BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*

BACKGROUND: There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. METHODS: This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children's Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22-0.51 ng/ml (low-passive smoker), 0.52-11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). RESULTS: Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. CONCLUSION Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.
Adult ; Attention Deficit Disorder with Hyperactivity ; epidemiology ; etiology ; physiopathology ; psychology ; Child, Preschool ; Cotinine ; blood ; Female ; Follow-Up Studies ; Humans ; Japan ; epidemiology ; Male ; Maternal Exposure ; adverse effects ; Mothers ; Pregnancy ; Pregnancy Trimester, Third ; Prenatal Exposure Delayed Effects ; epidemiology ; etiology ; Risk ; Sex Factors ; Tobacco Smoking ; adverse effects ; epidemiology

OBJECTIVETo investigate the cumulative effect regarding the family history of cardiovascular disease and smoking on ischemic stroke events in population with Mongolian ethnicity.

METHODSBased on data gathered from the baseline investigation, a 10-year prospective cohort follow-up project was conducted among 2 589 participants with Mongolian ethnicity. Ischemic stroke events were defined as the outcomes of the study. All the 2 589 participants were categorized into four subgroups: without family history of cardiovascular disease/nonsmokers, without family history of cardiovascular disease/smokers, with family history of cardiovascular disease/nonsmokers and with family history of cardiovascular disease/smokers, according to family history of cardiovascular disease and smoking status. Cumlative incidence rates of events among the four subgroups was described with Kaplan-Meier curves. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95%CI) of ischemic stroke events among the four subgroups.

RESULTSData from the Kaplan-Meier curves showed that the cumulative incidence rates of ischemic stroke were 1.17% (15/1 278), 3.83% (37/967), 5.70% (9/158) and 8.33% (15/180) for the groups of no family history of cardiovascular disease/nonsmokers, no family history of cardiovascular disease/smokers, with family history of cardiovascular disease/nonsmokers and with family history of cardiovascular disease/smokers, respectively. By cox proportional hazards model, after adjusting for age, male, drinking status, systolic and diastolic blood pressure, body mass index, fasting glucose, total cholesterol, triglycerides, LDL cholesterol factors, the HRs (95% CI) of ischemic stroke were 2.26 (1.19-4.28) and 2.45 (1.13-5.33) in the no family history of cardiovascular disease/smokers group, with family history of cardiovascular disease/smokers group when compared to the no family history of cardiovascular disease/nonsmokers group, respectively. The risk of ischemic stroke appeared the highest in the group with family history of cardiovascular disease/smokers (all P<0.05).

CONCLUSIONSmoking may increase the risk of ischemic stroke events among the population with family history of cardiovascular disease.

Alcohol Drinking ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; ethnology ; genetics ; Cholesterol ; Cholesterol, LDL ; Genetic Predisposition to Disease ; Humans ; Incidence ; Male ; Mongolia ; epidemiology ; Population Surveillance ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Smoking ; adverse effects ; epidemiology ; Stroke ; epidemiology ; genetics

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.
Adult ; Aged ; Case-Control Studies ; Cohort Studies ; Creatinine/blood ; Disease Progression ; Female ; Glomerulonephritis, IGA/blood/*diagnosis/epidemiology ; Humans ; Immunohistochemistry ; Kidney/*pathology ; Kidney Function Tests ; Kidney Glomerulus/*pathology ; Male ; Middle Aged ; Risk Factors ; Smoking/*adverse effects/epidemiology

