Mortality Burden Due to Short-term Exposure to Fine Particulate Matter in Korea.

OBJECTIVES: Excess mortality associated with long-term exposure to fine particulate matter (PM2.5) has been documented. However, research on the disease burden following short-term exposure is scarce. We investigated the cause-specific mortality burden of short-term exposure to PM2.5 by considering the potential non-linear concentration-response relationship in Korea. METHODS: Daily cause-specific mortality rates and PM2.5 exposure levels from 2010 to 2019 were collected for 8 Korean cities and 9 provinces. A generalized additive mixed model was employed to estimate the non-linear relationship between PM2.5 exposure and cause-specific mortality levels. We assumed no detrimental health effects of PM2.5 concentrations below 15 µg/m3. Overall deaths attributable to short-term PM2.5 exposure were estimated by summing the daily numbers of excess deaths associated with ambient PM2.5 exposure. RESULTS: Of the 2 749 704 recorded deaths, 2 453 686 (89.2%) were non-accidental, 591 267 (21.5%) were cardiovascular, and 141 066 (5.1%) were respiratory in nature. A non-linear relationship was observed between all-cause mortality and exposure to PM2.5 at lag0, whereas linear associations were evident for cause-specific mortalities. Overall, 10 814 all-cause, 7855 non-accidental, 1642 cardiovascular, and 708 respiratory deaths were attributed to short-term exposure to PM2.5. The estimated number of all-cause excess deaths due to short-term PM2.5 exposure in 2019 was 1039 (95% confidence interval, 604 to 1472). CONCLUSIONS: Our findings indicate an association between short-term PM2.5 exposure and various mortality rates (all-cause, non-accidental, cardiovascular, and respiratory) in Korea over the period from 2010 to 2019. Consequently, action plans should be developed to reduce deaths attributable to short-term exposure to PM2.5.

Association of long-term exposure to PM2.5 and survival following ischemic heart disease.

BACKGROUND: Numerous studies have suggested that long-term exposure to particulate matter ≤2.5 µm (PM2.5) may cause cardiovascular morbidity and mortality. However, susceptibility among those with a history of ischemic heart disease is less clearly understood. We aimed to evaluate whether long-term PM2.5 exposure is related to mortality among patients with ischemic heart disease. METHODS: We followed up 306,418 patients hospitalized with ischemic heart disease in seven major cities in South Korea between 2008 and 2016 using the National Health Insurance Database. We linked the modeled PM2.5 data corresponding to each patient's administrative districts and estimated hazard ratios (HRs) of cause-specific mortality associated with the long-term exposure to PM2.5 in time-varying Cox proportional hazard models after adjusting for individual- and area-level characteristics. We also estimated HRs by sex, age group (65-74 vs. ≥75 years), and household income. RESULTS: Of the patients with ischemic heart disease, mean age at the discharge was 76.8 years, and 105,913 died during a mean follow-up duration of 21.4 months. The HR of all-cause mortality was 1.10 [95% confidence intervals (CI): 1.07, 1.14] per 10 µg/m3 increase in a 12-month moving average PM2.5. The HRs of cardiovascular, stroke, and ischemic heart disease were 1.17 (95% CI: 1.11, 1.24), 1.17 (95% CI: 1.06, 1.30), and 1.25 (95% CI: 1.15, 1.35), respectively. The subgroup analyses showed that participants aged 65-74 years were more susceptible to adverse effects of PM2.5 exposure. We did not observe any differences in the risk by sex and household income. CONCLUSION: Mortality from all-cause and cardiovascular disease following hospitalization due to ischemic heart disease was higher among individuals with greater PM2.5 exposure in seven major cities in South Korea. The result supports the association of long-term exposure to air pollution with poor prognosis among patients with ischemic heart disease.

Effect modification of consecutive high concentration days on the association between fine particulate matter and mortality: a multi-city study in Korea.

