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Combustible cigarette and heated tobacco products (HTPs), the two most frequently used tobacco products, negatively affect bone healing. However, whether smoking cessation following fracture benefits bone healing is unclear. Therefore, this study investigated the effect of smoking cessation immediately after surgery on reduced fracture healing induced by smoking. Smoking combustible cigarettes and heated tobacco products generates cigarette smoking extracts (CSE) (extracts from combustible cigarettes [cCSE] and from HTPs [hCSE], respectively). In vivo, CSEs were injected intraperitoneally into rat models for 3 weeks before femoral midshaft osteotomy and fixation. The rats were then divided into CSE continuation and cessation groups postoperatively. Micro-computed tomography (μCT) and biomechanical analyses were performed 6 weeks postoperatively to assess bone union at the fracture site. In vivo study showed μCT assessment also revealed significantly higher cortical bone mineral density (p = 0.013) and content (p = 0.013), and a higher bone union score (p = 0.046) at the fracture site in the cCSE cessation group than in the cCSE continuation group. Biomechanical assessment revealed that elasticity at the fracture site was significantly higher in the cCSE cessation group than in the cCSE continuation group (p = 0.041). These findings provide that smoking cessation, particularly of combustible cigarette, immediately after a fracture accelerates bone fracture healing and increases mechanical strength at the fracture site., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The prevalence of cigarette smoking among adults aged ≥55 has remained stagnant over the past decade. National data modelling suggests no reduction in cigarette smoking prevalence attributable to e-cigarette use in the USA among people aged ≥45. Misperceptions about the absolute risks (ie, cigarettes are not harmful) and relative risks (ie, e-cigarettes are more harmful than cigarettes) of tobacco products may contribute to sustained smoking prevalence and hesitancy to switch from cigarettes to e-cigarettes among older adults., Methods: Participants reported cigarette use (n=8072) at Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health Study. Weighted multivariable logistic regressions included six age categories (independent variable) and cigarette and e-cigarette risk perceptions (outcomes). Additional models assessed the associations between dichotomous age (≥55 vs 18-54), risk perceptions and an interaction term (independent variables) with past 12-month quit attempts and past-month e-cigarette use (outcomes)., Results: Adults aged ≥65 were less likely than adults aged 18-24 to rate cigarettes as very/extremely harmful (p<0.05). Odds of rating e-cigarettes as more harmful than cigarettes among adults aged 55-64 and ≥65 were 1.71 (p<0.001) and 1.43 (p=0.024) greater than for adults aged 18-24. This misperception was negatively associated with past-month e-cigarette use and was stronger among adults aged ≥55 (p<0.001) than adults aged <55 (p<0.001)., Discussion: Adults aged ≥55 are more likely to have misperceptions about the absolute and relative risks of tobacco products, which may contribute to continued smoking. Health communications targeting this age group could modify beliefs about the perceived harms of tobacco products., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer 1,2 . Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA. We reveal a pattern highly indicative of tissue-context-based selection for ecDNAs, linking their genomic content to their tissue of origin. We show that not only is ecDNA a mechanism for amplification of driver oncogenes, but it also a mechanism that frequently amplifies immunomodulatory and inflammatory genes, such as those that modulate lymphocyte-mediated immunity and immune effector processes. Moreover, ecDNAs carrying immunomodulatory genes are associated with reduced tumour T cell infiltration. We identify ecDNAs bearing only enhancers, promoters and lncRNA elements, suggesting the combinatorial power of interactions between ecDNAs in trans. We also identify intrinsic and environmental mutational processes linked to ecDNA, including those linked to its formation, such as tobacco exposure, and progression, such as homologous recombination repair deficiency. Clinically, ecDNA detection was associated with tumour stage, more prevalent after targeted therapy and cytotoxic treatments, and associated with metastases and shorter overall survival. These results shed light on why ecDNA is a substantial clinical problem that can cooperatively drive tumour growth signals, alter transcriptional landscapes and suppress the immune system., (© 2024. The Author(s).)

Aim: We want to verify the correlation between the increasing use of novel nicotine-containing products (NNCPs) and non-nicotine delivery products (NNDPs) among young individuals and the escalating negative health consequences, necessitating their prohibition., Methods: We performed a comprehensive analysis of the most relevant literature about the utilisation of NNCPs and NNDPs among young individuals and their health effects., Results: Despite being initially seen as less harmful alternatives, for smokers aiming to quit, these products have become more popular due to misleading marketing claims. Teenagers using NNCPs and NNDPs, despite having no smoking history, are more likely to transition to tobacco smoking. Consistent use can lead to health issues like pulmonary damage, asthma, and cardiovascular and ocular problems., Conclusion: The EAP and the ECPCP endorse the WHO's appeal to outlaw these hazardous products. They urge European governments to forbid the sale of NNCPs and NNDPs to children and adolescents in order to safeguard their well-being. They also propose specific recommendations (box 4) to support this cause., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Vascular remodeling is a dynamic process involving cellular and molecular changes, including cell proliferation, migration, apoptosis and extracellular matrix (ECM) synthesis or degradation, which disrupt the homeostasis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Cigarette smoke exposure (CSE) is thought to promote vascular remodeling, but the components are complex and the mechanisms are unclear. In this review, we overview the progression of major components of cigarette smoke (CS), such as nicotine and acrolein, involved in vascular remodeling in terms of ECs injury, VSMCs proliferation, migration, apoptosis, and ECM disruption. The aim was to elucidate the effects of different components of CS on different cells of the vascular system, to discover the relevance of their actions, and to provide new references for future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections., Objectives: Does switching from cigarettes to HTPs improve responses to pulmonary infection., Methods: We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes., Main Results: Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12 h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group., Conclusions: This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products., (© 2024. The Author(s).)

