Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs

• Changes in fractional exhaled nitric oxide (FeNO) levels[ Time Frame: Baseline up to day 71 ]
  FeNO will be measured with the NIOX VERO. Descriptive statistics and clustering (e.g. PCA), will be performed for all biomarker data measured at the different visits. Baseline data (1st bronchoscopy) will then be compared between the five groups (4 conditions and control) using a one-way ANOVA. The non-parametric Kruskal-Wallis test (continuous or ordinal variables) or the chi-square test (categorical variables) will be applied when the normality assumption of the data is not met. Controls will be compared to complete substitution with the SREC (with and without nicotine) or NRT, or dual use conditions. GLM will be employed with measurement (cell count, gene expression, etc.) as the dependent variable, a covariable for baseline measure, and a main effect of arm.
• Changes in messenger (m) ribonucleic acid (RNA) and microRNA (miRNA) gene expression analyzed using sequencing[ Time Frame: Baseline up to day 71 ]
  Total RNA containing small RNAs will be extracted from bronchial brushing specimens using commercially available kits and used for both gene expression using the Affymetrix GeneChip Human Transcriptome Array and for miRNA expression using the Affymetrix GeneChip miRNA Array. Expression will separately be assessed through RNA sequencing. Total RNA will be extracted from lavage cells and saliva for comprehensive profiling of microbiome using commercially available kits. The ?omics? (miRNA, mRNA, and metabolomics) analysis and visualization of the data will be performed in the R statistical language. Data will be log2-transformed and normalized using either quantile normalization for gene expression (miRNA and mRNA) or normalization for metabolomics. Unsupervised clustering analysis, including PCA and hierarchical clustering will be performed to visualize natural clusters in the dataset and evaluate data quality.
• Changes in deoxyribonucleic acid (DNA) gene methylation[ Time Frame: Baseline up to day 71 ]
  Total DNA will be extracted using commercially available kits and used for genome-wide DNA methylation profiling. Total DNA including mitochondrial DNA (mtDNA) will be extracted using commercially available kits and used for mtDNA mutation using Hiseq Next Generation Sequencing (NGS) and for mtDNA contents using quantitative polymerase chain reaction (qPCR). For preliminary identification of patterns in DNA methylation, unsupervised hierarchical clustering among the groups of samples will be performed. The Euclidian distance among the groups of samples will be calculated by the average linkage. In order to assess variance among samples, PCA will be done.
• Changes in the microbiome in BAL cells and saliva[ Time Frame: Baseline up to day 71 ]
  Obtained via bronchoscopy with saline BAL and bronchial brushings. Samples will be analyzed to determine their bacterial composition.
• Changes in untargeted metabolomics using mass spectrometry[ Time Frame: Baseline up to day 71 ]
  Obtained via bronchoscopy with saline BAL and bronchial brushings. The omics (miRNA, mRNA, and metabolomics) analysis and visualization of the data will be performed in the R statistical language. Data will be log2-transformed and normalized using either quantile normalization for gene expression (miRNA and mRNA) or normalization for metabolomics. Unsupervised clustering analysis, including PCA and hierarchical clustering will be performed to visualize natural clusters in the dataset and evaluate data quality.

Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs

The Effects of a Standardized Research E-Cigarette on the Human Lung: A Clinical Trial With Bronchoscopic Biomarkers

This trial studies biomarkers obtained by bronchoscopy (bronchoalveolar lavage and lung brushings) to determine the effect of smoking e-cigarettes on the lungs. Studying samples of lung cells from participants who smoke e-cigarettes may help doctors learn more about changes that occur in deoxyribonucleic acid and identify biomarkers related to cancer.

• Procedure: Bronchoscopy with Bronchoalveolar Lavage
  Undergo bronchoscopy with bronchoalveolar lavage
• Drug: Cigarette
  Smoke usual brand
• Other: Electronic Cigarette
  Smoke SREC with nicotine
• Other: Electronic Cigarette
  Smoke SREC without nictoine
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Drug: Nicotine Replacement
  Receive NRT comprising patch, gum, or lozenge
• Other: Questionnaire Administration
  Ancillary studies

• Active Comparator: Group I (usual cigarette brand)
  Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
• Experimental: Group II (SREC with nicotine)
  Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
• Experimental: Group III (SREC without nicotine)
  Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
• Experimental: Group IV (usual cigarette brand, nicotine-containing SREC)
  Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the nicotine-containing SREC for 2 weeks and use both their usual brand of cigarettes and the nicotine-containing SREC starting day 15 for 8 weeks with the intention of smoking reduction to 5 cigarettes or less per day. Participants undergo a second bronchoscopy on day 71.
• Experimental: Group V (NRT)
  Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 2 days before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.