Background: The purpose of this study was to evaluate the status of smoking in the Russian Federation (RF), and to develop proposals for changing the strategy for primary and secondary prevention of smoking associated diseases in terms of motivation to quit smoking.

Material and Methods: The Russian Public Opinion Research Centre (VCIOM) presented the data of a monitoring survey on the smoking problems in the Russian Federation. The survey was posted on the website httpps://wciom.ru on July 12, 2022. Based on the obtained results, suggestions to change the strategy of primary and secondary prevention among smokers in terms of motivation to quit smoking were formulated.

Results: The share of smokers in the Russian Federation has remained unchanged for the last 5 years - 33%.

Since 2013, warning labels and ugly drawings have been added to cigarette packs. The share of smokers has decreased (2013 - 41%, 2022 - 33%). The proportion of people who quit smoking is also growing (2013 - 10%; 2022 - 17%). Among smokers, there is 20% of “heavy” smokers (a pack per day or more) and the proportion of occasional smokers (several cigarettes per day / week) has decreased from 20% to 13% since 2009. The portrait of a smoking Russian is as follows:

• Smoking is primarily a male habit (47% vs 21% among women).
• The proportion of smokers is higher among 25-59 year olds (37%-42%).
• Half of Russians with secondary education smoke (50%), while among people with higher education 24% smoke.

A typical heavy smoker is a man aged 35-44, living in a village (36% vs 28% among residents of both capitals), having a poor financial situation (43%).

The profile of a smoker has changed since 2009. If 13 years ago the group of 18-44 years old (48-50%) was the most smoking part of the population, today it is filled with 25-59 year olds (38-42%), that is, those who smoked 13 years ago and didn’t give up habit. This allows us to predict that young people aged 18-24 will become the driver of a new model of “non-smoking behavior”. In 2009 22% of 18-24 year olds smoked a pack per day, compared to 12% in 2022; the total share of smokers aged 18-24 decreased by 1.7 times from 48% to 29%. However, the proportion of people aged 18-24 who use devices to smoke (vape, electronic cigarette or tobacco heating system) hasn’t been studied separately, and therefore smoking may be underreported. The awareness of this category of people about the dangers of smoking also hasn’t been studied, and separate studies are required. 62% of Russians who smoke want to kick the habit. The share of those who don’t want to give up cigarettes increased 1.5 times from 19% to 31%. Moreover, smoking cessation is perceived as a forced measure: in 2017, many people had a strong desire, today health problems influence the decision to quit smoking to the same extent. Only 4% of smokers will be able to stop the growth in the cost of cigarettes, although among 18-24 year olds this option is mentioned by every third.

Conclusions: Thus, with respect to the decreasing proportion of people who want to quit smoking and the high percentage of heavy smokers, it is necessary to revise the approaches to motivate smokers to quit smoking, as well as develop a comprehensive harm reduction approach for those who don’t intend to quit smoking. The concept of harm reduction in this aspect is designed to reduce the harmful effects of smoking on the body due to the heating of tobacco and the absence of combustion, which can affect the reduction in the incidence of cardiovascular, bronchopulmonary and oncological diseases. Also, in the strategy of primary and secondary prevention of diseases associated with smoking, it is necessary to develop personalized recommendations for quitting smoking, depending on the patient's gender and age status, taking into account the degree of tobacco dependence and motivation to quit smoking; develop and implement harm reduction principles for those who do not intend to quit tobacco use and create conditions for this, including the opportunity to receive information about scientifically proven less harmful alternatives to traditional cigarettes.

AUTHOR: Anna Isaeva^1,2

AFFILIATIONS: ¹State Autonomous Healthcare Institution of the Sverdlovsk Region “Central City Hospital No. 20”, Yekaterinburg, Russian Federation || ²State Federal-Funded Educational Institution of Higher Professional Training “Ural State Medical University” of the Ministry of Health of the Russian Federation, Yekaterinburg, Russian Federation

Background: Over the last decades, a large body of evidence has already demonstrated the association between traditional tobacco cigarette smoking and cardiovascular events. Through the years, products have been developed with the goal of providing ‘relatively safer’ or ‘less harmful’ alternatives to traditional tobacco cigarettes (TTCs). More recently, modified-risk tobacco products such as heated tobacco products (HTPs) have been introduced, to potentially reduce exposure to harmful constituents in cigarette smoke and ultimately reduce the health burden of smoking-related diseases such as cardiovascular disease. This meta-analysis was done to determine the association of TTC and HTP smoking on known cardiovascular risk factors and find evidence of this benefit as claimed.

