Characterizing the effect of new and emerging tobacco products on airway innate mucosal defense

Abstract

Airway mucus/mucins serve as a barrier against smoke and other harmful substances that the respiratory tract is exposed to. In addition, airways exosomes have a role in the dynamic regulation of the airway tract response to a broad range of different possible environmental exposure of the body to such substances as smoke. This study ventured to characterize the effects of multiple brands of New and Emerging Tobacco Products (NETPs) on the airway epithelia at multiple levels using in vitro model. Accordingly, the viability and integrity of tight junctions of smoke-exposed epithelia were evaluated. Apical secretions from NETP-exposed cultures were collected and subjected to label-free quantification mass spectrometric analysis. Additionally, chemical composition analysis of different cigarillo brands was also performed. Furthermore, part of the collected apical secretions from NETP-exposed culture secretions were processed for isolation of the exosome using sequential differential centrifugation. The airway exosomal miRNA profile was identified by using HTG EdgeSeq technology and next-generation sequencing platforms. The differential expression analysis was performed by using a bioinformatics tool. Results showed that NETPs, in the form of little cigars, cigarillos, and waterpipe, collectively have greater effects than control air and cigarette smoke in terms of reduced cell viability and altered protein expression patterns. NETPs were also found to induce oxidative stress proteins and cause more profound alterations in the lung innate immune response. Furthermore, the analysis of different cigarillo tobacco products revealed compositional differences and greater nicotine delivery to cells that may be linked to the differential effects of these products on cellular viability and protein expression profiles, which are associated with a range of health risks in the context of airway biology. These study findings contradict the popular belief that NETPs are safer and less harmful than cigarettes. Instead, results indicated that NETP smoke leads to potential health risks and causes damage to the airways to an extent similar to or greater than that of cigarette smoke. These results could serve as a basis for the regulation of tobacco and NETPs and should inform considerations related to health risks and public perceptionDoctor of Philosoph