Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

Gut bacteria alleviate smoking-related NASH by degrading gut nicotine.

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.

Tobacco smoking and somatic mutations in human bronchial epithelium.

Tobacco smoking causes lung cancer1-3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented6-10, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

Evaluating interactions of polygenic risk scores and NAT2 genotypes with tobacco smoking in bladder cancer risk.

Tobacco smoking is the most important risk factor for bladder cancer. Previous studies have identified the N-acetyltransferase (NAT2) gene in association with bladder cancer risk. The NAT2 gene encodes an enzyme that metabolizes aromatic amines, carcinogens commonly found in tobacco smoke. In our study, we evaluated potential interactions of tobacco smoking with NAT2 genotypes and polygenic risk score (PRS) for bladder cancer, using data from the UK Biobank, a large prospective cohort study. We used Cox proportional hazards models to measure the strength of the association. The PRS was derived using genetic risk variants identified by genome-wide association studies for bladder cancer. With an average of 10.1 years of follow-up of 390 678 eligible participants of European descent, 769 incident bladder cancer cases were identified. Current smokers with a PRS in the highest tertile had a higher risk of developing bladder cancer (HR: 6.45, 95% CI: 4.51-9.24) than current smokers with a PRS in the lowest tertile (HR: 2.41, 95% CI: 1.52-3.84; P for additive interaction = <.001). A similar interaction was found for genetically predicted metabolizing NAT2 phenotype and tobacco smoking where current smokers with the slow NAT2 phenotype had an increased risk of developing bladder cancer (HR: 5.70, 95% CI: 2.64-12.30) than current smokers with the fast NAT2 phenotype (HR: 3.61, 95% CI: 1.14-11.37; P for additive interaction = .100). Our study provides support for considering both genetic and lifestyle risk factors in developing prevention measures for bladder cancer.

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses.

BACKGROUND: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian-Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. CONCLUSIONS: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

Does Tobacco Smoking Increase Social Isolation? A Mendelian Randomization Study.

In this study, we aimed to investigate the causal effect of smoking on social isolation among older adults in England. Data from older adults of European ancestry who participated in 1 or more waves of the English Longitudinal Study of Ageing, from wave 1 (2002/2003) to wave 9 (2018/2019), were analyzed (n = 43,687 observations from 7,008 individuals; mean age = 68.50 years). The effect of current smoking on social isolation (ranging from 0 to 5) was estimated by 2-stage least squares regression using a polygenic score (PGS) for smoking cessation as the instrument. A low PGS for smoking cessation predicted current smoking (per 1-standard-deviation lower PGS, coefficient = 0.023, 95% confidence interval (CI): 0.015, 0.030; F = 36.420). The second-stage regression showed that current smoking increased social isolation by 1.205 points (95% CI: 0.308, 2.101). The association was larger for persons with higher socioeconomic backgrounds: 2.501 (95% CI: -0.024, 5.026) and 0.696 (95% CI: -0.294, 1.686) for those with higher and lower educational levels, respectively. This study showed that current smoking instrumented by a PGS for smoking cessation was associated with social isolation. Assuming that the PGS served as a valid instrument in this study, the findings support an effect of smoking on social isolation.

Associations of social media use with smoking and e-cigarettes: a national longitudinal study.

