Combustible Cigarettes Research Articles

Evaluating the human abuse potential of concurrent use of electronic cigarettes and low nicotine cigarettes among adults who smoke.

The U.S. Food and Drug Administration has stated its intention to reduce the nicotine content of combustible cigarettes to render them less addictive. This study evaluated the impact of providing adults who smoke with both very low nicotine content cigarettes (VLNCCs) and electronic cigarettes (ECs) of varying nicotine content on measures of human abuse potential. Participants (n = 213) were adult combustible cigarette users. They smoked their usual brand cigarettes (UBCs) during Phase 1 (baseline; week 1) and were provided with and encouraged to exclusively use VLNCCs during Phase 2 (weeks 2-4). During dual-product Phases 3 (weeks 5-7) and 4 (weeks 8-10), participants received both VLNCCs and ECs (assigned to one of two EC devices in higher or lower nicotine concentrations and choice of flavor), with instructions to use them freely in Phases 3 and 4. Assessments included product use, exposure, acceptability, risk perception, and withdrawal-related measures. Results indicated that participants used significantly fewer UBCs during the VLNCC and dual-product phases and smoked fewer VLNCCs during the dual-product phases than the VLNCC-only phase. Neither EC liquid nicotine concentration nor flavor influenced product use. The three study product phases resulted in less product liking and more withdrawal symptoms than the UBC phase. These results suggest that adults who smoke are able to switch much of their tobacco product use from UBCs to VLNCCs and will substitute combustible UBCs and VLNCCs with noncombustible nicotine-containing ECs, but most remain dual users, at least in the short term. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The effects of electronic cigarette use patterns on health-related symptom burden and quality of life: analysis of US prospective longitudinal cohort study data

ObjectiveThis study aimed to examine the association between e-cigarette (EC) use patterns and health-related symptoms (fatigue, pain, and emotional problems) as well as general quality of life (QoL).MethodsData were analyzed from 7,225 adults across Waves 1–6 of the US Population Assessment of Tobacco and Health (PATH) study. Current combustible cigarette (CC) or EC use patterns included dual CC/EC use, exclusive EC use, non-current use of CC or EC, and exclusive CC smoking. Multivariate linear mixed-effects models were used to investigate longitudinal associations between EC use patterns, and symptom burdens/QoL scores.ResultsThose who were not currently smoking or vaping reported the lowest fatigue, pain, and emotional problems, and the best QoL, among the four groups (all p < 0.001). Compared to exclusive CC smoking, exclusive EC use was associated with a significant decrease of 0.065 units in average fatigue (95% confidence interval [CI]: −0.121, −0.009), of 0.206 units in average pain (95% CI: −0.355, −0.058), and of 0.103 units in average QoL scores (95% CI: −0.155, −0.051), with emotional problems similar over time.ConclusionExclusive EC users had less health-related symptoms and better QoL than those who were exclusive CC smokers. This should be taken into account when assessing the harm reduction potential of ECs.

Delay discounting validity and e-cigarette use: A comparison in e-cigarette users, combustible cigarette users, dual users, and nonusers.

Delay discounting refers to the devaluation of an outcome as temporal delay increases. Steep discounting is characterized by preferring a smaller, immediate outcome over a larger, delayed outcome and is associated with maladaptive behaviors such as tobacco use. Previous studies have compared delay discounting outcomes between combustible cigarette (CC) smokers and nonusers using various discounting tasks. With the growing use of electronic cigarettes (e-cigarettes [EC]) and various delay discounting tasks available to researchers, we extended previous work in delay discounting and EC use in two ways. The present study assessed delay discounting in a web-based sample of 259 participants to (a) establish convergent validity across four different delay discounting tasks and (b) compare the outcomes between four subgroups: dual users, exclusive EC users, exclusive CC users, and nonusers. The four delay discounting tasks (Monetary Choice Questionnaire, 5-Trial Adjusting Delay Discounting Task [ADT-5], Temporal Discounting Questionnaire, and Brief Intertemporal Choice Task [BRIC Task]) showed moderate to strong convergent validity (p < .001). Further, findings indicated significant differences between all four subgroups across the four different delay discounting tasks (p < .048) with small effect sizes. Pairwise comparisons showed that exclusive EC users exhibited significantly steeper discounting than nonusers in ADT-5 (p = .043) and BRIC Task (p = .029) and dual users exhibited significantly steeper discounting than nonusers on ADT-5 (p = .043) and BRIC Task (p = .030). Our findings replicate previous findings and suggest the potential role of delay discounting in explaining the behavioral mechanism underlying e-cigarette use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

“Reviving Old Tricks in New Tobacco Marketing: Presence of e-Cigarette Brand Names on Merchandise Promoted by Influencers on Social Media.”

