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Introduction Adherence to digital proximity tracing apps and preventive measures leading up to and following widespread SARS-CoV-2 vaccine rollout remains unclear. Our study aims to evaluate the relative effect of digital proximity tracing app use, SARS-CoV-2 vaccine uptake and adherence to additional preventive measures in a localized context of the pandemic. Methods We report findings from two population-based longitudinal cohorts in Switzerland, the Corona Immunitas Digital Follow-up eCohort (CI-DFU) and the COVID-19 Social Monitor (CSM) studies in 2021. Failure time analyses were conducted for each study cohort, stratified by age group. Cox proportional hazards regression models with time-varying covariates were used to estimate adjusted hazard ratios (aHR). The analyses assessed vaccine uptake and SwissCovid app uninstalling outcomes, with the outcomes interchanging as the exposures in two separate substudies. Results We observed a dichotomy of individuals who did not use the app during the study period and did not get vaccinated, and who used the SwissCovid app during the study period and got vaccinated during the study period. We found an increased uptake of the vaccine associated with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) or adherence to preventive measures (aHR, 1.44; 95% CI: 1.28–1.62 [CI-DFU]; aHR, 1.82; 95% CI: 1.52–2.18 [CSM]). Decreased SwissCovid uninstallation risk was observed for participants who received their first vaccine dose throughout the study period (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]). Conclusion In evolving pandemic contexts, these findings can assist public health authorities in designing evidence-based communication strategies to enable adoption of preventive measures and novel health technologies across all population groups.

Background Residential greenness has been associated with health benefits, but its biological mechanism is largely unknown. Investigation of greenness-related DNA methylation profiles can contribute to mechanistic understanding of the health benefits of residential greenness. Objective To identify DNA methylation profiles associated with greenness in the immediate surroundings of the residence. Methods We analyzed genome-wide DNA methylation in 1938 blood samples (982 participants) from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). We estimated residential greenness based on normalized difference vegetation index at 30 × 30 m cell (green30) and 500 m buffer (green500) around the residential address. We conducted epigenome-wide association study (EWAS) to identify differentially methylated CpGs and regions, and enrichment tests by comparing to the CpGs that previous EWAS identified as associated with allergy, physical activity, and allostatic load-relevant biomarkers. Results We identified no genome-wide significant CpGs, but 163 and 56 differentially methylated regions for green30 and green500, respectively. Green30-related DNA methylation profiles showed enrichments in allergy, physical activity, and allostatic load, while green500-related methylation was enriched in allergy and allostatic load. Conclusions Residential greenness may have health impacts through allergic sensitization, stress coping, or behavioral changes. Exposure to more proximal greenness may be more health-relevant.

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P-8) interactions with sex on lung function, and 21 showed suggestive interactions (P-6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV1) (P=3.15x10-15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV1 more in males (untransformed FEV1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10-6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.

International audience; Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

BackgroundSingle cardio-metabolic risk factors are each known modifiable risk factors for adverse health and quality of life outcomes. Yet, evidence on the clustered effect of these parameters and the metabolic syndrome (MetS) on health-related quality of life (HRQoL) is still limited and mostly cross-sectional. The objectives of this study were to identify clusters of cardio-metabolic physiological functioning, to assess their associations with HRQoL in comparison with the MetS, to elucidate the modifying role of physical activity, and to assess differences in health service utilization.MethodsThis study is based on longitudinal data from two time points (2010/11 & 2017/18) of the Swiss Study on Air Pollution and Lung and Heart Diseases (SAPALDIA). Latent class analysis (LCA) grouped participants based on a priori selected cardio-metabolic and MetS related physiological functioning variables(Body mass index, body fat, glycated hemoglobin, blood triglycerides, blood pressure). The 36-item Short-Form Health Survey (SF-36) was used to assess HRQoL. Quantile regressions were performed with and without adjustment for physical activity, to detect independent associations of the latent classes, MetS and physical activity with HRQoL. To assess the modifying role of physical activity, we additionally grouped participants based on the combination of physical activity and latent classes or MetS, respectively. Logistic regressions were used to investigate health service utilization as outcome.ResultsThe LCA resulted in three classes labeled “Healthy” (30% of participants in 2017/18), “At risk” and “Unhealthy” (29%). The Unhealthy class scored lowest in all physical component scores of HRQoL. Compared to healthy and active participants, inactive participants in the “Unhealthy” class showed lower scores in the physical functioning domain both cross-sectionally (− 9.10 (− 12.02; − 6.18)) and longitudinally. This group had an odds ratio of 2.69 (1.52; 4.74) for being hospitalized in the previous 12 months.ConclusionsThese results point to subjects with adverse cardio-metabolic physiological functioning and low activity levels as an important target group for health promotion and maintenance of well-being. The promotion of physical activity at the early stages of aging seems pivotal to mitigate the impact of the MetS on HRQoL at higher age.

