Thirdhand vaping exposures are associated with pulmonary and systemic inflammation in a mouse model

Abstract

Thirdhand smoke (THS) is the accumulation of secondhand smoke on surfaces that ages with time. THS exposure is a potential health threat to children, partners of smokers, and workers in environments with current or past smoking, and needs further investigation. In this study, we hypothesized that thirdhand Electronic Nicotine Delivery Systems (ENDS) exposures elicit lung and systemic inflammation due to resuspended particulate matter (PM) and inorganic compounds that remain after active vaping has ceased. To test our hypothesis, we exposed C57BL/6J mice to cotton towels contaminated with ENDS aerosols from unflavored vape fluid (6 mg nicotine in 50/50 propylene glycol/vegetable glycerin) for 1h/day, five days/week, for three weeks. We assessed protein levels in serum and bronchoalveolar lavage fluid (BALF) using a multiplex protein assay. The mean ± sd for PM₁₀ and PM_2.5 measurements in exposed mouse cages were 8.3 ± 14.0 and 4.6 ± 7.5 µg/m³, compared to 6.1 ± 11.2 and 3.7 ± 6.6 µg/m³ in control cages respectively. Two compounds, 4-methyl-1, 2-dioxolane and 4-methyl-cyclohexanol, were detected in vape fluid and on ENDS-contaminated towels, but not on control towels. Mice exposed to ENDS-contaminated towels had lower levels of serum Il-7 (P = 0.022, n = 7), and higher levels of Il-13 in the BALF (P = 0.006, n = 7) than those exposed to control towels (n = 6). After adjusting for sex and age, Il-7 and Il-13 levels were still associated with thirdhand vaping exposure (P = 0.010 and P = 0.017, respectively). This study provides further evidence that thirdhand ENDS aerosols can contaminate surfaces, and subsequently influence lung and systemic health upon exposure.

Keywords

E-cigarettes / blood cytokines / lung cytokines / mouse model / particulate matter / organic chemicals / thirdhand smoke / vaping

References

[1] Rowell TR.Will chronic e-cigarette use cause lung disease?.Am J Physiol Lung Cell Mol Physiol2015;309:L1398-409 PMCID:PMC4683316

[2] National Academies of Sciences, Engineering, and Medicine. Public health consequences of E-cigarettes. Washington, DC: The National Academies Press;2018.

[3] Park-Lee E,Sawdey MD.Notes from the field: E-cigarette use among middle and high school students-national youth tobacco survey, United States, 2021.MMWR Morb Mortal Wkly Rep2021;70:1387-9 PMCID:PMC8486384

[4] McKee M.Will E-cigarette regulation evolve in pace with new products?.Am J Public Health2020;110:782-3 PMCID:PMC7204469

[5] Ali FRM,Diaz MC,King BA.Trends in unit sales of cooling flavoured e-cigarettes, USA, 2017-2021.Tob Control2022;057395

[6] QuickStats: percentage distribution* of cigarette smoking status^† among current adult e-cigarette users, ^§by age group-national health interview survey, united states, 2021^¶.MMWR Morb Mortal Wkly Rep2023;72:270 PMCID:PMC10010756

[7] Hang B,Zhao Y,Mao JH.Thirdhand smoke: genotoxicity and carcinogenic potential.Chronic Dis Transl Med2020;6:27-34. PMCID:PMC7096322

[8] Acuff L,Hamblen J,Chen J.Third-hand smoke: old smoke, new concerns.J Community Health2016;41:680-7

[9] Martins-Green M,Frankos M.Cigarette smoke toxins deposited on surfaces: implications for human health.PLoS One2014;9:e86391 PMCID:PMC3906039

[10] Khachatoorian C,McWhirter KJ,Talbot P.E-cigarette fluids and aerosol residues cause oxidative stress and an inflammatory response in human keratinocytes and 3D skin models.Toxicol In Vitro2021;77:105234 PMCID:PMC8627378

[11] Goniewicz ML.Electronic cigarettes are a source of thirdhand exposure to nicotine.Nicotine Tob Res2015;17:256-8 PMCID:PMC4837997

[12] Glynos C,Katsaounou P.Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice.Am J Physiol Lung Cell Mol Physiol2018;315:L662-72

[13] Traboulsi H,Abou Rjeili M.Inhalation toxicology of vaping products and implications for pulmonary health.Int J Mol Sci2020;21:3495. PMCID:PMC7278963

[14] Lappas AS,Konstantinidi EM.Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma.Respirology2018;23:291-7.

