Smoking Cessation Pharmacotherapy Research Articles

Pilot Randomized Clinical Trial of a Text Messaging-Based Intervention for Smoking Cessation Among Young People Experiencing Homelessness.

Smoking rates are alarmingly high among young people experiencing homelessness (YEH), yet there are no evidence-based cessation programs for this population. This paper presents results from a pilot evaluation of a text messaging-based smoking cessation treatment, as an adjunct to brief group cessation counseling, to improve abstinence rates among 18-25-year-old smokers experiencing homelessness. The goal of this study was to estimate effect sizes for a larger trial and it was not powered to detect group differences. YEH smokers who had a working cell phone with them at recruitment were randomized to receive a group counseling session, nicotine patches, and written material on quitting (n = 37) or a similar program that also included a 6-week automated text messaging intervention (TMI) to provide ongoing support for quitting (n = 40). Smoking outcomes were evaluated through a 90-day follow-up. Seven-day point prevalence abstinence at 90-day follow-up was higher in the TMI condition than standard condition (17.50% vs. 8.11%, respectively; Cohen's h = .37); however, the 90-day continuous abstinence rate was not statistically different from zero in either condition. Reductions in the number of days smoked in the past 30 days from baseline to follow-up were greater in the TMI condition than the standard condition (-14.24 vs. -8.62, respectively; Cohen's d = .49). Adding a 6-week TMI support to a brief group counseling and pharmacotherapy protocol holds promise for smoking reduction and abstinence among YEH smokers. Results indicate that further development and evaluation of the TMI in this population is warranted. ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585. This is the first study to evaluate the feasibility of using a text messaging-based intervention (TMI) for behavior change with 18-25 year olds experiencing homelessness, and more specifically, the first to test a TMI to provide ongoing support for smoking cessation. Small to medium effect sizes for the TMI are promising in terms of implementing a TMI using participants' own cell phones, as well as the efficacy of this approach as an adjunct to standard care (brief group counseling and pharmacotherapy) for smoking cessation among YEH.

Nicotine Replacement Therapy during Pregnancy and Child Health Outcomes: A Systematic Review.

Tobacco smoking in pregnancy is a worldwide public health problem. A majority of pregnant smokers need assistance to stop smoking. Most scientific societies recommend nicotine replacement therapy (NRT) during pregnancy but this recommendation remains controversial because of the known fetal toxicity of nicotine. The objective of this systematic review was to provide an overview of human studies about child health outcomes associated with NRT use during pregnancy. The electronic databases MEDLINE, the Cochrane Database, Web of Science, and ClinicalTrials.gov were searched from the inception of each database until 26 December 2020. A total of 103 articles were identified through database searching using combination of keywords. Out of 75 screened articles and after removal of duplicates, ten full-text articles were assessed for eligibility and five were included in the qualitative synthesis. NRT prescription seems to be associated with higher risk of infantile colic at 6 months as in case of smoking during pregnancy, and with risk of attention-deficit/hyperactivity disorder. No association between NRT during pregnancy and other infant health disorders or major congenital anomalies has been reported. Well-designed controlled clinical trials with sufficient follows-up are needed to provide more information on the use of NRT or other pharmacotherapies for smoking cessation during pregnancy on post-natal child health outcomes.

Comparative Analysis of Three Different Drug Distribution Schemes for Smoking Cessation.

This study aimed to compare the success rate of 3 different drug prescription policies: Free drugs with online system prescription, free drugs with doctor's prescription, and drugs paid for by patients with doctor's prescription. The effect of 2 different Ministry of Health (MoH) projects with free-of-charge and self-payment pharmacotherapies for smoking cessation were compared. Patients who completed 6 months of pharmacotherapy and follow-up were evaluated. The first period was free-of-charge medication, which was determined by an online system, the following period was the self-payment period, and the third period was free medication, which was prescribed by a doctor. In all the groups, smoking habits in pack years and comorbidities of the patients were recorded, and pulmonary function tests (PFTs) and expiratory carbon dioxide (CO2) measurements were performed. Patients who had an expiratory CO2 level >5 ppm at the control visits were accepted as quitters. A total of 829 patients with 438 patients in the first free-of-charge period (group 1), 111 in the self-payment period (group 2), and 280 in the second free-of-charge period (group 3) were enrolled in the study. Smoking cessation rates were significantly higher in the self-payment medication group (25%) according to the MoH's free-of-charge project groups. There was no difference in smoking cessation rates between the 2 free-of-charge medication project groups (15% in group 1 and 11% of group 3). Among all the patients, we compared 124 patients who quit smoking with 705 patients who did not. The quitters were older, mostly male, and heavier smokers. In addition, the number of patients with chronic obstructive pulmonary disease and obstructive PFT rates were higher among the quitters. Their dependency score, PFTs, and the use of free medication was lower, and treatment duration was longer. Independent factors that increased smoking cessation success were longer treatment duration, lower dependency score, and self-payment of medication. Free medications provided via 2 different modalities did not increase the smoking cessation success. Paying for the medication, lower dependency score, and longer treatment duration increased smoking cessation success independently.

