Effect modification of air pollution on the association between heat and mortality in five European countries.

BACKGROUND: Evidence suggests that air pollution modifies the association between heat and mortality. However, most studies have been conducted in cities without rural data. This time-series study examined potential effect modification of particulate matter (PM) and ozone (O3) on heat-related mortality using small-area data from five European countries, and explored the influence of area characteristics. METHODS: We obtained daily non-accidental death counts from both urban and rural areas in Norway, England and Wales, Germany, Italy, and the Attica region of Greece during the warm season (2000-2018). Daily mean temperatures and air pollutant concentrations were estimated by spatial-temporal models. Heat effect modification by air pollution was assessed in each small area by over-dispersed Poisson regression models with a tensor smoother between temperature and air pollution. We extracted temperature-mortality relationships at the 5th (low), 50th (medium), and 95th (high) percentiles of pollutant distributions. At each air pollution level, we estimated heat-related mortality for a temperature increase from the 75th to the 99th percentile. We applied random-effects meta-analysis to derive the country-specific and overall associations, and mixed-effects meta-regression to examine the influence of urban-rural and coastal typologies and greenness on the heat effect modification by air pollution. RESULTS: Heat-related mortality risks increased with higher PM levels, rising by 6.4% (95% CI: -2.0%-15.7%), 10.7% (2.6%-19.5%), and 14.1% (4.4%-24.6%) at low, medium, and high PM levels, respectively. This effect modification was consistent in urban and rural regions but more pronounced in non-coastal regions. In addition, heat-mortality associations were slightly stronger at high O3 levels, particularly in regions with low greenness. CONCLUSION: Our analyses of both urban and rural data indicate that air pollution may intensify heat-related mortality, particularly in non-coastal and less green regions. The synergistic effect of heat and air pollution implies a potential pathway of reducing heat-related health impacts by improving air quality.

Temporal variations in the short-term effects of ambient air pollution on cardiovascular and respiratory mortality: a pooled analysis of 380 urban areas over a 22-year period.

BACKGROUND: Ambient air pollution, including particulate matter (such as PM10 and PM2·5) and nitrogen dioxide (NO2), has been linked to increases in mortality. Whether populations' vulnerability to these pollutants has changed over time is unclear, and studies on this topic do not include multicountry analysis. We evaluated whether changes in exposure to air pollutants were associated with changes in mortality effect estimates over time. METHODS: We extracted cause-specific mortality and air pollution data collected between 1995 and 2016 from the Multi-Country Multi-City (MCC) Collaborative Research Network database. We applied a two-stage approach to analyse the short-term effects of NO2, PM10, and PM2·5 on cause-specific mortality using city-specific time series regression analyses and multilevel random-effects meta-analysis. We assessed changes over time using a longitudinal meta-regression with time as a linear fixed term and explored potential sources of heterogeneity and two-pollutant models. FINDINGS: Over 21·6 million cardiovascular and 7·7 million respiratory deaths in 380 cities across 24 countries over the study period were included in the analysis. All three air pollutants showed decreasing concentrations over time. The pooled results suggested no significant temporal change in the effect estimates per unit exposure of PM10, PM2·5, or NO2 and mortality. However, the risk of cardiovascular mortality increased from 0·37% (95% CI -0·05 to 0·80) in 1998 to 0·85% (0·55 to 1·16) in 2012 with a 10 µg/m3 increase in PM2·5. Two-pollutant models generally showed similar results to single-pollutant models for PM fractions and indicated temporal differences for NO2. INTERPRETATION: Although air pollution levels decreased during the study period, the effect sizes per unit increase in air pollution concentration have not changed. This observation might be due to the composition, toxicity, and sources of air pollution, as well as other factors, such as socioeconomic determinants or changes in population distribution and susceptibility. FUNDING: None.

Socioeconomic Inequalities in the External Exposome in European Cohorts: The EXPANSE Project.

