Publications by authors named "Wilfried J Karmaus"

29 Publications

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Cohort Profile Update: The Isle of Wight Whole Population Birth Cohort (IOWBC).

Int J Epidemiol 2020 08;49(4):1083-1084

Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA.

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http://dx.doi.org/10.1093/ije/dyaa068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660140PMC
August 2020

Bisphenol a Exposure, DNA Methylation, and Asthma in Children.

Int J Environ Res Public Health 2020 01 1;17(1). Epub 2020 Jan 1.

Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, Taipei 242, Taiwan.

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with promoter methylation (β = -0.539, = 0.010). For the logistic regression analysis, methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) ( = 0.001). Mediation analysis suggested that methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of methylation.
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http://dx.doi.org/10.3390/ijerph17010298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981376PMC
January 2020

Epigenome-wide association study of lung function level and its change.

Eur Respir J 2019 07 4;54(1). Epub 2019 Jul 4.

Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and their ratio (FEV/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 ( (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV/FVC: p=3.96×10 and p=7.22×10). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV/FVC: p=2.65×10).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
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http://dx.doi.org/10.1183/13993003.00457-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610463PMC
July 2019

Inhaled corticosteroids may prevent lung cancer in asthma patients.

Ann Thorac Med 2018 Jul-Sep;13(3):156-162

Department of Respiratory Medicine, Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan.

Background: It is unclear whether inhaled corticosteroids (ICS) have chemopreventive effect on lung cancer (LC) development in humans. We investigated the association between the ICS use in asthma patients and the risk of LC.

Methods: We conducted a nationwide, population-based retrospective cohort study using the National Health Insurance database. We identified 4210 asthmatics who were initially free of LC and regularly used ICS between 2001 and 2005 and 37,228 asthmatics without regular ICS use. Patients with documented history of tobacco use were excluded from the analyses. Asthmatics were categorized into a mild and a severe asthma group. Each patient was tracked until the end of 2010 to identify incident cases of LC. Cox proportional hazards models were used to evaluate the effect of ICS on the risk of LC, further stratifying by asthma severity and comorbidities.

Results: During follow-up, we identified 747 incident cases of LC diagnosed in the asthma cohort. Compared with severe asthmatics without regular ICS use, the risk of LC for those with mild asthma with regular ICS use was lower (adjusted hazard ratio = 0.42, 95% confidence interval = 0.31-0.56, < 0.0001). The risk of LC was calculated among the following rankings of risk severe asthma without regular ICS use, low severity without regular ICS, high severity with regular ICS, and low severity with regular ICS group showed a decreasing trend of LC incidence ( = 0.041). Analyses stratified by comorbidities revealed that the protective effect of ICS was assessed with better precision and more pronounced in those with renal diseases, stroke, and hyperlipidemia.

Conclusions: For patients with asthma, regular ICS use might have a protective effect against LC. Further studies are required to assess this potential association from both immunohistopathological and clinical aspects.
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http://dx.doi.org/10.4103/atm.ATM_367_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073787PMC
August 2018

Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies.

Sci Rep 2018 02 19;8(1):3221. Epub 2018 Feb 19.

Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA.

Immune-specific genes as well as genes responsible for the formation and integrity of the epidermal barrier have been implicated in the pathogeneses of allergic sensitization. This study sought to determine whether an epistatic effect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) and filaggrin (FLG) genes predispose to the development of allergic sensitization. Data from two birth cohort studies were analyzed, namely the Isle of Wight (IOW; n = 1,456) and the Manchester Asthma and Allergy Study (MAAS; n = 1,058). In the IOW study, one interaction term (IL4R rs3024676 × FLG variants) showed statistical significance (interaction term: P = 0.003). To illustrate the observed epistasis, stratified analyses were performed, which showed that FLG variants were associated with allergic sensitization only among IL4R rs3024676 homozygotes (OR, 1.97; 95% CI, 1.27-3.05; P = 0.003). In contrast, FLG variants effect was masked among IL4R rs3024676 heterozygotes (OR, 0.53; 95% CI, 0.22-1.32; P = 0.175). Similar results were demonstrated in the MAAS study. Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the pathogenesis of allergic sensitization. Hence, genetic susceptibility towards defective epidermal barrier and deviated immune responses could work together in the development of allergic sensitization.
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http://dx.doi.org/10.1038/s41598-018-21459-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818621PMC
February 2018

Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes.

Int J Mol Sci 2018 Feb 6;19(2). Epub 2018 Feb 6.

Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, 301 Robison Hall, 3825 DeSoto Avenue Memphis, TN 38152, USA.

