Effectiveness of e-cigarettes as a stop smoking intervention in adults: a systematic review.

BACKGROUND: This systematic review aims to identify the benefits and harms of electronic cigarettes (e-cigarettes) as a smoking cessation aid in adults (aged ≥ 18 years) and to inform the development of the Canadian Task Force on Preventive Health Care's (CTFPHC) clinical practice guidelines on e-cigarettes. METHODS: We searched Ovid MEDLINE®, Ovid MEDLINE® Epub Ahead of Print, In-Process & Other Non-Indexed Citations, PsycINFO, Embase Classic + Embase, and the Cochrane Library on Wiley. Searches were conducted from January 2016 to July 2019 and updated on 24 September 2020 and 25 January 2024. Two reviewers independently performed title-abstract and full-text screening according to the pre-determined inclusion criteria. Data extraction, quality assessments, and the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed by one independent reviewer and verified by another. RESULTS: We identified 18 studies on 17 randomized controlled trials that compared e-cigarettes with nicotine to e-cigarettes without nicotine and e-cigarettes (with or without nicotine) to other interventions (i.e., no intervention, waitlist, standard/usual care, quit advice, or behavioral support). Considering the benefits of e-cigarettes in terms of smoking abstinence and smoking frequency reduction, 14 studies showed small or moderate benefits of e-cigarettes with or without nicotine compared to other interventions; although, with low, very low or moderate evidence certainty. With a focus on e-cigarettes with nicotine specifically, 12 studies showed benefits in terms of smoking abstinence when compared with usual care or non-nicotine e-cigarettes. In terms of harms following nicotine or non-nicotine e-cigarette use, 15 studies reported mild adverse events with little to no difference between groups and low to very low evidence certainty. CONCLUSION: The evidence synthesis on the e-cigarette's effectiveness shows data surrounding benefits having low to moderate evidence certainty for some comparisons and very low certainty for others, indicating that e-cigarettes may or probably increase smoking cessation, whereas, for harms, there is low to very low evidence certainty. Since the duration for outcome measurement varied among different studies, it may not be long-term enough for Adverse Events (AEs) to emerge, and there is a need for more research to understand the long-term benefits and potential harms of e-cigarettes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099692.

Inhalation of nicotine-containing electronic cigarette vapor exacerbates the features of COPD by inducing ferroptosis in ßENaC-overexpressing mice.

Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.

Nicotine Screening and Cessation Education Among Patients Awaiting Total Joint Arthroplasty: A Quality Improvement Project.

Orthopedic surgical patients who use nicotine are at a high risk for postoperative complications including infection, respiratory failure, cardiac arrest, and death. Periprosthetic joint infections may result from nicotine-induced immunosuppression and microvascular changes, increasing perioperative morbidity and mortality. These complications result in higher health care costs, increased length of stay, and loss of reimbursement due to readmissions. Four weeks of nicotine cessation prior to arthroplasty decreases these risks; however, perioperative teams may lack reliable nicotine screening and cessation education methods. This project identified inconsistencies in nicotine screening and cessation counseling in the preoperative setting, which contributed to surgery cancellations among patients who required to demonstrate nicotine cessation preoperatively. Standardization of preoperative nicotine screening and patient cessation education resources can improve the identification of orthopedic patients who use nicotine and provide concrete, proven methods of achieving nicotine cessation prior to elective primary arthroplasty. Investment from perioperative staff is essential to ensure success.

Effect of Flavored on! Nicotine Pouch Products on Smoking Behaviors: Protocol for a Sequential, Multiple Assignment, Randomized Controlled Trial.

BACKGROUND: Cigarette smoking is a leading cause of morbidity and mortality. For adults who smoke cigarettes and cannot or will not quit smoking, smoke-free products, such as nicotine pouches, have been recognized as a potential alternative to smoking combusted cigarettes to reduce harm due to cigarette smoking. The role of flavors in these smoke-free products in tobacco harm reduction has not been fully understood. OBJECTIVE: This study evaluates the effect of flavors in on! nicotine pouch products (research products) in the reduction of cigarette smoking among adults who smoke cigarettes in their natural environment. METHODS: This study uses a sequential, multiple assignment, randomized trial design. Approximately 400 eligible adults who smoke cigarettes will be enrolled and randomized to have access to either the Original (unflavored) on! nicotine pouch product only or a complete flavor profile (ie, Berry, Cinnamon, Citrus, Coffee, Mint, Original, and Wintergreen) of on! nicotine pouch products. After 3 weeks, participants in the Original-only arm will be randomized again, with half remaining in the Original-only arm and half having access to the complete flavor profile for another 3 weeks. Primary outcomes are expired-air carbon monoxide (CO) levels. Secondary outcomes are self-reported cigarette consumption and CO-verified cigarette abstinence. RESULTS: Recruitment and data collection started in September 2023 and is projected to last until March 2025. We anticipate completing the data analysis in 2025. As of May 2024, we have enrolled 314 participants. CONCLUSIONS: This study will provide empirical evidence about the effect that flavor availability in smoke-free products may have in reducing cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT06072547; https://clinicaltrials.gov/study/NCT06072547. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56565.

