Dissociation in the effect of nedocromil on mannitol-induced cough or bronchoconstriction in asthmatic subjects

Respirology. 2005 Sep;10(4):442-8. doi: 10.1111/j.1440-1843.2005.00724.x.

Abstract

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.

Methodology: 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / physiopathology*
  • Bronchial Provocation Tests
  • Constriction, Pathologic / chemically induced
  • Constriction, Pathologic / prevention & control
  • Cough / chemically induced*
  • Cough / prevention & control*
  • Double-Blind Method
  • Forced Expiratory Volume
  • Humans
  • Mannitol*
  • Middle Aged
  • Nedocromil / therapeutic use*
  • Spirometry

Substances

  • Anti-Asthmatic Agents
  • Nedocromil
  • Mannitol