Chronic smokers have increased risk of fibrosis-related atrial fibrillation. The use of heated-tobacco products (HTPs) is increasing exponentially, and their health impact is still uncertain. We aim to investigate the effects of circulating molecules in exclusive HTP chronic smokers on the fibrotic behavior of human atrial cardiac stromal cells (CSCs). CSCs were isolated from atrial tissue of elective cardiac surgery patients, and exposed to serum lots from young healthy subjects, stratified in exclusive HTP smokers, tobacco combustion cigarette (TCC) smokers, or nonsmokers (NS). CSCs treated with TCC serum displayed impaired migration and increased expression of pro-inflammatory cytokines. Cells cultured with HTP serum showed increased levels of pro-fibrotic markers, and reduced expression of connexin-43. Both TCC and HTP sera increased collagen release and reduced secretion of angiogenic protective factors from CSCs, compared to NS serum. Paracrine support to tube-formation by endothelial cells and to viability of cardiomyocytes was significantly impaired. Treatment with sera of both smokers groups impaired H 2 O 2 /NO release balance by CSCs and reduced early phosphorylation of several pathways compared to NS serum, leading to mTOR activation. Cotreatment with rapamycin was able to reduce mTOR phosphorylation and differentiation into aSMA-positive myofibroblasts in CSCs exposed to TCC and HTP sera. In conclusion, the circulating molecules in the serum of chronic exclusive HTP smokers induce fibrotic behavior in CSCs through activation of the mTOR pathway, and reduce their beneficial paracrine effects on endothelial cells and cardiomyocytes. These results point to a potential risk for cardiac fibrosis in chronic HTP users., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Biondi-Zoccai reports a relationship with Cardionovum, Crannmedical, Innovheart, Meditrial, Opsens Medical, Replycare, and Terumo that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tobacco smoking is a major worldwide health issue that contributes to millions of deaths annually. Electronic cigarettes (E-cigarettes) are also harmful. Smoke/vapor from E-cigarettes and tobacco products consists of free radicals and other toxic substances. Tissue damage in smokers, such as lungs, is highly observed and is linked to oxidative damage and inflammation., Methods: The inflammation and oxidative status of rat lung tissues was examined following whole-body smoke/vapor exposure via E-cigarette, cigarette, and waterpipe for 2 h daily, 5 days per week for 8 weeks., Results: Lung tissue damage was higher in cigarettes and waterpipe groups compared to the E-cigarette group. Collectively, there was a significant increase (p < 0.05) in the mRNA expression of pro-inflammatory mediators (TNF-α, NF-κB, IL-1β) with the exception of IL-1β in the E-cigarettes group. As for the anti-inflammatory mediators (Nrf2 and IL-10), a significant reduction (p < 0.05) of mRNA expression was observed with the exception of Nrf2 in the E-cigarette group. As for IL-6, there was a significant increase in its mRNA expression (p < 0.05) in the cigarette and waterpipe groups. There was also a significant decrease (p < 0.05) in the antioxidant activity of all antioxidants tested (GPx, SOD, and CAT) in all groups with the exception of SOD in the cigarette group., Conclusion: Smoke/vapor administered via E-cigarette, cigarette, and waterpipe elicits inflammation and oxidative stress in rat lungs that is accompanied by histopathological changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The use of electronic cigarettes (e-cigarettes) as a perceived safer alternative to traditional cigarettes has grown rapidly. However, the cardiovascular risks associated with e-cigarettes compared to regular cigarettes remain unclear., Objective: To systematically review and compare the cardiovascular outcomes of e-cigarette use versus traditional cigarette use, focusing on the risks of myocardial infarction, arrhythmias, and sudden death., Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Peer-reviewed studies published in English were included if they reported cardiovascular outcomes related to e-cigarette or traditional cigarette use. A total of 20 studies were included, covering observational and interventional studies focusing on heart rate variability, myocardial infarction, arrhythmias, and sudden cardiac events. The quality of the evidence was assessed using the GRADE criteria, and data were extracted and analyzed based on the PICOS (Population, Interventions, Comparisons, Outcomes, and Study designs) framework., Results: The systematic review found that both e-cigarettes and traditional cigarettes pose significant cardiovascular risks, with traditional cigarettes linked to a higher incidence of myocardial infarction, arrhythmias, and sudden cardiac death. E-cigarette users also face increased risks of arrhythmias and myocardial infarction compared to non-smokers, primarily due to the constituents of aerosolized e-liquid, including nicotine and flavorings, which contribute to adverse cardiac effects. Regular e-cigarette use, particularly in combination with traditional cigarette use, was associated with a heightened risk of myocardial infarction. Studies also reported heart function abnormalities, such as systolic and diastolic dysfunction, and reduced ejection fractions. Additionally, changes in heart rate variability, heart rate, and blood pressure were observed, indicating both acute and chronic effects of e-cigarettes on cardiovascular autonomic regulation., Conclusions: While e-cigarettes may present a lower cardiovascular risk compared to traditional cigarettes, they are not without harm. Both products are linked to increased risks of myocardial infarction and arrhythmias, though traditional cigarettes pose a higher overall threat. Given the limitations in the current evidence base, particularly concerning the long-term effects of e-cigarette use, further research is needed to clarify these cardiovascular risks and inform public health guidelines., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure., Methods: We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine., Results: Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes., Conclusion: These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit., (© 2024. The Author(s).)

The World No Tobacco Day 2022 theme emphasised tobacco's adverse environmental effects, including through agriculture, manufacturing, distribution, use and the disposal of tobacco product waste. A main concern regarding this toxic waste is the cigarette filter, which is attached to nearly all commercial cigarettes and is predominantly made from a plant-based plastic (cellulose acetate). Laboratory studies have demonstrated the chemical toxicity of discarded cigarette butts, and there is growing public concern regarding environmental plastic pollution resulting from single-use cellulose acetate filters. Important considerations are whether the filter has any protective role against the harms of smoking and whether it should be regulated as a plastic environmental pollutant. There is persistent misunderstanding among smokers and policy makers about the implied value of the cigarette filter. The cellulose acetate filter is simply a marketing tool that encourages smoking initiation and reduces intentions to quit smoking. This is because it makes smoking easier and implies added safety through the presumed filtration of inhaled smoke. The sale of filtered cigarettes should be prohibited to protect public health and the environment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system., Methods and Results: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine., Conclusions: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.

Background: The addictive potential of areca nut (AN) and tobacco is well-documented, but their combined neurobiological effects in AN-containing tobacco products (ANTP) remain obscure. This study employed a three-stage in silico approach to investigate the potential targets and pathways associated with the addictive properties of AN alone and in ANTP., Materials and Methods: Bioactive molecules were retrieved for AN and tobacco, followed by target prediction and pathway enrichment analysis. The identified biomolecules were categorized into AN and ANTP groups., Results: A total of 195 bioactive molecules were identifid (38 to AN, 157 to tobacco). Absorption, distribution, metabolism, and excretion (ADME) details were retrieved. Predicted bioactivity (gene/protein interaction probability ≥80%) was analysed, revealing 13 shared targets between AN and tobacco, 12 exclusive to AN, and 33 exclusive to tobacco. AN and ANTP influenced 21 and 27 pathways (FDR ≤ 0.05), respectively, with distinct footprints. Notably, GABAergic and cholinergic synapses, nicotine addiction, calcium signaling, and morphine addiction pathways were differentially enriched between AN and ANTP., Discussion: This study highlights the distinct and synergistic neurobiological effects of AN and tobacco in ANTP. The identified differences in target genes and pathways underscore the need for tailored interventions and cessation strategies for users of AN and ANTP products. Further research is warranted to validate these findings, explore interplay between diverse addiction factors, and develop effective prevention and treatment programs. (Neuropsychopharmacol Hung 2024; 26(3): 133-143)