OBJECTIVES: Smoking is known to be associated with nephropathy in patients with diabetes. The distinct effects of smoking before and after diabetes has been diagnosed, however, are not well characterized. We evaluated the association of cigarette smoking before and after a diagnosis of diabetes with the presence of diabetic nephropathy. METHODS: We analyzed data from the 2011-2013 editions of the Korea National Health and Nutrition Examination Survey. A total of 629 male patients diagnosed with diabetes were classified as non-smokers (90 patients), former smokers (225 patients), or continuing smokers (314 patients). A "former smoker" was a patient who smoked only before receiving his diagnosis of diabetes. A "continuing smoker" was a patient who smoked at any time after his diabetes had been diagnosed. Diabetic nephropathy was defined as the presence of albuminuria (spot urine albumin/creatinine ratio ≥30 mg/g) or low estimated glomerular filtration rate (<60 mL/min/1.73 m2). Multiple logistic regression models were used to assess the independent association after adjusting for age, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, medication for hypertension, and medication for dyslipidemia. Female patients were excluded from the study due to the small proportion of females in the survey who smoked. RESULTS: Compared to non-smokers, continuing smokers had significantly higher odds ratio ([OR], 2.17; 95% confidence interval [CI], 1.23 to 3.83) of suffering from diabetic nephropathy. The corresponding OR (95% CI) for former smokers was 1.26 (0.70 to 2.29). CONCLUSIONS: Smoking after diagnosis of diabetes is significantly associated with the presence of diabetic nephropathy in the Korean male population.
Aged ; Albumins/analysis ; Asian Continental Ancestry Group ; Blood Pressure ; Body Mass Index ; Creatinine/urine ; Diabetes Mellitus, Type 2/complications/*diagnosis ; Diabetic Nephropathies/epidemiology/*etiology ; Female ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated/analysis ; Humans ; Logistic Models ; Male ; Middle Aged ; Nutrition Surveys ; Odds Ratio ; Prevalence ; Republic of Korea ; Smoking/*adverse effects

OBJECTIVETo study the impact of preoperative fasting plasma glucose(FPG) on postoperative morbidity and outcome following surgical resection of esophageal squamous cell carcinoma (ESCC), and to analyze the risk factor of postoperative complication in ESCC.

METHODSClinicopathological data of 314 ESCC patients undergoing esophagectomy in our center between January 2011 and December 2012 were retrospectively collected. Patients were divided into two groups according to their preoperative FBG: normal FPG group (FPG<6.1 mmol/L, 252 cases) and high FBG group (FPG≥6.1 mmol/L, 62 cases, including 14 diabetes cases). Clinicopathological data and postoperative morbidity were analyzed and compared between two groups. Multivariate logistic regression analysis was used to evaluate risk factors for postoperative complications.

RESULTSThere were 278 male and 36 female patients with a median age of 59 years (range 42-83 years). As compared to normal FPG group, high FBG group had higher ratio of female [22.6%(14/62) vs. 8.7%(22/252), P=0.000], older median age (66 years vs. 59 years, P=0.010), lower ratio of smoking and alcohol drinking [48.4%(30/62) vs. 73.8%(186/252), 38.7%(24/62) vs. 69.0%(174/252), both P=0.000], higher ratio of comorbid diabetes and hypertension [51.6%(32/62) vs. 15.1%(38/252), 16.1%(10/62) vs. 1.6%(4/252), both P=0.000]. Pathology results showed 206 patients in normal FPG group (81.7%, 206/252) were moderate-poor differentiation, which was obviously lower than 93.5%(58/62) in high FPG group(P=0.023). Patients of two groups completed their operations successfully. Perioperative overall complication morbidity was 24.2%(76/314), and the most common was lung lesions (24 cases of pneumonia, 10 cases of respiratory failure), then was anastomotic leakage (28 cases) and incision infection (18 cases). Differences in overall and other complication morbidity were not significant between two groups (all P>0.05). Multivariate logistic regression analysis revealed that operation time was an independent risk factor of postoperative complications (P=0.047), anastomosis site was an independent risk factor of anastomotic leakage (P=0.036), and FPG was not a risk factor of postoperative complications(respectively, P=0.683, P=0.836, P=0.784, P=0.637).

CONCLUSIONSPreoperative control of FBG does not increase the postoperative complication morbidity. Shortening operation time and choosing appropriate surgical procedure are important to decrease postoperative complications.

Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking ; adverse effects ; Anastomotic Leak ; etiology ; Blood Glucose ; physiology ; Carcinoma, Squamous Cell ; complications ; surgery ; Comorbidity ; Diabetes Complications ; epidemiology ; Diabetes Mellitus ; Esophageal Neoplasms ; complications ; surgery ; Esophagectomy ; adverse effects ; Female ; Humans ; Hypertension ; complications ; Male ; Middle Aged ; Operative Time ; Pneumonia ; epidemiology ; etiology ; Postoperative Complications ; epidemiology ; Respiratory Insufficiency ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors ; Smoking ; adverse effects ; Surgical Wound Infection ; epidemiology ; Treatment Outcome

OBJECTIVETo investigate the penile erectile function of hospitalized male patients with cardiovascular diseases, the incidence of erectile dysfunction (ED) in this cohort, and the relationship of ED with cardiovascular diseases and its risk factors.

METHODSUsing a self-designed questionnaire, we conducted an investigation among the hospitalized patients in the Department of Cardiovascular Diseases of the First and Second Affiliated Hospitals of Xi'an Jiaotong University. We measured their body height, body mass index (BMI), waist circumference, hip circumference, and blood pressure, obtained their personal data, past history, metabolic indexes, and erectile function scores by IIEF-5, and analyzed the risk factors of ED using univariate and multivariate logistic regression and OR analyses.

RESULTSTotally, 225 valid questionnaires were included in this investigation, which showed a 66.7% incidence of ED, 15.8% mild, 27.0% mild to moderate, 17.6% moderate, and 6.3% severe. The incident rates of ED in the 18-35 yr, 36-49 yr, 50-65 yr, and > 65 yr age groups were 13.6%, 39.1%, 89.2%, and 91.2%, respectively. Univariate logistic regression analysis manifested that the risk factors of ED in the patients with cardiovascular diseases included age (OR = 3.122, 95% CI 2.040-4.779), smoking (OR = 1.768, 95% CI 1.209-2.584), BMI (OR = 1.261, 95% CI 1.114-1.427), total cholesterol (OR = 1.77, 95% CI 1.339-2.340), TC/HDL (OR =1.715, 95% CI 1.349-2.181), hypertension (OR = 1.717, 95% CI 1.110-2.658), and coronary heart disease (OR = 2.235, 95% CI 1.169-4.275), while multivariate logistic regression analysis showed the risk factors to be age (OR = 4.99, 95% CI 2.264-10.998), financial condition, (OR = 2.804, 95% CI 1.127-6.976), smoking (OR = 2.109, 95% CI 1.179-3.772), BMI (OR = 1.414, 95% CI 1.136-1.760), and TC/HDL (OR = 2.001, 95% CI 1.016-3.943).

CONCLUSIONThe incidence of ED is high in hospitalized patients with cardiovascular diseases and rises with the increase of age. Age, smoking, financial condition, BMI, and TC/HDL are the risk factors of both ED and cardiovascular diseases, and financial condition is closely associated with ED.

Adult ; Aged ; Blood Pressure ; Body Height ; Body Mass Index ; Cardiovascular Diseases ; complications ; Erectile Dysfunction ; epidemiology ; etiology ; Hospitalization ; Humans ; Hypertension ; complications ; Imidazoles ; Incidence ; Male ; Middle Aged ; Pyrimidines ; Regression Analysis ; Risk Factors ; Smoking ; adverse effects ; Waist Circumference ; Young Adult

PURPOSE: Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population. MATERIALS AND METHODS: Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status. RESULTS: Fibrinogen levels were positively associated with IMT-max (standardized beta=0.25, p=0.021) and IMT-tpm (standardized beta=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers. CONCLUSION: Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*statistics & numerical data ; Atherosclerosis/*ultrasonography ; Blood Pressure ; Body Mass Index ; Carotid Artery Diseases/*blood/epidemiology/ultrasonography ; Carotid Artery, Common ; *Carotid Intima-Media Thickness ; Cholesterol/blood ; Cholesterol, HDL ; Cross-Sectional Studies ; Fibrinogen/*analysis ; Humans ; Lipoproteins, HDL/blood ; Logistic Models ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Risk Factors ; Sex Factors ; Smoking/*adverse effects/blood/epidemiology ; Surveys and Questionnaires

