Cromolyn sodium suppresses eosinophilic inflammation in patients with aspirin-intolerant asthma

Background: Although administration of cromolyn sodium is one of the most useful drugs for the treatment of aspirin-intolerant asthma (AIA), both its pharmacologic mechanism of action and association with the pathogenesis remain obscure. Objective: This study was designed to investigate the protective effect of cromolyn sodium on airway responsiveness to the sulpyrine provocation test, and to examine whether its activity is associated with a reduction in eosinophilic inflammation. Methods: Patients were randomly assigned to receive cromolyn sodium (20 mg/2 mL, or 1 ampoule; Fujisawa, Osaka, Japan) or matching placebo (2 mL of saline) four times daily for 1 week. We evaluated the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate AIA; those who were in stable clinical condition were allocated to this study. A double-blind, randomized, crossover design was used. Blood and sputum samples were taken in the morning on the sulpyrine provocation testing day. Eosinophil counting and measurement of eosinophilic cationic protein (ECP) were performed. Results: Inhaled cromolyn sodium protect against aspirin-induced attacks of asthma through mechanisms not related to the bronchodilator property, but related to the improvement of the bronchial hypersensitivity, almost completely in all patients (P<0.001). After 1 week's treatment with cromolyn sodium, patients' symptoms, blood and sputum eosinophils counts, and sputum ECP levels were significantly decreased compared with both placebo and baseline. Conclusions: Cromolyn sodium has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This is the first report that cromolyn sodium reduces blood and sputum eosinophils counts and sputum ECP levels in AIA.