Estimated impact of a tobacco-elimination strategy on lung-cancer mortality in 185 countries: a population-based birth-cohort simulation study.

BACKGROUND: The tobacco-free generation aims to prevent the sale of tobacco to people born after a specific year. We aimed to estimate the impact of eliminating tobacco smoking on lung-cancer mortality in people born during 2006-10 in 185 countries. METHODS: For this population-based birth-cohort simulation study, we proposed a scenario in which tobacco sales were banned for people born between Jan 1, 2006, and Dec 31, 2010, and in which this intervention was perfectly enforced, quantified until Dec 31, 2095. To predict future lung-cancer mortality rates, we extracted lung-cancer mortality data by sex, 5-year age group, and 5-year calendar period for countries with at least 15 years of data from the WHO Mortality Database. For countries for which mortality data were not available, we extracted data on lung-cancer incidence from the Cancer Incidence in Five Continents. To establish the number of lung-cancer deaths that could be prevented in the birth cohort if tobacco smoking was eliminated, we subtracted reported age-specific rate of deaths in people who had never smoked tobacco (hereafter referred to as never smokers) from a previous study from the expected rate of lung-cancer deaths in our birth cohort and applied this difference to the size of the population. We computed population impact fractions (PIFs), the percentage of lung-cancer deaths that could be prevented, by dividing the number of preventable lung-cancer deaths by the expected lung-cancer deaths in the birth cohort. We also aggregated expected and prevented deaths into the four World Bank income groups (ie, high-income, upper-middle-income, lower-middle-income, and low-income). The primary outcome was the impact on lung-cancer mortality of implementing a tobacco-free generation. FINDINGS: Our birth cohort included a total population of 650 525 800 people. Globally, we predicted that 2 951 400 lung-cancer deaths could occur in the population born during 2006-10 if lung-cancer rates continue to follow trends observed during the past 15 years. Of these deaths, 1 842 900 (62·4%) were predicted to occur in male individuals and 1 108 500 (37·6%) were expected to occur in female individuals. We estimated that 1 186 500 (40·2%) of 2 951 400 lung-cancer deaths in people born during 2006-10 could be prevented if tobacco elimination (ie, a tobacco-free generation) was achieved. We estimated that more lung-cancer deaths could be prevented in male individuals (844 200 [45·8%] of 1 842 900 deaths) than in female individuals (342 400 [30·9%] of 1 108 500 deaths). In male individuals, central and eastern Europe had the highest PIF (48 900 [74·3%] of 65 800 deaths) whereas in female individuals, western Europe had the highest PIF (56 200 [77·7%] of 72 300 deaths). Middle Africa was the region with the lowest PIF in both male individuals (180 [2·1%] of 8600 deaths) and female individuals (60 [0·9%] of 6400 deaths). In both sexes combined, PIF was 17 400 (13·5%) of 128 900 deaths in low-income countries, 104 900 (15·8%) of 662 800 deaths in lower-middle-income countries, 650 100 (43·9%) of 1 482 200 deaths in upper-middle-income countries, and 414 100 (61·1%) of 677 600 deaths in high-income countries. INTERPRETATION: The implementation of a tobacco-free generation could substantially reduce global lung-cancer mortality. However, data from low-income countries were scarce and our estimates should be interpreted with caution. FUNDING: Spanish Society of Pneumology and Thoracic Surgery.

Incidence and risk factors for colorectal cancer in Africa: a systematic review and meta-analysis.

INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. There is a significant burden of mortality from colorectal cancer in Africa. Due to the heterogeneity of dietary and lifestyle practices throughout Africa, our work sought to define risk factors for the development of CRC in the African continent. METHODS: We systematically searched PubMed, Embase, Global Health, CINAHL, Cochrane CENTRAL, and African Index Medicus for studies written in English, examining the incidence and risk factors of CRC in Africa. A systematic analysis was done to compare different risk factors in constituent studies. A meta-analysis random effects model was fitted to estimate the pooled incidence of CRC. RESULTS: Of 2471 studies screened, 26 were included for the quantitative analysis; 20 in the incidence analysis, and six in the risk factor analysis. The overall ASIR per 100,000 person-years of CRC for males and females was 7.51 and 6.22, respectively. The highest incidence rates were observed between 2012 and 2021. Risk factors for CRC in Africa include tobacco smoking, and consumption of red meat, butter, and alcohol. Protective factors included, regular consumption of fruits and regular physical activity. CONCLUSION: The incidence of CRC in Africa is higher than that suggested by previous studies. Our study shows that nonmodifiable and modifiable factors contribute to CRC in Africa. High-quality studies conducted on generalizable populations that examine risk factors in a comprehensive fashion are required to inform primary and secondary prevention initiatives for CRC in Africa.

