Hiren Muzumdar

A randomized trial of adenotonsillectomy for childhood sleep apnea.

BACKGROUND Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. METHODS We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. RESULTS The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%). CONCLUSIONS As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).

Diagnostic issues in pediatric obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) in children includes a spectrum of respiratory disorders with significant morbidities. Diagnosis of OSAS is based on clinical suspicion, history, and physical findings, and confirmation is made by polysomnography. There has been significant progress in recent years in technologies available for diagnosis of OSAS since the consensus statement of the American Thoracic Society in 1996. The current review describes methodologies that are available today for assessment and diagnosis of OSAS in children and summarizes the most recent recommendations of the American Academy of Sleep Medicine Task Force regarding scoring sleep-related respiratory events in children.

Growth After Adenotonsillectomy for Obstructive Sleep Apnea: An RCT

BACKGROUND AND OBJECTIVES: Adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) may lead to weight gain, which can have deleterious health effects when leading to obesity. However, previous data have been from nonrandomized uncontrolled studies, limiting inferences. This study examined the anthropometric changes over a 7-month interval in a randomized controlled trial of adenotonsillectomy for OSAS, the Childhood Adenotonsillectomy Trial. METHODS: A total of 464 children who had OSAS (average apnea/hypopnea index [AHI] 5.1/hour), aged 5 to 9.9 years, were randomized to Early Adenotonsillectomy (eAT) or Watchful Waiting and Supportive Care (WWSC). Polysomnography and anthropometry were performed at baseline and 7-month follow-up. Multivariable regression modeling was used to predict the change in weight and growth indices. RESULTS: Interval increases in the BMI z score (0.13 vs 0.31) was observed in both the WWSC and eAT intervention arms, respectively, but were greater with eAT (P < .0001). Statistical modeling showed that BMI z score increased significantly more in association with eAT after considering the influences of baseline weight and AHI. A greater proportion of overweight children randomized to eAT compared with WWSC developed obesity over the 7-month interval (52% vs 21%; P < .05). Race, gender, and follow-up AHI were not significantly associated with BMI z score change. CONCLUSIONS: eAT for OSAS in children results in clinically significant greater than expected weight gain, even in children overweight at baseline. The increase in adiposity in overweight children places them at further risk for OSAS and the adverse consequences of obesity. Monitoring weight, nutritional counseling, and encouragement of physical activity should be considered after eAT for OSAS.

SLEEP, SLEEP DISORDERED BREATHING, AND NOCTURNAL HYPOVENTILATION IN CHILDREN WITH NEUROMUSCULAR DISEASES

Sleep disordered breathing (SDB) is now well recognized in children with neuromuscular diseases (NMD) and may lead to significant morbidity and increased mortality. Predisposing factors to SDB in children with NMD include reduced ventilatory responses, reduced activity of respiratory muscles during sleep and poor lung mechanics due to the underlying neuro-muscular disorder. SDB may present long before signs of respiratory failure emerge. When untreated, SDB may contribute to significant cardiovascular morbidities, neuro-cognitive deficits and premature death. One of the problems in detecting SDB in patients with NMD is the lack of correlation between lung function testing and daytime gas exchange. Polysomnography is the preferred method to evaluate for SDB in children with NMD. When the diagnosis of SDB is confirmed, treatment by non-invasive ventilation (NIV) is usually recommended. However, other modalities of mechanical ventilation do exist and may be indicated in combination with or without other supportive measures.

Changes in heart rate variability after adenotonsillectomy in children with obstructive sleep apnea.

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality, and increased sympathetic activity is considered to be a causative link in this association. Higher levels of sympathetic activity have been reported in children with OSAS. Sympathetic predominance is indicated on heart rate variability (HRV) analysis by increased heart rate (HR) and a higher ratio of low-frequency to high-frequency band power (LF/HF). Improvement in OSAS after adenotonsillectomy (AT) in children with OSAS could, therefore, be associated with reduced HR and reduced LF/HF. METHODS Changes in HR and time and frequency components of HRV were retrospectively analyzed in 2-min epochs free of respiratory events during light, deep, and rapid-eye-movement (REM) sleep in children with OSAS who underwent polysomnography before and after AT. RESULTS Eighteen children with OSAS, aged 4.9 ± 2.4 years (mean ± SD) were studied. After AT, the apnea-hypopnea index decreased from 31.9 ± 24.8 events/h to 4.1 ± 3.7 events/h. The HR decreased after AT in all stages of sleep (99.8 ± 16.9 beats/min to 80.7 ± 12.9 beats/min [light sleep]; 100.2 ± 15.4 beats/min to 80.5 ± 12.4 beats/min [deep sleep)]; and 106.9 ± 16.4 beats/min to 87.0 ± 12.1 beats/min [REM sleep]), as did the LF/HF (1.6 ± 2.7 to 0.6 ± 0.5 [light sleep]; 1.2 ± 1.6 to 0.5 ± 0.6 [deep sleep]; and 3.0 ± 5.4 to 1.4 ± 1.7 [REM sleep]). CONCLUSIONS The proportion of sympathetic activity of the autonomic nervous system declines in children with OSAS after AT in association with improvement in sleep-disordered breathing.

