Differences in the rate of nicotine metabolism among smokers with and without HIV.
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ABSTRACT:
SUBMITTER: Ashare RL
PROVIDER: S-EPMC6457129 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Differences in the rate of nicotine metabolism among smokers with and without HIV.
Ashare Rebecca L RL Thompson Morgan M Leone Frank F Metzger David D Gross Robert R Mounzer Karam K Tyndale Rachel F RF Lerman Caryn C Mahoney Martin C MC Cinciripini Paul P George Tony P TP Collman Ronald G RG Schnoll Robert R
AIDS (London, England) 20190501 6
<h4>Objective</h4>HIV-infected smokers lose more life years to tobacco use than to HIV infection. The nicotine metabolite ratio (NMR), a biomarker of CYP2A6, represents individual variation in the rate at which nicotine is metabolized and is associated with response to smoking cessation treatments. We evaluated whether HIV-infected smokers metabolize nicotine faster than HIV-uninfected smokers, which may contribute to the disproportionate smoking burden and may have important treatment implicati ...[more]
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Project description:IntroductionSmokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers.MethodsWe recruited pregnant women who smoked at least 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine (3HC)/cotinine)-a biomarker of nicotine metabolism-OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking.ResultsAmong 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n = 14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p = .0007), serum 3HC (81.0 vs. 42.0 ng/mL, p = .0001), and NMR (0.63 vs. 0.43, p < .0001). In addition, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p = .0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p = .012), specifically methadone-maintained smokers (p = .024), than non-OU smokers.ConclusionsOur preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance.ImplicationsAmong pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users-the majority of whom were on methadone maintenance-compared to nonusers, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.
| S-EPMC7249922 | biostudies-literature
Project description:BackgroundIndividual differences in the rate of nicotine metabolism contribute to differences in tobacco use, dependence, and efficacy of smoking cessation treatments and can be assessed using the nicotine metabolite ratio (NMR), a validated biomarker for CYP2A6 activity. Despite the high cigarette smoking rates observed in opioid users, no data have been reported on NMR among this population as they has been largely excluded from previous studies that have examined the relationship between tobacco use characteristics and rate of nicotine metabolism.MethodsA linear regression model was used to examine the relationship between tobacco use characteristics and NMR among smokers taking buprenorphine for opioid dependency (N=141). The relationship between buprenorphine dose and NMR was also examined. All participants were enrolled in an intervention designed to promote cigarette-smoking cessation, though participants did not need to stop smoking to enroll.Results and conclusionsRate of nicotine metabolism assessed using the NMR was positively associated with cigarettes smoked in the past 24h, but was not related to time to first cigarette or past year quit attempts. Dose of buprenorphine was not associated with NMR, suggesting no association with rate of nicotine metabolism. Our results suggest that NMR is related to tobacco use among persons enrolled in opioid treatment, as reported in general population smokers and may be a useful biomarker to include in future research assessing efficacy of tobacco cessation interventions in this population.
| S-EPMC5553616 | biostudies-literature
Project description:IntroductionPLWHA who smoke have shown lower cessation rates within placebo-controlled randomized trials of varenicline. Adherence and rate of nicotine metabolism may be associated with quit rates in such clinical trials.MethodsThis secondary analysis of a randomized placebo-controlled trial of varenicline for smoking among PLWHA (N = 179) examined the relationship between varenicline adherence (pill count, ≥80% of pills), nicotine metabolism (based on the nicotine metabolite ratio; NMR) and end-of-treatment smoking cessation (self-reported 7-day point prevalence abstinence, confirmed with carbon monoxide of ≤ 8 ppm, at the end of treatment; EOT).ResultsCombining varenicline and placebo arms, greater adherence (OR = 1.011, 95% CI:1.00-1.02, p = 0.051) and faster nicotine metabolism (OR = 3.08, 95% CI:1.01-9.37, p = 0.047) were related to higher quit rates. In separate models, adherence (OR = 1.009, 95% CI:1.004-1.01, p < 0.001) and nicotine metabolism rate (OR = 2.04, 95% CI:1.19-3.49, p = 0.009) interacted with treatment arm to effect quit rates. The quit rate for varenicline vs. placebo was higher for both non-adherent (19% vs. 5%; χ2[1] = 2.80, p = 0.09) and adherent (35% vs. 15%; χ2[1] = 6.51, p = 0.01) participants, but the difference between treatment arms was statistically significant only for adherent participants. Likewise, among slow metabolizers (NMR < 0.31), the varenicline quit rate was not significantly higher vs. placebo (14% vs. 5%; χ2[1] = 1.17, p = 0.28) but, among fast metabolizers (NMR ≥ 0.31), the quit rate for varenicline was significantly higher vs. placebo (33% vs. 14%; χ2[1] = 4.43, p = 0.04).ConclusionsIncreasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA.
