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Mortality and morbidity effects of long-term exposure to low-level PM2.5, Black Carbon, NO2 and O3: an analysis of European cohorts

Principal Investigator: 
,

University of Utrecht, Netherlands

This study will investigate health effects of low levels of air pollution in Europe using pooled data from 10 ESCAPE cohorts with individual covariate information, and 6 large administrative cohorts with less detailed information; resulting in a study population of about 25 million people. See also this Program Summary of HEI's research program on low levels of air pollution. 

Funded under
Status: 
Ongoing
Abstract
Abstract for the 2019 HEI Annual Conference. Please scroll down to view the two abstracts and posters.
 

Mortality, morbidity and low-level air pollution in a pooled cohort of 392,826 in Europe in the ELAPSE project

Bert Brunekreef1, Maciej Strak1(Presenter), Kathrin Wolf2, Ulla A. Hvidtfeldt3, Kees de Hoogh4,5, Sophia Rodopoulou6, Evi Samoli6, Klea Katsouyanni6,7, Marjan Tewis1, Jie Chen1, Gerard Hoek1, on behalf of the ELAPSE Project Team

1Utrecht University, the Netherlands; 2Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany; 3Danish Cancer Society Research Center, Copenhagen, Denmark; 4University of Basel, Switzerland; 5Swiss Tropical and Public Health Institute, Basel, Switzerland; 6University of Athens, Greece; 7King's College London, UK

Background. Cohort studies have consistently found associations between long-term exposure to outdoor air pollution and morbidity and mortality endpoints. However, uncertainty about the shape of the concentration response function exists at low concentrations. Within the multicentre Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigate associations between long-term exposure to low concentrations, defined as below current European Union, US Environmental Protection Agency (EPA), and World Health Organization limit values or guidelines, of several air pollutants and morbidity and mortality endpoints.

Methods. We pooled data from eight ESCAPE cohorts and the Danish Nurse Cohort, creating a total study population of up to 392,826 participants. We assessed residential exposure to air pollutants as annual 2010 mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3; including cold and warm season estimates) and black carbon (BC) based on estimates derived from Europe-wide hybrid land use regression models at a 100 m spatial scale. After harmonizing individual and area-level variables between cohorts, we applied Cox proportional hazard models with increasing adjustment for confounders to investigate the association between long-term air pollution exposure and natural mortality, coronary events and lung cancer incidence. We also assessed the shape of the concentration-response relationship using different methods, including subset analysis, threshold analysis, and spline approaches.

Results. The total study population contributed 7,518,024 person-year at risk (average follow-up 19 years). Average exposure to air pollution was 15.4 (SD 3.5) µg/m3 for PM2.5, 25.3 (8.2) µg/m3 for NO2, 1.6 (0.4) µg/m3 for BC, and 86.2 (9.4) µg/m3 for (warm season) O3. A 5 µg/m3 increase in PM2.5 was associated with a hazard ratio (HR) of 1.13 (95% CI: 1.11, 1.16) in natural mortality and a hazard ratio of 1.13 (95% CI: 1.05, 1.23) in lung cancer incidence, whereas the association with coronary events was not statistically significant (HR = 1.02; 95% CI: 0.95, 1.10). Associations with natural mortality remained significant when exposure was restricted to PM2.5 concentrations lower than the European annual mean limit value of 25 µg/m3 (HR = 1.13; 95% CI: 1.11, 1.16) and also below the EPA air quality standard of 12 µg/m3 (HR = 1.30; 95% CI: 1.14, 1.47). Significant positive associations were also found between natural mortality and NO2, natural mortality and BC, coronary events and NO2. Threshold analyses did not identify thresholds. Splines indicated no strong deviation from linearity.

Conclusions. Long-term exposure to outdoor air pollution is associated with morbidity and mortality, even at low concentrations.

POSTER

Poster by Brunekreef, Strak et al, 2019 Annual Conference


Mortality, morbidity and low-level air pollution in a population of 35 million in Europe – analysis of administrative cohorts in the ELAPSE project

Bert Brunekreef1, Danielle Vienneau2,3(Presenter), Nicole Janssen4, Massimo Stafoggia5, Mariska Bauwelinck6, Klea Katsouyanni7,8, Evi Samoli7, Sophia Rodopoulou7, Jie Chen1, Maciej Strak1, Gerard Hoek1, on behalf of the ELAPSE Project Team

1Utrecht University, the Netherlands; 2Swiss Tropical and Public Health Institute, Basel, Switzerland; 3University of Basel, Switzerland; 4National Institute for Public Health and the Environment, Bilthoven, the Netherlands; 5Lazio Region Health Service, Rome, Italy; 6Vrije Universiteit Brussel, Brussels, Belgium; 7University of Athens, Greece; 8King’s College London, UK

Background. Recent evaluations by the World Health Organization and the Global Burden of Disease study have suggested that associations between long-term exposure to outdoor air pollution and morbidity and mortality may persist at very low concentrations. ELAPSE aims to investigate the adverse health effects of long-term exposure to low levels of ambient air pollution in Europe. In addition to a pooled cohort of 392,826 participants, we analysed data from very large administrative cohorts geographically spread across Europe.

Methods. Seven large administrative cohorts (>35 million subjects) were included. Estimates of fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and black carbon (BC) derived from Europe-wide hybrid land use regression models were linked to subjects in each cohort based on their address-level geocodes. Variables in all cohorts were harmonized by implementing a common ELAPSE codebook. Data from the administrative cohorts were analysed locally using the exact same statistical scripts. We applied Cox proportional hazard models with successively more detailed control for individual- and area-level confounders to explore associations between exposure to pollutants and mortality as well as CVD and cancer incidence. Shapes of the concentration-response relationships were assessed using subset analysis, threshold analysis and spline approaches. Based on the main models, we further (1) applied multi-pollutant models to disentangle role of individual pollutants, (2) used other exposure metrics such as time-varying exposure and estimates from local exposure models, (3) evaluated the impact of measurement error on the magnitude of the effect estimates, (4) used health survey data to support indirect adjustment for potential confounders. The results from individual cohorts will be combined by meta-analysis.

Results. Five cohorts have completed the main analyses for natural mortality (Belgian, Danish, Dutch, Rome and Swiss; Norwegian and English in progress). As an example, the annual average concentrations were 20, 12, 1.0 and 67 µg/m3, respectively for NO2, PM2.5, BC, and O3, in the Danish cohort (2.8 million adults). Long-term exposure to PM2.5, BC and NO2 was significantly associated with increased risk of natural mortality in this cohort, the hazard ratio was 1.15 (1.12, 1.19) per 5 µg/m3 PM2.5. We anticipate to present results of meta-analyses across most or all of the administrative cohorts at the conference.

Conclusions. No conclusions can yet be drawn as the joint analyses are still proceeding.

POSTER

Poster by Brunekreef, Vienneau et al, 2019 Annual Conference


PUBLICATIONS

de Hoogh K, Chen J, Gulliver J, Hoffmann B, Hertel O, Ketzel M, Bauwelinck M, van Donkelaar A, Hvidtfeldt UA, Katsouyanni K, Klompmaker J, Martin RV, Samoli E, Schwartz PE, Stafoggia M, Bellander T, Strak M, Wolf K, Vienneau D, Brunekreef B, Hoek G. Spatial PM2.5, NO2, O3 and BC models for Western Europe - Evaluation of spatiotemporal stability. Environ Int. 2018 Jul 31;120:81-92. doi: 10.1016/j.envint.2018.07.036. [Epub ahead of print]