Systemic Lactate Elevation Induced by Tobacco Smoking during Rest and Exercise Is Not Associated with Nicotine.

Lactate is a metabolite produced during anaerobic glycolysis for ATP resynthesis, which accumulates during hypoxia and muscle contraction. Tobacco smoking significantly increases blood lactate. Here we conducted a counter-balanced crossover study to examine whether this effect is associated with inhaling nicotine or burned carbon particles. Fifteen male smokers (aged 23 to 26 years) were randomized into 3 inhalation conditions: tobacco smoking, nicotine vaping, and nicotine-free vaping, conducted two days apart. An electronic thermal evaporator (e-cigarette) was used for vaping. We have observed an increased blood lactate (+62%, main effect: p < 0.01) and a decreased blood glucose (−12%, main effect: p < 0.05) during thermal air inhalations regardless of the content delivered. Exercise-induced lactate accumulation and shuttle run performance were similar for the 3 inhalation conditions. Tobacco smoking slightly increased the resting heart rate above the two vaping conditions (p < 0.05), implicating the role of burned carbon particles on sympathetic stimulation, independent of nicotine and thermal air. The exercise response in the heart rate was similar for the 3 conditions. The results of the study suggest that acute hypoxia was induced by breathing thermal air. This may explain the reciprocal increases in lactate and decreases in glucose. The impaired lung function in oxygen delivery of tobacco smoking is unrelated to nicotine.

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM).

BACKGROUND We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). RESULTS Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). CONCLUSIONS This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.

Immature Circulating SP-B, Bound to HDL, Represents an Early Sign of Smoke-Induced Pathophysiological Alterations.

Cigarette smoking is a major independent risk factor for cardiovascular diseases (CVD). The underlying mechanisms, however, are not clearly understood. Lungs are the primary route of exposure to smoke, with pulmonary cells and surfactant being the first structures directly exposed, resulting in the leakage of the immature proteoform of surfactant protein B (proSP-B). Herein, we evaluated whether proSP-B joined the cargo of high-density lipoprotein (HDL) proteins in healthy young subjects (n = 106) without any CVD risk factor other than smoking, and if HDL-associated proSP-B (HDL-SPB) correlated with pulmonary function parameters, systemic inflammation, and oxidative stress. At univariable analysis, HDL-SPB resulted significantly higher in smokers (2.2-fold, p < 0.001) than in non-smokers. No significant differences have been detected between smokers and non-smokers for inflammation, oxidation variables, and alveolar-capillary diffusion markers. In a multivariable model, HDL-SPB was independently associated with smoking. In conclusion, HDL-SPB is not only a precocious and sensitive index of the acute effects of smoke, but it might be also a potential causal factor in the onset of the vascular damage induced by modified HDL. These findings contribute to the emerging concept that the quality of the HDL proteome, rather than the quantity of particles, plays a central role in CVD risk protection.

Analysis of Active and Passive Tobacco Exposures and Blood Pressure in US Children and Adolescents.

Importance: Hypertension is a leading cause of cardiovascular disease in adults; preclinical associations between hypertension and cardiovascular disease are seen in childhood. Nicotine is a known toxin, but its association with pediatric hypertension is unclear. Objective: To test the hypothesis that tobacco exposure is associated with the presence of elevated blood pressure in US children and adolescents and that this association is dose dependent. Design, Setting, and Participants: This cross-sectional study used data from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative sample of US children and adolescents. Children were eligible if they were aged 8 to 19 years at the time of participation in the main NHANES study. Exclusion criteria included those of the main NHANES study, inability to complete testing, or missing questionnaires. Of the 10 143 participants in NHANES aged 8 to 19 during the study years, 8520 were included in the analysis. Analysis was conducted from October 12, 2019, to July 9, 2020. Exposures: Tobacco exposure, defined as serum cotinine levels greater than 0.05 µg/L, or reporting living with a smoker or smoking themselves. Main Outcomes and Measures: Elevated blood pressure, classified as greater than 90% for a child's age, sex, and height according to the 2017 American Academy of Pediatrics Clinical Practice Guidelines. The a priori hypothesis that there is a positive association between tobacco exposure and elevated blood pressure in the study population was tested. Analysis included logistic regression with adjustment for possible confounders. Subgroup and sensitivity analyses were conducted. Results: A total of 8520 children were included in the analysis, representing 41 million US children. The mean (SD) age of the participants was 13.1 (0.05) years, 51% (95% CI, 49%-52%) were male, and 58% (95% CI, 54%-62%) were non-Hispanic White individuals. Participants with any tobacco smoke exposure were more likely than those without exposure to be older (mean [SD] age, 13.3 [0.07] years vs 12.8 [0.06] years), male (53% [95% CI, 51%-55%] vs 49% [95% CI, 47%-50%]), and non-Hispanic Black individuals (19% [95% CI, 16%-22%] vs 10% [95% CI, 8%-12%]). The odds of having elevated blood pressure was 1.31 (95% CI, 1.06-1.61) for any tobacco exposure after adjustment; odds were similar across subgroups and remained significant in multiple sensitivity analyses. Conclusions and Relevance: This study suggests that tobacco exposure is associated with elevated blood pressure in US children and adolescents. This modifiable risk factor represents a target for further research into reducing hypertension in children and adolescents.