| S-EPMC7572610 | biostudies-literature
Project description:BACKGROUND:Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. METHODS:Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). RESULTS AND CONCLUSIONS:There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6±1.3 vs 4.1±0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increase the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population.
| S-EPMC4880506 | biostudies-literature
Project description:RationalePeople with HIV (PWH) smoke cigarettes at much higher rates than the general population and evidence-based cessation methods are less effective, putting PWH at greater risk for negative health outcomes. It is critical to identify the factors that underlie this health disparity. Delay discounting-the decline in the value of a reward when it is delayed-may explain this disparity.ObjectivesThis study aimed to (1) compare delay discounting between adult smokers with HIV and without HIV and (2) evaluate whether acute smoking abstinence disproportionately increases delay discounting among smokers with HIV.MethodsThis sub-study was part of a larger study (NCT03169101) examining predictors of smoking cessation outcomes among smokers with HIV (n = 34) and smokers without HIV (n = 46) at two counterbalanced laboratory sessions (once smoking-as-usual and once following 24-h biochemically confirmed abstinence) then again, after 8 weeks of smoking cessation treatment.ResultsThere were no significant differences in delay discounting rates between HIV status groups (p = 0.49) or within-subject abstinence effects (p = 0.70). However, smokers without HIV exhibited a significant increase in delay discounting following smoking cessation treatment compared to baseline (p = 0.02), whereas the change among smokers with HIV did not reach statistical significance (p = 0.09).ConclusionsThese findings do not support differences in delay discounting as a reason for the lower success rates of HIV+ smokers at quitting. Although delay discounting may not explain the disparity in smoking rates between people with and without HIV, future work should focus on additional correlates of higher smoking rates and lower quit rates among people with HIV.
| S-EPMC7855959 | biostudies-literature
Project description:Background and objectivesPersons with current or past major depressive disorder (MDD) vs those without have higher smoking rates. The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD-). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD- smokers.MethodsUsing baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (N = 279) and MDD- (N = 1575) smokers. We also compared groups on and nicotine withdrawal and craving.ResultsMean NMR (β = -.02, 95% confidence interval [CI]: -0.05 to 0.01, P = .13) and the distribution of smokers across NMR quartiles (odds ratio [OR] = 0.76, 95% CI: 0.50 to 1.16, P = .21) were similar between MDD+ and MDD- samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (Ps < .05). MDD+ smokers had significantly higher withdrawal and craving than MDD- smokers (Ps < .05).Discussion and conclusionsWhile variability in NMR may not explain differences in smoking rates between MDD+ and MDD- smokers, MDD+ smokers report increased withdrawal and craving.Scientific significanceIn this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00-00).
| S-EPMC8243789 | biostudies-literature
Project description:BackgroundIn samples from controlled randomized clinical trials, a smoker's rate of nicotine metabolism, measured by the 3-hydroxycotinine to cotinine ratio (NMR), predicts response to transdermal nicotine. Replication of this relationship in community-based samples of treatment-seeking smokers may help guide the implementation of the NMR for personalized treatment for nicotine dependence.MethodsData from a community-based sample of treatment seeking smokers (N=499) who received 8weeks of transdermal nicotine and 4 behavioral counseling sessions were used to evaluate associations between the NMR and smoking cessation. Secondary outcomes included withdrawal and craving, depression and anxiety, side effects, and treatment adherence.ResultsThe NMR was a significant predictor of abstinence (OR=.56, 95% CI: 0.33-0.95, p=.03), with faster metabolizers showing lower quit rates than slower metabolizers (24% vs. 33%). Faster nicotine metabolizers exhibited significantly higher levels of anxiety symptoms over time during treatment, vs. slower metabolizers (NMR x Time interaction: F[3,357]=3.29, p=.02). NMR was not associated with changes in withdrawal, craving, depression, side effects, and treatment adherence (p's>.05).ConclusionsIn a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment program, vs. slower nicotine metabolizers. These results provide further evidence that transdermal nicotine is less effective for faster nicotine metabolizers and suggest the need to address cessation-induced anxiety symptoms among these smokers to increase the chances for successful smoking cessation.
