5.1 Objective measures and pediatric obstructive sleep apnea syndrome
Obesity, adenoid hypertrophy and tonsil enlargement play major roles in the pathophysiology of pediatric OSAS.6,26 Also, objective measures for obesity andadnototonsillar size provide a guidance for the treatment. Adenotonsillectomy is widely considered to be the first-line therapy for pediatric OSAS,41-46 while weight reduction is recommended in obese ones with OSAS. Previous studies examined correlations
between adenotonsillar size and pediatric OSAS.52-60 Nolan J et al.52 systemically reviewed twenty articles comparing tonsil size to over-night polysomnogram, and showed an association between tonsil size and OSAS. Kang et al.6 found the use of AN ratio for adenoid size measure is an easily applicable and non-invasive method in children and correlated well with pediatric OSAS. Obesity is an independent risk factor for OSAS in children.5,29 Adipose tissue deposited around the pharynx and neck, along with hypertrophic adenoids and tonsils, largely contribute to obstructive sleep
syndrome in obese children.5,68 Consequently, this study used obesity, adenoid
hypertrophy, and tonsil hypertrophy to build the objective model because of their major roles contributing to pediatric obstructive sleep disorders.
38
5.2 Subjective measures and pediatric obstructive sleep apnea syndrome
Snoring occurs in almost all children with SDB and is the main reason for caregivers to seek medical advices. Many reports observed high prevalence of snoring in children with OSAS as well as children with primary snoring.8,9,11,14,90-97 Nieminen et al.94 stated that half of the children or fewer with symptoms suggestive of OSASactually had the condition. Consequently, snoring alone is an insensitive indicator of OSAS and it is difficult to make a diagnosis of OSAS based on a history of snoring alone.14
Numerous studies have assessed the accuracy of clinical symptoms and signs in detecting pediatric OSAS.8,9,11,14,90-97 Brietzke et al.8 systemically reviewed pertinent literatures and stated that snoring had a sensitivity of 44% to 97% and specificity of 4%
to 58% in detecting pediatric OSAS. Besides, witness breathing pause had a sensitivity of 47% to 88% and specificity of 17% to 90%, whereas mouth breathing had a
sensitivity of 29% to 78% and specificity of 27% to 46% in detecting pediatric OSAS.8 In 2012, Certal et al.9 conducted a meta-analysis for clinical assessment in detecting pediatric OSAS and concluded that tonsil size and snoring reported by caregivers had high sensitivity but low specificity, while excessive daytime somnolence, observed apnea, and difficulty in breathing during sleep had high specificity but low sensitivity in diagnosing OSAS. This study showed snoring frequency had a sensitivity of 77% with specificity of 48%, tonsil size had a sensitivity of 77% with specificity of 65%, and observed apnea had a sensitivity of 42% with specificity of 88% in detecting pediatric OSAS. These findings were consistent with precious study as snoring and tonsil size had high sensitivity but low specificity, while observed apnea had specificity but low sensitivity in detecting pediatric OSAS. Based on findings in this study, we also agree
39
with the consensus that neither single symptoms or signs have satisfactory performance in detecting pediatric OSAS. Therefore, combining several symptoms or signs to develop a diagnostic tool for pediatric OSAS is highly desired.
40
5.3 Combined measures in detecting pediatric obstructive sleep apnea syndrome
Many studies examined diagnostic abilities of a combination of subjective symptoms or questionnaires in detecting pediatric OSAS.9,10,96,98-100 Brouilette et al.96 suggested combined difficulty breathing during sleep, apnea observed by parents, and snoring to derived the “OSA score” to facilitate selection of children for treatment for OSAS. Chervin et al.98 developed the “pediatric sleep questionnaire”, which was consist of scales from snoring, sleepiness, and behavior, and validated a reliable instrument to be used in clinical research when PSG is not feasible. Goldstein et al.12,99 used a 15 items “clinical assessment score” correctly diagnosed 72% of referred children compared to overnight PSG. Spruyt et al.100 developed the set of six hierarchically arranged questions with the area under the curve was 0.79 to aid the screening of children at risk for OSAS. This study combined symptoms of snoring frequency, snoring duration, awaken, and breathing pause for the subjective model and yielded the area under the curve was 0.72. Nevertheless, neither combined symptoms nor questionnaires have satisfactory performance in detecting pediatric OSAS.