To succeed, pregnancies need to initiate immune biases towards T helper 2 (Th2) responses, yet little is known about what establishes this bias. Using the Illumina 450 K platform, we explored changes in DNA methylation (DNAm) of Th1, Th2, Th17, and regulatory T cell pathway genes before and during pregnancy. Female participants were recruited at birth (1989), and followed through age 18 years and their pregnancy (2011-2015). Peripheral blood DNAm was measured in 245 girls at 18 years; from among these girls, the DNAm of 54 women was repeatedly measured in the first (weeks 8-21, = 39) and second (weeks 22-38, = 35) halves of pregnancy, respectively. M-values (logit-transformed β-values of DNAm) were analyzed: First, with repeated measurement models, cytosine-phosphate-guanine sites (CpGs) of pathway genes in pregnancy and at age 18 (nonpregnant) were compared for changes ( ≤ 0.05). Second, we tested how many of the 348 pathway-related CpGs changed compared to 10 randomly selected subsets of all other CpGs and compared to 10 randomly selected subsets of other CD4+-related CpGs (348 in each subset). Contrasted to the nonpregnant state, 27.7% of Th1-related CpGs changed in the first and 36.1% in the second half of pregnancy. Among the Th2 pathway CpGs, proportions of changes were 35.1% (first) and 33.8% (second half). The methylation changes suggest involvement of both Th1 and Th2 pathway CpGs in the immune bias during pregnancy. Changes in regulatory T cell and Th17 pathways need further exploration.
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http://dx.doi.org/10.3390/ijms19020477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855699PMC
February 2018

Interactions Between Bisphenol A Exposure and GSTP1 Polymorphisms in Childhood Asthma.

Allergy Asthma Immunol Res 2018 Mar;10(2):172-179

Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan.

Purpose: Bisphenol A (BPA) exposure may increase the risk of asthma. Genetic polymorphisms of oxidative stress-related genes, glutathione S-transferases (GSTM1, GSTP1), manganese superoxide dismutase, catalase, myeloperoxidase, and microsomal epoxide hydrolase may be related to BPA exposure. The aim is to evaluate whether oxidative stress genes modulates associations of BPA exposure with asthma.

Methods: We conducted a case-control study comprised of 126 asthmatic children and 327 controls. Urine Bisphenol A glucuronide (BPAG) levels were measured by ultra-performance liquid chromatography/tandem mass spectrometry, and genetic variants were analyzed by a TaqMan assay. Information on asthma and environmental exposure was collected. Analyses of variance and logistic regressions were performed to determine the association of genotypes and urine BPAG levels with asthma.

Results: BPAG levels were significantly associated with asthma (adjusted odds ratio [aOR], 1.29 per log unit increase in concentration; 95% confidence interval [CI], 1.081.55). Compared to the GG genotype, children with a GSTP1 AA genotype had higher urine BPAG concentrations (geometric mean [standard error], 12.72 [4.16] vs 11.42 [2.82]; P=0.036). In children with high BPAG, the GSTP1 AA genotype was related to a higher odds of asthma than the GG genotype (aOR, 4.84; 95% CI, 1.0223.06).

Conclusions: GSTP1 variants are associated with urine BPA metabolite levels. Oxidative stress genes may modulate the effect of BPA exposure on asthma.
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http://dx.doi.org/10.4168/aair.2018.10.2.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809766PMC
March 2018

Body Burden of Dichlorodiphenyl Dichloroethene (DDE) and Childhood Pulmonary Function.

Int J Environ Res Public Health 2017 11 14;14(11). Epub 2017 Nov 14.

School of Public Health, Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis, Memphis, TN 38152, USA.

Longitudinal studies have shown that early life exposure to dichlorodiphenyl dichloroethene (DDE) can lead to growth reduction during childhood and adolescence. In addition, DDE exposure has been linked to respiratory tract infections and an increased risk of asthma in children. Our aim was to understand the relationships between DDE exposure and pulmonary function in children, and, particularly, whether associations are mediated by the height of the children. We used data from an environmental epidemiologic study conducted in central Germany in children aged 8-10 years. The pulmonary function (forced vital capacity, FVC, and forced expiratory volume in one second, FEV1) were measured in three consecutive years. Blood DDE levels were measured at 8 and 10 years. We used linear mixed models for repeated measurements and path analyses to assess the association between blood levels of DDE and pulmonary function measurements. All models were adjusted for confounders. Linear mixed approaches and modelling concurrent effects showed no significant associations. The path analytical models demonstrated that DDE measured at eight years had significant, inverse, indirect, and total effects on FVC at ten years ( = 328; -0.18 L per μg/L of DDE) and FEV1 ( = 328; -0.17 L per μg/L of DDE), mediated through effects of DDE on height and weight. The DDE burden reduces pulmonary function through its diminishing effects on height and weight in children. Further studies are required to test these associations in other samples, preferably from a region with ongoing, high DDT application.
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http://dx.doi.org/10.3390/ijerph14111376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708015PMC
November 2017

The Effects of Pleural Plaques on Longitudinal Lung Function in Vermiculite Miners of Libby, Montana.

Am J Med Sci 2017 06 6;353(6):533-542. Epub 2017 Apr 6.

Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina; Environmental Biosciences Program, Medical University of South Carolina, Charleston, South Carolina.