BACKGROUND: Social media use is high among children and young people and might influence health behaviours. We examined social media use and use of tobacco and e-cigarettes in the UK. METHODS: We used data from participants aged 10-25 years from the UK Household Longitudinal Study (January 2015-January 2022). Participants were asked: "On a normal weekday, that is Monday to Friday, how many hours do you spend chatting or interacting with friends through a social website or app like that?". Specific social media platforms were not specified. Responses were none, less than 1 h, 1-3 h, 4-6 h, 7 h or more. Outcomes were current tobacco smoking and e-cigarette use. Generalised Estimating Equation (GEE) logistic regression models investigated associations of social media use with tobacco and e-cigarette use, and fixed effects analyses investigated changes in social media use with uptake of both products. Models included possible confounders such as age, sex, household income, ethnicity (White vs non-White) and use of tobacco or e-cigarettes by others within the home. All participants gave written informed consent. FINDINGS: The analytic sample included 10 808 participants with 27 962 observations (mean age 15·7 years [SD 3·8], 5080 [47%] male, 5728 [53%] female, and 7868 [73%] White). Current tobacco smoking was reported at one or more timepoints by 929 (8·6%) participants, and current e-cigarette use by 270 (2·5%) participants. In adjusted GEE models, all levels of social media use were associated with greater odds of current smoking than no use. This association was particularly apparent at higher levels of use adjusted odds ratio [aOR] 3·11, 95% CI 2·41-4·03 for ≥7 h use vs no use), with similar associations for e-cigarettes (aOR 3·04, 2·11-4·40 for ≥7 h use vs no use). Fixed effects analyses also found increased use of social media to be associated with increased uptake of both products (eg, changing to using social media for ≥7 h/day was associated with >2 times the odds of taking up tobacco smoking [aOR 2·33, 1·28-4·24]). INTERPRETATION: These analyses suggest an association between social media use and e-cigarette and tobacco use. Potential pathways include promotion of these products on social media. Further research with details on specific platforms would be useful as well as with longer follow-up time. FUNDING: Cancer Research UK.

The AGE-RAGE axis associates with chronic pulmonary diseases and smoking in the Rotterdam study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma associate with high morbidity and mortality. High levels of advanced glycation end products (AGEs) were found in tissue and plasma of COPD patients but their role in COPD and asthma is unclear. METHODS: In the Rotterdam Study (n = 2577), AGEs (by skin autofluorescence (SAF)), FEV1 and lung diffusing capacity (DLCOc and DLCOc /alveolar volume [VA]) were measured. Associations of SAF with asthma, COPD, GOLD stage, and lung function were analyzed using logistic and linear regression adjusted for covariates, followed by interaction and stratification analyses. sRAGE and EN-RAGE associations with COPD prevalence were analyzed by logistic regression. RESULTS: SAF associated with COPD prevalence (OR = 1.299 [1.060, 1.591]) but not when adjusted for smoking (OR = 1.106 [0.89, 1.363]). SAF associated with FEV1% predicted (ß=-3.384 [-4.877, -1.892]), DLCOc (ß=-0.212 [-0.327, -0.097]) and GOLD stage (OR = 4.073, p = 0.001, stage 3&4 versus 1). Stratified, the association between SAF and FEV1%predicted was stronger in COPD (ß=-6.362 [-9.055, -3.670]) than non-COPD (ß=-1.712 [-3.306, -0.118]). Association of SAF with DLCOc and DLCOc/VA were confined to COPD (ß=-0.550 [-0.909, -0.191]; ß=-0.065 [-0.117, -0.014] respectively). SAF interacted with former smoking and COPD prevalence for associations with lung function. Lower sRAGE and higher EN-RAGE associated with COPD prevalence (OR = 0.575[0.354, 0.931]; OR = 1.778[1.142, 2.768], respectively). CONCLUSIONS: Associations between SAF, lung function and COPD prevalence were strongly influenced by smoking. SAF associated with COPD severity and its association with lung function was more prominent within COPD. These results fuel further research into interrelations and causality between SAF, smoking and COPD. TAKE-HOME MESSAGE: Skin AGEs associated with prevalence and severity of COPD and lung function in the general population with a stronger effect in COPD, calling for further research into interrelations and causality between SAF, smoking and COPD.

Effects of educational interventions based on the theory of planned behavior on oral cancer-related knowledge and tobacco smoking in adults: a cluster randomized controlled trial.

