To our knowledge, this is the first study to find a physiologic response after inhaling from an e-cigarette. According to our findings, 5 min of use was sufficient to lead to an increase in lung flow resistance over a range of frequencies and was related to a decrease in Feno concentrations.
Impulse oscillometry as a methodologic approach has been used previously in clinical trials, can be used to diagnose obstructive lung disease, and has been shown to be superior to spirometry measurements during pulmonary assessment.[18–21] This is verified by the fact that e-cigarette usage was associated with increased flow resistance even though spirometry-assessed lung function was deemed normal, a finding corroborated by the fact that IOS can detect oncoming pathophysiologic changes of the respiratory system before spirometry. Indeed, it has been demonstrated that changes in flow resistance precede changes in PEF and FEV1 in experimentally induced airway obstruction, and it is possible that the changes we note in this study may indicate a similar preliminarily health effect. We must state, however, that while the differences within our study are of statistical significance, the clinical changes may be too small to be of major clinical importance (ie, to induce dyspnea or breathing difficulties). However, these measurements were performed after only 5 min of ad lib e-cigarette use. A normal consumer would use the product likely several times a day; thus, the clinical impact might be greater. We hypothesize that the increase in peripheral flow resistance is attributable to the acute narrowing of the diameter of the peripheral airways, which could be due to either localized mucosal edema, smooth muscle contraction (and bronchospasm), or secretions. In the regression analysis, there was a tendency for central airway resistance to increase; however, this was borderline nonstatistically significant. It is possible that increasing the study's sample size might have increased the statistical significance, or we might hypothesize that using an e-cigarette may have a greater impact on peripheral rather than central airways.
A strong point of our findings was that e-cigarette use was associated with an immediate decrease in Feno concentrations. Nitric oxide is a gaseous mediator that has an important role in several physiologic processes in the respiratory tract, including vascular regulation, neurotransmission, host defense, and cytotoxicity. Nitric oxide is an additional marker that has been implicated in the pathophysiology of airway diseases associated with smoking, is strongly correlated with eosinophilic inflammation and bronchial hyperreactivity, and has become an established marker for assessing oxidative stress, indicating the immediate effect e-cigarette usage might have on pulmonary homeostasis.[23–26]
As no standard definition of electronic nicotine delivery system exists, and as different manufacturers use different designs and incorporate a range of ingredients, there is limited evidence on the actual constituents of each brand. Although we identified the clinical changes in lung function due to electronic nicotine delivery system use, we can only hypothesize on the actual substances (or combination of substances) that could have caused the measured effect. One of the substances that was reported to be included in the e-cigarette we used was propylene glycol (other constituents included linalool, nicotine, tobacco essence, and methyl vanillin), and this could have played a role in the measured respiratory changes. Research has indicated that exposure to propylene glycol can induce respiratory irritation and increase the likelihood of developing asthma.[27,28] However, we cannot rule out the possibility that other constituents could be responsible or act in synergy with propylene glycol to induce the respiratory and oxidative responses that we noted.
This study has significant implications for product regulation and use and indicates a direction for further research. Our results were replicable and differed significantly in the bivariate analysis following exposure both within the experimental group (thus controlling for intersubject differences) and between groups (experimental vs control) and also in the regression analysis while controlling baseline characteristics. Controlling for baseline measurements allowed us to focus on the changes due to using the e-cigarette and not take into account underlying damage due to previous cigarette smoking or lung condition. The performed linear regression analysis furthermore allowed us to estimate the quantitative effects of using a single e-cigarette on mechanical and inflammatory measurable parameters. Moreover, the chemical composition of the cartridges used in e-cigarette be disclosed; knowledge of the contents enabled this study. However, despite these novel findings, our sample size remains relatively small, and further research is needed to investigate the mechanistic and toxicologic effects of long-term usage, which are potentially adverse and worthy of further investigation.
In conclusion, use of an e-cigarette for 5 min was found to cause an increase in impedance, peripheral airway flow resistance, and oxidative stress among healthy smokers. We must state, however, that although the differences within our study are of statistical significance, the clinical changes may be too small to be of major clinical importance. Notably, because these short-term effects were present even after only very limited usage, and a normal consumer would use the product most likely many times a day, it is possible that if e-cigarette use were a short-term bridge to smoking cessation, the long-term health benefits associated with their use might outweigh the short-term risks; however, this would need to be clarified. The FDA, as well as other international regulatory bodies, should pursue the regulation of the e-cigarette until manufacturers provide scientific evidence to support their claims. Additional research is warranted to obtain concrete evidence of an adverse health outcome.
Drs Vardavas and Behrakis take responsibility for the integrity of the data and accuracy of the data analysis.
Dr Vardavas: contributed to conception of the idea, data analysis, and manuscript preparation.
Dr Anagnostopoulos: contributed to performing laboratory measurements and helping draft the manuscript.
Dr Kougias: contributed to performing laboratory measurements and helping draft the manuscript.
Dr Evangelopoulou: contributed to performing laboratory measurements and helping draft the manuscript.
Dr Connolly: contributed to study design, data interpretation, and manuscript preparation.
Dr Behrakis: contributed to study supervision, study design, data interpretation, and manuscript preparation
This project was partially supported by internal funds of the Hellenic Cancer Society, Greece .
Role of sponsors
The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.
e-cigarette = electronic cigarette; FDA = US Food and Drug Administration; Feno = fraction of exhaled nitric oxide; IOS = impulse oscillometry system; MEF = maximal expiratory flow; PEF = peak expiratory flow; ppb = parts per billion; R5Hz = airway resistance at 5 Hz; R10Hz = airway resistance at 10 Hz; R20Hz = airway resistance at 20 Hz; Z5Hz = airway impedance at 5 Hz
CHEST. 2012;141(6):1400-1406. © 2012 American College of Chest Physicians