Background: Heated tobacco products (HTPs) have emerged as alternatives to conventional cigarettes. However, their health effects remain largely unknown. This study aimed to prospectively explore the association between the use of cigarettes and HTPs and the risk of hypertension., Methods: This cohort study analysed data from 30 152 workers (82.0% men, mean age 42.9 ± 11.0 years) who were initially free of hypertension, participating in the Japan Epidemiology Collaboration on Occupational Health Study. Participants were categorized into five groups based on their self-reported tobacco product use: never smokers, past smokers, exclusive cigarette smokers, exclusive HTP users and dual users of cigarettes and HTPs. Hypertension cases were identified using three data points from annual health checkup data collected between 2019 and 2021. Cox proportional hazards regression models were used to investigate the association between tobacco product use and hypertension., Results: During a mean follow-up of 2.6 years (range: 0.1-4.0 years), 3656 new cases of hypertension were identified. Compared with never smokers, the risk of hypertension was higher among exclusive cigarette smokers [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.13-1.41] and exclusive HTP users (HR 1.19, 95% CI 1.06-1.34). There was also a suggestion of increased risk of hypertension among dual users (HR 1.16, 95% CI 0.98-1.38). Furthermore, the risk of hypertension increased with the intensity of cigarette/HTP use in all tobacco product users., Conclusions: Similarly, both cigarette smoking and HTP use elevate the risk of hypertension. HTPs should not be regarded as less harmful alternatives to traditional cigarettes for preventing hypertension., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is caused by chronic exposure to toxic particles and gases, such as cigarette smoke. Free radicals, which are produced during a stress response to toxic particles, play a crucial role in disease progression. Measuring these radicals is difficult since the complex mixture of chemicals within cigarette smoke interferes with radical detection. We used a new quantum sensing technique called relaxometry to measure free radicals with nanoscale resolution on cells from COPD patients and healthy controls exposed to cigarette smoke extract (CSE) or control medium. Epithelial cells from COPD patients display a higher free radical load than those from healthy donors and are more vulnerable to CSE. We show that epithelial cells of COPD patients are more susceptible to the damaging effects of cigarette smoke, leading to increased release of free radicals.

Background: The aim of this study was to evaluate oral alterations among university students and explore possible associations with tobacco consumption in its various forms., Methods: A cross-sectional study was conducted in 2 phases: the first phase involved administering an electronic questionnaire to participants determine the prevalence of tobacco use and the second phase involved a physical examination of the participants. The participants were grouped on the basis of their reported habits and compared using statistical analysis (P < .05)., Results: Of the 620 participants, 57.1% reported using tobacco in some form, with 47.4% reporting electronic cigarette (e-cigarette) use. In the clinical phase, comparing the presence of oral changes in tobacco users vs nonusers, e-cigarette users had a higher proportion of white-spot caries lesions (P = .041) and gingivitis (P = .012). When e-cigarette use was combined with other forms of tobacco use, additional oral changes were more prevalent, including coated tongue and nicotinic stomatitis (P < .05)., Conclusions: The use of alternative forms of tobacco consumption is common among university students, with e-cigarette use being the most prevalent form, and may lead to detrimental effects on the oral cavity, such as caries and gingivitis, particularly when used in conjunction with other tobacco products., Practical Implications: The use of tobacco in alternative forms, such as e-cigarettes, can affect oral health directly or indirectly. Dentists should be familiar with the characteristics of this population and the potential oral repercussions associated with tobacco use to address the impact on health and raise awareness of the associated risks., Competing Interests: Disclosure None of the authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Objectives: In comparison to conventional combustible cigarettes, Electronic Nicotine Delivery Systems (ENDS) including both e-cigarettes (ECs) and heated tobacco products (HTPs) significantly reduce exposure to toxic chemical emissions. However, their impact on dental plaque remains unclear. This study measures dental plaque in ENDS (ECs and HTPs) users using quantitative light-induced fluorescence (QLF) technology, comparing them with current, former, and never smokers., Methods: This cross-sectional study compared dental plaque measurements using QLF technology (Q-ray cam™ Pro) among current smokers (≥10 cigarettes/day), former smokers (quit ≥6 months), never smokers, and exclusive ENDS users (quit ≥6 months). Dental plaque measurements were expressed as ΔR30 (total area of mature dental plaque) and ΔR120 (greater plaque thickness/maturation-calculus). The Simple Oral Hygiene (SOH) score was calculated by the QLF proprietary software. Statistical analyses including ANCOVA was performed by R version (4.2.3) with p < 0.05., Results: A total 30 smokers, 24 former smokers, 29 never smokers, and 53 ENDS users were included. Current smokers had significantly higher ΔR30 and ΔR120 values compared to other groups (p < 0.001). ENDS users showed plaque levels similar to never and former smokers (p > 0.05) but significantly lower than current smokers (p < 0.01). Although ENDS users showed a lower SOH score than smokers, this difference was not statistically significant. Daily toothbrushing and mouthwash usage were significant covariates., Conclusion: ENDS users exhibited reduced accumulation of dental plaque and calculus compared with current smokers., Clinical Significance: Exclusive ENDS use could less impact dental plaque accumulation compared to cigarette smoking. Further research is needed to confirm these findings and fully understand ENDS impact on dental plaque formation., Competing Interests: Declaration of competing interest GRMLR is a research fellow at the Department of Clinical and Experimental Medicine of the University of Catania. She declares no conflict of interest. ADS, DG, RE, VF, AA, HGY, RLG, SAP, EP, RG, JK declare no conflict of interest. RP is full tenured professor of Internal Medicine at the University of Catania (Italy) and Medical Director of the Institute for Internal Medicine and Clinical Immunology at the same University. He has received grants from U-BIOPRED and AIR-PROM, Integral Rheumatology & Immunology Specialists Network (IRIS), Foundation for a Smoke Free World, Pfizer, GlaxoSmithKline, CV Therapeu- tics, NeuroSearch A/S, Sandoz, Merk Sharp & Dohme, Boehringer Ingelheim, Novartis, Arbi Group Srl., Duska Therapeutics, Forest Laboratories and Ministero dell Universita’ e della Ricerca (MUR) Bando PNRR 3277/2021 (CUP E63C22000900006) and 341/2022 (CUP E63C22002080006), funded by NextGenerationEU, the European Union (EU) economic recovery package. He is founder of the Center for Tobacco Prevention and Treatment (CPCT) at the University of Catania and of the Center of Excellence for the Acceleration of Harm Reduction at the same university. He receives consultancy fees from Pfizer, Boehringer Ingelheim, Duska Therapeutics, Forest Laboratories, CV Therapeutics, and Sermo Inc. He is being paid textbook royalties from Elsevier. He is also involved in a patent application for ECLAT Srl. He is a pro bono scientific advisor for Lega Italiana Anti Fumo (LIAF) and the International Network of Nicotine Consumers Organizations (INNCO); and he is Chair of the European Technical Committee for Standardization on “Requirements and test methods for emissions of electronic cigarettes” (CEN/TC 437; WG4)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to evaluate and compare the impact of cigarette smoking (CS) and heated tobacco (HT) on the alteration of color and ultrastructural characteristics of human enamel and cementum., Background: According to tobacco companies, a less harmful substitute for CS is HT products. Nevertheless, comprehensive research on the effects of HT on tooth structures has been lacking. This study aimed to evaluate and compare the impact of CS and HT on the alteration of color and ultrastructural characteristics of human enamel and cementum., Materials and Methods: Thirty intact and noncarious human maxillary premolars extracted for orthodontic treatment purposes, previously disinfected, were used in the study. The specimens were randomly separated into six groups (n = 10), as follows: Group 1: enamel without smoking exposure; Group 2: enamel exposed to CS; Group 3: enamel exposed to HT; Group 4: cementum without smoking exposure; Group 5: cementum exposed to CS; and Group 6: cementum exposed to HT. The measurement of color change was conducted using a spectrophotometer. The surface alterations and mineral composition of enamel and cementum were evaluated using scanning electron microscopy and energy-dispersive X-ray spectroscopy. ANOVA test followed by Tukey's post hoc test was used to determine significant differences between groups., Results: Results showed that CS had a more pronounced effect on enamel and cementum color changes than HT. The impact of CS and HT on color changes was more evident in cementum than in enamel. Surface morphology of enamel and cementum showed alterations in histology following exposure to both smoking types. Moreover, the mineral content experienced a significant reduction after using CS and HT. The reduction in calcium content after CS and HT exposure was similar. However, HT led to a significant decrease in the phosphorus content of enamel when compared with CS. At the same time, CS exposure in cementum resulted in a more significant reduction in Ca/P ratio than HT., Conclusions: Although HT may appear to present a lower danger to hard dental tissues than CS, it is not entirely harmless. CS results in more color changes on the enamel and cementum of teeth. Both smoking methods affected the mineral content of teeth, with CS having a significant effect on the roots, while HT significantly affected the crowns' mineral composition., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Exposure to anthropogenic aerosols has been associated with a variety of adverse health effects, increased morbidity, and premature death. Although cigarette smoke poses one of the most significant public health threats, the cellular toxicity of particulate matter contained in cigarette smoke has not been systematically interrogated in a size-segregated manner. In this study, we employed a refined particle size classification to collect cigarette aerosols, enabling a comprehensive assessment and comparison of the impacts exerted by cigarette aerosol extract (CAE) on SH-SY5Y, HEK293T, and A549 cells. Exposure to CAE reduced cell viability in a dose-dependent manner, with organic components having a greater impact and SH-SY5Y cells displaying lower tolerance compared to HEK293T and A549 cells. Moreover, CAE was found to cause increased oxidative stress, mitochondrial dysfunction, and increased levels of apoptosis, pyroptosis, and autophagy, leading to increased cell death. Furthermore, we found that rutin, a phytocompound with antioxidant potential, could reduce intracellular reactive oxygen species and protect against CAE-triggered cell death. These findings underscore the therapeutic potential of antioxidant drugs in mitigating the adverse effects of cigarette aerosol exposure for better public health outcomes.

