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.

Non-microbial sources of microbial volatile organic compounds.

BACKGROUND: The question regarding the true sources of the purported microbial volatile organic compounds (MVOCs) remains unanswered. OBJECTIVE: To identify microbial, as well as non-microbial sources of 28 compounds, which are commonly accepted as microbial VOCs (i.e. primary outcome of interest is Σ 28 VOCs). METHODS: In a cross-sectional investigation of 390 homes, six building inspectors assessed water/mold damage, took air and dust samples, and measured environmental conditions (i.e., absolute humidity (AH, g/m(3)), temperature (°C), ventilation rate (ACH)). The air sample was analyzed for volatile organic compounds (µg/m(3)) and; dust samples were analyzed for total viable fungal concentration (CFU/g) and six phthalates (mg/g dust). Four benchmark variables of the underlying sources were defined as highest quartile categories of: 1) the total concentration of 17 propylene glycol and propylene glycol ethers (Σ17 PGEs) in the air sample; 2) 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MIB) in the air sample; 3) semi-quantitative mold index; and 4) total fungal load (CFU/g). RESULTS: Within severely damp homes, co-occurrence of the highest quartile concentration of either Σ17 PGEs or TMPD-MIB were respectively associated with a significantly higher median concentration of Σ 28 VOCs (8.05 and 13.38µg/m(3), respectively) compared to the reference homes (4.30 and 4.86µg/m(3), respectively, both Ps ≤0.002). Furthermore, the homes within the highest quartile range for Σ fungal load as well as AH were associated with a significantly increased median Σ 28 VOCs compared to the reference group (8.74 vs. 4.32µg/m(3), P=0.001). Within the final model of multiple indoor sources on Σ 28 VOCs, one natural log-unit increase in summed concentration of Σ17 PGEs, plus TMPD-MIB (Σ 17 PGEs + TMPD-MIB) was associated with 1.8-times (95% CI, 1.3-2.5), greater likelihood of having a highest quartile of Σ 28 VOCs, after adjusting for absolute humidity, history of repainting at least one room, ventilation rate, and mold index (P-value =0.001). Homes deemed severely mold damaged (i.e., mold index =1) were associated with 1.7-times (95% CI, 0.8-3.6), greater likelihood of having a highest quartile of Σ 28 VOCs, even though such likelihood was not significant (P-value =0.164). In addition, absolute humidity appeared to positively interact with mold index to significantly elevate the prevalence of the highest quartile category of Σ 28 VOCs. CONCLUSION: The indoor concentration of Σ 28 VOCs, which are widely accepted as MVOCs, are significantly associated with the markers of synthetic (i.e. Σ17 PGEs and TMPD-MIB), and to less extent, microbial (i.e., mold index) sources.

Mold populations and dust mite allergen concentrations in house dust samples from across Puerto Rico.

Lifetime childhood asthma prevalence (LCAP) percentages in Puerto Rico Health Regions (HR) are substantially higher in northeastern vs. southwestern HR. Higher average relative humidity in the northeast might promote mold and mite exposures and possibly asthma prevalence. To test this hypothesis, mold contamination, Environmental Relative Moldiness Index (ERMI) values were measured in floor dust (n = 26) and dust mite allergen concentrations in bed dust (n = 14). For this analysis, the eight HR were divided into those with LCAP > 30% (n = 3) and < 30% (n = 5). The average ERMI value was significantly greater (Wilcoxon Rank Sum, p < 0.001) in high than in low LCAP HR (14.5 vs. 9.3). The dust mite antigens Der p 1, Der f 1, and Blo t 5 were detected in 90% of bed samples, but the concentrations were not significantly different in high vs. low LCAP HR. Mold exposures might partially explain the differences in LCAP HR in Puerto Rico.

The integrated first year experience in the master of public health program.

Schools of Public Health historically introduced core curriculum courses in the first year of the Master of Public Health program as independent perspectives; these perspectives included epidemiology, biostatistics, environmental health, public health biology, health behaviors, and health policy. We performed a pilot project that integrated the core areas around diabetes as a cross-cutting public health issue to provide early exposure to the interdisciplinary nature of public health. In each core curriculum course, diabetes was explored in the curriculum and related to other core courses. Based on positive evaluations, this project will be replicated using a different health issue. Such an issue can be easily introduced as an overarching umbrella under which students are motivated to work through interdisciplinary collaboration.

Using semiparametric-mixed model and functional linear model to detect vulnerable prenatal window to carcinogenic polycyclic aromatic hydrocarbons on fetal growth.

