Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes

Abstract

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Keywords: Cigarette smoking; Cumulative vulnerability; Nicotine dependence; Reduced nicotine content cigarettes; Toxin exposure; Vulnerable populations.

Copyright © 2021. Published by Elsevier Inc.

Figures

Figure 1.

Total Cigarettes Per Day by Cumulative Vulnerabilities and Nicotine Dose Across Study Week Upper panel (A) shows mean number of total cigarettes (Study + Non-study) smoked per day (CPD) for each of the three cumulative-vulnerability categories (low, moderate, high) collapsed across nicotine-content cigarette doses (0.4, 2.4, and 15.8 mg/g) by study week. Data points are arithmetic means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing and in slope of linear trends. Lower panel (B) shows mean number of Total cigarettes (Study + Non-study) smoked per day (CPD) for each of the three nicotine-content-cigarette doses collapsed across cumulative-vulnerabilities categories (low, moderate, high) by study weeks. Data points are arithmetic means ± SEM. Data points not sharing a superscript letter differed in post-hoc testing at Week 12; data points not sharing a superscript number differed in linear slopes over time.

Figure 2.

Expired Breath Carbon Monoxide by Cumulative Vulnerabilities and Nicotine Dose Across Study Week Upper panel (A) shows mean expired breath carbon monoxide (CO) values for each of the three cumulative vulnerability categories (low, moderate, high) collapsed across study weeks and nicotine-content-cigarette doses. Data points are means + SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing. Lower panel (B) shows expired breath carbon monoxide (CO) values for each of the three nicotine-content-cigarette doses (0.4, 2.4, and 15.8 mg/g) at baseline and across study weeks. Data points are means + SEM. Data points not sharing a superscript letter differed in slope of linear trends across the 12-week study period.

Figure 3.

Biomarkers of Exposure as a Function of Cumulative Vulnerabilities and Nicotine Dose Upper left panel (A) shows mean total urinary cotinine values in each of the three cumulative vulnerability categories (low, moderate, high) collapsed across the three nicotine-content-cigarette doses (0.4, 2.4, and 15.8 mg/g). Upper right panel (B) shows mean total urinary cotinine values for each of the three nicotine content doses collapsed across the three cumulative-vulnerability categories. Data points are geometric means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing. Lower left panel (C) shows mean total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) values in each of the three cumulative vulnerability categories (low, moderate, high) collapsed across the three nicotine-content-cigarette doses. Lower right panel (D) shoes mean total NNAL values for each of the three study cigarette doses collapsed across the three cumulative-vulnerability categories. Data points are geometric means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing.

Figure 4.

Nicotine Dependence by Cumulative Vulnerabilities and Nicotine Dose Upper left panel (A) shows Fagerström Test for Nicotine Dependence (FTND) total scores (minus item 4) by cumulative-vulnerability categories (low, moderate, high) across study weeks collapsing across cigarette-nicotine-content dose (0.4, 2.4, and 15.8 mg/g). Data points are least-square means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing. Upper right panel (B) shows FTND total scores (minus item 4) by cigarette-nicotine-content dose collapsing across cumulative-vulnerability categories. Data points are arithmetic means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing. Lower left panel (C) shows Wisconsin Inventory of Smoking Dependence Motives (WISDM) total scores by cumulative-vulnerability categories collapsing across cigarette-nicotine-content dose. Data points are least-square means ± SEM. Data points not sharing a superscript letter differed significantly in post-hoc testing. Lower right panel (D) shows WISDM total scores by cigarette-nicotine-content dose at bi-weekly assessments collapsing across cumulative-vulnerability categories. Data points are arithmetic means ± SEM. Doses not sharing a superscript differed in slope of linear trends.

Figure 5.

Questionnaire of Smoking Urges Factor 2 Scores for Usual Brand Cigarettes by Cumulative Vulnerabilities Mean (±SEM) Questionnaire-on-Smoking-Urges (QSU) Factor-2 scores across repeated assessments during the 12-week study for each of the three dose conditions among participants in the low (upper panel), moderate (middle panel), and high (lower panel) cumulative-vulnerability categories. Data points are arithmetic means ± SEM. Doses not sharing a superscript differed in slope of linear trends.