Squamous Cell Carcinoma in Never Smokers: An Insight into SMARCB1 Loss.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting 85% of cases. Among NSCLCs, squamous cell carcinoma (SqCC) is strongly associated with smoking. However, lung cancer in never smokers (LCINS) represents approximately 25% of lung cancer cases globally and shows increasing incidence, particularly in East Asia. LCINS-SqCC is less well-characterized, especially regarding its genomic alterations and their impact on clinical outcomes. We conducted a retrospective analysis over a 20-year period (July 2003-July 2023) at two major tertiary centers in the UK. The cohort included 59 patients with LCINS-SqCC who underwent radical surgical resection. Data collected included demographic information, comorbidities, histopathological details, and outcome metrics such as disease-free and overall survival. Molecular sequencing of tumor specimens was performed to identify genomic aberrations. The cohort had a median age of 71 years (IQR 62-77) and a median BMI of 25.4 (IQR 22.8-27.8), with a slight male predominance (53%). The majority of patients (93%) had a preoperative MRC of 1-2. Recurrent disease was observed in 23 patients (39%), and 32 patients (54%) had died at a median follow-up of 3 years. Median disease-free survival was 545 days (IQR 132-1496), and overall survival was 888 days (IQR 443-2071). Preoperative creatinine levels were higher in patients who experienced recurrence (p = 0.037). Molecular analysis identified biallelic SMARCB1 loss in two younger patients, associated with rapid disease progression despite R0 resection. These patients' tumors were PDL1-negative, TTF-1-negative, and positive for cytokeratin, CD56, and p40. SMARCB1-deficient SqCC in never smokers represents a highly aggressive variant with poor disease-free survival, highlighting the importance of integrating advanced molecular diagnostics in clinical practice. This study underscores the necessity for personalized treatment strategies, including targeted therapies such as EZH2 inhibitors and immune checkpoint blockade, to address the unique molecular pathways in SMARCB1-deficient cancers. Further clinical trials are essential to optimize therapeutic approaches for this challenging subgroup of lung cancer.

Smoking paradox in coronary function and structure of acute ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

BACKGROUND: The Smoking paradox has generated inconsistent findings concerning the clinical prognosis of acute ST-segment elevation myocardial infarction (STEMI) patients, while providing limited insights into coronary anatomy and function which are crucial prognostic factors. Therefore, this study aimed to further investigate the existence of smoking paradox in coronary anatomy and function. METHODS: This study divided STEMI patients into smokers and non-smokers. Quantitative coronary angiography, angiography­derived microcirculatory resistance (AMR) and quantitative flow ratio (QFR) were utilized to analyze coronary anatomy and function. These parameters were compared using multivariable analysis and propensity score matching. The clinical outcomes were evaluated using Kaplan-Meier curve and Cox regression. RESULTS: The study included 1258 patients, with 730 in non-smoker group and 528 in smoker group. Smokers were significantly younger, predominantly male, and had fewer comorbidities. Without adjusting for confounders, smokers exhibited larger lumen diameter [2.03(1.45-2.57) vs. 1.90(1.37-2.49), P = 0.033] and lower AMR [244(212-288) vs. 260(218-301), P = 0.006]. After matching and multivariate adjustment, smokers exhibited inversely smaller lumen diameter [1.97(1.38-2.50) vs. 2.15(1.63-2.60), P = 0.002] and higher incidence of coronary microvascular dysfunction [233(53.9%) vs. 190(43.6%), P = 0.002], but showed similar AMR and clinical outcomes compared to non-smokers. There was no difference in QFR between two groups. CONCLUSION: Smoking among STEMI patients undergoing pPCI was associated with smaller lumen diameter and higher occurrence of coronary microvascular dysfunction, although it had no further impact on clinical prognosis. The smoking paradox observed in coronary anatomy or function may be explained by younger age, gender, and lower prevalence of comorbidities.

Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population.

Background Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population. Purpose To study the prevalence and size distribution of solid lung nodules by age and sex in a nonsmoking population. Materials and Methods Participants included nonsmokers (never or former smokers) from the population-based Imaging in Lifelines study conducted in the Northern Netherlands. Participants (age ≥ 45 years) with completed lung function tests underwent chest low-dose CT scans. Seven trained readers registered the presence and size of solid lung nodules measuring 30 mm3 or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm3), clinically relevant lung nodules (≥100 mm3), and actionable nodules (≥300 mm3) are presented by 5-year categories and by sex. Results A total of 10 431 participants (median age, 60.4 years [IQR, 53.8-70.8 years]; 56.6% [n = 5908] female participants; 46.1% [n = 4812] never smokers and 53.9% [n = 5619] former smokers) were included. Of these, 42.0% (n = 4377) had at least one lung nodule (male participants, 47.5% [2149 of 4523]; female participants, 37.7% [2228 of 5908]). The prevalence of lung nodules increased from age 45-49.9 years (male participants, 39.4% [219 of 556]; female participants, 27.7% [236 of 851]) to age 80 years or older (male participants, 60.7% [246 of 405]; female participants, 50.9% [163 of 320]). Clinically relevant lung nodules were present in 11.1% (1155 of 10 431) of participants, with prevalence increasing with age (male participants, 8.5%-24.4%; female participants, 3.7%-15.6%), whereas actionable nodules were present in 1.1%-6.4% of male participants and 0.6%-4.9% of female participants. Conclusion Lung nodules were present in a substantial proportion of all age groups in the Northern European nonsmoking population, with slightly higher prevalence for male participants than female participants. © RSNA, 2024 Supplemental material is available for this article.

Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers.

BACKGROUND: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. METHODS: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. RESULTS: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. CONCLUSIONS: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.

The genomic landscape of lung cancer in never-smokers from the Women's Health Initiative.

Over 200,000 individuals are diagnosed with lung cancer in the United States every year, with a growing proportion of cases, especially lung adenocarcinoma, occurring in individuals who have never smoked. Women over the age of 50 comprise the largest affected demographic. To understand the genomic drivers of lung adenocarcinoma and therapeutic response in this population, we performed whole genome and/or whole exome sequencing on 73 matched lung tumor/normal pairs from postmenopausal women who participated in the Women's Health Initiative. Somatic copy number alterations showed little variation by smoking status, suggesting that aneuploidy may be a general characteristic of lung cancer regardless of smoke exposure. Similarly, clock-like and APOBEC mutation signatures were prevalent but did not differ in tumors from smokers and never-smokers. However, mutations in both EGFR and KRAS showed unique allelic differences determined by smoking status that are known to alter tumor response to targeted therapy. Mutations in the MYC-network member MGA were more prevalent in tumors from smokers. Fusion events in ALK, RET, and ROS1 were absent, likely due to age-related differences in fusion prevalence. Our work underscores the profound effect of smoking status, age, and sex on the tumor mutational landscape and identifies areas of unmet medical need.

Dietary Patterns among Smokers and Non-Smokers: Findings from the National Health and Nutritional Examination Survey (NHANES) 2017-2018.

Diet behavior and nutrition are critical for maintaining health and improving quality of life. Cigarette smoking remains the leading cause of preventable death in the United States. Poor dietary choices, such as excessively frequenting restaurants, consuming ready-to-eat foods from grocery stores, and ingesting ultra-processed foods (like frozen meals and pizzas), can adversely impact health. Despite this, research comparing dietary behaviors between smokers and non-smokers is limited. Using data from the National Health and Nutritional Examination Survey 2017-2018, we analyzed diet behavior based on smoking status. Our findings reveal that smokers had a significant increase (90%) in the frequency of consuming frozen meals/pizzas in the past 30 days compared to non-smokers (coefficient: 1.9; 95% CI: 1.4, 2.6; p-value < 0.001). Additionally, over 70% of participants, regardless of their smoking status, were unaware of MyPlate, a nutritional guide created by the United States Department of Agriculture (USDA) to encourage Americans to make healthier food choices. There is an urgent need to increase public awareness of MyPlate and promote a better understanding of healthy dietary behaviors.

Facing an un-met need in lung cancer screening: The never smokers.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide and the second most common cancer in both men and women. In addition to smoking, other risk factors, such as environmental tobacco smoke, air pollution, biomass combustion, radon gas, occupational exposure, lung disease, family history of cancer, geographic variability, and genetic factors, play an essential role in developing LC. Current screening guidelines and eligibility criteria have limited efficacy in identifying LC cases (50 %), as most screening programs primarily target subjects with a smoking history as the leading risk factor. Implementing LC screening programs in people who have never smoked (PNS) can significantly impact cancer-specific survival and early disease detection. However, the available evidence regarding the feasibility and effectiveness of such programs is limited. Therefore, further research on LC screening in PNS is warranted to determine the necessary techniques for accurately identifying individuals who should be included in screening programs.

Clinical effects of omega-3 fatty acids supplementation in the periodontal treatment of smokers and non-smokers with periodontitis: a retrospective study.

