Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function

Abstract Electronic cigarettes (e-cigs) have been introduced as a safer alternative to traditional combustible cigarettes and have been growing in popularity. E-cig e-liquids all contain the carrier compounds, vegetable glycerin (VG), propylene glycol (PG), and nicotine, together with different flav...

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Main Authors: Abdo Durra, Caroline Cherry, Coline Luo, Emily Hou, Andrew Frauenpreis, Arunima Purkayastha, Isabella Passamano, Sara Makanani, Kristen Castillo, Andrew Lund, Woosuk Choi, Chandani Sen, Rachana Chandran, Tammy Rickabaugh, Prashant Kaushal, Mehdi Bouhaddou, Eszter K. Vladar, Brigitte N. Gomperts
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-025-03302-w
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author Abdo Durra
Caroline Cherry
Coline Luo
Emily Hou
Andrew Frauenpreis
Arunima Purkayastha
Isabella Passamano
Sara Makanani
Kristen Castillo
Andrew Lund
Woosuk Choi
Chandani Sen
Rachana Chandran
Tammy Rickabaugh
Prashant Kaushal
Mehdi Bouhaddou
Eszter K. Vladar
Brigitte N. Gomperts
author_facet Abdo Durra
Caroline Cherry
Coline Luo
Emily Hou
Andrew Frauenpreis
Arunima Purkayastha
Isabella Passamano
Sara Makanani
Kristen Castillo
Andrew Lund
Woosuk Choi
Chandani Sen
Rachana Chandran
Tammy Rickabaugh
Prashant Kaushal
Mehdi Bouhaddou
Eszter K. Vladar
Brigitte N. Gomperts
author_sort Abdo Durra
collection DOAJ
description Abstract Electronic cigarettes (e-cigs) have been introduced as a safer alternative to traditional combustible cigarettes and have been growing in popularity. E-cig e-liquids all contain the carrier compounds, vegetable glycerin (VG), propylene glycol (PG), and nicotine, together with different flavors, but the effects of inhalation of these compounds on the airway are not well understood. This study investigates the effects of e-cig exposure on primary human airway epithelial cells grown in air–liquid interface (ALI) cultures, specifically focusing on mucociliary clearance, the lung’s primary host defense mechanism whereby pathogens and particles trapped by mucus are cleared by unidirectional beating by ciliated cells. We developed a microcontroller-based exposure system to reproducibly examine cellular and molecular changes in ALI cultures from e-cig exposure. Here we show heterogeneous, donor-dependent effects of different e-cig flavors on airway epithelial cells. Examining the effects of the unflavored carrier compounds common to all e-cigs, we found that ALI airway cultures exposed to PG:VG (30:70 ratio) with 5% nicotine unflavored e-cigs show a reduction in ciliary beat frequency. Moreover, using transmission electron microscopy, we identified defects in ciliary ultrastructure induced by unflavored e-cigs. Phosphoproteomic analysis uncovered changes in phosphorylation of proteins involved in cadherin and actin binding and the Rho GTPase signaling pathway, which are all involved in cytoskeletal remodeling that may influence ciliary structure and function. Altogether, our findings suggest that exposure to all e-cigs reduces mucociliary clearance.
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spelling doaj-art-e54b8f9f63f54119a90ac5c755f1c5c42025-08-20T04:01:40ZengBMCRespiratory Research1465-993X2025-07-0126111410.1186/s12931-025-03302-wUnflavored electronic cigarette exposure induces alterations in airway ciliary structure and functionAbdo Durra0Caroline Cherry1Coline Luo2Emily Hou3Andrew Frauenpreis4Arunima Purkayastha5Isabella Passamano6Sara Makanani7Kristen Castillo8Andrew Lund9Woosuk Choi10Chandani Sen11Rachana Chandran12Tammy Rickabaugh13Prashant Kaushal14Mehdi Bouhaddou15Eszter K. Vladar16Brigitte N. Gomperts17Department of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalPrograms in Biomedical and Biological Sciences, University of Southern California Health SciencesDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Microbiology, Immunology, and Molecular Genetics, University of CaliforniaDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalDepartment of Microbiology, Immunology, and Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology, and Molecular Genetics, University of CaliforniaMedicine - Pulmonary Sciences & Critical Care Medicine, University of ColoradoDepartment of Pediatrics, David Geffen School of Medicine UCLA, UCLA Children’s Discovery and Innovation Institute, Mattel Children’s HospitalAbstract Electronic cigarettes (e-cigs) have been introduced as a safer alternative to traditional combustible cigarettes and have been growing in popularity. E-cig e-liquids all contain the carrier compounds, vegetable glycerin (VG), propylene glycol (PG), and nicotine, together with different flavors, but the effects of inhalation of these compounds on the airway are not well understood. This study investigates the effects of e-cig exposure on primary human airway epithelial cells grown in air–liquid interface (ALI) cultures, specifically focusing on mucociliary clearance, the lung’s primary host defense mechanism whereby pathogens and particles trapped by mucus are cleared by unidirectional beating by ciliated cells. We developed a microcontroller-based exposure system to reproducibly examine cellular and molecular changes in ALI cultures from e-cig exposure. Here we show heterogeneous, donor-dependent effects of different e-cig flavors on airway epithelial cells. Examining the effects of the unflavored carrier compounds common to all e-cigs, we found that ALI airway cultures exposed to PG:VG (30:70 ratio) with 5% nicotine unflavored e-cigs show a reduction in ciliary beat frequency. Moreover, using transmission electron microscopy, we identified defects in ciliary ultrastructure induced by unflavored e-cigs. Phosphoproteomic analysis uncovered changes in phosphorylation of proteins involved in cadherin and actin binding and the Rho GTPase signaling pathway, which are all involved in cytoskeletal remodeling that may influence ciliary structure and function. Altogether, our findings suggest that exposure to all e-cigs reduces mucociliary clearance.https://doi.org/10.1186/s12931-025-03302-wMotile ciliaE-cigarettesCiliary beating frequencyPhosphoproteomicsCytoskeletal remodelingRho GTPase
spellingShingle Abdo Durra
Caroline Cherry
Coline Luo
Emily Hou
Andrew Frauenpreis
Arunima Purkayastha
Isabella Passamano
Sara Makanani
Kristen Castillo
Andrew Lund
Woosuk Choi
Chandani Sen
Rachana Chandran
Tammy Rickabaugh
Prashant Kaushal
Mehdi Bouhaddou
Eszter K. Vladar
Brigitte N. Gomperts
Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
Respiratory Research
Motile cilia
E-cigarettes
Ciliary beating frequency
Phosphoproteomics
Cytoskeletal remodeling
Rho GTPase
title Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
title_full Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
title_fullStr Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
title_full_unstemmed Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
title_short Unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
title_sort unflavored electronic cigarette exposure induces alterations in airway ciliary structure and function
topic Motile cilia
E-cigarettes
Ciliary beating frequency
Phosphoproteomics
Cytoskeletal remodeling
Rho GTPase
url https://doi.org/10.1186/s12931-025-03302-w
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