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Theoretical Mechanism for Vaping Associated Lung Injury

Recently, there has been a significant amount of news media coverage on Vaping Associated Lung Injury (VALI) lately. We certainly are starting to see more cases. However, it is unclear if something has changed with the formulation of vaping liquids or if this disease has existed as long as vaping, but diagnosis availability limited the number of diagnoses made. Regardless, medical professionals and the media have taken a huge interest in VALI.

Typical features include: recent heavy vape use, cough, respiratory symptoms, hypoxia at rest or on exertion, GI upset, tachycardia, fever, leukocytosis, patches of bilateral ground glass opacities on chest CT. Often times patients will be diagnosed with a viral syndrome or community acquired pneumonia and be discharged from ED only to bounce back a few days later with more serious symptoms. It is also possible many diagnoses of VALI are mistakenly diagnosed as multifocal pneumonia with sepsis. The technical diagnostic criteria for VALI are a patient with respiratory symptoms, a history of vaping, ground glass opacities on CT, a negative infectious workup, and no other likely etiology for their presentation.

There have been numerous articles that show that vapor clouds contain significant amount of free radicals. Presumably this is due to direct exposure to thermal electromagnetic radiation on the heating coil. Many formulations now use tocopheryll acetate, which is then converted in vivo into tocopherol, or Vitamin E. Tocopherol is a free radical scavenger and is involved biochemical redox pathways that eventually deplete glutathione (see figure below). Some data show the higher level “mod” vaporizers produce as much free radicals as conventional cigarettes. However, the frequency and quantity of use amongst users, especially if perceived to be safe, may increased when compared to smokers of tobacco cigarettes.

Furthermore, given the clinical findings of lipid laden macrophages and their red stain with “oil red o” on bronchial alveolar lavage (BAL), it is also conceivable a mechanism of action is the deposition of diluents, leading to a multifocal lipoid pneumonia. Others have also suggested that nanometal particles from the heating coil may be inhaled, leading to lung injury.

Finally, steroids have been the mainstay of treatment. Normoxia should be maintained, but hyperoxia avoided to prevent the accumulation of free radicals. Typically antibiotics are given until infection is ruled out. Thus, if a contributory mechanism of injury is chronic depletion of glutathione, an treatment could be IV NAC in combination with aerosolized NAC (Mucomyst). NAC is well tolerated and unlikely to cause harm if administered correctly. However, a prospective trial that assesses the role of NAC for this indication needs to be performed.

Biochemical pathways for antioxidants in the lung demonstrating theoretical role for NAC in treatment of vaping associated lung injury (VALI). Please note the diluents of the vaping liquid are depositing on the air-lipid surface.