© 2005 American Thoracic Society doi: 10.1164/rccm.2505006
Is It Time to Consider a New Treatment for Children with Sleep-disordered Breathing?Albert Einstein College of Medicine, Children's Hospital at Montefiore, Bronx, New York In this issue of the Journal, Goldbart and colleagues (pp. 364–370) report their experience treating children with mild sleep-disordered breathing (5 > apnea–hypopnea index [AHI] > 1) with the selective leukotriene-1 receptor antagonist montelukast (1). In a parallel study, they assessed leukotriene receptor expression and leukotriene concentrations in adenoid and tonsillar tissues from children with more significant sleep-disordered breathing (AHI > 5) who underwent adenotonsillectomy. They have shown a significant improvement in the respiratory parameters on polysomnography after 16 weeks of therapy with montelukast. Moreover, immunologic studies indicated an increase in expression of leukotriene receptors LT1-R and LT2-R and higher concentrations of leukotriene LTB4 and LTC4/D4/E4 in the adenoids and tonsils of patients with sleep-disordered breathing compared with control subjects. These results, although preliminary, support the notion that obstructive sleep apnea syndrome (OSAS) in children with adenoid and tonsillar hypertrophy has an immunologic/inflammatory component, and that new approaches reducing inflammation should be considered in children with some forms of OSAS. OSAS affects approximately 2% of children (2). OSAS in children is most commonly associated with adenotonsillar hypertrophy and is frequently diagnosed in children between the ages of 2 and 8 years (3). However, other important etiologies include the following: craniofacial malformations that could lead to OSAS soon after birth, and obesity leading to OSAS, usually during adolescence. Treatment of childhood OSAS is directed primarily toward the suspected underlying cause of the condition. For children with OSAS and associated adenotonsillar hypertrophy, the recommended treatment continues to be surgical removal of the adenoids and tonsils (4). Interestingly, not all children who undergo adenotonsillectomy for OSAS are cured (5–7), suggesting that other factors play a role in the causation of the disorder, including anatomic modifiers restricting airway size or functional mechanisms increasing upper airway collapsibility. Is adenotonsillar hypertrophy in childhood physiologic or pathologic? In the past, it has been suggested to be a common and normal phenomenon of early childhood. This was based mainly on radiographic findings in healthy, normal children, suggesting that maximal adenoid and tonsils size relative to that of the airway occurs between the ages of 3 and 6 years (8). These findings seem reasonable because they correlate with the fact that most children who undergo adenotonsillectomy are in this age range. However, more recent studies using magnetic resonance imaging methodology able to more accurately measure the size of these tissues clearly show that this is not the case, and that the entire airway structure, including the airway, adenoid, tonsils, tongue, soft palate, and cranial skeleton, continues to grow linearly and proportionally in normal children through the prepubertal years (9, 10). Therefore, the phenomenon of overgrowth of the adenoids and tonsillar tissues leading to airway obstruction as seen in children with any degree of OSAS should be considered an aberration from normal development and a pathologic finding (11). In this issue, Goldbart and colleagues (1) provide data that support the previously described concept and suggest that inflammation could lead to adenotonsillar hypertrophy in children with OSAS. Interestingly, their findings in subjects with OSAS differ from those found in children with history of chronic tonsillitis and no OSAS, suggesting that bacterial/viral mechanisms are probably not the leading cause for the inflammatory changes noted in the OSAS group. Moreover, to test their concept, they treated the OSAS group for 16 weeks with montelukast, a selective antiinflammatory modifier, and showed significant reduction in adenoid size concomitant with increased airway size as well as significant reduction in the number of respiratory events during sleep as measured by polysomnography. The concept that upper airway inflammation plays a role in children with OSAS is not completely new. C-reactive protein levels are increased in both adults and in children with the disorder (12–14). In addition, studies in adults show that inflammatory changes extend throughout the entire upper airway, including the nasal turbinates and soft palate. It is therefore possible that inflammatory changes in children with OSAS are not limited only to the tonsils and adenoids as described in the present study, which may explain why, after adenotonsillectomy, a small but significant number of children still remain symptomatic. More evidence supporting inflammatory changes in the upper airway of children with OSAS comes from studies using nasal corticosteroids in children with moderate OSAS. These studies demonstrate significant improvement in clinical symptoms after several weeks of therapy, although they did not eliminate the disorder completely (15, 16). If adenotonsillar hypertrophy associated with OSAS is indeed an inflammatory disorder and not just a consequence of excessive physiologic development of these tissues, there is a rationale to use antiinflammatory modalities for some forms of the disorder. Leukotriene modifiers are especially attractive because they are both safe and effective in other common inflammatory airway disorders of childhood such as asthma and allergic rhinitis. However, more controlled studies are indicated to assess the efficacy of this group of medications with and without nasal corticosteroids. These future studies will need to address the clinical indications, doses, duration of therapy, and recommendation for follow-up of these patients once treatment is discontinued. At this time, the current recommendations to treat children with OSAS remain unchanged and adenotonsillectomy continues to be indicated when adenotonsillar hypertrophy is present. However, it is possible that antiinflammatory modalities will be introduced in the future for children with mild forms of the disorder, as a bridge until surgery is performed, or for a period of time after adenotonsillectomy to suppress any residual inflammation that could continue OSAS symptoms. FOOTNOTES Conflict of Interest Statement: R.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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