Assessment of exposure and DNA damage from second-hand smoke using potential biomarker in urine: cigarettes and heated tobacco products.

Second-hand smoke exposure is an established cause of several adverse health effects. Tobacco smoke exposure in the environment has been improved by the WHO Framework Convention on Tobacco Control. However, concerns have been raised regarding the health effects of heated tobacco products. Analysis of tobacco smoke biomarkers is critical for assessing the health effects of second-hand tobacco smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were analysed in the urine of non-smokers with or without passive exposure to cigarettes and heated tobacco products. In addition, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine were simultaneously measured as DNA damage markers. The results revealed higher levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in participants exposed to second-hand tobacco smoke (both cigarettes and heated tobacco products) at home. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be higher in the second-hand tobacco smoke-exposed group. The urinary levels of nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were high in workplaces with no protection against passive smoking. These biomarkers will be useful for evaluating passive exposure to tobacco products.

Association between Fathers' Use of Heated Tobacco Products and Urinary Cotinine Concentrations in Their Spouses and Children.

Heated tobacco products (HTPs) have become increasingly popular among smokers, especially among young adults in Japan in recent years. Assessments of secondhand tobacco smoke (SHS) exposure due to HTPs are scarce. The present study aimed to assess the urinary levels of total nicotine metabolites (TNMs) of non-smoking spouses and their children following SHS exposure due to their fathers' use of HTPs. A total of 41 families including 129 participants were recruited between 2018 and 2021. The number of non-smoking spouses and children of the fathers who smoke combustion cigarettes, the fathers who use HTPs, and the fathers who are non-users or have never smoked was 27, 66, and 36, respectively. The urinary levels of TNMs, including cotinine (Cot) and 3'-hydroxycotinine (3-OHCot), were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The spouses and children of fathers who use HTPs had significantly higher levels of TNMs in their urine compared to those with fathers who were non-smokers or non-users. The current study is the first to assess SHS exposure due to HTP use, and to suggest the importance of strategies to prevent exposure to SHS from HTP use in public places and educational strategies to protect non-smokers from secondhand HTP aerosol exposure in households and other private places.

Association Between Airflow Limitation and Carotid Intima-Media Thickness in the Japanese Population.

PURPOSE: This study aimed to reveal the association between airflow limitation (AL) and carotid intima-media thickness (IMT) according to smoking status in Japan. SUBJECTS AND METHODS: This cross-sectional study was performed in 2809 subjects, who underwent a comprehensive health examination with pulmonary function tests and carotid ultrasonographic measurement. AL was defined as forced expiratory volume in 1 s/forced vital capacity of <0.7. The subjects were divided into the following four groups: never smokers without AL, never smokers with AL, former/current smokers without AL, and former/current smokers with AL. Mean IMT, the maximum measurable IMT value in the left and right common carotid arteries (IMT-C max), and mean IMT-C max were measured by carotid ultrasonography. The carotid wall thickness as defined as follows: IMT ≥ 1.1 mm (IMT1.1), IMT-C max ≥ 1.2 mm (IMTc1.2), and IMT-C max > 1.5 mm (IMTc1.5), based on each measured region. The association between AL and the carotid wall thickness according to smoking status was assessed by logistic regression analysis. RESULTS: The mean carotid IMT and mean IMT-C max were significantly higher in never smokers with AL and former/current smokers with or without AL than in never smokers without AL. In logistic regression models adjusted for sex, age, body mass index, hypertension, dyslipidemia, hyperglycemia, physical activity, and alcohol consumption, the risk of carotid wall thickness (IMT1.1 [odds ratio {OR}: 1.55; 95% confidence interval {CI}: 1.07-2.24]; IMTc1.2 [OR: 1.52; 95% CI: 1.03-2.24]; IMTc1.5 [OR: 1.99; 95% CI: 1.15-3.46]) were significantly higher in former/current smokers with AL than in never smokers without AL. CONCLUSION: The present results suggest that greater IMT and risk of carotid wall thickness were associated with AL and smoking experience.

Associated Factors and Comorbidities of Airflow Limitation in Subjects Undergoing Comprehensive Health Examination in Japan - Survey of Chronic Obstructive Pulmonary Disease Patients Epidemiology in Japan (SCOPE- J).

