Factors affecting exposure to nicotine and carbon monoxide in adult cigarette smokers.

Exposure to cigarette smoke among smokers is highly variable. This variability has been attributed to differences in smoking behavior as measured by smoking topography, as well as other behavioral and subjective aspects of smoking. The objective of this study was to determine the factors affecting smoke exposure as estimated by biomarkers of exposure to nicotine and carbon monoxide (CO). In a multi-center cross-sectional study of 3585 adult smokers and 1077 adult nonsmokers, exposure to nicotine and CO was estimated by 24h urinary excretion of nicotine and five of its metabolites and by blood carboxyhemoglobin, respectively. Number of cigarettes smoked per day (CPD) was determined from cigarette butts returned. Puffing parameters were determined through a CreSS® micro device and a 182-item adult smoker questionnaire (ASQ) was administered. The relationship between exposure and demographic factors, smoking machine measured tar yield and CPD was examined in a statistical model (Model A). Topography parameters were added to this model (Model B) which was further expanded (Model C) by adding selected questions from the ASQ identified by a data reduction process. In all the models, CPD was the most important and highest ranking factor determining daily exposure. Other statistically significant factors were number of years smoked, questions related to morning smoking, topography and tar yield categories. In conclusion, the models investigated in this analysis, explain about 30-40% of variability in exposure to nicotine and CO.

Adaptive regression modeling of biomarkers of potential harm in a population of U.S. adult cigarette smokers and nonsmokers.

BACKGROUND: This article describes the data mining analysis of a clinical exposure study of 3585 adult smokers and 1077 nonsmokers. The analysis focused on developing models for four biomarkers of potential harm (BOPH): white blood cell count (WBC), 24 h urine 8-epi-prostaglandin F2alpha (EPI8), 24 h urine 11-dehydro-thromboxane B2 (DEH11), and high-density lipoprotein cholesterol (HDL). METHODS: Random Forest was used for initial variable selection and Multivariate Adaptive Regression Spline was used for developing the final statistical models RESULTS: The analysis resulted in the generation of models that predict each of the BOPH as function of selected variables from the smokers and nonsmokers. The statistically significant variables in the models were: platelet count, hemoglobin, C-reactive protein, triglycerides, race and biomarkers of exposure to cigarette smoke for WBC (R-squared = 0.29); creatinine clearance, liver enzymes, weight, vitamin use and biomarkers of exposure for EPI8 (R-squared = 0.41); creatinine clearance, urine creatinine excretion, liver enzymes, use of Non-steroidal antiinflammatory drugs, vitamins and biomarkers of exposure for DEH11 (R-squared = 0.29); and triglycerides, weight, age, sex, alcohol consumption and biomarkers of exposure for HDL (R-squared = 0.39). CONCLUSIONS: Levels of WBC, EPI8, DEH11 and HDL were statistically associated with biomarkers of exposure to cigarette smoking and demographics and life style factors. All of the predictors together explain 29%-41% of the variability in the BOPH.

Evaluation of biomarkers of exposure in adult cigarette smokers using Marlboro snus.

INTRODUCTION: It has been reported that adult smokers (AS) may be considering smokeless tobacco products as an alternative to smoking. The objective of this study was to evaluate the change in exposure in AS using Marlboro snus (MSNUS) (a tobacco pouch product in test market in June 2007). METHODS: AS were randomized into the following groups--CS: subjects (n = 30) continue smoking their own brand; DU: subjects (n = 60) reduced their daily cigarette consumption by >or=50% and were allowed to use MSNUS; SN: subjects (n = 15) stopped smoking their cigarettes but were allowed to use MSNUS; NT: subjects (n = 15) were not allowed to use any tobacco products for the entire duration of the 8-day study. Biomarkers of smoke exposure (BOE) measured at baseline and postbaseline were 24-hr urinary excretion of metabolites of N-nitrosamines, nicotine (urine and plasma), aromatic amines, benzene, and polycyclic aromatic hydrocarbon; urine mutagenicity; and carboxyhemoglobin at various timepoints. RESULTS: Statistically significant (p < .05) reductions in all the urinary BOE were observed in the DU group compared with the CS group. After correcting for the residual effect, a proportionate reduction (approximately 50%) in most of the biomarkers was observed. Even larger reductions, similar to the NT group, were observed in the SN group. DISCUSSION: The proportionate reduction in exposure when reducing the number of cigarettes by 50% and using MSNUS, under the consumption patterns observed, suggest that the AS did not appear to alter their smoking behavior. The added exposure from MSNUS usage in this group was minimal. The AS sustained substantial reductions in exposure when using MSNUS exclusively.

