Tobacco Smoking or Nicotine Phenotype and Severity of Clinical Presentation at the Emergency Department (SMOPHED): Protocol for a Noninterventional Observational Study.

BACKGROUND: In the last few years, several nicotine products have become available as alternatives to smoking tobacco. While laboratory and limited clinical studies suggest that these devices are less toxic compared to classic tobacco cigarettes, very little is known about their epidemiological impact. Visiting the emergency department (ED) often represents the first or even the only contact of patients with the health care system. Therefore, a study conducted at the ED to assess the impact of these products on health can be reliable and reflect a real-life setting. OBJECTIVE: The aim of this noninterventional observational study (SMOPHED study) is to analyze the association between the severity of clinical presentation observed during ED visits among patients using various nicotine products and the subsequent outcomes, specifically hospitalization and mortality. METHODS: Outcomes (hospitalization and mortality in the ED) will be examined in relation to various patterns of nicotine products use. We plan to enroll approximately 2000 participants during triage at the ED. These individuals will be characterized based on their patterns of tobacco and nicotine consumption, identified through a specific questionnaire. This categorization will allow for a detailed analysis of how different usage patterns of nicotine products correlate with the clinical diagnosis made during the ED visits and the consequent outcomes. RESULTS: Enrollment into the study started in March 2024. We enrolled a total of 901 participants in 1 month (approximately 300 potential participants did not provide the informed consent to participate). The data will be analyzed by a statistician as soon as the database is completed. Full data will be published by December 2024. CONCLUSIONS: There is substantial debate about the harm reduction potential of alternative nicotine products in terms of their smoking-cessation and risk-reduction potential. This study represents an opportunity to document epidemiological data on the link between the use of different types of nicotine products and disease diagnosis and severity during an ED visit, and thus evaluate the harm reduction potential claims for these products. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54041.

The association between tobacco smoking and systolic toe pressures in active foot ulceration.

Smoking may increase the risk of diabetic foot disease and ulceration. It does so by impairing glycaemic control and promoting the formation of advanced glycated end-products. Additionally, smoking is known to delay surgical wound healing and accelerate peripheral arterial disease. We aimed to determine whether toe pressures differed in smokers with a foot ulcer, when compared to non-smokers and ex-smokers, as well as ulcer outcomes at 12 months, among patients attending Blacktown Hospital High Risk Foot Service (HRFS). This study is a retrospective analysis of our prospectively collected clinic database. Eligible participants were adults attending the HRFS between June 2020 and April 2022. Participants were included if they had an ulcer, at least one systolic toe pressure reading completed at their initial visit and attended at least one follow-up visit. Participants were followed until healing, loss to follow-up or a minimum of 12 months. A total of 195 participants were included; 36 smokers, 82 ex-smokers, and 77 controls who had never smoked. Smoking status was by self-report. Current smokers were significantly younger at initial presentation (p = .002) and tended towards lower socioeconomic status (p = .067). Current smokers were significantly more likely to have ischaemic grade 3 toe pressures (< 30 mmHg) of their left foot (p = .027), suggestive of reduced perfusion. At the end of follow up period, smokers had the numerically highest rates of minor amputations. In conclusion, smokers ulcerate younger and are more likely to have grade 3 ischaemia. Collecting information about the brachial artery pressures and the time since the last cigarette may clarify any relationship between smoking and toe pressures.Trial registration: WSLHD HREC ethics approval 2111-02 and ANZCTR registration 382470. Registered on 15/09/2021.

Del-1 Plays a Protective Role against COPD Development by Inhibiting Inflammation and Apoptosis.

Neutrophilic inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD). Developmental endothelial locus-1 (Del-1) has been reported to limit excessive neutrophilic inflammation by inhibiting neutrophil adhesion to the vascular endothelial cells. However, the effects of Del-1 in COPD are not known. We investigated the role of Del-1 in the pathogenesis of COPD. Del-1 protein expression was decreased in the lungs of COPD patients, especially in epithelial cells and alveolar macrophages. In contrast to human lung tissue, Del-1 expression was upregulated in lung tissue from mice treated with cigarette smoke extracts (CSE). Overexpression of Del-1 significantly suppressed IL-8 release and apoptosis in CSE-treated epithelial cells. In contrast, knockdown of Del-1 enhanced IL-8 release and apoptosis. In macrophages, overexpression of Del-1 significantly suppressed inflammatory cytokine release, and knockdown of Del-1 enhanced it. This anti-inflammatory effect was mediated by inhibiting the phosphorylation and acetylation of NF-κB p65. Nuclear factor erythroid 2-related factor 2 (Nrf2) activators, such as quercetin, resveratrol, and sulforaphane, increased Del-1 in both cell types. These results suggest that Del-1, mediated by Nrf2, plays a protective role against the pathogenesis of COPD, at least in part through anti-inflammatory and anti-apoptotic effects.