Objective: To determine the effects of conventional cigarette smoking (CS) and recent heated tobacco products (HTPs) on the surface roughness and color stability of different indirect restorative materials., Materials and Methods: One hundred disc-shaped samples were constructed of three different restorative CAD/CAM materials: lithium disilicate glass-ceramic (IPS e.max CAD; Ivoclar Vivadent, Liechtenstein), zirconia (BruxZir® Zirconia, Glidewell, USA) and polyetheretherketone (BioHPP® bredent GmbH, Germany). Of the IPS e.max CAD and the Bruxzir samples, 20 samples were glazed, and 20 samples were polished, while the BioHPP samples were all polished according to the manufacturer's instructions. Fifty samples were subjected to conventional cigarette smoking (LM, Philip Morris International Inc., Egypt) (Groups: IPS e.max CAD&#95;Glazed exposed to CS (LD&#95;G&#95;Cig), IPS e.max CAD&#95;Polished exposed to CS (LD&#95;P&#95;Cig), Bruxzir&#95;Glazed exposed to CS (Zr&#95;G&#95;Cig), Bruxzir &#95;Polished exposed to CS (Zr&#95;P&#95;Cig) and BioHPP exposed to CS (PEEK&#95;Cig) and fifty samples were exposed to heated tobacco product smoking (Heets, Russet selection, Philip Morris International Inc., Italy) (Groups: IPS e.max CAD&#95;Glazed exposed to HTP (LD&#95;G&#95;HTP), IPS e.max CAD&#95;Polished exposed to HTP (LD&#95;P&#95;HTP), Bruxzir&#95;Glazed exposed to HTP (Zr&#95;G&#95;HTP), Bruxzir CAD&#95;Polished exposed to HTP (Zr&#95;P&#95;HTP) and BioHPP exposed to HTP (PEEK&#95;HTP).. Six hundred cigarettes/heets representing 30 days of medium smoking behavior (20 cigarettes/day) were used. Before and after exposure to smoke, the surface roughness of all the samples was measured using JITAI8101 surface roughness tester (Beijing Jitai Tech Detection Device Co., Ltd, China, and the color parameters were assessed using VITA Easyshade Advance 4.01 (VITA shade, VITA made, VITA). The data were analyzed using One-way ANOVA, paired sample t-test and independent sample t-test. The significance level was set at α < 0.05. The surface topography was evaluated by scanning electron microscopy (SEM) and analyzed using energy-dispersive X-ray (EDX) spectroscopy to determine changes in the surface chemical composition., Results: Both types of smoking caused significant increases in the surface roughness of all the samples. There was a significant difference in color change between CS and HTP for all materials with different surface finish (P < 0.01) and zirconia had the greatest effect on color change (P < 0.001). In contrast, polyetheretherketone (PEEK) "BioHPP" had the least effect (P < 0.001)., Conclusion: Exposure to different types of smoking induce changes in the surface topography and color of different esthetic restorative materials. Compared with HTP, conventional cigarette smoke has a greater effect on the surface roughness and color stability of esthetic restorative materials. The glazed surfaces showed less change in surface topography than did the polished surfaces. Zirconia showed better color stability when compared to polyetheretherketone (PEEK)., (© 2024. The Author(s).)

Competing Interests: SA, DT-HC, JG und FTF haben nichts offenzulegen.

Effective tobacco policies are important for reducing the harm of tobacco use and can have a broad impact at the population level. This review provides an overview of how clinical science can inform tobacco policies with a focus on policies related to flavored tobacco products, using menthol cigarettes as an illustrative example. Specifically, this review summarizes the role of flavors in tobacco use and the history of regulation of flavored tobacco products by the US Food and Drug Administration (FDA), provides an overview of clinical research methods used to contribute to the scientific evidence to inform FDA tobacco policies, discusses key findings related to menthol tobacco products using these methods, and proposes future directions for clinical research. As the tobacco marketplace continues to evolve with new products and flavor chemicals, ongoing clinical science will be essential for establishing evidence-based policies to protect public health and reduce tobacco-related health disparities.

Background: Smoking cessation reduces the risk of developing smoking-related diseases. Although smoking prevalence has declined, many continue smoking cigarettes. Switching completely to smoke-free alternatives like the Tobacco Heating System (THS) 2.2-a heated tobacco product for which there is evidence demonstrating significantly reduced formation and exposure to harmful chemicals compared to cigarettes-has the potential to reduce the harm caused by continuing to smoke cigarettes., Methods: We conducted a 6-month clinical study (NCT02396381) with a 6-month extension (NCT02649556), initially randomizing 984 adult smokers to continue smoking or switch to THS (non-mentholated), of which 672 continued into the extension study. Endpoints were evaluated at baseline and at 3, 6, and 12 months. We longitudinally assessed biomarkers of potential harm (BoPHs) known to be reversible upon smoking cessation as indicators of pathways involved in the pathogenesis of cardiovascular or respiratory diseases and carcinogenicity. The need to cough and safety profile were also assessed. Impact on eight key BoPHs was used as a proxy to evaluate harm reduction potential., Results: At 12 months, comparison of BoPH levels between the predominant THS use and cigarette smoking groups showed a positive effect in favor of switching, partially or in full, to THS., Conclusion: These results provide additional evidence of the harm reduction potential of THS for smokers who would otherwise continue smoking, but they need to be verified in long-term confirmatory studies., Clinical Trial Registration: Clinicaltrials.gov Identifier: NCT0264955. Date of registration: January 7, 2016 https://clinicaltrials.gov/ct2/show/NCT02649556.

