Risk Of Smoking-related Diseases Research Articles

Health Risks Associated with Tobacco Consumption in Humans: An Overview

Tobacco use remains a significant public health concern globally, with over 8 million anticipated deaths annually by 2030, despite declining rates in some high-income nations. Smoking is prevalent worldwide, particularly in developing and middle-income countries, where over 80% of smokers reside. The inhalation of tobacco substances leads to various diseases, including cancer and respiratory ailments, resulting in more deaths than AIDS, tuberculosis, and other major causes combined. Secondhand smoke exposure also poses significant health risks. The economic burden of tobacco-related deaths and diseases is substantial, especially in low- and middle-income economies, where almost 80% of tobacco-related deaths occur. Lack of awareness, societal influence, and ineffective enforcement of anti-tobacco laws contribute to widespread tobacco use. Although anti-tobacco campaigns and policies have shown some success, challenges persist, particularly in rural areas where tobacco dependence is high. In India, despite declining tobacco use attributed to awareness campaigns and increased taxes on cigarettes, certain demographics, such as middle-aged individuals, illiterates, and rural residents, continue to have high tobacco consumption rates due to inadequate implementation of anti-tobacco norms and limited access to information. Quitting smoking can significantly extend life expectancy and reduce the risk of smoking-related diseases. However, nicotine addiction poses a challenge, with only a small percentage of users successfully quitting without assistance. Professional support and cessation drugs can double the likelihood of successful quitting, and nicotine replacement therapy has shown effectiveness. Overall, there is no safe level of cigarette use, emphasizing the importance of comprehensive tobacco control efforts to mitigate the global health and economic impacts of tobacco use. This review deals with the health risks associated with tobacco consumption in humans. Keywords: Tobacco, Nicotine, Carcinogens, Cancer, Cardiovascular diseases.

State Medicaid Coverage for Tobacco Cessation Treatments and Barriers to Accessing Treatments - United States, 2018-2022.

The prevalence of cigarette smoking among U.S. adults enrolled in Medicaid is higher than among adults with private insurance; more than one in five adults enrolled in Medicaid smokes cigarettes. Smoking cessation reduces the risk for smoking-related disease and death. Effective treatments for smoking cessation are available, and comprehensive, barrier-free insurance coverage of these treatments can increase cessation. However, Medicaid treatment coverage and treatment access barriers vary by state. The American Lung Association collected and analyzed state-level information regarding coverage for nine tobacco cessation treatments and seven access barriers for standard Medicaid enrollees. As of December 31, 2022, a total of 20 state Medicaid programs provided comprehensive coverage (all nine treatments), an increase from 15 as of December 31, 2018. Only three states had zero access barriers, an increase from two; all three also had comprehensive coverage. Although states continue to improve smoking cessation treatment coverage and decrease access barriers for standard Medicaid enrollees, coverage gaps and access barriers remain in many states. State Medicaid programs can improve the health of enrollees who smoke and potentially reduce health care expenditures by providing barrier-free coverage of all evidence-based cessation treatments and by promoting this coverage to enrollees and providers.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS)

BackgroundTobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation.MethodsThis a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18–85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers.FindingsA representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome.InterpretationThe CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China.FundingChinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400). Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18–85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China.

Artificial neural network machine learning prediction of the smoking behavior and health risks perception of Indonesian health professionals.

