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Background: Studies have linked air pollution to lung cancer incidence and mortality, but few have compared these associations, which may differ due to cancer survival variations. We aimed to evaluate the association between long-term air pollution exposure and lung cancer incidence and compare findings with previous lung cancer mortality analyses within the same cohorts., Methods: We analyzed four population-based administrative cohorts in Denmark (2000-2015), England (2011-2017), Norway (2001-2016) and Rome (2001-2015). We assessed residential exposure to annual average fine particulate matter (PM 2.5 ), nitrogen dioxide (NO₂), black carbon (BC), and warm-season ozone (O 3 ) using Europe-wide land use regression models. We used Cox proportional hazard models to evaluate cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence identified using hospital admission records (English and Roman cohorts) or cancer registries (Danish and Norwegian cohorts). We evaluated the associations at low exposure levels using subset analyses and natural cubic splines. Cohort-specific HRs were pooled using random-effects meta-analyses, separately for incidence and mortality., Results: Over 93,733,929 person-years of follow-up, 111,949 incident lung cancer cases occurred. Incident lung cancer was positively associated with PM 2.5 , NO 2 and BC, and negatively associated with O 3 . The negative O 3 association became positive after adjustment for NO 2 . Associations were almost identical or slightly stronger for lung cancer incidence than mortality in the same cohorts, with respective meta-analytic HRs (95% CIs) of 1.14 (1.06, 1.22) and 1.12 (1.02, 1.22) per 5 μg/m 3 increase in PM 2.5 , and 1.10 (1.04, 1.16) and 1.09 (1.02, 1.16) per 10 μg/m 3 increase in NO 2 . Positive associations persisted for both incidence and mortality at low pollution levels with similar magnitude., Conclusions: We found similarly elevated risks of lung cancer incidence and mortality in association with residential exposure to PM 2.5 , NO 2 and BC in meta-analyses of four European administrative cohorts, which persisted at low pollution levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (O 3 ) 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 O 3 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (NO 2 ), black carbon (BC), ozone (O 3 ), particulate matter ≤2.5 μm (PM 2.5 ) and several elemental constituents of PM 2.5 . 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 PM 2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 μg/m 3 , BC (1.26 (1.03-1.53) per 0.5 × 10 - 5 /m), NO 2 (1.13 (0.93-1.38) per 10 μg/m 3 ) and inverse for O 3 (0.71 (0.54-0.93) per 10 μg/m 3 ). 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 PM 2.5 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 NO 2 , 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 (NO 2 ), fine particles (PM 2.5 ), black carbon (BC), and ozone (O 3 ) 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 NO 2 , 1.04 (0.82, 1.33) per 5 μg/m³ PM 2.5 , 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 O 3 ., Conclusions: We did not observe an association between long-term ambient air pollution exposure and incidence of multiple myeloma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Fine particulate matter (PM 2.5 ) is a well-recognized risk factor for premature death. However, evidence on which PM 2.5 components are most relevant is unclear., Methods: We evaluated the associations between mortality and long-term exposure to eight PM 2.5 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 PM 2.5 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 PM 2.5 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 PM 2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

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 (PM 2.5 ), nitrogen dioxide (NO 2 ), black carbon (BC), warm season ozone (O 3 ) and eight elemental components of PM 2.5 (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 NO 2 , PM 2.5 , BC and O 3 were 24.1 μg/m 3 (12.8-39.2), 15.3 μg/m 3 (8.6-19.2), 1.6 10 -5  m -1 (0.7-2.1), and 87.0 μg/m 3 (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 NO 2 , 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM 2.5 , 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 O 3 . We did not find associations between any of the elemental components of PM 2.5 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Evidence for the association between long-term exposure to ambient particulate matter components and mortality from natural causes is sparse and inconsistent. We evaluated this association in six large administrative cohorts in the framework of the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project. We analyzed data from country-wide administrative cohorts in Norway, Denmark, the Netherlands, Belgium, Switzerland and in Rome (Italy). Annual 2010 mean concentrations of copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V) and zinc (Zn) in fine particulate matter (PM 2.5 ) were estimated using 100 × 100 m Europe-wide hybrid land use regression models assigned to the participants' residential