Can a single dose response predict the effect of montelukast on exercise-induced bronchoconstriction?
BACKGROUND
Exercise-induced bronchoconstriction (EIB) can be prevented by a single dose of montelukast (MLK). The effect is variable, similar to the variable responsiveness observed after daily treatment with MLK. We hypothesized that the effect of a single MLK-dose (5 or 10 mg) on EIB could predict the clinical effectiveness of longer term once daily treatment.


METHODS
This was a prospective, open-label study. Twenty-four asthmatic adolescents (12-17 years) suboptimally controlled by low-dose inhaled corticosteroids, with ≥10% post-exercise fall in FEV1 , were included. They performed an exercise test at baseline, 20 hr after a single MLK-dose and 40-44 hr after the last dose of 4 weeks once daily treatment. The correlations between the effect of a single dose and 4 weeks treatment on area under the curve (AUC) and maximum % fall in FEV1 were calculated.


RESULTS
AUC0-20 min decreased significantly after a single MLK-dose (P = 0.001, CI: 64.9-218.2), but not after 4 weeks of treatment (P = 0.080, CI: -12.2 to 200.4). There was a moderate correlation between the effect of a single MLK-dose and 4 weeks treatment on AUC0-20 min , r = 0.49 (P = 0.011), and maximum % fall in FEV1 , r = 0.40 (P = 0.035).


CONCLUSIONS
The protection provided by a single MLK-dose against EIB only modestly predicts the effect of regular treatment against EIB in adolescent asthmatics on low-dose inhaled corticosteroids. If used on a daily base, MLK offered clinically significant protection against EIB in two thirds of adolescents suboptimally controlled by low-dose ICS.
Department of Pediatrics, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
Elin T G
ET
Kersten
Department of Pediatrics, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
Anne M
AM
Akkerman-Nijland
Department of Sports Medicine, Hospital De Tjongerschans, Heerenveen, the Netherlands.
Jean M M
JM
Driessen
Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund, Sweden.|Department of Clinical Pharmacy and Pharmacology and Department of General Practice, University Medical Centre Groningen, Groningen, the Netherlands.
Zuzana
Z
Diamant
Department of Pediatrics, Medisch Spectrum Twente, Enschede, the Netherlands.
Bernard J
BJ
Thio
D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects*; D002648:Child; D003521:Cyclopropanes; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast
Montelukast; asthma; children; exercise-induced bronchoconstriction