PATHOPHYSIOLOGY AND PATHOMORPHOLOGY OF THE LUNGS IN USERS OF ELECTRONIC NICOTINE DELIVERY DEVICES: CLINICAL AND EXPERIMENTAL DATA

Relevance. Currently, the use of tobacco and tobacco products has acquired the character of a global epidemic, and the number of diseases associated with this harmful habit is steadily growing. In the last 20 years, a trend has emerged worldwide to replace traditional cigarettes with electronic ones, positioned by marketers as less harmful. These devices, being fashionable and modern, have become especially popular among teenagers and young people. However, cases of severe lung pathology, including fatal ones, have been reported in users of electronic nicotine delivery systems.

Aim. To analyze and structure data on methods of electronic delivery of nicotine to the body, as well as on the pathogenesis of lung damage from various liquids for "vaping".

Results. Reusable devices have the most pathogenic effect on the body of users, especially when using liquids containing tetrahydrocannabinol, but even nicotine-free liquids are not harmless to health. More than 30 different substances with a potentially harmful effect on the body have been found in the aerosols of electronic liquids. In most cases, the picture of lung damage in "vapers" is represented by the development of diffuse alveolar damage, the pathogenesis of which involves both direct tissue damage by chemicals and a violation of the immune response and inflammatory mechanisms. E-cigarette users demonstrate a predominance of the pro-inflammatory phenotype of macrophages, an excess of pro-inflammatory cytokines and a lack of anti-inflammatory ones. Vapers using liquids based on tetrahydrocannabinol have foamy macrophages in the lung tissue and bronchoalveolar lavage that accumulate vitamin E acetate. Also, users of electronic nicotine delivery systems have been found to have multiple disturbances in gene expression by macrophages, as well as various damages to deoxyribonucleic acid in the epithelial cells of the oral mucosa, which may be an initiating factor in the development of malignant neoplasms and other types of pathology. In experiments on mice, it was shown that replacing conventional tobacco smoke with electronic aerosol does not improve the condition of the lung tissue in mice, and inhalation of aerosols containing nicotine is accompanied by an increase in platelet function.

Conclusion. Electronic nicotine delivery systems are not a safe replacement for regular cigarettes. Moreover, even nicotine-free fluids have a damaging effect.

1. Информационный бюллетень «Табак» [Organization WH. Tobacco. (In Russ.)] URL: https://www.who.int/europe/ru/news-room/fact-sheets/item/tobacco [access date 08.08.2025]

2. Салагай О.О., Сахарова Г.М., Антонов Н.С. Глобальное обследование употребления табака среди молодежи в Российской Федерации: 2004–2021 гг. [Salagai O.O., Sakharova G.M., Antonov N.S. Global survey of tobacco use among young people in the Russian Federation: 2004-2021. (In Russ.)] URL: https://iris.who.int/bitstream/handle/10665/376198/WHO-EURO-2024-8404-48176-71508-rus.pdf?sequence=1 [дата доступа 08.08.2025]

3. Горянская И.Я., Солдатова О.В., Алмасуд Р. и др. EVALI – болезнь вейперов: что известно на сегодняшний день? Лечебное дело. 2023;3:127-131 [Goryanskaya I.Ya., Soldatova O.V., Almasud R. et al. EVALI – Vapers’ Disease: What is Known Today? Medical practice. 2023;3:127-131 (In Russ.)] https://doi.org/10.24412/2071-5315-2023-12993

4. Доклад ВОЗ о глобальной табачной эпидемии, 2023 г.: защита людей от табачного дыма. Основные положения [WHO report on the global tobacco epidemic, 2023: protect people from tobacco smoke. Executive summary (In Russ.)]. URL: https://iris.who.int/bitstream/handle/10665/374312/9789240083295-rus.pdf?sequence=1 [access date 08.08.2025]

5. Duan Z., Berg C.J., Bar-Zeev Y. et al. Perceptions of Heated Tobacco Products (HTPs) Versus Cigarettes and e-Cigarettes in Relation to Likelihood of Trying HTPs or Suggesting HTPs to Those who Smoke Cigarettes. Nicotine Tob Res. 2024;26(10):1394-1403. https://doi.org/10.1093/ntr/ntae093

6. Ткаченко А.В., Слинькова Т.А., Шипкова Л.Н. Новый тренд: электронные системы доставки никотина. Медико-фармацевтический журнал «Пульс». 2023;25(4):102-107 [Tkachenko A.V., Slin'kova T.A., Shipkova L.N. New trend: electronic nicotine delivery systems. Medical and pharmaceutical journal "Pulse". 2023;25(4):102-107 (In Russ.)]. https://doi.org/10.26787/nydha-2686-6838-2023-25-4

7. Fuentes F., Xavier, Kashyap R. et al. VpALI — Vaping-related Acute Lung Injury: A New Killer Around the Block. Mayo Clinic Proceedings. 2019;94(12):2534-2545. https://doi.org/10.1016/j.mayocp.2019.10.010

8. Tommasi S., Blumenfeld H., Besaratinia A. Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users. Nicotine Tob Res. 2023;25(6):1145-1154. https://doi.org/10.1093/ntr/ntad003

