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Journal Details
Format
Journal
eISSN
2719-9509
First Published
01 Jan 1992
Publication timeframe
4 times per year
Languages
English

Search

Volume 31 (2022): Issue 1 (March 2022)

Journal Details
Format
Journal
eISSN
2719-9509
First Published
01 Jan 1992
Publication timeframe
4 times per year
Languages
English

Search

0 Articles
Open Access

An Experimental Analytical and In Vitro Approach to Bridge Between Different Heated Tobacco Product Variants

Published Online: 16 Apr 2022
Page range: 1 - 9

Abstract

Summary

Tobacco heating products (THPs) have reduced toxicant emissions relative to cigarettes. THPs are continually evolving, but safety and efficacy studies on each new variant involve considerable resources. As employed by the pharmaceutical industry, a “bridging” process could be used to demonstrate product equivalence.

Therefore, we investigated the feasibility of a bridging approach by evaluating aerosol emissions and in vitro cytotoxicity of five variant THPs in relation to a base product. All products were compared to a reference cigarette and a commercial benchmark. Relative to smoke, chemical reductions in THP aerosols were comparable among the THPs at 94–97%. The aerosols showed similar cytotoxicity in human lung tissues exposed at the air-liquid interface (p = 0.8378) but were significantly less toxic than smoke (p = 0.04). Relative to the THP benchmark, variant THPs showed lower cytotoxicity (p = 0.0141). Emissions and cytotoxicity data demonstrated that the variant THPs were comparable to the base THP, irrespective of consumable format or flavour. This dataset demonstrates the feasibility of a bridging approach and can inform an evidence-based strategy in developing sufficient data to predict similarity against an already established dataset. Therefore, avoiding repetition of vast data generation could ease authorisation requirements of newer products. Finally, we propose that more work is required to understand chemical, biological (in vitro), human consumption, and clinical data before the equivalence of these products (and others) can be definitively demonstrated. Future studies maybe needed to assess additional chemical and biological outputs and all data will need to be contextualised against human consumption data in terms of a bridging framework.

Keywords

  • analytical
  • tobacco heating products
  • cytotoxicity
Open Access

Nicotine and Inflammatory Disease in Humans: A Systematic Review

Published Online: 16 Apr 2022
Page range: 10 - 24

Abstract

Summary Introduction

Previous studies have shown that nicotine interacts in inflammatory pathways and may have both pro- and anti-inflammatory actions. The aim of this study was to carry out a systematic review of publications investigating the inflammatory effects of nicotine in models of human disease.

Methods

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklists were followed during the design and implementation of this study. Searches were carried out across PubMed, Science Direct, and the Cochrane Library. Articles were included if they were published in English, in peer-reviewed journals, reported an effect of nicotine in the treatment of a clinical condition, experimental studies or clinical trials which investigated an effect of nicotine administration in patients with a clinical condition or epidemiological studies which investigated an effect of nicotine administration in patients with a clinical condition.

Results

Thirty-eight studies were identified and categorized into disease areas before systematic review. Nineteen studies were related to digestive diseases (primarily Crohn’s disease and ulcerative colitis), six to atherosclerosis, five to skin and healing, four to pain and infection, three to pulmonary sarcoidosis, and three to multiple sclerosis (one study reported data on three disease areas). Risk of bias assessment was not carried out, but the general quality of the studies was low, mostly offering preliminary data in small numbers of participants. No consistent effects of nicotine treatment (primarily through use of transdermal nicotine patches or nicotine chewing gums) were reported across any of the disease models.

Conclusion

No reliable evidence of a pro- or anti-inflammatory effect of nicotine was observed in patients with any of the diseases included in this study.

Open Access

Does the Level of NNK in Tobacco and Tobacco Products Depend on the Level of Pseudooxynicotine or of Nicotine-1′-N-Oxide?