Background: This study was conducted to assess associations of pleural plaques (PP) and longitudinal lung function in vermiculite miners of Libby, Montana who are occupationally exposed to asbestos. High-resolution computed tomography (HRCT) was used to identify asbestos-related findings in former Libby vermiculite miners. We investigated annual lung function decline in miners with PP only and compared them to miners with normal HRCT findings.

Materials And Methods: HRCTs from 128 miners were categorized into the following 4 diagnostic groups: (1) normal computed tomography scan (n = 9); (2) PP only (n = 72); (3) PP and interstitial fibrosis (n = 26) and (4) additional HRCT abnormalities (n = 21) such as rounded atelectasis, diffuse pleural thickening, pleural effusions or pulmonary nodules or tumor >1cm in diameter. Random intercept and slope linear mixed-effect regression models identified differences in lung function decline between miners with asbestos-associated outcomes and those with normal HRCT. Models were adjusted for follow-up time, body mass index, smoking status, latent exposure period and employment years. Interactions for smoking status with age and smoking status with pleural plaque severity were examined.

Results: Miners with PP only did not have an accelerated decline in lung function between 40 and 80 years. Miners with PP and additional HRCT abnormalities displayed significantly accelerated declines in forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide (P = 0.05 and P < 0.01, respectively). Plaque severity did not affect lung function decline. However, smokers with extensive plaques displayed accelerated loss in diffusing capacity of the lungs for carbon monoxide and forced expiratory volume in 1 second when compared to nonsmoking miners with mild plaque formation.

Conclusions: PP alone did not significantly affect lung function decline in vermiculite miners of Libby, Montana.
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http://dx.doi.org/10.1016/j.amjms.2017.03.033DOI Listing
June 2017

Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life.

Environ Health 2017 05 30;16(1):50. Epub 2017 May 30.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

Background: In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life.

Methods: Genome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years).

Results: In total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = -0.063, p-value = 0.0021), cg10473311 (coeff.int = -0.021, p-value = 0.027).

Conclusion: In utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life.
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http://dx.doi.org/10.1186/s12940-017-0262-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450181PMC
May 2017

Comparison of different cell type correction methods for genome-scale epigenetics studies.

BMC Bioinformatics 2017 Apr 14;18(1):216. Epub 2017 Apr 14.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

Background: Whole blood is frequently utilized in genome-wide association studies of DNA methylation patterns in relation to environmental exposures or clinical outcomes. These associations can be confounded by cellular heterogeneity. Algorithms have been developed to measure or adjust for this heterogeneity, and some have been compared in the literature. However, with new methods available, it is unknown whether the findings will be consistent, if not which method(s) perform better.

Results: Methods: We compared eight cell-type correction methods including the method in the minfi R package, the method by Houseman et al., the Removing unwanted variation (RUV) approach, the methods in FaST-LMM-EWASher, ReFACTor, RefFreeEWAS, and RefFreeCellMix R programs, along with one approach utilizing surrogate variables (SVAs). We first evaluated the association of DNA methylation at each CpG across the whole genome with prenatal arsenic exposure levels and with cancer status, adjusted for estimated cell-type information obtained from different methods. We then compared CpGs showing statistical significance from different approaches. For the methods implemented in minfi and proposed by Houseman et al., we utilized homogeneous data with composition of some blood cells available and compared them with the estimated cell compositions. Finally, for methods not explicitly estimating cell compositions, we evaluated their performance using simulated DNA methylation data with a set of latent variables representing "cell types".

Results: Results from the SVA-based method overall showed the highest agreement with all other methods except for FaST-LMM-EWASher. Using homogeneous data, minfi provided better estimations on cell types compared to the originally proposed method by Houseman et al. Further simulation studies on methods free of reference data revealed that SVA provided good sensitivities and specificities, RefFreeCellMix in general produced high sensitivities but specificities tended to be low when confounding is present, and FaST-LMM-EWASher gave the lowest sensitivity but highest specificity.

Conclusions: Results from real data and simulations indicated that SVA is recommended when the focus is on the identification of informative CpGs. When appropriate reference data are available, the method implemented in the minfi package is recommended. However, if no such reference data are available or if the focus is not on estimating cell proportions, the SVA method is suggested.
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http://dx.doi.org/10.1186/s12859-017-1611-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391562PMC
April 2017

Lead exposure, IgE, and the risk of asthma in children.

J Expo Sci Environ Epidemiol 2017 09 12;27(5):478-483. Epub 2017 Apr 12.

Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Lead (Pb) has adverse effects on our nervous system and renal systems. Young children are more vulnerable to Pb exposure. However, the role of low-level Pb exposure in the immune system and allergic diseases in children is not well established. The aims of this study are to investigate the associations between Pb exposure and allergic diseases; between Pb and immunoglobulin E (IgE) as an intervening variable; and gender-based differences. We used multistage stratified random sampling to recruit kindergarten children nationwide in Taiwan. Information about allergic diseases and environmental exposures was collected by questionnaire. We compared children with and without allergic diseases for blood Pb levels measured by inductively coupled plasma mass spectrometry. The association between blood Pb and allergic diseases was assessed by logistic regression and those between Pb and IgE by generalized linear models. We also conducted mediation analysis to evaluate how much risk of allergic diseases related to Pb exposure is explained by IgE. A total of 930 children completed specimen collections. There was a positive association between Pb and asthma. Blood Pb were also positively linked with serum IgE (β=0.26 kU/l per ln-unit increase Pb concentration; 95% CI 0.009-0.50 kU/l), after adjusting for potential confounders. Analyses stratified by gender revealed that blood Pb correlated with IgE only in boys (β=0.40 kU/l; 95% CI 0.03-0.76 kU/l). We estimated that 38% of the total effect of Pb exposure on asthma is mediated by IgE levels. In conclusion, Pb exposure is associated with both blood IgE and asthma in boys. Moreover, the effect of Pb exposure on asthma may be mediated by IgE levels.
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http://dx.doi.org/10.1038/jes.2017.5DOI Listing
September 2017

Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma.

Int J Environ Res Public Health 2017 02 8;14(2). Epub 2017 Feb 8.

Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA.

Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione -transferase Mu 1 (), glutathione -transferase pi 1 (), superoxide dismutase 2 (), catalase (), myeloperoxidase (), and In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11-1.60). Children with the (rs1695) AA and (rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54-5.02)), we estimated whether variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on and , but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for TT was further elevated to 3.32 (1.75-6.32) when the residuals of MEHHP were high. Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of , considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma.
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http://dx.doi.org/10.3390/ijerph14020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334716PMC
February 2017

Polycyclic aromatic hydrocarbons exposure, oxidative stress, and asthma in children.

Int Arch Occup Environ Health 2017 Apr 7;90(3):297-303. Epub 2017 Feb 7.

Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic and teratogenic properties. However, little is known about the effect of PAH on our immune and respiratory systems. Hence, we investigated associations (1) between PAH exposure and IgE levels and asthma in children and (2) between PAH exposure and the oxidative stress marker 8OHdG potentially involved in disease pathogenesis stratifying by (3) sex-based differences.

Methods: A total of 453 kindergarten children were recruited and provided samples. Urine biomarker of PAH exposure (1-OHP levels) was measured by UPLC-MS/MS and a marker of oxidative stress (8OHdG) was measured by ELISA. Serum IgE were assessed and information on asthma was collected. Associations between 1-OHP levels, 8OHdG, IgE and asthma were analyzed by multivariate linear and logistic regression. A mediation analysis was conducted to evaluate whether the risk of increased IgE and asthma related to PAH exposure is explained by 8OHdG changes.

Results: Urine 1-OHP levels were positively related to 8OHdG levels (per ln-unit: β = 0.30kU/l, p = 0.002). Similar results were also found for 1-OHP levels with IgE levels (per ln-unit: β = 0.27 kU/l, p = 0.027). 1-OHP levels (per ln-unit) were significantly associated with asthma, with an OR (95% CI) of 1.42 (1.18-1.70). In addition, 1-OHP levels were associated with asthma. It is estimated that 35% of the effect of PAH exposure on asthma is mediated by 8OHdG levels.

Conclusion: Exposure to PAH may enhance oxidative stress and may induce asthma. The effect of PAH exposure on asthma may be mediated by oxidative stress.
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http://dx.doi.org/10.1007/s00420-017-1198-yDOI Listing
April 2017

Quantifying annual internal effective Cesium dose utilizing direct body-burden measurement and ecological dose modeling.

J Expo Sci Environ Epidemiol 2016 11 11;26(6):546-553. Epub 2015 Mar 11.

Department of Global Environmental Health Sciences: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.

The Chernobyl Nuclear Power Plant (CNPP) accident represents one of the most significant civilian releases of Cesium (Cs, radiocesium) in human history. In the Chernobyl-affected region, radiocesium is considered to be the greatest on-going environmental hazard to human health by radiobiologists and public health scientists. The goal of this study was to characterize dosimetric patterns and predictive factors for whole-body count (WBC)-derived radiocesium internal dose estimations in a CNPP-affected children's cohort, and cross-validate these estimations with a soil-based ecological dose estimation model. WBC data were used to estimate the internal effective dose using the International Commission on Radiological Protection (ICRP) 67 dose conversion coefficient for Cs and MONDAL Version 3.01 software. Geometric mean dose estimates from each model were compared utilizing paired t-tests and intra-class correlation coefficients. Additionally, we developed predictive models for WBC-derived dose estimation in order to determine the appropriateness of EMARC to estimate dose for this population. The two WBC-derived dose predictive models identified Cs soil concentration (P<0.0001) as the strongest predictor of annual internal effective dose from radiocesium validating the use of the soil-based EMARC model. The geometric mean internal effective dose estimate of the EMARC model (0.183 mSv/y) was the highest followed by the ICRP 67 dose estimates (0.165 mSv/y) and the MONDAL model estimates (0.149 mSv/y). All three models yielded significantly different geometric mean dose (P<0.05) estimates for this cohort when stratified by sex, age at time of exam and season of exam, except for the mean MONDAL and EMARC estimates for 15- and 16-year olds and mean ICRP and MONDAL estimates for children examined in Winter. Further prospective and retrospective radio-epidemiological studies utilizing refined WBC measurements and ecological model dose estimations, in conjunction with findings from animal toxicological studies, should help elucidate possible deterministic radiogenic health effects associated with chronic low-dose internal exposure to Cs.
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http://dx.doi.org/10.1038/jes.2015.6DOI Listing
November 2016

