The Journal of Allergy and Clinical Immunology
Volume 118, Issue 2 , Pages 347-353, August 2006

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

  • Paolo Montuschi, MD

      Affiliations

    • From the Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome
    • Corresponding Author InformationReprint requests: Paolo Montuschi, MD, Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, 00168 Rome, Italy.
    • ,
  • Chiara Mondino, MD

      Affiliations

    • Department of Immunodermatology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome
    • ,
  • Pierluigi Koch, MD

      Affiliations

    • Department of Pulmonology, Ospedale Pediatrico Bambino Gesù, Palidoro
    • ,
  • Peter J. Barnes, DM

      Affiliations

    • Department of Thoracic Medicine, Imperial College, School of Medicine, National Heart and Lung Institute, London
    • ,
  • Giovanni Ciabattoni, MD

      Affiliations

    • Department of Drug Sciences, School of Pharmacy, University “G. d'Annunzio,” Chieti

Received 5 July 2005; received in revised form 7 April 2006; accepted 13 April 2006. published online 05 July 2006.

Rome, Palidoro, and Chieti, Italy, and London, United Kingdom

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.

Key words: Leukotriene E4, prostanoids, exhaled breath condensate, exhaled nitric oxide, childhood asthma, airway inflammation, noninvasive markers, leukotriene receptor antagonists

Abbreviations used: CysLTs, Cysteinyl-leukotrienes, EBC, Exhaled breath condensate, FEF25%-75%, Forced expiratory flow between 25% and 75% of the vital capacity, FVC, Forced vital capacity, LT, Leukotriene, LTRAs, Leukotriene receptor antagonists, NO, Nitric oxide, PGE2, Prostaglandin E2

 

 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.

PII: S0091-6749(06)00862-1

doi:10.1016/j.jaci.2006.04.010

The Journal of Allergy and Clinical Immunology
Volume 118, Issue 2 , Pages 347-353, August 2006

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