Association of urinary biomarkers of tobacco exposure with lung cancer risk in African American and White cigarette smokers in the Southern Community Cohort Study.

BACKGROUND: After accounting for smoking history lung cancer incidence is greater in African Americans than Whites. In the Multiethnic Cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day (CPD). Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. METHODS: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White, 56% African American). TNE, the trans-3-hydroxycotinine:cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium, and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid (8-iso-PGF2α) were quantified in urine. Unconditional logistic regression was used to estimate the odds ratios and 95% confidence intervals for each biomarker and lung cancer risk. RESULTS: TNE, NNAL and cadmium were higher in cases than controls (adjusted for age, race, sex, body mass index (BMI) and CPD). Among cases, these levels were higher in African Americans compared to Whites. After accounting for age, sex, BMI and pack-years, a one-SD increase in log-TNE (OR=1.30; 95% CI: 1.10-1.54) and log-NNAL (OR=1.27; 95% CI: 1.03-1.58 with TNE adjustment) were associated with lung cancer risk. In this study, where NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. CONCLUSION: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. IMPACT: Urinary NNAL, TNE and cadmium concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

Sowing the Seeds of Recovery: A Qualitative Study of Women in Recovery From Addiction and Victimization.

The purpose of this study was to understand the lived experiences of women with histories of victimization and addiction who were recently admitted to a sober living home (SLH). From the 17 interviews conducted, five themes (i.e., experiences of violence, challenges leaving an abusive relationship, chaos, using substances to cope, and social support) and one constitutive pattern (i.e., sowing the seeds of recovery) emerged from the data. These results highlight the importance of social support in promoting recovery and that social support may foster positive relationships with safe and trustworthy individuals as well as empower and support others with similar experiences.

Epigenome-wide association study of total nicotine equivalents in multiethnic current smokers from three prospective cohorts.

The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10-8). The top significant sites were annotated to AHRR, F2RL3, RARA, GPR15, PRSS23, and 2q37.1, all of which had decreasing methylation with increasing TNEs. We identified 45 novel CpG sites, of which 42 were unique to the EPIC array and eight annotated to genes not previously linked with smoking-related DNA methylation. The most significant signal in a novel gene was cg03748458 in MIR383;SGCZ. Fifty-one of the 408 discovery sites were validated in the Singapore Chinese Health Study (n = 340) and the Southern Community Cohort Study (n = 394) (Bonferroni corrected p < 1.23 × 10-4). Significant heterogeneity by race and ethnicity was detected for CpG sites in MYO1G and CYTH1. Furthermore, TNEs significantly mediated the association between cigarettes per day and DNA methylation at 15 sites (average 22.5%-44.3% proportion mediated). Our multiethnic study highlights the transethnic and ethnic-specific methylation associations with internal nicotine dose, a strong predictor of smoking-related morbidities.

Tobacco smoke exposure, the lower airways microbiome and outcomes of ventilated children.

BACKGROUND: Tobacco smoke exposure increases the risk and severity of lower respiratory tract infections in children, yet the mechanisms remain unclear. We hypothesized that tobacco smoke exposure would modify the lower airway microbiome. METHODS: Secondary analysis of a multicenter cohort of 362 children between ages 31 days and 18 years mechanically ventilated for >72 h. Tracheal aspirates from 298 patients, collected within 24 h of intubation, were evaluated via 16 S ribosomal RNA sequencing. Smoke exposure was determined by creatinine corrected urine cotinine levels ≥30 µg/g. RESULTS: Patients had a median age of 16 (IQR 568) months. The most common admission diagnosis was lower respiratory tract infection (53%). Seventy-four (20%) patients were smoke exposed and exhibited decreased richness and Shannon diversity. Smoke exposed children had higher relative abundances of Serratia spp., Moraxella spp., Haemophilus spp., and Staphylococcus aureus. Differences were most notable in patients with bacterial and viral respiratory infections. There were no differences in development of acute respiratory distress syndrome, days of mechanical ventilation, ventilator free days at 28 days, length of stay, or mortality. CONCLUSION: Among critically ill children requiring prolonged mechanical ventilation, tobacco smoke exposure is associated with decreased richness and Shannon diversity and change in microbial communities. IMPACT: Tobacco smoke exposure is associated with changes in the lower airways microbiome but is not associated with clinical outcomes among critically ill pediatric patients requiring prolonged mechanical ventilation. This study is among the first to evaluate the impact of tobacco smoke exposure on the lower airway microbiome in children. This research helps elucidate the relationship between tobacco smoke exposure and the lower airway microbiome and may provide a possible mechanism by which tobacco smoke exposure increases the risk for poor outcomes in children.