Background Tobacco brand sharing or brand stretching involves the placement of tobacco brand names, logos, or other distinctive elements of tobacco brands, on nontobacco products, e.g., merchandize, such as clothing, sunglasses, or sporting goods. The Tobacco Master Settlement Agreement (MSA) imposed major restrictions on tobacco company marketing practices in 1999, including banning the sale and distribution of merchandize with combustible cigarette or smokeless tobacco brand names or logos. However, the MSA does not include restrictions on e-cigarette marketing, as these products were not yet on the market at the time of the settlement. Exposure to or use of e-cigarette branded merchandize advertised on social media could contribute to normalization of e-cigarette use by youth. Methods We estimated the prevalence of merchandize (e.g., t-shirts, caps, and key chains) with e-cigarette brand names or logos in 2000 TikTok videos (2021–2022) that featured U.S. and international micro-influencers (content creators with about 10,000–100,000 followers) who promoted e-cigarettes on behalf of e-cigarette brands. Results Of 152 (8%) promotional videos had merchandize with e-cigarette brand names or logos. Of 125 (6%) featured micro-influencers wearing branded clothing items, i.e., t-shirts, caps, beanies, hoodies, and sweatshirts; and 27 (2%) featured influencers wearing or showing branded accessories, i.e., face masks, stickers, pins, mugs, car air fresheners, lanyards, and key chains. Conclusions Tobacco control authorities should consider adopting provisions banning the sale, distribution, and direct (e.g., by e-cigarette brands) or indirect (e.g., by influencers) advertising of merchandize bearing e-cigarette brand names or logos.

Supplemental Material for Delay Discounting Validity and E-Cigarette Use: A Comparison in E-Cigarette Users, Combustible Cigarette Users, Dual Users, and Nonusers

Supplemental Material for Delay Discounting Validity and E-Cigarette Use: A Comparison in E-Cigarette Users, Combustible Cigarette Users, Dual Users, and Nonusers

Construction of a numerical model for cigarette smoking and combustion and simulation of combustion cone shape

Abstract Understanding the thermal conditions inside a burning cigarette is a top priority for controlling chemical emissions and cigarette design. Since experimental methods are difficult to observe in depth, this paper starts from the perspective of numerical simulation and models the structure of the tobacco distribution of the cigarette, integrating the end surface ignition model, puffing model, chemical reaction model, heat and mass transfer and diffusion model have established a three-dimensional comprehensive model that can represent the changes in combustion cone morphology during cigarette combustion. The model covers chemical reaction and mass transfer as well as generation, flow and reaction mechanism. The simulation results show that the model can better predict the temperature distribution, component distribution and combustion cone morphology changes during cigarette smoking and combustion. It provides an effective means for in-depth research on cigarette combustion.

Cerebral Cortical Vasodilation via Nicotinic Receptors by Heated Tobacco Product Aerosol Extract in Rats

Introduction: Smoking increases the risk of lung cancer due to a number of components of smoke. The use of novel heated tobacco products (HTPs), alternative to conventional combustion cigarettes, has increased in recent years. However, the in vivo biological effects of HTPs are poorly understood. This study aimed to clarify the acute effects of injecting aerosol extract prepared from an HTP on regional cerebral blood flow (rCBF) in rat cortex by comparing them to the effects of injecting smoke extract prepared from conventional combustible cigarettes. Methods: In urethane anesthetized rats, rCBF was measured using laser speckle contrast imaging simultaneously with arterial pressure. Results: Both cigarette smoke extract and HTP aerosol extract, at a dose equivalent to 30 μg nicotine/kg, injected intravenously, increased cortical rCBF without changing arterial pressure. The magnitude and time course of the increased rCBF response to both extracts were similar throughout the cortical area, and the rCBF increases were all abolished by dihydro-β-erythroidine, an α4β2-preferring nicotinic acetylcholine receptor (nAChR) antagonist. Conclusion: In conclusion, our study demonstrated that the effect of injecting aerosol extract prepared from an HTP, an acute increase in cortical rCBF, is mediated via activation of α4β2-like neuronal nAChRs in the brain.

