A Novel Bionebulizer Approach to Study the Effects of Natural Mineral Water on a 3D In Vitro Nasal Model from Allergic Rhinitis Patients

February 9, 2024


Joana Viegas 1, Elsa M. Cardoso 1,2, Lucile Bonneau 1, Ana Filipa Esteves 1, Catarina L. Ferreira 1,3, Gilberto Alves 1,3, António Jorge Santos-Silva 3,4, Marco Vitale 5,6, Fernando A. Arosa 1,3 and Luís Taborda-Barata 1,3,7,8,9,
1 CICS-UBI—Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal;
2 ESS-IPG-School of Health Sciences, Polytechnic Institute of Guarda, Rua da Cadeia, 6300-307 Guarda, Portugal
3 Faculty of Health Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal;
4 Unhais da Serra Thermal Spa, Avenida das Termas, 6215-574 Unhais da Serra, Portugal
5 Faculty of Medicine and Surgery, University Vita-Salute San Raffaele, 20132 Milan, Italy;
6 FoRST—Fondazione per la Ricerca Scientifica Termale, 00198 Rome, Italy
7 UBIAir—Clinical & Experimental Lung Centre, University of Beira Interior, Estrada Municipal 506, 6200-506 Covilhã, Portugal
8 CACB—Clinical Academic Centre of Beiras, Rua do Campo de Tiro, nº 6, 6200-506 Covilhã, Portugal
9 Department of Immunoallergology, Cova da Beira University Hospital Centre, Quinta do Alvito, 6200-251 Covilhã, Portugal

Sulfurous thermal waters (STWs) are used as a complementary treatment for allergic rhinitis. However, there is scant data on the effects of STW on nasal epithelial cells, and in vitro models are warranted. The main aim of this study was to evaluate the dose and time effects of exposure to 3D nasal inserts (MucilAirTM-HF allergic rhinitis model) with STW or isotonic sodium chloride solution (ISCS) aerosols. Transepithelial electrical resistance (TEER) and histology were assessed before and after nebulizations. Chemokine/cytokine levels in the basal supernatants were assessed by enzyme-linked immunosorbent assay. The results showed that more than four daily nebulizations of four or more minutes compromised the normal epithelial integrity. In contrast, 1 or 2 min of STW or ISCS nebulizations had no toxic effect up to 3 days. No statistically significant changes in release of inflammatory chemokines MCP-1/CCL2 > IL-8/CXCL8 > MIP-1α/CCL3, no meaningful release of “alarmins” (IL-1α, IL-33), nor of anti-inflammatory IL-10 cytokine were observed. We have characterized safe time and dose conditions for aerosol nebulizations using a novel in vitro 3D nasal epithelium model of allergic rhinitis patients. This may be a suitable in vitro setup to mimic in vivo treatments of chronic rhinitis with STW upon triggering an inflammatory stimulus in the future.

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