Reply to Commentary on "Adult Smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months After Initially Purchasing a JUUL e-Cigarette" and the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study.

BACKGROUND: This is authors' reply to the Commentary on our publication entitled "Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette." METHODS AND RESULTS: Analyses addressed questions about follow-up rates and missed responses in the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study. Results demonstrate limited potential for selection bias, as participants who missed surveys were similar to those with complete data, and re-contact of participants who missed a follow-up indicated almost half were not smoking. Imputing smoking behavior for missing data would likely introduce bias and is not appropriate. The study demonstrated that JUUL products can facilitate high rates of complete switching away from cigarettes as suggested in previous experimental and observational studies. The ADJUSST cohort, including baseline nonsmokers, demonstrates a net reduction in smoking prevalence. Moreover, population modeling considering both benefits and harms demonstrated a net population benefit. CONCLUSION: While the ADJUSST Study is not without limitations, the findings are consistent with multiple streams of real-world evidence that indicate that ENDS can facilitate switching among adults who smoke, and provide population benefits.

Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

Switching Away From Smoking and Reduction in Cigarette Consumption among US Adult Purchasers of the JUUL System across 24 Months Including Diverse Subpopulations Disproportionately Affected by Cigarette Smoking.

OBJECTIVES: Electronic nicotine delivery systems (ENDS) can reduce tobacco-related health risks for adults who smoke cigarettes (AWS) by facilitating complete switching away from cigarettes. However, little is known about ENDS use and switching among subpopulations that have been disproportionately affected by smoking. METHODS: AWS (age≥21 years) were recruited following their first purchase of a JUUL Starter Kit in 2018. Participants self-reported switching (no past-30-day cigarette smoking) at 1-, 2-, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-month follow-ups. Percent switched and percent with substantial smoking reduction (≥50% decrease in cigarettes/day among those who continued smoking) were calculated. Analyses focused on racial/ethnic minorities, persons with low income and education levels, sexual minorities, and those with mental and physical health conditions. RESULTS: Overall rates of switching away from cigarettes increased across follow-ups to 51.2% (Month-12) to 58.6% (Month-24, 87% of whom used ENDS). Among those who continued to smoke at 24 months, 45.4% reduced cigarettes/day by ≥50%. Rates of switching and substantial smoking reduction were largely similar across subgroups, with some statistically significant, but small, differences in Month-24 switching rates(e.g. education, mental/physical health conditions; switch rate range: 42~57%). CONCLUSIONS: AWS demonstrated progressively increasing switching rates over two years after purchasing JUUL products. Similar trends in switching and smoking reduction were observed across populations disproportionately affected by smoking. By facilitating switching and smoking reduction, ENDS products such as JUUL may provide an opportunity to reduce smoking-related harm among some populations disproportionately affected by smoking, potentially reducing tobacco-related health disparities. IMPLICATIONS: ENDS have the potential to benefit population health if they can replace cigarettes. This benefit must extend to populations disproportionately affected by smoking. In this real-world study, 59% of JUUL purchasers reported complete switching two years later (no past-30-day smoking, with most continuing to use ENDS). Further, 45% of those who continued to smoke reduced cigarette consumption by at least half. These rates of switching and smoking reduction were largely comparable across populations disproportionately affected by smoking (defined, e.g., by ethnicity and income). ENDS can serve as an effective harm reduction strategy to complement current efforts to reduce tobacco-related disparities.

Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette.