E-CIGARETTE SWITCHING AND FINANCIAL INCENTIVES TO PROMOTE COMBUSTIBLE CIGARETTE CESSATION AMONG ADULTS ACCESSING SHELTER SERVICES: A PILOT STUDY

BackgroundSmoking prevalence among U.S. adults experiencing homelessness is ≥70%. Interventions are needed to address persisting tobacco disparities. MethodsAdults who smoked combustible cigarettes (CC) daily (N=60) were recruited from an urban day shelter and randomly assigned to an e-cigarette switching intervention with or without financial incentives for carbon monoxide (CO)-verified CC abstinence (EC vs. EC+FI). All participants received an e-cigarette device and nicotine pods during the first 4 weeks post-switch; and those in the EC+FI group also received escalating weekly incentives for CC abstinence during the same period. Key follow-ups were conducted at 4- and 8-weeks post-switch. ResultsParticipants were predominantly male (75%), 50% were racially/ethnically minoritized, with an average age of 48.8 years. Descriptive analyses indicated that CC smoking abstinence rates among EC and EC+FI were 3.3% vs. 13.3% at 4 weeks (8.3% overall) and 10.0% vs. 13.3% at 8 weeks (11.7% overall) in the intent-to-treat analyses (missing considered smoking). Among those who completed follow-ups (51.7% and 45.0% at 4- and 8-weeks), CC abstinence rates in EC and EC+FI were 6.3% vs. 26.7% at 4 weeks (16.1% overall) and 21.4% vs. 30.8% at 8 weeks (25.9% overall). EC+FI participants reported fewer days of smoking, more days of e-cigarette use, and greater reductions in CO at 4-week follow-up. Most participants reported a high likelihood of switching to e-cigarettes (67.7%). ConclusionE-cigarette switching with financial incentives for CC cessation is a promising approach to tobacco harm reduction among adults accessing shelter services. Refinements are needed to improve engagement.

Vaping and smoking cue reactivity in young adult non-smoking electronic cigarette users: A functional neuroimaging study.

The rapid growth in the use of electronic cigarettes (e-cigarettes) among non-smoking young adults is concerning, as it raises the potential for chronic vaping and nicotine addiction. A key characteristic of drug addiction is the elevated neural response to conditioned drug-related cues (i.e., cue reactivity). Generalized reactivity to both vaping and smoking cues may signify an increased risk for smoking initiation in non-smoking vapers. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate brain responses to vaping and smoking cues in young adult non-smoking vapers. Sixty-six young adult non-smoking vapers underwent functional MRI while viewing visual cues pertaining to vaping, smoking, and nicotine-unrelated unconditioned reward (i.e., food). A priori region-of-interest analysis combined with exploratory whole-brain analysis was performed to characterize neural reactivity to vaping and smoking cues in comparison to food cues. The medial prefrontal cortex and the posterior cingulate cortex, regions that play a key role in drug cue reactivity, showed significantly increased neural response to vaping cues compared to food cues. The posterior cingulate cortex additionally showed increased neural responses to smoking cues compared to food cues. Despite not currently smoking combustible cigarettes, young adult vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems associated with cue reactivity. The findings shed light on the mechanisms underlying nicotine addiction and smoking initiation risk in this critical population and may contribute to the development of science-based interventions and regulatory measures in the future. The escalating vaping prevalence among US non-smoking young adults is alarming, due to its potential ramifications for nicotine addiction development. Nicotine addiction is characterized by elevated neural response to conditioned nicotine-related cues. Using functional neuroimaging, we showed that young adult non-smoking vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems previously associated with cue reactivity. Such cross-reactivity to both types of nicotine cues may serve as the mechanism underlying nicotine addiction and smoking initiation risk in this population. Our findings may contribute to the development of science-based interventions and regulatory measures addressing the vaping epidemic.