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of

Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AOpost-BD), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AOpost-BD was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AOpost-BD incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AOpost-BD incidence is expected to be half of AO incidence. ALEC has received funding from the European Union’s Horizon 2020 research and innovation programme [Grant Agreement No. 633212]. The co-ordination of the ECRHS was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). The SAPALDIA cohort was funded by The State Secretariat for Education, Research and Innovation (SERI), Switzerland. The principal investigators and team members of the ECRHS and SAPALDIA studies, and the national funders who supported data collection in the ECRHS and SAPALDIA studies are listed in the appendix available in the Supplementary Information.

Residential greenness and lung function in a prospective cohort of European adults : The ECRHS study

Adult lung function is highly heritable and 279 genetic loci were recently reported as associated with spirometry-based measures of lung function. Though lung development and function differ between males and females throughout life, there has been no genome-wide study to identify genetic variants with differential effects on lung function in males and females. Here, we present the first genome-wide genotype-by-sex interaction study on four lung function traits in 303,612 participants from the UK Biobank. We detected five SNPs showing genome-wide significant (P−8) interactions with sex on lung function, as well as 21 suggestively significant interactions (P−6). The strongest sex interaction signal came from rs7697189 at 4:145436894 on forced expiratory volume in 1 second (FEV1) (P = 3.15 × 10−15), and was replicated (P = 0.016) in 75,696 individuals in the SpiroMeta consortium. Sex-stratified analyses demonstrated that the minor (C) allele of rs7697189 increased lung function to a greater extent in males than females (untransformed FEV1β = 0.028 [SE 0.0022] litres in males vs β = 0.009 [SE 0.0014] litres in females), and this effect was not accounted for by differential effects on height, smoking or age at puberty. This SNP resides upstream of the gene encoding hedgehog-interacting protein (HHIP) and has previously been reported for association with lung function andHHIPexpression in lung tissue. In our analyses, whileHHIPexpression in lung tissue was significantly different between the sexes with females having higher expression (most significant probeset P=6.90 × 10−6) after adjusting for age and smoking, rs7697189 did not demonstrate sex differential effects on expression. Establishing the mechanism by whichHHIPSNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases, such as chronic obstructive pulmonary disease (COPD), in both sexes.

Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry. Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC

Background: The association of obesity and asthma has been described in children and adults. However, whether a different life course of weight in men and women may explain gender differences in asthma incidence, has not been addressed. Objectives: Using data from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, we investigated the role of overweight/obesity as measured by body silhouettes at different life stages in men and women for asthma incidence. Methods: Our analysis included 5417 subjects who were asthma free at age 8, followed up to 2011, and had complete covariate information. The main predictor of interest was self-reported body silhouettes at age 8, menarche, 30, 45, menopause, and 60, and additionally changes in body silhouette number across these different time points. Asthma incidence was defined as newly reported doctor-diagnosed asthma after the body silhouette time point. Asthma incidence and its association with body silhouettes was analysed using sex stratified logistic regression, adjusting for age, atopy, urbanity, smoking, parental asthma, education and study area. Results: Men at age 60 had an increased risk of asthma incidence per unit increase in body silhouette number (OR 1.93, 95% CI 1.13–3.30). This association was stronger in women at age 60 (OR 2.78, 95% CI 1.49–5.18) and observed also at menopause (OR 1.35, 95% CI 1.03–1.78), as well as per unit change in body silhouette number between age 45 – menopause (OR 1.74, 95% CI 1.15–2.63). Conclusion: In this longitudinal study, the risk of incident asthma increased in men and women with a larger body silhouette in late adulthood. In women, this risk appeared present between age 45 and menopause. At age 60, both men and women were at higher risk of asthma incidence per unit increase in body silhouette, the risk being more pronounced in women. The age-related increase of obesity may underlie gender differences in asthma incidence at higher ages. Keywords: Asthma, Incidence, Gender, Body silhouette, Obesity, Overweight

