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European Urology Aug 2023Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external... (Review)
Review
CONTEXT
Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention.
OBJECTIVE
To perform an up-to-date systematic review of BC's epidemiology and external risk factors.
EVIDENCE ACQUISITION
Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018.
EVIDENCE SYNTHESIS
Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy.
CONCLUSIONS
We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention.
PATIENT SUMMARY
Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.
Topics: Humans; Vehicle Emissions; Risk Factors; Urinary Bladder Neoplasms; Smoking; Tobacco Smoking; Occupational Exposure
PubMed: 37198015
DOI: 10.1016/j.eururo.2023.03.029 -
JAMA Jul 2023Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal.
OBJECTIVE
To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo.
DESIGN, SETTING, AND PARTICIPANTS
A 3-group, double-blind, placebo-controlled, randomized trial (ORCA-2) compared 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo, with follow-up to 24 weeks, among 810 adults who smoked cigarettes daily and wanted to quit. It was conducted at 17 US sites from October 2020 to December 2021.
INTERVENTIONS
Participants were randomized (1:1:1) to cytisinicline, 3 mg, 3 times daily for 12 weeks (n = 270); cytisinicline, 3 mg, 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks (n = 269); or placebo 3 times daily for 12 weeks (n = 271). All participants received behavioral support.
MAIN OUTCOMES AND MEASURES
Biochemically verified continuous smoking abstinence for the last 4 weeks of cytisinicline treatment vs placebo (primary) and from end of treatment to 24 weeks (secondary).
RESULTS
Of 810 randomized participants (mean age, 52.5 years; 54.6% female; mean of 19.4 cigarettes smoked daily), 618 (76.3%) completed the trial. For the 6-week course of cytisinicline vs placebo, continuous abstinence rates were 25.3% vs 4.4% during weeks 3 to 6 (odds ratio [OR], 8.0 [95% CI, 3.9-16.3]; P < .001) and 8.9% vs 2.6% during weeks 3 to 24 (OR, 3.7 [95% CI, 1.5-10.2]; P = .002). For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; P < .001) and 21.1% vs 4.8% during weeks 9 to 24 (OR, 5.3 [95% CI, 2.8-11.1]; P < .001). Nausea, abnormal dreams, and insomnia occurred in less than 10% of each group. Sixteen participants (2.9%) discontinued cytisinicline due to an adverse event. No drug-related serious adverse events occurred.
CONCLUSIONS AND RELEVANCE
Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering new nicotine dependence treatment options.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04576949.
Topics: Humans; Middle Aged; Alkaloids; Azocines; Duration of Therapy; Quinolizines; Smoking Cessation; Tobacco Use Disorder; Smoking Cessation Agents; Double-Blind Method; Treatment Outcome; Male; Female; Quinolizidine Alkaloids; Nicotine; Receptors, Nicotinic; Cigarette Smoking
PubMed: 37432430
DOI: 10.1001/jama.2023.10042 -
JAMA Jun 2023Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients... (Observational Study)
Observational Study
IMPORTANCE
Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown.
OBJECTIVE
To determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality.
DESIGN, SETTING, AND PARTICIPANTS
Observational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022.
EXPOSURES
Mucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease.
RESULTS
Among the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively.
CONCLUSIONS AND RELEVANCE
In participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.
Topics: Female; Humans; Male; Middle Aged; Airway Obstruction; Forced Expiratory Volume; Lung; Mucus; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies; Tomography, X-Ray Computed; Aged; Aged, 80 and over; Cigarette Smoking
PubMed: 37210745
DOI: 10.1001/jama.2023.2065 -
Clinical Oral Investigations Sep 2023This systematic review and meta-analysis examined the effects of electronic cigarettes on periodontal health compared to conventional cigarette smoke and a non-smoking... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review and meta-analysis examined the effects of electronic cigarettes on periodontal health compared to conventional cigarette smoke and a non-smoking population.
