Does adding antileukotriene agents to usual care when people are suffering an asthma attack in the emergency department help?

Current recommended treatment in the emergency department for people experiencing an asthma attack is beta2-agonists, systemic corticosteroids and oxygen. Unfortunately, some people do not get better with these standard treatments and so there is interest in developing additional treatments which will help people experiencing an asthma attack. One such treatment is antileukotrienes, which are available in tablet form to be taken orally; this drug is also made in injection form, however the intravenous form is not marketed and therefore not available.

This review considers the effect of antileukotriene agents, (normally used as add-on preventer therapy in chronic asthma), when used during acute asthma treated in emergency settings. We identified eight randomised controlled trials (RCTs) on 1470 adults and 470 children addressing this question, and in most of these studies participants were also given courses of corticosteroids at the time of treatment. We did not find a significant difference in the likelihood of being admitted to hospital between people treated with oral antileukotrienes and placebo or usual care. There was no significant difference in participants requiring additional care (including hospital admission or other treatment options) at the end of the studies between treatment and control groups. There was an improvement in lung function in people taking antileukotrienes compared to those on placebo. More research in this area is required, and the low number of studies recruiting children does not enable us to provide evidence on what effects this class of drugs has in children.

There were two trials that randomised 772 adults and 276 children to receive intravenous antileukotrienes and there was no statistically significant difference in hospital admissions, however there was an improvement in lung function in adults on antileukotrienes.

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.

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Background: 

Acute asthma presentation in the emergency setting frequently leads to hospital admission. Currently available treatment options include corticosteroid therapy, beta2-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 strategy: 

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 (FEV1) 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 FEV1 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).

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