The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing among COPD patients.

BACKGROUND: Particulate matter with a diameter of < 2.5 µm (PM2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM2.5 exposure and DNA methylation in CpG islands as well as explore the associated gene pathways. METHODS: A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM2.5 exposure levels were calculated for short-term (7 days), mid-term (35 days), and long-term (90 days). DNA methylation analysis was performed on the blood samples, which, after PCR amplification and hybridization, were finally sequenced using an Illumina NovaSeq 6000 system. Correlation between PM2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM2.5 exposure to identify the relevant biological functions or pathways. RESULTS: The number of CpG sites showing differential methylation was 36, 381, and 182 for the short-, mid-, and long-term indoor models, respectively, and 3, 98, and 28 for the short-, mid-, and long-term estimated exposure models, respectively. The representative genes were TMTC2 (p = 1.63 × 10-3, R2 = 0.656), GLRX3 (p = 1.46 × 10-3, R2 = 0.623), DCAF15 (p = 2.43 × 10-4, R2 = 0.623), CNOT6L (p = 1.46 × 10-4, R2 = 0.609), BSN (p = 2.21 × 10-5, R2 = 0.606), and SENP6 (p = 1.59 × 10-4, R2 = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer. CONCLUSION: A significant association was observed between PM2.5 exposure and DNA methylation upon short-term exposure, and the extent of DNA methylation was the highest upon mid-term exposure. Additionally, various pathways related to neurodegenerative diseases and cancer were associated with patients with COPD. GOV IDENTIFIER: NCT04878367.

Assessing the association between cigarette smoking and blood C-reactive protein levels using restructured cohort data.

INTRODUCTION: Cigarette smoke exposure is known to induce inflammation, leading to elevated levels of inflammatory markers such as white blood cell (WBC) count and C-reactive protein (CRP). Despite extensive research on this relationship, longitudinal studies are limited. We aimed to explore the association between cigarette smoke exposure and WBC count and CRP levels by restructuring community cohort data. METHODS: Data from a community cohort of the Korean population, followed biennially from 2001 to 2018, were utilized. Smoking status was determined through self-administered questionnaires. WBC and CRP levels were measured in a central laboratory with stringent quality control. Cohort data were restructured into pairs representing before and after measurements. We analyzed smoking effects on WBC and CRP using pairwise before-after tests based on changes in smoking status. Furthermore, parallel group analyses comparing changes in smoking status to no change were conducted. RESULTS: Analysis included 4336 pairs for WBC and 3068 pairs for CRP from 10,030 participants. Pairwise analysis showed a significant decrease in WBC transitioning from current smoker to non-smoker and an increase from non-smoker to current smoker. Parallel group analysis demonstrated a significant decrease in WBC transitioning from current smoker to non-smoker compared to remaining current smoker, and an increase from non-smoker to current smoker compared to remaining non-smoker. CRP did not exhibit significant associations in either analysis. CONCLUSIONS: In a community cohort, cigarette smoking was associated with elevated WBC count. However, CRP levels did not consistently reflect inflammation associated with cigarette smoking.

Evaluation on the Sex-Specific Association Between Cigarette Smoke Exposure and Inflammation Markers-C-Reactive Protein and White Blood Cell Count.

INTRODUCTION: Cigarette smoke increases peripheral white blood cell (WBC) count. However, the dose-dependent association between smoking and C-reactive protein (CRP), an important inflammatory marker, has been reported as inconsistent. AIMS AND METHODS: Here, we evaluated the associations between smoking and CRP using both smoking questionnaires and urine cotinine as exposure markers. The Korea National Health and Nutrition Examination Survey data were used for analyzing the associations. Multiple regression analyses were performed to examine the associations between cigarette smoke exposure, as assessed by questionnaires and urine cotinine, and health effects, as measured by CRP and WBC count, controlling for potential confounders. The confounders, including age, sex, body mass index, blood pressure, cholesterol, glucose, alanine aminotransferase, and uric acid, were selected a priori based on the literature. RESULTS: A total of 11 435 participants were included for analysis. For the exposure-response relationship, the results indicated a significant increase in CRP levels in male smokers compared to male nonsmokers (p = .002), whereas no significant increase was found in female smokers compared to female nonsmokers (p = .680). For the dose-response relationship, a significant positive association was observed between urine cotinine and CRP in male smokers (p = .018), whereas no significant association was found in female smokers (p = .508). WBC count consistently showed significant exposure-response and dose-response relationships in both sexes. CONCLUSIONS: WBC count was found to be a consistent effect marker of cigarette smoke exposure, while the association between CRP level and smoking was inconsistent and varied by sex. The sex-specific response to cigarette smoke exposure warrants further exploration in future studies. IMPLICATIONS: Cigarette smoke exposure is known to increase inflammation and has been thought to increase CRP, a significant inflammation marker. However, recent studies have reported conflicting results regarding the dose-dependent association between cigarette smoke exposure and CRP. This study found that the association between smoking and CRP is inconsistent and varies by sex, showing significant exposure response in men but not in women. Furthermore, the study suggests that WBC count is a more consistent marker for cigarette smoke exposure.

