RESUMEN
A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects' experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products (ClinicalTrials.gov Identifier: NCT02061917).
Asunto(s)
Biomarcadores/sangre , Biomarcadores/orina , Prevención del Hábito de Fumar , Dispositivos para Dejar de Fumar Tabaco/estadística & datos numéricos , Cese del Uso de Tabaco/métodos , Tabaco sin Humo/estadística & datos numéricos , Adulto , Aminas/sangre , Aminas/orina , Femenino , Humanos , Hidrocarburos Aromáticos/sangre , Hidrocarburos Aromáticos/orina , Masculino , Persona de Mediana Edad , Nicotina/sangre , Nicotina/orina , Factores de TiempoRESUMEN
A randomized, multi-center study was conducted to assess potential improvement in health status measures, as well as changes in biomarkers of tobacco exposure and biomarkers of biological effect, in current adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) evaluated over 24 weeks. Study design, conduct and methodology are presented here along with subjects' disposition, characteristics, compliance and safety results. This design and methodology, evaluating generally healthy adult smokers over a relatively short duration, proved feasible. Findings from this randomized study provide generalized knowledge of the risk continuum among various tobacco products (ClinicalTrials.gov Identifier: NCT02061917).
Asunto(s)
Proyectos de Investigación , Prevención del Hábito de Fumar , Dispositivos para Dejar de Fumar Tabaco/estadística & datos numéricos , Cese del Uso de Tabaco/métodos , Tabaco sin Humo/estadística & datos numéricos , Adulto , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) for 24 weeks was conducted. Evaluation of biomarkers of biological effect (e.g. inflammation, lipids, hypercoaguable state) indicated that the majority of consistent and statistically significant improvements over time within each group were observed in markers of inflammation. Consistent and statistically significant differences in pairwise comparisons between product groups were not observed. These findings are relevant to the understanding of biomarkers of biological effect related to cigarette smoking as well as the risk continuum across various tobacco products (ClinicalTrials.gov Identifier: NCT02061917).
Asunto(s)
Biomarcadores/sangre , Biomarcadores/orina , Prevención del Hábito de Fumar , Dispositivos para Dejar de Fumar Tabaco/estadística & datos numéricos , Cese del Uso de Tabaco/métodos , Tabaco sin Humo/estadística & datos numéricos , Adulto , Femenino , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/orina , Lípidos/sangre , Lípidos/orina , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
There are no large-scale, carefully designed cohort studies that provide evidence on whether menthol cigarette use is associated with a differential risk of initiating and/or progressing to increased smoking. However, questions of whether current menthol cigarette smokers initiated smoking at a younger age or are more likely to have transitioned from non-daily to daily cigarette use compared to non-menthol smokers can be addressed using cross-sectional data from U.S. government surveys. Analyses of nationally representative samples of adult and youth smokers indicate that current menthol cigarette use is not associated with an earlier age of having initiated smoking or greater likelihood of being a daily versus non-daily smoker. Some surveys likewise provide information on cigarette type preference (menthol versus non-menthol) among youth at different stages or trajectories of smoking, based on number of days smoked during the past month and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not appear to differ among new, less experienced youth smokers compared to established youth smokers. While there are limitations with regard to inferences that can be drawn from cross-sectional analyses, these data do not suggest any adverse effects for menthol cigarettes on measures of initiation and progression to increased smoking.
Asunto(s)
Mentol/efectos adversos , Fumar/efectos adversos , Fumar/epidemiología , Productos de Tabaco/efectos adversos , Tabaquismo/epidemiología , Adolescente , Adulto , Niño , Estudios Transversales , Recolección de Datos , Progresión de la Enfermedad , Femenino , Gobierno , Humanos , Masculino , Prevalencia , Estados Unidos , Adulto JovenRESUMEN
The National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, National Health Interview Survey and Tobacco Use Supplement to the Current Population Survey provide estimates of the proportions of U.S. smokers who currently use menthol cigarettes, overall and within demographic strata. Among adult past-month, regular and daily smokers, menthol cigarette use ranges from 26% to 30%, with statistically higher proportions of female versus male smokers (8-11 percentage points higher) currently using menthol cigarettes. Compared to adult smokers overall, statistically higher proportions of non-Hispanic Black smokers (72-79%) and statistically lower proportions of non-Hispanic White smokers (19-22%) currently use menthol cigarettes, with no differences among smokers of other race/ethnicity groups (18-20% to 28-30%, depending on the survey). Higher proportions of younger adult past-month, regular and daily smokers (aged 18-25years) currently use menthol cigarettes compared to older adult smokers (aged 26-29years and/or ⩾30years); however, differences are small in magnitude, with the vast majority of adult smokers (70-75%) who currently use menthol cigarettes being aged ⩾30years. Comparisons between youth and adult smokers are provided, although data for youth smokers are less available and provide less consistent patterns of menthol cigarette use.
