Never Smokers Research Articles

Uncovering molecular features driving lung adenocarcinoma heterogeneity in patients who formerly smoked

BackgroundAn increasing proportion of lung adenocarcinoma (LUAD) occurs in patients even after they have stopped smoking. Here, we aimed to determine whether tobacco smoking induced changes across LUADs from patients who formerly smoked correspond to different biological and clinical factors.MethodsRandom forest models (RFs) were trained utilizing a smoking associated signature developed from differentially expressed genes between LUAD patients who had never smoked (NS) or currently smoked (CS) from TCGA (n = 193) and BCCA (n = 69) cohorts. The RFs were subsequently applied to 299 and 131 formerly smoking patients from TCGA and MSKCC cohorts, respectively. FS were RF-classified as either CS-like or NS-like and associations with patient characteristics, biological features, and clinical outcomes were determined.ResultsWe elucidated a 123 gene signature that robustly classified NS and CS in both RNA-seq (AUC = 0.85) and microarray (AUC = 0.92) validation test sets. The RF classified 213 patients who had formerly smoked as CS-like and 86 as NS-like from the TCGA cohort. CS-like and NS-like status in formerly smoking patients correlated poorly with patient characteristics but had substantially different biological features including tumor mutational burden, number of mutations, mutagenic signatures and immune cell populations. NS-like formerly smoking patients had 17.5 months and 18.6 months longer overall survival than CS-like patients from the TCGA and MSKCC cohorts, respectively.ConclusionsPatients who had formerly smoked with LUAD harbor heterogeneous tumor biology. These patients can be divided by smoking induced gene expression to inform prognosis and underlying biological characteristics for treatment selection.

Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data

BackgroundObservational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior—specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD.MethodsFirstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared “pleiotropic SNPs” between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD.ResultsConsistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel “pleiotropic SNPs” (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk.ConclusionWe identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.

Prospective “common arm” comparison of US SWOG S0424 and Japanese JME studies in early-stage non-small cell lung cancer (NSCLC): Survival differences in the context of race, gender and smoking.

8036 Background: In NSCLC, overall frequencies and subtype distribution of EGFR and KRAS mutations differ significantly between Japanese and US patients. In many NSCLC clinical trials, Japanese patient outcomes appear superior to those in western populations. Since 2009, SWOG and Japanese investigators have used the “Common Arm” analytic method to interpret globally-conducted lung cancer clinical trials, providing a mechanism for direct patient-level comparisons in matching trials performed in the US and Japan. S0424 and the Japanese Molecular Epidemiology Study (JME) are large prospective molecular epidemiology studies conducted by SWOG and Japanese investigators and prospectively planned for “Common Arm” analysis. We investigated the effects of mutation distribution on overall survival in early stage NSCLC using data from JME and S0424. Methods: Both studies were designed to accrue representative proportions of ever-smokers (ES) versus never-smokers (NS) in male and female cohorts. Accrual to S0424 was completed in 2011 with 981 pts enrolled (Cheng et al JNCI 2018); JME was completed in 2012 with 957 pts (Kawaguchi et al JCO 2016). A comprehensive questionnaire was used to capture lifestyle, carcinogenic exposures, demographic and clinical data. Five years of follow-up was completed for each study. The association between baseline characteristics and mutation types were analyzed using multivariate logistic regression. The product-limit method was used to estimate overall survival and Cox regression models were fit to estimate hazard ratios. p-values were two-sided and p-values < 0.05 were considered significant. Results: Evaluable pts: 876 for JME; 957 for S0424. Demographic distribution: S0424: 87% Caucasian, 5% Asian, 4% Black; JME: 100% Japanese. As expected, multivariate logistic models adjusting for age, smoking status, gender and BMI showed JME were more likely to have EGFR mutations (p < 0.0001) and less likely to have KRAS mutations (p = 0.02). EGFR mutations were associated with never-smoking (p < 0.0001) and female sex (p < 0.0001); KRAS was associated with smoking (p < 0.0001). Adjusting for age, smoking status and gender, overall survival was greater in JME patients (p < 0.0001,HR = 0.49 (95% CI: 0.40-0.60)). In the subset of pts without an EGFR mutation, survival still favored the JME cohort (p < 0.001, HR = 0.68 (0.53-0.86). Conclusions: Patient level comparison of US (SWOG) and Japanese (JME) patients with early stage NSCLC demonstrated longer survival in Japanese patients even after adjusting for EGFR mutation frequency. Identification of factors that contribute to this finding are under investigation. Female sex remained a risk factor for EGFR mutation-driven disease in both populations. This analysis forms the basis for applying this population-related model in other clinical settings.