Health professionals (HPs) can play an important role in influencing the smoking behavior of their patients and the implementation of smoke-free workplace policies. In some countries physicians and dentists may not have a no-smoking policy in place. Breathing in other people's tobacco smoke (second-hand smokers) increase the risk of smoking related diseases. Environmental Tobacco smoke ETS causes a similar range of diseases to active smoking, including various cancers, heart disease, stroke, and respiratory diseases. Little is known about the smoking-related attitudes and clinical practices of HPs in Indonesia. Evidence suggests that high smoking rates remain among male HPs; however, the risk perceptions and attitudes to smoking among Indonesian HPs have not been investigated using prediction model artificial neural networks. For this reason, we developed and validated an artificial neural network (ANN) to identify HPs with smoking behavior. The study population consisted of 240 HPs, including 108 (45%) physicians, and 132 (55%) dentists, with more female (n=159) than male participants (n=81) for both professions. Participants were randomly divided into two sets, the training (192) and test (48) sets. The input variables included gender, profession (doctor or dentist), knowledge regarding smoking-related diseases and awareness of smoking provided to their patients, smoke-free policy in place at their workplace, and smoking status. ANN was constructed with data from the training and selection sets and validated in the test set. The performance of ANN was simultaneously evaluated by discrimination and calibration. After the training, we completed the process using the test dataset with a multilayer perceptron network, determined by 36 input variables. Our results suggested that our final ANN concurrently had good precision (89%), accuracy (81%), sensitivity (85%), and area under the curve (AUC; 70%). ANN can be used as a promising tool for the prediction of smoking status based on health risk perceptions of HPs in Indonesia.

Healthcare costs attributable to e-cigarette use and subsequent uptake of cigarette smoking by Australians who have never smoked.

Objective New legislation to curb the rapid increase in e-cigarette use among youth is underway. We estimated the future healthcare costs for chronic diseases from e-cigarette use among never smokers who transition to tobacco smoking. Methods Using population-attributable fractions, we estimated the health expenditure attributable to e-cigarettes based on the prevalence of e-cigarette use, uptake of tobacco smoking, and risk of smoking on developing chronic disease. Data for men and women were derived from published reports on e-cigarette use prevalence, risk of smoking-related disease and addiction, and health expenditure for 25 diseases. Sensitivity analyses were undertaken to address data input variation. Results Future healthcare costs attributed to new e-cigarette-initiated smokers were conservatively estimated to be (in Australian dollars) $179.6 million annually. Collectively, the estimated costs were highest for respiratory diseases ($102.2 million; 57% of total costs), malignant cancers ($49.6 million; 28%), and cardiovascular disease ($27.7 million; 15%). The uptake rate of e-cigarettes was more important in driving healthcare costs than the proportion moving from e-cigarettes to cigarette smoking. Conclusion High avoidable health system costs are predicted for the treatment of chronic conditions created by e-cigarette-initiated smoking. These costs exclude the immediate and direct healthcare harms of e-cigarette-related poisoning, lung injury, and respiratory problems, and costs associated with the unknown health harms of e-cigarette use alone. The proposed regulations to curb recreational e-cigarette use in Australia are set to prevent expensive health care arising sometime in the future from new cigarette smokers.

Hedgehog-interacting protein acts in the habenula to regulate nicotine intake

Hedgehog-interacting protein (HHIP) sequesters Hedgehog ligands to repress Smoothened (SMO)-mediated recruitment of the GLI family of transcription factors. Allelic variation in HHIP confers risk of chronic obstructive pulmonary disease and other smoking-related lung diseases, but underlying mechanisms are unclear. Using single-cell and cell-type-specific translational profiling, we show that HHIP expression is highly enriched in medial habenula (MHb) neurons, particularly MHb cholinergic neurons that regulate aversive behavioral responses to nicotine. HHIP deficiency dysregulated the expression of genes involved in cholinergic signaling in the MHb and disrupted the function of nicotinic acetylcholine receptors (nAChRs) through a PTCH-1/cholesterol-dependent mechanism. Further, CRISPR/Cas9-mediated genomic cleavage of the Hhip gene in MHb neurons enhanced the motivational properties of nicotine in mice. These findings suggest that HHIP influences vulnerability to smoking-related lung diseases in part by regulating the actions of nicotine on habenular aversion circuits.

What Cardiothoracic Radiologists Should Know About Imaging in Transgender Patients.