[15] Chen H,Allam VSRR.Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life.ERJ Open Res2020;6:00022-2020 PMCID:PMC7167212

[16] Thorpe AE,Kim RY.Third-hand exposure to E-Cigarette vapour induces pulmonary effects in mice.Toxics2023;11:749 PMCID:PMC10536515

[17] Alasmari F,Drummond CA.A computerized exposure system for animal models to optimize nicotine delivery into the brain through inhalation of electronic cigarette vapors or cigarette smoke.Saudi Pharm J2018;26:622-8. PMCID:PMC6035328

[18] Chong J,Xia J.Using metaboanalyst 4.0 for comprehensive and integrative metabolomics data analysis.Curr Protoc Bioinformatics2019;68:e86

[19] The R Project for Statistical Computing. Available from: https://www.R-project.org/ [Last accessed on 25 Oct 2023]

[20] Ashley DL,Hamar B.Using the blood concentration of 2,5-dimethylfuran as a marker for smoking.Int Arch Occup Environ Health1996;68:183-7

[21] Castellanos M,Fernández-Real JM.2,5-Dimethylfuran as a validated biomarker of smoking status.Nicotine Tob Res2019;21:828-34.

[22] Li L,Lin Y,Fadel NA.Impacts of electronic cigarettes usage on air quality of vape shops and their nearby areas.Sci Total Environ2021;760:143423. PMCID:PMC7937385

[23] Nguyen C,Sen CA,Zhu Y.Fine and ultrafine particles concentrations in vape shops.Atmos Environ2019;211:159-69.

[24] Díez-Izquierdo A,Lidón-Moyano C,Balaguer A.Update on thirdhand smoke: a comprehensive systematic review.Environ Res2018;167:341-71

[25] Marcham CL,Wood BL,Johnson DL.E-cigarette nicotine deposition and persistence on glass and cotton surfaces.J Occup Environ Hyg2019;16:349-54

[26] Yan B,Ilievski V.Identification of newly formed toxic chemicals in E-cigarette aerosols with Orbitrap mass spectrometry and implications on E-cigarette control.Eur J Mass Spectrom2021;27:141-8 PMCID:PMC9035225

[27] Martuzevicius D,Setyan A.Characterization of the spatial and temporal dispersion differences between exhaled E-cigarette mist and cigarette smoke.Nicotine Tob Res2019;21:1371-7 PMCID:PMC6751519

[28] Alkhedaide AQ.Tobacco smoking causes secondary polycythemia and a mild leukocytosis among heavy smokers in Taif City in Saudi Arabia.Saudi J Biol Sci2020;27:407-11 PMCID:PMC6933161

[29] Tymkiw KD,Johnson GK.Influence of smoking on gingival crevicular fluid cytokines in severe chronic periodontitis.J Clin Periodontol2011;38:219-28 PMCID:PMC3038432

[30] Nakamura M,Minematsu N.Plasma cytokine profiles related to smoking-sensitivity and phenotypes of chronic obstructive pulmonary disease.Biomarkers2014;19:368-77

[31] Mertens TCJ,Kistemaker LE,Taube C.Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells.Physiol Rep2017;5:e13347 PMCID:PMC5506530

[32] Khachatoorian C,Luo W,Talbot P.Tracing the movement of electronic cigarette flavor chemicals and nicotine from refill fluids to aerosol, lungs, exhale, and the environment.Chemosphere2022;286:131494. PMCID:PMC8787941