Smoking habits and osteoporosis in community-dwelling men subjected to dual-X-ray absorptiometry: a cross-sectional study.

Active and Environmental Tobacco Smoke (ETS) are a global cause of death. Osteoporosis (Op) is the most common metabolic bone disorder worldwide, impacting on mortality and disability, with high health and welfare costs. Active smoking is a known risk factor for Op, but there is few information regarding Op and ETS in men. The study aim is to evaluate the association between smoking habits and Op in community-dwelling men that have been subjected to Dual-X-ray Absorptiometry and completed a questionnaire about their own and cohabiter's smoking habits. We performed a cross-sectional study based on administrative data. This study is part of the SIMON protocol. The binary logistic regression analysis was used to estimate the role of ETS on the risk of Op, adjusting for age, body mass index (BMI), type 2 diabetes mellitus (T2DM) and eGFR. Four hundred sixteen men were selected and, based on questionnaire replies, 167 were classified as current smokers (CS), 93 as passive smokers (PS) and 156 as never smokers (NS). NS showed a lower prevalence of past fragility fracture, radiological features of osteoporosis and hypovitaminosis D compared to PS and CS (p < 0.05). NS showed a lower prevalence of Op compared to PS and CS, also after correction for age, BMI, T2DM and eGFR (p < 0.05). The study results demonstrate that PS and CS have a higher risk of Op, fragility fractures and vitamin D deficiency compared to NS.

Smoking may increase the usage of antidepressant: evidence from genomic perspective analysis.

This study uses the two-sample Mendelian randomization (TSMR) method to explore the causal relationships between smoking initiation (SMKI), never smoking (NSMK), past tobacco smoking (PTSMK), and the usage of antidepressants (ATD). Single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5E-08) related to SMKI, NSMK, and PTSMK were selected from the genome-wide association study (GWAS) database as instrumental variables (IVs). The main method, inverse variance weighted (IVW), was utilized to investigate the causal relationship. The results demonstrated a positive causal relationship between SMKI and ATD use, where SMKI leads to an increase in ATD use. Conversely, NSMK and PTSMK showed a negative causal relationship with ATD use, meaning that NSMK and PTSMK lead to a reduction in ATD use. Additionally, sensitivity analysis showed that the results of this study were robust and reliable. Using the TSMR method and from a genetic perspective, this study found that SMKI leads to an increase in ATD use, while NSMK and PTSMK reduce ATD use.

Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses

Cigarette smoking is a major preventable cause of morbidity and mortality. While quitting smoking is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor products is a viable harm reduction approach for smokers who would otherwise continue to smoke. A key challenge for the clinical assessment of NCAs is that self-reported product use can be unreliable, compromising the proper evaluation of their risk reduction potential. In this cross-sectional study of 205 healthy volunteers, we combined comprehensive exposure characterization with in-depth multi-omics profiling to compare effects across four study groups: cigarette smokers (CS), e-vapor users (EV), former smokers (FS), and never smokers (NS). Multi-omics analyses included metabolomics, transcriptomics, DNA methylomics, proteomics, and lipidomics. Comparison of the molecular effects between CS and NS recapitulated several previous observations, such as increased inflammatory markers in CS. Generally, FS and EV demonstrated intermediate molecular effects between the NS and CS groups. Stratification of the FS and EV by combustion exposure markers suggested that this position on the spectrum between CS and NS was partially driven by non-compliance/dual use. Overall, this study highlights the importance of in-depth exposure characterization before biological effect characterization for any NCA assessment study.

