Hexavalent chromium still a concern in Sweden - Evidence from a cross-sectional study within the SafeChrom project.

OBJECTIVES: Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown. METHODS: This cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance. RESULTS: The exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 µg/m3 (95% confidence interval: 0.11-0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 µg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 µg/L, 5th-95th percentile 0.10-3.20) and RBC concentrations (0.73 µg/L, 0.51-2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 µg/L, 0.06-0.56 and RBC 0.53 µg/L, 0.42-0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today. CONCLUSIONS: Our study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.

Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms: Results from a Nordic longitudinal population survey.

AIM: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive. METHODS: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline. RESULTS: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring. CONCLUSION: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms.

Long-term exposure to low-level air pollution and greenness and mortality in Northern Europe. The Life-GAP project.

BACKGROUND: Air pollution has been linked to mortality, but there are few studies examining the association with different exposure time windows spanning across several decades. The evidence for the effects of green space and mortality is contradictory. OBJECTIVE: We investigated all-cause mortality in relation to exposure to particulate matter (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) and greenness (normalized difference vegetation index - NDVI) across different exposure time windows. METHODS: The exposure assessment was based on a combination of the Danish Eulerian Hemispheric Model and the Urban Background Model for the years 1990, 2000 and 2010. The analysis included a complete case dataset with 9,135 participants from the third Respiratory Health in Northern Europe study (RHINE III), aged 40-65 years in 2010, with mortality follow-up to 2021. We performed Cox proportional hazard models, adjusting for potential confounders. RESULTS: Altogether, 327 (3.6 %) persons died in the period 2010-2021. Increased exposures in 1990 of PM2.5, PM10, BC and NO2 were associated with increased all-cause mortality hazard ratios of 1.40 (95 % CI1.04-1.87 per 5 µg/m3), 1.33 (95 % CI: 1.02-1.74 per 10 µg/m3), 1.16 (95 % CI: 0.98-1.38 per 0.4 µg/m3) and 1.17 (95 % CI: 0.92-1.50 per 10 µg/m3), respectively. No statistically significant associations were observed between air pollution and mortality in other time windows. O3 showed an inverse association with mortality, while no association was observed between greenness and mortality. Adjusting for NDVI increased the hazard ratios for PM2.5, PM10, BC and NO2 exposures in 1990. We did not find significant interactions between greenness and air pollution metrics. CONCLUSION: Long term exposure to even low levels of air pollution is associated with mortality. Opening up for a long latency period, our findings indicate that air pollution exposures over time may be even more harmful than anticipated.

Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults.

Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 µg/m³. A one interquartile range increase of 7 µg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Indoor Airborne Microbiome and Endotoxin: Meteorological Events and Occupant Characteristics Are Important Determinants.

Airborne bacteria and endotoxin may affect asthma and allergies. However, there is limited understanding of the environmental determinants that influence them. This study investigated the airborne microbiomes in the homes of 1038 participants from five cities in Northern Europe: Aarhus, Bergen, Reykjavik, Tartu, and Uppsala. Airborne dust particles were sampled with electrostatic dust fall collectors (EDCs) from the participants' bedrooms. The dust washed from the EDCs' clothes was used to extract DNA and endotoxin. The DNA extracts were used for quantitative polymerase chain (qPCR) measurement and 16S rRNA gene sequencing, while endotoxin was measured using the kinetic chromogenic limulus amoebocyte lysate (LAL) assay. The results showed that households in Tartu and Aarhus had a higher bacterial load and diversity than those in Bergen and Reykjavik, possibly due to elevated concentrations of outdoor bacterial taxa associated with low precipitation and high wind speeds. Bergen-Tartu had the highest difference (ANOSIM R = 0.203) in ß diversity. Multivariate regression models showed that α diversity indices and bacterial and endotoxin loads were positively associated with the occupants' age, number of occupants, cleaning frequency, presence of dogs, and age of the house. Further studies are needed to understand how meteorological factors influence the indoor bacterial community in light of climate change.

Inflammatory bowel disease and asthma. Results from the RHINE study.

BACKGROUND: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms. METHODS: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables. RESULTS: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038). CONCLUSIONS: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD.

