Regular Physical Activity Levels and Incidence of Restrictive Spirometry Pattern: A Longitudinal Analysis of 2 Population-Based Cohorts.

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 <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years.

Dental and periodontal health in a Swiss population-based sample of older adults: a cross-sectional study.

In this cross-sectional study, the prevalences of tooth loss, prosthetic dental restorations, and probing pocket depths (PPD) ≥4 mm, and their relationship to sociodemographic factors, were investigated in older Swiss adults. There were up to 1,673 participants aged ≥55 yr in the fourth survey of the Swiss Cohort Study on Air Pollution And Lung And Heart Disease In Adults (SAPALDIA4). Missing teeth, prosthetic dental restorations, and PPD ≥4 mm were recorded in clinical examinations conducted by field workers and compared with self-reported information from questionnaires. Examination data showed that participants were missing five teeth on average, 74.8% had a prosthetic dental restoration, and 21.1% had PPD of ≥4 mm. The mean number of missing teeth and the prevalences of tooth loss, fixed dental prostheses, and removable dental prostheses were associated with age, education level, smoking status, and time since last visit to a dentist. Comparison of data obtained by field workers and that from self-reports show a high level of agreement for the number of missing teeth and the prevalence of removable dental prostheses, but a lower level of agreement for self-reports of fixed dental prostheses and periodontitis.

Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.

BACKGROUND: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation. METHODS: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV1, FVC, and FEV1/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2. RESULTS: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs. CONCLUSIONS: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.

A systematic analysis of mutual effects of transportation noise and air pollution exposure on myocardial infarction mortality: a nationwide cohort study in Switzerland.

AIMS: The present study aimed to disentangle the risk of the three major transportation noise sources-road, railway, and aircraft traffic-and the air pollutants NO2 and PM2.5 on myocardial infarction (MI) mortality in Switzerland based on high quality/fine resolution exposure modelling. METHODS AND RESULTS: We modelled long-term exposure to outdoor road traffic, railway, and aircraft noise levels, as well as NO2 and PM2.5 concentration for each address of the 4.40 million adults (>30 years) in the Swiss National Cohort (SNC). We investigated the association between transportation noise/air pollution exposure and death due to MI during the follow-up period 2000-08, by adjusting noise [Lden(Road), Lden(Railway), and Lden(Air)] estimates for NO2 and/or PM2.5 and vice versa by multipollutant Cox regression models considering potential confounders. Adjusting noise risk estimates of MI for NO2 and/or PM2.5 did not change the hazard ratios (HRs) per 10 dB increase in road traffic (without air pollution: 1.032, 95% CI: 1.014-1.051, adjusted for NO2 and PM2.5: 1.034, 95% CI: 1.014-1.055), railway traffic (1.020, 95% CI: 1.007-1.033 vs. 1.020, 95% CI: 1.007-1.033), and aircraft traffic noise (1.025, 95% CI: 1.006-1.045 vs. 1.025, 95% CI: 1.005-1.046). Conversely, noise adjusted HRs for air pollutants were lower than corresponding estimates without noise adjustment. Hazard ratio per 10 µg/m³ increase with and without noise adjustment were 1.024 (1.005-1.043) vs. 0.990 (0.965-1.016) for NO2 and 1.054 (1.013-1.093) vs. 1.019 (0.971-1.071) for PM2.5. CONCLUSION: Our study suggests that transportation noise is associated with MI mortality, independent from air pollution. Air pollution studies not adequately adjusting for transportation noise exposure may overestimate the cardiovascular disease burden of air pollution.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute ß-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study.

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.

SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.

BACKGROUND: The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort. METHODS: DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models. RESULTS: Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing. CONCLUSIONS: The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.

Is there a gender-specific association between asthma and carotid intima media thickness in Swiss adolescents?

Respiratory diseases are associated with increased cardiovascular risk in adults, but little is known on the early impact on the vasculature in youth. The SAPALDIA Youth study, the offspring study of the Swiss Study on Air Pollution and Lung and Heart Disease In Adults (SAPALDIA), investigated the association between physician-diagnosed asthma status and common carotid artery intima media thickness (CIMT). Offspring underwent standardized clinical protocols and provided information on early life factors, health, and lifestyle. The association between per subject averages of CIMT and asthma was estimated using mixed linear regression analyses adjusting for main confounders, testing for interaction with gender and age. Of 257 offspring (mean age 15 years, 53% female), 11.5% reported doctor-diagnosed asthma (male 17%, female 7%). Mean CIMT was significantly different by gender (male 0.53 mm (± 0.045), female 0.50 mm (± 0.048); p < 0.001). Interaction was highly significant by gender (p = 0.001) with significantly increased CIMT in asthmatic vs. non-asthmatics boys (difference 0.023 mm, 95% CI 0.003; 0.043), as compared to girls. CONCLUSION: Our study suggests an increased risk for early vascular change in adolescent asthmatic boys. Whereas the small number of girls limits the interpretation, the result necessitates further research into sex-specific atherosclerotic burden related to respiratory health in adolescence. What is Known: • Evidence points to a significant impact of adult respiratory disease on cardiovascular health indicators as well as on endpoints. • Inflammation is a key pathway in vascular change across the life course. What is New: • We observe an adverse association between physician-diagnosed asthma and carotid intima media thickness in adolescent boys. • Albeit a limited number of asthmatic girls, we hypothesize the gender typical timing of asthma or a higher male cardiovascular vulnerability as possible explanations for the gender-specific results.

Hypertension, diabetes and lifestyle in the long-term - Results from a Swiss population-based cohort.

Healthy lifestyles are integral in preventing and treating common cardiovascular and metabolic diseases. The aim of this study was to observe smoking habits, alcohol intake, physical activity and body mass index over a 10-year period in a population-based cohort, particularly focusing on participants with hypertension and type 2 diabetes mellitus. Included were 4155 participants from the first (2001-2003) and second (2010-2011) follow-ups of the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA). Information was collected via health questionnaire; height and weight were measured. In a healthy lifestyle score one point was attributed per criterion; non-smoking, low risk alcohol consumption, BMI<25kg/m2, and regular physical activity. Overall in 2010-2011, 16.4% were smokers, 7.7% had at risk alcohol consumption, 25.5% were physically inactive and 57.8% were overweight or obese. Both those with hypertension and diabetes had lower mean healthy lifestyle scores than those without disease. Women with incident hypertension from 2001 to 2011 had lower odds of improving their healthy lifestyle score during this time period compared to those without this disease. In contrast, women with incident diabetes had higher odds of lifestyle score improvement. In men, neither hypertension nor diabetes was associated with change in lifestyle score. Our findings suggest that, irrespective of disease status, preventative attention is needed, particularly in regards to physical activity and bodyweight. These needs could be met by population-based interventions, a necessary and suitable option in both preventing and treating the non-communicable disease epidemic which currently faces countries worldwide.

Transportation noise exposure and cardiovascular mortality: a nationwide cohort study from Switzerland.

Most studies published to date consider single noise sources and the reported noise metrics are not informative about the peaking characteristics of the source under investigation. Our study focuses on the association between cardiovascular mortality in Switzerland and the three major transportation noise sources-road, railway and aircraft traffic-along with a novel noise metric termed intermittency ratio (IR), expressing the percentage contribution of individual noise events to the total noise energy from all sources above background levels. We generated Swiss-wide exposure models for road, railway and aircraft noise for 2001. Noise from the most exposed façade was linked to geocodes at the residential floor height for each of the 4.41 million adult (>30 y) Swiss National Cohort participants. For the follow-up period 2000-2008, we investigated the association between all noise exposure variables [Lden(Road), Lden(Rail), Lden(Air), and IR at night] and various cardiovascular primary causes of death by multipollutant Cox regression models adjusted for potential confounders including NO2. The most consistent associations were seen for myocardial infarction: adjusted hazard ratios (HR) (95% CI) per 10 dB increase of exposure were 1.038 (1.019-1.058), 1.018 (1.004-1.031), and 1.026 (1.004-1.048) respectively for Lden(Road), Lden(Rail), and Lden(Air). In addition, total IR at night played a role: HRs for CVD were non-significant in the 1st, 2nd and 5th quintiles whereas they were 1.019 (1.002-1.037) and 1.021 (1.003-1.038) for the 3rd and 4th quintiles. Our study demonstrates the impact of all major transportation noise sources on cardiovascular diseases. Mid-range IR levels at night (i.e. between continuous and highly intermittent) are potentially more harmful than continuous noise levels of the same average level.

