Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist. A randomized, double-blind, placebo-controlled trial
Dahlén, Sven-Erik, Malmstrom, Kerstin, Nizankowska, Ewa, Dahlén, Barbro, Kuna, Piotr, Kowalski, Marek, Lumry, William R., Picado, César, Stevenson, Donald D., Bousquet, Jean, Pauwels, Romain, Holgate, Stephen T., Shahane, Aditi, Zhang, Ji, Reiss, Theodore F. and Szczeklik, Andrew (2002) Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist. A randomized, double-blind, placebo-controlled trial. American Journal of Respiratory and Critical Care Medicine, 165, (1), 9-14.
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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 (FEV1) 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 FEV1 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 LTE4. Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.
|Keywords:||asthma therapy, leukotriene modifiers, glucocorticosteroids, airway inflammation|
|Subjects:||R Medicine > RM Therapeutics. Pharmacology
Q Science > QP Physiology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
|Date Deposited:||25 Apr 2006|
|Last Modified:||02 Mar 2012 13:06|
|Contact Email Address:||S.Holgate@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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