Sulphurous Thermal Water Research Articles

Sulphurous thermal water inhalation impacts respiratory metabolic parameters in heavy smokers.

Sulphurous thermal water inhalations have been traditionally used in the treatment of airway diseases. In vivo and in vitro studies reported that they ameliorate mucus rheology, mucociliary clearance and reduce inflammation. Cigarette smoking induces an inflammatory damage, with consequent remodeling of respiratory airways, which in turn affect pulmonary functions. Despite the anti-inflammatory effects of H2S are clinically documented in several airway inflammatory diseases, data on the effects of sulphurous thermal water treatment on pulmonary function and biomarkers of airways inflammation in smokers are still scant. Therefore, we investigated whether a conventional cycle of sulphurous thermal water inhalation produced changes in markers of respiratory inflammation and function. A cohort of 504 heavy current and former smokers underwent 10-day cycles of sulphurous thermal water inhalation. Pulmonary function and metabolic analyses on exhaled breath condensate were then performed at day 0 and after the 10-day treatment. Spirometric data did not change after spa therapy, while exhaled breath condensate analysis revealed that a single 10-day cycle of sulphurous water inhalation was sufficient to induce a statistically significant increase of citrulline levels along with a decrease in ornithine levels, thus shifting arginine metabolism towards a reduced nitric oxide production, i.e. an anti-inflammatory profile. Overall, sulphurous thermal water inhalation impacts on arginine catatabolic intermediates of airways cells, shifting their metabolic balance towards a reduction of the inflammatory activity, with potential benefits for smokers.

Immunological aspects of balneology

The skin is the biggest immune organ of the human body. On the one hand the different mineral waters have strong influence on the skin during the head out water immersion, on the other hand they can casue a lot of molecular changes in the human body, by the modulation of the immune system. On the basis of the available evidence among the inorganic elements the sulphur(and its derivatives) has one of the most pronounced effect on the skin and human body. The sulphurous water can inhibit the production of cytokines,especially IL-2 and interferon gamma (IFN-c) Hydrogen sulphide(H2S) decreases IL-1β-induced activation of fibroblast-like synoviocytes at patients suffering from osteoarthritis, which may have a beneficial effect for its treatment. H2S partially antagonizes IL-1β stimulation through selective manipulation of the MAPkinase. Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity. Sulfur bath therapy could reduce the oxidative stress, by alterations of SOD activities. The radon bath can reduce the activation marker of CD69 on T, B, and NK cells. Radon bath has a beneficial effect on clinical parameters in Rheumatoid arthritis. As account of a new study, it showed for the first time a modulation of the peripheral immune cells following standard radon spa therapy. Mud-bath therapy, can decrease the serum adiponectin and resistin levels at patients after mud bath treatment. Balneotherapy caused statistically significant and long lasting decrease in serum levels of C-reactive protein in patients treated with mineral thermal baths. Long-term bathing in CO2-enriched water proved a cellular protein response of epithelial cells in the epidermis. The heatwater has a possible immunomodulatory effect on keratinocytes during the progression of IL-17-mediated inflammatory skin diseases. Skin Microbiome can change in Patients with Psoriasis before and after Balneotherapy. Thermal stress has an immunosuppressive effect. There are growing numbers of studies when the balneotherapy was combined with anti- TNF therapy, and the results demonstrated that the combined therapy gave better results that the biological therapy alone.

Hydrogen sulphide decreases IL-1β-induced activation of fibroblast-like synoviocytes from patients with osteoarthritis.

Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA.

FRI0590-HPR Effects of Sulphurous Water Immersion Baths in Knee Osteoarthritis Patients: A Randomized and Controlled Clinical Trial

BackgroundOsteoarthritis is a degenerative disorder of synovial joints characterized by irreversible loss of articular cartilage and hypertrophic bone changes. As a non-invasive treatment, balneotherapy is used in various rheumatic diseases.ObjectivesEvaluate...

Thermal water applications in the treatment of upper respiratory tract diseases: a systematic review and meta-analysis.

