BACKGROUND: Although smoking rates have been declining worldwide, new types of tobacco products have been gradually spreading in recent years, especially in Japan, where heated tobacco products (HTPs) users are rapidly increasing. Oxidative stress caused by reactive oxygen species (ROS) is one of the causes of smoking-induced carcinogenesis, respiratory diseases, and cardiovascular diseases. However, information on the amount of ROS contained in mainstream smoke from HTPs is limited. In this study, we measured the amount of ROS generated from HTPs to evaluate the oxidative stress-related toxicity of HTPs. METHODS: IQOS ILUMA, glo hyper+, and Ploom X ADVANCED were used as the HTP devices. Mainstream smoke was collected from each HTP according to Health Canada Intense regime (smoke volume, 55 mL; smoke duration, 2 s). The collected ROS were reacted with 2,7'-dichlorodihydrofluorescein reagents, and the amount of ROS was calculated as H₂O₂ equivalent from the fluorescence intensity obtained. RESULTS: The ROS in the mainstream smoke from IQOS ILUMA, glo hyper+ (high-temperature mode), and Ploom X ADVANCED was found to be 48.8 ± 8.6, 86.6 ± 12.6, and 40.8 ± 5.7 nmol H₂O₂/stick, respectively (n = 6, mean ± standard deviation), with the highest being from glo hyper+ (high-temperature mode). The amount of ROS was significantly higher in the high-temperature mode of glo hyper+ than in the standard mode of glo hyper+. Additionally, the estimated amount of ROS from smoking 20 heated sticks per day (674-2160 nmol H₂O₂/day) was equivalent to 2.2-96 times the amount of daily exposure to ROS in the urban atmosphere (approximately 22-300 nmol H₂O₂/day). CONCLUSIONS We found that ROS is generated from HTPs of different devices. This study suggests that HTPs users may be exposed to much more ROS than they are exposed to in normal life.
Reactive Oxygen Species/analysis* ; Tobacco Products/analysis* ; Smoke/analysis* ; Hot Temperature ; Japan ; Oxidative Stress

BACKGROUND: In recent years, heated tobacco products (HTPs), which are widely used in Japan, have been sold by various brands using additives such as flavors. It has been reported that the components of mainstream smoke are different from those of conventional cigarettes. In this study, we established an analytical method for furans and pyridines in the mainstream smoke, which are characteristic of HTPs and particularly harmful among the generated components, and investigated the amount of component to which the smokers are exposed. METHODS: We established a simple analytical method for simultaneous analysis of gaseous and particulate compounds in the mainstream smoke of HTPs (IQOS, glo, ploom S) in Japan by combining a sorbent cartridge and glass fiber filter (Cambridge filter pad (CFP)). Both the sorbent cartridge and CFP were extracted using 2-propanol and analyzed via GC-MS/MS to determine the concentration of furans and pyridines generated from each HTP. RESULTS: The results showed that the levels of target furans such as furfural, 2-furanmethanol, 2(5H)-furanone, and 5-methylfurfural tended to be higher in the mainstream smoke of glo than in standard cigarettes (3R4F). Pyridine, which is generated at a high level in 3R4F as a combustion component, and 4-ethenylpyridine (EP), which is a known marker of environmental tobacco smoke, were detected. Among these components, 2-furanmethanol and pyridine are classified as Group 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer (IARC). Therefore, it is possible that they will contribute to the health effects caused by use of HTPs. CONCLUSIONS Using the new collection and analytical method for furans and pyridines in the mainstream smoke of HTPs, the level of each compound to which smokers are exposed could be clarified. By comprehensively combining information on the amount of ingredients and toxicity, it will be possible to perform a more detailed calculation of the health risks of using HTPs. In addition, the components detected in this study may be the causative substances of indoor pollution through exhaled smoke and sidestream smoke; therefore, environmental research on the chemicals generated from HTPs would be warranted in future studies.
Furans/analysis* ; Gas Chromatography-Mass Spectrometry ; Humans ; Japan ; Pyridines/analysis* ; Smoke/analysis* ; Tandem Mass Spectrometry ; Tobacco Products

PURPOSE: Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. MATERIALS AND METHODS: All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. RESULTS: Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P<0.001) whereas young age group (<50 years) had more IC lesion (84.5% vs. 47.6%, P<0.001). In multivariate analysis, seven variables including CS, male, old age, coronary heart disease, higher erythrocyte sedimentation rate, multiple lesions, and anterior lesion were independently associated with ECAS. In the propensity-score matched CS group had significant more EC lesion compared to non-CS group (65.7% vs. 47.9%) only in the old age subgroup. CONCLUSION: In contrast to a significant association between CS and severe symptomatic ECAS shown in old population, young patients did not show this association and showed relatively higher preference of ICAS.
Atherosclerosis ; Blood Sedimentation ; Cerebrovascular Circulation ; Constriction, Pathologic ; Coronary Disease ; Humans ; Intracranial Arteriosclerosis ; Logistic Models ; Male ; Multivariate Analysis ; Risk Factors ; Smoking ; Tobacco Products

