title: Combination Therapy with Budesonide and Salmeterol in Experimental Allergic Inflammation.
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.
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Pappová
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Jošková
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia.
authors.forename: I
authors.initials: I
authors.lastname: Kazimierová
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Šutovská
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Biomed, Martin, Slovakia. franova@jfmed.uniba.sk.|Department of Pharmacology, Jesseniu Faculty of Medicine in Martin, Comenius University in Bratislava, 4C Malá Hora, Martin, 036 01, Slovakia. franova@jfmed.uniba.sk.
authors.forename: S
authors.initials: S
authors.lastname: Fraňová
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D000068299:Salmeterol Xinafoate / Q000494:pharmacology*
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D010047:Ovalbumin
keywords: Airway reactivity; Ciliary beat frequency; Cough; Inhaled corticosteroids; Th2 cytokines