Partial Nicotine Reduction and E-Cigarette Users' Puffing Behaviors Among Adults Aged 21 to 35 Years: A Randomized Crossover Clinical Trial.

Importance: The advent of salt-based, high-nicotine electronic nicotine delivery systems [e-cigarettes] has contributed to their epidemic use among young people in the US, necessitating the need for policies to address the addictiveness of these products. Objective: To evaluate the effect of partial nicotine reduction on new-generation e-cigarette users' puffing behaviors. Design, Setting, and Participants: This randomized crossover clinical trial was conducted at the Clinical Research Lab for Tobacco Smoking at Florida International University in Miami between April 15, 2022, and October 17, 2023. Using a volunteering sampling method by distributing flyers and advertisements, current e-cigarette users (who preferred 5% nicotine concentration), aged 21 to 35 years, were included. Intervention: In a crossover design, participants completed 2 sessions of the same product (JUUL or NJOY) that differed by nicotine concentration (3% [JUUL] or 2.4% [NJOY] and 5% [JUUL or NJOY]) in random order. In each session, participants vaped up to 60 minutes ad libitum, preceded by 12 hours of nicotine abstinence. Main Outcomes and Measures: The primary outcomes were puffing topography parameters (eg, total session time, puffing time, total puffing number, interpuff interval, total inhaled volume, average puff volume, duration, and flow rate) measured during each session and plasma nicotine measured before and after each session. Results: Among 735 participants who were approached for eligibility, 675 were excluded, and 10 did not complete session 2. Of the 50 remaining current e-cigarette users (mean [SD] age, 23 [3] years; 56% men), 23 (46%) were low nicotine dependent. The median topography parameters were significantly higher during the e-cigarette use sessions with 3% or 2.4% nicotine concentration compared with 5% nicotine concentration for 3 outcomes: puffing time (1.3 minutes [IQR, 0.3-9.4 minutes] vs 1.2 minutes [IQR, 0.2-5.6 minutes]; P = .02), puff duration (2.6 seconds [IQR, 0.8-6.9 seconds] vs 2.4 seconds [IQR, 0.4-6.6 seconds]; P = .02), and total inhaled volume (1990.0 mL [IQR, 279.0-24 400.0 mL] vs 1490.0 mL [IQR, 148.0-14 300.0 mL]; P = .05). The median plasma nicotine boost observed in the 5% nicotine concentration condition (0.0060 mg/L [IQR, 0.0001-0.0249 mg/L]) was significantly higher than that in the 3% or 2.4% session (0.0043 mg/L [IQR, 0.0008-0.0225 mg/L]) (P = .001). Additionally, deeper puffing (increased average puff duration and average puff volume) was observed in participants with higher nicotine dependence (1.42 seconds [95% CI, 1.12-1.80 seconds]; P = .03) and male users (1.38 mL [95% CI, 1.09-1.75 mL]; P = .04) in response to nicotine reduction. Conclusions and Relevance: This randomized crossover clinical trial provides direct evidence that partial nicotine reduction in salt-based e-cigarettes was associated with acute compensatory puffing and the potential for increased exposure to toxicants. However, given the reduced nicotine delivery associated with nicotine reduction, the acute compensatory response observed in this study may not preclude a population benefit due to the marketing of less addictive products. These results suggest that at least for current e-cigarette users, partial nicotine reduction can lead to enhanced exposure to some toxicants in the short term. Trial Registration: ClinicalTrials.gov Identifier: NCT05205382.

Assessing the Relationship between Biomarkers of Exposure and Biomarkers of Potential Harm: PATH Study Wave 1 (2013 to 2014).

BACKGROUND: The adequacy of biomarkers of potential harm (BOPH) for assessing tobacco products was explored based on their ability to distinguish tobacco use from non-use, change with cessation, and to show biological gradient. METHODS: The sample included individuals with biomarker data in wave 1 of the Population Assessment of Tobacco Health study who never used tobacco, currently smoke cigarettes exclusively, used to smoke cigarettes exclusively (quit in past 12 months), currently use smokeless tobacco exclusively, and currently use e-cigarettes exclusively. We compared BOPH levels between groups and assessed the relationships between log-transformed biomarkers of exposure [BOE; total nicotine equivalents including seven nicotine metabolites (TNE-7), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol (NNAL), N-acetyl-S-(2-cyanoethyl)-L-cysteine, 1-hydroxypyrene, cadmium, and serum cotinine (SCOT)], and BOPH [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and 8-isoprostane]. RESULTS: Among people who smoke, both sICAM-1 and 8-isoprostane distinguished smoking from non-use and were associated with all six BOE. Among people who use smokeless tobacco, 8-isoprostane was associated with TNE-7 and NNAL whereas hs-CRP was associated with SCOT. Among people who use e-cigarettes, no associations between BOPH and BOE were observed. CONCLUSIONS: Both sICAM-1 and 8-isoprostane may be useful for assessing the use or changes in use of some tobacco products. Studies examining their predictive validity could further strengthen our understanding of these two biomarkers. IMPACT: We found that two biomarkers of potential harm, soluble intercellular adhesion molecule-1 and 8-isoprostane, may have utility in studies assessing the potential harm of tobacco use in absence of long-term epidemiological studies.

