Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 10 μm to 2.5 μm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 μg/m and for PM10, 1.22 (0.91-1.63) per 10 μg/m. In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6–11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6–11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.

Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV₁%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV₁% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV₁%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV₁%. Nine postnatal exposures were associated with lower FEV₁%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. European Community's Seventh Framework Programme (HELIX project).