More precise method of low-density lipoprotein cholesterol estimation for tobacco and electronic cigarette smokers: A cross-sectional study.

Smoking is associated with elevated low-density lipoprotein cholesterol (LDL-C) levels. However, the accuracies of the Friedewald, Sampson, and Martin LDL-C-estimating equations based on smoking status are unclear. We analyzed the accuracy of LDL-C levels estimated using these three equations based on tobacco and electronic cigarette smoking status. Data on LDL-C and other lipid components were obtained from the Korea National Health and Nutrition Examination Survey from January 2009 to December 2021. Direct LDL-C (dLDL-C) levels and smoking data of 12,325 participants were evaluated. Current smokers had higher triglyceride levels than never smokers. Electronic cigarette smokers had higher triglyceride and dLDL-C levels than never smokers. The Martin equation yielded more accurate mean absolute deviations than the other equations for the group with triglyceride levels <400 mg/dL as well as more accurate median absolute deviation values, except for the group with dLDL-C levels <40 mg/dL. Similar estimates were derived from the equations when the triglyceride levels were <150 mg/dL. However, the Martin equation may lead to the overestimation of LDL-C levels. In conclusion, the Martin equation is suitable for triglyceride levels <400 mg/dL regardless of the electronic cigarette/tobacco smoking status; if the triglyceride level is <150 mg, the Friedewald equation could also be considered, regardless of the electronic cigarette/tobacco smoking status.

Gene regulatory networks reveal sex difference in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. METHODS: Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. RESULTS: We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. CONCLUSIONS: These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Lung adenocarcinoma (LUAD) is a disease that affects males and females differently. Biological sex not only influences chances of developing the disease, but also how the disease progresses and how effective various therapies may be. We analyzed sex-specific gene regulatory networks consisting of transcription factors and the genes they regulate in both healthy lung tissue and in LUAD and identified sex-biased differences. We found that genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females. We also found that several genes that are drug targets in LUAD, are also regulated differently between males and females. Importantly, these differences are also influenced by an individual's smoking history. Extending our analysis using a drug repurposing tool, we found candidate drugs with evidence that they might work better for one sex or the other. These results demonstrate that considering the differences in gene regulation between males and females will be essential if we are to develop precision medicine strategies for preventing and treating LUAD.

End TB strategy: Role of tobacco control.

Tobacco use and Tuberculosis (TB) presents a huge public health challenge globally. Tobacco and TB have consistent and strong epidemiological evidence with smokers having higher odds of TB infection, disease, mortality, delayed diagnosis etc. Overall, limited evidence exists about the extent of TB-tobacco integration. The aim of the current short communication is to highlight comprehensive strategy for addressing TB-tobacco comorbidities.

Tobacco smoking is associated with sex- and plaque-type specific upregulation of CRLF1 in atherosclerotic lesions.

BACKGROUND AND AIMS: Tobacco smoking is a known risk factor for atherosclerotic disease, with more elevated risks in women compared to men. We hypothesized that atherosclerotic plaques from smokers show different gene expression patterns compared to non-smokers, in a sex-specific manner. METHODS: Gene expression data of 625 carotid plaques (151 females and 474 males) were analyzed for differential gene expression between current smokers (n = 226) and non-smokers (n = 399). All analyses were stratified by sex and by molecular plaque characteristics. Finally, we projected the activity of gene regulatory networks and utilized single-cell transcriptomics from 38 plaques (26 males and 12 females) to interpret the sex- and plaque-type specific signals. RESULTS: We observed higher expression levels of CRLF1 gene in atherosclerotic plaques from smokers compared to non-smokers (log2FC = 0.48, FDR = 0.012). CRLF1 upregulation was interacting with sex (p = 0.01) and was more pronounced in females (log2FC = 0.93, p = 1.53E-05) compared to males (log2FC = 0.35, p = 0.0018). Through single-cell RNA-seq analysis, we identified the highest CRLF1 expression within the transitioning and synthetic smooth muscle cell populations. CRLF1 expression was increased in fibro-inflammatory and fibro-cellular plaque types. Gene annotations pointed to increased expression of CRLF1 in networks with extracellular matrix related genes. CONCLUSIONS: Atherosclerotic plaques from current smokers show sex-dependent upregulation of smooth muscle cell gene CRLF1. This may explain the different contributions of smoking to cardiovascular risk in females.