BACKGROUND: The theory of planned behavior (TPB) is an effective model for facilitating behavioral change. The aim of the present study was to evaluate the impact of TPB-based educational interventions on oral cancer-related knowledge and tobacco smoking behavior in an Iranian adult population in 2022. METHODS: In this randomized controlled trial, a total of 400 healthy individuals were enrolled. The study was implemented in 20 urban health centers in the south of Tehran, Iran. The health centers were randomly allocated into two intervention groups. In group PowerPoint (PP), the participants received education through a 20-minute PowerPoint presentation complemented by a pamphlet. Group WhatsApp (WA) was educated via WhatsApp messages and images. Data was collected using a structured questionnaire at baseline, and at one- and three-month follow-ups. The outcomes were evaluated in terms of knowledge, tobacco smoking behavior, and the related model constructs i.e. intention, attitude, subjective norm, and perceived behavioral control. Generalized estimating equations (GEE) regression models were applied to assess the effect of interventions on repeated measurements of the outcomes. All analyses were conducted using STATA Software Version 17. RESULTS: Out of all the participants, 249 (62%) were women. The mean and standard deviation (SD) of age were 39.67 and 13.80 years. Overall, group PP had a significantly higher score of knowledge compared to group WA (ß = 0.43, p = 0.005). No significant differences were found between the groups with regard to tobacco smoking and the related TPB constructs, except for attitude with a higher score in group PP compared to group WA (ß = 0.50, p = 0.004). At the three-month follow-up, both interventions had significant effects on increasing knowledge (ß = 4.41), decreasing tobacco smoking (OR = 0.54), and increasing intention (ß = 1.11), attitude (ß = 1.22), subjective norm (ß = 1.37), and perceived behavioral control (ß = 1.08) (P < 0.001). CONCLUSIONS: Both interventions were effective in improving knowledge, tobacco smoking, and the TPB constructs after three months. Therefore, the application of both methods could be considered in the design and implementation of oral cancer prevention programs. TRIAL REGISTRATION: The trial protocol was registered in the Iranian Registry of Clinical Trials (IRCT) on 04/03/2022 (registration number: IRCT20220221054086N1).

Estimating smoking-attributable lung cancer mortality in Chinese adults from 2000 to 2020: a comparison of three methods.

BACKGROUND: Smoking is a significant public health concern in China and a leading cause of lung cancer deaths among adults. This study aims to employ three methods to estimate smoking-attributable lung cancer mortality among Chinese adults from 2000 to 2020. METHODS: Population attributable fractions (PAFs) of lung cancer deaths caused by smoking were estimated using lagged smoking prevalence, Peto-Lopez, and dose-response relationship methods, separately. Smoking exposure was obtained from national tobacco surveys in China, and relative risks (RR) were derived from a meta-analysis of state-of-the-art studies among the Chinese population. Finally, we estimated the sex- and age-stratified smoking-attributable lung cancer deaths in Chinese population in 2000, 2005, 2010, 2015, and 2020. RESULTS: The PAFs estimated using 5- and 10-year lagged smoking prevalence method (45-47%) and Peto-Lopez method (46-47%) were similar, while PAFs calculated using the dose-response method were highest (47-58%). The PAFs were consistently higher in males than in females. Age-specific PAFs estimated by lagged smoking prevalence method (54-60%) and the Peto-Lopez method (57-61%) in males were similar and relatively stable, with slight decreases in older populations, while the dose-response relationship-based PAFs increased with age and fluctuated by year. By using the above methods, smoking-attributable lung cancer deaths were estimated to be 134,100, 134,600, 136,600, and 155,300 in 2000 increasing to 310,300, 301,100, 306,000, and 314,700 in 2020, respectively. CONCLUSION: The estimation from dose-response methods could better reflect the smoking effect, however, high-quality data and accurate estimation of parameters are necessary.

Combining Inserts With Warning Labels on Cigarette Packs to Promote Smoking Cessation: A 2-Week Randomized Trial.

BACKGROUND: Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation. PURPOSE: To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes. METHODS: We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4-5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups. RESULTS: Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes. CONCLUSIONS: This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts.

Cigarette pack inserts (small leaflets inside packs) with messages about quitting benefits and tips to quit may promote smoking cessation. We randomly assigned 367 adult smokers to one of four groups: control group with small health warning labels (HWLs) on the side of packs; inserts with cessation messages and small HWLs; large picture HWLs showing health effects from smoking; inserts and large picture HWLs. Participants received a 14-day supply of their preferred cigarettes in packs that reflected their assigned group. Over 2 weeks, we surveyed participants 4­5 times a day during times when they smoked, asking their feelings about smoking and smoking-related harms, confidence to reduce cigarettes and quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported on the prior 24 hr: how often they thought about smoking harms and cessation benefits; conversations about smoking cessation or harms; and foregoing or stubbing out cigarettes before they finished smoking. People whose packs had inserts (with or without picture HWLs) were more likely than those whose packs did not include inserts (control group or picture HWLs only) to report foregoing or stubbing out of cigarettes. This study provides some evidence that inserts with cessation messages may promote smoking cessation.

