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

Marco Contoli, Giulia Gnesini, Giacomo Forini, Brunilda Marku, Alessia Pauletti, Anna Padovani, Paolo Casolari, Liliana Taurino, Andrea Ferraro, Milva Chicca, Adalberto Ciaccia, Alberto Papi, Silvano Pinamonti, Marco Contoli, Giulia Gnesini, Giacomo Forini, Brunilda Marku, Alessia Pauletti, Anna Padovani, Paolo Casolari, Liliana Taurino, Andrea Ferraro, Milva Chicca, Adalberto Ciaccia, Alberto Papi, Silvano Pinamonti

Abstract

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).

Figures

Figure 1
Figure 1
Superoxide anion production in COPD patients at the baseline, at the end of the inhalation treatment, and one month after the end of the treatment.
Figure 2
Figure 2
Total sputum cell counts in COPD patients at the baseline, at the end of the inhalation treatment, and one month after the end of the treatment.
Figure 3
Figure 3
Lung function parameters (postbronchodilator FEV1 and residual volume) in COPD patients at the baseline, at the end of the inhalation treatment, and one month after the end of the treatment.
Figure 4
Figure 4
COPD Assessment Test (CAT) questionnaire in COPD patients at the baseline, at the end of the inhalation treatment, and one month after the end of the treatment.
Figure 5
Figure 5
Correlation between changes in COPD Assessment Test (CAT) questionnaire score and superoxide anion production in exhaled breath condensate of COPD treated with sulphurous thermal water at one month after the end of the inhalatory treatment compared to baseline.

References

    1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. Bethesda, Md, USA: National Institutes of Health, National Heart, Lung and Blood Institute; 2001. (Publication no. 2701:1-108).
    1. Psarras S, Caramori G, Contoli M, Papadopoulos N, Papi A. Oxidants in asthma and in chronic obstructive pulmonary disease (COPD) Current Pharmaceutical Design. 2005;11(16):2053–2062.
    1. Barnes PJ. Chronic obstructive pulmonary disease. The New England Journal of Medicine. 2000;343(4):269–280.
    1. Hancock JT, Desikan R, Neill SJ. Role of reactive oxygen species in cell signalling pathways. Biochemical Society Transactions. 2001;29(2):345–350.
    1. Faux SP, Tai T, Thorne D, Xu Y, Breheny D, Gaca M. The role of oxidative stress in the biological responses of lung epithelial cells to cigarette smoke. Biomarkers. 2009;14(supplement 1):90–96.
    1. Hillas G, Nikolakopoulou S, Hussain S, Vassilakopoulos T. Antioxidants and mucolytics in COPD management: when (if ever) and in whom? Current Drug Targets. 2013;14(2):225–234.
    1. 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):216–221.
    1. Pellegrini M, Fanin D, Nowicki Y, et al. Effect of inhalation of thermal water on airway inflammation in chronic obstructive pulmonary disease. Respiratory Medicine. 2005;99(6):748–754.
    1. Braga PC, Sambataro G, Dal Sasso M, Culici M, Alfieri M, Nappi G. Antioxidant effect of sulphurous thermal water on human neutrophil bursts: chemiluminescence evaluation. Respiration. 2008;75(2):193–201.
    1. Valitutti S, Castellino F, Musiani P. Effect of sulfurous (thermal) water on T lymphocyte proliferative response. Annals of Allergy. 1990;65(6):463–468.
    1. Braga PC, Dal Sasso M, Culici M, et al. Effects of sulphurous water on human neutrophil elastase release. Therapeutic Advances in Respiratory Disease. 2010;4(6):333–340.
    1. Papi A, Contoli M, Gasparini P, et al. Role of xanthine oxidase activation and reduced glutathione depletion in rhinovirus induction of inflammation in respiratory epithelial cells. The Journal of Biological Chemistry. 2008;283(42):28595–28606.
    1. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. European Respiratory Journal. 2005;26(2):319–338.
    1. Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. European Respiratory Journal. 2005;26(3):511–522.
    1. Jones PW, Harding G, Berry P, Wiklund I, Chen W-H, Kline Leidy N. Development and first validation of the COPD Assessment Test. European Respiratory Journal. 2009;34(3):648–654.
    1. Jones PW, Brusselle G, Dal Negro RW, et al. Properties of the COPD assessment test in a cross-sectional European study. European Respiratory Journal. 2011;38(1):29–35.
    1. Fabbri LM, Romagnoli M, Corbetta L, et al. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2003;167(3):418–424.
    1. Efthimiadis A, Spanevello A, Hamid Q, et al. Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation. European Respiratory Journal, Supplement. 2002;20(37):19s–23s.
    1. Goldoni M, Caglieri A, Andreoli R, et al. Influence of condensation temperature on selected exhaled breath parameters. BMC Pulmonary Medicine. 2005;5, article 10
    1. Caglieri A, Goldoni M, Acampa O, et al. The effect of inhaled chromium on different exhaled breath condensate biomarkers among chrome-plating workers. Environmental Health Perspectives. 2006;114(4):542–546.
    1. Pinamonti S, Muzzoli M, Chicca MC, et al. Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease. Free Radical Biology and Medicine. 1996;21(2):147–155.
    1. Pellegrini M, Fanin D, Nowicki Y, et al. Effect of inhalation of thermal water on airway inflammation in chronic obstructive pulmonary disease. Respiratory Medicine. 2005;99(6):748–754.
    1. Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. Journal of Allergy and Clinical Immunology. 2006;117(3):522–543.
    1. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. The FASEB Journal. 2001;15(6):1110–1112.
    1. Marwick JA, Caramori G, Stevenson CS, et al. Inhibition of PI3Kδ restores glucocorticoid function in smoking-induced airway inflammation in mice. American Journal of Respiratory and Critical Care Medicine. 2009;179(7):542–548.
    1. Hille R, Nishino T. Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase. The FASEB Journal. 1995;9(11):995–1003.
    1. Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(20):10723–10728.
    1. Pinamonti S, Leis M, Barbieri A, et al. Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease. Free Radical Biology and Medicine. 1998;25(7):771–779.
    1. Ichinose M, Sugiura H, Yamagata S, et al. Xanthine oxidase inhibition reduces reactive nitrogen species production in COPD airways. European Respiratory Journal. 2003;22(3):457–461.
    1. Hassoun PM, Yu FS, Zulueta JJ, White AC, Lanzillo JJ. Effect of nitric oxide and cell redox status on the regulation of endothelial cell xanthine dehydrogenase. American Journal of Physiology—Lung Cellular and Molecular Physiology. 1995;268(5):L809–L817.
    1. Lee MM, Green FHY, Schürch S, et al. Comparison of inhibitory effects of oxygen radicals and calf serum protein on surfactant activity. Molecular and Cellular Biochemistry. 2004;259(1-2):15–22.
    1. Taube C, Holz O, Mücke M, Jorres RA, Magnussen H. Airway response to inhaled hypertonic saline in patients with moderate to severe chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2001;164(10):1810–1815.

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