Progression of atherosclerosis in smokers: a longitudinal nation-wide serial angiography study

Abstract Introduction Smoking is a modifiable risk factor for coronary artery disease (CAD). Cross-sectional studies have shown that prevalence of CAD is higher among smokers as is incidence of myocardial infarction. However, few studies have assessed how smoking affects the incidence of coronary artery plaque progression. Purpose To investigate how CAD progress in smokers. Method All coronary artery segments with &amp;lt;50% luminal stenosis in patients having a first-time coronary angiogram between 1989-2017 were identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and followed until a clinically indicated angiography within 15 years was performed or death or end of follow-up occurred. The patients were divided into cohorts based on smoking status and studied with regard to plaque progression defined as the occurrence of ≥50 luminal stenosis on subsequent coronary angiogram. Results A total of 2,272,518 coronary artery segments in 215,364 patients were included of whom 48.1% were never smokers (NS), 33.4% were previous smokers and 18.5% were active smokers (S). The plaque progression incidence rate (IR) was 2.1 (2.04-2.16) per 1000 segment years (SY) for S, 1.77 (1.73-1.81) per 1000 SY for PS, and 1.33 (1.30-1.36) per 1000 SY for NS. The largest increase in plaque progression IR per 1000 SY in relation to smoking status was the middle right coronary artery (RCA) segment (NS: 1.36 (1.27-1.45), PS: (2.23 (2.08-2.39), S: 3.25 (3.01-3.51)). Kaplan-Meier curves depict increased progression in the RCA among smokers (supplementary picture 1). Discussion: In this nationwide longitudinal coronary angiography study, plaque progression occurred more frequently in smokers and in whom the right coronary artery was more commonly affected by coronary atherosclerosis.Plaque progression in RCA vs LAD

Abstract PO-081: Patterns of immune susceptibility in young, non-smoking, oral cancer patients

Abstract Introduction: Oral squamous cell carcinoma (OSCC) is peculiarly increasing in non-smokers, many of whom are younger than traditional, smoking related OSCC. The cause of this trend is unknown, and it is unclear whether these cancers represent a distinct disease, as compared to smoking-related OSCC. We hypothesize that young non-smokers with OSCC have immunological differences that increase susceptibility to infectious and immunological disease (including cancer) as compared to smokers with OSCC. Therefore, we investigated the incidence of bacterial, viral, and autoimmune illness in young OSCC patients. Methods: We performed a retrospective cohort study at a single tertiary care institution of patients under age 55 diagnosed with OSCC from 2003-2021. Multiple encounters for the same ICD-10 code in the same year were counted as one. Bacterial infections included bacterial pneumonia (ICD-10 J13-J15), cellulitis and lymphangitis (L03), urinary tract infection (N39.0), and post-surgical infection (T81.4). Viral infections included viral pneumonia (J10-J12), skin herpesvirus (A60, A63, B00, B07), infectious mononucleosis (B27), herpes zoster-related infections (B02), HIV (B20), viral hepatitis (B15-19), CMV disease (B25), viral conjunctivitis (B30), and other unclassified viral diseases (B33-34). Autoimmune disease included rheumatoid arthritis (M05), systemic Lupus (M32, L93), psoriasis (L40), inflammatory bowel disease (K50-52), Sjogren disease (M35.0), type 1 diabetes (E10), multiple sclerosis (G35), myasthenia gravis (G70), and autoimmune thyroiditis (E06.3). When patients were known to be deceased, but date of death was unavailable, they were presumed deceased at date of last encounter. Kaplan Meier analysis was used to analyze survival. Poisson regression was used to model the incidence of illness. Results: In total, 749 patients were analyzed; 467 were never smokers (NS) and 282 were current or former smokers (S). In NS, median age (interquartile range) was 47.9 (40.4-51.9) and 267 (57.2%) were male. In S, median age was 49.3 (44.6-52.7) and 208 (73.8%) were male. Five-year OS was 89% (95% confidence interval 86-93%) in NS vs. 89% (85%-93%) in S (p=0.66). The incidence of bacterial infection was 25.9 per 1000 person-years (py) in NS vs. 37.0/1000py in S (p&amp;lt;0.01). The incidence of viral infection was 37.8/1000py in NS vs. 31.4/1000py in S (p=0.14). The incidence of autoimmune disease was 26.7/1000py in NS and 36.0/1000py in S (p=0.02). Conclusions: NS were more likely to be female vs. S. OS was similar between NS and S. The incidence of bacterial infections and autoimmune diseases were significantly higher in S vs. NS, in line with pre-existing evidence that smoking is associated with increased susceptibility to bacterial infection and increased incidence and severity of autoimmune disease. Interestingly, there was a trend towards increased viral infections in NS vs. S, although not statistically significant. In the context of pre-existing evidence showing that smoking increases risk of viral infection, this finding warrants further study. Citation Format: Maxwell Y. Lee, Fred M. Baik, John B. Sunwoo. Patterns of immune susceptibility in young, non-smoking, oral cancer patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-081.

