Regular inhaled salbutamol : effect on airway responsiveness to methacholine and adenosine 5'-monophosphate and tolerance to bronchoprotection.
OBJECTIVE
Regular treatment with inhaled beta(2)-agonists increases airway responsiveness consistently to indirect bronchoconstrictors (allergen, exercise, hypertonic saline solution, etc) and inconsistently to direct bronchoconstrictors (histamine, methacholine). Studies demonstrating tolerance to beta(2)-agonist bronchoprotection against the indirect bronchoconstrictor adenosine 5'-monophosphate (AMP) have not examined changes in baseline AMP responsiveness. This study assessed the effect of regular salbutamol on AMP and methacholine responsiveness and on tolerance to bronchoprotection.


METHODS
Double-blind, randomized, crossover study.


METHODS
University hospital bronchoprovocation laboratory.


METHODS
Fourteen atopic asthmatic subjects with FEV(1) > 65% predicted, and methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)) < 8 mg/mL.


METHODS
Salbutamol, 100 microg, and placebo inhalers, two puffs qid, each for 10 days.


METHODS
Methacholine PC(20) and AMP PC(20) measured 12 h after blinded inhaler after each treatment period. Methacholine PC(20) and AMP PC(20) repeated 10 min after salbutamol, 200 microg (eight subjects).


RESULTS
There was no difference between placebo and salbutamol treatment in geometric mean methacholine PC(20) (0.85 mg/mL vs 0.82 mg/mL, p = 0.86) or AMP PC(20) (22 mg/mL vs 17.4 mg/mL, p = 0.21; n = 14). The acute bronchoprotective effect of salbutamol was greater vs. AMP than vs methacholine (5.1 doubling concentrations vs. 3.5 doubling concentrations, p = 0.06) and loss of protective effect of salbutamol (mean +/- SD) was greater vs AMP than vs. methacholine (2.4 +/- 0.33 doubling concentration loss vs 0.8 +/- 0.21 doubling concentration loss, p = 0.008; n = 8).


CONCLUSIONS
Regular salbutamol (mean +/- SD) treatment did not enhance airway responsiveness to either the indirect bronchoconstrictor AMP or the direct bronchoconstrictor methacholine. Compared to its effect on methacholine, salbutamol had a greater acute protective effect vs AMP and produced greater loss of protection vs AMP when used regularly.
Jokic
R
R
Division of Respiratory Medicine, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
Swystun
V A
VA
Davis
B E
BE
Cockcroft
D W
DW
D000249:Adenosine Monophosphate / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D016210:Methacholine Chloride
D000318:Adrenergic beta-Agonists; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D000420:Albuterol