Socioeconomic inequalities in the exposome have been found to be complex and highly context-specific, but studies have not been conducted in large population-wide cohorts from multiple countries. This study aims to examine the external exposome, encompassing individual and environmental factors influencing health over the life course, and to perform dimension reduction to derive interpretable characterization of the external exposome for multicountry epidemiological studies. Analyzing data from over 25 million individuals across seven European countries including 12 administrative and traditional cohorts, we utilized domain-specific principal component analysis (PCA) to define the external exposome, focusing on air pollution, the built environment, and air temperature. We conducted linear regression to estimate the association between individual- and area-level socioeconomic position and each domain of the external exposome. Consistent exposure patterns were observed within countries, indicating the representativeness of traditional cohorts for air pollution and the built environment. However, cohorts with limited geographical coverage and Southern European countries displayed lower temperature variability, especially in the cold season, compared to Northern European countries and cohorts including a wide range of urban and rural areas. The individual- and area-level socioeconomic determinants (i.e., education, income, and unemployment rate) of the urban exposome exhibited significant variability across the European region, with area-level indicators showing stronger associations than individual variables. While the PCA approach facilitated common interpretations of the external exposome for air pollution and the built environment, it was less effective for air temperature. The diverse socioeconomic determinants suggest regional variations in environmental health inequities, emphasizing the need for targeted interventions across European countries.

Two Decades of Air Pollution Health Risk Assessment: Insights From the Use of WHO's AirQ and AirQ+ Tools.

Objectives: We evaluated studies that used the World Health Organization's (WHO) AirQ and AirQ+ tools for air pollution (AP) health risk assessment (HRA) and provided best practice suggestions for future assessments. Methods: We performed a comprehensive review of studies using WHO's AirQ and AirQ+ tools, searching several databases for relevant articles, reports, and theses from inception to Dec 31, 2022. Results: We identified 286 studies that met our criteria. The studies were conducted in 69 countries, with most (57%) in Iran, followed by Italy and India (∼8% each). We found that many studies inadequately report air pollution exposure data, its quality, and validity. The decisions concerning the analysed population size, health outcomes of interest, baseline incidence, concentration-response functions, relative risk values, and counterfactual values are often not justified, sufficiently. Many studies lack an uncertainty assessment. Conclusion: Our review found a number of common shortcomings in the published assessments. We suggest better practices and urge future studies to focus on the quality of input data, its reporting, and associated uncertainties.

External exposome and all-cause mortality in European cohorts: the EXPANSE project.

Background: Many studies reported associations between long-term exposure to environmental factors and mortality; however, little is known on the combined effects of these factors and health. We aimed to evaluate the association between external exposome and all-cause mortality in large administrative and traditional adult cohorts in Europe. Methods: Data from six administrative cohorts (Catalonia, Greece, Rome, Sweden, Switzerland and the Netherlands, totaling 27,913,545 subjects) and three traditional adult cohorts (CEANS-Sweden, EPIC-NL-the Netherlands, KORA-Germany, totaling 57,653 participants) were included. Multiple exposures were assigned at the residential addresses, and were divided into three a priori defined domains: (1) air pollution [fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and warm-season Ozone (warm-O3)]; (2) land/built environment (Normalized Difference Vegetation Index-NDVI, impervious surfaces, and distance to water); (3) air temperature (cold- and warm-season mean and standard deviation). Each domain was synthesized through Principal Component Analysis (PCA), with the aim of explaining at least 80% of its variability. Cox proportional-hazards regression models were applied and the total risk of the external exposome was estimated through the Cumulative Risk Index (CRI). The estimates were adjusted for individual- and area-level covariates. Results: More than 205 million person-years at risk and more than 3.2 million deaths were analyzed. In single-component models, IQR increases of the first principal component of the air pollution domain were associated with higher mortality [HRs ranging from 1.011 (95% CI: 1.005-1.018) for the Rome cohort to 1.076 (1.071-1.081) for the Swedish cohort]. In contrast, lower levels of the first principal component of the land/built environment domain, pointing to reduced vegetation and higher percentage of impervious surfaces, were associated with higher risks. Finally, the CRI of external exposome increased mortality for almost all cohorts. The associations found in the traditional adult cohorts were generally consistent with the results from the administrative ones, albeit without reaching statistical significance. Discussion: Various components of the external exposome, analyzed individually or in combination, were associated with increased mortality across European cohorts. This sets the stage for future research on the connections between various exposure patterns and human health, aiding in the planning of healthier cities.

