In this experimental study, we used mice model of chronic lung inflammation to explore the molecular and cellular pathways triggered by long-term use of combustible cigarettes (CCs) and electronic nicotine delivery devices (ENDS). Blood gas analysis, descriptive and quantitative histology, ELISA assay, intracellular staining, and flow cytometry analysis were used to determine the differences in immune cell-driven lung inflammation between experimental (CC and ENDS-exposed) and control (Air-exposed) mice. Continuous exposure to either CCs or ENDS caused a significant systemic inflammatory response, increased NLRP3 inflammasome activation in neutrophils and macrophages, and heightened dendritic cell-dependent activation of Th1 and Th17 cells in the lungs. The immunological response induced by ENDS was less strong than the inflammatory response elicited by CCs, resulting in less severe lung damage and inflammation. In ENDS-exposed animals, serum inflammatory cytokine concentrations were considerably reduced. ENDS recruited fewer circulating leukocytes in wounded lungs than CCs and were less capable of inducing CD14/TLR-2-dependent activation of the NLRP3 inflammasome in lung-infiltrated neutrophils and macrophages. Dendritic cells stimulated with ENDS demonstrated a lower potential for Th1 and Th17 cell-driven lung inflammation. Accordingly, in CCs-exposed mice, substantial immune cell-driven lung damage resulted in severe respiratory dysfunction, whereas ENDS resulted in mild respiratory dysfunction. This is the first study to examine the effects of CCs and ENDS on lung-infiltrated immune cells. Obtained results indicated that ENDS have a lower potential to induce a robust inflammatory response in the lungs than CCs.

AUTHORS: Nikolina Kastratovic¹, Vladimir Markovic¹, Aleksandar Arsenijevic¹, Ana Volarevic¹, Milica Dimitrijevic-Stojanovic², Vladimir Jakovljevic³, Vladislav Volarevic¹

AFFILIATIONS: ¹Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Serbia || ²Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Serbia || ³Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia

Background: Cigarette smoke increases the metabolism of phenytoin, a widely used anti-epileptic agent, by inducing cytochrome P450 enzymes in the liver. Therefore, cigarette smoke may reduce the clinical effect of phenytoin. Switching from cigarettes to combustion-free products (e.g., heat-not-burn, snus and e-cigarettes) is likely to have an impact on phenytoin metabolism. The absence of tobacco combustion in these products reduces the production of the chemicals that induce the metabolism of phenytoin. The primary objective of this study was to determine whether combustion-free products have a role to play in epileptic patients who take phenytoin and continue to smoke cigarettes.

Material and Methods: A literature review was conducted. The potential mechanisms underlying the effects of cigarette smoke and nicotine on phenytoin metabolism and the pathways for phenytoin metabolism were evaluated to determine overlapping mechanisms/pathways.

Results: Thirty-five studies were reviewed. Cigarette smoke influenced the metabolism of phenytoin by increasing the maximum metabolism rate of phenytoin by an average of 16% in humans. Cigarette smoke is known to contain several polycyclic aromatic hydrocarbons (PAHs), which can lead to faster elimination of numerous medicines, including phenytoin. The metabolic pathways of phenytoin and nicotine do not overlap indicating that nicotine does not influence the metabolism of phenytoin. Hence, complete switching to combustion-free products may reduce the influence smoking has on phenytoin metabolism in epileptic patients who take phenytoin and smoke.

Conclusions: The literature showed that the increase in metabolic rate of phenytoin due to tobacco smoke is probably attributable to PAHs and not nicotine. The reduced levels of PAHs in combustion-free products indicate that there is a role for combustion-free products in epileptic patients who take phenytoin and smoke.