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging.

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.

Inflammatory biomarker relationships with helper T cell GPR15 expression and cannabis and tobacco smoking.

OBJECTIVE: Smoking is associated with numerous inflammatory and autoimmune conditions. The goal of this study was to examine whether increased expression of G-protein-coupled receptor 15 (GPR15) on helper T cells in smokers could predispose to these conditions through its relationship with inflammatory biomarkers. METHODS: We used flow cytometric measurement of GPR15+CD3+CD4+ helper T cells and serum assays for C-reactive protein (CRP) and 17 cytokines drawn from peripheral blood samples from a cohort of n = 62 primarily African American young adults (aged 27-35 years). These variables were examined cross-sectionally in conjunction with serum biomarkers of tobacco (cotinine) and cannabis (tetrahydrocannabinol) use and lifestyle factors potentially impacting immune function in correlational analyses and linear regression models. RESULTS: Tobacco and cannabis smoking were strongly associated with increased GPR15 expression on helper T cells (p < 0.001), which was in turn was strongly associated with the ratio of pro-inflammatory to anti-inflammatory cytokines (p < 0.001). Mediation analyses indicated increased GPR15 expression accounted for roughly half of the relationship between smoking variables and pro-inflammatory to anti-inflammatory cytokine balance. CRP was not associated with cannabis or tobacco use or GPR15+ expression, but was associated with body mass index (p < 0.001). These relationships persisted after controlling for lifestyle and medical factors impacting immune function. CONCLUSIONS: Increased expression of GPR15 by helper T cells in smokers may mediate some of the relationship between smoking and a pro-inflammatory cytokine milieu. Better understanding of this relationship may help uncover how smoking increases the risk of inflammatory diseases.

Tobacco Smoking and Association between Betel Nut Chewing and Metabolic Abnormalities Among Military Males: The CHIEF Study.

AIM: To investigate the effect of smoking and alcohol intake on the association between betel nut chewing and each metabolic abnormality. BACKGROUND: Betel nut chewing has been associated with metabolic syndrome. OBJECTIVE: Whether the association is affected by tobacco or alcohol use is not clarified so far. METHODS: The authors conducted a cross-sectional study using 6,657 military males, aged 18-50 years in eastern Taiwan in 2013-2014. Metabolic syndrome was defined according to the International Diabetes Federation's ethnic criteria for Asians. The population was classified as non-betel nut chewers (N =5,749), current chewers with both tobacco and alcohol use (N =615), and current chewers without tobacco and/or alcohol use (N =293). Multiple logistic regression analyses were stepwise adjusted for the confounders including alcohol and tobacco use to determine the association of betel chewing with the metabolic abnormalities. RESULTS: As compared to the non-current chewers, the current chewers with both tobacco/alcohol use and those without had a higher risk of metabolic syndrome (odds ratios (OR) and 95% confidence intervals: 2.46 (2.00-3.02), and 2.04 (1.53-2.73), respectively) after controlling for age, service specialty, total cholesterol levels ≥200 mg/dL and exercise frequency (model 1). The association did not change much in the two chewing groups after additionally adjusting for alcohol consumption (model 2) (OR: 2.49 (1.99-3.12), and 2.04 (1.52-2.73), respectively), whereas the relationship reduced significantly in the chewers with both tobacco/alcohol use rather than those without after further adjusting for smoking (model 3) (OR: 2.18 (1.71-2.78) and 2.02 (1.51-2.71), respectively). This was in parallel with the pattern for the association of betel nut chewing with serum triglycerides >150 mg/dL in the chewers with both tobacco/alcohol use and those without in model 1 (OR: 2.90 (2.40-3.51) and 1.90 (1.45-2.49), respectively, p =0.011), in model 2 (OR: 2.82 (2.30-3.46) and 1.89 (1.44-2.49), respectively, p =0.040), and in model 3 (2.26 (1.81-2.81) and 1.87 (1.42-2.45), respectively, p =0.76). CONCLUSION: Our findings suggest that tobacco smoking but not alcohol intake could increase the relationship of betel nut chewing with metabolic syndrome, which is likely mediated by a synergic effect on increasing serum triglycerides levels.

