Current Knowledge and Challenges of Particle Size Measurements of Mainstream E-Cigarette Aerosols and Their Implication on Respiratory Dosimetry

Round 1

Reviewer 1 Report

This is the most comprehensive review on electronic nicotine delivery system aerosol physics, aerosol physical characteristics and relationship of physical characteristics of aerosols to function of the devices that produce the aerosols, and pulmonary aerosol deposition models that I have read to date. The only recommendation I have for the authors is that they reconsider the statement in lines 84-85:

1. Whether mass distribution is more useful than particle number distribution depends on the purpose of studying the exposure. As discussed in this manuscript, smaller particles, such as nanoparticles, deposit more deeply in the lung. When characteristics of the particles other than droplet size, such as particle toxicity, whether it is predominantly solid or liquid, are taken into consideration, particle number may be considered much more important than particle mass distribution. Between 25 and 30 years ago, Ferin et al, Oberdorster et al., Shimada et al., Zhang et al., and others have shown that due to greater ratio of surface area to particle diameter, smaller particles not only penetrate deeper in the airways, but if the particles are solid or toxic, they also exhibit greater toxicity or immunotoxicity characteristics per unit mass. Particles smaller than 100 nm were also shown by the above authors to penetrate lung epithelia and enter the interstitial tissue and passively enter cells, whereas larger particles more often were eliminated by macrophages and the mucociliary elevator in the bronchi. Therefore the number of particles of a given size (particle number distribution) may indeed be considered more highly important than particle mass distribution, depending on the purpose of the study. Therefore I recommend the authors reword the statement in lines 84-85.

Author Response

We appreciate the reviewer’s recognition of our work as one of the “most comprehensive reviews on ENDS aerosol physics and its respiratory depositions” We agree with the reviewer that “whether mass distribution is more useful than particle number distribution depends on the purpose of studying the exposure”. We modified the sentence as below

“The mass distribution is another useful indicator to quantify the particle exposure.” (Line 84)

Author Response File: Author Response.pdf

Reviewer 2 Report

The review reports an analysis on electronic cigarettes and the dynamics of particle formation. The formation and type of particles may be the basis of side effects at the level of the respiratory system. Furthermore, the authors point out the problems associated with dosimeters. The authors underline the importance of continuing to investigate the evolution of electronic cigarette technologies to make users more aware of the risks associated with their use.

The review is interesting and full of technical information on the aerosol system of electronic cigarettes. However, in my opinion I would emphasize the effects of e-cigarettes on the respiratory system more.

Author Response

We appreciate the comment from the reviewer that it would be better to “emphasize the effect of e-cigarettes on the respiratory system more”. As the reviewer summarized, the fundamental understanding of electronic cigarettes’ aerosol chemistry, particle physics,  pulmonary depositions and toxicology are prerequisites to understanding the consequential impact on the respiratory system. In this review, we link the particle size measurement of e-cigarette aerosols with its implication on respiratory dosimetry by summarizing the recent modeling results of the deposition of e-cigarette mainstream emissions. The health impacts of e-cigarette have been thoroughly reported and reviewed by many researchers, including a well-known review book published by National Academies of Sciences, as listed below. However, there is still a large gap between the particle size distribution and the effects of e-cigarettes on the respiratory system, given the limitation of particle size measurement and the dosimetry models. That is precisely why this review can contribute to fill the knowledge gap and hopefully inspire future studies in this field. We hope to submit more original studies in this field focusing on the effect of e-cigarette aerosols on the respiratory system, as multiple research projects are ongoing in our lab currently.

Author Response File: Author Response.pdf