title: Profiles of measured and perceived bronchodilation. A placebo-controlled cross-over trial comparing formoterol and salmeterol in moderate persistent asthma.
abstract: OBJECTIVE
  Long-acting beta(2)-agonists have acquired an indispensable position in the management of bronchial symptoms in patients with asthma. The objective of this study was to compare onset-of-action and clinical effectiveness of formoterol and salmeterol during 2 weeks of treatment. We also investigated the association between bronchodilator effects and perceived relieve of dyspnoea.
  
  
  METHODS
  A multi-centre randomized double-blind placebo-controlled cross-over trial was performed in 35 subjects with moderate persistent asthma. Treatment periods existed of 2 weeks formoterol (12 microg bid), salmeterol (50 microg bid) and placebo, all administered by pressurized metered dose inhaler. FEV(1) and Visual Analogue Scale (VAS) scores were repeatedly measured until 180 min post-bronchodilation (post-BD), before as well as after each treatment period. Onset-of-action was defined as a >/=15% increase in FEV(1). Subjects kept diaries of morning and evening PEFR values and use of rescue bronchodilator.
  
  
  RESULTS
  Formoterol and salmeterol both caused a significant increase in FEV(1) (0.45L [95% CI 0.01, 0.80] and 0.27L [95% CI 0.08, 0.62] respectively). At 3' post-BD, three times as many subjects demonstrated onset-of-action on formoterol compared to salmeterol (36% versus 13%, P = 0.063), at 6' post-BD 42% versus 27% (P = 0.063). VAS scores were similar for formoterol and salmeterol at pre-treatment assessment, but tended to be higher for formoterol after 2weeks treatment. No differences between formoterol and salmeterol were observed for PEFR values or use of rescue medication. 50% of the subjects preferred formoterol, 29% salmeterol (P < 0.001). Significant associations between FEV(1) and VAS ratings existed only at 10', 15' and 30' post-BD, not before or after these time points.
  
  
  CONCLUSIONS
  The earlier described faster onset-of-action of formoterol as compared to a equipotent dosage of salmeterol was confirmed in this study. Perception of decreasing airflow obstruction may be delayed after acute bronchodilation.
authors.affiliation: Department of General Practice-229/HAG, University Medical Centre Nijmegen, P O Box 9101, 6500 HB Nijmegen, The Netherlands. t.schermer@hag.umcn.nl
authors.forename: T R J
authors.initials: TR
authors.lastname: Schermer
authors.forename: W J
authors.initials: WJ
authors.lastname: Hoff
authors.forename: A P M
authors.initials: AP
authors.lastname: Greefhorst
authors.forename: J P H M
authors.initials: JP
authors.lastname: Creemers
authors.forename: A P
authors.initials: AP
authors.lastname: Sips
authors.forename: J
authors.initials: J
authors.lastname: Westbroek
authors.forename: C L A
authors.initials: CL
authors.lastname: van Herwaarden
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D000068299:Salmeterol Xinafoate; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate