PMID- 19237390
OWN - NLM
STAT- MEDLINE
DCOM- 20100301
LR  - 20211020
IS  - 1468-3296 (Electronic)
IS  - 0040-6376 (Print)
IS  - 0040-6376 (Linking)
VI  - 64
IP  - 9
DP  - 2009 Sep
TI  - Adverse effects of salmeterol in asthma: a neuronal perspective.
PG  - 763-9
LID - 10.1136/thx.2008.110916 [doi]
AB  - 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. CONCLUSION: Increased BDNF 
      concentrations may underly the adverse effects of salmeterol monotherapy on 
      airway responsiveness in asthma. TRIAL REGISTRATION NUMBER: NCT00736801.
FAU - Lommatzsch, M
AU  - Lommatzsch M
AD  - Abteilung fur Pneumologie, Klinik und Poliklinik fur Innere Medizin, Universitat 
      Rostock, D-18057 Rostock, Germany. marek.lommatzsch@med.uni-rostock.de
FAU - Lindner, Y
AU  - Lindner Y
FAU - Edner, A
AU  - Edner A
FAU - Bratke, K
AU  - Bratke K
FAU - Kuepper, M
AU  - Kuepper M
FAU - Virchow, J C
AU  - Virchow JC
LA  - eng
SI  - ClinicalTrials.gov/NCT00736801
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090222
PL  - England
TA  - Thorax
JT  - Thorax
JID - 0417353
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Androstadienes)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 6EW8Q962A5 (Salmeterol Xinafoate)
RN  - 820484N8I3 (Histamine)
RN  - CUT2W21N7U (Fluticasone)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
CIN - Thorax. 2009 Sep;64(9):738-9. PMID: 19717706
CIN - Thorax. 2009 Sep;64(9):739-41. PMID: 19717707
MH  - Adolescent
MH  - Adrenergic beta-2 Receptor Agonists
MH  - Adrenergic beta-Agonists/administration & dosage/*adverse effects
MH  - Adult
MH  - Albuterol/administration & dosage/adverse effects/*analogs & 
      derivatives/antagonists & inhibitors
MH  - Androstadienes/administration & dosage
MH  - *Asthma/drug therapy/physiopathology
MH  - Brain-Derived Neurotrophic Factor/blood
MH  - *Bronchial Hyperreactivity/chemically induced/physiopathology
MH  - Bronchial Provocation Tests
MH  - Bronchodilator Agents/administration & dosage
MH  - Drug Therapy, Combination
MH  - Female
MH  - Fluticasone
MH  - Forced Expiratory Volume
MH  - Histamine/metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - Male
MH  - Polymorphism, Genetic
MH  - Receptors, Adrenergic, beta-2/genetics
MH  - Salmeterol Xinafoate
MH  - Young Adult
PMC - PMC2730557
COIS- Competing interests: None.
EDAT- 2009/02/25 09:00
MHDA- 2010/03/02 06:00
PMCR- 2009/02/22
CRDT- 2009/02/25 09:00
PHST- 2009/02/25 09:00 [entrez]
PHST- 2009/02/25 09:00 [pubmed]
PHST- 2010/03/02 06:00 [medline]
PHST- 2009/02/22 00:00 [pmc-release]
AID - thx.2008.110916 [pii]
AID - tx110916 [pii]
AID - 10.1136/thx.2008.110916 [doi]
PST - ppublish
SO  - Thorax. 2009 Sep;64(9):763-9. doi: 10.1136/thx.2008.110916. Epub 2009 Feb 22.