Current issues of ACP Journal Club are published in Annals of Internal Medicine


Montelukast improved pulmonary function and asthma-specific quality of life in aspirin-intolerant asthma


ACP J Club. 2002 Jul-Aug;137:20. doi:10.7326/ACPJC-2002-137-1-020

Source Citation

Dahlén SE, Malmström K, Nizankowska E, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2002 Jan 1;165:9-14. [PubMed ID: 11779723] (All 2002 articles were reviewed for relevancy, and abstracts were last revised in 2008.)



In patients with aspirin-intolerant asthma (AIA) is montelukast effective for improving pulmonary function, asthma symptoms, and asthma-specific quality of life (QOL)?


Randomized (unclear allocation concealment*), blinded (clinicians and patients),* placebo-controlled trial with 4-week follow-up.


8 centers in Europe and 2 in the United States.


80 patients (age range 22 to 72 y, 68% women) who had a diagnosis of AIA with characteristic symptoms of chronic rhinosinusitis, asthma, and aspirin intolerance and 90% of whom were receiving moderate-to-high doses of glucocorticosteroids. Before inclusion in the study, patients were required to show a 12% improvement in FEV1 after inhalation of β-agonists, mild daytime asthma symptoms, and daily average use of ≥ 1 puff of β-agonists during a 2-week run-in period. Follow-up was 100%.


Patients were allocated to montelukast (10 mg) (n = 40) or placebo (n = 40) taken orally once daily at bedtime.

Main outcome measures

Pulmonary function (peak expiratory flow rate measured in the morning and evening and FEV1 measured once per wk), asthma symptoms, daily use of β-agonists, and asthma-specific QOL.

Main results

Analysis was by intention to treat. Improvement in pulmonary function was greater in the montelukast group than in the placebo group (Table). Improvement in asthma-specific QOL was greater in the montelukast group than in the placebo group (mean change from baseline for the average of 4 QOL domains 0.45 vs 0.08, P < 0.05 for the difference). A greater decrease in rescue use of inhaled β-agonists occurred in the montelukast group than in the placebo group (27.7% vs 1.6%, P < 0.05). The percentage of study days with asthma exacerbations was lower in the montelukast group than in the placebo group (8.3% vs 21.7%, P < 0.05). The groups did not differ for daytime asthma symptoms or awakenings per night.


In patients with aspirin-intolerant asthma (90% of whom were receiving moderate-to-high doses of glucocorticosteroids), montelukast was effective for improving pulmonary function and asthma-specific quality of life.

*See Glossary.

Source of funding: Merck Research Laboratories.

For correspondence: Professor S.E. Dahlén, National Institute of Environmental Medicine, Stockholm, Sweden. E-mail

Table. Montelukast vs placebo for aspirin-intolerant asthma at 4 weeks†

Outcomes Difference in LS means between groups (95% CI) P value
FEV1 10.2% (4.9 to 15.5) < 0.001
Morning PEFR (L/min) 28.0 (14.4 to 41.6) < 0.001
Evening PEFR (L/min) 23.1 (9.5 to 36.7) < 0.001
Montelukast Placebo RBI (CI) NNT (CI)
Patients with ≥ 5% improvement in FEV1 52.5% 27.5% 91% (9 to 247) 4 (3 to 30)

†LS = least squares; PEFR = peak expiratory flow rate. Other abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.


Many drugs are known to be effective as monotherapy for asthma. As new agents are introduced into practice, questions about their value compared with that of existing medications are common. Resolving these issues poses substantial challenges.

Accumulating evidence suggests that the recently introduced leukotriene antagonists may have limited clinical value. One systematic review concluded that leukotriene antagonists are probably inferior to inhaled corticosteroids for most clinical outcomes in mild-to-moderate asthma (1). A second review concluded that insufficient evidence existed to recommend currently licensed doses of leukotriene antagonists as add-on therapy to inhaled corticosteroids (2). However, the authors of both reviews emphasized the relative paucity of high-quality trials on which to base firm recommendations.

AIA is a variant form of asthma that affects about 5% of patients. Patients with AIA produce substantially more cysteinyl-leukotrienes than do those with aspirin-tolerant asthma at baseline and after challenge with aspirin. It follows that leukotriene antagonists might be particularly effective for AIA. The study by Dahlén and colleagues supports this conjecture by showing additional clinical benefits from montelukast in patients with AIA, 90% of whom were already taking corticosteroids.

The results are interesting, but caveats exist. With no direct comparison, we cannot conclude that leukotriene antagonists are superior to corticosteroids as the mainstay therapy in AIA. Furthermore, study patients were not allowed to take a long-acting β-agonist, so it remains unclear whether leukotriene antagonists are beneficial in AIA when added to what would usually be considered standard care.

Dennis E. Niewoehner, MD
Veterans Affairs Medical Center
Minneapolis, Minnesota, USA


1. Ducharme FM, Hicks GC. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma. Cochrane Database Syst Rev. 2000;(3):CD:002314. [PubMed ID: 10908555]

2. Ducharme F, Hicks G, Kakuma R. Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev. 2002(1):CD003133. [PubMed ID: 11869653]