To the Editor:
We read with great interest the research article by Miyashita et al. , in which the authors showed that e-cigarette aerosol emissions increase platelet-activating factor receptor (PAFR) expression and, consequently, Streptococcus pneumoniae adhesion to human airway epithelial cells. These findings led authors to conclude that e-cigarette use has the potential to increase susceptibility to pneumococcal infection. Unfortunately, the evidence presented in the paper is inadequate to provide much confidence in this conclusion.
Although the parameters for the generation of e-cigarette aerosol emissions for the in vitro exposure studies have not been specified, we estimated a very short inter-puff period (<10 s) for a round of 25 consecutive puffs during the 5-min procedure. Under such extreme experimental conditions, high-powered e-cigarettes are known to generate high levels of toxicants . That this is the case is also confirmed by the high levels of metals in the e-cigarette vapour extract reported by the authors themselves (see table S1 of that article). Therefore, it is not surprising that under abnormal conditions of use, e-cigarette vapour has the capacity to induce oxidative stress. We conclude that the in vitro experimental conditions of the study are unlikely to reflect normal conditions of airway exposure. The use of standardised regime  to generate e-cigarette aerosol emissions is recommended for more realistic in vitro experiments.
An additional challenge in interpreting the results is the highly variable level of adhesiveness of S. pneumoniae strain D39 to human airway epithelial cells (A549). Differences of several orders of magnitude have been reported by the same researchers and by others under similar experimental conditions [1, 4–7]. Consequently, even though statistically significant, findings by Miyashita et al.  cast more doubts than certainties about their effective microbiological predictivity.
The observed small increase in nasal epithelial PAFR expression shown after 5 min of vaping is essentially an indication of a nonspecific, transient cellular response, and is of no clinical relevance or prognostic significance. That this is the case is also confirmed by the authors’ own data. Nasal epithelial PAFR expression at baseline was no different between exclusive regular vapers and healthy never-smokers controls.
Last but not least, given that persistent airway exposure to cigarette smoke is known to promote infection susceptibility, it is not surprising that abstaining from tobacco smoking by switching to e-cigarettes may explain an attenuation in respiratory infections . Evidence from real-life surveys  and clinical studies of respiratory patients [10, 11] supporting a marked decrease in respiratory infections with regular e-cigarette use is in stark contrast with the concerns raised by Miyashita et al.  that e-cigarette use has the potential to increase susceptibility to pneumococcal infection. Moreover, despite millions of regular e-cigarette users worldwide, there has been no evidence of new emerging pneumonia outbreaks in recent years or reports of infectious pneumonia in the medical literature.