Investigating trends of incidence rates can help health care providers and decision makers forecast the burden of a disease. As part of the ALEC study (EU Horizon 2020 grant #633212), we evaluated trends of airflow obstruction (AO) incidence rates between 1992 and 2011 in 12 European countries, based on 4,364 males and 4,501 females aged 25-65 from the ECRHS and SAPALDIA cohort studies. These subjects had a pre-bronchodilator FEV1/FVC ratio ≥LLN (GLI-2012 equations) at baseline and no self-reported diagnosis of asthma at either baseline or follow-up contacts. A new case of AO was defined as a subject with a pre-bronchodilator FEV1/FVC ratio The overall AO incidence rate was 2.0 (95%CI: 1.2-2.7) and 2.3 (95%CI: 1.4-3.1) cases/1,000/year in males and females, respectively, with differences between ever smokers and non-smokers and by age (Figure 1). We observed a steeper increase with age of AO incidence rates in Europe for females compared to males, independently from smoking status.

© 2018 John Wiley & Sons Ltd Background: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. Objective: We performed a GWA study to develop insights in asthma remission. Methods: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. Results: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10−7) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. Conclusions and Clinical Relevance: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.

Introduction: A restrictive spirometry pattern is associated with high morbidity and mortality. Whether regular physical activity (PA) protects against this pattern has never been studied.Objective ...

A higher incidence of asthma is reported in women compared with men, but evidence in later adulthood is limited. We aimed to determine the 20-year cumulative incidence of adult asthma in Switzerland and its relation to sex, taking into account age and allergic sensitisation.We assessed incidence of self-report of doctor-diagnosed asthma between 1991/1992 and 2010/2011 in 5128 subjects without asthma, aged 18–60 years at baseline. The age-related probability of asthma onset was analysed by logistic regression adjusting for potential confounders and stratified by sex and allergic sensitisation at baseline.Over 20 years, 128 (5.1%) men and 198 (7.5%) women newly reported doctor-diagnosed asthma. The adjusted odds ratio for female sex was 1.99 (95% CI 1.54–2.57) overall, 3.21 (95% CI 2.12–4.85) among nonsensitised subjects, and 1.43 (95% CI 1.02–2.02) in sensitised subjects. The probability of asthma onset decreased with increasing baseline age in women but not in men. The higher probability of new asthma in sensitised compared with nonsensitised men was unrelated to age, whereas in women it decreased with age.Asthma incidence was higher in women than in men but decreased with increasing age. The female predominance was considerably stronger in nonsensitised adults compared with those with allergic sensitisation.

The Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), a population cohort study, used heated-wire spirometers in 1991 and 2002 and then ultrasonic spirometers in 2010 revealing measurement bias in healthy never smokers. To provide a practical method to control for measurement bias given the replacement of spirometer in long-term population studies, we built spirometer-specific reference equations from healthy never smokers participating in 1991, 2002, and 2010 to derive individualized corrections terms. We compared yearly lung function decline without corrections terms with fixed terms that were obtained from a quasi-experimental study and individualized terms. Compared with baseline reference equations, spirometer-specific reference equations predicted lower lung function. The mean measurement bias increased with age and height. The decline in forced expiratory volume in 1 second during the reference period of 1991-2002 was 31.5 (standard deviation (SD), 28.7) mL/year while, after spirometer replacement, uncorrected, corrected by fixed term, and individualized term, the declines were 47.0 (SD, 30.1), 40.4 (SD, 30.1), and 30.4 (SD, 29.9) mL/year, respectively. In healthy never smokers, ultrasonic spirometers record lower lung function values than heated-wire spirometers. This measurement bias is sizeable enough to be relevant for researchers and clinicians. Future reference equations should account for not only anthropometric variables but also spirometer type. We provide a novel method to address spirometer replacement in cohort studies.

Background: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. Objective: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. Methods: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. Results: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. Conclusions: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression. The ALEC Study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement no. 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. The SAPALDIA cohort has been funded since 1991 primarily by the Swiss National Science Foundation (grants no 33CS30-148470/1&2, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1). Other national funders who supported data collection in the original studies are listed in the supplement.

