Possible relationship between respiratory diseases and urinary concentrations of polycyclic aromatic hydrocarbon metabolites - a pilot study.

This study investigates the potential relationship between exposure to polycyclic aromatic hydrocarbons (PAHs), specifically monohydroxylated metabolites (OH-PAHs), in urine, and the prevalence of respiratory diseases in 2-year-old children residing in two locations within the Czech Republic - Ceské Budejovice (control location) and the historically contaminated mining district of Most. Despite current air quality and lifestyle similarities between the two cities, our research aims to uncover potential long-term health effects, building upon previous data indicating distinctive patterns in the Most population. A total of 248 urine samples were analysed for the presence of 11 OH-PAHs. Employing liquid-liquid extraction with ethyl acetate and clean-up through dispersive solid-phase extraction, instrumental analysis was conducted using ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The incidence of respiratory diseases was assessed through questionnaires administered by paediatricians. The concentrations of OH-PAHs were elevated in urine samples from 2-year-olds in Most compared to those from Ceské Budejovice. The incidence of respiratory diseases showed statistically significant higher levels of OH-PAHs in children from Most, together with a higher incidence of influenza. This association underlines the impact of environmental PAH exposure on children's respiratory health. It suggests that elevated urinary OH-PAH levels indicate an increased risk of developing respiratory diseases in the affected population. Further studies are needed to clarify the possible long-term health effects and to contribute to sound public health strategies.

Prenatal exposure to polycyclic aromatic hydrocarbons and growth parameters.

BACKGROUND AND OBJECTIVES: It has long been known that airborne polycyclic aromatic hydrocarbons (PAHs) can negatively affect pregnancy and birth outcomes, such as birth weight, fetal development, and placental growth factors. However, similar studies yield divergent results. Our goal was to estimate the amount of monohydroxylated PAH (OH-PAH) metabolites in the urine of pregnant women/mothers and their newborns in relation to birth outcomes, such as placenta weight, Apgar 5', and the growth parameters of children up to the age of two. METHODS: Two cohorts of children born in 2013 and 2014 during the summer and winter seasons in the Czech Republic in the cities Karviná (N = 144) and Ceské Budejovice (N = 198), which differ significantly in the level of air pollution, were studied. PAH exposure was assessed by the concentration of benzo[a]pyrene (B[a]P) in the air and the concentration of 11 OH-PAH metabolites in the urine of newborns and mothers. Growth parameters and birth outcomes were obtained from medical questionnaires after birth and from pediatric questionnaires during the following 24 months of the child's life. RESULTS: Concentrations of B[a]P were significantly higher in Karviná (p < 0.001). OH-PAH metabolites were significantly higher in the mothers' as well as in the newborns' urine in Karviná and during the winter season. Neonatal length was shorter in newborns in Karviná (p < 0.001), but this difference evened out during the next 3 to 24 months. Compared to Ceské Budejovice, newborns in Karviná showed significantly lower weight gain between birth and three months after delivery. The OH-PAH metabolites in mothers' or newborns' urine did not affect birth weight. The presence of seven OH-PAH (top 25% of values of concentrations higher than the median) metabolites in the newborns' urine is associated with decreased length of newborn. Nine OH-PAH metabolites decreased placenta weight, which was the most significant, while seven OH-PAH metabolites decreased Apgar 5'. CONCLUSION: We have shown a possible connection between higher concentration of OH-PAH metabolites in newborns' urine and decreased length, head circumference, placenta weight, and Apgar 5', but not birth weight.

Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution.

DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = -1.92, p = 8.30 × 10-4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.

Airborne Benzo[a]Pyrene may contribute to divergent Pheno-Endotypes in children.

BACKGROUND: Asthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes - T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) - warrants clarification. OBJECTIVES: To explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype). METHODS: In a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma-overweight/obese (OV/OB) combined outcomes. RESULTS: The non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9-11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7-428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG. CONCLUSIONS: Ambient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.

The Impact of Cesarean and Vaginal Delivery on Results of Psychological Cognitive Test in 5 Year Old Children.