Prenatal exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) through maternal inhalation induces higher risk for a wide range of fetotoxic effects. However, the most health-relevant dose function from chronic gestational exposure remains unclear. Whether there is a gestational window during which the human embryo/fetus is particularly vulnerable to PAHs has not been examined thoroughly. We consider a longitudinal semiparametric-mixed effect model to characterize the individual prenatal PAH exposure trajectory, where a nonparametric cyclic smooth function plus a linear function are used to model the time effect and random effects are used to account for the within-subject correlation. We propose a penalized least squares approach to estimate the parametric regression coefficients and the nonparametric function of time. The smoothing parameter and variance components are selected using the generalized cross-validation (GCV) criteria. The estimated subject-specific trajectory of prenatal exposure is linked to the birth outcomes through a set of functional linear models, where the coefficient of log PAH exposure is a fully nonparametric function of gestational age. This allows the effect of PAH exposure on each birth outcome to vary at different gestational ages, and the window associated with significant adverse effect is identified as a vulnerable prenatal window to PAHs on fetal growth. We minimize the penalized sum of squared errors using a spline-based expansion of the nonparametric coefficient function to draw statistical inferences, and the smoothing parameter is chosen through GCV.

Pulmonary oxidative stress and apoptosis in mice chronically exposed to hydrothermal volcanic emissions.

Recent studies have shown that exposure to hydrothermal emissions has a negative impact on the respiratory system. Still, volcanogenic air pollution studies are still outnumbered when compared to anthropogenic studies which can result in an unknown risk to the human populations living near volcanically active areas. This study was carried out in São Miguel Island, with noneruptive volcanically active environments, such as the Furnas volcano caldera. Its noneruptive volcanism presents itself as hydrothermal emissions, mainly by the release of nearly 1000 T d-1 of CO2 along with H2S, and the radioactive gas radon; metals [e.g., mercury (Hg), cadmium (Cd), copper (Cu), and zinc (Zn)] and particulate matter are also released in a daily basis. We test the hypothesis whether chronic exposure to hydrothermal emissions causes pulmonary oxidative stress, using Mus musculus as a surrogate species. Mus musculus was live-captured in two villages with hydrothermal emissions and one village without any type of volcanic activity. The level of pulmonary oxidative stress was immunohistochemically assessed by using an OxyIHCTM Oxidative stress detection kit, and the detection of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) was used to evaluate apoptosis in lung tissues. Mice chronically exposed to hydrothermal emissions presented increased levels of oxidative stress and amount of apoptotic cells. We demonstrate, for the first time, the high oxidative stress potential in the lungs of mice chronically exposed to hydrothermal emissions. This study highlights the usefulness of M. musculus as a bioindicator species and enforces the necessity of regularly biomonitor the inhabitants of hydrothermal areas to prevent respiratory pathologies.

Improved risk communications with a Bayesian multipollutant Air Quality Health Index.

Establishing an optimal indicator to communicate health risks of multiple air pollutants to public is much important. The Air Quality Health Index (AQHI) has been developed in many countries as a communication tool of multiple air pollutants related health risks. However, the current AQHI is based on the sum of the excess health risks which are typically derived from the single-pollutant statistical models. Such a strategy may overestimate the joint effect of multiple pollutants. We proposed an improved strategy to construct the AQHI based on a Bayesian multipollutant weighted model. Using this strategy, two improved indices - Bayesian multipollutant AQHI (BMP-AQHI) and Bayesian multipollutant AQHI with seasonal specificity (SBMP-AQHI) were calculated to present the multiple pollutants related health risks to the cardiovascular system based on data collected in Chengdu, China during 2013 to 2018. The two improved indices were compared to current Air Quality Index (AQI) and AQHI to evaluate the effectiveness of the improved indices in characterizing multipollutant health risks. The AQI risk classification suggested much smaller health risks than AQHIs. Among three AQHI types, the BMP-AQHI and SBMP-AQHI suggested slightly lower health risks to the cardiovascular system than the current AQHI. In the evaluation analysis, the SBMP-AQHI had the strongest association with the mortality of cardiovascular disease (CVD) (2.66%; 95%CI, 1.57%, 3.76%). In the subgroup analysis, an interquartile increase (IQR) of the SBMP-AQHI was associated with 3.21% (95%CI, 2.06%, 4.38%), 1.34% (95%CI, -0.13%, 2.82%), and 4.20% (95%CI, 2.59%, 5.84%) increases for CVD mortality in the elderly, male, and female subgroups, respectively. The study shows that the improved AQHIs can communicate the health information of multiple air pollutants more efficiently. The study also indicates the necessity to consider seasonal specificity in the construction of the AQHI.

