THE EFFECT OF SALMETEROL ON THE EARLY-PHASE AND LATE-PHASE REACTION TO BRONCHIAL ALLERGEN AND POSTCHALLENGE VARIATION IN BRONCHIAL REACTIVITY, BLOOD EOSINOPHILS, SERUM EOSINOPHIL CATIONIC PROTEIN, AND SERUM EOSINOPHIL PROTEIN-X

The late asthmatic response to bronchial allergen challenge and the associated increase in nonspecific bronchial reactivity provides a model for studying the acute inflammatory mechanisms in asthmatic airways. In 12 asthmatic patients (aged 22-37 years) with known dual reaction to allergen challenge, salmeterol 50 mug, 100 mug, or placebo was administered as a single dose 10 min before allergen challenge in a double-blind, randomized order on three different study days 2 weeks apart. The bronchial reactivity (BH) to histamine was measured the day before and 24 and 48 h after allergen challenge. Salmeterol significantly inhibited the early (P<0.02) and the late (P<0.05) asthmatic reactions. After placebo, mean BH was significantly increased above base line at 24 and 48 h (P<0.02). After 50 and 100 mug salmeterol, BH was less than base line at 24 h and returned to prechallenge values at 48 h. Blood eosinophils increased significantly (P < 0.05) 24 and 48 h after allergen challenge, and no difference was found between treatments. After pretreatment with placebo, serum eosinophil cationic protein (s-ECP) and serum eosinophil protein X (s-EPX) increased significantly (P < 0.05) 24 and 48 h after allergen challenge. After treatment with salmeterol 50 mug, s-EPX, but not s-ECP, increased significantly 24 h after challenge, but was normal at 48 h. After salmeterol 100 mug, no change in s-EPX or s-ECP was found. The results showed that salmeterol eliminated the allergen-induced dual asthmatic reaction and gave protection against increased BH. Measurement of blood eosinophils, s-ECP, and s-EPX indicated that salmeterol may modify this inflammatory cell activity, because raised s-levels of ECP and EPX may be finked to eosinophil activation and granule secretion. In addition to inducing a long-lasting bronchodilation, salmeterol may influence acute inflammation.