The "Gateway" hypothesis: evaluation of evidence and alternative explanations.

BACKGROUND: Electronic nicotine delivery systems (ENDS) offer a substantial harm reduction opportunity for adults who smoke and are unlikely to quit. However, a major concern about ENDS is their use by non-smoking youth, and particularly whether ENDS are acting as a "gateway" that leads youth to later start smoking cigarettes. However, evidence for the gateway hypothesis can be interpreted in alternative ways, e.g. that youth who have certain characteristics were already predisposed to use both ENDS and cigarettes ("common liability" explanation). AIMS: This commentary provides an evaluation of the gateway hypothesis that is accessible by a lay audience. This paper first reviews and evaluates the evidence interpreted as supporting the gateway hypothesis. Important alternative explanations (i.e., common liability) are discussed, as are different types of evidence (i.e., population-level trends) that can help differentiate between these competing explanations. OVERVIEW: Evidence for the gateway hypothesis is based on the finding that youth who use ENDS are more likely to also smoke cigarettes. However, this evidence suffers from an important flaw: these studies fail to fully account for some youths' pre-existing tendency to use products containing nicotine, and inappropriately interpret the results as ENDS use causing some youth to smoke. Common liability studies suggest that ENDS use does not, in and of itself, directly cause youth to later smoke cigarettes, beyond their pre-existing tendency to use products containing nicotine. Population-level trends show that youth cigarette smoking declined faster after ENDS use became common, which contradicts the central prediction of the gateway hypothesis (i.e. that youth smoking would be more common following ENDS uptake, than otherwise be expected). CONCLUSION: Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking.

Oral microbiome dysbiosis among cigarette smokers and smokeless tobacco users compared to non-users.

Tobacco use significantly influences the oral microbiome. However, less is known about how different tobacco products specifically impact the oral microbiome over time. To address this knowledge gap, we characterized the oral microbiome of cigarette users, smokeless tobacco users, and non-users over 4 months (four time points). Buccal swab and saliva samples (n = 611) were collected from 85 participants. DNA was extracted from all samples and sequencing was carried out on an Illumina MiSeq, targeting the V3-V4 region of the 16S rRNA gene. Cigarette and smokeless tobacco users had more diverse oral bacterial communities, including a higher relative abundance of Firmicutes and a lower relative abundance of Proteobacteria, when compared to non-users. Non-users had a higher relative abundance of Actinomyces, Granulicatella, Haemophilus, Neisseria, Oribacterium, Prevotella, Pseudomonas, Rothia, and Veillonella in buccal swab samples, compared to tobacco users. While the most abundant bacterial genera were relatively constant over time, some species demonstrated significant shifts in relative abundance between the first and last time points. In addition, some opportunistic pathogens were detected among tobacco users including Neisseria subflava, Bulleidia moorei and Porphyromonas endodontalis. Overall, our results provide a more holistic understanding of the structure of oral bacterial communities in tobacco users compared to non-users.

Association between lipid profiles and cigarette smoke among adults in the Persian cohort (Shahedieh) study.

OBJECTIVES: Exposure to cigarette smoke introduces a large amount of nicotine into the bloodstream through the lungs. So, smoking can be a risk factor for many diseases. The present study was conducted to investigate the effect of active and passive cigarette smoke on the blood lipid profile and dyslipidemia. METHODS: This cross-sectional study was performed on 5052 individuals who participated in the recruitment phase of the Shahedieh cohort study. A logistic regression model was used to investigate the relationship between smoking exposure status and lipid profiles. RESULTS: The prevalence of abnormal low-density lipoprotein-cholesterol (LDL-C), abnormal HDL-C, abnormal total cholesterol (TC), abnormal triglyceride (TG), and dyslipidemia were 254 (5.00%), 562 (11.10%), 470 (9.30%), 1008 (20.00%), and 1527 (30.20%), respectively. Adjusting for confounders, it was observed that current smokers had higher odds of having abnormal HDL-C [OR (95% CI), 2.90 (2.28-3.69)], abnormal TG [OR (95% CI), 1.71 (1.38-2.13)] and dyslipidemia [OR (95% CI), 1.86 (1.53-2.25)]. Ex-smokers also had greater odds of abnormal HDL-C [OR (95% CI), 1.51 (1.06-2.16)] compared to non-smokers who were not exposed to cigarette smoke. CONCLUSIONS: The findings indicated that current smokers had higher TG and lower HDL. So, necessary measures should be taken to reduce smoking. The findings also showed that the prevalence of abnormal TG and HDL in ex-smokers was lower than in current smokers. Therefore, the existence of incentive policies to quit smoking seems necessary.