Background: Electronic nicotine delivery systems (ENDS) have the potential to benefit public health if smokers completely switch from cigarettes to ENDS. Methods: A cohort of adult smokers (age ≥ 21) who purchased a JUUL Starter Kit was followed for 12 months after the initial purchase. We defined "switching" as past-30-day abstinence from smoking (even if JUUL use had stopped), and analyzed factors associated with achievement and maintenance of self-reported repeated point-prevalence switching (RPPS) at three follow-ups, i.e., no past-30-day smoking at months 6, 9, and 12. Results: RPPS was reported by 21.6% of the 12,537 evaluable smokers. Smokers with lighter smoking history and lower cigarette dependence at baseline were more likely to report RPPS. RPPS was also associated with daily use of JUUL (Month-3: OR = 2.32, 95% CI = 2.02-2.68; Month-6: OR = 1.73, 95% CI = 1.42-2.10), and with greater subjective reinforcing effects from JUUL use (assessed by the mCEQ, Month-3: OR = 1.46, 95% CI = 1.38-1.56; Month-6: OR = 1.11; 95% CI = 1.02-1.20). Even among smokers who did not meet the criteria of RPPS (i.e., who smoked at least once), 35.5% reported past 30-day point-prevalence switching on at least one follow-up, and their cigarette consumption was substantially reduced compared to baseline. Conclusions: Approximately one-fifth of adult smokers reported 30-day point-prevalence abstinence at 6, 9, and 12 months after purchasing JUUL. Greater use of JUUL and stronger subjective reinforcing effects were associated with nonsmoking, validating the potential for ENDS to substitute for smoking, with potential for positive impacts on individual and population health.

Comparing Adult Smokers Who Switched to JUUL versus Continuing Smokers: Biomarkers of Exposure and of Potential Harm and Respiratory Symptoms.

OBJECTIVES: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching. AIMS AND METHODS: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates. RESULTS: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers. CONCLUSIONS: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks. IMPLICATIONS: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk.

Randomized trial assessing the effect of the JUUL system on switching away from cigarettes and smoking reduction among U.S. adults who smoke cigarettes.

Observational studies show high rates of switching away from cigarettes among adult purchasers of JUUL-brand electronic nicotine delivery system (ENDS); data are needed to evaluate switching with JUUL in randomized general population trials. The association of ENDS flavor availability and switching is pertinent. This study assessed switch rates and smoking reduction among participants randomized to use JUUL in a choice of flavors or tobacco-only, compared to a condition provided smoking-cessation materials. U.S. adults who smoke cigarettes (N = 837; Mage [SD] = 45.99 years [11.48]; 18.76 cigarettes/day [SD = 7.86]; 50.2% female) from an address-based representative panel were randomized to receive JUUL for 6 months (5.0% nicotine; only Virginia Tobacco [N = 285] or choice of flavors [N = 281]), or smoking-cessation materials (quit advice [QA]; N = 271). Self-reported past 30-day smoking and cigarette consumption were assessed at 1, 3, and 6 months. Repeated-measure regressions assessed differences in smoking outcomes between groups. Only 2% of participants were planning to quit smoking within 30 days. Across the 6-month intervention, participants randomized to JUUL (vs. QA) had 6.57-fold greater odds of reporting past 30-day switching (95% CI [3.72-11.63]). Participants in the JUUL (vs. QA) group smoked 27% fewer cigarettes/day versus baseline (Rate Ratio [95% CI] = 0.73 [0.68-0.77]). Over half (51.8%) of the Virginia Tobacco group used other flavors (36.7% nontobacco flavors), contaminating randomized flavor-conditions. JUUL flavor groups did not differ in smoking outcomes (p > .48). Use of JUUL products may support complete switching away from cigarettes, including among those not ready to quit smoking. Results suggest a preference for nontobacco-flavored ENDS among adults who smoke, although smoking outcomes did not differ by flavor. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparison of biomarkers of exposure among US adult smokers, users of electronic nicotine delivery systems, dual users and nonusers, 2018-2019.

The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers'; 9 BOEs were not significantly different from nonusers. Among dual users smoking < 10 cigarettes/day, 15 of 18 non-nicotine BOEs were significantly lower than smokers', whereas in dual users smoking ≥ 10 cigarettes per day none of the BOEs significantly differed from smokers'. In this representative sample of US adults, exclusive use of ENDS (vs. cigarette smoking) was associated with much lower exposures to many harmful chemicals associated with smoking-related disease. BOE levels in dual users were directly related to their cigarette consumption. These BOE data provide further evidence that ENDS expose users to substantially lower levels of toxicants than combustible cigarettes, confirming their potential for harm reduction.

A New Questionnaire to Assess Respiratory Symptoms (The Respiratory Symptom Experience Scale): Quantitative Psychometric Assessment and Validation Study.