The efficacy and acceptability of pharmacological monotherapies and e-cigarette on smoking cessation: a systemic review and network meta-analysis.

Background and aims: Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation. E-cigarettes (EC) are increasingly explored by many RCTs for their potentiality in smoking cessation. In addition, some RCTs are attempting to explore new drugs for smoking cessation, such as cytisine. This network meta-analysis (NMA) aims to investigate how these drugs and e-cigarettes compare regarding their efficacy and acceptability. Materials and methods: This systematic review and NMA searched all clinical studies on smoking cessation using pharmacological monotherapies or e-cigarettes published from January 2011 to May 2022 using MEDLINE, COCHRANE Library, and PsychINFO databases. NRTs were divided into transdermal (TDN) and oronasal nicotine (ONN) by administrative routes, thus 7 network nodes were set up for direct and indirect comparison. Two different indicators measured the efficacy: prevalent and continuous smoking abstinence. The drop-out rates measured the acceptability. Results: The final 40 clinical studies included in this study comprised 77 study cohorts and 25,889 participants. Varenicline is more effective intervention to assist in smoking cessation during 16-32 weeks follow-up, and is very likely to prompt dropout. Cytisine shows more effectiveness in continuous smoking cessation but may also lead to dropout. E-cigarettes and oronasal nicotine are more effective than no treatment in encouraging prevalent abstinence, but least likely to prompt dropout. Finally, transdermal nicotine delivery is more effective than no treatment in continuous abstinence, with neither significant effect on prevalent abstinence nor dropout rate. Conclusion: This review suggested and agreed that Varenicline, Cytisine and transdermal nicotine delivery, as smoking cessation intervention, have advantages and disadvantages. However, we had to have reservations about e-cigarettes as a way to quit smoking in adolescents.

Modification of Electronic Nicotine Delivery Systems Among Adolescents and Young Adults.

OBJECTIVES: We assessed awareness and perceptions of, information sources about, and engagement in modifying electronic nicotine delivery systems (ENDS) among adolescents and young adults (AYAs). METHODS: AYAs (N = 1018) endorsing past-month ENDS use completed a survey on awareness and use of the following modifications: (1) refilling rechargeable cartridges/pods or (2) disposable pods, (3) rewicking or (4) recharging disposable pods, (5) modifying nicotine e-liquids (eg, changing propylene glycol/vegetable glycerin, nicotine), (6) combining nicotine and cannabis for simultaneous vaping, and (7) putting cannabis in ENDS designed for nicotine vaping. Logistic regression assessed how sources of information (eg, friends, social media, nonsocial media Web sites, vape shops) about and perceptions of ENDS modifications associated with ENDS modifications. RESULTS: Refilling (69.0% heard, 40.1% tried) and recharging the battery (66.4% heard, 35.8% tried) of disposable pods were most common. Friends (64.4%) and social media (46.7%) were the most common sources of information. Notable significant associations between information sources and modifications were: 1. nonsocial media Web sites and vape shops with rewicking and recharging disposable devices and modifying nicotine e-liquid; 2. nonsocial media Web sites with refilling rechargeable cartridges/pods and disposable pods; and 3. social media with recharging disposable devices and mixing nicotine and cannabis liquids. Perceptions of reduced harm and "coolness" were associated with various modifications. DISCUSSION: AYAs are aware of and modify ENDS for purposes unintended by manufacturers. ENDS policies should consider unintended ENDS use to safeguard public health. Prevention efforts should communicate about the potential harms of ENDS modifications.

Do Australians use the prescription pathway when using nicotine vaping products to quit smoking?

