title: Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults.
abstract: OBJECTIVE
  We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers.
  
  
  METHODS
  Fifteen patients with atopic persistent asthma were evaluated (mean age, 32.4 years; FEV(1), 75.2% predicted) in a randomized, double-blind, double-dummy, placebo-controlled crossover study with a 1-week placebo washout period, comparing the following once-daily nighttime treatments: (1) formoterol (FM), 12 microg, for 2 weeks and FM, 24 microg, for 2 weeks; or (2) budesonide (BUD), 400 microg, for 2 weeks and BUD, 800 microg, for 2 weeks; or (3) FM, 12 microg, plus BUD, 400 microg, for 2 weeks and FM, 24 microg, plus BUD, 800 microg, for 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitric oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment.
  
  
  RESULTS
  The results of AMP challenge (provocative concentration causing a 20% fall in FEV(1)) at 4 weeks showed significant (p<0.05) improvements after patients had received all active treatments compared to placebo (20 mg/mL), with FM plus BUD, 261 mg/mL, being superior (p<0.05) to FM alone, 82 mg/mL, but not to BUD, 201 mg/mL. NO and ECP showed significant (p<0.05) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone. Combination therapy was associated with optimal patient preference (rank order, FM plus BUD > FM > BUD; p<0.0005), highest domiciliary peak expiratory flow, and lowest rescue inhaler usage. All three treatments produced equivalent improvements in spirometry.
  
  
  CONCLUSIONS
  Patients preferred once-daily combination therapy, but this had no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting beta(2)-agonist.
authors.affiliation: Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
authors.forename: I
authors.initials: I
authors.lastname: Aziz
authors.forename: A M
authors.initials: AM
authors.lastname: Wilson
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000249:Adenosine Monophosphate / Q000097:blood*; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers; D001798:Blood Proteins / Q000378:metabolism*; D001944:Breath Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D011379:Prognosis; D012260:Ribonucleases; D013147:Spirometry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D001993:Bronchodilator Agents; D047091:Eosinophil Granule Proteins; D004983:Ethanolamines; D009569:Nitric Oxide; D000249:Adenosine Monophosphate; D019819:Budesonide; D012260:Ribonucleases; D000068759:Formoterol Fumarate