Value of metalloproteinases in predicting COPD in heavy urban smokers.

BACKGROUND: Emphysema in asymptomatic heavy smokers can be detected during CT-scan screening for lung cancer. Metalloproteinases (MMPs) have been found to play a role in the pathogenesis of chronic obstructive pulmonary disease and to possibly serve as biomarkers for emphysema. METHODS: The NYU Lung Cancer Biomarker Center enrolled study subjects over 50 years of age with lung cancer risk factors from January 1, 2010, to December 31, 2015. These subjects received chest multi-detector computed tomography, spirometry, and provided serum for immunoassays for metalloproteinases (MMP) -1, -2, -7, -9, -10 and tissue inhibitor of metalloproteinases (TIMP) -1 and -2. RESULTS: Three hundred sixteen study subjects were enrolled. Of the 222 patients who met the inclusion criteria, 46% had emphysema. Smokers with emphysema had increased pack-years of smoking compared to smokers without emphysema (51 ± 24 pack-years (mean ± sd) versus 37 ± 20; p < 0.0001). Smokers with emphysema also had lower FEV1/FVC percent compared to smokers without emphysema (68 ± 11 (mean ± sd) versus 75 ± 8; p < 0.0001). Increased age and pack-years of smoking were associated with increased odds of emphysema. None of the metalloproteinases or tissue inhibitors of metalloproteinases were useful to predict the presence of emphysema in smokers. CONCLUSION: Emphysema was detected by CT in almost half of heavy urban smokers. Serum MMP levels provided minimal additional information to improve the detection of mild emphysema among smokers given their clinical characteristics (age, pack-years, and FEV1/FVC ratio).

50-year-old man • foot pain • "purple" toe • history of smoking • Dx?

► Foot pain ► "Purple" toe ► History of smoking.

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients who smoke.

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.

Smoke exposure from chronic biomass burning induces distinct accumulative systemic inflammatory cytokine alterations compared to tobacco smoking in healthy women.

Long-term exposure to biomass-burning smoke (BS) is associated with chronic obstructive pulmonary disease (COPD), asthma, and other chronic inflammatory lung diseases. BS results from such processes as the burning of wood for indoor cooking and heating, with women and children having the highest exposure rate. This study aimed to analyze the accumulative alterations in cytokine levels associated with BS (from wood) compared to tobacco smoke (TS) in healthy adult women. The levels of 27 cytokines were analyzed in the serum of 100 women, including 40 tobacco smokers/non-exposed to BS (TS+/BS-), 30 never-smokers/exposed to BS (TS-/BS+) and 30 never-smokers/non-exposed to BS (TS-/BS-) as controls, using 27-Plex immunoassay. The chronic BS exposure index was rated at ≥100 h-years, and the tobacco-smoking index was ≥10 pack-years. Compared to TS-/BS-, TS+/BS- had higher levels of IL-2, IL-9, MCP-1, MIP-1ß, and VEGF, while TS-/BS+ showed higher levels of IL-1ra, IL-6, IL-8, Eotaxin, IP-10, RANTES, and VEGF, presenting a distinct inflammatory profile that may favor an eosinophil-derived inflammatory response to BS exposure. Compared to TS+/BS-, TS-/BS+ expressed higher levels of IP-10 and IL-8, but lower levels of IL-2 and MIP-1ß. Gene-disease database analysis showed that altered cytokines in both TS+/BS- and TS-/BS+ are associated with asthma, COPD, lung fibrosis, and lung cancer. In conclusion, chronic BS exposure induces distinct systemic inflammatory cytokine alterations compared to tobacco smokers in healthy women. These findings provide new insights into how long-term exposure to BS affects the inflammatory response-and potentially the health-of adult women.

Smoking-Related DNA Methylation is Differentially Associated with Cadmium Concentration in Blood.

