Smoking intensity and urinary nicotine metabolites by socioeconomic status in the Heinz Nixdorf Recall study.

BACKGROUND: Smoking intensity, which is generally based on self-reported average cigarettes per day (CPD), is a major behavioural risk factor and strongly related to socioeconomic status (SES). To assess the validity of the CPD measure, correlations with objective markers of tobacco smoke exposure - such as urinary nicotine metabolites - were examined. Yet, it remains unclear, whether this correlation is affected by SES, which may indicate imprecise or biased self-reports of smoking intensity. METHODS: We investigated the role of SES in the association between CPD and nicotine metabolites in current smokers among the participants of the population-based, prospective Heinz Nixdorf Recall Study. We determined urinary cotinine and additionally trans-3'-hydroxy-cotinine. SES was assessed by the International Socio-Economic Index of occupational status, and education. We calculated correlations (Pearson's r) between logarithmised CPD and cotinine in subgroups of SES and analysed SES and further predictors of cotinine in multiple linear regression models separately by gender. RESULTS: Median reported smoking intensity was 20 CPD in male and 19 CPD in female smokers. Men showed higher cotinine concentrations (median 3652 µg/L, interquartile range (IQR) 2279-5422 µg/L) than women (3127 µg/L, IQR 1692-4920 µg/L). Logarithmised CPD correlated moderately with cotinine in both, men and women (Pearson's r 0.4), but correlations were weaker in smokers with lower SES: Pearson's r for low, intermediate, and high occupational SES was 0.35, 0.39, and 0.48 in men, and 0.28, 0.43, and 0.47 in women, respectively. Logarithmised CPD and urinary creatinine were main predictors of cotinine in multiple regression models, whereas SES showed a weak negative association in women. Results were similar for trans-3'-hydroxy-cotinine. CONCLUSIONS: Decreasing precision of self-reported CPD was indicated for low SES in men and women. We found no strong evidence for biased self-reports of smoking intensity by SES.

Clarifying the Genetic Influences on Nicotine Dependence and Quantity of Use in Cigarette Smokers.

Nicotine dependence and smoking quantity are both robustly associated with the CHRNA5-A3-B4 gene cluster in the 15q25 region, and SNP rs16969968 in particular. The purpose of this paper is to use structural equation modeling techniques (SEM) to disentangle the complex pattern of relationships between rs16969968, nicotine quantity (as measured by the number of cigarettes an individual smokes per day; CPD) and nicotine dependence (as measured by the Fagerström Test for Nicotine Dependence; FTND). CPD is an indicator, but also a potential cause, of FTND, complicating the interpretation of associations between these constructs and requires a more detailed investigation than standard GWAS or general linear regression models can provide. FTND items and genotypes were collected in four samples, with a combined sample size of 5,373 respondents. A mega-analysis was conducted using a multiple group SEM approach to test competing hypotheses regarding the relationships between the SNP rs16969968, FTND and CPD. In the best fitting model, the FTND items loaded onto two correlated factors. The first, labeled "maintenance," assesses the motivation to maintain constant levels of nicotine through out the day. The second was labeled "urgency" as its items concern the urgency to restore nicotine levels after abstinence. We focus our attention on the "maintenance" factor, of which CPD was an indicator. The best fitting model included a negative feedback loop between the Maintenance factor and CPD. Accordingly, the motivation to maintain higher levels of nicotine increased the quantity of nicotine consumed, which subsequently decreases the maintenance motivation. The fact that the Maintenance-CPD feedback model fits the data best implies that there are at least two biological pathways that lead from rs16969968 to smoking behaviors. The model is consistent with a supply and demand system, which allows individuals to achieve a homeostatic equilibrium for their nicotine concentration.

A Paradox: α-Klotho Levels and Smoking Intensity.

Reports regarding smoking differences in α-klotho expression have provided conflicting results. In the current study we focused on the influence of smoking intensity to serum levels of the aging molecule α-klotho in healthy smokers. 40 middle aged healthy smokers without airway obstruction or restriction were selected for the analysis. Serum levels of soluble α-klotho were significantly higher in heavy smokers (P < 0.001). These results are in agreement with the possibility that α-klotho acts as anti-inflammatory molecule and strengthen the hypothesis that an increase of serum levels of α-klotho might be a compensatory response to smoking stress in healthy population.

Primary measures of dependence among menthol compared to non-menthol cigarette smokers in the United States.

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.

Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.

BACKGROUND: The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, epistatic, and gene-environment interactions. METHODS: To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome. RESULTS: Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230, that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000-2011. CONCLUSIONS: To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes.