Transgender and gender diverse (TGD) individuals may undergo a wide range of care during gender transition including mental health counseling, gender-affirming hormonal therapy, and various surgeries. Hormone therapy effectively converts the hormonal milieu into that of the affirmed gender and produces measurable alterations in serum markers for coronary artery disease and other hematologic conditions (eg, erythrocytosis, venous thrombosis). Although illegal in the United States, some transgender women may receive silicone injections for breast and soft tissue augmentation, which can lead to devastating local complications, as well as silicone migration, pulmonary embolism, systemic reactions, and death. Smoking rates are higher among transgender and sexual minority populations, placing them at elevated risk of smoking-related diseases, including lung cancer. Some opportunistic infections may be more common in the TGD populations, attributable to higher rates of coexisting infection with human immunodeficiency virus. Radiologists should be aware that these patients may develop cancer of their natal organs (eg, breast, prostate), especially as some of these tissues are not completely removed during gender-affirming surgery, which may manifest with thoracic involvement by secondary neoplasia. As more TGD patients seek medical care, thoracic radiologists can reasonably expect to interpret imaging performed in this population and should be aware of possible disease processes and potential complications of hormonal and surgical therapies.

Maternal tobacco smoke exposure is associated with increased DNA methylation at human metastable epialleles in infant cord blood.

Metastable epialleles (MEs) are genomic regions that are stochastically methylated prior to germ layer specification and exhibit high interindividual but low intra-individual variability across tissues. ME methylation is vulnerable to environmental stressors, including diet. Tobacco smoke (TS) exposure during pregnancy is associated with adverse impacts on fetal health and maternal micronutrient levels as well as altered methylation. Our objective was to determine if maternal smoke exposure impacts methylation at MEs. Consistent with prior studies, we observed reductions in one-carbon pathway micronutrients with gestational TS exposure, including maternal folate (P = 0.02) and vitamins B6 (P = 0.05) and B12 (P = 0.007). We examined putative MEs BOLA3, PAX8, and ZFYVE28 in cord blood specimens from 85 Newborn Epigenetics STudy participants. Gestational TS exposure was associated with elevated DNA methylation at PAX8 (+5.22% average methylation; 95% CI: 0.33% to 10.10%; P = 0.037). In human conceptal kidney tissues, higher PAX8 transcription was associated with lower methylation (Rs = 0.55; P = 0.07), suggesting that the methylation levels established at MEs, and their environmentally induced perturbation, may have meaningful, tissue-specific functional consequences. This may be particularly important because PAX8 is implicated in several cancers, including pediatric kidney cancer. Our data are the first to indicate vulnerability of human ME methylation establishment to TS exposure, with a general trend of increasing levels of methylation at these loci. Further investigation is needed to determine how TS exposure-mediated changes in DNA methylation at MEs, and consequent expression levels, might affect smoking-related disease risk.

Development and testing of relative risk-based health messages for electronic cigarette products

BackgroundHealth messages on e-cigarette packs emphasise nicotine addiction or harms using similar wording to warnings on cigarette packs. These may not be appropriate for e-cigarettes which constitute a reduced risk alternative for smokers. This research aimed to (1) develop and test a selection of relative risk messages for e-cigarette products; (2) compare these to the two current EU Tobacco Products Directive (TPD) nicotine addiction messages; and (3) explore differences between smokers, non-smokers and dual users.MethodTwenty-six messages focusing on either harm-reduction or cessation were developed and rated by multidisciplinary experts for accuracy, persuasiveness and clarity. The eight highest ranking messages were compared alongside the TPD messages in a sample of 983 European residents (316 smokers, 327 non-smokers, 340 dual users) on understandability, believability and convincingness.ResultsOn all three constructs combined, the two TPD messages rated the highest, closely followed by four relative risk messages “Completely switching to e-cigarettes lowers your risk of smoking related diseases”, “Use of this product is much less harmful than smoking”, “Completely switching to e-cigarettes is a healthier alternative to smoking”, and “This product presents substantially lower risks to health than cigarettes” which did not differ statistically from the TPD messages. Non-smokers rated TPD1 significantly higher overall than dual users. Dual users rated “This product is a safer alternative to smoking” significantly higher than non-smokers. Messages did not differ on understandability.ConclusionsThese alternative messages provide a useful resource for future research and for policy makers considering updating e-cigarette product labelling.

Increased Smoking Cessation Among Veterans With Large Decreases in Posttraumatic Stress Disorder Severity.

Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. Veterans Health Affairs (VHA) medical record data (2008-2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04-2.36). Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

In-vivo design feedback and perceived utility of a genetically-informed smoking risk tool among current smokers in the community

BackgroundThe use of genetically-informed personalized risk information for behavioral disorders, namely smoking and smoking-related behaviors, is a promising yet understudied area. The Genetics and Smoking Risk Profile, or RiskProfile, leverages genetic and environmental information to communicate one’s risk for smoking-related diseases. Although prior studies have examined attitudes toward genetic results, little research has investigated these perceptions through a lens of in-vivo testing; that is, user-centered design feedback in response to personalized genetic results being returned contemporaneously. This qualitative study engaged current smokers in usability testing of the RiskProfile within the context of concurrently receiving this personalized, genetically-informed smoking cessation intervention.MethodsEighty-nine participants who were current smokers responded to open-ended interview questions on perceptions of smoking-related genetic information and the content and format of the RiskProfile intervention that they had received moments before. Data were analyzed via the conventional content analysis approach in which themes were allowed to emerge throughout the analysis.ResultsParticipants were able to reference and offer design input on specific elements of the RiskProfile. Overall, current smokers perceived the RiskProfile to have high potential utility. Constructive feedback that current smokers offered about the tool centered around suggested improvements to optimize its usability and technical content.ConclusionsThe detailed and constructive feedback from participants highlights that in-vivo feedback offers a useful design approach that addresses concerns of rigor and relevance when returning genetic results. This unique method demonstrated perceived utility and constructive design feedback for the RiskProfile among current smokers and can play an important role in optimizing the design and implementation of personalized genetic risk interventions moving forward.

The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures

Goblet cell hyperplasia and overproduction of airway mucin are characteristic features of the lung epithelium of smokers and COPD patients. Tobacco heating products (THPs) are a potentially less risky alternative to combustible cigarettes, and through continued use solus THPs may reduce smoking-related disease risk. Using the MucilAir™ in vitro lung model, a 6-week feasibility study was conducted investigating the effect of repeated cigarette smoke (1R6F), THP aerosol and air exposure. Tissues were exposed to nicotine-matched whole aerosol doses 3 times/week. Endpoints assessed were dosimetry, tight-junction integrity, cilia beat frequency (CBF) and active area (AA), cytokine secretion and airway mucin MUC5AC expression. Comparison of incubator and air exposed controls indicated exposures did not have a significant effect on the transepithelial electrical resistance (TEER), CBF and AA of the tissues. Cytokine secretion indicated clear differences in secretion patterns in response to 1R6F and THP exposure. 1R6F exposure resulted in a significant decrease in the TEER and AA (p=0.000 and p=0.000, respectively), and an increase in MUC5AC positive cells (p=0.002). Repeated THP exposure did not result in a significant change in MUC5AC positive cells. This study demonstrates repeated cigarette smoke whole aerosol exposure can induce these morphological changes in vitro.

Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers

BackgroundCompared to white smokers, Black smokers are at disproportionately higher risk for smoking-related disease, despite consuming fewer cigarettes per day (CPD). To examine racial disparities in biobehavioral influences on smoking and disease risk, we analyzed the relationship between self-reported tobacco dependence and intensity of tobacco smoke exposure per cigarette, on the one hand, and intensity of nicotine intake per cigarette, on the other. MethodsIn 270 Black and 516 white smokers, smoke exposure was measured by expired carbon monoxide (CO), and nicotine intake was measured by plasma cotinine (COT) and cotinine+3′-hydroxycotinine ([COT + 3HC]). Using linear regression analyses, we analyzed how the Fagerström Test for Cigarette Dependence (FTCD) predicted intensity of smoke exposure per cigarette (CO/CPD) and intensity of nicotine intake per cigarette (COT/CPD; [COT + 3HC]/CPD), and how race moderated these relations. ResultsOverall, Black smokers consumed fewer CPD than white smokers and had higher levels of CO/CPD, COT/CPD, and [COT + 3HC]/CPD. These elevations were most pronounced at lower levels of dependence: amongst Black smokers, FTCD negatively predicted intensity of smoke exposure as measured by CO/CPD (B = −0.12, 95% CI = −0.18, −0.05, p = 0.0003) and intensity of nicotine intake as measured by [COT + 3HC]/CPD (B = −1.31, 95% CI = −2.15, −0.46, p = 0.002). ConclusionsLow-dependence Black smokers had higher intensities of both smoke exposure and nicotine intake per cigarette compared to similarly dependent white smokers, suggesting that measures of dependence, exposure, and intake underestimate incremental risk of each cigarette to Black smokers.

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects

BackgroundSmoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers.MethodA smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989–1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA).ResultsAltogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results.ConclusionThis study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Effect of Switching to the Tobacco Heating System Versus Continued Cigarette Smoking on Chronic Generalized Periodontitis Treatment Outcome: Protocol for a Randomized Controlled Multicenter Study.

BackgroundSmoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers and nonsmokers. Although only a few longitudinal studies have assessed the outcome of periodontal disease after smoking cessation, they indicated that recovery after nonsurgical treatment was more successful in those who had quit smoking. As part of tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful tobacco products is an approach complementary to cessation for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS), developed by Philip Morris International (commercialized as IQOS), is part of the heat-not-burn product category. The IQOS device electrically heats tobacco instead of burning it, at much lower temperatures than cigarettes, thereby producing substantially lower levels of harmful and potentially harmful constituents, while providing the nicotine, taste, ritual, and a sensory experience that closely parallel those of cigarettes. Phillip Morris International has published the results from a broad clinical assessment program, which was established to scientifically substantiate the harm reduction potential of the THS among adult healthy smokers switching to the THS. The program is now progressing toward including adult smokers with smoking-related diseases.ObjectiveThe goal of this study is to demonstrate favorable changes of periodontal endpoints in response to mechanical periodontal therapy in patients with generalized chronic periodontitis who completely switched to THS use compared with continued cigarette smoking.MethodsThis is a randomized controlled two-arm parallel-group multicenter Japanese study conducted in patients with chronic generalized periodontitis who switch from cigarettes to THS compared with smokers continuing to smoke cigarettes for 6 months. The patients were treated with mechanical periodontal therapy as per standard of care in Japan. The primary objective of the study is to demonstrate the beneficial effect of switching to THS use compared with continued cigarette smoking on pocket depth (PD) reduction in all sites with an initial PD≥4 mm. The secondary objectives include evaluation of other periodontal parameters (eg, clinical attachment level or gingival inflammation) and overall oral health status upon switching to THS. Safety was monitored throughout the study.ResultsIn total, 172 subjects were randomized to the cigarette (n=86) or THS (n=86) groups, and all 172 completed the study. The conduct phase of the study is completed, while data cleaning and analyses are ongoing.ConclusionsThis study is the first to test a heat-not-burn tobacco product in smokers with an already established disease. The results should further strengthen the evidence that switching to THS can significantly reduce the risk of smoking-related diseases if favorable changes in the evolution of chronic generalized periodontitis after mechanical therapy are found when compared with continued cigarette smoking.Trial RegistrationClinicalTrials.gov NCT03364751; https://clinicaltrials.gov/ct2/show/NCT03364751International Registered Report Identifier (IRRID)DERR1-10.2196/15350

α3* Nicotinic Acetylcholine Receptors in the Habenula-Interpeduncular Nucleus Circuit Regulate Nicotine Intake.