Tobacco smoking, a risk factor for several human diseases, can lead to alterations in DNA methylation. Smoking is a key source of cadmium exposure; however, there are limited studies examining DNA methylation alterations following smoking-related cadmium exposure. To identify such cadmium exposure-related DNA methylation, we performed genome-wide DNA methylation profiling using DNA samples from 50 smokers and 50 non-smokers. We found that a total of 136 CpG sites (including 70 unique genes) were significantly differentially methylated in smokers as compared to that in non-smokers. The CpG site cg05575921 in the AHRR gene was hypomethylated (Δ ß > - 0.2) in smokers, which was in accordance with previous studies. The rs951295 (within RNA gene LOC105370802) and cg00587941 sites were under-methylated by > 15% in smokers, whereas cg11314779 (within CELF6) and cg02126896 were over-methylated by ≥ 15%. We analyzed the association between blood cadmium concentration and DNA methylation level for 50 smokers and 50 non-smokers. DNA methylation rates of 307 CpG sites (including 207 unique genes) were significantly correlated to blood cadmium concentration (linear regression P value < 0.001). The four significant loci (cg05575921 and cg23576855 in AHRR, cg03636183 in F2RL3, and cg21566642) were under-methylated by > 10% in smokers compared to that in non-smokers. In conclusion, our study demonstrated that DNA methylation levels of rs951295, cg00587941, cg11314779, and cg02126896 sites may be new putative indicators of smoking status. Furthermore, we showed that these four loci may be differentially methylated by cadmium exposure due to smoking.

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning.

IL-17A is an important pro-inflammatory cytokine involved in the inflammatory response in chronic obstructive pulmonary disease (COPD). To evaluate the role played by single nucleotide polymorphisms of IL17A and protein levels in susceptibility to COPD, 1,807 subjects were included in a case-control study; 436 had COPD related to tobacco smoking (COPD-S) and 190 had COPD related to biomass burning (COPD-BB). Six hundred fifty-seven smokers without COPD (SWOC) and 183 biomass burning-exposed subjects (BBES) served as the respective control groups. The CC genotype and C allele of rs8193036 were associated with COPD (COPD-S vs. SWOC: p < 0.05; OR = 3.01, and OR = 1.28, respectively), as well as a recessive model (p < 0.01; OR = 2.91). Significant differences in serum levels were identified between COPD-S vs. SWOC, COPD-S vs. COPD-BB, and SWOC vs. BBES (p < 0.01). By comparing genotypes in the COPD-BB group TT vs. CC and TC vs. CC (p < 0.05), we found lower levels for the CC genotype. Logistic regression analysis by co-variables was performed, keeping the associations between COPD-S vs. SWOC with both polymorphisms evaluated (p < 0.05), as well as in COPD-BB vs. BBES but with a reduced risk of exacerbation (p < 0.05). In conclusion, polymorphisms in IL17A are associated with COPD. Serum levels of IL-17A were higher in smokers with and without COPD.

A Procedure to Standardize Puff Topography During Evaluations of Acute Tobacco or Electronic Cigarette Exposure.

INTRODUCTION: Documenting factors that influence differential sensitivity to acutely inhaled nicotine products requires carefully controlling the amount of exposure (dose), and thus a procedure by which to control such exposure. METHODS: We evaluated consistency of puff volume from intermittent acute exposures to smoked tobacco cigarettes (study 1, n = 45, plus a comparison study of uninstructed use with n = 59) and to vaped electronic cigarettes (e-cigarettes; study 2, n = 27 naive to e-cigarettes) in adult-dependent smokers. All in primary studies 1 and 2 participated in research administering different nicotine levels in each product under blind conditions, one per session using within-subject designs. In both studies, participants followed an automated instructional procedure on a computer monitor standardizing the timing and amount of exposure to each product during a given trial, with four trials per session, each separated by 20 minutes. Puff volume per trial via Clinical Research Support System (CReSS) was the primary dependent measure to determine consistency across trials via intraclass correlation coefficients (ICCs). RESULTS: Control over topography with both inhaled products was demonstrated by highly significant ICCs for puff volume across trials. Instructed control with own brand was generally better in study 1 than with uninstructed smoking in the comparison sample, as expected. As intended, reliability of puff volume generally did not differ by menthol preference or sex in either study, but ICCs in study 2 tended to be lower for some men using the placebo e-cigarette. CONCLUSIONS: This instructional procedure may substantially improve control over amounts of acute exposure to tobacco or e-cigarette use. IMPLICATIONS: Control over topography in studies of acute exposure to these inhaled products can potentially aid validity of research into differential sensitivity to use, so findings can be attributed to factors of interest and not to variable exposure. Our procedure minimized variability in exposure to the same product and between moderate nicotine products, but remaining differences suggest that compensation for very low or no nicotine commercial products may be difficult to totally eliminate with these instructions alone. Further study is needed to determine this procedure's utility with other inhaled products among experienced users and when comparing different products in between-groups analyses.

