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Biomedical subjects

Neal Benowitz

Publications and source records attributed to Neal Benowitz.

18 recordsLinked to original sources
PubMed2006

Menthol cigarettes, smoking cessation, atherosclerosis, and pulmonary function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: African American smokers are more likely to experience tobacco-related morbidity and mortality than European American smokers, and higher rates of menthol cigarette smoking may contribute to these disparities. METHODS: We prospectively measured cumulative exposure to menthol and nonmenthol cigarettes and smoking cessation behavior (1985-2000), coronary calcification (2000), and 10-year change in pulmonary function (1985-1995) in African American and European American smokers recruited in 1985 for the Coronary Artery Risk Development in Young Adults Study. RESULTS: We identified 1535 smokers in 1985 (972 menthol and 563 nonmenthol); 89% of African Americans preferred menthol vs 29% of European Americans (P<.001). After adjustment for ethnicity, demographics, and social factors, we found nonsignificant trends in menthol smokers toward lower cessation (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.49-1.02; P = .06) and recent quit attempt (OR, 0.77; 95% CI, 0.56-1.06; P = .11) rates and a significant increase in the risk of relapse (OR, 1.89; 95% CI, 1.17-3.05; P = .009). Per pack-year of exposure, however, we found no differences from menthol in tobacco-related coronary calcification (adjusted OR, 1.27; 95% CI, 1.01-1.60 for menthol cigarettes and 1.33; 95% CI, 1.06-1.68 for nonmenthol cigarettes per 10-pack-year increase; P = .75 for comparison) or 10-year pulmonary function decline (adjusted excess decline in forced expiratory volume in 1 second, 84 mL; 95% CI, 32-137 for menthol cigarettes and 80 mL; 95% CI, 30-129 for nonmenthol cigarettes, per 10-pack-year increase; P = .88 for comparison). CONCLUSION: Menthol and nonmenthol cigarettes seem to be equally harmful per cigarette smoked in terms of atherosclerosis and pulmonary function decline, but menthol cigarettes may be harder to quit smoking.

Adolescent↗
PubMed2006

Directly measured secondhand smoke exposure and COPD health outcomes.

BACKGROUND: Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease. Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown. METHODS: We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine. We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up. RESULTS: The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates. In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level. CONCLUSION: Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking. Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance. In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking.

Aged↗
PubMed2006

A genome-wide screen for nicotine dependence susceptibility loci.

Genome-wide model free linkage analysis was conducted for nicotine dependence and tobacco use phenotypes in 607 members of 158 nuclear families consisting of at least two ever smokers (100 or more cigarettes smoked in lifetime). DNA from whole blood was genotyped for 739 autosomal microsatellite polymorphisms with an average inter-marker distance of 4.6 cM. A peak LOD score of 2.7 was observed on chromosome 6 for scores for the Fagerström Test for Nicotine Dependence. Exploratory analyses were conducted to determine whether sequence variation at other loci affected other measures of dependence or tobacco use. Four additional loci with LOD scores of 2.7 or more were associated with alternative measures of nicotine dependence, one with current frequency of use, and one with smoking cessation. Several of the corresponding support intervals were near putative loci reported previously (on chromosomes 6, 7, and 8) while others appear to be novel (on chromosomes 5, 16, and 19).

Family Health↗
PubMed2006

Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation.

BACKGROUND: Nicotine is metabolized to cotinine, and cotinine is metabolized to 3'-hydroxycotinine (3-HC) by the liver enzyme cytochrome P450 (CYP) 2A6. More rapid metabolism of nicotine may result in lower nicotine blood levels from nicotine replacement products and poorer smoking cessation outcomes. This study evaluated the utility of the 3-HC/cotinine ratio as a predictor of the efficacy of nicotine replacement therapy as an aid for smoking cessation. METHODS: By use of an open-label design, 480 treatment-seeking smokers were randomly assigned to 8 weeks of transdermal nicotine or nicotine nasal spray use, plus behavioral group counseling. Assessments included demographics, smoking history, body mass index, and plasma nicotine, cotinine, and 3-HC concentrations, as well as CYP2A6 genotypes. Smoking cessation was biochemically verified at the end of treatment and at 6-month follow-up. RESULTS: The rate of nicotine metabolism, as indicated by pretreatment 3-HC/cotinine ratio derived from cigarette smoking, predicted the effectiveness of transdermal nicotine at both time points. The odds of abstinence were reduced by almost 30% with each increasing quartile of metabolite ratio (odds ratio, 0.72 [95% confidence interval, 0.57-0.90]; P=.005). Higher metabolite ratios also predicted lower nicotine concentrations (beta=-1.72, t(179)=-3.31, P<.001), as well as more severe cravings for cigarettes after 1 week of treatment (beta=0.32, t(190)=2.91, P=.004). The metabolite ratio did not predict cessation with use of nicotine nasal spray (odds ratio, 1.05 [95% confidence interval, 0.83-1.33]; P=.68). CONCLUSION: The nicotine metabolite ratio might be useful in screening smokers to determine likely success with a standard dose of transdermal nicotine.

