August 31, 2019

Stanton A. Glantz, PhD

More evidence that ecigs are as dangerous as cigarettes for human lung disease

Robert Tarran and his colleagues at UNC recently published “Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung” in American Journal of Respiratory and Critical Care Medicine.  They inserted bronchoscopes into the lungs of 14 e-cigarette users and measured levels of enzymes in their lungs.  They found high levels of protease, an enzyme that, when too high, cause emphysema by essentially dissolving lung tissue.  The levels were as high as observed in smokers.

They also studied the effect of nicotine on cultured immune cells from lungs and found that higher levels of nicotine produced more proteases.

These findings challenge the conventional wisdom among e-cigarette enthusiasts (and the FDA) that e-cigarettes are safer than cigarettes and that nicotine per se does not have any adverse health effects beyond being an addictive drug.

Here is the abstract:

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.

The full citation is:  Ghosh A, Coakley RD, Ghio AJ, Muhlebach MS, Esther CR Jr, Alexis NE, Tarran R. Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung. Am J Respir Crit Care Med. 2019 Aug 7. doi: 10.1164/rccm.201903-0615OC. [Epub ahead of print].  It is available here.



Does increasing proteolysis cause COPD directly, or are there other factors from smoking that accelerate COPD?


It is one part of the chain.

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