Smoking Across the Menopausal Transition in a 10-Year Longitudinal Sample: The Role of Sex Hormones and Depressive Symptoms.

INTRODUCTION: Current cigarette smoking rates among older women remain problematic, especially given that this population experiences increased smoking-related health consequences. Despite these increased health concerns, little research to date has explored smoking patterns across the menopausal transition (pre-, early-peri-, late-peri-, and postmenopausal) or the effect of unique factors such as sex hormones and depression during this transition. METHODS: This study used 10 yearly waves of data from the Study of Women's Health Across the Nation, a longitudinal dataset. Data included 1397 women endorsing ever smoking regularly at baseline. Random-effects logistic regression models were used to examine smoking transitions. RESULTS: Although there were no associations between menopausal transition stage and smoking behavior, increased estradiol was associated with an increased likelihood of quitting regular smoking (eg, transitioning from regular smoking to non-regular or no smoking; odds ratio [OR] = 1.28), whereas increased testosterone was associated with an increased likelihood of relapsing to regular smoking (eg, transitioning from former or nonregular smoking to regular smoking OR = 2.56). Depression was associated with increased likelihood of continued smoking (OR = 0.97) and relapse (OR = 1.03). CONCLUSIONS: The results emphasize the need to develop interventions to target initiated or continued smoking among women across the menopausal transition and specifically highlight the importance of developing treatments that target depressive symptoms in this population. In addition, although singular hormone measures were associated with smoking behavior, there is a need for future study of dynamic changes in hormones, as well as the impact of progesterone on smoking behaviors across the menopausal transition. IMPLICATIONS: To date, no studies have examined smoking behaviors across the menopausal transition. In this study, although menopausal transition status was not significantly related to transitions in smoking behavior, important relationships between sex hormones and depression were observed. Increased estradiol was associated with an increased likelihood of quitting regular smoking, whereas increased testosterone was associated with an increased likelihood of relapsing to regular smoking behavior. Higher depression scores were related to continued smoking and relapse to regular smoking behavior. These results highlight the need to develop interventions to target smoking cessation among women across the menopausal transition.

Self-Reported Smoking Compared to Serum Cotinine in Bariatric Surgery Patients: Smoking Is Underreported Before the Operation.

BACKGROUND: Smoking has been associated with postoperative complications and mortality in bariatric surgery. The evidence for smoking is based on self-report and medical charts, which can lead to misclassification and miscalculation of the associations. Determination of cotinine can objectively define nicotine exposure. We determined the accuracy of self-reported smoking compared to cotinine measurement in three phases of the bariatric surgery trajectory. METHODS: Patients in the phase of screening (screening), on the day of surgery (surgery), and more than 18 months after surgery (follow-up) were consecutively selected. Self-reported smoking was registered and serum cotinine was measured. We evaluated the accuracy of self-reported smoking compared to cotinine, and the level of agreement between self-report and cotinine for each phase. RESULTS: In total, 715 patients were included. In the screening, surgery, and follow-up group, 25.6%, 18.0%, and 15.5%, respectively, was smoking based on cotinine. The sensitivity of self-reported smoking was 72.5%, 31.0%, and 93.5% in the screening, surgery, and follow-up group, respectively (p < 0.001). The specificity of self-report was > 95% in all groups (p < 0.02). The level of agreement between self-report and cotinine was 0.778, 0.414, and 0.855 for the screening, surgery, and follow-up group, respectively. CONCLUSIONS: Underreporting of smoking occurs before bariatric surgery, mainly on the day of surgery. Future studies on effects of smoking and smoking cessation in bariatric surgery should include methods taking into account the issue of underreporting.

Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers.