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Effects of indoor environments and outdoor air pollutants in residential areas on acute exacerbation in patients with severe asthma.

This study aimed to determine the effects of indoor environment (IE) and outdoor air pollutants (OAPs) in residential areas on acute exacerbation (AE) in patients with severe asthma. A total of 115 participants were recruited. To characterize IE, we used structured questionnaires and estimated OAP concentrations using a land-use regression model. Participants who were exposed to passive smoking and lived in houses where the kitchen and living room were not separated showed a significantly higher rate of AE (p = 0.014 and 0.0016, respectively). The mean concentration of PM2.5 in residential areas during the last 3 years was significantly higher in participants with AE than that in those without AE (19.8 ± 3.1 vs. 21.0 ± 2.5 µg/m3, p = 0.033). Moreover, the serum level of 8-hydroxy-2'-deoxyguanosine significantly increased in participants with AE compared to those without AE (56.9 ± 30.0 vs. 94.7 ± 44.5 ng/mL, p = 0.0047) suggesting enhanced oxidative stress in those with AE.

Evaluation of Temporal Trends of Lead Exposure in Korean Workers Using Workplace Monitoring Data.

BACKGROUND: Lead, which is widely used in various industrial settings, is a major health hazard for manufacturing workers. Therefore, control of lead exposure has been implemented in an effort to prevent lead-related health problems. In this study, our aim was to evaluate temporal trends in occupational lead exposure in Korean lead workers using data from monitoring of workplace exposure. METHODS: A nationwide work environment monitoring database, data from a work environment monitoring institution, and data extracted from a review paper were utilized. Different versions of standard industrial classification codes were aligned with the 10th Korean Standard Industrial Classification, which is generally consistent with the 4th revision of the International Standard Industrial Classification. The multiple data sources were combined and temporal trends over the period from 1994-2021 were estimated. In addition, separate estimation of temporal trends in the storage battery manufacturing industry over the period from 1987-2021 was also performed. RESULTS: A total of 444,296 personal airborne lead measurements were used for the estimation process. The temporal trends in occupational exposure to lead declined by -6% annually over the study period. In particular, levels of lead exposure in the storage battery manufacturing industry showed a steeper decline of -12% annually. CONCLUSIONS: Findings of our study showed that occupational exposure to lead declined over the period from 1994 to 2021 in Korea. However, adverse effects of exposure to lead on health should be regarded with caution. The results will be useful in conduct of epidemiological studies examining lead-related effects on health.

Particulate matter exposure during pregnancy increases risk of childhood asthma: modified by gender and NRF2 genotype.

BACKGROUND: Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated. OBJECTIVE: We investigated whether prenatal exposure to PM10 increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene. METHODS: A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM10 during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM10 exposure and childhood asthma by gender and NRF2. RESULTS: Exposure to PM10 during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.001.06). Stratifying by gender and NRF2 genotype, exposure to PM10 during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype. CONCLUSIONS: A critical window for PM10 exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.

Case-only approach applied in environmental epidemiology: 2 examples of interaction effect using the US National Health and Nutrition Examination Survey (NHANES) datasets.