Published Online: 16 Apr 2022
Page range: 25 - 34

Abstract

Summary

4-(N’-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potentially carcinogenic tobacco specific nitrosamine (TSNA) and an important compound in the Harmful and Potentially Harmful Constituents (HPHCs) list of U.S. Food and Drug Administration (FDA). For this reason, significant effort is being made for an understanding of the formation of this compound and for the reduction of its level in tobacco products. Formation of NNK is assumed to be the result of nitrosation of 4-(methylamino)-1-(3-pyridyl)-1-butanone (pseudooxynicotine or PON). Present study evaluated the correlation between the levels of NNK and those of PON in a variety of tobaccos and tobacco products. Since nicotine-1′-N-oxide can be involved in the formation of PON, the correlation of the levels of this compound with the levels of NNK was also evaluated. Two original methods were developed for the quantitation of PON in tobacco and tobacco products and a well-established method has been used for the analysis of NNK. The correlation between the levels of NNK with that of PON was proven to be very poor. The same result was obtained for the correlation between NNK levels and nicotine-1′-N-oxide. This indicated that a higher level of PON or of nicotine-1′-N-oxide in tobacco or tobacco products does not lead to a higher level of NNK. The study does not prove that NNK in tobacco or tobacco products is not generated via PON, but it demonstrated that the limiting factor in the formation of NNK in tobacco and tobacco products is not the level of PON or that of nicotine-1′-N-oxide, and other factors are responsible for the effectiveness of NNK formation.

Open Access

Estimated Public Health Gains From German Smokers Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling

Published Online: 05 May 2022
Page range: 35 - 51

Abstract

Summary Background

Smoking is associated with cancer and cardio-respiratory mortality. Reducing smoking prevalence will lead to fewer deaths and more life-years. Here, we estimate the impact of hypothetical introduction of reduced-risk products (heat-not-burn products and e-cigarettes) in Germany from 1995 to 2015 on mortality from lung cancer, chronic obstructive pulmonary disease, ischaemic heart disease, and stroke in men and women aged 30–79 years.

Methods

We used a previously described population health impact model, with individuals with a defined baseline cigarette smoking distribution followed under a “Null Scenario”, with reduced-risk products never introduced, and various “Alternative Scenarios” where they are. Transition probabilities allow product use to change annually, with the individual product histories allowing estimation of risks, relative to never users, which are then used to estimate reductions in deaths and life-years lost for each Alternative Scenario.

Results

In the Null Scenario, we estimated 852,000 deaths from cigarette smoking (42,600 per year), with 8.61 million life-years lost. Had everyone ceased smoking in 1995, and with no use of reduced-risk products, these numbers would reduce by 217,000 and 2.88 million. Compared to the Null Scenario, the estimated reductions would be 159,000 and 2.06 million with an immediate complete switch to heat-not-burn products and 179,000 and 2.34 million with 50% of smokers immediately switching to heat-not-burn products and 50% to e-cigarettes. In four Scenarios with a more gradual switch, the estimated decreases were 39,800–81,000 deaths and 0.50–1.05 million life-years, representing 17.5%–37.5% of the effect of immediate cessation in 1995. These estimates assume that switching to heat-not-burn products and e-cigarettes involves risk decreases of 80% and 95% of those from quitting, respectively. The reductions in mortality would be greater with more diseases and a wider age range considered or with a longer follow-up period, as the decreases increased markedly with time. Various limitations are discussed, none affecting the conclusion that introducing these new products into Germany in 1995 could have substantially reduced deaths and life-years lost.

Conclusions

Deaths from cigarette smoking could be substantially reduced not only by cessation but additionally by switching to reduced-risk products. Respective public health campaigns might increase such switching.

Keywords

  • Smoking
  • public health
  • modelling
  • lung cancer
  • chronic obstructive pulmonary disease
  • ischaemic heart disease
  • stroke
  • e-cigarettes
  • heat-not-burn product
  • Germany
Open Access

Estimated Public Health Gains From Smokers in Germany Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling by Socioeconomic Group

Published Online: 05 May 2022
Page range: 52 - 67

Abstract

Summary Background

We previously estimated the impact of introducing heat-not-burn products and e-cigarettes in Germany on smoking-related disease mortality in men and women aged 30–79 years between 1995 and 2015. Here, we estimate the impact by socioeconomic group.

Methods

Individuals with a defined baseline cigarette smoking distribution were followed under a “Null Scenario” (no reduced-risk products) and “Alternative Scenarios” (reduced-risk products introduced). Transition probabilities allowed estimation of annual product use changes, with individual product histories used to estimate reductions in deaths and life-years lost. Here, however, individuals were classified into two socioeconomic groups defined by income and education, with allowance for variation by group in initial smoking prevalence and the probability of changing product use, or of changing socioeconomic group.

Results

With no allowance for socioeconomic group, deaths would have reduced by 217,000 (from 852,000 for continued smoking) had everyone immediately ceased smoking in 1995 and by 40,000 to 179,000 had one or two types of reduced-risk products – the heat-not-burn product and the e-cigarette – been adopted by smokers to varying extents. With such allowance, we estimate substantial drops in each socioeconomic group. Where all cigarette smokers switched immediately, half of them to heat-not-burn products, half to e-cigarettes, the estimated drops in deaths were 60,000 in group A (higher socioeconomic group) and 122,000 in group B (lower), about 82% of the drops associated with immediate cessation (73,000 in A and 148,000 in B). With more gradual conversion, the drops were 26,648 in A and 53,000 in B, about 35% of those from cessation. The drops in deaths and life-years saved were about 2 and 1.5 times higher in group B, respectively, associated with its greater numbers, older age, and higher smoking prevalence. The estimated reductions would increase upon considering more diseases, a wider age range, or longer follow-up. Methodological limitations would not affect the conclusion that introducing these products in 1995 in Germany could have substantially reduced deaths and life-years lost in both groups, more so in B.

Conclusions

Although cessation is optimal for reducing mortality, switching to reduced-risk products also provides substantial health gains. A public health approach encouraging lower socioeconomic group smokers to switch to reduced-risk products could diminish smoking-related health inequalities relative to continued smoking.

Keywords

  • Smoking
  • public health
  • smoking-related disease
  • modelling
  • respiratory disease
  • cardiovascular disease
  • e-cigarettes
  • heat-not-burn products
  • socioeconomic group
  • Germany
Open Access

Editors’ Note

Published Online: 05 May 2022
Page range: 1 - 1

Abstract

0 Articles
Open Access

An Experimental Analytical and In Vitro Approach to Bridge Between Different Heated Tobacco Product Variants

Published Online: 16 Apr 2022
Page range: 1 - 9

Abstract

Summary

Tobacco heating products (THPs) have reduced toxicant emissions relative to cigarettes. THPs are continually evolving, but safety and efficacy studies on each new variant involve considerable resources. As employed by the pharmaceutical industry, a “bridging” process could be used to demonstrate product equivalence.

Therefore, we investigated the feasibility of a bridging approach by evaluating aerosol emissions and in vitro cytotoxicity of five variant THPs in relation to a base product. All products were compared to a reference cigarette and a commercial benchmark. Relative to smoke, chemical reductions in THP aerosols were comparable among the THPs at 94–97%. The aerosols showed similar cytotoxicity in human lung tissues exposed at the air-liquid interface (p = 0.8378) but were significantly less toxic than smoke (p = 0.04). Relative to the THP benchmark, variant THPs showed lower cytotoxicity (p = 0.0141). Emissions and cytotoxicity data demonstrated that the variant THPs were comparable to the base THP, irrespective of consumable format or flavour. This dataset demonstrates the feasibility of a bridging approach and can inform an evidence-based strategy in developing sufficient data to predict similarity against an already established dataset. Therefore, avoiding repetition of vast data generation could ease authorisation requirements of newer products. Finally, we propose that more work is required to understand chemical, biological (in vitro), human consumption, and clinical data before the equivalence of these products (and others) can be definitively demonstrated. Future studies maybe needed to assess additional chemical and biological outputs and all data will need to be contextualised against human consumption data in terms of a bridging framework.

Keywords

  • analytical
  • tobacco heating products
  • cytotoxicity
Open Access

Nicotine and Inflammatory Disease in Humans: A Systematic Review

Published Online: 16 Apr 2022
Page range: 10 - 24

Abstract

Summary Introduction

Previous studies have shown that nicotine interacts in inflammatory pathways and may have both pro- and anti-inflammatory actions. The aim of this study was to carry out a systematic review of publications investigating the inflammatory effects of nicotine in models of human disease.

Methods

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklists were followed during the design and implementation of this study. Searches were carried out across PubMed, Science Direct, and the Cochrane Library. Articles were included if they were published in English, in peer-reviewed journals, reported an effect of nicotine in the treatment of a clinical condition, experimental studies or clinical trials which investigated an effect of nicotine administration in patients with a clinical condition or epidemiological studies which investigated an effect of nicotine administration in patients with a clinical condition.

Results

Thirty-eight studies were identified and categorized into disease areas before systematic review. Nineteen studies were related to digestive diseases (primarily Crohn’s disease and ulcerative colitis), six to atherosclerosis, five to skin and healing, four to pain and infection, three to pulmonary sarcoidosis, and three to multiple sclerosis (one study reported data on three disease areas). Risk of bias assessment was not carried out, but the general quality of the studies was low, mostly offering preliminary data in small numbers of participants. No consistent effects of nicotine treatment (primarily through use of transdermal nicotine patches or nicotine chewing gums) were reported across any of the disease models.

Conclusion

No reliable evidence of a pro- or anti-inflammatory effect of nicotine was observed in patients with any of the diseases included in this study.

Open Access

Does the Level of NNK in Tobacco and Tobacco Products Depend on the Level of Pseudooxynicotine or of Nicotine-1′-N-Oxide?

Published Online: 16 Apr 2022
Page range: 25 - 34

Abstract

Summary

4-(N’-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potentially carcinogenic tobacco specific nitrosamine (TSNA) and an important compound in the Harmful and Potentially Harmful Constituents (HPHCs) list of U.S. Food and Drug Administration (FDA). For this reason, significant effort is being made for an understanding of the formation of this compound and for the reduction of its level in tobacco products. Formation of NNK is assumed to be the result of nitrosation of 4-(methylamino)-1-(3-pyridyl)-1-butanone (pseudooxynicotine or PON). Present study evaluated the correlation between the levels of NNK and those of PON in a variety of tobaccos and tobacco products. Since nicotine-1′-N-oxide can be involved in the formation of PON, the correlation of the levels of this compound with the levels of NNK was also evaluated. Two original methods were developed for the quantitation of PON in tobacco and tobacco products and a well-established method has been used for the analysis of NNK. The correlation between the levels of NNK with that of PON was proven to be very poor. The same result was obtained for the correlation between NNK levels and nicotine-1′-N-oxide. This indicated that a higher level of PON or of nicotine-1′-N-oxide in tobacco or tobacco products does not lead to a higher level of NNK. The study does not prove that NNK in tobacco or tobacco products is not generated via PON, but it demonstrated that the limiting factor in the formation of NNK in tobacco and tobacco products is not the level of PON or that of nicotine-1′-N-oxide, and other factors are responsible for the effectiveness of NNK formation.

Open Access

Estimated Public Health Gains From German Smokers Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling

Published Online: 05 May 2022
Page range: 35 - 51

Abstract

Summary Background

Smoking is associated with cancer and cardio-respiratory mortality. Reducing smoking prevalence will lead to fewer deaths and more life-years. Here, we estimate the impact of hypothetical introduction of reduced-risk products (heat-not-burn products and e-cigarettes) in Germany from 1995 to 2015 on mortality from lung cancer, chronic obstructive pulmonary disease, ischaemic heart disease, and stroke in men and women aged 30–79 years.

Methods

We used a previously described population health impact model, with individuals with a defined baseline cigarette smoking distribution followed under a “Null Scenario”, with reduced-risk products never introduced, and various “Alternative Scenarios” where they are. Transition probabilities allow product use to change annually, with the individual product histories allowing estimation of risks, relative to never users, which are then used to estimate reductions in deaths and life-years lost for each Alternative Scenario.

Results

In the Null Scenario, we estimated 852,000 deaths from cigarette smoking (42,600 per year), with 8.61 million life-years lost. Had everyone ceased smoking in 1995, and with no use of reduced-risk products, these numbers would reduce by 217,000 and 2.88 million. Compared to the Null Scenario, the estimated reductions would be 159,000 and 2.06 million with an immediate complete switch to heat-not-burn products and 179,000 and 2.34 million with 50% of smokers immediately switching to heat-not-burn products and 50% to e-cigarettes. In four Scenarios with a more gradual switch, the estimated decreases were 39,800–81,000 deaths and 0.50–1.05 million life-years, representing 17.5%–37.5% of the effect of immediate cessation in 1995. These estimates assume that switching to heat-not-burn products and e-cigarettes involves risk decreases of 80% and 95% of those from quitting, respectively. The reductions in mortality would be greater with more diseases and a wider age range considered or with a longer follow-up period, as the decreases increased markedly with time. Various limitations are discussed, none affecting the conclusion that introducing these new products into Germany in 1995 could have substantially reduced deaths and life-years lost.

Conclusions

Deaths from cigarette smoking could be substantially reduced not only by cessation but additionally by switching to reduced-risk products. Respective public health campaigns might increase such switching.

Keywords

  • Smoking
  • public health
  • modelling
  • lung cancer
  • chronic obstructive pulmonary disease
  • ischaemic heart disease
  • stroke
  • e-cigarettes
  • heat-not-burn product
  • Germany
Open Access

Estimated Public Health Gains From Smokers in Germany Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling by Socioeconomic Group

Published Online: 05 May 2022
Page range: 52 - 67

Abstract

Summary Background

We previously estimated the impact of introducing heat-not-burn products and e-cigarettes in Germany on smoking-related disease mortality in men and women aged 30–79 years between 1995 and 2015. Here, we estimate the impact by socioeconomic group.

Methods

Individuals with a defined baseline cigarette smoking distribution were followed under a “Null Scenario” (no reduced-risk products) and “Alternative Scenarios” (reduced-risk products introduced). Transition probabilities allowed estimation of annual product use changes, with individual product histories used to estimate reductions in deaths and life-years lost. Here, however, individuals were classified into two socioeconomic groups defined by income and education, with allowance for variation by group in initial smoking prevalence and the probability of changing product use, or of changing socioeconomic group.

Results

With no allowance for socioeconomic group, deaths would have reduced by 217,000 (from 852,000 for continued smoking) had everyone immediately ceased smoking in 1995 and by 40,000 to 179,000 had one or two types of reduced-risk products – the heat-not-burn product and the e-cigarette – been adopted by smokers to varying extents. With such allowance, we estimate substantial drops in each socioeconomic group. Where all cigarette smokers switched immediately, half of them to heat-not-burn products, half to e-cigarettes, the estimated drops in deaths were 60,000 in group A (higher socioeconomic group) and 122,000 in group B (lower), about 82% of the drops associated with immediate cessation (73,000 in A and 148,000 in B). With more gradual conversion, the drops were 26,648 in A and 53,000 in B, about 35% of those from cessation. The drops in deaths and life-years saved were about 2 and 1.5 times higher in group B, respectively, associated with its greater numbers, older age, and higher smoking prevalence. The estimated reductions would increase upon considering more diseases, a wider age range, or longer follow-up. Methodological limitations would not affect the conclusion that introducing these products in 1995 in Germany could have substantially reduced deaths and life-years lost in both groups, more so in B.

Conclusions

Although cessation is optimal for reducing mortality, switching to reduced-risk products also provides substantial health gains. A public health approach encouraging lower socioeconomic group smokers to switch to reduced-risk products could diminish smoking-related health inequalities relative to continued smoking.

Keywords

  • Smoking
  • public health
  • smoking-related disease
  • modelling
  • respiratory disease
  • cardiovascular disease
  • e-cigarettes
  • heat-not-burn products
  • socioeconomic group
  • Germany
Open Access

Editors’ Note

Published Online: 05 May 2022
Page range: 1 - 1

Abstract