Electronic cigarette (e-cigarette) use continues to rise globally. E-cigarettes have been presented as safer alternatives to combustion cigarettes that can mitigate the harm associated with tobacco products; however, the degree to which e-cigarette use itself can lead to morbidity and mortality is not fully defined. Herein we describe how e-cigarettes function; discuss the current knowledge of the effects of e-cigarette aerosol on lung cell cytotoxicity, inflammation, antipathogen immune response, mucociliary clearance, oxidative stress, DNA damage, carcinogenesis, matrix remodelling and airway hyperresponsiveness; and summarise the impact on lung diseases, including COPD, respiratory infection, lung cancer and asthma. We highlight how the inclusion of nicotine or flavouring compounds in e-liquids can impact lung toxicity. Finally, we consider the paradox of the safer cigarette: the toxicities of e-cigarettes that can mitigate their potential to serve as a harm reduction tool in the fight against traditional cigarettes, and we summarise the research needed in this underinvestigated area., Competing Interests: Conflict of interest: K. Allbright reports grants from Burroughs Wellcome Fund and T32 (5T32HL007563-35), outside the submitted work. L.E. Crotty Alexander reports grants from NIH NHLBI R01, NIH NHLBI K24 and VA Merit Award, advisory board participation with Regeneron, and leadership roles with CHEST and ALA San Diego, outside the submitted work. M. Zhang reports support for the present article from Regeneron Pharmaceuticals. K.H. Benam has received grants from the US Food and Drug Administration, US National Institutes of Health, US Department of Defense and the Gordon and Betty Moore Foundation, royalties from Emulate Inc., consulting fees from Pneumax LLC, has received invited speaker honorarium from Colorado State University, has multiple pending and issued patent applications, has non-significant personal investments in a number of publicly traded companies, and is the founder of Pneumax LLC. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca 2+ ., Methods: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells., Results: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca 2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE., Conclusion: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca 2+ signaling and CaMKK2 pathways., (© 2024. The Author(s).)

Abstract: Cigarette burn lesions present forensic scenarios that are often difficult to investigate, both from a morphological diagnostic point of view and with regard to the mode of infliction, especially if the victim is unable to speak or has died. Although there may be the suspicion for a lesion to be produced by a lit cigarette, to date one can only rely on the morphological aspects that characterize it, and there is a lack of tools to reach the most evidence-based diagnosis possible. This limitation arose when managing a forensic autopsy case of possible child abuse that resulted in the death of the child, characterized by the presence of 3 suspicious cigarette burn lesions. We therefore decided to perform scanning electron microscopy/energy-dispersive x-ray (SEM/EDX) spectrometry analysis on these lesions and on the cigarette butt found at the crime scene. At the same time, SEM/EDX was applied to the analysis of an unlit cigarette in its entirety (obtained from the same source package as the cigarette butt), a positive control skin sample with an iatrogenic cigarette burn injury, and a negative control skin sample. Among the various compounds highlighted on compositional analysis, only sulfuric anhydride (SO 3 ) and phosphoric anhydride (P 2 O 5 ) showed a highly significant distribution pattern by being found in the autopsy samples, the cigarette butt, the tobacco of the unlit cigarette, and the positive skin control. Considering this, cigarette burns appear to follow Locard's principle as well, and similarly to other lesions, SEM/EDX allowed the diagnosis of cigarette burn lesions, already suspected morphologically, to be corroborated. Therefore, SEM/EDX is confirmed as a helpful tool in forensic pathology investigations., Competing Interests: Conflicts of interest/competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In recent years, Heated tobacco products (HTP) have gradually entered the market and become more and more popular with consumers because of their low risk (compared with traditional cigarette). With the increasing popularity and proportion of HTP in the international market, people pay more and more attention to the safety evaluation of HTP, but there is still a lack of systematic review of HTP safety research. In this review, the harmful components of HTP, multi-organ functional programming effects (including respiratory system, cardiovascular system, etc.), and mechanism of the effect generation (including oxidative stress, inflammatory response, etc.) were systematically reviewed, the safety effects of HTP and traditional cigarettes were compared in detail, and the shortcomings and future research directions in the field of HTP safety were discussed. In summary, this review conforms to the general trend of contemporary "tobacco and health", helps people to understand and evaluate HTP more systematically, and provides a strong theoretical support and literature basis for the tobacco industry to carry out HTP risk assessment and exposure improvement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

E-cigarette users predominantly also continue to smoke cigarettes. These Dual Users either consume e-cigarettes in locations where smoking is not allowed, but vaping is, or to reduce their consumption of cigarettes, believing it will lead to harm reduction. Whilst it is known that e-cigarette vapour is chemically less complex than cigarette smoke, it has a distinct chemical profile, and very little is known about the health impacts of exposure to both chemical profiles vs. either alone. We simultaneously exposed cells in vitro to non-toxic levels of e-cigarette vapour extract (EVE) and cigarette smoke extract (CSE) to determine their effects on 16HBE14o- airway epithelial cell metabolism and inflammatory response, as well as immune cell (THP-1 cells and monocyte-derived macrophages (MDM) from healthy volunteers) migration, phagocytosis, and inflammatory response. We observed increased toxicity, reduced metabolism (a marker of proliferation) in airway epithelial cells, and reduced monocyte migration, macrophage phagocytosis, and altered chemokine production after exposure to either CSE or EVE. These cellular responses were greater after dual exposure to CSE and EVE. The airway epithelial cells from smokers showed reduced metabolism after EVE (the Switcher model) and dual CSE and EVE exposure. When EVE and CSE were allowed to interact, the chemicals were found to be altered, and new chemicals were also found compared to the CSE and EVE profiles. Dual exposure to e-cigarette vapour and cigarette smoke led to worse functional outcomes in cells compared to either single exposure alone, adding to limited data that dual use may be more dangerous than smoking only.

Oxidative protein damage involving carbonylation of respiratory tract proteins typically accompanies exposure to tobacco smoke. Such damage can arise via multiple mechanisms, including direct amino acid oxidation by reactive oxygen species or protein adduction by electrophilic aldehydes. This study investigated the relative importance of these pathways during exposure of a model protein to fresh cigarette emission extracts. Briefly, protein carbonyl adducts were estimated in bovine serum albumin following incubation in buffered solutions with whole cigarette emissions extracts prepared from either a single 1R6F research cigarette or a single "Heat-not-Burn" e-cigarette. Although both extracts caused concentration-dependent protein carbonylation, conventional cigarette extracts produced higher adduct yields than e-cigarette extracts. Superoxide radical generation by conventional and e-cigarette emissions was assessed by monitoring nitro blue tetrazolium reduction and was considerably lower in extracts made from "Heat-Not-Burn" e-cigarettes. The superoxide dismutase/catalase mimic EUK-134 strongly suppressed radical production by whole smoke extracts from conventional cigarettes, however, it did not diminish protein carbonyl adduction when incubating smoke extracts with the model protein. In contrast, edaravone, a neuroprotective drug with strong carbonyl-trapping properties, strongly suppressed protein damage without inhibiting superoxide formation. Although these findings require extension to appropriate cell-based and in vivo systems, they suggest reactive aldehydes in tobacco smoke make greater contributions to oxidative protein damage than smoke phase radicals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The e-cigarette device and HEEET sticks used in these studies were donated by the tobacco company Philip Morris. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H945).