The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence / El uso de cigarrillos electrónicos como factor de riesgo de trastornos orales potencialmente malignos y cáncer oral: una revisión rápida de la evidencia clínica

Background: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens andyoung adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitroand in vivo studies have evidenced a variable quantity of potentially harmful components and some recognizedcarcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes mayplay active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapidreview aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentiallymalignant disorders (OPMD) and oral cancer.Material and Methods: A systematic search for English language articles published was performed in PubMed(MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelveclinical studies about OPMD and oral cancer risk in e-cigarette users.Results: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes,DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However,results were inconsistent compared to tobacco smokers and control groups.Conclusions: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes asa risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsiblyabout the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designedclinical studies are needed.(AU)

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.

Motivations for continued tobacco smoking and reasons for quitting among youths in Wakiso district, Uganda: a qualitative study.

BACKGROUND: Efforts have been invested towards cessation of tobacco use among youths aged 18-35 years, however, motivators for continued tobacco smoking and reasons for quitting are limited in Ugandan settings. Therefore, this study aimed to explore motivations for continued tobacco smoking and reasons for quitting in Wakiso district Uganda. METHODS: This study used explanatory sequential method. Data from a Population-based survey collected from October 2019 to September 2020 was used to select participants for this qualitative study. Twenty-three in-depths interviews were conducted from July to October 2021 among youths (18-35years old) who reported continued tobacco use and those who quit. Data were analyzed using a team-based thematic content approach with the help of NVivo. RESULTS: Data was collected from a total of twenty three participants, fourteen were tobacco quitters and nine were current tobacco smokers. Recurrent habit, desire to complement the use of other drugs, peer pressure, using smoking as a replacement for alcohol consumption, low tobacco prices, smoking as a tradition were reported as motivators for continued tobacco smoking. However, reported reasons for quitting smoking by youths included; packaging health warnings, school based prevention programs, fear of associated health risks due to tobacco use, embarrassment from family members. CONCLUSION: Targeted, and tailored tobacco prevention counselling through family support programs, intensified health education on the risks of smoking, and implementing stronger health warnings on tobacco packaging can be employed to reduce or stop tobacco use among urban youth.

The associations of parental smoking, quitting and habitus with teenager e-cigarette, smoking, alcohol and other drug use in GUI Cohort '98.

We analyse parental smoking and cessation (quitting) associations with teenager e-cigarette, alcohol, tobacco smoking and other drug use, and explore parental smoking as a mechanism for social reproduction. We use data from Waves 1-3 of Growing Up in Ireland (Cohort '98). Our analytic sample consisted of n = 6,039 participants reporting in all 3 Waves. Data were collected in Waves 1 and 2 when the children were 9 and 13 years old and in Wave 3 at age 17/18 years. Generalized Estimating Equations (GEE) models were used to analyse teenage substance use at Wave 3. Parental smoking was associated with significantly increased risk of all teenage substance use, adjusted odds ratios were aOR2.13 (ever e-cigarette use); aOR1.92 (ever alcohol use); aOR1.88 (current alcohol use); aOR1.90 (ever use of other drugs); aOR2.10 (ever-smoking); and aOR1.91 (current smoking). Primary caregiver smoking cessation (quitting) was associated with a lower risk for teenager current smoking aOR0.62, ever e-cigarette use aOR 0.65 and other drug use aOR 0.57. Primary caregiver smoking behaviour had greater associations than secondary, and age13 exposure more than age 9. Habitus seems to play a role and wealth was protective for teenage smoking. The findings suggest that prevention interventions should target both caregivers and their children.

Quitting smoking improves two-year survival after a diagnosis of non-small cell lung cancer.

