title: Mucociliary clearance in COPD can be increased by both a D2/beta2 and a standard beta2 agonists.
abstract: In addition to breathlessness and cough, excessive mucus production is one of the main symptoms of chronic obstructive pulmonary disease (COPD). Excess mucus coupled with deteriorating mucociliary clearance is associated with a decline in lung function and an increased risk of death from pulmonary infection. The effect of Viozan (Sibenadet HCl, AR-C68397AA), a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, on mucociliary clearance was investigated together with that of a beta2-adrenoceptor agonist, salbutamol. Using a double blind, parallel group study design, 15 patients with COPD, all habitual smokers, were randomised to receive nebulised sidenadet (3mg tid; n = 7) or salbutamol (5mg tid; n = 8) for 10 days. Lung mucociliary clearance rates were measured, by a standard radioaerosol technique, before and after the treatment period, as were 24-h sputum volumes. Both sibenadet and salbutamol therapies resulted in significant (P<0.02) enhancement of lung mucociliary clearance. The 24-h sputum volume was significantly reduced following sibenadet therapy (P<0.03) whereas salbutamol therapy had no effect. Our results, in addition to illustrating the effects of a standard beta2 agonist on mucociliary clearance, strongly suggest the potential dual benefit of dual-agonist compounds in lessening sputum production whilst simultaneously enhancing mucociliary clearance. For reasons unconnected with the present study, development work on this specific formulation is no Longer proceeding.
authors.affiliation: Department of Medical Physics and Thoracic Medicine, Royal Free and University College Medical School, London, UK. amer.alhasani@royalfree.nhs.uk
authors.forename: A
authors.initials: A
authors.lastname: Hasani
authors.forename: N
authors.initials: N
authors.lastname: Toms
authors.forename: J E
authors.initials: JE
authors.lastname: Agnew
authors.forename: J
authors.initials: J
authors.lastname: Lloyd
authors.forename: J P
authors.initials: JP
authors.lastname: Dilworth
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D010366:Peak Expiratory Flow Rate; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D000318:Adrenergic beta-Agonists; D013844:Thiazoles; C116267:sibenadet; D000420:Albuterol