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.

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.

Spirometer Replacement and Serial Lung Function Measurements in Population Studies: Results From the SAPALDIA Study.

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.

Gender differences in adult-onset asthma: results from the Swiss SAPALDIA cohort study.

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.

Serum bilirubin is associated with lung function in a Swiss general population sample.

Bilirubin is a strong antioxidant. Increased serum levels have been associated with lower respiratory disease and mortality risk. We studied the association of bilirubin with lung function in the Swiss study on Air Pollution and Lung Disease in adults (SAPALDIA) cohort. Associations between natural logarithmised bilirubin and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and mean forced expiratory flow between 25%-75% of FVC (FEF25-75%) were tested using multiple linear regression in the whole study population (n=4195) and strata of ever-smoking and high body mass index (BMI, defined by the highest distribution quartile). Associations were retested with single nucleotide polymorphism rs6742078, a genetic determinant of bilirubin. High bilirubin levels were significantly associated with higher FEV1/FVC and FEF25-75% overall. Upon stratification, significant associations persisted in ever-smokers, amounting to 1.1% (95% CI 0.1-2.2%) increase in FEV1/FVC, and 116.2 mL·s(-1) (95% CI -15.9-248.4 mL·s(-1)) in FEF25-75% per interquartile range of bilirubin exposure in smokers with high BMI. Associations were positive but nonsignificant in never-smokers with high BMI. Similarly, rs6742078 genotype TT was associated with increased FEV1/FVC and FEF25-75%. Our results suggest a possible protective role of bilirubin on lung tissue, which could be important for prevention and therapy.

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.

Occupational exposure to dusts, gases, and fumes and incidence of chronic obstructive pulmonary disease in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults.

RATIONALE: There is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures. OBJECTIVES: We evaluated the association between occupational exposures and incidence of COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). MEASUREMENTS AND MAIN RESULTS: Prebronchodilator ratio of forced expiratory volume in 1 second over forced vital capacity (FEV(1)/FVC) was measured in 4,267 nonasthmatic SAPALDIA participants ages 18-62 at baseline in 1991 and at follow-up in 2001-2003. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (FEV(1)/FVC < 0.70) and Quanjer reference equation (FEV(1)/FVC < lower limit of normal [LLN]), and categorized by severity (≥ 80% and <80% predicted FEV(1) for stage I and stage II+, respectively). Using a job-exposure matrix, self-reported occupations at baseline were assigned exposures to biological dusts, mineral dusts, gases/fumes, and vapors, gases, dusts, or fumes (VGDF) (high, low, or unexposed as reference). Adjusted incident rate ratios (IRRs) of stage I and stage II+ COPD were estimated in mixed Poisson regression models. Statistically significant (P < 0.05) IRRs of stage II+ GOLD and LLN-COPD, indicating risks between two- and fivefold, were observed for all occupational exposures at high levels. Occupational exposure-associated risk of stage II+ COPD was observed mainly in males and ages ≥ 40 years, and remained elevated when restricted to nonsmokers. CONCLUSIONS: In a Swiss working adult population, occupational exposures to biological dusts, mineral dusts, gases/fumes, and VGDF were associated with incidence of COPD of at least moderate severity.

Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.

Improvements in PM10 exposure and reduced rates of respiratory symptoms in a cohort of Swiss adults (SAPALDIA).