Purpose: To identify associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases in health examinees, and to describe the characteristics of each subgroup classified by comorbidities. Subjects and Methods: This was an observational cross-sectional survey carried out in multiple regions of Japan. Subjects aged 40 years older, undergoing comprehensive health examination, were recruited. Airflow limitation was defined as having forced expiratory volume in 1 s/forced vital capacity lower than 70%. Associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases were examined by logistic regression analysis. Subgroup classification by comorbidity patterns was conducted by hierarchical cluster analysis. Results: In a total of 22,293 subjects, 1520 (6.8%) had at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases. With this objective variable, the following explanatory variables were significantly associated: older age, higher total score in the chronic obstructive pulmonary disease assessment test (CAT) and coexistence of lung cancer (common in ever-smokers and never-smokers), higher pack-years, lower body mass index, higher C-reactive protein, without coexistence of diabetes mellitus (specific in ever-smokers), male sex, coexistence of anxiety, and sleep disorder (specific in never-smokers). Among the 1520 subjects, 1512 subjects with smoking history data were classified by comorbidity patterns into subgroups of "no comorbidities," "mixed comorbidities," "inflammatory comorbidities," "overweight," "underweight," and "chronic kidney disease." "Inflammatory comorbidities" were specific in ever-smokers, and "underweight" was specific in never-smokers. Conclusion: Several factors were identified as associated factors of having at least one of airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases and they were different between ever-smokers and never-smokers. Different comorbidity patterns were observed by smoking history. These findings could provide information to assist the management of subjects with COPD or at risk for COPD in the general population.

Chronic Cough and Phlegm in Subjects Undergoing Comprehensive Health Examination in Japan - Survey of Chronic Obstructive Pulmonary Disease Patients Epidemiology in Japan (SCOPE-J).

Purpose: The purpose of this study was to estimate the prevalence of subjects with chronic cough and phlegm and describe their characteristics including the presence or absence of airflow limitation among the general population in Japan. Subjects and Methods: This was an observational cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited. The existence of chronic cough and phlegm, airflow limitation, and treatment for respiratory diseases were examined. Chronic cough and phlegm were defined as having both symptoms for at least 3 months of the year and for at least 2 consecutive years, or as receiving any treatment for chronic bronchitis at the time of recruitment. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) less than 0.7. Results: In a total of 22,293 subjects, 380 subjects (1.7%) had chronic cough and phlegm. Among these 380 subjects, 21.8% received treatment for a respiratory disease, and 11.6% had airflow limitation. Compared to subjects without both chronic cough and phlegm but with airflow limitation, subjects with chronic cough and phlegm without airflow limitation were younger, more likely to be current smokers (39.6%), and had higher total scores on a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Scores of CAT questions 1-4 (cough, phlegm, chest tightness, breathlessness, respectively) were higher in subjects with chronic cough and phlegm regardless of airflow limitation. Conclusion: This study demonstrated that subjects identified to have chronic cough and phlegm in comprehensive health examination settings were symptomatic, while most of them did not receive any treatment for respiratory diseases and did not have airflow limitation. Screening subjects for chronic cough and phlegm in a comprehensive health examination followed by a detailed examination of screened subjects could be an effective approach for better management of chronic cough and phlegm. Smoking cessation should be included in the management, in consideration that around 40% of subjects with chronic cough and phlegm were current smokers.

Comorbidities according to airflow limitation severity: data from comprehensive health examination in Japan.

OBJECTIVES: The present study aimed to investigate the relationship between airflow limitation (AL) severity and comorbidities in comprehensive health examination. METHODS: This cross-sectional study included 6661 men and 6044 women aged 40-89 who underwent a lung function test during medical checkups. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. Logistic regression analysis was used to assess the association between AL severity and the presence of comorbidities. RESULTS: When compared with the normal lung function group, subjects with AL had a higher prevalence of lung cancer (odd ratio (OR) 9.88, 95% confidence interval (CI) 3.88-25.14) in men, hypertension (OR 1.63, 95% CI 1.26-2.10) in women, diabetes and hyperglycemia (OR 1.23, 95% CI 1.02-1.49 in men, OR 1.61, 95% CI 1.18-2.20 in women) in men and women after adjusting for potential confounders. In men, lung cancer and MetS (the Joint Interim Statement: JIS) were significantly associated with moderate-to-very severe AL after adjustment. In women, hypertension, diabetes and hyperglycemia, MetS (JIS), and MetS (the Japanese Committee of the Criteria for MetS: JCCMS) were significantly associated with mild AL after adjustment. Hypertension was significantly associated with moderate-to-very severe AL after adjustment in women. CONCLUSIONS: Significant relationships were found between AL severity and the presence of comorbid lung cancer in men, hypertension in women, diabetes and hyperglycemia, and MetS in men and women. Knowledge of comorbidities associated with AL should be widely publicized to raise the awareness of chronic obstructive pulmonary disease (COPD).