Experiences With Smoking Cessation Attempts and Prior Use of Cessation Aids in Smokers With HIV: Findings From a Focus Group Study Conducted in Durham, North Carolina.

Cigarette smoking remains disproportionately prevalent and is increasingly a cause of death and disability among people with HIV (PWH). Many PWH are interested in quitting, but interest in and uptake of first-line smoking cessation pharmacotherapies are varied in this population. To provide current data regarding experiences with and perceptions of smoking cessation and cessation aids among PWH living in Durham, North Carolina, the authors conducted five focus group interviews (total n = 24; 96% African American) using semistructured interviews. Interviews were recorded, transcribed, coded, and thematically analyzed. Major themes included ambivalence and/or lack of interest in cessation; presence of cessation barriers; perceived perceptions of ineffectiveness of cessation aids; perceived medication side effects; and conflation of the harms resulting from use of tobacco products and nicotine replacement therapy. Innovative and effective interventions must account for the aforementioned multiple barriers to cessation as well as prior experiences with and misperceptions regarding cessation aids.

Update on pharmacotherapy for smoking cessation

Cigarette smoking is the leading preventable cause of death, and smoking cessation is the only way to reduce the risk of developing and dying from smoking-related diseases. The binding of nicotine to <i>α</i>4<i>β</i>2 nicotinic acetylcholine receptors in the ventral tegmental area causes transmission of signals to nuclear accumbens, where neurotransmitters, such as dopamine, are released. Euphoric feelings and satisfaction acquired due to the released neurotransmitters make smokers reach for a cigarette once again after a short while, thereby completing a repeating cycle of addiction. Medications for smoking cessation, such as nicotine replacement therapy (NRT), bupropion, and varenicline, are designed to cope with nicotine addiction. NRT provides nicotine to ameliorate withdrawal symptoms, and all forms of NRT are equally effective in smoking cessation than placebo. Bupropion, originally developed as an antidepressant, decreases craving, leading to smoking cessation, which makes it one of the first-line drugs for smoking cessation. Many studies have shown that varenicline is the most effective agent for smoking cessation. No significant long-term adverse events have been reported for NRT, bupropion, or varenicline. However, bupropion should not be used in patients with an increased risk for seizure.

A Systematic Review and Scoping Analysis of Smoking Cessation after a Urological Cancer Diagnosis

Smoking cessation after a urologic cancer diagnosis significantly benefits patients. It is not well known how often patients quit after diagnosis or how urologists intervene to support patients' smoking cessation efforts. To examine rates of smoking cessation after diagnosis among patients with urologic cancers and to assess how often patients are given advice and support to quit smoking in the urology setting. Following the PRISMA guidelines, a systematic review was conducted of the available studies on smoking cessation after a urologic cancer diagnosis during April 2020 by a trained medical librarian using the MEDLINE, PsycInfo, Embase, and Cochrane CENTRAL databases. Studies were included based on three independent reviews and if they met a priori inclusion/exclusion criteria. In total, 2568 records were identified, 31 of which were included for final analysis. Four studies (patient n=587) reported outcomes related to the prospective implementation of a smoking cessation program with patient-level quit rates ranging from 3.2% to 47.3%. Twenty one studies reported outcomes of passive (no directed, active intervention) smoking cessation after the diagnosis of a urologic cancer (patient n=3669) with widely varying quit rates. In general, the quality of included studies was poor. There was no standardization of the measurement or timing of outcomes and few studies included validated survey instruments or biochemical confirmation of cessation. Seventeen studies included data on whether patients received advice to quit smoking after diagnosis. The proportion of patients in each study who were told to quit ranged from 2.8-78.3%. There are few smoking cessation interventions that have been prospectively implemented and reported in the urology literature and studies on quit rates after diagnosis are limited. The paucity of quality data and lack of smoking cessation interventions being used in routine urologic oncology care underscores the need for more rigorous study and implementation of evidence-based practices in this area.