Short term effects of reduced exposure to cigarette smoke on white blood cells, platelets and red blood cells in adult cigarette smokers.

UNLABELLED: Previous studies indicate that cigarette smokers have a 5-30% higher white blood cell counts (WBC) compared to non-smokers and higher red blood cell counts. METHODS: This study was to pool hematology data from three similar studies and analyze the data for effects on WBC, its subpopulations, platelets, red blood cell count (RBC) and hematocrit in adult cigarette smokers three days after using an electrically heated cigarette smoking system (EHCSS) as a potential reduced exposure product (PREP) or no-smoking compared to smoking a conventional cigarette. RESULTS: Lower exposure to cigarette smoke in adult, long term smokers, by using an EHCSS or stopping smoking, leads to statistically significant decreases of up to 9% in WBC, neutrophils, lymphocytes, platelets, RBC and hematocrit within three days. Switching from CC-smoking to EHCSS-smoking or no-smoking resulted in lower WBC and vice versa within 3 days. CONCLUSION: This clinical model may be used as a screening tool to find new technologies that could provide insights on changes in inflammation resulting from the change in cigarette smoke.

The effect of menthol containing cigarettes on adult smokers' exposure to nicotine and carbon monoxide.

UNLABELLED: There is limited information comparing biomarkers of exposure (BOE) to cigarette smoke in menthol (MS) and non-menthol cigarette smokers (NMS). OBJECTIVE: To compare BOE to nicotine and carbon monoxide in MS and NMS. METHODS: Cross-sectional, observational, ambulatory, multi-centre study in 3341 adult cigarette smokers. Nicotine equivalents (NE) in 24h urine, NE/cigarette, COHb and serum cotinine were measured. Statistical analyses included analysis of variance and Wilcoxon test. RESULTS: Analyses of variance revealed no statistically significant effects of mentholated cigarettes on NE/24h, COHb, serum cotinine and NE/cigarette. On average MS smoked 15.0 and NMS 16.8 cigarettes/day. The unadjusted mean differences were as follows: MS had lower NE/24h (5.4%) and COHb (3.2%), higher serum cotinine (3.0%) and NE/cigarette (5.7%) than NMS. African-Americans MS smoked 40% fewer cigarettes, showed lower NE/24h (24%) and COHb (10%) and higher NE/cig (29%) and serum cotinine (8%) levels than their White counterparts. CONCLUSIONS: Smoking mentholated cigarettes does not increase daily exposure to smoke constituents as measured by NE and COHb. These findings are consistent with the majority of epidemiological studies indicating no difference in smoking related risks between MS and NMS.

Population estimates for biomarkers of exposure to cigarette smoke in adult U.S. cigarette smokers.

INTRODUCTION: There are about 4,800 different chemical constituents in cigarette smoke. Therefore, the total systemic exposure evaluation of the population of smokers to cigarette smoke is challenging. Measurement of biomarkers as surrogates of cigarette smoke constituents is a realistic approach to assess exposure. OBJECTIVE: To estimate cigarette smoke exposure of the U.S. smoker population. METHODS: Stratified, cross-sectional, multicenter design (39 sites in 31 states); 3,585 adult cigarette smokers and 1,077 nonsmokers. Biomarkers were determined from 24-hr urine collections or blood samples. Population estimates were generated by weighting sample data with weights from a large U.S. probability sample (Behavioral Risk Factor Surveillance System). RESULTS: The adult smoker population estimates for tobacco-specific biomarkers were nicotine equivalents 13.3 mg/24 hr (SE 0.14), serum cotinine 184 ng/ml (1.8), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol 439 ng/24 hr (5.5). The population estimates for smokers and nonsmokers for nontobacco-specific biomarkers were 1-hydroxypyrene 317 (6.8) and 110 (7.1) ng/24 hr, 4-aminobiphenyl Hb adducts 43.1 (1.04) and 11.4 (1.5) pg/g Hb, carboxyhemoglobin 5.26(0.04) in percent of hemoglobin saturation and 1.45(0.02), 3-hydroxypropylmercapturic acid 2,030 (24) and 458 (17) microg/24 hr, monohydroxy-butenyl-mercapturic acid 3.61 (0.1) and 0.30 (0.02) microg/24 hr, and dihydroxy-butyl-mercapturic acid 556 (4.9) and 391 (5.5) microg/24 hr. On average, young adult smokers had lower exposure than older smokers; female smokers had lower exposure than males, and Black smokers had lower exposure than Whites. DISCUSSION: This study estimated the population exposure to cigarette smoke constituents in adult U.S. smokers and identified significant differences between subpopulations. The data may serve as a reference for monitoring the impact of changes in cigarette consumption and the introduction of potentially reduced exposure cigarettes.

