All-Cause and Cause-Specific Mortality Attributable to Seasonal Influenza: A Nationwide Matched Cohort Study.

BACKGROUND: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. METHODS: Individuals with influenza during four consecutive influenza seasons (2013-2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. RESULTS: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63-4.48), and 5.6% (95% CI, 4.5-6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40-17.55) and PAF (20.7%; 95% CI, 13.2-27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6-10.7%) for liver disease, 5.8% (95% CI, 2.9-8.5%) for respiratory disease, and 3.8% (95% CI, 1.4-6.1%) for cancer. CONCLUSION: Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

Long-term Effects of Cumulative Average PM2.5 Exposure on the Risk of Hemorrhagic Stroke.

BACKGROUND: Epidemiological studies have revealed associations between the fine particle (PM2.5; aerodynamic diameter <2.5 µm) exposure and cardiovascular disease. Researchers have also recently begun investigating the association between PM2.5 exposure and hemorrhagic stroke (HS) and identifying subpopulations vulnerable to PM2.5 exposure. Long-term cumulative average PM2.5 exposure may affect the risk of HS, and these effects may be modified by risk factors. METHODS: This retrospective study evaluated the effects of PM2.5 on the time-to-first-diagnosis of HS among 62,676 Seoul metropolitan city residents with 670,431 total person-years of follow-up; this cohort is a subset from a nationally representative cohort of 1,025,340 individuals from the Korean National Health Insurance Service database (2002-2013). A time-dependent Cox proportional hazards model was used to adjust for age, sex, household income, insurance type, body mass index, smoking status, medical history, and family history. The annual mean PM2.5 concentrations for 25 districts were used as the time-dependent variable. Subgroup analyses of the traditional risk factors of HS were performed to evaluate potential effect modifications. RESULTS: Each 10-µg/m increment in cumulative average PM2.5 exposure was noticeably associated with HS (hazard ratio [HR] = 1.43; 95% confidence interval [CI]: 1.09-1.88). The adverse effects of PM2.5 exposure were modified by ≥65 years of age (HR = 2.00; 95% CI = 1.32, 3.02) and obesity (body mass index ≥25 kg/m; HR = 1.91; 95% CI = 1.28, 2.84). CONCLUSIONS: Cumulative average PM2.5 exposure might increase the risk of HS. Elderly (≥65 years) and obese individuals may be more vulnerable to the effects of PM2.5 exposure.

Suicide loss, changes in medical care utilization, and hospitalization for cardiovascular disease and diabetes mellitus.

AIMS: The impact of suicide loss on family members' cardiometabolic health has little been evaluated in middle-aged and elderly people. We investigated the effect of suicide loss on risks for cardiovascular disease (CVD) and diabetes mellitus (DM) in suicide completers' family members using a national representative comparison group. METHODS AND RESULTS: The study subjects were 4253 family members of suicide completers and 9467 non-bereaved family members of individuals who were age and gender matched with the suicide completers in the Republic of Korea. National health insurance data were used to identify medical care utilization during the year before and after a suicide loss. A recurrent-events survival analysis was performed to estimate the hazard ratios (HRs) of hospitalizations for CVD, DM, or psychiatric disorders, after adjusting for age, residence, and socioeconomic status. Among subjects without a past history of CVD, DM, or psychiatric disorders, the increased risks of recurrent hospitalizations were observed for CVD [HR 1.343, 95% confidence interval (CI) 1.001-1.800 in men; HR 1.240, 95% CI 1.025-1.500 in women] and DM (HR 2.238, 95% CI 1.379-3.362 in men; HR 1.786, 95% CI 1.263-2.527 in women). In subjects with a past history of CVD, DM, or psychiatric disorders, the number of medical care visits decreased after a suicide loss, and suicide completers' family members showed lower rates of hospitalization for CVD and DM than the comparison group. CONCLUSION: Compared with non-bereaved family members, suicide completers' family members without a past history of CVD, DM, or psychiatric disorder showed a high risk of hospitalization for those conditions.

Decreased blood pressure associated with in-vehicle exposure to carbon monoxide in Korean volunteers.