Maternal and paternal tuberculosis is associated with increased asthma and respiratory symptoms in their offspring: a study from Northern Europe.

Background: Given the profound impact of tuberculosis (TB) on immunity and given murine studies suggesting that infections may influence immunity across generations, we hypothesize that parental TB might impact health and disease in future offspring. Objective: This study investigated the impact of maternal and paternal TB on offspring asthma and respiratory symptoms. Methods: We included data from the third follow-up of the Respiratory Health in Northern Europe study (RHINE). Information on own asthma status, asthma-like symptoms and other respiratory symptoms, as well as information about parental TB and asthma, were collected using standardized questionnaires. The associations between parental TB and RHINE participants' asthma and respiratory symptoms were analyzed using multiple logistic regression, with adjustment for parental education, smoking habits and asthma. Results: Of 8,323 study participants, 227 (2.7%) reported only paternal TB, 282 (3.4%) only maternal TB, and 33 (0.4%) reported that both parents had TB. We found a higher risk of asthma (aOR: 1.29, 95% CI: 1.05-1.57) in offspring with a history of parental TB as compared to offspring without parental TB., Parental TB was significantly associated with allergic asthma in offspring (aOR: 1.58, 95% CI: 1.29-2.05), while no significant association between parental TB and asthma without allergy (aOR: 1.00, 95% CI: 0.76-1.32) in offspring was observed. Conclusion: Results from this study indicate that parental TB might be a risk factor for offspring's asthma and respiratory symptoms. We raise the hypothesis that the immunological impact of infections might be transmitted to influence offspring phenotype in humans.

Traffic noise in the bedroom in association with markers of obesity: a cross-sectional study and mediation analysis of the respiratory health in Northern Europe cohort.

BACKGROUND: Previous research suggests an association between road traffic noise and obesity, but current evidence is inconclusive. The aim of this study was to assess the association between nocturnal noise exposure and markers of obesity and to assess whether sleep disturbance might be a mediator in this association. METHODS: We applied data from the Respiratory Health in Northern Europe (RHINE) cohort. We used self-measured waist circumference (WC) and body mass index (BMI) as outcome values. Noise exposure was assessed as perceived traffic noise in the bedroom and/or the bedroom window's location towards the street. We applied adjusted linear, and logistic regression models, evaluated effect modifications and conducted mediation analysis. RESULTS: Based on fully adjusted models we found that women, who reported very high traffic noise levels in bedroom, had 1.30 (95% CI 0.24-2.37) kg/m2 higher BMI and 3.30 (95% CI 0.39-6.20) cm higher WC compared to women, who reported no traffic noise in the bedroom. Women who reported higher exposure to road traffic noise had statistically significant higher odds of being overweight and have abdominal obesity with OR varying from 1.15 to 1.26 compared to women, who reported no traffic noise in the bedroom. For men, the associations were rather opposite, although mostly statistically insignificant. Furthermore, men, who reported much or very much traffic noise in the bedroom, had a statistically significantly lower risk of abdominal obesity. Sleep disturbance fully or partially mediated the association between noise in bedroom and obesity markers among women. CONCLUSION: Our results suggest that self-reported traffic noise in the bedroom may be associated to being overweight or obese trough sleep disturbance among women, but associations were inconclusive among men.

Previous tuberculosis infection associated with increased frequency of asthma and respiratory symptoms in a Nordic-Baltic multicentre population study.

Background: Tuberculosis (TB) infection induces profound local and systemic, immunological and inflammatory changes that could influence the development of other respiratory diseases; however, the association between TB and asthma is only partly understood. Our objective was to study the association of TB with asthma and respiratory symptoms in a Nordic-Baltic population-based study. Methods: We included data from the Respiratory Health in Northern Europe (RHINE) study, in which information on general characteristics, TB infection, asthma and asthma-like symptoms were collected using standardised postal questionnaires. Asthma was defined based on asthma medication usage and/or asthma attacks 12 months prior to the study, and/or by a report of ≥three out of five respiratory symptoms in the last 12 months. Allergic/nonallergic asthma were defined as asthma with/without nasal allergy. The associations of TB with asthma outcomes were analysed using logistic regressions with adjustments for age, sex, smoking, body mass index and parental education. Results: We included 8379 study participants aged 50-75 years, 61 of whom reported having had TB. In adjusted analyses, participants with a history of TB had higher odds of asthma (OR 1.99, 95% CI 1.13-3.47). The associations were consistent for nonallergic asthma (OR 2.17, 95% CI 1.16-4.07), but not for allergic asthma (OR 1.20, 95% CI 0.53-2.71). Conclusion: We found that in a large Northern European population-based cohort, persons with a history of TB infection more frequently had asthma and asthma symptoms. We speculate that this may reflect long-term effects of TB, including direct damage to the airways and lungs, as well as inflammatory responses.