9. Wang P., Williams R.J., Chen W. et al. Chemical Composition of Electronic Vaping Products From School Grounds in California, Nicotine Tob Res. 2024;26(8): 991–998. https://doi.org/10.1093/ntr/ntae042

10. Гамов Г.А., Смирнов Н.Н., Александрийский В.В., Шарнин В.А. Термическое разложение жидкости для электронных сигарет по данным ИК-спектроскопии. Изв. вузов. Химия и хим. технология. 2017; 60(2):7-12 [Gamov G. A., Smirnov N. N., Aleksandriiskii, V. V., Sharnin V. A. Thermal decomposition of liquid for electronic cigarettes according to IR spectroscopy data. Proceedings of universities. Chemistry and chemical technology. 2017;60(2):7-12 (In Russ.)]. https://doi.org/10.6060/tcct.2017602.5487

11. Ooi B.G., Dutta D., Kazipeta K., Chong N.S. Influence of the E-Cigarette Emission Profile by the Ratio of Glycerol to Propylene Glycol in E-Liquid Composition. ACS Omega. 2019; 4(8):13338-13348. https://doi.org/10.1021/acsomega.9b01504

12. Озерская И.В., Малахов А.Б., Седова А.Ю. и др. Вейп-ассоциированное поражение легких у подростка. Терапевтический архив. 2024;96(1):53-57 [Ozerskaia I.V., Malakhov A.B., Sedova Ayu et al. Vaping use-associated lung injury in a teenager. Case report. Therapeutic archive, 2024;96(1):53–57 (In Russ.)]. https://doi.org/10.26442/00403660.2024.01.202561

13. Williams M., Ventura J., Loza A. et al. Chemical Elements in Electronic Cigarette Solvents and Aerosols Inhibit Mitochondrial Reductases and Induce Oxidative Stress. Nicotine Tob Res. 2020; 22(1):14–24. https://doi.org/10.1093/ntr/ntaa193

14. Kassem N.O.F., Strongin R.M., Stroup A.M. et al. A Review of the Toxicity of Ingredients in e-Cigarettes, Including Those Ingredients Having the FDA's "Generally Recognized as Safe (GRAS)" Regulatory Status for Use in Food. Nicotine Tob Res. 2024;26(11):1445-1454. https://doi.org/10.1093/ntr/ntae123

15. Crotty Alexander L.E., Bellinghausen A.L., Eakin M.N. What are the mechanisms underlying vaping-induced lung injury? J Clin Invest. 2020;130(6):2754–2756. https://doi.org/10.1172/JCI138644

16. Marrocco A., Singh D., Christiani D.C., Demokritou P. E-cigarette vaping associated acute lung injury (EVALI): state of science and future research needs. Crit Rev Toxicol. 2022;52(3):188-220. https://doi.org/10.1080/10408444.2022.2082918

17. Карпенко М. А., Овсянников Д. Ю., Фролов П. А. и др. Повреждение легких, ассоциированное с вейпингом и электронными сигаретами. Туберкулёз и болезни лёгких. 2022;100(4):52-61 [Karpenko M. A., Ovsyannikov D. Yu., Frolov P. A. et al. Vaping and E-Cigarette-Associated Lung Injury. Tuberculosis and Lung Disease. 2022;100(4):52-61 (In Russ.)]. http://doi.org/10.21292/2075-1230-2022-100-4-52-61

18. Reagan-Steiner S., Gary J., Matkovic E. et al. Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series. Lancet Respir Med. 2020;8(12):1219-1232. http://doi.org/10.1016/S2213-2600(20)30321-0

19. Царькова С.А., Лещенко И.В., Иванова А.И. и др. Повреждение легких, связанное с потреблением электронных сигарет (EVALI): диагноз исключения. Пульмонология. 2025;35(1):110–117 [Tsarkova S.A., Leshchenko I.V., Ivanova A.I., et al. E-cigarette, or Vaping, product use-Associated Lung Injury (EVALI): a diagnosis of exclusion. Pulmonology. 2025;35(1):110–117 (In Russ.)]. http://doi.org/10.18093/0869-0189-2024-4604

20. Ni F., Ogura T., Lin W. Electronic Cigarette Liquid Constituents Induce Nasal and Tracheal Sensory Irritation in Mice in Regionally Dependent Fashion. Nicotine Tob Res. 2020;22(1):35–44. https://doi.org/10.1093/ntr/ntaa174

21. Marsden L., Michalicek Z.D., Christensen E.D. More on the Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2020;382(4):387-388. http://doi.org/10.1056/NEJMc1914980.

22. Priemer D.S., Gravenmier C., Batouli A., Hooper J.E. Overview of Pathologic Findings of Vaping in the Context of an Autopsy Patient With Chronic Injury. Arch Pathol Lab Med. 2020;144(11):1408-1413. http://doi.org/10.5858/arpa.2019-0637-RA.