OBJECTIVES: Omega-3 supplementation as an adjunct to nonsurgical periodontal treatment has been reported to have a positive effect on healing in periodontitis patients. However, there is a lack of information on the effects of periodontal healing in smokers with periodontitis. The aim of this retrospective study was to investigate the effect of omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment on clinical parameters in smoker and non-smoker periodontitis patients. METHODS: This study included a total of 80 periodontitis patients, 40 non-smokers and 40 smokers who were systemically healthy. In this study, patients were divided into 4 groups as follows: Group 1 (Subgingival instrumentation (SI) alone/nonsmoker), Group 2 (SI alone/smoker), Group 3 (SI + Omega-3/nonsmoker) and Group 4 (SI + Omega-3/smoker). Group 3 and 4 consumed 1320 mg Omega-3 capsule (640 mg EPA, 480 mg DHA) once a day for 3 months. Probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP %) were recorded at baseline, 1 month and 3 months after treatment. RESULTS: Significant improvement of all clinical parameters at 1 and 3 months was observed in all groups. Whole mouth CAL, GI and BOP% were significantly reduced in group 4 compared to group 2 at 1 and 3 months postoperatively (p < 0.05). For moderately deep pockets (4-6 mm) and deep pockets (7 mm≤), PD and CAL reductions were significantly greater in groups taking omega - 3 (group 3 and group 4) compared to groups not taking omega-3 (group 1 and group 2) between baseline and 1 month and between baseline and 3 months (p ˂ 0.05). CONCLUSION: Omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment provided significant benefit in the improvement of clinical parameters (especially for CAL and PD) in the short term in smokers and non-smokers with periodontitis. CLINICAL RELEVANCE: Nonsurgical periodontal treatment with omega-3 supplementation resulted in significant improvements in clinical parameters in smokers and non-smokers with periodontitis.

Impact of Smoking and Chronic Obstructive Pulmonary Disease on All-Cause, Respiratory, and Cardio-Cerebrovascular Mortality.

Introduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality. Methods: The study included participants aged ≥40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality. Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23-2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20-3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98-1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85-3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15-4.40). Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.

Sex difference in the associations among secondhand smoke with metabolic syndrome in non-smokers in a large Taiwanese population follow-up study.

Close associations among secondhand smoke (SHS) and metabolic syndrome (MetS) and its components have been demonstrated, however sex differences in these associations remain unclear. We collected 121,364 participants from the Taiwan Biobank, and excluded those with smoking history, the remaining 88,297 participants (male: 18,595; female: 69,702; mean age 50.1 ± 11.0 years) were included. SHS exposure was evaluated based on self-reported questionnaires. SHS was associated with MetS (odds ratio [OR], 1.268, p < 0.001 for males vs. 1.180, p < 0.001 for females), abdominal obesity (OR, 1.234, p < 0.001 for males vs. 1.199, p < 0.001 for females), low high-density lipoprotein cholesterol (OR, 1.183, p = 0.008 for males vs. 1.094, p = 0.011 for females), hyperglycemia (OR, 1.286, p < 0.001 for males vs. 1.234, p < 0.001 for females), but not with hypertriglyceridemia. SHS was associated with high blood pressure (BP) (OR, 1.278, p < 0.001) only in males, but not in females. Furthermore, significant interactions were found between sex x SHS on MetS (p = 0.023), abdominal obesity (p = 0.032), and elevated BP (p < 0.001). Moreover, the participants who were exposed to SHS for ≥1 hour per week were associated with a higher risk (OR = 1.316, p = 0.001 in males vs. OR = 1.220, p < 0.001 in females) of MetS compared to those with no exposure. These results showed an association between SHS and a high OR for MetS in both the males and females. Furthermore, sex differences were identified in the associations between SHS and MetS and its components, and SHS was more closely related to MetS, abdominal obesity, and high BP in males than in females.

Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.

PURPOSE: Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT). EXPERIMENTAL DESIGN: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening. RESULTS: Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts. CONCLUSIONS: Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers.

Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers.

BACKGROUND AND PURPOSE: The association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. MATERIALS AND METHODS: A prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. RESULTS: Among the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64-15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09-5.90]; p = 0.03) were significantly associated with severe acute toxicity. CONCLUSION: This study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

Endoscopic reflux esophagitis and decline in pulmonary function in nonsmokers: A retrospective cohort study.

BACKGROUND: The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an important clinical issue. METHODS: In this single-center retrospective cohort study, a medical examination database at Kameda Medical Center Makuhari was employed to identify nonsmokers who underwent upper gastrointestinal endoscopy and spirometry in 2010 and were followed up in 2015. Gastroenterologists carefully double-checked the diagnosis of reflux esophagitis. Multiple linear regression analyses were performed to compare the decline in the percentage of predicted vital capacity (%VC), forced vital capacity (%FVC), and forced expiratory volume in 1 s (%FEV1) between participants with reflux esophagitis and those without. Furthermore, using multivariable logistic regression analyses, we evaluated the factors associated with rapid decline in %VC, %FVC, and %FEV1, which is defined as a decrease of >10% in each parameter over the 5-year observation period. RESULTS: We identified 3098 eligible subjects, including 72 and 44 participants who had a Los Angeles classification grade A and B-C (severe) reflux esophagitis in 2010, respectively. The decline in %VC was significantly larger in the participants with severe reflux esophagitis than in the control subjects (standardized coefficient, -0.037; 95% confidence interval, -0.071 to -0.004). Moreover, reflux esophagitis was significantly associated with a rapid decline in %VC and %FVC but not in %FEV1 (P for trend: 0.009, 0.009, and 0.276, respectively). CONCLUSIONS: Severe reflux esophagitis among nonsmokers had clinical disadvantages in terms of a decline in %VC.