Heart rate variability increases with reductions in cigarette smoke exposure after 3 days.

BACKGROUND: Smoking has been shown to influence the tone of the autonomic nervous system as reflected by heart rate variability (HRV). To date, no information is available as to whether 24-hour HRV might differentiate users of different tobacco products. OBJECTIVE: To assess the differences in HRV derived from the 24-hour electrocardiogram (ECG) following the use of 2 tobacco products of potentially different exposures. METHODS: Thirty adult Caucasian male smokers (mean age: 42.8 + 5.7 years) smoking 20 to 40 cigarettes/ day were randomized in a 3-way crossover study design to either smoke a conventional cigarette (CC, tar: 11 mg, Nic: 0.8 mg), to use the Electrically Heated Cigarette Smoking System (EHCSS: tar: 5 mg, Nic: 0.3 mg, according to the Federal Trade Commission [FTC]), or to stop smoking (NS) for 3 days each. The 24 hours ECGs were recorded during the last 24 hours of each exposure period. RESULTS: A 24-hour ECG showed highest mean values for standard deviation of all normal-to-normal heart beat (NN) intervals (SDNN), standard deviation of all 5-minute averaged NN intervals in a 24-hour period (SDANN), mean of the standard deviations of the NN intervals calculated from all 5-minute segments in a 24-hour period (SDNNI), percentage (P) of all NN intervals that differ by 50 milliseconds of all NN (PNN50%), the square root of the mean of all squared differences between adjacent NN intervals in 24-hour period (RMSSD), and total number of all NN intervals divided by the height of the histogram of all NN intervals measured on a discrete scale with bins of 7 x 8125 ms (1/128 seconds; HRVTI) when participants stopped smoking followed by the use of the reduced exposure product and CC. CONCLUSION: Heart rate variability tended to increase with reduced smoke exposure.

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US.

UNLABELLED: Comprehensive data on human exposure to smoke constituents from different machine-measured tar yield cigarettes is limited. METHODS: This study used a stratified, cross-sectional, multi-center design to estimate biomarkers of exposure (BOE) from nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, acrolein, and 1,3-butadiene and their relationship to tar yield categories of cigarette in adult smokers in the U.S. 3625 adults smokers were enrolled into four tar categories < or =2.9 mg (T1), 3.0-6.9 mg (T2), 7.0-12.9 mg (T3), and > or =13.0mg (T4). Biomarkers were measured in blood (carboxyhemoglobin, 4-aminobiphenyl-hemoglobin (4-ABP-Hb)-adducts, serum cotinine) and 24h urine (nicotine and five metabolites, calculated as nicotine equivalents (NE), NNAL, 1-OH-pyrene, 3-HPMA, MHBMA and DHBMA). Data were analyzed using analysis of covariance (ANCOVA). RESULTS: Tar was a significant factor for most biomarkers in the ANCOVA models. The largest least square mean differences between tar categories was 35% for NE per day, 28% for NE per cigarette, 36% for serum cotinine, 42% for NNAL per day, 29% for NNAL per cigarette, 26% for 1-OHP, 24% for COHb, 14% for 3-HPMA and 40% for 4-ABP-Hb. Variability in BOE ranged from 41% to 154% CV. CONCLUSIONS: There was a statistically significant effect of machine-measured tar yield on most BOE, which were generally lower with lower tar yield.

A 12-month, randomized, controlled study to evaluate exposure and cardiovascular risk factors in adult smokers switching from conventional cigarettes to a second-generation electrically heated cigarette smoking system.

