Association of air pollution with incidence of end-stage kidney disease in two large European cohorts.

End-stage kidney disease (ESKD) poses a high burden on patients and health systems. While numerous studies indicate an association between air pollution and chronic kidney disease, studies on ESKD are rare. We investigated the association of long-term exposure to nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC) and ozone (O3) with ESKD incidence in two large population-based European cohorts. We followed individuals in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP) and the Italian Rome Longitudinal Study (RoLS) using dialysis and kidney transplant registries. Long-term exposure to pollutants was estimated at the home address using Europe-wide land use regression models at 100x100m scale. Hazard ratios (HR) were determined from Cox-proportional hazard models adjusted for individual and neighbourhood level confounders. We observed 501 events among 136,823 individuals in VHM&PP (mean age 42.1 years; crude incidence rate (IR) 0.14 per 1000 person-years) and 3231 events among 1,939,461 individuals in RoLS (mean age 52.4 years; IR 0.22 per 1000 person-years). In VHM&PP, there was no evidence of an association between PM2.5 or O3 and ESKD. There were elevated HRs but with large confidence intervals for BC (HR 1.17 [95 % confidence interval (CI): 0.98, 1.39] for 0.5*10-5/m), and for NO2 (HR 1.14 [95%CI: 0.96, 1.35] for 10 µg/m3). In RoLS, ESKD was associated with PM2.5 (HR 1.37 [95 % CI: 1.06, 1.76] for an increase of 5 µg/m3), while there was no evidence of association with BC, NO2, or O3 exposure. Our study suggests an association of air pollution with ESKD incidence, which differed between the two cohorts and may possibly be influenced by respective air pollution mixtures.

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.

Equity in the recovery of elective and oncological surgery volumes after the COVID-19 lockdown: a multicentre cohort study in Italy.

BACKGROUND: The COVID-19 pandemic has had, and still has, a profound impact on national health systems, altering trajectories of care and exacerbating existing inequalities in health. Postponement of surgeries and cancellation of elective surgical procedures have been reported worldwide. In Italy, the lock-down measures following the COVID-19 pandemic caused cancellations of surgical procedures and important backlogs; little is known about potential social inequalities in the recovery process that occurred during the post-lockdown period. This study aims at evaluating whether all population social strata benefited equally from the surgical volumes' recovery in four large Italian regions. METHODS: This multicentre cohort study covers a population of approximately 11 million people. To assess if social inequalities exist in the recovery of eight indicators of elective and oncological surgery, we estimated Risk Ratios (RR) through Poisson models, comparing the incidence proportions of events recorded during COVID-19 (2020-21) with those in pre-pandemic years (2018-19) for each pandemic period and educational level. RESULTS: Compared to 2018-19, volumes of elective surgery showed a U-shape with the most significant drops during the second wave or the vaccination phase. The recovery was socially unequal. At the end of 2021, incidence proportions among highly educated people generally exceeded the expected ones; RRs were 1.31 (95%CI 1.21-1.42), 1.24 (95%CI 1.17-1.23), 1.17 (95%CI 1.08-1.26) for knee and hip replacement and prostatic surgery, respectively. Among low educated patients, RR remained always < 1. Oncological surgery indicators showed a similar social gradient. Whereas volumes were preserved among the highly educated, the low educated were still lagging behind at the end of 2021. CONCLUSIONS: Surgical procedures generally returned to pre-pandemic levels but the low educated experienced the slowest recovery. An equity-oriented appraisal of trends in healthcare provision should be included in pandemic preparedness plans, to ensure that social inequalities are promptly recognised and tackled.

Covid-19 vaccination among migrants in Rome, Italy.

Migrants may be susceptible to vaccine barriers and hesitancy. We evaluated the association between migrant status, as measured by the citizenship from a High Migratory Pressure Country (HMPC), and COVID-19 vaccination uptake in the resident population in Rome, Italy. We also investigated sex differences. We followed participants for vaccination against COVID-19 in 2021. We calculated crude- and adjusted-vaccination rates and Cox hazard ratios of vaccination for migrants compared to Italians. Among migrants from HMPCs, we estimated HRs for females compared to males, stratifying by geographical area of origin. Models were adjusted for age and deprivation index and stratified by infection history. In 2021, among 1,731,832 18-64-year-olds, migrants were 55% less likely to uptake at least one COVID-19 vaccine dose than their Italian counterpart. Past SARS-CoV-2 infection reduced the difference between migrants and Italians to 27%. Among migrants from HMPCs, we observed a slight excess of vaccination uptake among females compared to males. Focusing on geographical areas, we observed that only females from central-western Asia were 9% less likely to uptake vaccination than males. Health communication strategies oriented to migrants and considering their different languages, cultures, and health literacy should be adopted for prevention before emergencies.