Association between abdominal and general obesity and respiratory symptoms, asthma and COPD. Results from the RHINE study.

INTRODUCTION: Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results. AIMS AND OBJECTIVES: We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men. METHODS: This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m2. RESULTS: There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease. CONCLUSIONS: General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men.

Asthma, allergic rhinitis and atopic dermatitis in association with home environment - The RHINE study.

We studied home environment exposures in relation to asthma, allergic rhinitis and atopic dermatitis among offspring of participants (parents) in the Respiratory Health in Northern Europe (RHINE) study (age ≤ 30 y). Totally 17,881 offspring from Iceland, Norway, Sweden, Denmark and Estonia were included. Home environment exposures, including dampness and mold, type of dwelling, construction year and indoor painting were registered through a questionnaire answered by parents in the first follow up (RHINE II). The parents reported ten years later with in the frame of RHINE III offspring's birth year and offspring's asthma, allergic rhinitis, atopic dermatitis. They also reported dampness and mold at home from RHINE II to RHINE III. The prevalence of offspring's asthma before 10 y, asthma after 10 y, allergic rhinitis at any age and atopic dermatitis at any age were 9.7 %, 4.3 %, 15.6 % and 17.3 %, respectively. Asthma before 10 y was related to any indoor painting at RHINE II (OR = 1.14, 95%CI (1.02, 1.29)). Asthma after 10 y was associated with dampness/mold at home (OR = 1.33-1.62) and living in the newest buildings (constructed in 1986-2001) (OR = 1.30, 95%CI (1.02, 1.66)). Allergic rhinitis was associated with living in newer buildings (constructed in 1961-2001) (OR = 1.16-1.24). Atopic dermatitis was associated with visible mold (OR = 1.35, 95%CI(1.12, 1.62)), dampness/mold at home (OR = 1.18-1.38), living in apartments (OR = 1.22, 95%CI(1.10, 1.35)) and living in newer buildings (constructed in 1961-2001) (OR = 1.14-1.25). There were dose-response effects of dampness and mold on offspring's asthma after 10 y and atopic dermatitis (20 years exposure vs. 10 years exposure). Older offspring had increased risk of developing asthma after 10 y and atopic dermatitis. In conclusion, home dampness and mold, living in apartments, living in newer buildings and indoor painting were associated with offspring's asthma or allergic diseases. Stronger health effects were found among offspring with prolonged exposure of dampness/mold.

Birch pollen, air pollution and their interactive effects on airway symptoms and peak expiratory flow in allergic asthma during pollen season - a panel study in Northern and Southern Sweden.

