The effect of hidden female smoking on the relationship between smoking and cardiovascular disease.

BACKGROUND: Smoking is a known risk factor for cardiovascular morbidity and mortality, but several Korean studies have shown differing results on the association of current smoking status and the risk of cardiovascular disease (CVD). The aim of the present study was to investigate the association between smoking status and CVD (myocardial infarction and stroke) using national representative populationbased samples. The aim was also to investigate the effects of hidden smokers on the association between CVD and smoking. METHODS: Data were acquired from 28,620 participants (12,875 men and 15,745 women), age 19 years or older, who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2008 to 2016. RESULTS: The multivariable logistic regression analysis showed that ex-smoking status was correlated with CVD when self-reported (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.20-2.19) and for survey-cotinine verified-smoking status (OR: 1.57; 95% CI: 1.20-2.19). Interestingly, the present study showed current smoking was not significantly associated with CVD. For the effect of sex on smoking and CVD, self-reported and survey-cotinine-verified ex-smoking status were correlated with CVD in males (OR: 1.45; 95% CI: 1.04-2.04 and OR: 1.43; 95% CI: 1.02-2.02) and in females (OR: 2.74; 95% CI: 1.59-4.71 and OR: 2.92; 95% CI: 1.64-5.18). The ratios of cotinine-verified to self-reported smoking rates were 1.95 for women and 1.08 for men. CONCLUSIONS: In the current study, while ex-smoking status was significantly associated with CVD, current smoking status was not. Female ex-smoking status had a higher adjusted odds ratio for CVD than males compared to non-smoking status. An effect of hidden female smoking was also found on the association between smoking status and CVD in Korean adults.

Epigenetic Role of Histone Lysine Methyltransferase and Demethylase on the Expression of Transcription Factors Associated with the Epithelial-to-Mesenchymal Transition of Lung Adenocarcinoma Metastasis to the Brain.

PURPOSE: The objective of this study was to investigate the epigenetic role of histone lysine methylation/demethylation on the expression of epithelial-to-mesenchymal transition (EMT) associated transcriptional factors (TFs) during the metastasis of lung adenocarcinoma to the brain. METHODS: Paired samples of lung adenocarcinoma and brain metastasis (BM) were analyzed in 46 individual patients. Both samples were obtained by surgical resection or biopsy of the lung and brain. The paraffin-fixed formalin-embedded samples were obtained from the pathology archives in our institute. In samples of lung adenocarcinoma and BM, immunohistochemical staining was performed for epithelial markers, mesenchymal markers, EMT-TFs, histone lysine methyltransferase and demethylase. RESULTS: The immunoreactivity of EMT-TFs such as Slug (15.6% vs. 42.6%, p = 0.005), Twist (23.6% vs. 45.9%, p = 0.010) and ZEB1 (15.0% vs. 55.9%, p = 0.002) was increased in BM compared with that in lung adenocarcinoma. Epigenetic inducers such as H3K4 methyltransferase (MLL4, p = 0.018) and H3K36me3 demethylase (UTX, p = 0.003) were statistically increased, and epigenetic repressors such as EZH2 (H3K27 methyltransferase, p = 0.046) were significantly decreased in BM compared with those in lung adenocarcinoma. The expression of UTX-ZEB1 (R2 linear = 1.204) and MLL4-Slug (R2 linear = 0.987) was increased in direct proportion, and EZH2-Twist (R2 linear = -2.723) decreased in reverse proportion. CONCLUSIONS: The results suggest that certain histone lysine methyltransferase/demethylase, such as MLL4, UTX, and EZH2, regulate the expression of EMT-TFs such as Slug, ZEB1, and Twist epigenetically, which may thereby influence cancer metastasis from the lung to the brain.

Associated factors for depression, suicidal ideation and suicide attempt among asthmatic adolescents with experience of electronic cigarette use.

INTRODUCTION: While electronic cigarette (EC) use is rapidly increasing among asthmatic adolescents, little is known about the links between EC use and depression or suicidality. We assessed associated factors for depression and suicidality in asthmatic adolescents with experience of EC use. METHODS: We analyzed the data from the 11th to 13th Korea Youth Risk Behavior Web-based Surveys, which were completed from 2015 to 2017. Data were obtained from a stratified, multistage, clustered sample. Students supplied 'yes or no' answers to questions about previous asthma diagnosis by a doctor. Associated factors for depression and suicidality were evaluated by logistic regression models after controlling for potential confounding factors. We targeted 203336 adolescents, and 195847 completed the survey. RESULTS: The proportion of asthma among the respondents was 8.9%. The rate of experience of EC use was higher among asthmatic respondents than non-asthmatic respondents (10.3% vs 8.6%). Asthmatic respondents with experience of EC use had a much higher proportion of negative mental health states including depression and suicidality than subjects without EC experience. In our adjusted models, perception of stress was most strongly associated with depression (adjusted odds ratio, AOR=4.79; 95% CI: 4.12-5.58), and perception of unhappiness was most strongly associated with suicidal ideation (AOR=5.24; 95% CI: 4.51-6.09) and suicide attempt (AOR=4.37; 95% CI: 3.36-5.69). CONCLUSIONS: Many Korean asthmatic adolescents with experience of EC use report relatively high depression and suicidal behaviors. A multidisciplinary approach, including psychological help, may be required to prevent suicide among this population, especially those who report associated factors.

