title: Adverse effects of salmeterol in asthma: a neuronal perspective.
abstract: BACKGROUND
  Regular use of inhaled beta(2)-agonists has been associated with a paradoxical loss of asthma control and a deterioration of airway hyper-responsiveness, but the underlying mechanism is unknown. The neurotrophin brain-derived neurotrophic factor (BDNF) has recently been identified as a mediator of airway hyper-responsiveness in asthma.
  
  
  METHODS
  Eighteen patients with mild allergic asthma who did not use any regular antiasthmatic therapy inhaled the long-acting beta(2)-agonist salmeterol for 2 weeks followed by 2 weeks of combination therapy with salmeterol and the corticosteroid fluticasone. Airway responsiveness to histamine and BDNF concentrations in blood were assessed prior to entry, after 14 days of salmeterol therapy and after 14 days of combination therapy. In a separate experiment, salmeterol effects on BDNF release by human peripheral blood mononuclear cells were assessed.
  
  
  RESULTS
  Monotherapy with salmeterol significantly increased BDNF concentrations in serum and platelets. This increase was abolished by the addition of fluticasone to the treatment. The findings were confirmed in vitro: salmeterol increased the release of BDNF by mononuclear cells, and this was inhibited by co-incubation with fluticasone. Increased BDNF concentrations in serum and platelets correlated with the deterioration of airway hyper-responsiveness following salmeterol monotherapy. In contrast, there was no association between beta(2)-receptor polymorphisms and changes in airway responsiveness.
  
  
  CONCLUSIONS
  Increased BDNF concentrations may underly the adverse effects of salmeterol monotherapy on airway responsiveness in asthma.
  
  
  BACKGROUND
  NCT00736801.
authors.affiliation: Abteilung für Pneumologie, Klinik und Poliklinik für Innere Medizin, Universität Rostock, D-18057 Rostock, Germany. marek.lommatzsch@med.uni-rostock.de
authors.forename: M
authors.initials: M
authors.lastname: Lommatzsch
authors.forename: Y
authors.initials: Y
authors.lastname: Lindner
authors.forename: A
authors.initials: A
authors.lastname: Edner
authors.forename: K
authors.initials: K
authors.lastname: Bratke
authors.forename: M
authors.initials: M
authors.lastname: Kuepper
authors.forename: J C
authors.initials: JC
authors.lastname: Virchow
mesh_terms: D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D000068299:Salmeterol Xinafoate; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D019208:Brain-Derived Neurotrophic Factor; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D006632:Histamine; D000068298:Fluticasone; D000420:Albuterol