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 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.

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.

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.

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 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.

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.

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.

Coarse Particulate Air Pollution and Daily Mortality: A Global Study in 205 Cities.

Rationale: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality are not fully understood on a global scale. Objectives: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide. Methods: We collected daily mortality (total, cardiovascular, and respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine PM. A two-stage time-series analytic approach was applied, with overdispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from copollutants (fine PM, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled, and regional analyses were conducted. Measurements and Main Results: A 10 µg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI], 0.18%-0.84%), 0.43% (95% CI, 0.15%-0.71%), and 0.41% (95% CI, 0.06%-0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all copollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds. Conclusions: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular, and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort: the ELAPSE project.

BACKGROUND: The evidence linking ambient air pollution to bladder cancer is limited and mixed. METHODS: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight PM2.5 elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders. RESULTS: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM2.5 and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93-1.27) per 5 µg/m3 for 2010 exposure and 1.06 (95% CI: 0.99-1.14) for baseline exposure. Effect estimates for NO2, BC and O3 were close to unity. A positive association was observed with PM2.5 zinc (HR 1.08; 95% CI: 1.00-1.16 per 10 ng/m3). CONCLUSIONS: We found suggestive evidence of an association between long-term PM2.5 mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM2.5 suggests the importance of industrial emissions.

Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.

BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality. METHODS: We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators. RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk. CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.

Long-Term Exposure to Source-Specific Fine Particles and Mortality─A Pooled Analysis of 14 European Cohorts within the ELAPSE Project.

We assessed mortality risks associated with source-specific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 µg/m3 increase) across five identified sources. On a 1 µg/m3 basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.

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.

Long-term exposure to air pollution and liver cancer incidence in six European cohorts.

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.

Long-term exposure to low-level air pollution and incidence of asthma: the ELAPSE project.

BACKGROUND: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults. METHODS: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders. RESULTS: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 µg·m-3 for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 µg·m-3 for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5×10-5 m-1 for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold. CONCLUSIONS: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.

Dietary Supplement Use after Cancer Diagnosis in Relation to Total Mortality, Cancer Mortality and Recurrence: A Systematic Review and Meta-Analysis.

To study post-diagnosis dietary supplement use in relation to total mortality, cancer mortality and recurrence among cancer survivors. PubMed and Cochrane Library were searched until April 2019 for observational studies (OS) and randomized clinical trials (RCT). Pooled risk ratios (RR) were calculated using random-effects models. Compared to no supplementation, calcium supplementation was associated with lower total (RR = 0.88, 95% confidence interval (CI): 0.77-1.00, I2=0%, four OS) and cancer mortality (RR = 0.71, 95% CI: 0.53-0.95, I2=0%, three OS) among all cancer survivors, and cancer mortality among colorectal cancer survivors (RR = 0.66, 95% CI: 0.47-0.94, I2=0%, two OS). Vitamin D supplementation was associated with lower total mortality (RR = 0.86, 95% CI: 0.76-0.99, I2=0%, three OS and two RCT). Among breast cancer survivors, supplementation with vitamin C (RR = 0.79, 95% CI: 0.68-0.92, I2=0%, four OS), D (RR = 0.85, 95% CI: 0.72-0.99, I2=0%, two OS), and E (RR = 0.76, 95% CI: 0.64-0.90, I2=0%, three OS) was associated with lower total mortality, while multivitamins (RR = 0.79, 95% CI: 0.64-0.97, I2=0%, two OS), vitamin C (RR = 0.76, 95% CI: 0.64-0.91, I2=0%, two OS), and E (RR = 0.69, 95% CI: 0.55-0.85, I2=0%, two OS) with lower cancer recurrence. Conclusions: Findings are mostly based on OS. More RCTs are needed to justify any recommendation for use.

Associations of air pollution and greenness with mortality in Greece: An ecological study.