Influencing Factors for Influenza Vaccination among South Korean Adolescents with Asthma Based on a Nationwide Cross-Sectional Study.

BACKGROUND: Influenza viral infection is a major public health problem with significant morbidity and mortality.Asthma is a risk factor for developing serious complications related to influenza infection. OBJECTIVE: We explored factors associated with influenza vaccination coverage among adolescents with asthma. METHODS: Data were obtained from 62,276 participants in the 13th Korean Youth Risk Behavior Web-Based Survey (KYRBS) conducted in 2017. KYRBS data were obtained from a stratified, multistage, clustered sample. We used multiple logistic regression analyses to identify variables potentially related to influenza vaccination in adolescents with asthma. RESULTS: The proportion of asthma was 8.8%, and the influenza vaccination rate overall was 37.9%. It was 41.8% in the asthma group and 37.5% in the nonasthma group (p < 0.001). After regression, male sex (odds ratio (OR) = 1.45; 95% CI 1.35-1.55), a high socioeconomic status (OR = 1.12; 95% CI 1.05-1.19), residence at an orphanage (OR = 1.93; 95% CI 1.38-2.29), regular breakfast consumption (OR = 1.09; 95% CI 1.02-1.17), and subjective good health (OR = 2.39; 95% CI 1.69-3.39) were associated with increased influenza vaccination, whereas current smoking (OR = 0.87; 95% CI 0.67-0.96) and a depressive mood (OR = 0.77; 95% CI 0.64-0.95) were inversely associated in adolescents with asthma. CONCLUSION: It is important to improve influenza vaccination in adolescents with asthma, especially females, those with a low socioeconomic status, independent residents, breakfast skippers, current smokers, and those who consider themselves unhealthy and have depressive moods.

Association between cataract and cotinine-verified smoking status in 11 435 Korean adults using Korea National Health and Nutrition Examination Survey data from 2008 to 2016.

PURPOSE: To investigate the association between cataract and cotinine-verified smoking status. SETTING: Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, South Korea. DESIGN: Retrospective study. METHODS: Participants were randomly selected using data collected by the Korea National Health and Nutrition Examination Survey from 2008 to 2016. Participants completed a questionnaire to self-report smoking status and a history of cataract, among other variables. To identify the relationship between cataract and smoking, a new variable was used to define smoking status, survey-cotinine-verified smoking status (SCS)-the combination of self-reported smoking status and cotinine-verified smoking status- and thus identify hidden smokers. RESULTS: In total, 11 435 participants were eligible for final analysis. The study comprised 4925 men and 6510 women; the mean age was 52.86 ± 16.83 years (median: 54 years). Of 2292 SCS smokers, 382 (16.7%) were nonsmokers according to their self-report. Notably, the ratio of the cotinine-verified to self-reported smoking rate of women was greater than that of men, 1.60 and 1.06, respectively. This indicated that female hidden smokers may affect the results of studies based on self-reported questionnaires. Multivariate logistic regression analysis showed that smoking was correlated with cataract (odds ratio [OR], 1.37 [95% CI, 1.07-1.76]; OR, 1.35 [CI, 1.12-1.64]; and OR, 1.36 [CI, 1.10-1.69]) for self-reported, cotinine-verified, and SCS, respectively. No statistically significant sex difference was found. CONCLUSION: Smoking was associated with cataract, but it did not vary by sex. Female hidden smoking must be considered when investigating the association between smoking and cataract based on self-reported questionnaires.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

Variability in sociodemographic factors and obesity in Korean children: a cross-sectional analysis of Korea National Health and Nutrition Examination survey data (2007-2015).

