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.

• Keywords
• 8-oxo-7,8-dihydro-2′-deoxyguanosine, Air pollution, Benzo[a]pyrene, Endotype;15-Ft2-isoprostane,
• MeSH
• 8-Hydroxy-2'-Deoxyguanosine urine   MeSH
• Benzo(a)pyrene analysis   MeSH
• Asthma blood   epidemiology   physiopathology   urine   MeSH
• Dinoprost analogs & derivatives   blood   MeSH
• Child MeSH
• Phenotype MeSH
• Infant MeSH
• Cotinine urine   MeSH
• Air Pollutants analysis   MeSH
• Humans MeSH
• Adolescent MeSH
• Lung physiopathology   MeSH
• Child, Preschool MeSH
• Case-Control Studies MeSH
• Environmental Exposure analysis   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• 8-epi-prostaglandin F2alpha MeSH Browser
• 8-Hydroxy-2'-Deoxyguanosine MeSH
• Benzo(a)pyrene MeSH
• Dinoprost MeSH
• Cotinine MeSH
• Air Pollutants MeSH

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.

• Keywords
• air pollution, asthma, gene-environment interaction, polycyclic aromatic hydrocarbon, single nucleotide polymorphism,
• MeSH
• Algorithms MeSH
• Benzo(a)pyrene toxicity   MeSH
• Asthma chemically induced   genetics   MeSH
• Child MeSH
• Genetic Predisposition to Disease * MeSH
• Gene-Environment Interaction MeSH
• Polymorphism, Single Nucleotide MeSH
• Air Pollutants toxicity   MeSH
• Humans MeSH
• Multifactorial Inheritance * MeSH
• Statistics as Topic MeSH
• Unsupervised Machine Learning MeSH
• Case-Control Studies MeSH
• Environmental Exposure adverse effects   MeSH
• Air Pollution adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Benzo(a)pyrene MeSH
• Air Pollutants MeSH

OBJECTIVES: To compare the morbidity of 66 Roma and 466 non-Roma children born and living in a diffused type of habitation in the district of Teplice. METHODS: For each child, a complete list of illnesses that pediatricians recorded using ICD-10 codes for all physician visits and/or hospitalizations was obtained. RESULTS: At the age 0-2 years the Roma/non-Roma rate ratios (RR) of the incidence of influenza (RR 1.6), otitis media (RR 2.3), intestinal infectious diseases (RR 1.7) and viral illnesses (RR 6.3) were statistically associated with ethnicity. The higher incidence of bronchitis (RR 1.7) and pneumonia (RR 2.2) in the Roma children was associated with the low education of mothers and not with ethnicity. CONCLUSIONS: At the age of 0-2 years the incidence of influenza, otitis media, intestinal infectious diseases and of viral diseases was significantly higher in Roma than in non-Roma children and was not associated with education of mothers. There was no increase in the morbidity of Roma children over the non-Roma children at the age of 2-6 years. The prevalence of allergies in Roma children was extremely low.

• MeSH
• Health Status Disparities * MeSH
• Child MeSH
• Incidence MeSH
• Communicable Diseases epidemiology   MeSH
• Infant MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Roma * MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH