Abstract
Tobacco smoking remains a major global health concern, causing preventable deaths and economic strain. Although new tobacco products such as heat-not-burn (HnB) are safer alternatives to traditional cigarettes, research on their associated risks remains limited. This study aimed to investigate the effects of HnB smoke exposure on the lungs compared to those of traditional cigarettes and the combined use of HnB and cigarettes using experiments with a mouse model. We quantitatively analyzed changes in the levels of 92 blood plasma proteins using the proximity extension assay method and observed significant changes in their levels in mice exposed to different smoke conditions; specifically, the levels of certain proteins, including Ccl20, Cxcl1, and Pdgfb, increased in the HnB smoke-exposed group, suggesting activation of nicotine pathways. Comparative analysis with traditional cigarette smoke-exposed mice further highlighted similarities and differences in their protein expression profiles. This study contributes to an improved understanding of the biological mechanisms underlying the harmful effects of alternative nicotine delivery systems and identifies potential biomarkers associated with the harmful effects of HnB smoke exposure. However, the precise impact of nicotine on the immune system may be influenced by various factors, necessitating further research.