The role of air pollution and lung function in cognitive impairment.

Air pollution has been associated with impaired lung and cognitive function, especially impairment in visuo-construction performance (VCP). In this article, we evaluate whether the effect of air pollution on VCP is mediated by lung function.We used data from the SALIA cohort (baseline 1985-1994 and follow-up 2007-2010) including 587 women aged 55 years at baseline. Particulate matter (PM) and nitrogen dioxide (NO2) exposures at baseline were estimated via land-use regression models. Lung function was characterised by averages between baseline and follow-up. We used age- and height-controlled Global Lung Initiative (GLI) z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC. VCP was assessed at follow-up with the CERAD-Plus neuropsychological test battery and causal mediation analysis was conducted.An increase of one interquartile range in FEV1 and FVC was positively associated with VCP (ß=0.18 (95% CI 0.02-0.34) and ß=0.23 (95% CI 0.07-0.39), respectively). The proportion of the association between NO2 on VCP mediated by FEV1 was 6.2% and this was higher in never smokers (7.2%) and non-carriers of the APOE-ε4 allele (11.2%). However, none of the mediations were statistically significant.In conclusion, air pollution associated VCP was partially mediated by lung function. Further studies on the mechanisms underlying this pathway are required to develop new strategies to prevent air pollution induced cognitive impairment.

A Time-Series Study of the Effect of Air Pollution on Outpatient Visits for Acne Vulgaris in Beijing.

BACKGROUND/AIMS: There is increasing evidence that exposure to air pollutants, including particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2), might aggravate preexisting skin diseases such as eczema and urticaria. Here we investigated if a possible link exists between air pollution and acne vulgaris. We assessed the association between ambient air pollutant concentrations and the number of visits of patients for acne vulgaris to a dermatological outpatient clinic in Beijing, China, from April 1, 2012 to April 30, 2014. METHODS: In this time period, 59,325 outpatient visits were recorded because of acne vulgaris. Daily air pollution parameters for PM10, PM2.5, SO2, and NO2 were obtained from the Beijing Municipal Environmental Monitoring Center. RESULTS: Increased concentrations of ambient PM2.5, PM10, and NO2 were significantly associated with increased numbers of outpatient visits for acne vulgaris over the 2 years. These effects could be observed for NO2 in a single-pollutant model and for PM2.5, PM10, and NO2 in 2-pollutant models, which are closer to real-life exposure. Of note, these effects were specific because they were not observed for increased SO2 concentrations, which even showed negative correlations in all test models. CONCLUSION: This study provides indirect evidence for a link between acne vulgaris and air pollution.

Genetic susceptibility for air pollution-induced airway inflammation in the SALIA study.

BACKGROUND: Long-term air pollution exposure has been associated with chronic inflammation providing a link to the development of chronic health effects. Furthermore, there is evidence that pathways activated by endoplasmatic reticulum (ER) stress induce airway inflammation and thereby play an important role in the pathogenesis of inflammatory diseases. OBJECTIVE: We investigated the role of genetic variation of the ER stress pathway on air pollution-induced inflammation. METHODS: We used the follow-up examination of the German SALIA study (N=402, age 68-79 years). Biomarkers of inflammation were determined in induced sputum. We calculated biomarker-specific weighted genetic risk scores (GRS) out of eight ER stress related single nucleotide polymorphisms and tested their interaction with PM2.5, PM2.5 absorbance, PM10 and NO2 exposure on inflammation by adjusted linear regression. RESULTS: Genetic variation of the ER stress pathway was associated with higher concentration of inflammation-related biomarkers (levels of leukotriene (LT)B4, tumor necrosis factor-α (TNF-α), the total number of cells and nitric oxide (NO) derivatives). Furthermore, we observed a significant interaction between air pollution exposure and the ER stress risk score on the concentration of inflammation-related biomarkers. The strongest gene-environment interaction was found for LTB4 (PM2.5: p-value=0.002, PM2.5 absorbance: p-value=0.002, PM10: p-value=0.001 and NO2: p-value=0.004). Women with a high GRS had a 38% (95%-CI: 16-64%) higher LTB4 level for an increase of 2.06µg/m³(IQR) in PM2.5 (no associations in women with a low GRS). CONCLUSION: These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung.

Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences.

Genetic and environmental risk factors contribute to the pathogenesis of Alzheimer's dementia. Besides known genetic risk factors like the apolipoprotein (APO) Eε4 allele, single nuclear polymorphisms (SNPs) of the estrogen receptors (ESRs) are candidate genetic risk factors, while air pollution represents an environmental risk factor for dementia. Effects of these risk factors and their interaction were investigated in the SALIA cohort of 834 non-demented elderly women. Cognitive function was assessed by the CERAD-plus test battery. Air pollution was estimated by land use regression (LUR) models. Genotyping was carried out for nine ESR1 and ESR2 SNPs and two ApoE SNPs. Carriers of minor ESR2 alleles showed significantly reduced cognitive performance in the CERAD total score with most pronounced deficits in semantic memory (rs1256062, rs10144225, and rs2274705) and executive function (rs1256062). The minor allele effects of ESR2 were stronger in carriers of APOEε4 for the cognitive domain 'executive function' (p value of interaction 0.023 for rs1256062). The investigated ESR1 SNPs were not associated with cognition. Furthermore, we found a significant gene-environment interaction between the ESR2 SNP rs1256062 and air pollution on cognition. Carriers of two major alleles of rs1256062 were more susceptible for an air pollution-induced decrease in performance of 'figure copying' than carriers of minor alleles (p value of interaction, e.g., 0.031 for PM2.5). In conclusion, ESR2 but not ESR1 minor alleles were associated with lower cognitive performance in elderly women with an indication of a gene-gene interaction with APOEε4. We also found indications for gene-environment interactions of ESR2 with traffic-related air pollution exposure on cognitive performance.

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

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

Association of air pollution with cognitive functions and its modification by APOE gene variants in elderly women.

BACKGROUND: Epidemiological studies have shown effects of long-term exposure to air pollution on cardiovascular and respiratory health. However, studies investigating the effects of air pollution on cognition and brain function are limited. We investigated if neurocognitive functions are associated with air pollution exposure and whether apolipoprotein E (ApoE) alleles modify the association of air pollution exposure with cognition. METHODS: We investigated 789 women from the SALIA cohort during the 22-year follow-up examination (2008-2009). Exposure to particulate matter (PM) size fractions and nitrogen oxides (NOx) were assigned to home addresses. Traffic indicators were used to assess residential proximity to high traffic load. Level of cognitive performance was assessed using the CERAD-Plus test. Air pollution effects on cognitive functioning were estimated cross-sectionally using adjusted linear regression models. RESULTS: Air pollution was negatively associated with cognitive function and cognitive performance in the subtests for semantic memory and visuo-construction. Significant associations could be observed for figure copying with an interquartile range increase of NO2 (ß=-0.28 (95%CI:-0.44;-0.12)), NOx (ß=-0.25 (95%CI:-0.40;-0.09)), PM10 (ß=-0.14 (95%CI:-0.26;-0.02)) and PM2.5 (ß=-0.19 (95%CI:-0.36;-0.02)). The association with traffic load was significant in carriers of one or two ApoE ɛ4 risk alleles. CONCLUSION: In this study of elderly women, markers of air pollution were associated with cognitive impairment in the visuospatial domain. The association of traffic exposure is significant in participants carrying the ApoE ε4 risk allele.

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts.

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PM(coarse) OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM(10) with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM(2.5abs) (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations.

Association of ambient air pollution with the prevalence and incidence of COPD.

The role of air pollution in chronic obstructive pulmonary disease (COPD) remains uncertain. The aim was to assess the impact of chronic exposure to air pollution on COPD in four cohorts using the standardised ESCAPE exposure estimates. Annual average particulate matter (PM), nitrogen oxides (NOx) and road traffic exposure were assigned to home addresses using land-use regression models. COPD was defined by NHANES reference equation (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal) and the Global Initiative for Chronic Obstructive Lung Disease criterion (FEV1/FVC <0.70) and categorised by severity in non-asthmatics. We included 6550 subjects with assigned NOx and 3692 with PM measures. COPD was not associated with NO2 or PM10 in any individual cohort. In meta-analyses only NO2, NOx, PM10 and the traffic indicators were positively, although not significantly, associated with COPD. The only statistically significant associations were seen in females (COPD prevalence using GOLD: OR 1.57, 95% CI 1.11-2.23; and incidence: OR 1.79, 95% CI 1.21-2.68). None of the principal results were statistically significant, the weak positive associations of exposure with COPD and the significant subgroup findings need to be evaluated in further well standardised cohorts followed up for longer time, and with time-matched exposure assignments.