BACKGROUND: Evidence of the role of interactions between air pollution and pollen exposure in subjects with allergic asthma is limited and need further exploration to promote adequate preventive measures. The objective of this study was to assess effects of exposure to ambient air pollution and birch pollen on exacerbation of respiratory symptoms in subjects with asthma and allergy to birch. METHODS: Thirty-seven subjects from two Swedish cities (Gothenburg and Umeå) with large variation in exposure to both birch-pollen and air pollutants, participated in the study. All subjects had confirmed allergy to birch and self-reported physician-diagnosed asthma. The subjects recorded respiratory symptoms such as rhinitis or eye irritation, dry cough, dyspnoea, the use of any asthma or allergy medication and peak respiratory flow (PEF), daily for five consecutive weeks during two separate pollen seasons and a control season without pollen. Nitrogen oxides (NOx), ozone (O3), particulate matter (PM2.5), birch pollen counts, and meteorological data were obtained from an urban background monitoring stations in the study city centres. The data were analysed using linear mixed effects models. RESULTS: During pollen seasons all symptoms and medication use were higher, and PEF was reduced in the subjects. In regression analysis, exposure to pollen at lags 0 to 2 days, and lags 0 to 6 days was associated with increased ORs of symptoms and decreased RRs for PEF. Pollen and air pollution interacted in some cases; during low pollen exposure, there were no associations between air pollution and symptoms, but during high pollen exposure, O3 concentrations were associated with increased OR of rhinitis or eye irritation, and PM2.5 concentrations were associated with increased ORs of rhinitis or eye irritation, dyspnea and increased use of allergy medication. CONCLUSIONS: Pollen and air pollutants interacted to increase the effect of air pollution on respiratory symptoms in allergic asthma. Implementing the results from this study, advisories for individuals with allergic asthma could be improved, minimizing the morbidities associated with the condition.

Personal exposure levels to O3, NOx and PM10 and the association to ambient levels in two Swedish cities.

Exposure to air pollution is of great concern for public health although studies on the associations between exposure estimates and personal exposure are limited and somewhat inconsistent. The aim of this study was to quantify the associations between personal nitrogen oxides (NOx), ozone (O3) and particulate matter (PM10) exposure levels and ambient levels, and the impact of climate and time spent outdoors in two cities in Sweden. Subjects (n = 65) from two Swedish cities participated in the study. The study protocol included personal exposure measurements at three occasions, or waves. Personal exposure measurements were performed for NOx and O3 for 24 h and PM10 for 24 h, and the participants kept an activity diary. Stationary monitoring stations provided hourly data of NOx, O3 and PM, as well as data on air temperature and relative humidity. Data were analysed using mixed linear models with the subject-id as a random effect and stationary exposure and covariates as fixed effects. Personal exposure levels of NOx, O3 and PM10 were significantly associated with levels measured at air pollution monitoring stations. The associations persisted after adjusting for temperature, relative humidity, city and wave, but the modelled estimates were slightly attenuated from 2.4% (95% CI 1.8-2.9) to 2.0% (0.97-2.94%) for NOx, from 3.7% (95% CI 3.1-4.4) to 2.1% (95% CI 1.1-2.9%) for O3 and from 2.6% (95% 0.9-4.2%) to 1.3% (95% CI - 1.5-4.0) for PM10. After adding covariates, the degree of explanation offered by the model (coefficient of determination, or R2) did not change for NOx (0.64 to 0.63) but increased from 0.46 to 0.63 for O3, and from 0.38 to 0.43 for PM10. Personal exposure to NOx, O3 and PM has moderate to good association with levels measured at urban background sites. The results indicate that stationary measurements are valid as measure of exposure in environmental health risk assessments, especially if they can be refined using activity diaries and meteorological data. Approximately 50-70% of the variation of the personal exposure was explained by the stationary measurement, implying occurrence of misclassification in studies using more crude exposure metrics, potentially leading to underestimates of the effects of exposure to ambient air pollution.

Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides.

BACKGROUND: We hypothesize that biological perturbations due to exposure to ambient air pollution are reflected in gene expression levels in peripheral blood mononuclear cells. METHODS: We assessed the association between exposure to ambient air pollution and genome-wide gene expression levels in peripheral blood mononuclear cells collected from 550 healthy subjects participating in cohorts from Italy and Sweden. Annual air pollution estimates of nitrogen oxides (NOx) at time of blood collection (1990-2006) were available from the ESCAPE study. In addition to univariate analysis and two variable selection methods to investigate the association between expression and exposure to NOx, we applied gene set enrichment analysis to assess overlap between our most perturbed genes and gene sets hypothesized to be related to air pollution and cigarette smoking. Finally, we assessed associations between NOx and CpG island methylation at the identified genes. RESULTS: Annual average NOx exposure in the Italian and Swedish cohorts was 94.2 and 6.7 µg/m, respectively. Long-term exposure to NOx was associated with seven probes in the Italian cohort and one probe in the Swedish (and combined) cohorts. For genes AHCYL2 and MTMR2, changes were also seen in the methylome. Genes hypothesized to be downregulated due to cigarette smoking were enriched among the most strongly downregulated genes from our study. CONCLUSION: This study provides evidence of subtle changes in gene expression related to exposure to long-term NOx. On a global level, the observed changes in the transcriptome may indicate similarities between air pollution and tobacco induced changes in the transcriptome.