Background: Prognostic models can be used to screen individuals at increased risk of developing an outcome. Aims and Objectives: To develop models predicting the probability of developing accelerated lung function decline in subjects exposed to occupational sensitizers. Methods: The study population consisted of subjects of the SAPALDIA cohort who were exposed to occupational high-molecular-weight (n = 347) or low-molecular-weight agents at baseline (n = 246) with a mean follow up of 10.9 years. According to ATS, a mean decline > 60 mL/year in pre-bronchodilation FEV1 between baseline and follow-up was defined as “accelerated”. We used logistic regression analysis to develop the questionnaire-based model. We evaluated the gain of adding atopy and respiratory function test results to it. Discriminative ability, calibration and internal validity of the models were evaluated. Results: 99 of 593 (16.7%) subjects had an accelerated decline in FEV1. The questionnaire model (including age, sex, smoking status, body mass index, pre-existing asthma and type of sensitizing agents at baseline) showed a reasonable discrimination (corrected area under receiver operating characteristic curve (AUC) of 0.716 (95% CI 0.693–0.739)). Adding high FEV1 (> 80% of predicted value) at baseline significantly increased the discriminative ability (corrected AUC 0.756 95% CI 0.736–0.807). Both models showed good calibration and internal validity. Conclusions: The questionnaire and FEV1 model quantifies individual probability of accelerated lung function decline with good calibration and internal validity in workers exposed to occupational sensitizers. External validation of the model is necessary.

Background: Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison. Objectives: Assess and compare the association between SEP and outdoor nitrogen dioxide (NO2) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries. Methods: Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO2. Heterogeneity across cities was assessed using the Higgins' I-squared test (I2). Results: The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO2. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I2 > 76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations. Conclusions: Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies. The ESCAPE study, funded by the European Community's Seventh Framework Program (FP7/2007-2011) under grant agreement no. 211250 (http://www.escapeproject.eu/).

Improved air quality has been found associated with attenuated age-related decline in lung function. But whether genetic polymorphisms strongly associated with lung function play a modifying role in this attenuation process has so far not been investigated.We selected ten single nucleotide polymorphisms derived from the largest genome-wide association studies on lung function and examined whether they modified the association between the change in exposure to particulate matter ≤10 μm (ΔPM10) and lung function decline. 4310 participants from the SAPALDIA cohort provided valid spirometry measurements, a detailed pulmonary health questionnaire both at baseline and 11 years later as well as blood samples for genetic testing. Spatially and temporally resolved air pollution exposures were assigned on an individual level based on participants' residences.Statistically significant interactions of moderate strength with ΔPM10 were detected for rs2284746. Individuals with the CC genotype had a 21 ml slower annual decline of the mid expiratory flow per 10 μg/m3 PM10 reduction over an 10-year period, while the benefits of CG and GG carriers were smaller (14 and 7 ml per year, respectively; Pinteraction = 0.04). The attenuated annual decline in the percentage of the forced expiratory volume in one second relative to the forced vital capacity (FEV1/FVC) was also increased with the presence of each C-allele (Pinteraction = 0.009). We observed further suggestive interactions of similar magnitude in never-smokers, but none of the results would remain statistically significant after correction for multiple testing.We could not find strong evidence that lung function benefits from improved air quality are modified by polymorphisms associated with lung function level in large meta-analyzed genome-wide association studies. Keywords: Air pollution, Lung function, Genetic polymorphism, Gene–environment interaction

Ambient air pollution is a leading environmental risk factor and its broad spectrum of adverse health effects includes a decrease in lung function. Socioeconomic status (SES) is known to be associated with both air pollution exposure and respiratory function. This study assesses the role of SES either as confounder or effect modifier of the association between ambient air pollution and lung function. Cross-sectional data from three European multicenter adult cohorts were pooled to assess factors associated with lung function, including annual means of home outdoor NO2. Pre-bronchodilator lung function was measured according to the ATS-criteria. Multiple mixed linear models with random intercepts for study areas were used. Three different factors (education, occupation and neighborhood unemployment rate) were considered to represent SES. NO2 exposure was negatively associated with lung function. Occupation and neighborhood unemployment rates were not associated with lung function. However, the inclusion of the SES-variable education improved the models and the air pollution-lung function associations got slightly stronger. NO2 associations with lung function were not substantially modified by SES-variables. In this multicenter European study we could show that SES plays a role as a confounder in the association of ambient NO2 exposure with lung function. SAPALDIA Research support: The Swiss National Science Foundation (grants no 33CS30-177506/1, 33CS30-148470/1&2, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1), the Federal Office for the Environment, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton’s government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton’s Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais, Graubünden and Zurich, Stiftung ehemals Bündner Heilstätten, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, Klinik Barmelweid, Hirslanden Klinik Aarau, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, Exposomics EC FP7 grant(Grant agreement No: 308610).