PURPOSE: Sociodemographic factors are well-known risk factors for childhood obesity, even though the relationship between sociodemographic factors and obesity varies among countries. The objective of this study was to evaluate the relationship between sociodemographic factors and obesity in Korean children. METHODS: This study is an analysis of cross-sectional data from the 2007-2009, 2010-2012, and 2013-2015 Korea National Health and Nutrition Examination Surveys. The sample included 14,482 children aged between 2 and 18 years (7652 boys and 6830 girls) and their parents. Sociodemographic factors were measured as a combination of demographic, economic, and sociological factors, including sex, age, residential area, family income, parent education level, and parent employment status. RESULTS: In 2013-2015, obesity among Korean children was associated with current maternal smoking (P < .001). Obesity categorized according to age group was positively associated with paternal education level/high school graduation (P = .026 for ages 7-12 years), maternal smoking (P = .003 for ages 7-12 years), maternal body mass index (all age groups), paternal body mass index (all age groups), and low monthly family income (P = .017 for ages 2-6 years). CONCLUSIONS: Current maternal smoking habits, paternal education, and low family income are potential risk factors for obesity in Korean children.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study.

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

The association of smoking and hypertension according to cotinine-verified smoking status in 25,150 Korean adults.

PURPOSE: The establishment of a definitive association between smoking and hypertension has been controversial in previous studies, many of which were based on self-reported smoking status and urine cotinine-verified smoking status. The aim of the current study was to evaluate the association between hypertension and smoking considering the effects of all kinds of smoker types, including hidden smokers, using new variables and a population-based sample. METHODS: Data were acquired from 25,150 men and women aged older than 29 years who participated in the Korea National Health and Nutrition Examination Survey (KNHANES). RESULTS: The prevalence of hypertension was 4.7%, that of self-reported smoking was 30.8%, and that of cotinine-verified smoking was 28.5%. Of the male cotinine-verified smokers, 5.6% were self-reported nonsmokers (1.5% never-smokers and 4.1% ex-smokers), whereas, of the female cotinine-verified smokers, 46.9% were self-reported nonsmokers (40.8% never-smokers and 6.1% ex-smokers). Multivariate logistic regression analysis revealed that, with respect to self-reported smoking status, smokers and ex-smokers were not correlated with hypertension [(odds ratio (OR): 1.25 (95% confidence interval (CI): 0.99-1.57) and OR: 1.20 (CI: 0.90-1.60), respectively]. When gender was considered, the adjusted OR of the association of smoking with hypertension in female participants was 1.44 (CI: 1.02-2.04) with respect to cotinine-verified smoking status. CONCLUSION: This large observational study found that smoking was not associated with hypertension in the overall population, but, when the gender was considered, female smokers were more likely to demonstrate hypertension.

The incidentally diagnosed adult congenital heart disease during routine medical health checkups in 27,897 Koreans at a single center over seven years.

BACKGROUND: The rate of incidentally diagnosed congenital heart disease (CHD) in adulthood has not been reported. The aim of this study was to investigate the detection rate of CHD in adults by routine, general health checkups. METHODS: Data was acquired from 222,401 patients older than 19 years who participated in general health checkups from January 2010 to December 2016. We excluded persons who did not undergo echocardiography during the general health checkups, who underwent echocardiography prior to the health checkups, and who were previously diagnosed with CHD. RESULTS: Among the 27,897 patients, who were included in the final analysis, 293 cases were newly diagnosed as CHD, and the overall detection rate was 1.05%. The mean age of patients with CHD was 48.7 ± 21.5 years, and most of them were female (n = 187, 63.8%). More than two-thirds were between the third and fifth decade of life, and only six patients (2.04%) were older than 70 years. The most common type was bicuspid aortic valve (n = 155). Interestingly, Ebstein's anomaly that required surgical repair was detected in five persons. CONCLUSIONS: During general health checkup, there were cases of severe CHD that required cardiac surgery upon diagnosis.

The Effect of Hidden Female Smoking on the Association between Smoking and Asthma.

BACKGROUND: The association between smoking and asthma remains controversial. In our previous study, we were not able to show an association between asthma and smoking in Korean adults. One Korean study demonstrated underreporting of smoking history by female adults. The aim of the present study was to investigate the effects of hidden female smoking on the association between asthma and smoking in Korean adults. METHODS: Data were acquired from 23,483 men and women aged ≥19 years who participated in the Korean National Health and Nutrition Examination Surveys (KNHANES). RESULTS: The prevalence of asthma was 1.5%, the self-reported smoking prevalence was 32.4%, and the cotinine-verified smoking prevalence was 30.3%. Of the male cotinine-verified smokers, 6.4% were self-reported nonsmokers (2.7% never smokers and 3.7% ex-smokers), whereas 48.8% of the female cotinine-verified smokers were self-reported nonsmokers (43.2% never smokers and 5.6% ex-smokers). In males, the adjusted odds ratio of the association between smoking and asthma was 0.738 (confidence interval, CI: 0.393-1.173) in self-reported and 0.767 (CI: 0.515-1.143) in cotinine-verified smoking; in females, the adjusted odds ratio was 1.945 (CI: 1.348-2.805) in self-reported and 1.531 (CI: 1.076-2.179) in cotinine-verified smoking. CONCLUSIONS: Our study showed smoking was associated with asthma in females but not in males.