This randomized, controlled, forced-switching, open-label, parallel-group study in 97 adult male and female smokers of conventional cigarettes evaluated biomarkers of tobacco smoke exposure and cardiovascular risk factors. After baseline measurements, smokers were either switched to a second-generation electrically heated cigarette smoking system (EHCSS) or continued smoking conventional cigarettes for 12 months. Biomarkers of exposure and cardiovascular risk factors were measured at 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 months. There was a rapid and sustained reduction in all biomarkers of exposure after switching to the EHCSS, with statistically significant reductions from baseline in nicotine equivalents (-18%), plasma cotinine (-16%), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (-73%), total 1-hydroxypyrene (-53%), urine mutagenicity (-52%), 4-aminobiphenyl hemoglobin adducts (-43%), carboxyhemoglobin AUC7-23 h (-80%), and 3-hydroxypropylmercapturic acid (-35%). These reductions in exposure in the EHCSS group were associated with statistically significant and pathophysiologically favorable changes in several cardiovascular risk factors, including white blood cell count (-0.78 x 10(3)/microL), hemoglobin (-0.16 g/dL), hematocrit (-0.44%), urine 11-dehydrothromboxane B2 (-374 ng/24 h), and high-density lipoprotein cholesterol (+5 mg/dL).

Environmental tobacco smoke (ETS) evaluation of a third-generation electrically heated cigarette smoking system (EHCSS).

This sub-study of a randomized, controlled, forced-switching, open-label, parallel-group, clinical study compared environmental tobacco smoke (ETS) produced when 60 male and female adult smokers switched to a third-generation electrically heated cigarette smoking system (EHCSS), continued to smoke a conventional cigarette (CC), or stopped smoking (No-smoking). Concentrations of air constituents including respirable suspended particulate (RSP), carbon monoxide (CO), ammonia and total volatile organic compounds (TVOCs) and ETS markers including solanesol-related particulate matter (Sol-PM), ultraviolet absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and 3-ethenyl pyridine (3-EP) were measured in a ventilated, furnished conference room over a 2-h period on separate occasions for each smoking condition. When the EHCSS was used, concentrations of CO and most ETS markers were in the same range as during no-smoking. Concentrations of ammonia were reduced by 41% and concentrations of other selected constituents of ETS were reduced by 87-99% in the air of a room in which EHCSS cigarettes were smoked as compared to concentrations in the same room when conventional cigarettes were smoked. Switching from conventional cigarette smoking to the EHCSS resulted in substantial reductions in concentrations of several markers of environmental tobacco smoke.

Short-term clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 100 male and female adult smokers evaluated 12 biomarkers of tobacco smoke exposure. We measured exposure to the following smoke constituents: nicotine, pyrene, tobacco-specific nitrosamines, three aromatic amines, carbon monoxide, benzene, acrolein, crotonaldehyde, and 1,3-butadiene. After baseline exposure determination, adult smokers of a conventional cigarette (CC) were switched to an electrically heated cigarette smoking system (EHCSS, Series K), continued smoking the CC, or stopped smoking (No-smoking) for 8 days in a controlled, confined, clinical setting. In the EHCSS group, the mean decrease from Baseline to Day 8 in the biomarkers of exposure ranged from 16% to 77% at Day 8 compared to Baseline. After adjusting for the residual effect (carryover effects due to long elimination half-life and non-tobacco confounding sources of exposure), the mean percent decrease from Baseline for all 12 biomarkers ranged from 47% to 90%. In conclusion, switching for 8 days from a conventional cigarette to the EHCSS substantially reduced exposure of adult smokers to several constituents of both the particulate and gas phases of cigarette smoke.

12-week clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 90 male and female adult smokers evaluated six biomarkers of tobacco smoke exposure over a 12-week period of unrestricted smoking in the participants' normal life setting. Baseline biomarker levels were measured, then participants were randomly assigned to switch to an electrically heated cigarette smoking system (EHCSS, Series K) or to continue smoking a conventional cigarette (CC) of similar tar yield (Federal Trade Commission method) for 12 weeks. Compared to Baseline, adult smokers who switched to the EHCSS for 12 weeks in their normal life setting had significantly reduced nicotine equivalents (-33%), total NNAL (a biomarker for NNK, -63%), 1-OHP (a surrogate biomarker for polycyclic aromatic hydrocarbons, -38%), carboxyhemoglobin (a biomarker for carbon monoxide, -23%), 3-HPMA (a biomarker for acrolein, -25%) and S-PMA (a biomarker for benzene, -49%), whereas exposure was stable in the CC control group.

Short-term clinical exposure evaluation of a second-generation electrically heated cigarette smoking system.

