Electronic Nicotine Delivery Systems Exhibit LowerToxicity Compared to Cigarettes: "The Replica Study Experience"

Alfio Distefano, Massimo Caruso, Rosalia Emma, Sonja Rust, Konstantinos Poulas, Fahad Zadjali, Silvia Boffo, Vladislav Volarevic, Konstantinos Mesiakaris, Georgios Karanasios, Mohammed Al Tobi, Najwa Albalushi, Antonio Giordano, Angelo Canciello, Aleksandar Arsenijevic, Aleksandar Ilic, Tancredi Caruso, Giuseppe Carota, Maria R. Spampinato, Pietro ZuccarelloMargherita Ferrante, Riccardo Polosa, Giovanni Li Volti

Research output: Contribution to journalArticlepeer-review


Electronic nicotine delivery systems (ENDS) can reduce the health risks associated with chronic smoke exposure, and their potential benefits are the subject of intense scientific debate. The international "Replica Study Group" replicated independently three relevant studies from the tobacco industry on the cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol. Our primary goal was to establish the reliability of the results and the robustness of the conclusions. In order to assess cytotoxicity of smoke and aerosol, we exposed human bronchial epithelial cell (H292) to cigarette smoke and to ENDS aerosol at air-liquid interface (ALI). Moreover, we aimed to assess different inflammatory and remodeling mediators release (IL-6, IL-8 and MMP-1) from cells exposed to whole smoke (WS) and to smoke deprived of total particulate matter (vapor phase; VP). We were able to replicate the results obtained in the original studies on cytotoxicity confirming that almost 80% of the cytotoxic effect of smoke is due to the vapor phase of smoke. Moreover, our results substantiated the significantly reduced cytotoxic effects of ENDS aerosol vs. cigarette smoke. However, our data were notably different in terms of inflammatory and remodeling activity triggered by smoke. Altogether, the data obtained independently in different laboratories clearly confirm the reduced toxicity of ENDS products compared to smoke, thus providing a valuable tool to the harm reduction strategies in smokers. Otherwise, we were not able to replicate the results on inflammatory and remodeling mediators released from smoke exposed cells. This could be due to the lack of normalization of the quantity of cytokines released, with the number of viable cells, in the original paper, since the production of cytokines itself requires the metabolic capability of cells.

Original languageEnglish
JournalFASEB Journal
Publication statusPublished - May 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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