Administration, Cutaneous↗
PubMed2006

Determinants of the rate of nicotine metabolism and effects on smoking behavior.

BACKGROUND: Studies on cytochrome P450 (CYP) 2A6 suggest that genotype affects the rate of nicotine metabolism and, consequently, cigarette consumption. However, known alleles of CYP2A6 associated with fast or slow metabolism are relatively uncommon, and there remains considerable variation in metabolic activity among those with presumed wild-type CYP2A6 alleles, suggesting that other genetic or environmental factors also influence the rate of nicotine metabolism. METHODS: We investigated determinants of the rate of nicotine metabolism and effects on smoking behavior in a United Kingdom cohort who participated in a placebo-controlled trial of smoking cessation via nicotine replacement therapy. Those who continued to smoke cigarettes at the 8-year follow-up formed our study group (N = 545). The ratio of the nicotine metabolite trans-3'-hydroxycotinine to cotinine in plasma was used as an index of CYP2A6 activity and thus as a marker of the rate of nicotine metabolism. RESULTS: The nicotine metabolite ratio was associated with sex (P < .0001), CYP2A6 genotype (*1B, *2, *4, *9, and *12) (P < .0001), CYP2B6 haplotype (*4-dominant) (P = .02), plasma nicotine concentration (P < .0001), and age (P = .02) but was not associated with dependence score (P > .20). The ratio also predicted the number of cigarettes smoked at will per day, although the association was weak (F(1, 492) = 4.05, P = .04). CONCLUSION: In this cohort the rate of nicotine metabolism is related to age, sex, CYP2A6 genotype, and CYP2B6 genotype and may affect the level of tobacco consumption.

Adult↗
PubMed2006

Salivary cotinine concentration versus self-reported cigarette smoking: Three patterns of inconsistency in adolescence.

The present study examined the extent and sources of discrepancies between self-reported cigarette smoking and salivary cotinine concentration among adolescents. The data are from household interviews with a cohort of 1,024 adolescents from an urban school system. Histories of tobacco use in the last 7 days and saliva samples were obtained. Logistic regressions identified correlates of three inconsistent patterns: (a) Pattern 1-self-reported nonsmoking among adolescents with cotinine concentration above the 11.4 ng/mg cutpoint (n = 176), (b) Pattern 2-low cotinine concentration (below cutpoint) among adolescents reporting having smoked within the last 3 days (n = 155), and (c) Pattern 3-high cotinine concentration (above cutpoint) among adolescents reporting not having smoked within the last 3 days (n = 869). Rates of inconsistency were high among smokers defined by cotinine levels or self-reports (Pattern 1 = 49.1%; Pattern 2 = 42.0%). Controlling for other covariates, we found that reports of nonsmoking among those with high cotinine (Pattern 1) were associated with younger age, having few friends smoking, little recent exposure to smokers, and being interviewed by the same interviewer as the parent and on the same day. Low cotinine concentration among self-reported smokers (Pattern 2) was negatively associated with older age, being African American, number of cigarettes smoked, depth of inhalation, and exposure to passive smoke but positively associated with less recent smoking and depressive symptoms. High cotinine concentrations among self-reported nonsmokers was positively associated with exposure to passive smoke (Pattern 3). The data are consonant with laboratory findings regarding ethnic differences in nicotine metabolism rate. The inverse relationship of cotinine concentration with depressive symptoms has not previously been reported. Depressed adolescent smokers may take in smaller doses of nicotine than nondepressed smokers; alternatively, depressed adolescents may metabolize nicotine more rapidly.