Material and Methods: Randomized controlled trials comparing TTCs and HTPs with outcomes on blood pressure (BP), heart rate, flow mediated dilatation (FMD), pulse wave velocity (PWV), and products of lipid metabolism -high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and total cholesterol- were searched through PubMed, Google Scholar and Cochrane database. A total of 11 studies were included in the meta-analysis.

Results: Pooled analysis of studies on adult smokers showed that HTP use showed significant difference compared to traditional tobacco cigarettes on heart rate (MD -3.16 with 95% CI of -15.41 to -0.91), FMD (MD 2.53 with 95% CI of 0.17 to 4.89) and HDL (MD 2.52 with 95% CI of 1.41 to 3.64). No significant differences were noted on systolic BP (MD -1.56 with 95% CI of -3.87 to 0.76), diastolic BP (MD -1.59 with 95% CI of -3.37 to 0.20), LDL (MD -2.24 with 95% CI of -6.26 to 1.78), triglycerides (MD 10.31 with 95% CI of -5.90 to 26.51) and total cholesterol (MD 10.31 with 95% CI of -5.90 to 26.51). Only 1 study had a complete report of outcomes on PWV also showing no significant difference.

Conclusions: The present study evaluated the effects of the use of HTPs compared to TTC on the outcomes of blood pressure, heart rate and other predictors of cardiovascular risk. The results have shown that HTP use, compared to TTC use showed benefits on heart rate, high density lipoprotein, and flow mediated dilatation, but no significant difference on the other cardiovascular risk factors analysed. Larger and long-term studies are still needed to support the cardiovascular benefits of alternative tobacco products such as HTPs.

AUTHORS: Marie A. Barrientos-Regala^1,2, Joan Dymphna P. Reaño^1,2, Reginald P. Arimado¹, Rafael R. Castillo^1,2,3

AFFILIATIONS: ¹CardioMetabolic Research Unit (CaMeRU), FAME Leaders Academy, Makati City, Philippines || ²Section of Adult Cardiology, Department of Internal Medicine, Manila Doctors Hospital, Manila, Philippines || ³College of Medicine, Adventist University of the Philippines, Silang, Cavite, Philippines

Recalcitrant smokers managed for their cardiovascular problems pose a serious challenge to practicing physicians in their efforts to effectively reduce cardiovascular and overall health risk in these patients. This problem has been magnified during the current pandemic, when the already increased health risk of active smokers is aggravated further in the event that they develop coronavirus disease 2019 (COVID-19). Active smoking increases the risk of developing severe COVID-19 by around two folds, and those with chronic obstructive pulmonary disease (COPD) -which many recalcitrant smokers are likely to have already- have a fourfold increase in risk translating to much poorer clinical outcomes. This is aggravated by the delay in diagnosis since the symptomatology in COPD with acute exacerbation and COVID-19 may significantly overlap.

This predicament with recalcitrant smokers during this pandemic has prompted us to reconsider our previous policy to give up on them after six months of making them quit smoking totally. The current pandemic highlighted the need to explore alternatives that could at least mitigate the cardiovascular and COVID-19 risk of recalcitrant smokers. Based on the potential to reduce health risk and also on patient feedback, we have allowed the use of heated tobacco products (HTPs) in our recalcitrant smokers who really could not attain total smoking cessation despite all known smoking cessation measures. Quite different from electronic cigarettes, HTPs produce aerosols, still containing nicotine, using a battery-powered heating system device. Based on studies, the amount of toxic substances a smoker gets is up to 95 percent less, compared to traditional tobacco smoking. Though HTPs may be considered a pragmatic middle ground for recalcitrant smokers, there is still some degree of addiction; hence, legislative and regulatory control measures are imperative, so as to prevent the youth and nonsmokers to be “seduced” into trying them. However, these regulatory measures should not be more stringent than what are currently imposed on tobacco smoking since it would defeat the purpose of getting current smokers out of this deadly vice.

AUTHORS: Rafael R. Castillo^1,2, Marie A. Barrientos-Regala^1,2, Joan Dymphna P. Reaño^1,2, Reginald P. Arimado²

AFFILIATIONS: ¹Manila Doctors Hospital, Manila, Philippines

²Cardio-Metabolic Research Unit (CaMeRU), FAME Leaders Academy, Makati City, Philippines

Background: The purpose of the study was to determine the incidence of BOS in the post-COVID period based on a comprehensive assessment of clinical, laboratory and functional parameters, as well as taking into account the existing risk factors for the development of BOS.

