Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Abstract

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.

Adenoidectomy: current approaches and review of the literature

“…Expression of cysteinyl leukotriene receptors was found increased in tonsillar tissues of children with OSA. [43] In a clinical trial, montelukast was used for 16 weeks in children with sleepdisordered breathing. Adenoid size was found to be decreased and obstructive apnea/hypopnea index, apnea index, respiratory-related arousal index, and sleep pressure scores were improved significantly with montelukast treatment.…”

A Four-Year-Old Boy with Unusually Severe Obstructive Sleep Apnea

“…Oral montelukast has been used in children with mild to moderate OSA. Previous clinical studies, [4][5][6][7] including double-blind and placebo-controlled trials, have shown that treatment with montelukast significantly reduced adenoid size and reduced respiratory-related sleep disturbances in children with mild to moderate OSA. An open study 4 reported that obstructive apnea index was reduced from 3.0 to 2.0 and the A/N ratio was decreased from 0.76 to 0.56 after 16 w of montelukast therapy.…”

Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

“…Indeed, increased levels of NO, IL-6, and 8-isopentane can be detected in exhaled condensates from the upper airway of adults with OSA (32)(33)(34), and increased numbers of neutrophils, as well as increased concentrations of bradykinin and vasointestinal peptide have been measured in nasal lavage fluid from such patients (35). Furthermore, adenotonsillar tissues of children with OSA display increased expression levels of leukotriene receptors along with increased concentrations of leukotrienes (36,37). Mechanoreceptors and sensory nerves are crucial for tonic and dynamic maintenance of upper airway patency (38), such that the abnormal varicose nerves that are found in the soft palate tissues of OSA patients suggest that alterations in innervation of the upper airway may lead to changes in upper airway protective function (39).…”