We examined the effects of nedocromil sodium, a new drug developed for the treatment of reversible obstructive airway disease, on allergen-induced early and late bronchial responses and the development of airway hyperresponsiveness 24 h after challenge in nine allergic sheep. On occasions >2 wk apart the sheep were treated with 1) placebo aerosol (buffered saline) before and 3 h after antigen challenge, 2) an aerosol of nedocromil sodium (1 mg/kg in 3 ml buffered saline) before antigen challenge and placebo 3 h after challenge, and 3) placebo aerosol before and nedocromil sodium aerosol 3 h after challenge. Early and late bronchial responses were determined by measuring specific lung resistance (sR(L)) before and periodically after challenge. Airway responsiveness was assessed by determining from dose-response curves the carbachol concentration (in % wt/vol) that increased sR(L) to 5 cmH2O/s. In the placebo trial, antigen challenge resulted in early and late increases in sRL over a base line of 353 ± 32 and 131 ± 17% (SE), respectively. Both early and late increases in sR(L) were blocked (P < 0.05) when the sheep were pretreated with nedocromil sodium. When nedocromil was given after the early response, the late response was reduced significantly. Eight of nine sheep developed airway hyperresponsiveness 24 h after antigen challenge. In these eight sheep, carbachol concentration before antigen challenge was 2.6 ± 0.3%, 24 h later carbachol concentration was significantly lower (1.8 ± 0.3%). Both nedocromil sodium treatments blocked (P < 0.05) this antigen-induced airway hyperresponsiveness. These findings indicate that nedocromil sodium is effective in the sheep model of allergic bronchoconstriction and therefore may be beneficial in the treatment of reversible obstructive airway disease.
ASJC Scopus subject areas
- Physiology (medical)