Residual radiation risk disparities across sex and race or ethnic groups for lifetime never-smokers on lunar missions

Missions to the Earth's moon are of scientific and societal interest, however pose the problem of risks of late effects for returning crew persons, most importantly cancer and circulatory diseases. In this paper, we discuss NSCR-2022 model risk estimates for lunar missions for US racial and ethnic groups comparing never-smokers (NS) to US averages for each group and sex. We show that differences within groups between men and women are reduced for NS compared to the average population. Race and ethnic group dependent cancer and circulatory disease risks are reduced by 10% to 40% for NS with the largest decrease for Whites. Circulatory disease risks are changed by less than 10% for NS and in several cases modestly increased due to increased lifespan for NS. Asian-Pacific Islanders (API) and Hispanics NS are at lower risk compared to Whites and Blacks. Differences between groups are narrowed for NS compared to predictions for average populations, however disparities remain especially for Blacks and to a lesser extent Whites compared to API or Hispanic NS groups.

A Functional Genomics Review of Non-Small-Cell Lung Cancer in Never Smokers.

There is currently a dearth of information regarding lung cancer in never smokers (LCINS). Additionally, there is a difference in somatic mutations, tumour mutational burden, and chromosomal aberrations between smokers and never smokers (NS), insinuating a different disease entity in LCINS. A better understanding of actionable driver alterations prevalent in LCINS and the genomic landscape will contribute to identifying new molecular targets of relevance for NS that will drastically improve outcomes. Differences in treatment outcomes between NS and smokers, as well as sexes, with NSCLC suggest unique tumour characteristics. Epidermal growth factor receptor (EGFR) tyrosine kinase mutations and echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) gene rearrangements are more common in NS and have been associated with chemotherapy resistance. Moreover, NS are less likely to benefit from immune mediators including PD-L1. Unravelling the genomic and epigenomic underpinnings of LCINS will aid in the development of not only novel targeted therapies but also more refined approaches. This review encompasses driver genes and pathways involved in the pathogenesis of LCINS and a deeper exploration of the genomic landscape and tumour microenvironment. We highlight the dire need to define the genetic and environmental aspects entailing the development of lung cancer in NS.

Long-term outcomes after lower extremity bypass in the actively smoking claudicant

ObjectiveSmoking is known to increase complications, including poor wound healing, coagulation abnormalities, and cardiac and pulmonary ramifications. Across specialties, elective surgical procedures are commonly denied to active smokers. Given the base population of active smokers with vascular disease, smoking cessation is encouraged but is not required the way it is for elective general surgery procedures. We aim to study the outcomes of elective lower extremity bypass (LEB) in actively smoking claudicants. MethodsWe queried the Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network LEB database from 2003 to 2019. In this database we found 609 (10.0%) never smokers (NS), 3388 (55.3%) former smokers (FS), and 2123 (34.7%) current smokers (CS) who underwent LEB for claudication. We performed two separate propensity score matches without replacement on 36 clinical variables (age, gender, race, ethnicity, obesity, insurance, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, previous coronary artery bypass graft, carotid endarterectomy, major amputation, inflow treatment, preoperative medications and treatment type), one of FS to NS and a second analysis of CS to FS. Primary outcomes included 5-year overall survival (OS), limb salvage (LS), freedom from reintervention (FR), and amputation-free survival (AFS). ResultsPropensity score matches resulted in 497 well-matched pairs of NS and FS. In this analysis we found no difference in terms of OS (HR, 0.93; 95% CI, 0.70-1.24; P = .61), LS (HR, 1.07; 95% CI, 0.63-1.82; P = .80), FR (HR, 0.9; 95% CI,0.71-1.21; P = .59), or AFS (HR, 0.93; 95% CI,0.71-1.22; P = .62). In the second analysis, we had 1451 well-matched pairs of CS and FS. There was no difference in LS (HR, 1.36; 95% CI,0.94-1.97; P = .11) or FR (HR, 1.02; 95% CI,0.88-1.19; P = .76). However, we did find a significant increase in OS (HR, 1.37; 95% CI,1.15-1.64, P <.001) and AFS (HR, 1.38; 95% CI,1.18-1.62; P < .001) in FS compared with CS. ConclusionsClaudicants represent a unique nonemergent vascular patient population that may require LEB. Our study found that FS have better OS and AFS when compared with CS. Additionally, FS mimic nonsmokers at 5-year outcomes for OS, LS, FR, and AFS. Therefore, structured smoking cessation should be a more prominent part of vascular office visits before elective LEB procedures in claudicants.