Asunto(s)
Mentol , Fumar/epidemiología , Productos de Tabaco/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Recolección de Datos , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Encuestas Nutricionales , Grupos Raciales/estadística & datos numéricos , Factores Sexuales , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Menthol in cigarettes has been examined for its potential to affect smoking dependence, measured primarily as number of cigarettes smoked per day and time to first cigarette after waking; the ability to quit smoking constitutes an additional measure of dependence. Successful quitting among menthol compared to non-menthol cigarette smokers is difficult to determine from the literature, due in part to the various definitions of quitting used by researchers. Nevertheless, intervention and follow-up studies of smoking cessation treatments generally indicate no differences in quitting success among menthol compared to non-menthol smokers, while cross-sectional studies suggest some differences within race/ethnicity groups. The association between menthol cigarette use and likelihood of being a former versus current smoker was examined based on data from the National Health Interview Survey and Tobacco Use Supplement to the Current Population Survey. Analyses stratified by race/ethnicity and limited to smokers who had quit at least one year prior to survey participation provided inconsistent results with regard to menthol cigarette use and quitting, both within surveys (i.e., comparing race/ethnicity groups) and between surveys (i.e., same race/ethnicity group across surveys). Evidence suggesting the existence or direction of an association between menthol in cigarettes and quitting depended on the data source.
Asunto(s)
Mentol , Fumar/epidemiología , Productos de Tabaco/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Humanos , Funciones de Verosimilitud , Proyectos de Investigación , Cese del Hábito de Fumar/estadística & datos numéricosRESUMEN
Previously published studies provide somewhat inconsistent evidence on whether menthol in cigarettes is associated with increased dependence. The National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, National Health Interview Survey, and Tobacco Use Supplement to the Current Population Survey collect data on current cigarette type preference and primary measures of dependence, and thus allow examination of whether menthol smokers are more dependent than non-menthol smokers. Analyses based on combined data from multiple administrations of each of these four nationally representative surveys, using three definitions for current smokers (i.e., smoked ⩾1day, ⩾10days and daily during the past month), consistently demonstrate that menthol smokers do not report smoking more cigarettes per day than non-menthol smokers. Moreover, two of the three surveys that provide data on time to first cigarette after waking indicate no difference in urgency to smoke among menthol compared to non-menthol smokers, while the third suggests menthol smokers may experience a greater urgency to smoke; estimates from all three surveys indicate that menthol versus non-menthol smokers do not report a higher Heaviness of Smoking Index. Collectively, these findings indicate no difference in dependence among U.S. smokers who use menthol compared to non-menthol cigarettes.
Asunto(s)
Mentol/efectos adversos , Fumar/epidemiología , Productos de Tabaco/efectos adversos , Tabaquismo/epidemiología , Adulto , Femenino , Humanos , Masculino , Encuestas Nutricionales , Fumar/efectos adversos , Nicotiana/efectos adversos , Estados Unidos , Adulto JovenRESUMEN
A simple, rapid liquid chromatography-tandem mass spectrometry method was developed to identify and quantitate in human urine the isoprostanes iPF(2 alpha)-III, 15-epi-iPF(2 alpha)-III, iPF(2 alpha)-VI, and 8,12-iso-iPF(2 alpha)-VI along with the prostaglandin PGF(2 alpha) and 2,3-dinor-iPF(2 alpha)-III, a metabolite of iPF(2 alpha)-III. Assay specificity, linearity, precision, and accuracy met the required criteria for most analytes. The urine sample storage stability and standard solution stability were also tested. The methodology was applied to analyze 24 h urine samples collected from smokers and nonsmokers on controlled diets. The results for iPF(2 alpha)-III obtained by our method were significantly correlated with results by an ELISA, although an approximately 2-fold high bias was observed for the ELISA data. For iPF(2 alpha)-III and its metabolite 2,3-dinor-iPF(2 alpha)-III, smokers had significantly higher concentrations than nonsmokers (513 +/- 275 vs. 294 +/- 104 pg/mg creatinine; 3,030 +/- 1,546 vs. 2,046 +/- 836 pg/mg creatinine, respectively). The concentration of iPF(2 alpha)-VI tended to be higher in smokers than in nonsmokers; however, the increase was not statistically significant in this sample set. Concentrations of the other three isoprostane isomers showed no trends toward differences between smokers and nonsmokers. Among smokers, the daily output of two type VI isoprostanes showed a weak correlation with the amount of tobacco smoke exposure, as determined by urinary excretion of total nicotine equivalents.