Factors Influencing Tobacco Smoking and Cessation Among People Living with HIV: A Systematic Review and Meta-analysis.

Tobacco smoking is highly prevalent among people living with HIV (PLWH), yet there is a lack of data on smoking behaviours and effective treatments in this population. Understanding factors influencing tobacco smoking and cessation is crucial to guide the design of effective interventions. This systematic review and meta-analysis of studies conducted in both high-income (HICs) and low- and middle-income countries (LMICs) synthesised existing evidence on associated factors of smoking and cessation behaviour among PLWH. Male gender, substance use, and loneliness were positively associated with current smoking and negatively associated with smoking abstinence. The association of depression with current smoking and lower abstinence rates were observed only in HICs. The review did not identify randomised controlled trials conducted in LMICs. Findings indicate the need to integrate smoking cessation interventions with mental health and substance use services, provide greater social support, and address other comorbid conditions as part of a comprehensive approach to treating tobacco use in this population. Consistent support from health providers trained to provide advice and treatment options is also an important component of treatment for PLWH engaged in care, especially in LMICs.

A prediction model for classifying maternal pregnancy smoking using California state birth certificate information.

BACKGROUND: Systematically recorded smoking data are not always available in vital statistics records, and even when available it can underestimate true smoking rates. OBJECTIVE: To develop a prediction model for maternal tobacco smoking in late pregnancy based on birth certificate information using a combination of self- or provider-reported smoking and biomarkers (smoking metabolites) in neonatal blood spots as the alloyed gold standard. METHODS: We designed a case-control study where childhood cancer cases were identified from the California Cancer Registry and controls were from the California birth rolls between 1983 and 2011 who were cancer-free by the age of six. In this analysis, we included 894 control participants and performed high-resolution metabolomics analyses in their neonatal dried blood spots, where we extracted cotinine [mass-to-charge ratio (m/z) = 177.1023] and hydroxycotinine (m/z = 193.0973). Potential predictors of smoking were selected from California birth certificates. Logistic regression with stepwise backward selection was used to build a prediction model. Model performance was evaluated in a training sample, a bootstrapped sample, and an external validation sample. RESULTS: Out of seven predictor variables entered into the logistic model, five were selected by the stepwise procedure: maternal race/ethnicity, maternal education, child's birth year, parity, and child's birth weight. We calculated an overall discrimination accuracy of 0.72 and an area under the receiver operating characteristic curve (AUC) of 0.81 (95% confidence interval [CI] 0.77, 0.84) in the training set. Similar accuracies were achieved in the internal (AUC 0.81, 95% CI 0.77, 0.84) and external (AUC 0.69, 95% CI 0.64, 0.74) validation sets. CONCLUSIONS: This easy-to-apply model may benefit future birth registry-based studies when there is missing maternal smoking information; however, some smoking status misclassification remains a concern when only variables from the birth certificate are used to predict maternal smoking.

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.

Support Provided by Stop-Smoking Practitioners to Co-users of Tobacco and Cannabis: A Qualitative Study.

INTRODUCTION: Co-use of tobacco and cannabis is highly prevalent among cannabis users and is associated with poorer tobacco cessation outcomes. This study explored the barriers and enablers influencing stop-smoking practitioners' ability to provide optimal support to co-users. AIMS AND METHODS: Online semi-structured interviews were audio recorded. Interviewees (n = 20) were UK-based certified stop-smoking practitioners. An interview schedule informed by the "capability", "opportunity", "motivation" (COM-B) model was designed to explore participants' perceived barriers and enablers in better supporting co-users to achieve abstinence of both substances or tobacco harm reduction. The transcripts were analyzed using framework analysis. RESULTS: Capability: Practitioners' lack of knowledge and skills undermines their delivery of smoking cessation interventions to co-users. Interestingly, when cannabis is used for medicinal reasons, practitioners feel unable to provide adequate support. Opportunity: Service recording systems play an important role in screening for co-use and supporting co-users. When responding to clients' specific needs and practitioners' uncertainties, a positive therapeutic relationship and a support network of peers and other healthcare professionals are needed. Motivation: supporting co-users is generally perceived as part of practitioners' roles but there are concerns that co-users are less likely to successfully stop smoking. CONCLUSIONS: Practitioners are willing to support co-users, but their lack of knowledge and access to an appropriate recording system are barriers to doing so. Having a supportive team and a positive therapeutic relationship is perceived as important. Identified barriers can be mostly addressed with further training to improve tobacco cessation outcomes for co-users.

