Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of salmeterol on allergen challenge

Chest. 1999 Mar;115(3):629-34. doi: 10.1378/chest.115.3.629.


Study objective: One week of regular treatment with salmeterol can induce tolerance to the protective effect of a beta2-agonist on early airway response to allergen (EAR). The objective was to assess whether inhaled corticosteroids revert tolerance to salmeterol.

Study design: The study had a randomized, double-blind, placebo-controlled design.

Patients and methods: 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 microg bid) (T2) in order to induce tolerance. Subjects were then randomized to receive either the same dose of salmeterol + beclomethasone dipropionate (BDP, 500 microg bid) (group 1, n = 6) or placebo + BDP (group 2, n = 6) for 1 week before sBPT (T3).

Results: 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 (MaxdeltaFEV1%) 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 MaxdeltaFEV1% 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) MaxdeltaFEV1% at T2 (median, 31%; range, 9 to 40%) and T3 (median, 31%; range, 3 to 42%; not significant).

Conclusions: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Beclomethasone / administration & dosage
  • Beclomethasone / pharmacology*
  • Bronchial Provocation Tests
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Drug Tolerance
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Humans
  • Male
  • Salmeterol Xinafoate


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Glucocorticoids
  • Salmeterol Xinafoate
  • Beclomethasone
  • Albuterol