RATIONALE: Reductions in mortality following improvements in air quality were documented by several studies, and our group found, in an earlier analysis, that decreasing particulate levels attenuate lung function decline in adults. OBJECTIVES: We investigated whether decreases in particulates with an aerodynamic diameter of less than 10 microm (PM10) were associated with lower rates of reporting respiratory symptoms (i.e., decreased morbidity) on follow-up. METHODS: The present analysis includes 7,019 subjects who underwent detailed baseline examinations in 1991 and a follow-up interview in 2002. Each subject was assigned model-based estimates of average PM10 during the 12 months preceding each health assessment and the difference was used as the exposure variable of interest (DeltaPM10). Analyses were stratified by symptom status at baseline and associations between DeltaPM10 and change in symptom status during follow-up were adjusted for important baseline characteristics, smoking status at follow-up, and season. We then estimated adjusted odds ratios for symptoms at follow-up and numbers of symptomatic cases prevented due to the observed reductions in PM10. MEASUREMENTS AND MAIN RESULTS: Residential exposure to PM10 was lower in 2002 than in 1991 (mean decline 6.2 microg/m3; SD = 3.9 microg/m3). Estimated benefits (per 10,000 persons) attributable to the observed changes in PM10-levels were: 259 (95% confidence interval [CI]: 102-416) fewer subjects with regular cough, 179 (95% CI, 30-328) fewer subjects with chronic cough or phlegm and 137 (95% CI, 9-266) fewer subjects with wheezing and breathlessness. CONCLUSIONS: Reductions in particle levels in Switzerland over the 11-year follow-up period had a beneficial effect on respiratory symptoms among adults.

Transportation noise exposure, noise annoyance and respiratory health in adults: A repeated-measures study.

Transportation noise leads to sleep disturbance and to psychological and physiological sustained stress reactions, which could impact respiratory health. However, epidemiologic evidence on associations of objective transportation noise exposure and also perceived noise annoyance with respiratory morbidity is limited. We investigated independent associations of transportation noise exposure and noise annoyance with prevalent respiratory symptoms and incident asthma in adults. Using 17,138 observations (from 7049 participants) from three SAPALDIA (Swiss Cohort Study on Lung and Heart Diseases in Adults) surveys, we assessed associations of transportation noise exposure and noise annoyance with prevalent respiratory symptoms, and with incident asthma (in 10,657 nested observations from 6377 participants). Annual day-evening-night transportation noise comprising road, railway and aircraft Lden (Transportation Lden) was calculated for the most exposed façade of participants' residence using Swiss noise models. Transportation noise annoyance was assessed using an 11-point scale, and participants reported respiratory symptoms and doctor-diagnosed asthma at each survey. We estimated associations with transportation Lden (as well as source-specific Lden) and noise annoyance, independent of air pollution and other potential confounders, using mutually-adjusted mixed logistic and Poisson models and applying random intercepts at the level of the participants. Prevalent respiratory symptoms ranged from 5% (nocturnal dyspnoea) to 23% (regular cough/phlegm). Transportation noise annoyance, but not Lden, was independently associated with respiratory symptoms and current asthma in all participants, with odds ratios (OR) and 95% confidence intervals (CI) ranging between 1.03 (95%CI: 1.01, 1.06) and 1.07 (95% CI: 1.04, 1.11) per 1-point difference in noise annoyance. Both noise annoyance and Lden showed independent associations with asthma symptoms among asthmatics, especially in those reporting adult-onset asthma [ORLden: 1.90 (95% CI: 1.25, 2.89) per 10 dB; p-value of interaction (adult-onset vs. childhood-onset): 0.03; ORnoise annoyance: 1.06 (95%CI: 0.97, 1.16) per 1-point difference; p-value of interaction: 0.06]. No associations were found with incident asthma. Transportation noise level and annoyance contributed to symptom exacerbation in adult asthma. This suggests both psychological and physiological noise reactions on the respiratory system, and could be relevant for asthma care. More studies are needed to better understand the effects of objective and perceived noise in asthma aetiology and overall respiratory health.

Alpha-1 antitrypsin deficiency: From the lung to the heart?

BACKGROUND AND AIMS: Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. METHODS: Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact. RESULTS: Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2% (95%-confidence interval -0.1-2.5) increase in CIMT per unit (p = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0-1.5) per unit (p = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9-1.9)). CONCLUSIONS: Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives.

Early menarche and new onset of asthma: Results from the SAPALDIA cohort study.