Background and objectives: The impact of cesarean and vaginal delivery on cognitive development was analyzed in 5 year old children. Materials and Methods: Two cohorts of 5 year old children born in the years 2013 and 2014 in Karvina (Northern Moravia) and Ceske Budejovice (Southern Bohemia) were studied for their cognitive development related to vaginal (n = 117) and cesarean types of delivery (n = 51). The Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used as psychological tests. Results: In the comparison of vaginal delivery vs. cesarean section, the children delivered by cesarean section scored lower and, therefore, achieved poorer performance in cognitive tests compared to those born by vaginal delivery, as shown in the RCPM (p < 0.001) and in the BG test (p < 0.001). When mothers' education level was considered, the children whose mothers achieved a university degree scored higher in both the RCPM test (p < 0.001) and the BG test (p < 0.01) compared to the children of mothers with lower secondary education. When comparing mothers with a university degree to those with higher secondary education, there was a significant correlation between level of education and score achieved in the RCPM test (p < 0.001), but not in the BG test. Conclusions: According to our findings, the mode of delivery seems to have a significant influence on performance in psychological cognitive tests in 5 year old children in favor of those who were born by vaginal delivery. Since cesarean-born children scored notably below vaginally born children, it appears possible that cesarean delivery may have a convincingly adverse effect on children's further cognitive development.

Ultrafine and Fine Particles and Hospital Admissions in Central Europe. Results from the UFIREG Study.

RATIONALE: Evidence of short-term effects of ultrafine particles (UFP) on health is still inconsistent and few multicenter studies have been conducted so far especially in Europe. OBJECTIVES: Within the UFIREG project, we investigated the short-term effects of UFP and fine particulate matter (particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) on daily cause-specific hospital admissions in five Central and Eastern European cities using harmonized protocols for measurements and analyses. METHODS: Daily counts of cause-specific hospital admissions focusing on cardiovascular and respiratory diseases were obtained for Augsburg and Dresden (Germany), 2011-2012; Chernivtsi (Ukraine), 2013 to March 2014; and Ljubljana (Slovenia) and Prague (Czech Republic), 2012-2013. Air pollution and meteorologic data were measured at fixed monitoring sites in all cities. We analyzed city-specific associations using confounder-adjusted Poisson regression models and pooled the city-specific effect estimates using metaanalysis methods. MEASUREMENTS AND MAIN RESULTS: A 2,750 particles/cm3 increase (average interquartile range across all cities) in the 6-day average of UFP indicated a delayed and prolonged increase in the pooled relative risk of respiratory hospital admissions (3.4% [95% confidence interval, -1.7 to 8.8%]). We also found increases in the pooled relative risk of cardiovascular (exposure average of lag 2-5, 1.8% [0.1-3.4%]) and respiratory (6-d average exposure, 7.5% [4.9-10.2%]) admissions per 12.4 µg/m3 increase (average interquartile range) in PM2.5. CONCLUSIONS: Our findings indicated delayed and prolonged effects of UFP exposure on respiratory hospital admissions in Central and Eastern Europe. Cardiovascular and respiratory hospital admissions increased in association with an increase in PM2.5. Further multicenter studies are needed using harmonized UFP measurements to draw definite conclusions on health effects of UFP.

Oxidative stress in newborns by different modes of delivery.

OBJECTIVES: The aim of our study is to investigate the impact of the type of delivery - vaginal vs. cesarean section on oxidative damage determined as the lipid peroxidation (15-F2t-isoprostane (15-F2t-IsoP) in the cord blood of newborns and venous blood from mothers in two localities with different levels of air pollution: Ceske Budejovice (CB), a locality with a clean air, and Karvina, a locality with high air pollution. RESUTLS: In Karvina, the concentration of PM2.5 was higher than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62 µg/m3, p<0.001) and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34 µg/m3, p<0.001). Similarly, the concentration of B[a]P was higher in Karvina than in CB in the summer 2013 (mean±SD: 1.16±0.91 vs. 0.16±0.26 ng/m3, p<0.001) and in the winter 2014 (5.36±3.64 vs. 1.45±1.19 ng/m3, p<0.001). Delivery procedures differed by the type of anesthesia; at the Cesarean section in CB was used general anesthesia in 73.8% vs. 20.8% in Karvina (p<0.001), epidural anesthesia in CB in 26.2% vs. 77.1% in Karvina (p<0.001), at vaginal delivery was local anesthesia used in CB in 58.9% vs. 14.1% in Karvina (p<0.001). In CB was oxidative stress higher after vaginal delivery (101.7±31.0 pg 15-F2t-isoP/ml plasma) vs. Cesarean section (83.9±26.9 pg 15-F2t-isoP/ml plasma, p<0.001), no difference between the type of delivery was observed in Karvina. CONCLUSION: No difference between the types of delivery was observed in mothers in CB as well as in Karvina. Oxidative stress in newborns in Karvina was significantly affected by the concentrations of PM2.5 and B[a]P in the polluted air.