Prognostic significance of phosphoinositide 3-kinase p110α and p110ß isoforms in non-small cell lung cancer.

The proteins p110α and p110ß are isoforms of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). Class I PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration, and their aberrant activation contributes to the oncogenesis of various human cancers. In this study, we assessed expression of p110α and p110ß in non-small cell lung cancer (NSCLC) and their association with clinicopathological factors and patient survival. Seventy-six NSCLC cases were analyzed by immunohistochemical staining for p110α and p110ß. Of the 76 tumors, 18 (23.7%) and 43 (56.6%) were classified in the high p110α and p110ß expression groups, respectively. Expression of p110α was higher in smokers compared with non-smokers (P = 0.042). No other clinicopathological factors showed significant association with p110α or p110ß expression. In univariate and multivariate survival analyses, high p110ß expression was associated with worse overall survival (OS) in stage I NSCLCs (P < 0.001), whereas the high p110α expression group had shorter OS in stage II to IV NSCLCs (P = 0.005). Our results suggest that p110α and p110ß play different roles depending on tumor stage, and that both p110α and p110ß have potential as independent prognostic biomarkers of NSCLC.

Association between depression and asthma in Korean adults.

PURPOSE: Asthma is a one of the most common allergic diseases, and depression is an important comorbidity with asthma. However, little is known about the prevalence of depression in Korean adults with asthma. This study was performed to find the association between asthma and depression in Korean adults and to investigate the demographic and socioeconomic characteristics in Korean adults with asthma and with depression. METHODS: Data were acquired from 47,351 men and women, ages >19 years, who participated in the Korea National Health and Nutrition Examination Survey, which was conducted from 2007 to 2014. The presence of asthma and depression was based on self-reported physician diagnosis in the Health Interview Surveys. RESULTS: The prevalence of asthma was 2.8% and of depression was 4.1%. Logistic regression analysis showed that single marital status (separated or divorced) (adjusted odds ratio [aOR] 1.291 [95% confidence interval {CI}, 1.077-1.547]), unemployment (aOR 1.226 [95% CI, 1.061-1.417]), under middle school graduated education level (aOR 2.433 [95% CI, 1.867-3.171]), middle school graduated education level (aOR 1.759 [95% CI, 1.330-2.327]), obesity (aOR 1.403 [95% CI, 1.196-1.647]), and depression (aOR 1.796 [95% CI, 1.422-2.267]) were significantly associated with adult asthma; however, sex, age, monthly family income, residential area, smoking status, hypertension, and diabetes mellitus were not associated with adult asthma. Compared with individuals without asthma and with depression, patients with asthma and with depression were prone to be single (separated or divorced) and to have a lower education level (p < 0.01) Conclusion: The present study showed that depression was associated with asthma in Korean adults.

EGFR-dependent ERK activation triggers hydrogen peroxide-induced apoptosis in OK renal epithelial cells.

Oxidative stress induces activation of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase families. However, it is unclear in renal epithelial cells whether the ERK activation is involved in cell survival or cell death in H2O2-treated cells. The present study was undertaken to determine the role of the ERK activation in H2O2-induced apoptosis of renal epithelial cells using opossum kidney (OK) cells, an established proximal tubular epithelial cell line. H2O2 resulted in a time- and dose-dependent apoptosis of OK cells. H2O2 treatment caused marked sustained activation of ERK. The ERK activation was prevented by PD98059 and U0126, inhibitors of ERK1/2 upstream kinase MEK1/2. Apoptosis caused by H2O2 was prevented by U0126. Transient transfection with constitutive active MEK1 increased the H2O2-induced apoptosis, whereas transfection with dominant-negative mutants of MEK1 decreased the apoptosis. H2O2 produced hyperpolarization of mitochondrial membrane potential and activation of caspases-3. H2O2-induced ERK activation was inhibited by the Src family selective inhibitor PP2 and the epidermal growth factor receptor inhibitor AG1478. The presence of AG1478, but not PP2, prevented H2O2-induced cell death. Taken together, our findings suggest that the ERK activation mediated by epidermal growth factor receptor plays an active role in inducing H2O2-induced apoptosis of OK cells and functions upstream of mitochondria-dependent pathway to initiate the apoptotic signal.