OBJECTIVES: Although there is substantial evidence for the short-term effect of fine particulate matter (PM2.5) on daily mortality, few epidemiological studies have explored the effect of prolonged continuous exposure to high concentrations of PM2.5. This study investigated how the magnitude of the mortality effect of PM2.5 exposure is modified by persistent exposure to high PM2.5 concentrations. METHODS: We analyzed data on the daily mortality count, simulated daily PM2.5 level, mean daily temperature, and relative humidity level from 7 metropolitan cities from 2006 to 2019. Generalized additive models (GAMs) with quasi-Poisson distribution and random-effects meta-analyses were used to pool city-specific effects. To investigate the effect modification of continuous exposure to prolonged high concentrations, we applied categorical consecutive-day variables to the GAMs as effect modification terms for PM2.5. RESULTS: The mortality risk increased by 0.33% (95% confidence interval [CI], 0.16 to 0.50), 0.47% (95% CI, -0.09 to 1.04), and 0.26% (95% CI, -0.08 to 0.60) for all-cause, respiratory, and cardiovascular diseases, respectively, with a 10 µg/m3 increase in PM2.5 concentration. The risk of all-cause mortality per 10 µg/m3 increase in PM2.5 on the first and fourth consecutive days significantly increased by 0.63% (95% CI, 0.20 to 1.06) and 0.36% (95% CI, 0.01 to 0.70), respectively. CONCLUSIONS: We found increased risks of all-cause, respiratory, and cardiovascular mortality related to daily PM2.5 exposure on the day when exposure to high PM2.5 concentrations began and when exposure persisted for more than 4 days with concentrations of ≥35 µg/m3. Persistently high PM2.5 exposure had a stronger effect on seniors.

Inhibition of the bromodomain and extra-terminal family of epigenetic regulators as a promising therapeutic approach for gastric cancer.

PURPOSE: Epigenetic dysregulation is a common characteristic of cancers, including gastric cancer (GC), and contributes to cancer development and progression. Although the efficacy of BET (an epigenetic regulator) inhibition has been demonstrated in various cancer types, predictive genetic markers of its efficacy in GC are currently lacking. Therefore, we aimed to identify markers that predict the response of BET inhibition in GC and, suggest an effective treatment regimen through combined therapy. METHODS: The effect of BET inhibition was evaluated using iBET-151, a small-molecule inhibitor of BET proteins, in a large panel (n = 49) of GC cell lines and xenograft mouse models. Comprehensive genetic information was used to identify cell lines sensitive to iBET-151. Flow cytometry, Western blotting, and colony-formation and migration assays were used to evaluate the effects of iBET-151 and/or paclitaxel. The synergistic effect of iBET-151 and paclitaxel was evaluated using an organoid model. RESULTS: We found that iBET-151 showed a modest growth-inhibitory effect in GC cells (73%, 36/49). iBET-151 inhibited tumorigenicity in vitro and significantly promoted cell cycle arrest and apoptosis. Based on comprehensive genetic information analysis in relation to BET family expression, we found that BRD4 was highly expressed in the iBET-151-sensitive cell lines. We also identified WNT5B and IRS2 as potential biomarkers that are predictive for sensitivity to iBET-151. In GC xenograft model mice, iBET-151 significantly decreased tumor volumes and Ki-67 and BRD4 expression. Combination treatment showed that iBET-151 increased the sensitivity of GC cells to paclitaxel in approximately 70% of the cell lines (34/49) tested. iBET-151 plus paclitaxel significantly promoted cell cycle arrest and apoptosis and suppressed c-Myc, Bcl-2 and Bcl-xL expression. In GC organoids, iBET-151 and paclitaxel showed a synergistic effect. CONCLUSIONS: Collectively, our data suggest that iBET-151 is a potential therapeutic agent for GC, especially in combination with paclitaxel, and that WNT5B and IRS2 may predict iBET-151 sensitivity.

Natural-killer cell cytotoxicity as a diagnostic and prognostic marker for adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective phase II observational study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated. METHODS: We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry. RESULTS: HLH (n = 60) was determined to be caused by Epstein-Barr virus (EBV) (n = 11), infection other than EBV (n = 16), malignancies (n = 19), and unknown (n = 14). Febrile diseases other than HLH (n = 63) were diagnosed as autoimmune disease (n = 22), malignancies (n = 21), infection (n = 12), non-malignant hematological diseases (n = 6), and unknown (n = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% versus 26.2%, p < 0.001). However, NK-cytotoxicity had a borderline effect on diagnosis of HLH, with an area under receiver operation characteristic curve of 0.689. It also showed no significant role for the prediction of survival outcome. Multivariate analysis revealed that malignant disease and high ferritin level were related with poor survival outcome. In non-malignant disease subgroups, old age, EBV-association, and low NK-cytotoxicity were related with poor survival. CONCLUSIONS: Febrile disease with cytopenia was associated with decreased NK-cytotoxicity, especially in adults with HLH; however, its diagnostic role for adult HLH is still arguable. The diagnostic criteria for adult HLH should be further discussed. TRIAL REGISTRATION: Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do), Korea, Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); https://cris.nih.go.kr/cris/index.jsp; Feb, 16th 2016; KCT0001886 (KC15TISE0936).