Tobacco Imagery in the 50 Most Popular Malaysian Movies Released During 2015-2019.

INTRODUCTION: Exposure to tobacco imagery creates a positive impression about smoking and is associated with youth smoking uptake. METHODS: From the list of movies released during 2015-2019, we selected the top 10 movies per year rated by the Malaysian Film Development Corporation. Two researchers coded tobacco imagery in each movie considering 5-minute time intervals as a unit. The 5-minute interval coding was adopted from previous research for comparability. Frequencies and the average occurrence of tobacco imagery were compared by movie language, genre, and age categorization. RESULTS: In 50 movies analyzed, there were a total of 1037 five-minute intervals of which 26 (52%) movies and 277 (26.7%) of intervals tobacco imagery were present. Brand appearances were absent and health warnings about tobacco use were present in just one movie. The proportions of intervals containing actual use, paraphernalia, and implied use were 63.5%, 22.0%, and 14.5%. Tobacco imagery of actual use, paraphernalia, and implied use was present in 25, 20, and 10 movies, respectively. In those movies with tobacco imagery, the average number of occurrences of actual use, paraphernalia, and implied use was 3 (interquartile range [IQR] 2-11.5), 2.5 (IQR 1.3-4.0), and 1 (IQR 1-4), respectively. Movies classified as "p13" (median 6, IQR 6-13) and "18" (median 5, IQR 0-15) had higher average occurrences of tobacco imagery than "U" movies (median 0, IQR 0-2; p = .028). CONCLUSIONS: The lack of health warnings despite the presence of tobacco imagery in Malaysian movies calls for measures to regulate tobacco-related content and reclassify such movies as "for adults-only." IMPLICATIONS: Tobacco imagery was prevalent in Malaysian movies that are allowed viewing by individuals aged 13 years and above. A review of the age categorization of Malaysian movies and the placement of health warnings in movies is needed. A comprehensive implementation of the ban on tobacco advertisements, promotion, and sponsorship should also include a ban on tobacco imagery in movies.

Racial and Ethnic Disparities in Adolescent Combustible Tobacco Smoking From 2014 to 2020: Declines Are Lagging Among Non-Hispanic Black Youth.

INTRODUCTION: We quantified the linear trend in combustible tobacco smoking among adolescents in the United States from 2014 to 2020, and then compared these trends across racial and ethnic categories. We also tested the effect of e-cigarette use on these trends for all-youth and across racial and ethnic categories. AIMS AND METHODS: We pooled and analyzed seven years of National Youth Tobacco Survey data for n = 124 151 middle and high school students from 2014 to 2020. Weighted logistic regression analyses calculated the annual change in combustible tobacco smoking (ie cigarettes, cigars, and hookah) from 2014 to 2020. Stratified analyses examined linear trends for non-Hispanic White (NHW), NH-Black (NHB), Hispanic/Latino, and NH-Other (NHO) youth. All-models controlled for sex, grade level, and past 30-day e-cigarette use. RESULTS: Combustible tobacco smoking from 2014 to 2020 dropped by more than 50% for NHW youth, more than 40% for Latino and NHO youth, compared to just 16% among NHB youth. From 2014 to 2020, the odds of combustible tobacco smoking declined by 21.5% per year for NHWs, which was significantly greater than Hispanic/Latinos (17% per year; p = .025), NHOs (15.4% per year; p = .01), and NHBs (5.1% per year; p < .001), adjusting for sex, grade, and e-cigarette use. Trends and disparities in trends by race and ethnicity were observed independent of e-cigarette use. CONCLUSIONS: Combustible tobacco smoking declined for all-youth but at significantly different rates across races and ethnicities. Notably, declines in combustible tobacco smoking are lagging among NHB youth. Interventions are critically needed to address this disparity. IMPLICATIONS: A direct, evidence-based intervention to reduce combustible tobacco smoking among NHB youth is critically needed. Such tobacco control initiatives should follow the Best Practices for Comprehensive Tobacco Control Framework, incorporating sustainable funding for school-based intervention, public health education, and adult cessation.