Prevalence and risk factors of airflow limitation in a Mongolian population in Ulaanbaatar: Cross-sectional studies.

The burden of chronic obstructive pulmonary disease (COPD) is expected to increase in the coming decades. In Ulaanbaatar, Mongolia, air pollution, which has been suggested to correlate with COPD, is a growing concern. However, the COPD prevalence in Ulaanbaatar is currently unknown. This study aims to estimate the prevalence of airflow limitation and investigate the association between airflow limitation and putative risk factors in the Mongolian population. Five cross-sectional studies were carried out in Ulaanbaatar. Administration of a self-completed questionnaire, body measurements, and medical examination including spirometry were performed in 746 subjects aged 40 to 79 years living in Ulaanbaatar. The age- and sex-standardized prevalence of airflow limitation in Ulaanbaatar varied widely from 4.0 to 10.9% depending on the criteria for asthma. Age, body mass index (BMI), and smoking habit were independent predictors for airflow limitation while residential area and household fuel type were not significant. In conclusion, prevalence of putative COPD was 10.0% when subjects with physician-diagnosed asthma were excluded from COPD. Older age, lower BMI, and current smoking status were putative risk factors for airflow limitation. This prevalence was consistent with reports from Asian countries.

Prevalence of airflow limitation in subjects undergoing comprehensive health examination in Japan: Survey of Chronic Obstructive pulmonary disease Patients Epidemiology in Japan.

PURPOSE: There are still evidence gaps on the prevalence of airflow limitation in Japan. The purpose of this survey was to estimate the prevalence of airflow limitation among healthy subjects in Japan and to show what proportion of subjects with airflow limitation had been diagnosed with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: This was an observational, cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited from 14 centers in Japan. Airflow limitation was defined as having forced expiratory volume in 1 second/forced vital capacity less than 70%. RESULTS: In a total of 22,293 subjects, airflow limitation was most prevalent in subjects aged over 60 years (8.7%), but was also observed in subjects aged 50-59 years (3.1%) and 40-49 years (1.7%). Overall prevalence was 4.3%. Among subjects with smoking history (n=10,981), the prevalence of airflow limitation in each age group (12.8% in those aged over 60 years, 4.4% in those aged 50-59 years, and 2.2% in those aged 40-49 years) and overall prevalence (6.1%) were higher than that of total subjects. Of the smokers with airflow limitation, 9.4% had been diagnosed with COPD/emphysema and 27.3% with other respiratory diseases. CONCLUSION: Among smokers undergoing comprehensive health examination, prevalence of airflow limitation reached 12.8% in those aged over 60 years and airflow limitation was observed in subjects aged 40-59 years as well, though their prevalence was lower than that in subjects aged over 60 years. We demonstrated that a significant proportion of smokers with airflow limitation had not been diagnosed with COPD/emphysema, suggesting that some of them can be diagnosed with COPD or other respiratory diseases by a detailed examination after comprehensive health examination. Screening for subjects at risk of COPD by spirometry in comprehensive health examination starting at 40 years of age, followed by a detailed examination, may be an effective approach to increase the diagnosis of COPD.

Relationship of airflow limitation severity with work productivity reduction and sick leave in a Japanese working population.