An Efficient Approach to Screening Epigenome-Wide Data.

Biomed Res Int 2016 13;2016:2615348. Epub 2016 Mar 13.

Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Zach Curlin Street, Memphis, TN 38152, USA.

Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in association with some covariate(s) is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s) and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk.
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http://dx.doi.org/10.1155/2016/2615348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808532PMC
December 2016

TSLP polymorphisms, allergen exposures, and the risk of atopic disorders in children.

Ann Allergy Asthma Immunol 2016 Feb 18;116(2):139-45.e1. Epub 2015 Dec 18.

Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tennessee.

Background: Thymic stromal lymphopoietin (TSLP) polymorphisms influence atopy risk. TSLP might constitute a key interface between the environment and the allergic immune response. However, whether the effects of TSLP polymorphisms on atopic dermatitis (AD) are modified by allergic sensitization is not clear.

Objective: To evaluate the joint effect of allergic sensitization and TSLP polymorphisms on AD and to test whether TSLP polymorphisms increase the risk of asthma in children with AD.

Methods: A total of 1,520 kindergarten children (375 with AD and 1,145 controls) selected from the Childhood Environment and Allergic Diseases Study cohort in 2010 were enrolled. Information about allergic diseases and environmental exposures was collected by questionnaire. Skin prick tests were performed to measure allergic sensitization. TSLP polymorphisms were genotyped by TaqMan assay. Logistic regressions were conducted to estimate the association among TSLP polymorphisms, allergic sensitization, and AD. For replication, a subsample of the British Isle of Wight birth cohort was used.

Results: The TSLP rs2289278 CC genotype increased the risk of AD (odds ratio 1.90, 95% confidence interval 1.12-3.22). In children sensitized to certain allergens, a genetic predisposition (rs2289278 genotype CC) significantly increased the risk of AD. These findings were replicated in the British subsample using rs2289276 genotypes TT and TC, which are in linkage disequilibrium with rs2289278. In subjects with AD, the rs2289278 C allele also significantly increased the risk of developing asthma (odds ratio 8.31, 95% confidence interval 1.08-64.13).

Conclusion: The association of rs2289278 with AD was stronger in children with allergic sensitization than in children without atopy. TSLP polymorphisms also increased the risk of asthma in children with AD.
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http://dx.doi.org/10.1016/j.anai.2015.11.016DOI Listing
February 2016

Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina.

Ann Am Thorac Soc 2016 Mar;13(3):356-63

3 Medical University of South Carolina, Charleston, and.

Rationale: On January 6, 2005 a train derailment led to an estimated 54,915-kg release of chlorine at a local textile mill in Graniteville, South Carolina.

Objectives: We used the employee health spirometry records of the textile to identify enduring effects of chlorine gas exposure resulting from the incident on the lung function of workers employed at the textile mill.

Methods: Spirometry records from 1,807 mill workers (7,332 observations) were used from 4 years before and 18 months after the disaster. Longitudinal analysis using marginal regression models produced annual population mean estimates for FEV1, FVC, and FEV1/FVC ratio. Covariate adjustment was made for sex, age, smoking, height, season tested, technician, obesity, season × year interactions, and smoker × year interactions. The increased prevalence of mill workers having accelerated FEV1 decline was also evaluated after the chlorine spill.

Measurements And Main Results: In the year of the accident, we observed a significant reduction in mean FEV1 (-4.2% predicted; P = 0.019) when compared with the year before the incident. In the second year, partial recovery in the mean FVC % predicted level was seen, but the cohort's average FEV1/FVC ratio continued to decrease over time. Severe annual FEV1 decline was most prevalent in the year of the accident, and independent of mill worker smoking status.

Conclusions: The Graniteville mill worker cohort revealed significant reductions in lung function immediately after the chlorine incident. Improvement was seen in the second year; but the proportion of mill workers experiencing accelerated FEV1 annual decline significantly increased in the 18 months after the chlorine incident.
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http://dx.doi.org/10.1513/AnnalsATS.201508-525OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015716PMC
March 2016

Reduced lung function in children associated with cesium 137 body burden.