Background: Cigarette smoking impairs rotator cuff healing, but no study, to our knowledge, has focused on the association between heated tobacco products and rotator cuff tears., Methods: This study retrospectively investigated 1,133 patients who underwent arthroscopic repair of symptomatic rotator cuff tears between March 2011 and April 2021. Patients were grouped on the basis of their smoking patterns as nonsmokers, cigarette smokers, and heated tobacco smokers. Propensity score matching was used to reduce selection bias, and 45 subjects were selected from each group via 1:1:1 matching. Functional scores and active range of motion were compared among the 3 groups preoperatively and at a 2-year follow-up. Postoperative magnetic resonance imaging was performed 6 months after the surgical procedure to assess structural integrity., Results: Except for sex, similar baseline characteristics were achieved after propensity score matching. There were no differences in the clinical scores or range of motion between the matched groups either preoperatively or at the 2-year follow-up. However, the retear rate for the matched nonsmoker group was significantly lower (8.9%) than those for the matched cigarette smoker group (31.1%) and the heated tobacco smoker group (28.9%) (p = 0.022). Multivariable logistic regression analysis revealed that the retear rates were 3.403 times higher for the cigarette smoker group and 3.397 times higher for the heated tobacco smoker group than that for the nonsmoker group., Conclusions: Heated tobacco users, like conventional cigarette smokers, have worse clinical outcomes with respect to rotator cuff healing than nonsmokers. Regardless of the type of cigarette, abstinence from smoking is necessary for patients undergoing rotator cuff repair surgery., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H938 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Understanding the harmful effects of using tobacco products (cigarettes, electronic cigarettes (e-cigarette) or vape, IQOS, hookah, etc.) by various segments of the population is one of the important ways to improve the condition of the tissues of the oral cavity, since smoking is an important risk factor for the occurrence of chronic destructive periodontal diseases. The purpose of our work was a study of the relationship between the state of the oral cavity and the use of tobacco products in different age groups based on the conducted questionnaire., Material and Methods: In order to conduct this research, an anonymous survey was conducted in the form of a Google document among people divided into three age groups: younger (under 21), middle (21-40) and older (over 40) with 1113 participants. In the survey, they answered questions about their lifestyle, the type of tobacco product used, visible changes of oral cavity if they were present., Results: Studies show that smoking and the use of tobacco products is a fairly common phenomenon in modern society and reflects a direct correlation between the intensity of this habit in people and the development of various pathological conditions of the mucous membranes of the mouth. A significant period of cigarette use, and the accompanying insufficiency of oral hygiene measures increase risk of oral cavity injury. More than 60% answered that they regularly brush their teeth twice a day. At the same time, at least half of all respondents answered that they use dental floss and mouthwashes irregularly, and also visit the dentist only when necessary. Among the first two age groups, it is noted that up to 52% of people consume various sweets and sweet drinks every day, which is a factor that contributes to the appearance of destructive changes in the oral cavity. Similar factors include the lack of an active lifestyle. So, from 30% to 50% in each age group don't have any physical exercise. Only up to 30% of people have up to 3 physical exercises a week or have morning exercise every day., Conclusions: The most pronounced correlative relationship for severity of changes in oral cavity was revealed between with experience of smoking (how long) - r=0.79, intensity of smoking (r=0.75) and oral hygiene practices (r=0.71). It is necessary to develop new methods of combating the consequences of long-term use of tobacco products, as well as preventing the appearance of uncompensated changes in the mucous membrane of the oral cavity.

Purpose: To compare the effects of using heated tobacco products (HTP) or traditional cigarettes (C) on maternal and neonatal outcomes., Methods: This is a retrospective, monocentric study conducted at San Marco Hospital from July 2021 to July 2022. We compared a cohort of pregnant patients who smoked HTP (HS), with pregnant women smoking cigarettes (CS), ex-smoker (ES) and non-smoker (NS) pregnant women. Biochemistry, ultrasound, and neonatal evaluations were performed., Results: In total, 642 women were enrolled, of which 270 were NS, 114 were ES, 120 were CS, and 138 were HS. CS had the greatest weight gain and had more difficulty getting pregnant. Smokers and ES experienced more frequently threats of preterm labor, miscarriages, temporary hypertensive spikes, and higher rates of cesarean sections. Preterm delivery was more associated with CS and HS groups. CS and HS had lower awareness of the risks to which the mother and the fetus are exposed. CS were more likely to be depressed and anxious. Biochemical parameters did not show significant differences between the groups. CS had the greatest difference in days between the gestational age calculated based on the last menstrual period and the one based on the actual ultrasound age. The average percentile newborn weight range of CS was lower, as well as the mean 1st minute and the 5th minute Apgar scores., Conclusion: The comparison of the data obtained between CS and HS underlines the greater danger of C. Nevertheless, we do not recommend HTP because the maternal-fetal outcomes are not superimposable to the NS outcomes., (© 2023. The Author(s).)

Introduction: Smoke from traditional cigarettes and e-cigarette aerosols have distinct chemical compositions that may impact blood pressure (BP) and heart rate (HR) differently., Aims: This study compared the impact of nicotine-containing e-cigarettes (EC+) versus nicotine-free (EC-) on BP, HR and endothelial markers, and assessed if EC+ posed fewer risks than tobacco cigarettes (TC)., Methods: Electronic databases were searched from inception until November 2023 for studies reporting changes in systolic and diastolic BP (SBP, DBP) and HR and endothelial parameters before and after the use of EC+, EC- and TC. Data were analyzed using weighted mean differences (WMDs) and 95% confidence intervals (CIs)., Results: Fifteen studies (n = 752) were included in our meta-analysis. We demonstrate that EC+ significantly increased systolic BP (WMD = 3.41, 95% CI [0.1,6.73], p = 0.04], diastolic BP (WMD = 3.42, 95% CI [1.75, 5.09]; p < 0.01], and HR (WMD = 5.36 BPM, 95% CI [1.87, 8.85]; p < 0.01) compared to EC-. However, EC+ was observed to cause less detrimental effect on SBP (WMD = - 4.72 mmHg, 95% CI [- 6.58, - 2.86], p < 0.01), and HR (WMD = - 3.11 BPM, 95% CI [- 4.54, - 1.68]; p < 0.01) as compared to TC with no difference on DBP (WMD = - 1.14 mmHg, 95% CI [- 2.38, 0.1]; p = 0.07). EC+ also led to greater deterioration of endothelial parameters as compared to EC- but to a lesser degree as compared to TC., Conclusion: EC+ shows greater impairment in hemodynamic and endothelial parameters than EC- but less than TC. Additional studies are needed to evaluate prolonged effects of EC use., (© 2024. Italian Society of Hypertension.)

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone.