addresses. We applied cohort-specific Cox proportional hazard models controlling for area- and individual-level covariates to evaluate associations with natural mortality. Two pollutant models adjusting for PM 2.5 total mass or nitrogen dioxide (NO 2 ) were also applied. We pooled cohort-specific estimates using a random effects meta-analysis. We included almost 27 million participants contributing more than 240 million person-years. All components except Zn were significantly associated with natural mortality [pooled Hazard Ratios (HRs) (95% CI): 1.037 (1.014, 1.060) per 5 ng/m 3 Cu; 1.069 (1.031, 1.108) per 100 ng/m 3 Fe; 1.039 (1.018, 1.062) per 50 ng/m 3 K; 1.024 (1.006, 1.043) per 1 ng/m 3 Ni; 1.036 (1.016, 1.057) per 200 ng/m 3 S; 1.152 (1.048, 1.266) per 100 ng/m 3 Si; 1.020 (1.006, 1.034) per 2 ng/m 3 V]. Only K and Si were robust to PM 2.5 or NO 2 adjustment [pooled HRs (95% CI) per 50 ng/m 3 in K: 1.025 (1.008, 1.044), 1.020 (0.999, 1.042) and per 100 ng/m 3 in Si: 1.121 (1.039, 1.209), 1.068 (1.022, 1.117) adjusted for PM 2.5 and NO 2 correspondingly]. Our findings indicate an association of natural mortality with most components, which was reduced after adjustment for PM 2.5 and especially NO 2 ., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Ambient air pollution exposure has been associated with higher mortality risk in numerous studies. We assessed potential variability in the magnitude of this association for non-accidental, cardiovascular disease, respiratory disease, and lung cancer mortality in a country-wide administrative cohort by exposure assessment method and by adjustment for geographic subdivisions., Methods: We used the Belgian 2001 census linked to population and mortality register including nearly 5.5 million adults aged ≥30 (mean follow-up: 9.97 years). Annual mean concentrations for fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), black carbon (BC) and ozone (O 3 ) were assessed at baseline residential address using two exposure methods; Europe-wide hybrid land use regression (LUR) models [100x100m], and Belgium-wide interpolation-dispersion (RIO-IFDM) models [25x25m]. We used Cox proportional hazards models with age as the underlying time scale and adjusted for various individual and area-level covariates. We further adjusted main models for two different area-levels following the European Nomenclature of Territorial Units for Statistics (NUTS); NUTS-1 (n = 3), or NUTS-3 (n = 43)., Results: We found no consistent differences between both exposure methods. We observed most robust associations with lung cancer mortality. Hazard Ratios (HRs) per 10 μg/m 3 increase for NO 2 were 1.060 (95%CI 1.042-1.078) [hybrid LUR] and 1.040 (95%CI 1.022-1.058) [RIO-IFDM]. Associations with non-accidental, respiratory disease and cardiovascular disease mortality were generally null in main models but were enhanced after further adjustment for NUTS-1 or NUTS-3. HRs for non-accidental mortality per 5 μg/m 3 increase for PM 2.5 for the main model using hybrid LUR exposure were 1.023 (95%CI 1.011-1.035). After including random effects HRs were 1.044 (95%CI 1.033-1.057) [NUTS-1] and 1.076 (95%CI 1.060-1.092) [NUTS-3]., Conclusion: Long-term air pollution exposure was associated with higher lung cancer mortality risk but not consistently with the other studied causes. Magnitude of associations varied by adjustment for geographic subdivisions, area-level socio-economic covariates and less by exposure assessment method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The health effects of acute exposure to temperature extremes are established; those of long-term exposure only recently received attention. We performed a systematic review to assess the associations of long-term (>3 months) exposure to higher or lower temperature on total and cardiopulmonary mortality and morbidity, screening 3455 studies and selecting 34. The studies were classified in those observing associations within a population over years with changing annual temperature indices and those comparing areas with a different climate. We also assessed the risk of bias, adapting appropriately an instrument developed by the World Health Organization for air pollution. Studies reported that annual temperature indices for extremes and variability were associated with annual increases in mortality, indicating that effects of temperature extremes cannot be attributed only to short-term mortality displacement. Studies on cardiovascular mortality indicated stronger associations with cold rather than hot temperature, whilst those on respiratory outcomes reported effects of both heat and cold but were few and used diverse health outcomes. Interactions with air pollution were not generally assessed. The few studies investigating effect modification showed stronger effects among the elderly and those socially deprived. Comparisons of health outcome prevalence between areas reported lower blood pressure and a tendency for higher obesity in populations living in warmer climates. Our review indicated interesting associations between long-term exposure to unusual temperature levels in specific areas and differences in health outcomes and cardiovascular risk factors between geographical locations with different climate, but the number of studies by design and health outcome was small. Risk of bias was identified because of the use of crude exposure assessment and inadequate adjustment for confounding. More and better designed studies, including the investigation of effect modifiers, are needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Epidemiological studies have documented the adverse effects of long-term exposure to fine particulate matter (PM 2.5 ) on health, while there has been less research on the effects of nitrogen dioxide (NO 2 ), black carbon (BC) and especially ozone (O 3 ). 