Role of reactive carbonyls and superoxide radicals in protein damage by cigarette smoke extracts: Comparison of Heat-not-Burn e-cigarettes to conventional cigarettes.

Oxidative protein damage involving carbonylation of respiratory tract proteins typically accompanies exposure to tobacco smoke. Such damage can arise via multiple mechanisms, including direct amino acid oxidation by reactive oxygen species or protein adduction by electrophilic aldehydes. This study investigated the relative importance of these pathways during exposure of a model protein to fresh cigarette emission extracts. Briefly, protein carbonyl adducts were estimated in bovine serum albumin following incubation in buffered solutions with whole cigarette emissions extracts prepared from either a single 1R6F research cigarette or a single "Heat-not-Burn" e-cigarette. Although both extracts caused concentration-dependent protein carbonylation, conventional cigarette extracts produced higher adduct yields than e-cigarette extracts. Superoxide radical generation by conventional and e-cigarette emissions was assessed by monitoring nitro blue tetrazolium reduction and was considerably lower in extracts made from "Heat-Not-Burn" e-cigarettes. The superoxide dismutase/catalase mimic EUK-134 strongly suppressed radical production by whole smoke extracts from conventional cigarettes, however, it did not diminish protein carbonyl adduction when incubating smoke extracts with the model protein. In contrast, edaravone, a neuroprotective drug with strong carbonyl-trapping properties, strongly suppressed protein damage without inhibiting superoxide formation. Although these findings require extension to appropriate cell-based and in vivo systems, they suggest reactive aldehydes in tobacco smoke make greater contributions to oxidative protein damage than smoke phase radicals.

Respiratory symptoms and outcomes among cigar smokers: findings from the Population Assessment of Tobacco and Health (PATH) study waves 2-5 (2014-2019).

BACKGROUND: The mechanisms by which cigarette smoking increases the risk of respiratory disease have been studied. However, less is known about risks of respiratory symptoms and outcomes associated with smoking cigars, and risks by cigar types have not been previously explored. The aim of this study was to examine associations between cigar use, including traditional cigars, cigarillos, filtered cigars, and dual cigar and cigarette use, and functionally important respiratory symptoms (FIRS), lifetime asthma diagnosis, uncontrolled asthma, and new cases of FIRS. METHODS: Data from Waves 2-5 (2014-19) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal study, were analyzed in two ways. For cross-sectional analysis, the analytic sample included adults 18 and older at each wave, resulting in 44,040 observations. Separately, longitudinal analyses were assessed among adults 18 and older at Wave 2, resulting in 7,930 individuals. Both analyses excluded adults with chronic obstructive pulmonary disease (COPD) or non-asthma respiratory disease. RESULTS: Current established cigarillo smokers had higher odds of having FIRS (Adjusted odds ratio (AOR): 1.72; 95% CI: 1.08, 2.74) compared to never smokers of cigarillos and cigarettes, after adjusting for covariates. Current established filtered cigar smokers had higher odds of asthma diagnosis (AOR: 1.35; 95% CI: 1.10, 1.66) while current established dual smokers of filtered cigars and cigarettes had higher odds of uncontrolled asthma (AOR: 5.13; 95% CI: 1.75, 15.02) compared to never smokers of filtered cigars or cigarettes. Both current established cigar smokers and current established dual smokers of cigarettes and cigars had higher odds of new FIRS compared to never cigar or cigarette smokers (AORs: 1.62; 95% CI: 1.02, 2.60 for exclusive cigars and 2.55; 95% CI 1.57, 4.14 for dual smokers). CONCLUSIONS: This study provides evidence that cigar smokers or dual smokers of cigars and cigarettes have greater odds of FIRS, asthma, and uncontrolled asthma and that new incidence of FIRS is higher among any cigar smokers compared to never cigar or cigarette smokers. Understanding health impacts associated with cigar use provides information for supporting policy development, as well as for designing clinical interventions focused on smoking cessation for cigars.

Association between heated tobacco product use and airway obstruction: a single-centre observational study, Japan.

BACKGROUND: While heated tobacco products (HTPs) may affect pulmonary function, the evidence supporting the utility of screening for HTP use in clinical settings is insufficient. We examined the association between HTP use and airway obstruction after switching from cigarettes. METHOD: The study subjects were patients aged ≥20 years undergoing surgery from December 2021 to September 2022 who completed spirometry and reported tobacco (cigarette and HTP) use status during the preoperative assessment. Airway obstruction was defined as forced expiratory volume in 1 s to forced vital capacity ratio below the lower limit of normal. Current tobacco use was defined as past-30-day use. Multivariable Poisson regression analysis was performed to examine the associations between HTP use and airway obstruction by adjusting for demographic characteristics, lifetime cigarette smoking (pack-year) and duration of smoking cessation. RESULTS: Overall (N=2850, 55.4% women, mean age 62.4), 4.6% and 10.7% reported current HTP use and cigarette smoking, respectively. 16.8% had airway obstruction. Airway obstruction was more common among current HTP-only users (adjusted prevalence ratio (APR)=2.32), current cigarette-only smokers (APR=2.57) and current dual users (APR=2.82) than never-tobacco users. Among current tobacco users (N=398), the prevalence of airway obstruction was not significantly different between HTP-only users and cigarette-only smokers. Among former cigarette smokers (>30-day cigarette quitters) (N=1077), current HTP users had 1.42 times the increased prevalence of airway obstruction than never-HTP users after adjusting for cigarette pack-year; a stronger association was observed when the analysis was restricted to ≥5-year cigarette quitters (N=772) (APR=1.96, vs never HTP users). CONCLUSION: Current HTP use was associated with airway obstruction among patients with cancer who had completely switched from cigarettes even after quitting smoking for a long period. Patients should be routinely screened for HTP use and advised to quit any tobacco.

Ingestion of heated tobacco sticks containing a micro-blade by children: the importance of performing a radiograph.

INTRODUCTION: Some tobacco sticks, such as TEREA™ heat sticks for IQOS ILUMA™, contain a blade. Both the nicotine part of the device and the micro-blade can be ingested by children. CASE SUMMARIES: We report two children, an 18-month-old boy and a 10-month-old girl, who ingested a heat stick containing a micro-blade. IMAGES: Radiography revealed the micro-blade to be in the child's mouth in the first case and the stomach in the second. Endoscopy was performed on the second child, confirming the presence of the blade in the stomach. CONCLUSION: We recommend performing a radiograph on all children who ingest tobacco sticks containing a micro-blade. If a metallic object is present, we recommend endoscopic removal to avoid traumatic lesions from the sharp edges.

Heated Tobacco Products Have Detrimental Effects on Rotator Cuff Healing, Similar to Conventional Cigarettes.

BACKGROUND: Cigarette smoking impairs rotator cuff healing, but no study, to our knowledge, has focused on the association between heated tobacco products and rotator cuff tears. METHODS: This study retrospectively investigated 1,133 patients who underwent arthroscopic repair of symptomatic rotator cuff tears between March 2011 and April 2021. Patients were grouped on the basis of their smoking patterns as nonsmokers, cigarette smokers, and heated tobacco smokers. Propensity score matching was used to reduce selection bias, and 45 subjects were selected from each group via 1:1:1 matching. Functional scores and active range of motion were compared among the 3 groups preoperatively and at a 2-year follow-up. Postoperative magnetic resonance imaging was performed 6 months after the surgical procedure to assess structural integrity. RESULTS: Except for sex, similar baseline characteristics were achieved after propensity score matching. There were no differences in the clinical scores or range of motion between the matched groups either preoperatively or at the 2-year follow-up. However, the retear rate for the matched nonsmoker group was significantly lower (8.9%) than those for the matched cigarette smoker group (31.1%) and the heated tobacco smoker group (28.9%) (p = 0.022). Multivariable logistic regression analysis revealed that the retear rates were 3.403 times higher for the cigarette smoker group and 3.397 times higher for the heated tobacco smoker group than that for the nonsmoker group. CONCLUSIONS: Heated tobacco users, like conventional cigarette smokers, have worse clinical outcomes with respect to rotator cuff healing than nonsmokers. Regardless of the type of cigarette, abstinence from smoking is necessary for patients undergoing rotator cuff repair surgery. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Comparison of the effects of active and passive smoking of tobacco cigarettes, electronic nicotine delivery systems and tobacco heating products on the expression and secretion of oxidative stress and inflammatory response markers. A systematic review.

OBJECTIVES: This work attempts to summarize current knowledge on the effects of active and passive smoking of cigarettes, electronic nicotine delivery systems and tobacco heating products on the expression and secretion of oxidative stress and inflammatory response mediators, and on their possible impact on chronic obstructive pulmonary disease development. MATERIALS AND METHODS: The literature was searched by the terms: 'smoking', 'active smoking', 'passive smoking', 'main-stream smoke', 'side-stream smoke', 'secondhand smoke', 'cigarette' 'THP', 'tobacco heating product', 'ENDS', 'electronic nicotine delivery system', 'e-cigarette', 'electronic cigarette', oxidative stress', inflammatory response' and 'gene expression'. RESULTS: Cigarette smoking (active and passive) induces oxidative stress and inflammatory response in the airways. We present the effect of active smoking of e-cigarettes (EC) and heat-not-burn (HnB) products on the increased expression and secretion of oxidative stress and inflammatory response markers. However, there is only a limited number of studies on the effect of their second-hand smoking, and those available mainly describe aerosol composition. DISCUSSION: The literature provides data which confirm that active and passive cigarette smoking induces oxidative stress and inflammatory response in the airways and is a key risk factor of COPD development. Currently, there is a limited number of data about ENDS and THP active and passive smoking effects on the health of smokers and never-smokers. It is particularly important to assess the effect of such products during long-term use by never-smokers who choose them as the first type of cigarettes, and for never-smokers who are passively exposed to their aerosol.

Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes.

Disease Odds for E-Cigarettes and Dual Use versus CigarettesE-cigarettes have been promoted as less harmful than cigarettes. In this meta-analysis, Glantz et al. show that for some diseases, e-cigarette disease risks were similar to cigarettes, and for others e-cigarettes were nearly as risky as cigarettes. The risks associated with dual use were higher than those for smoking alone.

Comparative systematic review on the safety of e-cigarettes and conventional cigarettes.

BACKGROUND: This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on the subject to provide a comprehensive analysis of potential health risks associated with both smoking methods. METHODS: The systematic review, incorporating searches in PubMed, Scopus, Web of Science, and the Cochrane Library up to July 2023, examines the results obtained in relevant studies, and provides a critical discussion of the results. RESULTS: E-cigarettes exhibit reduced exposure to harmful toxins compared to traditional cigarettes. CONCLUSION: However, concerns persist regarding respiratory irritation and potential health risks, especially among youth, emphasizing the need for comprehensive, long-term research and protective legislation.

Pilot Application of SEM/EDX Analysis on Suspected Cigarette Burns in a Forensic Autopsy Case of Child Abuse.

ABSTRACT: Cigarette burn lesions present forensic scenarios that are often difficult to investigate, both from a morphological diagnostic point of view and with regard to the mode of infliction, especially if the victim is unable to speak or has died. Although there may be the suspicion for a lesion to be produced by a lit cigarette, to date one can only rely on the morphological aspects that characterize it, and there is a lack of tools to reach the most evidence-based diagnosis possible. This limitation arose when managing a forensic autopsy case of possible child abuse that resulted in the death of the child, characterized by the presence of 3 suspicious cigarette burn lesions. We therefore decided to perform scanning electron microscopy/energy-dispersive x-ray (SEM/EDX) spectrometry analysis on these lesions and on the cigarette butt found at the crime scene. At the same time, SEM/EDX was applied to the analysis of an unlit cigarette in its entirety (obtained from the same source package as the cigarette butt), a positive control skin sample with an iatrogenic cigarette burn injury, and a negative control skin sample. Among the various compounds highlighted on compositional analysis, only sulfuric anhydride (SO 3 ) and phosphoric anhydride (P 2 O 5 ) showed a highly significant distribution pattern by being found in the autopsy samples, the cigarette butt, the tobacco of the unlit cigarette, and the positive skin control. Considering this, cigarette burns appear to follow Locard's principle as well, and similarly to other lesions, SEM/EDX allowed the diagnosis of cigarette burn lesions, already suspected morphologically, to be corroborated. Therefore, SEM/EDX is confirmed as a helpful tool in forensic pathology investigations.

An atlas of epithelial cell states and plasticity in lung adenocarcinoma.

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention.

Association between cigar use, with and without cigarettes, and incident diagnosed COPD: a longitudinal cohort study.

