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.

Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals.

BACKGROUND: Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial. OBJECTIVE: The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution. METHODS: A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined. RESULTS: While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45-0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase. CONCLUSION: The current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum parameters, the study proves the feasibility of the therapeutic approach in an aged study group.

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.

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.

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.