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

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

SARS-CoV-2 spread and area economic disadvantage in the italian three-tier restrictions: a multilevel approach.

BACKGROUND: To face the second wave of COVID-19, Italy implemented a tiered restriction system with different limitation levels (yellow = medium; orange = medium-high, red = high) at the beginning of November 2020. The restrictions systematically reduced the transmission of SARS-CoV-2 with increasing strength for increasing tier. However, it is unknown whether the effect of limitations was equal between provinces with different socioeconomic levels. Therefore, we investigated the association between the province's socioeconomic level and SARS-CoV-2 infection daily reproduction number in each restriction level. METHODS: We measured the province's socioeconomic level as the percentage of individuals whose 2019 total yearly income was lower than 10,000€, using the measure as a proxy of economic disadvantage. We estimated the daily reproduction number (Rt) at the province level using the SARS-CoV-2 daily incidence data from November 2020 to May 2021. We then used multilevel linear regression models with random intercepts stratified by restriction level to estimate the association between economic disadvantage and Rt. We also adjusted the analyses for potential confounders of the association between the province's economic disadvantage and the Rt: the percentage of people with 0-5 years, the quartiles of population density, and the geographical repartition. RESULTS: Overall, we found increasing Rt in yellow (+ 0.004 p < 0.01, from Rt = 0.99 to 1.08 in three weeks) and containing effects for the orange (-0.005 p < 0.01, from Rt = 1.03 to 0.93) and the red tier (-0.014 p < 0.01, from Rt = 1.05 to 0.76). More economically disadvantaged provinces had higher Rt levels in every tier, although non-significantly in the yellow level (yellow = 0.001 p = 0.19; orange = 0.002 p = 0.02; red = 0.004 p < 0.01). The results showed that the association between economic disadvantage and Rt differed by level of restriction. The number of days into the restriction and the economic disadvantage had statistically significant interactions in every adjusted model. Compared to better off, more economically disadvantaged provinces had slower increasing trends in yellow and steeper Rt reductions in orange, but they showed slower Rt reductions in the highest tier. CONCLUSION: Lower tiers were more effective in more economically disadvantaged provinces, while the highest restriction level had milder effects. These results underline the importance of accounting for socioeconomic level when implementing public health measures.

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

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

[Employment sector and respiratory mortality in Rome and Turin longitudinal metropolitan studies]. / Settore occupazionale e mortalità respiratoria negli studi longitudinali metropolitani di Roma e Torino.

OBJECTIVES: to assess the association between the occupational sector and respiratory mortality in the metropolitan longitudinal studies of Rome and Turin. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: the 2011 census cohorts of residents of Rome and Turin aged 30 years and older who had worked for at least one year in the private sector between 1970s and 2011 was analysed. The individuals included in the study were followed from 9 October 2011 to 31 December 2018. Occupational history was obtained from archives of private sector contributions at the National Social Insurance Agency (INPS) and then was linked to data from the longitudinal studies. MAIN OUTCOME MEASURES: the study outcome was non-malignant respiratory mortality. The exposure of interest was whether or not individuals had worked in one of the 25 occupational sectors considered (agriculture and fishing, steel industry, paper and printing, pharmaceuticals, manufacturing, textile, energy and water, food and tobacco industry, non-metal mining, glass & cement industry, metal processing, electrical construction, footwear and wood industry, construction, trade, hotel and restaurants, transportation, insurance, healthcare, services, laundries, waste management, hairdressing, cleaning services, and gas stations). The association between the occupational sector and respiratory mortality, adjusted for potential confounders (age, marital status, place of birth, educational level), was estimated using Cox models. All analyses were stratified by sex and city. RESULTS: a total of 910,559 people were analysed in Rome and 391,541 in Turin. During the eight years of follow-up, 4,133 people in Rome and 2,772 people in Turin died from respiratory causes. The sectors associated with high respiratory mortality in both cities among men were footwear and wood industry (adjusted HR for age: 1.37 (95%CI 1.07-1.76) and 1.48 (95%CI 1.08-2.03) in Rome and Turin, respectively), construction (HR: 1.31 (95%CI 1.20-1.44) in Rome and 1.51 (95%CI 1.31-1.74) in Turin), hotel and restaurant sector (HR: 1.25 (95%CI 1.07-1.46) in Rome and 1.68 (95%CI 1.20-2.33) in Turin), and cleaning services (HR: 1.57 (95%CI 1.19-2.06) in Rome and 1.97 (95%CI 1.51-2.58) in Turin). Some sectors had high respiratory mortality only in one of the two cities: in Rome, the food& tobacco industry, and gas stations, while in Turin, the metal processing industry. Among female workers, the cleaning services sector was associated with higher respiratory mortality in both Rome and Turin (HR: 1.52, 95%CI 1.27-1.82, e 1.58, 95%CI 1.17-2.12, respectively). CONCLUSIONS: the data confirm the previously known associations between occupational sectors and respiratory mortality for exposures characteristic of specific sectors, such as construction, hotel and restaurant sector, and cleaning services. The differences reported between the two cities reflect the different composition of the workforce and the size of the two study populations. Administrative social insurance data can provide helpful information for epidemiological studies of occupational exposure.