Ann Am Thorac Soc 2015 Jul;12(7):1050-7

3 Research Center for Radiation Medicine, Academy of Medical Sciences of Ukraine, Kyiv, Ukraine.

Rationale: We previously reported that obstructive and restrictive lung function findings were associated with radioactive Cesium 137 ((137)Cs) soil contamination from the 1986 Chernobyl disaster in a pediatric cohort residing in the Narodichesky district of Ukraine from 1993 to 1998.

Objectives: To determine whether these associations persist, we repeated the study and refined the exposure by measuring individual radiation concentration with a whole-body counter.

Methods: Basic and post-bronchodilator spirometry measurements were made for 517 children aged 8 to 17 years born in and living within this differentially contaminated study area during 2008 to 2010.

Measurements And Main Results: A γ-spectrometer equipped with a collimator was used for the measurement of whole-body radiation and adjusted for weight. General linear and logistic regression models were used to estimate the association between spirometry measures and the weight-adjusted (137)Cs whole-body burden (Bq/kg) while controlling for potential confounders. The geometric median weight-adjusted radiation concentration was 65.96 Bq/kg (95% confidence interval, 14.98-240.9 Bq/kg), equivalent to a geometric mean internal dose estimate of 0.165 mSv/yr (95% confidence interval, 0.037-0.602 mSv/yr). Decrements in percentage predicted FEV1/FVC and an increased odds of bronchodilator responsiveness, restrictive impairment, and FVC less than lower limit of normal were associated with a log increase in weight-adjusted (137)Cs whole-body burden after adjusting for potential confounders.

Conclusions: Our previous study of soil (137)Cs exposure and reduced lung function was corroborated herein with individual (137)Cs whole-body burden, although low, and annual internal dose data. Children in a region just outside of the closed Chernobyl contamination zone continued to have respiratory health deficits associated with (137)Cs whole-body burden as recently as 2010.
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http://dx.doi.org/10.1513/AnnalsATS.201409-432OCDOI Listing
July 2015

Response.

Chest 2015 Mar;147(3):e128-e129

Department of Medicine, the Department of Public Health Sciences, and the Environmental Biosciences Program, Medical University of South Carolina, Charleston, SC. Electronic address:

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http://dx.doi.org/10.1378/chest.14-2635DOI Listing
March 2015

Response.

Chest 2015 Mar;147(3):e124-e126

Department of Medicine, the Department of Public Health Sciences, and the Environmental Biosciences Program, Medical University of South Carolina, Charleston, SC. Electronic address:

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http://dx.doi.org/10.1378/chest.14-3041DOI Listing
March 2015

Early-life antibiotic use is associated with wheezing among children with high atopic risk: a prospective European study.

J Asthma 2015 Sep;52(7):647-52

a School of Food Science, Guangdong Pharmaceutical University , Zhongshan , China .

Background: Little is known about the relationship between antibiotic use and asthma in the children with a higher risk of allergic sensitization. We examine the association between the use of specific therapeutic antibiotics in the first year of life and development of wheezing by 36 months among children with a higher risk of allergic sensitization.

Methods: A multi-center prospective cohort study was conducted among children at high risk for allergic sensitization. A validated questionnaire was used to prospectively collect information on antibiotic use and potential risk factors for wheezing from parents or guardians of 606 children from three European countries at 6, 12, 24 and 36 months of age. Multivariate linear and logistic regression models were used to adjust for potential confounders and effect modifiers and to estimate the association of antibiotic use with the development of early childhood wheezing.

Results: Of the antibiotics assessed, only macrolide use in the first year of life was associated with increasing risk for wheezing by 36 months, after adjusting for gender, socioeconomic status, breast feeding >6 months, tobacco smoke exposure, family history of asthma, and respiratory infection (RR = 1.09; 95% CI 1.05-1.13). To avoid a bias by indication, we analyzed children with and without respiratory infection separately. Similar associations were observed for macrolides use in children who had no respiratory infection.

Conclusions: In European children with a familial risk for allergic sensitization, we found a positive association between macrolide use in the first year of life and wheezing until 36 months old which was independent of the effect of respiratory infection.
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http://dx.doi.org/10.3109/02770903.2014.999284DOI Listing
September 2015

Pleural plaques and their effect on lung function in Libby vermiculite miners.

Chest 2014 Sep;146(3):786-794

Department of Medicine, Medical University of South Carolina, Charleston, SC; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC; Environmental Biosciences Program, Medical University of South Carolina, Charleston, SC. Electronic address:

Background: Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners.

Methods: The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure.

Results: Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function.

Conclusions: Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.
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http://dx.doi.org/10.1378/chest.14-0043DOI Listing
September 2014

Incidence and predictive factors of Balkan endemic nephropathy: a longitudinal study.

Saudi J Kidney Dis Transpl 2014 Mar;25(2):343-52

Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, USA.