BACKGROUND: The aim of this study was to reveal the association between airflow limitation (AL) severity and reduction with work productivity as well as use of sick leave among Japanese workers. METHODS: This cross-sectional study included 1,378 workers who underwent a lung function test during a health checkup at the Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in 1 second/forced vital capacity of <0.7. Workers completed a questionnaire on productivity loss at work and sick leave. The quality and quantity of productivity loss at work were measured on a ten-point scale indicating how much work was actually performed on the previous workday. Participants were asked how many days in the past 12 months they were unable to work because of health problems. Logistic regression analysis was used to assess the associations between AL severity and the quality and quantity of productivity loss at work as well as use of sick leave. RESULTS: Compared with workers without AL, workers with moderate-to-severe AL showed a significant productivity loss (quality: odds ratio [OR] =2.04, 95% confidence interval [CI]: 1.12-3.71, P=0.02 and quantity: OR =2.19, 95% CI: 1.20-4.00, P=0.011) and use of sick leave (OR =2.69, 95% CI: 1.33-5.44, P=0.006) after adjusting for sex, age, body mass index, smoking status, hypertension, hyperglycemia, dyslipidemia, sleep duration, work hours per day, and workplace smoking environment. CONCLUSION: AL severity was significantly associated with work productivity loss and use of sick leave. Our findings suggested that early intervention in the subjects with AL at the workforce might be beneficial for promoting work ability.

Association between airflow limitation severity and arterial stiffness as determined by the brachial-ankle pulse wave velocity: a cross-sectional study.

Objective Chronic obstructive pulmonary disease (COPD) is often associated with concomitant systemic manifestations and comorbidities, such as cardiovascular disease. There are limited data regarding airflow limitation (AL) and atherosclerosis in Japanese patients, and the potential association between AL and arterial stiffness has not yet been investigated in Japanese patients. Therefore, the purpose of this study was to investigate the association between AL severity and arterial stiffness using the brachial-ankle pulse wave velocity (baPWV). Methods This cross-sectional study included 1,356 subjects aged 40-79 years without clinical cardiovascular diseases who underwent a comprehensive health screening that included spirometry, the baPWV measurement, and blood sampling during medical check-ups in 2009 at the Japanese Red Cross Kumamoto Health Care Center. AL was defined in accordance with the Global Initiative for COPD criteria (forced expiratory volume in one second / forced vital capacity of < 0.7). A cut-off baPWV value of >1,400 cm/s was used for risk prediction and screening. Results The average baPWV (SD) results were 1,578.0 (317.9), 1,647.3 (374.4), and 1,747.3 (320.1) cm/s in the patients with a normal pulmonary function, mild AL, and moderate-to-severe AL, respectively (p< 0.001). Using logistic regression models adjusted for the age, body mass index, smoking status, hypersensitive C-reactive protein levels, hypertension, hyperglycemia, and dyslipidemia, an increased baPWV (>1,400 cm/s) was significantly associated with moderate-to-severe AL compared with a normal pulmonary function (odds ratio=2.76; 95% confidence intervals, 1.37-5.55; p=0.004). Conclusion Our results indicated an association between AL and increased arterial stiffness. Arterial stiffness may therefore worsen with an increase in the severity of AL.

A large cohort study concerning age-dependent impacts of anthropometric variables on spirometric parameters in nonsmoking healthy adults.

BACKGROUNDS: Although height (H) has been considered the principal anthropometric variable governing lung function, the age-dependent differences in its influences on determining spirometric parameters (SPs) have not been conclusively investigated. Moreover, there has been no study centered on age-dependent effects of other anthropometric variables, including body weight (BW) and body fat mass (BFM) on SPs. In addition, the age-dependent influences of these anthropometric variables are anticipated to differ quantitatively between male and female participants. METHODS: A total of 16,919 nonsmoking healthy Japanese adults (men: 6,116, women: 10,803) were partitioned into six groups stratified by gender and age at intervals of 20-years: young-, middle-, and advanced-age groups of either gender. Using a model in which a SP was described by a logarithmic additive function of age, H, BW, and BFM, we determined the partial regression coefficients of the respective anthropometric variables to predict the reference means of SPs, including FVC, FEV1, FEV1/FVC, PEF, FEF50, and FEF75, in the six groups. RESULTS/DISCUSSION: Although the impact of H on FVC and FEV1 was relatively homogeneous irrespective of gender and age, its homogeneity faded for flow parameters, particularly in the female middle- and advanced-age groups, indicating that the age-dependent contribution of H to SPs was enhanced more in women. The impact of BW on SPs differed depending on age, and this effect was also more conspicuous for female participants. H and BW generally exerted positive effects on SPs, whereas BFM had negative effects. Opposite effects of BW and BFM were observed in the female middle-age group in particular. CONCLUSIONS: The effects of anthropometric variables on spirometric parameters are highly age-dependent, particularly in women, leading to the conclusion that the assumption of age-independent, constant partial regression coefficients of anthropometric variables while predicting the reference mean of a certain spirometric parameter may result in substantial errors.