USPSTF recommends pharmacotherapy for tobacco interventions in nonpregnant adults

Last week, the U.S. Preventive Services Task Force (USPSTF) issued a recommendation statement in JAMA updating its 2015 recommendation on tobacco smoking treatment. The recommendation statement concludes with high certainty that the net benefit of behavioral interventions and U.S. Food and Drug Administration (FDA)–approved pharmacotherapy for tobacco smoking cessation, alone or combined, in nonpregnant adults who smoke is substantial. The USPSTF recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco and provide behavioral interventions and FDA‐approved pharmacotherapy for cessation to nonpregnant adults who use tobacco, and that clinicians ask all pregnant persons about tobacco use, advise them to stop using tobacco and provide behavioral interventions for cessation to pregnant persons who use tobacco. However, the USPSTF found that the balance of benefits and harms of pharmacotherapy interventions for tobacco cessation in pregnant persons is insufficient.

Behavioural interventions for smoking cessation: an overview and network meta-analysis.

Behavioural interventions for smoking cessation: an overview and network meta-analysis.

An Open Trial of Metacognitive Remediation Therapy and Pharmacotherapy to Promote Smoking Cessation among Individuals with Psychotic-Spectrum Disorders.

Introduction Individuals with psychotic-spectrum disorders may smoke due to the ameliorating effect of nicotine on the cognitive deficits that accompany these illnesses. Metacognitive remediation therapy (MCR) has been shown to produce improvements in cognitive functioning among individuals with psychotic-spectrum disorders and provides a foundation for a novel smoking cessation intervention for this population. Aims To complete an open investigation of pharmacotherapy and a modified version of MCR [MCR to Quit (MCR-Q)] in promoting smoking cessation among individuals with psychotic-spectrum disorders. Methods Forty-nine individuals with a psychotic-spectrum disorder and who currently smoke cigarettes participated in MCR-Q while also receiving evidence-based smoking cessation pharmacotherapy. Tobacco use was assessed as follows: (i) prior to MCR-Q, (ii) immediately after completing MCR-Q, and (iii) six weeks after completion of MCR-Q. Results/Findings. During participation in MCR-Q, nearly 80% of participants made a 24-hour quit attempt. Following the completion of MCR-Q, participants experienced reductions in level of nicotine dependency and exhaled carbon monoxide, with reductions in nicotine dependency sustained six weeks after completion of MCR-Q. Over the course of their participation in MCR-Q, participants reported strong therapeutic alliance with their MCR-Q therapist and high levels of intrinsic motivation with regard to completing MCR-Q exercises. Conclusions The results from the current study suggest cautious optimism with regard to the use of MCR-Q in combination with medication for individuals with psychotic-spectrum disorders who want to quit smoking.

Transferability of Ancestry‐Specific and Cross‐Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations

The Nicotine Metabolite Ratio (NMR; 3-hydroxycotinine/cotinine), a highly heritable index of nicotine metabolic inactivation by the CYP2A6 enzyme, is associated with numerous smoking behaviors and diseases, as well as unique cessation outcomes. However, the NMR cannot be measured in nonsmokers, former smokers, or intermittent smokers, for example, in evaluating tobacco-related disease risk. Traditional pharmacogenetic groupings based on CYP2A6 * alleles capture a modest portion of NMR variation. We previously created a CYP2A6 weighted genetic risk score (wGRS) for European (EUR)-ancestry populations by incorporating independent signals from genome-wide association studies to capture a larger proportion of NMR variation. However, CYP2A6 genetic architecture is unique to ancestral populations. In this study, we developed and replicated an African-ancestry (AFR) wGRS, which captured 30-35% of the variation in NMR. We demonstrated model robustness against known environmental sources of NMR variation. Furthermore, despite the vast diversity within AFR populations, we showed that the AFR wGRS was consistent between different US geographical regions and unaltered by fine AFR population substructure. The AFR and EUR wGRSs can distinguish slow from normal metabolizers in their respective populations, and were able to reflect unique smoking cessation pharmacotherapy outcomes previously observed for the NMR. Additionally, we evaluated the utility of a cross-ancestry wGRS, and the capacity of EUR, AFR, and cross-ancestry wGRSs to predict the NMR within stratified or admixed AFR-EUR populations. Overall, our findings establish the clinical benefit of applying ancestry-specific wGRSs, demonstrating superiority of the AFR wGRS in AFRs.