Prevalence of tobacco smoking and associated factors among adults in Ethiopia: a systematic review and meta-analysis.

Introduction: The public health concern of tobacco smoking is more prevalent in low- and middle-income countries including Ethiopia. Various studies have investigated tobacco smoking in various parts of Ethiopia. However, the findings have been inconsistent and characterized by significant variability. Besides, there is no nationally representative data on the subject, which could deter the design of effective intervention strategies to reduce tobacco-related problems. Therefore, this study aimed to estimate the pooled prevalence of tobacco smoking and associated factors among adults in Ethiopia. Methods: The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols Guideline. A detailed search was conducted from international databases including PubMed, Cochrane Library, Science Direct, CINAHL, African Journals Online, HINARI, Global Health, and Google Scholar. The extracted data was analyzed using STATA 14 software. A random-effects model was used to estimate the effect size. The Egger regression test and I2 statistics were used to determine potential publication bias and heterogeneity among the reviewed articles, respectively. Results: A total of 32 studies with 69,897 study participants were included in this systematic review and meta-analysis. The pooled prevalence of lifetime tobacco smoking among adults in Ethiopia was 16.0% (95% confidence Interval (CI): 13.6-18.39) and there was significant heterogeneity among the included studies (I2 = 99.1%, p < 0.001). Male adults were three times more likely to smoke tobacco as compared with females [OR = 3.22 (95% CI: 2.06-5.03)]. Being an alcohol user [OR = 3.78 (95%CI: 1.27-11.24)] and having tobacco-smoking friends [OR = 7.21 (95%CI: 5.56-9.35)] are potential determinant factors for tobacco smoking. Conclusion: The pooled prevalence of lifetime and current tobacco smoking among adults in Ethiopia was high, which calls for urgent intervention. Therefore, prioritization of tobacco control strategies, such as creating awareness about the public health importance of tobacco smoking, can help prevent and mitigate the effects of tobacco smoking. Alcohol control law enforcement should also be strengthened.

The association of tobacco smoking and metabolite levels in the anterior cingulate cortex of first-episode psychosis patients: A case-control and 6-month follow-up 1H-MRS study.

Tobacco smoking is highly prevalent among patients with psychosis and associated with worse clinical outcomes. Neurometabolites, such as glutamate and choline, are both implicated in psychosis and tobacco smoking. However, the specific associations between smoking and neurometabolites have yet to be investigated in patients with psychosis. The current study examines associations of chronic smoking and neurometabolite levels in the anterior cingulate cortex (ACC) in first-episode psychosis (FEP) patients and controls. Proton magnetic resonance spectroscopy (1H MRS) data of 59 FEP patients and 35 controls were analysed. Associations between smoking status (i.e., smoker yes/no) or cigarettes per day and Glx (glutamate + glutamine, as proxy for glutamate) and total choline (tCh) levels were assessed at baseline in both groups separately. For patients, six months follow-up data were acquired for multi-cross-sectional analysis using linear mixed models. No significant differences in ACC Glx levels were found between smoking (n = 28) and non-smoking (n = 31) FEP patients. Smoking patients showed lower tCh levels compared to non-smoking patients at baseline, although not surving multiple comparisons correction, and in multi-cross-sectional analysis (pFDR = 0.08 and pFDR = 0.044, respectively). Negative associations were observed between cigarettes smoked per day, and ACC Glx (pFDR = 0.02) and tCh levels (pFDR = 0.02) in controls. Differences between patients and controls regarding Glx might be explained by pre-existing disease-related glutamate deficits or alterations at nicotine acetylcholine receptor level, resulting in differences in tobacco-related associations with neurometabolites. Additionally, observed alterations in tCh levels, suggesting reduced cellular proliferation processes, might result from exposure to the neurotoxic effects of smoking.

Cancers attributable to tobacco smoking in Italy in 2020.

