The effect of Inhaled Nicotine on Pulmonary Surfaces

吸入尼古丁对肺表面的影响

• 批准号: 10083514
• 负责人: Mehmet Kesimer
• 金额: $ 6.29万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-06 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083514
• 关键词: Acute; Affect; Antiinflammatory Effect; Antimicrobial Effect; Biological; Blood; Bronchiectasis; Cardiovascular Diseases; Cells; Chronic; Chronic Obstructive Airway Disease; Data; Disease; Drug Kinetics; Electronic cigarette; Epithelial; Epithelium; Escalator; General Population; Glycerol; Grant; Health; Human; Hydration status; Impairment; In Vitro; Inhalation; International; Journals; Knowledge; Leukocyte Elastase; Lung; Malignant neoplasm of lung; Mass Spectrum Analysis; Measures; Metabolic; Metabolism; Metalloproteases; Mucins; Mus; Nicotine; Nicotinic Receptors; Parents; Patients; Peer Review; Peptide Hydrolases; Pharmacodynamics; Phase; Play; Process; Property; Propylene Glycols; Proteins; Proteomics; Publications; Publishing; Pulmonary Emphysema; Research; Research Personnel; Respiratory System; Role; Sampling; Scientist; Smoking; Sputum; Structure; Surface; System; Testing; Tobacco; Toxic effect; Toxin; Urine; Vegetables; Western Blotting; Writing; absorption; addiction; airway epithelium; antimicrobial; base; biophysical techniques; bronchial epithelium; cell type; defense response; design; electronic cigarette use; experimental study; human subject; in vitro testing; interest; meetings; mortality; neutrophil; nicotine inhalation; nicotine use; parent grant; pathogen; pulmonary function; vaper; vaping

Abstract 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.

抽象的 在家长资助中，我们提议研究尼古丁对肺表面的影响。 建议使用以下方法来研究尼古丁对与肺部相关的先天防御关键成分的影响 我们随后要求对拨款进行修改。 包括人类受试者，以便我们还可以研究尼古丁对源自的先天防御细胞的影响 然而，在此期间，我们发现了一个主要的知识差距，即 我们并不完全了解吸电子烟期间和之后电子烟使用者肺部的尼古丁含量。 我们的研究遇到了障碍，因为我们不知道在体外添加多少浓度的尼古丁 因此，在本补充实验中，Abdelwahab 博士将测量吸电子烟的人和小鼠的尼古丁水平。 还将进行尼古丁在体外肺表面的药代动力学研究。 不仅对于我们的研究很重要，对于该领域的其他研究人员也很重要，因为知识并不存在。 决定如何进行药代动力学将是一个迭代过程，Abdelwahab 博士将 他还将决定如何使用质量来测量尼古丁。 光谱测定型方法，并将设计实验以确定尼古丁在体内停留的时间 这些研究将使 Abdelwahab 博士能够独立发展为一名科学家，因为他们将 让他能够设计和执行引起国际兴趣的重要实验。 如果这些实验能够成功，我们也完全期待他将有机会展示这些数据 在国内和国际会议上发表，并将其撰写在同行评审期刊上发表。