Inhaled Beclomethasone Dipropionate Reverts Tolerance to the Protective Effect of Salmeterol on Allergen Challenge

One week of regular treatment with salmeterol can induce tolerance to the protective effect of aβ 2-agonist on early airway response to allergen (EAR). The objective was to assess whether inhaled corticosteroids revert tolerance to salmeterol. The study had a randomized, double-blind, placebo-controlled design. Twelve subjects with mild allergic asthma and positive result of specific bronchial provocation test (sBPT) to allergen underwent three sBPTs, separated by 1 week. sBPT was done in all subjects after a single dose (T1) and after 1 week of regular treatment with inhaled salmeterol (50 μg bid) (T2) in order to induce tolerance. Subjects were then randomized to receive either the same dose of salmeterol + beclomethasone dipropionate (BDP, 500 μg bid) (group 1, n = 6) or placebo + BDP (group 2, n = 6) for 1 week before sBPT (T3). After a single dose of salmeterol (T1), all subjects were protected against EAR, whereas after 1 week of regular treatment, the protective effect of salmeterol was totally or partially lost (T2). Maximum FEV1 percent fall (MaxΔFEV1%) after allergen inhalation was significantly higher at T2 than at T1. All subjects except one of group 1 were protected against EAR after salmeterol + BDP (T3), and MaxΔFEV1% at T3 (median, 12%; range, 4 to 6%) was significantly lower than T2 (median, 22%; range, 12 to 43%; p < 0.05 by Wilcoxon test). Subjects of group 2 did not show any significant protection against EAR after placebo + BDP treatment (T3) MaxΔFEV1% at T2(median, 31%; range, 9 to 40%) and T3 (median, 31%; range, 3 to 42%; not significant). In conclusion, the addition of inhaled BDP partially restored the bronchoprotective effect of salmeterol on allergen challenge that was lost after 1 week of regular treatment with salmeterol alone. This ability of BDP in reverting tolerance cannot be ascribed to a direct effect of corticosteroids per se on allergen challenge in this group of asthmatics.