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 PM 2.5 , NO 2 , BC and O 3 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 PM 2.5 , NO 2 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 PM 2.5 and NO 2 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 O 3 (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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: An association between long-term exposure to fine particulate matter (PM 2.5 ) and lung cancer has been established in previous studies. PM 2.5 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 PM 2.5 and lung cancer incidence., Methods: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM 2.5 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/m 3 PM 2.5  K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m 3 PM 2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m 3 PM 2.5  S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m 3 PM 2.5  V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO 2 ). After adjustment for PM 2.5 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 PM 2.5 components may prove helpful in future lung cancer prevention strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sporadic studies suggest hydroxychloroquine (HCQ) may be effective for thrombosis prevention in patients with primary antiphospholipid syndrome (PAPS) and may lead to antiphospholipid antibody (aPL) titer reduction but data from randomized studies are lacking., Methods: We conducted a pilot open-label randomized prospective study aiming to evaluate the safety and efficacy of HCQ for thrombosis prevention in 50 patients with PAPS allocated 1:1 to HCQ plus standard care (systemic anticoagulation and/or antiplatelet therapy) vs. standard care alone, as well as the effect of HCQ on aPL titers of 50 PAPS patients and 15 asymptomatic aPL carriers., Results: HCQ use plus standard care was associated with lower incidence rate of thrombosis than standard care alone (0.001 vs. 0.007, log-rank p =0.048) over an average 2.6-year follow-up, and a multivariate hazard ratio of 0.09 (95% CI = 0.01-1.26, p = 0.074) after adjusting for the effect of age, sex, traditional cardiovascular risk factors, triple aPL positivity, history of recurrent thrombotic events at baseline, and poor anticoagulation quality (INR levels within therapeutic range for ≤80% of follow-up). No significant difference in safety outcomes was observed between the two groups. Long-term HCQ use was associated with a decrease in aPL titers except for IgM anticardiolipin antibodies, which tended to decrease overtime regardless of treatment allocation., Conclusions: HCQ may represent an effective adjuvant treatment for thrombosis prevention in patients with PAPS, which may be mediated via a reduction in aPL titers. Larger randomized trials are needed in order to corroborate this finding and investigate the thromboprotective role of HCQ in asymptomatic aPL carriers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Although there is evidence on the effects of short-term ozone (O 3 ) exposures on children's respiratory health, few studies have reported results on the effects of long-term exposures. We report the effects of long-term exposure to O 3 on respiratory health outcomes in 10-11-year old children., Methods: We conducted a panel study in a sample of the general population of school children in two cities with high average O 3 concentrations, Athens and Thessaloniki, Greece. All 186 participating students were followed up intensively for 5 weeks spreading across a school year. Data was collected through questionnaires, weekly personal O 3 measurements, spirometry, FeNO and time-activity diaries. Long-term O 3 exposure was assessed using fixed site measurements and modeling, calibrated for personal exposures. The associations between measured lung function parameters and lung function growth over the study period, as well as FeNO and the occurrence of symptoms with long-term O 3 exposure were assessed through the application of multiple mixed effects 2-level regression models, adjusting for confounders and for short-term exposures., Results: A 10 μg/m 3 increase in calibrated long-term O 3 exposure, using measurements from fixed site monitors was associated with lower FVC and FEV 1 by 17 mL (95% Confidence Interval: 5-28) and 13 mL (3-21) respectively and small decreases in lung growth: 0.008% (0.002-0.014%) for FVC and 0.006% (0.000-0.012%) in FEV 1 over the study period. No association was observed with PEF, FeNO or the occurrence