Quantitation of Ten Urinary Nicotine Metabolites, Including 4-Hydroxy-4-(3-pyridyl) Butanoic Acid, a Product of Nicotine 2'-Oxidation, and CYP2A6 Activity in Japanese Americans, Native Hawaiians, and Whites.

Smoking intensity varies across smokers and is influenced by individual variability in the metabolism of nicotine, the major addictive agent in tobacco. Therefore, lung cancer risk, which varies by racial ethnic group, is influenced by the primary catalyst of nicotine metabolism, cytochrome P450 2A6 (CYP2A6). In smokers, CYP2A6 catalyzes nicotine 5'-oxidation. In vitro, CYP2A6 also catalyzes, to a much lower extent, 2'-oxidation, which leads to the formation of 4-hydroxy-4-(3-pyridyl) butanoic acid (hydroxy acid). The urinary concentration of hydroxy acid has been quantified in only a few small studies of White smokers. To quantitatively assess the importance of nicotine 2'-oxidation in smokers, an LC-MS/MS-based method was developed for the analysis of nicotine and ten metabolites in urine. The concentrations of nicotine and these metabolites were measured in 303 smokers (99 Whites, 99 Native Hawaiians, and 105 Japanese Americans), and the relative metabolism of nicotine by four pathways was determined. Metabolism by these pathways was also compared across quartiles of CYP2A6 activity (measured as the plasma ratio of 3-hydroxycotinine to cotinine). As reported previously and consistent with their average CYP2A6 activity, nicotine 5'-oxidation was highest in Whites and lowest in Japanese Americans. Nicotine N-glucuronidation and N-oxidation increased with decreasing CYP2A6 activity. However, the relative urinary concentration of hydroxy acid (mean, 2.3%; 95% CI, 2.2-2.4%) did not vary by ethnic group or by CYP2A6 activity. In summary, CYP2A6 is not an important catalyst of nicotine 2'-oxidation in smokers, nor does nicotine 2'-oxidation compensate for decreased CYP2A6 activity.

The Impact of Reducing Nicotine Content on Adolescent Cigarette Smoking and Nicotine Exposure: Results From a Randomized Controlled Trial.

INTRODUCTION: As the science base around the potential benefits of a reduced-nicotine standard for cigarettes grows, information on the potential effects on adolescent smokers is a high priority. The aim of this randomized trial was to test the influence of 3-week exposure to reduced nicotine cigarettes in a sample of adolescent daily smokers. AIMS AND METHODS: In this double-blind, two-arm, randomized controlled trial (NCT0258731), following a 1-week baseline, adolescent daily smokers not currently intending to quit (ages 15-19 years, n = 66 randomized) were urn randomized to use either very low nicotine content (VLNC; 0.4 mg/g; n = 33) or normal nicotine content (NNC, 15.8 mg/g; n = 33) research cigarettes for 3 weeks. Participants attended five study sessions at our clinical laboratory. The primary outcome was average total cigarettes smoked per day (CPD; including both study and non-study cigarettes) at week 3. RESULTS: Stepwise regression results demonstrated that compared with NNC cigarettes (n = 31), assignment to VLNC cigarettes (n = 29), was associated with 2.4 fewer CPD on average than NNC assignment (p < .05) week 3 when controlling for covariates (p < .01, Cohen's d = 0.52 n = 60 completed all procedures). VLNC cigarettes were also associated with lower levels of craving reduction than NNC cigarettes (Questionnaire on Smoking Urges Factor 2, p < .05). No group differences were found for secondary outcomes. CONCLUSIONS: Adolescent participants assigned to VLNC use for 3 weeks smoked fewer total CPD relative to the NNC group. Overall, data suggest that a VLNC policy would reduce cigarette smoking in adolescents who smoke, but high rates of incomplete adherence suggest that youth may seek alternative sources of nicotine in this scenario. IMPLICATIONS: The US Food and Drug Administration may enact a reduced-nicotine product standard that would affect all commercially available cigarettes. One important population affected by this policy would be adolescents who smoke. This study, the first clinical trial of VLNC cigarettes in adolescents, demonstrates that adolescents switched to VLNC cigarettes for 3 weeks reduced their CPD relative to the normal-nicotine cigarette control group, without leading to increased respiratory symptoms or increased withdrawal. Biomarkers indicated the use of other sources of nicotine, suggesting that such a policy will need to consider approaches to assist in transitioning away from smoking.

