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Tolerance to the Protective Effect of Salmeterol on Allergen Challenge Can Be Partially Restored by the Withdrawal of Salmeterol Regular Treatment^*

^* From the Cardio-Thoracic Department, University of Pisa, Italy.

Correspondence to: Daniele Giannini, MD, U.O. Fisiopatologia Respiratoria Ospedale di Cisanello, via Paradisa 2, 56100 Pisa, Italy

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 ß₂-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 µg (T₁), and then underwent sBPT after 1 week of regular treatment with inhaled salmeterol, 50 µg bid (T₂); 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 µg (T₃).

Results: EAR to allergen (FEV₁ 20% with respect to postdiluent value) was completely abolished by a single dose of salmeterol (T₁; protection index [PI] 50% in all subjects), but it was still present after 1 week of regular treatment with salmeterol (T₂; PI < 50% in all subjects). The maximum FEV₁ percentage fall during sBPT with allergen was significantly lower after withdrawal of regular inhaled salmeterol (T₃) than after regular treatment with salmeterol (T₂) (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 < 0.05). However, the maximum FEV₁ percentage fall and PI were significantly different in T₃ than after T₁, and only 4 of 10 patients showed in T₃ a PI 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.

Key Words: allergen challenge • asthma • ß₂-agonist • tolerance

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				M. B. Bollinger Tolerance to the Protective Effect of Salmeterol on Allergen Challenge Can be Partially Restored by Withdrawal of Salmeterol Regular Treatment Pediatrics, August 1, 2002; 110(2): 459 - 459. [Full Text] [PDF]

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