Cigarette smoking is causally associated with a number of chronic diseases in which inflammation plays an important pathogenic role including pulmonary carcinoma, chronic bronchitis, emphysema, atherosclerosis, and thrombosis. In addition, cigarette smoking can exacerbate Crohn's disease and rheumatoid arthritis. In both the particulate and vapor phases, cigarette smoke contains a number of chemicals with proinflammatory or cytotoxic potential. In contrast with cigarette smoking, nicotine has been shown to ameliorate several inflammatory conditions via activation of α7- and α9-nicotinic cholinergic receptors. The chemistry of electronic cigarette (e-cigarette) vaping aerosols is comprised mainly of glycerol, propylene glycol, nicotine, and flavors. The nicotine can be found in either the free base or salt forms depending on the particular product design. E-cigarettes containing nicotine salts have the potential for nicotine exposure levels higher than cigarettes as the sensory cues associated with tobacco smoke nicotine (containing a mixture of free base nicotine and nicotine salts) have been dampened. In this review and analysis, the role of nicotine in inducing inflammation in the absence of other main-stream cigarette smoke constituents is examined. Established and putative mechanisms by which nicotine influences inflammatory pathways in users of nicotine-containing products are described toward better understanding nicotine's potential contribution to the risk profile. For the majority of diseases with an inflammatory component induced by cigarette smoking, evidence suggests that nicotine is not the causative agent. E-cigarette aerosols should limit the diversity of chemical constituents and minimize exposure to proinflammatory chemicals, e.g., acrolein, acetaldehyde, formaldehyde, and heavy metals.
Summary Background The Population Assessment of Tobacco and Health (PATH) is a commonly-used longitudinal survey on nicotine/tobacco product use meant to represent the US population. Accurate surveillance to prevent youth electronic nicotine delivery systems (ENDS) use requires understanding the impact of methodological differences in Wave 6 (∼2021), specifically older ages (14–17 vs. usual 12–17) and survey mode (some telephone interviews vs. usual self-completed). Methods Changes in past-30-day (P30D) youth ENDS prevalence and patterns of use (i.e., frequency, device type, flavors, and brand) were examined year-over-year and for the 3-year period (2019–2022). Analyses compared combined age groups and survey modes (i.e., among all youth in each wave regardless of methodological differences) with methodologically-comparable sub-groups (i.e., same age range and survey mode). The impact of age on point estimates and trends (i.e., interaction with wave) was examined. Results Youth P30D ENDS prevalence significantly declined over the prior 3 years, but not year-over-year in either the naïve or methodologically-comparable analyses. However, 14–17-year-olds reported higher prevalence and steeper declines (age-wave interaction p < 0.0001) over the past 3 years (12.2% to 7.5%) than 12–13-year-olds (1.7% to 1.2%). Age differences had more modest impacts on patterns of ENDS use. Discussion Methodological differences in PATH Wave 6 introduced artifacts in estimates of prevalence, and to a lesser extent, patterns of youth ENDS use. Waves 5 and 7 are approximately comparable (∼95% equivalent) with respect to these differences. Future research examining prevalence trends over these waves should account for differences in survey mode and age range.
Given the well-documented pharmacological differences between nicotine and nornicotine enantiomers, understanding their distribution is essential. This knowledge also helps authenticate the enantiomers’ source (natural or synthetic). To improve the quantitative determination methods for these distributions, the influence of additives, modifiers, and sample matrices on the chiral HPLC separation of the nornicotine enantiomers using UV detection is discussed. Changes on the order of 5–10% in selected alcohols as modifiers and selected amines (0.1% changes) as additives were found to have significant effect on the resolution and retention times of nornicotine enantiomers, while sample matrices demonstrated an impact on nornicotine enantiomer resolution (R). Systematic variation in the concentration of ethanol and isopropanol, as modifiers, along with variations in the concentration of diethylamine, triethylamine, and isopropylamine, as additives, revealed that the resolution (R) of the nornicotine enantiomers could be adjusted to values much greater than 2, using mobile phase flow rates of 0.8 and 1 mL/min. The retention times of the nornicotine enantiomer pairs could be varied between ~8 and 20 min, through modification of the mobile phase with the additives and modifiers. As expected, faster mobile phase flow rates of 1 mL/min moderately reduced retention times when compared with influences on retention time caused by changes in the amounts of modifier and additive, with an accompanying slight decrease in the R values. The %RSD values for both nornicotine resolution and retention times consistently remained below 3%. The detection limits for the nornicotine enantiomers were approximately 1 ng on column for each enantiomer. With the judiciously selected optimization of the levels of the hexane mobile phase additive, diethylamine, and modifier, ethanol, coupled with results from previously published results on nicotine and nornicotine alkaloid enantiomer separations, a simultaneous separation of both nornicotine and nicotine enantiomers having R values greater than 2 and an overall retention time of less than 15 min was attained. Noticeable influences on nornicotine enantiomer resolution and co-elution of tobacco extract components with nornicotine enantiomers as a function of mobile phase composition were illustrated and discussed. Previous published results in combination with this current body of work culminate in a well-rounded understanding of the influences of modifier and additive structure and concentration on the resolution as well as a simultaneous separation of nicotine and nornicotine enantiomers employing high performance liquid chromatography.
Descriptive Consumer-Reported Outcome Measures (CROM) are self-reported survey outcome measures intended to measure observable characteristics and behaviors in research on tobacco- and nicotine-containing products (TNPs). The wide variety of available TNPs and the continued development of new TNPs require a constant evolution of measures to assess TNP use and related constructs adequately. The guidelines aim to provide recommendations on the selection, development, implementation, and analysis of Descriptive CROM in research on TNPs.
Use behavior of loose or pouched moist smokeless tobacco (MST) products and its impact on biomarkers of exposure (BOE), specifically nicotine (nicotine equivalents; NE) and N-nitrosonornicotine (NNN), have not been well characterized. We assessed ad libitum use behavior (pinch mass/number of pouches, number of use occasions, and time in mouth) of own-brand loose/pouched MST products among adults who used MST (N = 229) during 24-h clinical confinement. We also examined the relationship between use behavior and BOEs. Loose MST use behavior (mean ± SD) was 4.3 ± 2.19 g/pinch, 6.5 ± 2.24 occasions/day, 28.1 ± 18.22 g/day, with 74.0 ± 33.88 min/use; pouch use was 2.2 ± 0.99 pouches/use, 69.1 ± 32.49 min/use, 6.0 ± 2.64 occasions/day, and 13.3 ± 7.38 pouches/day. Average NE was significantly lower, and NNN, while lower, was not significantly different in pouch users (NE = 20.4 mg/24 h; NNN = 61.0 ng/24 h) compared to loose MST users (NE = 26.3 mg/24 h; NNN = 78.0 ng/24 h). For loose MST, number of use occasions, average duration in mouth, and average pinch mass were the most significant factors impacting NE exposure (r2 = 0.4954); these factors and age were significant for NNN exposure (r2 = 0.3328). The amount and duration of loose and pouched MST use behavior parameters were higher than those in previously published reports. In addition, ~ 33–50% of the variability in daily exposure to nicotine and NNN can be explained by use behavior measured under the study conditions.
Psychometric consumer reported outcome measures (CROM), which aim to infer latent variables (e.g., psychological dependence) from self-report measurement instruments, play a key role in data collection in research on tobacco- and nicotine-containing products (TNPs). While guidelines are available for patient reported outcomes (PRO) to be used in health studies, no comprehensive guidelines exist for Psychometric CROM which consider specifics in the field of TNP research. The proposed guidelines aim to fill the current gap with the objective of enhancing the quality of empirical research on TNPs. The objective is to develop guidelines for researchers with respect to the selection, development, modification, and implementation of Psychometric CROM in TNP research. The guidelines were developed by a working group comprised of CORESTA (Cooperation Centre for Scientific Research Relative to Tobacco) CROM Task Force members by adopting an iterative and consensus driven approach. This involved reviewing relevant peer-reviewed publications, publicly available guidelines, and best practices published by prominent organizations from related fields and seeking active collaboration with subject matter experts representing public health, academia, and the tobacco industry. The draft guidelines were presented and discussed at various health and tobacco research conferences. Based on feedback and suggestions provided, the guidelines were continuously updated and revised. The resulting guidelines contain four sections, guiding the reader from construct definition to application and interpretation of Psychometric CROM. Emphasis is placed on crucial initial research stages, such as defining the ideal CROM characteristics based on the construct definition, the context of measurement, and the objectives of the study, to facilitate the researcher’s determination as to whether use of an existing CROM would be an appropriate choice for the study, or whether modifying an existing CROM or developing a new CROM would be warranted. While the guidelines provide direction for researchers who intend to use Psychometric CROM in their research, they also flag key measurement considerations and raise awareness of psychometric issues with the goal of advancing Psychometric CROM measurement science. Grounded in psychometric principles, these guidelines present best practices and provide guidance on the appropriate identification, development, modification, and application of Psychometric CROM in TNP research in a way that is consistent with good measurement practices. With the dissemination of the guidelines, we expect a more informed selection of CROM, a better-founded modification of existing CROM and development of new CROM, improved integration of CROM into TNP research and ultimately a better harmonization of consumer-reported measurement in the field of TNP research.
