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Background: Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA., Methods: Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA., Results: An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002)., Conclusion: Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.

Background: For the analysis of gene-environment (GxE) interactions commonly single nucleotide polymorphisms (SNPs) are used to characterize genetic susceptibility, an approach that mostly lacks power and has poor reproducibility. One promising approach to overcome this problem might be the use of weighted genetic risk scores (GRS), which are defined as weighted sums of risk alleles of gene variants. The gold-standard is to use external weights from published meta-analyses., Methods: In this study, we used internal weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression and thereby provided a method that can be used if there are no external weights available. We conducted a simulation study for the detection of GxE interactions and compared power and type I error of single SNPs analyses with Bonferroni correction and corresponding analysis with unweighted and our weighted GRS approach in scenarios with six risk SNPs and an increasing number of highly correlated (up to 210) and noise SNPs (up to 840)., Results: Applying weighted GRS increased the power enormously in comparison to the common single SNPs approach (e.g. 94.2% vs. 35.4%, respectively, to detect a weak interaction with an OR ≈ 1.04 for six uncorrelated risk SNPs and n = 700 with a well-controlled type I error). Furthermore, weighted GRS outperformed the unweighted GRS, in particular in the presence of SNPs without any effect on the phenotype (e.g. 90.1% vs. 43.9%, respectively, when 20 noise SNPs were added to the six risk SNPs). This outperforming of the weighted GRS was confirmed in a real data application on lung inflammation in the SALIA cohort (n = 402). However, in scenarios with a high number of noise SNPs (>200 vs. 6 risk SNPs), larger sample sizes are needed to avoid an increased type I error, whereas a high number of correlated SNPs can be handled even in small samples (e.g. n = 400)., Conclusion: In conclusion, weighted GRS with weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression were shown to be a powerful tool to detect gene-environment interactions in scenarios of high Linkage disequilibrium and noise.

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 PM 2.5 , PM 2.5 absorbance, PM 10 and NO 2 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)B 4 , 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 LTB 4 (PM 2.5 : p-value=0.002, PM 2.5 absorbance: p-value=0.002, PM 10 : p-value=0.001 and NO 2 : p-value=0.004). Women with a high GRS had a 38% (95%-CI: 16-64%) higher LTB 4 level for an increase of 2.06μg/m³(IQR) in PM 2.5 (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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Epidemiological studies have associated long-term exposure to ambient particulate matter with increased mortality from cardiovascular and respiratory disorders. Systemic inflammation is a plausible biological mechanism behind this association. However, it is unclear how the chemical composition of PM affects inflammatory responses., Objectives: To investigate the association between long-term exposure to elemental components of PM and the inflammatory blood markers high-sensitivity C-reactive protein (hsCRP) and fibrinogen as part of the European ESCAPE and TRANSPHORM multi-center projects., Methods: In total, 21,558 hsCRP measurements and 17,428 fibrinogen measurements from cross-sections of five and four cohort studies were available, respectively. Residential long-term concentrations of particulate matter <10μm (PM10) and <2.5μm (PM2.5) in diameter and selected elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, zinc) were estimated based on land-use regression models. Associations between components and inflammatory markers were estimated using linear regression models for each cohort separately. Cohort-specific results were combined using random effects meta-analysis. As a sensitivity analysis the models were additionally adjusted for PM mass., Results: A 5ng/m(3) increase in PM2.5 copper and a 500ng/m(3) increase in PM10 iron were associated with a 6.3% [0.7; 12.3%] and 3.6% [0.3; 7.1%] increase in hsCRP, respectively. These associations between components and fibrinogen were slightly weaker. A 10ng/m(3) increase in PM2.5 zinc was associated with a 1.2% [0.1; 2.4%] increase in fibrinogen; confidence intervals widened when additionally adjusting for PM2.5., Conclusions: Long-term exposure to transition metals within ambient particulate matter, originating from traffic and industry, may be related to chronic systemic inflammation providing a link to long-term health effects of particulate matter., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Environmental and lifestyle factors regulate the expression and release of immune mediators. It has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes. Therefore, we assessed the associations between air pollution, circulating immune mediators and impaired glucose metabolism., Methods: We analysed concentrations of 14 pro- and anti-inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the Study on the influence of Air pollution on Lung function, Inflammation and Aging (SALIA, Germany). Exposure data for a group of pollutants such as nitrogen oxides (NO2, NOx) and different fractions of particulate matter were available for the participants' residences. We calculated the association between the pollutants and impaired glucose metabolism by multiple regression models., Results: The study participants had a mean age of 74.1 (SD 2.6) years and 48% showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes. Only long-term exposure NO2 and NOx concentrations showed positive associations (NO2: OR 1.465, 95% CI 1.049-2.046, NOx: OR 1.409, 95% CI 1.010-1.967) per increased interquartile range of NO2 (14.65 µg/m(3)) or NOx (43.16 µg/m(3)), respectively, but statistical significance was lost after correction for multiple comparisons. Additional adjustment for circulating immune mediators or the use of anti-inflammatory medication had hardly any impact on the observed ORs., Conclusions: Our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism, but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings. Our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma.

Abstract: Animal studies have suggested that fine particulate matter (PM) can translocate from the upper respiratory tract to the brain and cause brain inflammation. Brain inflammation is involved in the pathogenesis of neurodegenerative diseases. Hypothesizing therefore that long-term exposure to fine PM might contribute to the development of Alzheimer''s disease (AD), the objective of this study was to investigate the association between exposure to fine PM and mild cognitive impairment (MCI) which is associated with a high risk of progression to AD. A study group of 399 women aged 68–79 years who lived for more than 20 years at the same residential address has been assessed for long-term exposure to PM and tested for MCI. The exposure assessment comprised background concentration of PM10 and traffic-related PM indicated by the distance of the residential address to the next busy road. The women were assessed for MCI by a battery of several neuropsychological tests and their odor identification ability. Consistent effects of traffic-related air pollution exposure on test performances including a dose–response relation were found. The associations were adjusted for potential confounders using regression analysis. These results indicate that chronic exposure to traffic-related PM may be involved in the pathogenesis of AD. [Copyright &y& Elsevier]

• Impaired skin barrier function drives the pathophysiology of atopic dermatitis. • Defects in skin barrier component genes lead to impaired skin barrier function. • Environmental factors may worsen atopic dermatitis through cutaneous exposure. • The cutaneous microbiome is an important component of the skin barrier function. • Several therapies for atopic dermatitis promote restoration of the skin barrier. Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]