of symptoms. A similar pattern was observed when the exposure estimates from the dispersion models were employed., Conclusions: Our study provides evidence that long-term O 3 exposure is associated with reduced lung volumes and growth., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To further quantify the association between physical activity (PA) after breast cancer diagnosis and all-cause mortality, breast cancer mortality and/or breast cancer recurrence., Methods and Results: PubMed was searched until November 2017 for observational studies investigating any type of PA in association with total mortality, breast cancer mortality and/or breast cancer recurrence among women with breast cancer diagnosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using random-effects models for highest versus lowest categories of PA. Ten studies were included in the meta-analysis. During an average follow-up ranging from 3.5 to 12.7 years there were 23,041 breast cancer survivors, 2,522 deaths from all causes, 841 deaths from breast cancer and 1,398 recurrences/remissions. Compared to women in the lowest recreational PA level (lowest quintile/quartile), women in the highest level had a lower risk of all-cause mortality (HR = 0.58, 95% CIs: 0.45-0.75; 8 studies), of death from breast cancer (HR = 0.60, 95% CIs 0.36-0.99; 5 studies) and a lower, albeit non-significant, risk of recurrence (HR = 0.79, 95% CIs 0.60-1.05; 5 studies). There was evidence of heterogeneity between the studies evaluating recreational PA and total mortality (Ι 2  = 52.4%) and even higher for breast cancer mortality (Ι 2  = 77.7%) or recurrence (Ι 2  = 66.4%)., Conclusion: Highest recreational PA after breast cancer diagnosis was associated with lower all-cause and breast cancer mortality. This finding probably reflects the favorable impact of PA on cardiovascular mortality, and a possible favorable role on breast cancer survival, though reverse causation cannot be excluded., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Urban areas in Europe are facing a range of environmental public health challenges, such as air pollution, traffic noise and road injuries. The identification and quantification of the public health risks associated with exposure to environmental conditions is important for prioritising policies and interventions that aim to diminish the risks and improve the health of the population. With this purpose in mind, the EURO-HEALTHY project used a consistent approach to assess the impact of key environmental risk factors and urban environmental determinants on public health in European metropolitan areas. A number of environmental public health indicators, which are closely tied to the physical and built environment, were identified through stakeholder consultation; data were collected from six European metropolitan areas (Athens, Barcelona, Lisbon, London, Stockholm and Turin) covering the period 2000-2014, and a health impact assessment framework enabled the quantification of health effects (attributable deaths) associated with these indicators. The key environmental public health indicators were related to air pollution and certain urban environmental conditions (urban green spaces, road safety). The air pollution was generally the highest environmental public health risk; the associated number of deaths in Athens, Barcelona and London ranged between 800 and 2300 attributable deaths per year. The number of victims of road traffic accidents and the associated deaths were lowest in the most recent year compared with previous years. We also examined the positive impacts on health associated with urban green spaces by calculating reduced mortality impacts for populations residing in areas with greater green space coverage; results in Athens showed reductions of all-cause mortality of 26 per 100,000 inhabitants for populations with benefits of local greenspace. Based on our analysis, we discuss recommendations of potential interventions that could be implemented to reduce the environmental public health risks in the European metropolitan areas covered by this study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Air Quality indicators or indices (AQIs) are mainly used for communicating the air pollution levels and risk to the general population. However, very few epidemiological studies have used AQIs for characterizing exposure., Objective: In the framework of the RESPOZE panel study we evaluated the association of daily ozone AQI levels with the daily occurrence of respiratory symptoms and Peak Expiratory Flow (PEF) and compared the effects with those estimated using measurements from fixed outdoor monitoring sites, in the city of Athens, Greece., Materials and Methods: A panel of 97 children, aged 10-11years, was followed intensively for 35days (5weeks) during the academic year 2013-14. PEF and symptoms were recorded daily by each child. Two ozone AQIs classifying the air quality into 7 categories of increasing severity, were calculated; one characterizing the whole Athens area and one the local area around the child's residence and school. Measurements from fixed sites were also used. Mixed effects models for repeated