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Assessments of protective effects of tiotropium bromide against methacholine- and neurokinin A-induced bronchoconstriction in patients with asthma

Eric Derom, Yannick Van Durme, Bihiyga Salhi, Christine Vander Stichele, Fre Bauters, Joyceline Sele, Roland Louis, Guy Joos
European Respiratory Journal 2011 38: p872; DOI:
Eric Derom
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Yannick Van Durme
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Bihiyga Salhi
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Christine Vander Stichele
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Fre Bauters
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Joyceline Sele
2Respiratory Medicine, CHU Sart Tilman, Liège, Belgium
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Roland Louis
2Respiratory Medicine, CHU Sart Tilman, Liège, Belgium
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Guy Joos
1Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Abstract

Rationale: Previous studies using short-acting anticholinergics have suggested a possible protective effect on bronchoconstriction induced by the sensory neuropeptide neurokinin A (NKA).

Aim: To assess the effect of tiotropium bromide, a longacting anticholinergic agent, on NKA-induced bronchoconstriction.

Methods: PC20 NKA and PC20 methacholine were investigated in asthmatic patients after 20 days of treatment with tiotropium bromide (18 μg/od) or placebo. PC20 was expressed in log2 doubling concentrations (DC). Values were reported as median with 25th-75th percentiles. Pairwise comparisons of the log2 PC20 values at screening and at the end of active and placebo treatments were performed.

Results: 16 patients with asthma (9 male; age: 24 (18-63) years) were included. PC20 NKA was 0.18 (0.06 - 0.29) μmol/ml at screening, 0.34 (0.09 - 3.34) μmol/ml after placebo, and 0.77 (0.08 - 3.34) μmol/ml after tiotropium bromide. PC20 methacholine was 0.5 (0.3 - 0.7) mg/ml at screening, 0.3 (0.2- 1.5) mg/ml after placebo, and 256.0 (11.7 – 256.0) mg/ml after tiotropium bromide. Differences between active treatment and screening log2PC20 were 2.4 (0.4 – 3.2) DC for NKA (p = 0.06) and 7.6 (4.8 – 9.0) DC for methacholine (p <0.0001). Differences between placebo treatment and screening for log2PC20 NKA and log2PC20 methacholine were not observed.

Conclusions: Inhaled tiotropium bromide protects against methacholine-induced bronchoconstriction, but not against bronchoconstriction induced by NKA, suggesting that cholinergic mechanisms are not involved in the contractile effects of NKA in patients with asthma.

  • © 2011 ERS
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Assessments of protective effects of tiotropium bromide against methacholine- and neurokinin A-induced bronchoconstriction in patients with asthma
Eric Derom, Yannick Van Durme, Bihiyga Salhi, Christine Vander Stichele, Fre Bauters, Joyceline Sele, Roland Louis, Guy Joos
European Respiratory Journal Sep 2011, 38 (Suppl 55) p872;

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Assessments of protective effects of tiotropium bromide against methacholine- and neurokinin A-induced bronchoconstriction in patients with asthma
Eric Derom, Yannick Van Durme, Bihiyga Salhi, Christine Vander Stichele, Fre Bauters, Joyceline Sele, Roland Louis, Guy Joos
European Respiratory Journal Sep 2011, 38 (Suppl 55) p872;
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