Salbutamol-induced increased airway responsiveness to allergen and reduced protection versus methacholine: dose response

J Allergy Clin Immunol. 1996 Jan;97(1 Pt 1):47-52. doi: 10.1016/s0091-6749(96)70282-8.


Background: Two adverse effects of inhaled beta 2-agonists are increased airway responsiveness to allergen and tolerance to the bronchoprotective effect of beta 2-agonists versus bronchoconstrictors (e.g., methacholine).

Objective: We studied three doses of inhaled salbutamol, 200, 400, and 800 micrograms/day, to determine dose-response curves for these two adverse effects.

Methods: Ten atopic patients with mild, stable asthma free of all asthma medications, allergen exposure, and respiratory tract infection for at least 4 weeks participated in a double-blind, random-order, crossover study. There were four 1-week treatment periods with a 1-week washout period: placebo, salbutamol 200 micrograms, 400 micrograms and 800 micrograms per day. After each treatment, we assessed FEV1, bronchodilation 10 minutes after administration of 200 micrograms of salbutamol, methacholine PC20, methacholine dose-shift after administration of 200 micrograms of salbutamol, and allergen PC20.

Results: There was no significant difference in baseline FEV1, bronchodilation, or methacholine PC20. The methacholine dose shift was maximum after the placebo (3.4 +/- 0.22 doubling doses) and was significantly greater (p < 0.01) than all salbutamol regimens (2.2 to 2.6), which were not significantly different from each other (p > 0.05). Allergen PC20 was significantly lower (p < 0.02) after salbutamol 800 micrograms/day (geometric mean = 288 protein nitrogen units [PNU]/ml) than each of the other treatments (447 to 550 PNU/ml), which were not significantly different from each other (p > 0.05).

Conclusion: Significant increase in airway responsiveness to allergen occurred only with the largest dose of inhaled salbutamol (800 micrograms/d); however, tolerance to the acute bronchoprotective effect of salbutamol was observed with all the three salbutamol regimens, even 200 micrograms/day. This suggests different mechanisms may be operative in producing these two effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Agonists / adverse effects*
  • Adult
  • Albuterol / adverse effects*
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents / administration & dosage*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Tolerance
  • Humans
  • Methacholine Chloride / administration & dosage*
  • Middle Aged


  • Adrenergic beta-Agonists
  • Allergens
  • Bronchoconstrictor Agents
  • Methacholine Chloride
  • Albuterol