A 7-month inhalation toxicology study in C57BL/6 mice demonstrates reduced pulmonary inflammation and emphysema following smoking cessation or switching to e-vapor products

Cigarette smoking causes serious diseases, including lung cancer, heart disease, and emphysema. While cessation remains the most effective approach to minimize smoking-related disease, alternative non-combustible tobacco-derived nicotine containing products may reduce disease risks among those unable or unwilling to quit. E-vapor aerosols typically contain significantly lower levels of smoke-related harmful and potentially harmful constituents; however, health risks of long-term inhalation exposures are unknown. We designed a 7-month inhalation study in C57BL/6 mice to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation or switching to an e-vapor product after 3 months of exposure to 3R4F cigarette smoke (CS). There were no significant changes in in-life observations (body weights, clinical signs) in e-vapor groups compared to the Sham Control. The 3R4F CS group showed reduced respiratory function during exposure and had lower body weight and showed transient signs of distress post-exposure. Following 7 months of exposure, e-vapor aerosols resulted in no or minimal increase in pulmonary inflammation, while exposure to 3R4F CS led to impairment of lung function and caused marked lung inflammation and emphysematous changes. Biological changes observed in the Switching group were similar to the Cessation group. 3R4F CS exposure dysregulated lung and nasal tissue transcriptome, while these molecular effects were substantially lower in the e-vapor group. Results from this study demonstrate that in comparison with 3R4F CS, e-vapor aerosols induce substantially lower biological responses including pulmonary inflammation and emphysema, and that complete switching from CS to e-vapor products significantly reduces biological changes associated with cigarette smoke in C57BL/6 mice.吸烟可引发多种严重疾病，包括肺癌、心脏病与肺气肿。戒烟仍是降低吸烟相关疾病风险的最有效手段，而对于无法或不愿戒烟的人群，非燃烧型烟草源性含尼古丁替代产品或可降低其患病风险。电子气溶胶（e-vapor aerosol）通常含有的烟气相关有害及潜在有害成分水平显著更低，但长期吸入暴露的健康风险尚不明确。本研究以C57BL/6小鼠为模型，开展了为期7个月的吸入暴露实验，旨在对比电子气溶胶与卷烟烟气的长期呼吸道毒性，并评估在暴露于3R4F卷烟烟气（CS）3个月后，戒烟或转换为电子雾化产品对机体的影响。与空白对照（Sham Control）组相比，电子气溶胶暴露组的活体观测指标（体重、临床体征）无显著变化。3R4F卷烟烟气暴露组在暴露期间出现呼吸功能下降，体重较低，且暴露后出现短暂的应激体征。经过7个月的暴露后，电子气溶胶暴露仅引发极轻微或未引发肺部炎症，而3R4F卷烟烟气暴露则导致肺功能受损，出现显著肺部炎症与肺气肿样病变。转换组（Switching group）观测到的生物学变化与戒烟组（Cessation group）相似。3R4F卷烟烟气暴露会干扰肺部与鼻腔组织的转录组，而电子气溶胶组的这类分子效应显著更弱。本研究结果表明，与3R4F卷烟烟气相比，电子气溶胶引发的包括肺部炎症与肺气肿在内的生物学效应显著更低；且在C57BL/6小鼠模型中，完全从卷烟烟气转换为电子雾化产品可显著降低与吸烟相关的生物学改变。