Allelic variation in CHRNA3, the gene encoding the α3 nicotinic acetylcholine receptor (nAChR) subunit, increases vulnerability to tobacco dependence and smoking-related diseases, but little is known about the role for α3-containing (α3*) nAChRs in regulating the addiction-related behavioral or physiological actions of nicotine. α3* nAChRs are densely expressed by medial habenula (mHb) neurons, which project almost exclusively to the interpeduncular nucleus (IPn) and are known to regulate nicotine avoidance behaviors. We found that Chrna3tm1.1Hwrt hypomorphic mice, which express constitutively low levels of α3* nAChRs, self-administer greater quantities of nicotine (0.4 mg kg-1 per infusion) than their wild-type littermates. Microinfusion of a lentivirus vector to express a short-hairpin RNA into the mHb or IPn to knock-down Chrna3 transcripts markedly increased nicotine self-administration behavior in rats (0.01-0.18 mg kg-1 per infusion). Using whole-cell recordings, we found that the α3β4* nAChR-selective antagonist α-conotoxin AuIB almost completely abolished nicotine-evoked currents in mHb neurons. By contrast, the α3β2* nAChR-selective antagonist α-conotoxin MII only partially attenuated these currents. Finally, micro-infusion of α-conotoxin AuIB (10 μm) but not α-conotoxin MII (10 μm) into the IPn in rats increased nicotine self-administration behavior. Together, these data suggest that α3β4* nAChRs regulate the stimulatory effects of nicotine on the mHb-IPn circuit and thereby regulate nicotine avoidance behaviors. These findings provide mechanistic insights into how CHRNA3 risk alleles can increase the risk of tobacco dependence and smoking-related diseases in human smokers.SIGNIFICANCE STATEMENT Allelic variation in CHRNA3, which encodes the α3 nicotinic acetylcholine receptor (nAChR) subunit gene, increases risk of tobacco dependence but underlying mechanisms are unclear. We report that Chrna3 hypomorphic mice consume greater quantities of nicotine than wild-type mice and that knock-down of Chrna3 gene transcripts in the habenula or interpeduncular nucleus (IPn) increases nicotine intake in rats. α-Conotoxin AuIB, a potent antagonist of the α3β4 nAChR subtype, reduced the stimulatory effects of nicotine on habenular neurons, and its infusion into the IPn increased nicotine intake in rats. These data suggest that α3β4 nAChRs in the habenula-IPn circuit regulate the motivational properties of nicotine.

Prevalence and Trends in Cigarette Smoking Among Adults with Epilepsy - United States, 2010-2017.

Cigarette smoking remains the leading cause of preventable disease and death in the United States (1). Although the percentage of all U.S. adults who smoke cigarettes has declined substantially since the mid-1960s (1,2), marked disparities persist, and declines have not been consistent across population groups (1,2). Studies have shown that cigarette smoking is as common, and sometimes more so, among adults with a history of epilepsy compared with those without a history of epilepsy, but reasons for this are unclear (3-6). Compared with adults without epilepsy, adults with epilepsy report lower household income, more unemployment and disability, worse psychological health, and reduced health-related quality of life (3,4,6,7). Trends in cigarette smoking among U.S. adults with epilepsy have not been previously assessed. CDC analyzed National Health Interview Survey (NHIS) data among 121,497 U.S. adults from 2010, 2013, 2015, and 2017 to assess current cigarette smoking by epilepsy status. From 2010 through 2017, the age-standardized percentages of current smoking were 24.9% among adults with active epilepsy, 25.9% among adults with inactive epilepsy, and 16.6% among adults with no history of epilepsy. After accounting for differences in data collection intervals and patterns in smoking status among subgroups, CDC found that current cigarette smoking declined significantly from 2010 to 2017 among adults with no history of epilepsy (19.3% to 14.0% [p<0.001]) and inactive epilepsy (29.2% to 16.2% [p = 0.03]), but declines among adults with active epilepsy were not statistically significant (26.4% to 21.8% [p = 0.2]). Epilepsy health and social service providers should promote smoking cessation resources to adults with active epilepsy who smoke cigarettes to help them quit smoking and to reduce their risk of smoking-related disease and death.

Exposure to secondhand smoke among school-going adolescents in Malaysia: Findings from the tobacco and e-cigarettes survey among Malaysian adolescents (TECMA).

