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. 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.