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Overlapping Airway Basal Cell Transcriptome Reprogramming in COPD and Lung Cancer

Principal Investigator: Ronald Crystal

Funding Mechanism: National Institutes of Health- Grant

ID number: 3 R01 HL107882-02S1

Award Date: 9/14/2012

Institution: Weill Medical College of Cornell University


Cigarette smoking causes major changes in the biology of the small airway epithelium (SAE), the primary site of pathology for smoking-induced lung diseases such as chronic obstructive pulmonary disease and lung cancer. In the parent grant, investigators compared the biology of SAE from cigarette smokers, smokers with chronic obstructive pulmonary disease (COPD), and smokers with lung cancer with and without COPD to that of healthy nonsmokers. The goals of this study supplement are to identify the effects of shisha and electronic cigarettes (e-cigarettes) on SAE and to compare these effects to those associated with cigarette smoking (as identified in previous research). Specific aims are: (1) to assess the hypothesis that smoking shisha disorders SAE biologic parameters, and that these changes are distinct from those in cigarette smokers; and (2) to evaluate the hypothesis that when smokers switch from cigarettes to e-cigarettes, there is a partial normalization of the disordered SAE biology, but that this partial normalization is different than that associated with complete smoking cessation. The study population will include 125 participants, 25 from each of five groups (nonsmokers, current cigarette smokers, current shisha smokers [non-cigarette smokers], current smokers who stop smoking, and current smokers who switch to e-cigarettes), who will provide SAE samples at baseline and three months. Investigators will compare SAE gene expression, DNA methylation, telomere length and cilia length in shisha smokers to the same parameters in matched nonsmokers and chronic cigarette smokers. Investigators will also compare the disordered SAE biology of cigarette smokers who switch to e-cigarettes to that of cigarette smokers who stop smoking, and will also compare these samples to those of matched nonsmokers and chronic cigarette smokers. This investigation will result in a molecular catalog of SAE changes associated with shisha and e-cigarette smoking, providing information to guide public health education and regulatory measures related to these alternative nicotine delivery mechanisms.


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