Another Warning Sign: High Nicotine Content in Electronic Cigarettes Disrupts Mucociliary Clearance, the Essential Defense Mechanism of the Lung.
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ABSTRACT:
SUBMITTER: Kesimer M
PROVIDER: S-EPMC6888647 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Another Warning Sign: High Nicotine Content in Electronic Cigarettes Disrupts Mucociliary Clearance, the Essential Defense Mechanism of the Lung.
American journal of respiratory and critical care medicine 20191101 9
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Project description:AimsTo compare the use of alternative nicotine products, smoking behavior and tobacco biomarker exposure in smokers unwilling to quit who were assigned randomly to normal nicotine content (NNC) cigarettes or very low nicotine content (VLNC) cigarettes.DesignRandomized, parallel-arm 8-week study with assignment to VLNC (VLNC 1, n = 53) or NNC (NNC, n = 27) with access to non-cigarette combusted and non-combusted tobacco/nicotine products or to VLNC with access to only non-combusted products (VLNC2, n = 56).SettingClinics in Minnesota, USA.ParticipantsSmokers uninterested in quitting smoking with a mean [± standard deviation (SD)] age of 44 (± 14) years and smoking 16 (± seven) cigarettes/day; 51% female, 72% white.MeasurementsDuring the experimental period, the measures taken included: rate of alternative products used, amount of and abstinence from combusted tobacco used and tobacco exposure biomarkers.FindingsThere were higher rates of non-combusted alternative tobacco/nicotine product use in both VLNC conditions versus the NNC condition [rate ratio (RR) = 2.18, 95% confidence interval (CI) = 1.94, 2.46 and RR = 1.64, 95% CI = 1.46, 1.85, respectively] and in VLNC1 versus VLNC2 condition (RR = 1.33, 95% CI = 1.23, 1.44), accompanied by reduced biomarkers of exposure primarily in VLNC2 condition compared to NNC condition (Ps < 0.05). Fewer combusted products were smoked at almost all visits (Ps ≤ 0.02) and there were higher rates of abstinence for both VLNC conditions compared with the NNC condition (VLNC1 versus NNC: RR = 9.96, 95% CI = 5.01, 19.81; VLNC2 versus NNC: RR = 11.23, 95% CI = 5.74, 21.97).ConclusionThe offer of, and instructions to use, reduced nicotine content cigarettes during an 8-week period led to greater use of alternative tobacco/nicotine products compared with continued use of normal nicotine cigarettes and also reductions in smoking rates.
| S-EPMC5249662 | biostudies-literature
Project description: Not available
| S-EPMC1569994 | biostudies-literature
Project description:IntroductionThe Food and Drug Administration has the authority to regulate tobacco product constituents, including nicotine, to promote public health. Reducing the nicotine content in cigarettes may lead to lower levels of addiction. Smokers however may compensate by smoking more cigarettes and/or smoking more intensely. The objective of this study was to test whether individual differences in the level of nicotine dependence (as measured by the Fagerstrom Test of Cigarette Dependence [FTCD]) and/or the rate of nicotine metabolism influence smoking behavior and exposure to tobacco toxicants when smokers are switched to reduced nicotine content cigarettes (RNC).MethodsData from 51 participants from a previously published clinical trial of RNC were analyzed. Nicotine content of cigarettes was progressively reduced over 6 months and measures of smoking behavior, as well as nicotine metabolites and tobacco smoke toxicant exposure, CYP2A6 and nicotinic CHRNA5-A3-B4 (rs1051730) genotype were measured.ResultsHigher baseline FTCD predicted smoking more cigarettes per day (CPD), higher cotinine and smoke toxicant levels while smoking RNC throughout the study, with no interaction by RNC level. Time to first cigarette (TFC) was associated with differences in compensation. TFC within 10 min was associated with a greater increase in CPD compared to TFC greater than 10 min. Neither rate of nicotine metabolism, nor CYP2A6 or nicotinic receptor genotype, had an effect on the outcome variables of interest.ConclusionsFTCD is associated with overall exposure to nicotine and other constituents of tobacco smoke, while a short TFC is associated with an increased compensatory response after switching to RNC.