[Health effects of ambient ultrafine particles--the project UFIREG]. / Vliv ultrajemných prachových cástic na zdraví--projekt UFIREG.

BACKGROUND: The project "Ultrafine particles--an evidence based contribution to the development of regional and European environmental and health policy" (UFIREG) started in July 2011 and ended in December 2014. It was implemented through the Central Europe Programme and co-financed by the European Regional Development Fund. Five cities in four Central European countries participated in the study: Augsburg (Germany), Chernivtsi (Ukraine), Dresden (Germany), Ljubljana (Slovenia) and Prague (Czech Republic). The aim of the UFIREG project was to improve the knowledge base on possible health effects of ambient ultrafine particles (UFP) and to raise overall awareness of environmental and health care authorities and the population. METHODS: Epidemiological studies in the frame of the UFIREG project have assessed the short-term effects of UFP on human mortality and morbidity, especially in relation to cardiovascular and respiratory diseases. Official statistics were used to determine the association between air pollution concentration and daily (cause-specific: respiratory and cardiovascular) hospital admissions and mortality. Associations of UFP levels and health effects were analysed for each city by use of Poisson regression models adjusting for a number of confounding factors. RESULTS: Results on morbidity and mortality effects of UFP were heterogeneous across the five European cities investigated. Overall, an increase in respiratory hospital admissions and mortality could be detected for increases in UFP concentrations. Results on cardiovascular health were less conclusive. CONCLUSION: Further multi-centre studies such as UFIREG are needed preferably investigating several years in order to produce powerful results.

Differences between the spectra of respiratory illnesses in children living in urban and rural environments.

A longitudinal study launched in 1994 within the framework of the Teplice Programme aimed at comparing the respiratory morbidity in children born (1994-1998) and living in the districts of Teplice (TE) and Prachatice (PRA) in the Czech Republic. Lists of all illnesses of 960 children from birth to 10 years of age were obtained from paediatric medical records. From 26,471 diagnoses (in ICD-10 codes), 34.7% were diagnoses of upper respiratory infections (URI, J00-02, J06), 11.3% of tonsillitis, 10.2% of influenza, 9.4% of bronchitis, 8.9% of laryngitis/tracheitis (J04), 2.7% of otitis media, and 0.5% of pneumonia. The more polluted district of Teplice was divided into two parts: the town itself (TE-town) and the rest of the district (TE-district). The cumulative incidence rates of the above respiratory illnesses per 100 children per 10 years were 2,212 in TE-town, 2,192 in PRA and 1,985 in TE-district. In the first two years of life, the children from TE-town had a significantly higher incidence of laryngitis/tracheitis, influenza, otitis media, and pneumonia and significantly lower incidence of bronchitis and tonsillitis than children living in PRA. The incidence rates of laryngitis/tracheitis and influenza in TE-town persisted as the highest among the three regions till the age of 10 years. The incidence rates of bronchitis (from the 1st to 5th year) and URI (from 4th to 10th year) were highest in children living in PRA. When compared to TE-town, children in TE-district had a higher incidence of upper respiratory infections (1-8 years) and lower incidence of bronchitis (6-8 years). Children in the district of Prachatice had a significantly higher prevalence of allergic rhinitis and a lower prevalence of wheezing than children in the district of Teplice. Thus, the three regions differed by the spectra of respiratory illnesses rather than by overall morbidity and, hypothetically, the effects of air pollution were obscurred by differences in the degree of urbanization.

Analysis of biomarkers in a Czech population exposed to heavy air pollution. Part I: bulky DNA adducts.

