and lost workdays from SHI data. To assess the impact of major depression symptoms and diabetes-related distress on health care costs and lost workdays, we adjusted regression models for age, sex, education, employment status, and diabetes duration, type, and severity. Major depression symptoms were associated with significantly higher costs (by a factor of 1.49; 95% CI: 1.18-1.88). Lost workdays were also more likely for respondents with depression symptoms (RR1.34; 0.97-1.86). Health care costs (by a factor of 0.81; 0.66-1.01) and the risk of lost workdays (RR 0.86; 0.62-1.18) may be lower among respondents with high diabetes-related distress. While major depression and diabetes-related distress have overlapping indicators, our results indicate different impacts on health care costs.

Long-term exposure to air pollution and incidence of gastric and the upper aerodigestive tract cancers in a pooled European cohort: The ELAPSE project.

Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 5,305,133 and 5,434,843 person-years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00-1.33) per 5 µg/m3 increase in PM2.5, 1.19 (1.08-1.30) per 10 µg/m3 increase in NO2, 1.14 (1.04-1.26) per 0.5 × 10-5 m-1 increase in BC and 0.81 (0.72-0.92) per 10 µg/m3 increase in O3w. We found no association between long-term ambient air pollution exposure and incidence of gastric cancer, while for long-term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.

Shaping urban environments to improve respiratory health: recommendations for research, planning, and policy.

Urban areas carry a large burden of acute (infectious) and chronic respiratory diseases due to environmental conditions such as high levels of air pollution and high population densities. Car-dominated cities often lack walkable areas, which reduces opportunities for physical activity that are fundamentally important for healthy lungs. The already restricted amount of green space available-with often poorly selected plants-could produce pollen and subsequently provoke or worsen allergic diseases. Less affluent neighbourhoods often carry a larger respiratory disease burden. A multisectoral approach with more diverse policy measures and urban innovations is needed to reduce air pollution (eg, low emission zones), to increase public space for walking and cycling (eg, low traffic neighbourhoods, superblocks, 15-minute cities, and car-free cities), and to develop green cities (eg, planting of low-allergy trees). Stricter EU air quality guidelines can push these transformations to improve the respiratory health of citizens. Advocacy by medical respiratory societies can also make an important contribution to such changes.

Long-term exposure to ambient air pollution and risk of leukemia and lymphoma in a pooled European cohort.

Leukemia and lymphoma are the two most common forms of hematologic malignancy, and their etiology is largely unknown. Pathophysiological mechanisms suggest a possible association with air pollution, but little empirical evidence is available. We aimed to investigate the association between long-term residential exposure to outdoor air pollution and risk of leukemia and lymphoma. We pooled data from four cohorts from three European countries as part of the "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration. We used Europe-wide land use regression models to assess annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) at residences. We also estimated concentrations of PM2.5 elemental components: copper (Cu), iron (Fe), zinc (Zn); sulfur (S); nickel (Ni), vanadium (V), silicon (Si) and potassium (K). We applied Cox proportional hazards models to investigate the associations. Among the study population of 247,436 individuals, 760 leukemia and 1122 lymphoma cases were diagnosed during 4,656,140 person-years of follow-up. The results showed a leukemia hazard ratio (HR) of 1.13 (95% confidence intervals [CI]: 1.01-1.26) per 10 µg/m3 NO2, which was robust in two-pollutant models and consistent across the four cohorts and according to smoking status. Sex-specific analyses suggested that this association was confined to the male population. Further, the results showed increased lymphoma HRs for PM2.5 (HR = 1.16; 95% CI: 1.02-1.34) and potassium content of PM2.5, which were consistent in two-pollutant models and according to sex. Our results suggest that air pollution at the residence may be associated with adult leukemia and lymphoma.

Long-term exposure to several constituents and sources of PM2.5 is associated with incidence of upper aerodigestive tract cancers but not gastric cancer: Results from the large pooled European cohort of the ELAPSE project.

It is unclear whether cancers of the upper aerodigestive tract (UADT) and gastric cancer are related to air pollution, due to few studies with inconsistent results. The effects of particulate matter (PM) may vary across locations due to different source contributions and related PM compositions, and it is not clear which PM constituents/sources are most relevant from a consideration of overall mass concentration alone. We therefore investigated the association of UADT and gastric cancers with PM2.5 elemental constituents and sources components indicative of different sources within a large multicentre population based epidemiological study. Cohorts with at least 10 cases per cohort led to ten and eight cohorts from five countries contributing to UADT- and gastric cancer analysis, respectively. Outcome ascertainment was based on cancer registry data or data of comparable quality. We assigned home address exposure to eight elemental constituents (Cu, Fe, K, Ni, S, Si, V and Zn) estimated from Europe-wide exposure models, and five source components identified by absolute principal component analysis (APCA). Cox regression models were run with age as time scale, stratified for sex and cohort and adjusted for relevant individual and neighbourhood level confounders. We observed 1139 UADT and 872 gastric cancer cases during a mean follow-up of 18.3 and 18.5 years, respectively. UADT cancer incidence was associated with all constituents except K in single element analyses. After adjustment for NO2, only Ni and V remained associated with UADT. Residual oil combustion and traffic source components were associated with UADT cancer persisting in the multiple source model. No associations were found for any of the elements or source components and gastric cancer incidence. Our results indicate an association of several PM constituents indicative of different sources with UADT but not gastric cancer incidence with the most robust evidence for traffic and residual oil combustion.