Substituting red meat with insects in burgers: Estimating the public health impact using risk-benefit assessment.

In Western societies, reducing red meat consumption gained prominence due to health, environmental, and animal welfare considerations. We estimated the public health impact of substituting beef with house cricket (Acheta domesticus) in European diets (Denmark, France, and Greece) using the risk-benefit assessment (RBA) methodology, building upon the EFSA-funded NovRBA project. The overall health impact of substituting beef patties with insect powder-containing patties was found to be impacted by the amount of cricket powder incorporated in the patties. While using high amounts of cricket powder in meat substitutes may be safe, it does not inherently offer a healthier dietary option compared to beef. Adjustment of cricket powder levels is needed to yield a positive overall health impact. The main driver of the outcome is sodium, naturally present in substantial amounts in crickets. Moreover, the way that cricket powder is hydrated before being used for the production of patties (ratio of powder to water), influences the results. Our study highlighted that any consideration for dietary substitution should be multidimensional, considering nutritional, microbiological and toxicological aspects, and that the design of new food products in the framework of dietary shifts should consider both health risks and benefits associated with the food.

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 ≤2.5 µm (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 5 µg/m3, BC (1.26 (1.03-1.53) per 0.5 × 10- 5/m), NO2 (1.13 (0.93-1.38) per 10 µg/m3) and inverse for O3 (0.71 (0.54-0.93) per 10 µg/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.

Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement.

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.

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.

The TsiogkaSpaeth grid for detection of neurological visual field defects: a validation study.

BACKGROUND: The TsiogkaSpaeth (TS) grid is a new, low-cost, and easy to access portable test for visual field (VF) screening which could be used by clinicians in everyday clinical practice. Our study aimed to determine the validity of an innovative screening grid test for identifying neurological disease-associated VF defects. METHODS: We enrolled two groups of participants: We assessed the one eye of ten consecutive adult patients with different types of neurological disease associated VF defects and ten eyes of controls in each group. The TS grid test was performed in each group. Sensitivity, specificity, and positive and negative predictive values of the TS grid scotoma area were assessed using the 24-2 VF Humphrey field analyzer (HFA) as the reference standard. RESULTS: Sensitivity and specificity of the TS grid test were 100% and 90.91%, respectively. The area under curve was 0.9545 with 95% CI 0.87-1.00. There was a significant correlation between the number of missed locations on the TS grid test and the visual field index of the HFA 24-2 (r = 0.9436, P < .0001). CONCLUSION: The sensitivity and specificity of the TS grid test were high in detecting VF defects in neurological disease. The TS grid test appears to be a reliable, low-cost, and easily accessed alternative to traditional VF tests in diagnosing typical neurological patterns of visual field defects. It would be useful in screening subjects for neurologically derived ocular morbidity in everyday clinical practice and in remote areas deprived of specialized health care services.

Sociodemographic Disparities in Adults with Kidney Failure: A Meta-Analysis.

This meta-analysis aims to assess current evidence regarding sociodemographic disparities among adults with kidney failure. Medline, Scopus, Web of Science, CENTRAL, and Google Scholar were systematically searched from inception to 20 February 2022. Overall, 165 cohort studies were included. Compared to White patients, dialysis survival was significantly better among Black (hazard ratio-HR: 0.68; 95% CI: 0.61-0.75), Asian (HR: 0.67; 95% CI: 0.61-0.72) and Hispanic patients (HR: 0.80; 95% CI: 0.73-0.88). Black individuals were associated with lower rates of successful arteriovenous fistula use, peritoneal dialysis and kidney transplantation, as well as with worse graft survival. Overall survival was significantly better in females after kidney transplantation compared to males (HR: 0.87; 95% CI: 0.84-0.90). Female sex was linked to higher rates of central venous catheter use and a lower probability of kidney transplantation. Indices of low SES were associated with higher mortality risk (HR: 1.22, 95% CI: 1.14-1.31), reduced rates of dialysis with an arteriovenous fistula, peritoneal dialysis and kidney transplantation, as well as higher graft failure risk. In conclusion, Black, Asian and Hispanic patients present better survival in dialysis, while Black, female and socially deprived patients demonstrate lower rates of successful arteriovenous fistula use and limited access to kidney transplantation. PROSPERO registration: CRD42022300839.

Modification of heat-related effects on mortality by air pollution concentration, at small-area level, in the Attica prefecture, Greece.

BACKGROUND: The independent effects of short-term exposure to increased air temperature and air pollution on mortality are well-documented. There is some evidence indicating that elevated concentrations of air pollutants may lead to increased heat-related mortality, but this evidence is not consistent. Most of these effects have been documented through time-series studies using city-wide data, rather than at a finer spatial level. In our study, we examined the possible modification of the heat effects on total and cause-specific mortality by air pollution at municipality level in the Attica region, Greece, during the warm period of the years 2000 to 2016. METHODS: A municipality-specific over-dispersed Poisson regression model during the warm season (May-September) was used to investigate the heat effects on mortality and their modification by air pollution. We used the two-day average of the daily mean temperature and daily mean PM10, NO2 and 8 hour-max ozone (O3), derived from models, in each municipality as exposures. A bivariate tensor smoother was applied for temperature and each pollutant alternatively, by municipality. Α random-effects meta-analysis was used to obtain pooled estimates of the heat effects at different pollution levels. Heterogeneity of the between-levels differences of the heat effects was evaluated with a Q-test. RESULTS: A rise in mean temperature from the 75th to the 99th percentile of the municipality-specific temperature distribution resulted in an increase in total mortality of 12.4% (95% Confidence Interval (CI):7.76-17.24) on low PM10 days, and 21.25% (95% CI: 17.83-24.76) on high PM10 days. The increase on mortality was 10.09% (95% CI: - 5.62- 28.41) on low ozone days, and 14.95% (95% CI: 10.79-19.27) on high ozone days. For cause-specific mortality an increasing trend of the heat effects with increasing PM10 and ozone levels was also observed. An inconsistent pattern was observed for the modification of the heat effects by NO2, with higher heat effects estimated in the lower level of the pollutant. CONCLUSIONS: Our results support the evidence of elevated heat effects on mortality at higher levels of PM10 and 8 h max O3. Under climate change, any policy targeted at lowering air pollution levels will yield significant public health benefits.

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.

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 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.

Assessing heat effects on respiratory mortality and location characteristics as modifiers of heat effects at a small area scale in Central-Northern Europe.

Background: Heat effects on respiratory mortality are known, mostly from time-series studies of city-wide data. A limited number of studies have been conducted at the national level or covering non-urban areas. Effect modification by area-level factors has not been extensively investigated. Our study assessed the heat effects on respiratory mortality at a small administrative area level in Norway, Germany, and England and Wales, in the warm period (May-September) within 1996-2018. Also, we examined possible effect modification by several area-level characteristics in the framework of the EU-Horizon2020 EXHAUSTION project. Methods: Daily respiratory mortality counts and modeled air temperature data were collected for Norway, Germany, and England and Wales at a small administrative area level. The temperature-mortality association was assessed by small area-specific Poisson regression allowing for overdispersion, using distributed lag non-linear models. Estimates were pooled at the national level and overall using a random-effect meta-analysis. Age- and sex-specific models were also applied. A multilevel random-effects model was applied to investigate the modification of the heat effects by area-level factors. Results: A rise in temperature from the 75th to 99th percentile was associated with a 27% (95% confidence interval [CI] = 19%, 34%) increase in respiratory mortality, with higher effects for females. Increased population density and PM2.5 concentrations were associated with stronger heat effects on mortality. Conclusions: Our study strengthens the evidence of adverse heat effects on respiratory mortality in Northern Europe by identifying vulnerable subgroups and subregions. This may contribute to the development of targeted policies for adaptation to climate change.

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.