Intrapartum Electronic Cigarette Use and Birth Outcomes: Evidence from a Population-Based Study

The harms of combustible cigarette (CC) use in pregnancy for fetal development are well studied. Less understood are the potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (ECs). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, and vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n = 26,394), CC (n = 2216), and EC (n = 493)) were compared on birth outcomes, controlling for background differences. Controls were defined as nonsmokers of ECs or CCs. Compared to the controls, the EC group had significantly lower birth weight, while the CC group had reduced birthweight and greater rates of arterial cord pH &lt; 7.1. Compared to EC users, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests ECs are not safer alternatives to CCs and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

Smoking cessation medicines and e-cigarettes in smokers with obesity

Abstract Purpose The interaction between obesity and smoking is complex. Aim of this study is to compare the abstinence rates of smoking cessation pharmacotherapies vs electronic cigarettes in obese smokers. Methods 57 obese smokers (aged 41±8 years, BMI: 33.8 ±2.4 Kg/m2) visiting our unit from January 2016 to November 2022 were randomized into three smoking cessation therapy groups: 1. NRT (nicotine patch), 2. NRT + bupropion (NRT+bupr) and 3. Electronic cigarette (EC). Results There were not significant differences in severity of nicotine dependence and cigarette consumption (pack-years) between the three treatment groups. Furthermore, the three groups had similar age and prevalence of traditional risk factors. At the end of treatment period (3 months), 5/19 (26 %) and 9/19 (47%) of subjects under therapy with NRT alone and NRT + bupropion combination respectively, were abstinent from smoking while 10/19 (53%) of individuals using EC did not smoke combustible cigarettes. Left plot shows the continuous abstinence rates at 6 months. Continuous abstinence rates were similar in the NRT and NRT+bupropion group at 6 months compared to 3 months (end of treatment), while 8/19 (42%) of individuals using EC did not smoke. Interestingly , at 6 months among users of EC 6 continued vaping nicotine alone, 7 continued to smoke tobacco cigarettes while vaping and 4 continued smoking cigarettes alone. Nevertheless only 2 out of 19 participants in that group stayed abstinent from both combustible cigarette smoking and vaping. Blood pressure remained unchanged in all groups while weight decreased in the group treated with the combination of bupropion and NRT compared to NRT alone and EC groups (right plot, P&amp;lt;0.01). Conclusions Our preliminary data indicate that continuous abstinence rates at 6 months were higher in obese smokers receiving NRT+bupropion combination therapy compared to those of individuals who used NRT alone. There is also a low abstinence rate of both cigarette smoking and vaping among individuals using EC as an aid for smoking cessation. The NRT+bupropion combination therapy was associated with a favorable effect on weight change in obese smokers.EC vs pharmacotherapy in obese smokers

Harm reduction for addictive consumption: When does it improve health and when does it backfire?

Some harm reduction strategies encourage individuals to switch from a harmful addictive good to a less harmful addictive good; examples include e-cigarettes (substitutes for combustible cigarettes) and methadone and buprenorphine (substitutes for opioids). These have proven to be controversial. Advocates argue that people struggling with addiction benefit because they can switch to a less harmful substance, but opponents argue that this could encourage abstainers to begin using the harm-reduction method or even, eventually, the original addictive good. This paper builds on theories of addiction to model the introduction of a harm reduction method, and demonstrates the conditions under which each side is correct.

Association of food insecurity with the use of tobacco products and urine cotinine-measured smoking intensity: evidence from a population-based study in South Korea, 2019–2021

IntroductionThis study explored the association between food insecurity and tobacco product use and urine cotinine-measured smoking intensity.MethodsThis cross-sectional study included 13 705 adults representative of the Korean population. The 18-item...

Use of E-Cigarette, Traditional Cigarettes, and C-Reactive Protein: The Cross Cohort Collaboration

This cross-sectional study included 18,797 participants from six longitudinal cohorts (CARDIA, FHS Gen III, HCHS/SOL, MESA, MiHeart, and REGARDS). 5,806 of them were with high-sensitivity C-reactive protein (hs-CRP) measurements. We found that among exclusive electronic cigarette (EC) use was associated with significantly lower high-sensitivity C-reactive protein (hs-CRP) levels compared to exclusive combustible cigarette use, suggesting a potentially lower inflammatory burden. hs-CRP levels in dual users and former smokers currently using EC were comparable to those observed in exclusive cigarette smokers. In contrast, individuals who exclusively used ECs showed no significant difference in hs-CRP levels compared to never smokers. These findings have important implications for tobacco regulation, public health, and clinical practice, highlighting the need for continued monitoring of EC-related health impacts.

