Smoking remains a leading cause of preventable morbidity and mortality worldwide. Despite a downward trend in cigarette use, less-regulated tobacco products, such as cigarillos, which are often flavored to appeal to specific demographics, such as younger people, are becoming increasingly popular. Cigar/cigarillo smoking has been considered a safer alternative to cigarettes; however, the health risks associated with cigar in comparison with cigarette smoking are not well understood. To address this knowledge gap, we characterized the effects of multiple brands of cigarillos on the airway epithelium using ex vivo and in vivo models. To analyze these effects, we assessed the cellular viability and integrity of smoke-exposed primary airway cell cultures. We also investigated the protein compositions of apical secretions from cigarillo-exposed airway epithelial cultures and BAL fluid of cigarillo-exposed mice through label-free quantitative proteomics and determined the chemical composition of smoke collected from the investigated cigarillo products. We found that cigarillo smoke exerts similar or greater effects than cigarette smoke in terms of reduced cell viability; altered protein levels, including those of innate immune proteins; induced oxidative-stress markers; and greater nicotine delivery to cells. The analysis of the chemical composition of the investigated cigarillo products revealed differences that might be linked to the differential effects of these products on cell viability and protein abundance profiles, which have been associated with a range of health risks in the context of airway biology. These findings contradict the assumption that cigarillos might be safer and less harmful than cigarettes. Instead, our results indicate that cigarillo smoke is associated with equal or greater health risks and the same or increased airway toxicity compared with cigarette smoke.

吸烟仍然是全世界可预防的发病率和死亡率的主要原因。尽管卷烟使用呈下降趋势，但管制较少的烟草产品（例如小雪茄）正变得越来越受欢迎，这些产品通常经过调味以吸引特定人群（例如年轻人）。吸雪茄/小雪茄被认为是比香烟更安全的替代品；然而，与吸烟相比，雪茄的健康风险尚不清楚。为了解决这一知识差距，我们使用离体和体内模型描述了多个品牌的小雪茄对气道上皮的影响。为了分析这些影响，我们评估了暴露于烟雾的初级气道细胞培养物的细胞活力和完整性。我们还通过无标记定量蛋白质组学研究了小雪茄暴露的气道上皮培养物和小雪茄暴露小鼠的支气管肺泡灌洗液的顶端分泌物的蛋白质组成，并确定了从所研究的小雪茄产品中收集的烟雾的化学成分。我们发现，在降低细胞活力方面，小雪茄烟雾与香烟烟雾具有相似或更大的影响。蛋白质水平改变，包括先天免疫蛋白质的水平；诱导氧化应激标记物；以及更多的尼古丁向细胞的输送。对所研究的小雪茄产品的化学成分进行的分析揭示了差异，这些差异可能与这些产品对细胞活力和蛋白质丰度谱的不同影响有关，而这些影响与气道生物学背景下的一系列健康风险有关。这些发现与小雪茄可能比香烟更安全、危害更小这一假设相矛盾。 相反，我们的结果表明，与香烟烟雾相比，小雪茄烟雾与相同或更大的健康风险以及相同或更高的气道毒性相关。