BACKGROUND: Smokers often experience respiratory symptoms (eg, morning cough), and those who stop smoking, including those who do so by switching completely to electronic nicotine delivery systems (ENDS), may experience reductions in symptoms. Existing respiratory symptom questionnaires may not be suitable for studying these changes, as they are intended for patient populations, such as those with chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study aimed to develop a respiratory symptom questionnaire appropriate for current smokers and for assessing changes when smokers stop smoking. METHODS: The Respiratory Symptom Experience Scale (RSES) was derived from existing instruments and subject matter expert input and refined through cognitive debriefing interviews (n=49). Next, for purposes of the quantitative psychometric evaluation, the RSES was administered to smokers (n=202), former smokers (no tobacco use in >6 months; n=200), and switchers (n=208, smokers who switched to ENDS for >6 months), all of whom had smoked for at least 10 years (mean age 33 years). Participants, who averaged 62 (SD 12) years of age, included 28% (173/610) with respiratory allergy symptoms and 17% (104/610) with COPD. Test-retest reliability was assessed by repeat assessment after 1 week in 128 participants. RESULTS: A generalized partial credit model confirmed that the response options were ordered, and a parallel analysis using principal components confirmed that the scale was unidimensional. With allowance for 2 sets of correlated errors between pairs of items, a 1-factor graded response model fit the data. Discrimination parameters were approximately 1 or greater for all items. Scale reliability was 0.80 or higher across a broad range of severity (standardized scores -0.40 to 3.00). Test-retest reliability (absolute intraclass correlation) was good, at 0.89. RSES convergent validity was supported by substantial differences (Cohen d=0.74) between those with and without a diagnosis of respiratory disease (averaging 0.57 points, indicating that differences of this size or smaller represent meaningful differences). RSES scores also strongly differentiated those with and without COPD (d=1.52). Smokers' RSES scores were significantly higher than former smokers' scores (P<.001). Switchers' RSES scores were significantly lower than smokers' scores (P<.001) and no different from former smokers' scores (P=.34). CONCLUSIONS: The RSES fills an important gap in the existing toolkit of respiratory symptom questionnaires; it is a reliable and valid tool to assess respiratory symptoms in adult current and former smokers, including those who have switched to noncombusted nicotine products. This suggests that the scale is sensitive to respiratory symptoms that develop in smokers and to their remission when smokers quit or switch to noncombusted nicotine products intended to reduce the harm of smoking. The findings also suggest that switching from cigarettes to ENDS may improve respiratory health.

Changes in dependence over one year among US adults who smoke cigarettes and switched completely or partially to use of the JUUL-brand electronic nicotine delivery system.

Background: Electronic nicotine delivery systems (ENDS) are substitute sources of nicotine for adults who smoke cigarettes. Understanding changes in dependence as people switch from cigarettes to ENDS is relevant to public health. This study assessed changes in dependence among adults who switched completely or partially (dual users) from cigarettes to JUUL-brand ENDS over 12 months. Methods: US adults who smoke and purchased a JUUL Starter Kit (n = 17,619) completed a baseline assessment and were invited to 1-, 2-, 3-, 6-, 9- and 12-month follow-ups. Dependence on cigarettes at baseline and on JUUL at follow-ups was assessed with the Tobacco Dependence Index (TDI; Range 1-5). Analyses estimated the minimal important difference (MID) for the scale, compared JUUL dependence to baseline cigarette dependence and assessed changes in JUUL dependence over 1-year, including among those using JUUL at all follow-ups. Results: Participants who switched at month 2 had month 1 JUUL TDI scores 0.24 points greater than those who continued smoking (p<0.001); thus MID=0.24. Among both switchers and dual users overall, dependence on JUUL 1 and 12 months later was lower than baseline dependence on cigarettes (ps<0.001); participants who smoked every day showed more consistent and larger reductions. Among participants who persistently used JUUL without smoking, dependence increased 0.01 points per month (p<0.001), but was leveling off over time. Conclusions: Dependence on JUUL was lower than baseline cigarette dependence. Increases in JUUL dependence were small over 12 months of continual JUUL use. These data indicate that ENDS, including JUUL, have lower dependence potential than cigarettes.