measurements were applied, adjusting for several confounders., Results: Increasing ozone levels were associated with increased incidence of symptoms, but the strongest and most statistically significant associations were found with the local air quality characterization with the AQI. Specifically, an increase in AQI-local by one category was associated with 34% (95% CI: 9%, 64%) increased odds of stuffy nose. When the AQI categories were "Bad" and "Severe", an increase in the incidence of cough was observed (OR 3.05 (95% CI: 1.29, 7.22) and 6.42 (95% CI: 1.47, 28.03) respectively). We did not observe a statistically significant association between AQI and PEF., Conclusion: Our results show that the use of an AQI based on local conditions may be advantageous over the use of only measurements when investigating the effects of air pollution on health outcomes for improving communication of risk to the public., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Assessment of the cumulative effect of correlated exposures is an open methodological issue in environmental epidemiology. Most previous studies have applied regression models with interaction terms or dimension reduction methods. The combined effect of pollutants has been also evaluated through the use of exposure scores that incorporate weights based on the strength of the component-specific associations with health outcomes., Methods: We compared three approaches addressing multi-pollutant exposures in epidemiological models: main effects models, the adaptive least absolute shrinkage and selection operator (LASSO) and a weighted exposure score. We assessed the performance of the methods by simulations under various scenarios for the pollutants' correlations. We further applied these methods to time series data from Athens, Greece in 2007-12 to investigate the combined effect of short-term exposure to six regulated pollutants on all-cause and respiratory mortality., Results: The exposure score provided the least biased estimate under all correlation scenarios for both mortality outcomes. The adaptive LASSO performed well in the case of low and medium correlation between exposures while the main effect model resulted in severe bias. In the real data application, the cumulative effect estimate was similar between approaches for all-cause mortality ranging from 0.7% increase per interquartile range (IQR) (score) to 1.1% (main effects), while for respiratory mortality conclusions were contradictive and ranged from - 0.6% (adaptive LASSO) to 2.8% (score)., Conclusions: Τhe use of a weighted exposure score to address cumulative effects of correlated metrics may perform well under different exposure correlation and variability in the health outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the wider framework of the RESPOZE (ReSPiratory effects of OZone Exposure in Greek children) panel study, we investigated possible determinants of O 3 exposure of school children, measured with personal passive samplers, in Athens and Thessaloniki, Greece., Methods: Personal exposure to O 3 was measured for five weeks spread along the academic year 2013-14, in 186 school children in Athens and Thessaloniki, Greece. At the same time, at-school outdoor measurements were performed and ambient levels of 8-h daily maximum O 3 from fixed sites were collected. We also collected information on lifestyle and housing characteristics through an extended general questionnaire (GQ) and each participant completed daily time activity diaries (TADs) during the study period., Results: Mean outdoor concentrations were higher during the warmer months, in the suburbs of the cities and in Athens. Personal exposure concentrations were significantly lower compared to outdoor. Daily levels of at-school outdoor and ambient levels of O 3 from fixed sites were significant determinants of personal exposure to O 3 . For a 10μg/m 3 increase in at-school outdoor O 3 concentrations and PM 10 measurements a 20.9% (95% CI: 13%, 28%) increase in personal exposure to O 3 was found. For a half an hour more spent in transportation an average increase of 7% (95% CI: 0.3%, 14.6%) in personal exposure to O 3 was observed. Among other possible determinants, time spent in transportation (TAD variable) and duration of open windows were the ones associated with personal O 3 exposure levels., Conclusions: Our results support the use of outdoor and ambient measurements from fixed sites in epidemiological studies as a proxy of personal exposure to O 3 , but this has to be calibrated taking into account personal measurements and time-activity patterns., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ozone exposure of 179 children in Athens and Thessaloniki, Greece was assessed during 2013-2014, by repeated weekly personal measurements, using passive samplers. O 3 was also monitored at school locations of participants to characterize community-level ambient exposure. Average personal concentrations in the two cities (5.0 and 2.8ppb in Athens and Thessaloniki, respectively) were considerably lower than ambient concentrations (with mean personal/ambient ratios of 0.13-0.15). The temporal variation of personal concentrations