Cigarette Smoking Among Pregnant Women During the Perinatal Period: Prevalence and Health Care Provider Inquiries - Pregnancy Risk Assessment Monitoring System, United States, 2021.

Cigarette smoking during pregnancy increases the risk for pregnancy complications and adverse infant outcomes such as preterm delivery, restricted fetal growth, and infant death. Health care provider counseling can support smoking cessation. Data from the 2021 Pregnancy Risk Assessment Monitoring System were analyzed to estimate the prevalence of smoking before, during, and after pregnancy; quitting smoking during pregnancy; and whether health care providers asked about cigarette smoking before, during, and after pregnancy among women with a recent live birth. In 2021, the prevalence of cigarette smoking was 12.1% before pregnancy, 5.4% during pregnancy, and 7.2% during the postpartum period; 56.1% of women who smoked before pregnancy quit smoking while pregnant. Jurisdiction-specific prevalences of smoking ranged from 3.5% to 20.2% before pregnancy, 0.4% to 11.0% during pregnancy, and 1.0% to 15.1% during the postpartum period. Among women with a health care visit during the associated period, the percentage of women who reported that a health care provider asked about smoking was 73.7% at any health care visit before pregnancy, 93.7% at any prenatal care visit, and 57.3% at a postpartum checkup. Routine assessment of smoking behaviors among pregnant and postpartum women can guide the development and implementation of evidence-based tobacco control measures at the jurisdiction and health care-system level to reduce smoking among pregnant and postpartum women.

Association between loneliness and cigarette smoking attitudes among university students in Iran: a cross-sectional study.

OBJECTIVES: During the last two decades, cigarette smoking witnessed a global increase in use, especially among youth. Loneliness is one of the possible psychosocial determinants of smoking. This study examined the association between loneliness and attitudes towards cigarette smoking among university students of Iran. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: This study was conducted among 538 university students, who were recruited using the cluster random sampling method. Loneliness and smoking attitudes of the samples were assessed using the revised version of the University of California Los Angeles Loneliness Scale and the Scale of Cigarette Smoking Attitude (CSA). Descriptive statistics, Pearson's correlation coefficient and multivariable regression analysis were used to analyse the data. RESULTS: From a total of 538 participants, 301 (59.9%) students were young women. The mean age of the students was 22.2±2.9 years. Only 56 (10.4%) of the students were married and 370 (87.9%) of them were lived with their families. 131 (24.3%) students experienced cigarette smoking. In terms of university-related characteristics, 205 (38.1%) of the students studied in the faculty of medicine. Also, 30% of the students had a positive or indifferent attitude towards smoking, while 26.4% of the students reported feeling lonely. The mean scores for loneliness and CSA were 41.42±11.29 and 48.64±11.2, respectively. Statistically, a significant positive correlation was found between loneliness and CSA (r=0.289; p<0.001). After controlling for potential confounders by regression analysis, loneliness scores were also positively associated with CSA scores (B: 0.14; 95% CI 0.097 to 0.18). CONCLUSIONS: According to the positive association between loneliness and students' CSA, paying more attention to the state of loneliness in college students, examining situations and reasons that increase it and identifying the interventions that might reduce it are necessary. Reducing loneliness among college students can correct their attitudes towards smoking.

The interaction between diet quality and cigarette smoking on the incidence of hypertension, stroke, cardiovascular diseases, and all-cause mortality.

