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Adverse effects of salmeterol in asthma: a neuronal perspective
  1. Marek Lommatzsch (marek.lommatzsch{at}med.uni-rostock.de)
  1. University of Rostock, Germany
    1. Yvonne Lindner
    1. University of Rostock, Germany
      1. Anke Edner
      1. University of Rostock, Germany
        1. Kai Bratke
        1. University of Rostock, Germany
          1. Michael Kuepper
          1. University of Rostock, Germany
            1. Johann C Virchow
            1. University of Rostock, Germany

              Abstract

              Background: Regular use of inhaled beta-2-agonists has been associated with a paradoxical loss of asthma control and a deterioration of airway hyperresponsiveness, but the underlying mechanism is unknown. The neurotrophin Brain-derived neurotrophic factor (BDNF) has recently been identified as a mediator of airway hyperresponsiveness in asthma.

              Methods: Eighteen patients with mild allergic asthma who did not use any regular anti-asthmatic therapy inhaled the long-acting beta-2-agonists 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 hyperresponsiveness following salmeterol monotherapy. In contrast, there was no association between beta-2-receptor polymorphisms and changes in airway responsiveness.

              Conclusion: Increased BDNF concentrations may underly the adverse effects of salmeterol monotherapy on airway responsiveness in asthma.

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