Acute and Chronic Effects of Oral Erdosteine on Ciliary Beat Frequency, Cough Sensitivity and Airway Reactivity

  • L. Pappová
  • I. Kazimierová
  • M. Jošková
  • M. Šutovská
  • S. FraňováEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1023)


Erdosteine as a mucolytic agent that decreases mucus viscosity and facilitates mucus expulsion from the airways by cough or ciliary movement. Our objective was to determine whether erdosteine can directly contribute to mucus clearance. We addressed the issue by monitoring acute and chronic effects of erdosteine on ciliary beat frequency (CBF), cough sensitivity, and airway smooth muscle reactivity. The experiments were performed in healthy guinea pigs. Erdosteine (10 mg/kg) was administrated orally in a single dose or daily through 7 days. The cough reflex and specific airway resistance were evaluated in vivo. The CBF in tracheal brushed samples and the contractile response of tracheal smooth muscle stripes to bronchoconstrictive mediators were evaluated in vitro. We found that neither acute nor chronic erdosteine treatment had a significant effect on cough sensitivity and airway reactivity. However, in the vitro condition, erdosteine increased CBF and reduced tracheal smooth muscle contractility; the effects were more pronounced after chronic treatment. We conclude that erdosteine may directly contribute to mucus clearance by CBF stimulation. Although erdosteine has no effect on cough reflex sensitivity, its mild bronchodilator and mucolytic properties may promote effective cough.


Airway reactivity Airway smooth muscles Ciliary beat frequency Cough sensitivity Erdosteine Mucus clearance 



Supported by grants: APVV 0305-12, VEGA 1/0165/14 a MZ 2012/35- UK, CERK II, UK/62/2016; by the project Biomedical Center Martin – ITMS: 26220220187 entitled ‘We support research activities in Slovakia’, co-financed from EU sources.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.