Objectives: We evaluated interactions between SERPINA1 PiMZ genotype, associated with intermediate α1-antitrysin deficiency, with outdoor particulate matter ≤10 μm (PM10), and occupational exposure to vapours, dusts, gases and fumes (VGDF), and their effects on annual change in lung function. Methods: Pre-bronchodilator spirometry was performed in 3739 adults of the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) for whom SERPINA1 genotypes were available. At baseline in 1991, participants were aged 18-62 years; follow-up measurements were conducted from 2001 to 2003. In linear mixed regression models of annual change in lung function, multiplicative interactions were evaluated between PiMZ genotype (PiMM as reference) and change in PM10 (μg/m3), and VGDF exposure (high-level, low-level or no exposure as reference) during follow-up. Results: Annual declines in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) (-82 mL/s, 95% CI -125 to -39) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) (-0.3%, 95% CI -0.6% to 0.0%) in association with VGDF exposure were observed only in PiMZ carriers (Pinteraction

Background: Inconsistent associations between socioeconomic position (SEP) and air pollution have been reported in Europe. We aimed to assess association between SEP and air pollution exposure at r...

Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.

Background Land Use Regression (LUR) is a popular method to explain and predict spatial contrasts in air pollution concentrations, but LUR models for ultrafine particles, such as particle number concentration (PNC) are especially scarce. Moreover, no models have been previously presented for the lung deposited surface area (LDSA) of ultrafine particles. The additional value of ultrafine particle metrics has not been well investigated due to lack of exposure measurements and models. Methods Air pollution measurements were performed in 2011 and 2012 in the eight areas of the Swiss SAPALDIA study at up to 40 sites per area for NO2 and at 20 sites in four areas for markers of particulate air pollution. We developed multi-area LUR models for biannual average concentrations of PM2.5, PM2.5 absorbance, PM10, PMcoarse, PNC and LDSA, as well as alpine, non-alpine and study area specific models for NO2, using predictor variables which were available at a national level. Models were validated using leave-one-out cross-validation, as well as independent external validation with routine monitoring data. Results Model explained variance (R2) was moderate for the various PM mass fractions PM2.5 (0.57), PM10 (0.63) and PMcoarse (0.45), and was high for PM2.5 absorbance (0.81), PNC (0.87) and LDSA (0.91). Study-area specific LUR models for NO2 (R2 range 0.52–0.89) outperformed combined-area alpine (R2 = 0.53) and non-alpine (R2 = 0.65) models in terms of both cross-validation and independent external validation, and were better able to account for between-area variability. Predictor variables related to traffic and national dispersion model estimates were important predictors. Conclusions LUR models for all pollutants captured spatial variability of long-term average concentrations, performed adequately in validation, and could be successfully applied to the SAPALDIA cohort. Dispersion model predictions or area indicators served well to capture the between area variance. For NO2, applying study-area specific models was preferable over applying combined-area alpine/non-alpine models. Correlations between pollutants were higher in the model predictions than in the measurements, so it will remain challenging to disentangle their health effects. Electronic supplementary material The online version of this article (doi:10.1186/s12940-016-0137-9) contains supplementary material, which is available to authorized users.

Although recent air pollution epidemiologic studies have embraced land-use regression models for estimating outdoor traffic exposure, few have examined the spatio-temporal variability of traffic related pollution over a long term period and the optimal methods to take these factors into account for exposure estimates. We used home outdoor NO2 measurements taken from eight geographically diverse areas to examine spatio-temporal variations, construct, and evaluate models that could best predict the within-city contrasts in observations. Passive NO2 measurements were taken outside of up to 100 residences per area over three seasons in 1993 and 2003 as part of the Swiss cohort study on air pollution and lung and heart disease in adults (SAPALDIA). The spatio-temporal variation of NO2 differed by area and year. Regression models constructed using the annual NO2 means from central monitoring stations and geographic parameters predicted home outdoor NO2 levels better than a dispersion model. However, both the regression and dispersion models underestimated the within-city contrasts of NO2 levels. Our results indicated that the best models should be constructed for individual areas and years, and would use the dispersion estimates as the urban background, geographic information system (GIS) parameters to enhance local characteristics, and temporal and meteorological variables to capture changing local dynamics. Such models would be powerful tools for assessing health effects from long-term exposure to air pollution in a large cohort.