Material and Methods: The study was conducted on the basis of the respiratory rehabilitation center of LLC Medical Association New Hospital in Yekaterinburg from July 2020 to December 2021. The study was approved by local ethical committee of OOO Medical Association New Hospital. Each patient signed an informed consent.

Inclusion Criteria: Adult patients 2-4 weeks after the end of treatment for COVID-19 of varying severity regardless of the % of lung involvement (according to CT scan). During the follow-up period 10,456 patients were examined, mean age 48.1±7.6 yo, including 6,259 women (59.8%). First-time detected BOS was registered in 7,506 patients (71.8%).

The patients were divided into 3 groups:

1. Group 1: patients who smoke or use alternative sources of nicotine delivery at the time of inclusion in the study, n=4135, of which: a. group 1.1 = 2150 using cigarettes, b. group 1.2 = 1985 using THS
2. Group 2: never smokers, n=3001
3. Group 3: patients who quit smoking more than 12 months ago, n=3320.

Patients of all groups were examined according to the protocol for managing patients with in the post-Covid period: laboratory, functional (spirometry with bronchodilator test, peak flowmetry) and clinical (need for short-acting β2-agonists, cough, shortness of breath, sputum discharge) parameters were studied.

For statistical processing “Statistica 12” was used.

Results: BOS was diagnosed in 71.8% of patients within 2 to 8 weeks after suffering COVID-19. In severe COVID-19 the incidence of BOS is significantly higher by 19.5%, than in mild cases. The frequency of development of virus-induced BOS was significantly higher in groups 1 and 3. In the 1st group the development of BOS was recorded in 56.4%, and in the 3rd group in 41.1%. In subgroup 1.1 the incidence of BOS was significantly higher by 15% compared with group 1.2. The relationship between the development of BOS in the post-COVID period and the presence of atopy, frequent acute respiratory viral infections in history before COVID-19, the number of peripheral blood eosinophils, the severity of the acute phase of COVID-19 and the presence of smoking at the time of inclusion in the study and in history was established. Moreover, using THS leads to a significantly lower incidence of BOS compared to smoking combustible cigarettes.

Conclusions: Smoking increases the risk of developing BOS and worsens the prognosis. The use of tobacco heating systems in those patients who do not quit smoking may lead to a lower risk of developing BOS.

AUTHOR: Natalya Esaulova

AFFILIATION: LLC Medical Association “New Hospital”, Yekaterinburg, Russian Federation

Despite public health efforts to reduce the health burden of cigarettes by encouraging smoking cessation, a proportion of smokers remain unwilling to quit. A shift from smoking cessation to tobacco harm reduction, based on smokers switching completely to potentially less harmful products such as electronic cigarettes (ECs), has been proposed as an alternative strategy. This is a single-centre, cross-sectional confinement study, involving healthy exclusive Vuse EC users and current, former, or never-smokers. Exclusive EC use and smoking status will be confirmed by urinary cotinine and exhaled carbon monoxide levels. Participants will be confined for 24 hours, during which they will use their usual product (EC or cigarette) as normal. Biomarkers of exposure and potential harm will be analysed in 24-hour urine and blood and compliance will be measured using N-(2-cyanoethyl)valine. The primary objective is to quantitatively assess differences between EC users and current smokers in urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 8-epi-prostaglandin F_2α Type III, exhaled nitric oxide, and carboxyhaemoglobin, white blood cell count, soluble intercellular adhesion molecule-1, and high-density lipoprotein. The secondary objectives are to quantitatively assess differences between EC users and current smokers in selected urinary biomarkers of tobacco exposure, 11-dehydrothromboxane B2, forced expiratory volume in 1 second as a percentage of predicted, carotid intima-media thickness and a quality-of-life questionnaire. Endpoints will also be compared between EC users and former and never-smokers. The results of this study are anticipated to add to the current knowledge about the role of ECs in tobacco harm reduction.