BACKGROUND: Carbon monoxide (CO) is one of the primary components of emissions from light-duty vehicles, and reportedly comprises 77% of all pollutants emitted in terms of concentration. Exposure to CO aggravates cardiovascular disease and causes other health disorders. The study was aimed to assess the negative effects by injecting different amounts of CO concentration directly to human volunteers boarding in the car. METHODS: Human volunteers were exposed to CO concentrations of 0, 33.2, and 72.4 ppm, respectively during the first test and 0, 30.3, and 48.8 ppm respectively during the second test while seated in the car. The volunteers were exposed to each concentration for approximately 45 min. After exposure, blood pressure measurement, blood collection (carboxyhemoglobin [COHb] analysis), medical interview, echocardiography test, and cognitive reaction test were performed. RESULT: In patients who were exposed to a mean concentration of CO for 72.4 ± 1.4 ppm during the first exposure test and 48.8 ± 3.7 ppm during the second exposure test, the COHb level exceeded 2%. Moreover, the diastolic blood pressure was decreased while increasing in CO concentration after exposure. The medical interview findings showed that the degree of fatigue was increased and the degree of concentration was reduced when the exposed concentration of CO was increased. CONCLUSION: Although the study had a limited sample size, we found that even a low concentration of CO flowing into a car could have a negative influence on human health, such as change of blood pressure and degree of fatigue.

Human exposure and risk assessment of cadmium for residents of abandoned metal mine areas in Korea.

The objective of this study is to find the Cd levels in agricultural crops compared to soil, to evaluate the relationship between daily intake dose through the multimedia/multi-pathway of human exposure and biomarker levels of the residents in mine vicinity area. We collected and cited the data of four out of ten health impact assessments for the residents of abandoned mine areas undertaken by the Korea Ministry of Environment in 2008. The Cd levels in soil were significantly decreased by the separation distance from the mines. The Cd levels in blood were significantly different between residents in mine areas and in comparative areas, but urinary Cd levels did not differ. The Cd levels in blood were related to the age; the separation distance from mine to residence; the daily intake dose via ingestion of drinking water, crops, and surface soil; and inhalation of ambient air of Cd, but urinary Cd levels were not relevant with various sociodemographic characteristics and exposure factors. The average hazard quotient (HQ) value of Cd in the mining site was below 1.0, but the maximum HQ was closed to 1.0. The results indicated that the ingestion of Cd-contaminated soil and agricultural crops by local inhabitants could pose potential adverse health effects to long-term residents consuming rice grown near to the mining areas.

Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation.

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague-Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200µg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5µg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10µmol/L, n=5), and active Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1µmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10µmol/L, n=5) and inactive CaMKII blockade, KN 92 (1µmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5µg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation.

Evaluation of transdermal exposure of phthalates in children's products.

In this study, 16 children's products with the highest detection potential of phthalates were selected, and a phthalate assay and transdermal delivery analysis (NIER, US EPA Wipe [stress condition], US EPA Wipe [physiological condition], and US EPA Hand Wipe) were conducted with these products. The content of 6 controlled phthalates (DBP, BBP, DEHP, DNOP, DINP, and DIDP) was measured and most products contained more phthalates than the regulated guidelines (a total content of 6 phthalates to be ≤0.1%). For transdermal delivery, all items were found to be lower in the NIER transdermal delivery test method compared to the US EPA Hand Wipe (stress condition and physiological condition) transdermal delivery test method. For the US EPA Hand Wipe (stress condition and physiological condition) transdermal delivery test method, a similar result was observed, except for DINP. The average daily dose (ADD) estimated by determining the exposure algorithm for each transdermal delivery test method was highest in mats with a large contacting surface area and a long exposure time in the respective test methods. Conclusively, there was a difference between the NIER transdermal delivery test method and the US EPA Wipe transdermal delivery test method.

Prevalence of allergic diseases among Korean school-age children: a nationwide cross-sectional questionnaire study.