Increased Levels of the Acrolein Metabolite 3-Hydroxypropyl Mercapturic Acid in the Urine of e-Cigarette Users.

Carcinogen and toxicant uptake by e-cigarette users have not been fully evaluated. In the study reported here, we recruited 30 e-cigarette users, 63 nonsmokers, and 33 cigarette smokers who gave monthly urine samples over a period of 4-6 months. Their product use status was confirmed by measurements of exhaled CO, urinary total nicotine equivalents, cyanoethyl mercapturic acid (CEMA), and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Urinary biomarkers of exposure to the carcinogens acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA), benzene (S-phenyl mercapturic acid, SPMA), acrylonitrile (CEMA), and a combination of crotonaldehyde, methyl vinyl ketone, and methacrolein (3-hydroxy-1-methylpropyl mercapturic acid, HMPMA) were quantified at each visit. Data from subject visits with CEMA > 27 pmol/mL were excluded from the statistical analysis of the results because of possible unreported exposures to volatile combustion products such as secondhand cigarette smoke or marijuana smoke exposure; this left 22 e-cigarette users with 4 or more monthly visits and all 63 nonsmokers. Geometric mean levels of 3-HPMA (1249 versus 679.3 pmol/mL urine) were significantly higher (P = 0.003) in e-cigarette users than in nonsmokers, whereas levels of SPMA, CEMA, and HMPMA did not differ between these two groups. All analytes were significantly higher in cigarette smokers than in either e-cigarette users or nonsmokers. The results of this unique multimonth longitudinal study demonstrate consistent significantly higher uptake of the carcinogen acrolein in e-cigarette users versus nonsmokers, presenting a warning signal regarding e-cigarette use.

Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study.

BACKGROUND: While cigarette smoking is the leading cause of lung cancer, the majority of smokers do not develop the disease over their lifetime. The inter-individual differences in risk among smokers may in part be due to variations in exposure to smoking-related toxicants. METHODS: Using data from a subcohort of 2,309 current smokers at the time of urine collection from the Multiethnic Cohort Study, we prospectively evaluated the association of ten urinary biomarkers of smoking-related toxicants [total nicotine equivalents (TNE), a ratio of total trans-3'-hydroxycotinine (3-HCOT)/cotinine (a phenotypic measure of CYP2A6 enzymatic activity), 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), S-phenylmercapturic acid (SPMA), 3-hydroxypropyl mercapturic acid (3-HPMA), phenanthrene tetraol (PheT), 3-hydroxyphenanthrene (PheOH), the ratio of PheT/PheOH, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid (8-iso-PGF2α)] with lung cancer risk (n = 140 incident lung cancer cases over an average of 13.4 years of follow-up). Lung cancer risk was estimated using Cox proportional hazards models. RESULTS: After adjusting for decade of birth, sex, race/ethnicity, body mass index, self-reported pack-years, creatinine, and urinary TNE (a biomarker of internal smoking dose), a one SD increase in log total 3-HCOT/cotinine (HR, 1.33; 95% CI, 1.06-1.66), 3-HPMA (HR, 1.41; 95% CI, 1.07-1.85), and Cd (HR, 1.45; 95% CI, 1.18-1.79) were each associated with increased lung cancer risk. CONCLUSIONS: Our study demonstrates that urinary total 3-HCOT/cotinine, 3-HPMA, and Cd are positively associated with lung cancer risk. These findings warrant replication and consideration as potential biomarkers for smoking-related lung cancer risk. IMPACT: These biomarkers may provide additional information on lung cancer risk that is not captured by self-reported smoking history or TNE. See related commentary by Etemadi et al., p. 289.

Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe.

INTRODUCTION: A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. AIMS AND METHODS: Tribal-academic collaboration was formed and during 2019-2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. RESULTS: Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. CONCLUSION: In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants' pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. IMPLICATIONS: Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Predicting nicotine metabolism across ancestries using genotypes.

BACKGROUND: There is a need to match characteristics of tobacco users with cessation treatments and risks of tobacco attributable diseases such as lung cancer. The rate in which the body metabolizes nicotine has proven an important predictor of these outcomes. Nicotine metabolism is primarily catalyzed by the enzyme cytochrone P450 (CYP2A6) and CYP2A6 activity can be measured as the ratio of two nicotine metabolites: trans-3'-hydroxycotinine to cotinine (NMR). Measurements of these metabolites are only possible in current tobacco users and vary by biofluid source, timing of collection, and protocols; unfortunately, this has limited their use in clinical practice. The NMR depends highly on genetic variation near CYP2A6 on chromosome 19 as well as ancestry, environmental, and other genetic factors. Thus, we aimed to develop prediction models of nicotine metabolism using genotypes and basic individual characteristics (age, gender, height, and weight). RESULTS: We identified four multiethnic studies with nicotine metabolites and DNA samples. We constructed a 263 marker panel from filtering genome-wide association scans of the NMR in each study. We then applied seven machine learning techniques to train models of nicotine metabolism on the largest and most ancestrally diverse dataset (N=2239). The models were then validated using the other three studies (total N=1415). Using cross-validation, we found the correlations between the observed and predicted NMR ranged from 0.69 to 0.97 depending on the model. When predictions were averaged in an ensemble model, the correlation was 0.81. The ensemble model generalizes well in the validation studies across ancestries, despite differences in the measurements of NMR between studies, with correlations of: 0.52 for African ancestry, 0.61 for Asian ancestry, and 0.46 for European ancestry. The most influential predictors of NMR identified in more than two models were rs56113850, rs11878604, and 21 other genetic variants near CYP2A6 as well as age and ancestry. CONCLUSIONS: We have developed an ensemble of seven models for predicting the NMR across ancestries from genotypes and age, gender and BMI. These models were validated using three datasets and associate with nicotine dosages. The knowledge of how an individual metabolizes nicotine could be used to help select the optimal path to reducing or quitting tobacco use, as well as, evaluating risks of tobacco use.

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.

The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8R/S)-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dGuo, 1) and the lipid peroxidation-related DNA adduct 1,N6-etheno-dAdo (εdAdo, 2) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

Surviving through story: Experiences of people with learning disabilities in the covid19 pandemic 2020-2021.

Background: History starts from where we are now - it is not just things that happened a long time ago. The global pandemic began in 2019. It has changed the lives of people with learning disabilities. We began our project during the first lockdown in April 2020. We came together to set up a website to collect stories and support and learn from each other about how to survive and keep strong. Storytelling is very important because it helps us understand what is going on. It is also a way to capture the history of people with learning disabilities at a very difficult time. We know that thousands of people with learning disabilities became ill and died in the flu epidemic of 1918. But nobody recorded their stories in their own words. We want to make sure this does not happen again, so we created an archive to help us remember. Methods: The project was managed with an advisory group of people with and without learning disabilities who met monthly to monitor the collection and analysis of stories on the site. A site audit was performed regularly to determine the themes in the stories and who had submitted. The article describes the progress of the project, the stories we have shared, and the challenges we have faced. Conclusions: We discuss how people with learning disabilities have been presented in the media and our views about the way we are not heard, or always shown as vulnerable victims. We have found many sad stories, but also positive ones about people being creative and supportive. We look forward to the future and share our ideas about how society could be different and more inclusive. Being part of this project has given us confidence to know we are not alone, and shown us how we can help with the recovery.

Assessing tobacco smoke exposure in pregnancy from self-report, urinary cotinine and NNAL: a validation study using the New Hampshire Birth Cohort Study.

OBJECTIVES: Accurate assessment of tobacco smoke exposure is key to evaluate its effects. We sought to validate and establish cut-offs for self-reported smoking and secondhand smoke (SHS) exposure during pregnancy using urinary cotinine and 4-(methylnitrosamino)-1-(-3-pyridyl)-1-butanol (NNAL) in a large contemporary prospective study from the USA, with lower smoking prevalence than has previously been evaluated. DESIGN: Prospective birth cohort. SETTING: Pregnancy clinics in New Hampshire and Vermont, USA. PARTICIPANTS: 1396 women enrolled in the New Hampshire Birth Cohort Study with self-reported smoking, urinary cotinine, NNAL and pregnancy outcomes. PRIMARY AND SECONDARY OUTCOME MEASURES: Cut-offs for urinary cotinine and NNAL concentrations were estimated from logistic regression models using Youden's method to predict SHS and active smoking. Cotinine and NNAL were each used as the exposure in separate multifactorial models for pregnancy outcomes. RESULTS: Self-reported maternal smoking was: 72% non-smokers, 5.7% ex-smokers, 6.4% SHS exposure, 6.2% currently smoked, 10% unreported. Cotinine and NNAL levels were low and highly intercorrelated (r=0.91). Geometric mean cotinine, NNAL were 0.99 ng/mL, 0.05 pmol/mL, respectively. Cotinine cut-offs for SHS, current smoking were 1.2 ng/mL and 1.8 ng/mL (area under curve (AUC) 95% CI: 0.52 (0.47 to 0.57), 0.90 (0.85 to 0.94)). NNAL cut-off for current smoking was 0.09 pmol/mL (AUC=0.82 (95% CI 0.77 to 0.87)). Using cotinine and NNAL cut-offs combined gave similar AUC to cotinine alone, 0.87 (95% CI 0.82 to 0.91). Cotinine and NNAL gave almost identical effect estimates when modelling pregnancy outcomes. CONCLUSIONS: In this population, we observed high concordance between self-complete questionnaire smoking data and urinary cotinine and NNAL. With respect to biomarkers, either cotinine or NNAL can be used as a measure of tobacco smoke exposure overall but only cotinine can be used to detect SHS.

