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Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 15036

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Special Issue Editors

Dr. Alexandra Noël

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Guest Editor

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA
Interests: inhalation toxicology and developmental toxicology; pulmonary effects of distinct emerging inhaled environmental pollutants, including nanoparticles, second-hand smoke, electronic cigarette aerosols, and hookah smoke

Dr. Meghan Rebuli

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Guest Editor

Department of Pediatrics, Center for Environmental Medicine, Asthma and Lung Biology and Curriculum in Toxicology & Environmental Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Interests: respiratory toxicology; clinical, ex vivo, and in vitro e-cigarette respiratory immune toxicity and e-cigarette effects on host defense responses to viral infection

Special Issue Information

Dear Colleagues,

Electronic nicotine delivery devices (ENDS), including electronic cigarettes (e-cigs), were introduced to the US market in 2007. Ever since, the ENDS landscape has evolved quickly to satisfy users’ recreational and smoking cessation needs. Currently, over 13 million Americans, including teenagers and adults, use ENDS. In 2019, there was an outbreak of e-cig or vaping-associated lung injury (EVALI) across the U.S., with more than 2,800 cases of lung injury plus 65 associated deaths. EVALI has been diagnosed in patients since 2012 and is observed in nicotine-exclusive ENDS users. Clearly, all ENDS are not “safe”, and more research on vaping health outcomes is urgently needed. The scientific evidence for future regulations related to ENDS products is based on in vitro and in vivo experiments, as well as clinical and epidemiological studies. It is imperative to investigate the potential adverse health effects of ENDS use because of the increasing popularity of ENDS among youths and young adults, some of whom are never-smokers, as well as in dual-users of cigarette and e-cig products. Furthermore, as a result of the rapid evolution of ENDS products, there is a continuing need to evaluate health effects as new products emerge. In addition, there is a paucity of data related to the health effects of inhaled ENDS aerosols, including the effects related to the cardiopulmonary and reproductive systems and second-hand exposure. This Special Issue, entitled: “Health Effects of Electronic Nicotine Delivery Systems (ENDS):What Can Be Learned from Human and Experimental Studies?”, aims to advance this scientific field by providing additional knowledge and bridging the research gap related to the toxicity mechanisms of ENDS products on human health.

Dr. Alexandra Noël
Dr. Meghan Rebuli
Guest Editors

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Keywords

electronic nicotine delivery devices (ENDS)
electronic cigarettes
e-cigarettes
vaping
respiratory system
cardiovascular system
health effects
in vivo
in vitro
epidemiology

Published Papers (6 papers)

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Research

20 pages, 4003 KiB

Open AccessArticle

Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

by Alexandra Noël, Sultan Yilmaz, Tori Farrow, Matthew Schexnayder, Oliver Eickelberg and Tomislav Jelesijevic

Int. J. Environ. Res. Public Health 2023, 20(4), 3710; https://doi.org/10.3390/ijerph20043710 - 20 Feb 2023

