Biology of the Oral Epithelium of E-Cigarette Smokers

Electronic cigarettes (EC) are battery powered nicotine delivery devices that aerosolize nicotine and other flavor constituents. Despite the increasing use of EC, little attention has been paid to their possible adverse effects on human health. Theoretically, the risk relates to nicotine per se and/or the propellants or contaminants in the EC aerosol. The hypothesis underlying the proposal is that chronic EC smoking disorders the biology of the oral epithelium, the first cell population exposed to inhaled EC vapors. Using a cross-sectional, cohort-comparison of EC smokers compared to age-, gender- and ethnicity-matched never smokers, the investigators propose to assess the oral epithelium obtained by punch biopsy or brushing from 100 EC smokers and 25 nonsmoker controls. The EC study cohort will be restricted to young adults (age 21-35 yr) with no prior history of tobacco smoking, but who have smoked EC for \>6 months.

There is compelling evidence to support this hypothesis: (1) EC vapors contain nicotine, the oral epithelium expresses nicotine receptors, and exposure of epithelia to nicotine activates the nicotine pathway; (2) EC vapors also contain chemical contaminants that can potentially effect oral epithelial biology; and (3) in vitro studies suggest that EC vapors modify epithelial biology and data generated by our laboratory demonstrates that even a brief, acute exposure of healthy nonsmokers to EC vapors induces significant changes in the airway epithelial transcriptome, including the expression of genes in the nicotine and p53 pathways. With the knowledge that disordering of cell biology occurs long before clinical disease,the investigators will evaluate the oral epithelium at the transcriptome (mRNA and miRNA) levels. They will then identify gene(s)/pathways/communities disordered by EC vapors.

Eligibility Criteria:
Inclusion Criteria:

* HEALTHY VOLUNTEER RESEARCH SUBJECTS:

Inclusion Criteria:

* Males and females, ages 21 to 35
* Must be capable of providing informed consent
* Self-reported never-smokers of any type, including chewing tobacco, with current smoking status validated by the absence of nicotine metabolites in urine (nicotine \<2 ng/ml and cotinine \<5 ng/ml)
* No bleeding diathesis
* Normal physical examination
* Good overall health without history of oral or lung disease
* Normal routine laboratory evaluation, including general hematologic studies, general serologic/immunologic studies, general biochemical analyses, and urine analysis
* Not taking any medications relevant to lung disease or having an effect on the airway epithelium
* Normal chest X-ray (PA and lateral)
* Normal electrocardiogram (sinus bradycardia, premature atrial contractions are permissible)
* Females - not pregnant
* Willingness to participate in the study

  * HEALTHY VOLUNTEER E-CIGARETTE SMOKING SUBJECTS:

Inclusion Criteria:

* Males and females, ages 21 to 35
* Must be capable of providing informed consent
* E-cigarette smokers with current smoking status validated by nicotine metabolites in urine (nicotine \>20 ng/ml and cotinine \>30 ng/ml)
* No bleeding diathesis
* Normal routine laboratory evaluation, including general hematologic studies, general serologic/immunologic studies, general biochemical analyses, and urine analysis
* Good overall health without history of oral disease
* Normal spirometry
* All individuals have chest X-ray (PA and lateral)
* Normal electrocardiogram (sinus bradycardia, premature atrial contractions are permissible)
* Females - not pregnant
* Willingness to participate in the study

Exclusion Criteria:

* HEALTHY VOLUNTEER RESEARCH SUBJECTS:

Exclusion Criteria:

* Unable to meet the inclusion criteria
* Have smoked any form of tobacco
* Current marijuana smokers (within the last three months)
* Current active infection or acute illness of any kind
* Evidence of malignancy, including oral cancer
* Current pregnancy

  * HEALTHY VOLUNTEER E-CIGARETTE SMOKING SUBJECTS:

Exclusion criteria:

* Unable to meet the inclusion criteria
* Have smoked any form of tobacco
* Current marijuana smokers (within the last three months)
* Current active infection or acute illness of any kind
* Evidence of malignancy, including oral cancer
* Current Pregnancy