Methodological issues in studies of air pollution and reproductive health.

In the past decade there have been an increasing number of scientific studies describing possible effects of air pollution on perinatal health. These papers have mostly focused on commonly monitored air pollutants, primarily ozone (O(3)), particulate matter (PM), sulfur dioxide (SO(2)), carbon monoxide (CO), and nitrogen dioxide (NO(2)), and various indices of perinatal health, including fetal growth, pregnancy duration, and infant mortality. While most published studies have found some marker of air pollution related to some types of perinatal outcomes, variability exists in the nature of the pollutants and outcomes associated. Synthesis of the findings has been difficult for various reasons, including differences in study design and analysis. A workshop was held in September 2007 to discuss methodological differences in the published studies as a basis for understanding differences in study findings and to identify priorities for future research, including novel approaches for existing data. Four broad topic areas were considered: confounding and effect modification, spatial and temporal exposure variations, vulnerable windows of exposure, and multiple pollutants. Here we present a synopsis of the methodological issues and challenges in each area and make recommendations for future study. Two key recommendations include: (1) parallel analyses of existing data sets using a standardized methodological approach to disentangle true differences in associations from methodological differences among studies; and (2) identification of animal studies to inform important mechanistic research gaps. This work is of critical public health importance because of widespread exposure and because perinatal outcomes are important markers of future child and adult health.

Benzo[a]pyrene is associated with dysregulated myelo-lymphoid hematopoiesis in asthmatic children.

BACKGROUND: The extent to which ambient benzo[a]pyrene (B[a]P) contributes to mechanistically distinct de novo asthma remains unknown. OBJECTIVES: To identify molecular signatures and regulatory networks underlying childhood exposure to ambient B[a]P and asthma, using robust and unbiased systems biology approaches. METHODS: Clinically confirmed asthmatic (n = 191) vs. control (n = 194) children (aged, 7-15) were enrolled from a polluted urban center and semi-rural region in Czech Republic. Contemporaneous B[a]P concentration, gene expressions, DNA methylation data were analyzed against asthma diagnosis, as well as a modified prognostic index of asthma, using integrative multiscale co-expression network analysis. Sample-wise cell type compositions were inferred by a machine learning approach (i.e. CIBERSORT) with reference gene expressions of purified 38 distinct hematopoietic cell states from umbilical cord (i.e. stem cell/progenitors) or peripheral blood (i.e. lymphocytes). RESULTS: The median outdoor B[a]P was increased near the homes of the urban children with 'moderate' or 'severe' prognostic markers of asthma, but not in the urban controls. An elevated B[a]P induced epigenetic suppression of NF-κB inflammation, decreased Natural Killer T (NKT) cells and activated anti-inflammatory IL10-secreting CD8+ T effective memory cells. B[a]P was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appears to promote concurrent increase of neutrophilic metamyelocyte and mature CD71low erythroid cells. Furthermore, erythroid-specific master transcription regulator gene (GATA1), glutathione transferase genes (GSTM1 and GSTM3) and Eosinophil marker (IL5RA) were simultaneously activated in the urban asthma cases. CONCLUSIONS: B[a]P might contribute to concurrent suppression of pro-inflammatory (e.g. NF-κB mediated NKT cells), and activation of anti-inflammatory pathways (e.g. IL10-secreting CD8+ T cells) in the urban asthmatic children. In addition, B[a]P appears to elevate heme biosynthesis, which in turn, promotes neutrophilic metamyelocyte expansion and reduction of CD71+ erythroids.