Pharmacokinetic and subjective assessment of prototype JUUL2 electronic nicotine delivery system in two nicotine concentrations, JUUL system, IQOS, and combustible cigarette.

RATIONALE: Electronic nicotine delivery systems and heated tobacco products are noncombustible alternatives for adult smokers. Evidence suggests sufficient nicotine delivery and satisfying effects are necessary to facilitate switching away from smoking; nicotine delivery varies across electronic nicotine delivery systems within limited nicotine concentrations. OBJECTIVES: To assess the nicotine delivery and subjective effects of prototype JUUL2 System in two nicotine concentrations, currently-marketed US JUUL System ("JUUL"), IQOS-brand heated tobacco product, and combustible cigarettes. METHODS: Adult smokers (N = 40) completed a 5-arm cross-over product-use laboratory confinement study. Nicotine pharmacokinetics and subjective effects were assessed following use of: (1) JUUL2 prototype 18 mg/mL nicotine; (2) JUUL2 prototype 40 mg/mL; (3) JUUL 59 mg/mL; (4) IQOS 18 mg/g; and (5) usual brand combustible cigarette, each evaluated during ad libitum (10 min) and controlled (5 min, 10 standardized puffs) use. RESULTS: Nicotine delivery was greatest for combustible cigarettes, followed by JUUL2 prototype 40 mg/mL, IQOS, JUUL2 prototype 18 mg/mL, and JUUL 59 mg/mL. Nicotine delivery from JUUL2 prototype 18 mg/mL was significantly greater than JUUL 59 mg/mL after ad libitum use. JUUL products were significantly more satisfying and effective at reducing craving than IQOS. JUUL2 prototype 40 mg/mL was significantly more aversive than other JUUL products. CONCLUSIONS: Prototype JUUL2 and JUUL 59 mg/mL products were rated higher than IQOS on subjective measures associated with switching away from smoking. The JUUL2 prototype 40 mg/mL produced aversive responses and would require modifications to be a viable product for adult smokers. Nicotine delivery and subjective responses to JUUL2 prototype 18 mg/mL suggest a product based on this prototype may facilitate increased switching among adult smokers.

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System.

OBJECTIVES: Studies have assessed switching away from cigarettes among adult smokers who use electronic nicotine delivery systems (ENDS), but there is little data assessing differences in likelihood of switching or ENDS use characteristics by menthol smoking. METHODS: Adult (age ≥ 21) established smokers who purchased a JUUL Starter Kit (N = 15,036) completed baseline and 1-, 2-, 3-, 6-, 9- and 12-month assessments. Switching (no past-30-day cigarette smoking) and flavor use were assessed at each follow-up. Repeated-measure logistic regression models evaluated association of menthol smoking and switching across 1 year. RESULTS: Across the 6 follow-ups, more menthol smokers primarily used Menthol/Mint-flavored JUULpods (53.8%) than nonmenthol smokers (22.9%). Only 6.4% of menthol smokers primarily used Tobacco flavors (vs. 25.9% of nonmenthol smokers). Across all follow-ups menthol smokers (41.2% of sample) were more likely to switch than nonmenthol smokers (42.6% vs. 38.8%: OR [95% CI] = 1.17 [1.11, 1.23]); this association remained significant after adjustment for sociodemographic, smoking and JUUL use covariates (aOR [95% CI] = 1.13 [1.05, 1.21]). Nonmenthol smokers, but not menthol smokers, were significantly more likely to switch when primarily using Menthol/Mint-flavored (vs. Tobacco-flavored) JUULpods (aOR [95% CI] = 1.14 [1.04, 1.25]). Differences in baseline smoking characteristics between menthol and nonmenthol smokers were small in magnitude. CONCLUSIONS: Adult menthol (vs. nonmenthol) smokers using JUUL were more likely to switch. More than twice as many menthol (vs. nonmenthol) smokers primarily used Menthol/Mint-flavor JUULpods; few menthol smokers used tobacco flavors. Given these pronounced differences in flavor preferences, availability of ENDS in menthol flavors may be particularly important for menthol smokers, but may also benefit some nonmenthol smokers.

Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers.

INTRODUCTION: Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants. METHODS: This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers. RESULTS: In JUUL groups, median percent reductions in primary BOEs (Day 6-Baseline) were 90%-≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps < 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs. CONCLUSION: This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking. IMPLICATIONS: This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System ("JUUL") in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.

Differences in Switching Away From Smoking Among Adult Smokers Using JUUL Products in Regions With Different Maximum Nicotine Concentrations: North America and the United Kingdom.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) may improve public health if they facilitate smokers switching away from cigarettes. Conceptually, switching is facilitated when ENDS provide adequate nicotine delivery. Switching rates among smokers who purchased the JUUL System ("JUUL") were compared in the United Kingdom (UK), where regulations limit nicotine concentration to 20 mg/mL versus North America (N.Am.; United States and Canada), where higher concentrations are available. AIMS AND METHODS: Adult established smokers (age ≥21, smoked ≥100 cigarettes, smoking some days or every day at baseline) who newly purchased JUUL were recruited into a longitudinal study (UK: N = 1247; N.Am.: N = 8835). Complete switching (no smoking for ≥30 days) was assessed 1, 3, and 6 months after purchase; propensity score matching (PSM) and logistic regression compared switching after adjusting for baseline characteristics. RESULTS: In both N.Am. and UK, ≥82% of participants reported using the highest JUUL nicotine concentration available (UK: 18 mg/mL; N.Am.: 59 mg/mL). Unadjusted switching rates did not differ at 1 month (17%-18%); unadjusted and adjusted rates were significantly higher in N.Am. (vs. UK) at 3 and 6 months. In the PSM sample, after additional covariate adjustment, rates were significantly higher in N.Am. (vs. UK) at 3 months (31.5% vs. 22.7%; odds ratio [95% confidence interval, CI] = 1.59 [1.25, 2.02]) and 6 months (38.0% vs. 26.0%; odds ratio [95% CI] = 1.79 [1.37, 2.35]). CONCLUSIONS: These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Differences in smoking and ENDS use characteristics did not explain associations of location and switching; however, between-country differences may be affected by unmeasured factors. IMPLICATIONS: Switching rates were lower among smokers who purchased the JUUL System ("JUUL") in the UK, where regulations limit nicotine concentration to 20 mg/mL versus N.Am. (United States and Canada), where higher concentrations are available-before and after controlling for differences in smoking and ENDS use characteristics. These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Between-country differences may be affected by unmeasured factors; future research should consider these factors and the extent to which regulatory policy environments may explain differences in switching among adult smokers.

The Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study: Methods and Analysis of Loss-to-Follow-up.

Objectives: The Adult JUUL System User Switching and Smoking Trajectories (ADJUSST) study assessed the smoking and JUUL use trajectories of adults who purchased JUUL. In this paper, we describe study methods, characterize the sample, and assesses potential for bias due to loss to follow-up. Methods: We entered 55,414 US adults (≥ age 21) who purchased a JUUL Starter Kit for the first time (online or at retail) in 2018 into a naturalistic, longitudinal observational study, irrespective of baseline smoking status. Participants were invited for follow-ups 1, 2, 3, 6, 9, and 12 months later, focused on assessing past-30-day smoking and JUUL use. Analyses assessed potential bias due to non-response. Results: Over 90% of participants had a history of smoking; 62.8% were past-30-day smokers; 23.3% were former smokers. Participants' average age was 30; 75% were white. Most participants (77.6%) completed some follow-ups; 25% completed all follow-ups. Baseline differences among complete responders (N = 13,729), partial responders (N = 29,252), and complete non-responders (N = 12,433) were small. When recontacted, few 12-month non-responders said their non-response was due to smoking; many reported no past-30-day smoking. Conclusions: The study may elucidate smoking trajectories of adult JUUL users. The potential for bias due to loss to follow-up in ADJUSST was limited.

Switching away from Cigarettes across 12 Months among Adult Smokers Purchasing the JUUL System.

