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. 2022 Oct 6;11(10):e39785.
doi: 10.2196/39785.

Biomarkers of Exposure and Potential Harm in Exclusive Users of Nicotine Pouches and Current, Former, and Never Smokers: Protocol for a Cross-sectional Clinical Study

David Azzopardi  1 , Linsey Ellen Haswell  1 , Justin Frosina  1 , Michael McEwan  1 , Nathan Gale  1 , Jesse Thissen  1 , Filimon Meichanetzidis  1 , George Hardie  1
Affiliations

Biomarkers of Exposure and Potential Harm in Exclusive Users of Nicotine Pouches and Current, Former, and Never Smokers: Protocol for a Cross-sectional Clinical Study

David Azzopardi et al. JMIR Res Protoc. .

Abstract

Background: Tobacco harm reduction (THR) aims to reduce the health burden of cigarettes by encouraging smokers to switch to using alternative tobacco or nicotine products. Nicotine pouches (NPs) are smokeless, tobacco-free, oral products that may be beneficial as part of a THR strategy.

Objective: This 2-center, cross-sectional confinement study conducted in Denmark and Sweden aimed to determine whether biomarkers of exposure (BoEs) to tobacco toxicants and biomarkers of potential harm (BoPHs) in exclusive users of NPs show favorable differences compared with current smokers.

Methods: Participants were healthy NP users (target n=100) and current, former, or never smokers (target n=40 each), as confirmed by urinary cotinine and exhaled carbon monoxide concentrations. During a 24-hour confinement period, participants were asked to use their usual product (NP or cigarette) as normal, and BoEs and BoPHs were measured in blood and 24-hour urine samples, with compliance determined using anabasine, anatabine, and N-(2-cyanoethyl)valine. BoEs and BoPHs were compared between NP users and current, former, and never smokers. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (BoE to nicotine-derived nitrosamine ketone) and urinary 8-epi-prostaglandin F2α type III, exhaled nitric oxide, blood carboxyhemoglobin, white blood cell count, soluble intercellular adhesion molecule-1, and high-density lipoprotein cholesterol (BoPHs) were evaluated as primary outcomes. Other measures included urinary 11-dehydrothromboxane B2, forced expiratory volume, carotid intima-media thickness, self-reported quality of life, and oral health.

Results: The results of this study were received in mid-2022 and will be published in late 2022 to early 2023.

Conclusions: The results of this study will provide information on toxicant exposure and biomarkers associated with the development of smoking-related diseases among users of NPs compared with smokers, as well as on the potential role of NPs in THR.

Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN16988167; https://www.isrctn.com/ISRCTN16988167.

International registered report identifier (irrid): DERR1-10.2196/39785.

Keywords: biomarkers of exposure; biomarkers of potential harm; cross-sectional clinical study; nicotine pouches; tobacco harm reduction.

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Conflict of interest statement

Conflicts of Interest: British American Tobacco (BAT) was the sponsor of this study and provided funding. All authors were employees of BAT at the point of manuscript submission, except for JT who was a BAT employee during the design of the study and throughout the clinical phase. BAT is a company that manufactures tobacco and nicotine products.

Figures

Figure 1
Figure 1
Illustration of a typical nicotine pouch: (A) as sold in container with lid, and (B) individual pouch. It is from “Chemical characterization of tobacco-free “modern” oral nicotine pouches and their position on the toxicant and risk continuums” by David Azzopardi, Chuan Liu & James Murphy David Azzopardi, Chuan Liu & James Murphy (2021) taken from Drug and Chemical Toxicology (2022), Vol45:5, Informa UK Limited, trading as Taylor & Francis Group (2022), reprinted by permission of the publisher.
See this image and copyright information in PMC

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