The Berlin-Brandenburg Air Study-A Methodological Study Paper of a Natural Experiment Investigating Health Effects Related to Changes in Airport-Related Exposures.

Objectives: This paper presents the study design of the Berlin-Brandenburg Air study (BEAR-study). We measure air quality in Berlin and Brandenburg before and after the relocation of aircraft (AC) traffic from Tegel (TXL) airport to the new Berlin-Brandenburg airport (BER) and investigate the association of AC-related ultrafine particles (UFP) with health outcomes in schoolchildren. Methods: The BEAR-study is a natural experiment examining schoolchildren attending schools near TXL and BER airports, and in control areas (CA) away from both airports and associated air corridors. Each child undergoes repeated school-based health-examinations. Total particle number concentration (PNC) and meteorological parameters are continuously monitored. Submicrometer particle number size distribution, equivalent black carbon, and gas-phase pollutants are collected from long-term air quality monitoring stations. Daily source-specific UFP concentrations are modeled. We will analyze short-term effects of UFP on respiratory, cardiovascular, and neurocognitive outcomes, as well as medium and long-term effects on lung growth and cognitive development. Results: We examined 1,070 children (as of 30 November 2022) from 16 schools in Berlin and Brandenburg. Conclusion: The BEAR study increases the understanding of how AC-related UFP affect children's health.

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.

Multiple myeloma risk in relation to long-term air pollution exposure - A pooled analysis of four European cohorts.

BACKGROUND: Air pollution is a growing concern worldwide, with significant impacts on human health. Multiple myeloma is a type of blood cancer with increasing incidence. Studies have linked air pollution exposure to various types of cancer, including leukemia and lymphoma, however, the relationship with multiple myeloma incidence has not been extensively investigated. METHODS: We pooled four European cohorts (N = 234,803) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone (O3) and multiple myeloma. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 4,415,817 person-years of follow-up (average 18.8 years), we observed 404 cases of multiple myeloma. The results of the fully adjusted linear analyses showed hazard ratios (95% confidence interval) of 0.99 (0.84, 1.16) per 10 µg/m³ NO2, 1.04 (0.82, 1.33) per 5 µg/m³ PM2.5, 0.99 (0.84, 1.18) per 0.5 10-5 m-1 BCE, and 1.11 (0.87, 1.41) per 10 µg/m³ O3. CONCLUSIONS: We did not observe an association between long-term ambient air pollution exposure and incidence of multiple myeloma.

Long-term exposure to air pollution and prevalent nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is a disease characterized by lipid accumulation within hepatocytes, ranging from simple steatosis to steatohepatitis, in the absence of secondary causes of hepatic fat accumulation. Although air pollution (AP) has been associated with several conditions related to NAFLD (e.g., metabolic syndrome, type 2 diabetes mellitus), few studies have explored an association between AP and NAFLD. The aim of the study was to investigate whether exposure to AP is associated with NAFLD prevalence. Methods: We used baseline cross-sectional data (2000-2003) of the Heinz-Nixdorf-Recall cohort study in Germany (baseline n = 4,814), a prospective population-based cohort study in the urbanized Ruhr Area. Mean annual exposure to size-fractioned particulate matter (PM10, PM2.5, PMcoarse, and PM2.5abs), nitrogen dioxide, and particle number was assessed using two different exposure models: a chemistry transport dispersion model, which captures urban background AP exposure on a 1 km2 grid at participant's residential addresses, and a land use regression model, which captures point-specific AP exposure at participant's residential addresses. NAFLD was assessed with the fatty liver index (n = 4,065), with NAFLD defined as fatty liver index ≥60. We estimated ORs of NAFLD per interquartile range of exposure using logistic regression, adjusted for socio-demographic and lifestyle variables. Results: We observed a NAFLD prevalence of 31.7% (n = 1,288). All air pollutants were positively associated with NAFLD prevalence, with an OR per interquartile range for PM2.5 of 1.11 (95% confidence interval [CI] = 1.00, 1.24) using chemistry transport model, and 1.06 (95% CI = 0.94, 1.19) using the land use regression model, respectively. Conclusion: There was a positive association between long-term AP exposure and NAFLD.

