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Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial cells
  1. Noel J Leigh,
  2. Phillip L Tran,
  3. Richard J O’Connor,
  4. Maciej Lukasz Goniewicz
  1. Department of Health Behavior, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
  1. Correspondence to Dr Maciej Lukasz Goniewicz, Department of Health Behavior, Division of Cancer Prevention and Population Sciences, Roswell Park Comprehensive Cancer, Buffalo, NY 14203, USA; maciej.goniewicz{at}


Background Heated tobacco product(s) (HTP), also called heat-not-burn products, are a re-emerging class of tobacco products that purport to reduce health risk compared with smoking combustible tobacco products. This study examined the potential toxic effects of inhaling emissions from an HTP in comparison with electronic and combustible tobacco cigarettes.

Methods Inhalation toxicity of HTP (IQOS; tobacco flavour), e-cigarette (MarkTen; tobacco flavour) and tobacco cigarette (Marlboro Red) was examined in vitro using an air–liquid interface with human bronchial epithelial cells (H292). Cells were exposed directly to 55 puffs from the e-cigarette, 12 puffs from the HTP and 8 puffs from the tobacco cigarette to equilibrate nicotine delivery to the cells across products. Cytotoxicity was measured using neutral red uptake and trypan blue assays. Cytotoxic effects of each tested product (HTP, e-cigarette and tobacco cigarette) were compared with an air control. Release of inflammatory markers (cytokines) was measured using ELISA.

Results The HTP showed higher cytotoxicity compared with the air controls using the neutral red assay. The HTP also showed higher cytotoxicity than the e-cigarette, but lower cytotoxicity than the combustible cigarettes using the same assay. A significant increase in cytokines levels, compared with air controls, was observed postexposure to tobacco smoke but not to emissions from HTP or e-cigarette aerosol.

Discussion Using limited cytotoxic measures, the HTP showed reduced cytotoxicity relative to a combustible cigarette but higher toxicity than an e-cigarette. More comprehensive testing is needed to determine long-term effects of inhaling emissions from HTP.

  • non-cigarette tobacco products
  • toxicology
  • nicotine

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  • Contributors MLG contributed to the conception of the work. MLG and NJL contributed to data analysis. MLG, NJL and RJO drafted the manuscript. NJL and PLT ran all experiments. All authors approved the final version of the manuscript. MLG has full access to all study data and takes responsibility for the integrity of the data and accuracy of the data analysis.

  • Funding Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P01 CA 200512 and P30 CA 016056.

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests MLG reports grants from and served as an advisory board member to pharmaceutical companies that manufacture smoking cessation drugs. RJO was a member of the FDA Tobacco Products Scientific Advisory Committee which considered Philip Morris International’s modified risk application for IQOS in January 2018. Other authors declare no conflict of interest.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.