Socioeconomic inequalities in health status and survival: a cohort study in Rome.

OBJECTIVES: To analyse the association between individual and contextual socioeconomic position (SEP) with health status and to investigate the role of SEP and baseline health status on survival. DESIGN: Cross-sectional and cohort study. SETTING: Rome, Italy. PARTICIPANTS, PRIMARY AND SECONDARY OUTCOMES: We selected the 25-99 year-olds included in the Rome 2011 census cohort. As a measure of health status on the census reference date (09 October 2011), we used the presence of chronic or rare conditions from the Disease-Related Co-payment Exemption Registry, a database implemented to provide free care to people with chronic or rare diseases. We used logistic regression to analyse the association between both individual (educational attainment) and contextual SEP (neighbourhood real estate price quintiles) with baseline health status. We analysed the role of SEP and the presence of chronic or rare conditions on 5-year survival (until 31 December 2016) using accelerated failure time models with Weibull distribution, reporting time ratios (TRs; 95% CI). RESULTS: In middle-aged, subjects with low SEP (either individual or contextual) had a prevalence of chronic conditions comparable with the prevalence in high SEP individuals 10 years older. Adjusted logistic models confirmed the direct association between SEP and baseline health status in both women and men. The lowest educated were up to 67% more likely to have a chronic condition than the highest educated, while the difference was up to 86% for lowest versus highest contextual SEP. Low SEP and the presence of chronic conditions were associated with shorter survival times in both sexes, lowest versus highest educated TR was TR=0.79 for women (95% CI: 0.77 to 0.81) and TR=0.71 for men (95% CI: 0.70 to 0.73). The contextual SEP shrunk survival times by about 10%. CONCLUSION: Inequalities were present in both baseline health and survival. The association between SEP and survival was independent of baseline health status.

Indirect impact of the COVID-19 pandemic and its containment measures on social inequalities in hospital utilisation in Italy.

BACKGROUND: The pandemic may undermine the equity of access to and utilisation of health services for conditions other than COVID-19. The objective of the study is to evaluate the indirect impact of COVID-19 and lockdown measures on sociodemographic inequalities in healthcare utilisation in seven Italian areas. METHODS: In this multicentre retrospective study, we evaluated whether COVID-19 modified the association between educational level or deprivation and indicators of hospital utilisation and quality of care. We also assessed variations in gradients by sex and age class. We estimated age-standardised rates and prevalence and their relative per cent changes comparing pandemic (2020) and pre-pandemic (2018-2019) periods, and the Relative Index of Inequalities (RIIs) fitting multivariable Poisson models with an interaction between socioeconomic position and period. RESULTS: Compared with 2018-2019, hospital utilisation and, to a lesser extent, timeliness of procedures indicators fell during the first months of 2020. Larger declines were registered among women, the elderly and the low educated resulting in a shrinkage (or widening if RII <1) of the educational gradients for most of the indicators. Timeliness of procedures indicators did not show any educational gradient neither before nor during the pandemic. Inequalities by deprivation were nuanced and did not substantially change in 2020. CONCLUSIONS: The socially patterned reduction of hospital utilisation may lead to a potential exacerbation of health inequalities among groups who were already vulnerable before the pandemic. The healthcare service can contribute to contrast health disparities worsened by COVID-19 through more efficient communication and locally appropriate interventions.

