Dissociation in the effect of nedocromil on mannitol-induced cough or bronchoconstriction in asthmatic subjects.
OBJECTIVE
Inhaled mannitol induces both bronchoconstriction and cough. Nedocromil sodium greatly attenuates mannitol-induced bronchoconstriction. Knowledge about the effect of nedocromil on mannitol-provoked cough might, therefore, clarify the mechanisms of this response.


METHODS
Inhalation challenges with mannitol powder were performed after inhalation of 8 mg of nedocromil or its placebo in 24 subjects with asthma. The study was double-blind, randomised, and placebo-controlled. The mannitol-provoked coughs were manually recorded and the mannitol-induced bronchoconstriction was measured with a spirometer.


RESULTS
The cumulative dose of mannitol that provoked at least two coughs tended to be higher on the nedocromil day than on the placebo day (34 (22--53) mg vs 26 (18--37) mg, P=0.051). The cumulative number of coughs per dose of mannitol was slightly, but significantly, lower on the nedocromil than on the placebo day (4.2 (2.8--6.3) coughs/100 mg vs 6.1 (4.0--9.4) coughs/100 mg, P=0.037). However, when analysed on a constant-dose basis, nedocromil provided no protection for coughing (-1% protection), whereas the protection for bronchoconstriction was clear (55% protection).


CONCLUSIONS
Nedocromil strongly attenuates mannitol-induced bronchoconstriction but has a negligible effect on mannitol-provoked cough. Therefore, these responses seem to have different pathways in asthma. Recording of both provoked coughs and induced bronchoconstriction during mannitol challenge may provide supplementary information about a patient's disease.
Koskela
Heikki O
HO
Department of Respiratory Medicine, Kuopio University Hospital, Kuopio, Finland. heikki.koskela@kuh.fi
Martens
Ruth
R
Brannan
John D
JD
Anderson
Sandra D
SD
Leuppi
Joerg
J
Chan
Hak-Kim
HK
D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D003251:Constriction, Pathologic / Q000139:chemically induced / Q000517:prevention & control; D003371:Cough / Q000139:chemically induced* / Q000517:prevention & control*; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D008353:Mannitol; D008875:Middle Aged; D017835:Nedocromil / Q000627:therapeutic use*; D013147:Spirometry
D018927:Anti-Asthmatic Agents; D017835:Nedocromil; D008353:Mannitol