The purpose of this study was to investigate the nationwide prevalence of childhood asthma, eczema and other allergic diseases in Korean school-age children (8-11 yr old) and to assess the difference between residential areas. Among 6,279 elementary schools, 427 schools were randomly selected according to residential area (metropolitan, provincial, rural, and industrial area) by the cluster sampling method. Parents of students completed a modified Korean version of a questionnaire formulated by the International Study of Asthma and Allergies in Childhood (ISAAC). Among 50,200 subjects, 31,026 (61.8%) responded, and 30,893 (99.6%) were analyzed. The 12-month prevalence of wheeze, flexural rash, and allergic rhinitis symptoms were 4.8%, 15.3%, and 32.9%, respectively. The prevalence of diagnosis of allergic diseases in boys was higher than that in girls, with the exception of eczema. In both boys and girls, the difference of the prevalence of allergic diseases among industrial, metropolitan and provincial areas was not statistically significant, but the differences between rural area and other areas were significant. Our results support the importance of contextual effect associated with residential area as causative agents of allergic diseases among Korean school-age children.

Association between body mass index and asthma symptoms among Korean children: a nation-wide study.

The purpose of this study was to investigate the association between body mass index (BMI) and the prevalence of wheeze using nation-wide cross-sectional study in Korean children. Total 50,200 children from 427 elementary schools were randomly selected according to residential areas (metropolitan, provincial, rural, and industrial areas) by the cluster sampling method. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to measure the prevalence of wheeze. Among 31,026 respondents, 25,322 were analyzed. BMI was classified into quartiles based on BMI-for-age percentile. In all residential areas, pets at home and visible mold or moisture were associated with an increased prevalence of wheeze in both genders. However, other living environment factors were not consistently associated among residential areas and gender. Among girls, lowest BMI was negatively associated with prevalence of wheeze and highest BMI was positively associated in all residential areas. In multilevel logistic regression analysis, environmental tobacco smoking exposure, pets at home, visible mold or moisture, and being in the lowest and highest BMI quartile were significantly associated with the prevalence of wheeze in both genders. BMI has become an important risk factor for asthma symptoms among Korean children.

Evaluating the PM damage cost due to urban air pollution and vehicle emissions in Seoul, Korea.

This study evaluated the prospective damage costs of PM(2.5) inhalation. We performed a health risk assessment based on an exposure-response function to estimate the annual population risk in the Seoul metropolitan city, Korea. Also, we estimated a willingness-to-pay (WTP) amount for reducing the mortality rate in order to evaluate a statistical life value. We combined the annual population risk and the value-of-statistical-life to calculate the damage cost estimate. In the health risk assessment, we applied the PM(2.5) relative risk to evaluate the annual population risk. We targeted an exposure population of 5,401,369 persons who were over the age of 30. Using a Monte-Carlo simulation for uncertainty analysis, we estimated that the population risk of PM(2.5) inhalation during a year in Seoul is 2181 premature deaths for acute exposure and 18,510 premature deaths for chronic exposure. The monthly average WTP for 5/1000 mortality reduction over ten years is $20.20 USD (95% C.I: $16.60-24.50) and the implied value-of-statistical-life (VSL) is $485,000 USD (95% C.I: $398,000-588,000). The damage cost estimate due to risk from PM(2.5) inhalation in Seoul is about $1057 million USD per year for acute exposure, and $8972 million USD per year for chronic exposure. It is important to note that this cost estimate does not reflect all health damage cost estimates in this urban area. This recommendation is a model for evaluating a mortality risk reduction and as such we must re-evaluate an integrated application of morbidity risk.

Estimating the disease burden of lung cancer attributable to residential radon exposure in Korea during 2006-2015: A socio-economic approach.

Estimating the lung cancer disease burden can provide evidence for public health practitioners, researchers, and policymakers. This study uses claim data from lung cancer patients for 2006-2015 from the Korean National Health Insurance Service to estimate the lung cancer burdens attributable to residential radon in Korea using disability-adjusted life years (DALY) and patients' annual economic burden with societal perspectives using the cost-of-illness (COI) method. The number of patients increased during our study period (from 35,866 to 59,168). The disease burden and that attributable to residential radon, respectively, increased from 517.57 to 695.74 and 64.62 (95%; CIs 61.33-67.69) to 86.99 (95%; CIs 82.7-91.1) DALYs per 100,000 patients. The percentage of years lost due to disability among the DALY doubled from 8% to 17%. The cost for all the patients was US$2.33 billion, with US$292 (95%; CIs 278-306) million attributable to residential radon. During the last decade, the lung cancer disease burden increased by 1.34 times, with a doubled percentage of non-fatal burden and average annual growth rate of 9.5% of the total cost. Hence, the burden and cost of lung cancer in Korean provinces have been steadily increasing. The findings could be used as input data for future cost-effectiveness analysis of policies regarding radon reduction.