| S-EPMC4542742 | biostudies-literature
Project description:Objective: We estimated whether recent cannabis use moderates response to cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among smokers with concurrent affective disorders, opioid dependence, or socioeconomic disadvantage. Methods: We conducted a secondary analysis of a multi-site, double-blind, laboratory study examining acute response to reduced nicotine content cigarettes (RNCC) in 169 adult smokers with co-morbid conditions. Participants positive for recent cannabis use or self-reported past 30-day cannabis use at baseline were categorized as current cannabis users (N = 63). Repeated measures analysis of variance tests assessed whether baseline cannabis use moderated cigarette reinforcement, tobacco withdrawal, craving, smoking topography, or carbon monoxide boost. Results: Cannabis users were younger, less educated, and had more depression and anxiety than non-users (p < .05). Cannabis use status did not moderate the effects of nicotine dose on concurrent choice testing, subjective effects of RNCCs, or smoking topography. After adjusting for sociodemographic characteristics, cannabis users had higher ratings on Smoking Satisfaction, Enjoyment of Respiratory Tract Sensations, and Craving Reduction across all nicotine doses. Cannabis users reported longer withdrawal symptom duration and more rapid decline of carbon monoxide boost than non-users. Conclusions: Findings suggest RNCCs decrease the addiction potential of cigarettes in vulnerable populations independent of cannabis use status.
| S-EPMC6219758 | biostudies-literature
Project description:A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.
| S-EPMC10275576 | biostudies-literature
Project description:There has been long-standing interest in a reduced-nicotine product standard for combusted tobacco, which is within the regulatory purview of the Food and Drug Administration (FDA). In weighing whether to establish this standard, it is important to consider potential responses among people who are at elevated risk for tobacco-related health harms. In this narrative review, we summarize studies of very low nicotine content (VLNC) cigarettes conducted between 2010 and 2021 in groups that the FDA has identified as vulnerable populations. Studies conducted to date in adults with mental health conditions, adults with opioid use disorder, socioeconomically-disadvantaged adults, and youth or young adults indicate that immediate switching to VLNC cigarettes decreases smoking, with minimal or no unintended negative consequences. Few studies have investigated the effects of VLNC cigarettes in racial or ethnic minorities, people who smoke menthol cigarettes, and pregnant women, but initial findings suggest that responses of these individuals are similar to responses observed in other vulnerable populations. We are not aware of studies that have investigated VLNC cigarettes in military/veteran populations, sexual or gender minority individuals, or people living in underserved rural environments. Future research directions include understanding how to promote cessation in the context of a reduced-nicotine standard, and how to correct VLNC misperceptions in vulnerable populations. Nevertheless, the evidence to date indicates that a reduced-nicotine standard is likely to have the same beneficial effects on smoking reductions as it does in less vulnerable populations, which should provide some confidence in pursuing this regulatory approach.
| S-EPMC9699899 | biostudies-literature
Project description:BackgroundThe reduction of the nicotine content of cigarettes to nonaddicting levels is a potential federal regulatory intervention to reduce the prevalence of cigarette smoking and related disease. Many clinical trials on the effects and safety of nicotine reduction are ongoing. An important methodologic concern is noncompliance with reduced nicotine content cigarettes in the context of freely available conventional cigarettes. We propose two approaches using biomarkers to estimate noncompliance in smokers of very low nicotine content (VLNC) cigarettes in a clinical trial.MethodsData from 50 subjects in a study of gradual nicotine reduction were analyzed. Using plasma cotinine concentrations measured at baseline and while smoking VLNC cigarettes, we compared within-subject ratios of plasma cotinine comparing usual brand to VLNC in relation to nicotine content of these cigarettes. In another approach, we used nicotine pharmacokinetic data to estimate absolute plasma cotinine/cigarettes per day (CPD) threshold values for compliance based on the nicotine content of VLNC.ResultsThe two approaches showed concordance, indicating at least 60% noncompliance with smoking VLNC. In a sensitivity analysis assuming extreme compensation and extreme values for nicotine metabolic parameters, noncompliance was still at least 40%, much higher than self-reported noncompliance.ConclusionBiomarker analysis demonstrates a high degree of noncompliance with smoking VLNC cigarettes, indicating that smokers are supplementing these with conventional cigarettes.ImpactWe propose a practical approach to assessing compliance with smoking VLNC in clinical trials of nicotine reduction.
| S-EPMC4323626 | biostudies-literature
Project description:BackgroundReducing the nicotine content in cigarettes could improve public health by reducing smoking and toxicant exposure, but may also have unintended consequences on alcohol use. The primary objective of this study was to examine the effect of reducing the nicotine content in cigarettes on alcohol outcomes. The secondary aim was to examine whether the effects of these cigarettes on alcohol outcomes were mediated by changes in nicotine exposure, smoking behavior, or withdrawal.MethodsBetween June 2013 and July 2014, we conducted a 7-arm, double-blind, randomized clinical trial at 10 U.S.-based sites. Daily smokers not currently interested in quitting (n = 839) were assigned to equally sized groups to smoke for 6 weeks cigarettes containing either normal nicotine content (NNC; 15.8 mg/g, 9 mg tar), moderate nicotine content (5.2 mg/g nicotine, 9 mg tar), or very low nicotine content (VLNC; 0.4 to 2.4 mg/g, 9 to 13 mg tar). This investigation focused on a subsample of current drinkers (n = 403). Each reduced nicotine content cigarette condition was compared to the NNC control condition with respect to trajectories over the 6-week period of average daily alcohol use and occurrence of binge drinking. Moderating variables were considered. Mediation analyses tested potential explanatory processes including changes in nicotine exposure, cigarettes per day, and withdrawal.ResultsOver time, reduced nicotine exposure and smoking rate mediated effects of VLNC cigarette use on reduced alcohol use. There was no evidence of compensatory drinking in response to nicotine reduction or nicotine withdrawal, even among subgroups expected to be at greater risk (e.g., relatively heavier drinkers, highly nicotine-dependent individuals).ConclusionsThe findings suggest that compensatory drinking is unlikely to occur in response to switching to VLNC cigarettes. In contrast, reducing the nicotine content of cigarettes may reduce alcohol use (clinicalTrials.gov number, NCT01681875).
| S-EPMC5347256 | biostudies-literature
Project description:The lung is continuously exposed to particles, toxicants, and microbial pathogens that are cleared by a complex mechanical, innate, and acquired immune system. Mucociliary clearance, mediated by the actions of diverse conducting airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system by secreting fluids, electrolytes, antimicrobial and antiinflammatory proteins, and mucus onto airway surfaces. The mucociliary escalator removes particles and pathogens by the mechanical actions of cilia and cough. Abnormalities in mucociliary clearance, whether related to impaired fluid secretion, ciliary dysfunction, lack of cough, or the disruption of epithelial cells lining the respiratory tract, contribute to the pathogenesis of common chronic pulmonary disorders. Although mucus and other airway epithelial secretions play a critical role in protecting the lung during acute injury, impaired mucus clearance after chronic mucus hyperproduction causes airway obstruction and infection, which contribute to morbidity in common pulmonary disorders, including chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis, and primary ciliary dyskinesia. In this summary, the molecular and cellular mechanisms mediating airway mucociliary clearance, as well as the role of goblet cell metaplasia and mucus hyperproduction, in the pathogenesis of chronic respiratory diseases are considered.
| S-EPMC6322033 | biostudies-literature
Project description:IntroductionMany people incorrectly think that very low nicotine content (VLNC) cigarettes are less carcinogenic than current cigarettes. This risk misperception by people who smoke could reduce motivation to quit under a nicotine reduction policy. We qualitatively examined perspectives on campaign messages designed to reduce misperceptions.Aims and methodsAdults who smoke from North Carolina participated in online interviews. After being introduced to the idea of a VLNC policy, participants were shown VLNC messages and asked about their perceptions on the clarity, understandability, persuasiveness, and meaning of the messages. We conducted a thematic content analysis of the transcripts.ResultsThirty adults who smoke cigarettes participated (15 females, 13 males, 2 nonbinary) with a mean age of 43 years. Central themes that emerged were: (1) Confusion about the proposed VLNC cigarette policy affected how messages were interpreted; (2) Messages that promote self-efficacy for quitting rather than guilt or fear were better received; and (3) Direct and succinct messages were seen as more able to grab attention and inform people who smoke. Some participant concerns focused on whether VLNC cigarettes would relieve their nicotine cravings and whether they would need to smoke more VLNC cigarettes to feel satisfied.ConclusionCampaign messages to educate the public about the harmful effects of smoking VLNC cigarettes may be more effective if people who smoke are informed about the policy's rationale to understand why nicotine is removed rather than the other harmful chemicals. Messages should also acknowledge the difficulty of quitting and be short and direct to capture attention.ImplicationsAdults who smoke have some confusion about nicotine reduction in cigarettes and this affects how they perceive potential communication campaign messages about the risk of smoking VLNC cigarettes. In our qualitative research, we found that adults who smoke prefer messages about VLNC cigarettes that acknowledge the challenge of quitting and that are direct and succinct. With further development, campaign messages may be able to reduce misperceptions about VLNC cigarettes and maximize the public health benefit of a nicotine reduction policy.
| S-EPMC9653078 | biostudies-literature