Introduction
Our previous publication [1] highlighted a novel biological property of Treignac thermal water concentrated by reverse osmosis: its suppressive effect on cytokine release (IL-6, IL-8, TNF-α) by activated normal bronchial cells. This anti-inflammatory activity complements other biological properties previously demonstrated in vitro and in vivo.
The main aim of the present paper is to provide more details about our objectives and the clinical trial we intend to set up in order to test the effect of an aerosol of this concentrated mineral water in vivo, in humans, on nasal and bronchi mucosa.
Current Therapeutic Arsenal in Otorhinolaryngology and Pulmonology
The nasal and bronchial mucosa consist mainly of ciliated epithelial cells and mucus-secreting goblet cells [2], supported by basal stem cells in both upper and lower airways [3]. In COPD, subsets of basal cells secrete IL-13 and IL-33 [4].
The epithelium acts as a first line of defense, clearing inhaled particles, regulating ionic and water exchanges, and secreting antimicrobial molecules [5].
The periciliary fluid and mucus layer forms a continuous protective interface at the airway surface [6].
A pro-regenerative strategy of the surface epithelium seeks not only to repair damage but also to reconstitute a functional epithelial structure through coordinated processes of cell migration, proliferation, and differentiation. These are regulated by growth factors, cytokines, extracellular matrix proteins, and proteolytic enzymes.
According to international reports, inhaled short-acting inhaled B2 agonists with or without short-acting anticholinergics are recommended to treat chronic obstructive pulmonary disease (COPD) exacerbations [7–19] complemented more recently by biotherapies. In acute and chronic rhinosinusitis, the medical management is mainly based on the use of antibiotics, local corticoids and even general corticoids as adjunctive therapy. Saline nasal irrigation may be also helpful as a post-operative treatment.
The treatment of these inflammatory diseases is therefore essentially based on chemotherapy and biotherapy, and a natural long-term therapy would certainly have its place.
Why Mineral Waters and Interest of Aerosol Therapy?
The main therapeutic objectives of thermal spa centers are the regeneration and healing of the respiratory mucosa, the reduction of inflammation, the improvement of nasal permeability and sustained airway ventilation while limiting infections and relapses.
An extensive review of papers dealing with in vitro and in vivo biological effects of thermal waters suggest that inhalation of thermal waters may have some beneficial effect, and particularly significant improvements were observed for nasal mucociliary transport time, in chronic and acute rhinitis [20–22] and in asthma and COPD [23– 25]. In bronchiectasis, as in cystic fibrosis, efficacy of hypertonic saline aerosol has been demonstrated to enhance mucociliary clearance. An in vitro study [26] showed that mineral waters from Ledesma, Paracuellos and Archena spas, three Spanish health resorts, induced a significant increase on human lung fibroblasts, a significant increase of cell proliferation and an increase of the release of mediators (MIF, IL-6, CL-1, CCL-5 and ICAM-) involved in proliferation, wound healing, and cell migration.
In thermal spas, hydrotherapy is based on the use of aerosols, nasal baths, nasal irrigation, inhalation techniques, spraying, sniffing, nebulization, pharyngeal showers, gargling, and exposure to a thermal water mist in a vaporarium.
These different arguments underline the potential interest of hydrotherapy by mineral waters.
What is Known about Concentrated Treignac Water®
Mineral waters are classified as weakly mineralized (<500 mg/L), moderately mineralized (between 500 and 1500 mg/L) and highly mineralized (>1500 mg/L). Treignac natural mineral water is the less mineralized mineral water in France (22 mg/L of dry residue at 180°C), hydroxysilicic acid representing about 32% of total residue (Table 1).