INTRODUCTION: By substituting the general 'susceptibility factor' concept for the conventional 'gene' concept in the case-only approach for gene-environment interaction, the case-only approach can also be used in environmental epidemiology. Under the independence between the susceptibility factor and environmental exposure, the case-only approach can provide a more precise estimate of an interaction effect. METHODS: Two analysis examples of the case-only approach in environmental epidemiology are provided using the 2015-2016 and 2017-2018 US National Health and Nutritional Examination Survey (NHANES): (i) the negative interaction effect between blood chromium level and glycohemoglobin level on albuminuria and (ii) the positive interaction effect between blood cobalt level and old age on albuminuria. The second part of the methods (theoretical backgrounds) summarized the logic and equations provided in previous studies about the case-only approach. RESULTS: (i) When a 1 µg/L difference of both blood chromium level (mcg/L) and a 1% difference in blood glycohemoglobin level coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 0.72 (95% CI 0.35-1.60), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 0.59 (95% CI 0.28-0.95), with a statistical significance (a negative interaction effect). (ii) When a 1 µg/L difference of both blood cobalt levels and a 1-year difference in age coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 1.13 (95% CI 0.99-1.37), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 1.21 (95% CI 1.06-1.51), with a statistical significance (a positive interaction effect). DISCUSSION: The discussion suggested the theoretical background and previous literature about the possible protective interaction effect between blood chromium levels and blood glycohemoglobin levels on the incidence of albuminuria and the possible aggravating interaction effect between blood cobalt levels and increasing ages on the incidence of albuminuria. If the independence assumption between a susceptibility factor and environmental exposure in a study with cases and non-cases is kept, the case-only approach can provide a more precise interaction effect estimate than conventional approaches with both cases and non-cases.

The impact of life behavior and environment on particulate matter in chronic obstructive pulmonary disease.

BACKGROUND: The effect of exposure to particulate matter (PM) on human health is a global public health concern. To develop an effective strategy to reduce PM exposure, we performed detailed questionnaire surveys regarding the type of lifestyle required to avoid PM exposure in patients with chronic obstructive pulmonary disease (COPD). We correlated the data with real-time PM concentration during the winter season. METHODS: We enrolled 104 patients with COPD aged 40 years or older. Detailed questionnaire surveys were conducted among participants, and internet of things-based sensors were installed at their homes to measure the indoor PM2.5 concentration, which was continuously monitored between December 2019 and February 2020. The associations among PM2.5 concentration, patients' lifestyles, and the impact of both concentration and lifestyle on COPD exacerbation were analyzed. RESULTS: Mean outdoor PM2.5 concentration was higher than mean indoor PM2.5 concentration during the study period (21.28 ± 5.09 µg/m3 vs. 12.75 ± 7.64 µg/m3), with a mean difference of 8.53 ± 7.99 µg/m3. Among the various social factors and practices that aim to avoid exposure to PM, six practices and economic statuses were confirmed to reduce indoor PM2.5 concentration compared to outdoor concentration; Contrarily, these practices created a significant difference between the outdoor and indoor PM2.5 concentrations. The six practice items that showed a significant difference were 1) checking air quality forecast (the difference: -13.31 ± 1.35 µg/m3, p = 0.013), 2) indoor air filter operated (-15.43 ± 1.32 µg/m3, p < 0.001), 3) ventilating home by opening the windows (-13.14 ± 1.28 µg/m3, p = 0.013), 4) checking filters of the air filter (-13.95 ± 1.50 µg/m3, p = 0.002), 5) refraining from going out when outside PM is high (-12.52 ± 1.37 µg/m3, p = 0.039), 6) wearing a mask when going out (-13.38 ± 1.32 µg/m3, p = 0.017). The higher the household income and economic level, the more significant the difference in the PM2.5 concentration. Severe exacerbation was more prevalent among patients with acute exacerbation as the exposure time of PM2.5≥35 µg/m3 or PM2.5≥75 µg/m3. CONCLUSION: Lifestyle and economic levels can affect the indoor PM2.5 concentration, which may impact COPD exacerbation.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Prenatal PM2.5 exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

BACKGROUND: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 µm to 2.5 µm (PM2.5) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM2.5 exposure and AD in an offspring. OBJECTIVE: To determine the critical windows of prenatal PM2.5 exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring. METHODS: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM2.5 was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta. RESULTS: PM2.5 exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM2.5 exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM2.5 and low CB vitamin D. CONCLUSION: Higher PM2.5 during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.

Association between exposure to traffic-related air pollution and pediatric allergic diseases based on modeled air pollution concentrations and traffic measures in Seoul, Korea: a comparative analysis.