Background: The mechanisms by which cigarette smoking increases the risk of respiratory disease have been studied. However, less is known about risks of respiratory symptoms and outcomes associated with smoking cigars, and risks by cigar types have not been previously explored. The aim of this study was to examine associations between cigar use, including traditional cigars, cigarillos, filtered cigars, and dual cigar and cigarette use, and functionally important respiratory symptoms (FIRS), lifetime asthma diagnosis, uncontrolled asthma, and new cases of FIRS., Methods: Data from Waves 2-5 (2014-19) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal study, were analyzed in two ways. For cross-sectional analysis, the analytic sample included adults 18 and older at each wave, resulting in 44,040 observations. Separately, longitudinal analyses were assessed among adults 18 and older at Wave 2, resulting in 7,930 individuals. Both analyses excluded adults with chronic obstructive pulmonary disease (COPD) or non-asthma respiratory disease., Results: Current established cigarillo smokers had higher odds of having FIRS (Adjusted odds ratio (AOR): 1.72; 95% CI: 1.08, 2.74) compared to never smokers of cigarillos and cigarettes, after adjusting for covariates. Current established filtered cigar smokers had higher odds of asthma diagnosis (AOR: 1.35; 95% CI: 1.10, 1.66) while current established dual smokers of filtered cigars and cigarettes had higher odds of uncontrolled asthma (AOR: 5.13; 95% CI: 1.75, 15.02) compared to never smokers of filtered cigars or cigarettes. Both current established cigar smokers and current established dual smokers of cigarettes and cigars had higher odds of new FIRS compared to never cigar or cigarette smokers (AORs: 1.62; 95% CI: 1.02, 2.60 for exclusive cigars and 2.55; 95% CI 1.57, 4.14 for dual smokers)., Conclusions: This study provides evidence that cigar smokers or dual smokers of cigars and cigarettes have greater odds of FIRS, asthma, and uncontrolled asthma and that new incidence of FIRS is higher among any cigar smokers compared to never cigar or cigarette smokers. Understanding health impacts associated with cigar use provides information for supporting policy development, as well as for designing clinical interventions focused on smoking cessation for cigars., (© 2024. The Author(s).)

Background: To reduce smoking and the harms it causes, countries, including the USA, are considering policies to reduce nicotine in combustible tobacco to minimally addictive levels. Effective messages about very low nicotine cigarettes (VLNCs) and this policy are crucial in combating misperceptions threatening the policy's effectiveness., Data and Methods: A discrete choice experiment assessed messages about VLNCs. Participants were 590 adults who smoked exclusively, 379 adults who both smoked and used e-cigarettes, 443 adults who formerly smoked and 351 young adults who never smoked (total n=1763). Seven message attributes were varied systematically (source, harm, chemicals, nicotine, satisfaction, addictiveness and quitting efficacy). Outcomes were selection of messages that generated the most positive attitude towards reduced nicotine policy, the greatest perceived harmfulness of VLNCs, and most strongly motivated quitting and initiating behaviour for VLNCs., Results: Information about specific harms and chemicals of VLNCs had the largest effects on selection of messages as eliciting more negative attitudes towards VLNCs policy, increasing perceived VLNC harmfulness, increasing motivation to quit VLNCs and decreasing motivation to try VLNCs. Messages with information about quitting efficacy were selected as more motivating to quit among those who smoke, but also more motivating to try VLNCs among those who do not smoke., Conclusion: Harm and chemical information can be prioritised to ensure VLNCs are not misperceived as less harmful than regular cigarettes. Messages about increased quitting efficacy and reduced addictiveness associated with VLNCs may backfire if presented to those who do not smoke., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: US tobacco manufacturers can seek authorization from the US Food and Drug Administration (FDA) to market products using modified risk tobacco product (MRTP) claims. To inform regulatory decisions, we examined the impact of MRTP claim specificity and content, including whether the claims produced halo effects (ie, inferring health benefits beyond what is stated)., Aims and Methods: Participants were 3161 US adult cigarette smokers. Using a two (general vs. specific) × 2 (risk vs. exposure) plus independent control design, we randomized participants to view one message from these conditions: general risk claim (eg, "smoking-related diseases"), general exposure claim (eg, "chemicals in smoke"), specific risk claim (eg, "lung cancer"), specific exposure claim (eg, "arsenic"), or control. Claims described the benefits of completely switching from cigarettes to the heated tobacco product IQOS., Results: MRTP claims of any sort elicited a higher willingness to try IQOS relative to control (d = 0.09, p = .043). Claims also elicited lower perceived risk of disease and exposure to harmful chemicals for completely switching from cigarettes to IQOS (d = -0.32 and -0.31) and partially switching (d = -0.25 and d = -0.26; all p < .05). Relative to specific MRTP claims, general MRTP claims led to lower perceived risk and exposure for complete switching (d = -0.13 and d = -0.16) and partial switching (d = -0.14 and d = -0.12; all p < .05). Risk and exposure MRTP claims had similar effects (all p > .05)., Discussion: MRTP claims led to lower perceived risk and exposure, and higher willingness to try IQOS. General claims elicited larger effects than specific claims. MRTP claims also promoted unintended halo effects (eg, lower perceived risk of disease and chemical exposure for partial switching)., Implications: We found evidence that MRTP claims promoted health halo effects. In light of these findings, the FDA should require research on halo effects prior to authorization. Further, if an MRTP claim is authorized, FDA should require tobacco manufacturers to conduct post-market surveillance of how the claim affects consumer understanding, including partial switching perceived risk and exposure beliefs, as well as monitoring of dual-use behaviors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: IQOS was the first heated tobacco product to receive Food and Drug Administration (FDA) authorisation for 'reduced exposure' marketing claims, which has been exploited globally., Methods: In November-December 2021, we conducted a survey-based 3×3 factorial experiment among US (n=1128) and Israeli adults (n=1094). We presented: (1) reduced exposure, reduced risk and control messaging and (2) 2 variations of FDA endorsement and control messaging. Each participant was randomly assigned to evaluate 2 ads (displayed on different ad imagery), then completed assessments of perceived relative harm, exposure and disease risk and likelihood of personally trying or suggesting IQOS to smokers. Ordinal logistic regression examined messaging conditions and their interactions, on the 5 outcomes, respectively, adjusting for covariates., Results: Control (vs reduced exposure) messaging resulted in higher perceived relative harm (adjusted OR (aOR)=1.29, 95% CI=1.12 to 1.48), exposure (aOR=1.34, 95% CI=1.17 to 1.54) and disease risk (aOR=1.23; 95% CI=1.08 to 1.40), and lower likelihood of suggesting IQOS to smokers (aOR=0.85; 95% CI=0.74 to 0.97). Reduced risk (vs exposure) messaging resulted in lower perceived relative harm (aOR=0.86; 95% CI=0.75 to 0.99). One FDA endorsement message ('IQOS (completed) the US FDA examination of tobacco products. FDA concluded that IQOS is a better choice for adult smokers') was associated with greater likelihood of suggesting IQOS to smokers, relative to control (aOR=1.19; 95% CI=1.04 to 1.37). No interactions between risk/exposure messaging and FDA endorsement messaging were found. Additionally, Israeli participants, cigarette users and men perceived lower relative harm and exposure and greater likelihood of trying or suggesting IQOS to smokers., Conclusions: Regulators must monitor direct and indirect advertising content of modified risk tobacco product-authorised products and prevent potentially harmful misinterpretations., Competing Interests: Competing interests: HL had received fees for lectures from Pfizer Israel Ltd (distributor of a smoking cessation pharmacotherapy in Israel) in 2017. YB-Z has received fees for lectures from Pfizer, Novartis NCH and GSK Consume Health (distributors of pharmacotherapy in Israel) in the past (2012–July 2019). LCA receives royalties for the sale of Text2Quit. No other conflicts of interest are declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: While heated tobacco products (HTPs) may affect pulmonary function, the evidence supporting the utility of screening for HTP use in clinical settings is insufficient. We examined the association between HTP use and airway obstruction after switching from cigarettes., Method: The study subjects were patients aged ≥20 years undergoing surgery from December 2021 to September 2022 who completed spirometry and reported tobacco (cigarette and HTP) use status during the preoperative assessment. Airway obstruction was defined as forced expiratory volume in 1 s to forced vital capacity ratio below the lower limit of normal. Current tobacco use was defined as past-30-day use. Multivariable Poisson regression analysis was performed to examine the associations between HTP use and airway obstruction by adjusting for demographic characteristics, lifetime cigarette smoking (pack-year) and duration of smoking cessation., Results: Overall (N=2850, 55.4% women, mean age 62.4), 4.6% and 10.7% reported current HTP use and cigarette smoking, respectively. 16.8% had airway obstruction. Airway obstruction was more common among current HTP-only users (adjusted prevalence ratio (APR)=2.32), current cigarette-only smokers (APR=2.57) and current dual users (APR=2.82) than never-tobacco users. Among current tobacco users (N=398), the prevalence of airway obstruction was not significantly different between HTP-only users and cigarette-only smokers. Among former cigarette smokers (>30-day cigarette quitters) (N=1077), current HTP users had 1.42 times the increased prevalence of airway obstruction than never-HTP users after adjusting for cigarette pack-year; a stronger association was observed when the analysis was restricted to ≥5-year cigarette quitters (N=772) (APR=1.96, vs never HTP users)., Conclusion: Current HTP use was associated with airway obstruction among patients with cancer who had completely switched from cigarettes even after quitting smoking for a long period. Patients should be routinely screened for HTP use and advised to quit any tobacco., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Heated tobacco products (HTPs) are novel alternative tobacco products being promoted as an alternative to cigarettes. To evaluate the impact of HTP use on vascular function, we investigated the effects of a brief HTP usage on arterial stiffness and platelet thrombus formation in healthy volunteers., Methods: In a randomised crossover study, twenty-four healthy young adults with occasional tobacco use smoked the HTP IQOS 3 Multi (Phillip Morris Int.) and "no-exposure" was used as a control, with a wash-out period of at least one week in-between. Arterial stiffness was assessed through pulse wave velocity and pulse wave analysis. Blood samples, collected at baseline and 5 min following exposure, were analysed with the Total-Thrombus-formation analysis system evaluating platelet and fibrin-rich thrombus formation tendency., Results: HTP exposure caused immediate heightened pulse wave velocity (+0.365 m/s, 95% CI: +0.188 to 0.543; p = 0.004) and enhanced augmentation index corrected to heart rate (+6.22%, 95% CI: +2.33 to 10.11; p = 0.003) compared to the no-exposure occasion. Similarly, blood pressure and heart rate transiently increased immediately following HTP inhalation. Platelet thrombus formation significantly increased following HTP exposure (area under the curve +59.5, 95% CI: +25.6 to 93.4; p < 0.001) compared to no-exposure. No effect was seen on fibrin-rich thrombus formation following HTP-exposure., Conclusions: Brief HTP use in healthy young adults had immediate adverse effects on vascular function resulting in increased arterial stiffness and platelet thrombus formation, known risk factors for the development of atherosclerosis. Further research is needed to address long term health impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies 1 . Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8 + alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8 + cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention., (© 2024. The Author(s).)

