Molecular Imaging of Pulmonary Inflammation: Claiming That Vaping Is More Harmful Than Smoking Is Unsupported

TO THE EDITOR: We read with interest the recent pilot study by Wetherill et al. (1). The authors used ¹⁸F-6-(1/2)(2-fluoropropyl)-4-methylpyridin-2-amine (¹⁸F-NOS) PET imaging to quantify inducible nitric oxide synthase expression to characterize oxidative stress and inflammation in the lungs of 5 electronic cigarette (EC) users, 5 tobacco cigarette (TC) smokers, and 5 controls who had never smoked or vaped. PET imaging showed much greater ¹⁸F-NOS nondisplaceable binding potential in the lungs of EC users than in TC smokers, but contrary to expectations, no difference between TC smokers and controls was found.

The reported absence of difference in ¹⁸F-NOS nondisplaceable binding potential between TC smokers and controls is inconsistent with the suggestion given by enhanced nondisplaceable binding potential on ¹⁸F-NOS imaging that there is oxidative stress and inflammation in the lungs, given that smoking causes both inflammatory responses and oxidative stress. This issue renders interpretation of the study’s findings invalid. In consideration of the very small sample size and low reproducibility of ¹⁸F-NOS PET imaging, the likelihood of chance findings is very high. There would have been more confidence in the interpretation if former smokers had been included in the study design; however, this was not done. Important confounders, such as allergies of the upper respiratory tract with inducible nitric oxide synthase upregulation and high levels of exhaled nitric oxide (2) and prior and present exposure to tobacco smoking among EC users (3)—who are typically either former smokers or dual users—were not taken into consideration. As it is impossible to decouple the lung health impact of EC aerosol emissions from prior tobacco smoke exposure, only long-term follow-up of exclusive EC users who have never smoked TCs in their life would have been a better-suited study design to verify potential harm caused by EC use. In a 3.5-y prospective clinical trial, daily exclusive EC users who had never smoked TCs did not exhibit any increase in exhaled nitric oxide (4).

Additionally, given the cross-sectional design of the study, the observed correlation between EC use and improved ¹⁸F-NOS PET imaging does not infer causation.

The results of the study are inconsistent with the evidence that cigarette smoking reduces, not increases, inducible nitric oxide synthase expression and NO production from lung epithelial cells (5), as well as with the evidence that smoking is consistently linked to low levels of exhaled nitric oxide that return to normal after smoking is stopped (6–8).

Therefore, this pilot study does not support the argument that vaping is more harmful than smoking, and it contradicts clinical evidence showing that ECs may have some benefits in minimizing the harm caused by cigarette smoke and are unlikely to cause serious respiratory issues (3,4,9).

• © 2023 by the Society of Nuclear Medicine and Molecular Imaging.

• Received for publication February 2, 2023.
• Revision received February 2, 2023.
• Accepted for publication February 7, 2023.