Physical activity is associated with lower arterial stiffness in older adults: results of the SAPALDIA 3 Cohort Study.

Associations of physical activity (PA) intensity with arterial stiffness in older adults at the population level are insufficiently studied. We examined cross-sectional associations of self-reported PA intensities with arterial stiffness in elderly Caucasians of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults. Mixed central and peripheral arterial stiffness was measured oscillometrically by the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). The self-reported International Physical Activity Questionnaire long version was administered to classify each subject's PA level. We used univariable and multivariable mixed linear and logistic regression models for analyses in 1908 persons aged 50 years and older. After adjustment for several confounders moderate, vigorous and total PA were inversely associated with CAVI (p = 0.02-0.03). BaPWV showed negative and marginally significant associations with vigorous and moderate PA (each p = 0.06), but not with total PA (p = 0.28). Increased arterial stiffness (CAVI ≥ 9, upper tertile) was inversely and significantly associated with vigorous PA [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.48-0.88], and marginally significantly with total PA (OR 0.76, 95% CI 0.57-1.02) and moderate PA (OR 0.75, 95% CI 0.56-1.01). The odds ratio for baPWV ≥ 14.4 was 0.67 (95% CI 0.48-0.93) across the vigorous PA levels, and was non-significant across the total (OR 0.91, 95% CI 0.66-1.23) and moderate PA levels (OR 0.94, 95% CI 0.69-1.28). In this general Caucasian population of older adults higher levels especially of vigorous PA were associated with lower arterial stiffness. These data support the importance of PA for improving cardiovascular health in elderly people.

Long-term physical activity is associated with reduced arterial stiffness in older adults: longitudinal results of the SAPALDIA cohort study.

BACKGROUND: longitudinal analyses of physical activity (PA) and arterial stiffness in populations of older adults are scarce. We examined associations between long-term change of PA and arterial stiffness in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). METHODS: we assessed PA in SAPALDIA 2 (2001-03) and SAPALDIA 3 (2010-11) using a short questionnaire with a cut-off of at least 150 min of moderate-to-vigorous PA per week for sufficient activity. Arterial stiffness was measured oscillometrically by means of the brachial-ankle pulse wave velocity (baPWV) in SAPALDIA 3. We used multivariable mixed linear regression models adjusted for several potential confounders in 2,605 persons aged 50-81. RESULTS: adjusted means of baPWV were significantly lower in persons with sufficient moderate-to-vigorous PA (i) in SAPALDIA 2 but not in SAPALDIA 3 (P = 0.048) and (ii) in both surveys (P = 0.001) compared with persons with insufficient activity in both surveys. There was a significant interaction between sex and the level of change in PA concerning baPWV (P = 0.03). The triples of parameter estimates describing the association between level of PA change and baPWV were not significantly different between the two sex-specific models (P = 0.07). CONCLUSIONS: keeping up or adopting a physically active lifestyle was associated with lower arterial stiffness in older adults after a follow-up of almost a decade. Increasing the proportion of older adults adhering to PA recommendations incorporating also vigorous PA may have a considerable impact on vascular health at older age and may contribute to healthy ageing in general.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project.

BACKGROUND: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 µm (PM2.5), less than 10 µm (PM10), and between 10 µm and 2.5 µm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 µg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 µg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 µg/m(3) (1.07, 1.01-1.13). INTERPRETATION: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING: European Community's Seventh Framework Program (FP7/2007-2011).

Long-term smoking cessation and heart rate dynamics in an aging healthy cohort: Is it possible to fully recover?