Balkan endemic nephropathy (BEN) is a chronic kidney disease that progresses slowly. There are no known clinical markers to identify an early disease development. We evaluated the relationship between parental history of BEN and clinical markers as predictors of new occurrences of BEN. A 5-year prospective study in the offsprings of BEN and control patients was conducted in Vratza, Bulgaria, between 2003 and 2009 using markers in years one and three to predict new cases of BEN in the year five. We defined incident cases of BEN based on parental history, reduced kidney size and reduced kidney function, distinguishing probable and definite BEN, both combined as total incidence. The data were analyzed by Cox regression models using age as time scale and controlling for gender. We estimated hazard ratios and their 95% confidence intervals. The incidence of BEN was 17.4%. Paternal history was strongly associated with all three incidence groups (hazards ratio: 27-68, P <0.05). A reduction of kidney size of 1 mm resulted in a 5% increased hazard. However, taking parental history of BEN into account, these associations lost their significance. No kidney function measures were associated with new onset of BEN. A parental history of BEN is more important than clinical markers predicting the incidence of BEN. Without this information, kidney length forecasts probable BEN and the total incidence, while none of any clinical markers was related to definite BEN.
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http://dx.doi.org/10.4103/1319-2442.128539DOI Listing
March 2014

The Immediate Pulmonary Disease Pattern following Exposure to High Concentrations of Chlorine Gas.

Pulm Med 2013 9;2013:325869. Epub 2013 Dec 9.

Department of Global Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2100, New Orleans, LA 70112, USA.

Background. Classification of pulmonary disease into obstructive, restrictive, and mixed patterns is based on 2005 ATS/ERS guidelines and modified GOLD criteria by Mannino et al. (2003), but these guidelines are of limited use for simple spirometry in situations involving mass casualties. Aim. The purpose of this study was to apply these guidelines to patients who underwent simple spirometry following high concentration of chlorine gas inhalation after a train derailment in Graniteville, South Carolina. Methods. We retrospectively investigated lung functions in ten patients. In order to classify pulmonary disease pattern, we used 2005 ATS/ERS guidelines and modified GOLD criteria along with our own criteria developed using available simple spirometry data. Results. We found predominant restrictive pattern in our patients with both modified GOLD and our criteria, which is in contrast to other chlorine exposure studies where obstructive pattern was more common. When compared to modified GOLD and our criteria, 2005 ATS/ERS guidelines underestimated the frequency of restrictive disease. Conclusion. Diagnosis of pulmonary disease patterns is of importance after irritant gas inhalation. Acceptable criteria need to be developed to evaluate pulmonary disease through simple spirometry in events leading to mass casualty and patient surge in hospitals.
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http://dx.doi.org/10.1155/2013/325869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872415PMC
January 2014

Respiratory symptoms and lung function 8-10 months after community exposure to chlorine gas: a public health intervention and cross-sectional analysis.

BMC Public Health 2013 Oct 9;13:945. Epub 2013 Oct 9.

University of South Carolina, Columbia, SC, USA.

Background: We implemented a community based interventional health screening for individuals located within one mile of a 54 metric tons release of liquid chlorine following a 16 tanker car train derailment on 6 January, 2005 in Graniteville, South Carolina, USA. Public health intervention occurred 8-10 months after the event, and provided pulmonary function and mental health assessment by primary care providers. Its purpose was to evaluate those exposed to chlorine for evidence of ongoing impairment for medical referral and treatment. We report comparative analysis between self-report of respiratory symptoms via questionnaire and quantitative spirometry results.

Methods: Health assessments were obtained through respiratory symptom and exposure questionnaires, simple spirometry, and physical exam. Simple spirometry was used as the standard to identify continued breathing problems. Sensitivity, specificity, positive and negative predictive values were applied to evaluate the validity of the respiratory questionnaire. We also identified the direction of discrepancy between self-reported respiratory symptoms and spirometry measures. Generalized estimation equations determined prevalence ratios for abnormal spirometry based on the presence of participant persistent respiratory symptoms. Covariate adjustment was made for participant age, sex, race, smoking and educational status.

Results: Two hundred fifty-nine people participated in the Graniteville health screening; 53 children (mean age = 11 years, range: <1-16), and 206 adults (mean age = 50 years, range: 18-89). Of these, 220 (85%) performed spirometry maneuvers of acceptable quality. Almost 67% (n = 147) displayed abnormal spirometry, while 50% (n = 110) reported persistent new-onset respiratory symptoms. Moreover, abnormal spirometry was seen in 65 participants (29%) who did not report any discernible breathing problems. This represented a net 16.8% underreporting of symptoms. Sensitivity and specificity of questionnaire self-report of symptoms were low at 55.8% and 61.6%, respectively. Persistent cough (41%) and shortness of breath (39%) were the most frequently reported respiratory symptoms.

