On 2017 Feb 10, Richard Holliday commented:

As highlighted by the previous comments there are several weaknesses with this study. I would like to add a few further observations:

-There is inadequate choice of e-liquids and controls. The cells were exposed to three conditions: air control, e-liquid [tobacco, 16mg] and e-liquid [menthol, 0mg nicotine]. There are two variables here (nicotine concentration and flavour) making any analysis of the results impossible.

-In the methods, a menthol, 13-16 mg nicotine e-liquid is mentioned but this is not mentioned anywhere else in the paper, nor presented in the results.

-The main conclusion of this paper is that ‘flavoured e-cigs’ gave a ‘greater response’. As there was no unflavoured control this conclusion is invalid. Likewise, if the authors are trying to say ‘menthol flavour’ gave a greater response than ‘tobacco flavour’ this is again invalid as nicotine concentration is a confounding factor in their study design.

The UK E-cigarette Research Forum (an initiative developed by Cancer Research UK in partnership with Public Health England and the UK Centre for Tobacco and Alcohol Studies) recently reviewed this paper. The full review can be found here (see review 5 with further comments in the final paragraph of the overview).

On 2016 Dec 27, Clive Bates commented:

There are several weaknesses in this paper and the surrounding commentary, and it caused unwarranted alarmist news coverage, which has not been corrected: New e-cigarettes alert as experts warn that the exposure to chemicals could trigger severe gum disease and even increase the risk of mouth cancer, Daily Mail, 17 December 2016.

Comparators. The study lacks adequate comparators - for example, coffee and/or cigarette smoke could have been used. That would have allowed these observations to be placed in a meaningful comparative context. Given that the vast majority of users or potential users are smokers, the comparison with smoking is most relevant. Further, if the effect of vaping is no different to that arising from an everyday habit like drinking coffee then we would be correspondingly reassured.

Interpretation of cell study. These effects on cells in vitro will not necessarily translate into material oral health risks in live subjects and the authors do not show evidence that the effects observed at the magnitudes measured are a realistic proxy for human gum disease risk. If human cells are exposed to any aversive environment, some effect is likely. But it is heroic to interpolate that to a human disease risk associated with normal use of the product. Ames (Ames BN, 2000) explains why:

Humans have many natural defenses that buffer against normal exposures to toxins and these are usually general, rather than tailored for each specific chemical. Thus they work against both natural and synthetic chemicals. Examples of general defenses include the continuous shedding of cells exposed to toxins. The surface layers of the mouth, esophagus, stomach, intestine, colon, skin and lungs are discarded every few days; DNA repair enzymes, which repair DNA that was damaged from many different sources; and detoxification enzymes of the liver and other organs which generally target classes of chemicals rather than individual chemicals.

Professor Brad Rodu elaborates further: Imaginary Hobgoblins From E-Cigarette Liquid Lab Tests, February 2016.

Methodology The lead author's commentary speaks of 'burning' e-liquid and 'smoking' e-cigarettes. This does not inspire much confidence that the authors understand this non-combustible technology or that they have operated the device in realistic conditions for humans. There have been other studies where the devices have been operated at higher temperature than would be possible for human users, and then measurements of unrealistic levels of thermal decomposition products reported - see for example, Jensen RP, 2015. The authors provide little reassurance that have not fallen into the same methodological pit. The discussion of the methodology followed is thin and insufficient to allow replication.

Overpromoting results. So in the absence of useful comparators and no link from these observations to disease risk it hard to see what this study adds. Further, it is unclear how it justifies the alarmist over-confident commentary First-ever Study Shows E-cigarettes Cause Damage to Gum Tissue that accompanied it and led to the news coverage cited above. This promotes the implicit claim (in the absence of an explicit caveat) that e-cigarette use would damage the gums in the mouth of a living person.

Failure to provide a rounded view when communicating with the public. Other studies suggest that switching from smoking to vaping has a beneficial effect on oral health. For example, see Tatullo M, 2016:

At the end of the study, we registered a progressive improvement in the periodontal indexes, as well as in the general health perception. Finally, many patients reported an interesting reduction in the need to smoke.In the light of this pilot study, the e-cigarette can be considered as a valuable alternative to tobacco cigarettes, but with a positive impact on periodontal and general health status.

And this study, Wadia R, 2016 which found an increase in gingival inflammation when tobacco smokers switched from smoking to vaping for two weeks but noted that this was similar to the effects observed when people quit smoking:

The clinical findings from the current study are similar to those that occur following verified smoking cessation. For example, during a successful period of quitting smoking, gingival bleeding doubled from 16% to 32% in a group of 27 smokers followed for 4–6 weeks, even though there were some improvements in the subjects’ plaque control. Results from this study are also consistent with studies that suggest a fairly rapid recovery of the inflammatory response following smoking cessation. (emphases added)

The benefits of switching from smoking to vaping are pervasive and include improvements in oral health.

On 2016 Dec 27, Clive Bates commented:

There are several weaknesses in this paper and the surrounding commentary, and it caused unwarranted alarmist news coverage, which has not been corrected: New e-cigarettes alert as experts warn that the exposure to chemicals could trigger severe gum disease and even increase the risk of mouth cancer, Daily Mail, 17 December 2016.

Comparators. The study lacks adequate comparators - for example, coffee and/or cigarette smoke could have been used. That would have allowed these observations to be placed in a meaningful comparative context. Given that the vast majority of users or potential users are smokers, the comparison with smoking is most relevant. Further, if the effect of vaping is no different to that arising from an everyday habit like drinking coffee then we would be correspondingly reassured.

Interpretation of cell study. These effects on cells in vitro will not necessarily translate into material oral health risks in live subjects and the authors do not show evidence that the effects observed at the magnitudes measured are a realistic proxy for human gum disease risk. If human cells are exposed to any aversive environment, some effect is likely. But it is heroic to interpolate that to a human disease risk associated with normal use of the product. Ames (Ames BN, 2000) explains why:

Humans have many natural defenses that buffer against normal exposures to toxins and these are usually general, rather than tailored for each specific chemical. Thus they work against both natural and synthetic chemicals. Examples of general defenses include the continuous shedding of cells exposed to toxins. The surface layers of the mouth, esophagus, stomach, intestine, colon, skin and lungs are discarded every few days; DNA repair enzymes, which repair DNA that was damaged from many different sources; and detoxification enzymes of the liver and other organs which generally target classes of chemicals rather than individual chemicals.

Professor Brad Rodu elaborates further: Imaginary Hobgoblins From E-Cigarette Liquid Lab Tests, February 2016.

Methodology The lead author's commentary speaks of 'burning' e-liquid and 'smoking' e-cigarettes. This does not inspire much confidence that the authors understand this non-combustible technology or that they have operated the device in realistic conditions for humans. There have been other studies where the devices have been operated at higher temperature than would be possible for human users, and then measurements of unrealistic levels of thermal decomposition products reported - see for example, Jensen RP, 2015. The authors provide little reassurance that have not fallen into the same methodological pit. The discussion of the methodology followed is thin and insufficient to allow replication.

Overpromoting results. So in the absence of useful comparators and no link from these observations to disease risk it hard to see what this study adds. Further, it is unclear how it justifies the alarmist over-confident commentary First-ever Study Shows E-cigarettes Cause Damage to Gum Tissue that accompanied it and led to the news coverage cited above. This promotes the implicit claim (in the absence of an explicit caveat) that e-cigarette use would damage the gums in the mouth of a living person.

Failure to provide a rounded view when communicating with the public. Other studies suggest that switching from smoking to vaping has a beneficial effect on oral health. For example, see Tatullo M, 2016:

At the end of the study, we registered a progressive improvement in the periodontal indexes, as well as in the general health perception. Finally, many patients reported an interesting reduction in the need to smoke.In the light of this pilot study, the e-cigarette can be considered as a valuable alternative to tobacco cigarettes, but with a positive impact on periodontal and general health status.

And this study, Wadia R, 2016 which found an increase in gingival inflammation when tobacco smokers switched from smoking to vaping for two weeks but noted that this was similar to the effects observed when people quit smoking:

The clinical findings from the current study are similar to those that occur following verified smoking cessation. For example, during a successful period of quitting smoking, gingival bleeding doubled from 16% to 32% in a group of 27 smokers followed for 4–6 weeks, even though there were some improvements in the subjects’ plaque control. Results from this study are also consistent with studies that suggest a fairly rapid recovery of the inflammatory response following smoking cessation. (emphases added)

The benefits of switching from smoking to vaping are pervasive and include improvements in oral health.

On 2017 Feb 10, Richard Holliday commented:

As highlighted by the previous comments there are several weaknesses with this study. I would like to add a few further observations:

-There is inadequate choice of e-liquids and controls. The cells were exposed to three conditions: air control, e-liquid [tobacco, 16mg] and e-liquid [menthol, 0mg nicotine]. There are two variables here (nicotine concentration and flavour) making any analysis of the results impossible.

-In the methods, a menthol, 13-16 mg nicotine e-liquid is mentioned but this is not mentioned anywhere else in the paper, nor presented in the results.

-The main conclusion of this paper is that ‘flavoured e-cigs’ gave a ‘greater response’. As there was no unflavoured control this conclusion is invalid. Likewise, if the authors are trying to say ‘menthol flavour’ gave a greater response than ‘tobacco flavour’ this is again invalid as nicotine concentration is a confounding factor in their study design.

The UK E-cigarette Research Forum (an initiative developed by Cancer Research UK in partnership with Public Health England and the UK Centre for Tobacco and Alcohol Studies) recently reviewed this paper. The full review can be found here (see review 5 with further comments in the final paragraph of the overview).