AUTHORS: Nathan Gale, Linsey E. Haswell, Michael McEwan, David Azzopardi, Jesse Thissen, George Hardie

AFFILIATION: R&D Centre, B.A.T. (Investments) Limited, Southampton, United Kingdom

Background: According to modern data, “multifocal atherosclerosis” (MFA) is a hemodynamically significant atherosclerotic damage of arteries. To assess the MFA, the patient was assessed on three scales: Diamond-Forrester, Duke model, SADC2. The Duke model had the maximum efficiency in predicting atherosclerotic damage (92.5±3.43%), while Diamond-Forrester was in second place (84.2±2.2%), and CADC2 was in third place (64.2±4.4%). All presented scales had a limitation - they were developed to assess stenosing atherosclerosis of the coronary arteries and could only theoretically serve as a guideline for MFA screening. The purpose of the study was to assess the effect of smoking on lipid profile parameters and the development of multifocal atherosclerosis in active smokers compared to patients who used THS.

Material and Methods: The study included 102 patients with stable angina [62 male (60.8%) and 40 female (39.2%)]. Mean age was 64.2±12.7 years, mean smoking history 10.2±3.4. 52 patients had multifocal atherosclerosis, which corresponded to the minimum level of statistical significance p<0.05 according to the method of K.A. Otdelnova. The basis for the MFA detection scale was taken from the Diamond-Forrester, Duke, CADC models for assessing the risk of coronary artery stenosis, as well as the SMART scale, since endpoint predictors should be associated with atherosclerosis, however, such a relationship was statistically significant only for total cholesterol (TC) (r=0.519; p<0.001), low-density lipoproteins (LDL) (r=0.586; p<0.001), gender (r=0.195; p=0.049). The atherogenic coefficient (CA), not included in these scales, had a fairly high correlation coefficient r=0.384 (p=0.048). The sample of patients was divided into two subgroups: 1. Patients who smoked traditional cigarettes (n=70), and 2. Patients who used tobacco heating systems (n=32).

Results: The development of MFA had an effect 6.77 times higher on the blood’s level of TC, compared with the opposite situation, and the same holds true for LDL (4.94 times). The degree of mutual influence of factors and multifocal atherosclerosis looked as follows. For total cholesterol, the influence of the factor on the development of multifocal atherosclerosis was 3.549 at p=0.040, while the reverse situation was 24.012 at p<0.001; thus leading to a ratio of 1:6.77; the same pattern is typical for LDL - Factor → MFA - 3.593 at p=0.032, while MFA → factor 17.744 at p<0.001. The same pattern was observed for KA: 4.318 at p=0.048 and 4.165 at p=0.023. The CA level had a mutual influence of 1:1.04.

The level of high density lipoproteins did not affect the development of MFA (F=1.80, p=0.19). In patients with MFA, the male predominated (F=3.960, p=0.049). This model was tested using ROC analysis: the area under the curve was 0.798, which corresponded to a “good” score on the area under the curve scale.

As a result, various degrees of severity of multifocal atherosclerosis in patients were revealed. In a sample of cigarette smokers, the number of patients with severe multifocal atherosclerosis was statistically significantly higher than with alternative methods of nicotine delivery: 54 (77.1%) cases versus 145 (43.8%) cases.

Conclusions: 1) Multifocal atherosclerosis is a factor that increases the blood content of TC (6.77:1) and LDL (4.94:1). 2) In male the risk of developing MFA is higher than in female (1.037:1). 3) The use of tobacco heating systems in patients who are not motivated to quit smoking may reduce the risk of developing multifocal atherosclerosis and the associated increase in cholesterol and LDL.

AUTHOR: Elizaveta G. Skorodumova

AFFILIATION: I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint Petersburg, Russian Federation

Background: Head and neck squamous cell carcinomas (HNSCCs) are particularly aggressive epithelial tumors that affect more than half a million patients worldwide each year. They represent a multi-factorial group of tumors caused by: alcohol, tobacco, and human papillomavirus (HPV) infections.

Discussion: Over the last ten years the overall 5-year survival rate of HNSCCs remained ~40-50%, in spite of significant improvement in clinical outcome of many tumor types. There are recent data that claim how some of these cells fulfill a suppressive role in the antitumor immune response. It is interesting that new clinical studies demonstrated that HPV (+) HNSCCs were among tumors with the highest immune infiltrates, while HPV (-) presented a reduced number of immune infiltrating cells.