AIM: To evaluate the long-term influence of smoking cessation on the regulation of the autonomic cardiovascular system in an aging general population, using the subpopulation of lifelong non-smokers as control group. METHODS: We analyzed 1481 participants aged ≥50 years from the SAPALDIA cohort. In each participant, heart rate variability and heart rate dynamics were characterized by means of various quantitative analyzes of the inter-beat interval time series generated from 24-hour electrocardiogram recordings. Each parameter obtained was then used as the outcome variable in multivariable linear regression models in order to evaluate the association with smoking status and time elapsed since smoking cessation. The models were adjusted for known confounding factors and stratified by the time elapsed since smoking cessation. RESULTS: Our findings indicate that smoking triggers adverse changes in the regulation of the cardiovascular system, even at low levels of exposure since current light smokers exhibited significant changes as compared to lifelong non-smokers. Moreover, there was evidence for a dose-response effect. Indeed, the changes observed in current heavy smokers were more marked as compared to current light smokers. Furthermore, full recovery was achieved in former smokers (i.e., normalization to the level of lifelong non-smokers). However, while light smokers fully recovered within the 15 first years of cessation, heavy former smokers might need up to 15-25 years to fully recover. CONCLUSION: This study supports the substantial benefits of smoking cessation, but also warns of important long-term alterations caused by heavy smoking.

Reproducibility of oscillometrically measured arterial stiffness indices: Results of the SAPALDIA 3 cohort study.

BACKGROUND: There is an increasing interest in oscillometric arterial stiffness measurement for cardiovascular risk stratification. We assessed reproducibility of the cuff-based arterial stiffness measures cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV) and peripheral augmentation index (pAI) in a subsample of the second follow-up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). METHODS: CAVI, baPWV and pAI were measured twice within 90 days in a representative subsample (n = 105) of SAPALDIA 3 with a mean age of 63 years (52.4% female). RESULTS: The mean coefficient of variation for CAVI was 4.4%, baPWV 3.9%, and pAI 7.4%. The intraclass correlation coefficient ranged from 0.6 for pAI to 0.8 for CAVI, and 0.9 for baPWV. The mixed linear model revealed that 68.7%/80.1%/55.0% of the CAVI/baPWV/pAI variance was accounted for by the subject, 5.2%/8.1%/ < 0.01% by the fieldworker, 6.7%/7.8%/28.5% by variation between measurement days, and 19.4%/4%/16.5% by measurement error. Bland-Altman plots showed no particular dispersion patterns except for pAI. CONCLUSIONS: Oscillometric arterial stiffness measurement by CAVI and baPWV has proved to be highly reproducible in Caucasians. Results of the pAI showed lower reproducibility. CAVI and baPWV can be implemented as easy-to-apply arterial stiffness measures in population wide cardiovascular risk assessment in Caucasians.

Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts.

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

Environmental tobacco smoke exposure and diabetes in adult never-smokers.

BACKGROUND: Active smoking has been linked to type 2 diabetes mellitus (T2DM) but only few recent studies have shown environmental tobacco smoke (ETS) to be associated with DM in never-smokers. We assessed the association between long term ETS exposure and DM, and explored effect modifications of this association in our sample. METHODS: We analysed 6392 participants of the Swiss study on air pollution and lung and heart diseases in adults (SAPALDIA). We used mixed logistic regression models to assess the cross-sectional association between ETS and DM. Selected variables were tested for effect modification and several sensitivity analyses were performed, mostly treating participants' study area as a random effect. RESULTS: The prevalence of DM and ETS in the sample was 5.5% and 47% respectively. There were 2779 never-smokers with 4% diabetes prevalence. Exposure to ETS increased risk of DM in never-smokers by 50% [95% confidence interval (CI): 1.00, 2.26], and we observed a positive dose-response relationship between ETS exposure level and DM in never-smokers. Associations were strengthened (more than three-folds) by older age and chronic obstructive pulmonary disease, and were stronger in post-menopausal, obese, hypertriglyceridaemic and physically inactive participants. Estimates of association were robust across all sensitivity analyses (including inverse probability weighting for participation bias and fixed-effect analysis for study area). ETS had no substantial associations in current and ex-smokers in our study. CONCLUSIONS: We found a positive association between ETS exposure and DM in never smokers. Additional longitudinal studies involving biomarkers are needed to further explore underlying mechanisms and susceptibilities.

Removable dental prostheses and difficulties with chewing among frail individuals: Results from the Swiss SAPALDIA cohort.

