RT Journal Article
SR Electronic
T1 Assessments of protective effects of tiotropium bromide against methacholine- and neurokinin A-induced bronchoconstriction in patients with asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p872
VO 38
IS Suppl 55
A1 Derom, Eric
A1 Van Durme, Yannick
A1 Salhi, Bihiyga
A1 Vander Stichele, Christine
A1 Bauters, Fre
A1 Sele, Joyceline
A1 Louis, Roland
A1 Joos, Guy
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p872.abstract
AB 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.