Conclusion: Eight to ten months after acute chlorine exposure, the Graniteville health screening participants under-reported respiratory symptoms when compared to abnormal spirometry results. Sensitivity and specificity were low, and we determined that relying upon the self-report questionnaire was not adequate to objectively assess the lung health of our population following irritant gas exposure.
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http://dx.doi.org/10.1186/1471-2458-13-945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851981PMC
October 2013

Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: a prospective birth cohort study.

Allergy Asthma Clin Immunol 2010 Apr 20;6(1). Epub 2010 Apr 20.

Department of Epidemiology and Biostatistics, Norman J Arnold School of Public Health, University of South Carolina, USA.

Background: Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction.

Objective: To investigate the interaction of IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years.

Methods: Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data (at birth, age 4, 10, 18); skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 were collected. Three SNPs were selected from IL13: rs20541 (exon 4, nonsynonymous SNP), rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs).

Results: Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy (sensitization to one or more food or aeroallergens) increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 on SPT was restricted only to first-born children (p = 0.007; adjusted PR = 1.35; 95%CI = 1.09, 1.69). Similar findings were noted for firstborns regarding elevated total serum IgE at age 10 (p = 0.007; PR = 1.73; 1.16, 2.57) and specific inhalant screen (p = 0.034; PR = 1.48; 1.03, 2.13).

Conclusions: This is the first study to show an interaction between birth order and IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene.
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http://dx.doi.org/10.1186/1710-1492-6-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874524PMC
April 2010

137Cesium exposure and spirometry measures in Ukrainian children affected by the Chernobyl nuclear incident.

Environ Health Perspect 2010 May 25;118(5):720-5. Epub 2010 Jan 25.

Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208 , USA.

Background: After the Chernobyl accident in 1986, children of the contaminated Narodichesky region of Ukraine were obliged to participate in a yearly medical screening. They have been exposed to 137cesium (137Cs; half-life = 30 years) in contaminated soils, air, and food.

Objective: Using a "natural experiment" approach and a longitudinal prospective cohort study design, we investigated the association of soil 137Cs and spirometry measures for 415 children using 1,888 repeated measurements from 1993 to 1998.

Methods: Mean baseline village soil 137Cs measurements, which varied from 29.0 to 879 kBq/m2, were used as exposure indicators. A standardized spirometry protocol and prediction equations specific to Ukrainian children were used by the same pulmonologist in all screenings.

Results: Children living in villages with the highest quintile of soil 137Cs were 2.60 times more likely to have forced vital capacity (FVC) < 80% of predicted [95% confidence interval (CI), 1.07-6.34] and 5.08 times more likely to have a ratio of forced expiratory volume in 1 sec (FEV1) to FVC% < 80% (95% CI, 1.02-25.19). We found statistically significant evidence of both airway obstruction (FEV1/FVC%, peak expiratory flow, and maximum expiratory flow at 25%, 50%, and 75% of FVC) and restriction (FVC) with increasing soil 137Cs.

Conclusions: These findings are unique and suggest significant airway obstruction and restriction consequences for children chronically exposed to low-dose radioactive contaminants such as those found downwind of the Chernobyl Nuclear Power Plant.
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http://dx.doi.org/10.1289/ehp.0901412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866691PMC
May 2010

Increased blood pressure in adult offspring of families with Balkan endemic nephropathy: a prospective study.

BMC Nephrol 2006 Aug 23;7:12. Epub 2006 Aug 23.

National Center of Public Health Protection, 15 Acad. Ivan Geshov Street, Sofia, Bulgaria.

Background: Previous studies have linked smaller kidney dimensions to increased blood pressure. However, patients with Balkan Endemic Nephropathy (BEN), whose kidneys shrink during the course of the disease, do not manifest increased blood pressure. The authors evaluated the relationship between kidney cortex width, kidney length, and blood pressure in the offspring of BEN patients and controls.

Methods: 102 offspring of BEN patients and 99 control offspring of non-BEN hospital patients in the Vratza District, Bulgaria, were enrolled in a prospective study and examined twice (2003/04 and 2004/05). Kidney dimensions were determined using ultrasound, blood pressure was measured, and medical information was collected. The parental disease of BEN was categorized into three groups: mother, father, or both parents. Repeated measurements were analyzed with mixed regression models.

Results: In all participants, a decrease in minimal kidney cortex width of 1 mm was related to an increase in systolic blood pressure of 1.4 mm Hg (p = 0.005). There was no association between kidney length and blood pressure. A maternal history of BEN was associated with an increase in systolic blood pressure of 6.7 mm Hg (p = 0.03); paternal BEN, +3.2 mm Hg (p = 0.35); or both parents affected, +9.9 mm Hg (p = 0.002). There was a similar relation of kidney cortex width and parental history of BEN with pulse pressure; however, no association with diastolic blood pressure was found.

Conclusion: In BEN and control offspring, a smaller kidney cortex width predisposed to higher blood pressure. Unexpectedly, a maternal history of BEN was associated with average increased systolic blood pressure in offspring.
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http://dx.doi.org/10.1186/1471-2369-7-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1560117PMC
August 2006