The utility of methacholine airway responsiveness measurements in evaluating anti-asthma drugs.
BACKGROUND
Measurements of airway responsiveness are frequently used to evaluate anti-asthma drugs.


OBJECTIVE
This study investigated the utility of methacholine airway responsiveness measurements in evaluating anti-asthma medications, both in terms of a bronchoprotective effect and the ability to attenuate allergen-induced methacholine airway hyperresponsiveness.


METHODS
Methacholine airway responsiveness was measured as PC20 on two occasions (separated by 35+/-17 days, mean +/- SD) in 40 subjects with mild, stable asthma. Additional subjects had PC20 measurements made before and after administration of either inhaled salbutamol (200 microg) (n = 20) or allergen inhalation challenge (n = 31).


RESULTS
The reproducibility of the methacholine PC20 with this method was high (intraclass correlation coefficient = 0.94). The average shift in PC20 after salbutamol was 4.11 doubling concentrations (SD = 1.08). On the basis of these results, a sample size of 12 subjects would be required to demonstrate a 1 doubling concentration difference in the bronchoprotective effect of two drugs with a 90% power. The average shift in PC20 after allergen was 1.29 doubling concentrations. On the basis of these results and an estimated SD of 0.96, a sample size of 24 subjects would be required to demonstrate that a drug is effective in attenuating 50% of allergen-induced airway hyperresponsiveness with a 90% power.


CONCLUSIONS
These results confirm the high reproducibility of methacholine PC20 measurements in subjects with mild, stable asthma and demonstrate its utility in evaluating the effects of anti-asthma drugs.
Inman
M D
MD
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Hamilton
A L
AL
Kerstjens
H A
HA
Watson
R M
RM
O'Byrne
P M
PM
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods*; D005541:Forced Expiratory Volume; D006801:Humans; D016210:Methacholine Chloride / Q000494:pharmacology; D015203:Reproducibility of Results
D000318:Adrenergic beta-Agonists; D000485:Allergens; D018927:Anti-Asthmatic Agents; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000420:Albuterol