BACKGROUND: While regular cigar smoking is believed to carry similar health risks as regular cigarette smoking, the impact of cigar use, alone or in combination with cigarettes, on obstructive pulmonary disease (COPD) has not been well characterized. The purpose of this study was to examine the prospective association between exclusive and dual cigar and cigarette use and incident self-reported diagnosed COPD. METHODS: This study used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative survey of U.S. adults. Longitudinal data from adults aged 40 to 79 at Wave 1, without a pre-existing COPD diagnosis who participated at follow-up interview were analyzed. A time-varying current tobacco exposure, lagged by one wave and categorized as: (a) never/non-current use; (b) exclusive cigar use; (c) exclusive cigarette use; and (d) dual cigar/cigarette use. Multivariable models adjusted for demographics (age, sex, race or ethnicity, education), clinical risk factors (asthma, obesity), and smoking-related confounders (second-hand smoke exposure, other combustible tobacco product use, e-cigarette use, time since quitting, cigarette pack-years). The incidence of self-reported diagnosed COPD was estimated using discrete-time survival models, using a general linear modeling (GLM) approach with a binomial distribution and a complementary log-log link function. RESULTS: The analytic sample consisted of 9,556 adults with a mean (SD) age of 56 (10.4), who were predominately female (52.8%) and Non-Hispanic White (70.8%). A total of 906 respondents reported a diagnosis of COPD at follow-up. In the fully adjusted model, exclusive cigar use (adjusted hazard ratio (aHR) = 1.57, 95% CI: 0.77, 3.21) was not associated with increased COPD risk compared to non-use, while exclusive cigarette use (aHR = 1.48, 95% CI: 1.13, 1.93) and dual cigar/cigarette use (aHR = 1.88, 95% CI: 1.24, 2.85) were. CONCLUSIONS: Exclusive cigarette use and dual cigar/cigarette use were associated with diagnosed incident COPD. These results suggest that cigars, when used in combination with cigarettes, may be associated with poorer COPD health outcomes. Dual use may promote a higher likelihood of inhaling cigar smoke, and future research would benefit from examining whether inhalation of cigar smoke increases COPD risk.

Vuse Solo e-cigarettes do not provide net benefits to public health: a scientific analysis of FDA's marketing authorisation.

In October 2021, the US Food and Drug Administration (FDA) authorised marketing of RJ Reynolds Vapor Company's (RJR) Vuse Solo e-cigarette through FDA's Premarket Tobacco Product Application (PMTA) pathway. FDA concluded that RJR demonstrated Vuse products met the statutory standard of providing a net benefit to public health. A review of FDA's scientific justification reveals deficiencies: (1) not adequately considering Vuse's popularity with youth and evidence that e-cigarettes expanded the nicotine market and stimulate cigarette smoking; (2) trading youth addiction for unproven adult benefit without quantifying these risks and benefits; (3) not considering design factors that appeal to youth; (4) not addressing evidence that e-cigarettes used as consumer products do not help smokers quit and promote relapse in former smokers; (5) not discussing evidence that dual use is more dangerous than smoking; (6) narrowly focusing on the fact that e-cigarettes deliver lower levels of some toxicants without addressing direct evidence on adverse health effects; (7) downplaying significant evidence of other substantial harms; (8) not acting on FDA's own study showing no all-cause mortality benefit of reducing (but not stopping) cigarette use; and (9) improperly considering e-cigarettes' high abuse liability and potential for high youth addiction and undermining tobacco cessation. Because marketing these products is not appropriate for the protection of the public health, FDA should reconsider its Vuse marketing order as statutorily required and not use it as a template for other e-cigarette PMTAs. Policymakers outside the USA should anticipate that tobacco companies will use FDA's decision to try to weaken tobacco control regulation of e-cigarettes and promote their products.

Examining Perceptions of Uncertain Language in Potential E-Cigarette Warning Labels: Results from 16 Focus Groups with Adult Tobacco Users and Youth.

