Bartosz Koszowski

Elimination kinetics of the tobacco-specific biomarker and lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is tobacco specific and has a longer half-life than other tobacco biomarkers studied thus far. An accurate measurement of the NNAL half-life is important for optimal use to assess exposure to tobacco smoke. We determined the half-life of NNAL in urine in eight daily smokers on a clinical research ward and in five occasional smokers in a real-life environment. Total NNAL in urine was monitored for 14 days in daily smokers after stopping smoking and for up to 60 days in occasional smokers. The average half-life for the terminal phase in the daily smoker group using a two-compartmental body model was 10.3 days (beta phase), and using a noncompartmental model, it was 9.1 days. In the occasional group, these values were 17.6 and 16.0 days, respectively. The alpha-phase half-lives were 14.3 and 27.8 hours for the two groups, respectively. The inter-subject coefficient of variation of the NNAL terminal half-life ranged from 14% to 30%, and the intra-subject coefficient of variation ranged from 3% to 18%. There was very good agreement between the plasma and urinary half-lives in two subjects with plasma analyses: 7.4 versus 7.9 days and 9.2 versus 10.7 days. Mean renal clearance of NNAL was 13 ± 2.3 mL/min. The terminal half-life of NNAL of 10 to 18 days indicates that this biomarker can be used to detect tobacco smoke exposure for 6 to 12 weeks after cessation of exposure and requires a similar time to assess the steady levels of NNAL after switching from one tobacco product to another. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3421–5)

Comparison of urine cotinine and the tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and their ratio to discriminate active from passive smoking.

OBJECTIVES Cotinine is the most widely used biomarker to distinguish active versus passive smoking. However, there is an overlap in cotinine levels when comparing light or occasional smokers versus heavily exposed passive smokers. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. The aim of the study was to determine optimal cutoff points to discriminate active versus passive smokers and to compare sensitivity and specificity for the use of cotinine, NNAL, and the ratio of the NNAL/cotinine in urine. METHODS Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers. RESULTS Geometric mean cotinine levels were 2.03 ng/ml (interquartile interval: 0.43-8.60) and 1,043 ng/ml (658-2,251) and NNAL levels were 5.80 pg/ml (2.28-15.4) and 165 pg/ml (90.8-360) pg/ml in passive and active smokers, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 vs. 0.16, p < .01). The receiver operating characteristics analysis determined optimal cutoff points to discriminate passive versus active smokers: 31.5 ng/ml for cotinine (sensitivity: 97.1% and specificity: 93.9%), 47.3 pg/ml for NNAL (87.4% and 96.5%), and 0.74 x 10⁻³ for NNAL/cotinine ratio (97.3% and 87.3%). CONCLUSIONS Both urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure. Cotinine is the best overall discriminator when biomarkers are measured while a person has ongoing exposure to tobacco smoke. NNAL because of its long half-life would be particularly useful when there is a delay between exposure and biomarker measurement. The NNAL/cotinine ratio provides similar sensitivity but poorer specificity at discriminating passive versus active smokers when compared with NNAL alone.

Urine Cotinine Underestimates Exposure to the Tobacco-Derived Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Passive Compared with Active Smokers

Objectives: Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke. Methods: Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers. Results: Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 × 103 versus 0.16 × 103, P < 0.0001). Conclusions: Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking. Impact: Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking. Cancer Epidemiol Biomarkers Prev; 19(11); 2795–800. ©2010 AACR.

Nicotine and carbon monoxide exposure from inhalation of cigarillo smoke.

BACKGROUND There has been an increase in the use of cigarillos in the US. People who smoke cigarillos typically also regularly smoke cigarettes (dual users). METHODS We compared puffing topography, biomarkers of acute exposure [exhaled carbon monoxide (COex) and plasma nicotine] and physiologic effects from usual brand cigarette and Black & Mild cigarillo smoking in dual users (N=23) in two laboratory sessions. RESULTS Participants (21 men) smoked an average of 17.5cigarettes/day. Cigarillo consumption varied widely from as few as 1/week to daily. Participants were highly nicotine dependent (average FTND score: 6.3). There were statistically significant differences in smoking behavior between cigarette and cigarillo smoking in time to smoke, number of puffs, and total puff volume (all P<0.001). Average puff duration, interpuff interval average puff volume, and puff velocity did not differ between cigarettes and cigarillos. Nicotine boost was similar after both cigarettes and cigarillos. COex boost was significantly greater after cigarillo smoking compared to cigarette smoking (P<0.001). CONCLUSIONS The smoking pattern and exposure profile indicate that dual users inhale cigarillo smoke just as they inhale cigarette smoke thereby exposing themselves to considerable amounts of nicotine and other components of tobacco smoke. COex exposure results imply that cigarillo smoking may be associated with higher exposure to smoke-delivered volatile components of mainstream cigarillo smoke including carcinogens when compared to cigarettes. IMPACT The findings that cigarillos and cigarettes are smoked similarly in dual users are relevant to health and regulatory considerations on cigar products.