Effects of Modified Risk Tobacco Product Claims on Consumer Responses.

INTRODUCTION: US tobacco manufacturers can seek authorization from the US Food and Drug Administration (FDA) to market products using modified risk tobacco product (MRTP) claims. To inform regulatory decisions, we examined the impact of MRTP claim specificity and content, including whether the claims produced halo effects (ie, inferring health benefits beyond what is stated). AIMS AND METHODS: Participants were 3161 US adult cigarette smokers. Using a two (general vs. specific) × 2 (risk vs. exposure) plus independent control design, we randomized participants to view one message from these conditions: general risk claim (eg, "smoking-related diseases"), general exposure claim (eg, "chemicals in smoke"), specific risk claim (eg, "lung cancer"), specific exposure claim (eg, "arsenic"), or control. Claims described the benefits of completely switching from cigarettes to the heated tobacco product IQOS. RESULTS: MRTP claims of any sort elicited a higher willingness to try IQOS relative to control (d = 0.09, p = .043). Claims also elicited lower perceived risk of disease and exposure to harmful chemicals for completely switching from cigarettes to IQOS (d = -0.32 and -0.31) and partially switching (d = -0.25 and d = -0.26; all p < .05). Relative to specific MRTP claims, general MRTP claims led to lower perceived risk and exposure for complete switching (d = -0.13 and d = -0.16) and partial switching (d = -0.14 and d = -0.12; all p < .05). Risk and exposure MRTP claims had similar effects (all p > .05). DISCUSSION: MRTP claims led to lower perceived risk and exposure, and higher willingness to try IQOS. General claims elicited larger effects than specific claims. MRTP claims also promoted unintended halo effects (eg, lower perceived risk of disease and chemical exposure for partial switching). IMPLICATIONS: We found evidence that MRTP claims promoted health halo effects. In light of these findings, the FDA should require research on halo effects prior to authorization. Further, if an MRTP claim is authorized, FDA should require tobacco manufacturers to conduct post-market surveillance of how the claim affects consumer understanding, including partial switching perceived risk and exposure beliefs, as well as monitoring of dual-use behaviors.

Changes in patient profiles in the cardiology department of the University Hospital Gabriel Touré (UH-GT) : results of two cross-sectional studies of 2010 and 2022.

BACKGROUND: Little is known about patient profile changes in medical facilities in our country, leading to this study to describe and compare patient profiles in 2010 and 2022. PATIENTS AND METHODS: This was a cross-sectional study with new outpatients aged 15 years and more seen in the cardiology department of the UH-GT. Measurements included height, weight and body mass index (BMI). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. Quantitative data are presented as the mean with standard deviation, and categorical one as proportions. Statistical tests were the t test to compare means and chi-test for categorical variables. The level of significance was set to 0.05. RESULTS: The sample consisted of 515 new patients (199 in 2010 and 316 in 2022) with 59.1% female in 2010 and 60.1% in 2022 (p = 0.821). We noticed an increase in hypertension (59.1-71.8%, p = 0.003) and a decrease in tobacco smoking (from 13 to 05.4%, p = 0.002) and stroke (from 05.8 to 02.2%, p = 0.033). Height increased significantly from 1.59 m to 1.66 m, p = 0.002. SBP and DBP showed significant decreases in their means from 155.43 to 144.97 mmHg, p = < 0.001 for SBP and from 95.53 to 89.02 mmHg, p = < 0.001 for DBP. CONCLUSIONS: Cardiovascular risk factors showed different trends with decreasing tobacco smoking, similar to systolic and diastolic blood pressure, albeit with an increase in hypertension prevalence. Other CVrf values increased. Awareness campaigns must be reinforced and maintained to obtain their decrease.