title: Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial.
abstract: Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.
authors.affiliation: Experimental Asthma and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. se.dahlen@imm.ki.se
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Kerstin
authors.initials: K
authors.lastname: Malmström
authors.forename: Ewa
authors.initials: E
authors.lastname: Nizankowska
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
authors.forename: Marek
authors.initials: M
authors.lastname: Kowalski
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.forename: César
authors.initials: C
authors.lastname: Picado
authors.forename: Donald D
authors.initials: DD
authors.lastname: Stevenson
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: Romain
authors.initials: R
authors.lastname: Pauwels
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Aditi
authors.initials: A
authors.lastname: Shahane
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Reiss
authors.forename: Andrew
authors.initials: A
authors.lastname: Szczeklik
mesh_terms: D000085:Acetates / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D003521:Cyclopropanes; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000150:complications* / Q000175:diagnosis; D016903:Drug Monitoring; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011788:Quality of Life; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D017999:Leukotriene E4; C093875:montelukast; D001241:Aspirin