| S-EPMC4558221 | biostudies-literature
Project description:IntroductionIndividuals with psychiatric conditions smoke at higher rates than the general population and may need more intensive treatment to quit. We examined whether or not extended treatment with nicotine patch, combined with behavior counseling, would disproportionally benefit smokers with versus without a lifetime psychiatric condition.MethodsWe conducted a secondary analysis of data from an effectiveness trial of treatment with 12 counseling sessions (48 weeks) and 21-mg nicotine patch (8, 24, or 52 weeks) among 525 adult daily smokers. A structured clinical interview assessed past and current psychiatric disorders (major depression, generalized anxiety disorder, alcohol abuse and/or dependence, and substance abuse and/or dependence), as described in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Abstinence was bioverified at week 52. Logistic regression evaluated the effect of the psychiatric status × treatment duration interaction on abstinence at week 52, covarying for sociodemographics, baseline psychological symptoms, and treatment adherence.ResultsAt baseline, 115 (21.9%) participants were diagnosed with one or more psychiatric conditions. The psychiatric status × treatment duration interaction was significant for week 52 abstinence (p = .027). Abstinence rates between smokers with versus without a psychiatric condition in the 24-week treatment arm (9.3% vs. 31.5% abstinent) significantly differed from the 8-week treatment arm (18.8% vs. 22.3%), p = .017. Abstinence rates for smokers with (22.5%) versus without a psychiatric condition (19.7%) in the 52-week treatment arm did not differ from those in the 8-week arm.ConclusionsTargeted smoking cessation treatment, rather than extending treatment duration, may be especially warranted to optimize treatment for smokers with comorbid mood, anxiety, and substance use disorders.ImplicationsIndividuals with psychiatric conditions smoke at higher rates and have greater difficulty quitting compared to those in the general population, but little is known about how to best optimize treatment for this high tobacco burden population. The present study found that cessation response to extended duration treatment with the transdermal nicotine patch did not differ for smokers with versus without comorbid anxiety, mood, and substance use disorders in a large-scale clinical effectiveness trial. Development of targeted behavioral treatments may be required to optimize abstinence outcomes for this high-risk population, rather than simply extending the duration of pharmacotherapy treatments.
| S-EPMC7297011 | biostudies-literature
Project description:BackgroundNicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on nicotine metabolism profiles in vivo and the importance of genetic variants in nicotine-metabolizing enzyme genes on urinary nicotine metabolites levels.MethodsUrine samples from 722 smokers who participated in the Singapore Chinese Health Study were analyzed using UPLC-MS/MS to detect nicotine and eight of its urinary metabolites, and a total of 58 variants in 12 genes involved in nicotine metabolism were investigated in 475 of these subjects with informative genotyping data.ResultsUrine samples stratified by the ratio of 3HC/cotinine exhibited a 7-fold increase in nicotine-N'-oxide, a 6-fold increase in nicotine-Glucuronide (Gluc), and a 5-fold decrease in 3HC-Gluc when comparing the lower versus upper 3HC/cotinine ventiles. Significant (P < 0.0001) associations were observed between functional metabolizing enzyme genotypes and levels of various urinary nicotine metabolites, including CYP2A6 genotype and levels of nicotine, nicotine-Gluc, nicotine-N'-oxide and 3HC, UGT2B10 genotype and levels of cotinine, nicotine-Gluc and cotinine-Gluc, UGT2B17 genotype and levels of 3HC-Gluc, FMO3 genotype and levels of nicotine-N'-oxide, and CYP2B6 genotype and levels of nicotine-N'-oxide and 4-hydroxy-4-(3-pyridyl)-butanoic acid.ConclusionsThese data suggest that several pathways are important in nicotine metabolism.ImpactGenotype differences in several nicotine-metabolizing enzyme pathways may potentially lead to differences in nicotine dependence and smoking behavior and cessation.
| S-EPMC9827107 | biostudies-literature
Project description:BackgroundSocioeconomic status (SES) is a major determinant of tobacco use but little is known whether SES affects nicotine exposure and the degree of nicotine dependence.MethodsThe Pennsylvania Adult Smoking Study is a cross-sectional study of smoke exposure and nicotine dependence among adults conducted in central Pennsylvania between June 2012 and April 2014. The study included several measures of SES, including assessments of education and household income, as well as occupation, home ownership, health insurance, household density and savings accounts. Measurements included saliva for the nicotine metabolites cotinine (COT), 3-'hydroxycotinine (3HC) and total metabolites (COT +3HC). Puffing behavior was determined using portable smoking topography devices.ResultsThe income levels of lighter smokers (< 20 cigarettes per day) was $10,000 more than heavier smokers. Higher Fagerström Test for Nicotine Dependence scores were associated with lower income and job status, scores ranged from 5.4 in unemployed, 4.4 in blue-collar, and 3.8 in white-collar workers. In principal components analysis used to derive SES indicators, household income, number in household, and type of dwelling were the major SES correlates of the primary component. Job category was the major correlate of the second component. Lower SES predicted significantly higher adjusted total nicotine metabolite levels in the unemployed group. Job category was significantly associated with total daily puffs, with the highest level in the unemployed, followed by blue-collar workers, after adjustment for income.ConclusionsAmong smokers, there was a relationship between lower SES and increased nicotine dependence, cigarettes per day and nicotine exposure, which varied by job type.
| S-EPMC6448228 | biostudies-literature