Short-term exposure to air pollution and hospital admission for heart failure among older adults in metropolitan cities: a time-series study.

PURPOSE: We aimed to investigate the association between air pollution concentration levels and hospital admissions for heart failure (HF) among older adults in metropolitan cities in South Korea. METHODS: We used hospital admission data of 1.8 million older adults in seven metropolitan cities from 2008 to 2016, derived from the National Health Insurance Service of South Korea. Daily HF admission data were linked to air pollutants concentrations for the respective dates, including particulate matter less than 2.5 µm in size (PM2.5), 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone. We estimated the association between air pollutants and daily HF admissions using quasi-Poisson generalized additive models for each city. RESULTS: During the study period, 142,490 hospital admissions for HF were noted. Increases of 10 µg/m3 of PM2.5 and PM10, and 10 ppb of SO2, NO2, and CO were associated with an increased risk of HF admission by 0.93% ([95% confidence intervals 0.51-1.36], 0.55% [0.31-0.80], 6.04% [2.15-10.08], 1.10% [0.38-1.82], and 0.05% [0.01-0.09]), respectively, on the same day. Increases in mean exposure to PM2.5, PM10, and SO2 for 8 days from the concurrent day were also significantly associated with HF admissions. During the warm season, the risk of HF admissions increased shortly after an increase in PM2.5, whereas prolonged effects were observed during the cold season. CONCLUSION: Our study suggests the adverse effects of air pollution on HF. Moreover, the evidence of seasonality may help tailor protection guidelines for older adults.

Particulate air pollution and survival after stroke in older adults: A retrospective cohort study in Korea.

Although many studies have evaluated the effects of ambient particulate matter with diameters of less than 2.5 µm (PM2.5) on stroke mortality in the general population, little is known about the mortality effects of PM2.5 in post-stroke populations. Therefore, a retrospective cohort was constructed using information from the health insurance database to evaluate whether exposure to PM2.5 is associated with increased mortality in aged stroke survivors residing in seven Korean metropolitan cities. A total of 45,513 older adults (≥65 years) who visited emergency rooms due to stroke and who were discharged alive between 2008 and 2016 were followed up. By using district-level modeled PM2.5 concentrations and a time-varying Cox proportional hazard model, associations between 1-month and 2-month moving average PM2.5 exposures and mortality in stroke survivors were evaluated. The annual average concentration of PM2.5 was 27.9 µg/m3 in the seven metropolitan cities, and 14,880 subjects died during the follow-up period. A 10 µg/m3 increase in the 1-month and 2-month moving average PM2.5 exposures was associated with mortality hazard ratios of 1.07 (95% confidence interval: 1.05, 1.09) and 1.06 (95% confidence interval: 1.03, 1.08), respectively. The effects of PM2.5 were similar across types of stroke (ischemic and hemorrhagic), age groups (65-74, 75-84, and ≥85), and income groups (low and high) but were greater in women than in men. This study highlights the adverse health effects of ambient PM2.5 in post-stroke populations. Active avoidance behaviors against PM2.5 are recommended for aged stroke survivors.

Long-term exposure to fine particulate matter and incident asthma among elderly adults.

RATIONALE: Although an association of fine particulate matter (PM2.5) with asthma incidence has been assumed, there is insufficient evidence regarding the effect of long-term exposure to PM2.5 on incident asthma among elderly adults. OBJECTIVES: This study aimed to investigate an association between long-term exposure to PM2.5 and incident asthma among elderly adults in South Korea. METHODS: Adults ≥65 years of age (n = 1,220,645) who did not visit hospitals for asthma during a washout period (between 2008 and 2010) were followed up until 2016 using data from the National Health Insurance System in South Korea. Incident asthma was defined as the number of patients with a primary diagnostic code of asthma who visited hospitals more than twice. We linked the health data with district-level PM2.5 concentrations and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident asthma after adjusting for potential confounders in time-varying Cox proportional hazard models. MEASUREMENTS AND MAIN RESULTS: Over 5,942,256 person-years, 54,522 patients developed asthma, with an incidence of 9.2 cases/1000 person-years. A 10 µg/m3 increase in the 36-month mean PM2.5 concentration was significantly associated with a 9% increase in incident asthma (HR = 1.09, 95% CI: 1.04-1.14). This association was found to be robust for different definitions of incident asthma and washout periods. CONCLUSION: Long-term exposure to PM2.5 was associated with the incidence of asthma in elderly adults. This finding provides evidence of an association between PM2.5 and adult-onset asthma.