A Pilot Cross-Sectional Study of Immunological and Microbiome Profiling Reveals Distinct Inflammatory Profiles for Smokers, Electronic Cigarette Users, and Never-Smokers.

Smokers (SM) have increased lung immune cell counts and inflammatory gene expression compared to electronic cigarette (EC) users and never-smokers (NS). The objective of this study is to further assess associations for SM and EC lung microbiomes with immune cell subtypes and inflammatory gene expression in samples obtained by bronchoscopy and bronchoalveolar lavage (n = 28). RNASeq with the CIBERSORT computational algorithm were used to determine immune cell subtypes, along with inflammatory gene expression and microbiome metatranscriptomics. Macrophage subtypes revealed a two-fold increase in M0 (undifferentiated) macrophages for SM and EC users relative to NS, with a concordant decrease in M2 (anti-inflammatory) macrophages. There were 68, 19, and 1 significantly differentially expressed inflammatory genes (DEG) between SM/NS, SM/EC users, and EC users/NS, respectively. CSF-1 and GATA3 expression correlated positively and inversely with M0 and M2 macrophages, respectively. Correlation profiling for DEG showed distinct lung profiles for each participant group. There were three bacteria genera-DEG correlations and three bacteria genera-macrophage subtype correlations. In this pilot study, SM and EC use were associated with an increase in undifferentiated M0 macrophages, but SM differed from EC users and NS for inflammatory gene expression. The data support the hypothesis that SM and EC have toxic lung effects influencing inflammatory responses, but this may not be via changes in the microbiome.

Long-term Outcomes in the Smoking Claudicant After Elective Lower Extremity Bypass

Smoking is known to increase complications, including poor wound healing, coagulation abnormalities, and cardiac and pulmonary ramifications. Across specialties, elective surgical procedures are commonly denied to active smokers. Given the base population of active smokers with vascular disease, smoking cessation is encouraged but is not required the way it is in general surgery. We aim to study the outcomes of elective lower extremity bypass (LEB) in actively smoking claudicants. We queried the Vascular Quality Initiative VISION LEB database from 2003 to 2019. In this database we found 609 (10.0%) never smokers (NS), 3388 (55.3%) former smokers (FS), and 2123 (34.7%) current smokers (CS) who underwent LEB for claudication. We performed two separate propensity score matches without replacement on 25 clinical variables (age, gender, race, ethnicity, treatment setting, obesity, insurance, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, previous coronary artery bypass grafting, carotid endarterectomy, major amputation, inflow treatment, preoperative medications and treatment type), one of FS to NS and a second analysis of CS to FS. Primary outcomes included 5-year overall survival (OS), limb salvage (LS), freedom from target lesion reintervention (FTR) and amputation-free survival (AFS). Propensity score matches resulted in 497 well-matched pairs of NS and FS. In this analysis we found no difference in terms of OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P = .61), LS (HR, 1.08; 95% CI, 0.63-1.82; P = .80), FTR (HR, 0.95; 95% CI, 0.73-1.23; P = .69), or AFS (HR, 0.93; 95% CI, 0.71-1.2; P = .62) (Fig 1). In the second analysis, we had 1451 well-matched pairs of CS and FS. There was no difference in LS (HR, 1.36; 95% CI, 0.94-1.97; P = .10) or FTR (HR, 1.02; 95% CI, 0.87-1.19; P = .85). However, we did find a significant increase in OS (HR, 1.37; 95% CI, 1.15-1.64; P < .001) and AFS (HR, 1.38; 95% CI, 1.18-1.62; P < .001) (Fig 2) in FS compared to CS. Claudicants represent a unique nonemergent vascular patient population who can require LEB. Our study found that former smokers have better overall survival and amputation free survival when compared to current smokers, while former smokers mimic never smokers at 5-year outcomes for OS, LS, FTR, and AFS. Therefore, structured smoking cessation should be a more prominent part of vascular office visits before and after LEB and can even be considered a requirement prior to elective LEB procedures in claudicants.Fig 2Amputation-free survival (AFS) (5 years) for former smokers (FS) and current smokers (CS) after propensity score matching.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Small-area models to assess the geographical distribution of tobacco consumption by sex and age in Spain.