Differences in mortality between temporary and permanent workers: results from the Rome Longitudinal Study.

OBJECTIVE: Precarious employment is characterised by instability, lack of protection and economic vulnerability. The objective of this study was to assess the association between temporary contracts and mortality. DESIGN: Cohort study. SETTING: Rome, Italy. PARTICIPANTS: All employees, aged 25-65 years, from the Rome Longitudinal Study, followed from 21 October 2001 to the first date among death, migration from Rome, or 31 December 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: We investigated all-cause, cardiovascular and accidental mortality. We considered gender, age, place of birth, education, temporary versus permanent contract and sector of employment. We used Cox models to investigate the association between type of contract and total, cardiovascular and accidental mortality in men and women, overall and by employment sector. RESULTS: We analysed 597 834 subjects. The proportion of temporary contracts varied by gender (9.6% in men and 13.3% in women) and by employment sector, ranging from 4.5% (public administration) to 27% (recreational, cultural, sports activities) in men. During the study period, 21 136 subjects died. Men with temporary contracts, compared with those with permanent positions, had greater overall mortality risk (HR=1.16, 95% CI 1.09 to 1.24), cardiovascular mortality (HR=1.29, 95% CI 1.14 to 1.45) and accidental mortality (HR=1.27, 95% CI 1.04 to 1.57). In men, the association varied widely among different economic sectors, with greater risks in the industry, building constructions and social services sectors. In women, there was no evidence of association between temporary contracts and mortality. A statistically significant association between temporary contracts and mortality in women was found in the sector of sales and transports only. CONCLUSIONS: Temporary work should be considered a determinant of health, particularly for specific economic sectors.

Educational Inequalities in COVID-19 Vaccination: A Cross-Sectional Study of the Adult Population in the Lazio Region, Italy.

Several studies reported socioeconomic inequalities during the COVID-19 pandemic. We aimed at investigating educational inequalities in COVID-19 vaccination on 22 December 2021. We used the cohort of all residents in the Lazio Region, Central Italy, established at the beginning of the pandemic to investigate the effects of COVID-19. The Lazio Region has 5.5 million residents, mostly distributed in the Metropolitan Area of Rome (4.3 million inhabitants). We selected those aged 35 years or more who were alive and still residents on 22 December 2021. The cohort included data on sociodemographic, health characteristics, COVID-19 vaccination (none, partial, or complete), and SARS-CoV-2 infection. We used adjusted logistic regression models to analyze the association between level of education and no vaccination. We investigated 3,186,728 subjects (54% women). By the end of 2021, 88.1% of the population was fully vaccinated, and 10.3% were not vaccinated. There were strong socioeconomic inequalities in not getting vaccinated: compared with those with a university degree, residents with a high school degree had an odds ratio (OR) of 1.29 (95% confidence interval, CI, 1.27-1.30), and subjects with a junior high or primary school attainment had an OR = 1.41 (95% CI: 1.40-1.43). Since a comprehensive vaccination against COVID-19 could help reduce socioeconomic inequalities raised with the pandemic, further efforts in reaching the low socioeconomic strata of the population are crucial.

Incidence of SARS-CoV-2 Infection and Related Mortality by Education Level during Three Phases of the 2020 Pandemic: A Population-Based Cohort Study in Rome.

Evidence on social determinants of health on the risk of SARS-CoV-2 infection and adverse outcomes is still limited. Therefore, this work investigates educational disparities in the incidence of infection and mortality within 30 days of the onset of infection during 2020 in Rome, with particular attention to changes in socioeconomic inequalities over time. A cohort of 1,538,231 residents in Rome on 1 January 2020, aged 35+, followed from 1 March to 31 December 2020, were considered. Cumulative incidence and mortality rates by education were estimated. Multivariable log-binomial and Cox regression models were used to investigate educational disparities in the incidence of SARS-CoV-2 infection and mortality during the entire study period and in three phases of the pandemic. During 2020, there were 47,736 incident cases and 2281 deaths. The association between education and the incidence of infection changed over time. Till May 2020, low- and medium-educated individuals had a lower risk of infection than that of the highly educated. However, there was no evidence of an association between education and the incidence of SARS-CoV-2 infection during the summer. Lastly, low-educated adults had a 25% higher risk of infection from September to December than that of the highly educated. Similarly, there was substantial evidence of educational inequalities in mortality within 30 days of the onset of infection in the last term of 2020. In Rome, social inequalities in COVID-19 appeared in the last term of 2020, and they strengthen the need for monitoring inequalities emerging from this pandemic.

Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people: results from seven large European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). METHODS: In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000-11; follow-up until 2011-17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. FINDINGS: We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021-1·085) per 5 µg/m3 increment in PM2·5, 1·044 (1·019-1·069) per 10 µg/m3 NO2, and 1·039 (1·018-1·059) per 0·5 × 10-5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 µg/m3) and NO2 (40 µg/m3) were 1·078 (1·046-1·111) per 5 µg/m3 PM2·5 and 1·049 (1·024-1·075) per 10 µg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032-1·092) for exposure lower than 1·5× 10-5/m, and 1·081 (0·966-1·210) for exposure lower than 1·0× 10-5/m. INTERPRETATION: Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions. FUNDING: Health Effects Institute.

Long-term exposure to fine particle elemental components and mortality in Europe: Results from six European administrative cohorts within the ELAPSE project.

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 (PM2.5) 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 PM2.5 total mass or nitrogen dioxide (NO2) 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/m3 Cu; 1.069 (1.031, 1.108) per 100 ng/m3 Fe; 1.039 (1.018, 1.062) per 50 ng/m3 K; 1.024 (1.006, 1.043) per 1 ng/m3 Ni; 1.036 (1.016, 1.057) per 200 ng/m3 S; 1.152 (1.048, 1.266) per 100 ng/m3 Si; 1.020 (1.006, 1.034) per 2 ng/m3 V]. Only K and Si were robust to PM2.5 or NO2 adjustment [pooled HRs (95% CI) per 50 ng/m3 in K: 1.025 (1.008, 1.044), 1.020 (0.999, 1.042) and per 100 ng/m3 in Si: 1.121 (1.039, 1.209), 1.068 (1.022, 1.117) adjusted for PM2.5 and NO2 correspondingly]. Our findings indicate an association of natural mortality with most components, which was reduced after adjustment for PM2.5 and especially NO2.

Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 µg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 µg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 µg/m3 for PM2·5 and 40 µg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.

Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

Predicting Mortality Risk in Older Hospitalized Persons With COVID-19: A Comparison of the COVID-19 Mortality Risk Score with Frailty and Disability.

OBJECTIVES: To assess the association of pre-morbid functional status [Barthel Index (BI)] and frailty [modified Frailty Index (mFI)] with in-hospital mortality and a risk scoring system developed for COVID-19 in patients ≥75 years diagnosed with COVID-19. DESIGN: Retrospective bicentric observational study. SETTING AND PARTICIPANTS: Data on consecutive patients aged ≥75 years admitted with COVID-19 at 2 Italian tertiary care centers were collected from February 22 to May 30, 2020. METHODS: Overall, 221 consecutive patients with COVID-19 aged ≥75 years were admitted to 2 hospitals in the study period and were included in the analysis. Clinical, functional (BI), frailty (mFI), laboratory, and imaging data were collected. Mortality risk on admission was assessed with the COVID-19 Mortality Risk Score (COVID-19 MRS), a dedicated score developed for hospital triage. RESULTS: Ninety-seven (43.9%) patients died. BI, frailty, age, dementia, respiratory rate, Pao2/Fio2 ratio, creatinine, and platelet count were associated with mortality. Analysis of the area under the receiver operating characteristic (AUC) indicated that the predictivity of age was modest and the combination of BI, mFI, and COVID-19 MRS yielded the highest prediction accuracy (AUCCOVID-19MRS+BI+mFI vs AUCAge: 0.87 vs 0.59; difference: +0.28, lower bound-upper bound: 0.17-0.34, P < .001). CONCLUSIONS AND IMPLICATIONS: Premorbid BI and mFI are associated with mortality and improved the accuracy of the COVID-19 MRS. Functional status may prove useful to guide clinical management of older individuals.

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.