Long-term exposure to moderate fine particulate matter concentrations and cause-specific mortality in an ageing society.

BACKGROUND: Long-term exposure to particulate matter <2.5 µm in size (PM2.5) is considered a risk factor for premature death. However, only a few studies have been conducted in areas with moderate PM2.5 concentrations. Moreover, an ageing society may be more susceptible to environmental exposure and future burden of mortality due to PM2.5. METHODS: This study estimates hazard ratios (HRs) for all-cause and cause-specific mortality from long-term exposure to moderate PM2.5 concentrations in the elderly populations of seven cities in South Korea. We also projected nationwide elderly mortality caused by long-term exposure to PM2.5, accounting for population ageing until 2045. Mortality in 1 720 230 elderly adults aged ≥65 years in 2008 was monitored across 2009-16 and linked to modelled PM2.5 concentrations. RESULTS: A total of 421 100 deaths occurred in 2009-16, and the mean of annual PM2.5 concentration ranged between 21.1 and 31.9 µg/m3 in most regions. The overall HR for a 10 µg/m3 increase in a 36-month PM2.5 moving average was 1.024 (95% confidence intervals: 1.009, 1.039). We estimated that 11 833 all-cause nationwide elderly deaths were attributable to PM2.5 exposure. Annual death tolls may increase to 17 948 by 2045. However, if PM2.5 is reduced to 5 µg/m3 by 2045, the tolls may show a lower increase to 3646. CONCLUSIONS: Long-term exposure to moderately high levels of PM2.5 was associated with increased mortality risk among the elderly. Thus, PM2.5 reduction in response to the projected ageing-associated mortality in South Korea is critical.

Associations between surrounding residential greenness and intelligence quotient in 6-year-old children.

BACKGROUND: Residential greenness has been reported to be positively associated with health benefits for children, including improved cognitive function. We investigated the association between the intelligence quotient (IQ) of 6-year-old children in Seoul, South Korea and surrounding greenness currently and during the mothers' pregnancy. We also analyzed whether these effects differed by the type of greenness, such as natural or built greenness. METHODS: This study considered 189 mother-child dyads from the Environment and Development of Children Cohort study, who lived in Seoul during the prenatal period and when the child was 6 years old. We defined surrounding greenness using Landsat image data from Korean Arirang satellite images with buffers within 100 m - 2000 m of the radius of each participant's residential address. We separately analyzed two types of greenness, namely natural and built greenness. The children's IQ (total, verbal, and performance IQ) was measured using the Korean Educational Developmental Institute's Wechsler Intelligence Scale for Children. RESULTS: Prenatal exposure to built greenness in 500 m and 1000 m buffers was associated with children's total IQ in a full model [difference in IQ (95% CI): 3.46(0.68, 6.24) and 3.42 (0.53, 6.31) per interquartile increase in proportion of greenness]. However, postnatal exposure to built greenness in all buffers was associated in children's total IQ. We found a stronger association between children's total IQ and built greenness rather than natural greenness. CONCLUSIONS: We found that 6-year-old children tended to score higher on total IQ if they lived in greener neighborhoods. The results provide further evidence of the health benefits of greenness and provide support for urban planning and public health to build healthy urban cities for children and pregnant women.

p16 methylation is a potential predictive marker for abemaciclib sensitivity in gastric cancer.

Cell cycle control is often disrupted in gastric cancer (GC), making it an attractive therapeutic target. Abemaciclib is a specific CDK4/6 inhibitor that has been shown to improve treatment efficacy in hormone receptor-positive advanced breast cancer; however, its potential therapeutic value and predictive markers have not yet been revealed in GC. In this study, we investigated the efficacy of abemaciclib using preclinical GC models representing defined molecular subtypes from The Cancer Genome Atlas. In these 49 GC cell lines, Epstein-Barr virus (EBV) and high microsatellite instability (MSI-H)-type cell lines were p16 methylated and sensitive to abemaciclib; further, genomically stable (GS), and chromosomal instability (CIN)-type cell lines with p16 methylation and intact Rb were also found to be responsive. In addition, we found that GC patients with p16 methylation often displayed a poor prognosis. Collectively, these data provide a foundation for clinical trials to assess the therapeutic efficacy of abemaciclib in GC and suggest that p16 methylation could be used as a predictive marker to identify patients with GC who may benefit from abemaciclib-based therapies.