followed the -typical for low-latitude areas- pattern of cold-warm seasons. However, differences were detected between temporal distributions of personal and ambient concentrations, since personal exposures were affected by additional factors which present seasonal variability, such as outdoor activity and house ventilation. Significant spatial contrasts were observed between urban and suburban areas, for personal concentrations in Athens, with higher exposure for children residing in the N-NE part of the area. In Thessaloniki, spatial variations in personal concentrations were less pronounced, echoing the spatial pattern of ambient concentrations, a result of complex local meteorology and the smaller geographical expansion of the study area. Ambient concentration was identified as the most important factor influencing personal exposures (correlation coefficients between 0.36 and 0.67). Associations appeared to be stronger with ambient concentrations measured at school locations of children, than to those reported by the nearest site of the air quality monitoring network, indicating the importance of community-representative outdoor monitoring for characterization of personal-ambient relationships. Time spent outdoors by children was limited (>90% of the time they remained indoors), but -due to the lack of indoor sources- it was found to exert significant influence on personal concentrations, affecting inter-subject and spatiotemporal variability. Additional parameters that were identified as relevant for the determination of personal concentrations were indoor ventilation conditions (specifically indoor times with windows open) and the use of wood-burning in open fireplaces for heating as an ozone sink., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Heart disease and stroke mortality and morbidity rates in Arkansas are among the highest in the U.S. While the effect of air pollution on cardiovascular health was identified in traffic-dominated metropolitan areas, there is a lack of studies for populations with variable exposure profiles, demographic and disease characteristics., Objective: Determine the short-term effects of air pollution on cardiovascular and respiratory morbidity in the stroke and heart failure belt., Methods: We investigated the associations of fine particles and ozone with respiratory and cardiovascular emergency room visits during the 2002-2012 period for adults in Central Arkansas using Poisson generalized models adjusted for temporal, seasonal and meteorological effects. We evaluated sensitivity of the associations to mutual pollutant adjustment and effect modification patterns by sex, age, race and season., Results: We found effects on cardiovascular and respiratory emergencies for PM2.5 (1.52% [95% (confidence interval) CI: -1.10%, 4.20%]; 1.45% [95%CI: -2.64%, 5.72%] per 10 μg/m3) and O3 (0.93% [95%CI: -0.87%, 2.76%]; 0.76 [95%CI: -1.92%, 3.52%] per 10 ppbv) during the cold period (October-March). The effects were stronger among whites, except for the respiratory effects of O3 that were higher among Blacks/African-Americans. Effect modification patterns by age and sex differed by association. Both pollutants were associated with increases in emergency room visits for hypertension, heart failure and asthma. Effects on cardiovascular and respiratory emergencies were observed during the cold period when particulate matter was dominated by secondary nitrate and wood burning., Conclusion: Outdoor particulate pollution during winter had an effect on cardiovascular morbidity in central Arkansas, the region with high stroke and heart disease incidence rates., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Previous studies reported significant variability of air pollutants across Europe with the lowest concentrations generally found in Northern Europe and the highest in Southern European countries. Within the MED-PARTICLES project the spatial and temporal variations of long-term PM and gaseous pollutants data were investigated in traffic and urban background sites across Southern Europe. The highest PM levels were observed in Greece and Italy (Athens, Thessaloniki, Turin and Rome) while all traffic sites showed high NO2 levels, frequently exceeding the established limit value. High PM2.5/PM10 ratios were calculated indicating that fine particles comprise a large fraction of PM10, with the highest values found in the urban background sites. It seems that although in traffic sites the concentrations of both PM2.5 and PM10 are significantly higher than those registered in urban background sites, the coarse fraction PM2.5-10 is more important at the traffic sites. This fact is probably due to the high levels of resuspended road dust in sites highly affected by traffic, a phenomenon particularly relevant for Mediterranean countries. The long-term trends of air pollutants revealed a significant decrease of the concentration levels for PM, SO2 and CO while for NO2 no clear trend or slightly increasing trends were observed. This reduction could be attributed to the effectiveness of abatement measures and strategies and also to meteorological conditions and to the economic crisis that affected Southern