BACKGROUND: Blacks bear a disproportionate burden of smoking-related diseases and experience greater difficulty quitting smoking than Whites. Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence. The aim of this study was to evaluate the hypothesis that melanin affects nicotine disposition kinetics in humans. METHODS: Forty-four Black participants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma concentrations of nicotine and cotinine were measured, and pharmacokinetic parameters were estimated. The constitutive and facultative melanin indexes were measured using a dermaspectrophotometer. RESULTS: The median constitutive melanin index was 60.7 (32.8-134.7) and the median facultative melanin index 68.1 (38.6-127.1). The mean (±SD) nicotine elimination half-life was 136 min (±33.5), clearance was 1237 mL/min (±331), and Vss was 204 L (±66), or 2.6 L/kg (±0.7). No evidence of significant differences was found in nicotine pharmacokinetic parameters by comparing participants in different melanin index quartiles (outliers with very high melanin index had similar pharmacokinetic values to others). Differences were not statistically significant when adjusted for age, BMI, sex and CYP2A6 genotype or the nicotine metabolite ratio (NMR), and no evidence of significant correlations were found between melanin (facultative or constitutive) and the pharmacokinetic parameters of nicotine or cotinine or tobacco dependence measures. CONCLUSIONS: Based on our finding in this group of Black smokers, we could not confirm the hypothesis that melanin significantly affects nicotine disposition kinetics or measures of tobacco dependence.

Racial/Ethnic Differences in Physiological Stress and Relapse among Treatment Seeking Tobacco Smokers.

Stress is robustly associated with tobacco smoking and relapse. African Americans experience greater difficulty quitting compared to whites, yet no studies have examined race differences in physiological stress biomarkers during a quit attempt. This pilot study compared cortisol levels among treatment-seeking African American and white smokers, and relapse rates. Adult smokers (N = 115; n = 72 African American, n = 43 White) received eight sessions of group cognitive behavioral therapy plus transdermal nicotine patches. Assessments included demographics, salivary cortisol (collected at session 1, the end-of-therapy [EOT], and one-month post-therapy), and carbon monoxide-verified smoking relapse. Overall, cortisol levels declined over the course of the day at baseline, the EOT, and the one-month follow-up. African Americans exhibited lower cortisol levels compared to Whites at baseline and the EOT, but not at the one-month follow-up. In addition, African American smokers exhibited flatter slopes compared to Whites at each time point. Relapse rates were greater among African Americans at the EOT and one-month follow-up. The attenuated cortisol pattern observed in African Americans may indicate hypothalamic-pituitary-adrenal axis (HPA) exhaustion and aid our understanding of tobacco-related disparities. There is a need to focus on stress mechanisms and specific intervention approaches in order to eliminate racial/ethnic differences.

Positive plasma cotinine during platinum-based chemotherapy is associated with poor response rate in advanced non-small cell lung cancer patients.

INTRODUCTION: Patients with advanced non-small cell lung cancer (NSCLC) are most of the time treated with a first-line cytotoxic chemotherapy. Tobacco use is responsible for 90% of lung cancer. The aim of this study was to evaluate the impact of smoking continuation during first-line chemotherapy on tumor response in advanced-stage NSCLC. MATERIALS AND METHODS: All patients with an advanced-stage NSCLC (IIIb or IV), treated with first-line platinum-based chemotherapy in our Department between June 2013 and July 2017 were included. Smoking status was assessed at inclusion by self-report, then at the tumor assessment consultation after 2 months of treatment, by both self-report and plasmatic cotinine measurement. Chemotherapy response, progression-free survival (PFS), overall survival (OS) and stage 3-4 toxicity were registered. RESULTS: Ninety-seven patients were included: 8 (8%) declared to be non-smokers, 56 (58%) current smokers and 33 (34%) former smokers at diagnosis. At the first tumor evaluation, 24 (25%) self-reported as active smokers and 73 (75%) as non-smokers; overall response rate (ORR) was respectively 38% and 48% (p = 0.373). Fifty-four patients had a plasmatic cotinine evaluation at the first tumor evaluation. Seventeen patients (32%) had a positive cotinine rate (median 108ng/mL, IQR 31-236). Six patients (35%) had positive cotinine rate whereas declaring to be non-smokers at the first tumor evaluation. ORR was 18% in case of positive cotinine rate, and 57% when negative (p = 0.007). Regardless of the method for smoking status evaluation, PFS, OS and grade 3-4 toxicities were similar between smoker and non-smoker patients at the first tumor evaluation. CONCLUSION: Smoking continuation during platinum-based chemotherapy, reflected by positive plasma cotinine rate, was associated with a poor ORR.