title: Efficacy of the pan-selectin antagonist Bimosiamose on ozone-induced airway inflammation in healthy subjects--a double blind, randomized, placebo-controlled, cross-over clinical trial.
abstract: Selectins, a family of cell adhesion molecules, are involved in the activation and extravasation of leukocytes in inflammatory diseases. Inhalation of ozone induces an inflammation of the airways, which is dominated by neutrophils. We investigated the effect of repeated inhalations of the pan-selectin antagonist Bimosiamose on ozone-induced airway inflammation in healthy volunteers. In a double-blind, placebo-controlled, randomized, cross-over study Bimosiamose (10 mg bid) was inhaled via a breath actuated nebulizer (AKITA2 APIXNEB(®)) for 4 days. Treatment was followed by inhalation of ozone (250 ppb) for 3 h with intermittent exercise. Induced sputum was collected 3 h post ozone challenge for analysis of cellular and non-cellular composition. 18 subjects were randomized and completed the study. All treatments were safe and well tolerated. Compared to placebo Bimosiamose reduced the numbers of sputum neutrophils by 40% (p = 0.068) and concentrations of interleukin-8 and matrix-metalloproteinase-9 in sputum supernatant by 35% (p = 0.004) and 46% (p = 0.022), respectively. Inhalation of Bimosiamose showed favourable anti-inflammatory effects on ozone-induced airway inflammation in healthy volunteers. Further studies have to proof and translate this anti-inflammatory effect of Bimosiamose into a clinical benefit in patients with chronic obstructive pulmonary disease. (ClinTrialgov Ident: NCT01108913).
authors.affiliation: Pulmonary Research Institute at Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Woehrendamm 80, Grosshansdorf, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kirsten
authors.forename: Henrik
authors.initials: H
authors.lastname: Watz
authors.forename: Gunther
authors.initials: G
authors.lastname: Kretschmar
authors.forename: Frauke
authors.initials: F
authors.lastname: Pedersen
authors.forename: Daniel
authors.initials: D
authors.lastname: Bock
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyer-Sabellek
authors.forename: Helgo
authors.initials: H
authors.lastname: Magnussen
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006586:Hexanes / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D019570:Inhalation Exposure; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009504:Neutrophils / Q000276:immunology; D010126:Ozone / Q000009:adverse effects*; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology; D013183:Sputum / Q000276:immunology
chemical_list: D006586:Hexanes; D016209:Interleukin-8; D010126:Ozone; C496819:bimosiamose; D020780:Matrix Metalloproteinase 9; D008358:Mannose