Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD.

Abstract

Selectins, a family of cell adhesion molecules, are involved in leukocyte extravasation to sites of inflammation. We investigated the safety and efficacy of the inhaled pan-selectin antagonist Bimosiamose in patients with chronic obstructive pulmonary disease (COPD). 77 COPD patients (mean forced expiratory volume in 1 s, 57% pred.) were enrolled in a cross-over, double-blind, randomized, Placebo-controlled, multi-center trial. Bimosiamose (10 mg) or Placebo was inhaled twice daily via the breath actuated nebulizer Akita2 Apixneb™ for 28 days on top of standard bronchodilator therapy. Efficacy was assessed by measurement of inflammatory parameters in induced sputum (differential cell count, interleukin-8, matrix-metalloproteinase-9, myeloperoxidase) and lung function at day 28 of both treatment periods. The total adverse event ratio of Bimosiamose compared to Placebo treatment was balanced. Compared to Placebo, treatment with Bimosiamose led to a decrease of the interleukin-8 concentration (-9.49 ng/mL, 95%CI -18.8 to -2.7 ng/mL, p = 0.008), for the neutrophil count a difference of -0.368 × 10(6) cells/mL (95%CI -1.256 to 0.407 × 10(6)/mL, p = 0.313) was found. The macrophage count decreased by -0.200 × 10(6) cells/mL (95%CI -0.365 to -0.044 × 10(6) cells/mL, p = 0.012). Most lung function parameters showed a small numeric increase. Inhalation of Bimosiamose for 28 days was safe and well tolerated in patients with COPD. It led to an attenuation of airway inflammation (EudraCT 2009-017257-35; NCT ID: NCT01108913).

• Authors: Henrik Watz, Daniel Bock, Michael Meyer, Katrin Schierhorn, Karin Vollhardt, Christiane Woischwill, Frauke Pedersen, Anne Kirsten, Kai-Michael Beeh, Wolfgang Meyer-Sabellek, Helgo Magnussen, Jutta Beier
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 26 Issue 2 Pg. 265-70 (Apr 2013) ISSN: 1522-9629 [Electronic] England
• PMID: 23257347 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Hexanes
• Interleukin-8
• Selectins
• bimosiamose
• Matrix Metalloproteinase 9
• Mannose

Topics

• Administration, Inhalation
• Aged
• Asthma (drug therapy)
• Cross-Over Studies
• Double-Blind Method
• Female
• Hexanes (administration & dosage, adverse effects, therapeutic use)
• Humans
• Interleukin-8 (analysis)
• Male
• Mannose (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Matrix Metalloproteinase 9 (analysis)
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (drug therapy)
• Selectins (physiology)