Secondhand Nicotine Absorption From E-Cigarette Vapor vs Tobacco Smoke in Children.

Importance: With the prevalence of e-cigarette use (vaping) increasing worldwide, there are concerns about children's exposure to secondhand vapor. Objective: To compare nicotine absorption among children who are (1) exposed to secondhand tobacco smoke only or (2) exposed to secondhand vapor only with (3) those exposed to neither. Design, Setting, and Participants: The US Continuous National Health and Nutrition Examination Survey (NHANES) is a repeat cross-sectional survey. Participants are interviewed in their homes and, several days after, visit a mobile examination center to provide biological specimens. This study uses data from a nationally representative sample of US households from 2017 to 2020. Participants were children aged 3 to 11 years with serum cotinine levels incompatible with current firsthand nicotine use (ie, <15 µg/L). The final analysis was conducted on January 9, 2024. Exposures: Reported exposure to secondhand smoke or vapor indoors in the past 7 days (only secondhand smoke, only secondhand vapor, or neither). Covariates included age, sex, ethnicity, family income, body weight, and height. Main Outcomes and Measures: The primary outcome was serum cotinine concentration, an objective biomarker of nicotine absorption. Geometric mean cotinine levels and 95% CIs were calculated using log-normal tobit regression, accounting for the complex survey design and weights. Results: The mean (SD) age of the 1777 children surveyed was 7.4 (2.6) years, 882 (49.6%) were female, and 531 (29.9%) had family incomes below the poverty level. Nicotine absorption, as indexed by serum cotinine level, was highest among children only exposed to secondhand smoke (0.494 µg/L µg/L; 95% CI, 0.386-0.633 µg/L), followed by those exposed only to secondhand vapor (0.081 µg/L; 95% CI, 0.048-0.137 µg/L), equating to 83.6% (95% CI, 71.5%-90.5%; P < .001) lower nicotine absorption. Among children with no reported secondhand exposure, the geometric mean cotinine level was 0.016 µg/L (95% CI, 0.013-0.021 µg/L), or 96.7% (95% CI, 95.6%-97.6%; P < .001) lower than for those with exposure to secondhand smoke. Results were similar after covariate adjustment. Conclusions and Relevance: In this cross-sectional study of US children, nicotine absorption was much lower in children who were exposed to secondhand vapor vs secondhand smoke, but higher than in those exposed to neither. These findings suggest that switching from smoking to vaping indoors may substantially reduce, but not eliminate, children's secondhand exposure to nicotine and other noxious substances.

Arrhythmogenic effects of acute electronic cigarette compared to tobacco cigarette smoking in people living with HIV.

The leading cause of death in people living with HIV (PLWH) is cardiovascular disease, and the high prevalence of tobacco cigarette (TC) smoking is a major contributor. Switching to electronic cigarettes (ECs) has been promoted as a harm reduction strategy. We sought to determine if acute EC compared to TC smoking had less harmful effects on arrhythmogenic risk factors including acute changes in hemodynamics, heart rate variability (HRV), and ventricular repolarization (VR). In PLWH who smoke, changes in hemodynamics, HRV, and VR were compared pre/post acutely using an EC, TC, or puffing on an empty straw on different days in random order, in a crossover study. Thirty-seven PLWH (36 males, mean age 40.5 ± 9.1 years) participated. Plasma nicotine was greater after TC versus EC use (10.12 ± 0.96 vs. 6.18 ± 0.99 ng/mL, respectively, p = 0.004). HR increased significantly, and similarly, after acute EC and TC smoking compared to control. Changes in HRV that confer increased cardiac risk (LF/HF ratio) were significantly smaller after acute EC versus TC use, consistent with a harm reduction effect. In a post-hoc analysis of PLWH with and without positive concurrent recreational drug use as indicated by point of care urine toxicology testing, this differential effect was only seen in PLWH not currently using recreational drugs. Changes in VR were not different among the three exposures. In PLWH who smoke, EC compared to TC smoking resulted in smaller adverse changes in HRV. This differential effect was accompanied by a smaller increase in plasma nicotine, and was negated by concurrent recreational drug use. Additional studies are warranted in this vulnerable population disproportionately affected by tobacco-related health disparities.