MATERIALS AND METHODS
MEDLINE, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were screened for literature. Eligibility criteria included clinical studies published between 2006 and 2022 that compare e-cigarettes and conventional cigarettes on periodontal health (bleeding on probing (BoP), plaque index (PI), probing depth (PD), attachment loss (AL), marginal bone loss (MBL), tooth loss, molecular inflammation markers, salivary flow rate). Meta-regression analysis was used to examine the influence of moderator variables.
RESULTS
Sixteen studies were found to be eligible for qualitative synthesis. Individual analyses showed that cigarette smokers had significantly higher PI, PD, AL, and MBL and increased concentrations of proinflammatory mediators than e-cigarette users and non-smokers. Meta-analysis revealed a 0.33-fold lower chance for BoP in e-cigarette users compared to smokers (p = 0.03), whereby meta-regression failed to detect any effects regarding the age of users and frequency of smoking. A 0.01-fold decreased chance for positive BoP in e-cigarette users compared with non-smokers was seen (p < 0.01).
CONCLUSIONS
The current findings suggest that that e-cigarette use might be considered a healthier alternative to cigarette smoking concerning periodontal health. Even so, harmful effects of electronic nicotine delivery system (ENDS) usage on periodontal health were seen as well. However, a definitive decision on this research question remains elusive due to the absence of randomized controlled trials.
CLINICAL RELEVANCE
Electronic cigarettes, marketed as a safer alternative to traditional cigarettes, are becoming increasingly popular. Evidence on the use of electronic cigarettes as a cessation aid and its beneficial impact compared to cigarette smoke remains inconclusive, so the analysis conducted in this review addresses a recent question of high clinical relevance.
Topics: Humans; Electronic Nicotine Delivery Systems; Cigarette Smoking; Tobacco Products; Smokers; Electronics
PubMed: 37526741
DOI: 10.1007/s00784-023-05162-4 -
European Journal of Public Health Aug 2023
Topics: Humans; Europe; Tobacco Use; Tobacco Products
PubMed: 37279360
DOI: 10.1093/eurpub/ckad068 -
JAMA Oncology Oct 2023Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and...
The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.
IMPORTANCE
Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.
OBJECTIVE
To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.
EVIDENCE REVIEW
The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.
FINDINGS
In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.
CONCLUSIONS AND RELEVANCE
In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Topics: Adult; Female; Humans; Male; Global Burden of Disease; Global Health; Incidence; Lip; Pharyngeal Neoplasms; Quality-Adjusted Life Years; Risk Factors; Tobacco Use
PubMed: 37676656
DOI: 10.1001/jamaoncol.2023.2960 -
Adicciones Dec 2023
Topics: Humans; Adolescent; Cannabis; Smoking; Marijuana Smoking; Ethanol; Alcohol Drinking; Tobacco Use
PubMed: 38224185
DOI: 10.20882/adicciones.2035 -
British Journal of Cancer Oct 2023Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood.
BACKGROUND
Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood.
METHODS
We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship. Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication.
RESULTS
Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses. Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking. Genetically predicted methylation at CpG site cg17823346 [ZMIZ1] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk. Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ZMIZ1] as well as cg02149899 and CRC risk.
DISCUSSION
Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk.
Topics: Humans; Smoking; DNA Methylation; Prospective Studies; Colorectal Neoplasms; Tobacco Smoking; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37608097
DOI: 10.1038/s41416-023-02397-6 -
The Lancet. Global Health Jun 2023Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have...
BACKGROUND
Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have adopted policies beyond the WHO Framework Convention on Tobacco Control, which has been instrumental in reducing smoking prevalence. The impact of these policies (within and outside the Framework Convention on Tobacco Control) on smokeless tobacco use remains unclear. We aimed to systematically review policies that are relevant to smokeless tobacco and its context and investigate their impact on smokeless tobacco use.
