Abstract
The aim of this study was to determinate bronchodilator, antitussive, and ciliomodulatory activity of inhaled combination therapy with budesonide and salmeterol, and to correlate the results with the anti-inflammatory effect. The experiments were performed using two models of allergic inflammation (21 and 28 days long sensitization with ovalbumine) in guinea pigs. The animals were treated daily by aerosols of budesonide (1 mM), salmeterol (0.17 mM), and a half-dose combination of the two drugs. Antitussive and bronchodilator activities were evaluated in vivo. The ciliary beat frequency (CBF) was assessed in vitro in tracheal brushed samples, and inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, and TNF-α) were determined in bronchoalveolar lavage fluid (BALF). We found that the combination therapy significantly decreased the number of cough efforts, airway reactivity, and the level of inflammatory cytokines in both models of allergic asthma. Three weeks long sensitization led to an increase in CBF and all three therapeutic approaches have shown a ciliostimulatory effect in order: salmeterol < budesonid < combination therapy. Four weeks long ovalbumine sensitization, on the other hand, decreased the CBF, increased IL-5, and decreased IL-13. In this case, only the combination therapy was able to stimulate the CBF. We conclude that a half-dose combination therapy of budesonide and salmeterol shows comparable antitussive, bronchodilator, and the anti-inflammatory effect to a full dose therapy with budesonide alone, but had a more pronounced stimulatory effect on the CBF.
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References
Barnes PJ (1999) Effect of β agonists on inflammatory cells. J Allergy Clin Immunol 104:10–17
Barnes PJ (2011a) Pathophysiology of allergic inflammation. Immunol Rev 242:31–50
Barnes PJ (2011b) Glucocorticosteroids: current and future directions. Br J Pharmacol 163:29–43
Braiman A, Priel Z (2008) Efficient mucociliary transport relies on efficient regulation of ciliary beating. Respir Physiol Neurobiol 163:202–207
Chung KF, Caramori G, Adcock IM (2009) Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future. Eur J Clin Pharmacol 65:853–871
Durham AL, Caramori G, Chung KF, Adcock IM (2015) Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Transl Res 167:192–203
Erle DJ, Sheppard D (2014) The cell biology of asthma. J Cell Biol 205:621–631
Franova S, Joskova M, Sadlonova V, Pavelcikova D, Mesarosova L, Novakova E, Sutovska M (2013) Experimental model of allergic asthma. Adv Exp Med Biol 756:49–55
GINA (2015) From the global strategy for asthma management and prevention, global initiative for asthma. Available from http://www.ginasthma.org. Accessed on 27 September 2015
Gomperts BN, Kim LJ, Flaherty SA, Hackett BP (2007) IL-13 regulates cilia loss and foxj1 expression in human airway epithelium. Am J Respir Cell Mol Biol 37:339–346
Halwani R, Al-Muhsen S, Al-Jahdali H, Hamid Q (2011) Role of transforming growth factor-β in airway remodeling in asthma. Am J Respir Cell Mol Biol 44:127–133
Holgate ST (2011) The sentinel role of the airway epithelium in asthma pathogenesis. Immunol Rev 242:205–219
Koopmans JG, Lutter R, Jansen HM, van der Zee JS (2006) Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma. Thorax 61:306–312
Laoukili J, Perret E, Willems T, Minty A, Parthoens E, Houcine O, Coste A, Jorissen M, Marano F, Caput D, Tournier F (2001) IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells. J Clin Invest 108:1817–1824
Mattes J, Yang M, Siqueira A, Clark K, MacKenzie J, McKenzie AN, Webb DC, Matthaei KI, Foster PS (2001) IL-13 induces airways hyperreactivity independently of the il-4rα chain in the allergic lung. J Immunol 167:1683–1692
Mazzone SB (2005) An overview of the sensory receptors regulating cough. Cough 1:2
Pennock BE, Cox CP, Rogers RM, Cain WA, Wells JH (1979) A non-invasive technique for measurement of changes in specific airway resistance. J Appl Physiol 46:399–406
Rogers DF (2004) Airway mucus hypersecretion in asthma: an undervalued pathology? Curr Opin Pharmacol 4:241–250
Sin DD, Man SF (2006) Corticosteroids and adrenoceptor agonists: the compliments for combination therapy in chronic airways diseases. Eur J Pharmacol 533:28–35
Strehl C, Buttgereit F (2013) Optimized glucocorticoid therapy: teaching old drugs new tricks. Mol Cell Endocrinol 380:32–40
Svartengren M, Ericsson CH, Philipson K, Mossberg B, Carmer P (1989) Tracheobronchial clearance in asthma-discordant monozygotic twins. Respiration 56:70–79
Tamm M, Richards DH, Beghé B, Fabbri L (2012) Inhaled corticosteroid and long-acting β2-agonist pharmacological profiles: effective asthma therapy in practice. Respir Med 106:9–19
Theron AJ, Steel HC, Tintinger GR, Feldman C, Anderson R (2013) Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting? Drug Des Devel Ther 7:1387–1398
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
Wohlsen A, Hirrle A, Tenor H, Marx D, Beume R (2010) Effect of cyclic AMP-elevating agents on airway ciliary beat frequency in central and lateral airways in rat precision-cut lung slices. Eur J Pharmacol 635:177–183
Acknowledgements
This work was supported by the Slovak Research and Development Agency under the contract APVV 0305–12; CERK II- Project co-financed from EU sources; grant VEGA 1/0165/14; grant MZ 2012/35-UKMA-12; and opportunities for career growth in research and development in the medical sciences co-financed from EU sources.
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The authors declare no conflicts of interest in relation to this article.
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Pappová, L., Jošková, M., Kazimierová, I., Šutovská, M., Fraňová, S. (2016). Combination Therapy with Budesonide and Salmeterol in Experimental Allergic Inflammation. In: Pokorski, M. (eds) Pulmonary Infection and Inflammation. Advances in Experimental Medicine and Biology(), vol 935. Springer, Cham. https://doi.org/10.1007/5584_2016_24
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DOI: https://doi.org/10.1007/5584_2016_24
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