tobacco products research articles

MINI REVIEW article

Heated tobacco products: a review of current knowledge and initial assessments.

• Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany

The health risks of tobacco smoking have been documented in numerous studies and smoking rates have declined in developed countries over the last 50 years. Today, we know that cigarette smoking is the major cause of preventable deaths due to tobacco smoke induced diseases. As a consequence of an increased awareness of smoking-related health risks, heated tobacco products (HTPs) are marketed as reduced toxicant alternatives to conventional tobacco products. Manufacturers claim that levels of toxicants and hazardous compounds are significantly reduced, implying that inhalation of the modified aerosol is less harmful compared to conventional cigarettes. In this manuscript, previous assessments of HTPs are briefly summarized, including a short discussion on challenges with the adaption of standard analytical methods used for tobacco smoke. The reliability of analytical data is important for risk assessment approaches that are based on reduced toxicant exposure. In order to assess a putative reduction of health risks, an integrated study design is required that should include clinical studies and epidemiology data. One manufacturer applied for a classification as a Modified Risk Tobacco Product (MRTP) in the United States, based on extensive toxicological studies that have also been published. However, data are not yet sufficient for a reliable assessment or recognition of putatively reduced health risks. Challenges regarding a classification in Europe are also discussed briefly in this review.

Introduction

Although most smokers are aware that tobacco smoking is harmful to their health, it is still the leading cause of premature death worldwide and claims the lives of more than 6 million people every year due to cancer, heart disease, stroke, chronic bronchitis, and emphysema ( 1 – 4 ). A recent study has shown that tobacco smoking increases not only the risk for lung cancer, but also for at least 17 different malignant diseases in humans ( 5 ); therefore, successful tobacco control can save millions of lives. With the Framework Convention on Tobacco Control (FCTC), the World Health Organization (WHO) has initiated a comprehensive tobacco control strategy ( 6 ). Articles 9 and 10 of the FCTC include specific policy measures to curb tobacco use by regulating the ingredients and the emissions of tobacco products. The overall aim is to decrease toxicity, addictiveness, and appeal to consumers. Parties of this convention have committed themselves to restrict the supply and demand of tobacco products through a wide range of policies and measures. Although FCTC was successfully applied to conventional tobacco products, uncertainties remain on how to cover novel products. In October 2018, Conference of Parties (COP) 8 explicitly proposed to extend the scope of the according legislations to Heated Tobacco Products (HTPs) ( 7 ).

The chemical complexity of cigarette smoke depends on heating conditions inside the lit cigarette. In a conventional cigarette the burning of tobacco leads to combustion at temperatures up to 700–950°C during puffs (see Figure 1A ). While combustion is limited to the tip of a burning cigarette, pyrolysis and thermal decomposition occur in the oxygen deficient distillation zone. In this part of the cigarette temperatures decrease from 600 to about 200°C. The majority of smoke toxicants are generated here. Below 350°C, condensation of less volatile compounds generates a dense aerosol consisting of growing droplets and solid particles ( 8 ). As a consequence, cigarette smoke consists of “particulate” and “vapor” phases. The mainstream smoke comprises all constituents inhaled during a puff. One way to reduce the exposure to harmful and potential harmful compounds (HPHCs) in the mainstream smoke of tobacco products is to lower the temperature applied to the tobacco. This approach had previously been tried but could not find acceptance on the market as the technology was not yet advanced ( 9 , 10 ).

Figure 1 . Temperature zones in a combustible cigarette (A) in comparison to different Heated Tobacco Products (B) .

Recently, a new generation of HTPs has been introduced to the market which differs widely in product design and temperatures applied to the tobacco. In some devices the tobacco is heated up to 350°C via an electrical heating source ( 11 , 12 ) or different sources like carbon ( 13 ), whereas in other devices vapor is passed through the tobacco and extracts compounds including flavors and nicotine at lower temperatures ( 14 , 15 ). Three different device designs which are currently present on the market are displayed in Figure 1B . These products contain real tobacco that does not undergo a self-sustaining exothermic combustion.

In accordance with the principle of temperature dependence of HPHC generation in tobacco products, the question of reduced HPHC levels in the emissions was raised. While manufacturers provided the initial studies ( 15 – 18 ), more and more independent investigations have now been published for commercially available products ( 19 – 29 ). These studies were focused on levels of well-known HPHCs in comparison with other tobacco products. Analyzed HPHCs were adopted from the FDA preliminary HPHC list ( 30 ) and recommendations by the WHO Study Group on tobacco product regulation (TobReg) ( 31 ). Important carcinogens, such as aldehydes and volatile organic compounds, were found to be reduced by about 80 to over 99% ( 25 ). The lowest reduction with only about 80–90% was reported for acetaldehyde, classified as possibly carcinogenic to humans by the International Agency for Research on Cancer (IARC) ( 32 ). Toxicants like tobacco-specific N-nitrosamines (TSNAs), formed primarily during curing and processing of tobacco rather than by combustion, were also present in the filler of HTP consumables. However, compared to cigarette mainstream smoke TSNA levels were reduced by about 80–90% ( 20 ). Metals like cadmium and mercury are taken up by the tobacco plants and are therefore naturally present in products that contain tobacco ( 33 , 34 ). Again, levels were reduced in HTP devices. Whereas cadmium was below detection limit, indicating a reduction of over 99% ( 16 , 17 ), reduction of mercury was ~75% as published for one device ( 17 ). Polycyclic aromatic hydrocarbons (PAHs) and carbon monoxide are typical products of incomplete combustion. Although reduced by more than 90%, they are still present in HTP emissions ( 17 ). Other substances, such as propylene glycol, glycidol, acetol, and 2-propen-1-ol have been shown to be elevated in comparison to the combustible reference cigarette in at least one device, due to the higher amount of humectants in the tobacco filler of the HTP consumable ( 35 ). Influence on indoor air quality was assessed by the manufacturers and found to be significantly reduced compared to combustible cigarette smoke ( 14 , 36 , 37 ). Concerns for the use in small and poorly ventilated rooms have been raised by an independent group ( 38 ).

Reliability and reproducibility of emission data is a crucial factor for a subsequent risk assessment. To benefit most from the increasing pool of independent studies, a common standard for measurements should be agreed on. The first open question arises regarding the machine puffing protocol. There are different arguments for and against various standard protocols, such as ISO ( 39 ) or Health Canada Intense ( 40 ). Since some of these devices turn off by themselves after a certain time, a smoking regimen with a higher frequency like HCI can help to collect enough material per consumable to pass thresholds set by the analytical instruments. However, the HCI regime could lead to overestimated reductions, due to blocked filter ventilation in conventional or reference cigarettes. Since this modification results in higher toxicant levels in cigarette smoke, the calculated relative reductions of toxicants in the emissions appear bigger. A new puffing protocol, especially tailored for HTPs, would be possible as well. Importantly, these standard protocols do not mimic average smoking behavior and are not meant to provide a realistic estimate of exposure ( 41 ). The purpose of defined smoking regimes is to provide standards to compare key parameters of different products when analyzed in different laboratories. However, recent investigations of the puffing topography ( 42 , 43 ) might suggest further refinements for a better adoption of machine smoking to HTP. ISO/TC126 and CORESTA have started to work on standardized methods.

Since aerosols of HTPs contain a comparatively high proportion of water, standard analytical procedures cannot be easily applied here. Water is trapped on the glass fiber filter and therefore accounts for the total particulate matter (TPM). When the filter is processed further, water loss can occur leading to a reduced analyzed water content. Although not a toxicant, water becomes important when the nicotine-free dried particulate matter, commonly referred to as “tar,” is calculated by the subtraction of water and nicotine from TPM ( 44 ), though the tobacco industry has developed methods in order to avoid water loss ( 45 , 46 ). When special equipment is required, implementation as a standard method by independent laboratories becomes difficult. Despite these technical challenges, industry and independent laboratories have come to mostly comparable results when using standard procedures that were designed for the analysis of conventional cigarettes. This indicates that these procedures could be a basis for dedicated analytical standards for HTPs.

Risk Assessment Approaches

As discussed, most harmful substances that are known to occur in cigarette mainstream smoke were shown to be lowered by one or two orders of magnitude in HTP emissions. Promoted by the manufacturers, there are discussions if this means a reduction of health risks for HTP consumers followed by controversies whether HTPs can be seen as part of harm reduction strategies. The underlying idea of harm reduction strategies in tobacco control is that the damage caused by tobacco consumption should be at least reduced when it cannot be prevented. Toxicant reduction is not necessarily linked to decreased health risk. Although levels of tar had decreased in combustible cigarettes since the 1950 by nearly two thirds, this was not correlated with corresponding decrease in lung cancer incidences ( 47 ). One strategy to assess modified health risks is to compare the tumor potencies of aerosols, as previously applied by Fowles and Dybing to rank the relevant carcinogens and toxicants in cigarette smoke. These calculations are based on individual detection levels in mainstream smoke and on cancer potency factors as indicators of the carcinogenic risk for each smoke constituent ( 48 ). The German Federal Institute for Risk Assessment confirmed in its previous study substantially reduced toxicant levels for selected HTPs and provided an initial assessment in 2017 ( 49 ). The profound reduction (>99%) of key carcinogens according to Fowles and Dybing, such as benzene and 1,3-butandien, as well as substantial overall reduction of toxicants is expected to affect health risks, if people abstain completely from other tobacco products. Nicotine levels are still in the range of conventional cigarettes, limiting the risk to switch back to conventional smoking tobacco ( 25 ). In a detailed modeling assessment, Stephens compared relative harmfulness of different nicotine products with a model based on exposure data and cancer potencies. The calculated lifetime cancer risk of the HTP, using one data set by the manufacturer, was one to two orders of magnitude lower compared to combustible cigarettes but higher compared to e-cigarettes ( 50 ). Lachenmeier et al. calculated the combined margin of exposure (MOE) for the HTP and for combustible cigarettes ( 51 ). The obtained ratio between exposure and toxicity effect levels, which could be interpreted as a “safety buffer” ( 52 ), was 10-fold higher for the HTP as compared to combustible cigarettes ( 51 ). As noted by Stephens, these models only consider toxicants levels and neglect particle effects ( 50 ). In addition, there is growing consensus that a complete switch to HTP can reduce toxicant exposure, as confirmed in recent investigations on biomarkers of exposure in smokers ( 53 – 57 ). Haziza et al. reported reductions of 51 to 96% for selected HPHC-related biomarkers over a 90-days ambulatory study. However, compliance of participants was decreasing over the ambulatory period, suggesting that relapse to tobacco and/or dual use could counteract potential benefits in real life settings ( 54 ). During two 90-days studies, biomarkers of potential harm were additionally assessed ( 58 , 59 ). The results of longer switching studies to detect significant reductions of biomarkers of potential harm are anticipated ( 60 ).

In the United states, the Family Smoking Prevention and Tobacco Control Act ( 61 ) requires tobacco products to not only “ significantly reduce harm and the risk of tobacco-related disease to individual tobacco users ” but also to “ benefit the health of the population as a whole taking into account both users of tobacco products and persons who do not currently use tobacco products ” in order to market that product with modified risk claims in the United States. The required scientific evidence for defined claims and additional data that have to be provided by the applicant are described by the FDA in detail in a guidance document ( 62 ). Scientific standards for analysis of potential Modified Risks Tobacco Products were also outlined by the Institute of Medicine in 2012 ( 63 ). Required data (summarized in Figure 2 ) include a comprehensive analysis of smoke chemistry ( 64 ) as well as data on specified biomarkers of exposure. There is a framework for preclinical studies, proposing in vitro tests of genotoxicity, oxidative stress, and inflammation. The in vitro test battery comprising assays for bacterial mutagenicity, mammalian cytogenetics/mutation, and mammalian cytotoxicity, that has been suggested by a CORESTA task force in 2004 ( 65 ), has been conducted by the manufacturers ( 17 , 18 , 66 – 70 ). Some in vitro tests can specifically address smoking related adverse effects, as biphasic culture of airway epithelial cells or assays on endothelial activation as conducted by the manufacturers ( 13 , 71 – 74 ) and independent researchers ( 75 , 76 ). Further, 3D in vitro cultured lungs tissues are now available by several commercial suppliers. Consequently, the necessity for animal testing of tobacco products should be questioned, in line with a general shift of focus in modern toxicology ( 77 ). In some countries including Germany, animal studies have been prohibited for tobacco products. However, animal studies have been conducted by the tobacco industry ( 78 – 81 ) and independent researchers ( 82 ). To address public health questions, population models have been applied ( 83 – 86 ) and publically discussed ( 87 ).

Figure 2 . Schematic overview of required data and studies to facilitate risk assessments of tobacco products. Epidemiological data are most conclusive but can usually only be used retrospectively. Therefore, risk assessments rely on models that consider emissions, pre-clinical and clinical studies. Meanwhile numerous studies on smoke chemistry and in vitro toxicology have been published by industry and independent researchers. In contrast, in vivo and clinical studies are far more complex. No sufficient independent data are available.

In Europe, toxicological assessments of tobacco products are aimed to exclude elevated risks in relation to conventional products, but not to confirm less hazardous product properties. As long as relevant adverse effects cannot be excluded, even modified health risks still remain an issue of concern. In contrast to the United States, products can be placed on the market more easily. Consumers who use these products need to accept all characterized and not yet identified health risks. Also manufacturers might attempt to gain classification as “smokeless tobacco,” resulting in less stringent health warnings. In public perception, this could probably be understood as an official acknowledgment of reduced health risks. Such acknowledgment would be premature from the perspective of risk assessment. In the USA, the assessment framework is required to acknowledge reduced/modified risks, if manufacturers can support their claims. Consequently, additional issues, as for example risk perception and communication, behavioral assessments of addictiveness or clinical studies ( 63 ) need to be considered.

In May 2017, one manufacturer submitted a Modified Risk Tobacco Product Application (MRTPA) for his HTP ( 88 ) and in January 2018, the Tobacco Product Scientific Advisory Committee (TPSAC) met to give a recommendation. Due to the lack of human studies, TPSAC was not convinced to support the statement “ Scientific studies have shown that switching completely from cigarettes to the IQOS system can reduce the risks of tobacco-reduced diseases ,” although potential is seen. The relevance of the animal studies to human smokers has been questioned ( 89 ). Two 90-days studies as mentioned above ( 58 , 59 ) did not demonstrate a relevant reduction in biomarkers of potential harm in regard to inflammation and lung function ( 90 ). This could also be linked to the continual inhalation of nicotine and remaining toxicants. Reductions of biomarkers of potential harm were also low in the smoking abstinence groups, possibly due to the short study period. Biological relevance needs to be demonstrated with longer exposure studies. However, biomarkers of exposure that have been assessed in various studies were shown to be reduced similarly to cessation level ( 35 ), especially markers that are relevant for carcinogenic risks. The less strong claim “ Switching completely to IQOS presents less risks of harm than continuing to smoke cigarettes ” has therefore been supported by about half of the committee members ( 89 ). While the evidence has mostly been seen as strong enough to support a reduced exposure claim, the link to morbidity and mortality has not been seen to be adequately demonstrated ( 89 ). The final decision on the MRTPA has not been made by the FDA yet, however the first HTP was authorized in April 2019 for sale, without modified risk status. In Europe, it is widely accepted that current HTPs do not bear additional or other health risks in relation to conventional products. European legislation does not define a modified risk classification. On the contrary, information on the product and package, as well as presentation must not imply reduced hazards compared to any other tobacco product. Although a risk-benefit assessment is required for new tobacco products, permission on the market does not depend on modified risks.

Although a 99% reduction of some major carcinogens is expected to affect health risks, the magnitude or relevance of such putative reduction is not yet clear. A benefit is likely seen for especially the subset of long-term smokers that are unable to quit or to switch to another nicotine source with less HPHC exposure. However, referring back to the tumor potency models, it should be kept in mind that substantial and relevant health risks are still present. Consequently, HTPs should not be the first option to decrease smoking-associated harm.

Author Contributions

NM prepared the draft manuscript. EP and FH-S contributed sections to the draft. NM, EP, CH, FH-S, and AL created the concept for this article and contributed to manuscript revision and approval of the final version.

This study was financially supported by intramural funding of the German Federal Institute for Risk Assessment (BfR) (SFP Grant no. 1322-535).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank A. Midha for valuable comments on the manuscript.

1. Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, et al. A review of human carcinogens–Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. (2009) 10:1033–4. doi: 10.1016/S1470-2045(09)70326-2

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Lim SS, Mokdad AH. Socioeconomic inequalities and infectious disease burden. Lancet. (2012) 379:1080–1. doi: 10.1016/S0140-6736(12)60151-2

3. Pesch B, Kendzia B, Gustavsson P, Jockel KH, Johnen G, Pohlabeln H, et al. Cigarette smoking and lung cancer–relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. (2012) 131:1210–9. doi: 10.1002/ijc.27339

4. Agudo A, Bonet C, Travier N, Gonzalez CA, Vineis P, Bueno-de-Mesquita HB, et al. Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study. J Clin Oncol. (2012) 30:4550–7. doi: 10.1200/JCO.2011.41.0183

5. Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I, Nik-Zainal S, et al. Mutational signatures associated with tobacco smoking in human cancer. Science. (2016) 354:618–22. doi: 10.1126/science.aag0299

6. World-Health-Organization. Work in Progress in Relation to Articles 9 and 10 of the WHO FCTC . Moscow (2014).

7. Conference of the Parties to the WHO Framework Convention on Tobacco Control. FCTC/COP8(22) Novel and Emerging Tobacco Products. (2018). Available online at: https://www.who.int/fctc/cop/sessions/cop8/FCTC__COP8(22).pdf (accessed September 30, 2019).

8. Baker RR, Bishop LJ. The pyrolysis of tobacco ingredients. J Anal Appl Pyrolysis. (2004) 71:223–331. doi: 10.1016/S0165-2370(03)00090-1

CrossRef Full Text | Google Scholar

9. Caputi TL. Industry watch: heat-not-burn tobacco products are about to reach their boiling point. Tob Control. (2016) 26:609–10. doi: 10.1136/tobaccocontrol-2016-053264

10. Henkler F, Luch A. Alternativen zu Zigaretten und herkömmlichen Tabakerzeugnissen–Ein kurzer historischer und aktueller Überlick. Rundsch Fleischhygiene Lebensmittelüberwachung. (2015) 67:39–41.