Toxicant exposure from smoking a little cigar: further support for product regulation

Background Although numerous studies have documented the prevalence and increasing use of little cigars and other cigar products, the present study is the first direct, head-to-head laboratory comparison of little cigar and cigarette smoking. The study addressed a fundamental objective to compare exposure and use characteristics of little cigar and cigarette smoking. Methods Smoking patterns, toxicant exposure and subjective measures were collected and analysed in 21 adults after smoking a little cigar (Winchester) and a cigarette (own brand). Participants were dual users of little cigars and cigarettes. Results Similar to cigarettes, little cigars delivered substantial nicotine and relatively more carbon monoxide. Puff volume, puff duration and time to smoke were significantly greater after cigarettes, but the temporal pattern of smoking more intensively at the beginning was similar in little cigars and cigarettes. Both little cigars and cigarettes reduced urge to smoke. Participants consistently mentioned that the lower cost of little cigars was a reason for initiation and continuation of their use. Conclusions The results support the notion that regulation of little cigars is appropriate in light of public health considerations.

Make Your Own Cigarettes: Toxicant Exposure, Smoking Topography, and Subjective Effects

Background: Despite considerable use of make your own (MYO) cigarettes worldwide and increasing use in the United States, relatively little is known about how these cigarettes are smoked and the resultant toxicant exposure. Methods: In a laboratory study, we compared two types of MYO cigarettes—roll your own (RYO) and personal machine made (PMM)—with factory-made (FM) cigarettes in three groups of smokers who exclusively used RYO (n = 34), PMM (n = 23), or FM (n = 20). Within each group, cigarettes were smoked in three conditions: (i) after confirmed overnight tobacco abstinence; (ii) in an intense smoking paradigm; and (iii) without restrictions. All cigarettes were smoked ad lib through a smoking topography unit. Results: Plasma nicotine significantly increased after cigarettes in all conditions except PMM in the intense smoking paradigm. Puff volume, puff duration, total puff volume, and puff velocity did not differ between cigarette types but the puffs per cigarette and time to smoke were significantly smaller for RYO compared with PMM and FM. Regardless of the cigarette, participants consumed the first three puffs more vigorously than the last three puffs. Conclusions: Despite the belief of many of their consumers, smoking MYO cigarettes is not a safe alternative to FM cigarettes. Like FM, MYO cigarettes expose their users to harmful constituents of tobacco smoke. Despite differences in size and design their puffing profiles are remarkably similar. Impact: These data are relevant to health and regulatory considerations on the MYO cigarettes. Cancer Epidemiol Biomarkers Prev; 23(9); 1793–803. ©2014 AACR.

Simultaneous determination of nicotine and 3-vinylpyridine in single cigarette tobacco smoke and in indoor air using direct extraction to solid phase

The aim of the present study was to develop a new analytical method of chromatographic determination of two important markers of ETS exposure: nicotine and 3-vinylpyridine (3-ethenylpyridine, 3-EP) in mainstream (MS) and sidestream (SS) smoke of one single cigarette and in indoor air using direct solid phase extraction combined with gas chromatography. The method can be utilised for both nicotine and 3-EP determination in SS and MS of one single cigarette as well as it allows for a precise determination of compound distribution in indoor air. The application of the same analytical method for both kinds of samples allows anticipating indoor air distribution of both analysed compounds in a very precise way. The precision of the method (calculated as a relative standard deviation) was 9.78% for nicotine and 2.67% for 3-EP; whereas the accuracy (evaluated by a recovery study conducted at three different levels) was 70.1 and 87.3%, respectively. The limit of detection was 0.06 µg per cigarette for both nicotine and 3-EP. The method was evaluated by determining the compounds of interest in two commercially available brands of cigarettes as well as in the reference cigarettes 3R4F and also in indoor air polluted with tobacco smoke. Determined levels of compounds of interest in MS varied from 586 to 772 (nicotine) µg per cigarette and from 3.5 to 10.7 (3-EP) µg per cigarette. In SS smoke the level varied from 14,370 to 22,590 (nicotine) µg per cigarette and from 185 to 550 (3-EP) µg per cigarette, whereas levels in indoor air polluted with tobacco smoke varied from 50.1 to 157.3 (nicotine) µg m−3and from 7.7 to 20.8 (3-EP) µg m−3.