Neurogenetic underpinnings of nicotine use severity: Integrating the brain transcriptomes and GWAS variants via network approaches.

Our study focused on human brain transcriptomes and the genetic risks of cigarettes per day (CPD) to investigate the neurogenetic mechanisms of individual variation in nicotine use severity. We constructed whole-brain and intramodular region-specific coexpression networks using BrainSpan's transcriptomes, and the genomewide association studies identified risk variants of CPD, confirmed the associations between CPD and each gene set in the region-specific subnetworks using an independent dataset, and conducted bioinformatic analyses. Eight brain-region-specific coexpression subnetworks were identified in association with CPD: amygdala, hippocampus, medial prefrontal cortex (MPFC), orbitofrontal cortex (OPFC), dorsolateral prefrontal cortex, striatum, mediodorsal nucleus of the thalamus (MDTHAL), and primary motor cortex (M1C). Each gene set in the eight subnetworks was associated with CPD. We also identified three hub proteins encoded by GRIN2A in the amygdala, PMCA2 in the hippocampus, MPFC, OPFC, striatum, and MDTHAL, and SV2B in M1C. Intriguingly, the pancreatic secretion pathway appeared in all the significant protein interaction subnetworks, suggesting pleiotropic effects between cigarette smoking and pancreatic diseases. The three hub proteins and genes are implicated in stress response, drug memory, calcium homeostasis, and inhibitory control. These findings provide novel evidence of the neurogenetic underpinnings of smoking severity.

Latent constructs identified in older individuals who smoke cigarettes and are eligible for lung cancer screening: Factor analysis of baseline data from the PLUTO smoking cessation trial.

Introduction: Lung cancer screening (LCS) combined with smoking cessation intervention is currently recommended for older individuals with a history of heavy smoking. Tailoring tobacco treatment for this patient population of older, people who smoke (PWS) may improve cessation rates while efficiently using limited smoking cessation resources. Although some older people who smoke will need more intensive treatment to achieve sustained abstinence, others may be successful with less intensive treatment. A framework to identify them a priori would be helpful to distribute smoking cessation resources accordingly. Methods: Baseline demographic, smoking, and health data are reported from a randomized clinical trial of longitudinal smoking cessation interventions delivered in the setting of LCS. Candidate variables were factor analyzed to identify latent factors, or constructs, to identify subgroups of older participants among the heterogenous population of older people who smoke. Results: We identified three factor-derived constructs: self-reported health status, heaviness of smoking, and nicotine dependence. Nicotine dependence was moderately correlated with both of the other two factors. Conclusions: This factor analysis of baseline participant characteristics identified a set of latent constructs - based on a few practical clinical variables -- that can be used to classify the heterogenous population of older people who smoke to identify. We propose this framework to identify subgroups of people who smoke who might successfully quit with less intense treatment at the time of lung cancer screening.

A cross-sectional investigation of softening indicators among South African smokers: Results from the South African Social Attitudes Survey between 2007 and 2018.

Recent studies have shown softening among smokers in different countries and in different population groups i.e., as smoking prevalence declined remaining smokers made more quit attempts and smoked fewer cigarettes per day (CPD), as opposed to hardening. We examined tobacco use-related cross-sectional data from five waves of the South African Social Attitudes Survey (SASAS 2007-2018, N = 14,822). Accounting for the SASAS's complex survey design, we ran logistic and linear regressions for smoking prevalence, and for the following indicators of softening: plans to quit smoking within a month, time to first cigarette (5 min, TTFC) and cigarettes smoked per day (CPD). We controlled for survey wave, age, sex, race, marital status, educational level and urban/rural residence. Smoking prevalence remained stable from 2007 (20.7%) to 2018 (22.2%) in the overall population of smokers (p = 0.197), and within sex and race group of smokers. In the adjusted model, there was a significant decline in CPD over time, 0.12 cigarettes per year. There was also a significant decrease in TTFC among males over time. Among women, CPD declined significantly by 0.32 cigarettes per year. The proportion of Asians/Indians planning to quit also decreased over time. South African smokers do not consistently show significant change in the softening indicators overall. Stronger tobacco control policies and better-tailored smoking cessation interventions are needed to achieve a significant decrease in smoking prevalence across sex and other subpopulations in South Africa.

Examining moment to moment affective determinants of smoking rate following a quit attempt among homeless daily smokers.