Quality of life and obstructive sleep apnea symptoms after pediatric adenotonsillectomy

BACKGROUND AND OBJECTIVES: Data from a randomized, controlled study of adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) were used to test the hypothesis that children undergoing surgery had greater quality of life (QoL) and symptom improvement than control subjects. The objectives were to compare changes in validated QoL and symptom measurements among children randomized to undergo adenotonsillectomy or watchful waiting; to determine whether race, weight, or baseline OSAS severity influenced changes in QoL and symptoms; and to evaluate associations between changes in QoL or symptoms and OSAS severity. METHODS: Children aged 5 to 9.9 years with OSAS (N = 453) were randomly assigned to undergo adenotonsillectomy or watchful waiting with supportive care. Polysomnography, the Pediatric Quality of Life inventory, the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire, the 18-item Obstructive Sleep Apnea QoL instrument, and the modified Epworth Sleepiness Scale were completed at baseline and 7 months. Changes in the QoL and symptom surveys were compared between arms. Effect modification according to race and obesity and associations between changes in polysomnographic measures and QoL or symptoms were examined. RESULTS: Greater improvements in most QoL and symptom severity measurements were observed in children randomized to undergo adenotonsillectomy, including the parent-completed Pediatric Quality of Life inventory (effect size [ES]: 0.37), the 18-item Obstructive Sleep Apnea QoL instrument (ES: –0.93), the modified Epworth Sleepiness Scale score (ES: –0.42), and the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire (ES: –1.35). Effect modification was not observed by obesity or baseline severity but was noted for race in some symptom measures. Improvements in OSAS severity explained only a small portion of the observed changes. CONCLUSIONS: Adenotonsillectomy compared with watchful waiting resulted in significantly more improvements in parent-rated generic and OSAS-specific QoL measures and OSAS symptoms.

The Effect of Adenotonsillectomy for Childhood Sleep Apnea on Cardiometabolic Measures.

STUDY OBJECTIVES Obstructive sleep apnea syndrome (OSAS) has been associated with cardiometabolic disease in adults. In children, this association is unclear. We evaluated the effect of early adenotonsillectomy (eAT) for treatment of OSAS on blood pressure, heart rate, lipids, glucose, insulin, and C-reactive protein. We also analyzed whether these parameters at baseline and changes at follow-up correlated with polysomnographic indices. DESIGN Data collected at baseline and 7-mo follow-up were analyzed from a randomized controlled trial, the Childhood Adenotonsillectomy Trial (CHAT). SETTING Clinical referral setting from multiple centers. PARTICIPANTS There were 464 children, ages 5 to 9.9 y with OSAS without severe hypoxemia. INTERVENTIONS Randomization to eAT or Watchful Waiting with Supportive Care (WWSC). MEASUREMENTS AND RESULTS There was no significant change of cardiometabolic parameters over the 7-mo interval in the eAT group compared to WWSC group. However, overnight heart rate was incrementally higher in association with baseline OSAS severity (average heart rate increase of 3 beats per minute [bpm] for apnea-hypopnea index [AHI] of 2 versus 10; [standard error = 0.60]). Each 5-unit improvement in AHI and 5 mmHg improvement in peak end-tidal CO2 were estimated to reduce heart rate by 1 and 1.5 bpm, respectively. An increase in N3 sleep also was associated with small reductions in systolic blood pressure percentile. CONCLUSIONS There is little variation in standard cardiometabolic parameters in children with obstructive sleep apnea syndrome (OSAS) but without severe hypoxemia at baseline or after intervention. Of all measures, overnight heart rate emerged as the most sensitive parameter of pediatric OSAS severity. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov (#NCT00560859).