Prenatal exposure to airborne polycyclic aromatic hydrocarbons and risk of intrauterine growth restriction.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants generated by combustion of organic material, including fossil fuel. OBJECTIVES: It has been an open question whether prenatal exposure to air pollution in general and PAHs in particular significantly increases the risk of intrauterine growth restriction, including small size for gestational age (SGA), and preterm delivery. Here, we have examined this hypothesis in a cohort of mothers and newborns in New York City. METHODS: Subjects were young, nonsmoking, healthy African-American (n = 224) and Dominican (n = 392) mother-newborn pairs residing in New York City whose prenatal PAH exposures were estimated by personal air monitoring. Questionnaire and medical record data were obtained. RESULTS: A 1 natural-log (ln)-unit increase in prenatal PAH exposure was associated with a 2-fold increase in risk of symmetric intrauterine growth restriction (i.e., SGA and fetal growth ratio < 85%) among full-term African Americans (p < 0.05). Preterm delivery risk was 5-fold greater among African Americans per ln-unit increase in prenatal PAH exposure. The same unit increase in exposure significantly increased the ratio of head circumference to birth weight by 0.04% in African Americans. These effects were not observed in Dominicans. CONCLUSION: Prenatal PAH exposure is likely to contribute to the occurrence of SGA as well as preterm births among African Americans. The lack of an association in Dominicans might reflect modification of the risk by healthful cultural practices among recent Dominican immigrants. Given that PAHs are globally generated and distributed pollutants, our observations have potential implications for environmental health and energy policies.

Estimating individual-level exposure to airborne polycyclic aromatic hydrocarbons throughout the gestational period based on personal, indoor, and outdoor monitoring.

OBJECTIVES: Current understanding on health effects of long-term polycyclic aromatic hydrocarbon (PAH) exposure is limited by lack of data on time-varying nature of the pollutants at an individual level. In a cohort of pregnant women in Krakow, Poland, we examined the contribution of temporal, spatial, and behavioral factors to prenatal exposure to airborne PAHs within each trimester and developed a predictive model of PAH exposure over the entire gestational period. METHODS: We monitored nonsmoking pregnant women (n = 341) for their personal exposure to pyrene and eight carcinogenic PAHs-benz[a]anthracene, chrysene/isochrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene [B(a)P], indeno[1,2,3-c,d]pyrene, dibenz[a,h]anthracene, and benzo[g,h,i]perylene-during their second trimester for a consecutive 48-hr period. In a subset (n = 78), we monitored indoor and outdoor levels simultaneously with the personal monitoring during the second trimester with an identical monitor. The subset of women was also monitored for personal exposure for a 48-hr period during each trimester. We repeatedly administered a questionnaire on health history, lifestyle, and home environment. RESULTS: The observed personal, indoor, and outdoor B(a)P levels we observed in Krakow far exceed the recommended Swedish guideline value for B(a)P of 0.1 ng/m(3). Based on simultaneously monitored levels, the outdoor PAH level alone accounts for 93% of total variability in personal exposure during the heating season. Living near the Krakow bus depot, a crossroad, and the city center and time spent outdoors or commuting were not associated with higher personal exposure. During the nonheating season only, a 1-hr increase in environmental tobacco smoke (ETS) exposure was associated with a 10-16% increase in personal exposure to the nine measured PAHs. A 1 degrees C decrease in ambient temperature was associated with a 3-5% increase in exposure to benz[a]anthracene, benzo[k]fluoranthene, and dibenz[a,h]anthracene, after accounting for the outdoor concentration. A random effects model demonstrated that mean personal exposure at a given gestational period depends on the season, residence location, and ETS. CONCLUSION: Considering that most women reported spending < 3 hr/day outdoors, most women in the study were exposed to outdoor-originating PAHs within the indoor setting. Cross-sectional, longitudinal monitoring supplemented with questionnaire data allowed development of a gestation-length model of individual-level exposure with high precision and validity. These results are generalizable to other nonsmoking pregnant women in similar exposure settings and support reduction of exposure to protect the developing fetus.

Characterizing air pollution in two low-income neighborhoods in Accra, Ghana.

Sub-Saharan Africa has the highest rate of urban population growth in the world, with a large number of urban residents living in low-income "slum" neighborhoods. We conducted a study for an initial assessment of the levels and spatial and/or temporal patterns of multiple pollutants in the ambient air in two low-income neighborhoods in Accra, Ghana. Over a 3-week period we measured (i) 24-hour integrated PM(10) and PM(2.5) mass at four roof-top fixed sites, also used for particle speciation; (ii) continuous PM(10) and PM(2.5) at one fixed site; and (iii) 96-hour integrated concentration of sulfur dioxide (SO(2)) and nitrogen dioxide (NO(2)) at 30 fixed sites. We also conducted seven consecutive days of mobile monitoring of PM(10) and PM(2.5) mass and submicron particle count. PM(10) ranged from 57.9 to 93.6 microg/m(3) at the four sites, with a weighted average of 71.8 microg/m(3) and PM(2.5) from 22.3 to 40.2 microg/m(3), with an average of 27.4 microg/m(3). PM(2.5)/PM(10) ratio at the four fixed sites ranged from 0.33 to 0.43. Elemental carbon (EC) was 10-11% of PM(2.5) mass at all four measurement sites; organic matter (OM) formed slightly less than 50% of PM(2.5) mass. Cl, K, and S had the largest elemental contributions to PM(2.5) mass, and Cl, Si, Ca, Fe, and Al to coarse particles. SO(2) and NO(2) concentrations were almost universally lower than the US-EPA National Ambient Air Quality Standards (NAAQS), with virtually no variation across sites. There is evidence for the contributions from biomass and traffic sources, and from geological and marine non-combustion sources to particle pollution. The implications of the results for future urban air pollution monitoring and measurement in developing countries are discussed.