BACKGROUND: Smoking at diagnosis is associated with worse survival in lung cancer but the effects of quitting smoking on survival remain unclear. METHODS: In a UK multi-centre study (NCT01192256) we followed all 2751 patients with newly diagnosed non-small cell lung cancer (NSCLC) for up to 2 years or until death as part of the observational trial. Patients were offered smoking cessation advice and treatments according to national guidelines and local services. Smoking status was verified by exhaled carbon monoxide levels. Kaplan-Meier survival analysis and Cox Proportional Hazards Modelling examined the effects of quitting smoking on survival at 2 years. FINDINGS: 646 were current smokers at the time of diagnosis. The unadjusted two-year Kaplan-Meier survivor functions for quitters (0.45, 95 %CI 0.37 to 0.53) and continuers (0.32, 0.28 to 0.36) were significantly different (log-rank test p < 0.01). Median survival times were 659 days for quitters and 348 days for continuers. After adjusting for age, sex, stage, performance status, curative intent surgery, radical radiotherapy and comorbidity, the hazard ratio for quitting at diagnosis (0.75, 95 % CI 0.58 to 0.98) indicated a statistically significant reduction in the risk of death across the two-year study period. INTERPRETATION: Quitting smoking is independently and significantly associated with improved survival regardless of stage in NSCLC. We recommend that smoking cessation advice and treatments should be offered to smokers with lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01192256. FUNDING: This work was supported by a 2010 Global Research Award for Nicotine Dependence (GRAND), Pfizer.

The influence of various endocrine disruptors on the reproductive system.

Various stimulants (VS) are chemicals that disrupt the endocrine system - endocrine homeostasis of the reproductive system - which also known as endocrine-disrupting chemicals (EDCs). These substances are found in the human body, in both the blood and urine, amniotic fluid, or, among others, the adipose tissue. This article presents the current state of knowledge of the effect of EDCs and additional factors such as smoking, alcohol consumption, and cannabis on the gonads. The article is an overview of the impact of EDCs and their mechanism of action, with particular emphasis on gonads, based on databases such as PubMed, EMBASE and Google Scholar, and Web of Science available until May 2022. The impact of human exposure to bisphenol A (BPA) is not fully understood, but it has been shown that phthalates show a negative correlation in anti-androgenic activity in the case of men and women for the anti-Müllerian hormone (AMH). Smoking cigarettes and passive exposure to tobacco have a huge impact on the effects of endocrine disorders in both women and men, especially during the reproductive time. Also, the use of large amounts of cannabinoids during the reproductive years can lead to similar disorders. It has been documented that excessive alcohol consumption leads to disturbed function of the hypothalamus-pituitary-gonadal axis (HPG). Excess caffeine consumption may adversely affect male reproductive function, although this is not fully proven. Therefore, the following publication presents various stimulants (BPA, phthalates, nicotine, alcohol, cannabis) that disrupt the function of the endocrine system and, in particular, affect the function of the gonads.

Household adult smoking behaviors and prevalence of asthma in Greek schoolchildren: five surveys during 1998-2018.

OBJECTIVE: Environmental tobacco smoke exposure is a well-recognized risk factor for asthma development and poor asthma control in children. However, the relationship between changes in parental smoking habits over time and the prevalence of childhood asthma remains largely unknown. Our objective was to investigate the trends of parental smoking behaviors in relation to childhood wheeze/asthma rates over a 20-year period. SUBJECTS AND METHODS: A standardized questionnaire on household overall smoking and household indoor tobacco smoking (HITS) habits was distributed to 8-9-years-old school children in the context of five cross-sectional surveys conducted in 1998 (n=3,076), 2003 (n=2,725), 2008 (n=2,688), 2013 (n=2,554) and 2018 (n=2,648). RESULTS: The parental overall smoking and HITS rates have substantially decreased during the study period (p-for-trend<0.001). However, while HITS declined among the fathers of asthmatic and non-asthmatic children as well as among the mothers of non-asthmatic ones (p-for-trend<0.001), it remained unchanged in the case of the mothers of asthmatic participants (p-for-trend 0.283). The mothers of asthmatic children consistently reported more HITS than those of non-asthmatic participants, while prevalence changes of current wheeze/asthma over the surveillance period were in complete agreement with changes in maternal HITS (cross-correlation coefficient 0.918 at zero-year lag) but not with paternal smoking behaviors. CONCLUSIONS: Overall and indoor smoking rates of school children's adult family members declined substantially during the 1998-2018 period in Greece. However, no such trend was noted among mothers of asthmatic children, while temporal changes in maternal indoor smoking rates occurred in parallel with those of childhood asthma prevalence.

Association Between Tobacco Smoking and Dental Caries in the Indonesian Population: Results of a National Study in 2018.