Utility of symptoms to predict treatment outcomes in obstructive sleep apnea syndrome

BACKGROUND AND OBJECTIVES: Polysomnography defines the pathophysiology of obstructive sleep apnea syndrome (OSAS) but does not predict some important comorbidities or their response to adenotonsillectomy. We assessed whether OSAS symptoms, as reflected on the Sleep-Related Breathing Disorders Scale of the Pediatric Sleep Questionnaire (PSQ), may offer clinical predictive value. METHODS: Baseline and 7-month follow-up data were analyzed from 185 participants (aged 5–9 years with polysomnographically confirmed OSAS) in the surgical treatment arm of the multicenter Childhood Adenotonsillectomy Trial. Associations were assessed between baseline PSQ or polysomnographic data and baseline morbidity (executive dysfunction, behavior, quality of life, sleepiness) or postsurgical improvement. RESULTS: At baseline, each 1-SD increase in baseline PSQ score was associated with an adjusted odds ratio that was ∼3 to 4 times higher for behavioral morbidity, 2 times higher for reduced global quality of life, 6 times higher for reduced disease-specific quality of life, and 2 times higher for sleepiness. Higher baseline PSQ scores (greater symptom burden) also predicted postsurgical improvement in parent ratings of executive functioning, behavior, quality of life, and sleepiness. In contrast, baseline polysomnographic data did not independently predict these morbidities or their postsurgical improvement. Neither PSQ nor polysomnographic data were associated with objectively assessed executive dysfunction or improvement at follow-up. CONCLUSIONS: PSQ symptom items, in contrast to polysomnographic results, reflect subjective measures of OSAS-related impairment of behavior, quality of life, and sleepiness and predict their improvement after adenotonsillectomy. Although objective polysomnography is needed to diagnose OSAS, the symptoms obtained during an office visit can offer adjunctive insight into important comorbidities and likely surgical responses.

Severe Asthma With Fungal Sensitization in a Child: Response to Itraconazole Therapy

People with severe asthma with fungal sensitization may represent an underdiagnosed subset of patients with refractory disease. It is important to know that such patients may benefit from adjunct treatment with antifungal agents. We describe here the case of a child with refractory asthma, persistent airway obstruction, a serum immunoglobulin E level of >20000 IU/mL, and severe eosinophilic airway infiltration. Although he did not meet diagnostic criteria for allergic bronchopulmonary aspergillosis, he demonstrated evidence of sensitization to several fungi and responded dramatically to the addition of itraconazole therapy. We also discuss emerging hypotheses regarding fungal-induced asthma.

Adenotonsillectomy in Obese Children with Obstructive Sleep Apnea Syndrome: Magnetic Resonance Imaging Findings and Considerations

OBJECTIVE The reasons why adenotonsillectomy (AT) is less effective treating obese children with obstructive sleep apnea syndrome (OSAS) are not understood. Thus, the aim of the study was to evaluate how anatomical factors contributing to airway obstruction are affected by AT in these children. METHODS Twenty-seven obese children with OSAS (age 13.0 ± 2.3 y, body mass index Z-score 2.5 ± 0.3) underwent polysomnography and magnetic resonance imaging of the head during wakefulness before and after AT. Volumetric analysis of the upper airway and surrounding tissues was performed using commercial software (AMIRA®). RESULTS Patients were followed for 6.1 ± 3.6 mo after AT. AT improved mean obstructive apnea-hypopnea index (AHI) from 23.7 ± 21.4 to 5.6 ± 8.7 (P < 0.001). Resolution of OSAS was noted in 44% (12 of 27), but only in 22% (4 of 18) of those with severe OSAS (AHI > 10). AT increased the volume of the nasopharynx and oropharynx (2.9 ± 1.3 versus 4.4 ± 0.9 cm(3), P < 0.001, and 3.2 ± 1.2 versus 4.3 ± 2.0 cm(3), P < 0.01, respectively), reduced tonsils (11.3 ± 4.3 versus 1.3 ± 1.4 cm(3), P < 0.001), but had no effect on the adenoid, lingual tonsil, or retropharyngeal nodes. A small significant increase in the volume of the soft palate and tongue was also noted (7.3 ± 2.5 versus 8.0 ± 1.9 cm(3), P = 0.02, and 88.2 ± 18.3 versus 89.3 ± 24.4 cm(3), P = 0.005, respectively). CONCLUSIONS This is the first report to quantify volumetric changes in the upper airway in obese children with OSAS after adenotonsillectomy showing significant residual adenoid tissue and an increase in the volume of the tongue and soft palate. These findings could explain the low success rate of AT reported in obese children with OSAS and are important considerations for clinicians treating these children.