Investigating the spill-over hypothesis: analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma.

Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis. Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables. Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥-0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin. In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.

Air pollution and subclinical airway inflammation in the SALIA cohort study.

BACKGROUND: The association between long-term exposure to air pollution and local inflammation in the lung has rarely been investigated in the general population of elderly subjects before. We investigated this association in a population-based cohort of elderly women from Germany. METHODS: In a follow-up examination of the SALIA cohort study in 2008/2009, 402 women aged 68 to 79 years from the Ruhr Area and Borken (Germany) were clinically examined. Inflammatory markers were determined in exhaled breath condensate (EBC) and in induced sputum (IS). We used traffic indicators and measured air pollutants at single monitoring stations in the study area to assess individual traffic exposure and long-term air pollution background exposure. Additionally long-term residential exposure to air pollution was estimated using land-use regression (LUR) models. We applied multiple logistic and linear regression analyses adjusted for age, indoor mould, smoking, passive smoking and socio-economic status and additionally conducted sensitivity analyses. RESULTS: Inflammatory markers showed a high variability between the individuals and were higher with higher exposure to air pollution. NO derivatives, leukotriene (LT) B4 and tumour necrosis factor-α (TNF-α) showed the strongest associations. An increase of 9.42 µg/m3 (interquartile range) in LUR modelled NO2 was associated with measureable LTB4 level (level with values above the detection limit) in EBC (odds ratio: 1.38, 95% CI: 1.02 -1.86) as well as with LTB4 in IS (%-change: 19%, 95% CI: 7% - 32%). The results remained consistent after exclusion of subpopulations with risk factors for inflammation (smoking, respiratory diseases, mould infestation) and after extension of models with additional adjustment for season of examination, mass of IS and urban/rural living as sensitivity analyses. CONCLUSIONS: In this analysis of the SALIA study we found that long-term exposure to air pollutants from traffic and industrial sources was associated with an increase of several inflammatory markers in EBC and in IS. We conclude that long-term exposure to air pollution might lead to changes in the inflammatory marker profile in the lower airways in an elderly female population.

High frequency of diastolic dysfunction in a population-based cohort of elderly women--but poor association with the symptom dyspnea.

BACKGROUND: The European Society of Cardiology recently proposed a new algorithm "How to diagnose heart failure with normal ejection fraction". Central element of the diagnostic strategy is the demonstration of diastolic dysfunction, either by tissue Doppler-derived indices in first line, or in second line by a combination of elevated blood levels of natriuretic peptide with abnormal tissue Doppler findings. We thought to use this diagnostic flowchart in a population-based cohort of elderly women, in whom the prevalence of diastolic dysfunction and heart failure is believed to be high. The purpose was to evaluate the association of dyspnea with the presence of diastolic dysfunction. METHODS: The study cohort recruited from a cross-sectional follow-up examination of the SALIA cohort (study on the influence of air pollution on lung function, inflammation, and aging). Participants with cardiac or pulmonary disease were excluded, 291 participants formed the final study group (all women, age range 69 to 79 years, all in sinus rhythm, LV ejection fraction > 50%, LV enddiastolic volume index < 97 mL/m2). Quality of life was assessed by the Minnesota living with heart failure questionnaire, and actual symptoms by a structural questionnaire; the examination consisted of a physical examination, measurement of B-type natriuretic peptide, ECG and tissue Doppler echocardiography. Diastolic dysfunction was assumed when the E/E' ratio exceeded 15 as derived from tissue Doppler. In case, tissue Doppler yielded an E/E' ratio ranging from 8 to 15, additional non-invasive parameters had to be fulfilled: left atrial volume index > 40 ml/m2 body surface, or left ventricular mass index > 122 g/m2 body surface, or transmitral E/A ratio < 0.5 plus deceleration time > 280 ms, or blood level of brain natriuretic peptide (BNP) > 200 pg/mL. RESULTS: The examinations were concordant with the presence of diastolic dysfunction in 122/291 participants (41.9%). The diagnosis based in 94% of cases on two criteria: in 50 cases on the criterion "E/E' ratio > 15", and in 65 cases on the criterion "15 > E/E'>8 and LV mass index > 122 g/m2". The participants with diastolic dysfunction had on average a higher body mass index, more frequent a history of arterial hypertension and of hospitalization for congestive heart failure, poorer quality of life, and higher BNP blood levels as compared to those participants without signs of diastolic dysfunction. The number of participants complaining exertional dyspnea, however, was similar distributed among the subgroups with and without signs of diastolic dysfunction (40.2 vs 40.8%; p = n.s). In a logistic regression model, the symptom dyspnea was best predicted by systolic pulmonary artery pressure, followed by left atrial volume index, BNP, and body mass index. CONCLUSION: The demonstration of diastolic dysfunction showed only a poor association with the symptom dyspnea in a cohort of elderly women with otherwise normal systolic function. Additional structural or hemodynamic changes are necessary to "explain" the symptom dyspnea. It is unclear whether these additional factors are secondary to a more advanced stage of diastolic dysfunction, or are related to cardiovascular co-morbidities, or both.