|
Calcium |
8.33 mg/L |
Chloride |
27 mg/L |
|
Magnesium |
3.52 mg/L |
Sulfates |
5.05 mg/L |
|
Sodium |
20.40 mg/L |
Nitrates |
26.8 mg/L |
|
Potassium |
2.34 mg/L |
Dry residue at 180°C |
182 mg/L |
|
Silica |
53.8 mg/L |
pH |
6.9 |
|
Hydrogenocarbonates |
26.2 mg/L |
Resistivity (ρ) |
47 Ω.m |
Several arguments [1] were in favor of the involvement of hydroxysilicic acid in the biological properties of Treignac mineral water leading us to prepare a concentrated form with a concentration factor of around height. This process has been patented (European patent [27]) in 2024. Concentrated Treignac mineral water (CTMW) is a weakly mineralized solution with an increase hydroxysilicic acid concentration (6.9 mg/L in the natural water to 53.8 mg/L in the concentrated form). We have chosen a factor of height (Table 1) due to the risk of spontaneous silica condensation for higher concentrations [27]. Even concentrated, Treignac water remains slightly mineralized and so is hypo-osmolar as compared to saline (9 g/L) but keeps its salt equilibrium as in the natural water.
After production, CTMW is quickly sterilized by gamma ray irradiation and is stable (composition and bacteriology) at least for seven years.
The production of a concentrated mineral water by reverse osmosis containing a high concentration of soluble hydroxysilicic acid and maintaining its original ionic balance, while remaining very weakly mineralized due to the risk of ionic interference which could affect the activity of this active molecule, requires starting with a very low-mineralized mineral water such as Treignac mineral water.
Mechanistic Hypothesis
The main potential active molecule contained in CTMW is soluble hydroxysilicic acid whose condensation, leading to its film-forming property, has been extensively confirmed. This property seems to be original as not observed in a lot of other mineral waters [28] even having a similar chemical composition (drinking waters or mineral waters used as a cosmetic base).
We have previously shown that an aerosol of concentrated Treignac water was markedly active on sensitive skin together with a protective action, a soothing effect, and prolonged moisturization.
Moreover, these biological activities do not allow us to prejudge of its mechanism of action on mucosa or on a cellular layer as in the study of cytokine synthesis (IL-6, IL-8, TNF-α) inhibition by bronchial cells [1].
Soluble silica can associate with macromolecules, affecting their tertiary or quaternary structures—notably with collagen, elastin, glycoproteins, and membrane phospholipids [29].
A biosilicification (condensation of soluble silica) in the presence of biological polymers has been described [30] and has to be considered as an interesting hypothesis.
As, on the basis of these biological effects, we plan to test the activity of an aerosol of CTMW on inflammatory pathologies of the respiratory tract, we have now to complete the next two steps on human mucosal explants in order to confirm in vitro the absence of potential toxicity due to its hypo-osmolarity (180 mg/L of dry residue) although we have previously demonstrated the absence of toxicity in vivo on rabbit lung, and also to test its efficacy (antibacterial and/or cytokine release inhibition).
Moreover, on intestinal mucosa, low-salt waters have been shown to reduce intestinal permeability in atopic patients [31].
Aerosol Standardization
Thermal waters aerosols are applied in spas either individually (using a personal aerosol generator with a mask) or collectively in a closed room, where compressed air-powered misters create a thick fog.
Generally, protocols used in spas are based on aerosol generators delivering particles of 2 to 20 µm, thus ensuring good coverage of the upper and middle respiratory tract. Treatment lasts 10 to 20 minutes and the course of treatment is around 18 days. The particle size is essential for reaching deep airways (particles <5 µ) or to limit the treatment to sinus mucosa (particles >10–15 µ) [32]. For clinical studies we will use standardized aerosol generators. Clinical trials protocols will include different doses of CTMW aerosol taking account of the differences of surfaces between nasal (120 cm2 et bronchi (300 m2) mucosa but they have not yet been determined.
At least in France, in spite of the use in routine of mineral waters aerosols in spas, the only authorized solution for aerosol treatment is saline [32] which is widely used either as a vehicle for certain drugs or on its own for nasal irrigation and bronchial clearance. Treignac concentrated water differs mainly by its biological properties, which may be based on dissolved hydroxysilicic acid as an active molecule.