INTRODUCTIONMany studies have revealed that exposure to secondhand smoke (SHS) substantially increases the risk of smoking related diseases especially among the vulnerable groups, yet data on the location of SHS exposure among youth in Malaysia are still lacking. The study aims to describe the prevalence and factors associated with SHS exposure at home, outside the home, and inside the school among school-going adolescents in Malaysia.METHODSWe derived the data from the TECMA study, which used a cross-sectional study design and multi-stage sampling method to obtain a representative sample of school-going adolescents aged 11–19 years in Malaysia in 2016. Data were collected through a self-administered approach using a pre-validated standard questionnaire. Descriptive and multivariate analyses were used to analyze the data, and results are presented as adjusted odds ratio (AOR) with 95% confidence interval (95% CI).RESULTSSHS exposure for the past seven days was higher outside the home (51.2%; 95% CI: 49.2–53.2) compared to at home (37.8%; 95% CI: 35.8–39.9) while 27.3% (95% CI: 25.1–29.5) of school-going adolescents reported exposure to SHS inside the school in the past one month. In the regression analyses, older adolescents, those of Malay and Bumiputra Sarawak ethnicities, adolescents from rural areas and current smokers had higher likelihood of exposure to SHS at home, outside home and inside the school. Our study also found that adolescents who were current smokers had higher odds of being exposed to SHS at home (AOR=2.87; 95% CI: 2.57–3.21), outside the home (AOR=3.46; 95% CI: 3.05–3.92) and in the school (AOR=2.25; 95% CI: 2.01–2.51).CONCLUSIONSHealth promotion measures should target parents/guardians and household members to reduce SHS exposure among adolescents. In addition, smoke-free regulation should be fully enforced in school. Furthermore, more public places should be designated non-smoking areas to reduce SHS exposure and denormalize smoking behavior.

Assessing the impact of switching to the Tobacco Heating System on cardiovascular disease: Translating basic science into clinical benefit

Cigarette smoke (CS) is causally linked to the development of cardiovascular diseases (CVD). Tobacco harm reduction, by virtue of substituting cigarettes with less harmful products, is a complementary approach to current strategies for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS) 2.2 is a novel tobacco product that heats tobacco instead of burning it, never allowing the temperature to exceed 350 °C, thereby preventing the combustion process from occurring and producing substantially lower levels of toxicants than CS. Philip Morris International's (PMI) assessment program aims to demonstrate that switching to THS has the potential to reduce the risk of smoking-related diseases compared with continued smoking. The program includes in vitro/in vivo toxicology testing methods that follow OECD guidelines and GLP, a systems toxicology approach, and randomized, controlled clinical studies that follow the principles of GCP. The results of the THS assessment program demonstrated that cardiovascular toxicants are reduced by an average of > 92% in THS aerosol vs. CS. The effects of THS aerosol on the adhesion of monocytic cells to human coronary endothelial cells in vitro are significantly reduced. Switching to THS halted the progression of CS-induced atherosclerotic changes in ApoE-/- mice in vivo. Biomarkers linked to the development of smoking-related diseases were analyzed following a 6-month randomized, controlled clinical study with THS, which demonstrated a consistent improvement of biomarkers in different mechanistic pathways. The evidence available to date indicates that switching to THS has the potential to reduce the risk of smoking-related diseases such as CVD. As a next step, PMI will complement its THS assessment program with cardiovascular outcome studies intended to further support the clinical benefits of switching to THS over continuous smoking.

A cell-type deconvolution meta-analysis of whole blood EWAS reveals lineage-specific smoking-associated DNA methylation changes

Highly reproducible smoking-associated DNA methylation changes in whole blood have been reported by many Epigenome-Wide-Association Studies (EWAS). These epigenetic alterations could have important implications for understanding and predicting the risk of smoking-related diseases. To this end, it is important to establish if these DNA methylation changes happen in all blood cell subtypes or if they are cell-type specific. Here, we apply a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven large EWAS. We find that most of the highly reproducible smoking-associated hypomethylation signatures are more prominent in the myeloid lineage. A meta-analysis further identifies a myeloid-specific smoking-associated hypermethylation signature enriched for DNase Hypersensitive Sites in acute myeloid leukemia. These results may guide the design of future smoking EWAS and have important implications for our understanding of how smoking affects immune-cell subtypes and how this may influence the risk of smoking related diseases.