Effect of olodaterol on the relaxation of small airways

Olodaterol (Ol) is a novel, selective, β 2 -agonist which offers bronchoprotection in mild asthmatics with duration of action of at least 24h. Small airways are the major site of obstruction in patients with COPD. Thus novel bronchodilators that act on the small airways may be of benefit for COPD. Therefore, this study compared the effect of Ol and formoterol (Fm) on human and rat small airways. Precision cut lung slices (PCLS) were obtained from rat lungs and human lung tissue obtained following resection. Videomicroscopy was used to measure small airway relaxation. Rat small airways were contracted to increasing concentrations of carbachol (EC 50 = 0.11±0.04μM, n=6). Carbachol contraction was then repeated on the same airways following pre-treatment of PCLS with Ol or Fm (1nM). Both agonists significantly (p 50 = 0.19±0.05μM and Fm: 0.34±0.07μM, n=6). Carbachol contracted human small airways with an EC 50 of 0.08±0.03μM (n=6) which was significantly inhibited (p 50 = 0.7±0.3μM, n=6) and 1nM Fm (EC 50 = 1.0±0.6μM, n=6). Following pre-contraction of rat small airways with 0.1μM carbachol both β 2 -agonists induced relaxation ∼45% of maximal contraction (n=6). By contrast, carbachol-induced pre-contraction of human small airways was completely reversed by both agonists with EC 50 values of 4.3±5.7pM (n=6) and 46.1±37.9pM (n=6) for Ol and Fm respectively (P Both Ol and Fm had significant bronchodilatory effects on rat and human small airways. Ol was comparable to Fm and showed significantly increased relaxation following partial pre-contraction of human small airways to carbachol.