The study by Lee et al. seeks to establish much needed information about the association between vaping and asthma and lung function in a sample of 519 Australian adults.1 The authors reported no significant associations with asthma symptoms, uncontrolled asthma (Asthma Control Questionnaire-7 > 1.5) and spirometry, but found associations with self-reported asthma, chest tightness and airway reactance. We would like to raise some concerns about the significance of these findings.

Sample size of daily vapers

In this study, reported associations rest on a very small number of cases. Only 5–7 vapers are likely to have vaped daily, making the findings of questionable value as only daily exposure is consequential. The frequency of vaping is not provided; however, the 2019 National Drug Strategy Household Survey found that only one in four current vapers and 10% of ever-vapers vaped daily.2

In this study, it is therefore likely that only 2–3 out of 10 current vapers and 3–4 of the 36 remaining ever-vapers had been daily vapers. Multivariate analysis on such small numbers will produce inaccurate results.

Clinical significance

While 10 respiratory symptoms were included in the logistic regression analyses, only one showed a statistically significant difference between the ever-vapers and non-users, and no adjustment was made for multiple comparisons. This makes correct computation and interpretation of the results highly unlikely.

The authors selectively reported only positive forced oscillation technique (FOT) measures—more negative reactance at low frequencies (X5) and the associated area of reactance (Ax)—and ignored the absence of a difference between groups in R5 − R20 difference (a common FOT index of peripheral airflow obstruction that surely must have been measured along with Rr5). Their conclusion that e-cigarettes may have potential adverse effects on lung mechanics is not supported by the evidence.

Moreover, the claimed findings of respiratory harm are not consistent with clinical studies showing improvements in patients with asthma who have switched to daily vaping3 and randomized trials showing improved respiratory symptoms.4

Confounding by smoking status

The authors claim to have controlled for smoking status. However, almost all of the ever-daily vapers in their study were current smokers or former smokers and differences in this important confounder can never really be completely adjusted for in statistical analyses. It is far more likely that, if a biological effect is identified, it was caused by smoking.

Inadequate study design

The cross-sectional design of the study lacked the necessary temporal sequence between cause (i.e., vaping) and effect (i.e., disease outcomes). No conclusions about causality can be reached.

Reverse causation

The possibility of reverse causation must be considered. For example, smokers with respiratory symptoms may try vaping because they have heard that it might provide some relief.

E-cigarette, or Vaping-Associated Lung Injury (EVALI) misrepresentation

The authors correctly identify that EVALI was caused by vitamin E acetate in tetrahydrocannabinol vaping, but push for e-cigarette policy change based on EVALI where there is no connection.

In conclusion, better quality research is needed to provide quantitative estimates about health risks and benefits of e-cigarettes.

CONFLICT OF INTEREST

Colin Paul Mendelsohn has received payments for teaching, consulting and conference expenses from Pfizer Australia, Perrigo Australia, GlaxoSmithKline and Johnson & Johnson Pacific and has served on Pfizer Australia's Champix Advisory Board. He was an unpaid Board member of the Australian Tobacco Harm Reduction Association (ATHRA) until January 2021. ATHRA accepted unconditional funding from the retail vape industry to establish the charity. Funding ceased in March 2020. ATHRA also received a donation in March 2018 from Knowledge-Action-Change (KAC), a private UK harm reduction organisation. KAC had previously accepted a research grant in 2012 from a subsidiary of British American Tobacco to evaluate the use of a nicotine delivery device in Scottish Prisons; and a grant from the Foundation for a Smoke-Free World (FSFW; funded by Philip Morris International) to prepare the 2018 Global State of Tobacco Harm Reduction report. CM has never received any funding or commercial benefits from the vaping or tobacco industries.

Jaymin Bhagwanji Morjaria has received honoraria for speaking and financial support to attend meetings/advisory boards from Wyeth, Chiesi, Pfizer, MSD, Boehringer Ingelheim, Teva, GSK/Allen & Hanburys, Napp, Almirall, AstraZeneca, Trudell, Cook Medical, Medela AG and Novartis. He has been an expert witness for a solicitor company acting for BATSA and all proceeds of the work were donated to the charity ASH UK.

Riccardo Polosa has received lecture fees and research funding from Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A/S, Sandoz, MSD, Boehringer Ingelheim, Novartis, Duska Therapeutics, and Forest Laboratories. Lecture fees from a number of European EC industry and trade associations (including FIVAPE in France and FIESEL in Italy) were directly donated to vaping advocacy non-profit organizations. He has received grants from European Commission initiatives (U-BIOPRED and AIRPROM) and from the Integral Rheumatology and Immunology Specialists Network (IRIS) initiative. He has served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, CV Therapeutics, Boehringer Ingelheim, Novartis, Duska Therapeutics, ECITA (Electronic Cigarette Industry Trade Association, in the UK), Arbi Group Srl and Health Diplomats. He has served on the medical and scientific advisory board of Cordex Pharma, CV Therapeutics, Duska Therapeutics, Pfizer and PharmaCielo. He is a founder of the Center for Tobacco prevention and treatment (CPCT) at the University of Catania and of the Center of Excellence for the acceleration of Harm Reduction (CoEHAR) at the same university, which has received support from the Foundation for a Smoke-Free World to conduct eight independent investigator-initiated research projects on harm reduction. Foundation for a Smoke-Free World (FSFW) is a US non-profit 501(c)(3) private foundation, which accepts charitable gifts from Phillip Morris International Global Services Inc. (PMI); under FSFW's Bylaws and Pledge Agreement with PMI, FSFW is independent from PMI and the tobacco industry. FSFW grantees are free to publish the results of their independently conducted research, regardless of outcome, or negative impact on any business or industry. The contents, selection, and presentation of facts, as well as any opinions expressed are the sole responsibility of the authors and under no circumstances shall be regarded as reflecting the positions of the Foundation for a Smoke-Free World. He is currently involved in a patent application concerning a smartphone app tracker for smoking behaviour developed for ECLAT. He is also involved in the following pro bono activities: scientific advisor for Lega Italiana Anti Fumo, the Consumer Advocates for Smoke-free Alternatives and the International Network of Nicotine Consumers Organizations; and Chair of the European Technical Committee for standardization on ‘Requirements and test methods for emissions of electronic cigarettes’ (CEN/TC 437; WG4).