  1. Balsamo R, Lanata L, Egan CG (2010) Mucoactive drugs. Eur Respir Rev 19:127–133CrossRefPubMedGoogle Scholar
  2. Bolser DC (2006) Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest 129:238S–249SCrossRefPubMedPubMedCentralGoogle Scholar
  3. Braga PC, Dal Sasso M, Sala MT, Gianelle V (1999) Effects of erdosteine and its metabolites on bacterial adhesiveness. Arzneimittelforschung 49:344–350PubMedGoogle Scholar
  4. Braga PC, Dal Sasso M, Zuccotti T (2000) Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. Arzneimittelforschung 50:739–746PubMedGoogle Scholar
  5. Braiman A, Priel Z (2008) Efficient mucociliary transport relies on efficient regulation of ciliary beating. Respir Physiol Neurobiol 163:202–207CrossRefPubMedGoogle Scholar
  6. Dal Negro RW (2008) Erdosteine: antitussive and anti-inflammatory effects. Lung 186(Suppl 1):S70–S73CrossRefPubMedGoogle Scholar
  7. Dal Negro RW, Visconti M, Trevisan F, Bertacco S, Micheletto C, Tognella S (2008) Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD. Ther Adv Respir Dis 2:271–277CrossRefPubMedGoogle Scholar
  8. Davies L, Calverley PMA (2010) The evidence for the use of oral mucolytic agents in chronic obstructive pulmonary disease (COPD). Br Med Bull 93:217–227CrossRefPubMedGoogle Scholar
  9. Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881CrossRefPubMedGoogle Scholar
  10. Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, Page CP (2014) Antitussive drugs-past, present, and future. Pharmacol Rev 66:468–512CrossRefPubMedGoogle Scholar
  11. Fahy JV, Dickey BF (2010) Airway mucus function and dysfunction. N Engl J Med 363:2233–2247CrossRefPubMedPubMedCentralGoogle Scholar
  12. Franova S, Kazimierova I, Pappova L, Joskova M, Plank L, Sutovska M (2016) Bronchodilatory, antitussive and anti-inflammatory effect of morin in the setting of experimentally induced allergic asthma. J Pharm Pharmacol 68:1064–1072CrossRefPubMedGoogle Scholar
  13. Hosoe H, Kaise T, Ohmori K, Isohama Y, Kai H, Takahama K, Miyata T (1999) Mucolytic and antitussive effects of erdosteine. J Pharm Pharmacol 51:959–966CrossRefPubMedGoogle Scholar
  14. Joskova M, Sutovska M, Durdik P, Koniar D, Hargas L, Banovcin P, Hrianka M, Khazaei V, Pappova L, Franova S (2016) The role of ion channels to regulate airway ciliary beat frequency during allergic inflammation. Adv Exp Med Biol 921:27–35CrossRefPubMedGoogle Scholar
  15. Kazimierová I, Jošková M, Pecháňová O, Šutovská M, Fraňová S (2015) Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma. Adv Exp Med Biol 838:27–34CrossRefPubMedGoogle Scholar
  16. King M (2006) Physiology of mucus clearance. Paediatr Respir Rev 7(Suppl 1):S212–S214CrossRefPubMedGoogle Scholar
  17. Moretti M, Marchioni CF (2007) An overview of erdosteine antioxidant activity in experimental research. Pharmacol Res 55:249–254CrossRefPubMedGoogle Scholar
  18. Morice AH, Fontana GA, Belvisi MG et al (2007) ERS guidelines on the assessment of cough. Eur Respir J 29:1256–1276CrossRefPubMedGoogle Scholar
  19. Munkholm M, Mortensen J (2014) Mucociliary clearance: pathophysiological aspects. Clin Physiol Funct Imaging 34:171–177CrossRefPubMedGoogle Scholar
  20. Olivieri D, Del Donno M, Casalini A, D’Ippolito R, Fregnan GB (1991) Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis. Respir Int Rev Thorac Dis 58:91–94Google Scholar
  21. Pappová L, Jošková M, Kazimierová I, Šutovská M, Fraňová S (2016) Combination therapy with budesonide and Salmeterol in experimental allergic inflammation. Adv Exp Med Biol 935:25–34CrossRefPubMedGoogle Scholar
  22. Park JS, Park MY, Cho YJ, Lee JH, Yoo CG, Lee CT, Lee SM (2016) Anti-inflammatory effect of erdosteine in lipopolysaccharide-stimulated RAW 264.7 cells. Inflammation 39:1573–1581CrossRefPubMedGoogle Scholar
  23. Pennock BE, Cox CP, Rogers RM, Cain WA, Wells JH (1979) A noninvasive technique for measurement of changes in specific airway resistance. J Appl Physiol Respir Environ Exerc Physiol 46(2):399–406PubMedGoogle Scholar
  24. Polverino M, Polverino F, Fasolino M, Andò F, Alfieri A, De Blasio F (2012) Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Respir Med 7:5CrossRefPubMedPubMedCentralGoogle Scholar
  25. Reinero CR, Lee-Fowler TM, Dodam JR, Cohn LA, DeClue AE, Guntur VP (2011) Endotracheal nebulization of N-acetylcysteine increases airway resistance in cats with experimental asthma. J Feline Med Surg 13:69–73CrossRefPubMedGoogle Scholar
  26. Rogers DF (2004) Airway mucus hypersecretion in asthma: an undervalued pathology? Curr Opin Pharmacol 4:241–250CrossRefPubMedGoogle Scholar
  27. Rogers DF (2007) Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 52:1176–1193PubMedGoogle Scholar
  28. Rubin BK (2010) The role of mucus in cough research. Lung 188(Suppl 1):S69–S72CrossRefPubMedGoogle Scholar
  29. Rubin BK (2014) Secretion properties, clearance, and therapy in airway disease. Transl Respir Med 2:6CrossRefPubMedPubMedCentralGoogle Scholar
  30. Salathe M (2007) Regulation of mammalian ciliary beating. Annu Rev Physiol 69:401–422CrossRefPubMedGoogle Scholar
  31. Seagrave J, Albrecht HH, Hill DB, Rogers DF, Solomon G (2012) Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells. Respir Res 13:98CrossRefPubMedPubMedCentralGoogle Scholar
  32. Thomas B, Rutman A, Hirst RA, Haldar P, Wardlaw AJ, Bankart J, Brightling CE, O’Callaghan C (2010) Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. J Allergy Clin Immunol 126:722–729.e2CrossRefPubMedGoogle Scholar
  33. Thornton DJ, Sheehan JK (2004) From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc Am Thorac Soc 1:54–61CrossRefPubMedGoogle Scholar
  34. Van der Schans CP (2007) Bronchial mucus transport. Respir Care 52:1150–1156PubMedGoogle Scholar
  35. Workman AD, Cohen NA (2014) The effect of drugs and other compounds on the ciliary beat frequency of human respiratory epithelium. Am J Rhinol Allergy 28:454–464CrossRefPubMedGoogle Scholar
  36. Yuan S, Hollinger M, Lachowicz-Scroggins ME, Kerr SC, Dunican EM, Daniel BM, Ghosh S, Erzurum SC, Willard B, Hazen SL, Huang X, Carrington SD, Oscarson S, Fahy J (2015) Oxidation increases mucin polymer cross-links to stiffen airway mucus gels. Sci Transl Med 7:276ra27CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • L. Pappová
    • 1
    • 2
  • I. Kazimierová
    • 1
    • 2
  • M. Jošková
    • 1
    • 2
  • M. Šutovská
    • 1
    • 2
  • S. Fraňová
    • 1
    • 2
    Email author
  1. 1.Biomedical Center Martin, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  2. 2.Department of Pharmacology, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia

Personalised recommendations