BACKGROUND: Pediatric allergic diseases are a major public health concern, and previous studies have suggested that exposure to traffic-related air pollution (TRAP) exposure is a risk factor. These studies have typically assessed TRAP exposure using traffic measures, such as distance to major roads, or by modeling air pollutant concentrations; however inconsistent associations with pediatric allergic diseases have often been found. Using road proximity and density, we previously found an association between TRAP and atopic eczema among approximately 15,000 children living in Seoul, Korea, heavily populated and highly polluted city in which traffic is a major emission source. We aimed to conduct a parallel analysis using modeled air pollution concentrations and thus examine the consistency of the association. Specifically, we examined the associations of individual-level annual-average concentrations of NO2, PM10, and PM2.5 with symptoms and diagnoses of three pediatric allergic diseases including asthma, allergic rhinitis, and atopic eczema. METHODS: The study population included 14,614 children from the Seoul Atopy Friendly School Project Survey in Seoul, Korea, in 2010. To assess individual exposures to TRAP among these children, we predicted annual-average concentrations of NO2, PM10, and PM2.5 at the children's home addresses in 2010 using universal kriging and land use regression models along with regulatory air quality monitoring data and geographic characteristics. Then, we estimated odds ratios (ORs) of the three allergic diseases for interquartile increases in air pollution concentrations after adjusting for individual risk factors in mixed effects logistic regression. RESULTS: Symptoms and diagnoses of atopic eczema symptoms showed an association with NO2 (OR = 1.07, 95% confidence interval = 1.02-1.13; 1.08, 1.03-1.14) and PM10 (1.06, 1.01-1.12; 1.07, 1.01-1.13). ORs of PM2.5 were positive but not statistically significant (1.01, 0.95-1.07; 1.04, 0.98-1.10). No association was found between asthma and allergic rhinitis, although PM2.5 showed a marginal association with allergic rhinitis. CONCLUSIONS: Our consistent findings regarding the association between TRAP and the prevalence of atopic eczema using traffic measures and surrogate air pollutants suggested the effect of TRAP on children's health. Follow-up studies should elucidate the causal link, to support subsequent policy considerations and minimize adverse health effects in children.

Effects of Particulate Respirator Use on Cardiopulmonary Function in Elderly Women: a Quasi-Experimental Study.

BACKGROUND: Individual particulate respirator use may offer protection against exposure to particulate matter < 2.5 µm in diameter (PM2.5). Among elderly Korean women, we explored individual particulate respirator use and cardiopulmonary function. METHODS: Recruited in Seoul, Korea, 21 elderly, non-smoking women wore particulate respirators for six consecutive days (exlcuding time spent eating, sleeping, and bathing). We measured resting blood pressure before, during, and after respirator use and recorded systolic and diastolic blood pressure, mean arterial blood pressure, pulse pressure, and lung function. We also measured 12-hour ambulatory blood pressure at the end of the 6-day long experiment and control periods. Additionally, we examined physiological stress (heart rate variability and urinary 8-hydroxy-2'-deoxyguanosine) while wearing the particulate respirators. Person- and exposure-level covariates were also considered in the model. RESULTS: After the 6-day period of respirator use, resting blood pressure was reduced by 5.3 mmHg for systolic blood pressure (P = 0.013), 2.9 mmHg for mean arterial blood pressure (P = 0.079), and 3.6 mmHg for pulse pressure (P = 0.024). However, particulate respirator use was associated with changes in physiological stress markers. A parasympathetic activity marker (high frequency) significantly decreased by 24.0% (P = 0.029), whereas a sympathetic activity marker (ratio of low-to-high frequency) increased by 50.3% (P = 0.045). An oxidative stress marker, 8-hydroxy-2'-deoxyguanosine, increased by 3.4 ng/mg creatinine (P = 0.021) during the experimental period compared with that during the control period. Lung function indices indicated that wearing particulate respirators was protective; however, statistical significance was not confirmed. CONCLUSION: Individual particulate respirator use may prevent PM2.5-induced blood-pressure elevation among elderly Korean women. However, the effects of particulate respirator use, including physiological stress marker elevation, should also be considered. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003526.

Prenatal particulate matter affects new asthma via airway hyperresponsiveness in schoolchildren.