A systematic review and meta-analysis of the association between e-cigarette use among non-tobacco users and initiating smoking of combustible cigarettes.

INTRODUCTION: The rapid increase in e-cigarette use over the past decade has triggered an important public health question on the potential association between e-cigarette use and combustible cigarette smoking. Following AMSTAR 2 and PRISMA guidelines, this evidence synthesis sought to identify and characterize any associations between e-cigarette use among individuals not smoking cigarettes and initiation of cigarette smoking. METHODS: The protocol was registered on September 24, 2018 (PROSPERO 2018 CRD42018108540). Three databases were queried from January 01, 2007 to April 26, 2023. Search results were screened using the PICOS review method. RESULTS: Among 55 included studies (40 "good" and 15 "fair"; evidence grade: "high") that adjusted for gender, age, and race/ethnicity between groups, generally, there was a significant association between non-regular e-cigarette use and initiation of cigarette smoking, further supported by the meta-analytic results (AOR 3.71; 95% CI 2.86-4.81). However, smoking initiation was most often measured as ever/current cigarette smoking. Two studies (quality: 2 "good") evaluated progression to regular cigarette smoking among individuals with regular use of e-cigarettes, and generally found no significant associations. One study ("good") evaluated smoking initiation among individuals with regular use of e-cigarettes, finding an increasing probability of ever smoking cigarettes with increased e-cigarette use. Twelve studies (10 "good" and two "fair") examining progression to regular smoking among individuals with non-regular use of e-cigarettes reported inconsistent findings. CONCLUSIONS: Numerous methodological flaws in the body of literature limit the generalizability of these results to all individuals who are not smoking cigarettes with few studies measuring established/regular use/smoking of e-cigarettes and cigarettes. Further, studies did not control adequately for specific confounding variables representing common liabilities between e-cigarette use and cigarette smoking, nor did they account for sufficient follow-up durations. Collectively, these flaws limit the generalizability of findings to the question of an association between e-cigarette use and cigarette smoking initiation.

Evaluation of Oral Mucosal Lesions in Iranian Smokers and Non-smokers.

BACKGROUND: Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking. AIMS: Considering the high prevalence rate of tobacco-associated problems in the oral cavity and few studies on the Iranian population regarding the effects of smoking on the oral cavity, this study aimed to evaluate the relationship between smoking and oral lesions in the Iranian population. MATERIALS AND METHODS: Observational study. In this observational study, the oral cavities of 200 participants (smokers = 100 and non-smokers = 100) were examined by a trained dental student under the supervision of an oral and maxillofacial medicine expert, and the presence of coated tongue, leukoedema, leukoplakia, smoker's palate, smoker's melanosis, erythroplakia, frictional hyperkeratosis, acute pseudomembranous candidiasis, and erythematous candidiasis were recorded. Xerostomia was evaluated based on participants' self-reporting through a questionnaire. All data were analyzed using T-test, Chi-square test, odd ratio, 95% confidence interval, Fisher's exact test, and Spearman's rank correlation coefficient. RESULTS: The results of this study showed smoking is significantly associated with an increased risk of coated tongue (OR: 1.80, 95% CI: 1.32-3.54, P = 0.005), smoker's melanosis (OR: 6.176, 95% CI: 3.28-11.62, P = 0.00002), and frictional hyperkeratosis (OR: 1.33, 95% CI: 0.68-2.60, P = 0.005). However, no significant association was observed between smoking and leukoedema (OR: 1, 95% CI: 0.51-1.94, P = 1). None of the participants presented smoker's palate, erythroplakia, and candidiasis. CONCLUSIONS: This study's results showed that smokers exhibited a greater chance of developing oral lesions compared to non-smokers.

Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study.

BACKGROUND: To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. METHODS: Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1ß, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. RESULTS: Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively). CONCLUSION: Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.

Comparison of smokers' mortality with non-smokers following out-of-hospital cardiac arrests: a systematic review and meta-analysis.

OBJECTIVE: Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. METHODS: The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. RESULTS: Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61-0.96; P < 0.05). Egger's test showed no publication bias in the relationship between smoking and mortality after OHCAs. CONCLUSIONS: After experiencing OHCAs, smokers had lower mortality than non-smokers. However, due to the lack of data, this 'smoker's paradox' still needs other covariate effects and further studies to be considered valid.