RT Journal Article
SR Electronic
T1 Protection against allergen-induced airway hyperresponsiveness (AHR) by olodaterol in guinea pigs is synergistically enhanced by tiotropium
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2130
VO 40
IS Suppl 56
A1 Marieke Smit
A1 Annet Zuidhof
A1 Sophie Bos
A1 Harm Maarsingh
A1 Reinoud Gosens
A1 Johan Zaagsma
A1 Herman Meurs
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P2130.abstract
AB The ultra-long acting β2-agonist olodaterol has shown to be effective in asthma and COPD. Increased cholinergic tone, common to these diseases, may reduce β2-agonist responsiveness. In a guinea pig model of asthma, we investigated the protection of allergen (ovalbumin, OA)-induced AHR by olodaterol, alone and in combination with the long acting anticholinergic tiotropium. Airway responsiveness (PC100) was assessed at baseline (24h before OA) and after the early (EAR, 6h after OA) and late (LAR, 24h after OA) asthmatic reactions. 1h before OA, animals were treated with PBS (control), 1 mM olodaterol and/or 0.1 mM tiotropium (nebulizer concentrations, 3 min). OA induced AHR to histamine after the EAR (4.9-fold decrease in PC100 compared to baseline), which was fully protected by olodaterol (2.3-fold increase in PC100) and tiotropium (1.3-fold increase). When combined, a synergistic 4.8-fold increase in PC100 was observed. After the LAR, AHR (2.8-fold decrease), was also protected by olodaterol, tiotropium and their combination (1.5-, 1.3- and 1.6-fold increase in PC100, respectively). OA-induced infiltration of inflammatory cells, measured by BAL after the LAR, was not affected by any treatment. In conclusion, in a guinea pig model of asthma olodaterol and tiotropium protect against allergen-induced AHR after the EAR and LAR, without affecting inflammatory cell influx. Synergism between the drugs was found after the EAR, indicating that acetylcholine reduces the effectiveness of the β2-agonist and that the combination of olodaterol and tiotropium may be beneficial in the treatment of allergic asthma. (supported by Boehringer Ingelheim Pharma).