Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.
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ABSTRACT:
SUBMITTER: Philibert R
PROVIDER: S-EPMC4822186 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.
Philibert Robert R Hollenbeck Nancy N Andersen Eleanor E McElroy Shyheme S Wilson Scott S Vercande Kyra K Beach Steven R H SR Osborn Terry T Gerrard Meg M Gibbons Frederick X FX Wang Kai K
Frontiers in psychiatry 20160406
Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers' progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer ...[more]
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Project description:BackgroundNumerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood.MethodsCord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model.ResultsMethylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E-13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (- 4.1%, p = 1.8E-02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E-09) and nRBCs (p = 4.8E-08), as well as cotinine levels (regression p = 1.1E-07 and p = 3.6E-04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation.ConclusionsPrenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.
| S-EPMC6558773 | biostudies-literature
Project description:Smoking is the largest preventable cause of mortality and the largest environmental driver of epigenetic aging. Contingency management-based strategies can be used to treat smoking but require objective methods of verifying quitting status. Prior studies have suggested that cg05575921 methylation reverts as a function of smoking cessation, but that it can be used to verify the success of smoking cessation has not been unequivocally demonstrated. To test whether methylation can be used to verify cessation, we determined monthly cg05575921 levels in a group of 67 self-reported smokers undergoing biochemically monitored contingency management-based smoking cessation therapy, as part of a lung imaging protocol. A total of 20 subjects in this protocol completed three months of cotinine verified smoking cessation. In these 20 quitters, the reversion of cg05575921 methylation was dependent on their initial smoking intensity, with methylation levels in the heaviest smokers reverting to an average of 0.12% per day over the 3-month treatment period. In addition, we found suggestive evidence that some individuals may have embellished their smoking history to gain entry to the study. Given the prominent effect of smoking on longevity, we conclude that DNA methylation may be a useful tool for guiding and incentivizing contingency management-based approaches for smoking cessation.
| S-EPMC7760261 | biostudies-literature
Project description:Genetic Architecture of Smoking and Smoking Cessation
| PRJNA75689 | ENA
Project description:BackgroundThe number of mobile apps that support smoking cessation is growing, indicating the potential of the mobile phone as a means to support cessation. Knowledge about the potential end users for cessation apps results in suggestions to target potential user groups in a dissemination strategy, leading to a possible increase in the satisfaction and adherence of cessation apps.ObjectiveThis study aimed to characterize potential end users for a specific mobile health (mHealth) smoking cessation app.MethodsA quantitative study was conducted among 955 Dutch smokers and ex-smokers. The respondents were primarily recruited from addiction care facilities and hospitals through Web-based media via websites and forums. The respondents were surveyed on their demographics, smoking behavior, and personal innovativeness. The intention to use and the attitude toward a cessation app were determined on a 5-point Likert scale. To study the association between the characteristics and intention to use and attitude, univariate and multivariate ordinal logistic regression analyses were performed.ResultsThe multivariate ordinal logistic regression showed that the number of previous quit attempts (odds ratio [OR] 4.1, 95% CI 2.4-7.0, and OR 3.5, 95% CI 2.0-5.9) and the score on the Fagerstrom Test of Nicotine Dependence (OR 0.8, 95% CI 0.8-0.9, and OR 0.8, 95% CI 0.8-0.9) positively correlates with the intention to use a cessation app and the attitude toward cessation apps, respectively. Personal innovativeness also positively correlates with the intention to use (OR 0.3, 95% CI 0.2-0.4) and the attitude towards (OR 0.2, 95% CI 0.1-0.4) a cessation app. No associations between demographics and the intention to use or the attitude toward using a cessation app were observed.ConclusionsThis study is among the first to show that demographic characteristics such as age and level of education are not associated with the intention to use and the attitude toward using a cessation app when characteristics related specifically to the app, such as nicotine dependency and the number of quit attempts, are present in a multivariate regression model. This study shows that the use of mHealth apps depends on characteristics related to the content of the app rather than general user characteristics.
| S-EPMC5913574 | biostudies-literature
Project description:BackgroundGamification in smoking cessation apps has been found to improve cognitive outcomes associated with higher odds of quitting. Although some research has shown that gamification can also positively impact behavioral outcomes such as smoking cessation, studies have largely focused on physical activity and mental health. Only a few studies have explored the effects of gamification on smoking cessation outcomes, of which the majority have adopted qualitative methodologies and/or assessed engagement with apps using self-report.ObjectiveThis study aimed to explore levels of user engagement with gamification features in a smoking cessation app via in-app metrics. Specifically, the objective of this paper was to investigate whether higher engagement with gamification features is associated with the likelihood of quitting in the short term.MethodsData from a larger online study that recruited smokers seeking to quit were analyzed to address the objectives presented in this paper. The study took place between June 2019 and July 2020, and participants were primarily recruited via social media posts. Participants who met the eligibility criteria used 1 of 2 mobile apps for smoking cessation. In-app metrics shared by the developer of one of the smoking cessation apps, called Kwit, were used to assess engagement with gamification features. Out of 58 participants who used the Kwit app, 14 were excluded due to missing data or low engagement with the app (ie, not opening the app once a week). For the remaining 44 participants, mean (SD) values were calculated for engagement with the app using in-app metrics. A logistic regression model was used to investigate the association between engagement with gamification and 7-day smoking abstinence.ResultsIn total, data from 44 participants who used the Kwit app were analyzed. The majority of participants were male, married, and employed. Almost 30% (n=13) of participants self-reported successful 7-day abstinence at the end of the study. On average, the Kwit app was opened almost 31 (SD 39) times during the 4-week study period, with the diary feature used the most often (mean 22.8, SD 49.3). Moreover, it was found that each additional level unlocked was associated with approximately 22% higher odds of achieving 7-day abstinence after controlling for other factors such as age and gender (odds ratio 1.22, 95% CI 1.01-1.47).ConclusionsThis study highlights the likely positive effects of certain gamification elements such as levels and achievements on short-term smoking abstinence. Although more robust research with a larger sample size is needed, this research highlights the important role that gamification features integrated into mobile apps can play in facilitating and supporting health behavior change.
| S-EPMC9932870 | biostudies-literature
Project description:Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders.