11. Eaton D, Jakaj B, Forster M, Nicol J, Mavropoulou E, Scott K, et al. Assessment of tobacco heating product THP1.0. Part 2: product design, operation and thermophysical characterisation. Regul Toxicol Pharmacol. (2017) 93:4–13. doi: 10.1016/j.yrtph.2017.09.009

12. Smith MR, Clark B, Ludicke F, Schaller JP, Vanscheeuwijck P, Hoeng J, et al. Evaluation of the tobacco heating system 2.2. Part 1: description of the system and the scientific assessment program. Regul Toxicol Pharmacol. (2016) 81(Suppl. 2):S17–26. doi: 10.1016/j.yrtph.2016.07.006

13. Iskandar AR, Martin F, Leroy P, Schlage WK, Mathis C, Titz B, et al. Comparative biological impacts of an aerosol from carbon-heated tobacco and smoke from cigarettes on human respiratory epithelial cultures: a systems toxicology assessment. Food Chem Toxicol. (2018) 115:109–26. doi: 10.1016/j.fct.2018.02.063

14. Ichitsubo H, Kotaki M. Indoor air quality (IAQ) evaluation of a novel tobacco vapor (NTV) product. Regul Toxicol Pharmacol. (2018) 92:278–94. doi: 10.1016/j.yrtph.2017.12.017

15. Poynton S, Sutton J, Goodall S, Margham J, Forster M, Scott K, et al. A novel hybrid tobacco product that delivers a tobacco flavour note with vapour aerosol (Part 1): product operation and preliminary aerosol chemistry assessment. Food Chem Toxicol. (2017) 106(Pt A):522–32. doi: 10.1016/j.fct.2017.05.022

16. Forster M, Fiebelkorn S, Yurteri C, Mariner D, Liu C, Wright C, et al. Assessment of novel tobacco heating product THP1.0. Part 3: comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions. Regul Toxicol Pharmacol. (2017) 93:14–33. doi: 10.1016/j.yrtph.2017.10.006

17. Schaller JP, Keller D, Poget L, Pratte P, Kaelin E, McHugh D, et al. Evaluation of the tobacco heating system 2.2. Part 2: chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regul Toxicol Pharmacol. (2016) 81(Suppl. 2):S27–47. doi: 10.1016/j.yrtph.2016.10.001

18. Takahashi Y, Kanemaru Y, Fukushima T, Eguchi K, Yoshida S, Miller-Holt J, et al. Chemical analysis and in vitro toxicological evaluation of aerosol from a novel tobacco vapor product: a comparison with cigarette smoke. Regul Toxicol Pharmacol. (2018) 92:94–103. doi: 10.1016/j.yrtph.2017.11.009

19. Auer R, Concha-Lozano N, Jacot-Sadowski I, Cornuz J, Berthet A. Heat-not-burn tobacco cigarettes: smoke by any other name. JAMA Intern Med. (2017) 177:1050–2. doi: 10.1001/jamainternmed.2017.1419

20. Bekki K, Inaba Y, Uchiyama S, Kunugita N. Comparison of chemicals in mainstream smoke in heat-not-burn tobacco and combustion cigarettes. J UOEH. (2017) 39:201–7. doi: 10.7888/juoeh.39.201

21. Farsalinos KE, Yannovits N, Sarri T, Voudris V, Poulas K. Nicotine delivery to the aerosol of a heat-not-burn tobacco product: comparison with a tobacco cigarette and e-cigarettes. Nicotine Tob Res. (2018) 20:1004–9. doi: 10.1093/ntr/ntx138

22. Farsalinos KE, Yannovits N, Sarri T, Voudris V, Poulas K, Leischow SJ. Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette. Addiction. (2018) 113:2099–106. doi: 10.1111/add.14365

23. Leigh NJ, Palumbo MN, Marino AM, O'Connor RJ, Goniewicz ML. Tobacco-specific nitrosamines (TSNA) in heated tobacco product IQOS. Tob Control. (2018) 27(Suppl. 1):s37–8. doi: 10.1136/tobaccocontrol-2018-054318

24. Li X, Luo Y, Jiang X, Zhang H, Zhu F, Hu S, et al. Chemical analysis and simulated pyrolysis of tobacco heating system 2.2 compared to conventional cigarettes. Nicotine Tob Res. (2019) 21:111–8. doi: 10.1093/ntr/nty005

25. Mallock N, Boss L, Burk R, Danziger M, Welsch T, Hahn H, et al. Levels of selected analytes in the emissions of “heat not burn” tobacco products that are relevant to assess human health risks. Arch Toxicol. (2018) 92:2145–9. doi: 10.1007/s00204-018-2215-y

26. Simonavicius E, McNeill A, Shahab L, Brose LS. Heat-not-burn tobacco products: a systematic literature review. Tob Control. (2018) 28:582–94. doi: 10.1136/tobaccocontrol-2018-054419

27. Uchiyama S, Noguchi M, Takagi N, Hayashida H, Inaba Y, Ogura H, et al. Simple determination of gaseous and particulate compounds generated from heated tobacco products. Chem Res Toxicol. (2018) 31:585–93. doi: 10.1021/acs.chemrestox.8b00024

28. Ishizaki A, Kataoka H. A sensitive method for the determination of tobacco-specific nitrosamines in mainstream and sidestream smokes of combustion cigarettes and heated tobacco products by online in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry. Anal Chim Acta. (2019) 1075:98–105. doi: 10.1016/j.aca.2019.04.073

29. Salman R, Talih S, El-Hage R, Haddad C, Karaoghlanian N, El-Hellani A, et al. Free-base and total nicotine, reactive oxygen species, and carbonyl emissions from IQOS, a heated tobacco product. Nicotine Tob Res. (2018) 21:1285–8. doi: 10.1093/ntr/nty235

30. Food and Drug Administration. Harmful and Potentially Harmful Constituents (HPHCs) . (2018). Available online at: https://www.fda.gov/tobacco-products/products-ingredients-components/harmful-and-potentially-harmful-constituents-hphcs (accessed September 30, 2019).

World Health Organization. WHO study group on tobacco product regulation. Report on the scientific basis of tobacco product regulations: fifth report of a WHO Study Group. WHO Technical Report Series, no. 955 (2015). p. 1–234.

Google Scholar

32. IARC. Monograph 71, Acetaldehyde . (1999). Available online at: https://monographs.iarc.fr/wp-content/uploads/2018/06/TR42-12.pdf (accessed September 30, 2019).

33. Chiba M, Masironi R. Toxic and trace elements in tobacco and tobacco smoke. Bull World Health Organ. (1992) 70:269–75

PubMed Abstract | Google Scholar

34. Golia EE, Dimirkou A, Mitsios† IK. Heavy-metal concentration in tobacco leaves in relation to their available soil fractions. Commun Soil Sci Plant Anal. (2009) 40:106–20. doi: 10.1080/00103620802623570

35. Food and Drug Administration. FDA Briefing Document: January 24-25, 2018 TPSAC Meeting . (2018). Available online at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/UCM593109.pdf (accessed September 30, 2019).

36. Forster M, McAughey J, Prasad K, Mavropoulou E, Proctor C. Assessment of tobacco heating product THP1.0. Part 4: characterisation of indoor air quality and odour. Regul Toxicol Pharmacol. (2018) 93:34–51. doi: 10.1016/j.yrtph.2017.09.017

37. Mitova MI, Campelos PB, Goujon-Ginglinger CG, Maeder S, Mottier N, Rouget EG, et al. Comparison of the impact of the tobacco heating system 2.2 and a cigarette on indoor air quality. Regul Toxicol Pharmacol. (2016) 80:91–101. doi: 10.1016/j.yrtph.2016.06.005

38. Cancelada L, Sleiman M, Tang X, Russell ML, Montesinos VN, Litter MI, et al. Heated tobacco products: volatile emissions and their predicted impact on indoor air quality. Environ Sci Technol. (2019) 53:7866–76. doi: 10.1021/acs.est.9b02544

39. ISO 3308. Routine Analytical Cigarette-Smoking Machine–Definitions and Standard Conditions. Geneva: International Organisation for Standardisation (2012).

40. Health Canada. Tobacco Reporting Regulations, SOR/2000–273 . Ottawa, ON: Government of Canada (2000). Available online at: https://laws-lois.justice.gc.ca/eng/regulations/SOR-2000-273/

41. Hammond D, Wiebel F, Kozlowski LT, Borland R, Cummings KM, O'Connor RJ, et al. Revising the machine smoking regime for cigarette emissions: implications for tobacco control policy. Tob Control. (2007) 16:8–14. doi: 10.1136/tc.2005.015297

42. Zenzen V, Diekmann J, Gerstenberg B, Weber S, Wittke S, Schorp MK. Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 2: smoke chemistry and in vitro toxicological evaluation using smoking regimens reflecting human puffing behavior. Regul Toxicol Pharmacol. (2012) 64(2 Suppl.):S11–34. doi: 10.1016/j.yrtph.2012.08.004

43. Gee J, Prasad K, Slayford S, Gray A, Nother K, Cunningham A, et al. Assessment of tobacco heating product THP1.0. Part 8: study to determine puffing topography, mouth level exposure and consumption among Japanese users. Regul Toxicol Pharmacol. (2018) 93:84–91. doi: 10.1016/j.yrtph.2017.08.005

44. ISO 4387. Cigarettes — Determination of Total and Nicotine-Free Dry Particulate Matter Using a Routine Analytical Smoking Machine. Geneva: International Organisation for Standardisation (2000).

45. Gasparyan H, Mariner D, Wright C, Nicol J, Murphy J, Liu C, et al. Accurate measurement of main aerosol constituents from heated tobacco products (HTPs): implications for a fundamentally different aerosol. Regul Toxicol Pharmacol. (2018) 99:131–41. doi: 10.1016/j.yrtph.2018.09.016

46. Ghosh D, Jeannet C. An improved Cambridge filter pad extraction methodology to obtain more accurate water and “Tar” values: in situ Cambridge filter pad extraction methodology. Beiträge Tabakforschung Int/Contrib Tob Res . (2014) 26:38–49. doi: 10.2478/cttr-2014-0008

47. Hoffmann D, Hoffmann I, El-Bayoumy K. The less harmful cigarette: a controversial issue. a tribute to Ernst L. Wynder. Chem Res Toxicol. (2001) 14:767–90. doi: 10.1021/tx000260u

48. Fowles J, Dybing E. Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tob Control. (2003) 12:424–30. doi: 10.1136/tc.12.4.424

49. German Federal Institute for Risk Assessment (BfR). Vorläufige Risikobewertung von Tobacco Heating-Systemen als Tabakprodukte. (2017). Available online at: https://mobil.bfr.bund.de/cm/343/vorlaeufige-risikobewertung-von-tobacco-heating-systemen-als-tabakprodukte.pdf (accessed September 30, 2019).

50. Stephens WE. Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke. Tob Control. (2018) 27:10–17. doi: 10.1136/tobaccocontrol-2017-053808

51. Lachenmeier DW, Anderson P, Rehm J. Heat-not-burn tobacco products: the devil in disguise or a considerable risk reduction? Int J Alcohol Drug Res. (2018) 7:8–11. doi: 10.7895/ijadr.250

52. EPA. Framework Manual EPA-748-B12-001 13. Quantitative Risk Assessment Calculations. (2012). Available online at: https://www.epa.gov/sites/production/files/2015-05/documents/13.pdf (accessed September 30, 2019).

53. Gale N, McEwan M, Eldridge AC, Fearon IM, Sherwood N, Bowen E, et al. Changes in biomarkers of exposure on switching from a conventional cigarette to tobacco heating products: a randomized, controlled study in healthy Japanese subjects. Nicotine Tob Res. (2018) 21:1220–7. doi: 10.1093/ntr/nty104

54. Haziza C, de La Bourdonnaye G, Donelli A, Poux V, Skiada D, Weitkunat R, et al. Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol tobacco heating system 2.2 for three months (Part 1). Nicotine Tob Res. (2018) 2:161–72. doi: 10.1093/ntr/ntz013

CrossRef Full Text

55. Haziza C, de La Bourdonnaye G, Skiada D, Ancerewicz J, Baker G, Picavet P, et al. Evaluation of the tobacco heating system 2.2. Part 8: 5-day randomized reduced exposure clinical study in Poland. Regul Toxicol Pharmacol. (2016) 81(Suppl. 2):S139–50. doi: 10.1016/j.yrtph.2016.11.003

56. Ludicke F, Picavet P, Baker G, Haziza C, Poux V, Lama N, et al. Effects of switching to the tobacco heating system 2.2 menthol, smoking abstinence, or continued cigarette smoking on biomarkers of exposure: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (Part 1). Nicotine Tob Res. (2018) 20:161–72. doi: 10.1093/ntr/ntw287

57. Miura N, Yuki D, Minami N, Kakehi A, Futamura Y. A study to investigate changes in the levels of biomarkers of exposure to selected cigarette smoke constituents in Japanese adult male smokers who switched to a non-combustion inhaler type of tobacco product. Regul Toxicol Pharmacol. (2015) 71:498–506. doi: 10.1016/j.yrtph.2015.02.007

58. Haziza C, de La Bourdonnaye G, Donelli A, Skiada D, Poux V, Weitkunat R, et al. Favorable changes in biomarkers of potential harm to reduce the adverse health effects of smoking in smokers switching to the menthol tobacco heating system 2.2 for three months (Part 2). Nicotine Tob Res. (2019). doi: 10.1093/ntr/ntz084. [Epub ahead of print].

59. Ludicke F, Picavet P, Baker G, Haziza C, Poux V, Lama N, et al. Effects of switching to the menthol tobacco heating system 2.2, smoking abstinence, or continued cigarette smoking on clinically relevant risk markers: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (Part 2). Nicotine Tob Res. (2018) 20:173–82. doi: 10.1093/ntr/ntx028

60. Newland N, Lowe FJ, Camacho OM, McEwan M, Gale N, Ebajemito J, et al. Evaluating the effects of switching from cigarette smoking to using a heated tobacco product on health effect indicators in healthy subjects: study protocol for a randomized controlled trial. Intern Emerg Med. (2019) 14:885–98. doi: 10.1007/s11739-019-02090-8

61. United States Public Laws. Family Smoking Prevention and Tobacco Control Act (FSPTCA) Pub. L. 111-31, 21 U.S.C. 387 Et Seq . (2009). Available online at: https://www.govinfo.gov/content/pkg/PLAW-111publ31/pdf/PLAW-111publ31.pdf (accessed September 30, 2019).

62. U.S. Food & Drug Administration. Modified Risk Tobacco Product Applications: Draft Guidance for Industry. (2012). Available online at: https://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM297751.pdf (accessed September 30, 2019).

63. IOM (Institute of Medicine). Scientific Standards for Studies on Modified Risk Tobacco Products. Washington, DC: The National Academies Press (2012).

64. Food and Drug Administration. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List . (2012). Available online at: https://www.govinfo.gov/content/pkg/FR-2012-04-03/pdf/2012-7727.pdf

65. CORESTA. The Rationale and Strategy for Conducting In Vitro Toxicology Testing of Tobacco Smoke . (2004). Available online at: https://www.coresta.org/sites/default/files/technical_documents/main/IVT_TF_Rationale-IVT-Testing-Tob.-Smoke_Report_Jun04.pdf (accessed September 30, 2019).

66. Jaunky T, Adamson J, Santopietro S, Terry A, Thorne D, Breheny D, et al. Assessment of tobacco heating product THP1.0. Part 5: in vitro dosimetric and cytotoxic assessment. Regul Toxicol Pharmacol. (2018) 93:52–61. doi: 10.1016/j.yrtph.2017.09.016

67. Taylor M, Jaunky T, Hewitt K, Breheny D, Lowe F, Fearon IM, et al. A comparative assessment of e-cigarette aerosols and cigarette smoke on in vitro endothelial cell migration. Toxicol Lett. (2017) 277:123–8. doi: 10.1016/j.toxlet.2017.06.001

68. Taylor M, Thorne D, Carr T, Breheny D, Walker P, Proctor C, et al. Assessment of novel tobacco heating product THP1.0. Part 6: a comparative in vitro study using contemporary screening approaches. Regul Toxicol Pharmacol. (2018) 93:62–70. doi: 10.1016/j.yrtph.2017.08.016

69. Thorne D, Breheny D, Proctor C, Gaca M. Assessment of novel tobacco heating product THP1.0. Part 7: comparative in vitro toxicological evaluation. Regul Toxicol Pharmacol. (2018) 93:71–83. doi: 10.1016/j.yrtph.2017.08.017

70. Thorne D, Leverette R, Breheny D, Lloyd M, McEnaney S, Whitwell J, et al. Genotoxicity evaluation of tobacco and nicotine delivery products: Part two. In vitro micronucleus assay. Food Chem Toxicol. (2019) 132:110546. doi: 10.1016/j.fct.2019.05.054

71. Kogel U, Gonzalez Suarez I, Xiang Y, Dossin E, Guy PA, Mathis C, et al. Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells. Toxicol In Vitro. (2015) 29:2102–15. doi: 10.1016/j.tiv.2015.08.004

72. van der Toorn M, Sewer A, Marescotti D, Johne S, Baumer K, Bornand D, et al. The biological effects of long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product. Toxicol In Vitro. (2018) 50:95–108. doi: 10.1016/j.tiv.2018.02.019

73. Marescotti D, Gonzalez Suarez I, Acali S, Johne S, Laurent A, Frentzel S, et al. High Content screening analysis to evaluate the toxicological effects of harmful and potentially harmful constituents (HPHC). J Vis Exp. (2016) 111:53987. doi: 10.3791/53987

74. Iskandar AR, Titz B, Sewer A, Leroy P, Schneider T, Zanetti F, et al. Systems toxicology meta-analysis of in vitro assessment studies: biological impact of a candidate modified-risk tobacco product aerosol compared with cigarette smoke on human organotypic cultures of the aerodigestive tract. Toxicol Res. (2017) 6:631–53. doi: 10.1039/C7TX00047B

75. Leigh NJ, Tran PL, O'Connor RJ, Goniewicz ML. Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial cells. Tob Control. (2018) 27(Suppl. 1):s26–9. doi: 10.1136/tobaccocontrol-2018-054317