A Pilot Randomized Clinical Trial of Remote Varenicline Sampling to Promote Treatment Engagement and Smoking Cessation.

Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling. Smokers (N = 99), both motivated to quit and not, were recruited and randomized to varenicline sampling versus not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2-4 wks), with minimally suggestive guidance on use. Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5 mg to 2 mg. Relative to control, varenicline sampling increased motivation (p = 0.006) and confidence to quit (p = 0.02), and decreased cigarette smoking (p = 0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in cigarettes per day (CPD), both immediately following the sampling exercise (Adjusted Odds Ratio [AOR] = 4.12; 95% CI: 1.39 to 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 to 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not. Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting. Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that nicotine replacement therapy (NRT) sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial. NCT #03742154.

Training general practitioners in the ABC versus 5As method of delivering stop-smoking advice: a pragmatic, two-arm cluster randomised controlled trial.

This study assessed the effectiveness of a 3.5-h training session for general practitioners (GPs) in providing brief stop-smoking advice and compared two methods of giving advice – ABC versus 5As – on the rates of delivery of such advice and of recommendations of evidence-based smoking cessation treatment during routine consultations.A pragmatic, two-arm cluster randomised controlled trial was carried out including a pre-/post-design for the analyses of the primary outcome in 52 GP practices in Germany. Practices were randomised (1:1) to receive a 3.5-h training session (ABC or 5As). In total, 1937 tobacco-smoking patients, who consulted trained GPs in these practices in the 6 weeks prior to or following the training, were included. The primary outcome was patient-reported rates of GP-delivered stop-smoking advice prior to and following the training, irrespective of the training method. Secondary outcomes were patient-reported receipt of recommendation/prescription of behavioural therapy, pharmacotherapy or combination therapy for smoking cessation, and the effectiveness of ABC versus 5As regarding all outcomes.GP-delivered stop-smoking advice increased from 13.1% (n=136 out of 1039) to 33.1% (n=297 out of 898) following the training (adjusted odds ratio (aOR) 3.25, 95% CI 2.34–4.51). Recommendation/prescription rates of evidence-based treatments were low (<2%) pre-training, but had all increased after training (e.g. behavioural support: aOR 7.15, 95% CI 4.02–12.74). Delivery of stop-smoking advice increased non-significantly (p=0.08) stronger in the ABC versus 5As group (aOR 1.71, 95% CI 0.94–3.12).A single training session in stop-smoking advice was associated with a three-fold increase in rates of advice giving and a seven-fold increase in offer of support. The ABC method may lead to higher rates of GP-delivered advice during routine consultations.

Smoking and Nicotine Effects on Surgery: Is Nicotine Replacement Therapy (NRT) a Safe Option?

Smoking and Nicotine Effects on Surgery: Is Nicotine Replacement Therapy (NRT) a Safe Option?

Abstract 16363: An 18-month Smoking Cessation Intervention Incorporating Pharmacotherapy and Behavioral Counseling Improves Tobacco Abstinence Rates in Adult Smokers With Serious Mental Illness (smi) in Community Mental Health Settings: Results of a Randomized Clinical Trial

Introduction: Tobacco smoking is the largest contributor to markedly elevated CVD and preventable death in persons with SMI. Trials of combined pharmacologic and behavioral treatments improve abstinence rates, but have targeted those ready to quit right away, and evidence-based treatments are rarely used in the community. Weight gain often accompanies abstinence. Our objective was to determine the effectiveness of an 18m smoking cessation pharmacotherapy and behavioral counseling intervention incorporating weight management and physical activity in persons with SMI. Hypothesis: The active intervention is more effective than control in achieving biochemically validated, 7-day point prevalence smoking abstinence at 18m. Methods: We conducted an RCT in 4 community mental health settings in 192 smokers with SMI, stratified by readiness to quit within 30d or in 1 to 6m. The active intervention group was offered 18m of 1 st -line cessation pharmacotherapy, smoking cessation and weight management counseling tailored to readiness to quit, and support for physical activity. Controls received a quit line referral. Results: Mean(SD) age was 49.6(11.7); cigarettes/day 12.1(9.5); BMI 32.0(7.6) kg/m 2 ; 49% were male, 48% African-American, 62% willing to quit in 30d, 95% completed 18m follow-up. At 18m, 27.8% of active group and 6.3% of controls achieved 7d smoking abstinence (p&lt;0.0001); adjusted odds ratio 6.0 (95% CI: 2.3 –15.6; p=0.0002). There was no significant modification of intervention effect on abstinence by readiness to quit. Mean difference in weight change over 18m between active and control was not significant (3.5 lbs, 95% CI: -3.3 –10.3; p=0.32). Conclusions: Offering 18m of evidence-based cessation treatment in the community substantially increased smoking abstinence without significant weight gain in SMI. Implementing best practice guidelines to treat all smokers regardless of readiness to quit should improve CVD health in this high-risk population.