What relates to length of stay in a sober living home among women with histories of victimization and addiction? A longitudinal analysis.

Despite preliminary research suggesting that length of stay in sober living homes (SLHs) is related to sustained sobriety, little research has examined factors that relate to length of stay in SLHs. The purpose of the proposed exploratory study was to prospectively examine baseline characteristics of women with histories of addiction and victimization as correlates of length of stay in a trauma-informed, gender-responsive SLH. Participants (N = 45) were surveyed three times over a 1-year period. Women were invited to participate within a week of their arrival to the SLH. Nearly two-thirds (62.2%, n = 28) of women stayed under 3 months, and 37.8% (n = 17) of women stayed over 3 months. Whereas older age and greater financial worries were associated with staying over 3 months at the SLH, other variables (e.g., demographics, mental health, recent victimization, recent substance use) were unrelated. Findings indicate that efforts may be needed to ensure that younger women as well as women with less financial worries, who may be less likely to stay for longer periods of times at SLHs, have adequate support for sobriety.

A Randomized Trial of Nicotine versus No-nicotine E-cigarettes Among African American Smokers: Changes in Smoking and Tobacco Biomarkers.

INTRODUCTION: The objective of this clinical trial was to compare the effects of e-cigarettes with and without nicotine on patterns of combustible cigarette use and biomarkers of exposure to tobacco toxicants among African American smokers. METHODS: African American smokers (n = 234) were enrolled in a 12-week, single blind, randomized controlled trial and assigned to ad lib use of nicotine e-cigarettes with or without menthol (2.4% nicotine [equivalent to combustible cigarettes], n = 118), or no-nicotine e-cigarettes (n = 116) for 6 weeks. Surveys were administered at baseline, 2, 6, and 12 weeks, and urinary biomarkers 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and total nicotine equivalents (TNE) were assessed at baseline and 6 weeks. RESULTS: Participants smoked an average of 11.4 cigarettes per day (CPD) and 88% used menthol cigarettes at baseline. At Week 6, the nicotine group reported using e-cigarettes 9.1 times per day compared to 11.4 times in the no-nicotine group (p = 0.42). Combustible cigarette smoking decreased 3.0 CPD in the nicotine group compared to 2.7 CPD in the no-nicotine group (p = 0.74). Neither TNE nor NNAL changed significantly between baseline and Week 6. There were no differences in nicotine withdrawal symptoms between treatment groups. Smoking reduction persisted in both groups at Week 12. CONCLUSIONS: Contrary to our hypotheses, nicotine e-cigarettes did not significantly reduce the use of combustible cigarettes compared to no-nicotine e-cigarettes in this cohort of African American smokers. Findings suggest e-cigarettes are modestly associated with the decreased use of combustible cigarettes among non-treatment seeking smokers, regardless of nicotine content, but without a reduction in tobacco toxicants. IMPLICATIONS: Although e-cigarettes have the potential to reduce harm if substituted for combusted cigarettes (or if they promoted cessation) because of lower levels of tobacco toxicants, this study suggests ad lib use of e-cigarettes among African American smokers, with or without nicotine, results in modest smoking reduction but does not change toxicant exposure in a cohort where smoking cessation or reduction is not the goal. These data suggest that testing future harm reduction interventions using e-cigarettes should include more specific behavioral change coaching, including substituting for or completely stopping combusted cigarettes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov - NCT03084315.

Cigarette Smokers Versus Cannabis Smokers Versus Co-users of Cigarettes and Cannabis: A Pilot Study Examining Exposure to Toxicants.