This study aimed to examine the interaction between diet quality indices (DQIs) and smoking on the incidence of hypertension (HTN), stroke, cardiovascular diseases, and all-cause mortality. We prospectively followed 5720 participants and collected dietary data via a validated food frequency questionnaire to calculate DQI-international (DQI-I) and DQI-revised (DQI-R). Considering an interaction analysis, we classified participants based on diet quality (median: higher/lower) and smoking status. Over 9 years of follow-up, higher diet quality scores were associated with a lower risk of stroke and mortality. While current smokers had a higher risk of stroke and mortality but had a lower risk of developing HTN. Compared to the current smokers with lower diet quality, nonsmokers with higher diet quality according to the DQI-I [HR 0.24; 95% CI (0.08, 0.66)], and DQI-R [HR 0.20; 95% CI (0.07, 0.57)] had a lower risk of stroke. Moreover, the lower risk of mortality was more evident in nonsmokers with higher DQI-I [HR 0.40; 95% CI (0.22-0.75)] and DQI-R scores [HR 0.34; 95% CI (0.18-0.63)] compared to nonsmokers with lower diet quality. While higher DQI-I and DQI-R scores were associated with a lower risk of stroke and mortality, this beneficial effect may be negated by smoking.

A miRNA-21-Mediated PTEN/Akt/NF-κB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis.

Background: This study sought to explore the underlying mechanism of miR-21 mediated apoptosis and inflammation in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS). Methods: We detected levels and PTEN/Akt/NF-κB axis protein levels in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Western blotting assay was used to determine the expression of cleaved caspase-3. IL-6 and IL-8 protein was detected in cell supernatant from cells by ELISA. HBE cells were transfected with a miR-21 inhibitor, and co-culture with A549. Results: Increased miR-21 expression, reduced PTEN expression and following activation of Akt in in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Inhibition of miR-21 showed enhanced PTEN levels and reduced the expression of phosphorylated form of Akt and NF-κB. Decreased expression of cleaved caspase-3, IL-6 and IL-8 in A549 cells co cultured with HBE cells transfected with miR-21 inhibitor compared with transfected with miR-21 control inhibitor. Conclusion: MiR-21 contributes to COPD pathogenesis by modulating apoptosis and inflammation through the PTEN/Akt/NF-κB pathway. Targeting miR-21 may increase PTEN expression and inhibit Akt/NF-κB pathway, offering potential diagnostic and therapeutic value in COPD management.

Cigarette smoke impairs the hematopoietic supportive property of mesenchymal stem cells via the production of reactive oxygen species and NLRP3 activation.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in tissue homeostasis by providing a supportive microenvironmental niche for the hematopoietic system. Cigarette smoking induces systemic abnormalities, including an impeded recovery process after hematopoietic stem cell transplantation. However, the role of cigarette smoking-mediated alterations in MSC niche function have not been investigated. METHODS: In the present study, we investigated whether exposure to cigarette smoking extract (CSE) disrupts the hematopoietic niche function of MSCs, and pathways impacted. To investigate the effects on bone marrow (BM)-derived MSCs and support of hematopoietic stem and progenitor cells (HSPCs), mice were repeatedly infused with the CSE named 3R4F, and hematopoietic stem and progenitor cells (HSPCs) supporting function was determined. The impact of 3R4F on MSCs at cellular level were screened by bulk-RNA sequencing and subsequently validated through qRT-PCR. Specific inhibitors were treated to verify the ROS or NLRP3-specific effects, and the cells were then transplanted into the animal model or subjected to coculture with HSPCs. RESULTS: Both direct ex vivo and systemic in vivo MSC exposure to 3R4F resulted in impaired engraftment in a humanized mouse model. Furthermore, transcriptomic profile analysis showed significantly upregulated signaling pathways related to reactive oxygen species (ROS), inflammation, and aging in 3R4F-treated MSCs. Notably, ingenuity pathway analysis revealed the activation of NLRP3 inflammasome signaling pathway in 3R4F-treated MSCs, and pretreatment with the NLRP3 inhibitor MCC950 rescued the HSPC-supporting ability of 3R4F-treated MSCs. CONCLUSION: In conclusion, these findings indicate that exposure to CSE reduces HSPCs supportive function of MSCs by inducing robust ROS production and subsequent NLRP3 activation.

A systematic review and meta-analysis of the association between e-cigarette use among non-tobacco users and initiating smoking of combustible cigarettes.