BACKGROUND: In Australia, nicotine vaping products (NVPs) are only legally available to those with a prescription from a doctor. We investigated the proportion of people using NVPs to quit smoking who had a prescription, and whether this increased following regulatory changes in 2021 that strengthened the prescription requirement. METHODS: Australian data from the 2018, 2020 and 2022 International Tobacco Control (ITC) Project Survey were analysed using GEE models with Poisson regressions to analyze differences between years. Data from participants who reported making a quit attempt in the previous two years and reported use of NVPs on their last quit attempt were included (480 observations across 418 individuals). Participants reported whether they had a prescription for NVPs on their last quit attempt. In 2022, they were also asked whether they sourced their prescription from their usual medical practice. RESULTS: Among those using NVPs for a quit attempt, use with a prescription increased significantly from 2020 to 2022 (IRR = 0.35 (0.17-0.73), p = .005) but was still low at 16.5 % (95 % CI 11.4-23.1). In 2022, among the small number who reported getting a prescription for NVPs, 27 % reported getting it from their regular practice; the remainder from a specialist online doctor service. CONCLUSION: There was a modest increase in obtaining a prescription among those who used NVPs for their last quit attempt after regulations were strengthened, however most NVP use for quitting was without a prescription.

The effect of e-cigarettes on cognitive function: a scoping review.

AIM: Much research has been conducted on the acute effects of nicotine on human cognitive performance, demonstrating both enhancing and impairing cognitive effects. With the relatively recent introduction of electronic cigarettes ('e-cigarettes') as a smoking cessation device, little is known about the cognitive effects of e-cigarettes specifically, either as a nicotine replacement device or in the absence of nicotine. The purpose of this review was to present an overview of evidence from empirical studies on the effect of e-cigarettes on cognitive function. APPROACH: Guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines (PRISMA-ScR), SCOPUS, PubMed, and EBSCOhost were searched from 2006, the year e-cigarettes were introduced, to June 2023 for relevant papers, along with reference lists checked for additional papers. KEY FINDINGS: Seven experimental and four cross-sectional survey studies were identified and included. The majority of the studies only include regular and current cigarette smokers and primarily assessed the acute cognitive effect of e-cigarettes relative to nicotine. While the findings primarily suggest either no or positive effect of e-cigarettes on cognition in cigarette smokers, associations between e-cigarettes and cognitive impairments in memory, concentration and decision making were reported in both cigarette smokers and never-smokers. IMPLICATIONS AND CONCLUSIONS: The acute cognitive effect of e-cigarettes on regular cigarette smokers appears minimal. However, long-term cognitive effect and their effects on never-smokers are unclear. Given that the increased numbers of e-cigarette users are non-smokers and/or adolescents, research with those naïve to nicotine and a developmentally vulnerable adolescent population on its long-term effect is needed.

Fluorocitrate inhibition of astrocytes reduces nicotine self-administration and alters extracellular levels of glutamate and dopamine within the nucleus accumbens in male wistar rats.

Emerging evidence suggests an important role of astrocytes in mediating behavioral and molecular effects of commonly misused drugs. Passive exposure to nicotine alters molecular, morphological, and functional properties of astrocytes. However, a potential involvement of astrocytes in nicotine reinforcement remains largely unexplored. The overall hypothesis tested in the current study is that astrocytes play a critical role in nicotine reinforcement. Protein levels of the astrocyte marker glial fibrillary acidic protein (GFAP) were examined in key mesocorticolimbic regions following chronic nicotine intravenous self-administration. Fluorocitrate, a metabolic inhibitor of astrocytes, was tested for its effects on behaviors related to nicotine reinforcement and relapse. Effects of fluorocitrate on extracellular neurotransmitter levels, including glutamate, GABA, and dopamine, were determined with microdialysis. Chronic nicotine intravenous self-administration increased GFAP expression in the nucleus accumbens core (NACcr), but not other key mesocorticolimbic regions, compared to saline intravenous self-administration. Both intra-ventricular and intra-NACcr microinjection of fluorocitrate decreased nicotine self-administration. Intra-NACcr fluorocitrate microinjection also inhibited cue-induced reinstatement of nicotine seeking. Local perfusion of fluorocitrate decreased extracellular glutamate levels, elevated extracellular dopamine levels, but did not alter extracellular GABA levels in the NACcr. Fluorocitrate did not alter basal locomotor activity. These results indicate that nicotine reinforcement upregulates the astrocyte marker GFAP expression in the NACcr, metabolic inhibition of astrocytes attenuates nicotine reinforcement and relapse, and metabolic inhibition of astrocytes disrupts extracellular dopamine and glutamate transmission. Overall, these findings suggest that astrocytes play an important role in nicotine reinforcement and relapse, potentially through regulation of extracellular glutamate and dopamine neurotransmission.