BACKGROUND: Tobacco smoking is still frequent in Italy and a major cause of cancer globally. We estimated the burden of smoking-related cancer in Italy. METHODS: To calculate the population attributable fraction (PAF), we adopted a counterfactual scenario for which all individuals never smoked. The PAF of current and former smoking and second-hand smoke (SHS) was estimated for cancers associated with these habits according to the International Agency for Research on Cancer. Relative risk estimates and prevalence of exposure were derived from large-scale studies and national surveys, respectively. A 20-year latency period between exposure and cancer was considered. Cancer incidence data for 2020 and mortality data for 2017 were obtained from the Italian Association of Cancer Registries. RESULTS: Tobacco smoking caused, in men and women respectively, 90.0 % and 58.3 % of lung; 67.8 % and 53.5 % of pharyngeal; 47.0 % and 32.2 % of bladder; 45.9 % and 31.7 % of oral; 36.6 % and 23.6 % of esophageal; 23.0 % and 14.0 % of pancreatic cancer and lower percentages of cancers at other sites. Tobacco smoking accounted for 23.9 % and 7.7 % of new cancer cases in 2020, and 32.1 % and 11.3 % of cancer deaths in 2017 in men and women, respectively, corresponding to 17.3 % of cases and 24.5 % of cancer deaths overall. The PAF of lung cancer due to SHS in never smoking women married with smokers was 13.0 %. CONCLUSIONS: Tobacco smoking is a primary cause of cancer in Italy in both sexes. Tobacco control policies are warranted.

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

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

Tobacco smoking and tooth loss in adults and elderly in Brazil: a populational-based cross-sectional study.

OBJECTIVES: To determine the association between smoking and tooth loss in individuals aged 18 years or more living in Brazil. METHODS: Secondary analysis of the 2019 Brazilian National Health Survey data. The outcome was self-reported tooth loss, and the main independent variable was tobacco smoking. Family income, schooling, sex and age were covariates. Multiple linear regression analysis determined the association between tobacco smoking and the number of missing teeth and then the average number of missing teeth was predicted according to smoking status. RESULTS: The mean number of missing teeth in 88,531 individuals aged 18 or more was 7.7 (95%CI: 7.6-7.8). At least one missing tooth was identified in 72.0% (95%CI: 71.4-72.6) of the population, 21.3% (95%CI: 20.9-21.7) had a non-functional dentition, 14.2% (95%CI: 13.9-14.6) had severe tooth loss and 10.3% (95%CI: 10.0-10.6) were edentulous. The adjusted regression coefficients for number of missing teeth showed that current or former smokers, individuals with low family income and schooling, older age and females exhibited higher tooth loss. Current and former smokers had 1.40 (95%CI: 1.35-1.46) and 1.13 (95%CI: 0.54-0.98) times more lost teeth than never smokers, respectively. CONCLUSIONS: Both tooth loss and smoking are common in Brazilians and are associated. Unfavorable socioeconomic status and demographic factors also predict tooth loss.

Temporal Trends in Tobacco Smoking Prevalence During the Period 2010-2020 in Vietnam: A Repeated Cross-Sectional Study.

Objectives: This study used repeated cross-sectional data from three national surveys in Vietnam to determine tobacco smoking prevalence from 2010 to 2020 and disparities among demographic and socioeconomic groups. Methods: Tobacco smoking temporal trends were estimated for individuals aged 15 and over and stratified by demographic and socioeconomic status (SES). Prevalence estimates used survey weights and 95% confidence intervals. Logistic regression models adjusted for survey sample characteristics across time were used to examine trends. Results: Tobacco smoking prevalence dropped from 23.8% in 2010 to 22.5% in 2015 and 20.8% in 2020. The adjusted OR for 2015 compared to 2010 was 0.87, and for 2020 compared to 2010 was 0.69. Smoking decreased less for employed individuals than unemployed individuals in 2020 compared to 2010. Smoking was higher in the lower SES group in all 3 years. Higher-SES households have seen a decade-long drop in tobacco use. Conclusion: This prevalence remained constant in lower SES households. This highlights the need for targeted interventions to address the specific challenges faced by lower-SES smokers and emphasizes the importance of further research to inform effective policies.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

[Prevalence of tobacco smoking and related factors in people aged 15 years and above in Beijing, 2014-2021].