METHODS
In this systematic review, we searched 11 electronic databases and grey literature between Jan 1, 2005, and Sept 20, 2021, in English and key south Asian languages, to summarise smokeless tobacco policies and their impact. Inclusion criteria were all types of studies on smokeless tobacco users that mentioned any smokeless tobacco relevant policies since 2005, except systematic reviews. Policies issued by organisations or private institutions were excluded as well as studies on e-cigarettes and Electronic Nicotine Delivery System except where harm reduction or switching were evaluated as a tobacco cessation strategy. Two reviewers independently screened articles, and data were extracted after standardisation. Quality of studies was appraised using the Effective Public Health Practice Project's Quality Assessment Tool. Outcomes for impact assessment included smokeless tobacco prevalence, uptake, cessation, and health effects. Due to substantial heterogeneity in the descriptions of policies and outcomes, data were descriptively and narratively synthesised. This systematic review was registered in PROSPERO (CRD42020191946).
FINDINGS
14 317 records were identified, of which 252 eligible studies were included as describing smokeless tobacco policies. 57 countries had policies targeting smokeless tobacco, of which 17 had policies outside the Framework Convention on Tobacco Control for smokeless tobacco (eg, spitting bans). 18 studies evaluated the impact, which were of variable quality (six strong, seven moderate, and five weak) and reported mainly on prevalence of smokeless tobacco use. The body of work evaluating policy initiatives based on the Framework Convention on Tobacco Control found that these initiatives were associated with reductions in smokeless tobacco prevalence of between 4·4% and 30·3% for taxation and 22·2% and 70·9% for multifaceted policies. Two studies evaluating the non-Framework policy of sales bans reported significant reductions in smokeless tobacco sale (6·4%) and use (combined sex 17·6%); one study, however, reported an increased trend in smokeless tobacco use in the youth after a total sales ban, likely due to cross-border smuggling. The one study reporting on cessation found a 13·3% increase in quit attempts in individuals exposed (47·5%) to Framework Convention on Tobacco Control policy: education, communication, training, and public awareness, compared with non-exposed (34·2%).
INTERPRETATION
Many countries have implemented smokeless tobacco control policies, including those that extend beyond the Framework Convention on Tobacco Control. The available evidence suggests that taxation and multifaceted policy initiatives are associated with meaningful reductions in smokeless tobacco use.
FUNDING
UK National Institute for Health Research.
Topics: Adolescent; Humans; Tobacco, Smokeless; Tobacco Control; Electronic Nicotine Delivery Systems; Smoking; Policy
PubMed: 37202029
DOI: 10.1016/S2214-109X(23)00205-X -
The European Respiratory Journal Nov 2023COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans,...
BACKGROUND
COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the human gene correlate with an increased susceptibility to develop COPD.
METHODS
We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs. The development of emphysema and PH was investigated in and (FGF receptor 2b) mice upon chronic exposure to cigarette smoke. In addition, we overexpressed FGF10 in mice following elastase- or cigarette smoke-induced emphysema and pulmonary hypertension (PH).
RESULTS
We found impaired FGF10 expression in human lung alveolar walls and in primary interstitial COPD lung fibroblasts. In contrast, FGF10 expression was increased in large pulmonary vessels in COPD lungs. Consequently, we identified impaired FGF10 signalling in alveolar walls as an integral part of the pathomechanism that leads to emphysema and PH development: mice with impaired FGF10 signalling ( and ) spontaneously developed lung emphysema, PH and other typical pathomechanistic features that generally arise in response to cigarette smoke exposure.
CONCLUSION
In a therapeutic approach, FGF10 overexpression successfully restored lung alveolar and vascular structure in mice with established cigarette smoke- and elastase-induced emphysema and PH. FGF10 treatment triggered an initial increase in the number of alveolar type 2 cells that gradually returned to the basal level when the FGF10-mediated repair process progressed. Therefore, the application of recombinant FGF10 or stimulation of the downstream signalling cascade might represent a novel therapeutic strategy in the future.
Topics: Humans; Animals; Mice; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Pancreatic Elastase; Fibroblast Growth Factor 10; Receptor, Fibroblast Growth Factor, Type 2; Cigarette Smoking; Pulmonary Emphysema; Lung; Emphysema; Mice, Inbred C57BL
PubMed: 37884305
DOI: 10.1183/13993003.01606-2022