Variability and Correlation in Biomarkers of Exposure from Two Randomized Controlled Studies of JUUL Electronic Nicotine Delivery Systems

The data included in this analysis were from two clinical studies (Study A and Study B), which evaluated JUUL electronic nicotine delivery systems (ENDS) against combustible cigarettes. In both studies, biomarkers of exposure including nicotine equivalents, NNAL, 3-HPMA, MHBMA, S-PMA and COHb were measured. Coefficients of variation (CV) of the biomarkers were calculated and compared. Pearson correlation analysis was used to examine the correlation between the biomarkers. Seven out of the nine biomarkers of exposure in Study A were highly variable (CV > 30%). Higher variability was observed in NNAL, MHBMA and S-PMA than in other biomarkers. After adult cigarette smokers switched from combustible cigarettes to JUUL ENDS, the correlation between nicotine equivalents and other biomarkers became weaker. A similar trend was observed between NNAL and other biomarkers. In Study B, the participants in the 5% ENDS group had higher nicotine equivalent levels than those in the 3% ENDS group. The higher nicotine levels did not result in a substantial increase in the levels of other biomarkers (except 1-OHP). The correlations between nicotine equivalents and 3-HPMA, MHBMA, S-PMA, COHb, HMPMA, and 1-OHP were weak in both the 5% and 3% ENDS groups.

Assessment of tobacco heating system 2.4 on osteogenic differentiation of mesenchymal stem cells and primary human osteoblasts compared to conventional cigarettes

BACKGROUND Cigarette smoking(CS)is the most common method of consuming tobacco.Deleterious effects on bone integrity,increased incidence of fractures,and delayed fracture healing are all associated with CS.Over 150 of the 6500 molecular species contained in cigarette smoke and identified as toxic compounds are inhaled by CS and,via the bloodstream,reach the skeletal system.New technologies designed to develop a reduced-risk alternative for smokers are based on electronic nicotine delivery systems,such as e-cigarettes and tobacco heating systems(THS).THS are designed to heat tobacco instead of burning it,thereby reducing the levels of harmful toxic compounds released.AIM To examine the effects of THS on osteoprogenitor cell viability and function compared to conventional CS.METHODS Human immortalized mesenchymal stem cells(n=3)and primary human preosteoblasts isolated from cancellous bone samples from BG Unfall Klinik Tübingen(n=5)were osteogenically differentiated in vitro with aqueous extracts generated from either the THS 2.4“IQOS”or conventional“Marlboro”cigarettes for up to 21 d.Cell viability was analyzed using resazurin conversion assay(mitochondrial activity)and calcein-AM staining(esterase activity).Osteogenic differentiation and bone cell function were evaluated using alkaline phosphatase(AP)activity,while matrix formation was analyzed through alizarin red staining.Primary cilia structure was examined by acetylatedα-tubulin immunofluorescent staining.Free radical production was evaluated with 2’,7’-dichlorofluoresceindiacetate assay.RESULTS Our data clearly show that THS is significantly less toxic to bone cells than CS when analyzed by mitochondrial and esterase activity(P<0.001).No significant differences in cytotoxicity between the diverse flavors of THS were observed.Harmful effects from THS on bone cell function were observed only at very high,non-physiological concentrations.In contrast,extracts from conventional cigarettes significantly reduced the AP activity(by two-fold)and matrix mineralization(four-fold)at low concentrations.Additionally,morphologic analysis of primary cilia revealed no significant changes in the length of the organelle involved in osteogenesis of osteoprogenitor cells,nor in the number of ciliated cells following THS treatment.Assessment of free radical production demonstrated that THS induced significantly less oxidative stress than conventional CS in osteoprogenitor cells.CONCLUSIONTHS was significantly less harmful to osteoprogenitor cells during osteogenesisthan conventional CS. Additional studies are required to confirm whether THS isa better alternative for smokers to improve delays in bone healing followingfracture.

Electronic cigarettes — myocardial infarction, hemodynamic compromise during pregnancy, and systolic and diastolic dysfunction: Minireview

The aim of this study was to review the most recent literature on the safety of electronic cigarettes(ECs)in the context of cardiovascular disease and in the context as a tool for smoking cessation and recreational purposes.The format of this review begins with relevant research from the basic sciences and follows through with a pertinent review of clinical trials.Daily use of ECs has implications in myocardial infarction(MI)with an odds ratio of 1.70 compared to healthy,nonsmokers and even worse risk for MI with dual use of combustible cigarettes together with EC with an odds ratio of 4.62.Studies measuring cardiac function with echocardiography reported both systolic and diastolic dysfunction along with reduced ejection fractions.Platelet aggregation,endothelial function,and hemodynamics during pregnancy were all but some of the pernicious cardiovascular implications of EC exposure.Though more studies need to be done on the topic of EC use and cardiovascular disease,the majority of studies considered in this review concluded some level of harm albeit in some instances less than that of traditional combustible cigarettes.ECs are toxic to human beings and their harmful effects cannot be overlooked.There is some favorable evidence of efficacy in smoking cessation though mixed with concern of chronic EC use.It will take decades to collect data for chronic EC use on long term sequelae,such as lung cancer.Though more and more reports of acute lung injury and hospitalizations related to EC use have been reported.Due to undergoing investigations of possible harm and life threatening complications of EC use,we cannot recommend ECs as safer or a more efficacious method of smoking cessation to traditional nicotine replacement therapies.A notable consideration for much of the literature reviewed are that standardization of EC use is difficult as device generation and battery voltage,frequency of use,and contents of ECliquid are just some of the vast complicating factors that limit the ability to effectively compare data.

Health outcomes of electronic cigarettes

The usage of electronic cigarettes(e-cigarettes)sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019.With e-cigarettes becoming more and more popular,smokers have more options other than conventional cigarettes.Under these circumstances,a comprehensive evaluation of the general safety of new tobacco and tobacco-related products,represented by e-cigarettes,to human health is necessary.In this review,we summarize the current research on potential negative impacts of e-cigarette exposure on human health.In particular,studies detailing the relationship between e-cigarettes and the digestive system are summarized,with mechanisms mainly including hepatic metabolic dysfunction,impaired gut barrier,and worsened outcomes of inflammatory bowel disease(IBD).Although believed to be safer than traditional cigarettes,e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma,cardiovascular disease,and IBD.Moreover,nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes.However,non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.