Objective: To evaluate the effect of the implementation of Beijing Smoking Control Regulation in 2015 on the smoking prevalence in people aged ≥15 years in Beijing during 2014-2021, and explore factors associated with tobacco use behavior in local population. Methods Using a pooled cross-sectional design, data from Beijing Adult Tobacco Survey in 2014, 2016, 2019 and 2021 (4 surveys) were combined into one dataset. The 4 surveys used same multistage cluster sampling procedure. After complex survey weighting, multiple logistic regression models were constructed to analyze factors influencing smoking status. Results: A total of 8 484, 9 372, 8 534 and 10 551 respondents were included in the surveys in 2014, 2016, 2019 and 2021, respectively. The smoking prevalence rate was 23.4%, 22.3%, 20.3% and 19.9%, respectively, in Beijing residents aged ≥15 years, exhibiting a linear declining trend (P=0.010). Factors associated with current smoking in men were age 25-44 years (OR=2.22, 95%CI: 1.68-2.95) and 45-64 years, (OR=2.64, 95%CI: 2.06-3.39), educational level of high school (OR=0.69, 95%CI: 0.49-0.95) and undergraduate and above (OR=0.46, 95%CI: 0.33-0.63), and awareness of smoking causing stroke (OR=0.71, 95%CI: 0.61-0.81), and awareness of smoking causing lung cancer (OR=0.53, 95%CI: 0.42-0.66), the differences were significant (all P<0.05). After controlling interfering factors, the current smoking prevalence in men in 2019 (OR=0.73, 95%CI: 0.63-0.87, P<0.001) and 2021 (OR=0.72, 95%CI: 0.61-0.88, P<0.001) were significantly lower than that in 2014. Factors associated with current smoking in women were living alone (OR=1.80, 95%CI: 1.33-2.44), educational level of undergraduate and above (OR=0.43, 95%CI: 0.27-0.69), other occupations except doctor and teacher (OR=8.54, 95%CI: 2.80-26.02) or being retired/unemployed (OR=9.39, 95%CI: 3.19-27.65), and awareness of smoking causing cardiovascular events (OR=0.58, 95%CI: 0.39-0.84), and awareness of smoking causing lung cancer (OR=0.54, 95%CI: 0.35-0.83), the differences were significant (all P<0.05). No significant change in smoking status in women was found in 4 surveys. Conclusions: The smoking prevalence rate in men in Beijing has declined since the implementation of Beijing Smoking Control Regulation 5 years, indicating the effectiveness of legislative approach in tobacco control. Socio-demographic factors and the awareness level of tobacco harm could influence smoking status. Future tobacco control programs should target the people with lower education level, young men, women living alone, and those with occupations other than teachers/doctors or the unemployed/retired and include more comprehensive health education.

The role of tobacco smoking in anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

A Bivariate Twin Study of Lifetime cannabis Initiation and Lifetime Regular Tobacco Smoking Across Three Different Countries.

Regular cigarette smoking and cannabis consumption are strongly positively related to each other, yet few studies explore their underlying variation and covariation. We evaluated the genetic and environmental decomposition of variance and covariance of these two traits in twin data from three countries with different social norms and legislation. Data from the Netherlands Twin Register, FinnTwin12/16, and the Minnesota Center for Twin Family Research (total N = 21,617) were analyzed in bivariate threshold models of lifetime regular smoking initiation (RSI) and lifetime cannabis initiation (CI). We ran unstratified models and models stratified by sex and country. Prevalence of RSI was lowest in the Netherlands and prevalence of CI was highest in Minnesota. In the unstratified model, genetic (A) and common environmental factors (C) contributed substantially to the liabilities of RSI (A = 0.47, C = 0.34) and CI (A = 0.28, C = 0.51). The two liabilities were significantly phenotypically (rP = 0.56), genetically (rA = 0.74), and environmentally correlated in the unstratified model (rC = 0.47and rE = 0.48, representing correlations between common and unique environmental factors). The magnitude of phenotypic correlation between liabilities varied by country but not sex (Minnesota rP ~ 0.70, Netherlands rP ~ 0.59, Finland rP ~ 0.45). Comparisons of decomposed correlations could not be reliably tested in the stratified models. The prevalence and association of RSI and CI vary by sex and country. These two behaviors are correlated because there is genetic and environmental overlap between their underlying latent liabilities. There is heterogeneity in the genetic architecture of these traits across country.

Waterpipe Tobacco Smoking and Risk of Cancer Mortality.