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.

Gene expression profiling in healthy newborns from diverse localities of the Czech Republic.

Prenatal exposure to air pollution is associated with intrauterine growth restriction and low birth weight. Gene expression changes in newborns in relation to air pollution have not been sufficiently studied. We analyzed whole genome expression in cord blood leukocytes of 202 newborns from diverse localities of the Czech Republic, differing among other factors in levels of air pollution: the district of Karvina (characterized by higher concentration of air pollutants) and Ceske Budejovice (lower air pollution levels). We aimed to identify differentially expressed genes (DEGs) and pathways in relation to locality and concentration of air pollutants. We applied the linear model to identify the specific DEGs and the correlation analysis, to investigate the relationship between the concentrations of air pollutants and gene expression data. An analysis of biochemical pathways and gene set enrichment was also performed. In general, we observed modest changes of gene expression, mostly attributed to the effect of the locality. The highest number of DEGs was found in samples from the district of Karvina. A pathway analysis revealed a deregulation of processes associated with cell growth, apoptosis or cellular homeostasis, immune response-related processes or oxidative stress response. The association between concentrations of air pollutants and gene expression changes was weak, particularly for samples collected in Karvina. In summary, as we did not find a direct effect of exposure to air pollutants, we assume that the general differences in the environment, rather than actual concentrations of individual pollutants, represent a key factor affecting gene expression changes at delivery. Environ. Mol. Mutagen. 59:401-415, 2018. © 2018 Wiley Periodicals, Inc.

Pre-pregnancy dietary vitamin A intake may alleviate the adverse birth outcomes associated with prenatal pollutant exposure: epidemiologic cohort study in Poland.

A cohort study assessed the relationship between dietary intake of vitamin A in 493 healthy mothers before and around conception and adverse birth outcomes associated with environmental toxicant exposures. The cohort, non-smoking women with singleton pregnancies, aged 18-35 years, gave birth at 34-43 weeks of gestation. The women were asked about their diets over one year preceding pregnancy. Measurements of PM2.5 were carried out during the second trimester. Birth outcomes were adjusted for potential confounding factors, including gestational age. Standardized beta regression coefficients confirmed an inverse association between PM2.5 and birth weight (beta = -172.4, p = 0.02), but the effect of vitamin A on birth weight was positive (beta = 176.05, p = 0.05), when the two were adjusted for each other. The negative effect of higher prenatal PM2.5 exposures (above third tertile) on birth weight was significant in women below the third tertile of vitamin A intakes (beta = -185.1, p = 0.00), but not in women with higher intakes (beta = 38.6, p = 0.61). The negative effect of higher PM2.5 exposure on length at birth was significant with lower vitamin A intakes (beta = -1.1, p = 0.00) but not with higher intakes (beta = -0.3, p = 0.56). Prepregnancy nutrition of mothers may modulate the harmful effects of prenatal exposures to pollutants on birth outcomes.

Personal exposure to fine particles and benzo[a]pyrene. Relation with indoor and outdoor concentrations of these pollutants in Kraków.