BACKGROUND: Cigarette smoking disproportionately affects homeless individuals, who have a higher smoking prevalence, fewer resources, and increased stressors compared to domiciled smokers. Little is known about how to facilitate smoking cessation among this population although some findings support focusing efforts on affective variables as well as alternate outcomes in order to optimize interventions for this group. METHODS: Participants were homeless adults recruited from a Dallas, TX, shelter (N = 57, 61.4% male, Mage = 48.8 ± 9.0) to participate in tobacco cessation classes using an American Cancer Society-based therapy and support group with nicotine replacement therapy. Moment-to-moment changes in affect [e.g., negative affect (NA), positive affect (PA), and stress] were recorded via Ecological Momentary Assessments to assess whether they were associated with concurrent changes in cigarettes smoked per day (CPD) following a specific quit attempt. Separate generalized linear models (GLM) were evaluated for each predictor to examine the associations between affective variables and CPD in covariate-adjusted analyses. RESULTS: Significant interaction effects of time and affect were found for all variables (NA: p = 0.0011, PA: p = 0.0006, stress: p = 0.0259), whereby the association of affect and CPD were significant in the early part of the week but the effects faded as time progressed. With regard to main effects, only increases in PA during the post-quit week significantly predicted fewer CPD (adjusted incidence rate ratio = 0.924, SE = 0.027, p = 0.0032). CONCLUSIONS: Homeless smokers may be more likely to decrease their cigarette consumption during periods of greater PA throughout the post-quit week. Relationship between positive affect and reduction in CPD suggest focus on affective variables with homeless smokers may be an effective avenue for change in smoking behaviors, particularly in the days immediately following a quit attempt. Time effects should be further investigated to determine when these interventions might best be implemented.

Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium.

While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (rg = 0.159; P = 5.05 × 10-10), cigarettes-smoked-per-day (rg = 0.094; P = 0.006), and age-of-onset of smoking (rg = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg = 0.624, P = 0.002) and cigarettes-smoked-per-day (rg = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10-5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10-8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.

Depressive symptoms predict smoking cessation in a 20-year longitudinal study of adult twins.

Depression has been suggested to hinder smoking cessation, especially when co-occurring with nicotine dependence. The study aimed to examine the longitudinal association of depressive symptoms with smoking cessation among daily smokers. The study utilized adult Finnish twin cohort where 1438 daily smokers (mean age: 38.3, range: 33-45) in 1990 were re-examined for their smoking status in 2011. We assessed baseline depressive symptoms with the Beck Depression Inventory, and the self-reported smoking status at follow-up. The methods included multinomial logistic regression and time to event analyses, adjusted for multiple covariates (age, sex, marital status, social class, heavy drinking occasions, and health status) and smoking heaviness at baseline assessed by cigarettes per day (CPD). Additionally, within-twin-pair analyses were conducted. Results indicated that moderate/severe depressive symptoms at baseline were associated with a lower likelihood of smoking cessation two decades later. Adjusting for covariates, those with moderate/severe depressive symptoms (vs. no/minimal depressive symptoms) had 46% lower likelihood of quitting (relative risk ratio, RRR = 0.54, 95% CI: 0.30-0.96). After including CPD, the association of depressive symptoms with smoking cessation attenuated modestly (RRR = 0.62, 95% CI: 0.34-1.12). Further, time to event analysis for quitting year since baseline yielded similar findings. In the within-pair analysis, depressive symptoms were not associated with quitting smoking. The results suggest that reporting more depressive symptoms is associated with a lower likelihood of smoking cessation during a 20-year period. The baseline amount of smoking and familial factors partly explain the observed association. Smoking cessation programs should monitor depressive symptoms.

Measures of dependence in menthol and nonmenthol smokers - A comprehensive narrative review.

Introduction. More than a decade ago, concerns were raised that menthol in cigarettes might enhance addiction to smoking. This article provides a comprehensive review of published studies examining cigarette dependence among menthol and nonmenthol smokers. The purpose of the review is to evaluate the scientific evidence to determine if menthol increases cigarette dependence. Materials and Methods. The published literature was searched in 2019 for studies that provide evidence on cigarette dependence among menthol compared to nonmenthol smokers. Included in this review are published studies that compare menthol and nonmenthol smokers based on widely accepted and validated measures of dependence, or other established predictors of dependence (age of smoking initiation [first cigarette]/age of progression [regular/daily smoking]) and indicators of dependence (smoking frequency, cigarettes smoked per day, time to first cigarette after waking, night waking to smoke, smoking duration). Results and Conclusion. Based on a review of the available studies, including those with adjusted results and large representative samples, reliable and consistent empirical evidence supports a conclusion that menthol smokers are not more dependent than nonmenthol smokers and thus menthol in cigarettes does not increase dependence.

