Nicotine products relative risk assessment: a systematic review and meta-analysis

Abstract

Background: Nicotine products have been the subject of considerable innovation over the past few decades. While the health risks of combustible cigarettes and most tobacco-based products are well characterized, there is less clarity regarding newer nicotine products, and how they compare with the traditional forms. Methods: In this study, we have developed a relative risk hierarchy (RRH) of 13 nicotine products based on systematic review of the scientific literature and analysis of the best available evidence. In total, 3980 publications were identified and screened, with 320 studies being carried through to the final analysis. The health risk data for each product was extracted and the level assessed. The products were analyzed in terms of their toxin emissions and epidemiological data, which were combined on an arbitrary scale from 0 to 100 (low to high risk) to derive a combined risk score for each nicotine product. Results: Combustible tobacco products dominate the top of the RRH, with combined risk scores ranging from 40 to 100. The most frequently consumed products generally score highest. Dipping and chewing tobacco place considerably lower on the hierarchy than the combustible products with scores of 10 to 15, but significantly above heat-not-burn devices and snus, which score between 3 and 4. The lowest risk products have scores of less than 0.25 and include electronic cigarettes, non-tobacco pouches and nicotine replacement therapy. Conclusions: The RRH provides a framework for the assessment of relative risk across all categories of nicotine products based on the best available evidence regarding their toxin emissions and the observed risk of disease development in product users. As nicotine products continue to evolve, and more data comes to light, the analyses can be updated to represent the best available scientific evidence.

Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke

“…This is consistent with the current scientific evidence base underpinning the HTP category and reflects the previously described substantial reductions in the levels and numbers of toxicants present in the aerosols of p-HTPs compared to 1R6F smoke correlating with reduced toxicological outcomes observed across a range of in vitro models ( Chapman et al, 2023 ). As may be expected, although the p-HTPs do not exhibit the same level of reduction in toxicological responses as typically observed with ENDS ( Czekala et al, 2021 ), the data in this manuscript does supports the proposed placement of nicotine delivery products across a relative risk scale ( Abrams et al, 2018 ; Murkett et al, 2020 ). However, HTPs, as demonstrated in this study, still offer substantially reduced harm nicotine delivery compared to combustible cigarette smoking ( Committee On Toxicity, 2017 ).…”

“…This is achieved through offering adult smokers nicotine delivery innovations, or next-generation products (NGPs), which deliver satisfactory levels of nicotine but with substantially reduced levels of, and fewer, toxicants compared to combustible cigarette smoke ( O’Leary and Polosa, 2020 ). Further to this, nicotine delivery products are proposed to sit on a product risk scale relative to one another, with medically licenced nicotine replacement therapies, such as gum and patches, at the lower risk end, combustible cigarette smoking at the highest risk by a large margin, and NGPs in between ( McNeill and Munafò, 2013 ; Abrams et al, 2018 ; Zeller, 2019 ; Murkett et al, 2020 ). NGPs which deliver nicotine via the inhalation route and do not involve tobacco combustion include e-cigarettes and heated tobacco products (HTPs).…”

Nicotine products relative risk assessment: an updated systematic review and meta-analysis

“…The objective of this relative risk assessment of nicotine products is to systematically gather and appraise the best available evidence from the scientific literature regarding the risks of cancer and non-cancer tobacco-related diseases in healthy current users of a single nicotine product, compared with never and non-users of any nicotine product, at average consumption levels. In the first iteration of this study published in 2020, a systematic review, literature appraisal and analysis protocol were developed, which generates a combined risk score for each nicotine product based on the lifetime cancer risk (LCR), modelled from toxin emissions/content data, and epidemiological evidence of disease risk in exposed groups 16 . In the 2020 study, the combined risk score was calculated for 13 categories of nicotine products: combustible cigarettes, cut tobacco, cigarillos, western pipe tobacco, water pipe tobacco, cigars, dipping tobacco, chewing tobacco, heat-not-burn devices, snus, electronic cigarettes, non-tobacco pouches and…”

Modeling the population health impact of nicotine misperceptions

“…This estimate is derived from the epidemiological evidence for smokeless tobacco products (40) which is a reasonable and conservative assumption, representative of other SFPs. Current estimates of the relative risk of the various SFPs (e.g., snus and ENDS products) have been reported to be slightly lower than smokeless tobacco (29,40,41).…”