Background. Thermal water inhalations and irrigations have a long tradition in the treatment of airway diseases. Currently there exists no systematic review or meta-analysis on the effectiveness of thermal water treatment in upper respiratory tract diseases. Methods. A systematic search in the databases of MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and MedPilot was accomplished. Results. Eight evaluable outcome parameters from 13 prospective clinical studies were identified for 840 patients. Mucociliary clearance time improves significantly (P < 0.01) for the pooled thermal water subgroup and the sulphurous subgroup after 2 weeks (−6.69/minutes) and after 90 days (−8.33/minutes), not for isotonic sodium chloride solution (ISCS). Nasal resistance improved significantly after 2 weeks (Radon, ISCS, and placebo), after 30 days (sulphur and ISCS), and after 90 days (sulphur). Nasal flow improved significantly with the pooled thermal water, radon alone, and ISCS subgroups. For the IgE parameter only sulphurous thermal water (P < 0.01) and ISCS (P > 0.01) were analyzable. Adverse events of minor character were only reported for sulphurous treatment (19/370). Conclusion. Thermal water applications with radon or sulphur can be recommended as additional nonpharmacological treatment in upper airway diseases. Also in comparison to isotonic saline solution it shows significant improvements and should be investigated further.

Sulphurous Thermal Water Increases the Release of the Anti-Inflammatory Cytokine IL-10 and Modulates Antioxidant Enzyme Activity

The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p less than 0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties.

The Antioxidant Activity of Sulphurous Thermal Water Protects against Oxidative DNA Damage: A Comet Assay Investigation

Various studies have recently shown that sulphurous waters acts against the oxidants released during respiratory bursts of human neutrophils, and free radicals such as HO•, O2¯•, Tempol and Fremy's salt. However, there is still a lack of data concerning their direct protection of DNA. The aim of this study was to investigate the antigenotoxicity effects of sulphurous water, which has never been previously investigated for this purpose, using the alkaline single cell gel electrophoresis (SCGE) approach (comet assay). The comet assay is a sensitive method for assessing DNA fragmentation in individual cells in genotoxicity studies but can also be used to investigate the activity of agents that protect against DNA damage. The extent of migration was measured by means of SCGE, and DNA damage was expressed as tail moment. All of these assays were made using natural sulphurous water, degassed sulphurous water (no detectable HS), and reconstituted sulphurous water (degassed plus NaHS). DNA damages was significantly inhibited by natural water with HS concentrations of 5.0 and 2.5 μg/mL. The use of degassed water did not lead to any significant differences from baseline values, whereas the reconstituted water led to significant results overlapping those obtained using natural water. These findings confirm the importance of the presence of an HS group (reductive activity) and indicate that, in addition to their known mucolytic activity and trophic effects on respiratory mucosa, HS groups in sulphurous water also protect against oxidative DNA damage and contribute to the water's therapeutic effects on upper and lower airway inflammatory diseases.

Reducing Agents Decrease the Oxidative Burst and Improve Clinical Outcomes in COPD Patients: A Randomised Controlled Trial on the Effects of Sulphurous Thermal Water Inhalation

Background. Inhalation of thermal water with antioxidant properties is empirically used for COPD. Aims. To evaluate the effects of sulphurous thermal water (reducing agents) on airway oxidant stress and clinical outcomes in COPD. Methods. Forty moderate-to-severe COPD patients were randomly assigned to receive 12-day inhalation with sulphurous thermal water or isotonic saline. Patients were assessed for superoxide anion (O2 −) production in the exhaled breath condensate and clinical outcomes at recruitment, the day after the conclusion of the 12-day inhalation treatment, and one month after the end of the inhalation treatment. Results. Inhalation of reducing agents resulted in a significant reduction of O2 − production in exhaled breath condensate of COPD patients at the end of the inhalatory treatment and at followup compared to baseline. A significant improvement in the COPD assessment test (CAT) questionnaire was shown one month after the end of the inhalatory treatment only in patients receiving sulphurous water. Conclusion. Thermal water inhalation produced an in vivo antioxidant effect and improvement in health status in COPD patients. Larger studies are required in order to evaluate whether inhalation of thermal water is able to modify relevant clinical outcomes of the disease (the study was registered at clinicaltrial.gov—identifier: NCT01664767).

The effect of sulphurous water in patients with osteoarthritis of hand. Double-blind, randomized, controlled follow-up study

The aim of the study was to demonstrate the effectiveness of sulphurous water in patients with osteoarthritis of the hand. Forty-seven patients with osteoarthritis of the hand were enrolled into the double-blind, randomized, controlled study, satisfying ACR criteria. One group of the patients (n = 24) received balneotherapy, bathing in sulphurous thermal water for 20 min per occasion, 15 times in all during a period of 3 weeks. The control group (n = 21) had a bath exclusively in warm tap water. Assessments were carried out in both groups on four occasions: at the beginning and at the end of the treatment, and 3 and 6 months after the beginning of the treatment. The parameters studied were the following: pain in the hand, morning stiffness in the joints, grip strength of both hands, and Health Assessment Questionnaire Disability Index (HAQ) and AUSCAN Hand Osteoarthritis Index and EuroQol quality of life questionnaire. At the end of treatment, the improvement was more pronounced in the patient group treated with the sulphurous water. After 3 months, significant improvement could be detected in all parameters, except the morning stiffness and EQ5D. After 6 months, the values of pain, HAQ and AUSCAN continued to be significantly better in comparison with the baseline values. The improvement in quality of life was significant only at the end of the treatment, 6 months later not any longer. The difference between the two groups was significant after 3 months in point of pain and EQVAS. Balneotherapy and within this the sulphurous spa water alone may be effective for the attenuation of pain in patients with hand osteoarthrosis.