Socioeconomic position and outdoor nitrogen dioxide (NO2) exposure in Western Europe: A multi-city analysis.

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.

Father's environment before conception and asthma risk in his children: a multi-generation analysis of the Respiratory Health In Northern Europe study.

Background: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception. Methods: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family. Results: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries. Conclusions: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.

Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden: A Longitudinal Study.

BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia. OBJECTIVES: We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden. METHODS: Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed using a land-use regression model with a spatial resolution of 50 m × 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) were used as markers for long-term exposure to air pollution. RESULTS: Out of 1,806 participants at baseline, 191 were diagnosed with Alzheimer's disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the group with the highest exposure were more likely than those in the group with the lowest exposure to be diagnosed with dementia (Alzheimer's disease or vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the highest vs. the lowest quartile). The estimates were similar for Alzheimer's disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A subanalysis that excluded a younger sample that had been retested after only 5 years of follow-up suggested stronger associations with exposure than were present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the lowest quartile). CONCLUSIONS: If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer's disease.

Exposure to traffic and lung function in adults: a general population cohort study.

OBJECTIVES: To investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region. DESIGN: Cross-sectional results from a cohort study. SETTING: The adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001-2008 in Gothenburg, Sweden. Exposure was expressed as the distance from participants' residential address to the nearest road with dense traffic (>10,000 vehicles per day) or very dense traffic (>30,000 vehicles per day). The exposure categories were: low (>500 m; reference), medium (75-500 m) or high (<75 m). PARTICIPANTS: The source population was a population-based cohort of adults (n=6153). The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates. OUTCOME MEASURES: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination. The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status. RESULTS: We identified a significant dose-response trend between exposure category and FEV1 (p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates. High exposure was associated with lower FEV1 (-1.0%, 95% CI -2.5% to 0.5%) and lower FVC (-0.9%, 95% CI -2.2% to 0.4%). The effect appeared to be stronger in women. In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (-4.5%, 95% CI -8.8% to -0.1%). CONCLUSIONS: High traffic exposure at the residential address was associated with lower than predicted FEV1 and FVC lung function compared with living further away in a large general population cohort. There were particular effects on women and individuals with obstructive disease.

Is there a threshold concentration of cat allergen exposure on respiratory symptoms in adults?

BACKGROUND AND OBJECTIVE: Cat allergen concentrations higher than 8 µg/g in settled house dust, have been suggested to provoke exacerbation of allergic respiratory symptoms. However, whether the 8 µg/g of indoor cat allergen concentration is indeed the minimal exposure required for triggering the asthma related respiratory symptoms or the development of sensitization has not yet been confirmed. We studied the associations between domestic cat allergen concentrations and allergic symptoms in the European Community Respiratory Health Survey II, with the aim of confirming this suggested threshold. METHODS: Cat allergen concentrations were measured in the mattress dust of 3003 participants from 22 study centres. Levels of specific immunoglobulin E to cat allergens were measured in serum samples using an immunoassay. Information on allergic symptoms, medication use, home environment and smoking was obtained from a face-to-face interview. RESULTS: Domestic cat allergen concentrations were not associated with allergic/ asthmatic symptoms in the entire study population, nor in the subset sensitized to cat allergen. We also found no association among individuals exposed to concentrations higher than 8 µg/g. However, exposure to medium cat allergen concentrations (0.24-0.63 µg/g) was positively associated with reported asthmatic respiratory symptoms in subjects who have experienced allergic symptoms when near animals. CONCLUSIONS: The proposed 8 µg/g threshold of cat allergen concentrations for the exacerbation of allergic/ respiratory symptoms was not confirmed in a general European adult population. Potential biases attributable to avoidance behaviours and an imprecise exposure assessment cannot be excluded.

Inflammatory markers in relation to long-term air pollution.

Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 µg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 µg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.