Nedocromil sodium prevents airway hyperreactivity induced by cigarette smoke in anaesthetized guinea-pigs

Increased airway reactivity and influx of inflammatory cells into the airways have been demonstrated both in smokers and after smoke exposure in animal studies. We investigated the ability of nedocromil sodium and hydrocortisone to protect from the pathological alterations induced by direct cigarette smoke exposure in anaesthetized guinea-pigs. Active inhalation of cigarette smoke (15 s/min for 10 min) induced airway hyperreactivity, as shown by the enhanced bronchoconstrictor effect of histamine and was associated with an increase in total cells, macrophages and eosinophils in the BAL fluid. Nedocromil sodium given by aerosol (3 and 10 mg/ml for 30 s) completely prevented the ability of cigarette smoke to potentiate histamine induced bronchoconstriction. In parallel, nedocromil sodium inhibited the development of the inflammatory reaction triggered by smoke exposure. Hydrocortisone pretreatment (50 mg/kg s.c. twice) did not abolish the smoke induced airway hyperreactivity, nor did it inhibit the recruitment of proinflammatory cells within the airway lumen. Sensory neuropeptides have been demonstrated to be involved in the development of smoke induced airway hyperreactivity. The efficacy of nedocromil sodium in this model might depend on its ability to modulate the activation of the peptidergic system.