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A large body of evidence underscores the adverse effect of long-term exposure to ambient particulate matter (PM) air pollution on respiratory health (Brunekreef and Forsberg 2005; Gotschi et al. 2008). Among adults in Switzerland, we have previously demonstrated cross-sectionally that residents of more polluted areas have lower lung function (Ackermann-Liebrich et al. 1997). More recently, we presented evidence from the same population-based cohort [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA)] that decreasing exposure to airborne PM attenuated the average age-related decline in lung function. The associations were strongest for respiratory function tests reflecting small-airway function, namely, FEF25–75 [forced expiratory flow between 25% and 75% of forced vital capacity (FVC)] (Downs et al. 2007). Similar results from studies following interventions such as building bypasses for congested traffic routes (Burr et al. 2004; Hedley et al. 2002) or banning environmental tobacco smoke (ETS) exposure (Goodman et al. 2007; Menzies et al. 2006) showed that the improvements in air quality were accompanied by a decrease in cardiopulmonary mortality and an improvement in respiratory symptoms and lung function. However, it is still unknown whether all subjects benefit equally from a reduction in air pollution. Variation in genes mediating the pathobiological effect of air pollution in the lung may codetermine the degree to which a person benefits from better air quality. Experimental evidence indicates that PM alters expression of tumor protein gene p53, cyclin-dependent kinase inhibitor 1A gene (p21), and the cyclin D1 gene (CCND1) and subsequently affects cell proliferation and apoptosis of lung fibroblasts, lymphocytes, and alveolar epithelial cells (Bayram et al. 2006; Dagher et al. 2006; Nyunoya et al. 2006; Rosas Perez et al. 2007; Soberanes et al. 2006). PM is furthermore well known to induce oxidative stress in the airways (Li et al. 2008). In fact, the expression of all three gene candidates, p53, p21, and CCND1, in bronchial epithelial cells and lung fibroblasts seems to be regulated in part by redox-dependent mechanisms (Jiao et al. 2008; Ranjan et al. 2006; Yao et al. 2008). The tumor suppressor p53, a nuclear transcription factor, binds to response elements in the promoter region of many genes and plays a pivotal role in apoptosis. It induces up-regulation of the expression of many pro-apoptotic genes and down-regulation of anti-apoptotic genes (Oren et al. 2002). CCND1 (cyclin D1) is known to promote cell proliferation through cell cycle G1–S phase transition. The protein p21 (also known as Waf1 or Cip1) is a direct functional counterpart of CCND1 and an important downstream effector of p53 action that negatively regulates cell proliferation. CCND1, p21, and p53 all harbor polymorphisms of hypothesized functional relevance that have been extensively studied in the context of cancer (Choi et al. 2008; Lu et al. 2008; Zhou et al. 2007). In this study, we examined whether these polymorphisms modified the degree to which the age-related FEF25–75 decline was attenuated by reduced exposure to PM with aerodynamic diameter ≤ 10 μm (PM10).

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

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown. Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction. Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, ≥ 50 years of age, who answered a detailed questionnaire regarding their use of household cleaning products in their homes. The adjusted average percent changes in standard deviation of all normal-to-normal intervals in 24 hr (24-hr SDNN) and total power (TP) were estimated in multiple linear regression in association with frequency [< 1, 1–3, or 4–7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products. Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4–7 days/week was associated with 11% [95% confidence interval (CI): –20%, –2%] and 29% (95% CI: –46%, –8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p < 0.05 for interactions). Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptible.