The health of human populations living in industrial regions is negatively affected by exposure to environmental air pollutants. In this study, we investigated the impact of air pollution on a cohort of subjects living in Ostrava, a heavily polluted industrial region and compared it with a cohort of individuals from the relatively clean capital city of Prague. This study consisted of three sampling periods differing in the concentrations of major air pollutants (winter 2009, summer 2009 and winter 2010). During all sampling periods, the study subjects from Ostrava region were exposed to significantly higher concentrations of benzo[a]pyrene (B[a]P) and benzene than the subjects in Prague as measured by personal monitors. Pollution by B[a]P, particulate matter of aerodynamic diameter <2.5 µm (PM2.5) and benzene in the Ostrava region measured by stationary monitors was also higher than in Prague, with the exception of PM2.5 in summer 2009 when concentration of the pollutant was significantly elevated in Prague. To evaluate DNA damage in subjects from both locations we determined the levels of bulky DNA adducts in peripheral blood lymphocytes using the (32)P-postlabeling method. Despite higher B[a]P air pollution in the Ostrava region during all sampling periods, the levels of B[a]P-like DNA adducts per 10(8) nucleotides were significantly higher in the Ostrava subjects only in winter 2009 (mean ± SD: 0.21 ± 0.06 versus 0.28 ± 0.08 adducts/10(8) nucleotides, P < 0.001 for Prague and Ostrava subjects, respectively; P < 0.001). During the other two sampling periods, the levels of B[a]P-like DNA adducts were significantly higher in the Prague subjects (P < 0.001). Multivariate analyses conducted among subjects from Ostrava and Prague separately during all sampling periods revealed that exposure to B[a]P and PM2.5 significantly increased levels of B[a]P-like DNA adducts in the Ostrava subjects, but not in subjects from Prague.

Comparison of child morbidity in regions of Ostrava, Czech Republic, with different degrees of pollution: a retrospective cohort study.

BACKGROUND: To confirm or refute the hypothesis that the morbidity of children (since birth to age 5) born and living in the heavily polluted (PM10, benzo[a]pyrene) eastern part of Ostrava, Czech Republic, was higher than the morbidity of children living in other parts of the city. METHODS: Ten pediatricians in 5 districts of Ostrava abstracted the medical records of 1878 children born in 2001-2004 to list all illnesses of each child in ICD-10 codes. The children were divided into four groups according to their residence at birth and thereafter. Most of the children in the eastern area were living in the city district Radvanice and Bartovice. RESULTS: We report on the incidence of acute illnesses in 1535 children of Czech ethnicity in the first 5 years of life. The most frequent acute illnesses (over 45% of all diagnoses) were upper respiratory infections (URI: J00-J02, J06). In the first year of life, the incidence of URI in 183 children in the eastern area - 372 illnesses/100 children/year - was more than twice as high as in the other 3 areas with a total number of 1352 children. From birth to the age of 5 years, the incidences of pneumonia, tonsillitis, viral infections (ICD-10 code B34) and intestinal infectious diseases were also several times higher in children living in the eastern part of Ostrava. The lowest morbidity was found in children living in the less polluted western part of the city. CONCLUSIONS: The children born and living in the eastern part of the city of Ostrava had from birth through 5 years significantly higher incidence rates of acute illnesses than children in other parts of Ostrava. They also had a higher prevalence of wheezing, atopic dermatitis and allergic rhinitis.

Effects of various environments on epigenetic settings and chromosomal damage.

Air pollution is a dominant environmental exposure factor with significant health consequences. Unexpectedly, research in a heavily polluted region of the Czech Republic, with traditional heavy industry, revealed repeatedly the lowest frequency of micronuclei in the season with the highest concentrations of air pollutants including carcinogenic benzo[a]pyrene (B[a]P). Molecular findings have been collected for more than 10 years from various locations of the Czech Republic, with differing quality of ambient air. Preliminary conclusions have suggested adaptation of the population from the polluted locality (Ostrava, Moravian-Silesian Region (MSR)) to chronic air pollution exposure. In this study we utilize the previous findings and, for the first time, investigate micronuclei (MN) frequency by type: (i) centromere positive (CEN+) MN, representing chromosomal losses, and (ii) centromere negative (CEN-) MN representing chromosomal breaks. As previous results indicated differences between populations in the expression of XRCC5, a gene involved in the non-homologous end-joining (NHEJ) repair pathway, possible variations in epigenetic settings in this gene were also investigated. This new research was conducted in two seasons in the groups from two localities with different air quality levels (Ostrava (OS) and Prague (PG)). The obtained new results show significantly lower frequencies of chromosomal breaks in the OS subjects, related to the highest air pollution levels (p < 0.001). In contrast, chromosomal losses were comparable between both groups. In addition, significantly lower DNA methylation was found in 14.3% of the analyzed CpG loci of XRCC5 in the population from OS. In conclusion, the epigenetic adaptation (hypomethylation) in XRCC5 involved in the NHEJ repair pathway in the population from the polluted region, was suggested as a reason for the reduced level of chromosomal breaks. Further research is needed to explore the additional mechanisms, including genetic adaptation.