Background Experimental studies suggest that glutathione S-transferase (GST) genotypes modify nasal allergen responses induced by secondhand smoke (SHS) exposure. Objective We aimed to investigate whether GSTs affected systemic IgE and allergic rhinitis (AR) in SHS-exposed individuals from a population-based cohort. Methods Analyses comprised 2309 never-smokers from the Swiss study on air pollution and health in adults cohort, reporting SHS status at baseline and 11 years later. Outcomes were defined by total serum IgE100 kU/L, specific serum IgE determined by Phadiatop((R)) 0.35 kU/L and self-reported AR. GSTP1 Ile105Val, GSTM1 and GSTT1 gene deletion genotypes were identified at the follow-up survey. Results After adjustment for relevant covariates, the homozygous GSTP1 105-Val genotype was negatively associated with high total IgE and high-specific IgE by Phadiatop((R)) , notably in subjects persistently exposed to SHS (OR: 0.20, 95% CI 0.05-0.75; P=0.02, for high total IgE and OR: 0.29, 95% CI 0.10-0.89; P=0.03, for high specific IgE by Phadiatop((R)) ). Carrying at least one copy of the GSTM1 gene (non-null) showed a similar association for high specific IgE by Phadiatop((R)) (OR: 0.41, 95% CI 0.22-0.76; P=0.004). No significant associations were found between GSTs and rhinitis. Conclusion and Clinical Relevance In this large cohort, homozygosity for GSTP1 105-Val or carrying the GSTM1 non-null genotype decreased the risk of high total IgE or high specific IgE using Phadiatop((R)) by nearly half in subjects exposed to SHS, as compared with subjects carrying opposite alleles. These findings underline the value of genetic susceptibility when evaluating the effects of environmental exposure on allergic illness. The potential long-term effects of persistent SHS exposure in genetically vulnerable individuals may be of public health relevance

BACKGROUND: Diseases of the skin are important and often preventable conditions occurring among workers with dermal exposures to irritant and sensitizing agents. OBJECTIVE: We conducted this analysis to assess the associations between metalworking exposures and current and persistent skin symptoms among male and female participants in two population-based epidemiologic studies. METHODS: We pooled data from the European Community Respiratory Health Survey II (ECRHS II) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults 2 (SAPALDIA 2), two prospective cohort studies in Europe. Each participant completed interviewer-administered questionnaires to provide information about symptoms and exposures related to selected occupations, including metalworking, during the follow-up periods. We assessed associations between skin symptoms and the frequency of metalworking exposures among 676 ECRHS II/SAPALDIA 2 respondents. RESULTS: Current skin symptoms were reported by 10% of metalworkers and were associated with frequent use, defined as four or more days per week, of oil-based metalworking fluids [prevalence ratio (PR): 1.76, 95% confidence interval (CI): 1.25-2.49)] and organic solvent/degreasing agents (PR: 2.06, 95% CI: 1.21-3.50). CONCLUSIONS: Skin symptom prevalence is associated with increasing frequency of oil-based metalworking fluid and degreasing agent use. Our findings justify assessing strategies for reducing the frequency of metal-related exposures.

Air pollution has been associated with impaired health, including reduced lung function in adults. Moving to cleaner areas has been shown to attenuate adverse effects of air pollution on lung function in children but not in adults.We conducted a prospective study of 9651 adults (18 to 60 years of age) randomly selected from population registries in 1990 and assessed in 1991, with 8047 participants reassessed in 2002. There was complete information on lung volumes and flows (e.g., forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1 as a percentage of FVC, and forced expiratory flow between 25 and 75% of the FVC [FEF25-75]), smoking habits, and spatially resolved concentrations of particulate matter that was less than 10 microm in aerodynamic diameter (PM10) from a validated dispersion model assigned to residential addresses for 4742 participants at both the 1991 and the 2002 assessments and in the intervening years.Overall exposure to individual home outdoor PM10 declined over the 11-year follow-up period (median, -5.3 mug per cubic meter; interquartile range, -7.5 to -4.2). In mixed-model regression analyses, with adjustment for confounders, PM10 concentrations at baseline, and clustering within areas, there were significant negative associations between the decrease in PM10 and the rate of decline in FEV1 (P=0.045), FEV1 as a percentage of FVC (P=0.02), and FEF25-75 (P=0.001). The net effect of a decline of 10 microg of PM10 per cubic meter over an 11-year period was to reduce the annual rate of decline in FEV1 by 9% and of FEF25-75 by 16%. Cumulative exposure in the interval between the two examinations showed similar associations.Decreasing exposure to airborne particulates appears to attenuate the decline in lung function related to exposure to PM10. The effects are greater in tests reflecting small-airway function.