E-cigarette use among youth presents a public health risk. Yet, cigarette smokers who substantially reduce their smoking or switch completely from traditional combustible cigarettes could benefit. As science about e-cigarettes is continually emerging, any potential warnings are likely to contain uncertain language. Hedged verbiage may impact decision making. To assess reactions, we conducted 16 online focus groups; 8 with youth (n = 32, grouped by gender and by vaping experience) and 8 with adult tobacco users (n = 37, grouped by smokers, dual users of e-cigarettes and cigarettes, and former smokers who switched to e-cigarettes). Each focus group viewed and discussed 8 potential warnings messages. We conducted an inductive thematic analysis of the reactions to warning messages that contain uncertain language. Respondents' reactions were often negative, but varied based on specific usages of uncertainty, existing beliefs about uncertainty in law and science, and smoking/vaping use patterns that supported the use of uncertainty related to e-cigarettes. Many youth (and some adults) believed that uncertain language enabled audiences to minimize the likelihood of harm or interpreted it as meaning there are both healthy and unhealthy e-cigarettes. This qualitative study provides evidence that the use of types of uncertain language, the frequency of that use, and/or the selection of particular words in warnings, might not achieve the intended public health aims of increasing understanding of risk, deterring youth uptake, and/or facilitating a substantial switch from cigarettes. The use of certain types of uncertain language appears to have significant potential to bring unintended consequences. Suggestions for research and policy are included.

[Research progress on the prevalence and harm of heated tobacco products].

Heated tobacco products (HTP) are a new type of tobacco product, also known as heat-not-burn (HnB) tobacco products. They are devices that use an electronic heat source to heat tobacco and produce aerosols containing nicotine for smokers to inhale. Currently, traditional combustible cigarettes and electronic nicotine delivery systems (ENDS) are increasingly being regulated under the Framework Convention on Tobacco Control. Tobacco companies have responded by actively promoting heated tobacco products worldwide, which pose new challenges to global tobacco control efforts and may become a challenge for tobacco control work in China. In reviewing the situation and the potential harm of heated tobacco products, it was noted that HTP are rapidly gaining popularity worldwide, and that their harmfulness may be underestimated. Compared to combustible cigarettes (CC) and ENDS, the long-term health effects of HTP are not fully understood, and they may pose new health risks. Potential health risks include an increase in smoking prevalence, the presence of harmful and potentially harmful compounds not found in CC, and the potential gateway effect on non-smokers. Due to differences in laws, regulations, health policies, institutions, and cultural factors related to the tobacco industry in different countries and regions, attitudes, and regulatory measures towards HTP also vary. It is essential for countries and regions around the world to develop appropriate policies to strengthen control of HTP and prevent their widespread use.

What Can Current Biomarker Data Tell Us About the Risks of Lung Cancer Posed by Heated Tobacco Products?

INTRODUCTION: Heated tobacco products (HTPs) are marketed as less harmful alternatives to cigarettes, but the lung cancer risk of HTPs is unknown. In the absence of epidemiological data, assessing the risks of HTPs relies on biomarker data from clinical trials. This study examined existing biomarker data to determine what it tells us about the lung cancer risk posed by HTPs. AIMS AND METHODS: We identified all biomarkers of exposure and potential harm measured in HTP trials and evaluated their appropriateness based on ideal characteristics for measuring lung cancer risk and tobacco use. The effects of HTPs on the most appropriate biomarkers within cigarette smokers switched to HTPs and compared to continued cigarette smoking or cessation were synthesized. RESULTS: Sixteen out of eighty-two biomarkers (7 exposure and 9 potential harm) measured in HTP trials have been associated with tobacco use and lung cancer, dose-dependently correlated with smoking, modifiable upon cessation, measured within an appropriate timeframe, and had results published. Three of the exposure biomarkers significantly improved in smokers who switched to HTPs and were not significantly different from cessation. The remaining 13 biomarkers did not improve-in some instances worsening upon switching to HTPs-or were inconsistently affected across studies. There were no appropriate data to estimate the lung cancer risk of HTPs in non-smokers. CONCLUSIONS: The appropriateness of existing biomarker data in assessing lung cancer risk of HTPs, both relative to cigarettes and their absolute risk, is limited. Furthermore, findings on the most appropriate biomarkers were conflicting across studies and largely showed no improvement following a switch to HTPs. IMPLICATIONS: Biomarker data are fundamental to assessing the reduced risk potential of HTPs. Our evaluation suggests much of the existing biomarker data on HTPs is inappropriate for determining the risk of lung cancer posed by HTPs. In particular, there is a paucity of data on the absolute lung cancer risk of HTPs, which could be obtained from comparisons to smokers who quit and never smokers exposed to or using HTPs. There is an urgent need for further exploration of the lung cancer risks posed by HTPs, via clinical trials and, in the long-term, confirmation of these risks via epidemiological studies. However, careful consideration should be given to biomarker selection and study design to ensure both are appropriate and will provide valuable data.