Deregulation of gene expression induced by environmental tobacco smoke exposure in pregnancy.

INTRODUCTION: Environmental tobacco smoke (ETS) exposure in pregnant women may have detrimental effects such as spontaneous abortion, lower birth weight, stillbirth, and reduced infant lung function. To extend our knowledge on the molecular effects of tobacco smoke exposure in pregnancy, we analyzed transcriptome alterations in passive smokers (PS) and compared them with those in active smokers (AS). METHODS: Using Illumina Expression Beadchips with 24,526 transcript probes, gene expression patterns were assayed in placentas from PS (N = 25) exposed to ETS throughout pregnancy and nonexposed (NS) counterparts (N = 34) and in cord blood cells from their newborns. ETS exposure was evaluated by questionnaire disclosure and cotinine measurement in maternal and cord blood. RESULTS: A total of 158 genes were significantly deregulated in the placentas of PS compared with NS. These genes were associated with the extracellular matrix, apoptosis, placental function, blood clotting, response to stress, and lipid metabolism. Cord blood of the newborns of PS displayed differential expression of 114 genes encoding mainly adhesion molecules and regulators of immunologic response. A comparison of the affected pathways between PS and AS indicated that ETS exposure and active smoking in pregnancy partly employ the same molecular mechanisms. CONCLUSIONS: This study demonstrates that even low dose exposure to ETS during pregnancy leads to significant deregulation of transcription in placental and fetal cells. These data suggest that the effect of ETS on the fetus is primarily indirect, mediated via deregulation of placental functions.

A possible link between cognitive development in 5 years old children and prenatal oxidative stress.

BACKGROUND: To study the impact of oxidative damage associated with particulate matter< 2.5 µm (PM2.5) during prenatal period on the cognitive development in five years old children. METHODS: Two cohorts of children aged five years, born in the years 2013 and 2014, were studied for their cognitive development in the polluted district Karvina and the control district Ceske Budejovice. Exposure to PM2.5 in the ambient air was measured for each mother during the 3rd trimester of pregnancy. Oxidative damage was determined from the level of biomarkers at delivery in mothers´ and newborns´ urine as 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and in plasma as 15-F2t-isoprostane levels (15-F2t-IsoP). The Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used as psychological cognitive tests. RESULTS: Average concentrations of PM2.5 ± SD in the 3rd trimester of mothers´ pregnancies were 37.7 ± 14.7 µg/m3 and 17.1 ± 4.8 µg/m3 in Karvina and Ceske Budejovice, respectively (p < 0.001). The maternal level of 15-F2t-IsoP in plasma at the time of delivery was significantly associated with the results of the RCPM test (p < 0.05) and the BG test (p < 0.05) in five years old children. CONCLUSIONS: Lipid peroxidation in maternal plasma at the time of delivery has an adverse effect on the results of psychological cognitive tests in five years old children.

Oxidative Stress and Antioxidant Response in Populations of the Czech Republic Exposed to Various Levels of Environmental Pollutants.

We aimed to identify the variables that modify levels of oxidatively damaged DNA and lipid peroxidation in subjects living in diverse localities of the Czech Republic (a rural area, a metropolitan locality, and an industrial region). The sampling of a total of 126 policemen was conducted twice in two sampling seasons. Personal characteristics, concentrations of particulate matter of aerodynamic diameter <2.5 µm and benzo[a]pyrene in the ambient air, activities of antioxidant mechanisms (superoxide dismutase, catalase, glutathione peroxidase, and antioxidant capacity), levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), concentrations of persistent organic pollutants in blood plasma, and urinary levels of polycyclic aromatic hydrocarbon metabolites were investigated as parameters potentially affecting the markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine) and lipid peroxidation (15-F2t-isoprostane). The levels of oxidative stress markers mostly differed between the localities in the individual sampling seasons. Multivariate linear regression analysis revealed IL-6, a pro-inflammatory cytokine, as a factor with the most pronounced effects on oxidative stress parameters. The role of other variables, including environmental pollutants, was minor. In conclusion, our study showed that oxidative damage to macromolecules was affected by processes related to inflammation; however, we did not identify a specific environmental factor responsible for the pro-inflammatory response in the organism.