INTRODUCTION: Studies suggest tobacco and cannabis co-users may experience greater toxicant exposure than exclusive cigarette (ET) smokers. No study has systematically tested differences in toxicant exposure among co-users, exclusive cannabis (ECa) smokers, and ET smokers. AIMS AND METHODS: Adult daily cigarette smokers and/or weekly cannabis smokers completed two laboratory visits. Co-users (n = 19) tested positive for urinary 11-nor-9-carboxy-Δ 9-tetrahydrocannabinol (THCCOOH), self-reported cannabis use ≥1 per week, and smoked ≥5 cigarettes per day (CPD). ET smokers (n = 18) denied past month cannabis use, tested negative for urinary THCCOOH and smoked ≥5 CPD. ECa smokers (n = 16) tested positive for urinary THCCOOH, self-reported cannabis use ≥1 per week, and denied past month tobacco use (NicAlert <3). Self-reported tobacco and cannabis use were collected at both visits. First morning urinary tobacco and combustion-related biomarkers of exposure were compared following a cannabis or tobacco smoking session (visit 2). RESULTS: Co-users and ET smokers had higher levels of exhaled carbon monoxide, total nicotine equivalents, metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL), and all four measured mercapturic acids (measures of volatile organic compounds) than ECa smokers (ps < .005). ET smokers (geometric mean = 7220.2 pmol/mg) had higher levels of 2-hydroxypropylmercapturic acid than co-users (geometric mean = 5348.7 adjusted p = .009). Phenanthrene tetraol did not differ by group (p > .05). CONCLUSIONS: Co-users and ET smokers demonstrated comparable levels of biomarkers of exposure to harmful constituents despite smoking similar amounts of tobacco. ECa smokers demonstrated lower levels of toxicant exposure for most biomarkers. IMPLICATIONS: Although ECa smokers are exposed to significantly lower levels of harmful constituents compared with co-users and exclusive cigarette smokers, this group is still exposed to higher levels of toxicants than observed in studies of nonsmokers. Additionally, these three groups were exposed to similar levels of phenanthrene tetraol. It is important to account for cannabis use in studies examining biomarkers of exposure among cigarette smokers. Additionally, further research is needed examining exposure to harmful chemicals among various types of cannabis and tobacco users.

Post-traumatic Growth in Women With Histories of Addiction and Victimization Residing in a Sober Living Home.

Research consistently documents the deleterious sequelae of interpersonal trauma, including domestic and sexual violence (DSV). More recently, however, researchers and practitioners have focused on positive outcomes, such as post-traumatic growth (PTG), in survivors of DSV. Although research has begun to document the prevalence and correlates of PTG, no study to our knowledge has explored PTG in a sample of women with histories of addiction and victimization residing in a trauma-informed sober living home (SLH). The purpose of the current study was to examine this gap in the literature. Participants were 59 women (89.8% White; 86.4% heterosexual; mean age = 41.6) who completed a survey while residing in a SLH. Most women reported moderate to high levels of PTG. At the bivariate level PTG was related to less depression, post-traumatic stress disorder, and financial worries, and greater active coping, and sense of community. PTG was also related to the absence of past 6-month physical intimate partner violence. In regression analyses, PTG was related to less depression and greater sense of community. These data offer insights into modifiable factors such as fostering a sense of community while also promoting mental health treatment that could be the focus of interventions to increase PTG in women with histories of addiction and victimization residing in SLHs.

Multiethnic Prediction of Nicotine Biomarkers and Association With Nicotine Dependence.

INTRODUCTION: The nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, and exposure research in studies without measured biomarkers. AIMS AND METHODS: We screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants, age, ethnicity and sex, and, in additional modeling, cigarettes per day (CPD), (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles and evaluated external validity using dependence measures in 1864 treatment-seeking smokers in two ethnic groups. RESULTS: The genomic regions with the most selected and included variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68) and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and included. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD and predicted TNE (without CPD) with CPD, time-to-first-cigarette, and Fagerström total score. CONCLUSIONS: Nicotine metabolites, genome-wide data, and statistical learning approaches developed novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations helped define genetically influenced components of nicotine dependence. IMPLICATIONS: We demonstrate development of robust models and multiethnic prediction of the uNMR and TNE using statistical and machine learning approaches. Variants included in trained models for nicotine biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites, and related disease. Association of the two predicted nicotine biomarkers with Fagerström Test for Nicotine Dependence items supports models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.