This randomized, controlled, forced-switching, open-label, parallel-group study in 100 adult male and female smokers of conventional cigarettes evaluated 8 biomarkers of tobacco smoke exposure. After baseline exposure determinations, adult smokers were switched to a second-generation electrically heated cigarette smoking system (EHCSS) for 8 days in a clinical setting. After 8 days of smoking the EHCSS biomarkers of exposure decreased by 43% to 85% compared to baseline. After correction for residual effects (carryover effects due to long elimination half-life and non-tobacco-confounding sources of exposure), reductions in exposure ranged from 59% to 97%. Results from this short-term clinical exposure study indicate that switching from a conventional cigarette to a second-generation electrically heated cigarette smoking system substantially reduced the exposure to several measured potentially harmful constituents of tobacco smoke.

Respiratory retention of nicotine and urinary excretion of nicotine and its five major metabolites in adult male smokers.

Urinary excretion of nicotine and its five major metabolites (nicotine-N-glucuronide, cotinine, cotinine-N-glucuronide, trans-3'-hydroxycotinine, and trans-3'-hydroxycotinine-O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the relationship between nicotine retention from smoking and urinary excretion of NE in adult smokers. After a 4-day washout period, 16 adult male smokers smoked 6 cigarettes per day for four consecutive days according to three predefined smoking patterns: no inhalation (Pattern A), normal inhalation (Pattern B), and deep inhalation (Pattern C). The amount of nicotine retained in the respiratory tract during smoking was estimated from the difference between the amounts of nicotine delivered and exhaled. The daily excretion of urinary NE was measured in 24h urine samples by LC-MS/MS. The mean (+/-S.D.) amount of nicotine retained was 0.126+/-0.167, 0.960+/-0.214, and 1.070+/-0.223mg/cig for Patterns A, B, and C, respectively. The mean (+/-S.D.) relative retention (the amount retained relative to the amount delivered) was 11.2+/-14.7%, 98.0+/-1.6%, and 99.6+/-0.3% for Patterns A, B, and C, respectively. On the fourth day of smoking, an average of 86+/-20% of the total daily amount of retained nicotine was recovered as NE in 24h urine. Nicotine equivalents was treated as a single component and the data was described by a first-order elimination pharmacokinetic model which assumed instantaneous input and distribution. Based on this model, the elimination half-life of NE was 19.4+/-2.6h, and the NE excretion had reached approximately 96% of the steady state levels by Day 4. Our results suggest that most of the nicotine inhaled from a cigarette is retained (> or =98%) in the lung, and at steady state, daily urine NE excretion reflects approximately 90% of the retained nicotine dose from cigarette smoking.

Effects of levels of cigarette smoke exposure on symptom-limited spiroergometry.

Previous investigations demonstrated reduced exposure to selected cigarette smoke constituents in adult smokers switching from conventional cigarettes (CC) to an electrically heated cigarette smoking system (EHCSS). This study investigated whether reduced exposure and no smoking (NS) would improve exercise performance. In a 3-period crossover study, 18 male adult smokers (age, 43.6+/-5.3 years) of CC were randomized to smoke CC (tar, 11 mg; nicotine, 0.8 mg; carbon monoxide, 11 mg), to use EHCSS (tar, 3 mg; nicotine, 0.2 mg; carbon monoxide, 0.4 mg [Federal Trade Commission method]), or to NS for 3 days before performing symptom-limited spiroergometry. NS and EHCSS vs CC resulted in less severe dyspnea (NS, 44.4% [P<.01 vs CC;] EHCSS, 50% [P=.03 vs CC;] CC, 88.9%), higher working capacity (NS, 2.92+/-0.4 W/kg [P=.06 vs CC;] ECHSS, 2.92+/-0.4 W/kg [P=.04 vs CC;] CC, 2.86+/-0.5 W/kg), higher peak oxygen uptake (NS, 2694+/-466 mL O(2)/min [P=.08 vs CC;] EHCSS, 2830+/-606 mL O(2)/min [P=.03 vs CC;] CC, 2682+/-492 mL O(2)/min), higher anaerobic threshold (NS, 1324+/-306 mL O(2)/min; EHCSS, 1396+/-312 mL O(2)/min [P=.03 vs CC;] CC, 1315+/-290 mL O(2)/min), and higher maximum rate-pressure product (NS, 30.1+/-2.7 x 10(3) mm Hg/min; EHCSS, 2.8 x 10(3) mm Hg/min [P<.01 vs CC;] CC, 30.7+/-29.2+/-3.6 x 10(3) mm Hg/min) indicating that reduced exposure from tobacco smoke and NS for 3 days may improve cardiovascular function as detected by symptom-limited spiroergometry.