Prognosis after switching to electronic cigarettes following percutaneous coronary intervention: a Korean nationwide study.

Despite the increasing popularity of electronic cigarettes (E-cigarettes), the prognostic impact of switching to E-cigarettes in smokers with coronary artery disease who have undergone percutaneous coronary intervention (PCI) remains unclear. Using a nationwide cohort from the Korean National Health Insurance database, 17 973 adults (≥20 years) identified as smokers (based on a health screening examination within 3 years before PCI) who underwent health screening within 3 years after PCI were enrolled to determine changes in smoking habits. Patients were classified as continued combustible cigarette users, successful quitters, or switchers to E-cigarettes. The group switching to E-cigarettes was further divided into dual users (using both combustible and E-cigarettes) and those exclusively using E-cigarettes. Primary outcomes included major adverse cardiac events (MACEs), a composite of all-cause death, spontaneous myocardial infarction, and repeat revascularization. Among the total population, 8951 patients (49.8%) continued using combustible cigarettes, 1694 (9.4%) were switched to E-cigarettes, and 7328 (40.7%) successfully quit smoking after PCI. During a median follow-up of 2.4 years, the cumulative incidence of MACE was lower among E-cigarette switchers (10%) or quitters (13.4%) than among continued combustible cigarette users (17%). When continued combustible cigarette users were used as the reference, the multivariable-adjusted hazard ratios with 95% confidence intervals for MACE were 0.82 (0.69-0.98) for switchers to E-cigarettes and 0.87 (0.79-0.96) for successful quitters. Compared with dual users, entirely switching to E-cigarettes was associated with a significantly lower MACE risk (hazard ratio 0.71; 95% confidence interval 0.51-0.99). Among smokers who underwent PCI for coronary artery disease, switching to E-cigarette use (particularly complete transition) or quitting smoking was associated with reduced MACE risk than with continued combustible cigarette use. ClinicalTrials.gov NCT06338761.

Can switching from cigarettes to heated tobacco products reduce consequences of pulmonary infection?

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. Does switching from cigarettes to HTPs improve responses to pulmonary infection. 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. 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 12h 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. 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.

Prenatal tobacco and tobacco-Cannabis co-exposure and unpredictability in maternal anger/hostility: Implications for toddler reactivity

Tobacco and cannabis are frequently used together during pregnancy. However, relatively little is known about how co-use and related maternal risk factors impact toddler reactivity. One understudied risk factor is maternal experience of anger/hostility, despite evidence suggesting that individuals who use substances experience more anger/hostility. In addition, mood unpredictability in anger/hostility (MUA), a relatively novel construct, may be particularly important for mothers who use substances as they attempt to cut down or quit during pregnancy and may also impact toddler reactivity. Importantly, prenatal exposures may also impact toddler outcomes via continued postnatal exposure and infant reactivity. We examined a conceptual model linking prenatal tobacco and tobacco-cannabis co-use, maternal anger/hostility, and unpredictability in anger/hostility with toddler reactivity in a sample (N = 247 at recruitment, 190 at toddler age; N = 247 for model testing) of dyads recruited during the first trimester of pregnancy into a tobacco group (use of combustible cigarettes; including sub-group of women who also used cannabis) and a non-substance use group. Results indicated a direct effect of prenatal co-exposure on blunted toddler reactivity for males only. Mothers who used substances prenatally had the highest levels of anger/hostility and MUA. Prenatal anger/hostility and MUA were associated with higher reactivity at infancy which in turn, was associated with higher toddler reactivity. Prenatal co-exposure and higher prenatal maternal anger/hostility was associated with continued postnatal exposure to cannabis which in turn, was associated with higher reactivity at toddlerhood. Results highlight the importance of examining prenatal co-exposure and continued postnatal cannabis exposure as well as associated maternal risk factors such as anger/hostility and MUA for toddler developmental outcomes.