Adolescent↗
PubMed2006

Exposure to second-hand smoke air pollution assessed from bar patrons' urinary cotinine.

We used physical and pharmacokinetic modeling to estimate personal exposures to respirable particle (RSP) and carcinogenic particulate polycyclic aromatic hydrocarbon (PPAH) air pollution from second-hand smoke (SHS) from the increase in urinary cotinine of eight patrons of three bars in Bismarck, North Dakota. We compared SHS-RSP levels to the U.S. Air Quality Index (AQI), used to forecast outdoor air pollution conditions. We measured smoker density and air exchange rates to generalize our results. Urinary cotinine increased by an average of 4.28 ng/ml to 6.88 ng/ml to 9.55 ng/ml above preexposure background from 6-hr exposures in the three bars. Corresponding estimated SHS-RSP levels were, respectively, 246 microg/m3, 396 microg/m3, and 549 microg/m3, comparable to those measured in 6 Wilmington, Delaware, bars and in 14 western New York bars. Estimated personal SHS-RSP air pollution exposures for the eight subjects, when converted to the 24-hr averaging time of the AQI, were "code red" (unhealthy). Measured outdoor air quality RSP levels for the same period were 1%-3% of the indoor RSP levels in the three bars, and were AQI "code green" (healthy). Estimated SHS-PPAH levels were comparable to peak 3-hr PPAH levels reported at a highway tollbooth. Bismarck cotinine-estimated SHS-RSP varied with smoker density, as did measured SHS-RSP levels in smoking bars in Delaware and New York. Our results show that smoking in bars produces levels of personal air pollution for bar patrons that merit air pollution alerts when sustained in the outdoor air.

Adult↗
PubMed2005

Ethnic differences in nicotine metabolic rate among New Zealanders.

AIMS: To estimate (a) the prevalence of gene variants associated with slow nicotine metabolism in the general Maori population and (b) nicotine intake and metabolic rate in Maori and European smokers. METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3'-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke's Bay Region (6 Maori and 6 European). RESULTS: (a) The frequencies of the slow nicotine metabolising variants, CYP2A6*9 and *4, were significantly higher in Maori compared to European (p<0.01). Indeed, the prevalence of the CYP2A6*9 variant in these Maori was among the highest in the world (approximately 20%). (b) In smokers, the Maori group had approximately 35% lower 3-HC:COT ratios indicating a reduced metabolic rate, as well as 2-fold lower cotinine levels per cigarette smoked, indicating reduced nicotine intake (p<0.05). The CYP2A6*9 allele was significantly more frequent in Maori smokers (70%) compared to Europeans (30%), p=0.03. CONCLUSIONS: The findings of this study provide evidence that Maori are genetically slower nicotine metabolisers compared to Europeans. Although more research is required, this study may help explain ethnic differences in smoking initiation and may also have important implications for smoking cessation programs - since metabolic differences between groups with varying ancestry implies that different optimal dosages of nicotine replacement therapy may be required for successful quitting.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial.

BACKGROUND: Despite the well-documented efficacy and different pharmacokinetic and pharmacodynamic properties of different forms of nicotine replacement therapy, empirical data are insufficient to guide practitioners in selecting a particular form of treatment for individual patients with tobacco dependence. OBJECTIVE: To evaluate the comparative efficacy of transdermal nicotine and nicotine nasal spray and identify predictors of treatment outcome. DESIGN: Randomized, open-label clinical trial with a 6-month follow-up period. SETTING: 2 university-based smoking cessation research programs. PARTICIPANTS: 299 treatment-seeking smokers who were followed for 6 months after the target quit date. INTERVENTION: Behavioral group counseling and 8 weeks of therapy with nicotine nasal spray or transdermal nicotine. MEASUREMENTS: Demographic characteristics, smoking history, depression symptoms, and body mass index were measured at baseline. Smoking practices were biochemically verified at the end of treatment and at 6 months after the target quit date. RESULTS: Abstinence rates for the transdermal nicotine and nicotine nasal spray groups were not significantly different at 6-month follow-up (15.0% vs. 12.2%, respectively; P > 0.2). Interactions in abstinence rates for subgroups of smokers were statistically significant (P < 0.05). Smokers who had low to moderate dependence levels, were not obese, and were white achieved higher abstinence rates with transdermal nicotine, whereas smokers who were highly dependent, obese, or members of minority groups achieved higher abstinence rates with nasal spray. LIMITATIONS: The subgroup findings need confirmation in additional large studies before they are routinely applied. CONCLUSIONS: Ethnicity, weight, and level of nicotine dependence may help identify smokers who have greater or lesser abstinence rates with either transdermal or nasal spray nicotine.