Long-term smoking cessation rates in elderly versus other adult smokers: A 3-year follow-up study in Taiwan.

INTRODUCTION: Smoking cessation improves life expectancy at any age. There is some evidence that elderly smokers have at least as good a chance of successfully stopping as other smokers but direct comparisons with long-term follow up are rare. This study aimed to compare success rates up to 3 years in smokers aged 65+ versus other adult smokers with and without adjustment for a range of other smoker characteristics. METHODS: This was a prospective study of 1065 smokers who attended a stop-smoking clinic in Taiwan. Participants (896 < 65 years, 169 65+ years) were followed up by telephone 3, 6, 12 and 36 months after the initial quit date. Prolonged abstinence (abstinent at all follow-ups) and point prevalence abstinence (7 days prior to final follow up) were compared between 'elderly' participants aged 65+ years versus 'non-elderly' participants aged <65 years with and without adjustment for a range of baseline smoker characteristics (sex, educational level, previous quit attempts, cigarette dependence score). Non-responders were considered to be smoking. RESULTS: Prolonged 36-month abstinence rates were 20.1% (N = 34) and 15.3% (N = 137) in the elderly and non-elderly participants respectively (p = 0.137). Point prevalence 36-month abstinence rates were 37.3% (N = 63) and 26.5% (N = 237) in the elderly and non-elderly participants respectively (p = 0.005). The odds ratios comparing elderly versus non-elderly abstinence rates after adjustment for baseline variables were 1.17 (95%CI = 0.75-1.83) and 1.52 (95%CI = 1.05-2.20) for prolonged abstinence and point prevalence abstinence respectively. CONCLUSIONS: Elderly smokers attending smoker clinics in Taiwan appear to be at least as likely to achieve long-term abstinence as other adult smokers.

The Importance of Filter Collection for Accurate Measurement of Cigarette Smoking.

OBJECTIVES: We examined the impact of cigarette filter collection on reports of cigarettes per day (CPD) versus self-reported CPD and to assess the utility of a pre-intervention baseline period in smoking studies. METHODS: Using baseline data from 522 non-treatment seeking smokers, we assessed differences in self-reported CPD via phone screen (CPD PS) and during baseline (CPD BL). We analyzed self-reported cigarette measures to predict carbon monoxide (CO), a measure of smoke exposure. RESULTS: On average, CPD PS was 2.8 CPD more than CPD BL, and reporting multiples of 10 were more often found in CPD PS compared with CPD BL (54.7% vs17.2%, respectively). CPD BL was more strongly associated with CO than self-report CPD. Number of cigarettes smoked today, time since last cigarette, and nicotine dependence were significantly associated with CO. CONCLUSIONS: CPD BL using filter collection is a more accurate measure of cigarette consumption than self-report, which may have implications for assessment of nicotine dependence. When feasible, studies should include a pre-intervention baseline period for comparison data with study outcomes. In addition to CPD BL, studies should assess time since last cigarette and the number of cigarettes smoked today when using CO as a biological measure of smoke exposure.

Cigarette smoking among female students in five medical and nonmedical colleges.

OBJECTIVES: This study was conducted to determine the prevalence of smoking, knowledge about the ill effects of smoking on health, and the influence of family members' smoking habits among Saudi female students. METHODS: This is a type of cross-sectional study. A sample of 1,070 female students was selected by a nonrandom and convenient sampling method from five colleges (Medicine, Business and Administration, Computer Sciences, Education, and Languages and Translation) of King Saud University, Riyadh, Saudi Arabia. A self-administrated questionnaire was used to determine the personal, social, and educational characteristics of the respondents. In addition, questions about their smoking types, status, duration of smoking, knowledge about the ill effects of smoking, daily cigarette consumption, and reasons for quitting smoking were included. RESULTS: The students' response rate was 85%. The prevalence of current smoking was 4.3% and 5.6% for cigarettes and water-pipes, respectively, whereas 3.9% of the participants were ex-smokers. The prevalence of current smoking was highest in the College of Business and Administration (10.81%) and lowest in the College of Medicine (0.86%). The majority (77%) of the smokers' parents (current and ex-smokers) were also smokers. More than half (54%) of the smokers started their smoking habit for entertainment, and 44.4% of the participants did not know that smoking causes serious health problems. The most common factors for quitting smoking were health concerns (54%), religious beliefs (29%), and parent's advice (17%). CONCLUSION: The study concludes that the prevalence of smoking varies in different subject streams and that family and friends have a great influence on individuals starting or stopping smoking. Extensive health education programs are needed to educate young women on the health hazards of smoking and help stop them from smoking.