Cost Effectiveness of Case Detection Strategies for the Early Detection of COPD.

The value of early detection and treatment of chronic obstructive pulmonary disease (COPD) is currently unknown. We assessed the cost effectiveness of primary care-based case detection strategies for COPD. A previously validated discrete event simulation model of the general population of COPD patients in Canada was used to assess the cost effectiveness of 16 case detection strategies. In these strategies, eligible patients (based on age, smoking history, or symptoms) received the COPD Diagnostic Questionnaire (CDQ) or screening spirometry, at 3- or 5-year intervals, during routine visits to a primary care physician. Newly diagnosed patients received treatment for smoking cessation and guideline-based inhaler pharmacotherapy. Analyses were conducted over a 20-year time horizon from the healthcare payer perspective. Costs are in 2019 Canadian dollars ($). Key treatment parameters were varied in one-way sensitivity analysis. Compared to no case detection, all 16 case detection scenarios had an incremental cost-effectiveness ratio (ICER) below $50,000/QALY gained. In the most efficient scenario, all patients aged ≥ 40years received the CDQ at 3-year intervals. This scenario was associated with an incremental cost of $287 and incremental effectiveness of 0.015 QALYs per eligible patient over the 20-year time horizon, resulting in an ICER of $19,632/QALY compared to no case detection. Results were most sensitive to the impact of treatment on the symptoms of newly diagnosed patients. Primary care-based case detection programs for COPD are likely to be cost effective if there is adherence to best-practice recommendations for treatment, which can alleviate symptoms in newly diagnosed patients.

Smoking cessation treatment for individuals with comorbid diabetes and serious mental illness in an integrated health care delivery system

IntroductionSmoking is a significant modifiable risk factor for mortality for persons with serious mental illness (SMI), who have a life expectancy 15–20 years shorter than the general population. Individuals with SMI and comorbid diabetes who are smokers face an even higher risk of cardiovascular complications and early death. Yet despite high rates of smoking among people with SMI, tobacco cessation interventions have not been broadly offered to this population. MethodsWe conducted a retrospective cohort study using electronic health records from 2014 in a large integrated care delivery system to examine whether use of smoking cessation pharmacotherapy among smokers with type 2 diabetes varies by serious mental illness (SMI) diagnosis. We analyzed smoking cessation medication prescription fills among adult smokers with diabetes, comparing those with SMI (N = 634) and without SMI (N = 18,021). Risk ratios were adjusted for age, gender, race, urban area type, and medical facility. ResultsOf the SMI group, 19.09% filled at least one smoking cessation prescription compared to 9.73% of the non-SMI group (adjusted risk ratio 1.80 [95% CI 1.52–2.13]; p < .001). For the SMI group, primary care providers wrote 80.24% of prescriptions, while psychiatrists wrote 8.81% of prescriptions. ConclusionsThese findings offer an example of a delivery system with higher uptake of smoking cessation pharmacotherapy among people with SMI than without SMI, and highlight the opportunity to provide more smoking cessation interventions in mental health care settings.

High-dose and low-dose varenicline for smoking cessation in adolescents: a randomised, placebo-controlled trial