Effects of sulphurous water on human neutrophil elastase release

Molecules bearing a sulphide (HS) group, such as glutathione, play a fundamental role in the defensive system of human airways, as shown by the fact that the lining fluid covering the epithelia of the respiratory tract contains very high concentrations of glutathione: the lungs and nose, respectively, contain about 140 and 40 times the concentrations found in plasma. Consequently, various low-weight soluble molecules bearing an HS group (including N-acetylcysteine, mesna and thiopronine, and prodrugs such as stepronine and erdosteine) have been used for therapeutic purposes. HS groups can also be therapeutically administered by means of sulphurous thermal water containing HS groups. The aim of this study was to investigate the direct activity of such water on the release of elastase by activated human neutrophils. After the neutrophils were incubated with increasing amounts of sulphurous water or the HS/hydrogen sulphide donor sodium hydrosulphide (NaHS), elastase release was initiated by N-formyl-methionyl-leucyl-phenylalanine and measured by means of spectrofluorimetry using methylsuccinylalanylprolylvalyl-methylcoumarin amide as the fluorogenic substrate. To verify the presence of direct action on elastase we determined the diameter of the area of elastinolysis on elastine-agarose gel plates. The sulphurous water significantly inhibited elastase release at HS concentrations ranging from 4.5 to 18 μg/ml, as assayed using the iodometric method; in the case of NaHS, the inhibition was significant at HS concentrations ranging from 2.2 to 18 μg/ml. The concentration-effect regression lines of both were parallel and neither showed any direct elastolytic activity. Previous claims concerning the activity of sulphurous water have been based on the patients' subjective sense of wellbeing and on symptomatic (or general) clinical improvements that are not easy to define or quantify exactly. Our findings indicate that, in addition to its known mucolytic and antioxidant activity, sulphurous water also has an anti-elastase activity that may help to control the inflammatory processes of upper and lower airway diseases.

Sulphurous thermal water inhalations in the treatment of chronic rhinosinusitis

The aim of this study was to evaluate the efficiency of sulphurous thermal water in the treatment of chronic rhinosinusitis (CRS). Eighty patients with CRS were included and randomly assigned into two groups. Patients underwent a 12-day course of warm vapour inhalations and nasal irrigations with sulphurous thermal water in group A, and a physiological solution in group B. Compared with group B, in group A the results were as follows: serum concentration of IgE was significantly lower (p<0.05) 12 days (76.27+26.3 mg/dl vs. 97.44±45.4) and 3 months after the beginning of the treatment (75.48+26.1 mg/dl vs. 98.37±41.4); IgA titers were not significantly higher 12 days (231.09±120.3 mg/dl vs. 220.44+114.4 mg/dl) and 3 months after the beginning of the treatment (235.44±118.5 mg/dl vs. 214.51±111.8 mg/dl); VAS scores were significantly (p<0.05) improved at 12 days (1.7+0.18 vs. 6.9±0.51) and 3 months after the start (1.8+0.22 vs. 7.1±0.59); NMIT was normal at 12 days (11.54±1.59 min vs. 17.38+1.83 min) and 3 months after the beginning of the treatment (11.46+2.07 min vs. 17.43±2.01 min); total nasal resistances were significantly (p<0.05) decreased at 12 days and 3 months. Our results indicate the efficiency and applicability of sulphurous thermal water in the treatment of CRS.