Are people interested in receiving advice from their general practitioner on how to protect their health during heatwaves? A survey of the German population.

OBJECTIVE: Climate change increases the frequency, intensity and length of heatwaves, which puts a particular strain on the health of vulnerable population groups. General practitioners (GPs) could reach these people and provide advice on protective health behaviour against heat. Data is lacking on whether and what topic of GP advice people are interested in, and whether specific person characteristics are associated with such interests. DESIGN: Cross-sectional, nationwide, face-to-face household survey, conducted during winter 2022/2023. SETTING: Germany. PARTICIPANTS: Population-based sample of 4212 respondents (aged 14-96 years), selected by using multistratified random sampling (50%) combined with multiquota sampling (50%). MAIN OUTCOME MEASURE: Interest in receiving GP advice on health protection during heatwaves (yes/no), and the topic people find most important (advice on drinking behaviour, nutrition, cooling, cooling rooms, physical activity or medication management). Associations between predefined person characteristics and the likelihood of interest were estimated using adjusted logistic regressions. RESULTS: A total of 4020 respondents had GP contact and provided data on the outcome measure. Of these, 23% (95% CI=22% to 25%) expressed interest in GP advice. The likelihood of expressing interest was positively associated with being female, older age (particularly those aged 75+ years: 38% were interested), having a lower level of educational attainment, having a migration background, living in a more urban area, and living in a single-person household. It was negatively associated with increasing income. Advice on medication management received highest interest (25%). CONCLUSIONS: During winter season 2022/2023, around one quarter of the German population with GP contact-and around 40% of those aged 75+ years-was estimated to have a stated interest in receiving GP advice on protective health behaviour during heatwaves, especially on medication management. Climate change is creating new demands for healthcare provision in general practice. This study provides initial relevant information for research and practice aiming to address these demands.

Environmental Burden of Disease due to Emissions of Hard Coal- and Lignite-Fired Power Plants in Germany.

Objectives: The study estimated the environmental burden of disease (EBD) attributable to a long-term exposure of the population to nitrogen dioxide (NO2) and fine particulate matter (PM2.5) emissions from hard coal- and lignite-fired power plants in Germany for the year 2015. Methods: The contribution of coal-fired power plants to the total air pollutant concentration was modelled using a chemical transport model and then combined with population data to assess the corresponding population exposure. We calculated years of life lost (YLL), years of life with disability, or disability-adjusted life years for different health outcomes with a strong evidence for an association with the exposure. Results: The burden of disease from PM2.5 emissions from lignite is 1.2 times higher than that from hard coal emissions (7,866 YLL compared to 6,412 YLL). NO2 emissions from lignite, cause a burden of disease 2.3 times higher than hard coal NO2-emission (13,537 YLL compared to 5,906 YLL). The EBD for both pollutants is dominated by diseases of the cardiovascular system. Conclusion: Abandoning energy generation by coal-fired power plants would lower the burden of disease in Germany.

[Health protection and climate change require ambitious limit values for air pollutants in Europe : Opinion on the revision of the Directive on Air Quality and Clean Air for Europe of the Environmental Public Health commission of the Robert Koch Institute and the Federal Environment Agency]. / Gesundheitsschutz und Klimawandel erfordern ambitionierte Grenzwerte für Luftschadstoffe in Europa : Stellungnahme zur Revision der Richtlinie über Luftqualität und saubere Luft für Europa der Kommission Environmental Public Health des Robert Koch-Instituts und des Umweltbundesamtes.

Based on scientific findings, the World Health Organization (WHO) has recommended stricter guideline values for air quality in 2021. Significant reductions in the annual mean values of particulate matter (particle size 2.5 µm or smaller, PM2.5) and long-term exposure to nitrogen dioxide (NO2) and ozone (O3) were put forward. The risk of mortality already increases above the WHO guideline values, as shown in studies investigating low concentrations of air pollutants. In Germany, the 2021 WHO guideline values for PM2.5 and NO2 were clearly exceeded in 2022.In this position paper we give the following recommendations for the European Air Quality Directive: (1) set binding limit values according to WHO 2021, (2) apply the limit values to the whole of Europe, (3) continue and expand the established country-based monitoring networks, (4) expand air quality measurements for ultrafine particles and soot particles, and (5) link air pollution control and climate protection measures.Stricter limits for air pollutants require societal and political changes in areas such as mobility, energy use and generation, and urban and spatial planning. Implementation according to WHO 2021 would lead to a net economic benefit of 38 billion euros per year.Ambitious limit values for air pollutants also have an impact on climate change mitigation and its health impacts. The Environmental Public Health commission concludes that more ambitious limit values are crucial to enable effective health protection in Germany and calls for air pollutant limit values in line with the 2021 WHO recommendations to become binding in Europe.