E-Cigarette Use, Small Airway Fibrosis, and Constrictive Bronchiolitis

Hariri, Lida P.; Flashner, Bess M.; Kanarek, David J.; O’Donnell, Walter J.; Soskis, Alyssa; Ziehr, David R.; Frank, Angela; Nandy, Sreyankar; Berigei, S.R.; Sharma, Amita; Mathisen, Douglas J.; Keyes, Colleen; Lanuti, Michael; Muniappan, Ashok; Shepard, Jo-Anne O.; Mino‐Kenudson, Mari; Ly, Amy; Hung, Yin P.; Castelino, Flavia V.; Ott, Harald C.; Medoff, Benjamin D.; Christiani, David C.

doi:10.1056/evidoa2100051

Cited by 17 publications

(13 citation statements)

References 39 publications

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“…Additionally treatments with cinnamaldehyde-containing e-liquids decreased phagocytotic capability of macrophages and neutrophils with concomitant increases in pro-inflammatory cytokine/chemokine secretion in the latter (Clapp et al 2019). E-cigarette use is also beginning to be associated with lung remodeling and fibrotic-like events along with an increased risk in developing respiratory diseases (Bhatta and Glantz 2020; Hariri et al 2022; Osei et al 2020; Wang et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Nose-only Exposure to Cherry and Tobacco Flavored E-cigarettes Induced Lung Inflammation in Mice in a Sex-dependent Manner

Lamb

Meehan-Atrash

Muthumalage

et al. 2022

Preprint

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Flavoring chemicals utilized in electronic nicotine delivery systems (ENDS) have been shown to result in an increase in cellular inflammation, meanwhile, the effects of fruit and tobacco flavors on lung inflammation by nose-only exposures to mice are relatively unknown. We hypothesized that C57BL/6J mice exposed to flavored e-cigarettes would result in an increase in lung inflammation. C57BL/6J mice were exposed to air, propylene glycol/vegetable glycerin (PG/VG), and e-liquids Apple, Cherry, Strawberry, Wintergreen, and Smooth & Mild Tobacco, for one hour per day for a three day exposure. Quantification of flavoring chemicals was measured by proton nuclear magnetic resonance spectroscopy (1H NMR), differential cell counts by flow cytometry, pro-inflammatory cytokines/chemokines by ELISA, and matrix metalloproteinase levels by western blot. Exposure to PG/VG, Apple, and Smooth & Mild Tobacco resulted in an increase in neutrophil cell count in lung bronchoalveolar lavage fluid (BALF). Strawberry exposure increased KC levels in BALF while in lung homogenate KC levels were increased in PG/VG, Cherry, and Smooth & Mild Tobacco exposure. Exposure to PG/VG and Cherry increased IL-6 levels and in all exposed mice there was a male-specific decrease in MCP-1 levels in lung homogenate. Mice exposed to PG and VG, Apple, Cherry, and Wintergreen resulted in an increase in MMP2 levels. Our results indicate that female mice exposed to cherry flavored e-liquids and male mice exposed to tobacco flavored e-liquids resulted in an increase in inflammation, while exposure to mint flavored e-liquids resulted in a decrease in inflammatory cytokine and an increase in tissue repair proteins. This study revealed that flavored-based e-cigarette exposure elicited sex-specific alterations in lung inflammation, with cherry flavors/benzaldehyde eliciting female-specific increases in inflammation. This highlights the toxicity of flavored chemicals and the further need for regulation of flavoring chemicals.

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Section: Introductionmentioning

confidence: 99%

Nose-only Exposure to Cherry and Tobacco Flavored E-cigarettes Induced Lung Inflammation in Mice in a Sex-dependent Manner

Lamb

Meehan-Atrash

Muthumalage

et al. 2022

Preprint

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“…In a recent clinical study, four patients with a 3–8 year history of e-cig use were all found to have constrictive bronchiolitis and MUC5AC overexpression in the respiratory epithelium 54 . Interestingly, one patient only vaped e-liquid containing PG and VG, without nicotine, flavors, or other substances.…”

Section: Discussionmentioning

confidence: 99%

The combination of propylene glycol and vegetable glycerin e-cigarette aerosols induces airway inflammation and mucus hyperconcentration