Functional and Histologic Assessment of Rat Gastric Mucosa after Chronic Treatment with Sulphurous Thermal Water

The effect of a chronic (4 weeks) administration of sulphurous thermal water on gastric acid secretion and mucosal defense was investigated in rats. Animals were randomized to receive daily intake of tap water or of thermal water obtained from a local spa center (Tabiano, Parma, Italy). Rats were followed for one month as for water and food consumption, body weight and general conditions. At the end of the watering period, the following study protocols were carried out: (a) study of basal and stimulated gastric acid secretion under general anesthesia, and (b) study of the gastric mucosal resistance against the damage induced by ethanol and indomethacin in conscious rats. Basal acid secretion and the acid response to pentagastrin or to histamine were similar in rats assuming ordinary drinking water or thermal water. As for resistance to gastric damage, histological, but not macroscopic, evaluation revealed that rats which assumed thermal water were slightly more resistant to the gastrolesive effect of ethanol (either absolute or diluted). Again, when indomethacin was used as a noxious stimulus, no difference was noted between the two groups as for macroscopic damage; only a nonsignificant reduction of damage was observed histologically in stomachs of rats assuming thermal water. In conclusion, these results indicate that chronic treatment of rats with thermal water, rich in sulphur compounds, may have only minimal effects on the rat gastric mucosa and did not significantly affect mucosal defense mechanisms. The observed tendency to gastroprotection would possibly need further investigation with longer periods of administration.

Sulphurous water inhalations in the prophylaxis of recurrent upper respiratory tract infections

The aim of this study was to evaluate the efficacy and the effect of sulphurous thermal water inhalations in the treatment of the recurrent upper respiratory tract (RURT) infections in children. A total of 100 children with RURT infections were included. All children underwent a 12-day course warm vapour inhalations. For the inhalations, we used sulphurous thermal water in the group A, while physiological solution in the group B. At the beginning, at the end and 3 months after start, all children underwent medical history, ENT examination, plasma levels of immunoglobulins class E, G, A, M (IgE, IgG, IgA, IgM), subjective assessment of symptoms (VAS), nasal mucociliar transport time (NMTT) determination, and evaluation of frequency, duration, severity and social impact of RURT episodes. Compared with group B, after the treatment and at the end of the study, in children treated with sulphurous thermal water, the serum concentration of IgE was significantly (p<0.05) lower (75.13+/-27.1mg/dl vs 96.87+/-41.3mg/dl; 74.23+/-26.2mg/dl vs 98.24+/-42.7 mg/dl), IgA titers were higher (238.14+/-122.1mg/dl vs 218.62+/-115.8 mg/dl; 239.72+/-119.7 mg/dl vs 210.46+/-107.3mg/dl), serum concentrations of IgG and IgM unchanged, VAS scores presented a significant (p<0.05) improvement (1.8+/-0.19 vs 6.8+/-0.54; 1.9+/-0.21 vs 6.9+/-0.61), NMTT was normal (11.15+/-1.59 min vs 17.63+/-2.17; 11.25+/-2.10 min vs 17.77+/-2.19 min) and frequency, duration, severity and social impact of RURT episodes were significantly (p<0.05) lower. Our findings indicate that, in addition to their known effects, the sulphurous water also have an immunomodulant activity that contributes to their therapeutic effects.

Antioxidant Effect of Sulphurous Thermal Water on Human Neutrophil Bursts: Chemiluminescence Evaluation

Background: The activities of the HS (sulfhydryl or thiolic) group in the cysteine of glutathione or various low-weight soluble molecules (thiolic drugs), such as N-acethylcysteine, mesna, thiopronine and dithiotreitol or stepronine and erdosteine (prodrugs), include its antioxidant activity in the airways during the release of reactive oxygen or nitrogen species (ROS, RNS) by polymorphonuclear neutrophils (PMNs) activated in response to exogenous or endogenous stimuli. Objective: In addition to being administered by means of thiolic molecules, the HS group can also be given by means of the inhalation of sulphurous thermal water. The aim of this study was to investigate the effect of sulphurous thermal water on the release of ROS and RNS during the bursts of human PMNs. Methods: The luminol-amplified chemiluminescence methodology was used to investigate the ROS and RNS released by PMNs stimulated with N-formyl-methionyl-leucyl-phenylalanine and phorbol-12-myristate-13-acetate, before and after incubation with sulphurous water. Effects on cell-free systems were also investigated. Results: The water significantly reduced the luminol-amplified chemiluminescence of N-formyl-methionyl-leucyl-phenylalanine- andphorbol-12-myristate-13-acetate-activated PMNs on average from 0.94 to 15.5 µg/ml of HS, even after the addition of L-arginine, a nitric oxide (NO) donor. Similar findings have also been obtained in a cell-free system, thus confirming the importance of the presence of the HS group (reductive activity). Conclusions: The positive effects of the activity of sulphurous thermal waters has been partially based on the patients’ subjective sense of wellbeing and partially on not always easy to quantify symptomatic (or general) clinical improvements. Our findings indicate that, in addition to their known mucolytic activity and trophic effects on respiratory mucosa, the HS groups present in the sulphurous thermal water of this spring also have antioxidant activity that contributes to the therapeutic effects of the water in upper and lower airway inflammatory diseases.