76. Sohal SS, Eapen MS, Naidu VGM, Sharma P. IQOS exposure impairs human airway cell homeostasis: direct comparison with traditional cigarette and e-cigarette. ERJ Open Res. (2019) 5:00159-2018. doi: 10.1183/23120541.00159-2018

77. Krewski D, Acosta D Jr, Andersen M, Anderson H, Bailar JC III, Boekelheide K, et al. Toxicity testing in the 21st century: a vision and a strategy. J Toxicol Environ Health B Crit Rev. (2010) 13:51–138. doi: 10.1080/10937404.2010.483176

78. Kogel U, Schlage WK, Martin F, Xiang Y, Ansari S, Leroy P, et al. A 28-day rat inhalation study with an integrated molecular toxicology endpoint demonstrates reduced exposure effects for a prototypic modified risk tobacco product compared with conventional cigarettes. Food Chem Toxicol. (2014) 68:204–17. doi: 10.1016/j.fct.2014.02.034

79. Phillips B, Veljkovic E, Boue S, Schlage WK, Vuillaume G, Martin F, et al. An 8-month systems toxicology inhalation/cessation study in Apoe −/− mice to investigate cardiovascular and respiratory exposure effects of a candidate modified risk tobacco product, THS 2.2, compared with conventional cigarettes. Toxicol Sci. (2016) 149:411–32. doi: 10.1093/toxsci/kfv243

80. Phillips B, Veljkovic E, Peck MJ, Buettner A, Elamin A, Guedj E, et al. A 7-month cigarette smoke inhalation study in C57BL/6 mice demonstrates reduced lung inflammation and emphysema following smoking cessation or aerosol exposure from a prototypic modified risk tobacco product. Food Chem Toxicol. (2015) 80:328–45. doi: 10.1016/j.fct.2015.03.009

81. Phillips BW, Schlage WK, Titz B, Kogel U, Sciuscio D, Martin F, et al. A 90-day OECD TG 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of the aerosol from the carbon heated tobacco product version 1.2 (CHTP1.2) compared with cigarette smoke. I. Inhalation exposure, clinical pathology and histopathology. Food Chem Toxicol. (2018) 116(Pt B):388–413. doi: 10.1016/j.fct.2018.04.015

82. Nabavizadeh P, Liu J, Havel CM, Ibrahim S, Derakhshandeh R, Jacob P Iii, et al. Vascular endothelial function is impaired by aerosol from a single IQOS HeatStick to the same extent as by cigarette smoke. Tob Control. (2018) 27(Suppl. 1):s13–9. doi: 10.1136/tobaccocontrol-2018-054325

83. Djurdjevic S, Sponsiello-Wang Z, Lee PN, Fry JS, Weitkunat R, Ludicke F, et al. Modeling the impact of changes in tobacco use on individual disease risks. Regul Toxicol Pharmacol. (2018) 97:88–97. doi: 10.1016/j.yrtph.2018.06.001

84. Lee PN, Fry JS, Hamling JF, Sponsiello-Wang Z, Baker G, Weitkunat R. Estimating the effect of differing assumptions on the population health impact of introducing a reduced risk tobacco product in the USA. Regul Toxicol Pharmacol. (2017) 88:192–213. doi: 10.1016/j.yrtph.2017.06.009

85. Martin F, Vuillaume G, Baker G, Sponsiello-Wang Z, Ricci PF, Ludicke F, et al. Quantifying the risk-reduction potential of new modified risk tobacco products. Regul Toxicol Pharmacol. (2018) 92:358–69. doi: 10.1016/j.yrtph.2017.12.011

86. Weitkunat R, Lee PN, Baker G, Sponsiello-Wang Z, Gonzalez-Zuloeta Ladd AM, Ludicke F. A novel approach to assess the population health impact of introducing a modified risk tobacco product. Regul Toxicol Pharmacol. (2015) 72:87–93. doi: 10.1016/j.yrtph.2015.03.011

87. Max WB, Sung HY, Lightwood J, Wang Y, Yao T. Modelling the impact of a new tobacco product: review of Philip Morris International's Population Health Impact Model as applied to the IQOS heated tobacco product. Tob Control. (2018) 27(Suppl. 1):s82–6. doi: 10.1136/tobaccocontrol-2018-054572

88. U.S. Food & Drug Administration. Philip Morris Products S.A. Modified Risk Tobacco Product (MRTP) Applications. (2018). Available online at: https://www.fda.gov/TobaccoProducts/Labeling/MarketingandAdvertising/ucm546281.htm (accessed September 30, 2019).

89. Tobacco Product Scientific Advisory Committee. Meeting Transcript . (2018). Available online at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/UCM599235.pdf (accessed September 30, 2019).

90. Glantz SA. PMI's own in vivo clinical data on biomarkers of potential harm in Americans show that IQOS is not detectably different from conventional cigarettes. Tob Control. (2018) 27(Suppl. 1):s9–12. doi: 10.1136/tobaccocontrol-2018-054413

Keywords: heated tobacco products, emissions, harm reduction, risk assessment, tobacco smoke

Citation: Mallock N, Pieper E, Hutzler C, Henkler-Stephani F and Luch A (2019) Heated Tobacco Products: A Review of Current Knowledge and Initial Assessments. Front. Public Health 7:287. doi: 10.3389/fpubh.2019.00287

Received: 26 March 2019; Accepted: 20 September 2019; Published: 10 October 2019.

Reviewed by:

Copyright © 2019 Mallock, Pieper, Hutzler, Henkler-Stephani and Luch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Nadja Mallock, nadja.mallock@bfr.bund.de

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Tobacco, Nicotine, and E-Cigarettes Research Report Introduction

In 2014, the Nation marked the 50th anniversary of the first Surgeon General’s Report on Smoking and Health. In 1964, more than 40 percent of the adult population smoked. Once the link between smoking and its medical consequences—including cancers and heart and lung diseases—became a part of the public consciousness, education efforts and public policy changes were enacted to reduce the number of people who smoke. These efforts resulted in substantial declines in smoking rates in the United States—to half the 1964 level. 1

However, rates of cigarette smoking and other tobacco use are still too high, 2 and some populations are disproportionately affected by tobacco’s health consequences. Most notably, people with mental disorders—including substance use disorders—smoke at higher rates than the general population. 3–6 Additionally, people living below the poverty line and those with low educational attainment are more likely to smoke than those in the general population. As tobacco use is the leading preventable cause of mortality in the United States, 1 differential rates of smoking and use of other tobacco products is a significant contributor to health disparities among some of the most vulnerable people in our society.

• Open access
• Published: 30 July 2021

Impact of tobacco and/or nicotine products on health and functioning: a scoping review and findings from the preparatory phase of the development of a new self-report measure

• Esther F. Afolalu   ORCID: orcid.org/0000-0001-8866-4765 1 ,
• Erica Spies 1 ,
• Agnes Bacso 1 ,
• Emilie Clerc 1 ,
• Linda Abetz-Webb 2 ,
• Sophie Gallot 1 &
• Christelle Chrea 1  

Harm Reduction Journal volume  18 , Article number:  79 ( 2021 ) Cite this article

14k Accesses

4 Citations

10 Altmetric

Metrics details

Measuring self-reported experience of health and functioning is important for understanding the changes in the health status of individuals switching from cigarettes to less harmful tobacco and/or nicotine products (TNP) or reduced-risk products (RRP) and for supporting tobacco harm reduction strategies.

This paper presents insights from three research activities from the preparatory phase of the development of a new self-report health and functioning measure. A scoping literature review was conducted to identify the positive and negative impact of TNP use on health and functioning. Focus groups ( n  = 29) on risk perception and individual interviews ( n  = 40) on perceived dependence in people who use TNPs were reanalyzed in the context of health and functioning, and expert opinion was gathered from five key opinion leaders and five technical consultants.

Triangulating the findings of the review of 97 articles, qualitative input from people who use TNPs, and expert feedback helped generate a preliminary conceptual framework including health and functioning and conceptually-related domains impacted by TNP use. Domains related to the future health and functioning measurement model include physical health signs and symptoms, general physical appearance, functioning (physical, sexual, cognitive, emotional, and social), and general health perceptions.

Conclusions

This preliminary conceptual framework can inform future research on development and validation of new measures for assessment of overall health and functioning impact of TNPs from the consumers’ perspective.

As a leading cause of preventable morbidity and mortality worldwide, smoking remains a major public health problem. Compared with those who do not smoke, people who smoke are significantly more likely to develop heart diseases, lung cancer, chronic obstructive pulmonary disease (COPD), and other diseases [ 1 , 2 ]. It is well established that the best way to avoid the health risks associated with smoking is for people to never start and for those who smoke to quit [ 1 , 3 ]. Tobacco harm reduction is one way to alleviate the health risk for individuals who choose not to quit smoking [ 4 ], by providing less harmful tobacco and/or nicotine products (TNP), such as reduced-risk products (RRP) (used here to refer to products that present, are likely to present, or have the potential to present, less risk of harm to people who smoke and switch to these products versus continued smoking) or modified risk tobacco products (MRTP).

Several smokeless tobacco products and a heated tobacco product were recently authorized for marketing with modified risk claims through the United States (US) Food and Drug Administration (FDA) MRTP pathway [ 5 ]. The guidance on MRTP applications [ 6 ] specifies that health outcomes should be assessed during premarket evaluation and postmarket surveillance of modified risk TNPs such as these. These health outcomes comprise not only objective clinical and biological measures but also self-reported outcomes [ 6 , 7 ]. Studies and reports have recently started providing evidence on the health impact of new TNPs [ 8 ]. For instance, recent papers have investigated the effects of e-cigarettes and heated tobacco products on cardiopulmonary outcomes [ 9 , 10 , 11 , 12 , 13 , 14 ]. However, the papers have mainly focused on clinical measurements, such as spirometry and other lung function tests; consumer perception is rarely explored or the focus of the research. Measuring self-reported experience is important for understanding the changes in the health status of individuals switching from cigarettes to RRPs and is a key component of tobacco harm reduction strategies [ 7 ]. Self-reported ratings of RRP effectiveness or adverse events might differ from clinical measures and provide another perspective as useful as the clinicians. In addition, consumer perception of positive changes in health status, functioning and other behavioral outcomes will also subsequently influence use behaviors and switching to RRPs rather than continuing smoking.

Self-perceived health status is a complex concept to define and measure, particularly within the context of TNP use [ 15 ]. While generic health status measures, such as the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), have been used to evaluate the health status of people who smoke [ 16 , 17 ], comparisons have mainly been made between those who currently smoke, those who used to smoke, and those who never smoked [ 18 , 19 ]. Results from these studies strongly suggest that, in healthy populations, existing generic measures are not sensitive enough to detect change over time when stopping or switching from cigarettes to other TNPs, owing to high ceiling effects [ 20 ]. While a few smoking-specific quality of life measures have been developed, these measures have not been widely implemented or standardized [ 15 , 17 , 21 , 22 ], and the application of these smoking-specific measures to different TNP use across the risk continuum is scarce [ 20 ].

As part of the A ssessment of B ehavioral OU tcomes related to T obacco and Nicotine Products (ABOUT™) Toolbox initiative [ 23 ], the present project aims at developing a new self-report measure (ABOUT™— Health and Functioning ) to address the current gap and assess the impact of TNPs on health and functioning (including health status, functional status and other health-related quality of life constructs). This paper presents insights from three research activities [ 24 , 25 ] from the preparatory phase of development of the measure—that is, a scoping literature review, reanalysis of consumer focus groups/interviews, and expert opinion. These three activities serve as background research to support the development of a preliminary conceptual framework of health and functioning associated with the use of TNPs.

Scoping literature review

The purpose of the review was to address two main questions among individuals who use TNPs:

What are the positive and negative health and functioning impacts of TNP use?

What concepts are evaluated by measures used to assess the positive and negative impacts of TNP use?

Given the nature and breadth of the research questions and the number of potentially relevant publications, a scoping literature review was used as it provides a means of identifying the literature and mapping the concepts and evidence on a topic by using an informative and iterative research process [ 26 ]. The scoping review involved a PubMed search (August 2018) and application of Sciome’s rapid Evidence Mapping (rEM) [ 27 ], followed by additional manual screening and review. rEM is a proprietary methodology developed by Sciome ( https://www.sciome.com/ ) to rapidly summarize and produce a quantitative representation of the available body of scientific evidence in a particular area. The study by Lam et al. demonstrated a proof-of-concept application of the rEM methodology [ 27 ]. The PubMed search terms targeted qualitative and quantitative research among people who use TNPs (Table 1 ). This was supplemented by a second, parallel step of manually identifying relevant literature through other known sources. Table 2 describes the general inclusion and exclusion criteria that were applied to the scoping literature review.

After the initial rEM exercise, two reviewers (EC, SG) further manually screened the titles and abstracts of the articles identified through the automated rEM exercise against the inclusion and exclusion criteria. Finally, the selected publications underwent a full screening by two reviewers (VL and DF) for determining their relevance to the research questions for data extraction and one of the co-authors (LA-W) cross-checked the screening and resolved differences in opinion among the reviewers.

The World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) [ 28 ] framework and the revised Wilson and Cleary [ 29 , 30 ] model were used as a guide to broadly inform categories for data extraction from the literature on TNP use and health and functioning. These established models enable the conceptualization and description of health status and functioning (the combination of which is often referred to as health-related quality of life) [ 31 , 32 ], and related outcomes and determinants. To complement and refine this and to ensure relevance to those who use TNPs, the data extracted from the literature was also grouped and labeled based on the contents of the literature reviewed.

The elements extracted from the selected papers were as follows:

Author, citation details, and publication type

Objectives and/or research questions

Sample type, size, and principle demographics

Type(s) of TNP and definitions of levels of consumption

Methodology, questionnaires, and statistical methods used

Main results

Results grouped in broad categories: Health Signs and Symptoms; General Health Perceptions; Quality of Life, Health-Related Quality of Life, and Functional Status; Individual Characteristics; Environmental and Social Characteristics; Biomarkers and Biological Endpoints.

Reanalysis of focus groups/in-depth interviews

The objective of the secondary analyses of existing qualitative data in people who use TNPs was to inform the drafting of the initial conceptual framework, as well as interview guides for planned concept elicitation qualitative studies to identify concepts and develop items to detect what is relevant to measure in this context. Two sets of qualitative data containing information related to health and functioning were reanalyzed and participants had consented for their data to be used in future studies. The first was from 29 focus groups (total number of participants n  = 229) that were originally designed to discuss perceived risk, appeal, and intent to use TNPs [ 33 , 34 ]. The focus groups—stratified by smoking status—were conducted in the United States (US; n  = 12), Japan ( n  = 4), Italy ( n  = 4), and the United Kingdom (UK; n  = 9) between December 2012 and August 2013. The second dataset included 40 in-depth interviews conducted in North Carolina, USA, with people who use TNPs, to discuss issues centered on perceived dependence on TNPs [ 35 ]. While 21 interviewees were people who were poly-TNPs users, 19 were people who were exclusive users of one of the following types of TNPs: cigarettes ( n  = 5), smokeless tobacco ( n  = 5), e-cigarettes ( n  = 5), or another type of TNP (pipes, waterpipes, or nicotine replacement therapy [NRT] products; n  = 4). These interviews were conducted in August 2017. The demographics of both data sets are presented in Table 3 . For reanalyzing the data, an initial codebook guided by the literature review data extraction categories was developed; however, new codes were created to complement these categories based on the thematic content analysis of the transcripts. The qualitative analysis software Quirkos [ 36 ] was used for the reanalysis.

Expert panel review

An expert panel consisting of five key opinion leaders (KOL) and five technical consultants was convened in August 28, 2018, in Neuchâtel, Switzerland. The KOLs were subject matter experts in the fields of nicotine and smoking cessation ( n  = 1), Patients Reported Outcomes (PRO) evaluation and scale development ( n  = 3), and health economics ( n  = 1). The consultants were experts on nicotine dependence ( n  = 1), psychometric validation ( n  = 2), market research ( n  = 1), and PRO development and validation ( n  = 1). The meeting followed an agenda and semi-structured discussion guide to facilitate conversations. First, the panel was presented with the principles underlying the tobacco harm reduction assessment strategy [ 4 ]. This session was followed by an open elicitation phase, during which two experienced moderators asked the panel to identify and discuss concepts related to health and functioning in people who use TNPs that different stakeholders might find important. Then, the panel was asked to review and respond to the concepts identified in the literature review and in the qualitative research reanalysis. These findings were discussed in depth to arrive at a consolidated preliminary conceptual framework. Each concept was presented, and the experts were asked to rank and agree on concepts to be included and how the concepts should be grouped by domains in the framework. In generating the framework, the project team and expert panel considered the themes and concepts identified under each of the categories from the scoping literature review, specific concepts from the secondary analyses of the qualitative data, and the expert panel meeting. The authors then synthesized and re-organized concepts emerging from the different preparatory phase activities under main health and functioning and conceptually-related domains. The participants also provided their input on the best strategies for planned qualitative studies to inform and support the development and validity of the proposed health and functioning measure.

The literature search identified 4761 articles. Figure  1 (flow diagram) depicts the results of the search and screening process. Titles and abstracts were screened by the rEM exercise until the machine learning algorithms predicted 97.7% relevant references; thus, 707 abstracts were not screened. After applying the inclusion/exclusion criteria to the remaining 4,054 abstracts, 281 were identified as part of the rEM exercise. After additional manual screening and review of the abstracts and articles against the inclusion/exclusion criteria, 90 full-text articles were included for data extraction [ 20 , 37 – 125 ]. Seven additional full-text articles were also included on the basis of a manual search [ 126 , 127 , 128 , 129 , 130 , 131 , 132 ]. Findings are summarized in Table 4 and a detailed description and data extracted from all the articles from the literature review is presented in Additional File 1 .