BACKGROUND: Smokers with lung adenocarcinoma have a worse prognosis than those who have never smoked; the reasons for this are unclear. We aimed to elucidate the impact of smoking on patients’ prognosis and the association between smoking and clinicopathologic factors, particularly histologic subtypes. METHODS: We reviewed the records of 233 patients with pathologic stage T1-4N0-2M0 lung adenocarcinomas who underwent surgery between January 2004 and July 2015. The histologic subtypes of tumors were reassessed according to the 2015 World Health Organization classification. RESULTS: In total, 114 patients had a history of smoking. The overall survival probabilities differed between never-smokers and ever-smokers (80.8% and 65.1%, respectively; p=0.003). In multivariate analyses, the predominant histologic subtype was an independent poor prognostic factor. Smoking history and tumor size >3 cm were independent predictors of solid or micropapillary (SOL/MIP)-predominance in the logistic regression analysis. Smoking quantity (pack-years) in patients with SOL/MIP-predominant tumors was greater than in those with lepidic-predominant tumors (p=0.000). However, there was no significant difference in smoking quantity between patients with SOL/MIP-predominant tumors and those whose tumors had non-predominant SOL/MIP components (p=0.150). CONCLUSION: Smoking was found to be closely associated with SOL/MIP-predominance in lung adenocarcinoma. Greater smoking quantity was related to the presence of a SOL/MIP component.
Adenocarcinoma ; Classification ; Humans ; Logistic Models ; Lung Neoplasms ; Lung ; Multivariate Analysis ; Prognosis ; Smoke ; Smoking ; Tobacco Products ; World Health Organization

BACKGROUND: Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC). METHODS: We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking. RESULTS: The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05). CONCLUSIONS: The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.
Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; DNA ; DNA Damage ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Lymph Nodes ; Male ; Multivariate Analysis ; Risk Factors ; Smoke ; Smoking ; Tobacco Products

BACKGROUND: Cadmium is a toxic element in cigarette smoke associated with ischemic vascular disease. Its association with cerebral aneurysm is unknown. METHODS: We retrospectively analyzed the medical records of patients with headache who underwent imaging studies between March 2014 and August 2016. An unruptured intracranial aneurysm (UIA) was confirmed by brain magnetic resonance angiography or computed tomography angiography. A control group included age- and sex-matched patients without an UIA. Whole blood and random urine tests were used for detection of cadmium and arsenic levels, respectively. Student t-test was used to compare subject characteristics, mean cadmium and arsenic levels between groups, and differences between groups with small (<4-mm) and large (≥4-mm) UIAs. Multivariate regression analysis was used to identify risk factors for aneurysm incidence. RESULTS: Of 238 patients, 25 had an UIA. Those with an UIA had more pack-years of smoking (19.5±3.8 vs. 12.5±6.8, P=0.044) and higher mean serum cadmium levels (1.77±0.19 vs. 0.87±0.21 µg/L, P=0.027). Arsenic levels showed no difference between groups. (67.4±23.5 vs. 62.2±18.3 µg/L, P=0.458). There were no significantly different demographic, clinical, or laboratory characteristics between small and large aneurysm groups. According to multivariate analysis, smoking (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.06–2.33; P=0.047) and serum cadmium >2.0 mcg/L (OR, 1.39; 95% CI, 1.15–1.84; P=0.043) were associated with aneurysm incidence. CONCLUSION: UIA incidence was associated with pack-years of smoking and serum cadmium level, but aneurysm size was not associated with serum cadmium level.
Aneurysm ; Angiography ; Arsenic ; Brain ; Cadmium ; Headache ; Humans ; Incidence ; Intracranial Aneurysm ; Magnetic Resonance Angiography ; Medical Records ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Tobacco Products ; Vascular Diseases

OBJECTIVE: To assess clinical feasibility of low-attenuation cluster analysis in evaluation of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Subjects were 199 current and former cigarette smokers that underwent CT for quantification of COPD and had physiological measurements. Quantitative CT (QCT) measurements included low-attenuation area percent (LAA%) (voxels ≤ −950 Hounsfield unit [HU]), and two-dimensional (2D) and three-dimensional D values of cluster analysis at three different thresholds of CT value (−856, −910, and −950 HU). Correlation coefficients between QCT measurements and physiological indices were calculated. Multivariable analyses for percentage of predicted forced expiratory volume at one second (%FEV1) was performed including sex, age, body mass index, LAA%, and D value had the highest correlation coefficient with %FEV1 as independent variables. These analyses were conducted in subjects including those with mild COPD (global initiative of chronic obstructive lung disease stage = 0–II). RESULTS: LAA% had a higher correlation coefficient (-0.549, p < 0.001) with %FEV1 than D values in subjects while 2D D−910HU (−0.350, p < 0.001) revealed slightly higher correlation coefficient than LAA% (−0.343, p < 0.001) in subjects with mild COPD. Multivariable analyses revealed that LAA% and 2D D value−910HU were significant independent predictors of %FEV1 in subjects and that only 2D D value−910HU revealed a marginal p value (0.05) among independent variables in subjects with mild COPD. CONCLUSION: Low-attenuation cluster analysis provides incremental information regarding physiologic severity of COPD, independent of LAA%, especially with mild COPD.
Body Mass Index ; Cluster Analysis ; Forced Expiratory Volume ; Pulmonary Disease, Chronic Obstructive ; Tobacco Products