2015-11-23 | GSE53519 | GEO
Project description:ObjectiveThere is some evidence for biomarker feedback when combined with cessation counseling for reducing smoking in pregnancy. This randomized controlled pilot study evaluated feasibility and potential efficacy of a social-cognitive theory (SCT)-based biomarker feedback intervention among pregnant Alaska Native (AN) smokers.MethodsParticipants were randomly assigned to receive three study calls (10-20 min each): (1) biomarker feedback intervention (n = 30) including personalized cotinine results and feedback on their baby's likely exposure to carcinogen metabolite NNAL, or (2) contact control usual care condition based on the 5As (n = 30). Assessments were conducted at baseline, post-treatment, and delivery.ResultsHigh rates of treatment compliance, study retention, and treatment acceptability were observed in both groups. 7-day point prevalence smoking abstinence rates at delivery verified with urinary cotinine were the same in both study groups (20% intent-to-treat analysis, 26% per-protocol). SCT-based measures did not change differentially from baseline by study group.ConclusionThis trial supports the feasibility and acceptability of providing biomarker feedback within the clinical care delivery system, but the intervention did not promote increased smoking cessation during pregnancy compared to usual care.Practice implicationsEfforts are needed to promote the usual care and to develop alternative biomarker feedback messaging for pregnant AN women.
| S-EPMC6421103 | biostudies-literature
Project description:Introduction:The prevalence of smoking during pregnancy for Alaska Native (AN) women is more than triple that of non-Native Alaska women. In this qualitative study, we solicited input from AN women and others to determine how best to present findings from an earlier study demonstrating a strong correlation between biomarkers for maternal smoking (cotinine) and neonatal exposure to a tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) to motivate cessation. Methods:We developed a brochure incorporating generalized biomarker information. Using in-depth individual interviews with pregnant and postpartum AN women and partners/family members, we explored applicability and acceptability of the information. Postpartum women, who had participated in the earlier correlation study, additionally received their individual biomarker results. We assessed whether being presented general or individual biomarker information would motivate cessation using content analysis. Results:We conducted 39 interviews: 16 pregnant women, 12 postpartum women, and 11 partners/family members. Overall, participants agreed the biomarker information was new, but understandable as presented. Postpartum women shared that learning their personal results inspired them to want to quit or cut back smoking while pregnant women indicated the generalized correlation information was less helpful in motivating cessation. Conclusion:Generalized information about fetal exposure to carcinogens may be more effective in motivating pregnant women to quit smoking when combined with individual cotinine testing. Implications:Using feedback from this study, we refined and are currently evaluating an intervention incorporating generalized correlation information from Phase I and cotinine testing to determine its effectiveness in motivating smoking cessation among pregnant AN women.
| S-EPMC5896456 | biostudies-literature
Project description:Despite being highly motivated to quit, many of my patients struggle with smoking cessation during pregnancy. Can you comment on the current treatment options and discuss their safety and efficacy during pregnancy?Given the considerable and well-documented adverse effects of antenatal smoking on mother and fetus, pharmacotherapy for smoking cessation should be considered. Available medications include nicotine replacement therapy, sustained-release bupropion, and varenicline. Nicotine replacement therapy and bupropion do not appear to increase the risk of major malformations; however, there is currently limited evidence on the use of varenicline during pregnancy. Given that these agents are only marginally successful in smoking cessation, their use should always be accompanied by behavioural counseling and education to maximize quit rates.
| S-EPMC3352787 | biostudies-other
Project description:People who smoke make up a significant number of those admitted to hospital (NICE 2014). Being admitted to hospital can present a unique opportunity to attempt to stop smoking. Many smokers find quitting very difficult (Rigotti et al 2007), in large part due to them living and working in environments that contain many cues and triggers associated with nicotine consumption and smoking behaviours. Hospitals generally do not contain such environmental prompts to smoke. In the community, smokers have access to numerous types of support including GP's, pharmacies and Stop Smoking Services (SSS). Once admitted to hospital access to such support is significantly diminished. Given that many patients may be highly motivated to attempt to stop smoking due to heightened concerns about their health and being in an environment not associated with their smoking habits, it seems prudent to ensure there is access to all the levels of smoking cessation support available outside of the hospital. Not providing such support neglects implementing an evidence based, cost-effective health intervention in a major health setting (NICE 2014). A SSS pathway was designed that enabled existing hospital healthcare staff to be trained to identify patients that smoke, ask if the patient is considering quitting or abstaining whilst in hospital. If motivated to quit or abstain, to complete an assessment. This being based around dependence to nicotine and motivation to quit. Access to all available stop smoking medications should be included. Medication should only be provided alongside some level of motivational support up to discharge. Training core staff was felt to be the best option. They are available outside of office hours and access hospital systems such as pharmacy more readily than satellite staff. On discharge the patient is 'handed over' to SSS for continued contact and support once at home. Over 200 staff are trained to complete the assessment and support inpatients to stop or abstain. Approximately 30-35 referrals are made to the local SSS each month, the quit rate at 4 weeks averaging around 40-45%. Most referrals are seen from cardiology and respiratory. All hospital departments should identify staff to be trained to offer cessation support to their patients .
| S-EPMC4645840 | biostudies-other