Complete and accurate data on smoking prevalence at a local level would enable health authorities to plan context-dependent smoking interventions. However, national health surveys do not generally provide direct estimates of smoking prevalence by sex and age groups at the subnational level. This study uses a small-area model-based methodology to obtain precise estimations of smoking prevalence by sex, age group and region, from a population-based survey. The areas targeted for analysis consisted of 180 groups based on a combination of sex, age group (15-34, 35-54, 55-64, 65-74, and ≥75 years), and Autonomous Region. Data on tobacco use came from the 2017 Spanish National Health Survey (2017 SNHS). In each of the 180 groups, we estimated the prevalence of smokers (S), ex-smokers (ExS) and never smokers (NS), as well as their coefficients of variation (CV), using a weighted ratio estimator (direct estimator) and a multinomial logistic model with random area effects. When smoking prevalence was estimated using the small-area model, the precision of direct estimates improved; the CV of S and ExS decreased on average by 26%, and those of NS by 25%. The range of S prevalence was 11-46% in men and 4-37% in women, excluding the group aged ≥75 years. This study proposes a methodology for obtaining reliable estimates of smoking prevalence in groups or areas not covered in the survey design. The model applied is a good alternative for enhancing the precision of estimates at a detailed level, at a much lower cost than that involved in conducting large-scale surveys. This method could be easily integrated into routine data processing of population health surveys. Having such estimates directly after completing a health survey would help characterize the tobacco epidemic and/or any other risk factor more precisely.

Early immune pressure initiated by tissue-resident memory Tcells sculpts tumor evolution in non-small cell lung cancer.

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associatedmutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Influence of smoking on disease activity and prognosis of antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study.

Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of autoimmune diseases characterized by inflammation of small blood vessels. Smoking is a potential trigger for such diseases, however, its link with AAV remains controversial. The aim of this study was to analyze the link between AAV and smoking based on clinical characteristics, disease activity, and mortality. This retrospective study included 223 AAV patients. Their smoking status was assessed at diagnosis and they were classified as ever smokers (ESs), including current or past smokers, and never smokers (NSs). Information regarding clinical presentation, the disease activity, immunosuppressive therapy, and survival was collected. The ESs had similar organ involvement to the NSs, except for significantly greater frequency of renal replacement therapy (31% vs 14%; P = 0.003). Median (interquartile range [IQR]) time from symptom onset to diagnosis was significantly shorter in the ESs than the NSs (4 [2-9.5] vs 6 [3-13] months; P = 0.03), with significantly higher mean (SD) value of the Birmingham Vasculitis Activity Score version 3 (19.5 [7.93] vs 17.25 [8.05]; P = 0.04). The ESs were more likely to receive cyclophosphamide therapy (P = 0.03), and had significantly higher morality than the NSs (hazard ratio, 2.89; 95% CI, 1.47-5.72; P = 0.002). There were no significant differences between the current and past smokers. The multivariable Cox proportional regression analysis found ever smoking and male sex to be independent predictors of mortality in AAV patients. Ever smoking is associated with increased AAV activity and more frequent renal replacement therapy and immunosuppressive treatment, resulting in a poorer survival prognosis in AAV patients. Future multicenter studies are required to further characterize the clinical, biological, and prognostic impact of smoking on AAV.

Novel use of chloro-aluminum phthalocyanine assisted photodynamic therapy helps in periimplant healing among smoking patients.

To evaluate the clinical and biochemical peri‑implant parameters using chloro‑aluminum phthalocyanine-(CAP) mediated antimicrobial photodynamic therapy (PDT) as an adjunct to non-surgical mechanical debridement (NSD) in cigarette smokers (CS) and never-smokers (NS) with peri‑implantitis. Thirty-two patients with peri‑implantitis [Group CS - 16 and Group NS - 16] were recruited for the trial. The study participants underwent two therapies: PDT+NSD and NSD alone. The clinical peri‑implant parameters assessed in this clinical trial were bleeding on probing (BP), crestal bone loss (CBL) peri‑implant pocket depth (PD), and peri‑implant plaque scores (PS), respectively. Peri-implant crevicular fluid was sampled and the quantification of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α) was performed using enzyme linked immunosorbent assay (ELISA). BP was significantly reduced at 6 months after PDT+NSD in CS groups. Mean PD significantly reduced after both PDT+NSD and NSD subgroups within both NS and CS groups. Only at 6 months did PDT+NSD showed statistically significantly reduced IL-1β levels in the NS group. TNF-α levels significantly reduced in CS group with PDT+NSD and NSD alone at both 3 months and 6 months follow up. CAP-assisted PDT helped to improve the clinical and cytokine levels after non-surgical peri‑implant mechanical debridement in treating peri‑implantitis patients in smokers.