Future Clinical Perspectives and Scientific Program
Whereas numerous therapeutic approaches aim to restore the mucosal barrier through pharmacological means, our purpose is to advocate for future clinical trials in order to evaluate a natural potentially safe background treatment mainly in chronic and acute rhinitis and COBP (Chronic Obstructive Broncho Pneumopathy). In parallel, we intend to start a scientific program in order to elucidate the original condensation properties of hydroxysilicic acid contained in Treignac water and its role in Treignac water’s cellular reactivity modulation
Conclusion
The treatment protocol proposed here mirrors current spa practices but introduces a standardized mineral water aerosol with proven biological properties.
Such a protocol—defined by controlled particle size and dosage—may represent a safe, natural, and complementary therapy in both otorhinolaryngology and pulmonology, paving the way for a new thermal water treatment potentially devoid of adverse effects in line with the already described beneficial effects of hydrotherapy [33].
References
2. Hellings PW, Steelant B. Epithelial barriers in allergy and asthma. J Allergy Clin Immunol. 2020 Jun;145(6):1499–509.
3. Rogers DF. The airway goblet cell. Int J Biochem Cell Biol. 2003 Jan;35(1):1–6.
4. Byers DE, Alexander-Brett J, Patel AC, Agapov E, Dang-Vu G, Jin X, et al. Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease. J Clin Invest. 2013 Sep;123(9):3967–82.
5. Coraux C, Hajj R, Lesimple P, Puchelle E. Réparation et régénération de l'épithélium respiratoire [Repair and regeneration of the airway epithelium]. Med Sci (Paris). 2005 Dec;21(12):1063–9. French.
6. Puchelle E, Gaillard D, Ploton D, Hinnrasky J, Fuchey C, Boutterin MC, et al. Differential localization of the cystic fibrosis transmembrane conductance regulator in normal and cystic fibrosis airway epithelium. Am J Respir Cell Mol Biol. 1992 Nov;7(5):485–91.
7. Barjaktarevic IZ, Milstone AP. Nebulized Therapies in COPD: Past, Present, and the Future. Int J Chron Obstruct Pulmon Dis. 2020 Jul 12;15:1665–77.
8. Berlinski A. 2019 Year in Review: Aerosol Therapy. Respir Care. 2020 May;65(5):705–12.
9. Martin A, Lupfer C, Amen R. Inhaled sodium pyruvate reduces oxygen radicals and inflammatory cytokines in COPD patients. Eur J Respir Med 2022;4:320–6.
10. Haidl P, Schönhofer B, Siemon K, Köhler D. Inhaled isotonic alkaline versus saline solution and radioaerosol clearance in chronic cough. Eur Respir J. 2000 Dec;16(6):1102–8.
11. Lupfer CR, Nadler R, Amen R, Martin A. Inhalation of sodium pyruvate to reduce the symptoms and severity of respiratory diseases including COVID-19, long COVID, and pulmonary fibrosis. Eur J Respir Med. 2021;3(3):229–37.
12. Fesyun AD, Solimene U, Grishechkina IA, Lobanov AA, Andronov SV, Popov AI, et al. Mineral water inhalations for bronchial asthma: a meta-analysis. Eur J Transl Myol. 2023 Jun 23;33(2):11460.
13. Kellett F, Robert NM. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. Respir Med. 2011 Dec;105(12):1831–5.
14. Máiz Carro L, Martínez-García MA. Nebulized hypertonic saline in noncystic fibrosis bronchiectasis: a comprehensive review. Ther Adv Respir Dis. 2019 Jan-Dec;13:1753466619866102.
15. Chang AB, Fortescue R, Grimwood K, Alexopoulou E, Bell L, Boyd J, et al. European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. Eur Respir J. 2021 Aug 26;58(2):2002990.
16. GOLD Global Initiative for Chronic Obstructive Lung Disease (GOLD). https://goldcopd.org/2024-gold-reports.
17. Vogelmeier CF, Román-Rodríguez M, Singh D, Han MK, Rodríguez-Roisin R, Ferguson GT. Goals of COPD treatment: Focus on symptoms and exacerbations. Respir Med. 2020 May;166:105938.
