Effects of e-cigarette use on exhaled nitric oxide

Friday, 13 June 2014 19:54

Effects of e-cigarette use on exhaled nitric oxide

By Dr Farsalinos

A study was recently published in Toxicology and Applied Pharmacology examining the effects of using e-cigarettes and tobacco cigarettes on exhaled nitric oxide (FeNO). They found that similar reductions in FeNO are observed after e-cigarette and tobacco cigarette use. The authors concluded that in the aspect of FeNO), e-cigarettes are not safer than tobacco cigarettes, and mentioned that this finding is indicative that lung function is affected by e-cigarette use.

The conclusions of the authors are arbitrary and completely wrong. FeNO is a marker of inflammation to the lungs, most commonly used in asthmatics. However, inflammation is characterized by high levels of FeNO. Reductions in FeNO are observed in asthmatics after corticosteroid therapy, indicating that there is a response to the therapy and inflammation is reduced. Low levels are indicative of either no inflammation at all, or is a false negative finding of non-eosinophilic inflammation in patients with symptoms of respiratory disease. In any case, all participants in the study had normal FeNO levels, while a further reduction means absolutely nothing. By definition, it does not mean that there is a decline in lung function, because FeNO cannot be used as a marker of respiratory function; it just measures inflammation.  Moreover, a significant problem in the statistical analysis should be mentioned. In a study evaluating different interventions in the same population, you do NOT use student t-tests but you perform repeated measures ANOVA. I would not expect the journal to accept such an analysis. Finally, it should be mentioned that while this study is inline with findings from Vardavas et al., it is contradictory to findings by Schober et al. and Flouris et al. Schober found elevation in FeNO levels after e-cigarette use. As we explained in a letter to the editor, it is controversial to expect that both a reduction and an elevation of any biomarker mean the same thing!!

Of course, FeNO levels have nothing to do with NO production and effects on the endothelium of the arteries and on cardiovascular disease incidence, and, as mentioned above, do not indicate lung dysfunction. Anyone, making such statements, such as Stanton Glantz, is probably confused and is ignoring some basic facts. For the current study he mentions: “… the fact that exposure to e-cigarette aerosol reduces exhaled NO in the lungs may help explain why people who use e-cigarettes have a drop in lung function.  (The fact that smoke reduces NO production in arteries is an important reason that smoking and passive smoking contribute to heart attacks)”. Amazing statements for a study that did not find any drop in lung function, because they did not measure lung function. Moreover, they did not assess NO production or effects on the endothelium of blood vessels and thus the results are completely irrelevant to the cardiovascular system. Obviously, he is underestimating the intellectual abilities of regulators because he submitted his theories to the FDA as "scientific evidence". 

In the past Glantz was once again shouting about the adverse effects of e-cigarette use when the Schober et al. study was published, which showed the exact opposite results compared to the current study (Schober showed elevated FeNO after e-cigarette use). In that case he mentioned: “They also found increased measures of inflammatory processes in the people using e-cigarettes, which could indicate lung irritation.  (Increase levels of inflammation could also have effects on blood and blood vessels in ways that increase the risk of triggering a heart attack)”.

In reality the data are completely irrelevant to his arguments. No study evaluated any cardiovascular effects and FeNO is not a marker of systemic inflammation. Still, he jumps from the respiratory to the cardiovascular system and back. Finally, he needs to decide what he considers as problem arising from e-cigarette use? Elevated or reduced FeNO?

I must regretfully say that this is not science…