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.

摘要 在母基金中，我们建议研究尼古丁对肺表面的影响。也就是我们要 建议使用一种新的方法来研究尼古丁对与肺相关的先天防御关键成分的影响。 各种细胞生物学和生物物理学技术。我们其后要求修订拨款额， 包括人类受试者，这样我们也可以研究尼古丁对先天防御细胞的影响， 人类包括中性粒细胞。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烟者在吸烟期间和之后肺部的尼古丁水平。这是一 阻碍了我们的研究，因为我们不知道尼古丁的浓度添加到我们的体外 实验因此，在这种补充中，Abdelwahab博士将测量人类和小鼠的尼古丁水平 并将在体外进行尼古丁在肺表面的药代动力学研究。这些研究报告将 这不仅对我们的研究很重要，而且对该领域的其他研究人员也很重要，因为这些知识并不存在。 决定如何进行药代动力学将是一个迭代过程，Abdelwahab博士将 如何以及何时收集尼古丁。他还将决定如何使用质量来测量尼古丁 光谱类型的方法，并将设计实验，以确定多久尼古丁停留在周围 气道表面。这些研究将使Abdelwahab博士能够作为一名科学家独立发展，因为他们将 让他设计和执行重要的实验，这将是国际利益。此外，应 如果这些实验成功，我们也完全可以期待他有机会展示这些数据。 在国家和国际会议上发表，并将其撰写在同行评审的期刊上发表。