INTRODUCTION: The rapid increase in e-cigarette use over the past decade has triggered an important public health question on the potential association between e-cigarette use and combustible cigarette smoking. Following AMSTAR 2 and PRISMA guidelines, this evidence synthesis sought to identify and characterize any associations between e-cigarette use among individuals not smoking cigarettes and initiation of cigarette smoking. METHODS: The protocol was registered on September 24, 2018 (PROSPERO 2018 CRD42018108540). Three databases were queried from January 01, 2007 to April 26, 2023. Search results were screened using the PICOS review method. RESULTS: Among 55 included studies (40 "good" and 15 "fair"; evidence grade: "high") that adjusted for gender, age, and race/ethnicity between groups, generally, there was a significant association between non-regular e-cigarette use and initiation of cigarette smoking, further supported by the meta-analytic results (AOR 3.71; 95% CI 2.86-4.81). However, smoking initiation was most often measured as ever/current cigarette smoking. Two studies (quality: 2 "good") evaluated progression to regular cigarette smoking among individuals with regular use of e-cigarettes, and generally found no significant associations. One study ("good") evaluated smoking initiation among individuals with regular use of e-cigarettes, finding an increasing probability of ever smoking cigarettes with increased e-cigarette use. Twelve studies (10 "good" and two "fair") examining progression to regular smoking among individuals with non-regular use of e-cigarettes reported inconsistent findings. CONCLUSIONS: Numerous methodological flaws in the body of literature limit the generalizability of these results to all individuals who are not smoking cigarettes with few studies measuring established/regular use/smoking of e-cigarettes and cigarettes. Further, studies did not control adequately for specific confounding variables representing common liabilities between e-cigarette use and cigarette smoking, nor did they account for sufficient follow-up durations. Collectively, these flaws limit the generalizability of findings to the question of an association between e-cigarette use and cigarette smoking initiation.

GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.

BACKGROUND: Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3 pulmonary hypertension (PH). And G protein pathway suppressor 2 (GPS2) could suppress G-protein signaling such as Ras and MAPK, but its role in cigarette smoking -induced PVR (CS-PVR) is unclear. METHODS: An in vivo model of smoke-exposed rats was constructed to assess the role of GPS2 in smoking-induced PH and PVR. In vitro, the effects of GPS2 overexpression and silencing on the function of human pulmonary arterial smooth cells (HPASMCs) and the underlying mechanisms were explored. RESULTS: GPS2 expression was downregulated in rat pulmonary arteries (PAs) and HPASMCs after CS exposure. More importantly, CS-exposed rats with GPS2 overexpression had lower right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness (WT%) than those without. And enhanced proliferation and migration of HPASMCs induced by cigarette smoking extract (CSE) can be evidently inhibited by overexpressed GPS2. Besides, GPS2siRNA significantly enhanced the proliferation, and migration of HPASMCs as well as activated Ras and Raf/ERK signaling, while these effects were inhibited by zoledronic acid (ZOL). In addition, GPS2 promoter methylation level in rat PAs and HPASMCs was increased after CS exposure, and 5-aza-2-deoxycytidine (5-aza) inhibited CSE-induced GPS2 hypermethylation and downregulation in vitro. CONCLUSIONS: GPS2 overexpression could improve the CS-PVR, suggesting that GPS2 might serve as a novel therapeutic target for PH-COPD in the future.

Tobacco policies and changes in the tendency of smoking cessation in cigarette users in Chile: a longitudinal cross-sectional study.

OBJECTIVE: To assess the impact of tobacco control regulations and policy implementation on smoking cessation tendencies in cigarette users born between 1982 and 1991 in Chile. DESIGN: Longitudinal cross-sectional study. SETTING: National level. PARTICIPANTS: Data from the National Survey of Drug Consumption (Service of Prevention and Rehabilitation for Drug and Alcohol Consumption). A pseudo-cohort of smokers born between 1982 and 1991 (N=17 905) was tracked from 2002 to 2016. PRIMARY AND SECONDARY OUTCOMES MEASURES: Primary outcome was the tendency to cease smoking conceptualised as the report of using cigarettes 1 month or more ago relative to using cigarettes in the last 30 days. The main exposure variable was the Tobacco Policy Index-tracking tobacco policy changes over time. Logistic regression, controlling for various factors, was applied. RESULTS: Models suggested a 14% increase in the smoking cessation tendency of individuals using cigarettes 1 month or more ago relative to those using cigarettes in the last 30 days (OR 1.14, CI 95% CI 1.10 to 1.19) for each point increment in the Tobacco Policy index. CONCLUSIONS: Our study contributes to documenting a positive impact of the implementation of interventions considered in the MPOWER strategy in the progression of smoking cessation tendencies in smokers born between 1982 and 1991 in Chile.

Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex.

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10-4) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10-3). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10-3). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.

The role of interoceptive awareness in shaping the relationship between desire thinking and cigarette consumption.

Interoception, the ability to sense and interpret bodily sensations, has recently emerged as a crucial factor in substance use disorders, including smoking. However, the role of interoceptive awareness in tobacco use remains poorly understood. The relationship between interoceptive ability and addictive behavior is complex, and attempting to conceptualize it as a linear association is unlikely to fully capture the complexity of the mechanisms underlying cravings and urges. We hypothesized that the role played by interoceptive awareness in tobacco use is deeply linked to desire thinking, that is, the conscious and voluntary cognitive process orienting to prefigure images, information, and memories about positive target-related experiences. Desire thinking is typically observed in addiction, where it may contribute to interpreting specific bodily sensations, such as the perceived need for a cigarette. From this perspective, the physiological impact and inclination toward desire thinking contribute to a higher daily cigarette consumption, particularly in situations of low interoceptive awareness. To test this hypothesis, we assessed the physiological activation, the tendency toward desire thinking about smoking, cigarette consumption, and the interoceptive abilities of smoking volunteers. Through a moderation analysis, we showed that desire thinking about smoking predicts a higher number of cigarettes per day in individuals with lower interoceptive awareness (p < .05). These findings suggest that the relationship between desire thinking and interoceptive awareness is a fundamental component of tobacco use, highlighting the importance of taking into account the bodily feedback deriving from the cognitive representation of smoking in addiction research and therapy.

Smoking-Attributable Health Care Expenditures for US Adults With Chronic Lower Respiratory Disease.

Importance: Cigarette smoking is a primary risk factor for chronic lower respiratory disease (CLRD) and is associated with worse symptoms among people with CLRD. It is important to evaluate the economic outcomes of smoking in this population. Objective: To estimate smoking prevalence and cigarette smoking-attributable health care expenditures (SAHEs) for adults with CLRD in the US. Design, Setting, and Participants: This cross-sectional study used data from the 2014-2018 and 2020 National Health Interview Surveys (NHIS) and the 2020 Medical Expenditure Panel Survey. The final study population, stratified by age 35 to 64 years and 65 years or older, was extracted from the 2014-2018 NHIS data. The data analysis was performed between February 1 and March 31, 2024. Exposures: Cigarette smoking, as classified into 4 categories: current smokers, former smokers who quit less than 15 years ago, former smokers who quit 15 or more years ago, and never smokers. Main Outcomes and Measures: Smoking-attributable health care expenditures were assessed using a prevalence-based annual cost approach. Econometric models for the association between cigarette smoking and health care utilization were estimated for 4 types of health care services: inpatient care, emergency department visits, physician visits, and home health visits. Results: In the 2014-2018 NHIS study sample of 13 017 adults, 7400 (weighted 62.4%) were aged 35 to 64 years, 5617 (weighted 37.6%) were 65 years or older, and 8239 (weighted 61.9%) were female. In 2020, among 11 211 222 adults aged 35 to 64 with CLRD, 3 508 504 (31.3%) were current smokers and 3 496 790 (31.2%) were former smokers. Total SAHEs in 2020 for this age group were $13.6 billion, averaging $2752 per current smoker and $1083 per former smoker. In 2020, 7 561 909 adults aged 65 years or older had CLRD, with 1 451 033 (19.2%) being current smokers and 4 104 904 (54.3%) being former smokers. Total SAHEs in 2020 for the older age group were $5.3 billion, averaging $1704 per current smoker and $682 per former smoker. In sum, SAHEs for adults with CLRD aged 35 years or older amounted to $18.9 billion in 2020. Conclusions and Relevance: In this cross-sectional study of adults with CLRD, cigarette smoking was associated with a substantial health care burden. The higher per-person SAHEs for current smokers compared with former smokers suggest potential cost savings of developing targeted smoking cessation interventions for this population.