RATIONALE: The association between early menarche and new onset of asthma warrants further investigation in those aged >30 years. OBJECTIVES: Using data from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), we investigated whether early menarche was associated with new onset of asthma in women aged 18-60 years at baseline. METHODS: Our analysis included 2492 women with information on age at menarche and doctor-diagnosed asthma, who had been asthma free at the time of menarche and had complete covariate information. New onset of asthma was defined as newly reported doctor-diagnosed asthma which occurred at least one year after menarche. Asthma incidence and its association with early menarche was analysed using logistic regression, adjusting for age, atopy, smoking, BMI, parental asthma, urbanity, education and study area, and additionally stratifying by atopy and BMI. RESULTS: After adjustment of relevant confounders, women with early menarche did not have a significantly higher risk of onset of asthma than women without early menarche (OR 1.23, 95% CI 0.85-1.80). Young atopic women with early menarche appeared to have an increased risk of asthma compared with non-atopic women (OR 2.21, 95% CI 0.90-5.43); however, our results did not reach statistical significance. CONCLUSION: We could not substantiate an association of early menarche with new onset of asthma in this Swiss population-based cohort aged 18-60 years at baseline. Future studies may need to prospectively assess age of menarche to investigate the association with new onset of asthma in those aged >30 years.

The adverse impact of obesity on heart rate variability is modified by a NFE2L2 gene variant: The SAPALDIA cohort.

BACKGROUND: Overweight has been associated with an increase in inflammatory markers and with an imbalance in the autonomic nervous system, such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of a genetic variation in a major anti-inflammatory marker gene, NFE2L2, on the relationship between overweight and HRV. METHODS: We analyzed participants of the SAPALDIA cohort aged 50years and older, twice in 2002/2003 (N=1472) and 2010/2011 (N=1235). We included persons with valid genotype data, who underwent ambulatory 24-h electrocardiogram monitoring, and reported on medical history and lifestyle. The association between HRV and BMI, measured as standard deviation of normal-to-normal intervals (SDNN) by BMI and the modifying effect of the cardiovascular health-related NFE2L2 gene variant rs2364723 were tested, applying multivariable mixed linear regression models. RESULTS: We found study participants with overweight (BMI>25) over two follow-up surveys 10years apart to have a negative association between SDNN, calculated as geometric means, with BMI. The examined NFE2L2 variant sustainably modified (pinteraction=0.014) the found inverse association between a BMI increment and SDNN, causing a stronger decrement in SDNN for participants with the CC genotype (-20.7%; 95%-confidence interval: -12.33 to -28.28) compared with participants carrying the GC (-7.43; 95%CI: -3.56 to -11.15) or GG (-11.26%; 95%CI: -7.68 to -14.7) genotype, estimated for the difference from the 90th to the 10th percentile of BMI by the NFE2L2 variant. CONCLUSIONS: Our results are consistent with the hypothesis that overweight decreases heart rate variability through inflammatory processes.

Factors associated with cessation of smoking among Swiss adults between 1991 and 2011: results from the SAPALDIA cohort.

INTRODUCTION: Smoking is still the most preventable cause of disease and premature death in Switzerland, as elsewhere. We aimed to assess the main determinants of smoking cessation in the population-based cohort of SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). METHODS: The SAPALDIA study was initiated in 1991 with 9651 participants aged 18 to 60 years from eight areas (S1). Follow-up assessments were conducted in 2002 (S2; 8047 participants) and 2010/11 (S3; 6088 participants). At each survey, detailed information on health and potential health-related factors was collected and lung function measured. Using logistic regression, we assessed predictors of smoking cessation between S1 and S2 and between S2 and S3. RESULTS: In both periods, highest educational level (summary odds ratio [OR] 1.49, 95% confidence interval [CI] 1.08-2.06; ref. lowest level), FEV1/FVC <0.5 (OR 6.19, 95% CI 2.44-15.7, ref. FEV1/FVC ≥0.7), higher age in men (OR 1.02, 95% CI 1.01-1.03, per year) and overweight (OR 1.38, 95% CI 1.16-1.64) were significant predictors of smoking cessation. Nicotine dependence (OR 0.97, 95% CI 0.96-0.98, per cigarette smoked a day) and female sex between age 45 and 60 (e.g., OR 0.74, 95% CI 0.61-0.91, at age 50) were negatively associated with smoking cessation. Moreover, smokers at S2 reporting a diagnosis of depression were less likely to quit smoking by S3 (OR 0.53, 95% CI 0.30-0.93). CONCLUSIONS: Prospective tobacco control policies in Switzerland should be addressed to women, younger persons and persons of lower education.

Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study.

BACKGROUND: The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. METHODS: In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18-60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. RESULTS: In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002). CONCLUSION: There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

Infectious diseases are associated with carotid intima media thickness in adolescence.

OBJECTIVE: Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence. STUDY DESIGN: 288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex. RESULTS: Youth (mean age 14.8 yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported ≥3 infectious diseases (p = 0.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p = 0.567). Sex-stratified analyses yielded significantly increased CIMT in boys with ≥3 infectious diseases vs. none (0.046 mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011 mm, 95%CI -0.015; 0.036). CONCLUSION: The SAPALDIA Youth study complements current evidence on infectious origins of atherosclerosis in adults. The larger effects observed in boys may relate to a higher vulnerability of the vasculature and/or to infectious pathogens. Our data are suggestive of an early impact of childhood infectious diseases on vascular health.

Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

BACKGROUND: Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date. OBJECTIVES: We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample. METHODS: A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the forced mid-expiratory flow (FEF25-75%) was the main end point. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure. RESULTS: We identified a cluster of variants intronic to the CDH13 gene as the only locus with genome-wide significant interactions. The strongest interaction was observed for rs2325934 (p = 8.8 × 10(-10)). Replication of the interaction between this CDH13 variant and cumulative PM10 exposure on annual decline in FEF25-75% was successful (p = 0.008). The interaction was not sensitive to adjustment for smoking or body weight. CONCLUSIONS: CDH13 is functionally linked to the adipokine adiponectin, an inflammatory regulator. Future studies need to confirm the interaction and assess how the result relates to previously observed interactions between air pollution and obesity on respiratory function.

Is there a differential impact of parity on blood pressure by age?

OBJECTIVE: In pregnancy, women experience metabolic and hemodynamic changes of potential long-term impact. Conflicting evidence exists on the impact on blood pressure (BP). We investigated the association between parity and BP in the Swiss Study on Air Pollution And Lung and Heart Disease In Adults cohort. METHODS: Multilevel linear and logistic regression analyses were performed in 2837 women aged 30-73 years, with data on parity, number of births, BP, and doctor-diagnosed hypertension adjusting for potential confounders. Hypertension was defined as at least 140/90 mmHg, doctor diagnosed or taking relevant treatment. Stratified analyses were performed by age (<40, 40-59, and ≥60 years) and menopausal status. RESULTS: Parous women had a mean of 2.3 pregnancies (SD 0.95, range 1-7). A total of 26% were nulliparous. Mean BP was 119/76 mmHg in nulliparous and 121/76 mmHg in parous women. Parity had a significant adverse effect on BP in women at least 60 years [SBP 5.6 mmHg, 95% confidence interval (CI) 2.3 to 8.9; DBP 1.8 mmHg, 95% CI 0.1 to 3.6] and protective effect in women below 40 years (SBP -3.4 mmHg, 95% CI -5.8 to -1.0; DBP -0.2 mmHg, 95% CI -1.0 to 0.6). With increasing number of births, SBP (mmHg/birth; 95% CI) increased in older (1.2, 95% CI 0.2 to 2.2) and decreased in younger women (-1.6, 95% CI -2.6 to -0.5). Opposite effects of parity were also found for diagnosed hypertension. No interaction by menopausal status was found. CONCLUSION: Our analyses yield differential effects of parity on BP in older vs. younger women. Reductions in BP in younger parous women have been described before; the opposite impact in older women is new. The findings may constitute biological mechanisms in an aging population or reflect birth cohort effects.