Smoking Cessation After Initial Treatment Failure With Varenicline or Nicotine Replacement: A Randomized Clinical Trial.

Importance: Most people who smoke do not quit on their initial attempt. Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT). Design, Setting, and Participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic. Interventions: The initial treatment was 2 mg/d of varenicline or the combined replacement therapy of a 21-mg patch plus 2-mg lozenge. The rerandomized participants either continued with their initial therapies, switched between varenicline and CNRT, or increased dosages either to 3-mg or more of varenicline or to a 42-mg patch and lozenges. All received weekly brief counseling. Main Outcomes and Measures: Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks. Results: The 490 randomized participants (210 female [43%], 287 non-Hispanic White [58%], mean age, 48.1 years) smoked an average of 20 cigarettes per day. After the first phase, 54 participants in the CNRT group were abstinent and continued their therapy; of the 191 who were not abstinent, 151 were rerandomized, and the 40 who did not return for rerandomization were assigned to continue their initial CNRT condition in phase 2. The end-of-treatment abstinence rate for the 191 phase 1 nonabstainers was 8% (95% credible interval [CrI], 6% to 10%) for the 90 (47%) who continued at the dosage condition, 14% (CrI, 10% to 18%) for the 50 (33%) who increased their dosage, and 14% (95% CrI, 10% to 18%) for the 51 (34%) who switched to varenicline (absolute risk difference [RD], 6%; 95% CrI, 6% to 11%) with more than 99% posterior probability that either strategy conferred benefit over continuing the initial dosage. After the first phase, 88 participants in the varenicline group were abstinent and continued their therapy; of the 157 who were not abstinent, 122 were rerandomized and 35 who did not return for rerandomization were assigned to continue with the varenicline condition. The end-of-treatment abstinence rate for the 157 phase 1 nonabstainers was 20% (95% CrI, 16% to 26%) for the 39 (32%) who increased their varenicline dosage, 0 (95% CrI, 0 to 0) for the 41 (34%) who switched CNRT, and 3% (95% CrI, 1% to 4%) for the 77 (49%) who were assigned to the continued varenicline condition (absolute RD, -3%; 95% CrI, -4% to -1%) with more than 99% posterior probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage. Furthermore, increasing the varenicline dosage had an absolute RD of 18% (95% CrI, 13% to 24%) and a more than 99% posterior probability of conferring benefit. The secondary outcome of continuous abstinence at 6 months indicated that only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages. Conclusions and Relevance: For individuals who smoked but did not achieve abstinence after treatment with varenicline, increasing the dosage enhanced abstinence vs continuing, whereas for nonabstainers initially treated with CNRT, a dosage increase or switch to varenicline enhanced abstinence and may be viable rescue strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT02271919.

Sources of exposure to non-tobacco nicotine electronic nicotine delivery systems and associations with susceptibility to use and use behaviors among young adults in the United States.

INTRODUCTION: The Electronic Nicotine Delivery Systems (ENDS) industry recently introduced non-tobacco nicotine (NTN), which is not tobacco-derived and is often marketed as "tobacco-free nicotine." Given its novelty, it is important to understand where young adults learn about NTN ENDS. This study examined sources of exposure to NTN ENDS and relationships with NTN ENDS use and susceptibility. METHODS: We analyzed online survey data collected in Fall 2021 from 642 young adults (18-25 years) who had heard of NTN ENDS. We assessed 9 sources of NTN ENDS exposure (e.g., retail stores, social media) and examined associations between sources of exposure and NTN current (past-month) use, lifetime (non-current) use, and susceptibility to use, adjusting for demographics and other tobacco product use. RESULTS: Participants reported current NTN ENDS use (37.4%), lifetime use (12.0%), susceptibility (18.5%), or no susceptibility to use (32.1%). The most common sources of NTN ENDS exposure were retail stores (87.7%) and social media (81.0%). Exposure to NTN ENDS via social media was associated with greater odds of current NTN ENDS use (vs. no susceptibility) (aOR = 1.83, 95%CI: 1.02-3.28). Exposure via online streaming platforms was associated with greater odds of current (aOR = 1.75, 95%CI: 1.08-2.82) and lifetime NTN ENDS use (aOR = 2.42, 95%CI: 1.25-4.68). CONCLUSIONS: Young adults were exposed to and learned about NTN ENDS from diverse sources, primarily retail shops and social media. Further, exposure via social media and streaming platforms were associated with NTN ENDS use. Future studies should explore the content of NTN information from various sources to inform prevention efforts.

Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues.

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.