Estimation of urinary cotinine cut-off points distinguishing non-smokers, passive and active smokers

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 µg l^-1 (differentiation of non-smokers from passive smokers), 170 µg l^-1 (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 µg l^-1 (differentiation of passive smokers from active smokers), and 2100 µg l^-1 (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.     

Preliminary studies on the effect of moderate physical activity on blood levels of glutathione

Molecular epidemiological approaches are being used to study how physical activity may protect against cancer. Prior epidemiological data suggest that physical activity protects against lung cancer; however, interpretation of these data is complicated by potential confounding by smoking. Glutathione (GSH) detoxifies cigarette smoke carcinogens and the paper tests whether physical activity levels are associated with blood GSH levels. Study subjects were enrolled in a chemoprevention trial testing whether antioxidant micronutrient supplementation reduces genetic damage from cigarette smoking. Physical activity data were collected by questionnaire from 178 subjects at 12 months of follow-up in the trial. Total GSH (tGSH), which is the sum of free and protein-bound GSH and glutathione disulfide levels, was measured using the 5,5′-dithiobis-(2-nitrobenzenoic acid) colormetric assay with red blood cell samples collected at the 12-month time point. In multivariate linear regression analyses that controlled for gender and cigarettes smoked per day, tGSH was positively associated with hours per week of moderate intensity activity (β=0.005, p=0.02). Hours per week of vigorous intensity activity were unassociated with tGSH and the effect of moderate activity remained after control for vigorous activity. The results are consistent with prior research showing differential effects of moderate and vigorous activity and suggest a mechanism through which physical activity may influence lung cancer risk.     

Revised and extended serum cotinine cut-offs to classify smokers and non-smokers

Purpose: To revise and extend the previously published serum cotinine cut offs to classify smokers and non-smokers for US adolescents and adults.

Materials and methods: Cross-sectional data (N?=?10171) from National Health and Nutrition Examination Survey for 2011–2014 were used to compute serum cotinine cut-offs to classify smokers and non-smokers for US adults aged ≥20?years and 2007–2014 (N?=?4583) data were used to compute serum cotinine cut-offs for US adolescents aged 12–19?years.

Results: Specificities and sensitivities for the cut-offs among adults were ≥95% and ≥75% among adolescents. For adults, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 3.3 for the total population, 4.13 for males, 2.99 for females, 4.03 for non-Hispanic whites, 8.85 for non-Hispanic blacks, 0.377 for Mexican Americans, 1.72 for other Hispanics and 1.41 for non-Hispanic Asians. For adolescents, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 0.765 for the total population, 1.1 for males, 0.408 for females, 1.2 for non-Hispanic whites, 1.98 for non-Hispanic blacks, 0.215 for Mexican Americans and 0.321 for other Hispanics.

Conclusions: Serum cotinine cut-offs to distinguish smokers from non-smokers for US adults and adolescents were developed.     

Evaluating the relationship between biomarkers of potential harm and biomarkers of tobacco exposure among current,past, and nonsmokers: data from the National Health and Nutrition Examination Survey 2007–2012

Potential long-term health effects from tobacco products can be estimated by measuring changes in biochemical indicators of disease mechanisms like inflammation. This study assesses the potential relationships between biomarkers of potential harm (BOPH) and biomarkers of cigarette smoke exposure (BOE) based on data from the NHANES (2007–2012, n?=?17,293 respondents). Statistically significant relationships were observed between white blood cells (WBC) and high-density lipoprotein (HDL) and BOE; between WBC and high-sensitivity C-reactive protein and smoking status; and between WBC and HDL and smoking intensity. This analysis suggests that WBC and HDL are useful BOPH in studies assessing the health risks of cigarette smoking.     

Perinatal mortality and adverse pregnancy outcomes in a low‐income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low‐income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Increased frequency of sister chromatid exchanges in peripheral lymphocytes of alcoholics and cigarette smokers

Sister chromatid exchange (SCE) is a sensitive indicator of genotoxicity. In this study we investigated the effects of alcohol consumption and cigarette smoking on the frequency of SCE in cultures of peripheral lymphocytes. The rate was higher in alcoholics who smoked (10.89+/-2.46) and in smokers (positive controls) (7.64+/-1.01) than in healthy non-smokers (negative controls) (6.96+/-2.18). Statistical analysis suggested that the increases were related to alcohol consumption and cigarette smoking (p<0.05).     

Understanding the contribution of native tracheobronchial structure to lung function: CT assessment of airway morphology in never smokers

Background

Computed tomographic (CT) airway lumen narrowing is associated with lower lung function. Although volumetric CT measures of airways (wall volume [WV] and lumen volume [LV]) compared to cross sectional measures can more accurately reflect bronchial morphology, data of their use in never smokers is scarce. We hypothesize that native tracheobronchial tree morphology as assessed by volumetric CT metrics play a significant role in determining lung function in normal subjects. We aimed to assess the relationships between airway size, the projected branching generation number (BGN) to reach airways of <2mm lumen diameter –the site for airflow obstruction in smokers- and measures of lung function including forced expiratory volume in 1 second (FEV₁) and forced expiratory flow between 25% and 75% of vital capacity (FEF 25–75).

Methods

We assessed WV and LV of segmental and subsegmental airways from six bronchial paths as well as lung volume on CT scans from 106 never smokers. We calculated the lumen area ratio of the subsegmental to segmental airways and estimated the projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized tracheobronchial tree model. Regression analysis was used to assess the relationships between airway size, BGN, FEF 25–75, and FEV₁.