Chemical toxicants released into the environment during the use of tobacco and nicotine products potentially give rise to an elevated health risk among non-users. The aim of this study was to assess the levels of a wide range of chemical toxicants in the indoor air of an unventilated testing facility during various scenarios of tobacco and nicotine product use, including the use of conventional waterpipes, electronic vaping products (EVPs, also known as e-cigarettes), an electronic waterpipe which uses electrical heating of shisha tobacco instead of conventional charcoal heating, and combustible-cigarettes. In the one-occupant scenarios, increases in PM10 and PM2.5 were greatest during conventional waterpipe use, approximately 40% lower for OOKA electronic waterpipe use, and lowest for EVP use. An increase in the combustion by-product CO was greatest for conventional waterpipe use, and substantially lower for EVP and OOKA electronic waterpipe use, with the latter generating only a negligible amount of CO. The increase in formaldehyde levels was greatest for conventional waterpipe use, and substantially lower for OOKA electronic waterpipe use. In ten-occupant product use scenarios, increases in PM10 and PM2.5 were greatest for EVP use and slightly lower for OOKA electronic waterpipe use, lower during the cigarette smoking scenario, and lowest for the unattended conventional waterpipes scenario. Increases in CO and formaldehyde were highest for the conventional waterpipes scenario, substantially lower during cigarette smoking, and negligible for OOKA electronic waterpipe and EVP use. Increases in several other volatile organic compounds and some polycyclic aromatic hydrocarbons were mainly seen only during cigarette smoking and were negligible during the other product use scenarios. This pattern was similar for the tobacco-specific nitrosamines NNN, NNK, and NAT. These findings have important implications concerning the potential for secondhand toxicant exposure among waterpipe non-users, and for understanding how to potentially reduce health risks associated with such exposure. [Contrib. Tob. Nicotine Res. 34 (2025) 230–241]
Currently low-powered pods and disposables overwhelmingly dominate consumer preference of vaping products. Yet, despite its marginal usage, third generation high power low resistance (sub-ohm) devices are still used frequently to generate aerosols for assessing the toxicity of vaping aerosols. All these studies operate these devices under the CORESTA Recommended Method 81 protocol or with slight modifications, with airflow rates around 1 L/min. This experimental set up is concerning, since we have published various articles showing that much higher airflow rates (around 10 L/min) are a necessary experimental condition for these devices to generate aerosols that avoid overheating and large production of toxic byproducts. In a previous recent article, we replicated aerosol generation from a high-powered device integrated into a computerized exposure system used to expose in in vitro and in vivo systems. After careful calibration, we identified the experimental conditions for this device to avoid generating aerosols under an Overheating Regimen that would generate a repellent aerosol for human users. Applying the experimental results of this study, we show in this critical review that all studies using this same device exposed biological systems to overheated and aldehyde-loaded aerosols, with about half of the studies also delivering excessive nicotine concentrations. Some studies reported the presence of carbon monoxide, suggesting evidence of advanced wick pyrolysis. Most of the reviewed studies are irreproducible for failing to provide sufficient information of their aerosol generation procedures. Our results raise questions on the relevance of this literature to assess the risk profile of vaping products. Finally, we provide guidelines to improve the protocols of aerosol generation methodology in emission and exposure studies. [Contrib. Tob. Nicotine Res. 34 (2025) 202–221]