Although cigarette smoking typically begins in adolescence, evidence for successful pharmacological smoking cessation interventions for this population is scarce. In adult smokers, varenicline is the most effective single pharmacotherapy. The aim of this study was to assess the efficacy and tolerability of varenicline for smoking cessation in adolescents. We did a randomised, placebo-controlled trial with adolescent smokers aged 12-19 years who were seeking treatment to quit at 57 outpatient centres (in the USA, Russia, South Korea, Taiwan, Canada, and Georgia). Participants were randomly assigned (1:1:1) to receive 12 weeks of high-dose varenicline (1 mg twice daily; 0·5 mg twice daily if bodyweight ≤55 kg), low-dose varenicline (0·5 mg twice daily; 0·5 mg once daily if bodyweight ≤55 kg), or placebo, then followed up for 40 additional weeks. At all visits, participants received brief, developmentally tailored smoking cessation counselling (<10 min per session) delivered by a trained counsellor. The primary efficacy outcome was continuous abstinence from weeks 9 to 12, measured via a Nicotine Use Inventory and confirmed by urine cotinine testing. The primary tolerability outcome was frequency of treatment-emergent adverse events, including neuropsychiatric adverse events, occurring after the first dose and within 30 days of the last dose of study medication. This trial is registered with ClinicalTrials.gov, NCT01312909. Between April 26, 2011, and Jan 18, 2018, 312 participants were enrolled and completed participation in the study: 109 in the high-dose varenicline group, 103 in the low-dose varenicline group, and 100 in the placebo group. The continuous abstinence rates from week 9 to 12 were 20% (22 of 109) in the high-dose varenicline group, 27% (28 of 103) in the low-dose varenicline group, and 18% (18 of 100) in the placebo group. Abstinence rates between high-dose varenicline and placebo groups (odds ratio [OR] 1·18 [95% CI 0·59-2·37]; p=0·63) and between low-dose varenicline and placebo groups (1·73 [0·88-3·39]; p=0·11) did not differ significantly. Treatment-emergent adverse events occurred in 65 (60%) of 108 participants in the high-dose group, 53 (53%) of 100 in the low-dose group, and 52 (53%) of 99 in the placebo group, and most were rated as mild. Neuropsychiatric treatment-emergent adverse events occurred in 18 (17%) of 108 participants in the high-dose group, 11 (11%) of 100 in the low-dose group, and 12 (12%) of 99 in the placebo group, and none was rated as severe. This trial did not show an advantage in abstinence with varenicline compared with placebo among adolescent smokers. The rates of treatment-emergent adverse events were similar to those in previous trials of adult smokers, raising no new tolerability signals. These findings do not support the use of varenicline as a first-line pharmacotherapy for smoking cessation in adolescents. Pfizer.

Early Life Exposure to Nicotine: Postnatal Metabolic, Neurobehavioral andRespiratory Outcomes and the Development of Childhood Cancers.

Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy and electronic nicotine delivery systems (e-cigarettes) have been developed as a pharmacotherapy for smoking cessation and are considered safer alternatives for women to smoke during pregnancy. The safety of nicotine replacement therapy use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring and increases the risk of adverse neurobehavioral outcomes, dysmetabolism, respiratory illness, and cancer. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health.

Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and progressive airflow obstruction. Tobacco smoking is the leading cause but not the only one. A postbronchodilator FEV1-FVC ratio less than 0.70 is required for a diagnosis of COPD. Inhaler therapy is the backbone of treatment and should be complemented by a multifaceted management strategy that includes counseling and pharmacotherapy for smoking cessation, pulmonary rehabilitation, treatment of comorbidities, administration of influenza and pneumococcal immunizations, and prescription of long-term oxygen therapy in hypoxemic patients.

Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo-Controlled Trial.

It is unclear if genetic variants affect smoking cessation treatment response. This study tested whether variants in the cholinergic receptor nicotinic alpha 5 subunit (CHRNA5)predict response to smoking cessation medication by directly comparing the two most effective smoking cessation pharmacotherapies. In this genotype-stratified randomized, double-blind, placebo-controlled clinical trial (May 2015-August 2019 in St Louis, Missouri), smokers were randomized by genotype in blocks of six (1:1:1 ratio) to three conditions: 12weeks of placebo (n=273), combination nicotine patch and lozenge (combination nicotine replacement therapy, cNRT, n=275), or varenicline (n=274). All participants received counseling and were followed for 12months. The primary end point was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT, week 12). Trial registration and eligibility criteria are on clinicaltrials.gov (https://clinicaltrials.gov/) (NCT02351167). We conducted the genetic analyses separately for 516 European ancestry (EA) smokers and 306 non-EA smokers (including 270 African American smokers). In African American smokers, there was a genotype-by-treatment interaction for EOT abstinence (χ2 =10.7, degrees of freedom=2. P=0.0049): specifically, cNRT was more effective in smokers with rs16969968 GG genotype than was placebo, while varenicline was more effective in smokers of GA/AA genotypes. In EA ancestry smokers, there was no significant genotype-by-treatment interaction. In the whole sample, although both were effective at EOT, only varenicline, and not cNRT, was significantly effective relative to placebo at 6-month follow-up. Importantly, this study suggests that genetic information can further enhance smoking cessation treatment effectiveness.