Marco Scala

Introduction Tobacco smoking remains one of the leading preventable causes of disease and premature mortality worldwide. Over the past decades, comprehensive tobacco control policies have contributed to a substantial decline in smoking prevalence in many high-income countries, including Italy. However, the tobacco and nicotine market has undergone profound changes in recent years with the introduction and rapid diffusion of novel tobacco and nicotine products (NTNPs), particularly electronic cigarettes (e-cigarettes) and heated tobacco products (HTPs). These products are often promoted as less harmful alternatives to conventional cigarettes and as tools that may support smoking cessation under a “harm reduction” framework. The tobacco and nicotine industry has strongly embraced this narrative, presenting NTNPs as part of a transition toward a “smoke-free future”. However, the real-world impact of these products on smoking behaviour, population health, and tobacco control policies remains highly debated. At the same time, concerns have emerged regarding their potential health effects, their uptake among adolescents and young people, and the role played by the tobacco industry in shaping the scientific and policy debate surrounding these products. Understanding how NTNPs are used in the population, their potential health consequences, and the broader context in which they are promoted is therefore essential to inform public health policies and tobacco control strategies. These issues are introduced and framed within the broader scientific and policy context in Chapter 1 (Introduction), which outlines the rationale, background, and objectives of the dissertation. Aims and Data This PhD dissertation aimed to investigate the role of NTNPs in the context of tobacco control and public health. The research focused specifically on three main areas: the patterns of NTNP use in the population; the potential health effects associated with NTNP use; and the influence of the tobacco and nicotine industries on the scientific evidence surrounding these products. The dissertation is based on seven scientific articles presented in Chapters 2–8. These studies employed various methodological approaches, including cross-sectional surveys, epidemiological analyses, and systematic reviews with meta-analyses. Several studies used data from nationally representative surveys conducted in Italy to assess the prevalence and patterns of cigarette, e-cigarette and HTP use among adults (Chapter 3) and adolescents (Chapter 4). A systematic review examined patterns of use of HTPs at the international level (Chapter 2). Other studies analysed adverse events associated with the use of different nicotine products (Chapter 5), and the potential relationship between NTNP use and SARS-CoV-2 infection and COVID-19 outcomes (Chapter 6). In addition, one study assessed public attitudes towards tobacco control policies in Italy (Chapter 7), while another investigated the presence of conflicts of interest in the scientific literature on NTNPs and their association with the conclusions reported in published articles (Chapter 8). Together, these studies provide a comprehensive overview of the evolving landscape of tobacco and nicotine products, contributing new evidence on their implications for public health. The role of novel tobacco and nicotine products on tobacco control Although these products are often presented as tools that may support smoking cessation and reduce harm, emerging evidence from population-based studies suggests a more complex picture. In Italy, smoking prevalence had declined substantially in the last decades, largely due to robust tobacco control policies. However, in the last decade this downward trend has slowed, with smoking prevalence showing signs of stagnation in recent years. At the same time, the use of NTNPs, particularly e-cigarettes and HTPs, has increased among adults. Evidence from nationally representative surveys analysed in this dissertation shows that NTNPs are often used alongside conventional cigarettes rather than as a replacement for them. The dual use of cigarettes and e-cigarettes or HTPs is common among adult smokers, suggesting that these products often complement rather than substitute traditional smoking. This pattern raises concerns about the effectiveness of NTNPs as smoking cessation tools in real-world settings. Even more concerning is the widespread use of NTNPs among adolescents and underage students. Despite legal restrictions prohibiting the sale of nicotine products to minors, a significant proportion of underaged students reported using cigarettes, e-cigarettes or HTPs. Dual and poly-product use are also common among adolescents. The prevalence of NTNP use among high school students exceeds that observed in the adult population, highlighting the appeal of these products to younger generations. These findings suggest that NTNPs may perpetuate nicotine addiction among existing smokers while simultaneously facilitating its initiation among young people. Consequently, their overall impact on tobacco control and population health may be far less favourable than claimed. Health effects of e-cigarettes and HTPs In addition to their implications for tobacco control, NTNPs raise important health and safety concerns. Although these products are sometimes perceived as a safer alternative to conventional cigarettes, there is growing evidence to suggest that they are not risk-free. The research presented in this dissertation contributes to the understanding of the health effects associated with e-cigarette and HTP use. One study examined the association between NTNP use and SARS-CoV-2 infection and COVID-19 outcomes through a systematic review and meta-analysis of the available literature. The results suggested that the use of NTNPs may be associated with an increased risk of infection and adverse disease outcomes. Another study analysed short-term adverse events associated with cigarettes, e-cigarettes and HTPs. The findings showed that NTNP users reported various symptoms, and that adverse events were particularly prevalent among dual or poly-product users. These results suggest that using multiple nicotine products may increase the burden of short-term health symptoms. Overall, while the long-term health effects of NTNPs remain incompletely understood due to their recent market introduction, the available evidence indicates that these products expose users to toxic substances and pose risks to human health. The role of the tobacco industry on scientific evidence The tobacco industry has a well-documented history of attempting to influence scientific research and public debate to protect its commercial interests. As part of this dissertation, a systematic review was conducted to examine the relationship between conflicts of interest (COI) and the conclusions reported in the scientific literature on NTNPs. The results revealed a strong association between industry involvement and favourable conclusions regarding these products. While the vast majority of independent studies expressed concerns about NTNPs, publications with declared COI were far more likely to support these products. Industry influence was evident not only through direct funding, but also through indirect links, such as research funded by organisations with financial ties to the tobacco industry. Often, these connections are not clearly disclosed, which make it difficult for readers and peer reviewers to identify potential sources of bias. These findings emphasise the tobacco and nicotine industry's ongoing efforts to influence the evidence base surrounding NTNPs and harm reduction. They also underline the importance of transparency and strict conflict-of-interest policies, as well as independent funding for research in this field. Conclusions This dissertation presents new evidence on the evolving role of NTNPs in tobacco control and public health. While these products are frequently promoted as safer alternatives to cigarettes and potential smoking cessation tools, their real-world use indicates a different picture. In Italy, smoking prevalence has stopped declining, while the use of e-cigarettes and HTPs has increased. At the same time, NTNPs have become popular among adolescents and minors, raising concerns about early nicotine dependence. The available evidence also suggests that NTNPs are associated with health risks through exposure to toxic substances. Further research is needed to understand their long-term impact fully, but the idea that these products are harmless alternatives to smoking is not supported by current scientific evidence. Finally, the dissertation emphasises the ongoing influence of the tobacco and nicotine industry on the scientific and policy discourse surrounding NTNPs. In Chapter 9 (General Discussion), the findings from all studies are integrated and critically discussed, highlighting their implications for tobacco control, research, and policy, as well as identifying key research gaps and providing recommendations for public health practice. To protect public health, independent research on NTNPs must be strengthened, policies must be kept free from industry interference, evidence-based tobacco and nicotine control measures must be implemented, and clear and accurate communication about the risks associated with NTNPs must be promoted to the public.