This Article Full Text Full Text (PDF) All Versions of this Article: 200408-1064OCv1 172/3/364    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goldbart, A. D. Articles by Gozal, D. Search for Related Content PubMed PubMed Citation Articles by Goldbart, A. D. Articles by Gozal, D.

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Kosair Children's Hospital Research Institute, Department of Pediatrics; Division of Ear, Nose, and Throat, Department of Surgery; and Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky

Correspondence and requests for reprints should be addressed to David Gozal, M.D., Kosair Children's Hospital Research Institute, University of Louisville, 570 South Preston Street, Suite 321, Louisville, KY 40202. E-mail: david.gozal{at}louisville.edu

Background: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. Methods: Twenty-four 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 before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, 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 was 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 obstructive sleep apnea. 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 antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.

Key Words: leukotriene receptors • lymphoid hyperplasia • sleep apnea • adenotonsillectomy • tonsils

This article has been cited by other articles:

				A. R. Smyth, A. Barbato, N. Beydon, H. Bisgaard, K. de Boeck, P. Brand, A. Bush, B. Fauroux, J. de Jongste, M. Korppi, et al. Respiratory medicines for children: current evidence, unlicensed use and research priorities Eur. Respir. J., February 1, 2010; 35(2): 247 - 265. [Abstract] [Full Text] [PDF]

				A. G. Kaditis, E. Alexopoulos, K. Chaidas, G. Ntamagka, A. Karathanasi, I. Tsilioni, T. S. Kiropoulos, E. Zintzaras, and K. Gourgoulianis Urine Concentrations of Cysteinyl Leukotrienes in Children With Obstructive Sleep-Disordered Breathing Chest, June 1, 2009; 135(6): 1496 - 1501. [Abstract] [Full Text] [PDF]

				L. Kheirandish-Gozal, L. D. Serpero, E. Dayyat, J. Kim, J. L. Goldman, A. Snow, R. Bhattacharjee, and D. Gozal Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea Eur. Respir. J., May 1, 2009; 33(5): 1077 - 1084. [Abstract] [Full Text] [PDF]

				E. Dayyat, L. D. Serpero, L. Kheirandish-Gozal, J. L. Goldman, A. Snow, R. Bhattacharjee, and D. Gozal Leukotriene Pathways and In Vitro Adenotonsillar Cell Proliferation in Children With Obstructive Sleep Apnea Chest, May 1, 2009; 135(5): 1142 - 1149. [Abstract] [Full Text] [PDF]

				P Gringras When to use drugs to help sleep Arch. Dis. Child., November 1, 2008; 93(11): 976 - 981. [Abstract] [Full Text] [PDF]

				A. G. Kaditis, M. G. Ioannou, K. Chaidas, E. I. Alexopoulos, M. Apostolidou, T. Apostolidis, G. Koukoulis, and K. Gourgoulianis Cysteinyl Leukotriene Receptors Are Expressed by Tonsillar T Cells of Children With Obstructive Sleep Apnea Chest, August 1, 2008; 134(2): 324 - 331. [Abstract] [Full Text] [PDF]

				L. Kheirandish-Gozal and D. Gozal Intranasal Budesonide Treatment for Children With Mild Obstructive Sleep Apnea Syndrome Pediatrics, July 1, 2008; 122(1): e149 - e155. [Abstract] [Full Text] [PDF]

				E. S. Katz and C. M. D'Ambrosio Pathophysiology of Pediatric Obstructive Sleep Apnea Proceedings of the ATS, February 15, 2008; 5(2): 253 - 262. [Abstract] [Full Text] [PDF]

				O. S. Capdevila, L. Kheirandish-Gozal, E. Dayyat, and D. Gozal Pediatric Obstructive Sleep Apnea: Complications, Management, and Long-term Outcomes Proceedings of the ATS, February 15, 2008; 5(2): 274 - 282. [Abstract] [Full Text] [PDF]

				A. C. Halbower, S. L. Ishman, and B. M. McGinley Childhood Obstructive Sleep-Disordered Breathing: A Clinical Update and Discussion of Technological Innovations and Challenges Chest, December 1, 2007; 132(6): 2030 - 2041. [Abstract] [Full Text] [PDF]

				D. Gozal, L. Kheirandish-Gozal, L. D. Serpero, O. Sans Capdevila, and E. Dayyat Obstructive Sleep Apnea and Endothelial Function in School-Aged Nonobese Children: Effect of Adenotonsillectomy Circulation, November 13, 2007; 116(20): 2307 - 2314. [Abstract] [Full Text] [PDF]

				H. E. Montgomery-Downs, V. M. Crabtree, O. S. Capdevila, and D. Gozal Infant-Feeding Methods and Childhood Sleep-Disordered Breathing Pediatrics, November 1, 2007; 120(5): 1030 - 1035. [Abstract] [Full Text] [PDF]

				A M Li, E Hung, T Tsang, J Yin, H K So, E Wong, T F Fok, and P C Ng Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea Thorax, January 1, 2007; 62(1): 75 - 79. [Abstract] [Full Text] [PDF]

				Z. Xu, D. K. L. Cheuk, and S. L. Lee Clinical Evaluation in Predicting Childhood Obstructive Sleep Apnea Chest, December 1, 2006; 130(6): 1765 - 1771. [Abstract] [Full Text] [PDF]

				A. D. Goldbart, J. Krishna, R. C. Li, L. D. Serpero, and D. Gozal Inflammatory Mediators in Exhaled Breath Condensate of Children With Obstructive Sleep Apnea Syndrome. Chest, July 1, 2006; 130(1): 143 - 148. [Abstract] [Full Text] [PDF]

				R. L. Horner and T. D. Bradley Update in sleep and control of ventilation 2005. Am. J. Respir. Crit. Care Med., April 15, 2006; 173(8): 827 - 832. [Full Text] [PDF]

				A. G. Kaditis, E. I. Alexopoulos, and G. A. Syrogiannopoulos Assessing the Role of Antiinflammatory Medications in Children with Mild Sleep-disordered Breathing Am. J. Respir. Crit. Care Med., February 1, 2006; 173(3): 358 - 358. [Full Text] [PDF]

				A. D. Goldbart and D. Gozal Assessing the Role of Antiinflammatory Medications in Children with Mild Sleep-disordered Breathing Am. J. Respir. Crit. Care Med., February 1, 2006; 173(3): 358a - 359. [Full Text] [PDF]

				L. Kheirandish, A. D. Goldbart, and D. Gozal Intranasal Steroids and Oral Leukotriene Modifier Therapy in Residual Sleep-Disordered Breathing After Tonsillectomy and Adenoidectomy in Children Pediatrics, January 1, 2006; 117(1): e61 - e66. [Abstract] [Full Text] [PDF]

				R. Arens Is It Time to Consider a New Treatment for Children with Sleep-disordered Breathing? Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 264 - 265. [Full Text] [PDF]