BACKGROUND Studies on perimenstrual asthma are inconsistent and different methodologies limit comparisons. OBJECTIVE To investigate cyclic variations in bronchial hyperreactivity (BHR) to methacholine in premenopausal women in a population based cohort and assess effect modification by oral contraceptives (OCs). METHODS Day of menstruation cycle at the time of methacholine challenge was calculated in 571 menstruating women without hormonal treatment age 28 to 58 years on the basis of questionnaire data from the Swiss cohort study on Air Pollution And Lung Disease In Adults (SAPALDIA) cohort 2001/2002. A window of risk was defined 3 days before and after the first day of menstruation. Logistic and linear regression analyses were performed adjusting for main predictors of BHR and stratifying for asthma status. The impact of OCs was studied in the same sample enlarged by 130 women taking OCs. RESULTS The prevalence of BHR was 13 (fall of > or =20 in FEV(1) up to a maximal cumulative dose of 2 mg) and 6 had asthma. A total of 143 women had undergone methacholine challenge within the risk window. We observed a significant increase in BHR within the window of risk (odds ratio [OR] 2.3; 95 CI 1.27 4.29). A cyclic association pattern was confirmed by trigonometric functions. Effect modification by asthma status and oral contraceptive use was found with lower OR in subjects without asthma and OR

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

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been shown to increase the risk for cardiovascular diseases and death, and autonomic dysfunction (specifically, reduced heart rate variability (HRV)) is a predictor of increased cardiac risk. This study tests the hypothesis that ETS exposure reduces HRV in the general population and discusses possible pathways. METHODS: This cross-sectional study was conducted between 2001 and 2003 and is part of the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung Diseases in Adults) study. The analysis included 1218 randomly selected non-smokers aged 50 and above who participated in 24-h electrocardiogram recordings. Other examinations included an interview, investigating health status (especially respiratory and cardiovascular health and health relevant behaviours and exposure to ETS) and measurements of blood pressure, body height and weight. RESULTS: Subjects exposed to ETS at home or at work for more than 2 h/day had a difference of -15% in total power (95%CI: -26 to -3%), low frequency power (-28 to -1%), low/high frequency ratio (-26 to -3%) and -18% (-29 to -4%) in ultralow frequency power of HRV compared with subjects not exposed to ETS at home or work. We also found a 2.7% (-0.01 to 5.34%) higher heart rate during the recording in exposed subjects. CONCLUSIONS: Exposure to ETS at home and work is associated with lower HRV and with higher heart rate in an ageing population. Our findings suggest that exposure to ETS increases cardiac risk through disturbances in the autonomic nervous system.

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.

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

In air pollution epidemiology, estimates of long term exposure are often based on measurements made at one fixed site monitor per area. This may lead to exposure misclassification. The present paper validates a questionnaire-based indicator of ambient air pollution levels and its applicability to assess their within-area variability. Within the framework of the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cross-sectional study (1991), 9,651 participants reported their level of annoyance caused by air pollution on an 11-point scale. This subjective measure was compared with annual mean concentrations of particulate matter less than 10 μm in diameter (PM 10 ) and nitrogen dioxide. The impact of individual factors on reported scores was evaluated. Nitrogen dioxide concentrations at home outdoors (measured in 1993), smoking, workplace dust exposure, and respiratory symptoms were found to be predictors of individual annoyance scores. Regression of population mean annoyance scores against annual mean PM 10 and nitrogen dioxide concentrations (measured in 1993 and 1991, respectively) across areas showed a linear relation and strong correlations (r> 0.85). Analysis within areas yielded consistent results. The observed associations between subjective and objective air pollution exposure estimates suggest that population mean scores, but not individual scores, may serve as a simple tool for grading air quality within areas. Reported annoyance due to air pollution should be considered an indicator for a complex environmental condition and thus might be used for evaluating the implementation of environmental policies.

Question under study Pulmonary function testing (PFT) in longitudinal studies involves the repeated use of spirometers over long time periods. We assess the comparability of PFT results taken under biologic field conditions using thirteen certified devices of various technology and age. Comparability of measurements across devices and over time is relevant both in clinical and epidemiological research. Methods Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1) and Forced Expiratory Flow 50% (FEF50) were compared before and after the data collection of the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) and the European Community Respiratory Health Survey (ECRHS) cohort studies. Three test series were conducted with 46, 50 and 56 volunteers using various combinations of spirometers to compare the eight flow-sensing spirometers (Sensormedics 2200) used in the SAPALDIA cross-sectional and follow-up, two new flow-sensing instruments (Sensormedics Vmax) and three volume displacement spirometers (two Biomedin/Baires and one Sensormedics 2400). Results The initial comparison (1999/2000) of eight Sensormedics 2200 and the follow-up comparison (2003) of the same devices revealed a maximal variation of up to 2.6% for FVC, 2.4% for FEV1 and 2.8% for FEF50 across devices with no indication of systematic differences between spirometers. Results were also reproducible between Biomedin, Sensormedics 2200 and 2400. The new generation of Sensormedics (Vmax) gave systematically lower results. Conclusions The study demonstrates the need to conduct spirometer comparison tests with humans. For follow-up studies we strongly recommend the use of the same spirometers.

