Electronic cigarette vapor appeared to trigger immune responses in human lungs similar to those elicited by cigarette smoke in a novel study which compared sputum samples from cigarette smokers, e-cigarette users, and never-smokers.

Sputum samples from e-cigarette users and cigarette smokers both exhibited elevated neutrophil activity associated with chronic inflammatory lung diseases like COPD, reported Mehmet Kesimer, PhD, of the University of North Carolina School of Medicine Center for Tobacco Regulatory Science and Lung Health (TCORS) in Chapel Hill, and colleagues.

The analysis of differentially expressed proteins revealed that a group of innate defense proteins of neutrophilic origin were highly represented in the e-cigarettes users.

Action Points Electronic cigarette vapor appeared to trigger immune responses in human lungs similar to those elicited by cigarette smoke in a small study which compared sputum samples from cigarette smokers, e-cigarette users and never-smokers.

These findings challenge the concept that switching from cigarettes to e-cigarettes is a healthier alternative and reverses smoking-induced adverse health effects.

"Most prominently, primary neutrophilic granule enzymes, such as NE, PRTN3 and MPO, showed significantly higher levels in e-cigarette users than in non-smokers," Kesimer and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

They asserted that their study "clearly demonstrates a unique e-cigarette-induced innate lung response that includes markers of an aberrant neutrophilic response."

"Taken together, our results indicate that the effects of e-cigarettes are both overlapping with and distinct from what is observed in otherwise healthy cigarette smokers," they wrote.

Kesimer told MedPage Today that the research is the first to explore the effects of e-cigarette vapor exposure on human airway secretions, and argued that it raises serious doubts about the safety of e-cigarettes, and their promotion for harm reduction and smoking cessation.

The FDA recently announced a shift in tobacco policy that treats cigarette smoke as a more important health threat than nicotine, with the latter considered problematic mainly because its addictive properties keep people smoking. Consequently, the agency has suggested that e-cigarettes may be useful for helping smokers kick the habit, although more research is needed to confirm it.

"Our results challenge the concept that e-cigarettes are a healthier alternative to cigarettes and reverse smoking-induced adverse health effects," Kesimer and colleagues wrote.

Since the airway epithelium is one of the first parts of the body that comes into contact with inhaled smoke and e-cigarette vapor, the researchers noted that it made sense to study mucus secretions which act as the first line of defense against inhaled substances.

"Analysis of the changes in the airway secretion proteome as a result of e-cigarette vaping can identify potential biomarkers associated with adverse health effects," they wrote.

The researchers examined sputum samples collected as part of the TCORS program, including 14 samples from current cigarette smokers, 15 samples from current e-cigarette users and 15 never smokers.

Total mucin concentrations in the sputum samples were analyzed by size-exclusion chromatography/differential refractory (SEC-MALLS/dRI) measurements. Individual concentrations of MUC5AC and MUC5B were measured using stable-isotope-labeled mass spectrometry with parallel reaction monitoring analysis.

Neutrophils from 11 healthy non-smokers, seven smokers, and 12 e-cigarette users were isolated from venous blood, and incubated for 30 minutes prior to challenge. Wells were assayed for extracellular chromatin content every hour during a 4 hour challenge to assess neutrophil extracellular traps (NETs) formation.

Body mass index values in the e-cigarette users were similar to the other two groups. Use averaged approximately 280 vapor puffs daily, compared to approximately 11 cigarettes among the smokers. Twelve of the e-cigarettes users identified themselves as former smokers and five reported occasionally smoking cigarettes.

E-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress related proteins associated with cigarette smoke compared to non-smokers.

"The levels of innate defense proteins associated with COPD, such as elastase and matrix metalloproteinase-9, were significantly elevated in e-cigarette uses as well," the researchers wrote. "E-cigarette users' sputum also uniquely exhibited significant increases in neutrophil granulocyte- and NT-related proteins, such as myeloperoxidase, azurocidin, and protein-arginine deiminase 4, despite no significant elevation in neutrophil cell counts."

Peripheral neutrophils from e-cigarette users also showed increased sensitivity to PMA-induced NETosis, and the researchers also observed elevated concentrations of MUC5AC in both cigarette smokers and e-cigarette users.

Funding for this research was provided by the NIH and the Family Smoking Preventio0n and Tobacco Control Act. The researchers declared no relevant relationships with industry related to this study.