BACKGROUND: E-cigarettes are promoted as less harmful than cigarettes. There has not been a direct comparison of health effects of e-cigarettes or dual use (concurrently using e-cigarettes and cigarettes) with those of cigarettes in the general population. METHODS: Studies in PubMed, EMBASE, Web of Science, and PsychINFO published through October 1, 2023, were pooled in a random-effects meta-analysis if five or more studies were identified with a disease outcome. We assessed risk of bias with Risk Of Bias In Non-randomized Studies of Exposure and certainty with Grading of Recommendations, Assessment, Development, and Evaluations. Outcomes with fewer studies were summarized but not pooled. RESULTS: We identified 124 odds ratios (94 cross-sectional and 30 longitudinal) from 107 studies. Pooled odds ratios for current e-cigarette versus cigarette use were not different for cardiovascular disease (odds ratio, 0.81; 95% confidence interval, 0.58 to 1.14), stroke (0.73; 0.47 to 1.13), or metabolic dysfunction (0.99; 0.91 to 1.09) but were lower for asthma (0.84; 0.74 to 0.95), chronic obstructive pulmonary disease (0.53; 0.38 to 0.74), and oral disease (0.87; 0.76 to 1.00). Pooled odds ratios for dual use versus cigarettes were increased for all outcomes (range, 1.20 to 1.41). Pooled odds ratios for e-cigarettes and dual use compared with nonuse of either product were increased (e-cigarette range, 1.24 to 1.47; dual use, 1.49 to 3.29). All included studies were assessed as having a low risk of bias. Results were generally not sensitive to study characteristics. Limited studies of other outcomes suggest that e-cigarette use is associated with additional diseases. CONCLUSIONS: There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use.

Background: This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on the subject to provide a comprehensive analysis of potential health risks associated with both smoking methods., Methods: The systematic review, incorporating searches in PubMed, Scopus, Web of Science, and the Cochrane Library up to July 2023, examines the results obtained in relevant studies, and provides a critical discussion of the results., Results: E-cigarettes exhibit reduced exposure to harmful toxins compared to traditional cigarettes., Conclusion: However, concerns persist regarding respiratory irritation and potential health risks, especially among youth, emphasizing the need for comprehensive, long-term research and protective legislation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Josef Yayan reports financial support was provided by University Witten Herdecke Faculty of Health. Josef Yayan reports a relationship with University Witten Herdecke Faculty of Health that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

E-cigarette use among youth presents a public health risk. Yet, cigarette smokers who substantially reduce their smoking or switch completely from traditional combustible cigarettes could benefit. As science about e-cigarettes is continually emerging, any potential warnings are likely to contain uncertain language. Hedged verbiage may impact decision making. To assess reactions, we conducted 16 online focus groups; 8 with youth ( n  = 32, grouped by gender and by vaping experience) and 8 with adult tobacco users ( n  = 37, grouped by smokers, dual users of e-cigarettes and cigarettes, and former smokers who switched to e-cigarettes). Each focus group viewed and discussed 8 potential warnings messages. We conducted an inductive thematic analysis of the reactions to warning messages that contain uncertain language. Respondents' reactions were often negative, but varied based on specific usages of uncertainty, existing beliefs about uncertainty in law and science, and smoking/vaping use patterns that supported the use of uncertainty related to e-cigarettes. Many youth (and some adults) believed that uncertain language enabled audiences to minimize the likelihood of harm or interpreted it as meaning there are both healthy and unhealthy e-cigarettes. This qualitative study provides evidence that the use of types of uncertain language, the frequency of that use, and/or the selection of particular words in warnings, might not achieve the intended public health aims of increasing understanding of risk, deterring youth uptake, and/or facilitating a substantial switch from cigarettes. The use of certain types of uncertain language appears to have significant potential to bring unintended consequences. Suggestions for research and policy are included.