Association of a genetic variant of CYP19A1 with multicentric development of lung adenocarcinomas.

BACKGROUND: The detection rate of multiple lung adenocarcinomas, which display multiple ground glass opacity nodules in the peripheral lung, is increasing because of advances in high resolution computed tomography. The genetic backgrounds of multiple nodules and the mechanisms that underlie their multicentric development are unknown. In this study, we examined single nucleotide polymorphisms (SNPs) of the cytochrome P450 19A1 gene to determine if they are associated with multiple adenocarcinomas risk. METHODS: Fifty-one cases of multiple adenocarcinomas with lepidic growth, 62 cases of a single adenocarcinoma with lepidic growth, and 126 control cases were analyzed. Three SNPs were analyzed by using a 5' nuclease assay with TaqMan minor-groove-binder probe. The expression level of CYP19A1 in the noncancerous lung was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: A minor allele of SNP rs3764221, which is located in the CYP19A1 gene, was significantly associated with multiple adenocarcinomas risk (adjusted odds ratio = 3.06; P = 0.006). Other polymorphisms of CYP19A1 were not significantly associated with the risk of multiple adenocarcinomas. A minor allele of SNP rs3764221 was also associated with a higher level of CYP19A1 messenger RNA expression (P = 0.03). CONCLUSIONS: SNP rs3764221 contributes to the development of multicentric adenocarcinomas in the peripheral lung by causing higher levels of CYP19A1 expression.

Application of the COOP/WONCA charts to aged patients with chronic obstructive pulmonary disease: a comparison between Japanese and Chinese populations.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is similar in Japan and China and is increasing due to high rates of smoking in these countries. Reducing COPD is an important public health issue. The goals of this study were to verify the reliability and validity of the Japanese version of the COOP/WONCA charts, a tool for measuring health status, and to examine the qualitative differences in health status between Japanese and Chinese patients with COPD and between these patients and healthy subjects. METHODS: From 2008 to 2011, we examined the factors affecting the health status of Japanese and Chinese populations living in six cities. Participants were patients with COPD staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (140 Japanese, 201 Chinese) and healthy subjects (243 Japanese, 199 Chinese), all 50 to 79 years old. Health status was measured by using the COOP/WONCA charts, and basic information such as smoking status and medical history was reported by the participants. RESULTS: The Japanese and Chinese versions of the COOP/WONCA charts were shown to be reliable and valid by test-retest, comparison with the SF-36 and respiratory symptoms, and correlation of results obtained from patients and their physicians. Stepwise multiple regression analyses demonstrated that "Physical fitness", "Daily activities", and "Social activities" were predicted by COPD status and/or respiratory symptoms; "Feelings" by nationality and respiratory symptoms; "Pain" by sex and respiratory symptoms; and "Overall health" by nationality. When the COOP/WONCA scores were stratified by nationality, age, sex, and COPD status, the difference of each score between the patients and healthy subjects was larger for the Chinese subjects than for the Japanese. The physical, psychosocial activities, and pain scores increased significantly as COPD status worsened in Chinese subjects, whereas these scores were not affected by sex, age, or COPD status for Japanese subjects. Brinkman index and use of smoky fuel indoors affected the COOP/WONCA scores in Chinese patients but not in Japanese patients. CONCLUSIONS: The Japanese COOP/WONCA charts are reliable and valid. COPD more severely affected the health status of Chinese participants than of Japanese participants. These results suggest that countermeasures against insufficient health care and smoky environments may improve the health status of Chinese patients with COPD.

The reliability and validity of the Japanese version of the Diabetes Family Behavior Checklist (DFBC) for assessing the relationship between type 2 diabetes mellitus patients and their families with respect to adherence to treatment regimen.