Objectives: In this study, we assessed complete switching away from cigarette smoking among adult smokers who purchased a JUUL Starter Kit (JSK). Methods: Adult (age ≥ 21) established smokers (smoked ≥ 100 lifetime cigarettes) who purchased a JSK in 2018 were invited to complete online surveys 1, 2, 3, 6, 9 and 12 months after initial JSK purchase. Point prevalence of switching (no past 30-day smoking) was assessed at each follow-up. Repeated measures logistic regression models evaluated associations of sociodemographic factors, baseline smoking characteristics and time-varying JUUL System ("JUUL") use characteristics and switching across the 12-month period. Results: Respondents (N = 17,986) were 55.0% male, 78.3% white, mean age = 32.65 years (SD = 10.81), mean baseline cigarettes/day = 11.10 (SD = 8.16). The proportion self-reporting switching increased over time: one-month (27.2%[3718/13,650]), 2-month (36.4%[4926/13,533]), 3-month (41.0%[5434/13,257]), 6-month (46.6%[5411/11,621]), 9-month (49.4%[6017/12,186]), and 12-month (51.2%[6106/11,919]); 33.1% reported switching at both 9-month and 12-month follow-ups. In prospective analyses, smokers with lower cigarette dependence, shorter smoking history, lower cigarette consumption, more frequent JUUL use, greater satisfaction from initial JUUL use, and higher JUUL dependence were significantly more likely to switch. Conclusions: Rates of switching with JUUL increased over time. Over 50% of respondents reported complete switching away from cigarettes 12 months following purchase. Greater use of and dependence on JUUL predicted switching.

Cigarette Smoking Trajectories in Adult Former Smokers Using the JUUL System.

Objective: In this study, we assessed cigarette smoking over 12 months among adult former smokers who newly purchased a JUUL Starter Kit (JSK). Methods: Prevalence of past 30-day smoking and factors associated with smoking were assessed among adult (age ≥ 21) former established smokers, stratified as recent (quitting ≤ 12 months) and long-term quitters (> 12 months), who purchased a JSK and completed ≥ 1 of 6 follow-up assessments (N = 4786). Results: Recent quitters had higher rates (16.6%-19.9%) of past 30-day smoking than long-term quitters (6.4%-9.2%) across the 12-month period; smoking prevalence did not significantly increase over time in either subgroup. Few participants (6.5% of recent quitters, 2.8% of long-term quitters) reported smoking at both 9 and 12 months, a pattern that might indicate persistent smoking. Past 30-day JUUL use remained high (≥ 87%) across the 12 months. Participants who used JUUL more frequently were less likely to smoke. Conclusions: Among former smokers who purchased JUUL, prevalence rates of smoking were low and stable across the 12-month period, suggesting there was not a growing cohort of former smokers resuming smoking. Smoking was more common in recent quitters than long-term quitters. Greater use of JUUL was associated with reduced odds of smoking resumption.

Transitions in Smoking among Adults Newly Purchasing the JUUL System.

Objectives: In this study, we prospectively assessed changes in smoking a year after US adults' first-time purchase of a JUUL Starter Kit (JSK). Methods: Descriptive analyses assessed transitions in smoking status at 12 months among adult (age ≥21) JSK purchasers providing baseline and 12-month follow-up data (N = 27,164 [49.0% of baseline]), stratified by baseline smoking status. Baseline regular use of other ENDS was also considered. Results: Purchasers included baseline past 30-day smokers (65.2%), former smokers (12.0%), and never smokers (9.7%); over 90% were ever-smokers. One year later, the majority (58%) of those smoking at baseline reported no longer smoking. Former smokers or never smokers who were smoking at 12 months represented less than 2% of respondents. Former and current smokers who were regularly using other ENDS at baseline were less likely to report smoking at 12 months. Conclusions: Past 30-day smoking prevalence in a large longitudinal study of first-time JSK purchasers fell by more than half over 12 months. Analyzing the sample composition at purchase and transitions within subgroups defined by smoking status allows for a detailed understanding to help inform assessments of the population health impact of ENDS.