Background: Because of changing world demographics, the elderly population is steadily increasing. Few studies have assessed the prevalence of atopy and allergic diseases in elderly persons with objective measures. The aim of this paper is to describe the prevalence of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma in persons over the age of 60 in Switzerland. Methods: The cross-sectional examination of the Swiss Study on Air Pollution and Health in Adults (SAPALDIA 1), performed in 1991, included 9,651 adults aged 18-60 years. In 2001-2002 the same subjects were invited for a follow-up examination (SAPALDIA 2). Serum samples collected at baseline and follow-up were tested for specific IgE sensitization with the Phadiatop® (Phadia, Uppsala, Sweden, now Thermo Fisher Scientific) assay containing a mixture of common respiratory allergens (grass, birch, mugwort, Parietaria and olive pollen, dog, cat, horse, Cladosporium herbarum, house dust mite and flour mite). Atopy was defined as a positive result in the Phadiatop test according to guidelines by the manufacturer. The prevalence rates of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma were evaluated by sex and age group (≤60 or >60 years). Results: 7,667 subjects (men = 3,692/women = 3,975) participated in the follow-up by responding to a detailed questionnaire (80% of SAPALDIA 1 participants). Phadiatop results were available for 5,835 participants (men = 2,839/women = 2,996). Prevalence rates of atopy (Phadiatop positive) were 36.4% in men aged ≤60 years versus 26.2% in men aged >60 years and 30.6 and 18.1% in women, respectively (both p < 0.001). Prevalence rates of self-reported allergic rhinitis in subjects >60 years old were 13.0% for men and 15.4% for women (p = 0.12), and for doctor's diagnosed asthma 6.6% versus 7.6%, respectively (p = 0.40). Both rhinitis and asthma prevalences were higher in persons Conclusions: According to our estimates, the prevalence of allergic rhinitis among persons aged between 60 and 70 years in Switzerland in the present cohort is of the order of 13-15% and should not be underestimated, although it is lower than in age groups ≤60 years.

Background Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. Methods In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels ≤ 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. Results Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking. Conclusion The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

Reproductive characteristics play an aetiological role for many diseases, including reproductive cancers. They have been shown to vary internationally and nationally, but have not yet been described for the whole Swiss population.The study investigated the variability of reproductive characteristics, their patterns, and main determinants across a population-based female study population in Switzerland.Reproductive characteristics obtained from 3119 women (28-72 years) participating in the SAPALDIA cohort survey in 2001-2003 are described across birth cohorts, study areas, language regions, and levels of urbanization. Determinants of age at menopause were analysed by Cox regression.Reported median age at menarche was 13 years and median age at natural menopause was 52 years. The prevalence of nulliparity was 27%, and the fertility rate 1.6. Across birth cohorts there was a decline of menarcheal age and fertility rates, and an increase of nulliparity and age at last pregnancy. All characteristics varied across study areas, language regions, and levels of urbanization. Smoking, parity, and physical exercise were stronger predictors of earlier (52 years) than older (52 years) menopausal age.Reproductive events show secular and geographic variation within Switzerland. Smoking, parity and physical activity significantly predict age at natural menopause, particularly before age 52. The secular trend of earlier menarche and increased nulliparity may result in a higher risk of reproductive cancers in younger generations.

BackgroundAtopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations.MethodsTwo prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis.ResultsWe confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever.ConclusionComprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes.