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Meta-Analysis
. 2012 May 16;2012(5):CD006100.
doi: 10.1002/14651858.CD006100.pub2.

Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children

Kirsty Watts  1 , Richard J P G Chavasse
Affiliations
Meta-Analysis

Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children

Kirsty Watts et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute asthma presentation in the emergency setting frequently leads to hospital admission. Currently available treatment options include corticosteroid therapy, beta(2)-agonists and oxygen. Antileukotriene agents are beneficial in chronic asthma as additional therapy to inhaled steroids. Their value when used orally or intravenously in the acute setting requires evaluation.

Objectives: To determine if the addition of a leukotriene receptor antagonist (LTRA) produces a beneficial effect in children and adults with acute asthma who are currently receiving inhaled bronchodilators and systemic corticosteroids.

Search methods: We searched the Cochrane Airways Group's Specialised Register of trials with predefined terms. Searches are current to February 2012.

Selection criteria: We included randomised trials comparing antileukotrienes and standard acute asthma care versus placebo and standard care in people with acute asthma of any age. We considered any dose and method of delivery of the leukotriene agent.

Data collection and analysis: Two authors independently assessed studies for inclusion in the review and extracted data. We then checked data and resolved disagreements by discussion. We contacted study authors where necessary to provide additional information and data.

Main results: Eight trials, generating 10 treatment-control comparisons, that recruited 1470 adults and 470 children met the entry criteria. These studies were of mixed quality, and there was heterogeneity in the severity of asthma exacerbation.For oral treatment, there was no significant difference in hospital admission between LTRAs and control in three trials on 194 children (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.21 to 3.52). Using a broader composite outcome which measured requirement for additional care there was no significant difference between treatments (RR 0.87; 95% CI 0.60 to 1.28). Results demonstrated some indication of improvement in lung function with a significant difference in forced expiratory volume in one second (FEV(1)) favouring LTRAs in two trials on 641 adults (mean difference (MD) 0.08; 95% CI 0.01 to 0.14). There were insufficient data to assess this outcome in children. The most common adverse event described was headache; however, there was no significant difference between LTRAs and control (RR 0.81; 95% CI 0.22 to 2.99). Due to insufficient numbers, we were unable to conduct a subgroup analysis based on age.The combined results of two trials of intravenous treatment in 772 adults and one trial in 276 children demonstrated a reduction in the risk of hospital admission which was not quite statistically significant (RR 0.78; 95% CI 0.61 to 1.01). There was a statistically significant small difference in FEV(1) in the adult studies (MD 0.12; 95% CI 0.06 to 0.17), but not in the single trial in children (MD 0.01; 95% CI -0.06 to 0.08).

Authors' conclusions: Presently, the available evidence does not support routine use of oral LTRAs in acute asthma. Further studies are required to assess whether intravenous treatment can reduce the risk of hospital admission, and what the most appropriate dose regimen is. Additional research is also needed into safety and efficacy of additional doses for those on maintenance therapy, and larger paediatric trials are required to allow subgroup analysis. Prolonged studies would be required to establish other health economic outcomes in admitted patients.

PubMed Disclaimer

Conflict of interest statement

None known. The authors are neither involved with the makers of antileukotriene agents nor involved in the primary publications included in the review.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of comparison: 1 Oral montelukast or zafirlukast in addition to usual care, outcome: 1.1 Hospital admission (primary outcome).
4
4
Forest plot of comparison: 1 Oral montelukast or zafirlukast in addition to usual care, outcome: 1.3 FEV1.
5
5
Forest plot of comparison: 2 Intravenous montelukast in addition to usual care, outcome: 2.1 Hospital admission (Primary outcome).
6
6
Forest plot of comparison: 2 Intravenous montelukast in addition to usual care, outcome: 2.3 Change in FEV1 (litres).
1.1
1.1. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 1 Hospital admission (primary outcome).
1.2
1.2. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 2 Requirement for additional care at end of study.
1.3
1.3. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 3 FEV1.
1.4
1.4. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 4 Change in FEV1 (predicted).
1.5
1.5. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 5 Change in pulmonary index score (final assessment).
1.6
1.6. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 6 Change in respiratory rate (final assessment).
1.7
1.7. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 7 Number of beta2‐agonist administrations.
1.8
1.8. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 8 Symptom scores.
1.9
1.9. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 9 Headache.
1.10
1.10. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 10 Withdrawals.
1.11
1.11. Analysis
Comparison 1 Oral montelukast or zafirlukast in addition to usual care, Outcome 11 Relapse (within 7 days).
2.1
2.1. Analysis
Comparison 2 Intravenous montelukast in addition to usual care, Outcome 1 Hospital admission (Primary outcome).
2.2
2.2. Analysis
Comparison 2 Intravenous montelukast in addition to usual care, Outcome 2 Requirement for additional care at end of study.
2.3
2.3. Analysis
Comparison 2 Intravenous montelukast in addition to usual care, Outcome 3 Change in FEV1 (litres).
2.4
2.4. Analysis
Comparison 2 Intravenous montelukast in addition to usual care, Outcome 4 Withdrawals.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Camargo 2003b {published data only}
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    1. Anonymous. High‐dose zafirlukast in emergency department provides small benefit in acute asthma. The Journal of Family Practice 2005;54(4):304‐6. - PubMed
    1. Korenblatt PE, Silverman RA, Nowak RM, Chen Y, Bonuccelli CM, Miller CJ, et al. Zafirlukast improves outpatient outcomes after acute asthma treatment. Annals of Allergy, Asthma and Immunology 2000;84(1):18.
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Todi 2010 {published data only}
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References to studies excluded from this review

Bacharier 2008 {published data only}
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Gulati 2005 {published data only}
    1. Gulati A, Kabwa S, Jacob BK. A randomised controlled trial of zafirlukast in acute asthma. European Respiratory Journal 2005;26(Suppl 49):254s.
Matsunga 2004 {published data only}
    1. Matsunga K, Nishimoto T, Hirano T, Nakanishi M, Yamagata T, Kuroda M, et al. Effect of a leukotriene receptor antagonist on the prevention of recurrent asthma attacks after an emergency room visit. Allergology International 2004;53(4):341‐7.
Ramsay 2007 {published data only}
    1. Ramsay C, Pearson D, Wilson A. Oral montelukast in patients with acute asthma. European Respiratory Society, 17th European Respiratory Society Annual Congress, Stockholm, Sweden, September 14‐19, 2007. 2007; Vol. 30 (suppl 51):615s [P3609].
Robertson 2007 {published data only}
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Schuh 2009 {published data only}
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