OBJECTIVE: This technical report describes the procedures involved in developing recommendations on the management of childhood obstructive sleep apnea syndrome (OSAS). METHODS: The literature from 1999 through 2011 was evaluated. RESULTS AND CONCLUSIONS: A total of 3166 titles were reviewed, of which 350 provided relevant data. Most articles were level II through IV. The prevalence of OSAS ranged from 0% to 5.7%, with obesity being an independent risk factor. OSAS was associated with cardiovascular, growth, and neurobehavioral abnormalities and possibly inflammation. Most diagnostic screening tests had low sensitivity and specificity. Treatment of OSAS resulted in improvements in behavior and attention and likely improvement in cognitive abilities. Primary treatment is adenotonsillectomy (AT). Data were insufficient to recommend specific surgical techniques; however, children undergoing partial tonsillectomy should be monitored for possible recurrence of OSAS. Although OSAS improved postoperatively, the proportion of patients who had residual OSAS ranged from 13% to 29% in low-risk populations to 73% when obese children were included and stricter polysomnographic criteria were used. Nevertheless, OSAS may improve after AT even in obese children, thus supporting surgery as a reasonable initial treatment. A significant number of obese patients required intubation or continuous positive airway pressure (CPAP) postoperatively, which reinforces the need for inpatient observation. CPAP was effective in the treatment of OSAS, but adherence is a major barrier. For this reason, CPAP is not recommended as first-line therapy for OSAS when AT is an option. Intranasal steroids may ameliorate mild OSAS, but follow-up is needed. Data were insufficient to recommend rapid maxillary expansion.

OBJECTIVES: This revised clinical practice guideline, intended for use by primary care clinicians, provides recommendations for the diagnosis and management of the obstructive sleep apnea syndrome (OSAS) in children and adolescents. This practice guideline focuses on uncomplicated childhood OSAS, that is, OSAS associated with adenotonsillar hypertrophy and/or obesity in an otherwise healthy child who is being treated in the primary care setting. METHODS:Of 3166 articles from 1999-2010, 350 provided relevant data. Most articles were level II-IV. The resulting evidence report was used to formulate recommendations. RESULTS AND CONCLUSIONS:The following recommendations are made. (1) All children/adolescents should be screened for snoring.(2) Polysomnography should be performed in children/adolescents with snoring and symptoms/signs of OSAS; if polysomnography is not available, then alternative diagnostic tests or referral to a specialist for more extensive evaluation may be considered.

Background VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional F508del-CFTR in vitro. Methods A randomised, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis (n=89) who were homozygous for the F508del-CFTR mutation. Subjects were randomised to one of four VX-809 28 day dose groups (25, 50, 100 and 200 mg) or matching placebo. Results The type and incidence of adverse events were similar among VX-809- and placebo-treated subjects. Respiratory events were the most commonly reported and led to discontinuation by one subject in each active treatment arm. Pharmacokinetic data supported a once-daily oral dosing regimen. Pharmacodynamic data suggested that VX-809 improved CFTR function in at least one organ (sweat gland). VX-809 reduced elevated sweat chloride values in a dose-dependent manner (p=0.0013) that was statistically significant in the 100 and 200 mg dose groups. There was no statistically significant improvement in CFTR function in the nasal epithelium as measured by nasal potential difference, nor were there statistically significant changes in lung function or patient-reported outcomes. No maturation of immature F508del-CFTR was detected in the subgroup that provided rectal biopsy specimens. Conclusions In this study, VX-809 had a similar adverse event profile to placebo for 28 days in F508del-CFTR homozygous patients, and demonstrated biological activity with positive impact on CFTR function in the sweat gland. Additional data are needed to determine how improvements detected in CFTR function secondary to VX-809 in the sweat gland relate to those measurable in the respiratory tract and to long-term measures of clinical benefit. Clinical trial number NCT00865904

OSAS is common in children and is associated with significant sequelae. Overnight PSG is currently the only reliable diagnostic modality that can differentiate OSAS from primary snoring. However, the PSG criteria for OSAS have not been definitively validated, and it is not clear that primary snoring without PSG-defined OSAS is benign. Adenotonsillectomy is the first-line treatment for OSAS but requires careful postoperative monitoring because of the high risk of respiratory complications. Adenotonsillectomy is usually curative, but children with persistent snoring (and perhaps with severely abnormal preoperative PSG results) should have PSG repeated postoperatively.