Changes in Dependence as Smokers Switch from Cigarettes to JUUL in Two Nicotine Concentrations.

Objectives: In this study, we assessed changes in dependence as smokers transitioned from cigarette smoking to exclusive use of the JUUL System ("JUUL"), contrasting users of 5.0% versus 3.0% nicotine concentration pods. Methods: Overall, 5246 adult (age ≥ 21) established smokers (> 100 cigarettes lifetime) who purchased a JUUL device completed online surveys at baseline, when smoking, and one and 3 months later; 1758 reported no past-30-day smoking ('switching') at one or both timepoints. Analyses compared dependence on cigarettes (at baseline) and JUUL (at follow-up), as assessed by the 4-item PROMIS scale (Range: 0-4). Results: Switching increased from Month 1 (18.3%) to Month 3 (28.6%); switchers at one month (Difference = 0.23) and 3 months (0.24) showed lower mean baseline cigarette dependence. Dependence decreased significantly (ps < .001) from baseline cigarette dependence to JUUL dependence at both one (from 1.82 to 1.59) and 3 months (1.97 to 1.73); changes did not significantly differ between users of 5.0% and 3.0% (ps > .43). Dependence on JUUL did not change significantly from Month 1 to Month 3. Conclusions: Dependence decreased as smokers transitioned from smoking to exclusive use of JUUL, similarly for users of both nicotine concentrations. Smokers who switch to JUUL may reduce their nicotine dependence.

An Open-Label, Randomized, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers.

INTRODUCTION: This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers. METHODS: At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session. RESULTS: Maximum plasma nicotine concentration (Cmax-BL), total nicotine exposure (AUC0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and "Enough Nicotine" for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes. CONCLUSIONS: Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes. IMPLICATIONS: It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.

Developmental patterns of tobacco product and cannabis use initiation in high school.

AIMS: To identify prototypical developmental patterns of tobacco product and cannabis use and co-use initiation during adolescence, and determine risk factors for and consequences of these initiation patterns. DESIGN: Prospective repeated-measures cohort with eight semi-annual assessments during high school. Multiple-event process survival mixture modeling identified latent initiation classes with distinct patterns of variation in timing of use initiation of tobacco products and cannabis. We then estimated: (1) associations of baseline risk factors with membership in initiation classes and (2) differences between initiation classes in frequency of cannabis and tobacco product use at the final assessment. SETTING: Ten high schools in the Los Angeles, CA, USA metropolitan area, 2013-17. PARTICIPANTS: Students [1031 (45.4%) males; mean (standard deviation) age at baseline = 14.6 (0.39) years] who had never used any tobacco products or cannabis at baseline 9th grade assessment (n = 2272). MEASUREMENTS: Self-report measures of electronic cigarette (e-cigarette), combustible cigarette, hookah, cigar/cigarillos and cannabis use were collected at each assessment. FINDINGS: Four distinct tobacco and cannabis use initiation classes were identified: (1) early and high-risk cannabis and polytobacco initiators (n = 116; 5.1%); (2) early cannabis and polytobacco initiators (n = 172; 7.6%); (3) late cannabis and e-cigarette initiators (n = 431; 19.0%); and (4) abstainers (n = 1553; 68.4%). At baseline, older age for the early and high-risk cannabis and polytobacco initiators [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.10, 1.35, P < 0.001], peer cannabis use (OR = 1.60, 95% CI = 1.23, 2.08, P < 0.001) and delinquent behavior (OR = 1.30, 95% CI = 1.08, 1.55, P = 0.004) were associated with membership in the three initiation classes (versus abstainers). Membership in the early and high-risk cannabis and polytobacco initiators class (versus three other classes) was significantly associated with increased past 30-day frequency and daily intensity of use at the final assessment (P-values < 0.001). CONCLUSIONS: Older age, peer cannabis use and delinquent behavior appear to be risk factors for the initiation of tobacco/cannabis product use among high school students in the Los Angeles metropolitan region. Early and higher-risk polyproduct use initiation appears to be associated with greater escalation of past 30-day and daily tobacco and cannabis use at the end of the high school.