23. Butt Y.M., Smith M.L., Tazelaar H.D. et al. Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2019;381(18):1780-1781. http://doi.org/1056/NEJMc1913069

24. Blount B.C., Karwowski M.P., Shields P.G., et al. Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI. N Engl J Med. 2020;382(8):697-705. http://doi.org/10.1056/NEJMoa1916433.

25. Wu D., O'Shea D.F. Potential for release of pulmonary toxic ketene from vaping pyrolysis of vitamin E acetate. Proc Natl Acad Sci USA. 2020;117(12):6349-6355. http://doi.org/10.1073/pnas.1920925117.

26. Davis E.S., Ghosh A., Coakley R.D. et al. Chronic E-Cigarette Exposure Alters Human Alveolar Macrophage Morphology and Gene Expression. Nicotine Tob Res. 2022;24(3):395–399. https://doi.org/10.1093/ntr/ntab186

27. Сарбаева Н.Н., Пономарева Ю.В., Милякова М.Н. Макрофаги: разнообразие фенотипов и функций, взаимодействие с чужеродными материалами. Гены и клетки. 2016;11(1):9-17 [Sarbaeva N.N., Ponomareva Yu.V., Milyakova M.N. Macrophages: diversity of phenotypes and functions, interaction with foreign materials. Genes and cells. 2016;11(1):9-17 (In Russ.)] https://doi.org/10.23868/gc120550

28. Галагудза М.М., Бельский Ю.П., Бельская Н.В. Индуцибельная NO-синтаза как фармакологическая мишень противовоспалительной терапии: надежда не потеряна? Сибирский журнал клинической и экспериментальной медицины. 2023;38(1):13–20 [Galagudza M.M., Belsky Y.P., Belsky N.V. Inducible NO synthase as a pharmacological target of anti-infl ammatory therapy: hope is not lost? The Siberian Journal of Clinical and Experimental Medicine. 2023;38(1):13–20 (In Russ.)]. https://doi. org/10.29001/2073-8552-2023-38-1-13-20

29. Horiuchi H., Parajuli B., Komiya H. et al. Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation. Front Immunol. 2021;12:615898. http://doi.org/10.3389/fimmu.2021.615898

30. Zhong Y., Zhang X., Chong W. Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases. Int J Mol Sci. 2022;23(2):627. http://doi.org/10.3390/ijms23020627.

31. Cambier S., Gouwy M., Proost P. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention. Cell Mol Immunol. 2023;20:217–251. https://doi.org/10.1038/s41423-023-00974-6

32. Chehboun S., Labrecque-Carbonneau J., Pasquin S. et al. Epstein-Barr virus-induced gene 3 (EBI3) can mediate IL-6 trans-signaling. J Biol Chem. 2017;292(16):6644-6656. http://doi.org/10.1074/jbc.M116.762021

33. Shimizu Y., Dobashi K. CC-chemokine CCL15 expression and possible implications for the pathogenesis of IgE-related severe asthma. Mediators Inflamm. 2012;2012:475253. http://doi.org/10.1155/2012/475253

34. Chang S.H., Dong C. IL-17F: regulation, signaling and function in inflammation. Cytokine. 2009;46(1):7-11. http://doi.org/10.1016/j.cyto.2008.12.024

35. Bhat T.A., Kalathil S.G., Bogner P.N. et al. An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury. N Engl J Med. 2020;382(12):1175-1177. http://doi.org/10.1056/NEJMc2000231

36. Erhabor J., Yao Zh., Tasdighi E. et al. E-cigarette Use and Incident Cardiometabolic Conditions in the All of Us Research Program. Nicotine Tob Res. 2025;15:ntaf067. https://doi.org/10.1093/ntr/ntaf067

37. Podguski S., Kaur G., Muthumalage T. et al. Noninvasive systemic biomarkers of e-cigarette or vaping use-associated lung injury: a pilot study. ERJ Open Res. 2022;8:00639-2021. http://doi.org/10.1183/23120541.00639-2021

38. Husari A., El-Harakeh M., Shihadeh A. et al. The Substitution of Fifty Percent of Combustible Tobacco Smoke Exposure With Either Electronic Cigarettes or Heated tobacco Products Did Not Attenuate Acute Lung Injury in an Animal Model. Nicotine Tob Res. 2023;25(7):1361–1368. https://doi.org/10.1093/ntr/ntad045

39. Jasper A., Scott A., Thickett D. Exposure to electronic cigarette vapour induces functional changes in neutrophils at a sub-cytotoxic dose. European Respiratory Journal. 2019;54(suppl 63):PA2404. https://doi.org/10.1183/13993003.congress-2019.PA2404

40. Curley E.O., Aboud O.A., Chmiel K.J. et al. Heated Tobacco Product IQOS Induces Unique Metabolic Signatures in Human Bronchial Epithelial Cells. ERJ Open Res. 2024;10(2):00805-2023. http://doi.org/10.1183/23120541.00805-2023

41. Seeliger B., Pape T., Horn P. et al. Exposure to nicotine containing e-cigarette vapor leads to endothelial barrier dysfunction and increased susceptibility to LPS in-vitro. European Respiratory Journal. 2022;60(66):2327. https://doi.org/10.1183/13993003.congress-2022.2327