BACKGROUND: Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. METHODS: We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. FINDINGS: After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4·4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE).Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis.We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m−3 increase in NO2 exposure was associated with lower levels of FEV1 (−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m−3 in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons.This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.

Exposure to outdoor air pollutants remains an important concern in Europe, as limit values for NO2 and PM10 continue to be exceeded. Few studies have addressed the long-term spatial contrasts in PM2.5, PM absorbance, PM coarse coarse and especially ultrafine particles. This scarcity of data hampers the possibility to conduct epidemiological studies, assessing the health relevance of these markers of potentially harmful pollutants. Air pollution measurements were performed in eight geographically distinct areas of the Swiss Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) in Switzerland. NO2 was measured in all eight areas at 40 sites per area, and PM2.5, PM2.5 absorbance, PM10 and ultrafine particles (particle number concentration (PNC) and lung deposited surface area (LDSA)) were measured in 4 of these areas, at a subset of 20 out of 40 sites. Each site was sampled three times during different seasons of the year, using the same equipment, sampling protocols and the same central facilities for analysis of samples. We assessed the spatial variability between areas and between individual sites, as well as pollution contrasts between the seasons and correlations between different pollutants. Within-area spatial contrasts (defined as the ratio between the 90th and 10th percentile) were highest for NO2 (3.14), moderate for PMcoarse (2.19), PNC (2.00) and PM2.5 absorbance (1.94), and lowest for LDSA (1.63), PM2.5 (1.50) and PM10 (1.46). Concentrations in the larger cities were generally higher than in smaller towns and rural and alpine areas, and were higher in the winter than in the summer and intermediate seasons, for all pollutants. Between-area differences accounted for more variation than within-area differences for all pollutants except NO2 and PMcoarse. Despite substantial within-area contrasts for PNC and LDSA, 74.7% and 83.3% of the spatial variance was attributed to between-area variability, respectively. Coefficients of determination between long-term adjusted pollutants were high (R-2>0.70) between NO2, PM2.5 absorbance, PNC and LDSA and between PM2.5 and PM10. The measurement of spatial patterns for this large range of outdoor air pollutants will contribute to a highly standardized estimation of individual long-term exposure levels for SAPALDIA cohort participants. (C) 2015 Elsevier Ltd. All rights reserved.

The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), conducted in 1991 (SAPALDIA 1) in eight areas among 9,651 randomly selected adults aged 18-60 years, reported associations among the prevalence of respiratory symptoms, nitrogen dioxide, and particles with an aerodynamic diameter of less than 10 microg/m3. Later, 8,047 subjects reenrolled in 2002 (SAPALDIA 2). The effects of individually assigned traffic exposures on reported respiratory symptoms were estimated, while controlling for socioeconomic and exposure- and health-related factors. The risk of attacks of breathlessness increased for all subjects by 13% (95% confidence interval: 3, 24) per 500-m increment in the length of main street segments within 200 m of the home and decreased in never smokers by 12% (95% confidence interval: 0, 22) per 100-m increment in distance from home to a main street. Living within 20 m of a main street increased the risks of regular phlegm by 15% (95% confidence interval: 0, 31) and wheezing with breathing problems by 34% (95% confidence interval: 0, 79) in never smokers. In 2002, the effects related to road distance were different from those in 1991, which could be due to changes in the traffic pollution mixture. These findings among a general population provide strong confirmation that living near busy streets leads to adverse respiratory health effects.

Summary.: Objectives: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution. Methods: The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50years and older. Concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates. Results: Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6528 individuals (70%) agreed to the health examination and 5973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5kg in 11years and 28% of smokers in 1991 had quit by the time of the reassessment

Background: In epidemiological studies investigating long term effects of air pollution, Gaussian dispersion and land-use regression modeling are generally used. Their applications typically assume...