Results

We found that in models adjusted for demographics, LV and WV of segmental and subsegmental airways were directly related to FEV₁ (P <0.05 for all the models). In adjusted models for age, sex, race, LV and lung volume or height, the projected BGN was directly associated with FEF 25–75 and FEV₁ (P = 0.001) where subjects with lower FEV₁ had fewer calculated branch generations between the subsegmental bronchus and small airways. There was no association between airway lumen area ratio and lung volume.

Conclusion

We conclude that in never smokers, those with smaller central airways had lower airflow and those with lower airflow had less parallel airway pathways independent of lung size. These findings suggest that variability in the structure of the tracheobronchial tree may influence the risk of developing clinically relevant smoking related airway obstruction.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0181-y) contains supplementary material, which is available to authorized users.     

Association between circulating microRNA-126 expression level and tumour necrosis factor alpha in healthy smokers

Introduction: Smoking contributes to the death of a million people worldwide each year. Smokers experience an alteration in tumour necrosis factor-alpha (TNF-α), and the risk of expected lung cancer. The study aimed at investigating the expression levels of mir-126 and mir-124, as well as TNF-α as possible biomarkers of expected smoking-related diseases.

Methods: Twenty-five male smokers’ age and sex-matched with 25 non-smokers were recruited for the present study. Plasma expression levels of mir-126 and mir-124 were evaluated using quantitative real-time PCR. Lipid profile, TNF-α, interleukin-6 and C-reactive protein were assessed in plasma of each participant.

Results: Plasma miR-126 was statistically down-regulated in smokers relative to non-smokers; however, mir-124 did not show any significant changes between groups. Among the measured parameters, mir-126 and tumour necrosis factor alpha (TNF-α) displayed a good discrimination and sensitivity between smokers and non-smokers (AUC = 0.809 (95% CI: 0.668–0.95; p?<?0.001) and 0.742(95% CI: 0.584–0.9; p?<?0.01), respectively. Also, the combined evaluation of miR-126 and TNF-α levels showed high discrimination (AUC= 0.889 (95% CI: 0.779–1.00; p?<?0.0001), sensitivity = 85%, and specificity = 80% in the diagnosis of smokers with non-smokers.

Conclusions: MiR-126 and TNF-α are potential biomarkers of smoking-related diseases and are important in assessing the expected tobacco-related harm.     

Carcinogen mmetabolism and DNA adducts in human lung tissues as affected by tobacco smoking or metabolic phenotype: a case-control study on lung cancer patients

Individual variations in activity of pulmonary enzymes that metabolize tobacco-derived carcinogens may affect an individual's cancer risk from cigarette smoking. To investigate whether some of these enzymes (e.g., cytochrome P450IA-related) can serve as markers for carcinogen-induced DNA damage accumulating in the lungs of smokers, non-tumorous lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (n = 54) or non-neoplastic lung disease (n = 20). Phase I (AHH, ECDE) and phase II (EH, UDPGT, GST) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were analyzed for DNA adducts, using ³²P-postlabeling.

Data analysis of subsets or the whole group of patients yielded the following results. (1) Phase I and II drug-metabolizing enzyme (AHH, EH, UDPGT, GST) activities in histologically normal surgical specimens of lung parenchyma were correlated with the respective enzyme activities in bronchial tissues of the same subject. (2) In lung parenchyma, enzyme (AHH, ECDE, EH, UDPGT) activities were significantly and positively related to each other, implying a similar regulatory control of their expression. (3) Mean activities of pulmonary enzymes (AHH, ECDE) were significantly (2- and 7-fold, respectively) higher in lung cancer patients who had smoked within 30 days before surgery (except GST, which was depressed) than in cancer-free subjects with a similar smoking history. (4) In the cancer patients, the time required for AHH, EH and UDPGT activities to return to the level found in non-smoking subjects was several weeks. (5) Bronchial tree and peripheral lung parenchyma preparations exhibited a poor efficiency in activating promutagens to bacterial mutagens in Salmonella. However, they decreased the mutagenicity of several direct-acting mutagens, an effect which was more pronounced in tissue from recent smokers. GSH concentration and GST activity were positively correlated with mutagen inactivation in the same sample. (6) In recent smokers, AHH activity in lung parenchyma was positively correlated with the level of tobacco smoke-derived DNA adducts. (7) Pulmonary AHH and EH activity had prognostic value in tobacco-related lung cancer patients. (8) An enhanced level of pro-oxidant state in the lungs was associated with recent cigarette smoking. Malondialdehyde level in lung parenchyma was associated with the degree of small airway obstruction, suggesting a common free radical-mediated pathway for both lung cancer induction and small airway obstruction.

These results demonstrate the pronounced effect of recent cigarette smoke exposure on pulmonary xenobiotic metabolism and lipid peroxidation and lend further support to the hypothesis that the inducibility of pulmonary AHH activity (cytochrome P450IA1 levels) in tobacco smokers is associated with lung cancer risk. Results on DNA adducts in smokers' lung tissue may help to explain why a certain metabolic phenotype accumulates more DNA damage in lung cells.     

Comparison of plasma from healthy nonsmokers,smokers, and lung cancer patients: Pattern-based differentiation profiling of low molecular weight proteins and peptides by magnetic bead technology with MALDI-TOF MS

Context: Smoking is the major contributor of lung cancer (LC), which accounts for millions of death.

Objective: This study focused on the correlation between the proteomic profiling of LC patients, and healthy nonsmokers and smokers.

Method: Pattern-based peptide profiling of 186 plasma samples was performed through reversed-phase chromatography-18 magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and resulted data were evaluated statistically by ClinProTool.

Results: Marker peaks at m/z 1760, 5773, 5851, 2940, and 7172 were found with an excellent statistical figure.

Conclusion: Selected marker peaks can be served as a differentiated tool of LC patients with high sensitivity and specificity.