Dataset Information

Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage.

ABSTRACT:

Introduction

This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage.

Aims and methods

FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period.

Results

FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified.

Conclusions

Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings.

Trial registration

Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered.

Implications

Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.

SUBMITTER: Oliver AC

PROVIDER: S-EPMC8826384 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThis study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels.ObjectiveTo examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage.Design, setting, and participantsThese 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated: individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifying smokers with socioeconomic disadvantage. Data were analyzed from September 2019 to July 2020.InterventionsRandom assignment to 1 of 3 study cigarettes provided weekly at no cost for 12 weeks.Main outcomes and measuresThe primary outcome was between-group differences in mean total cigarettes smoked daily (CPD) during week 12; secondary outcomes included CPD for study and nonstudy cigarettes and dependence severity across weeks analyzed using analysis of covariance, random coefficients growth modeling, or repeated measures analysis of variance.ResultsA total of 775 participants were included (mean [SD] age, 35.59 [11.05] years; 551 [71.10%] women [owing to 1 population being exclusively women]); participants smoked a mean (SD) of 17.79 (9.18) CPD at study intake. A total of 286 participants were randomized to 0.4 mg/g, 235 participants were randomized to 2.4 mg/g, and 254 participants were randomized to 15.8 mg/g. Participants randomized to VLNC cigarettes had decreased mean [SEM] total CPD during week 12 across populations (Cohen d = 0.61; P < .001). At week 12, mean (SEM) CPD decreased to 17.96 (0.98) CPD in the 0.4 mg/g group and to 19.53 (1.07) CPD in the 2.4 mg/g group, both of which were significantly different from the 15.8 mg/g group (25.08 [1.08] CPD at week 12) but not each other (0.4 mg/g adjusted mean difference: -7.54 [95%CI, -9.51 to -5.57]; 2.4 mg/g adjusted mean difference: -5.34 [95% CI, 7.41 to -3.26]). Several secondary outcomes differed across populations randomized to VLNCs, including mean total CPD across weeks, with linear trends lower in participants receiving 0.4 mg/g (-0.28 [95%CI, -0.39 to -0.18]; P < .001) and 2.4 mg/g (-0.13 [95%CI, -0.25 to -0.01]; P < .001) doses compared with those receiving the 15.8 mg/g dose (0.30 [95% CI, 0.19 to 0.41]). Fagerström Test of Nicotine Dependence mean total scores were significantly lower in participants who received VLNCs (Cohen d = 0.12; P < .001), with those who received the 0.4 mg/g dose (mean [SD] score, 3.99 [0.06]; P < .001 vs 15.8 mg/g) or 2.4 mg/g dose (mean [SD] score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other.Conclusions and relevanceThese findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation.Trial registrationClinicalTrials.gov Identifiers: NCT02232737, NCT02250664, NCT02250534.

Project description:BACKGROUND:The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure. The effectiveness of this strategy needs to be demonstrated in different populations whose response to RNC cigarettes might be substantially mediated by personal or environmental factors, such as low socioeconomic status (SES) populations. This study aims to evaluate the response to a reduced nicotine intervention in low SES smokers, as defined here as those with less than 16 years of education, by switching smokers from high nicotine commercial cigarettes to RNC cigarettes. METHODS/DESIGN:Adults (N?=?280) who have smoked five cigarettes or more per day for the past year, have not made a quit attempt in the prior month, are not planning to quit, and have less than 16 years of education are recruited into a two-arm, double-blinded randomized controlled trial. First, participants smoke their usual brand of cigarettes for 1 week and SPECTRUM research cigarettes containing a usual amount of nicotine for 2 weeks. During the experimental phase, participants are randomized to continue smoking SPECTRUM research cigarettes that contain either (1) usual nicotine content (UNC) (11.6 mg/cigarette) or (2) RNC (11.6 to 0.2 mg/cigarette) over 18 weeks. During the final phase of the study, all participants are offered the choice to quit smoking with nicotine replacement therapy, continue smoking the research cigarettes, or return to their usual brand of cigarettes. The primary outcomes of the study include retention rates and compliance with using only research cigarettes and no use of other nicotine-containing products. Secondary outcomes are tobacco smoke biomarkers, nicotine dependence measures, smoking topography, stress levels, and adverse health consequences. DISCUSSION:Results from this study will provide information on whether low SES smokers can maintain a course of progressive nicotine reduction without increases in incidence of adverse effects. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01928719 . Registered on 21 August 2013.

Project description:IntroductionThe Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC).MethodsA 33 week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation.ResultsThe RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%).ConclusionsThis study supports a VLNC standard in cigarettes.ImplicationsDifferential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.

Project description:Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of respiratory tract inflammation, originally designated to identify eosinophilic airway inflammation and to predict steroid response. The main field of application of this biomarker is asthma, but FeNO has also been used for other allergic and non-allergic pulmonary disorders such as chronic obstructive pulmonary disease, hypersensitivity pneumonitis and interstitial lung disease. A substantial part of respiratory diseases are related to work, and FeNO, a safe and easy measure to conduct, is a potential valid examination in an occupational setting.This systematic review assesses the value of measuring FeNO related to three types of airborne exposures: allergens, irritants, and respiratory particles inhaled during occupational activities. The review covers results from longitudinal and observational clinical studies, and highlights the added value of this biomarker in monitoring effects of exposure and in the diagnostic criteria of occupational diseases. This review also covers the possible significance of FeNO as an indicator of the efficacy of interventions to prevent work-related respiratory diseases.Initially, 246 articles were identified in PUBMED and SCOPUS. Duplicates and articles which covered results from the general population, symptoms (not disease) related to work, non-occupational diseases, and case reports were excluded. Finally, 39 articles contributed to this review, which led to the following conclusions:a) For occupational asthma there is no consensus on the significant value of FeNO for diagnosis, or on the magnitude of change needed after specific inhalation test or occupational exposure at the workplace. There is some consensus for the optimal time to measure FeNO after exposure, mainly after 24 h, and FeNO proved to be more sensitive than spirometry in measuring the result of an intervention. b) For other occupational obstructive respiratory diseases, current data suggests performing the measurement after the work shift. c) For interstitial lung disease, the evaluation of the alveolar component of NO is probably the most suitable.

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