Europe., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants., Methods: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis., Findings: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13)., Interpretation: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value., Funding: European Community's Seventh Framework Program (FP7/2007-2011)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Doña Ana County in New Mexico regularly experiences severe air pollution episodes associated with windblown dust and fires. Residents of Hispanic/Latino origin constitute the largest population group in the region. We investigated the associations of ambient particulate matter and ozone with hospital emergency room and admissions for respiratory and cardiovascular visits in adults., Methods: We used trajectories regression analysis to determine the local and regional components of particle mass and ozone. We applied Poisson generalized models to analyze hospital emergency room visits and admissions adjusted for pollutant levels, humidity, temperature and temporal and seasonal effects., Results: We found that the sources within 500km of the study area accounted for most of particle mass and ozone concentrations. Sources in Southeast Texas, Baja California and Southwest US were the most important regional contributors. Increases of cardiovascular emergency room visits were estimated for PM10 (3.1% (95% CI: -0.5 to 6.8)) and PM10-2.5 (2.8% (95% CI: -0.2 to 5.9)) for all adults during the warm period (April-September). When high PM10 (>150μg/m(3)) mass concentrations were excluded, strong effects for respiratory emergency room visits for both PM10 (3.2% (95% CI: 0.5-6.0)) and PM2.5 (5.2% (95% CI: -0.5 to 11.3)) were computed., Conclusions: Our analysis indicated effects of PM10, PM2.5 and O3 on emergency room visits during the April-September period in a region impacted by windblown dust and wildfires., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Placental weight has been associated with mammographic pattern and coronary heart disease in the adult offspring, but the mechanisms are unknown. We evaluated the associations of maternal and cord blood hormones with placental weight in normal pregnancies., Methods: Prospective study of 167 normal singleton pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at the 27th gestational week were available for all pregnancies. Cord blood measurements were available for 86 pregnancies in Boston and 104 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with placental weight were calculated., Results: Maternal levels of estriol, testosterone, and progesterone (P < .05) were positively associated with placental weight. There was no such evidence for adiponectin, prolactin, and insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely associated with placental weight, the results being statistically significant for testosterone (P < .05). There was a marginally significant positive association of cord blood IGF-I with placental weight. Reported results were adjusted for study center., Conclusions: Placental weight appears to be positively correlated with maternal steroids. Its correlation with cord blood steroids, however, appears inverse, compatible with negative feedback mechanisms. There is also a suggestion for placental weight to be positively associated with cord blood IGF-I., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Recent reports investigate whether windblown desert dust may exacerbate the short-term health effects associated with particulate pollution in urban centers. We have tested this hypothesis by using daily air pollution and mortality data for Athens, Greece during the period 2001-2006. We investigated the effects of exposure to particulate matter with aerodynamic diameter <0μg/m(3) (PM(10)) on total and cause specific mortality, during days with and without windblown desert dust, for all ages, stratified by age groups and by sex. We identified 141 dust days between 2001 and 2006. We used Poisson regression models with penalized splines to control for possible confounding by season, meteorology, day of the week and holiday effect. A 10μg/m(3) increase in PM(10) was associated with a 0.71% (95% confidence interval (CI): 0.42% to 0.99%) increase in all deaths. The effects for total and cause specific mortality were greater for those ≥ 75years of age, while for total mortality higher effects were observed among females. The main effect of desert dust days and its interaction with PM(10) concentrations were significant in all cases except for respiratory mortality and cardiovascular mortality among those < 75years. The negative interaction pointed towards lower particle effects on mortality during dust events. We found evidence of modification of the adverse health effects of PM(10) on mortality in Athens, Greece with desert dust events: the particle effects were significantly higher during non-desert dust days. Our analyses indicate that traffic related particles, which prevail on non-desert dust days, have more toxic effects than the ones originating from long-range transport, such as Sahara dust., (Copyright © 2011 Elsevier B.V. All rights reserved.)