Kim,

Chung,

Baumlin

et al. 2024

Sci Rep

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Despite concerns over their safety, e-cigarettes (e-cigs) remain a popular tobacco product. Although nicotine and flavors found in e-cig liquids (e-liquids) can cause harm in the airways, whether the delivery vehicles propylene glycol (PG) and vegetable glycerin (VG) are innocuous when inhaled remains unclear. Here, we investigated the effects of e-cig aerosols generated from e-liquid containing only PG/VG on airway inflammation and mucociliary function in primary human bronchial epithelial cells (HBEC) and sheep. Primary HBEC were cultured at the air–liquid interface (ALI) and exposed to e-cig aerosols of 50%/50% v/v PG/VG. Ion channel conductance, ciliary beat frequency, and the expression of inflammatory markers, cell type-specific markers, and the major mucins MUC5AC and MUC5B were evaluated after seven days of exposure. Sheep were exposed to e-cig aerosols of PG/VG for five days and mucus concentration and matrix metalloproteinase-9 (MMP-9) activity were measured from airway secretions. Seven-day exposure of HBEC to e-cig aerosols of PG/VG caused a significant reduction in the activities of apical ion channels important for mucus hydration, including the cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels. PG/VG aerosols significantly increased the mRNA expression of the inflammatory markers interleukin-6 (IL6), IL8, and MMP9, as well as MUC5AC. The increase in MUC5AC mRNA expression correlated with increased immunostaining of MUC5AC protein in PG/VG-exposed HBEC. On the other hand, PG/VG aerosols reduced MUC5B expression leading overall to higher MUC5AC/MUC5B ratios in exposed HBEC. Other cell type-specific markers, including forkhead box protein J1 (FOXJ1), keratin 5 (KRT5), and secretoglobin family 1A member 1 (SCGB1A1) mRNAs, as well as overall ciliation, were significantly reduced by PG/VG exposure. Finally, PG/VG aerosols increased MMP-9 activity and caused mucus hyperconcentration in sheep in vivo. E-cig aerosols of PG/VG induce airway inflammation, increase MUC5AC expression, and cause dysfunction of ion channels important for mucus hydration in HBEC in vitro. Furthermore, PG/VG aerosols increase MMP-9 activity and mucus concentration in sheep in vivo. Collectively, these data show that e-cig aerosols containing PG/VG are likely to be harmful in the airways.

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“…One of these patients was using e-cigarettes without known additives such as nicotine, tetrahydrocannabinol (THC) or flavourings. This raises the possibility of a cohort of e-cigarette users being diagnosed with only partially reversible chronic lung disease manifestations in the future [ 24 ].…”

Section: Vaping-related Harmsmentioning

confidence: 99%

Why and how should children be protected from the deluge of vaping related media and marketing overexposure?

White,

Bush,

Smyth

et al. 2023

Breathe

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E-cigarettes are products delivering nicotineviainhalation and are devised to mimic tobacco smoking. While they were initially introduced as a device putatively to aid with smoking cessation, their use is now far broader than that. Use by children is significantly increasing. There is growing evidence of the potential harms of vaping. E-liquids used for e-cigarettes contain a wide range of harmful substances, and the clinical consequences of this are now being increasingly demonstrated, such as the rise in cases of e-cigarette- or vaping-associated lung injury. In addition, early use may result in long-term nicotine addiction. Vaping companies utilise marketing methods that distinctly target young people, and weak legislation in the UK allows them free rein to expose children to vaping.In this review we demonstrate why children must be protected from vaping. We must have stringent legislation to prevent easy access to e-cigarettes, including banning the convenience and affordability disposable vapes provide, and prevent marketing that does not warn about the potential health effects. The Australia approach of prescription or pharmacy only access for smoking cessation should be considered to limit exposure of children and minimise use by nonsmokers.

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E-Cigarette Use, Small Airway Fibrosis, and Constrictive Bronchiolitis

Cited by 17 publications

References 39 publications

Nose-only Exposure to Cherry and Tobacco Flavored E-cigarettes Induced Lung Inflammation in Mice in a Sex-dependent Manner

Nose-only Exposure to Cherry and Tobacco Flavored E-cigarettes Induced Lung Inflammation in Mice in a Sex-dependent Manner

The combination of propylene glycol and vegetable glycerin e-cigarette aerosols induces airway inflammation and mucus hyperconcentration

Why and how should children be protected from the deluge of vaping related media and marketing overexposure?

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