Use of Menthol Cigarettes and Accessories Among Youth Who Smoked After the Menthol Cigarette Ban in England and Canada, 2021: Implications for Health Equity.

INTRODUCTION: This study examined menthol cigarette use among youth who smoked, after menthol cigarette bans were implemented in England (May 2020) and Canada (October 2017). AIMS AND METHODS: Cross-sectional data come from 2021 ITC Youth Tobacco and Vaping Survey respondents aged 16-19 who smoked in the past 30 d in England (N = 715) and Canada (N = 419). Adjusted logistic regression models, estimated separately for each country, examined sociodemographic correlates of usually smoking menthol cigarettes (reporting currently most often smoking menthol cigarettes) overall, and by past 30-d use of any menthol accessories (e.g., filters, capsules). Youth reported the cigarette variety they smoked most often, coded as menthol or nonmenthol. RESULTS: Almost no youth who smoked in the past 30 d reported most often smoking a cigarette variety coded as menthol. However, 34.5% (95% CI: 30.4% to 38.9%) of youth who smoke in England and 30.9% (26.0%-36.3%) in Canada reported usually smoking menthol cigarettes, with greater odds of use among those identifying as black, or other race/ethnicity, respectively, compared to white in England (60.0%, aOR = 3.08, p = .001; 47.4%, aOR = 2.27, p = .011) and Canada (43.6%, aOR = 2.44, p = .046; 51.2%, aOR = 2.92, p = .001). Among those who reported usually smoking menthol cigarettes in England (N = 223) and Canada (N = 108), 71.7% (64.0%-78.2%) and 51.5% (41.1%-61.7%) reported using menthol accessories. CONCLUSIONS: After menthol cigarette bans in England and Canada, approximately one-third of youth who smoked reported usually smoking menthol cigarettes, with disproportionately higher use among those identifying as black and other race/ethnicity. Menthol accessories accounted for most menthol cigarette use. Closing regulatory loopholes is critical to advancing public health equity. IMPLICATIONS: Use of menthol cigarette accessories (eg, filters, cards, capsules) among youth who smoked was prevalent after implementation of menthol cigarette bans in England and Canada, and there was disproportionately higher use among those who identified as black and any other race/ethnicity. Efforts are therefore required to close regulatory loopholes of menthol cigarette bans. Findings further support countries, such as the United States, proposing menthol cigarette bans which extend coverage to accessories. More comprehensive menthol bans that also restrict accessories are likely to be more effective in reducing flavored tobacco use among young people and in advancing health equity.

Long COVID among US adults from a population-based study: Association with vaccination, cigarette smoking, and the modifying effect of chronic obstructive pulmonary disease (COPD).

OBJECTIVE: Post-COVID Conditions (or Long COVID) have been widely reported, but population-based studies exploring the relationship between its risk factors are lacking. We examined the associations between Long COVID, chronic obstructive pulmonary disease [COPD], vaccination status, and cigarette smoking. We also tested for the modifying effect of COPD status. METHODS: Data from the 2022 US nationwide Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Our primary outcome was Long COVID (Yes/No) after a positive COVID-19 diagnosis. Predictor variables were COPD, coronary heart disease (CHD), diabetes, asthma, body mass index, cigarette smoking status, and number of COVID-19 vaccinations (0-4). Weighted multivariable logistic regression models were used and adjusted for sociodemographic factors. Regression models were used to explore the modifying effects of COPD status. RESULTS: The weighted prevalence of Long COVID among survivors (N = 121,379) was 21.8% (95%CI: 21.4, 22.3), with tiredness/fatigue (26.2% [95%:25.1, 27.2]) as the most common symptom. Respondents with COPD (aOR: 1.71 [95%CI: 1.45, 2.02]), current daily smokers (aOR: 1.23 [95%CI:1.01, 1.49]), and former smokers (aOR: 1.24 [95%CI:1.12, 1.38]) (vs. never established smokers) had higher odds of Long COVID. However, respondents who had received three (aOR: 0.75 [95%CI:0.65, 0.85]) and four (aOR: 0.71 [95%CI:0.58, 0.86]) vaccine doses (vs. no vaccine) had lower odds of Long COVID. COPD had a modifying effect on the relationship between cigarette smoking and Long COVID (p-value: 0.013). CONCLUSION: Our findings underscore a complex interaction between COPD, cigarette smoking, and Long COVID. Further, COVID-19 vaccination may be protective against Long COVID.