Effect of Socioeconomic Status and Underlying Disease on the Association between Ambient Temperature and Ischemic Stroke.

PURPOSE: Inconsistent findings have been reported regarding the effect of ambient temperature on ischemic stroke. Furthermore, little is known about how underlying disease and low socioeconomic status influence the association. We, therefore, investigated the relationship between ambient temperature and emergency department (ED) visits for ischemic stroke, and aimed to identify susceptible populations. MATERIALS AND METHODS: Using medical claims data, we identified ED visits for ischemic stroke during 2005-2009 in Seoul, Korea. We conducted piecewise linear regression analyses to find optimum ambient temperature thresholds in summer and winter, and estimated the relative risks (RR) and 95% confidence intervals (CI) per a 1°C increase in temperature above/below the thresholds, adjusting for relative humidity, holidays, day of the week, and air pollutant levels. RESULTS: There were 63564 ED visits for ischemic stroke. In summer, the risk of ED visits for ischemic stroke was not significant, with the threshold at 26.8°C. However, the RRs were 1.055 (95% CI, 1.006-1.106) above 25.0°C in medical aid beneficiaries and 1.044 (1.007-1.082) above 25.8°C in patients with diabetes. In winter, the risk of ED visits for ischemic stroke significantly increased as the temperature decreased above the threshold at 7.2°C. This inverse association was significant also in patients with hypertension and diabetes mellitus above threshold temperatures. CONCLUSION: Ambient temperature increases above a threshold were positively associated with ED visits for ischemic stroke in patients with diabetes and medical aid beneficiaries in summer. In winter, temperature, to a point, and ischemic stroke visits were inversely associated.

The study to estimate the floating population in Seoul, Korea.

Traffic-related pollutants have been reported to increase the morbidity of respiratory diseases. In order to apply management policies related to motor vehicles, studies of the floating population living in cities are important. The rate of metro rail transit system use by passengers residing in Seoul is about 54% of total public transportation use. Through the rate of metro use, the people-flow ratios in each administrative area were calculated. By applying a people-flow ratio based on the official census count, the floating population in 25 regions was calculated. The reduced level of deaths among the floating population in 14 regions having the roadside monitoring station was calculated as assuming a 20% reduction of mobile emission based on the policy. The hourly floating population size was calculated by applying the hourly population ratio to the regional population size as specified in the official census count. The number of people moving from 5 a.m. to next day 1 a.m. could not be precisely calculated when the population size was applied, but no issue was observed that would trigger a sizable shift in the rate of population change. The three patterns of increase, decrease, and no change of population in work hours were analyzed. When the concentration of particulate matter less than 10 µm in aerodynamic diameter was reduced by 20%, the number of excess deaths varied according to the difference of the floating population. The effective establishment of directions to manage the pollutants in cities should be carried out by considering the floating population. Although the number of people using the metro system is only an estimate, this disadvantage was supplemented by calculating inflow and outflow ratio of metro users per time in the total floating population in each region. Especially, 54% of metro usage in public transport causes high reliability in application.

Types of household humidifier disinfectant and associated risk of lung injury (HDLI) in South Korea.

From 2002 through 2015, hundreds of people died of fatal lung injuries associated with the use of humidifier disinfectants (HDs) in Korea. Several chemical disinfectants used for household humidifiers were later clinically confirmed to cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the registered lung disease cases and to compare the distribution of HDLI patients, including deaths, by HD use characteristics including types of HD and HD brands categorized by age group. A total of 530 registered were clinically examined through two rounds of investigations conducted from July 2013 until April 2015. Information on HD use was obtained from a structured questionnaire and home investigations. Approximately one-half of the patients (n=221) were clinically confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and pre-school children≤6years old (n=128, 58%) accounted for most of the HD-associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI patients developed HDLI after less than one year of HD use. HD products containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2-ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%). Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients (n=85, 38.5%) was found to use only Oxy Saksak® products containing PHMG. The development of HDLI was clinically found to be associated with the use of several HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.