Administration, Cutaneous↗
PubMed2004

High rates of sustained smoking cessation in women hospitalized with cardiovascular disease: the Women's Initiative for Nonsmoking (WINS).

BACKGROUND: Although men hospitalized with cardiovascular disease (CVD) show high smoking-cessation rates, similar data for women are lacking. We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD. METHODS AND RESULTS: In this randomized controlled trial conducted from 1996 to 2001, 277 women diagnosed with CVD (mean age 61+/-10 years) were randomly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group (UG; n=135) or intervention group (IG; n=142). Baseline histories were obtained, and interviews to ascertain self-reported smoking status occurred at 6, 12, 24, and 30 months after hospitalization. The UG received strong physician's advice, a self-help pamphlet, and a list of community resources. The IG received strong physician's advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside, with telephone contact at intervals after discharge. The groups were similar demographically and had smoked cigarettes for a median of 38 (IG) or 40 (UG) years. Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis, and risk differences between groups were determined. Time smoke-free was significantly greater for the IG than the UG (P=0.038). Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG (P>0.15 at all times). CONCLUSIONS: Cognitive behavioral intervention resulted in longer average times to resumption of smoking, but in these 2 groups of older women with limited social and financial resources, long-term success rates were similar. Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time.

Adult↗
PubMed2003

Vagal modulation of spinal nicotine-induced inhibition of the inflammatory response mediated by descending antinociceptive controls.

Noxious stimuli activate neuroendocrine axes, inhibiting inflammation, an effect that is powerfully attenuated by ongoing activity in subdiaphragmatic vagal afferents. To evaluate whether this inhibitory effect of vagal afferent activity is mediated by descending antinociceptive control, we tested whether antagonizing descending antinociceptive controls: (i) enhances the inhibition of inflammation produced by spinal nicotine (which stimulates central terminals of nociceptors) and (ii) occludes the enhancing effect of subdiaphragmatic vagotomy, in the rat. Spinal intrathecal co-administration of the alpha-adrenergic receptor antagonist phentolamine and the non-selective opioid receptor antagonist naloxone, and acute subdiaphragmatic vagotomy each produced enhancement, with similar magnitude, of nicotine-induced inhibition of plasma extravasation, produced by the potent inflammatory mediator, bradykinin. The combination of subdiaphragmatic vagotomy and intrathecal receptor antagonists, however, produced no further enhancement compared to each treatment alone. These findings support the suggestion that activity in descending antinociceptive controls modulates noxious stimulus-induced inhibition of inflammation and the vagal modulation of noxious stimulus-induced inhibition of inflammation is mediated by descending antinociceptive controls.

Adrenergic alpha-Antagonists↗
PubMed2003

Individual differences in nicotine intake per cigarette.

The increase in levels of blood nicotine that occurs from smoking a single cigarette, sometimes referred to as a "nicotine boost," is an individualized measure of how much nicotine has been extracted from smoking a cigarette. This study investigated the demographic, smoking status, and psychological predictors of nicotine boost in a sample of 190 treatment-seeking smokers. Boost was assessed by comparing plasma nicotine levels before and after participants smoked one of their own brand cigarettes ad libitum. Positive affect (mood) was a significant positive predictor of nicotine boost, controlling for baseline cotinine levels and cigarette brand (Federal Trade Commission) nicotine delivery. However the proportion of variability accounted for in the model was relatively small (5%). Future research on individual differences in nicotine boost is warranted to clarify the role of psychological, physiological, and cigarette-related determinants.

Adolescent↗
PubMed2003

Environmental and genetic determinants of tobacco use: methodology for a multidisciplinary, longitudinal family-based investigation.

