E-cigarette ‘vaping’ is widely assumed to be safer than cigarette smoking, but scientists at the University of North Carolina School of Medicine have uncovered evidence suggesting that vaping promotes the same cellular responses found in smokers who suffer with emphysema.
In the study, the UNC scientists found that the lungs of vapers – like the lungs of smokers – have elevated levels of protease enzymes, a condition known to cause emphysema in smokers. The researchers also found that the nicotine in vaping liquids is responsible for the increase in protease enzymes.
“Our findings in this study indicate that vaping may not be safer than cigarette smoking,” said study senior author Dr Robert Tarran, a professor in the department of cell biology and physiology and member of the Marsico Lung Institute at the UNC School of Medicine.
The US Centres for Disease Control and Prevention (CDC) has estimated that in 2014 about 9m adults in the country were regular vapers and that close to 30m had tried vaping at least once. But vaping on this scale has been going on for less than a decade, and so the long-term health effects of vaping are not yet well understood.
Tarran and colleagues in the study measured levels of three key protease enzymes in lung fluid sampled from 41 subjects – non-smokers, smokers, and vapers. The three protease enzymes are neutrophil elastase and matrix metalloproteases 2 and 9. Immune cells in the lungs are known to secrete these enzymes at higher levels in a reaction to cigarette smoke. Chronic over activity of these protein-chewing enzymes damages the tiny sensitive air sac structures in the lungs that allow people to breathe. In smokers, this damage is thought to be the cause of emphysema, a form of chronic obstructive pulmonary disease (COPD) involving progressive shortness of breath and for which there is no cure.
The UNC scientists found that the levels of these three proteases were significantly elevated in both smokers and vapers, but not in non-smokers. This finding suggests vaping, like smoking, may promote emphysema.
The scientists also found evidence that nicotine in vaping liquids is the cause of the elevated-protease reaction. When Tarran’s team administered nicotine to immune cells cultured in the laboratory – at concentrations like those seen in vapers sputum and lung fluid – they observed that the cells overproduced the proteases. And this overproduction increased when the researchers exposed the immune cells to higher nicotine levels.
Vaping is thought to be much safer than cigarette smoking, which involves the high-temperature burning of tobacco leaves and the creation of toxic and carcinogenic combustion products. Some researchers have urged that smokers switch to vaping as a much less harmful alternative. The jury is still very much out when it comes to cancer risk associated with vaping. But this latest study suggests that the potential harm of vaping may have been underestimated, especially when it comes to emphysema and COPD, two of the most common debilitating conditions historically associated with smoking.
Tarran noted that the findings are not the first to warn of vaping’s potential adverse health effects. A different study in 2018, from a team led by UNC Marsico Lung Institute researcher Dr Mehmet Kesimer, found that sputum from vapers and smokers contained elevated levels of emphysema-promoting proteases and other immune defence proteins.
Moreover, a study from Tarran’s lab last year found evidence of toxic compounds in commonly used vaping liquids, and the CDC currently is investigating about 100 recent cases in the US of sudden, serious lung disease in otherwise healthy young vapers.
Tarran and his colleagues plan to follow up their study with a larger study of lung protease levels in hundreds of participants.
Chronic e-cigarette use increases neutrophil elastase and matrix metalloprotease levels in the lung
American Journal of Respiratory and Critical Care Medicine
Rationale: Proteolysis is a key aspect of the lung’s innate immune system. Proteases, including neutrophil elastase and matrix metalloproteases (MMPs), modulate cell signaling, inflammation, tissue remodeling and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. The effect of e-cigarettes (vaping) on proteolysis is unknown.
Objectives: We used protease levels as biomarkers of harm to determine the impact of vaping on the lung. Methods: We performed research bronchoscopies on healthy non-smokers, cigarette smokers and e-cigarette users (vapers) and determined protease levels in bronchoalveolar lavage (BAL). In parallel, we studied the effects of e-cigarette components on protease secretion in isolated human blood neutrophils and BAL-derived macrophages. We also analyzed the nicotine concentration in induced sputum and BAL. Measurements and Main Results: Neutrophil elastase, MMP-2 and MMP-9 activities/protein levels were equally elevated in both vapers’ and smokers’ BAL relative to non-smokers. In contrast, antiprotease levels were unchanged. We also found that exposure of isolated neutrophils and macrophages to nicotine elicited dose-dependent increases in protease release. After vaping, measurable levels of nicotine were detectable in sputum and BAL, which corresponded to the EC50s for protease release seen in immune cells.
Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.
Arunava Ghosh, Raymond D Coakley, Andrew J Ghio, Marianne S Muhlebach, Charles R Esther Jr, Neil E. Alexis, Robert Tarran