PURPOSE: We investigated the prevalence rate of benign prostatic hyperplasia (BPH) among Korean males in a rural area through a cross-sectional, community-based epidemiologic survey and analyzed the correlation with epidemiologic factors. MATERIALS AND METHODS: A total of 779 males who lived in Yangpyeong County participated in a prostate examination campaign. Targeting these men, we collected the International Prostate Symptom Score (IPSS), medical history, demographic information, serum prostate-specific antigen, and prostate volume as measured by transrectal ultrasonography. The data for 599 participants were analyzed, excluding 180 men who had a possibility of prostate cancer. BPH was defined as an IPSS of 8 points or higher and a prostate volume of 25 mL or more. RESULTS: The prevalence rate of BPH was 20.0%. The prevalence rate increased with age. There were 2 subjects (4.4%) in the age group of 40-49 years, 18 subjects (10.9%) in the age group of 50-59 years, 44 subjects (22%) in the age group of 60-69 years, and 56 subjects (26.6%) in the age group of over 70 years; this increase with age was statistically significant (p<0.001). In the BPH group, the average IPSS was 14.67+/-5.95, the average prostate volume was 37.04+/-11.71 g, and the average prostate-specific antigen value was 1.56+/-0.88 ng/mL. In the analysis of correlations between the epidemiologic factors and the risk of BPH, smoking was the only statistically significant factor. CONCLUSIONS: The total prevalence rate of BPH in this study was 20.0%, which was a little lower than the rate reported in other cities or rural areas.
Adult ; Age Distribution ; Aged ; Community-Based Participatory Research ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Prevalence ; Prostate/ultrasonography ; Prostate-Specific Antigen/blood ; Prostatic Hyperplasia/*epidemiology ; Republic of Korea/epidemiology ; Rural Population/statistics & numerical data ; Smoking/adverse effects

BACKGROUND/AIMS: Many patients are diagnosed with cryptogenic hepatocellular carcinoma (HCC) without metabolic syndrome (MS). We investigated the risk factors for cryptogenic HCC in patients with a low body mass index (BMI) or without MS. METHODS: Thirty-six patients were diagnosed with cryptogenic HCC over a 10-year period at a tertiary research hospital. Data including BMI score and risk factors for MS were analyzed retrospectively. Patients with fewer than two risk factors for MS (n = 16) were compared with those with two or more risk factors (n = 20). Patients with high BMI (> or = 23 kg/m2, n = 20) were also compared with those with lower BMI (n = 16). RESULTS: Patients with fewer than two risk factors for MS were significantly more likely to smoke and be hepatitis B surface antibodies (anti-HBs)-positive vs. patients with two or more risk factors. However, only smoking was statistically significant on multivariate analysis. Peaks of BMI were observed in two regions. Lower BMI was significantly associated with the presence of anti-HBs compared with high BMI, although this association was not statistically significant on multivariate analysis. CONCLUSIONS: Smoking is a potential risk factor for cryptogenic HCC in patients without MS. Remote hepatitis B virus infection may be a risk factor for cryptogenic HCC in patients without MS or with a low BMI.
Aged ; Aged, 80 and over ; *Body Mass Index ; Carcinoma, Hepatocellular/*epidemiology ; Chi-Square Distribution ; Female ; Hepatitis B/diagnosis/epidemiology ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/immunology ; Humans ; Liver Neoplasms/*epidemiology ; Logistic Models ; Male ; Metabolic Syndrome X/*epidemiology ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoking/adverse effects/epidemiology ; Time Factors