Investigating the impact of e-cigarettes on lung cells: a combined in vitro and computational study

The increasing use of electronic cigarettes (ECs), particularly among youth, has raised concerns about their impact on respiratory health. This thesis investigates the effects of EC aerosol exposure on the alveolar epithelium using a combination of in silico modelling and in vitro experimentation. A computational model of aerosol transport and deposition in the human respiratory tract was applied to estimate regional dosimetry under direct-to-lung (DTL) and mouth-to-lung (MTL) vaping regimens. DTL produced higher overall deposition, particularly in distal lung regions, while MTL led to greater deposition in the upper airways. These differences reflected DTL’s higher flow rates and larger puff volumes. Deposited particle mass ranged from 1×10−7 to 4×10−3 mg, highlighting the importance of dose targeting based on lung region. To investigate the effects of EC aerosols on human alveolar type II (ATII) epithelial cells, a custom-built Electronic Cigarette Aerosol Machine (ECAM) was integrated with a British American Tobacco (BAT) cell chamber to enable precise control of puff profiles, flow rates, and aerosol concentrations. ATII cells cultured at the air–liquid interface (ALI) were exposed to aerosols containing combinations of PG/VG, nicotine, nicotine salts, and tobacco flavour. Biological responses were assessed via transepithelial electrical resistance (TEER), lactate dehydrogenase (LDH) release, IL-8 secretion, and gene expression. Nicotine salt and flavoured aerosols significantly reduced TEER, increased LDH and IL-8 levels, and downregulated OCLN, TJP1, SCNN1A, ATP1A1, AQP3, and CHRNA5, indicating barrier disruption, cytotoxicity, and inflammation. In contrast, nicotine alone caused only mild increases in LDH and IL-8, and upregulated SCNN1A, ATP1A1, AQP3, and CHRNA5, suggesting a compensatory mechanism to restore ion and fluid homeostasis. ACE2 expression was also downregulated in response to nicotine salt and flavour. This study presents a novel framework integrating in silico dosimetry with biologically relevant in vitro models. The ECAM–cell chamber platform provides a physiologically meaningful tool for future inhalation toxicology studies and regulatory assessments.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Bioengineering

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2025

Author dc:creator

• Aghababaie, Marzieh

Advisors dc:contributor.advisor

• Burrowes, Kelly
• Suresh, Vinod
• McGlashan, Sue

• Vaping
• E-cigarette
• Particle transport
• lung
• alveolar epithelial cells
• nicotine
• Gene expression
• in vitro
• Air Liquid Interface (ALI)
• Ion channels

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/75264

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/75264