Neurofunctional alterations of cognitive down-regulation of craving in quitting motivated smokers.

Cognitive down-regulation of craving involves a neural network within the prefrontal cortex. Tobacco use disorder (TUD) and trait impulsivity have been associated with prefrontal cortex impairments and down-regulation deficits. However, general deficits in down-regulation of craving (regarding non-drug-related cues) compared to never-smokers (NS), differential alterations between drug-related and non-drug-related cues, as well as its links to subject characteristics (smoking severity, trait impulsivity) have so far sparsely been investigated in TUD. In this study, 78 subjects (37 TUD & 42 NS) underwent functional magnetic resonance imaging while performing a down-regulation of craving task. Two reward cue-types were presented (drug cues and alternative rewards). Subjects applied down-regulation of craving during a LATER condition and up-regulated their craving during a NOW condition. Subjective craving ratings were assessed after each trial. To evaluate down-regulation of craving, we investigated the LATER versus NOW condition. TUD subjects showed no differences in down-regulation on a behavioral level, neither compared to NS nor between the two reward cue-types. On a neurofunctional level, we found a stronger BOLD response in the middle temporal gyrus in TUD subjects compared to NS in the alternative reward condition. No differences between the two reward cue-types were found within TUD subjects. During down-regulation across both reward cue-types, we identified significant negative associations between activation of control areas and smoking severity. Results neither indicate evidence for the expected general alterations in down-regulation of craving in TUD, compared to NS, nor specific alterations between drug-related and alternative reward cues on a neurofunctional level. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

SummaryBackgroundMitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use.MethodsBronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression. Ingenuity pathway analysis was used for enriched pathways. GEO and TCGA respiratory disease datasets were used to explore the involvement of mtCN-associated signatures.FindingsmtCN was higher in SM than NS, but EC was not statistically different from either. Overall there was a negative association of mtCN with a point mutation in the D-loop but no difference within groups. Positive associations of mtCN with IL-2 and IL-4 were found in EC only. mtCN was significantly associated with 71,487 CpGs and 321 transcripts. 263 CpGs were correlated with nearby transcripts for genes enriched in the immune system. EC-specific mtCN-associated-CpGs and genes were differentially expressed in respiratory diseases compared to controls, including genes involved in cellular movement, inflammation, metabolism, and airway hyperresponsiveness.InterpretationSmoking may elicit a lung toxic effect through mtCN. While the impact of EC is less clear, EC-specific associations of mtCN with nuclear biomarkers suggest exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks.FundingThe National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds.

Assessing Smoking Status and Risk of SARS-CoV-2 Infection: A Machine Learning Approach among Veterans.

The role of smoking in the risk of SARS-CoV-2 infection is unclear. We used a retrospective cohort design to study data from veterans’ Electronic Medical Record to assess the impact of smoking on the risk of SARS-CoV-2 infection. Veterans tested for the SARS-CoV-2 virus from 02/01/2020 to 02/28/2021 were classified as: Never Smokers (NS), Former Smokers (FS), and Current Smokers (CS). We report the adjusted odds ratios (aOR) for potential confounders obtained from a cascade machine learning algorithm. We found a 19.6% positivity rate among 1,176,306 veterans tested for SARS-CoV-2 infection. The positivity proportion among NS (22.0%) was higher compared with FS (19.2%) and CS (11.5%). The adjusted odds of testing positive for CS (aOR:0.51; 95%CI: 0.50, 0.52) and FS (aOR:0.89; 95%CI:0.88, 0.90) were significantly lower compared with NS. Four pre-existing conditions, including dementia, lower respiratory infections, pneumonia, and septic shock, were associated with a higher risk of testing positive, whereas the use of the decongestant drug phenylephrine or having a history of cancer were associated with a lower risk. CS and FS compared with NS had lower risks of testing positive for SARS-CoV-2. These findings highlight our evolving understanding of the role of smoking status on the risk of SARS-CoV-2 infection.