BACKGROUND: Epidemiological studies have documented the adverse effects of long-term exposure to fine particulate matter (PM2.5) on health, while there has been less research on the effects of nitrogen dioxide (NO2), black carbon (BC) and especially ozone (O3). Furthermore, there is limited evidence for the synergistic effects of exposure to pollutants and greenness. We investigated the association of long-term exposure to air pollution and greenness with natural-cause, cardiovascular and respiratory mortality in Greece using an ecological study design. METHODS: Mortality and socioeconomic data were obtained from 1035 municipal units from the 2011 census data. Annual average PM2.5, NO2, BC and O3 concentrations for 2010 were derived from 100 × 100 m surfaces predicted by hybrid LUR models. The normalized difference vegetation index was used to assess greenness. We applied Poisson regression models on standardized mortality rates adjusted for socioeconomic indicators and lung cancer rates, accounting for spatial autocorrelation. The analysis was conducted initially for the whole country and then separately for urban and rural areas. We assessed interactions between pollutants and greenness and applied two-exposure models. RESULTS: An interquartile range (IQR) increase in PM2.5, NO2 and BC was associated with increases in natural-cause mortality (Relative Risk (RR) 1.09, 95% confidence interval (CI): 1.08, 1.11; RR 1.03 (95% CI: 1.03, 1.04) and RR 1.02 (95% CI: 1.02, 1.03), respectively), while PM2.5 and NO2 were also associated with cause-specific mortality. Greenness was associated with lower natural-cause (RR 0.95, 95% CI: 0.94, 0.96 per IQR) and cause-specific mortality. For all outcomes we estimated a protective association with O3 (natural-cause mortality RR 0.79, 95% CI: 0.76, 0.82 per IQR). All associations were stronger in urban areas. We estimated negative statistically significant interactions between air pollution and greenness for respiratory morality and positive ones for cardiovascular mortality. Estimates were mostly robust to co-exposure adjustment. CONCLUSIONS: Our findings support associations of air pollution and greenness with mortality, both in urban and rural areas of Greece. Further research is needed to elaborate on the synergies in cause-specific mortality. Our results on the interactions between pollutants and greenness may imply differential biological mechanisms for cause-specific mortality and warrant further investigation.

Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort.

BACKGROUND: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. METHODS: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). RESULTS: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. CONCLUSIONS: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.

Spatio-temporal associations of air pollutant concentrations, GP respiratory consultations and respiratory inhaler prescriptions: a 5-year study of primary care in the borough of Lambeth, South London.

BACKGROUND: Although the associations of outdoor air pollution exposure with mortality and hospital admissions are well established, few previous studies have reported on primary care clinical and prescribing data. We assessed the associations of short and long-term pollutant exposures with General Practitioner respiratory consultations and inhaler prescriptions. METHODS: Daily primary care data, for 2009-2013, were obtained from Lambeth DataNet (LDN), an anonymised dataset containing coded data from all patients (1.2 million) registered at general practices in Lambeth, an inner-city south London borough. Counts of respiratory consultations and inhaler prescriptions by day and Lower Super Output Area (LSOA) of residence were constructed. We developed models for predicting daily PM2.5, PM10, NO2 and O3 per LSOA. We used spatio-temporal mixed effects zero inflated negative binomial models to investigate the simultaneous short- and long-term effects of exposure to pollutants on the number of events. RESULTS: The mean concentrations of NO2, PM10, PM2.5 and O3 over the study period were 50.7, 21.2, 15.6, and 49.9 µg/m3 respectively, with all pollutants except NO2 having much larger temporal rather than spatial variability. Following short-term exposure increases to PM10, NO2 and PM2.5 the number of consultations and inhaler prescriptions were found to increase, especially for PM10 exposure in children which was associated with increases in daily respiratory consultations of 3.4% and inhaler prescriptions of 0.8%, per PM10 interquartile range (IQR) increase. Associations further increased after adjustment for weekly average exposures, rising to 6.1 and 1.2%, respectively, for weekly average PM10 exposure. In contrast, a short-term increase in O3 exposure was associated with decreased number of respiratory consultations. No association was found between long-term exposures to PM10, PM2.5 and NO2 and number of respiratory consultations. Long-term exposure to NO2 was associated with an increase (8%) in preventer inhaler prescriptions only. CONCLUSIONS: We found increases in the daily number of GP respiratory consultations and inhaler prescriptions following short-term increases in exposure to NO2, PM10 and PM2.5. These associations are more pronounced in children and persist for at least a week. The association with long term exposure to NO2 and preventer inhaler prescriptions indicates likely increased chronic respiratory morbidity.