A collaborative study among twelve laboratories was conducted to establish a recommended method for determination of oxides of nitrogen (NOx) in mainstream cigarette smoke. Three cigarette samples, with ISO 3308 total particulate matter yields ranging from 2–17 mg/cig, were evaluated under both a non-intense (ISO 3308) and an intense (ISO 20778) smoking regime to assess the method’s applicability across a range of conditions. Mainstream cigarette smoke was either passed through an in-line detector or collected in a gas-tight system for offline determination of NOx by chemiluminescence. Optional use of glass fiber filter pads enabled gravimetric determination of total particulate matter. Statistical analyses were performed according to ISO 5725 to determine repeatability (r) and reproducibility (R), and z-scores. Reproducibility, expressed as a percentage of mean yield across all products, smoking regimes, and analysis types, ranged from 15.1–49.7%. NOx yields ranged from 71–437 μg/cig and followed expected trends with respect to total particulate matter and smoking intensity. These results demonstrate the robustness of the proposed method and support its adoption as CORESTA Recommended Method CRM N° 104. [Contrib. Tob. Nicotine Res. 34 (2025) 222–229]
1,2-Propylene glycol (PG) is one of the most utilized humectants in the tobacco industry.
To investigate the effect of the airflow velocity on the mechanism through which aerosol is released in granule-based heated tobacco products (HTPs), experiments were conducted using two airflow pathways: open-ended and closed-ended configurations. The patterns of release of aerosol collected mass (ACM) and key aerosol components (nicotine, water, glycerol, and propylene glycol) and the distribution patterns of nicotine, glycerol, and propylene glycol in smoked cigarettes were measured. The results indicated that for the open-ended pathway, the airflow velocity did not strongly affect the total release amounts of ACM and its key components. The distribution of each component in the cigarette after it was smoked was also found to be relatively unaffected by the airflow velocity. However, for the closed-ended pathway, as the airflow velocity was decreased, the ACM and its total release amount decreased, and the residual amounts of each component in the tobacco granules and filter rod increased. In addition, the puff-by-puff release patterns of aerosols and their key components were different for the two airflow pathways. Specifically, for both pathways, the puff-by-puff ACM and water release gradually decreased after peaking quickly, whereas the levels of glycerol gradually increased, peaking at 7 or 8 puffs. The amounts of propylene glycol and nicotine first increased and then decreased for the open-ended pathway, reaching a peak at 4 or 5 puffs, whereas for the closed-ended pathway, these amounts gradually increased and peaked at 7 or 8 puffs. The aerosol particle size distribution results revealed that due to different processes of aerosol condensation and nucleation, as the airflow velocity was decreased, the aerosol number concentration and volume concentration decreased for both pathways but the median particle size increased. The closed-ended pathway resulted in a greater decrease or increase than did the open-ended pathway.
Tobacco cigarette smoking continues to be the global leading cause of morbidity and mortality. Despite the awareness of its grave consequences, smokers find it extremely challenging to quit the addiction. A human-centric approach is crucial to fight against tobacco harm. Eventually, the global landscape of smoke-free alternative tobacco products like tobacco heating systems, electronic cigarettes, nicotine pouches and snus have significantly evolved. Unlike conventional cigarettes, these products except snus and nicotine pouches utilize heating instead of combustion, generating a less toxic aerosol. This mitigates the development of chronic obstructive pulmonary disease, lung cancer, cardiovascular and periodontal diseases. This review article elaborates the effectiveness, benefits and potential harm reduction of smoke-free alternative tobacco products associated with smoking cessation, biomarkers of exposure and health-related diseases in comparison to tobacco cigarettes. The controversial debate and related concerns of abuse liability and addiction among youth by smoke-free alternative products is explored. Creating awareness and management through better regulatory policies is crucial.
