In the parent grant, we have proposed to study the effect of nicotine on pulmonary surfaces. That is, we have proposed to look at the effects of nicotine on key components of innate defense relevant to the lung using a variety of cell biological and biophysical techniques. We have subsequently requested a revision to the grant to include human subjects so that we can also study the effects of nicotine on innate defense cells derived from humans including neutrophils. In the interim however, we have identified a major knowledge gap, namely that we do not fully appreciate the levels of nicotine that occur in vapers? lungs during and after vaping. This is an impediment to our research since we do not know which concentrations of nicotine to add to our in vitro experiments. Thus, in this supplement, Dr. Abdelwahab will measure nicotine levels in vaped humans and mice and will also perform pharmacokinetic studies of nicotine on pulmonary surfaces in vitro. These studies will be important not only for our research but for other researchers in the field since the knowledge does not exist. Deciding how to perform the pharmacokinetics will be an iterative process and Dr. Abdelwahab will have intellectual input into how and when to collect nicotine. He will also decide how to measure nicotine using mass spectrometry-type approaches and will design the experiments to determine how long nicotine stays around on airway surfaces. These studies will enable Dr. Abdelwahab to develop independent as a scientist since they will allow him to design and execute important experiments that will be of international interest. Moreover, should these experiments be successful, it is also fully expected that he will have the opportunity to present these data at national and international meetings and to write them up for publication in peer-reviewed journals.

Public Health Relevance

Tobacco inhalation is causative in a myriad of diseases including lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. Nicotine is the principle addictive compound in tobacco that keeps people smoking, yet the effects of nicotine on the lung are poorly understood. We propose to better understand nicotine pharmacodynamics during vaping.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1)
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Postow, Lisa
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Ghosh, Arunava; Coakley, Raymond C; Mascenik, Teresa et al. (2018) Chronic E-Cigarette Exposure Alters the Human Bronchial Epithelial Proteome. Am J Respir Crit Care Med 198:67-76
Rowell, Temperance R; Reeber, Steven L; Lee, Shernita L et al. (2017) Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol 313:L52-L66