Evaluation of micronuclei, cytomorphometric and cytologic changes of the oral mucosa in hookah and cigarette smokers.

OBJECTIVE: To analyze the effect of hookah and cigarettes on the oral mucosa of smokers through the use of exfoliative cytology. STUDY DESIGN: Smear samples were collected by exfoliative cytology from the tongue of 33 hookah smokers, 22 cigarette smokers, and 30 non-smokers. The selected analyses include micronuclei (MN), metanuclear anomalies, epithelial maturation, and cytomorphology (nuclear area [NA], cytoplasmic area [CA], and NA/CA ratio). RESULTS: The largest differences observed for MN and metanuclear anomalies were between cigarette smokers and the control group (notably 1 MN P = .04; total cells with MN P = .039; total MN P = .042; karyorrhexis and binucleation, P = .0001). The hookah group, compared with the control group, showed the greatest differences for karyolysis (P = .0023), binucleation (P = .0003), and broken egg (P = .008). Significant differences were found between the smokers and the control groups regarding changes in the superficial cell without nucleus, perinuclear halo, vacuolization, color change, mucus, and keratohyalin granules. There was a significant increase in the NA and NA/CA ratio in the smoker groups. CONCLUSION: This study showed that a combined analysis of exfoliative cytology associated with other diagnostic methods is a useful tool for studying oral carcinogenesis. Hookah and cigarettes showed similar effects in terms of displaying substantial cytogenetic and cytotoxic damage.

FBXL19 Targeted STK11 Degradation Enhances Cigarette Smoke-Induced Airway Epithelial Cell Cytotoxicity.

Objective: To investigate the effects of cigarette smoke (CS) on Serine/Threonine Kinase 11 (STK11) and to determine STK11's role in CS-induced airway epithelial cell cytotoxicity.Methods: STK11 expression levels in the lung tissues of smokers with or without COPD and mice exposed to CS or room air (RA) were determined by immunoblotting and RT-PCR. BEAS-2Bs-human bronchial airway epithelial cells were exposed to CS extract (CSE), and the changes in STK11 expression levels were determined by immunoblotting and RT-PCR. BEAS-2B cells were transfected with STK11-specific siRNA or STK11 expression plasmid, and the effects of CSE on airway epithelial cell cytotoxicity were measured. To determine the specific STK11 degradation-proteolytic pathway, BEAS-2Bs were treated with cycloheximide alone or combined with MG132 or leupeptin. Finally, to identify the F-box protein mediating the STK11 degradation, a screening assay was performed using transfection with a panel of FBXL E3 ligase subunits.Results: STK11 protein levels were significantly decreased in the lung tissues of smokers with COPD relative to smokers without COPD. STK11 protein levels were also significantly decreased in mouse lung tissues exposed to CS compared to RA. Exposure to CSE shortened the STK11 mRNA and protein half-life to 4 h in BEAS-2B cells. STK11 protein overexpression attenuated the CSE-induced cytotoxicity; in contrast, its knockdown augmented CSE-induced cytotoxicity. FBXL19 mediates CSE-induced STK11 protein degradation via the ubiquitin-proteasome pathway in cultured BEAS-2B cells. FBXL19 overexpression led to accelerated STK11 ubiquitination and degradation in a dose-dependent manner.Conclusions: Our results suggest that CSE enhances the degradation of STK11 protein in airway epithelial cells via the FBXL19-mediated ubiquitin-proteasomal pathway, leading to augmented cell death.HIGHLIGHTSLung tissues of COPD-smokers exhibited a decreased STK11 RNA and protein expression.STK11 overexpression attenuates CS-induced airway epithelial cell cytotoxicity.STK11 depletion augments CS-induced airway epithelial cell cytotoxicity.CS diminishes STK11 via FBXL19-mediated ubiquitin-proteasome degradation.