E-cigarette flavored pods induce inflammation, epithelial barrier dysfunction, and DNA damage in lung epithelial cells and monocytes

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Abstract

E-cigarette flavored pods are increasing in use among young adults. Although marketed as a safer alternative to conventional cigarettes, the health effects of e-cigarette flavored pods are unknown. We hypothesized that e-cigarette flavored pods would cause oxidative stress, barrier dysfunction, and an inflammatory response in monocytes and lung epithelial cells. JUUL pod flavors (Fruit Medley, Virginia Tobacco, Cool Mint, Crème Brulee, Cool Cucumber, Mango, and Classic Menthol) and similar pod flavors (Just Mango-Strawberry Coconut and Caffé Latte) were tested. These pod flavors generated significant amounts of acellular ROS and induced significant mitochondrial superoxide production in bronchial epithelial cells (16-HBE). Lung epithelial cells (16-HBE, BEAS-2B) and monocytes (U937) exposed to various pod aerosols resulted in increased inflammatory mediators, such as IL-8 or PGE2. JUUL pod flavors, Crème Brulee and Cool Cucumber, caused epithelial barrier dysfunction in 16-HBE cells. Moreover, tested flavors also showed DNA damage upon exposure in monocytes. We determined the chemical constituents present in various flavors. Our data suggest that these constituents in flavored pods induce oxidative stress, inflammation, epithelial barrier dysfunction, and DNA damage in lung cells. These data provide insights into the regulation of e-cigarette flavored pods, as well as constituents in these flavors.

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Inflammatory responses and inflammation-associated diseases in organs

Linlin Chen, Huidan Deng, Hengmin Cui … (2017)

Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.

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Reactive oxygen species: role in the development of cancer and various chronic conditions

Gulam Waris, Haseeb Ahsan (2006)

Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention.

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Notes from the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students — United States, 2011–2018

Karen A Cullen, Bridget K Ambrose, Andrea S. Gentzke … (2018)

Electronic cigarettes (e-cigarettes) are battery-powered devices that provide nicotine and other additives to the user in the form of an aerosol ( 1 ). E-cigarettes entered the U.S. marketplace in 2007 ( 1 ), and by 2014, e-cigarettes were the most commonly used tobacco product among U.S. youths ( 2 ). Data from the 2011–2018 National Youth Tobacco Survey (NYTS), a cross-sectional, voluntary, school-based, self-administered, pencil-and-paper survey of U.S. middle and high school students, were analyzed to determine the prevalence of current use (≥1 day in past 30 days) of e-cigarettes,* current use of any tobacco product, † frequency of (number of days during the preceding 30 days) e-cigarette use, and current use (any time during preceding 30 days) of any flavored e-cigarettes among U.S. middle school (grades 6–8) and high school (grades 9–12) students. Logistic regression (2011–2018) and t-tests (2017–2018) were performed to determine statistically significant differences (p 0.05) (Figure). Current use of any tobacco product among middle school students was 7.5% (870,000 students) in 2011 and 7.2% (840,000 students) in 2018 (p>0.05). During 2017–2018, overall tobacco product use increased by 38% among high school students (from 19.6% to 27.1%, p<0.001) and by 29% among middle school students (from 5.6% to 7.2%, p = 0.008). Current e-cigarette use increased considerably among U.S. middle and high school students during 2017–2018, reversing a decline observed in recent years and increasing overall tobacco product use ( 3 ). Moreover, during 2017–2018, frequent e-cigarette use increased among high school students. Although e-cigarettes have the potential to benefit adult smokers if used as a complete substitute for combustible tobacco smoking, the use of any form of tobacco product among youths, including e-cigarettes, is unsafe ( 1 ). The Surgeon General has concluded that e-cigarette use among youths and young adults is of public health concern; exposure to nicotine during adolescence can cause addiction and can harm the developing adolescent brain ( 1 ). The rise in e-cigarette use during 2017–2018 is likely because of the recent popularity of e-cigarettes shaped like a USB flash drive, such as JUUL; these products can be used discreetly, have a high nicotine content, and come in flavors that appeal to youths ( 4 ). In September 2018, the Food and Drug Administration (FDA) issued more than 1,300 warning letters and civil money penalty fines to retailers who illegally sold e-cigarette products to minors, the majority of which were blu, JUUL, Logic, MarkTen XL, and Vuse; this was the largest coordinated enforcement effort in FDA’s history ( 5 ). Sustained implementation of proven population-based strategies, in coordination with the regulation of tobacco products by FDA, is key to reducing all forms of tobacco product use and initiation, including e-cigarettes, among U.S. youths ( 1 ).