Decline in air pollution and change in prevalence in respiratory symptoms and chronic obstructive pulmonary disease in elderly women.

BACKGROUND: While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases. We investigated whether different declines in air pollution levels in industrialised and rural areas in Germany were associated with changes in respiratory health over a period of about 20 years. METHODS: We used data from the SALIA cohort study in Germany (Study on the influence of Air pollution on Lung function, Inflammation and Aging) to assess the association between the prevalence of chronic obstructive pulmonary disease (COPD) and chronic respiratory symptoms and the decline in air pollution exposure. In 1985-1994, 4874 women aged 55-years took part in the baseline investigation. Of these, 2116 participated in a questionnaire follow-up in 2006 and in a subgroup of 402 women lung function was tested in 2008-2009. Generalized estimating equation (GEE) models were used to estimate the effect of a reduction in air pollution on respiratory symptoms and diseases. RESULTS: Ambient air concentrations of particulate matter with aerodynamic size < 10 microm (PM10) declined in average by 20 microg/m3. Prevalence of chronic cough with phlegm production and mild COPD at baseline investigation compared to follow-up was 9.5% vs. 13.3% and 8.6% vs. 18.2%, respectively. A steeper decline of PM10 was observed in the industrialized areas in comparison to the rural area, this was associated with a weaker increase in prevalence of respiratory symptoms and COPD. Among women who never smoked, the prevalence of chronic cough with phlegm and mild COPD was estimated at 21.4% and 39.5%, respectively, if no air pollution reduction was assumed, and at 13.3% and 17.5%, respectively, if air pollution reduction was assumed. CONCLUSION: We concluded that parallel to the decline of ambient air pollution over the last 20 years in the Ruhr area the age-related increase in chronic respiratory diseases and symptoms appears to attenuate in the population of elderly women.

The SCINEXA: a novel, validated score to simultaneously assess and differentiate between intrinsic and extrinsic skin ageing.

BACKGROUND: Studies on the pathogenesis of skin ageing as well as efficacy testing of cosmetic and aesthetic measures to prevent or reverse skin ageing require - as an easy to use method - a validated non-invasive clinical score, which allows to simultaneously assess and differentiate between intrinsic (=chronological) and extrinsic (=photo-) skin ageing. Such an ideal score, however, does currently not exist. OBJECTIVES: We developed a novel skin ageing score 'SCINEXA' comprising 5 items indicative of intrinsic and 18 items highly characteristic of extrinsic skin ageing. These items were used to define an index (index(discr)) that allowed differentiating between intrinsic versus extrinsic skin ageing. In order to validate the 'SCINEXA', we asked whether it can be used to discriminate regular sunbed users, which have been chronically exposed to ultraviolet radiation and thus are prone to photoageing, from non-sunbed users, which were considered paradigmatic for intrinsic skin ageing. METHODS: For this purpose, 58 non-sunbed users and 16 regularly sunbed users were assessed. In addition to the clinical examination of the 23 score items potential confounders were considered by questionnaire. RESULTS: By employing the index(discr), we were able to classify 92% of all study subjects correctly as sunbed or non-sunbed users. Specifically, an index above 2 was associated with sunbed use and thus extrinsic skin ageing, whereas an index below 2 indicated intrinsic skin ageing. CONCLUSION: The novel 'SCINEXA' is suitable for the simultaneous assessment of intrinsic and extrinsic skin ageing.