Oral healthcare among the frail is an underestimated geriatric care element. While neglected oral health (OH) is a well-established risk factor for frailty, frailty can be a risk factor for subsequent OH problems. The cross-sectional investigation nested into the SAPALDIA sub-cohort of citizens aged 52 years and older, aims to stimulate longitudinal research into aspects that accelerate poor OH among frail individuals. The hypothesis investigated was that (pre-) frail individuals are more likely to have missing teeth replaced with removable dental prostheses (RDP) resulting in difficulties with chewing. The study included 1489 participants undergoing geriatric assessments and oral examination. The main predictor was frailty status (non-frail; pre-frail; frail), based on Fried's frailty phenotype. The main outcomes of interest were non-functional dentition (presence of ≤ 19 natural teeth), presence of any RDP and self-reported difficulties with chewing. Pre-frailty and frailty were not associated with the presence of ≤ 19 natural teeth, but were associated with a higher RDP prevalence. The presence of at least one complete denture (CD) had 1.71 fold and 2.54 folds higher odds among pre-frail and frail, respectively, compared to non-frail individuals. Frail individuals with CD reported chewing difficulties 7.8 times more often than non-frail individuals without CD. The results are in line with the hypothesis that (pre-) frail individuals may be more likely to have tooth loss restored by RDPs. Future longitudinal research needs to assess potential barriers to oral hygiene and fixed dental prostheses among (pre-) frail and to study their oral health-related quality of life.

Cross-Sectional but Not Prospective Association of Accelerometry-Derived Physical Activity With Quality of Life in Children and Adolescents.

Objectives: This study aims to quantify the cross-sectional and prospective associations between quality of life (QoL) and moderate-to-vigorous physical activity (MVPA). Methods: This study was based on the Swiss children's Objectively measured PHYsical Activity cohort. The primary endpoint is the overall QoL score and its six dimensions. The main predictor is the average time spent in MVPA per day. Linear mixed effects and linear regression models respectively were used to investigate the cross-sectional and prospective associations between MVPA and QoL. Results: There were 352 participants in the study with complete data from baseline (2013-2015) and follow-up (2019). MVPA was positively associated with overall QoL and physical wellbeing (p = 0.023 and 0.002 respectively). The between-subject MVPA was positively associated with the overall QoL, physical wellbeing, and social wellbeing (p = 0.030, 0.017, and 0.028 respectively). Within-subject MVPA was positively associated with physical wellbeing and functioning at school (p = 0.039 and 0.013 respectively). Baseline MVPA was not associated with QoL 5 years later. Conclusion: Future longitudinal studies should employ shorter follow-up times and repeat measurements to assess the PA and QoL association.

Inhaled glucocorticoids during pregnancy and offspring pediatric diseases: a national cohort study.

RATIONALE: Glucocorticoid inhalation is the preferred asthma treatment during pregnancy. Previous studies on its safety focused on obstetric outcomes and offspring malformations. OBJECTIVES: To determine whether glucocorticoid inhalation during pregnancy is a risk factor for offspring pediatric diseases. METHODS: We studied offspring (live singletons) of pregnant women suffering from asthma during pregnancy (prevalence = 6.3%; n = 4,083 mother-child pairs) from the Danish National Birth Cohort (births, 1996-2002; prospective data). We estimated the associations between use of inhaled glucocorticoids for asthma treatment during pregnancy (n = 1231; 79.9% budesonide, 17.6% fluticasone, 5.4% beclomethasone, and 0.9% other or unspecified glucocorticoids) and offspring diseases (International Classification of Diseases-10th Revision, diagnoses) during childhood. We conducted Cox or logistic regression analyses for each International Classification of Diseases-10th Revision category, controlling for use of non-glucocorticoid-containing inhalants, and confirmed results by addressing confounding by treatment indication using propensity score. MEASUREMENTS AND MAIN RESULTS: Offspring median age at end of follow-up was 6.1 (range, 3.6-8.9) years. Glucocorticoid inhalation was not associated with offspring disease risk in most categories, except for offspring endocrine, metabolic, and nutritional disorders (hazard ratio, 1.84; 95% confidence interval, 1.13-2.99). When repeating analyses with the major subgroup that used budesonide only, association estimates were of similar magnitude. CONCLUSIONS: Regarding most disease categories, data are reassuring, supporting the use of inhaled glucocorticoids during pregnancy. In line with animal data, glucocorticoid inhalation during pregnancy may be a risk factor for offspring endocrine and metabolic disturbances, which should be considered further.