Short-Term Exposure to Fine Particulate Matter and Hospitalizations for Acute Lower Respiratory Infection in Korean Children: A Time-Series Study in Seven Metropolitan Cities.

Although several studies have evaluated the association between fine particulate matter (PM2.5) and acute lower respiratory infection (ALRI) in children, their results were inconsistent Therefore, we aimed to evaluate the association between short-term exposure to PM2.5 and ALRI hospitalizations in children (0-5 years) living in seven metropolitan cities of Korea. The ALRI hospitalization data of children living in seven metropolitan cities of Korea from 2008 to 2016 was acquired from a customized database constructed based on National Health Insurance data. The time-series data in a generalized additive model were used to evaluate the relationship between ALRI hospitalization and 7-day moving average PM2.5 exposure after adjusting for apparent temperature, day of the week, and time trends. We performed a meta-analysis using a two-stage design method. The estimates for each city were pooled to generate an average estimate of the associations. The average PM2.5 concentration in 7 metropolitan cities was 29.0 µg/m3 and a total of 713,588 ALRI hospitalizations were observed during the 9-year study period. A strong linear association was observed between PM2.5 and ALRI hospitalization. A 10 µg/m3 increase in the 7-day moving average of PM2.5 was associated with a 1.20% (95% CI: 0.71, 1.71) increase in ALRI hospitalization. While we found similar estimates in a stratified analysis by sex, we observed stronger estimates of the association in the warm season (1.71%, 95% CI: 0.94, 2.48) compared to the cold season (0.31%, 95% CI: -0.51, 1.13). In the two-pollutant models, the PM2.5 effect adjusted by SO2 was attenuated more than in the single pollutant model. Our results suggest a positive association between PM2.5 exposure and ALRI hospitalizations in Korean children, particularly in the warm season. The children need to refrain from going out on days when PM2.5 is high.

Assessment of Relative Asthma Risk in Populations Living Near Incineration Facilities in Seoul, Korea.

While incineration is among the most commonly used technologies for waste disposal, there is ongoing public concern regarding the adverse health impact. The aim of this study is thus to use health statistics to assess the relative risk of asthma-related hospitalization for those living in close proximity to incineration facilities. We also examine differences in asthma risk related to age demographics. The spatial relationship between incineration facilities and asthma-related hospital admissions in Seoul is analyzed for the period of 2009-2011 using the Rapid Inquiry Facility (RIF) and SaTScan software. The relative risk of asthma-related hospitalization decreased with increasing distance from incinerators, but increased among those living within a 2-km radius. The relative risks of asthma-related hospitalization were 1.13 (95% confidence interval (CI): 1.10-1.17), 1.12 (95% CI: 1.08-1.17), and 1.18 (95% CI: 1.10-1.27) for all ages, those aged below 15 years, and those aged 65 years and older, respectively. This study is the first to observe an increased risk of asthma-related hospitalization in relation to a person's distance from an incinerator in Seoul, Korea. It is clear that asthma should be considered an adverse health outcome during health impact assessments of incineration plants.

Recalibration and validation of the Charlson Comorbidity Index in an Asian population: the National Health Insurance Service-National Sample Cohort study.

Weights assigned to comorbidities in predicting mortality may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified version of the Charlson Comorbidity Index (CCI) using an Asian nationwide database (mCCI-A), enabling the precise prediction of mortality rates in this population. The main data source used in this study was the National Health Insurance Service-National Sample Cohort (NHIS-NSC) obtained from the National Health Insurance database, which includes health insurance claims filed between January 1, 2002, and December 31, 2013, in Korea. Of the 1,025,340 individuals included in the NHIS-NSC, 570,716 patients who were hospitalized at least once were analyzed in this study. In total, 399,502 patients, accounting for 70% of the cohort, were assigned to the development cohort, and the remaining patients (n = 171,214) were assigned to the validation cohort. The mCCI-A scores were calculated by summing the weights assigned to individual comorbidities according to their relative prognostic significance determined by a multivariate Cox proportional hazard model. The modified index was validated in the same cohort. The Cox proportional hazard model provided reassigned severity weights for 17 comorbidities that significantly predicted mortality. Both the CCI and mCCI-A were correlated with mortality. However, compared with the CCI, the mCCI-A showed modest but significant increases in the c statistics. According to the analyses using continuous net reclassification improvement, the mCCI-A improved the net mortality risk reclassification by 44.0% (95% confidence intervals (CI), 41.6-46.5; p < 0.001). The mCCI-A facilitates better risk stratification of mortality rates in Korean inpatients than the CCI, suggesting that the mCCI-A may be a preferable index for use in clinical practice and statistical analyses in epidemiological studies.

Prenatal exposure to traffic-related air pollution and risk of congenital diseases in South Korea.

BACKGROUND: Previous studies have suggested links between exposure to ambient air pollutants and increased risk of congenital heart defects. However, few studies have investigated the association between other congenital diseases and traffic-related air pollution. In this study, we assessed the relationship between prenatal exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with congenital diseases in South Korea. METHODS: Patients with one or more congenital diseases and a control group of patients with non-infective gastroenteritis and colitis with a case:control ratio of 1:3 were obtained from the National Health Insurance Service data for 2008-2013 in South Korea. We estimated the associations of PM2.5 and NO2 exposures with congenital diseases using generalized estimation equations after controlling for covariates. RESULTS: Maternal PM2.5 exposure during the first and second trimester showed positive associations with overall congenital diseases, with changes of 14.7% (95% confidence intervals (CI), 9.3%, 20.3%) and 16.2% (95% CI, 11.0%, 21.7%), respectively, per 11.1 µg/m3 and 10.2 µg/m3 increase of PM2.5 interquartile range (IQR). Similarly, NO2 exposure during the first and second trimester was associated with increased numbers of overall congenital anomalies, with 8.2% (95% CI, 4.2%, 12.3%) and 15.6% (95% CI, 9.3%, 22.2%) more cases, respectively, per 10.6 ppb increase of NO2. We found that maternal PM2.5 exposure during the first and second trimesters of pregnancy was significantly associated with increased risk of specific congenital diseases, including subtypes affecting the circulatory, genitourinary, and musculoskeletal system. However, no significant associations were observed during the third trimester. Maternal NO2 exposure across the entire pregnancy was associated with malformations of the musculoskeletal system. CONCLUSIONS: Our study identified significant links between in utero exposure to PM2.5 and NO2 and certain congenital diseases, and suggests that stricter controls on PM2.5 and NO2 concentrations are required.

Source country-specific burden on health due to high concentrations of PM2.5.

Asian countries face frequent spikes in concentrations of particulate matter smaller than 2.5 µm (PM2.5), which may consist of domestic emissions, transported pollutants from neighboring countries, and secondary aerosol formation (SAF). We aimed to estimate the burden on health in South Korea due to PM2.5 exposure from source countries. We computed the health benefits of meeting air quality guidelines during high pollution periods or spike periods. We used daily mortality counts, PM2.5 concentrations, and primary and secondary contributions to pollutant levels in seven cities and nine provinces in South Korea during 2006-2016. Generalized additive mixed modeling with a Poisson distribution and random effects in 16 regions was used to examine the short-term effects of PM2.5 on mortality. We computed attributable burden due to PM2.5 exposure and the potential benefits of meeting the air quality guidelines set by the World Health Organization (WHO, 25 µg/m3) and the Korea Ministry of Environment (50 and 35 µg/m3 before and after 2015, respectively). A concentration-response curve showed a non-linear relationship between daily mortality counts and PM2.5 levels. The short-term health impacts of PM2.5 were suggested to be 1638 non-accidental deaths in 2016 in South Korea due to daily domestic emissions and pollutants transported from neighboring countries. Of these, 1509, 995, or 238 deaths could have been prevented if the daily mean PM2.5 concentration had been kept below 25, 35, or 50 µg/m3. After accounting for the contribution of SAF to PM2.5, primary sources of PM2.5 resulted in 258-860 and 26-88 deaths due to pollution transported from China and North Korea, respectively, and 162-538 deaths were due to domestic emissions. Meeting the air quality guidelines of the WHO could have prevented most of these deaths.

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells.

BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Estimation of heat-related deaths during heat wave episodes in South Korea (2006-2017).