BACKGROUND: The most relevant time of PM10 exposure to affect airway hyperresponsiveness (AHR) and new development of asthma in school-aged children is unclear. The aims of this study were to investigate the most critical time of PM10 exposure to affect AHR and new diagnosis of asthma from AHR in school-aged children. METHODS: Elementary schoolchildren (n = 3570) have been enrolled in a nationwide prospective 4-year follow-up survey in Korea from 2005 to 2006. Individual annual PM10 exposure was estimated by using an ordinary kriging method from the prenatal period to 7 years of age. AHR at 7 years was defined by a methacholine PC20 ≤8 mg/mL. RESULTS: PM10 exposure during pregnancy and at 1 year of age showed significant effects on AHR (aOR: 1.694, 95% CI: 1.298-2.209; and aOR: 1.750, 95% CI: 1.343-2.282, respectively). PM10 exposure during pregnancy was associated with the risk of a new diagnosis of asthma (aOR: 2.056, 95% CI: 1.240-3.409), with the highest risk in children with AHR at age 7 (aOR: 6.080, 95% CI: 2.150-17.195). PM10 exposure in the second trimester was associated with the highest risk of a new diagnosis of asthma in children with AHR at age 7 (aOR: 4.136, 95% CI: 1.657-10.326). CONCLUSIONS: Prenatal PM10 exposure in the second trimester is associated with an increased risk of a new diagnosis of asthma in school-aged children with AHR at 7 years. This study suggests that PM10 exposure during a specific trimester in utero may affect the onset of childhood asthma via AHR.

Cohort profile: Beyond birth cohort study - The Korean CHildren's ENvironmental health Study (Ko-CHENS).

The Korean CHildren's ENvironmental health Study (Ko-CHENS) is a nationwide prospective birth cohort showing the correlation between the environmental exposures and the health effects to prevent the environmental diseases in children, and it provides the guidelines for the environmental hazardous factors, applying the life-course approach to the environmental-health management system. The Ko-CHENS consists of 5000 Core and 65,000 Main Cohorts. The children in the Core Cohort are followed up at 6 months, every year before their admission into the elementary school, and every 3 years from the first year after this admission. The children in the Cohort will be followed up through the data links (Statistics Korea, National Health Insurance Service [NHIS], and Ministry of Education). The individual biospecimens will be analyzed for 19 substances. The long-term-storage biological samples will be used for the further substance analysis. The Ko-CHENS will investigate whether the environmental variables including the perinatal outdoor and indoor factors and the greenness contribute causally to the health outcomes in the children and adolescents. In addition to the individual surveys, the assessments of the outdoor exposures and health outcomes will use the national air-quality monitoring data and claim data of the NHIS, respectively. The two big-data forms of the Ko-CHENS are as follows: The Ko-CHENS data that can be linked with the nationally registered NHIS health-related database, including the medical utilization and the periodic health screening, and the birth/mortality database in the Statistics; the other is the Big-CHENS dataset that is based on the NHIS mother delivery code, for which the follow-up of almost 97% of the total birth population is expected. The Ko-CHENS is a very cost-effective study that fully exploits the existing national big-data systems with the data linkage.

Estimates of the Prevalence, Intensity and the Number of Workers Exposed to Cigarette Smoking across Occupations and Industries in Korea.

BACKGROUND: Tobacco smoking affects the incidence of various illnesses such as lung cancer, respiratory diseases, and cardiovascular diseases. In an effort to prevent smoking-related cancers, we aimed to estimate the smoking prevalence, intensity, and number of workers exposed to smoking, which would be specific to the occupational and industrial circumstances in Korea. METHODS: We used the Korean Working Condition Survey (KWCS) and Korea's Census data. Smoking prevalence and intensity were estimated using the KWCS data. The number of smokers was estimated by multiplying smoking prevalence with the number of workers in the occupation or industry. Smoking prevalence, intensity, and number of smokers were estimated for major, sub-major, and minor groups of occupation and industry. RESULTS: Of the total labor force in 2010, 52.66% of men and 5.24% of women workers were estimated to be current smokers. Men workers smoked 15.42 cigarettes/day, and women workers 11.29 cigarettes/day. In terms of occupation, "craft and related trades workers" demonstrated the highest smoking prevalence (52.24%). "Managers" smoked the highest number of cigarettes (16.63 cigarettes/day) and "equipment, machine operating, and assembling workers" comprised the largest number of estimated smokers (1,368,726 workers). In terms of industry, "mining and quarrying" had the highest smoking prevalence (69.27%). Those in "construction" smoked the highest number of cigarettes (17.16 cigarettes/day) and those in "manufacturing" comprised the largest number of estimated smokers (1,629,893 workers). CONCLUSION: Our results may help in setting priorities for smoking prevention-related activities. In addition, these results can be used for epidemiological studies controlling for the effect of smoking by occupation or industry.

Effects of traffic-related air pollution on susceptibility to infantile bronchiolitis and childhood asthma: A cohort study in Korea.