OBJECTIVES: The 2018 Basic Health Research (RISKESDAS), conducted by the Ministry of Health of the Republic of Indonesia showed a high prevalence of dental caries (88.8%) in Indonesia and suggested that smoking tobacco was associated with an increased risk of dental caries. This study analyzed the association between tobacco smoking and dental caries in the Indonesian population. METHODS: This was a cross-sectional analysis of secondary data collected from RISKESDAS 2018. The study population included 35 391 Indonesians aged ≥10 years from all 34 provinces. The decayed, missing, and filled teeth (DMFT) index was used to measure dental caries. Smoking status was assessed qualitatively based on smoking activity, and the level of smoking exposure was assessed based on the Brinkman index. A multivariable logistic regression analysis was employed to examine the relationships of smoking status and smoking exposure levels with the DMFT index. RESULTS: Of the population aged ≥10 years, 36% had a DMFT≥8 (females: 37.5%, males: 33.9%). Almost one-fourth (23.4%) were current smokers, and 4.1% were ex-smokers. Furthermore, 26.4% had a Brinkman index ≥400, indicating heavy smoking. According to the multivariate analysis, current smoking status was associated with the risk of DMFT≥8 in males (adjusted odds ratio [aOR], 1.40; 95% CI, 1.27 to 1.55; p<0.001) and overall (aOR, 1.07; 95% CI, 1.00 to 1.14; p=0.037). In females, ex-smoking was associated with a 41% higher risk of DMFT≥8 (aOR, 1.41; 95% CI, 1.07 to 1.84; p=0.014). Heavy smoking was associated with a higher risk of DMFT≥8 in males (aOR, 1.38; 95% CI, 1.25 to 1.52; p<0.001) and females (aOR, 1.24; 95% CI, 1.03 to 1.50; p=0.022). CONCLUSIONS: Tobacco smoking was associated with dental caries in the Indonesian population.

Trends in social inequality in mortality in Denmark 1995-2019: the contribution of smoking- and alcohol-related deaths.

BACKGROUND: During the past decades, social inequality in mortality has increased in several countries, including Denmark. Modifiable risk factors, such as smoking and harmful alcohol consumption, have been suggested to moderate the association between socioeconomic position and health-related outcomes. The present study aims to investigate the contribution of smoking- and alcohol-related deaths to the trends in educational inequality in mortality in Denmark 1995-2019 among individuals aged 30-74 years. METHODS: Nationwide data on mortality and highest attained educational level divided into quartiles were derived from administrative registers. Alcohol-related mortality was directly estimated using information on alcohol-related deaths from death certificates. Smoking-related mortality was indirectly estimated using the Peto-Lopez method. The contribution of smoking- and alcohol-related deaths to the social inequality gap in mortality 1995-2019 was calculated. RESULTS: Alongside a decrease in all-cause mortality in Denmark 1995-2019, absolute differences in the mortality rate (per 100 000 person-year) between the lowest and the highest educational quartile increased from 494 to 607 among men and from 268 to 376 among women. Among both men and women, smoking- and alcohol-related deaths explained around 60% of the social inequality in mortality and around 50% of the increase in mortality inequality. CONCLUSION: Smoking and harmful alcohol consumption continue to be important risk factors and causes of social inequality in mortality, with around half of the increase in Denmark 1995-2019 being attributable to smoking- and alcohol-related deaths. Future healthcare planning and policy development should aim at reducing social inequality in modifiable health risk behaviours and their negative consequences.

Genetic mutations in smoking-associated prostate cancer.