Tropospheric ozone and skin aging: Results from two German cohort studies.

During the last two decades, it has been well established that a short-term exposure to ozone (O3) elicits an oxidative stress response in human and mouse skin, which leads to aberrant transcriptional expression of genes consistent with increased skin aging. Whether a long-term exposure to ambient O3 is associated with any skin aging traits, has remained unclear. We addressed this question in two elderly German cohorts: the SALIA study (806 women aged 66-79 years), and the BASE-II study (1207 men and women aged 60-84 years). Five-year mean residential exposure to O3 was modeled as the number of days with maximum daily 8-h mean O3 concentrations ≥120 µg/m3 per year in the wider neighborhood (5-digit postcode) of a participant's residence. Extrinsic (environmentally induced) skin aging traits - coarse wrinkles and pigment spots (lentigines) on the face - were assessed by means of SCINEXA™, a validated visual score previously shown to be well suited to measure extrinsic facial skin aging in cohort studies. We observed positive associations of O3 exceedances with coarse wrinkles in the face, but not with pigment spots. These associations were present in each cohort as well as in the combined sample of both cohorts. They were independent of chronic ultraviolet radiation exposure as the most obvious confounder, and also of co-pollutants such as particulate matter and nitrogen dioxide. Thus, long-term exposure to elevated concentrations of tropospheric O3 appears to contribute to skin aging.

Traffic-related air pollution and eczema in the elderly: Findings from the SALIA cohort.

Childhood eczema results from an interplay of genetic and environmental factors including Traffic-Related Air Pollution (TRAP). In contrast, little is known about eczema in the elderly in general and its association with TRAP in particular. Animal experiments indicate that the arylhydrocarbon receptor (AHR) might link TRAP and eczema. We investigated (i) incidence and prevalence of eczema in elderly women, (ii) its association with long-term TRAP exposure and (iii) the effect modification by AHR polymorphism rs2066853. The study is based on the SALIA cohort. The women's average age was 55 years at baseline (1985-1994) and 74 years at follow-up (2008-2009) examination. Incidence and prevalence of eczema were assessed by an adapted version of the International Study of Asthma and Allergies in Childhood (ISAAC) symptom questionnaire. TRAP was determined using land-use regression models. Adjusted logistic regression models were used. After age 55, the incidence and prevalence of eczema symptoms were 7.9% and 8.8%, respectively. Significant associations (p < 0.05) were found between all parameters of TRAP at the baseline visit and eczema incidence. The risk was higher for minor allele carriers of rs2066853 e.g. NOx: OR = 3.75, p = 0.030 vs. OR = 1.34, p = 0.317 in non-carriers (p(interaction) = 0.122). These results indicate a high incidence for eczema in elderly women, which is associated with chronic exposure to TRAP and possibly mediated by AHR.

Genetic variants associated with skin aging in the Chinese Han population.

BACKGROUND: The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. OBJECTIVE: To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. METHODS: We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene AHR and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of BNC2 and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of COL1A2, and laxity of eyelids. CONCLUSIONS: Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians.

Indoor PM2.5 exposure affects skin aging manifestation in a Chinese population.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

Applicability of the Global Lung Initiative 2012 Reference Values for Spirometry for Longitudinal Data of Elderly Women.

