Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy.

BACKGROUND: Exposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. METHODS: We conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. RESULTS: There was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65-3.25 per IQR-difference of 1.2 µg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70-6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64-5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48-16.13), although they remained uncertain. CONCLUSIONS: This was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

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.

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.

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.

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.

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 air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts.

BACKGROUND: Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown. METHODS: We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0-191.9/C71.0-C71.9, 192.0/C72.2-C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 µg/m³ NO2, 1.17 (0.96, 1.41) per 5 µg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10-5m-1 BC, and 0.99 (0.84, 1.17) per 10 µg/m³ O3. CONCLUSIONS: We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.

Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 µg/m3 (PM10), 20.1 ± 5.6 µg/m3 (PM2.5), 27.2 ± 9.7 µg/m3 (NO2), and 70.8 ± 4.2 µg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10 µg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 µg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.

Sector of Employment and Mortality: A Cohort Based on Different Administrative Archives.

Administrative data can be precious in connecting information from different sectors. For the first time, we used data from the National Social Insurance Agency (INPS) to investigate the association between the occupational sectors and both non-accidental and accidental mortality. We retrieved information on occupational sectors from 1974 to 2011 for private sector workers included in the 2011 census cohort of Rome. We classified the occupational sectors into 25 categories and analyzed occupational exposure as ever/never have been employed in a sector or as the lifetime prevalent sector. We followed the subjects from the census reference day (9 October 2011) to 31 December 2019. We calculated age-standardized mortality rates for each occupational sector, separately in men and women. We used Cox regression to investigate the association between the occupational sectors and mortality, producing hazard ratios (HRs) and 95% confidence intervals (95%CI). We analyzed 910,559 30+-year-olds (53% males) followed for 7 million person-years. During the follow-up, 59,200 and 2560 died for non-accidental and accidental causes, respectively. Several occupational sectors showed high mortality risks in men in age-adjusted models: food and tobacco production with HR = 1.16 (95%CI: 1.09-8.22), metal processing (HR = 1.66, 95%CI: 1.21-11.8), footwear and wood (HR = 1.19, 95%CI: 1.11-1.28), construction (HR = 1.15, 95%CI: 1.12-1.18), hotels, camping, bars, and restaurants (HR = 1.16, 95%CI: 1.11-1.21) and cleaning (HR = 1.42, 95%CI: 1.33-1.52). In women, the sectors that showed higher mortality than the others were hotels, camping, bars, and restaurants (HR = 1.17, 95%CI: 1.10-1.25) and cleaning services (HR = 1.23, 95%CI: 1.17-1.30). Metal processing and construction sectors showed elevated accidental mortality risks in men. Social Insurance Agency data have the potential to characterize high-risk sectors and identify susceptible groups in the population.

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.

Long-term exposure to elemental components of fine particulate matter and all-natural and cause-specific mortality in a Danish nationwide administrative cohort study.

BACKGROUND: Fine particulate matter (PM2.5) is a well-recognized risk factor for premature death. However, evidence on which PM2.5 components are most relevant is unclear. METHODS: We evaluated the associations between mortality and long-term exposure to eight PM2.5 elemental components [copper (Cu), iron (Fe), zinc (Zn), sulfur (S), nickel (Ni), vanadium (V), silicon (Si), and potassium (K)]. Studied outcomes included death from diabetes, chronic kidney disease (CKD), dementia, and psychiatric disorders as well as all-natural causes, cardiovascular disease (CVD), respiratory diseases (RD), and lung cancer. We followed all residents in Denmark (aged ≥30 years) from January 1, 2000 to December 31, 2017. We used European-wide land-use regression models at a 100 × 100 m scale to estimate the residential annual mean levels of exposure to PM2.5 components. The models were developed with supervised linear regression (SLR) and random forest (RF). The associations were evaluated by Cox proportional hazard models adjusting for individual- and area-level socioeconomic factors and total PM2.5 mass. RESULTS: Of 3,081,244 individuals, we observed 803,373 death from natural causes during follow-up. We found significant positive associations between all-natural mortality with Si and K from both exposure modeling approaches (hazard ratios; 95% confidence intervals per interquartile range increase): SLR-Si (1.04; 1.03-1.05), RF-Si (1.01; 1.00-1.02), SLR-K (1.03; 1.02-1.04), and RF-K (1.06; 1.05-1.07). Strong associations of K and Si were detected with most causes of mortality except CKD and K, and diabetes and Si (the strongest associations for psychiatric disorders mortality). In addition, Fe was relevant for mortality from RD, lung cancer, CKD, and psychiatric disorders; Zn with mortality from CKD, RD, and lung cancer, and; Ni and V with lung cancer mortality. CONCLUSIONS: We present novel results of the relevance of different PM2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark.

Relationship of long-term air pollution exposure with asthma and rhinitis in Italy: an innovative multipollutant approach.