Importance: There has been an increasing trend of using noncigarette products, including waterpipe tobacco (WTP), worldwide. While cigarette smoking is a well-established risk factor for numerous cancers, little is known about the association between WTP smoking and cancer mortality. Objective: To assess the association between WTP smoking and risk of cancer mortality in Vietnam. Design, Setting, and Participants: This cohort study was based on data from the Hanoi Prospective Cohort Study, an ongoing study with a median (range) follow-up of 11.0 (0.1-11.6) years for participants aged 15 years or older in Northern Vietnam from 2007 through 2019. Data were analyzed from June 1 to September 1, 2023. Exposures: Tobacco smoking and WTP smoking statuses. Main Outcomes and Measures: Overall and site-specific cancer mortality. Cox proportional regression models were used to calculate the hazard ratio (HR) and 95% CIs for the associations between WTP smoking alone, cigarette smoking alone, and dual WTP and cigarette smoking and the risk of cancer death. Results: A total of 554 cancer deaths were identified among the 39 401 study participants (mean [SD] age, 40.4 [18.8] years; 20 616 females [52.3%]). In multivariable models, compared with never smokers, ever smokers had a significantly increased risk of cancer mortality (HR, 1.87; 95% CI, 1.48-2.35). Exclusive WTP smokers had the highest risk of cancer mortality compared with never smokers (HR, 2.66; 95% CI, 2.07-3.43). Risk of cancer mortality was higher for dual smokers of WTP and cigarettes (HR, 2.06; 95% CI, 1.53-2.76) than for exclusive cigarette smokers (HR, 1.86; 95% CI, 1.41-2.45). As most smokers (95.6% [8897 of 9312]) were male, these patterns were more apparent in male participants. Compared with never smokers, exclusive WTP smoking among males was associated with an elevated risk of death from liver cancer (HR, 3.92; 95% CI, 2.25-6.85), lung cancer (HR, 3.49; 95% CI, 2.08-5.88), nasopharyngeal carcinoma (HR, 2.79; 95% CI, 1.27-6.12), and stomach cancer (HR, 4.11; 95% CI, 2.04-8.27). For exclusive WTP smokers, the risk of cancer mortality was highest among those who smoked 11 to 15 sessions per day (HR, 3.42; 95% CI, 2.03-5.75), started smoking at age 26 to 30 years (HR, 4.01; 95% CI, 2.63-6.11), smoked for 9 to 20 years (HR, 4.04; 95% CI, 2.16-7.56), and smoked 61 to 160 sessions annually (HR, 3.68; 95% CI, 2.38-5.71). For males, the risk of cancer death was lower for those who had quit smoking for more than 10 years, compared with those who quit smoking within 1 year (HR, 0.27; 95% CI, 0.11-0.66; P for trend < .001). Conclusion and Relevance: In this cohort study in Vietnam, WTP smoking alone or in combination with cigarette smoking was associated with an increased risk of cancer death due to liver cancer, lung cancer, nasopharyngeal carcinoma, and stomach cancer. A tailored program to control WTP smoking is warranted in Vietnam and low- and middle-income countries with a high prevalence of smoking and modest resources to address smoking-related issues.

The effects of aerobic exercise training on inflammatory markers in adult tobacco smokers: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Aerobic exercise training may reduce systemic inflammation, but the effects of this on systemic inflammatory markers in adult tobacco smokers has not been systematically reviewed. Therefore, we evaluated the effects of aerobic exercise training on C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) in adult tobacco smokers using a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive literature search was carried out using PubMed/Medline, Web of Science, EMBASE, Google Scholar, and hand search of bibliographies of the retrieved English or Persian articles up to August 2023. This review only included randomized controlled trials which investigated the effect of aerobic exercise training on CRP and TNF-α in adult smokers, based on a predefined inclusion and exclusion criteria. RESULTS: A total of 1641 articles were identified. Six studies were included in the review and four evaluated CRP and two evaluated TNF-α in only males. The meta-analysis demonstrated that aerobic exercise training significantly decreased TNF-α concentrations in males (MD = -6.68, 95 % CI = -13.90 to -0.54, P = 0.05). CRP concentrations did not decrease significantly when the data from the four studies were pooled (MD = -0.17, 95 % CI = -0.37 to 0.03, P = 0.09). CONCLUSION: Aerobic exercise training may reduce the concentration of TNF-α in male smokers, but it does not have a significant effect on CRP concentrations. However, these findings are based upon a small number of studies, that enrolled either exclusively male or female participants, and further investigation is necessary to increase statistical inference.