A new method for estimating the retention of selected smoke constituents in the respiratory tract of smokers during cigarette smoking.

This report describes a new method for estimating the retention of selected mainstream smoke constituents in the respiratory tract of adult smokers during cigarette smoking. Both particulate-phase (PP) constituents including nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonornicotine (NNN), two tobacco-specific nitrosamines (TSNA), and gas-vapor-phase (GVP) constituents including carbon monoxide (CO), isoprene (IP), acetaldehyde (AA), and ethylene, were studied. To estimate the amounts of smoke constituents delivered during smoking, we used predetermined linear relationships between the measured cigarette filter solanesol content and machine-generated mainstream deliveries of these selected compounds. To determine the amounts of smoke constituents exhaled, the expired breath was directed through a Cambridge filter pad (CFP) attached to an infrared spectrometer. PP compounds were trapped on the CFP for later analysis and GVP compounds were analyzed in near real time. The smokers' respiratory parameters during smoking, such as inhalation/exhalation volume and time, were monitored using LifeShirt(R), a respiratory inductive plethysmography (RIP) device. The retention of each smoke constituent, expressed as a percentage, was then calculated as the difference between the amount delivered (estimated) and the amount exhaled relative to the amount delivered. We studied 16 adult male smokers who smoked cigarettes according to 3 predefined smoking patterns: no inhalation (pattern A), normal inhalation (pattern B), and deep inhalation (pattern C). For the three PP constituents, the mean retentions for pattern A ranged between 10 and 20%; and while the mean retentions of the two TSNAs were significantly higher for pattern C (84% for NNK and 97% for NNN) than those for pattern B (63% for NNK and 84% for NNN), the mean retentions of nicotine were basically the same between patterns B and C, which were both greater than 98%. For the GVP constituents, the retentions were similar between pattern B and pattern C, although different constituents were retained to different degrees (average values of 33%, 52%, 79%, and 99% for ethylene, IP, CO, and AA, respectively). The differences in the retention between different constituents could be interpreted in terms of each constituent's physical properties such as volatility and solubility. In conclusion, the method described is suitable for studying the retention of selected mainstream smoke constituents in the respiratory tract of smokers.

Short-term exposure evaluation of adult smokers switching from conventional to first-generation electrically heated cigarettes during controlled smoking.

This randomized, controlled study in 110 male and female adult smokers evaluated biomarkers of tobacco smoke exposure (carbon monoxide [CO], carboxyhemoglobin [CO-Hb], nicotine, urine mutagenicity) under controlled smoking conditions when adult smokers of 1 conventional cigarette brand (CC1) were switched to an electrically heated cigarette smoking system (EHCSS) or a low-tar conventional cigarette (CC2). Baseline exposure was determined while all subjects smoked CC1. Subjects then were stratified for gender and cigarette consumption and randomized to 1 of 5 groups-EHCSS1, EHCSS2, CC1, CC2, or no smoking-and monitored for 8 days. Compared to baseline, biomarkers of exposure on day 8 decreased 53% to 93% (P < .0001) for EHCSS groups and 18% to 39% (P < .02) for CC2. Environmental tobacco smoke arising from the smoking activities of the different study groups was measured in the air of a separate smoking room over 1-hour periods. Concentrations of respirable suspended particulates in both EHCSS groups were about 90% lower than in the CC1 and CC2 groups, similar to the 95% reduction in the no-smoking group. CO was undetectable in the EHCSS and no-smoking groups. Results from this short-term clinical study indicate that switching from a conventional cigarette to a first-generation EHCSS reduces the generation of environmental tobacco smoke and can reduce the exposure to the measured, potentially harmful constituents in tobacco smoke if smokers do not compensate by numbers of cigarettes. The study design was found to be suitable for the evaluation of the exposure of adult smokers to the measured smoke constituents and to allow the differentiation of different cigarette designs.

Variability of peripheral arterial tonometry in the measurement of endothelial function in healthy men.