Residential radon and environmental burden of disease among Non-smokers.

BACKGROUND: Lung cancer was the second highest absolute cancer incidence globally and the first cause of cancer mortality in 2014. Indoor radon is the second leading risk factor of lung cancer after cigarette smoking among ever smokers and the first among non-smokers. Environmental burden of disease (EBD) attributable to residential radon among non-smokers is critical for identifying threats to population health and planning health policy. METHODS: To identify and retrieve literatures describing environmental burden of lung cancer attributable to residential radon, we searched databases including Ovid-MEDLINE, -EMBASE from 1980 to 2016. Search terms included patient keywords using 'lung', 'neoplasm', exposure keywords using 'residential', 'radon', and outcomes keywords using 'years of life lost', 'years of life lost due to disability', 'burden'. Searching through literatures identified 261 documents; further 9 documents were identified using manual searching. Two researchers independently assessed 271 abstracts eligible for inclusion at the abstract level. Full text reviews were conducted for selected publications after the first assessment. Ten studies were included in the final evaluation. REVIEW: Global disability-adjusted life years (DALYs)(95 % uncertainty interval) for lung cancer were increased by 35.9 % from 23,850,000(18,835,000-29,845,000) in 1900 to 32,405,000(24,400,000-38,334,000) in 2000. DALYs attributable to residential radon were 2,114,000(273,000-4,660,000) DALYs in 2010. Lung cancer caused 34,732,900(33,042,600 ~ 36,328,100) DALYs in 2013. DALYs attributable to residential radon were 1,979,000(1,331,000-2,768,000) DALYs for in 2013. The number of attributable lung cancer cases was 70-900 and EBD for radon was 1,000-14,000 DALYs in Netherland. The years of life lost were 0.066 years among never-smokers and 0.198 years among ever-smoker population in Canada. CONCLUSION: In summary, estimated global EBD attributable to residential radon was 1,979,000 DALYs for both sexes in 2013. In Netherlands, EBD for radon was 1,000-14,000 DALYs. Smoking population lost three times more years than never-smokers in Canada. There was no study estimating EBD of residential radon among never smokers in Korea and Asian country. In addition, there were a few studies reflecting the age of building, though residential radon exposure level depends on the age of building. Further EBD study reflecting Korean disability weight and the age of building is required to estimate EBD precisely.

Short-term Effects of Ambient Air Pollution on Emergency Department Visits for Asthma: An Assessment of Effect Modification by Prior Allergic Disease History.

OBJECTIVES: The goal of this study was to investigate the short-term effect of ambient air pollution on emergency department (ED) visits in Seoul for asthma according to patients' prior history of allergic diseases. METHODS: Data on ED visits from 2005 to 2009 were obtained from the Health Insurance Review and Assessment Service. To evaluate the risk of ED visits for asthma related to ambient air pollutants (carbon monoxide [CO], nitrogen dioxide [NO2], ozone [O3], sulfur dioxide [SO2], and particulate matter with an aerodynamic diameter <10 µm [PM10]), a generalized additive model with a Poisson distribution was used; a single-lag model and a cumulative-effect model (average concentration over the previous 1-7 days) were also explored. The percent increase and 95% confidence interval (CI) were calculated for each interquartile range (IQR) increment in the concentration of each air pollutant. Subgroup analyses were done by age, gender, the presence of allergic disease, and season. RESULTS: A total of 33 751 asthma attack cases were observed during the study period. The strongest association was a 9.6% increase (95% CI, 6.9% to 12.3%) in the risk of ED visits for asthma per IQR increase in O3 concentration. IQR changes in NO2 and PM10 concentrations were also significantly associated with ED visits in the cumulative lag 7 model. Among patients with a prior history of allergic rhinitis or atopic dermatitis, the risk of ED visits for asthma per IQR increase in PM10 concentration was higher (3.9%; 95% CI, 1.2% to 6.7%) than in patients with no such history. CONCLUSIONS: Ambient air pollutants were positively associated with ED visits for asthma, especially among subjects with a prior history of allergic rhinitis or atopic dermatitis.