AUTHOR: Praneet Valodia

AFFILIATION: Praneet Valodia Consulting, South Africa

It is uncertain if smoking has a negative impact on mesenchymal stem cell (MSC)-dependent immunosuppression in inflamed liver. We investigated the molecular processes behind cigarette smoke’s deleterious effects on MSC-dependent immunomodulation using α-galactosylceramide (α-GalCer)-induced immune cell-driven liver damage, a well-established mouse model of fulminant hepatitis. MSC which were cultured in cigarette whole smoke-exposed medium (MSC^WS-CM) developed a pro-inflammatory phenotype, were unable to optimally produce immunosuppressive cytokines (TGF-β, HGF, IL-10, NO, KYN), and secreted significantly more inflammatory cytokines (IFN-γ, TNF-α, IL-17, IL-6) than MSC that were grown in standard, cigarette smoke-non exposed medium (MSC^CM). Unlike MSC^CM, which effectively suppressed α-GalCer-induced hepatitis, MSC^WS-CM did not prevent hepatocyte damage and liver inflammation. MSC^WS-CM demonstrated a lower ability to inhibit inflammatory, liver-infiltrated macrophages, dendritic cells (DCs), and lymphocytes. Although the livers of α-GalCer+MSC^CM-treated mice had a significantly lower number of IL-12-producing macrophages and DCs, TNF-α, IFN-γ or IL-17-producing CD4+ and CD8+T lymphocytes, NK and NKT cells, this phenomenon was not observed in α-GalCer-injured mice that received MSC^WS-CM. MSC^WS-CM did not generate the same increase of anti-inflammatory IL-10-producing FoxP3+CD4+ and CD8+ T regulatory cells as MSC^CM and did not produce an immunosuppressive milieu in the liver. In similar manner as it was observed in mice, MSC^WS-CM were unable to optimally decrease production of inflammatory and hepatotoxic cytokines in activated human Th1/Th17 and NKT1/NKT17 cells, validating the idea that exposition to cigarette smoke considerably reduces capacity of MSC to suppress immune cell-driven inflammation.

AUTHORS: Vladimir Markovic¹, Dragica Pavlovic¹, Dragana Papic¹, Nikolina Kastratovic¹, Milica Dimitrijevic-Stojanovic², Aleksandar Arsenijevic¹, Ana Volarevic¹, Vladimir Jakovljevic³, Vladislav Volarevic¹

AFFILIATIONS: ¹Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Serbia || ²Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Serbia || ³Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia

Background: According to the INTERHEART study, smoking is the second most important predictor of myocardial infarction. Smoking men between the ages of 35 and 74 live less than 17.7 years on average. Our purpose was to conduct a sub-analysis of the multi-center study of ESSE - RF in Krasnoyarsk and study the prevalence of smoking among the adult population of Krasnoyarsk, taking into account age and gender (according to prof. Shtarik S. Yu, Krasnoyarsk).

Material and Methods: In 4 polyclinics in the city of Krasnoyarsk, 1,123 patients aged 25 to 64 were examined. The material was collected as part of the multi-center observational study “ESSAY RF-2012”. Persons were considered smokers if they smoked at least one cigarette per day. According to the patient, the smoking status (“smokes now”, “quit smoking”, “smokes”) and the intensity of smoking were determined: low - up to 10 cigarettes per day, moderate - 10-20 cigarettes per day, high - more than 20 cigarettes per day.

Results: All 1,123 patients gave information about their attitude to the bad habit: 54.8% never smoked (28.9% of men and 69.6% of women, p=0.000), 21.3% quit smoking (31.8% of men and 15.4% of women, p=0.000) and 23.9% were smokers at the time of examination. Among men, smoking rates were significantly higher than among women (39.4% vs 15.0%, p=0.000). The median age of male smoking onset was 17 (14; 19) years old, while median age of smoking onset for women was 18 (16; 20) years, that is, men used to join a bad habit (p=0.000 according to the Mann-Whitney criterion). On average, male smokers smoked 2 times more cigarettes compared to female smokers (16 (10; 20) vs 8 (4; 15), p=0.000 according to Mann-Whitney criterion). 84.5% of men and 70.8% of women (p=0.000) used tobacco products daily.