Cited by 3 | Viewed by 1994

Abstract

Currently, approximately 8 million adult Americans use electronic cigarettes (e-cigs) daily, including women of childbearing age. It is known that more than 10% of women smoke during their pregnancy, and recent surveys show that rates of maternal vaping are similar to rates of maternal cigarette smoking. However, the effects of inhaling e-cig aerosol on the health of fetuses remain unknown. The objective of the present study was to increase our understanding of the molecular effects caused by in utero exposures to e-cig aerosols on developing mouse lungs and, later in life, on the offspring’s susceptibility to developing asthma. Methods: Pregnant mice were exposed throughout gestation to either filtered air or vanilla-flavored e-cig aerosols containing 18 mg/mL of nicotine. Male and female exposed mouse offspring were sacrificed at birth, and then the lung transcriptome was evaluated. Additionally, once sub-groups of male offspring mice reached 4 weeks of age, they were challenged with house dust mites (HDMs) for 3 weeks to assess asthmatic responses. Results: The lung transcriptomic responses of the mouse offspring at birth showed that in utero vanilla-flavored e-cig aerosol exposure significantly regulated 88 genes in males (62 genes were up-regulated and 26 genes were down-regulated), and 65 genes were significantly regulated in females (17 genes were up-regulated and 48 genes were down-regulated). Gene network analyses revealed that in utero e-cig aerosol exposure affected canonical pathways associated with CD28 signaling in T helper cells, the role of NFAT in the regulation of immune responses, and phospholipase C signaling in males, whereas the dysregulated genes in the female offspring were associated with NRF2-mediated oxidative stress responses. Moreover, we found that in utero exposures to vanilla-flavored e-cig aerosol exacerbated HDM-induced asthma in 7-week-old male mouse offspring compared to respective in utero air + HDM controls. Conclusions: Overall, these data demonstrate that in utero e-cig aerosol exposure alters the developing mouse lung transcriptome at birth in a sex-specific manner and provide evidence that the inhalation of e-cig aerosols is detrimental to the respiratory health of offspring by increasing the offspring’ susceptibility to developing lung diseases later in life. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

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18 pages, 2004 KiB

Open AccessArticle

Carbonyl Profiles of Electronic Nicotine Delivery System (ENDS) Aerosols Reflect Both the Chemical Composition and the Numbers of E-Liquid Ingredients–Focus on the In Vitro Toxicity of Strawberry and Vanilla Flavors

by Alexandra Noël and Arpita Ghosh

Int. J. Environ. Res. Public Health 2022, 19(24), 16774; https://doi.org/10.3390/ijerph192416774 - 14 Dec 2022

Cited by 6 | Viewed by 1949

Abstract

Propylene glycol (PG) and glycerin (G) are the most widely used humectants in electronic nicotine delivery system (ENDS) devices. Carbonyls are present in aerosols produced when ENDS devices heat PG and G. Whether aerosolized PG and G are innocuous to the lungs has not been established. Here, we determined the chemical profiles of ENDS aerosols containing three humectant ratios (30/70, 50/50 and 70/30, PG/VG), for three flavors (strawberry, vanilla and Catalan cream) containing either 12 or 18 mg/mL of nicotine. Additionally, we examined the in vitro toxicity of the strawberry- and vanilla-flavored ENDS aerosol in human lung epithelial cells (BEAS-2B) exposed at the air-liquid interface for 1 h. For strawberry- and vanilla-flavored aerosols produced by a 3rd-generation ENDS device with the same PG/G ratio, the e-liquid nicotine content of 12 and 18 mg/mL did not transfer to the aerosol with substantial differences in concentrations. Our data also indicate the presence of carbonyls in all three flavored e-cig aerosols analyzed, with levels exceeding 1 µg/puff for acetone, butyraldehyde, and acetaldehyde, in strawberry-, vanilla, and Catalan cream-flavored e-cig aerosols, respectively. Furthermore, closed-system ENDS of the fourth generation emitted trace levels of carbonyls in the aerosols (<0.3 µg/puff), while open-system tank-style ENDS of the third generation produced elevated levels of harmful chemicals, including acrolein (>1 µg/puff), formaldehyde (>5 µg/puff), and m- & p-tolualdehyde (>4 µg/puff). Moreover, under non-cytotoxic conditions, BEAS-2B cells exposed to strawberry-flavored aerosols exhibited significantly increased reactive oxygen and nitric oxide species (ROS/NOS) levels in cell media compared to air controls, while vanilla-flavored ENDS aerosols up-regulated the expression of pro-inflammatory and oxidative stress markers. Our data suggest (a) that ENDS aerosol chemical composition will vary based upon the presence and concentration of the initial e-liquid ingredients, with a pronounced impact of the flavoring components; and (b) short-term exposures to flavored ENDS aerosols may impair lung cells’ redox signaling in a flavor-specific manner. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