Conclusions: Recent research proves that tumor microenvironment of HNSCC has an important role in tumor progression, aggressivity, metastasis process, in addition to genetic aberrations and molecular alterations of cancer cells. New research in stromal composition of the HNSCC may be useful in understanding mechanisms of different responses to therapy, also can be used as a target for therapeutic purposes. Cancer-associated fibroblasts and immune cells, as well as their products found in neck squamous cell carcinoma significantly influence the biological properties of this tumor. Quitting is hard – even for people with cancer. Smokers diagnosed with cancer continue to smoke. Promoting smoking cessation should become an essential contributor to the treatment of cancer in all oncologic pathologies. In cases when patients can’t quit smoking completely within the shortest possible period of time, doctors should focus on harm reduction strategies – tobacco harm reduction.

AUTHOR: Dumitru Brînza

AFFILIATION: Institute of Oncology, Republic of Moldova

Compared to conventional cigarette smoke, tobacco heating products (THPs) generate lower levels of toxicants. In two 5-day, confined clinical studies and a 6-month, ambulatory clinical study, the glo THP has been shown to expose users to lower levels of particulate matter and harmful and potentially harmful compounds compared with smoking cigarettes. However, it is not known whether such exposure reductions lead to changes in biomarkers of potential harm (BoPH).

This controlled, randomised study investigated whether BoPH are modified when smokers switch from smoking cigarettes to using the glo THP in a real-world setting. Control groups consisted of never smokers and smokers who, after enrolment, abstained from cigarette smoking. Levels of the haemoglobin adduct N-(2-cyanoethyl)valine (CEVal) were used to determine compliance with smoking restrictions. Various BoPH related to oxidative stress, cancer, cardiovascular and respiratory diseases were assessed at a baseline study visit and here we report findings for these BoPH after 12-months.

By 12-months, favourable changes in the BoPH 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 8-epi-Prostaglandin F2α type III, white blood cell count and fractional concentration of exhaled nitric oxide were observed in smokers switching to using glo when compared with those who continued smoking. Levels of 11-dehydrothromboxane B2 were also reduced compared with continued smoking and, whilst not statistically assessed, favourable trends directionally consistent with beneficial changes in health effects were observed in soluble intercellular adhesion molecule-1 and high-density lipoprotein with unfavourable trends seen in continuing smokers. For several of these BoPH, the changes were comparable to those experienced by smokers who abstained from cigarette smoking for the same twelve-month period.

Our findings, alongside chemical and toxicological studies undertaken on the THP used in this study, lead to the conclusion that smokers who would have otherwise continued to smoke and instead switch entirely to the use of this THP, will reduce their exposure to tobacco smoke toxicants and as a consequence are reasonably likely to reduce disease risks compared to those continuing to smoke.

AUTHORS: George Hardie, Nathan Gale, Michael McEwan, Sharon Goodall

AFFILIATION: British American Tobacco (Investments) Limited, Research and Development, Southampton, United Kingdom

A recent review, “Should IQOS^TM Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence”, by Uguna and Snape suggested that IQOS emissions fit the definition of both aerosol and smoke. Furthermore, the authors suggest that Harmful and Potentially Harmful Constituent (HPHC) levels in the IQOS aerosol are underestimated without considering how the product is actually used. In this review, the authors misinterpreted or misrepresented the data from some of the referenced publications while omitting publications that are relevant to the topic which leads to an incorrect conclusion. They rely on data that were generated using incorrect methodologies, misrepresent the findings from an air quality study as evidence for the existence of black carbon in IQOS emission, and compare IQOS aerosol to cigarette smoke using data sets generated from two separate studies. In fact, smoke from a cigarette contains approximately 5,000 chemicals above 100 ng per stick and carbon-based solid particles generated during tobacco combustion, while IQOS aerosol contains substantially fewer chemicals and no carbon-based solid particles – an aerosol chemistry study identified only 532 compounds at levels above 100 ng per stick for one variant of HeatSticks^TM. Moreover, with regard to estimations of HPHCs present in IQOS aerosol, the product design and product use data indicate that a 1:1 comparison between cigarettes and HeatSticks^TM is appropriate when estimating the relative reduction in HPHC emissions. It is vital that scientific studies and reviews are comprehensive, accurate, and provide a complete understanding of the subject matter. This extends past maintaining scientific integrity and impacts people who rely on accurate information to make decisions. Publications that misinterpret, misrepresent, or do not consider the totality of scientific evidence add to the confusion surrounding smoke-free products, and may jeopardize public health by discouraging adult smokers from switching to non-combustible alternatives.

AUTHORS: Carrie Wade, Markus Nordlund

AFFILIATION: Philip Morris International