In 2016, South Korea experienced extremely high temperatures and the Korea Centre for Disease Control and Prevention (KCDC) reported 17 heat-caused deaths during these heat waves, most due to heat stroke. Because the reported number of heat-caused deaths is only part of the total deaths associated with heat waves, we aimed to estimate attributable deaths during heat wave episodes. We linked mortality to meteorological data in 16 regions in South Korea and estimated relative risk at or above threshold of maximum temperature during summer using generalized linear regression models after controlling for confounders. We computed overall, age-, sex-, and cause-specific attributable deaths from 2006 to 2017. With a 1.5% increase in all-cause mortality per 1 °C increase in concurrent days' maximum temperature during summer, this study estimates a total of 1440 all-cause deaths associated with heat waves during the 2006-2017 study period in South Korea. We estimate that 343 deaths in 2016 can be ascribed to heat waves, which is approximately 20 times more than the number reported by the KCDC (17 heat-caused deaths). This study addresses attributable heat wave deaths in South Korea and illustrates that the reports of medically classified heat-caused deaths seriously underestimate the number of deaths attributable to heat waves. Our findings may enable the implementation and reinforcement of government- and individual-level management strategies for heat waves.

Spatial and Temporal Trends of Number of Deaths Attributable to Ambient PM2.5 in the Korea.

BACKGROUND: We aimed to evaluate the spatial and temporal trends of the health burden attributable to particulate matter less than 2.5 µm in diameter (PM2.5) in the metropolitan cities and provinces of the Korea. METHODS: We used modeled PM2.5 concentration data for the basic administrative levels, comprising the cities and the provinces of Korea, the corresponding annual population census data for each level, and the age and cause specific mortality data. We applied cause-specific integrated exposure-response functions to calculate the premature mortality attributable to ambient PM2.5 for four disease end points (ischemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], lung cancer [LC], and cerebrovascular disease [stroke]) for the year 2015. Moreover, the temporal trends of the health burden from 2006 to 2015 were assessed. RESULTS: The annual average PM2.5 concentration for Korea was 24.4 µg/m3, and 11,924 premature deaths were attributable to PM2.5 exposure in 2015. By simulating the reduction in the annual mean values of PM2.5 to 10 µg/m3, about 8,539 premature deaths were preventable. There was spatial variation in mortality burden attributable to PM2.5 across the sub-national regions of Korea. In particular, the high burden was concentrated at Seoul and Gyeonggi province due to the high population density. However, decreasing trends were noted for most of the metropolitan cities and provinces of Korea since 2006. CONCLUSION: Our findings show that further actions to improve air quality in Korea would substantially improve the health burden due to particulate matter.

Vascular and cardiac autonomic function and PM2.5 constituents among the elderly: A longitudinal study.

BACKGROUND: Although epidemiologic studies have shown an association between the total mass of particulate matter <2.5µm in aerodynamic diameter (PM2.5) and cardiovascular disease, few studies have examined PM2.5 constituents associated with vascular and cardiac autonomic dysfunction. METHODS: In this longitudinal study, we investigated the relationship between PM2.5 constituents and blood pressure (BP), and markers of the autonomic nervous system. In 466 elderly subjects residing in communities in Seoul, Korea, we examined 16 constituents, seven sources, and total mass concentrations of PM2.5. We measured the BP, heart rate (HR), and indices of heart rate variability (HRV), such as the standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive NN intervals (rMSSD), and two frequency-domain variables (low frequency [LF] and high frequency [HF]). We used linear mixed effects models to assess the association of PM2.5 constituents and sources with cardiovascular markers. RESULTS: BP, HR, and rMSSD were associated with concentration of total mass of PM2.5. For each increase of the interquartile range in PM2.5 constituents, systolic and diastolic BP, and HR increased by 2.1-3.3mmHg, 1.2-2.3mmHg, and 1.2-1.9bpm, respectively, while the rMSSD, LF, and HF decreased by 8.1-9.3%, 16.6%, and 20.4%, respectively. Particularly, elemental carbon, sulfate, ammonium, lead, and strontium in the PM2.5 constituents and emissions from oil combustion and incineration were associated with increased BP, HR, and decreased HRV. CONCLUSIONS: Our results suggest an association between specific PM2.5 constituents and vascular and cardiac autonomic functions. These findings may provide supportive evidence for developing a pollution reduction plan to prevent cardiovascular diseases.