Article Text

PDF

Urinary leukotriene LTE4 levels in non-responders to antileukotriene therapy
  1. D K C Lee1
  1. 1Ipswich Hospital, Ipswich IP4 5PD, UK;dkcleedoctors.org.uk
  1. S A Green2
  1. 2Respiratory and Allergy, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ, USA; stuart_greenmerck.com

Statistics from Altmetric.com

I read with interest the recent article by Green et al1 showing that, in acute asthma, activation of leukotriene pathways correlated with the degree of airflow obstruction and a reduction in leukotriene levels was associated with resolution of asthma exacerbation. However, no analysis was performed on patients categorised as being in the treatment failure group which was reported to be as high as 10% of patients receiving intravenous montelukast.2 The importance of this analysis cannot be understated as not everyone with asthma responds to antileukotriene therapy3,4 and non-responders have been reported to be as high as 50% in chronic asthma.5

It would have been interesting to observe urinary leukotriene LTE4 levels in the treatment failure group as it has been shown that cysteinyl leukotriene release from leucocytes of responders was higher than from non-responders which, in turn, correlated with the response to antileukotriene therapy.5

References

Authors’ reply

We thank Dr Lee for his interest in our reports.1,2 However, he appears to confuse the terms “treatment failure” and “non-responder”. “Treatment failure”, as defined in the original report for our study,1 referred to a clinical outcome (a composite end point of hospitalisation, need for excluded medication, or need for prolonged acute asthma treatment in the emergency setting). In contrast, “non-responder” generally refers to a subset of patients who fail to surpass a defined threshold of response. As we have commented previously using chronic asthma as an example, simplistic “responder/non-responder” analyses often fail to account for clinically important aspects of disease variability and the impact of a treatment intervention.3 Moreover, in our initial report of intravenous montelukast in acute asthma,1 a systematic analysis of baseline variables did not identify any factor which predicted response to intravenous montelukast in terms of either forced expiratory volume in 1 second (FEV1) or treatment failures, with the exception of baseline FEV1.

The present report2 addressed the relationship between FEV1 and cysteinyl leukotriene production as measured by LTE4 excretion. A similar analysis of treatment failures and LTE4 levels is complicated by the fact that, unlike baseline FEV1 which was measured before administration of the study drug, treatment failures tended to be reduced by intravenous montelukast.1 Nevertheless, 27 of 201 patients (15 (11.1%) in the montelukast group and 12 (18.2%) in the placebo group) met one or more of the criteria for treatment failure during the study. Of these, 20 patients had LTE4 data for analyses. Compared with patients who did not meet the criteria for treatment failures and who had LTE4 data available (n = 161), LTE4 levels were numerically higher at baseline in the treatment failure group although this did not reach statistical significance (121.6 pg/mg creatinine (95% CI 91.5 to 161.6) v 111.6 pg/mg creatinine (95% CI 100.0 to 128.5)). If Dr Lee’s hypothesis is correct, LTE4 levels should have been lower among the treatment failures. The data therefore suggest that, rather than serving as a useful predictor of clinical outcome, increased LTE4 levels are more likely to be a marker of worsened acute asthma severity, consistent with our analyses of LTE4 levels and FEV1.2 Taken together, the data provide a strong biological rationale for the observed benefit of antileukotriene therapy in acute asthma.1

REFERENCES

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.