Project 2: Oxidative Stress and Harmful Constituent Levels Associated with Little Cigars

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Project Summary/Abstract: Project 2 The overall goal of this project is to determine the toxicity and harm associated with little cigars, with an emphasis on measuring the oxidants in mainstream smoke delivery and their biological effects. The project is responsive to the RFA Scientific Domains of “Toxicity” and “Addiction.” The project helps form the integrative theme of the overall TCORS that focuses on harm generated from tobacco-related oxidants and the development of reliable methods for product testing. Little cigars have become an increasingly popular tobacco product because they offer price advantages compared to traditional cigarettes. However, emerging evidence by our group and the Tobacco Products Laboratory of the Centers for Disease Control implicate little cigars as more toxic than even cigarettes. However, there is still much to be determined about the relative harm from little cigars including their effects on oxidative stress, damage and inflammation. Our specific aims are: Aim1. Determine the levels of gas phase and particulate phase free radicals and other Harmful and Potentially Harmful Constituents (carbonyls, PAHs, NNK,NNN) in the smoke of the 40 most common little cigar brands under machine-smoked protocols (FTC, CI). The effects of physical and chemical product features such as filter ventilation level, rod length and tobacco nitrate levels, which can be regulated under FDA authority, will be modelled against levels of these constituents. Aim2. Determine the effects of little cigar features on human exposure to tobacco smoke oxidants. In a balanced randomized cross-over study design in diverse smokers, subjects will be assigned to 6 exposure groups. These include a high oxidant unflavored little cigar exposure condition, a low oxidant unflavored little cigar exposure condition, a high oxidant flavored exposure condition, a low oxidant flavored exposure little cigar exposure condition, their usual cigarette, and a control condition (unlit little cigar). Following the smoking of each product, exhaled breath condensate samples will be collected at baseline (-15), 30, 60, 90, 120 and 150 minutes. Samples will be analyzed for levels of oxidant/inflammatory markers including hydrogen peroxide, 8-isoprostanes, and C-reactive protein, as well as nicotine, NNK and NNN. Aim 3. Determine the levels of biomarkers of potential harm in current users of little cigars relative to other tobacco products, including cigarettes and e-cigarettes in the Population and Tobacco Health Study (PATH). Aim 3a. Using Wave 1 and Wave 5 data, we will analyze and compare biomarkers of potential harm including oxidative stress (8-isoprostane) and inflammation (Soluble intercellular adhesion molecule-1, Interleukin 6). Secondary outcomes will include biomarkers of other tobacco smoke toxicants and nicotine metabolites, and behavioral measures of tobacco addiction. Aim 3b. Determine the effect of nitrate levels and rod length on biomarkers of potential harm.