BACKGROUND: The ammonia contained in tobacco fillers and mainstream and sidestream cigarette smoke accelerates nicotine dependence in cigarette smokers. Ammonia has been included in the non-exhaustive priority list of 39 tobacco components and emissions of cigarette published by the World Health Organization (WHO) Study Group on Tobacco Product Regulation. The development of a simple ammonia detection method will contribute to the establishment of tobacco product regulation under tobacco control policies and allow surveys to be conducted, even by laboratories with small research budgets. METHODS: We developed a simple colorimetric method based on the salicylate-chlorine reaction and absorption spectrometry with two reagents (sodium nitroprusside and sodium dichloroisocyanurate). To compare this method to conventional ion chromatography, we analyzed the ammonia levels in tobacco fillers extracted from 35 Japanese commercially marketed cigarette brands manufactured by four tobacco companies (Japan Tobacco (JT) Inc., British American Tobacco (BAT), Philip Morris Japan, and Natural American Spirit). We also analyzed the ammonia levels in the sidestream smoke from cigarettes of the brands that were found to contain high or low tobacco filler ammonia levels. RESULTS: The ammonia levels in the reference cigarette (3R4F) measured by our method and ion chromatography were similar and comparable to previously reported levels. The ammonia levels in tobacco fillers extracted from 35 cigarette brands ranged from 0.25 to 1.58 mg/g. The mean ammonia level of JT cigarette brands was significantly higher (0.83 ± 0.28 mg/g) than that of Natural American Spirit cigarette brands (0.30 ± 0.08 mg/g) and lower than those in the other two cigarette brands (1.11 ± 0.19 mg/g for BAT and 1.24 ± 0.15 mg/g for Philip Morris) (p < 0.001 by Bonferroni test). The ammonia levels in the sidestream smoke of CABIN, Marlboro Black Menthol, American Spirit Light, and Seven Stars were 5.89 ± 0.28, 5.23 ± 0.12, 6.92 ± 0.56, and 4.14 ± 0.19 mg/cigarette, respectively. The ammonia levels were higher in sidestream smoke than in tobacco filler. CONCLUSIONS Our simple colorimetric could be used to analyze ammonia in tobacco fillers and sidestream smoke. There were significant differences between the ammonia levels of the 35 commercially marketed cigarette brands in Japan manufactured by four tobacco manufacturers. Over 90% of the ammonia in sidestream smoke was in gaseous phase.
Ammonia ; analysis ; Colorimetry ; methods ; Japan ; Smoke ; analysis ; Spectrophotometry ; methods ; Tobacco ; chemistry ; Tobacco Products ; analysis

OBJECTIVE: The effect of transdermal nicotine patch on sleep physiology is not well established. The current study aimed to examine the influence of nicotine patch on homeostatic sleep propensity and autonomic nervous system. METHODS: We studied 16 non-smoking young healthy volunteers with nocturnal polysomnography in a double blind crossover design between sleep with and without nicotine patch. We compared the sleep variables, sleep EEG power spectra, and heart rate variability. RESULTS: The night with nicotine patch showed significant increase in sleep latency, wake after sleep onset, and stage 1 sleep; and decrease in total sleep time, sleep efficiency, and percentage of REM sleep. Also, spectral analysis of the sleep EEG in the night with nicotine patch revealed decreased slow wave activity in stage 2 and REM sleep and increased alpha activity in the first NREM-REM sleep cycle. Heart rate variability showed no differences between the 2 nights, but the low to high ratio (a parameter indicative of sympathetic nervous system activity) positively correlated with wake after sleep onset in night with nicotine patch. CONCLUSION: Transdermal nicotine patch significantly disrupts sleep continuity, sleep architecture, and homeostatic sleep propensity. The overactivation of the sympathetic nervous system may be responsible for these changes.
Adult* ; Autonomic Nervous System ; Cross-Over Studies ; Electroencephalography* ; Healthy Volunteers ; Heart Rate* ; Heart* ; Humans ; Male* ; Nicotine* ; Physiology ; Polysomnography ; Sleep, REM ; Spectrum Analysis ; Sympathetic Nervous System ; Tobacco Use Cessation Products*

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects