On 2016 May 02, Riccardo Polosa commented:

The assessment of pulmonary function and airway inflammation in healthy smokers before and after e-cigarette use by Vardavas and colleagues[1], is a perfect example of what clinical researchers should do to expand the current knowledge base of these products. Good quality research on e-cigarettes must be conducted in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Unfortunately, the work illustrated by Vardavas and colleagues are not conclusive due to the small number of subjects studied, the choice of study outcomes of unclear clinical relevance, together with the lack of appropriate controls.

The authors state that the e-cigarettes tested in their study <have immediate adverse physiologic effects after short term use that are similar to some of the effects seen with tobacco smoking>. The reported 16% decrease in FeNO (i.e. 2.1ppb in absolute term!) and 11% increase in peripheral flow resistance (IOS) (i.e. 0.025kPa/L/s in absolute term!) after e-cigarette use from baseline are so small and well within tests variability[2,3] that it is highly unlikely to have meaningful adverse effects. Of note, no changes were detected by canonical pulmonary function testing after e-cigarette use. Toxicology characterization demonstrates that their primary components (i.e. water, propylene glycol, and nicotine) are not harmful, and this is in agreement with the detailed analysis of e-cigarette toxicology by Cahn and Siegel[4]. Moreover, clinical safety assessment of one such product showed only minor side effects (e.g. oral irritation and dry cough) in the initial few weeks of use[5] and switching to e-cigarette use led to a near-normalization of exhaled carbon monoxide levels[5]. Thus, authors’ conclusions are not fully supported by the data, and the accumulating evidence rather supports a good safety profile for these products.

The small changes in FeNO and IOS may be non specific. The mist generated by the e-cigarette per se might have contributed to these changes. In a series of pilot studies we have noted that nebulization of saline can reduce FeNO up to 25% from baseline (personal observation). Consequently, authors should have included a more pertinent control (e.g. saline mist generated by an ultrasonic nebulizer) in their study. Also, another reasonable comparator that should have been used as control could have been the participants’ own brand cigarette.

We agree that large and carefully conducted long-term prospective studies will be required before a definite answer about safety of these products can be formulated[6]. Nevertheless, it is not in the best interests of public health to halt marketing of e-cigarettes until these long-term studies are completed. Obviously, other valid options for tackling nicotine dependence in smokers exist, but it is still a personal choice how to reduce or eliminate his or her own smoking. Switching to an e-cigarette is a far better option than smoking.

References

1. Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012 Jun;141(6):1400-6.
2. Oostveen E, MacLeod D, Lorino H, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J 2003; 22:1026-1041.
3. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-15.
4. Cahn Z, Siegel M. Electronic cigarettes as a harm reduction strategy for tobacco control: A step forward or a repeat of past mistakes? J Public Health Policy. 2011;32(1):16-31.
5. Polosa R, Caponnetto P, Morjaria JB, Papale G, Campagna D, Russo C. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011;11:786.
6. Caponnetto P, Campagna D, Papale G, Russo C, Polosa R. The emerging phenomenon of electronic cigarettes. Expert Rev Respir Med. 2012 Feb;6(1):63-74.

On 2016 May 02, Riccardo Polosa commented:

The assessment of pulmonary function and airway inflammation in healthy smokers before and after e-cigarette use by Vardavas and colleagues[1], is a perfect example of what clinical researchers should do to expand the current knowledge base of these products. Good quality research on e-cigarettes must be conducted in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Unfortunately, the work illustrated by Vardavas and colleagues are not conclusive due to the small number of subjects studied, the choice of study outcomes of unclear clinical relevance, together with the lack of appropriate controls.

The authors state that the e-cigarettes tested in their study <have immediate adverse physiologic effects after short term use that are similar to some of the effects seen with tobacco smoking>. The reported 16% decrease in FeNO (i.e. 2.1ppb in absolute term!) and 11% increase in peripheral flow resistance (IOS) (i.e. 0.025kPa/L/s in absolute term!) after e-cigarette use from baseline are so small and well within tests variability[2,3] that it is highly unlikely to have meaningful adverse effects. Of note, no changes were detected by canonical pulmonary function testing after e-cigarette use. Toxicology characterization demonstrates that their primary components (i.e. water, propylene glycol, and nicotine) are not harmful, and this is in agreement with the detailed analysis of e-cigarette toxicology by Cahn and Siegel[4]. Moreover, clinical safety assessment of one such product showed only minor side effects (e.g. oral irritation and dry cough) in the initial few weeks of use[5] and switching to e-cigarette use led to a near-normalization of exhaled carbon monoxide levels[5]. Thus, authors’ conclusions are not fully supported by the data, and the accumulating evidence rather supports a good safety profile for these products.

The small changes in FeNO and IOS may be non specific. The mist generated by the e-cigarette per se might have contributed to these changes. In a series of pilot studies we have noted that nebulization of saline can reduce FeNO up to 25% from baseline (personal observation). Consequently, authors should have included a more pertinent control (e.g. saline mist generated by an ultrasonic nebulizer) in their study. Also, another reasonable comparator that should have been used as control could have been the participants’ own brand cigarette.

We agree that large and carefully conducted long-term prospective studies will be required before a definite answer about safety of these products can be formulated[6]. Nevertheless, it is not in the best interests of public health to halt marketing of e-cigarettes until these long-term studies are completed. Obviously, other valid options for tackling nicotine dependence in smokers exist, but it is still a personal choice how to reduce or eliminate his or her own smoking. Switching to an e-cigarette is a far better option than smoking.

References

1. Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012 Jun;141(6):1400-6.
2. Oostveen E, MacLeod D, Lorino H, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J 2003; 22:1026-1041.
3. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-15.
4. Cahn Z, Siegel M. Electronic cigarettes as a harm reduction strategy for tobacco control: A step forward or a repeat of past mistakes? J Public Health Policy. 2011;32(1):16-31.
5. Polosa R, Caponnetto P, Morjaria JB, Papale G, Campagna D, Russo C. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011;11:786.
6. Caponnetto P, Campagna D, Papale G, Russo C, Polosa R. The emerging phenomenon of electronic cigarettes. Expert Rev Respir Med. 2012 Feb;6(1):63-74.