Asunto(s)
Cromatografía Liquida/métodos , Isoprostanos/orina , Fumar/orina , Espectrometría de Masas en Tándem/métodos , Adulto , Dinoprost/orina , Estabilidad de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Renal excretion mechanisms are xenobiotic-specific; therefore, accurate exposure assessment requires an understanding of relationships of xenobiotic biomarker concentration and excretion rate to urine flow, specific gravity and creatinine concentration. Twenty-four-hour urine collection for xenobiotic exposure assessment is considered the "gold standard" procedure. Random spot-urine collection is convenient and minimizes subject compliance concerns but requires that normalization techniques be employed to account for diuresis and diurnal variation in xenobiotic biomarker excretion. This paper examines and makes recommendations concerning normalization techniques and conditions under which spot-urine results most accurately reflect 24-h urine results. Specific gravity, creatinine, and xenobiotic biomarkers were determined in smokers' spot and 24-h urines. Normalization techniques were applied, variance-component analyses were performed to estimate variability, spot urines were pooled mathematically to simulate 24-h urines and analyses of variance were performed to evaluate spot urines' ability to reflect 24-h urine concentrations. For each xenobiotic biomarker concentration, log-linear relationships were observed with urine flow, specific gravity, and creatinine. For most xenobiotic biomarker excretion rates, log-linear relationships were observed with urine flow; creatinine, however, was unaffected by urine flow. The conventional creatinine ratio-normalization technique demonstrated greater variability (within-day, between-day and between-subject) than other normalization techniques. Comparisons of simulated 24-h urines to spot urines suggest that spot-urine collection be performed only between 2 p.m. and 2 a.m. and that the modified specific-gravity-adjusted-creatinine ratio-normalization technique and the creatinine-regression normalization technique yield the best agreement between spot- and simulated 24-h urine results.
Asunto(s)
Creatinina/orina , Fumar/orina , Xenobióticos/orina , Biomarcadores/orina , Ritmo Circadiano , Simulación por Computador , Femenino , Humanos , Masculino , Modelos Biológicos , Análisis de Regresión , Reproducibilidad de los Resultados , Fumar/metabolismo , Gravedad Específica , Urinálisis/métodos , Urodinámica , Xenobióticos/metabolismoRESUMEN
Cigarettes that burn tobacco produce a complex mixture of chemicals, including mutagens and carcinogens. Cigarettes that primarily heat tobacco produce smoke with marked reductions in the amount of mutagens and carcinogens and demonstrate reduced mutagenicity and carcinogenicity in a battery of toxicological assays. Chemically induced oxidative stress, DNA damage, and inflammation may alter cell cycle regulation and are important biological events in the carcinogenic process. The objective of this study was to characterize and compare the effects of smoke condensates from cigarettes that burn tobacco and those that primarily heat tobacco on gene expression in NHBE cells. For this comparison, we used quantitative RT/PCR and further evaluated the effects on cell cycling using flow cytometry. Cigarette smoke condensates (CSCs) were prepared from Kentucky 1R4F cigarettes (a tobacco-burning product designed to represent the average full-flavor, low "tar" cigarette in the US market) and Eclipse (a cigarette that primarily heats tobacco) using FTC machine smoking conditions. The CSC from 1R4F cigarettes induced statistically significant increases in the mRNA levels of genes responsive to DNA damage (GADD45) and involved in cell cycle regulation (p21;WAF1/CIP1), compared to the CSC from Eclipse cigarettes. In addition, genes coding for cyclooxygenase-2 (COX-2) and interleukin 8 (IL-8), which are associated with oxidative stress and inflammation, respectively, were increased statistically significantly more by CSC from 1R4F than by that from Eclipse. Furthermore, a dose-dependent increase in IL-8 protein secretion into cell culture media was stimulated by 1R4F exposure, whereas minimal IL-8 protein was secreted after Eclipse treatment. The biological relevance of the differential effect on gene expression was reflected in differential cell cycle regulation, as cells exposed to 1R4F CSC exhibited more significant S phase and G2 phase accumulation than cells exposed to Eclipse CSC. These data indicate that the simplified smoke chemistry of the tobacco-heating Eclipse cigarette yields statistically significant reductions in the expression of key genes involved in DNA damage, oxidative stress, inflammatory response, and cell cycle regulation in normal human bronchial epithelial cells compared to a representative tobacco-burning cigarette.
