# E-cig flavors and their effects on respiratory innate immune responses

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $495,668

## Abstract

Project Summary/Abstract
Many of the flavoring chemicals in e-cigarettes present a class of chemicals unique to e-cigarettes, potentially
causing distinct adverse health effects. Several e-liquid flavoring compounds are α,β-unsaturated aldehydes, a
class of chemicals with known adverse effects on respiratory immune function. Among those flavoring
compounds is cinnamaldehyde (CA), an α,β-unsaturated aldehyde often contained in popular cinnamon or
spicy flavored e-liquids and with known immune modulating activities. However, potential effects of CA on
respiratory immune responses present a critical knowledge gap, which will be the focus of this application. We
will use tightly linked mechanistic in vitro and human in vivo studies to determine adverse effects of CA on
respiratory innate immune functions, with specific focus on two components: 1) the mucociliary component
consisting of ciliated epithelial cells lining the airways and 2) the cellular component consisting of resident and
infiltrating leukocytes, such as macrophages (Macs). Our data demonstrate that CA-containing e-liquids greatly
affect ciliary beating and respiratory immune cell function at doses that do not cause overt cytotoxicity. These
effects were associated with modified mitochondrial respiration and could be inhibited by thiol reducing
reagents. Thus, based on existing knowledge and our own data we hypothesize that CA-containing e-liquids
suppress innate mucosal immune function by CA-induced inhibition of mitochondrial respiration and thiol
modification of cellular proteins. We will test this hypothesis in two specific aims: SA1 will determine CA-
induced effects on epithelial ciliary function and mucociliary clearance (MCC) and identify the mechanisms
mediating these responses. To achieve this aim we will expose well-differentiated human bronchial epithelial
cells (HBECs) to CA-containing e-liquids, assess changes in ciliary beating, and determine the role of
mitochondrial respiration and thiol modification in these responses. To translate these findings into humans in
vivo, we propose to have healthy adult volunteers undergo controlled inhalation of Technetium-99m sulfur
colloid (Tc99m-SC) particles after inhalation of CA-containing e-cigarettes, followed by tracking the egress of
the radiolabeled particles as a measure of MCC using gamma scintigraphy. SA2 will determine CA-induced
modulation of Macs and the mechanisms mediating these responses. To achieve this aim we will stimulate
human Macs with CA-containing e-liquids ex vivo and examine changes in immune function, and determine the
role of thiol modification and mitochondrial respiration in these responses. Macs obtained through induced
sputum (IS) from human subjects undergoing controlled vaping exposure to CA-containing e-liquids will be
used to translate the mechanistic findings obtained in Macs ex vivo into humans in vivo. Data derived from
these highly integrated translational studies will yield important mechanisti...

## Key facts

- **NIH application ID:** 10011941
- **Project number:** 5R01HL139369-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** ILONA JASPERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $495,668
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011941

## Citation

> US National Institutes of Health, RePORTER application 10011941, E-cig flavors and their effects on respiratory innate immune responses (5R01HL139369-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10011941. Licensed CC0.

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