Conclusions: The prevalence of smoking among the adult population of Krasnoyarsk is 23.9%. Among men, smoking rates are higher than among women (39.4% vs 15.0%). The identified patterns actualize the need to introduce deeper measures aimed at preventing smoking in Krasnoyarsk. An alternative is to modify this risk factor and use electronic tobacco heating systems (manufactured by Philip Morris) to reduce the content of harmful substances and carcinogens.

AUTHORS: Anna Chernova, Svetlana Nikulina

AFFILIATION: Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation

Background: Tobacco heating products (THPs), which heat rather than burn tobacco, have been demonstrated by a number of studies to produce an aerosol with substantially lower levels of toxicants and reduced cytotoxicity relative to cigarette smoke. As they evolve in design and function, however, it is important to verify that variant THPs maintain sufficient equivalence to the original product if we are to leverage existing foundational datasets. Recent studies suggest that a bridging approach, in which a variant is shown to be comparable to the original product on which a large foundational dataset has been generated, might be used to ensure that the same product-related claims apply.

Material and Methods: In this study, emissions and consumer behaviour were assessed for two variants of glo^TM THPs: an extensively tested glo^TM type 1 (glo 2.0), and glo^TM type 3 (glo hyper) in base and boost modes. Emissions testing was conducted by measuring the percentage reduction of TobReg9 toxicants, relative to a 1R6F reference cigarette.

Results: Consumer behaviour, including puffing topography, average daily consumption (ADC) and mouth level exposure (MLE) to NFDPM and nicotine, was measured among 63 regular glo^TM users in Tokyo, Japan. Emissions testing showed a substantial reduction in TobReg9 toxicants compared to the reference cigarette (95.5-97.3%), whilst there were no substantial differences in the ADC, puffing behaviour or MLE among the three THPs.

Conclusions: Emissions analysis based on TobReg9 toxicants and consumer behaviour data provide evidence that the glo^TM type 3 is comparable to glo^TM type 1, indicating the possibility of using a bridging approach for the analysis of variant THPs based on use behaviour alone.

AUTHOR: Lauren Edward, Krishna Prasad, Adam Grey, Carol Goss

AFFILIATION: British American Tobacco Co Ltd (BAT), UK

Pharmacists are the most accessible health professionals in Canada. Although Canadian pharmacists frequently provide smoking cessation support, they have historically had little ability to assist patients who are unable or unwilling to quit smoking. In recent years Reduced Risk Products (RRPs) have emerged as an option for patients who continue to use tobacco or nicotine. Most health professionals in Canada, including pharmacists, have little knowledge on RRPs. Improving knowledge of RRPs would allow pharmacists to incorporate tobacco harm reduction when working with patients who smoke but are unable or unwilling to quit.

In February 2022, The Centre for Addiction and Mental Health (CAMH) published the first ever Canadian guidelines on RRPs. The Lower-Risk Nicotine Use Guidelines (LRNUG) are intended to guide health professionals and patients on how to lower the risk associated with various nicotine products. The products included in these guidelines were e-cigarettes (vapes), heated tobacco products and smokeless tobacco.

To improve pharmacist knowledge of RRPs and the LRNUG, a 1.25-hour professional development (PD) program was developed titled “Emerging Trends in Tobacco Use Disorder”. This program was granted national accreditation in June 2022 after peer review by 2 independent pharmacists.

This PD program reviews smoking prevalence, smoking harms, pharmacology of nicotine, clinical assessment of tobacco use status and pharmacotherapy for smoking cessation. This program also reviews RRPs including associated harms and risk compared to conventional cigarettes. Finally, the program introduces how RRPs can be incorporated into clinical practice to ensure patient-centred care.

As of June 2023, this program has been presented to over 1,000 pharmacists in Canada. The program evaluations are consistently positive with 92.7% of participants reporting “The information presented in this course will be helpful in my pharmacy practice.”

AUTHOR: Todderick Prochnau

AFFILIATION: Todderick B. Prochnau Pharmacy LTD, Alberta, Canada