Asunto(s)
Bronquios/metabolismo , Expresión Génica , Nicotiana , Humo , Secuencia de Bases , Bronquios/citología , Ciclo Celular , Células Cultivadas , Cartilla de ADN , Células Epiteliales/metabolismo , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
An SPE-LC-MS/MS method was developed, validated and applied to the determination of nicotine and five major metabolites in human urine: cotinine, trans-3'-hydroxycotinine, nicotine-N-glucuronide, cotinine-N-glucuronide and trans-3'-hydroxycotinine-O-glucuronide. A 500 microL urine sample was pH-adjusted with phosphate buffer (1.5 mL) containing nicotine-methyl-d3, cotinine-methyl-d3 and trans-3'-hydroxycotinine-methyl-d3 internal standards. For the unconjugated metabolites, an aliquot (800 microL) of the buffered solution was applied to a 30 mg Oasis HLB-SPE column, rinsed with 2% NH4OH/H2O (3.0 mL) and H2O (3.0 mL) and eluted with methanol (500 microL). The eluate was analyzed isocratically (100% methanol) by LC-MS/MS on a diol column (50 x 2.1 mm). For the total metabolites, a beta-glucuronidase/buffer preparation (100 microL) was added to the remaining buffered solution and incubated at 37 degrees C (20 h). An aliquot (800 microL) of the enzymatically treated buffered solution was extracted and analyzed in the same manner. The conjugated metabolites were determined indirectly by subtraction. The quantitation range of the method (ng/mL) was 14-10,320 for nicotine, 15-9800 for cotinine and 32-19,220 for trans-3'-hydroxycotinine. The validated method was used to observe diurnal variations from a smoker's spot urine samples, elimination half-lives from a smoker's 24 h urine samples and metabolite distribution profiles in the spot and 24 h urine samples.
Asunto(s)
Nicotina/orina , Fumar/orina , Fraccionamiento Químico , Cromatografía Liquida , Ritmo Circadiano , Creatinina/orina , Congelación , Humanos , Espectrometría de Masas , Nicotina/aislamiento & purificación , Nicotina/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Cese del Hábito de FumarRESUMEN
A specific and rapid liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed and validated for NNAL, a metabolite of the tobacco-specific nitrosamine metabolite NNK. The metabolite was detected in smokers' urine with a limit of quantitation (LOQ) of 20 pg ml(-1) and a linear range up to 1000 pg ml(-1). The method features a single solid-phase extraction step and MS/MS monitoring following electrospray ionization. Fragmentation pathways for the protonated molecular ion are proposed. The sample preparation is simpler than that for gas chromatographic methods reported in the literature and maintains sensitivity adequate for determining NNAL in smokers' urine. By using enzyme hydrolysis to determine total NNAL in urine, the amount of NNAL-glucuronide was calculated. A standard pooled smokers' urine sample used for development gave values of 176 +/- 8 pg ml(-1) free NNAL and 675 +/- 26 pg ml(-1) total NNAL following enzyme hydrolysis. The method was applied to a group of seven smokers; the free NNAL level for the group was 101-256 pg ml(-1) with NNAL-glucuronides at 247-566 pg ml(-1). The ratio of conjugated to free NNAL was in the range 0.98-2.95. The variability in total daily amount of NNAL excreted (ng per 24 h) had RSDs of 6-21% for free NNAL, 7-22% for conjugated NNAL and 6-20% for total NNAL excreted. When normalized to the number of cigarettes smoked, the amounts of NNAL excreted per cigarette smoked were in the range of amounts of NNK yields reported for cigarettes in the literature.