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Published ahead of print on May 5, 2005, doi:10.1164/rccm.200408-1064OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 3, August 2005, 364-370

A more recent version of this article appeared on August 1, 2005
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Submitted on August 16, 2004
Accepted on May 2, 2005

Leukotriene Modifier Therapy for Mild Sleep-Disordered-Breathing in Children

Aviv D Goldbart1, Julie L Goldman2, Maria C Veling2, and David Gozal3*

1 Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA, 2 Department of Surgery, Division of Ear, Nose and Throat, University of Louisville, Louisville, KY, USA, 3 Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA

* To whom correspondence should be addressed. E-mail: david.gozal{at}louisville.edu.

Background- Children with mild sleep-disordered-breathing (SDB), who may not be recommended for adenotonsillectomy (T&A), frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions such as leukotriene modifier therapy. Methods- 24 children with SDB completed an open label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral x-ray films of the neck were obtained prior to and following treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea (SA) or recurrent throat infections (RI) were subjected to qPCR, immunohistochemistry and western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. Results- Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA were similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with SA. Conclusions- Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double blind, placebo controlled trials will be needed to corroborate current findings and solidly establish anti-inflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for T&A.
Key words: leukotriene receptors; sleep apnea; lymphoid hyperplasia; tonsils; adenoids;




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