OBJECTIVE: This study examined the role of exposure to traffic-related air pollution (TRAP) on susceptibility to asthma in children with past episodes of bronchiolitis. METHODS: The baseline data included 2,627 school children aged 6-14 years who had participated in the longitudinal follow-up survey of the Children's Health and Environmental Research of Korea. Lifetime wheezing, past episodes of bronchiolitis, and doctor-diagnosed asthma were evaluated using an International Study of Asthma and Allergies in Childhood questionnaire. We used generalized linear regression with binomial distribution to calculate the relative risk (RR) between TRAP, assessed by proximity to a main road and the total length of roads, and asthma. RESULTS: Compared with the subjects who had less than 100 m of road length within 200-m radius from their home, those with more than 500 m of road length had significantly increased odds for infantile bronchiolitis (adjusted OR [aOR]: 1.57, 95% confidence interval [CI]: 1.01-2.42). Positive exposure-response relationships were found between residential proximity to the main road and asthma (aOR: 1.79, 95% CI: 1.05-3.06; <75 m vs. >700 m from a main road, P for the trend = 0.02). Closer residential proximity to the main road (<75 m) and bronchiolitis combined increased the risks of newly diagnosed asthma (adjusted RR: 3.62, 95% CI: 1.07-12.26) compared with those without bronchiolitis and living ≥ 75 m away from the main road. CONCLUSIONS: TRAP appeared to be associated with an increased asthma among children with bronchiolitis, indicating the importance of modifying effects of bronchiolitis in asthma pathogenesis.

Increased prevalence of some birth defects in Korea, 2009-2010.

BACKGROUND: Birth defects are a leading cause of neonatal and infant mortality, and several studies have indicated an increase in the prevalence of birth defects; more recent investigations have suggested that the trends of some defects are increasing in rapidly industrialized areas. This study estimates the prevalence rate and types of birth defects in Korea. METHODS: This study used medical insurance benefit data of 403,250 infants aged less than one year from the National Health Insurance Corporation from seven metropolitan areas in Korea for 2009 and 2010. RESULTS: The prevalence rate of birth defects was 548.3 per 10,000 births (95% CI: 541.1-555.6), 306.8 among boys and 241.5 among girls. Anomalies of the circulatory system (particularly septal defects) were the most common (180.8 per 10,000), followed by defects of the genitourinary tract (130.1 per 10,000) (particularly obstructive genitourinary and undescended testis), musculoskeletal system (105.7 per 10,000), digestive system (24.7 per 10,000), and central nervous system (15.6 per 10,000). CONCLUSIONS: Relatively higher rates of some birth defects were found in the metropolitan areas. The high differences of birth prevalences for septal heart defects and undescended testis are probably due in part to progress in clinical management and more frequent prenatal diagnosis. Environmental exposure might play a critical role in the development of some birth defects. In attempting to describe the prevalence and spatio-temporal variations of birth defects in Korea, establishment of a registry system of birth defects and environmental surveillance are needed.

Impact of prenatal exposure to polycyclic aromatic hydrocarbons from maternal diet on birth outcomes: a birth cohort study in Korea.

OBJECTIVE: Polycyclic aromatic hydrocarbons (PAH) are common dietary exposures that cross the human placenta and are classified as a probable human carcinogen. The aim of the present study was to investigate the potential impact of exposure to PAH-containing meat consumed during pregnancy on birth outcomes. DESIGN: Prospective birth cohort study. Only non-smoking women with singleton pregnancies, who were free from chronic disease such as diabetes and hypertension, were included in the study. Maternal consumption of PAH-rich meat was estimated through FFQ. Multiple linear regression was used to assess factors related to higher intake and the association between dietary PAH and birth outcomes. SETTING: Republic of Korea, 2006-2011. SUBJECTS: Pregnant women (n 778) at 12-28 weeks of gestation enrolled in the Mothers and Children's Environmental Health (MOCEH) study. RESULTS: The multivariable regression model showed a significant reduction in birth weight associated with higher consumption level of foods rich in PAH, such as grilled or roasted meat, during pregnancy (ß=-17·48 g, P<0·05 for every 1 point higher in meat score). Further adjusting for biomarkers of airborne PAH did not alter this association. There was no evidence that higher consumption level of PAH-rich meat shortens the duration of gestation (P=0·561). Regression models performed for birth length and head circumference produced negative effects that were not statistically significant. CONCLUSIONS: Consumption of higher levels of barbecued, fried, roasted and smoked meats during pregnancy was associated with reduced birth weight. Dietary risk of PAH exposure in Korean women is of concern.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BACKGROUND: This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. METHODS/DESIGN: The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child's genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child's exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child's neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child's microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures. DISCUSSION: The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.