Therefore, alternative diagnostic models are needed to improve the accuracy.
Several recently studies combined subjective (e.g. symptoms or questionnaires) and objective (e.g. physical examinations or radiological findings) measures in detecting pediatric OSAS.9-11,13,99 Xu et al.11 asserted combining clinical and radiologic findings might be helpful in detecting pediatric OSAS. Yang et al.101 screened children for OSAS based on questionnaire, physical examination and electronic nasopharyngoscopy.
Villa et al.13 used the “sleep clinical record” consist of physical examination, subjective symptoms, and clinical history, to screen patients as candidates for PSG study. Although
41
combining subjective and objective measures have been used repeatedly for pediatric OSAS screening in precious literatures, none of them compared diagnostic abilities between objective and subjective measures. By using traditional and novel statistical methods, this study provides a comprehensive view of models based on objective and subjective measures. This study further confirmed the usefulness and feasibility to combine both objective and subjective measures for screening pediatric OSAS. Based on our findings, physicians should utilize a combined objective and subjective measures when developing a screen tool for pediatric OSAS to optimize its diagnostic abilities.
42
5.4 Strength and Limitations
To our best knowledge, the present study is the first study elaborating diagnostic abilities of objective measures, subjective measures, and combined objective and subjective measures in detecting pediatric OSAS. This study demonstrated that combined objective and subjective measures, as compared to objective measures or subjective measures, provide incremental value for disease discrimination and
reclassification. From a clinical perspective, these findings warrant the need of use both objective and subjective measures in developing a screen tool for pediatric OSAS in order to optimize the diagnostic abilities of the tool.
The strength of this study is the application of a variety of statistical method for this important topic in pediatric sleep medicine. We used global model fit, discrimination (C index), calibration (Hosmer-Lemeshow goodness-of-fit statistic), and reclassification statistics for assessing diagnostic abilities of clinical measures in pediatric population.
Specifically, the ability to reclassify risk, as showed in this study, offers increases in clinical utility of diagnostic tool to detect pediatric OSAS. The validation process is also worthy to mention. We applied three different statistical methods for internal validation and all showed fair performance of the model. Furthermore, this study comprises a large sample size, which is well representative of pediatric population and allow clinicians to have a comprehensive understanding of obstructive sleep disorders in children.
This study has certain limitations. First, this study was conducted in a single, tertiary referral medical center. Therefore, cross-cultural and racial differences of clinical measures in children with obstructive sleep disorders were not obtained. Second, this study did not examine nasal or tongue base conditions, although correlations between
43
nasal or tongue base structure and OSAS have not been well established in pediatric population.102 Third, objective measures in this study only reflect the upper airway structure in two dimensions. Three-dimensional imaging, including computed
tomography or magnetic resonance imaging, although high cost and thus not routinely used, may be more accurate for upper airway evaluations.103,104 Fourth, our patients were recruited from clinics, which were located in a tertiary medical referral center rather than from the community. The associations between objective or subjective measures and pediatric OSAS in normal populations require further study.
44
5.5 Future Perspectives
Pediatric OSAS is an upper airway disorders. This study elucidated correlations between objective measures and pediatric OSAS. However, objective measures included in this study were mainly 2-dimentional. Recently, cone beam computed tomography (CBCT) emerged as a useful tool in diagnosis and treatment planning of maxillofacial diseases.104 It may also offer more detailed assessment of 3-dimentional upper airway structures than traditional 2-dimentional measures does in assessing airway patency of children with SDB. In the future, we will conduct a prospective study investigating relationships between pediatric SDB and upper airway patency
determined by CBCT.
Untreated OSAS in children is associated with adverse cardiovascular consequences.
Also, child obesity increases the risk of OSAS.3 Obesity is associated with alterations in endocrine and inflammatory process of fat cells, many of which may modulate blood pressure and respiratory control.2,3 Nowadays, Childhood obesity is increasingly recognized to be associated with both pediatric OSAS and hypertension.2,3 As obesity related OSAS is highly prevalent, more research is needed to understand the interaction of these two conditions with its connections to adverse cardiovascular events. In the future, we will conduct prospective studies to further clarify associations between obesity, pediatric OSAS, and adverse cardiovascular consequences.
45