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12 pages, 904 KiB

Open AccessArticle

A Survey on the Actual Use of and Reasons for Heated Tobacco Products in Patients with Rheumatoid Arthritis

by Hisaaki Isaji and Kiyofumi Yamada

Int. J. Environ. Res. Public Health 2022, 19(19), 12465; https://doi.org/10.3390/ijerph191912465 - 30 Sep 2022

Viewed by 1394

Abstract

The actual use of heated tobacco products (HTPs) among smokers with rheumatoid arthritis (RA) is little known. The objective of this study was to clarify the prevalence and reasons for HTP use among smokers with RA. We administered a web survey to a research company panel in Japan between December 2020 and January 2021. After 170,000 panelists completed a primary questionnaire regarding smoking and disease status, 198 smokers with RA completed a secondary questionnaire regarding the reasons for HTP use and perceptions about the harmfulness of HTPs. The primary questionnaire revealed that smokers with RA were more likely to use HTPs than smokers without RA, and the adjusted odds ratio of RA for HTP use was one of the highest factors among other diseases (adjusted OR: 2.34, 95% CI: 1.92–2.85, p < 0.001). The secondary questionnaire revealed that 43.7% of HTP smokers with RA had considered using HTPs due to their RA, and 42.0% of them felt that starting HTPs relieved the symptoms of RA. These results indicated that smokers with RA tend to start using HTPs due to their RA, despite the lack of evidences that HTPs are safer alternatives. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

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22 pages, 7040 KiB

Open AccessArticle

Effects of E-Cigarette Flavoring Chemicals on Human Macrophages and Bronchial Epithelial Cells

by Anna M. Morris, Stephen S. Leonard, Jefferson R. Fowles, Theresa E. Boots, Anna Mnatsakanova and Kathleen R. Attfield

Int. J. Environ. Res. Public Health 2021, 18(21), 11107; https://doi.org/10.3390/ijerph182111107 - 22 Oct 2021

Cited by 18 | Viewed by 3328

Abstract

E-cigarettes utilize a wide range of flavoring chemicals with respiratory health effects that are not well understood. In this study, we used pulmonary-associated cell lines to assess the in vitro cytotoxic effects of 30 flavoring chemicals. Human bronchial epithelial cells (BEAS-2B) and both naïve and activated macrophages (THP-1) were treated with 10, 100, and 1000 µM of flavoring chemicals and analyzed for changes in viability, cell membrane damage, reactive oxygen species (ROS) production, and inflammatory cytokine release. Viability was unaffected for all chemicals at the 10 and 100 µM concentrations. At 1000 µM, the greatest reductions in viability were seen with decanal, hexanal, nonanal, cinnamaldehyde, eugenol, vanillin, alpha-pinene, and limonene. High amounts of ROS were elicited by vanillin, ethyl maltol, and the diketones (2,3-pentanedione, 2,3-heptanedione, and 2,3-hexanedione) from both cell lines. Naïve THP-1 cells produced significantly elevated levels of IL-1β, IL-8, and TNF-α when exposed to ethyl maltol and hexanal. Activated THP-1 cells released increased IL-1β and TNF-α when exposed to ethyl maltol, but many flavoring chemicals had an apparent suppressive effect on inflammatory cytokines released by activated macrophages, some with varying degrees of accompanying cytotoxicity. The diketones, L-carvone, and linalool suppressed cytokine release in the absence of cytotoxicity. These findings provide insight into lung cell cytotoxicity and inflammatory cytokine release in response to flavorings commonly used in e-cigarettes. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

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15 pages, 350 KiB

Open AccessArticle

“Don’t Know” Responses for Nicotine Vaping Product Features among Adult Vapers: Findings from the 2018 and 2020 ITC Four Country Smoking and Vaping Surveys

by Nicholas J. Felicione, K. Michael Cummings, Shannon Gravely, David Hammond, Ann McNeill, Ron Borland, Geoffrey T. Fong and Richard J. O’Connor

