Best mode of expression of acute reversibility of airway obstruction in patients with asthma: application to a new beta-2 agonist, RU 42 173.
Lung function tests must distinguish a true drug-induced bronchial response from changes not related to the drug itself, mainly due to intra-individual variability. We compared the variability and ability to detect true drug-induced bronchodilation of 3 modes of expression of the increase in forced expiratory volume in 1 second (delta FEV1) following administration of a 0.25 mg single oral dose of RU 42 173, a new beta 2-agonist. The study was performed in 12 patients with reversible obstructive asthma in a double-blind, crossover, placebo-controlled, randomized manner. The variability of each index was assessed by calculating the coefficient of variation (SD/mean). True drug-induced bronchodilation was assessed by calculating the F value of each index corresponding to the ratio of between-treatment to within-group differences. Three modes of expression of delta FEV1 were compared: delta FEV1 (L) = the absolute increase in FEV1, delta FEV1 (% baseline) and delta FEV1 (% predicted) where delta FEV1 (L) is divided by baseline FEV1 or predicted FEV1, respectively. A statistically significant increase in FEV1 was found up to respectively 3, 2 and 4 hours after dosing when using delta FEV1 (L), delta FEV1 (% baseline) and delta FEV1 (% predicted). The highest F value was obtained for delta FEV1 (% predicted). The coefficient of variation was lower with delta FEV1 (% predicted) than delta FEV1 (L) and delta FEV1 (% baseline). In conclusion, RU 42 173 showed a bronchodilating effect which appears to be clinically relevant. delta FEV1 (% predicted) was to be the least variable and most powerful index and should be preferred to delta FEV1 (L) and even more to delta FEV1 (% baseline) to assess the acute airway response to a bronchodilator drug.
Lurie
A
A
Eclimed-Institut de Recherche Thérapeutique, Hôpital Universitaire Cochin, Paris, France.
Vivet
P
P
Letrait
M
M
Venot
A
A
de Lauture
D
D
Lockhart
A
A
Marsac
J
J
Srauch
G
G
D000318:Adrenergic beta-Agonists; D000328:Adult; D000402:Airway Obstruction / Q000188:drug therapy*; D001249:Asthma / Q000188:drug therapy*; D001562:Benzimidazoles / Q000627:therapeutic use*; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008875:Middle Aged
D000318:Adrenergic beta-Agonists; D001562:Benzimidazoles; C058948:RU 42173