AIMS: An appropriate questionnaire for assessing family support of self-management behavior of Japanese Type 2 diabetes patients has yet to be developed. We produced a Japanese version of the Diabetes Family Behavior Checklist (DFBC) and tested its reliability and validity. METHODS: The study enrolled Japanese patients with Type 2 diabetes mellitus who were living with their families: 158 patients in the Insulin Group and 169 in the Oral Hypoglycemic Agents Group. The external validity of the DFBC was tested with questionnaires of self-managed dietary and exercise behaviors, the Appraisal of Diabetes Scale (ADS), and HbA1c. RESULTS: The DFBC comprised two components: "Negative" and "Positive" feedbacks. Cronbach's alpha in the subcategories was ≥0.93, and the test-retest showed an intraclass correlation coefficient of 0.89. "Positive" and "Negative" scores correlated with self-managed dietary and/or exercise behaviors, the ADS scores in the both Groups. For patients having HbA1c levels of ≤6.8% there was a correlation between their "Positive" and "Negative" scores and the scores of their families in both Groups. CONCLUSION: The DFBC showed evidence of validity and reliability and may be a useful tool for quick assessment of self-managed treatment behavior of Japanese Type 2 diabetes patients and support received from their family.

Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population.

OBJECTIVES: Arylamines are considered to be the primary causative agent of bladder cancer in tobacco smokers. To test the hypothesis that variation in the genes that metabolize tobacco carcinogens contribute to bladder cancer, we examined the effects of single nucleotide polymorphisms in the genes of four key enzymes: cytochrome P450 1A2, N-acetyltransferase (NAT) 2, sulfotransferase 1A1, and UDP-glucuronosyltransferase (UGT) 2B7. METHODS: In this study, 282 Japanese patients with transitional cell carcinoma, the most common bladder cancer, and 257 healthy controls were surveyed and compared for frequencies of the genotypes of the four enzymes. Genotypes were determined using PCR-restriction fragment length polymorphism and TaqMan assays. Smoking information was collected by personal interview. Logistic regression analysis and the chi-square test were employed as statistical methods. RESULTS: The NAT2 slow genotype was significantly associated with the risk of bladder cancer [odds ratio (OR) 3.41, 95 % confidence interval (95 % CI) 1.68-6.87; p < 0.05). The NAT2 slow genotype also significantly increased the risk of bladder cancer in heavy smokers (OR 8.57, 95 % CI 1.82-40.25; p < 0.05). Among the different combinations of the four enzyme genotypes, the highest OR (4.20; 95 % CI 1.34-13.14; p < 0.05) was obtained with the NAT2 slow genotype when present in combination with the UGT2B7 *2/*2 or *1/*2 genotype. CONCLUSIONS: Our results suggest that individuals with different genotypes for the enzymes involved in metabolizing carcinogenic arylamines have a different risk of developing bladder cancer. In particularly, the combination of the NAT2 slow genotype with UGT2B7 *1/*2 or *2/*2 genotype is a high risk factor for bladder cancer.

Novel regression equations predicting lung age from varied spirometric parameters.

Although lung age calculated backward from regression formulas constructed for FEV(1) estimation is widely used, it possesses a couple of faults. We developed novel equations predicting lung age from varied spirometric parameters (spirometry-derived lung age (SDL-age)). Applying multiple regression analysis, equations predicting SDL-age were invented using data from 8015 never-smokers with normal spirometry (group I). Validation was made based on data from 6398 never-smokers with normal spirometry (group II). Equations were further applied for 446 subjects with airflow limitation. FEV(1), FEV(1)/FVC, FEF(50), and PEF were selected as explanatory variables for reference value of SDL-age. Normal limits of difference between SDL-age and chronological-age were ± 13.4 years in the male and ± 15.0 years in the female. Established equations predicted SDL-age of group II. SDL-age was older than chronological-age only in subjects with severe airflow limitation. Novel regression equations allowing prediction of reference value of SDL-age and normal limits of difference between SDL-age and chronological-age were elaborated in both genders.

C-reactive protein levels, airflow obstruction, and chronic kidney disease.

