Montelukast protects against nasal lysine-aspirin challenge in patients with aspirin-induced asthma.
Aspirin-induced asthma (AIA) is associated with increased production of cysteinyl leukotrienes (CysLT). Although leukotriene CysLT1-receptor antagonists improve lower airway outcomes in AIA, their effects and dose-response in the upper airway is less well documented. The present study evaluated the dose-response for montelukast (ML) against nasal lysine-aspirin challenge in patients with AIA. A total of 12 patients with a clear-cut history of AIA were randomised in double-blind cross-over fashion to receive single doses of ML 10 mg, ML 40 mg, or placebo (PL), with nasal lysine-aspirin challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF), nasal blockage visual analogue scale (VAS) and forced expiratory volume in one second (FEV1) were made over 120 min after nasal lysine-aspirin challenge. Prechallenge values for mean+/-SEM PNIF (L x min(-1)) were not significantly different comparing all groups: ML 10 mg (132+/-10), ML 40 mg (125+/-12) and PL (132+/-11). There was no significant difference comparing the maximum % PNIF fall from baseline between screening (46+/-6) and PL (45+/-6). The maximum % PNIF fall from baseline was significantly greater with PL (45+/-6) compared to either ML 10 mg (34+/-6) or ML 40 mg (32+/-5). There was also a significantly greater mean % PNIF response over 120 min after lysine-aspirin challenge for PL (26+/-7) compared to either ML 10 mg (14+/-6) or ML 40 mg (17+/-6). There were no significant differences for the maximum or mean % PNIF fall from baseline comparing ML 10 mg and ML 40 mg. A significant increase in nasal blockage VAS score was observed between baseline and 60 min or 120 min with PL but not with ML 10 mg or ML 40 mg. There were no significant differences for either the maximum or mean % FEV1 over 120 min as change from baseline comparing all groups. A single 10 mg dose of montelukast partially protected against the local effects of nasal lysine-aspirin challenge, with no further benefit at 40 mg. Nasal lysine-aspirin challenge appeared to be a reproducible and safe method in assessing patients with aspirin-induced asthma.
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
D K C
DK
Lee
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Haggart
F M
FM
Robb
B J
BJ
Lipworth
D000085:Acetates / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000328:Adult; D001241:Aspirin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced* / Q000517:prevention & control*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003521:Cyclopropanes; D003545:Cysteine / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008239:Lysine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests; D010366:Peak Expiratory Flow Rate; D011804:Quinolines / Q000008:administration & dosage*; D012016:Reference Values; D015203:Reproducibility of Results; D013147:Spirometry; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; C112381:cysteinyl-leukotriene; D008239:Lysine; D003545:Cysteine; C093875:montelukast; D001241:Aspirin; C010395:acetylsalicylic acid lysinate