# Molecular mechanisms for E-cigarette vapor-induced mucociliary dysfunction: role of nicotinic acetylcholine and TRP receptors

> **NIH NIH F32** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $72,006

## Abstract

Use of e-cigarettes (E-cigs), known as “vaping”, is becoming widely adopted amongst adolescents who are
attracted by their novelty, synthetic flavors, and belief of reduced toxicity. Previous smokers also use E-cigs as
a smoking cessation tool that is an alternative nicotine delivery system with milder social stigma. However,
“vaping” is an emerging public health problem, especially concerning young people with no smoking history,
due to the lack of informative respiratory studies on E-cig vapor components. Past inhaled nicotine studies
examined its effects mainly on airway smooth muscle and the central nervous system as opposed to the
ciliated airway epithelia, the major barrier for inhaled E-cig vapor, and few studies investigated nicotine in
isolation of tobacco smoke constituents. Additionally, toxicology studies of most E-cig flavorings were never
completed for inhalation exposure. This research proposal, which doubles as a mentored postdoctoral training
plan, aims to elucidate effects of E-cig vapor on the functional human ciliated airway epithelium.
 The airway epithelium expresses several isoforms of nicotinic acetylcholine receptors (nAChRs), transient
receptor potential (TRP) cation channel member A1 (TRPA1), and other TRP channels, which are all calcium
(Ca2+)-permeant. Nicotine is reported to stimulate both nAChRs and TRPA1, and some E-cig flavors are TRP
agonists, such as cinnamaldehyde (TRPA1), vanillin (TRPV1), and menthol (TRPM8). The basic hypothesis
of this proposal is that E-cig vapor components nicotine and cinnamaldehyde compromise mucociliary
function by stimulating nAChRs and TRPA1 to cause sustained Ca2+ influx. Research goals for this study
are to identify a molecular mechanism(s) for how E-cig vapor impairs mucociliary function and to develop novel
high-throughput methodology for establishing continuous mucociliary transport in vitro. The latter will be used
to probe adverse/therapeutic effects of aerosolized compounds. These goals will be tested in primary human
bronchial epithelial cells differentiated at the air-liquid interface, using physiologically-relevant exposures, and
measuring in vitro parameters of mucociliary function such as mucociliary transport, ciliary beating, and airway
surface hydration. Training goals for this proposal are to develop expertise in studying pulmonary effects of
inhaled toxicants and to become immersed in translational research by working in a diverse team composed of
clinicians and scientists.
 Completion of this study will fulfill the unmet need for clarification and information regarding effects of
inhaled nicotine and E-cig flavorings. Use of relevant exposures and primary cultures will provide a compelling
biological rationale to adapt public health policy. It will also inform clinicians on the `pro & cons' of E-cigs as
smoking cessation tools as well as the impact on young never-smoking subjects who take up “vaping”. Lastly,
completion of this training plan will generate data and ...

## Key facts

- **NIH application ID:** 9674213
- **Project number:** 5F32HL140729-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Samuel Chung
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,006
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9674213

## Citation

> US National Institutes of Health, RePORTER application 9674213, Molecular mechanisms for E-cigarette vapor-induced mucociliary dysfunction: role of nicotinic acetylcholine and TRP receptors (5F32HL140729-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9674213. Licensed CC0.

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