Int. J. Environ. Res. Public Health 2021, 18(15), 7928; https://doi.org/10.3390/ijerph18157928 - 27 Jul 2021

Cited by 2 | Viewed by 2398

Abstract

Nicotine vaping products (NVPs) have evolved rapidly, and some vapers have difficulty reporting about their NVP. NVP knowledge may be important for providing accurate survey data, understanding the potential risks of NVP use, and assessing legal and regulated products. This paper examines current vapers who responded “don’t know” (DK) regarding their NVP features. Data are from adult daily/weekly vapers in Waves Two (2018, n = 4192) and Three (2020, n = 3894) of the ITC Four Country Smoking and Vaping Survey. Analyses assessed DK responses for NVP features (e.g., type/appearance, nicotine) and consumption. A DK index score was computed based on the percent of all features with DK responses, which was tested for associations with demographics, smoking/vaping status, NVP features, purchase location, and knowledge of NVP relative risks. NVP description and appearance were easily identified, but DK was more common for features such as nicotine content (7.3–9.2%) and tank/cartridge volume capacity (26.6–30.0%). DK responses often differed by vaping/smoking status, NVP type/appearance, purchase location, and country. Vapers who are younger, use box-shaped NVPs, purchase online, and exclusive daily vapers were associated with lower DK index scores. Higher DK index scores were associated with poorer knowledge of relative health risks of NVP use. The diversity of the NVP market and wide variation in how products are used makes it challenging to capture information from users about device features, such as nicotine content and capacity, in population surveys. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

13 pages, 1000 KiB

Open AccessArticle

A Descriptive Analysis of Transitions from Smoking to Electronic Nicotine Delivery System (ENDS) Use: A Daily Diary Investigation

by Tamlin S. Conner, Jiaxu Zeng, Mei-Ling Blank, Vicky He and Janet Hoek

Int. J. Environ. Res. Public Health 2021, 18(12), 6301; https://doi.org/10.3390/ijerph18126301 - 10 Jun 2021

Cited by 8 | Viewed by 2916

Abstract

Objectives: We aimed to examine patterns in smoking and electronic nicotine delivery system (ENDS) use over an extended period of time (up to 20 weeks) in people who smoked and who had never previously made a successful quit attempt using an ENDS. Design and setting: We conducted a longitudinal mixed-methods study in Dunedin, New Zealand, during 2018 and 2019. Participants: Purposively selected participants (N = 45; age (≥18 years), gender, ethnicities, cigarettes/day) who wished to quit smoking. Interventions: Participants were provided with a second-generation ENDS device (vape pen or starter “tank” device) at the start of their quit attempt, and asked to complete smartphone-based daily diary surveys assessing smoking and ENDS use. Outcome measures: Sunburst plots and a sequence plot were used to describe weekly and daily patterns of smoking and ENDS use (smoking only, ENDS use only, dual use, abstinent). Results: The most frequently reported movements among participants, classified according to their study week behaviour, occurred between dual use and exclusive ENDS use (and vice versa). A smaller group reported moving from dual use to exclusive smoking (and often back to dual use), and a small number reported moving between abstinence and different ENDS and smoked tobacco usage behaviours. Data visualisations focussing on those participants who had provided data during each of weeks 9–12 indicate that only a minority reported sustained dual use; instead, most participants indicated varied smoked tobacco and ENDS use, which included periods of dual use. Conclusions: The considerable variety observed within and between study participants suggests that high variability is typical rather than exceptional. Transitions from smoking to ENDS use may involve considerable periods of dual use, which is likely to be dynamic and potentially sustained over several months. Full article

(This article belongs to the Special Issue Health Effects of Electronic Nicotine Delivery Systems (ENDS): What Can Be Learned from Human and Experimental Studies?)

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