Measurement of endothelial function using peripheral arterial tonometry (PAT) has been reported to be significantly correlated with coronary blood flow. Repetitive PAT measurements were performed in 22 healthy male subjects at test intervals of 1 hour (5 times within a day) and 0.5 hours (7 times within a day) to evaluate the variability of the reactive hyperemia index (RHI). A total of 10 subjects underwent additional repetitive PAT at 2 hour intervals (7 times within a day) for 3 consecutive days to evaluate the diurnal effects and day-to-day reproducibility. The RHI from each test was computed automatically based on a 15 minute recording of pulse wave amplitude changes of the fingers in response to reactive hyperemia induced by a 5 minute occlusion of the brachial artery. Intrasubject variability of RHI at different test intervals, defined as the coefficient of variation (CV) was 15.3% +/- 5.3%, 16.1%+/- 7.8%, and 22.6% +/- 3.9% for the tests at 0.5 hour, 1 hour, and 2 hour intervals, respectively. Reactive hyperemia indices measured at the same time points on each of the 3 days were not statistically significant. The interday reproducibility, presented as intraclass correlation coefficients (ICC) ranged from - 0.07 to 0.47. We conclude that repetitive PAT measurements have no carryover effect on RHI at 1 hour, and 2 hour intervals, and the RHI measured at 0.5 hour intervals is associated with a trend of increase. The interday reproducibility is relatively low and the intrasubject variability of RHI is similar to those observed in studies of flow-mediated dilation using brachial artery ultrasound scanning.

The effect of cigarette burn time on exposure to nicotine and carbon monoxide in adult smokers.

Cigarette burn time (CBT), conventionally defined as the time a cigarette burns during smoking, can be affected by cigarette design and smoking behavior. A previous study showed a strong negative correlation between CBT and nicotine yield under machine smoking conditions. This study for the first time examined the relationship of CBT and exposure to nicotine and carbon monoxide in adult smokers in a controlled clinical study. 24h nicotine equivalents excretion (NE), carboxyhemoglobin (COHb) and CBT were measured in two groups of 20 adults smoking Marlboro Lights and 20 adults smoking Marlboro Ultra on two consecutive days. Approximately 20% of the total variability in CBT was attributed to cigarette brand, 34% to smokers and 1% to study day. The exposure index, defined as the number of cigarettes smoked per day divided by average daily CBT for each smoker, accounted for a large proportion of the total variability in NE (R(2)=0.79-0.91) and COHb (R(2)=0.85-0.90). We conclude that CBT has an important influence on levels of NE and COHb in adult smokers. CBT, along with the number of cigarettes smoked per day, can be used to estimate adult smokers' exposure to nicotine and carbon monoxide.

CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin adduct levels in smokers and non-smokers.

Some aromatic amines are considered to be putative bladder carcinogens. Hemoglobin (Hb) adducts of 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP) have been used as biomarkers of exposure to aromatic amines from cigarette smoke. One of the goals of this study was to determine intra- and inter-individual variability in 3-ABP and 4-ABP Hb adducts and to explore the predictability of ABP Hb adduct levels based on caffeine phenotyping. The study was conducted in adult smokers (S, n = 65) and non-smokers (NS, n = 65). The subjects were phenotyped for CYP1A2 and NAT2 using urinary caffeine metabolites. Blood samples were collected twice within 6 weeks and adducts measured by GC/MS. The levels of 4-ABP Hb adducts were significantly (p < 0.0001) greater in S (34.5 +/- 21.06 pg/g Hb) compared to NS (6.3 +/- 3.02 pg/g Hb). The levels of 3-ABP Hb adducts were below the limit of quantification (BLOQ) in most (82%) of the NS and about 10-fold lower in S (3.6 +/- 3.29 pg/g Hb) compared to 4-ABP Hb adducts. No differences were observed in the adduct levels between weeks 1 and 6 in the smokers, suggesting that a single sample would be adequate to monitor cigarette smoke exposure. The regression model developed with CYP1A2, NAT2 phenotype and number of cigarettes smoked (NCIG) accounted for 47% of the variability in 3-ABP adducts, whereas 32% variability in 4-ABP adducts was accounted by CYP1A2 and NCIG. The ratio of 4-ABP Hb adducts in adult S:NS was approximately 5:1, whereas 3-ABP Hb adducts levels were BLOQ in some S, exhibited large interindividual variability ( approximately 91% compared to 57% for 4-ABP Hb) and poor dose response relationship. Therefore, 4-ABP Hb adduct levels may be a more useful biomarker of aminobiphenyl exposure from cigarette smoke.