Flow diagram Sciome’s rapid Evidence Mapping (rEM) and manual screening processes of the scoping literature review

Fifty-six publications (56/97; 58%) presented data related to health signs and symptoms . These are grouped under five core areas: mental health and cognitive functioning (28/97; 29%); pain and physical trauma (6/97; 6%); respiratory, cardiovascular and inflammatory conditions (5/97; 5%); “other” health conditions , which included insomnia, liver disease, eye health, and hearing loss (5/97; 5%); and oral health (4/97; 4%). There were also eight publications related to the effects of smoking cessation on health signs and symptoms, mostly benefits of cessation but also including perceived dependence, addiction, and withdrawal symptoms (8/97; 8%). Overall, the burden and impact of cigarette smoking on both physical and mental health symptoms was negative and generally worse among people who smoke relative to those who do not smoke. On the other hand, quitting smoking was accompanied by improvements in general physical health and psychological wellbeing. However, in spite of the positive impact of quitting smoking, loss of moments of pleasure, struggle to manage stress, the social aspects of smoking, and withdrawal symptoms were seen as barriers to quitting.

The general health perceptions of various adults who use TNPs were reported in 18 of the 97 articles (18%), with 9 of them detailing the general health perceptions related to cigarettes and 9 being related to e-cigarettes and other TNPs. Perceptions were determined by questionnaires and focus groups for evaluating the health impacts, fear of diseases, harm to others and self, social impacts (both positive [e.g., inclusion and looking “cool”] and negative [e.g., stigma and exclusion]), and other reasons for taking up or considering/attempting smoking cessation.

Quality of life, health-related quality of life, and functional status was studied in 9 of the 97 included articles (9%). These studies mostly demonstrated with generic and specific QoL, HRQoL, or functional status questionnaires that cigarette smoking was associated with a worse quality of life and that smoking cessation often resulted in an improved quality of life. However, in some cases, the use of TNPs also reportedly enabled individuals to manage their levels of anxiety and improve some aspects of social engagement and functional status.

Individual, environmental and social characteristics were found to influence the decision to smoke and/or consider or attempt to quit smoking or switching to other TNPs, as reported in 8 (8%) and 11 (11%) of 97 publications, respectively. Some key characteristics and determinants of smoking behavior included low socioeconomic status, male sex, living alone, family, and close social environment, societal stigma, and local regulations.

Finally, 12 of the 97 publications (12%) were related to studies on biomarkers and biological endpoints in people who use TNPs and showed that smoking cigarettes negatively influenced cardiovascular, respiratory, oral, renal, stress, metabolic, and inflammatory-related biomarkers and physiological assessments.

The themes from this reanalysis are summarized below and organized on the basis of the narrative of the participants of their experiences.

Perceived negative impact of smoking

Other than health, the biggest and most salient reported negative impact of smoking was the perceived lack of control related to addiction and emotional health and wellbeing. Participants reported feeling that cigarette smoking was running their lives or “holding them hostage.” They reported that this perceived lack of a sense of control or willpower often led to feelings of weakness or a feeling that they were a “slave” to cigarettes. Many respondents reported smoking even when they did not necessarily want to and experiencing feelings of obsession and craving.

Perceived lack of control and addiction were also related to the activities of the participants throughout the day. People who smoke often reported altering their activities to smoke because of patterns of behavior or routine and the experienced need for a smoke. They reported that the “need for a smoke” sensation would cause them to leave work or social events early, not attend events if smoking was not allowed, interrupt what they were doing to smoke, and get up in the middle of the night.

Fear of withdrawal symptoms, with a strong emphasis on mental/emotional health, was also prominent among reported negative impacts of smoking. This fear was often reported as limiting the willingness of individuals to try to quit smoking or facilitating a return to prior smoking behavior. Individuals reported fearing the following symptoms they associated with withdrawal: mood swings and irritability, violent or aggressive behavior, inability to concentrate, anxiety, anger, and weight gain.

Perceived benefits of smoking

Several perceived benefits were identified that keep individuals smoking or using cigarettes. These included perceptions of enhanced cognitive functioning, relaxation, a way to take a break, use as a coping strategy, a social function, a weight management tool, the perception that it feels good, and being part of one’s identity. It is also important to note that the perceived benefits of smoking often outweighed the risks and the feeling of lack of control in the participant discussions. Even people who used to smoke noted they missed the relaxation and breaks they associated with smoking.

Recognition of symptoms/diseases related to smoking

Table 5 summarizes the negative symptoms and diseases related to smoking recognized by participants in both the focus groups and interviews. These were mostly related to six main body systems (cardiovascular, digestive, oral, neurological, reproductive, and respiratory).

Impacts on physical functioning

The participants noted how smoking impacts their physical functioning. In particular, they noted how their exercise capacity during running, playing sports, walking upstairs, and general physical activity was diminished. They also reported reduced stamina and endurance, decreased physical strength, and feeling tired more easily.

Effects on emotional health

The participants also described how smoking impacts their emotional health and wellbeing. People who smoke reported feelings of shame, guilt, weakness, and a lack of control or powerlessness. They also reported feelings of depression and anxiety associated with worry about health risks. Furthermore, the participants indicated that they experienced a fear of going to places where they could not smoke, being a bad role model for their children, and (in case of people who used to smoke) going back to smoking.

Positive and negative social impacts

Smoking was perceived to have both negative and positive impacts on the social lives of participants. Smoking impacted life negatively when it was not allowed in certain environments, such as in homes, at work, and in cars and airplanes. Stigma was also associated with smoking in an environment where peers and family members do not smoke, but it was also seen as a source of group identity within social networks that had a higher prevalence of smoking behaviors. Participants reported that smoking had some positive impacts on their social interaction, because it facilitated work breaks and increased communication with peers.

Reasons people decided to try to quit

Throughout the focus groups and interviews, individuals identified several reasons why they tried to quit smoking. These included: health, diagnosis of cancer (self, family, or friend), gum disease, pregnancy, hospital stay, worry that it will “kill me,” dislike of taste or odor, social reasons, change in surroundings (fewer smoking spaces), and price.

Reasons people do not like alternatives to cigarettes

The participants’ reasons for not liking alternatives to cigarettes (i.e., less harmful TNPs/RRPs) included perceptions that the alternatives did not work (i.e., the participants still had cravings and experienced withdrawal symptoms), made them feel or get ill (nausea and vomiting), were not “the same” as cigarettes in terms of the ritual, taste, or “feeling,” or were inconvenient/too big to carry.

The conclusions of the expert panel widely supported the findings of the literature review and the input from the reanalyzed focus groups and interviews. Some of the experts working in field of tobacco and nicotine provided additional insights based on their extensive experience with people who use TNPs; they highlighted the importance of the enjoyment of smoking for people who find it difficult to quit, the positive immediate benefits of quitting, and the smoking-related biomarkers that might be on a causal pathway between switching and changes in health and functioning status.

The following main areas were discussed and agreed during the meeting: (1) utility of use, referring to the perceived satisfaction and enjoyment of smoking (e.g., craving relief, weight control, and social affiliation); (2) signs and symptoms of withdrawal (e.g., anxiety, depression, and anger) and the positive immediate physical health effects of quitting smoking (e.g., better general and oral hygiene, less coughing, and improved exercise capacity); (3) functioning, including cognitive, physical, sexual, social, emotional, and role functioning; (4) worry associated with smoking and smoking-related diseases; (5) general health perceptions and quality of life; (6) association with smoking-related biomarkers that could be on the causal pathway between switching and changes in health and functioning; and (7) TNP use patterns and maintenance of switching to RRPs.

Generation of the preliminary conceptual framework

Triangulation of the findings from the literature review, qualitative input from people who use TNPs, and expert panel feedback helped generate a preliminary descriptive conceptual framework that includes the health and functioning and conceptually-related domains impacted by TNP use (Fig.  2 ).

Health and functioning conceptual framework related to tobacco and/or nicotine product use from the preparatory phase research findings

Four domains related to the future health and functioning measurement model for TNP use are indicated in grey rectangular boxes and include (moving down from proximal to distal parameters) physical health symptoms (e.g., oral and respiratory symptoms), general physical condition (e.g., appearance and hygiene), functioning (physical, sexual, cognitive, emotional, and social functioning), and general health perceptions, which will be the most distal measure of health and functioning. The preparatory phase research also identified six conceptually-related domains (in dashed rectangular boxes), which are not direct indicators of health status but might influence the impact of TNP use on health and functioning. These include attitudinal variables (worry about the health risks of using TNPs and perceived dependence/fear of withdrawal symptoms associated with quitting smoking), and utilitarian ones (perceived appeal, satisfaction, and benefits of TNP use). In addition, personal factors (e.g., sociodemographic) and environmental factors (e.g., peer/family influence, policies and regulations and sociocultural context) are also reflected in the conceptual framework as indirect indicators of health and functioning.

The framework further indicates that specific behavioral indicators (i.e., TNP use patterns over time) might influence any impact of TNP use on health and functioning. Whilst other causal and reciprocal relationships and hierarchies might exist within the domains, these are not explicitly characterized in this initial draft of the framework and will have to be tested with further empirical data. Finally, identified biomarkers of potential harm (in italics and dashed box) are also integrated in this conceptual framework as part of the conceptually-related domains, because they are on a causal pathway between TNP use and changes in health and functioning [ 133 , 134 ]. Biomarkers are not part of the measurement model that will be considered for a new self-report measure; however, because they are the most proximal parameters to health and functioning, they will be assessed independently as appropriate endpoints by objective clinical or biological analyses.

Triangulation of published literature, reanalysis of qualitative data, and expert opinion helped develop the presented preliminary conceptual framework as the foundation for a new measure to assess the impact of TNPs on self-reported health and functioning. This is essential for identifying relevant concepts and understanding what is important to measure in people who use TNPs. The findings reveal the importance of not only the perceived impacts of TNP use on physical health and physical functioning, but also on aspects of mental health and social interactions and functioning, and general perceptions of health and health-related quality of life.

For the literature review, the WHO ICF [ 28 ] and Wilson and Cleary model [ 29 , 30 ] served as useful guides to develop categories for data abstraction. The scoping literature review yielded 97 articles on TNP use and the relationship to health, perceptions of health, social and individual functioning, and quality of life. Overall, most studies had focused on the known negative effects of cigarette smoking (e.g., mental, respiratory, and oral health) and the rationale and motivation to quit smoking. The WHO ICF and Wilson and Clearly models were not always sufficient for identifying the breadth of relevant concepts, especially from the perspective of TNP use. Development of new codes for the reanalysis of existing qualitative data allowed for the development, extension, and exploration of the topic and provided valuable insights reported in the qualitative data reanalysis, such as the perceived benefits/satisfaction from cigarette smoking, and the rationale for quitting smoking or switching to an RRP. The findings show how this manner of secondary analysis can be valuable in health-related fields where the topic is broad and an existing body of knowledge can contribute by offering a different perspective [ 135 ].

The presentation of the preliminary conceptual framework from this preparatory phase is specific to TNP use and marks a slight departure from the established norms and characterization of the variables typically observed in existing generic health and functioning and health-related quality of life models, such as the WHO ICF and Wilson and Clearly models. Notably, specific hypothesized relationships and the hierarchy between domains are not explicitly characterized in the current draft of the framework. The framework provided an exploratory representation of the current findings to reflect a measurement instrument in people who use TNPs that would ideally be able to assess and demonstrate improvements in self-reported health and functioning status, stability of perceived positive aspects of using TNPs, and no worsening in key areas of physical and emotional health and functioning upon switching to RRPs. Nevertheless, the framework could still undergo further refinement to support the development and validation of a new measure and to further characterize and test the relationships and hierarchies between domains.

This work is not without limitations. For the scoping literature review, among the reviewed articles, not many reported on the use of e-cigarettes and other alternative tobacco or nicotine-delivery devices, because most studies had focused exclusively on cigarettes. It is possible that concepts associated with health and functioning that are relevant to other TNPs were not identified. This is most likely the consequence of the large number of publications related to cigarette use. Some concepts might also have been missed, given the large evidence base on health and functioning-related themes and concepts. However, this was also not a systematic literature search; a scoping review is generally broader than a systematic review in terms of the former having a less-defined research question, broader inclusion and exclusion criteria, and no systematic appraisal of study quality [ 26 ]. Nevertheless, the present scoping review methodology provides a lens on the overall evidence base, and regular updates on the search—specifically related to RRPs and novel TNPs and their health and functioning impacts—could be considered for fully understanding the evolving state of the art in this context. The reanalysis of existing qualitative data also has limitations related to data fit and completeness of preexisting data [ 136 ]. The insights collected from these reanalyzed studies were originally for a different purpose several years prior to the present research, and this might not completely and accurately reflect the objectives of the new project.

Considering the findings of the current research, the development of a health and functioning measure can continue to follow the FDA’s Guidance on PRO measures. As specified within the guideline, gaining input directly from the intended use populations through concept elicitation is a critical activity for ensuring content validity during the development of any new self-reported measure [ 137 ]. Continuous engagement with an expert panel can also support the refinement of the conceptual framework as well as the development of the draft and final measure.

The goal of this research was to identify from varied research activities key concepts and aspects of health and functioning and related changes associated with the use of TNPs. The resulting preliminary conceptual framework provides the basis for informing future research to further understand health and functioning concepts important to measure in individual who switch to RRPs and to develop a new self-report measure to assess this from the consumers’ perspective.

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Abbreviations

Assessment of Behavioral OUtcomes related to Tobacco and Nicotine Products Toolbox

Chronic obstructive pulmonary disease

Food and Drug Administration

Health-related quality of life

International Classification of Functioning, Disability and Health

• Modified risk tobacco products

Nicotine replacement therapy

Patient-Reported Outcomes

Quality of life

Reduced-risk products

Rapid Evidence Mapping

• Tobacco and/or nicotine products

United Kingdom

United States

36-Item Short-Form Health Survey

World Health Organization

U.S. Department of Health and Human Services. The health consequences of smoking: 50 years of progress. A report of the surgeon general. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.

Google Scholar  

Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJL, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;6(4):e1000058.

Article   PubMed   PubMed Central   Google Scholar  

Bilano V, Gilmour S, Moffiet T, d’Espaignet ET, Stevens GA, Commar A, et al. Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet. 2015;385(9972):966–76.

Article   PubMed   Google Scholar  

Zeller M, Hatsukami D. The strategic dialogue on tobacco harm reduction: a vision and blueprint for action in the US. Tob Control. 2009;18(4):324–32.

Food and Drug Administration. Modified risk orders 2020. https://www.fda.gov/tobacco-products/advertising-and-promotion/modified-risk-orders .

Food and Drug Administration. Modified risk tobacco product applications: draft guidance for industry 2012. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/modified-risk-tobacco-product-applications .

Institute of Medicine. Scientific standards for studies on modified risk tobacco products. Washington, DC: The National Academies Press; 2012. p. 370.

Stratton K, Kwan LY, Eaton DL, editors. National Academies of Sciences Engineering and Medicine. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press; 2018. p. 774.

Lappas AS, Tzortzi AS, Konstantinidi EM, Teloniatis SI, Tzavara CK, Gennimata SA, et al. Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma. Respirology. 2018;23(3):291–7.

Meo SA, Ansary MA, Barayan FR, Almusallam AS, Almehaid AM, Alarifi NS, et al. Electronic cigarettes: impact on lung function and fractional exhaled nitric oxide among healthy adults. Am J Men’s Health. 2019;13(1):1557988318806073.

Article   Google Scholar  

Polosa R, Cibella F, Caponnetto P, Maglia M, Prosperini U, Russo C, et al. Health impact of E-cigarettes: a prospective 3.5-year study of regular daily users who have never smoked. Sci Rep. 2017;7(1):13825.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Sharman A, Zhussupov B, Sharman D, Kim I, Yerenchina E. Lung function in users of a smoke-free electronic device with HeatSticks (iQOS) versus smokers of conventional cigarettes: protocol for a longitudinal cohort observational study. JMIR Res Protoc. 2018;7(11):e10006.

Skotsimara G, Antonopoulos AS, Oikonomou E, Siasos G, Ioakeimidis N, Tsalamandris S, et al. Cardiovascular effects of electronic cigarettes: a systematic review and meta-analysis. Eur J Prev Cardiol. 2019;26(11):1219–28.

Wang JB, Olgin JE, Nah G, Vittinghoff E, Cataldo JK, Pletcher MJ, et al. Cigarette and e-cigarette dual use and risk of cardiopulmonary symptoms in the Health eHeart Study. PLoS ONE. 2018;13(7):e0198681.

Ware JE Jr, Gandek B, Kulasekaran A, Guyer R. Evaluation of smoking-specific and generic quality of life measures in current and former smokers in Germany and the United States. Health Qual Life Outcomes. 2015;13:128.

Frendl DM, Ware JE Jr. Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey. Med Care. 2014;52(5):439–45.

Goldenberg M, Danovitch I, IsHak WW. Quality of life and smoking. Am J Addict. 2014;23(6):540–62.

Olufade AO, Shaw JW, Foster SA, Leischow SJ, Hays RD, Coons SJ. Development of the smoking cessation quality of life questionnaire. Clin Ther. 1999;21(12):2113–30.

Article   CAS   PubMed   Google Scholar  

Sarna L, Bialous SA, Cooley ME, Jun HJ, Feskanich D. Impact of smoking and smoking cessation on health-related quality of life in women in the Nurses’ Health Study. Qual Life Res. 2008;17(10):1217–27.

Kulasekaran A, Proctor C, Papadopoulou E, Shepperd CJ, Guyer R, Gandek B, et al. Preliminary evaluation of a new german translated tobacco quality of life impact tool to discriminate between healthy current and former smokers and to explore the effect of switching smokers to a reduced toxicant prototype cigarette. Nicotine Tob Res. 2015;17(12):1456–64.

Edelen MO. The PROMIS smoking assessment toolkit–background and introduction to supplement. Nicotine Tob Res. 2014;16(Suppl 3):S170–4.

Shaw JW, Coons SJ, Foster SA, Leischow SJ, Hays RD. Responsiveness of the Smoking Cessation Quality of Life (SCQoL) questionnaire. Clin Ther. 2001;23(6):957–69.

Chrea C, Acquadro C, Afolalu EF, Spies E, Salzberger T, Abetz-Webb L, et al. Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUT Toolbox initiative. F1000Res. 2018;7:1878.

Food and Drug Administration. Patient-reported outcome measures: use in medical product development to support labeling claims 2009. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims .

Food and Drug Administration. Patient-focused drug development: methods to identify what is important to patients guidance for industry, Food and Drug Administration Staff, and Other Stakeholders 2019. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-methods-identify-what-important-patients-guidance-industry-food-and .

Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018;18(1):143.

Lam J, Howard BE, Thayer K, Shah RR. Low-calorie sweeteners and health outcomes: a demonstration of rapid evidence mapping (rEM). Environ Int. 2019;123:451–8.

World Health Organisation. International classification of functioning, disability and health (ICF) 2001. https://www.who.int/classifications/icf/en/ .

Ferrans CE, Zerwic JJ, Wilbur JE, Larson JL. Conceptual model of health-related quality of life. J Nurs Scholarsh. 2005;37(4):336–42.

Wilson IB, Cleary PD. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA. 1995;273(1):59–65.

Karimi M, Brazier J. Health, health-related quality of life, and quality of life: what is the difference? Pharmacoeconomics. 2016;34(7):645–9.

Moons P. Why call it health-related quality of life when you mean perceived health status? Eur J Cardiovasc Nurs. 2004;3(4):275–7.

Cano S, Chrea C, Salzberger T, Alfieri T, Emilien G, Mainy N, et al. Development and validation of a new instrument to measure perceived risks associated with the use of tobacco and nicotine-containing products. Health Qual Life Outcomes. 2018;16(1):192.

Salzberger T, Chrea C, Cano SJ, Martin M, Atkison M, Emilien G, et al. Perceived risks associated with the use of tobacco and nicotine-containing products: findings from qualitative research. Tobacco Sci Technol. 2017;50:32–42.

Chrea C, Salzberger T, Abetz-Webb L, Afolalu EF, Cano S, Rose J, et al. PRM183—development of a fit-for-purpose tobacco and nicotine products dependence instrument. Barcelona: ISPOR Europe; 2018.

Book   Google Scholar  

Quirkos 2.3.1 [Computer Software] 2020. https://www.quirkos.com .

Abu-Helalah MA, Alshraideh HA, Al-Serhan AA, Nesheiwat AI, Da’na M, Al-Nawafleh A. Epidemiology, attitudes and perceptions toward cigarettes and hookah smoking amongst adults in Jordan. Environ Health Prev Med. 2015;20(6):422–33.

Akturk E, Yağmur J, Açıkgöz N, Ermi N, Cansel M, Karaku Y, et al. Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in smokers. J Interv Card Electrophysiol. 2012;34(2):247–53.

Aubin HJ, Peiffer G, Stoebner-Delbarre A, Vicaut E, Jeanpetit Y, Solesse A, et al. The French Observational Cohort of Usual Smokers (FOCUS) cohort: French smokers perceptions and attitudes towards smoking cessation. BMC Public Health. 2010;10(100):1–8.

Becoña E, Vázquez MI, Míguez MC, Fernández del Río E, López-Durán A, Martínez Ú, et al. Smoking habit profile and health-related quality of life. Psicothema. 2013;25(4):421–6.

PubMed   Google Scholar  

Bennasar Veny M, Pericas Beltrán J, González Torrente S, Segui González P, Aguiló Pons A, Tauler RP. Self-perceived factors associated with smoking cessation among primary health care nurses: a qualitative study. Rev Latino-Am Enfermagem. 2011;19(6):1437–44.

Bommelé J, Schoenmakers TM, Kleinjan M, van Straaten B, Wits E, Snelleman M, et al. Perceived pros and cons of smoking and quitting in hard-core smokers: a focus group study. BMC Public Health. 2014;14:175–85.

Borland R, Yong HH, O’Connor RJ, Hyland A, Thompson ME. The reliability and predictive validity of the Heaviness of Smoking Index and its two components: findings from the International Tobacco Control Four Country study. Nicotine Tob Res. 2010;12(Suppl 1):S45-50.

Bot M, Vink J, Milaneschi Y, Smit JH, Kluft C, Neuteboom J, et al. Plasma cotinine levels in cigarette smokers: impact of mental health and other correlates. Eur Addict Res. 2014;20(4):183–91.

Brody AL, Olmstead RE, Abrams AL, Costello MR, Khan A, Kozman D, et al. Effect of a history of major depressive disorder on smoking-induced dopamine release. Biol Psychiatry. 2009;66(9):898–901.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Brook DW, Rubenstone E, Zhang C, Brook JS. Trajectories of cigarette smoking in adulthood predict insomnia among women in late mid-life. Sleep Med. 2012;13(9):1130–7.

Brotman RM, He X, Gajer P, Fadrosh D, Sharma E, Mongodin EF, et al. Association between cigarette smoking and the vaginal microbiota: a pilot study. BMC Infect Dis. 2014;14:471–82.

Brown-Johnson CG, Cataldo JK, Orozco N, Lisha NE, Hickman NJ 3rd, Prochaska JJ. Validity and reliability of the Internalized Stigma of Smoking Inventory: an exploration of shame, isolation, and discrimination in smokers with mental health diagnoses. Am J Addict. 2015;24(5):410–8.

Bush T, Hsu C, Levine MD, Magnusson B, Miles L. Weight gain and smoking: perceptions and experiences of obese quitline participants. BMC Public Health. 2014;14:1229.

Caldirola D, Cavedini P, Riva A, Di Chiaro NV, Perna G. Cigarette smoking has no pro-cognitive effect in subjects with obsessive-compulsive disorder: a preliminary study. Psychiatr Danub. 2016;28(1):86–90.

Caldirola D, Daccò S, Grassi M, Citterio A, Menotti R, Cavedini P, et al. Effects of cigarette smoking on neuropsychological performance in mood disorders: a comparison between smoking and nonsmoking inpatients. J Clin Psychiatry. 2013;74(2):e130–6.

Carpenter MJ, Gray KM. A pilot randomized study of smokeless tobacco use among smokers not interested in quitting: changes in smoking behavior and readiness to quit. Nicotine Tob Res. 2010;12(2):136–43.

Croucher R, Haque MF, Kassim S. Oral pain before and after smokeless tobacco cessation in U.K.-resident Bangladeshi women: cross-sectional analyses. Nicotine Tobacco Res. 2013;15(5):896–903.

Article   CAS   Google Scholar  

Depp CA, Bowie CR, Mausbach BT, Wolyniec P, Thornquist MH, Luke JR, et al. Current smoking is associated with worse cognitive and adaptive functioning in serious mental illness. Acta Psychiatr Scand. 2015;131(5):333–41.

Ditre JW, Zale EL, Heckman BW, Hendricks PS. A measure of perceived pain and tobacco smoking interrelations: pilot validation of the pain and smoking inventory. Cogn Behav Ther. 2017;46(6):339–51.

Doiron M, Dupré N, Langlois M, Provencher P, Simard M. Smoking history is associated to cognitive impairment in Parkinson’s disease. Aging Ment Health. 2017;21(3):322–6.

Gonzalez A, Zvolensky MJ, Vujanovic AA, Leyro TM, Marshall EC. An evaluation of anxiety sensitivity, emotional dysregulation, and negative affectivity among daily cigarette smokers: relation to smoking motives and barriers to quitting. J Psychiatr Res. 2008;43(2):138–47.

Grogan S, Fry G, Gough B, Conner M. Smoking to stay thin or giving up to save face? Young men and women talk about appearance concerns and smoking. Br J Health Psychol. 2009;14(1):175–86.

Hawari FI, Obeidat NA, Ghonimat IM, Ayub HS, Dawahreh SS. The effect of habitual waterpipe tobacco smoking on pulmonary function and exercise capacity in young healthy males: A pilot study. Respir Med. 2017;122:71–5.

Heffernan TM, O’Neill TS, Moss M. Smoking-related prospective memory deficits in a real-world task. Drug Alcohol Depend. 2012;120(1–3):1–6.

Highland KB, McChargue DE. Stress-induced cardiovascular reactivity among African American smokers. Am J Health Behav. 2011;35(1):51–9.

Holley AL, Law EF, Tham SW, Myaing M, Noonan C, Strachan E, et al. Current smoking as a predictor of chronic musculoskeletal pain in young adult twins. J Pain. 2013;14(10):1131–9.

Ichikawa Y, Kitagawa K, Kato S, Dohi K, Hirano T, Ito M, et al. Altered coronary endothelial function in young smokers detected by magnetic resonance assessment of myocardial blood flow during the cold pressor test. Int J Cardiovasc Imaging. 2014;30:73–80.

Javed F, Abduljabbar T, Vohra F, Malmstrom H, Rahman I, Romanos GE. Comparison of periodontal parameters and self-perceived oral symptoms among cigarette smokers, individuals vaping electronic cigarettes, and never-smokers. J Periodontol. 2017;88(10):1059–65.

Johnson AL, McLeish AC. Differences in panic psychopathology between smokers with and without asthma. Psychol Health Med. 2017;22(1):110–20.

Kahler CW, Daughters SB, Leventhal AM, Rogers ML, Clark MA, Colby SM, et al. Personality, psychiatric disorders, and smoking in middle-aged adults. Nicotine Tob Res. 2009;11(7):833–41.

Karadoğan D, Önal Ö, Şahin D, Yazıcı S, Kanbay Y. Evaluation of school teachers’ sociodemographic characteristics and quality of life according to their cigarette smoking status: a cross-sectional study from eastern Black Sea region of Turkey. Tuberkuloz ve toraks. 2017;65(1):18–24.

Kim J, Gall SL, Dewey HM, Macdonell RA, Sturm JW, Thrift AG. Baseline smoking status and the long-term risk of death or nonfatal vascular event in people with stroke: a 10-year survival analysis. Stroke. 2012;43(12):3173–8.

Kim J, Lee S. Using focus group interviews to analyze the behavior of users of new types of tobacco products. J Prev Med Public Health. 2017;50(5):336–46.

Kralikova E, Novak J, West O, Kmetova A, Hajek P. Do e-cigarettes have the potential to compete with conventional cigarettes?: a survey of conventional cigarette smokers’ experiences with e-cigarettes. Chest. 2013;144(5):1609–14.

Lao XQ, Jiang CQ, Zhang WS, Adab P, Lam TH, Cheng KK, et al. Smoking, smoking cessation and inflammatory markers in older Chinese men: The Guangzhou Biobank Cohort Study. Atherosclerosis. 2009;203(1):304–10.

Lappan S, Thorne CB, Long D, Hendricks PS. Longitudinal and reciprocal relationships between psychological well-being and smoking. Nicotine Tob Res. 2018;22(1):18–23.

Article   PubMed Central   Google Scholar  

Lynch ME, Johnson KC, Kable JA, Carroll J, Coles CD. Smoking in pregnancy and parenting stress: maternal psychological symptoms and socioeconomic status as potential mediating variables. Nicotine Tob Res. 2011;13(7):532–9.

Lyvers M, Carlopio C, Honours VB, Edwards MS. Mood, mood regulation, and frontal systems functioning in current smokers, long-term abstinent ex-smokers, and never-smokers. J Psychoactive Drugs. 2014;46(2):133–9.

Martin LM, Sayette MA. A review of the effects of nicotine on social functioning. Exp Clin Psychopharmacol. 2018;26(5):425–39.

Martinasek MP, McDermott RJ, Bryant CA. Antecedents of university students’ hookah smoking intention. Am J Health Behav. 2013;37(5):599–609.

Mattey DL, Dawson SR, Healey EL, Packham JC. Relationship between smoking and patient-reported measures of disease outcome in ankylosing spondylitis. J Rheumatol. 2011;38(12):2608–15.

McCann SJ. Subjective well-being, personality, demographic variables, and American state differences in smoking prevalence. Nicotine Tob Res. 2010;12(9):895–904.

McDonald EA, Ling PM. One of several “toys” for smoking: young adult experiences with electronic cigarettes in New York City. Tob Control. 2015;24(6):588–93.

McLeish AC, Zvolensky MJ, Del Ben KS, Burke RS. Anxiety sensitivity as a moderator of the association between smoking rate and panic-relevant symptoms among a community sample of middle-aged adult daily smokers. Am J Addict. 2009;18(1):93–9.

Melis M, Lobo SL, Ceneviz C, Ruparelia UN, Zawawi KH, Chandwani BP, et al. Effect of cigarette smoking on pain intensity of TMD patients: a pilot study. Cranio. 2010;28(3):187–92.

Memon A, Barber J, Rumsby E, Parker S, Mohebati L, de Visser RO, et al. What factors are important in smoking cessation and relapse in women from deprived communities? A qualitative study in Southeast England. Public Health. 2016;134:39–45.

Mendiondo MS, Alexander LA, Crawford T. Health profile differences for menthol and non-menthol smokers: findings from the National Health Interview Survey. Addiction. 2010;105(Suppl 1):124–40.

Miyatake N, Numata T, Nishii K, Sakano N, Suzue T, Hirao T, et al. Influence of cigarette smoking on estimated glomerular filtration rate (eGFR) in Japanese male workers. Acta Med Okayama. 2010;64:385–90.

CAS   PubMed   Google Scholar  

Mohammadi S, Mazhari MM, Mehrparvar AH, Attarchi MS. Cigarette smoking and occupational noise-induced hearing loss. Eur J Public Health. 2009;20(4):452–5.

Mohammadnezhad M, Tsourtos G, Wilson C, Ratcliffe J, Ward P. “I have never experienced any problem with my health. So far, it hasn’t been harmful”: older Greek-Australian smokers’ views on smoking: a qualitative study. BMC Public Health. 2015;15:304–15.

Morris MC, Mielock AS, Rao U. Salivary stress biomarkers of recent nicotine use and dependence. Am J Drug Alcohol Abuse. 2016;42(6):640–8.

Muir S, Marshall B. Changes in health perceptions of male prisoners following a smoking cessation program. J Correct Health Care. 2016;22(3):247–56.

Nelson JP, Pederson LL, Lewis J. Tobacco use in the Army: illuminating patterns, practices, and options for treatment. Mil Med. 2009;174(2):162–9.

Nemeth JM, Liu ST, Klein EG, Ferketich AK, Kwan MP, Wewers ME. Factors influencing smokeless tobacco use in rural Ohio Appalachia. J Community Health. 2012;37(6):1208–17.

Nikcevic AV, Spada MM. Metacognitions about smoking: a preliminary investigation. Clin Psychol Psychother. 2010;17(6):536–42.

Nunes SO, Vargas HO, Brum J, Prado E, Vargas MM, de Castro MR, et al. A comparison of inflammatory markers in depressed and nondepressed smokers. Nord J Psychiatry. 2012;14:540–6.

CAS   Google Scholar  

Oh DL, Heck JE, Dresler C, Allwright S, Haglund M, Del Mazo SS, et al. Determinants of smoking initiation among women in five European countries: a cross-sectional survey. BMC Public Health. 2010;10(74):1–11.

Pasco JA, Williams LJ, Jacka FN, Ng F, Henry MJ, Nicholson GC, et al. Tobacco smoking as a risk factor for major depressive disorder: population-based study. Br J Psychiatry. 2008;193(4):322–6.

Pina JA, Namba MD, Leyrer-Jackson JM, Cabrera-Brown G, Gipson CD. Social influences on nicotine-related behaviors. Int Rev Neurobiol. 2018;140:1–32.

Poole-Di Salvo E, Liu YH, Brenner S, Weitzman M. Adult household smoking is associated with increased child emotional and behavioral problems. J Dev Behav Pediatr. 2010;31(2):107–15.

Rahman MA, Mahmood MA, Spurrier N, Rahman M, Choudhury SR, Leeder S. Why do Bangladeshi people use smokeless tobacco products? Asia-Pacific J Public Health. 2015;27(2):NP2197–209.

Rollini F, Franchi F, Cho JR, Degroat C, Bhatti M, Ferrante E, et al. Cigarette smoking and antiplatelet effects of aspirin monotherapy versus clopidogrel monotherapy in patients with atherosclerotic disease: results of a prospective pharmacodynamic study. J Cardiovasc Transl Res. 2014;7(1):53–63.

Romijnders K, van Osch L, de Vries H, Talhout R. Perceptions and reasons regarding e-cigarette use among users and non-users: a narrative literature review. Int J Environ Res Public Health. 2018;15(6):1190.

Rooke C, Cunningham-Burley S, Amos A. Smokers’ and ex-smokers’ understanding of electronic cigarettes: a qualitative study. Tob Control. 2016;25:e60–6.

Roth B, Bengtsson M, Ohlsson B. Diarrhoea is not the only symptom that needs to be treated in patients with microscopic colitis. Eur J Intern Med. 2013;24(6):573–8.

Sales MP, Oliveira MI, Mattos IM, Viana CM, Pereira ED. The impact of smoking cessation on patient quality of life. J Bras Pneumol. 2009;35(5):436–41.

Schane RE, Prochaska JJ, Glantz SA. Counseling nondaily smokers about secondhand smoke as a cessation message: a pilot randomized trial. Nicotine Tob Res. 2013;15(2):334–42.

Schnoll RA, Goren A, Annunziata K, Suaya JA. The prevalence, predictors and associated health outcomes of high nicotine dependence using three measures among US smokers. Addiction. 2013;108(11):1989–2000.

Segarra R, Zabala A, Eguíluz JI, Ojeda N, Elizagarate E, Sánchez P, et al. Cognitive performance and smoking in first-episode psychosis: the self-medication hypothesis. Eur Arch Psychiatry Clin Neurosci. 2011;261(4):241–50.

Sherratt FC, Newson L, Marcus MW, Field JK, Robinson J. Perceptions towards electronic cigarettes for smoking cessation among Stop Smoking Service users. Br J Health Psychol. 2015;21(2):421–33.

Soneji SS, Sung HY, Primack BA, Pierce JP, Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS ONE. 2018;13(3):e0193328.

Talati A, Wickramaratne PJ, Keyes KM, Hasin DS, Levin FR, Weissman MM. Smoking and psychopathology increasingly associated in recent birth cohorts. Drug Alcohol Depend. 2013;133(2):724–32.

Tan QH. Smoking spaces as enabling spaces of wellbeing. Health Place. 2013;24:173–82.

Tatullo M, Gentile S, Paduano F, Santacroce L, Marrelli M. Crosstalk between oral and general health status in e-smokers. Medicine. 2016;95(49):e5589.

Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ. 2014;348:g1151-g.

Thompson TP, Greaves CJ, Ayres R, Aveyard P, Warren FC, Byng R, et al. An exploratory analysis of the smoking and physical activity outcomes from a pilot randomized controlled trial of an exercise assisted reduction to stop smoking intervention in disadvantaged groups. Nicotine Tob Res. 2016;18(3):289–97.

Torigian DA, Green-McKenzie J, Liu X, Shofer FS, Werner T, Smith CE, et al. A study of the feasibility of FDG-PET/CT to systematically detect and quantify differential metabolic effects of chronic tobacco use in organs of the whole body—a prospective pilot study. Acad Radiol. 2017;24:930–40.

Ulvik A, Ebbing M, Hustad S, Midttun Ø, Nygård O, Vollset SE, et al. Long- and short-term effects of tobacco smoking on circulating concentrations of B vitamins. Clin Chem. 2010;56(5):755–63.

Vidrine JI, Businelle MS, Cinciripini P, Li Y, Marcus MT, Waters AJ, et al. Associations of mindfulness with nicotine dependence, withdrawal, and agency. Subst Abus. 2009;30(4):318–27.

Volkman JE, DeRycke EC, Driscoll MA, Becker WC, Brandt CA, Mattocks KM, et al. Smoking status and pain intensity among OEF/OIF/OND veterans. Pain Med. 2015;16(9):1690–6.

Vujanovic AA, Marshall-Berenz EC, Beckham JC, Bernstein A, Zvolensky MJ. Posttraumatic stress symptoms and cigarette deprivation in the prediction of anxious responding among trauma-exposed smokers: a laboratory test. Nicotine Tob Res. 2010;12(11):1080–8.

Wadsworth E, Neale J, McNeill A, Hitchman SC. How and why do smokers start using e-cigarettes? Qualitative study of Vapers in London, UK. Int J Environ Res Public Health. 2016;13(7):661–74.

Article   PubMed Central   CAS   Google Scholar  

Xie X, Dijkstra AE, Vonk JM, Oudkerk M, Vliegenthart R, Groen HJ. Chronic respiratory symptoms associated with airway wall thickening measured by thin-slice low-dose CT. Am J Roentgenol. 2014;203(4):W383–90.

Yang T, Shiffman S, Rockett IR, Cui X, Cao R. Nicotine dependence among Chinese city dwellers: a population-based cross-sectional study. Nicotine Tob Res. 2011;13(7):556–64.

Yu A, Cai X, Zhang Z, Shi H, Liu D, Zhang P, et al. Effect of nicotine dependence on opioid requirements of patients after thoracic surgery. Acta Anaesthesiol Scand. 2015;59(1):115–22.

Zhang X, Kahende J, Fan AZ, Barker L, Thompson TJ, Mokdad AH, et al. Smoking and visual impairment among older adults with age-related eye diseases. Prev Chronic Dis. 2011;8(4):A84.

PubMed   PubMed Central   Google Scholar  

Zhao L, Xu L, Lai Y, Che C, Zhou Y. Temporal changes of smoking status and motivation in Chinese patients with hepatitis B: relationship with anxiety and depression. J Clin Nurs. 2012;21(15–16):2193–201.

Zorlu N, Cropley VL, Zorlu PK, Delibas DH, Adibelli ZH, Baskin EP, et al. Effects of cigarette smoking on cortical thickness in major depressive disorder. J Psychiatr Res. 2017;84:1–8.

Miyatake N, Numata T, Nishii K, Sakano N, Suzue T, Hirao T, et al. Relation between cigarette smoking and ventilatory threshold in the Japanese. Environ Health Prev Med. 2011;16(3):185–90.

Bjørngaard JH, Gunnell D, Elvestad MB, Davey Smith G, Skorpen F, Krokan H, et al. The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study. Psychol Med. 2012;43(4):711–9.

Chen SC, Chen HF, Peng HL, Lee LY, Chiang TY, Chiu HC. Psychometric testing of the Chinese-Version Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ-C) for the identification of nicotine dependence in adult smokers in Taiwan. Int J Behav Med. 2017;24(2):272–9.

Doran N, Spring B, McChargue D, Pergadia M, Richmond M. Impulsivity and smoking relapse. Nicotine Tob Res. 2004;6:641–7.

Haller CS, Etter JF, Courvoisier DS. Trajectories in cigarette dependence as a function of anxiety: a multilevel analysis. Drug Alcohol Depend. 2014;139:115–20.

Jamal M, Van der Does AJW, Cuijpers P, Penninx BW. Association of smoking and nicotine dependence with severity and course of symptoms in patients with depressive or anxiety disorder. Drug Alcohol Depend. 2012;126(1–2):138–46.

Krishnan-Sarin S, Reynolds B, Duhig A, Smith A, Liss T, McFetridge A, et al. Behavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers. Drug Alcohol Depend. 2007;88:79–82.

Tidey JW, Pacek LR, Koopmeiners JS, Vandrey R, Nardone N, Drobes DJ, et al. Effects of 6-week use of reduced-nicotine content cigarettes in smokers with and without elevated depressive symptoms. Nicotine Tob Res. 2017;19(Suppl 1):59–67.

Chang CM, Cheng YC, Cho TM, Mishina EV, Del Valle-Pinero AY, van Bemmel DM, et al. Biomarkers of potential harm: summary of an FDA-sponsored public workshop. Nicotine Tob Res. 2019;21(1):3–13.

Haziza C, de La Bourdonnaye G, Donelli A, Skiada D, Poux V, Weitkunat R, et al. Favorable changes in biomarkers of potential harm to reduce the adverse health effects of smoking in smokers switching to the menthol tobacco heating system 2.2 for three months (part 2). Nicotine Tob Res. 2019;22(4):549–59.

Bishop L, Kuula-Luumi A. Revisiting qualitative data reuse: a decade on. SAGE Open. 2017;7(1):1–15.

Sherif V. Evaluating preexisting qualitative research data for secondary analysis. In: Forum: qualitative social research, vol. 19, no. 2. 2018.

Patrick D, Burke L, Gwaltney C, Leidy N, Martin M, Molsen E, et al. Content validity—establishing and reporting the evidence in newly developed patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR PRO good research practices task force report: part 1—eliciting concepts for a new PRO instrument. Value Health. 2011;14(8):967–77.

Download references

Acknowledgements

We thank the team at Sciome LLC for their assistance and contribution to the literature review. We thank Vivienne Law and David Floyd for their contributions to the literature review, reanalysis of qualitative data, and assistance with review of the draft manuscript. We thank Catherine Acquadro for her review of the draft manuscript. We also thank John Ware, Jed Rose, Ashley Slagle, Donald Patrick, Karl Fagerström, Stefan Cano, and Thomas Salzberger for their input and review.

Philip Morris International is the sole source of funding and sponsor of this research.

Author information

Authors and affiliations.

PMI R&D, Philip Morris Product S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland

Esther F. Afolalu, Erica Spies, Agnes Bacso, Emilie Clerc, Sophie Gallot & Christelle Chrea

Patient-Centered Outcomes Assessments Ltd., 1 Springbank, Bollington, Macclesfield, Cheshire, SK10 5LQ, UK

Linda Abetz-Webb

You can also search for this author in PubMed   Google Scholar

Contributions

EA, ES and CC performed conceptualization. EA, ES and LA-W performed methodology. EA, ES, SG, EC and LA-W were involved in the investigation. EA and ES were involved in writing—original draft. EA, EC, LA-W and CC were involved in writing—review & editing. EA performed visualization. ES and CC performed supervision. AB, EC and SG were involved in data curation. AB and EC were involved in project administration. LA-W performed formal analysis. CC was involved in funding acquisition. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Esther F. Afolalu .

Ethics declarations

Ethics approval and consent to participate.

Not applicable.

Consent for publication

Competing interests.

Esther F. Afolalu, Emilie Clerc, and Christelle Chrea are employees of Philip Morris International. Agnes Bacso, Erica Spies, and Sophie Gallot completed the work during prior employment with Philip Morris International. Linda Abetz-Webb is a consultant for Philip Morris International.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Work completed during prior affiliation with PMI R&D: Erica Spies, Agnes Bacso, Sophie Gallot.

Supplementary Information

Additional file 1..

Summary tables of results of scoping literature review

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Afolalu, E.F., Spies, E., Bacso, A. et al. Impact of tobacco and/or nicotine products on health and functioning: a scoping review and findings from the preparatory phase of the development of a new self-report measure. Harm Reduct J 18 , 79 (2021). https://doi.org/10.1186/s12954-021-00526-z

Download citation

Received : 14 October 2020

Accepted : 21 July 2021

Published : 30 July 2021

DOI : https://doi.org/10.1186/s12954-021-00526-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Health and functioning
• Scoping review
• Qualitative research
• Conceptual framework

Harm Reduction Journal

ISSN: 1477-7517

• Submission enquiries: [email protected]

Subscribe Follow Watch

Tobacco Regulatory Science Program

Tobacco regulatory research priorities.

TRSP supports research applications that will inform the FDA in regulation of the manufacture, marketing, and distribution of tobacco products to reduce the public health toll from tobacco product use in the United States.

FAQs: Responsiveness to FDA’s Center for Tobacco Products Regulatory Authority

These  FAQs (PDF)  clarify research that is and is not within scope of the FDA’s Center for Tobacco Products (CTP) regulatory authority. Only research that is within the regulatory authority of the FDA CTP will be considered for funding.

Research is encouraged in the following scientific domains. These domains were updated in August 2022. Only applications with research aims that are within FDA's Center for Tobacco Products regulatory authority will be considered for TRSP funding opportunities.

Product Composition and Design

Understanding the chemical constituents in tobacco products and the methods for measuring them across products with diverse characteristics.*

Priorities include:

• Determination of smoking, heat-generating, or aerosol-generating regimen to be used for measuring harmful and potentially harmful constituents (HPHC) in smoke (e.g., cigarettes, pipes) and aerosols (e.g., ENDS, heated tobacco products).
• Identification, quantification, and determination of the formation of the chemical constituents of novel tobacco products including ENDS aerosols or other aerosol-generating tobacco products.
• Determination of relationship between the nonadjustable or user adjustable design parameters of heating element temperature/wicking material/air flow of ENDS devices or other aerosol-generating tobacco products and constituent yields/particle size in the aerosol.
• Determination of the relationship between waterpipe materials/design of waterpipe devices and constituent yields in the waterpipe smoke.
• Development of internationally recognized analytical methods applicable to various tobacco types.
• Development of methods to evaluate nicotine release across different smokeless tobacco products (e.g., snuff/dip, snus, chew).
• Characterization of the antimicrobial activity of propylene glycol (PG), vegetable glycerin (VG), and flavor ingredients.
• Determination of relationship between humectant concentration or type and water activity of waterpipe, pipe, and cigar tobacco.
• Characterization of the relationship between intrinsic/extrinsic factors (e.g., battery design; environmental conditions, use conditions [e.g., changing battery, charging]) and ENDS battery overheating, fire, or explosion incidents.

Understanding how tobacco products and changes to tobacco product characteristics* affect their potential to cause morbidity and mortality in users and nonusers through secondary exposure; including animal (in vivo) and cell culture (in vitro) models, as well as novel alternative toxicology approaches that test the toxicity of tobacco smoke (other than cigarette), aerosols, or specific constituents in tobacco and the tobacco product.

• Evaluation of toxicity from exposures to complex mixtures of tobacco-related constituents in ENDS aerosol, waterpipe smoke, cigar smoke, and smokeless tobacco using toxicological assays such as in vivo, in silico, as well as in vitro models that are more physiologically relevant to humans.
• How product design characteristics* (variation(s) in those characteristics*) impact constituent exposure and toxicity from tobacco products.
• Biomarkers to assess exposure, as well as biomarkers to assess harm or toxicity of products other than conventional cigarettes, including ENDS and waterpipes; and toxicological impact of nicotine, flavors, and other constituents across different concentrations, patterns of use behavior (dual/poly use, product switching) and routes of exposure.

Understanding the effect of tobacco product characteristics* on addiction and abuse liability across populations.

• Impact of changes in tobacco product characteristics* (such as flavors, product design, and nicotine formulation) on dependence and use behaviors.
• Correlation of ENDS use behaviors with pharmacokinetic and pharmacodynamics effects of nicotine and other HPHCs delivered by ENDS; and the relationship between specific flavor categories in ENDS (including, but not limited to, tobacco, menthol, fruit, and sweet/dessert) and adult users’ interest in cessation as well as quit attempts, reduced cigarette use and/or switching to potentially less harmful tobacco products.
• ENDS users’ biomarkers of exposure during ENDS experimentation, regular ENDS use, and dual use of ENDS and cigarettes (with reduced cigarettes per day and maintaining cigarettes per day).
• Impact of synthetic coolants in ENDS and cigarettes on product abuse liability (e.g., nicotine pharmacokinetics, product subjective effects), dependence, and use behaviors (such as progression to regular product use, switching, and cessation).

Health Effects

Understanding the short- and long-term health effects of tobacco products (excluding conventional cigarettes) with priority on longitudinal data. Areas of interest include cardiovascular, cancer, neurological (e.g., seizures), oral, reproductive, and respiratory health effects (including inflammation and lung disorders [e.g., asthma, COPD]).

• Impact of tobacco product characteristics* (such as e-liquid non-tobacco flavors, product design, e-liquid nicotine concentration, nicotine formulation) on human health.
• Impact of novel product use (e.g., ENDS, heated tobacco products) on biomarkers of exposure and biomarkers of potential harm.
• Association between exclusive products other than conventional cigarette-related exposures and disease risk; association between dual/poly use of tobacco products and disease risk.
• Identifying biomarkers of potential harm to assess short- and long-term health effects of tobacco products, with a focus on products other than conventional cigarettes, including deemed products or other novel products.
• Association between cigar sub-types use and disease risk.
• Association between waterpipe and waterpipe materials use and disease risk.

Understanding the knowledge, attitudes, perceptions, and behaviors related to tobacco product use and the impact of tobacco product characteristics* on behaviors across populations, as appropriate.

• The impact of tobacco product characteristics* (such as e-liquid flavors, product design, nicotine concentration, and formulations) on tobacco use preferences and behaviors (such as intentions to use, experimentation, initiation, progression, dual/poly tobacco use, switching, and cessation-related behaviors) among youth, young adults, and adults.
• Innovative methods, measures, and study designs to assess tobacco use knowledge, attitudes, perceptions, and behaviors; including measures to best predict future use of tobacco products other than conventional cigarettes (e.g., cigars, waterpipe, heated tobacco products, ENDS).
• Innovative measures, methods, or study designs to assess the likely impact of ENDS and heated tobacco products, other novel products, and/or potential modified risk tobacco products on relevant outcomes, including precursors to tobacco use (e.g., perceptions, intentions, susceptibility), and tobacco use behaviors including experimentation, initiation, progression, dual/poly use, complete switching, and cessation-related behaviors.

Communications

Understanding how to effectively communicate to the public regarding nicotine and the health effects of tobacco products through media campaigns and digital media.

 Priorities include:

• Identifying effective tobacco education messages, message components, and communication channels to prevent initiation and to counter uptake of ENDS use and other novel product use by youth and young adults.
• Developing methods to measure and track attention to tobacco education messages delivered on digital channels.
• Developing strategies to increase attention to and engagement with tobacco education messages delivered on digital channels.
• Identifying messages to effectively communicate about the risks associated with nicotine use and the potential relative harms of tobacco products other than conventional cigarettes use.
• Developing methods and messages for communicating complex scientific concepts to the general public, including information about the relative risks and harms of tobacco use (e.g., continuum of harm/harm reduction) while assessing and minimizing unintended consequences of such messages.
• Evaluating the effectiveness of text and pictorial warnings for tobacco products other than conventional cigarettes.
• Developing effective messages and communication for educating consumers about the health effects of cigars, waterpipe, heated tobacco products, ENDS, and novel tobacco products; and their relative harms as compared to cigarettes.

Marketing Influences

Understanding the impact of marketing on susceptibility to and initiation of using tobacco products (both classes of products and products within classes) and transitions between experimentation, initiation, regular use, product switching, dual use, and cessation-related behaviors among different populations. Topics may include marketing such as advertising, digital media, and promotions.

• Methods, measures, and study designs to best assess the impact of tobacco product marketing (advertising and promotion) restrictions on users and non-users of tobacco with attention to populations that bear disproportionate burden of tobacco product risk and harm (if appropriate), including marketing of new/novel tobacco products.
• Understanding what components of ENDS marketing have the greatest impact on youth and young adults’ ENDS knowledge, attitudes, perceptions, beliefs, and behaviors.
• Understanding how labeling, marketing, and advertising impact abuse liability, appeal, perceptions, and intentions to use different tobacco products.
• Examining the impact of potential marketing restrictions of new/novel tobacco products on various initiation and use behaviors (e.g., experimentation, initiation, use, and cessation) across developmental age groups (e.g., youth, young adult, non-user), as well as on adult continued use, dual use, switching, and cessation.
• Examining the impact of exposure to digital tobacco marketing on youth tobacco initiation and sustained use, including prevalence and frequency of exposure on different digital channels and the impact of social media influencers and other marketing partners (e.g., musicians).

Impact Analysis

Understanding the potential or actual impact of FDA regulatory actions.

• Evaluation of local, state, federal, and international policies that are relevant to FDA CTP regulatory authorities (e.g., flavor bans, specific constituent changes or bans, minimum legal sales age, FDA-required cigarette health warnings), with a focus on effects on tobacco use/behavioral outcomes, including tobacco initiation and increasing use among youth and young adults, cigarette cessation and product switching among users, and prevalence change in populations that bear disproportionate burden of tobacco product risk and harm; as well as unintended consequences;
• Evaluation of tobacco product marketing authorizations of new/novel products (e.g., PMTA, MRTPA), such as potential impact on health outcomes and effects on tobacco use/behavioral outcomes, including patterns of use among users (e.g., dual use vs. switching) and initiation among unintended users (e.g., use by youth).
• Behavioral economics experiments and population-based modeling studies to estimate the range of potential impacts on behavior and health of potential FDA regulatory actions such as product standards addressing toxicity, appeal, and addiction (e.g., such as a ban on flavored cigars, a ban on menthol in cigarettes and cigars, lowering nicotine in combustible cigarettes, and ban on flavors that appeal to youth in any tobacco product).
• Evaluations of the differential impact and/or possible unintended consequences of tobacco regulatory actions among specific populations and, as appropriate, addressing how such actions may affect populations that bear disproportionate burden of tobacco product risk and harm.
• Health risk analysis at the population level to estimate the potential public health impacts of FDA regulatory actions such as tobacco product marketing authorizations of new/novel products (e.g., PMTA).

* The term "characteristic" encompasses materials, ingredients (including additives, nicotine formulations, and flavors), design, composition, heating source, and other features of a tobacco product, including harmful and potentially harmful constituents. Product characteristics can be incorporated into all the above topics.

FDA encourages research studies to include, where appropriate to the research question, vulnerable populations, including (but not limited to): youth and young adults, those from lower socioeconomic backgrounds (e.g., those with lower household incomes or lower educational attainment), racial or ethnic minorities, sexual and/or gender minorities, rural populations, those pregnant or trying to become pregnant, active-duty military or veterans, those who are or have been incarcerated, and those with mental health conditions or substance use disorders.

If a vulnerable population will be included, applicants will be expected to identify the population and how the population is important to the research question, considering the impact on population health. Health disparity considerations can be incorporated into all the research priorities.

Our top issues

In our fight to end smoking, vaping and nicotine addiction, we focus on the issues that matter most. We constantly monitor the latest topics and trends in tobacco and substance use.

• Youth vaping, smoking & nicotine use
• Menthol & flavored tobacco products
• Harm reduction
• Tobacco & social justice
• Tobacco-free communities & campuses
• Tobacco industry interference
• Tobacco in pop culture
• Quitting smoking & vaping
• Opioids crisis

Truth Initiative is America's largest nonprofit public health organization committed to making tobacco use and nicotine addiction a thing of the past.

• Our mission
• Our history
• Annual reports

Research & resources

Get the latest facts and analyses on the most important issues related to smoking, vaping, nicotine and substance use.

Search by keywords

• Emerging tobacco products
• Traditional tobacco products
• Targeted communities
• Smoking by region
• Quitting smoking / vaping

We give young people the facts about smoking, vaping, nicotine and the tobacco industry, engage individuals and groups to make change in their communities, innovate ways to end nicotine addiction and join forces with collaborators committed to a future where tobacco and nicotine addiction are a thing of the past.

Truth Initiative Schroeder Institute®

truth® campaign

• Community & youth engagement
• Quit smoking & vaping tools
• Corporate tobacco cessation programs
• Truth Initiative Impact Series
• Partnerships

Get involved

Enlist in our movement, explore youth activism programs, share quitting resources and learn about more ways you can get involved.

• Take action
• Partner with us
• Request a training
• Participate in our research
• Apply for grants or scholarships

Join our newsletter

Search our site.

Top Searches

• Quit vaping
• Youth Activism
• Grants & Scholarships
• Featured Community Projects
• Quit smoking & vaping tools
• Featured Partnerships
• Partnership Opportunities
• Why Partner With Us
• Youth vaping, smoking & nicotine use
• Menthol & flavored tobacco products
• Harm Reduction
• Tobacco & social justice
• Tobacco-free communities & campuses
• Quitting smoking & vaping
• Opioid crisis
• Popular topics
• News & Insights
• Fact sheets
• Research articles
• Help Quitting
• Opioid Crisis
• Curriculums

Sign up for our newsletter

• Research and resources

How the tobacco industry’s new products could be leading to more nicotine addiction

• Emerging Tobacco Products
• E-cigarettes / Vaping

RELATED MATERIALS

What is synthetic nicotine and what does it mean for the youth vaping epidemic?

E-cigarettes: facts, stats, and regulations

Faced with declines in cigarette use – the youth smoking rate dropped from nearly 23% in 2000 to an all-time low of 2.3% in 2021 – the tobacco industry has expanded its product offerings to include flashy e-cigarettes, flavored nicotine-containing products such as oral nicotine pouches and lozenges, and the heated tobacco device IQOS, dramatically changing the product landscape. Companies have also begun to manufacture products with synthetic nicotine – nicotine created in a laboratory and not derived from tobacco – and market those products as “tobacco-free,” a claim that could imply lower-risk.

Youth nicotine use in any form is unsafe. Nicotine is harmful to developing brains – young nicotine users are more likely to become addicted, have more difficulty quitting, and may be at higher risk for addiction to other substances in the future.

Public health leaders and researchers joined Truth Initiative to discuss the proliferation of new tobacco products that threaten to reverse years of progress made toward ending nicotine addiction. “Nicotine Nation: How the Tobacco Industry May Be Addicting a New Generation and Keeping Americans Hooked,” the latest Truth Initiative Impact Series, included Truth Initiative CEO and President Robin Koval, Associate Vice Chancellor for Research at the University of Illinois Chicago Dr. Jonathan D. Klein, and Director of the National Institute on Drug Abuse Dr. Nora D. Volkow. Lauren Etter, an investigative reporter for Bloomberg News and the author of The Devil’s Playbook: Big Tobacco, Juul, and the Addiction of a New Generation , moderated.

Proliferation of non-combustible tobacco products

The tobacco industry has mounted a campaign to try to transform its image with non-combustible tobacco products and claims that it can be part of the “public health solution” to end smoking. With new products like e-cigarettes, heated tobacco devices, and oral nicotine products the tobacco industry is attempting to position itself as working alongside public health while aggressively growing its market base among youth and young adults. Companies have also switched to synthetic nicotine to exploit a former regulatory loophole and keep selling the types of sweet and fruity flavored products that helped ignite the youth vaping epidemic that continues today.

“Nicotine is nicotine, so whether you add it from the plant or you do it synthetically, it’s exactly the same chemical structure and you are going to be having the same pharmacological effects,” said Dr. Volkow.

Many of these newer products contain high nicotine concentrations, which is not restricted in the U.S. For example, nicotine levels in some e-cigarettes match or exceed levels found in combustible cigarettes. A study by Truth Initiative and the Centers for Disease Control and Prevention found that the average nicotine concentration in e-cigarettes sold in U.S. retailers more than doubled from 2013 to 2018.

The tobacco industry also continues to cultivate influence with the general public, thought leaders, the scientific community and policy makers, lobbying against policies that strengthen tobacco control efforts, seeking  publication in scientific journals  and running million-dollar “advertorial” content campaigns across national media outlets aimed to influence the public about the health dangers of its products .

Need for harm reduction

The experts discussed how the tobacco industry has defended e-cigarettes and seized upon the term “ harm reduction ” – the proven public health strategy of providing evidence-based, lower harm alternatives for those who do not quit harmful substances – as a proxy for a vision of a lightly regulated market in nicotine products that provides for continued and robust growth of nicotine as a commercial product. Truth Initiative forcefully rejects that notion and believes that a genuine harm reduction approach requires a measured and careful deployment of nicotine alternatives that are designed and promoted with controls to ensure they are not attractive to non-users prior to introduction into the market.

Despite it being well-established that flavors play a significant role in enticing youth and young adults to try and use tobacco products, many open system and disposable e-cigarettes come in an array of candy, fruit, dessert and cocktail flavors , such as sour apple, cherry, grape, chocolate, strawberry margarita, appletini, pina colada, cotton candy, and cinnamon roll.

“There’s absolutely no reason to market flavors to teenagers if your goal is to provide alternative or safer products to adults who are addicted smokers,” said Dr. Klein.

Nicotine and mental health

In addition to the negative physical health effects of tobacco, nicotine can negatively affect mental health. A body of peer-reviewed research highlights how nicotine can worsen anxiety symptoms and can intensify feelings of depression . The prevalence of depression and anxiety symptoms has doubled among youth during the COVID-19 pandemic, a JAMA study shows, and the National Youth Tobacco Survey reports that 1.7 million high schoolers vape and more than 43% of those who vape do so 20-30 days per month. A Truth Initiative survey also shows that 4 in 5 young people who had vaped said they started vaping to lessen their stress, anxiety, or depression.

“During our nation’s worsening youth mental health crisis, the thing many young people have turned to because they believe it will alleviate their symptoms can actually make them worse,” said Koval, giving the reasoning behind the latest youth e-cigarette education campaign from truth .

It’s Messing with Our Heads exposed nicotine’s role as a contributor to the worsening youth mental health crisis through the launch of a fake vaping company called Depression Stick! Breath of Stress Air is an effort that expands on It’s Messing with Our Heads , debunking the marketing of e-cigarettes as stress relievers and calling out the tobacco industry for selling vaping as a way to deal with stress, especially during the COVID-19 pandemic.

Truth Initiative’s Impact Series

The Truth Initiative Impact Series is a robust, recurring event that brings together key stakeholders and experts to engage in thought-provoking conversations about ways we can innovate and inspire action to achieve a culture where young people reject smoking, vaping, and nicotine. The goal of this thought leadership series is to convene diverse partners in tobacco control and other public health organizations, parents, teachers, and policy makers who can benefit from Truth Initiative’s work.

In case you missed it, watch our previous Impact Series events: “ Vaping: Know the Truth – Empowering Students with the Facts on E-cigarettes & Tools to Quit ,” “ Thrive: A Youth Mental-Health Summit ,” “ Unvaping America’s Youth ,” and “ Not Buying It: The Tobacco Industry’s Rebrand .”

More in emerging tobacco products

New study: E-cigarette use linked to prior mental illness diagnosis among college students

Local restrictions on flavored tobacco and e-cigarette products

Youth have easy access to e-cigarettes online through lax age verification and concealed deliveries

• Skip to main content
• Skip to FDA Search
• Skip to in this section menu
• Skip to footer links

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

U.S. Food and Drug Administration

•   Search
•   Menu
• Tobacco Products
• CTP Newsroom

FDA Launches Searchable Tobacco Products Database

Database Lists Tobacco Products—Including E-Cigarettes—That May Be Legally Marketed

March 28, 2024

Today, FDA launched the Searchable Tobacco Products Database , a new user-friendly list of tobacco products—including e-cigarettes—that may be legally marketed in the United States. The database is designed to serve the public—especially retailers—by providing this key information in a single location, with easy-to-use search capabilities. The database, which can be accessed at www.fda.gov/searchtobacco , will be updated on a monthly basis.

Within the database, FDA provides information on three categories of products: 1) new tobacco products that received marketing authorization through one of FDA’s three pathways to market a new tobacco product ; 2) pre-existing tobacco products established through a voluntary determination program (commercially marketed as of Feb. 15, 2007); and 3) provisional tobacco products that were removed from review . 

“CTP remains committed to enhanced transparency in a way that is useful, timely, and user-friendly,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products. “We hope that this database will be an asset to stakeholders—including retailers—that will be used to help facilitate compliance with the law.”

At the time of launch, the database contains nearly 17,000 tobacco products, with over 12,000 being pre-existing tobacco products. For each entry, FDA provides available information on the tobacco product, including the product name, company, category, sub-category, the authority permitting its sale in the U.S., and the date of FDA action. Additionally, the database also includes links to regulatory and scientific documents, such as the Order Letter and Decision Summary, as well as the Environmental Assessment (EA) and related documents associated with a tobacco product application.  

To help explain some of the terminology and context about the content of the database, FDA has also developed the Searchable Tobacco Products Database – Additional Information webpage. The webpage also includes answers to potential questions about the database, including a question related to unauthorized products with pending applications. In general, FDA is unable to provide information on pending applications in order to protect confidential commercial information. Moreover, for new products that require authorization, a pending application does not create a safe harbor to sell that product.  

The launch of this public database is part of the Center’s continued commitment to providing regulated industry with resources and providing clear communication about the agency’s actions to the public. Additional recent activities to enhance transparency include those listed in the Center’s quarterly updates on activities in response to the Reagan-Udall Foundation evaluation .   

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 02 November 2023

Dental Public Health

Is the use of tobacco products, especially electronic nicotine delivery systems (ENDS), associated with the incidence of oral health outcomes among US adults?

• C. Albert Yeung   ORCID: orcid.org/0000-0002-5482-019X 1  

Evidence-Based Dentistry volume  24 ,  pages 161–162 ( 2023 ) Cite this article

435 Accesses

Metrics details

• Gum disease
• Tobacco cessation in dentistry

Cohort study.

Sample selection

Data were pooled from wave (W) 1 to W5 (2013–2019) of the Population Assessment of Tobacco and Health Study Restricted-Use Files. The W1 cohort respondents were interviewed at all five waves who were aged 18 years and older without a lifetime history of each of the six oral health outcomes (gum disease, precancerous oral lesions, bone loss around teeth, bleeding after brushing or flossing, loose teeth, number of teeth removed because of tooth decay or gum disease).

Data analysis

Data analysis was performed from October 2021 to September 2022. To assess associations between current established tobacco use and incidence of adverse oral health outcomes at the next wave, adjusted hazard ratios (AHRs) and 95% CIs were calculated using Cox proportional hazards models.

Cigarette smoking was positively associated with incidence of gum disease diagnosis (AHR, 1.33; 95% CI, 1.11–1.60), loose teeth (AHR, 1.35; 95% CI, 1.05–1.75), and one or more teeth removed (AHR, 1.43; 95% CI, 1.18–1.74). Smoking any cigars was positively associated with incidence of precancerous oral lesions (AHR, 2.18; 95% CI, 1.38–3.43). Hookah smoking was positively associated with incidence of gum disease diagnosis (AHR, 1.78; 95% CI, 1.20–2.63). Use of electronic nicotine delivery systems (ENDS) was positively associated with incidence of bleeding after brushing or flossing (AHR, 1.27; 95% CI, 1.04–1.54). Snus and smokeless tobacco (excluding snus) were not significantly associated with incidence of gum disease diagnosis or precancerous oral lesions.

Conclusions

This cohort study confirmed associations of current combustible tobacco use with incidence of adverse oral health outcomes. It also showed an association between current ENDS use and incidence of bleeding after brushing or flossing.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 4 print issues and online access

251,40 € per year

only 62,85 € per issue

Buy this article

Purchase on Springer Link

Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

WHO global report on trends in prevalence of tobacco use 2000–2025, 4th ed. Geneva: World Health Organization; 2021.

Miranda-Filho A, Bray F. Global patterns and trends in caners of the lip, tongue and mouth. Oral Oncol. 2020;102:104551.

Article   PubMed   Google Scholar  

GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1223–49.

Article   Google Scholar  

US Food and Drug Administration. FDA and NIH Study: Population Assessment of Tobacco and Health. September 2023. https://www.fda.gov/tobacco-products/research/fda-and-nih-study-population-assessment-tobacco-and-health .

von Elm E, Altman DG, Egger M, Pocork SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7.

Download references

Author information

Authors and affiliations.

Public Health Directorate, NHS Lanarkshire, Kirklands, Fallside Road, Bothwell, G71 8BB, UK

C. Albert Yeung

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to C. Albert Yeung .

Ethics declarations

Competing interests.

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Yeung, C.A. Is the use of tobacco products, especially electronic nicotine delivery systems (ENDS), associated with the incidence of oral health outcomes among US adults?. Evid Based Dent 24 , 161–162 (2023). https://doi.org/10.1038/s41432-023-00949-6

Download citation

Received : 22 October 2023

Accepted : 24 October 2023

Published : 02 November 2023

Issue Date : December 2023

DOI : https://doi.org/10.1038/s41432-023-00949-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

California Democrats urge Biden not to scrap chips R&D funding

Get weekly news and analysis on the U.S. elections and how it matters to the world with the newsletter On the Campaign Trail. Sign up here.

Reporting by David Shepardson and Alexandra Alper; editing by Costas Pitas

Our Standards: The Thomson Reuters Trust Principles. , opens new tab

Taiwan's strongest earthquake in 25 years kills 9 people, 50 missing

Taiwan's biggest earthquake in at least 25 years killed nine people on Wednesday and injured more than 900, while 50 workers travelling in minibuses to a hotel in a national park were missing.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• v.15(3); 2021 Mar

Tobacco control policies in the 21st century: achievements and open challenges

Armando peruga.

1 Tobacco Control Research Group, Epidemiology and Public Health Research Programme, Institut d'Investigació Biomèdica de Bellvitge‐IDIBELL, Barcelona Spain

2 Consortium of Centers for Biomedical Research on Respiratory Diseases (CIBERES), Madrid Spain

3 Center for Epidemiology and Health Policies, Clínica Alemana School of Medicine, Universidad del Desarrollo, Santiago Chile

María José López

4 Evaluation and Intervention Methods Service, Agència de Salut Pública de Barcelona, Spain

5 Consortium of Centers for Biomedical Research on Epidemiology and Public Health, CIBERESP, Madrid Spain

6 Institut d'Investigació Biomèdica de Sant Pau (IIB Sant Pau), Barcelona Spain

Cristina Martinez

7 Tobacco Control Unit, WHO Collaborating Center on Tobacco Control, Institut Català d'Oncologia‐ICO, Barcelona Spain

8 School of Medicine and Health Sciences, Campus of Bellvitge, Universitat de Barcelona, Spain

Esteve Fernández

Noncommunicable diseases (NCDs), including cancer, are responsible for almost 70% of all deaths worldwide. Tobacco use is a risk factor common to most NCDs. This article discusses tobacco control policies and highlights major achievements and open challenges to reduce smoking prevalence and attributable morbidity and mortality in the 21st century. The introduction of the WHO Framework Convention on Tobacco Control in 2005 has been a key achievement in the field and has already facilitated a drop in both smoking prevalence and exposure to secondhand smoke. Indicatively, the size of the worldwide population benefiting from at least one cost‐effective tobacco control policy has quadrupled since 2007. In addition, plain cigarette packaging has been successfully introduced as a tobacco control policy, surmounting efforts of the tobacco industry to challenge this based on trade and investment law. Nevertheless, tobacco control still faces major challenges. Smoking prevalence needs to be further reduced in a rather expedited manner. Smoke‐free environments should be extended, and the use of plain tobacco packaging with large pictorial health warnings for all tobacco products should be further promoted in some parts of the world. Some of these measures will require prompt determination and diligence. For example, bold political decisions are needed to significantly increase real prices of tobacco products through excise taxes, ban added ingredients that are currently used to increase the attractiveness of tobacco products and ban the tobacco industry's corporate social responsibility initiatives. Finally, the debate on harm reduction strategies for tobacco control still needs to be resolved.