The Role of Pharmacists in Smoking Cessation in Poland

In Poland, 38.0% of men and 25.6% of women smoke daily. One method for expanding access to smoking cessation services is through community-based pharmacists. Surveys were administered in 2007—2008 to (a) current smokers, (b) members of a pharmacy association, and (c) pharmacy students in their final year of training. Pharmacists were the highest ranked health professionals to whom Polish smokers reported they would turn for information about pharmacological support for smoking cessation. Most pharmacists (79%) reported their knowledge allowed them to provide basic smoking cessation information to their patients. Pharmacy students reported being more able to provide information about the health consequences of tobacco smoking than to help patients quit smoking (85% vs. 61%). In Poland, community-based pharmacists are positioned to provide smoking cessation interventions to all segments of the population. To extend and promote smoking cessation efforts, comprehensive tobacco cessation training should be a required component of the pharmacy school curriculum.

Large Cigars: Smoking Topography and Toxicant Exposure.

Background Cigar smoking in the United States continues despite decreases in cigarette smoking and increased tobacco control efforts. We compared large cigar and cigarette smoking for use patterns, smoking topography, and toxicant exposure. Methods Dual users (n = 17, 94% men, 77% African American) smoked ad libitum either their usual cigarette brand or a study large cigar (Phillies Blunt) in two laboratory sessions. Plasma nicotine and exhaled carbon monoxide were collected before and after smoking. Smoking topography measures of puff volume, puff duration, puff velocity, and interpuff interval were also collected. Results Both cigarettes and large cigars significantly increased plasma nicotine and carbon monoxide and significantly decreased the urge to smoke. Cigarettes delivered more nicotine per gram of tobacco smoked and per 1000 mL of puff volume. Number of puffs, time to smoke, puff volume, and puff velocity were significantly larger and interpuff interval was significantly shorter in large cigar smoking. The temporal pattern of puffing more intensely at the beginning of smoking was similar for both large cigars and cigarettes. Conclusions People who regularly use both large cigars and cigarettes adapt their smoking pattern such that they are exposed to similar levels of nicotine from each product. The immediate increase in plasma nicotine and carbon monoxide suggest significant inhalation of large cigar smoke. These data call to question the assumption that cigar smoking is less toxic than cigarette smoking. By smoking large cigars, dual users expose themselves to toxic components that have been linked with the addiction risk, morbidity, and mortality of cigarette smoking. Implications This study found that dual users of large cigars and cigarettes inhale significant quantities of carbon monoxide, nicotine, and presumably other components of mainstream smoke. Large cigar smoke exposure may lead to or sustain nicotine addiction as wells as subject large cigar consumers to similar risks associated with cigarette smoking such as lung cancer and cardiovascular disease.

Nicotine Absorption from Smokeless Tobacco Modified to Adjust pH

INTRODUCTION Nicotine delivery from smokeless tobacco (ST) products leads to addiction and the use of ST causes pathology that is associated with increased initiation of cigarette smoking. The rapid delivery of nicotine from ST seems to be associated with the pH of the aqueous suspension of the products - high pH is associated with high nicotine absorption. However, early studies compared nicotine absorption from different commercial products that not only differed in pH but in flavoring, nicotine content, and in format-pouches and loose tobacco. METHODS The present study compared nicotine absorption from a single unflavored referent ST product (pH 7.7) that was flavored with a low level of wintergreen (2 mg/g) and the pH was amended to either high (8.3) or low (5.4) pH with sodium carbonate or citric acid, respectively. RESULTS In a within-subject clinical study, the higher pH products delivered more nicotine. No significant differences were seen between perceived product strengths and product experience in all conditions. Heart rate increased by 4 to 6 beats per minute after the high pH flavored and the un-amended product but did not change after the low pH flavored product. CONCLUSIONS These results indicate that pH is a primary determinant of buccal nicotine absorption. The role of flavoring and other components of ST products in nicotine absorption remain to be determined.