18. Celli BR, Fabbri LM, Aaron SD, Agusti A, Brook R, Criner GJ, et al. An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal. Am J Respir Crit Care Med. 2021 Dec 1;204(11):1251–8.
19. Brightling C, Greening N. Airway inflammation in COPD: progress to precision medicine. Eur Respir J. 2019 Aug 1;54(2):1900651.
20. Varricchio A, Brindisi G, Brunese FP, Daglia M, Dinardo G, Drago L, et al. Thermal water inhalation for allergic rhinitis and recurrent respiratory infections: a narrative review of the evidence. Ital J Pediatr. 2025 Oct 22;51(1):290–6.
21. Fontana M, Vitali M, Del Prete J, Borzì S, Pozzoli A, Vitale K, et al. Beneficial effects of thermal waters on respiratory diseases: a systematic review. Int J Biometeorol. 2025 May;69(5):915–46.
22. Ciprandi G, Cristofolini M, Mira E. Comano thermal water inhalations in the treatment of allergic rhinitis: preliminary results. Eur Ann Allergy Clin Immunol. 2016 Nov;48(6):220–3.
23. Calzetta L, Di Daniele N, Chetta A, Vitale M, Gholamalishahi S, Cazzola M, et al. The Impact of Thermal Water in Asthma and COPD: A Systematic Review According to the PRISMA Statement. J Clin Med. 2024 Feb 14;13(4):1071–90.
24. Viegas J, Esteves AF, Cardoso EM, Arosa FA, Vitale M, Taborda-Barata L. Biological Effects of Thermal Water-Associated Hydrogen Sulfide on Human Airways and Associated Immune Cells: Implications for Respiratory Diseases. Front Public Health. 2019 Jun 5;7:128–32.
25. Guarnieri G, Ferrazzoni S, Scarpa MC, Lalli A, Maestrelli P. Effects of inhalation of thermal water on exhaled breath condensate in chronic obstructive pulmonary disease. Respiration. 2010;79(3):216–21.
26. Melgar-Sánchez LM, García-Ruiz I, Pardo-Marqués V, Agulló-Ortuño MT, Martínez-Galán I. Influence of mineral waters on in vitro proliferation, antioxidant response and cytokine production in a human lung fibroblasts cell line. Int J Biometeorol. 2019 Sep;63(9):1171–80.
27. Sainte-Laudy J, Pons A, Redziniak G, Kita W et Chéron M. Eau de source ou minérale concentrée enrichie en acide hydroxysilicique naturel. Brevet N° EP3432989 (10 Janvier 2024).
28. Smith A, Abir FZ, El Hafiane Y, Launay Y, Faugeron-Girard C, Gloaguen V, et al. Fractal structures and silica films formed by the Treignac water on inert and biological surfaces. Nanoscale Adv. 2020 Aug 12;2(9):3821–8.
29. Schwarz K. A bound form of silicon in glycosaminoglycans and polyuronides. Proc Natl Acad Sci U S A. 1973 May;70(5):1608–12.
30. Annenkov VV, Danilovtseva EN, Pal'shin VA, Verkhozina OG, Zelinskiy SN, Krishnan UM. Silicic acid condensation under the influence of water-soluble polymers: From biology to new materials. RSC Advances. 2017;7(34):20995–1027.
31. Dupuy P, Cassé M, André F, Dhivert-Donnadieu H, Pinton J, Hernandez-Pion C. Low-salt water reduces intestinal permeability in atopic patients. Dermatology. 1999;198(2):153–5.
32. Dautzenberg B, Becquemin MH, Chaumuzeau JP, Diot P; Membres du GAT. Bonnes pratiques de l'aérosolthérapie par nébulisation [Good practice for aerosol therapy by nebulisation]. Rev Mal Respir. 2007 Jun;24(6):751–7. French.
33. Mooventhan A, Nivethitha L. Scientific evidence-based effects of hydrotherapy on various systems of the body. N Am J Med Sci. 2014 May;6(5):199–209.