Tremendous, although insufficient, progress has been made on tobacco control during the past twenty years. Nevertheless, there are still open challenges, and several measures remain to be implemented soon: increasing tobacco taxes, banning the use of additives, implementing plain packaging, banning tobacco industry's corporate social responsibility activities, and counteracting the undermining tactics of the tobacco industry.

Abbreviations

1. introduction.

The 1964 US Surgeon General's Report [ 1 ] and numerous other reports have established the terrible consequences of smoking on the health of smokers and nonsmokers. At the end of the 20th century, tobacco had caused 100 million deaths worldwide, becoming a leading cause of totally preventable premature deaths. It has been predicted that without any additional tobacco control efforts, one billion people could die from causes related to tobacco by the end of the 21st century, such as cancer, heart disease, stroke, lung diseases, diabetes, and chronic obstructive pulmonary disease [ 2 ].

An extremely profitable industry fueled the tobacco epidemic by selling a highly addictive product taking advantage of globalization in the second half of the 20th century. Governments and public health organizations became aware of the globalization and the severe consequences of the tobacco epidemic and its evolution into a large‐scale pandemic [ 3 ]. The significant economic toll of tobacco, which today amounts to US$1436 billion, or 1.8% of the world's annual gross domestic product [ 4 ], was soon realized. At the same time, governments and public health organizations recognized that the pandemic needed a global and coordinated high‐level response.

In 1999, WHO initiated the proceedings to create the Framework Convention for Tobacco Control (FCTC), the first international treaty under WHO auspices. Followingly, the global community recognized tobacco use as a severe threat to global health, as well as a social and economic problem, and began to take joint international action. This work highlights achievements in tobacco control in the 21st century and discusses open challenges (Fig.  1 ).

Tremendous, although insufficient, progress has been made on tobacco control during the past 20 years. Nevertheless, there are still open challenges, and several measures remain to be implemented soon: increasing tobacco taxes, banning the use of additives, implementing plain packaging, banning tobacco industry's corporate social responsibility activities, and counteracting the undermining tactics of the tobacco industry.

2. Achievements of tobacco control efforts during the first 20 years of the 21st century

2.1. galvanizing global political will around international law.

The WHO FCTC entered into force in 2005 as binding law for all treaty parties. As of January 2021, the treaty was adopted by 181 WHO member states and the European Union, thereby covering more than 90% of the world's population. The Protocol to Eliminate Illicit Trade in Tobacco Products, also known as Illicit Trade Protocol (ITP), was introduced under the WHO FCTC in 2018. As of January 2021, 62 WHO FCTC parties had also become parties to the protocol.

Galvanizing the global political will for implementing the WHO FCTC and the ITP has been a key success in tobacco control. These treaties redefine the role of international law in preventing disease and promoting health. Both treaties seek to establish cooperation among countries to tackle, for example, cross‐border advertising and illicit trade. Importantly, they seek to establish international cooperation on matters that would otherwise be subject to national regulation because the sovereignty of nations to protect public health is often challenged by the interests of the powerful transnational tobacco industry. The tobacco companies often seek to expand the tobacco market through various tactics, including intensive targeting of women, children, and the poorer parts of society [ 5 ]. Therefore, the WHO FCTC and the ITP have solidified global governance of health matters and the foundation for countries to enact comprehensive, effective national tobacco control measures that span across all government sectors.

2.2. Quadrupling the number of people benefiting from at least one cost‐effective tobacco control policy since 2007

In 2008, WHO introduced the MPOWER package to assist in implementing the six best‐practice cost‐effective interventions defined in the WHO FCTC. The six MPOWER measures are as follows: (a) Monitor tobacco use and prevention policies (M); (b) Protect people from tobacco smoke (P); (c) Offer help to quit tobacco use (O); (d) Warn about the dangers of tobacco (W); (e) Enforce bans on tobacco advertising, promotion and sponsorship (E); and (f) Raise taxes on tobacco (R) (see Table  1 for an overview of MPOWER measures and how they relate to the WHO FCTC provisions) [ 6 ]. To track the global improvement in the implementation of MPOWER measures, WHO measures the level of policy achievement for each measure in each country. In each country, an MPOWER measure is considered to be mandated at the highest level when the law requires implementing all policy components that render such measure most efficacious in reducing the demand for tobacco products, that is, reducing the prevalence of tobacco use. For example, the MPOWER measure to protect the population from tobacco smoke is mandated at the highest level when the law requires a complete indoor smoking ban for all workplaces and public places and not only for some of them. Similarly, the measure to warn about the dangers of tobacco is mandated at the highest level when the law requires that health warnings cover an average of at least 50% of the front and back of the package and has four or more desired features. These features include changing the health warning periodically or including pictures or pictograms. Tobacco taxes are mandated at the highest level when excise tobacco taxes amount to at least 75% of the retail price of a cigarette pack. The closer each country is to the highest level of policy achievement, the higher is the MPOWER score the country receives. A detailed description of the MPOWER scores has been explained elsewhere [ 7 ].

Description of the WHO FCTC articles and their inclusion in the MPOWER measures.

About 5 billion people living in 136 countries, an equivalent to 65% of the world's population, are currently benefiting from at least one of these MPOWER measures implemented at the highest level. This is a fivefold increase from the 1.1 billion people benefiting from tobacco control measures back in 2007.

The world's population profiting from a basic comprehensive policy to assist smoking cessation, or a comprehensive ban of tobacco advertising, promotion, and sponsorship has increased about sixfold between 2007 and 2018. The proportion of the world's population benefitting from a comprehensive smoke‐free policy or a legal mandate to have large graphic labels with strong health warnings on tobacco packages has increased more than eight times in the same period.

While the increase in cigarette taxes is the most effective tobacco control measure [ 8 ], it was also the least applied in 2018. The total population worldwide affected by a cigarette tax representing at least 75% of the retail price has almost doubled since 2007. Another way to look at the impact of tobacco taxes is to assess whether tax increases are able to decrease the affordability of tobacco products. By 2018, 44.3% of the global population lived in countries where cigarettes became less affordable in the last 10 years. However, most decreases in cigarette affordability were small. When considering at least a 10% relative decrease in cigarette affordability, the world's population living in countries achieving this breakthrough is 3.1% [ 7 ].

Noticeably, the proportion of the world's population exposed to a best‐practice mass media campaign decreased from 2010 until 2018. Few countries run mass media campaigns regularly, probably due to the high costs of such campaigns. Only four countries (Australia, Turkey, the United Kingdom, and Viet Nam) have run best‐practice mass media campaigns repeatedly since 2010.

2.3. Reducing the prevalence of smoking and exposure to secondhand smoke

According to the latest WHO estimates that compared smoking prevalence across countries in 2015, the age‐standardized prevalence of current tobacco smoking had decreased gradually by 5.9 percentage points since the beginning of the 21st century, that is, a relative reduction of 25% or an average decrease of 0.4 percentage points per year. WHO estimates that 19.8% of the world's population aged ≥ 15 years were current smokers in 2015 [ 9 ]. Denmark, Norway, and Uruguay were the only countries where current smoking prevalence among persons aged ≥ 15 years had been reduced by ten or more percentage points between 2005 and 2015. During this period, Denmark and Panama approached most closely the endgame prevalence target of 5%, covering more than half of the gap between current smoking prevalence and target [ 10 ].

A recent study [ 11 ] estimated that in countries with higher initial tobacco control preparedness, as measured by an early MPOWER implementation, the prevalence of daily smoking decreased by between 0.39 and 0.50 percentage points for each increase in the MPOWER score, which indicates the strength of the adopted policies. By contrast, countries with initially low tobacco control preparedness and high daily smoking prevalence seem to be struggling to reduce prevalence despite progress in MPOWER implementation. Another study indicated that the adoption of at least one highest level MPOWER policy in 88 countries between 2007 and 2014 resulted in almost 22 million fewer projected smoking‐attributable deaths [ 12 ].

The health impact of smoke‐free policies has been impressive. The proportion of people protected by smoke‐free legislations worldwide has increased from 3.0% in 2007 to 21.1% in 2018 (Table  2 ). The largest countries in the world report significant decreases in the proportion of people exposed to secondhand smoke [ 13 , 14 , 15 , 16 ]. Existing evidence shows that countries that enact national legislative smoking bans reduce the population exposure to passive smoke and benefit from improved health outcomes, specifically of cardiovascular diseases [ 17 ].

Global progress in the implementation of selected tobacco control policies at the highest level a . Change between 2007 and 2018 in the population living in countries with selected policy in billions and as a percentage of the world's population.

2.4. Tobacco plain packaging has resisted challenges under trade and investment law

In 2012, Australia became the first country to implement tobacco plain packaging to counter the tobacco industry's use of packaging for both selling cigarettes and undercutting health warnings. The Australian legislation bans logos, brand imagery, symbols, other images, colors, and promotional text on tobacco products and tobacco product packaging. It also requires that graphic health warnings cover 75% of the front and 90% of the back of the tobacco pack [ 18 ].

Australia's plain packaging legislation underwent three sets of legal challenges. First, big tobacco companies filed a lawsuit in the Australian High Court. Second, Philip Morris Asia sought to bring down the Australian legislation under an existing investment treaty between Australia and Hong Kong. Third, Cuba, the Dominican Republic, Honduras, Indonesia, and Ukraine filed a dispute through the World Trade Organization (WTO). The constitutional challenge was dismissed in August 2012 [ 19 ], and the investment challenge was rejected in December 2015 [ 20 ]. The WTO decided in June 2020 that Australia's plain packaging laws are likely to improve public health and that they are not unfairly restrictive to trade [ 21 ]. The decisions in the case of Australia are not just a success for public health. They also bring hope for continuing efforts to defend tobacco control policies against the attempts of the wealthy tobacco transnationals.

3. Immediate challenges for further reducing the burden to tobacco‐attributable diseases

The successes described above are significant accomplishments. However, key challenges still need to be addressed to reduce the burden of tobacco‐attributable diseases worldwide in a timely manner.

3.1. Accelerating the decline of smoking prevalence

The WHO set a relative reduction goal of 30% in tobacco use and smoking for the period between 2010 and 2025 [ 22 ]. Accordingly, the global prevalence of current smokers should be 15.1% by 2025. However, based on existing trends, the WHO projects that current smokers would be 17.1% of the global population by 2025 [ 7 ]. Therefore, the projected decrease is not fast enough to reach the 2025 reduction goals set by the WHO.

The reduction in smoking prevalence has been, so far, attributed primarily to the increase in the total population and not necessarily to a reduction in the number of smokers. It is projected that the total number of smokers will decrease from 1082 million in 2000 to 1058 million in 2025, a reduction of about 24 million or 2.2% [ 7 ]. While the number of smokers in the Americas and Europe will substantially decrease, a net increase in male smokers in the African, Eastern Mediterranean, and South‐East Asian regions is expected to hinder a more significant global decrease. Considering these figures, and that almost one third of the countries of the world—59 countries in total—have not yet adopted any MPOWER measures at the highest level of achievement, the implementation of cost‐effective tobacco control measures needs to be expedited.

Strengthening tobacco denormalization through smoke‐free environments and disseminating plain packaging and large pictorial warnings for all tobacco products could spearhead progress in many countries. It seems, however, that a few measures will require prompt unique determination and diligence. In our opinion, bolder moves are needed to:

• significantly increase real prices of all tobacco products through tobacco taxes. Since increasing taxes is the most effective tobacco control measure, the tobacco industry devotes many efforts to derail this measure [ 23 , 24 ]. The main tactics employed by these companies depend on the tax structure and administration of each country and the type of competition they face from other manufacturers [ 25 ].
• disrupt strategies currently applied to engineer the attractiveness of tobacco products by banning ingredients that may increase their palatability, including additives and particularly characterizing flavors.
• ban the most insidious form of tobacco promotion: the tobacco industry's corporate social investment or responsibility (CSR) initiatives. The tobacco industry has always conceived CSR as a public relations tool to further its business objectives [ 26 ]. It is a form of advertising, promotion, and sponsorship that should be banned. Whether supporting empowering women [ 27 ], disaster relief and preparedness [ 28 ], infectious disease prevention [ 29 ], or efforts against COVID‐19 [ 30 ], the tobacco industry's CSR activities do little to address the death and suffering caused by tobacco use [ 31 ].

To accelerate the implementation of these and other measures and the decline of smoking, some consider that a harm reduction strategy should be added to the existing mix of policies. A harm reduction approach to tobacco control encourages those smokers that cannot or are unwilling to stop smoking to switch to using nicotine in a less harmful form than combustible tobacco [ 32 ]. The public health community is divided over the value of such a strategy within the parameters of the existing alternative products, market forces driving the use of all tobacco and nicotine products, the strength of tobacco control policies, and the room of these to significantly and quickly drive a reduction in smoking [ 33 ]. Resolving this debate is a challenge too. Meanwhile, there are at least three things that should be considered to expedite the implementation of the WHO FCTC, as discussed below.

3.2. Positioning tobacco control in the global health and development agendas

The global success of the WHO FCTC will be partially determined by the extent to which governments and the international community realize that the tobacco pandemic is a threat to development and the achievement of the United Nations Sustainable Development Goals (SDG) [ 34 ]. Tobacco use increases healthcare costs and decreases productivity. Moreover, it feeds into the vicious circle of poverty. The most disadvantaged people spend comparatively less on necessities such as food, education, and health care to pay for their addiction to tobacco products [ 35 ]. Furthermore, tobacco farming destroys the environment upon which the poorest rely to survive. The large amounts of pesticides and fertilizers required to grow tobacco are toxic and pollute water supplies, in addition to the deforestation of their habitat to make room for a nonstaple crop and to cure tobacco [ 36 ]. Despite the inclusion of a specific target for implementing the WHO FCTC in the SDGs, for most governments, tobacco control remains merely a health issue instead of a development goal [ 37 ].

Noncommunicable diseases presently make up 7 of the world's top ten causes of death, and tobacco use is a risk factor for many NCDs [ 38 ]. However, tobacco control is often not prioritized in the health policy agenda [ 32 ]. The global health agenda is presently dominated by the ‘unfinished agenda’ of communicable disease and maternal and child health in low‐ and middle‐income countries. Considering the threats of tobacco use to the public health systems, tobacco control's contribution to building stronger economies and more equitable societies will help to address the ‘unfinished agenda’ and will be crucial for the recovery from the COVID‐19 pandemic in low‐ and middle‐income countries [ 39 ].

The exposure of high‐income countries to the COVID‐19 pandemic has highlighted the importance of controlling communicable diseases also in these nations. However, this should not distract us from the fact that COVID‐19 has hit the hardest people with NCDs, for which tobacco use is the main common risk factor. Smoking increases the risk of hospitalization, disease severity, and mortality from COVID‐19 [ 40 ]. Therefore, the COVID‐19 pandemic highlights the importance of investing equal efforts in tackling communicable diseases and NCDs, as the latter impact on the health outcomes of the former, as well as on the capacity of healthcare systems.

Tobacco control, and NCD prevention, in general, involves the regulation of industries that produce goods whose consumption may affect human health. Some of these industries and their allies are self‐servingly reminding us that the priority for global health is to prevent communicable disease [ 41 ] and responding quickly and decisively to outbreaks [ 42 ] instead of tobacco control or NCDs [ 43 , 44 ].

3.3. Overcoming the false ‘health versus economy’ dilemma: the need for a whole‐government approach

The response to the COVID‐19 pandemic has made us painfully aware of the fallacy of presenting the response to health problems as a trade‐off between lives saved and the economic cost of trying to save those lives—the health versus the economy dilemma. Positioning tobacco control within the overall—mainly economic—priorities of each government is a challenge, mainly given the intricacies of the broader context of the economic globalization that governments must navigate.

Parties to the WHO FCTC recognize that a critical challenge to implementing the treaty in their countries is the weakness of their multisectoral coordination and the insufficient support to the implementation of the WHO FCTC from sectors outside health [ 45 ]. A whole‐government approach is needed to succeed in declining smoking prevalence.

3.4. Countering the Tobacco Industry's Tactics to undermine tobacco control measures

The interests of the tobacco industry are irreconcilable with tobacco control and public health [ 46 ]. Consequently, governments should protect the implementation of their tobacco control policies from the commercial and other vested interests of the tobacco industry as mandated by the WHO FCTC. Countering the tobacco industry's tactics to undermine tobacco control measures is not a new challenge [ 47 ], but it has evolved with time. From the same that claimed at some point that tobacco is not damaging to health [ 48 ], nor addictive [ 49 ] or denied targeting youth [ 50 ], we get now that they are committed to a ‘smoke‐free future’ [ 51 ]. Their claims are not credible as long as the industry continues to fight proven policies and programs that reduce smoking. Equally, their proclamations are not convincing while they misrepresent regulatory agency decisions about the novel tobacco products such as heated tobacco products as less harmful than cigarettes [ 52 ]. Ultimately, if anyone in the tobacco industry is really dedicated to a smoke‐free future, it should immediately stop all marketing of any kind of cigarettes.

4. Conclusions

Tremendous, although insufficient, progress has been made on tobacco control during the past twenty years (Fig.  1 ). Nevertheless, there are still open challenges, and several measures remain to be implemented soon: increasing the real price of all tobacco products through tobacco taxes, banning the use of additives in tobacco products, implementing plain packaging for all tobacco products, and banning tobacco industry's corporate social responsibility activities. While implementing these measures, governments and public health policymakers should be prepared to counteract undermining tactics of the tobacco industry.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

AP, MJL, CM, and EF contributed to the conception and outline of the manuscript. AP prepared the first version of the manuscript. AP, MJL, CM, and EF edited and revised the manuscript, and approved its final version.

Acknowledgements

The Tobacco Control Research Group is partly supported by the Ministry of Business and Knowledge from the Government of Catalonia [2017SGR319] and by Instituto de Salud Carlos III, Government of Spain (CIBERES CB19/06/00004). EF was also supported by the Instituto de Salud Carlos III, Government of Spain, co‐funded by the European Regional Development Fund (FEDER) [INT16/00211 and INT17/00103]. CM was also supported by the Instituto de Salud Carlos III, Government of Spain, co‐funded by the European Regional Development Fund (FEDER) [INT17/00116] and Ministry of Health from the Government of Catalonia [PERIS No. 9015‐586920/2017]. We thank CERCA Programme/Generalitat de Catalunya for institutional support.