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects.

Transdermal nicotine patches (TNPs), administering nicotine into the bloodstream through skin, have been widely used as nicotine replacement therapy, and exposure to nicotine can be detected by measurement of plasma cotinine concentration. In animal studies, nicotine treatment could increase the number of endothelial progenitor cells (EPCs), but the effect of TNPs on circulating EPCs and their activity in humans remained unclear. This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers. In parallel, pulse wave analysis (PWA) was applied to evaluate the vascular effect of TNP treatments. Twenty-one participants (25.8 ± 3.6 years old, 10 males) used TNP (nicotine: 4.2 mg/day) for 7 consecutive days. During the treatment, the CD34+ EPCs progressively increased in number. In addition, the number of EPCs positive for CD34/KDR, CD133, and CD34/CD133 were also increased on day 7 of the treatment. Furthermore, the early EPC colony-forming function and migration activity were increased with the plasma cotinine level positively correlating with change in colony-forming unit number. PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits

Abstract Purpose: To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Methods: Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. Results: The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Conclusion: Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

New experimental model of exposure to environmental tobacco smoke

PURPOSE: To describe a new model to passive smoking for rodents. METHODS: Twenty rats were distributed into two study groups (N=10): control group (CG), that was not exposed to tobacco smoke and used as normal standard for biochemical and histological analysis; Experimental Group (EG), that Animals were exposed to the passive smoking; Euthanasia was performed after 14 days of exposure. The serum level of nicotine and histological analysis were performed. RESULTS: There was a statistical difference on the nicotine serum levels between Experimental and Control group, with level of 286 ±23 nanograma/mL in the EG and undetectable on CG (p<0.01). The histological study suggested the model efficacy producing alveolar destruction and emphysema in the EG compared with the insignificant lesions in the CG's lung. CONCLUSION: The model of exposure to environmental tobacco smoke for rodents induced easily the changes related to secondhand smoke.

Histologic evaluation of the effect of nicotine administration on bone regeneration: a study in dogs

O objetivo do presente estudo foi avaliar histometricamente a influência da nicotina sobre a regeneração óssea de defeitos criados cirurgicamente em rebordos alveolares edêntulos de cães. Defeitos ósseos foram criados cirurgicamente em um dos lados da mandíbula de dezesseis cães e foram deixados para que curassem espontanea-mente. Os animais foram aleatoriamente designados para um dos seguintes grupos: Grupo 1 - controle (n = 8) e Grupo 2 - administração subcutânea de nicotina (2 mg/kg) duas vezes ao dia durante 4 meses (n = 8). Os animais foram sacrificados, e secções semi-seriadas descalcificadas, obtidas. Os parâmetros histométricos avaliados foram altura, largura, área e densidade do tecido ósseo neoformado. A análise intergrupos (Mann-Whitney "rank sum test") demonstrou que a administração de nicotina não influenciou altura, largura e área de tecido ósseo neoformado (p > 0,05). Entretanto, a administração de nicotina influenciou significativamente a densidade do tecido ósseo neoformado (p < 0,001). Dentro dos limites do presente estudo, pode-se concluir que a nicotina pode afetar, mas não impedir a regeneração de defeitos ósseos criados cirurgicamente em mandíbulas edêntulas de cães.

Effect of nicotine in randomized skin flaps in rats

This study analyzed the perfusion of randomized skin flaps in rats after nicotine injections, in doses that could be compared with heavy and light smorkers. A skin flap was elevated after 12 weeks of nicotine adminsitration and the percentage of necrotic area was determined thereafter. There was a statistically significant difference between "heavy smokers" in the preoperative (G3) and preoperative and postoperative periods (G5), suggesting a deleterious effect of nicotine in the postoperative period

Exposición nicotinica al humo de cigarrillos en fumadores y no fumadores / Exposure to cigarette smoke nicotine in smokers and nonsmokers

Como una actividad de apoyo al programa de reducción de la mortalidad por cáncer y a la campaña de reducción del hábito de fumar se realizó una investigación en individuos fumadores y no fumadores con el objetivo de determinar los niveles de nicotina en sangre en ambos grupos. Se describe el método utilizado para la determinación, así como los resultados a los que se arribaron y se observó una elevada concentración en el caso de los fumadores y en los no fumadores expuestos al humo de cigarrillos. Estos resultados son comparables con los informados en la literatura