Micronuclei levels in mothers and their newborns from regions with different types of air pollution.

The aim of this study was to analyze genetic damage in human lymphocytes measured using automated image analysis of micronuclei (MN) in a group of 178 mothers and their newborns from two locations in the Czech Republic. The concentrations of benzo[a]pyrene (B[a]P), particulate matter of aerodynamic diameter <2.5 µm (PM2.5) and benzene were measured by stationary monitoring in the winter season of 2008/2009 in the capital city of Prague and in Ceske Budejovice, a regional city in a rural area. The 3-month mean concentration of B[a]P before delivery was lower in Prague in comparison with Ceske Budejovice: 1.9 ± 0.5ng/m³ vs. 3.2 ± 0.2ng/m³ (p<0.001). The opposite trend was found for PM2.5 and benzene: 27.0 ± 2.5µg/m³ and 2.5 ± 0.5µg/m³ vs. 24.5 ± 0.7µg/m³ and 2.1 ± 0.8µg/m³ (p<0.001) for Prague vs. Ceske Budejovice, respectively. The average age of the mothers was 31 years (range, 18-49 years). The frequencies of MN per 1000 binucleated cells were 8.35 ± 3.06 vs. 6.47 ± 2.35 (p<0.001) for mothers from Prague and Ceske Budejovice, respectively, and 2.17 ± 1.32 vs. 3.82 ± 2.43 (p<0.001) for newborns from Prague and Ceske Budejovice, respectively. Other factors, including vitamin intake, exposure to tobacco smoke, body mass index (BMI) before pregnancy, the education level of the mothers and the impact of the mothers' and fathers' ages were analyzed in our study. The results suggest that the different sensitivity of the study groups to various mixtures of carcinogenic pollutants could be affected by significant differences in lifestyle factors. Possible higher genetic damage was analyzed in newborns of smoking mothers, and the birth weight of this group was 7.4% lower (p<0.05) in comparison with the newborns of nonsmoking mothers. No impact of the age of the mothers or fathers on MN frequency in the newborns was observed.

The effects of age on DNA fragmentation, the condensation of chromatin and conventional semen parameters in healthy nonsmoking men exposed to traffic air pollution.

BACKGROUND: Numerous studies have investigated age-based declines in semen traits, but the impact of paternal age on semen parameter values remains inconclusive. OBJECTIVES: The aim of this study was to detect an impact of age on semen quality was studied in healthy nonsmoking men exposed to traffic air pollution. METHODS: Semen samples from 150 Prague City policemen aged 23 to 63 years were examined for standard semen parameters, sperm DNA fragmentation and high DNA stainability. RESULTS: A significant positive correlation was found between age and %DFI (r = .359, P < .001), and negative correlations were found between age and sperm vitality (r = -.247, P < .001), the % acrosome-intact sperm (r = -.202, P = .013) and the % normal sperm heads (r = -.204, P = .012). A weak but significant negative correlation was found for high DNA stainability (% HDS) vs age (r = -.161, P = .050). No significant correlation was detected between male age and the other investigated semen quality parameters. At ages of 23 to 30, 31 to 40, 41 to 50, and 51 to 63 years, the mean %DFI values were 12.7 ± 7.18, 14.7 ± 7.42, 19.6 ± 11.25, and 34.2 ± 15.08, respectively. CONCLUSION: Our study shows a strong relationship (P < .001) between the age of men and sperm DNA fragmentation in an occupational cohort at risk of exposure to heavy traffic-related air pollution in a large city center.

Effect of Polycyclic Aromatic Hydrocarbons Exposure on Cognitive Development in 5 Years Old Children.

Objectives: To analyze the impact of polycyclic aromatic hydrocarbons (PAHs) in ambient air at the time of delivery and five years of age on cognitive development in five year old children. Materials and Methods: Two cohorts of children born in the years 2013 and 2014 from Karvina (Northern Moravia, n = 70) and Ceske Budejovice (Southern Bohemia, n = 99) were studied at the age of five years for their cognitive development related to the exposure to PAHs, determined in the ambient air as the concentration of benzo[a]pyrene (B[a]P) and OH-PAH (hydroxy-PAH) metabolites in urine of the newborns at the time of delivery. As psychological tests, the Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used. Results: Concentrations of B[a]P in the third trimester of mother's pregnancies were 6.1 ± 4.53 ng/m3 in Karvina, and 1.19 ± 1.28 ng/m3 (p < 0.001) in Ceske Budejovice. Neither the outcome of the RCPM test nor the BG test differed between children in Karvina vs. Ceske Budejovice, or boys vs. girls. Cognitive development in five year old children was affected by the higher exposure to PM2.5 during the third trimester in girls in Karvina. Conclusions: We did not observe any significant effect of prenatal PAH exposure on psychological cognitive tests in five year old children.

Modeling Unobserved Heterogeneity in Susceptibility to Ambient Benzo[a]pyrene Concentration among Children with Allergic Asthma Using an Unsupervised Learning Algorithm.

Current studies of gene × air pollution interaction typically seek to identify unknown heritability of common complex illnesses arising from variability in the host's susceptibility to environmental pollutants of interest. Accordingly, a single component generalized linear models are often used to model the risk posed by an environmental exposure variable of interest in relation to a priori determined DNA variants. However, reducing the phenotypic heterogeneity may further optimize such approach, primarily represented by the modeled DNA variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also identify single nucleotide polymorphisms (SNP) associated with phenotype subgroups. Specifically, we first apply an unsupervised learning algorithm method and a non-parametric regression to find a biclustering structure of children according to their allergy and asthma severity. We then identify a set of SNPs most closely correlated with each sub-group. We subsequently fit a logistic regression model for each group against the healthy controls using benzo[a]pyrene (B[a]P) as a representative airborne carcinogen. Application of such approach in a case-control data set shows that SNP clustering may help to partly explain heterogeneity in children's asthma susceptibility in relation to ambient B[a]P concentration with greater efficiency.

Greater susceptibility of girls to airborne Benzo[a]pyrene for obesity-associated childhood asthma.

BACKGROUND: Sexually dimorphic risk of obesity-associated asthma is posited to accelerate around puberty. Yet, the role of air pollution on the lean and obese asthmatic children has never been examined. OBJECTIVE: To compare whether a unit exposure to airborne benzo[a]pyrene (B[a]P) is associated with altered risks of asthma across the overweight/obese (OV/OB) control, lean asthmatic, and OV/OB asthmatic children, respectively, compared to the lean controls, before and after adjusting for oxidant stress markers (i.e. 15­F2t­IsoP, 8­oxo­dG, and Carbonyl). METHODS: Asthmatic and healthy control children, recruited from polluted urban and rural areas, were matched to ambient concentration of B[a]P. A unit increase in B[a]P and multinomial logistic regression on OV/OB control, lean asthmatic, and OV/OB asthma were compared across the sex- and age-groups. RESULTS: The median B[a]P was associated with a linear increase among the female children, according to OV/OB and asthma, respectively, and together, compared to the lean control girls (p = 0.001). While B[a]P was associated with positive relationship with 15­F2t­IsoP level among the OV/OB boys, the same exposure-outcome association was inverse among the OV/OB girls. One natural log-unit increase in ambient B[a]P was associated with 10.5-times greater odds (95% CI, 2.6-39.6; p = 0.001) the adolescent OV/OB boys, compared to the unit odds among the lean controls. In contrast, the adolescent OV/OB girls were associated with highest adjusted odds of the asthma (aOR = 15.4; 95% CI, 2.9-29.1; p < 0.001) compared to the lean control girls. An adjustment for 15­F2t­IsoP, and Carbonyls was associated with greater odds of asthma per unit exposure for the adolescent OV/OB girls (aOR = 16.2; 95% CI, 1.4-181.8; p = 0.024). CONCLUSIONS: B[a]P exposure was associated with a leap in the odds of asthma among the OV/OB adolescents, particularly the girls, after adjusting for 15­F2t­IsoP and Carbonyls.