This article describes the ongoing collaborative effort of six research teams to operationalize and execute an integrative approach to the study of gene x environment interactions in the development of tobacco dependence. At the core of the project is a longitudinal investigation of social and behavioral risk factors for tobacco use in individuals who were, on average, 13 years of age at intake and for whom smoking outcomes extending from early adolescence to young adulthood have been characterized previously (current average age of the cohort is 29 years). The conceptual framework for the integrative approach and the longitudinal investigation on which the study is based is presented. A description is also provided of the methods used to: (a) recruit participants and families to provide DNA samples and information on tobacco use; (b) assess participants for relevant tobacco-related phenotypes including smoking history, current use of tobacco, and nicotine metabolism; (c) assess the quality of the DNA samples collected from participants for genome-wide scanning and candidate gene analysis; (d) examine several research questions concerning the role of genetic and environmental factors in the onset and maintenance of tobacco use; and (e) ensure adherence to local and federal guidelines for ethical and legal investigations of genotypic associations with tobacco-related phenotypes in families. This investigation is unique among ongoing studies of the genetics of tobacco dependence in the extent to which equal importance has been assigned to both phenotypic and genotypic measurements.

Adolescent↗
PubMed2002

Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum.

Significant arterio-venous differences in nicotine concentrations have been observed during and after cigarette smoking, nicotine nasal spray, and intravenous nicotine administration. In this paper we describe a novel mathematical method for estimating arterial blood levels from venous blood level data. The model allows to quantify: (i) the influence of the microcirculation in the hands and forearm on the distribution of nicotine, and (ii) the influence of disregarding the venous to arterial circulation in the estimate of systemic inputs. We also (iii) propose a general method to predict arterial concentrations and inputs given venous data. The basic model we adopt is based on the relationship Cv = T * Ca, where Cv and Ca are the concentration in the venous and arterial site, respectively, T is the arterio-venous transfer function and * indicates convolution. We use empirical data to estimate T. We then compare estimates of systemic inputs to the venous site obtained taking into account the transfer function or, as usually done, disregarding it. The relationship we use to compare estimated inputs are: Cv = T * ka * A (where Ka is the arterial disposition function and A the systemic input), and Cv = Kv * A (where Kv is the venous disposition function), respectively. Finally, the estimated transfer function allows to estimate (average) Ca or A given arbitrary venous data. (i) Our analysis suggests that a bi-exponential T is needed to describe observed arterial-venous differences. The estimated transfer function indicates that no elimination of nicotine is involved in the forearm. (ii) Disregarding T, as usually done, erroneously obtains too complex venous input functions (because these input functions incorporate T). (iii) Disregarding T erroneously estimates significantly higher total inputs. (iv) Using the proposed model and previously published venous nicotine level data we predict substantial arterial-venous differences in blood nicotine levels for smokeless tobacco and nicotine gum. The use of disposition functions obtained from venous data may lead to erroneous estimation of the rates of entry into the circulation and systemic bioavailability for many drugs.

Administration, Intranasal↗
PubMedDate not supplied

Women's Initiative for Nonsmoking (WINS V): under-use of nicotine replacement therapy.

OBJECTIVE: The purpose of this study was to assess the use of nicotine replacement therapy (NRT) in a nurse-managed smoking cessation program. DESIGN: A cohort design nested within the WINS randomized clinical trial was used with follow-up at 2, 7, 21, 28, and 90 days. SETTING: The study took place in 10 hospitals in the San Francisco Bay Area. SUBJECTS: Participants included 142 women hospitalized with cardiovascular disease (CVD). OUTCOME MEASURE: The outcome measure was the use of NRT after having been assessed as eligible for its use. INTERVENTION: NRT was used as an adjunct in the behavioral intervention protocol. NRT was recommended during the hospital intervention and during the 90-day outpatient phase. RESULTS: Of 142 women in the intervention group, 127 met the criteria for NRT use. During the 5 follow-up assessments, the reported NRT use ranged from 9% to 22%. CONCLUSION: A low NRT use rate among women with CVD is evident. The results suggest that future research about NRT myths pertaining to women is needed. Nurses can help patients dispel these myths and prevent smoking relapse in women with CVD.

Administration, Cutaneous↗