The National Youth Tobacco Survey (NYTS) collects self-reported data from U.S. middle and high school students on past-30-day e-cigarette use, including device type used most often, all flavors used, and all brands used. These data are central to regulatory decision-making by the U.S. Food and Drug Administration (FDA) when assessing the population-level risks of e-cigarettes, which underscores the importance of verifying that estimates from the survey are accurate. The current analyses assessed the 2023 and 2022 NYTS estimates of youth e-cigarette use to examine whether the reported brand used is consistent with the reported device type and flavors used among past-30-day only brand and usual brand users of Vuse, JUUL, Elf Bar (2023), and Puff Bar (2022) e-cigarettes. In 2023, 333 respondents (1.5% of all youth) reported any past-30-day use of Vuse e-cigarettes, with 134 (0.6% of all youth) reporting Vuse as their only or usual brand. Among these 134 only or usual brand users, 84 (0.3% of all youth) provided responses for device type and flavors used that were consistent with use of Vuse. Past-30-day use of JUUL e-cigarettes was reported by 237 respondents (1.2% of all youth), with 42 (0.3% of all youth) reporting JUUL as their only or usual brand. Among these 42 only or usual brand users, 3 (< 0.1% of all youth) provided responses for device type and flavors used that were consistent with use of JUUL. For Elf Bar e-cigarettes, 839 respondents (4.2% of all youth) reported past-30-day use, with 478 (2.3% of all youth) reporting Elf Bar as their only or usual brand. Among these 478 only or usual brand users, 392 (2.0% of all youth) provided responses for device type that were consistent with use of Elf Bar (flavors could not be validly assessed). Analyses of the 2022 NYTS data showed similarly low levels of consistency in reporting for Vuse, JUUL, and Puff Bar e-cigarettes. Thus, substantial proportions of youth in both survey years provided responses for device type used most often and flavors used during the past 30 days that were not consistent with the reported brand used. These findings raise significant concerns regarding the accuracy of the brand-specific prevalence estimates derived from the NYTS data, especially given the weight that the FDA places on these data during its regulatory decision-making.
Nicotine consumption is known to be a risk factor for cardiovascular disease. β-Caryophyllene (BCP), a sesquiterpene with anti-inflammatory properties, was investigated in a randomized, double-blind, placebo-controlled trial to see if smoking cigarettes with BCP-containing capsules could improve aortic stiffness. In this study, 84 adult smokers were randomly assigned to either a BCP group or a placebo group. They smoked capsule-loaded cigarettes for 12 weeks, and various health parameters were measured every 4 weeks. The primary focus was on changes in brachial-ankle pulse wave velocity (baPWV), which measures arterial stiffness. The results showed that blood BCP levels increased only in the BCP group, while nicotine levels rose in both groups. For participants with a high baseline baPWV (≥ 1,400 cm/s), significant reductions in baPWV were observed in the BCP group at weeks 4 and 8. Additionally, baPWV at week 4 was significantly lower in the BCP group compared to the placebo group. No adverse effects were reported. In conclusion, smoking BCP-containing cigarettes improved arterial stiffness in participants with high baseline baPWV without causing any adverse effects.
Nicotine pharmacokinetics and subjective effects are important factors in assessing the abuse liability of tobacco products such as electronic nicotine delivery systems (ENDS). In addition, an abuse liability determination is informative in assessing the ability of ENDS to support switching from cigarette smoking.
In this study we developed a novel carrier material that can be used to regulate nicotine release profile to provide a more constant release. Bacterial cellulose (BC) was produced by fermentation of tobacco waste, nicotine was derived from the backfilling of tobacco extracts. Citric acid (CA) has been used to react with bacterial cellulose to prepare an aerogel (CA-BC) which showed to possess sustained nicotine release by varying CA and its crosslinking ratio with BC. Aerogels prepared at 10% CA/BC ratios during crosslinking exhibited significant sustained nicotine release effects. Another notable finding was that the sustained-release of nicotine for the CA-BC aerogel with high nicotine contents significantly outperformed that of low nicotine contents. The Weibull model and Gallagher-Corrigan model were used to elucidate the mechanism of nicotine dissolution from CA-BC aerogels. Material characterization revealed that the CA-BC aerogel had an improved thermal stability and decreased water absorption, a 3D fiber network structure at the microscopic level with an optimal average pore size of 30 μm was used to explain this difference.
