Asthma diagnosis and treatment
Effects of a leukotriene receptor antagonist on exhaled leukotriene E4 and prostanoids in children with asthma

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Background

Leukotriene (LT) E4 and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown.

Objective

(1) To study the effect of montelukast, a LTRA, on exhaled LTE4, 8-isoprostane, and prostaglandin E2 in children with asthma and atopic children; (2) to measure exhaled nitric oxide.

Methods

An open-label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in 17 atopic children with asthma and 16 atopic children without asthma.

Results

Pretreatment exhaled LTE4 (P < .0001) and 8-isoprostane (P < .0001) values were higher in atopic children with asthma than in atopic children without asthma. In atopic children with asthma, montelukast reduced exhaled LTE4 by 33% (P < .001), and this reduction was correlated with pretreatment LTE4 values (r = −0.90; P = .0001). Posttreatment exhaled LTE4 levels in children with asthma were higher than pretreatment LTE4 values in atopic children without asthma (P < .004). Montelukast had no effect on exhaled LTE4 in atopic children without asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P = .94; atopic children without asthma, P = .55) and PGE2 (atopic children with asthma, P = .56; atopic children without asthma, P = .93) in both groups. In atopic children with asthma, exhaled nitric oxide concentrations were reduced by 27% (P < .05) after montelukast.

Conclusion

Leukotriene receptor antagonists decrease exhaled LTE4 in atopic children with asthma. This reduction is dependent on baseline exhaled LTE4 values.

Clinical implications

Measurement of exhaled LTE4 might help identify children with asthma most likely to benefit from LTRAs.

Section snippets

Study subjects

Two groups of children were included in the montelukast study: 18 white atopic children with stable mild intermittent asthma and 18 atopic children without asthma. Seventeen atopic children with asthma and 16 atopic children without asthma completed the study (Table I; see the Methods section in the Online Repository at www.jacionline.org). Atopic children were recruited from the Allergy Outpatient Clinic of the Istituto Dermopatico dell'Immacolata, Rome, Italy, and the Asthma and Allergy

Results

No α-amylase concentrations were detected in any study sample, excluding gross salivary contamination.

Discussion

We sought to investigate the effect of montelukast on exhaled LTE4, 8-isoprostane, and PGE2 in atopic children with and without asthma. In the current study, median exhaled LTE4 values were decreased by 33% after montelukast in children with asthma, whereas treatment had no effect on exhaled LTE4 in atopic children without asthma. Montelukast had no effect on exhaled 8-isoprostane and PGE2 in both groups of children. In children with asthma, there was a strong correlation between reduction in

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    Supported by the Catholic University of the Sacred Heart, Rome, Italy academic grant 2004-2005.

    Disclosure of potential conflict of interest: P. J. Barnes has received grant support from GlaxoSmithKline, AstraZeneca, Pfizer, Novartis, and Boehringer-Ingelheim, and is on the advisory board for GlaxoSmithKline, Pfizer, Boehringer-Ingelheim, and Altana. The rest of the authors have declared that they have no conflict of interest.

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