Use of cigarettes and heated tobacco products during pregnancy and maternal-fetal outcomes: a retrospective, monocentric study.

PURPOSE: To compare the effects of using heated tobacco products (HTP) or traditional cigarettes (C) on maternal and neonatal outcomes. METHODS: This is a retrospective, monocentric study conducted at San Marco Hospital from July 2021 to July 2022. We compared a cohort of pregnant patients who smoked HTP (HS), with pregnant women smoking cigarettes (CS), ex-smoker (ES) and non-smoker (NS) pregnant women. Biochemistry, ultrasound, and neonatal evaluations were performed. RESULTS: In total, 642 women were enrolled, of which 270 were NS, 114 were ES, 120 were CS, and 138 were HS. CS had the greatest weight gain and had more difficulty getting pregnant. Smokers and ES experienced more frequently threats of preterm labor, miscarriages, temporary hypertensive spikes, and higher rates of cesarean sections. Preterm delivery was more associated with CS and HS groups. CS and HS had lower awareness of the risks to which the mother and the fetus are exposed. CS were more likely to be depressed and anxious. Biochemical parameters did not show significant differences between the groups. CS had the greatest difference in days between the gestational age calculated based on the last menstrual period and the one based on the actual ultrasound age. The average percentile newborn weight range of CS was lower, as well as the mean 1st minute and the 5th minute Apgar scores. CONCLUSION: The comparison of the data obtained between CS and HS underlines the greater danger of C. Nevertheless, we do not recommend HTP because the maternal-fetal outcomes are not superimposable to the NS outcomes.

Organic, Earth-Friendly Tobacco With a Charcoal Filter and Smooth Taste: A Randomized Experiment Testing Effects of Natural American Spirit's "Sky" Cigarette Advertising on Consumer Perceptions.

INTRODUCTION: The Natural American Spirit (NAS) brand has a history of marketing tactics that may convey reduced harm. While no longer allowed to use "additive-free" or natural descriptors (except in the brand name), it continues promoting potentially misleading attributes. This study examined perceptions of NAS's newer "Sky" style, promoted as organic tobacco with a charcoal filter. AIMS AND METHODS: In an online experiment, we randomized 1927 adult past 30-day tobacco or nicotine product users to one of six conditions showing Sky ads with different descriptors: (1) charcoal filter, (2) charcoal + organic, (3) charcoal + earth-friendly, (4) charcoal + smooth taste, (5) charcoal + all other descriptors, and (6) no-descriptor control (Sky ads without target descriptors). Product perceptions were compared by condition. Participants also reported perceived benefits of charcoal filters. RESULTS: Overall, 28% of participants indicated Sky is less harmful and 38% believed it exposes users to fewer chemicals. Participants in the "charcoal + organic," "charcoal + earth-friendly," and the all-descriptor conditions had higher odds of believing Sky reduces chemical exposure (respectively, 43%, 40%, and 42%), relative to the no-descriptor control. Fewer control participants endorsed beliefs that Sky has a "better filter" and is "more environmentally friendly". Many believed cigarettes with charcoal filters could confer benefits relative to other cigarettes, such as reducing chemical exposure, or being cleaner, purer or safer (though research on relative safety of charcoal filters in cigarettes is inconclusive). CONCLUSIONS: Sky marketing may promote misperceptions about product safety and composition, and ads using both charcoal and organic text may particularly reinforce them. IMPLICATIONS: This study examined the impact of new cigarette advertising promoting the use of charcoal filters and organic tobacco along with other suggestive claims ("environmentally friendly," "smooth taste") on tobacco users' perceptions of the advertised product-NAS Sky cigarettes. Our study provides new data about positive consumer perceptions of charcoal-filtered cigarettes, and results suggest that combinations of these marketing terms evoke perceptions about reduced harm and reduced exposure to harmful chemicals that may be misleading to the public. Our findings underscore a need for additional regulatory action regarding tobacco marketing that makes use of natural-themed marketing.