OBJECTIVES: There is some evidence that chronic obstructive pulmonary disease and chronic kidney disease (CKD) may be related, perhaps through systemic inflammation, which is common to both. However, this relationship has not yet been clearly demonstrated. The aim of this study was to investigate the association between airflow obstruction, CKD, and C-reactive protein (CRP) levels in Japanese men. METHODS: The study included 11,587 men, aged 40-88 years, who underwent a health check-up. Airflow obstruction was defined as a forced expiratory volume in 1 s/forced vital capacity of <70%, and its severity was based on the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD). CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). RESULTS: Airflow obstruction was present in 7.9% of the participants, and 10.6% of the participants had CKD. The average CRP levels were 0.11 ± 0.36, 0.13 ± 0.41, and 0.18 ± 0.41 mg/L for subjects with normal lung function, GOLD stage I, and GOLD stage II-IV, respectively. With regard to CKD, the average CRP levels were 0.11 ± 0.32 and 0.18 ± 0.6 mg/L for subjects without and with CKD, respectively. Analysis of covariance showed no significant differences between the CRP level and lung function status or CKD after age was adjusted for. Logistic regression analysis showed no association among subjects with the three different lung function statuses after age, body mass index, hypertension, diabetes, hyper-low-density-lipoprotein-cholesterolemia, smoking, physical activity, and alcohol intake were controlled for. CONCLUSIONS: Based on the results of this study, we conclude that there is no interrelationship between CRP level, airflow obstruction, and CKD.

Association between frequency of drinking alcohol and chronic kidney disease in men.

OBJECTIVES: Chronic kidney disease (CKD) is a major public health problem. Epidemiological studies of the relationship between alcohol intake and CKD are scarce in Japan. This cross-sectional study aims to investigate the relationship between frequency of drinking alcohol and CKD in Japanese men. METHODS: The subjects were 9,196 men (mean ± standard deviation age, 57.9 ± 5.1 years) who underwent a health check-up. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2). Frequency of alcohol drinking was obtained from questionnaire and divided into five categories: nondrinkers, once or twice a week, three or four times a week, five or six times a week, and everyday drinkers. RESULTS: Multivariable-adjusted [age, body mass index, hypertension, diabetes, hyper-low-density lipoprotein (LDL) cholesterolemia, smoking, and physical activity] odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Compared with the results for the nondrinkers, the multivariable-adjusted odds ratios of CKD were as follows: 0.76 (95% CI 0.60-0.95) for 1-2 drinks per week, 0.74 (95% CI 0.59-0.93) for 3-4 drinks per week, 0.79 (95% CI 0.64-0.97) for 5-6 drinks per week, and 0.60 (95% CI 0.51-0.71) for everyday drinkers. There was a significant inverse trend across increasing frequency of drinking alcohol (p = 0.001 for trend). CONCLUSIONS: An inverse association was found between frequency of drinking alcohol and CKD in apparently healthy men.

Twelve-year cumulative incidence of airflow obstruction among Japanese males.

BACKGROUND: To date, there is very limited longitudinal data on COPD and incidence estimates in Japan. The aim of this study was to investigate the 12-year cumulative incidence of airflow obstruction (COPD) in Japanese males. METHODS: This study included 913 male subjects, aged 30-76 years, who underwent lung function tests at a medical check-up in 1994 (baseline), 1999, and 2006. The study group consisted of 263 persistent never smokers, 296 early quitters, 117 late quitters, and 237 persistent smokers without airflow obstruction at baseline. The 12-year cumulative incidence of airflow obstruction was estimated. The spirometric criteria for diagnosis of airflow obstruction were forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of <0.7 and 5th percentile lower limit of normal (FEV(1)/FVC

A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers.

OBJECTIVES: Both genetic and lifestyle factors have been shown to influence bone mineral density (BMD). We investigated the correlations between BMD and low-density lipoprotein receptor-related protein 5 (LRP5) A1330V (rs3736228) polymorphism, exercise, smoking, and alcohol intake in Japanese male workers. METHODS: The subjects were 829 male employees (aged 20-59 years) of a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual-energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time, and genomic DNA was isolated from peripheral leukocytes. RESULTS: Mean ± standard deviation (SD) BMD was 0.557 ± 0.059 g/cm(2). The genotype frequencies of LRP5 gene polymorphism were 51, 42, and 7% for AA, AV, and VV, respectively. Analysis of variance and post hoc Tukey test indicated that mean BMD was significantly lower in subjects with VV genotype than in those with AA genotype (0.540 ± 0.048 versus 0.562 ± 0.062 g/cm(2)). According to multiple linear regression analysis, LRP5 A1330V polymorphism was an independent determinant of BMD, after adjusting for age, body mass index (BMI), and lifestyle variables. Exercise (past or current) also influenced BMD. CONCLUSIONS: These findings suggest that LRP5 A1330V polymorphism and exercise may influence BMD in Japanese male workers.