A collaborative study among 18 participating laboratories from five countries was conducted to publish a recommended method for the determination of hydrogen cyanide in mainstream cigarette smoke. Seven cigarette samples (CM9, KR 1R6F, KR 2R5F and four commercial cigarettes) covering a wide range of blends and cigarette design constructions under two smoking regimes (ISO 3308 and ISO 20778) were employed in the study. The improved method involved smoke collection, using a combination of glass fiber filter pad and impinger trap containing dilute sodium hydroxide solution (“pad+impinger”) or using two glass fiber filter pads (one pad treated with an ethanol-water solution of sodium hydroxide plus one blank pad; “pad+pad”). Hydrogen cyanide was determined using a continuous flow analyzer based on the colorimetric detection of the reactants of cyanides with chromogenic reagents such as isonicotinic acid/1,3-dimethyl barbituric acid and pyridine/pyrazolone. Results from smoke collection using the “pad+pad” collection and the “pad+impinger” collection are consistent with each other under both regimes, which suggests each of the two method subtypes can be adopted in the determination of hydrogen cyanide in mainstream cigarette smoke. Statistical analysis was carried out following ISO 5725-2 to generate repeatability (r) and reproducibility (R) data for results from linear and rotary smoking. For reproducibility (R) expressed as a percentage of mean yield across all of the studied products and both smoking regimes, values ranged from 13.6–32.3%. The lowest “tar”-yielding products provided the most variable data. Though the labs were not all using the same smoke collection subtype, the repeatability and reproducibility suggested that the test results were within the range that would likely be deemed acceptable on a long-term basis. Results supporting a robust method for hydrogen cyanide are reported herein and support establishment of a standardized method.
Summary Some next generation electronic nicotine delivery systems (ENDS) are capable of providing measurements of selected device parameters related to classical puffing topography variables (e.g., number of puffs, puff duration, etc.) and estimated aerosol mass. The JUUL2 ® System can provide some of this information via a mobile phone application. A laboratory study was used to compare and translate selected device measurements into classical puffing topography variables for the breath activated JUUL2 ® device. The sensitivity of the pressure sensors that activate the device were determined using 7 flowrates in a pressure-flow testing apparatus using 30 JUUL2 ® devices. The JUUL2 ® device tracks activation duration as a proxy for puff duration. Comparison of puff duration from a puffing machine to device activation duration was performed using three different puffing regimens for 15 JUUL2 ® devices with a tobacco and menthol formulation. An ISO 20768 square wave, sine wave, and gap wave puffing regimens were used. The gap wave was created from the ISO 20768 square wave puffing regimen with a 0.5-s gap in the middle of the 3-s puff (gap puffing regimen with a 2.5-s puff duration), and all puff regimens were 3 seconds in duration. For each puffing regimen, the gravimetrically determined device mass loss and aerosol collected mass was compared to the estimate of generated aerosol mass provided by the JUUL2 ® device. Pressure-flow testing demonstrated that device activation occurred at a pressure drop of 95–150 Pa, which corresponded to a flowrate of 7.5–10 cm 3 /s. The duration of JUUL2 ® device’s activation averaged 95% and 76.4% of the 3-s puff duration of the square wave and sine wave regimens, respectively. For the gap wave regimen, the JUUL2 ® activation duration averaged 91% of the 2.5-s puffing regimen. There were small but statistically significant differences in device activation duration between the Virginia Tobacco and Menthol formulations using the square wave and gap wave puffing regimen. For a few puffs, the JUUL2 ® device recorded two activations, rather than one, with the incidence more pronounced for the sine wave than the square wave puffing regimen. A simple algorithm was developed that combined split device activations so that they perfectly matched puff counts during the square wave and sine wave puffing regimens. For each formulation (tobacco and menthol) and puffing regimen, there was a different correlation between the estimated aerosol mass from the JUUL2 ® device and the gravimetrically measured device mass loss. When puffing regimens were combined for each flavor, there was good correlation between measured device mass loss or aerosol collected mass and the estimated aerosol mass from the JUUL2 ® device. In conclusion, selected JUUL2 ® device measured parameters can be translated into classical puffing topography variables (i.e., number of puffs and puff duration), as well as provide an estimated aerosol mass generated by the JUUL2 System.
