Tolerance to the protective effect of salmeterol on allergen challenge can be partially restored by the withdrawal of salmeterol regular treatment

Study objective: To assess whether the withdrawal of salmeterol treatment for 3 days (72 h) can restore its bronchoprotective ability on specific bronchial provocative test (sBPT) with allergen, which was completely lost after 1 week of regular treatment with salmeterol. Study design: Single-blind design, Patients and methods: We investigated 10 nonsmoking subjects (8 men and 2 women; mean +/- SD age, 24 +/- 8 years) with mild intermittent allergic asthma in the stable phase of the disease, who were never previously treated with regular beta (2)-agonists. Subjects with a previous positive early airway response (EAR) to a screening allergen challenge were considered. They underwent sBPT with allergen after a single dose of inhaled salmeterol, 50 mug (T-1), and then underwent sBPT after 1 week of regular treatment with inhaled salmeterol, 50 mug bid (T-2); after that, they continued inhaled salmeterol treatment for 4 days, and then changed to inhaled salmeterol with placebo (two puffs bid) for 3 days (72 h) and underwent sBPT with allergen after a single dose of salmeterol, 50 betag (T-3). Results: EAR to allergen (Delta FEV1 greater than or equal to 20% with respect to postdiluent value) was completely abolished by a single dose of salmeterol (T-1; protection index [PI] greater than or equal to 50% in all subjects), but it was still present after 1 week of regular treatment with salmeterol (T-2; PI < 50% in all subjects). The maximum FEV, percentage fall during sBPT with allergen was significantly lower after withdrawal of regular inhaled salmeterol (T-3) than after regular treatment with salmeterol (T-2) (mean, 23% vs 29.5%; range, 4to 41% vs 18 to 49%, respectively; p < 0.05); a similar result was obtained considering the PI of salmeterol on sBPT with allergen (mean, 44% vs 20%; range, 2 to 86% vs - 11 to 49%, respectively; p <less than> 0.05). However, the maximum FEV1, percentage fall and Pt were significantly different in T-3 than after T-1, and only 4 of 10 patients showed in T-3 a PI greater than or equal to 50%. Conclusions: The bronchoprotective effect of salmeterol on allergen-induced EAR, completely lost after 1 week of regular treatment with salmeterol, may be partially restored by the withdrawal of salmeterol therapy for 3 days (72 h), However, this withdrawal time period is not sufficient to recover the baseline bronchoprotective efficacy of the first dose of salmeterol.