BACKGROUND AND OBJECTIVES: Lung function depends nonlinearly on age and height, so that the use of age and height specific reference values is required. The widely used age and height specific GLI (Global Lung Initiative) z-scores derived from cross-sectional data, however, have not been proven for validity in an elderly population or for longitudinal data. Therefore, we aimed to test their validity in a population of elderly women followed prospectively for more than 20 years. METHODS: We used spirometric data (forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and FEV1/FVC) from the SALIA cohort of German women (baseline: 1985-1994 (aged 55 years), follow-up: 2008/2009 and 2012/2013). We calculated GLI-z-scores for baseline and follow-up examination separately (cross-sectional evaluation) and individual differences in z-scores between baseline and follow-up (longitudinal evaluation) for healthy never-smoking women. RESULTS: GLI reference values for FEV1, FVC and FEV1/FVC were cross-sectionally and longitudinally equivalent with our SALIA data. The mean change in z-scores between baseline and follow-up was 0.33 for FEV1, 0.38 for FVC and -0.10 for FEV1/FVC. CONCLUSIONS: In conclusion, GLI z-scores fit cross-sectionally and longitudinally with FEV1, FVC and FEV1/FVC measured in women from Germany which indicates that they can be used in longitudinal association analyses.

Air pollution and diastolic function in elderly women - Results from the SALIA study cohort.

BACKGROUND: Studies linking particulate matter (PM) with heart failure (HF) show inconsistent results. However, the association of air pollution with diastolic function, an important determinant of heart failure, has not been studied yet and is addressed in the presented study. METHODS: 402 women (69-79 years) of the clinical follow-up (2007-2010) of the ongoing population-based prospective SALIA (Study on the influence of Air pollution on Lung function, Inflammation and Ageing) cohort were examined using Doppler echocardiography: Of the 291 women with preserved ejection fraction, the ratio of peak early diastolic filling velocity and peak early diastolic mitral annulus velocity (E/E') was collected in 264 and left atrial volume index (LAVI) in 262 women. Residential long-term air pollution exposure (nitrogen oxides, size-fractioned PM) was modeled at baseline and at follow-up, applying land use regression models. We used linear regression to model the cross-sectional associations of air pollutants per interquartile range (IQR) with different measures of diastolic function, adjusting for personal risk factors. RESULTS: Median concentrations of annual NOx, NO2, PM2.5, and PM10 at follow-up were 37.7, 25.9, 17.4 and 26.4µg/m(3), respectively. In the fully adjusted models, LAVI was associated with an IQR increase in PM2.5 (1.05 [0.99; 1.12]) and NOx (1.04 [1.00; 1.09]) at follow-up, and with NOx and NO2 (both 1.05 [1.00; 1.11]) at baseline. None of the pollutants were clearly associated with E/E'. CONCLUSIONS: In this analysis of elderly women, we found suggestive evidence for an association of air pollution with impaired diastolic function.

Extrinsic skin ageing in German, Chinese and Japanese women manifests differently in all three groups depending on ethnic background, age and anatomical site.

BACKGROUND: It has been suggested that extrinsic skin ageing manifests differently in Caucasians versus East Asians. In particular, from previous studies it was concluded that Caucasians are more prone to develop wrinkles, whereas pigment spot formation is the hallmark of extrinsic skin ageing in East Asians. However, these assumptions are based on a very limited number of studies which did not include different East Asian populations. OBJECTIVE: We here compare the manifestation of extrinsic skin ageing signs in German, Japanese and Chinese women by specifically elucidating the age and anatomical site dependence of any potential ethnic difference. METHODS: In the present study, we assessed skin ageing in N=902 German, N=165 Japanese and N=1260 Chinese women ranging from 30 to 90 years by means of SCINEXA™. Linear regression analysis was used to test for ethnic differences and their age and site dependence adjusted for educational level, sun exposure, smoking and sun protection behaviours. RESULTS: Pigment spots and wrinkles on the face were present among all three ethnic groups and differences were influenced by age and anatomical sites independently of further influencing factors. Pigment spots on the forehead were most pronounced over the whole age range in Chinese and German women and least developed in Japanese. Pigment spots on cheeks were a typical extrinsic skin an ageing sign in the two East Asian populations in all age groups. However, in older German women they reach the same level as observed in the two East Asian populations. In contrast, pigment spots on arms and hands were significantly more pronounced in German women ≥45years of age. Wrinkles were not exclusively a skin an ageing sign of German women, but were also very pronounced in Chinese women on forehead, between the eyebrows and in the crow's feet area. CONCLUSION: These results corroborate the previous notion that the occurrence of pigments spots and wrinkles is different between Caucasians and East Asians. In addition, this study shows that this difference depends on age and anatomical site and that it also differs between different ethnic groups from East Asia.