OBJECTIVES: This study assessed personal exposure of pregnant women to fine particles (PM(25)) and benzo[a]pyrene (B[a]P) and the relationship between pollutant concentrations in ambient and indoor air. MATERIALS AND METHODS: In a group of 78 pregnant women, simultaneous 48 h measurements of personal, indoor, and outdoor exposure to PM(25) and B[a]P were carried out in the second trimester of pregnancy. The results show that participants were exposed to varying concentrations of PM(25) and B[a]P, with higher exposure in the winter season. Overall, the mean personal PM(25) level was 30.4 microg/m(3) and B[a]P 2.1 ng/m(3). The winter/summer ratios for mean personal exposures were 1.4 (35.6 microg/m(3) vs. 25.8 microg/m(3)) and 5.4 (4.9 ng/m(3) vs. 0.9 ng/m(3)), respectively. As for indoor levels, the winter/summer ratios were 1.4 (33.2 microg/m(3) vs. 24.4 microg/m(3)) for PM(25) and 5.4 (4.3 ng/m(3) vs. 0.8 ng/m(3)) for B[a]P, and for outdoor concentrations, the respective values were 1.5 (40.3 microg/m(3) vs. 26.4 microg/m(3), and 6.8 (6.1 ng/m(3) vs 0.9 ng/m(3)). A stronger correlation was found between personal PM(25) exposure and the pollutant concentration indoors (r = 0.89; 95% CI: 0.83-0.93) than outdoors (r = 0.75; 95% CI: 0.64-0.83). The correlations between personal B[a]P exposure and its indoor or outdoor levels were similar (0.95-0.96) and significant. The markedly higher exposure to B[a]P in Kraków in winter than in summer can be explained by the massive use of coal for heating in the cold season. CONCLUSION: We conclude that although ambient PM(25) measurements provide an adequate indicator of outdoor air quality for use in epidemiologic studies, they may not be adequate for studies on relationship between non-ambient pollution and health effects. Since only about 20% of variability in personal B[a]P exposure could be explained by personal PM(25) level, the extrapolation of personal exposure to B[a]P from personal PM(25) data may be greatly underestimated.

Linking childhood allergic asthma phenotypes with endotype through integrated systems biology: current evidence and research needs.

Asthma and other complex diseases results from a complex web of interactions involving inflammation, immunity, cell cycle, apoptosis, and metabolic perturbations across multiple organ systems. The extent to which various degrees of the age at onset, symptom severity, and the natural progression of the disease reflect multiple disease subtypes, influenced by unique process of development remains unknown. One of the most critical challenges to our understanding stems from incomplete understanding of the mechanisms. Within this review, we focus on the phenotypes of childhood allergic asthma as the basis to better understand the endotype for quantitative define subtypes of asthma. We highlight some of the known mechanistic pathways associated with the key hallmark events before the asthma onset. In particular, we examine how the recent advent of multiaxial -omics technologies and systems biology could help to clarify our current understanding of the pathway. We review how a large volume of molecular, genomic data generated by multiaxial technologies could be digested to identify cogent pathophysiologic molecular networks. We highlight some recent successes in application of these technologies within the context of other disease conditions for therapeutic interventions. We conclude by summarizing the research needs for the predictive value of preclinical biomarkers.

Volatile organic compounds of possible microbial origin and their risks on childhood asthma and allergies within damp homes.

BACKGROUND: Risk of indoor exposure to volatile organic compounds of purported microbial origin on childhood symptoms of wheezing, rhinitis, and/or eczema, and doctor-diagnosed asthma, rhinitis, and eczema, respectively, remain unclear. OBJECTIVE: To test hypotheses that total sum of 28 microbial volatile organic compounds (Σ26 MVOCs): 1) poses independent risk on doctor-diagnosed asthma, rhinitis, and eczema, respectively, as well as multiple symptom presentation with a minimum of the two of the above conditions (i.e. case); 2) is associated with significant interaction with absolute humidity (AH) on additive scale. METHODS: In a case-control investigation, 198 cases and 202 controls were examined during November 2001 - March 2002 period through home indoor air sampling, air quality inspection, and health outcome ascertainment. RESULTS: Not only the Σ28 MVOCs but also the global MVOC index were significantly higher within the homes of the cases with a high AH, compared to the controls with a low AH (all Ps<0.001). Only the cases, but not the controls, were associated with a dose-dependent increase in the exposure variables of interest (Σ28 MVOCs) per quartile increase in AH (P<0.0001 for the cases; P=0.780 for the controls). Only among the children who live in a high AH homes, a natural log (ln)-unit of Σ 28 MVOCs was associated with 2.5-times greater odds of the case status (95% CI, 1.0-6.2; P=0.046), compared to 0.7-times the odds (95% CI, 0.4-1.0; P=0.074) of the same outcome among the low AH homes. Specifically, joint exposure to a high MVOCs and high AH was associated with 2.6-times greater odds of the doctor-diagnosed asthma status (95% CI, 0.7-8.91; P=0.137). CONCLUSION: Joint occurrence of high Σ28 MVOCs and AH was associated with a significant increase in the case status and asthma risks in an additive scale.

Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms.

BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS: Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS: The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS: The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.