Add-on montelukast to inhaled corticosteroids protects against excessive airway narrowing.
BACKGROUND
Excessive airway narrowing in response to broncho-active stimuli is a predictor for severe exacerbations in asthma. Leukotriene receptor antagonists (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma control.


OBJECTIVE
The LTRA montelukast may provide an additional protection against excessive airway narrowing. We tested the add-on effects of montelukast on the maximal response plateau and PD(20) to inhaled methacholine in asthmatics on a stable dose of ICS.


METHODS
Thirty-one patients with allergic asthma [14M/17F, 19-50 years, forced expiratory volume in 1 s (FEV(1)) >70% pred., PD(20) <3.9 micromol methacholine], with a twice documented response plateau to methacholine, were randomized in a double-blind (montelukast 10 mg or matching placebo once daily), 12-week parallel study. Bronchoprovocation tests with methacholine (0.03-256 micromol or > or =40% decline in FEV(1)) were repeated every 4 weeks and after wash-out. The main study objectives were changes from baseline in maximal FEV(1) decline at the response plateau (i.e. >2 post-dose FEV(1) values within 5%) and PD(20) to methacholine after 12 weeks' treatment.


RESULTS
Neither treatment affected baseline FEV(1) (P=0.62). Compared with placebo, montelukast significantly decreased the maximal response plateau to methacholine (mean difference 9.4%; 95% confidence interval 3.9-15.7; P<0.005), improved the FEV(1) decline (mean change in FEV(1) decline was 2.1% [montelukast] and -0.8% [placebo], respectively, P<0.05), and increased PD(20) methacholine (mean change in PD(20) of 5.3 [montelukast] and 1.4 [placebo] doubling doses, respectively, P<0.001).


CONCLUSIONS
Add-on montelukast to ICS has disease-modifying effects in adults with persistent asthma, and hence reduces the risk of excessive airway narrowing (NCT 00913328).
Department of Respiratory Diseases, Hvidovre Hospital, Copenhagen, Denmark.
C S
CS
Ulrik
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Diamant
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use; D013440:Sulfides; D016896:Treatment Outcome; D055815:Young Adult
D000085:Acetates; D000305:Adrenal Cortex Hormones; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D016210:Methacholine Chloride; C093875:montelukast