BACKGROUND: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants. AIM: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches. METHODS: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM10, PM2.5, NO2 and mean summer concentrations of O3 (µg/m3) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts. RESULTS: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 µg/m3 for PM2.5, 29.2 ± 7.0 µg/m3 for PM10, 28.0 ± 11.2 µg/m3 for NO2, and 70.9 ± 4.3 µg/m3 for summer O3. Through the multipollutant models the following associations emerged: PM10 and PM2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models. CONCLUSIONS: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses.

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Breast Cancer Incidence in Relation to Long-Term Low-Level Exposure to Air Pollution in the ELAPSE Pooled Cohort.

BACKGROUND: Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. METHODS: We conducted a pooled analysis among six European cohorts (n = 199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a HR (95% confidence interval) of 1.03 (1.00-1.06) per 10 µg/m³ NO2, 1.06 (1.01-1.11) per 5 µg/m³ PM2.5, 1.03 (0.99-1.06) per 0.5 10-5 m-1 BC, and 0.98 (0.94-1.01) per 10 µg/m³ O3. The effect estimates were most pronounced in the group of middle-aged women (50-54 years) and among never smokers. CONCLUSIONS: The results were in support of an association between especially PM2.5 and breast cancer. IMPACT: The findings of this study suggest a role of exposure to NO2, PM2.5, and BC in development of breast cancer.

[BIGEPI project: environmental and health data]. / Progetto BIGEPI: dati ambientali e dati sanitari.

OBJECTIVES: the BIGEPI project, co-funded by INAIL, has used big data to identify the health risks associated with short and long-term exposure to air pollution, extreme temperatures and occupational exposures. DESIGN: the project consists of 5 specific work packages (WP) aimed at assessing: 1. the acute effects of environmental exposures over the national territory; 2. the acute effects of environmental exposures in contaminated areas, such as Sites of National Interest (SIN) and industrial sites; 3. the chronic effects of environmental exposures in 6 Italian longitudinal metropolitan studies; 4. the acute and chronic effects of environmental exposures in 7 epidemiological surveys on population samples; 5. the chronic effects of occupational exposures in the longitudinal metropolitan studies of Rome and Turin. SETTING AND PARTICIPANTS: BIGEPI analyzed environmental and health data at different levels of detail: the whole Italian population (WP1); populations living in areas contaminated by pollutants of industrial origin (WP2); the entire longitudinal cohorts of the metropolitan areas of Bologna, Brindisi, Rome, Syracuse, Taranto and Turin (WP3 and WP5); population samples participating in the epidemiological surveys of Ancona, Palermo, Pavia, Pisa, Sassari, Turin and Verona (WP4). MAIN OUTCOME MEASURES: environmental exposure: PM10, PM2,5, NO2 and O3 concentrations and air temperature at 1 Km2 resolution at national level. Occupational exposures: employment history of subjects working in at least one of 25 sectors with similar occupational exposures to chemicals/carcinogens; self-reported exposure to dust/fumes/gas in the workplace. Health data: cause-specific mortality/hospitalisation; symptoms/diagnosis of respiratory/allergic diseases; respiratory function and bronchial inflammation. RESULTS: BIGEPI analyzed data at the level of the entire Italian population, data on 2.8 million adults (>=30 yrs) in longitudinal metropolitan studies and on about 14,500 individuals (>=18 yrs) in epidemiological surveys on population samples. The population investigated in the longitudinal metropolitan studies had an average age of approximately 55 years and that of the epidemiological surveys was about 48 years; in both cases, 53% of the population was female. As regards environmental exposure, in the period 2013-2015, at national level average values for PM10, PM2.5, NO2 and summer O3 were: 21.1±13.6, 15.1±10.9, 14.7±9.1 and 80.3±17.3 µg/m3, for the temperature the average value was 13.9±7.2 °C. Data were analyzed for a total of 1,769,660 deaths from non-accidental causes as well as 74,392 incident cases of acute coronary event and 45,513 of stroke. Epidemiological investigations showed a high prevalence of symptoms/diagnoses of rhinitis (range: 14.2-40.5%), COPD (range: 4.7-19.3%) and asthma (range: 3.2-13.2%). The availability of these large datasets has made it possible to implement advanced statistical models for estimating the health effects of short- and long-term exposures to pollutants. The details are reported in the BIGEPI papers already published in other international journals and in those published in this volume of E&P. CONCLUSIONS: BIGEPI has confirmed the great potential of using big data in studies of the health effects of environmental and occupational factors, stimulating new directions of scientific research and confirming the need for preventive action on air quality and climate change for the health of the general population and the workers.

Long term exposure to air pollution and kidney parenchyma cancer - Effects of low-level air pollution: a Study in Europe (ELAPSE).

BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited. METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: The participants were followed from baseline (1985-2005) to 2011-2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5-95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 µg/m3 (12.8-39.2), 15.3 µg/m3 (8.6-19.2), 1.6 10-5 m-1 (0.7-2.1), and 87.0 µg/m3 (70.3-97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 µg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 µg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10-5 m-1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 µg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma. CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer.

Exposure to surrounding greenness and natural-cause and cause-specific mortality in the ELAPSE pooled cohort.

BACKGROUND: The majority of studies have shown higher greenness exposure associated with reduced mortality risks, but few controlled for spatially correlated air pollution and traffic noise exposures. We aim to address this research gap in the ELAPSE pooled cohort. METHODS: Mean Normalized Difference Vegetation Index (NDVI) in a 300-m grid cell and 1-km radius were assigned to participants' baseline home addresses as a measure of surrounding greenness exposure. We used Cox proportional hazards models to estimate the association of NDVI exposure with natural-cause and cause-specific mortality, adjusting for a number of potential confounders including socioeconomic status and lifestyle factors at individual and area-levels. We further assessed the associations between greenness exposure and mortality after adjusting for fine particulate matter (PM2.5), nitrogen dioxide (NO2) and road traffic noise. RESULTS: The pooled study population comprised 327,388 individuals who experienced 47,179 natural-cause deaths during 6,374,370 person-years of follow-up. The mean NDVI in the pooled cohort was 0.33 (SD 0.1) and 0.34 (SD 0.1) in the 300-m grid and 1-km buffer. In the main fully adjusted model, 0.1 unit increment of NDVI inside 300-m grid was associated with 5% lower risk of natural-cause mortality (Hazard Ratio (HR) 0.95 (95% CI: 0.94, 0.96)). The associations attenuated after adjustment for air pollution [HR (95% CI): 0.97 (0.96, 0.98) adjusted for PM2.5; 0.98 (0.96, 0.99) adjusted for NO2]. Additional adjustment for traffic noise hardly affected the associations. Consistent results were observed for NDVI within 1-km buffer. After adjustment for air pollution, NDVI was inversely associated with diabetes, respiratory and lung cancer mortality, yet with wider 95% confidence intervals. No association with cardiovascular mortality was found. CONCLUSIONS: We found a significant inverse association between surrounding greenness and natural-cause mortality, which remained after adjusting for spatially correlated air pollution and traffic noise.

Long-term exposure to air pollution and mortality in a Danish nationwide administrative cohort study: Beyond mortality from cardiopulmonary disease and lung cancer.

BACKGROUND: The association between long-term exposure to air pollution and mortality from cardiorespiratory diseases is well established, yet the evidence for other diseases remains limited. OBJECTIVES: To examine the associations of long-term exposure to air pollution with mortality from diabetes, dementia, psychiatric disorders, chronic kidney disease (CKD), asthma, acute lower respiratory infection (ALRI), as well as mortality from all-natural and cardiorespiratory causes in the Danish nationwide administrative cohort. METHODS: We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (warm season) were estimated using European-wide hybrid land-use regression models (100 m × 100 m) and assigned to baseline residential addresses. We used Cox proportional hazard models to evaluate the association between air pollution and mortality, accounting for demographic and socioeconomic factors. We additionally applied indirect adjustment for smoking and body mass index (BMI). RESULTS: During 47,023,454 person-years of follow-up, 803,881 people died from natural causes. Long-term exposure to PM2.5 (mean: 12.4 µg/m3), NO2 (20.3 µg/m3), and/or BC (1.0 × 10-5/m) was statistically significantly associated with all studied mortality outcomes except CKD. A 5 µg/m3 increase in PM2.5 was associated with higher mortality from all-natural causes (hazard ratio 1.11; 95% confidence interval 1.09-1.13), cardiovascular disease (1.09; 1.07-1.12), respiratory disease (1.11; 1.07-1.15), lung cancer (1.19; 1.15-1.24), diabetes (1.10; 1.04-1.16), dementia (1.05; 1.00-1.10), psychiatric disorders (1.38; 1.27-1.50), asthma (1.13; 0.94-1.36), and ALRI (1.14; 1.09-1.20). Associations with long-term exposure to ozone (mean: 80.2 µg/m3) were generally negative but became significantly positive for several endpoints in two-pollutant models. Generally, associations were attenuated but remained significant after indirect adjustment for smoking and BMI. CONCLUSION: Long-term exposure to PM2.5, NO2, and/or BC in Denmark were associated with mortality beyond cardiorespiratory diseases, including diabetes, dementia, psychiatric disorders, asthma, and ALRI.

Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden.

Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, Setting, and Participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 µm [PM2.5], particulate matter with diameter ≤10 µm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main Outcomes and Measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] µg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] µg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] µg/m3 on case days; and for NOx, 8.2 [5.6-14.1] µg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] µg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] µg/m3 for PM10, 0.2 [IQR, 0.2-0.4] µg/m3 for BC, and 7.7 [IQR, 5.3-12.8] µg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and Relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.