Evaluating chronic disease approaches to ameliorate tobacco-related health disparities: Study protocol of a hybrid type 1 implementation-effectiveness trial

BackgroundBlack, Indigenous, and People of Color (BIPOC) communities experience higher prevalence of cardiovascular disease and related chronic conditions compared to White communities due to disparities in tobacco exposure. Smoking can be effectively treated but evidence-based treatments are less likely to be offered to or used by BIPOC patients. We present the study protocol of the Smoking Cessation Outreach for Racial Equity (SCORE) trial that tests the effect of adding longitudinal care coordination to current standard of care for smoking cessation to promote health equity among BIPOC patients. MethodsLongitudinal Proactive Outreach (LPO; 4 culturally tailored outreach call cycles over one year by motivational interviewing trained counselors to connect patients to cessation counseling and medication) will be added to the current standard of care, Ask-Advise-Connect (AAC; primary care providers asking all patients if they smoke, and if smoking, advising to quit and connecting to treatment). We will conduct a hybrid type 1 implementation-effectiveness trial to examine the direct effect of AAC + LPO (a multilevel health system intervention) vs. AAC on population-level combustible tobacco abstinence at 18 months and treatment utilization among 2000 BIPOC adults who smoke across two healthcare systems in Minnesota. Participants will be surveyed at 6, 12, and, 18 months post-enrollment to assess outcomes. The primary outcome is biochemically confirmed combustible cigarette abstinence at 18 months. DiscussionLPO has potential to promote health equity by addressing barriers caused by structural racism, including access to care, care fragmentation, and provider racism, by systematically reaching out to all BIPOC patients who smoke. ClinicaltrialsgovNCT05671380.

Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC-MS/MS Analysis.

Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC-MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjects̀ compliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.

Statistical Analyses Plan for “MAGnItude of cigarette substitutioN after Initiation oF e-cigarettes and its ImpaCt on biomArkers of exposure and potenTial harm in dual users”: MAGNIFICAT trial

BackgroundThe substitution of combustible cigarettes (CC) with non-combustible nicotine alternatives, such as e-cigarettes (EC), significantly lowers exposure to harmful chemicals. However, many individuals who use ECs continue smoking CCs, becoming dual users and remaining at increased risk of toxin exposure. This study will examine how the reduction in cigarettes smoked per day (CPD) after switching to ECs correlates with changes in biomarkers of exposure (BoE) and potential harm (BoPH) to evaluate the extent of harm in dual users. MethodsThe study is a prospective, non-randomised, observational, longitudinal cohort study in which 250 CC smokers will be invited to use EC as part of a smoking reduction/cessation strategy. Participants will be grouped in five dual use categories based on the change from baseline in CPD at 1, 3 and 6 months, based on self-reported use in the preceding 30 days. The primary outcome of interest is the mean absolute urinary 2-cyanoethyl mercapturic acid (2CyEMA), a well-validated BoE, also assessed at 1, 3 and 6 months. Other BoE will be assessed, together with exploration of the association between varying intensities of dual use and BoPH. The association between the dual use category and levels of BoE will be evaluated using analysis of variance (ANOVA), in order to understand which BoE are best suited to identifying different levels of dual use. Exploratory assessment of the value of BoPH will similarly be evaluated, to assess whether their predictive power extends from the binary smoker/non-smoker categorization to a more nuanced dual use categorization. The specific details of the own-brand CC will be available once smokers' enrollment in the study is complete. The EC used in the study will be the KIWI 2 Pen refillable pod system, with participants given the option to choose from three different flavored e-liquids: LEAF, MIDWAY, and GLACIAL, all containing 0.9% nicotine. For specialized equipment used for biomarker analysis please refer our previous publication: https://pubmed.ncbi.nlm.nih.gov/38584934/ ConclusionEC are increasingly adopted as a harm reduction strategy in CC smokers who wish to quit smoking, the outlined Statistical Analysis Plan (SAP) provides a robust approach to understand the impact of EC on CC use and to quantify the impact of dual use on clinical outcomes using BoPH. For statistical calculations we will use R software.The subject of this SAP manuscript – trial research – due to planned medical procedures, is a subject of verification by proper ERB (Ethics Review Board) in Poland and gained required approval prior to the start of the actions. The positive opinion was granted on 22nd February 2024, with the signature number 04/24.