OBJECTIVES: Tobacco smoking is known to cause cancers potentially predisposed by genetic risks. We compared the frequency of gene mutations using a next generation sequencing database of smokers and nonsmokers with prostate cancer (PCa) to identify subsets of patients with potential genetic risks. MATERIALS AND METHODS: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry was analyzed. The GENIE registry contains clinically annotated sequenced tumor samples. We included 1832 men with PCa in our cohort, categorized as smokers and nonsmokers, and compared the frequency of mutations (point mutations, copy number variations, and structural variants) of 47 genes with more than 5% mutation rate between the two categories and correlated with overall survival using logistic regression analysis. RESULTS: Overall, 1007 (55%) patients were nonsmokers, and 825 (45%) were smokers. The mutation frequency was significantly higher in smokers compared to nonsmokers, 47.6% and 41.3%, respectively (p = 0.02). The median tumor mutational burden was also significantly higher in the samples from smokers (3.59 mut/MB) compared to nonsmokers (1.87 mut/MB) (p < 0.001). Patients with a smoking history had a significantly higher frequency of PREX2, PTEN, AGO2, KMT2C, and a lower frequency of adenomatous polyposis coli (APC) and KMT2A mutations than compared to nonsmokers. The overall mortality rate (28.5% vs. 22.8%) was significantly higher among smokers (p = 0.006). On a multivariate logistic regression analysis, the presence of metastatic disease at the time of diagnosis (OR: 2.26, 95% CI: 1.78-2.89, p < 0.001), smoking history (OR: 1.32, 95% CI: 1.05-1.65, p = 0.02), and higher frequency of PTEN somatic gene mutation (OR: 1.89, 95% CI: 1.46-2.45, p < 0.001) were independent predictors of increased overall mortality among patients with PCa. Patients with PTEN mutation had poorer overall survival compared to men without PTEN mutations: 96.00 (95% CI: 65.36-113.98) and 120.00 (95% CI: 115.05-160.00) months, respectively (p < 0.001) irrespective of smoking history although the G129R PTEN mutation was characteristically detected in smokers. CONCLUSIONS: PCa patients with a tobacco smoking history demonstrated a significantly higher frequency of somatic genetic mutations. Whereas mutations of PREX2, KMT2C, AGO2, and PTEN genes were higher in smokers, the APC and KMT2A mutations were higher in nonsmokers. The PTEN somatic gene mutation was associated with increased overall mortality among patients with PCa irrespective of smoking history. We found that G129R PTEN mutation known to reduce the PTEN phosphatase activity and K267Rfs*9 a frameshift deletion mutation in the C2 domain of PTEN associated with membrane binding exclusively detected in smokers and nonsmokers, respectively. These findings may be used to further our understanding of PCa associated with smoking.

Association between tobacco smoking and alcohol consumption with arterial stiffness.

Few investigations have been performed between tobacco smoking, alcohol, and arterial stiffness. The purpose of our study was to investigate the association between smoking use and alcohol with arterial stiffness index (ASI) in a middle-age population. Smoking pack-years and cigarettes per day were defined as alcohol consumption in units/day. Sex associations between smoking and alcohol with ASI were estimated using multiple linear regressions. Interactions and synergistic effects were investigating. 98 039 individuals of the UK Biobank cohort were included (45 457 men and 52 582 women). ASI levels were higher in men than in women (9.91 vs. 8.71 m/s, p < .001), and showed higher relationship to smoking tobacco in multiple linear regression models in women than in men (FDR logworth 78.4 vs. 52.7). The findings revealed that ASI was higher among current smokers than never smokers in both sex and after adjustment for all covariates (in men 10.4 vs. 9.6 and in women 9.5 vs. 8.5 m/s, p < .001). Alcohol consumption per day was positively associated with higher levels of ASI in both sex, but with a less relationship (FDR logworth for men = 2.8, for women = 2.5). An interaction was observed between smoking information and alcohol in men but not in women. Synergistic effects were observed by adding smoking information on alcohol consumption models in men and women (p = .029, p < .001, respectively). Smoking and alcohol were associated with higher ASI in both sex but with a higher relationship among women. The findings suggest the importance of considering smoking and alcohol consumption cessation in cardiovascular diseases prevention.

The role of modifiable risk factors in incident cancer in transport, rescue, and security industries.

PURPOSE: Examine the risk for site-specific incident cancer across representative transport, rescue, and security industries. METHODS: This Danish nationwide register-based study included all 302,789 workers from transport, rescue and security industries in 2001-2015 and 2,230,877 individuals aged 18-64 years from a total sample of the economically active population for comparison. We used Cox models to estimate the hazard ratios (HRs) of incident cancers. We categorized site-specific cancers by using population-attributable fraction (PAF) estimates from the previous literature. RESULTS: During an average follow-up of 13.4 years, 22,116 incident cancer cases were recorded in these industries. Compared with the reference population, the age-adjusted cancer incidence with a high PAF was higher among men in seafaring (HR 1.28; 95% CI 1.14-1.43), and land transport (HR 1.32; 95% CI: 1.26-1.37), and among women in seafaring (HR 1.26; 95% CI: 1.01-1.57), land transport (HR 1.21; 95% CI: 1.12-1.32), aviation (HR 1.22; 95% CI: 1.05-1.41), and police force (HR 1.21; 95% CI: 1.04-1.40). Overall, tobacco and physical inactivity were the most significant risk factors of cancer. CONCLUSIONS: Regardless of considerable disparities in incident cancer attributable to modifiable risk factors across industries, the total incident cancer rate was elevated in all industries in both sexes.