Toxic in vitro effects of flavoured-air inhalers containing essential oils in differentiated human nasal epithelial cells at air-liquid interface.

Flavoured-air inhalers containing essential oils are marketed as safe, natural alternatives to smoking and vaping, yet their potential respiratory toxicity remains effectively unexamined. Manufacturers claim safety based on "100% natural" ingredients, despite evidence that essential oil inhalation can cause adverse respiratory effects. Our objective was to assess the in vitro toxicity of six commercially available flavoured-air products on human nasal airway epithelial cells. Differentiated air-liquid interface cultures of primary nasal airway epithelial cells from eight healthy adults were exposed for one hour to air (control) or flavoured air from three devices (Füm, Lio, Cigtrus; two flavours each) generated by drawing air through essential oil-infused cores at a continuous airflow of 1 L/min for one hour into an 1000 mL exposure chamber. Outcomes included transepithelial electrical resistance, cytotoxicity, protein release, cytokine/chemokine profiling and histological assessment. Chemical analysis characterised the chemical composition of device cores and identified 29 compounds across the six products, including the possible carcinogen pulegone and cytotoxic cinnamaldehyde. Five of six flavours significantly reduced transepithelial electrical resistance indicating compromised epithelial barrier integrity. Mediator responses were compartment-specific: apical surfaces showed predominantly pro-inflammatory profiles while basal release was broadly suppressed. Histological analysis revealed reduced cilia coverage, fewer mucus-producing cells, and decreased epithelial thickness across multiple treatments. This study shows that a single one-hour exposure to flavoured-air vapour led to epithelial barrier dysfunction, immune dysregulation, and structural damage in healthy human nasal airway epithelial cells, contradicting manufacturer safety claims. Rigorous toxicological evaluation of these products is urgently needed.