title: 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.affiliation: Pulmonary Research Institute at Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Airway Research Center North, German Center for Lung Research, D-22927 Grosshansdorf, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Watz
authors.forename: Daniel
authors.initials: D
authors.lastname: Bock
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Katrin
authors.initials: K
authors.lastname: Schierhorn
authors.forename: Karin
authors.initials: K
authors.lastname: Vollhardt
authors.forename: Christiane
authors.initials: C
authors.lastname: Woischwill
authors.forename: Frauke
authors.initials: F
authors.lastname: Pedersen
authors.forename: Anne
authors.initials: A
authors.lastname: Kirsten
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Beeh
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyer-Sabellek
authors.forename: Helgo
authors.initials: H
authors.lastname: Magnussen
authors.forename: Jutta
authors.initials: J
authors.lastname: Beier
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006586:Hexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D019087:Selectins / Q000502:physiology*
chemical_list: D006586:Hexanes; D016209:Interleukin-8; D019087:Selectins; C496819:bimosiamose; D020780:Matrix Metalloproteinase 9; D008358:Mannose