Current Treatment for Childhood Obstructive Sleep Apnea Li-Ang Lee, Yu-Shu Huang,
Transcription
Current Treatment for Childhood Obstructive Sleep Apnea Li-Ang Lee, Yu-Shu Huang,
REVIEW ARTICLE Current Treatment for Childhood Obstructive Sleep Apnea Li-Ang Lee,1,2 Yu-Shu Huang,1,3 Kin-Sun Wong,1,4 Cheng-Hui Lin,1,5 Ning-Hung Chen,1,6 Hsueh-Yu Li1,2 Sleep Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Division of Pediatric Otolaryngology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 3 Division of Child Psychiatry, Department of Psychiatry, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 4 Division of Pediatric Pulmonology, Department of Pediatrics and Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 5 Division of Craniofacial Surgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 6 Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 1 2 Abstract About 5% of children are affected by obstructive sleep apnea (OSA) and it has been the most common disorders encountered at sleep centers. Snoring, mouth breathing, labored breathing, and witnessed apnea are the core symptoms and signs of OSA in children. The true mechanism of childhood OSA remains elusive and is probably multifactorial. Adenotonsillar hypertrophy, nasal obstruction, craniofacial anomaly, obesity, and neuromuscular disorder are possible reasons. An overnight polysomnography confirms the diagnosis of OSA when apnea-hypopnea index >1 episodes/h. OSA are associated with inattention, hyperactivity, learning problem, elevated blood pressure, inadequate somatic growth and nocturnal enuresis. Weight control, anti-inflammatory therapy, nasal continuous positive airway pressure, oral appliance, rapid maxillary expansion, supraglottoplasty, craniofacial reconstruction, and tracheostomy have been proven effective for the treatment of pediatric OSA; however, adenotonsillectomy continues to be the primary treatment of childhood OSA. Despite snoring and respiratory difficulty are greatly reduced by adenotonsillectomy, residual disease is common. This evidencebased article provides a systemic review of the literature regarding indications, timing, postoperative management, and complications of OSA therapy in children, and we propose a clinical guideline on the treatment for childhood OSA at a tertiary sleep center. (J Pediatr Resp Dis 2012;8:98-111) Key words: obstructive sleep apnea, prevalence, polysomnography, treatment, adenotonsillectomy. INTRODUCTION Childhood obstructive sleep apnea (OSA) is a common disease characterized by intermittent Correspondence: Hsueh-Yu Li, MD, FACS. Address: Department of Otolaryngology, Chang Gung Memorial Hospital, No. 5, Fu-Shin Street, Kweishan, Taoyuan, Taiwan. Tel: 886-3-3281200 ext 3968. Fax: 886-3-3979361. E-mail: [email protected]. Received: October 26, 2012. Accepted: November 26, 2012. snoring and respiratory disturbance during sleep. In the past, most parents perceived that OSA as serious, however only a small percentage (15%) of them considered themselves to be “very knowledgeable” or “knowledgeable”, particularly about symptoms, consequences, and treatment.1 In one of our recent unpublished studies, we performed an internet-based survey (http://www.pollster.com.tw/; study period: October 20, 2011-November 2, 2011; total 766 mothers with snoring sleep partners interviewed): 37% Journal compilation © 2012 Taiwan Society of Pediatric Pulmonology Lee LA, et al. of mothers had at least one child who present with snoring, and 21% of pediatric snorers had habitual snoring. Unfortunately, about 90% of mothers with snoring children did not consider snoring as a sign of OSA and they were casually related with obesity. This highlights the importance that sleep physicians need to educate both clinicians and parents more proactively. Primary snoring and OSA are the most common manifestations of sleep-disordered breathing (SDB), whereas upper airway resistance syndrome and obstructive hypoventilation were unusual. The epidemiology, symptoms and signs of OSA in children are not well defined and they are different from the adult population. According to a systematic review by Marcus et al., an estimated population prevalence of OSA was 1 to 5%.2 Moreover, OSA is more prevalent among obesed boys than girls. Nocturnal sleep study by polysomnography (PSG) is the golden standard of diagnosis, and has been recommended for all children with snoring.2 Notably, there are many co-existing predisposing factors of OSA, such as adenotonsillar hypertrophy, allergic rhinitis, obesity, craniofacial anomalies, laryngomalacia, neuromuscular disease, and hereditary genetic disorders.2-4 Moreover, intermittent hypopnea and obstructive apnea impair ventilation during sleep, while changes in sleep architecture and long-term upper airway obstruction may lead to significant morbidities such as systemic elevation of arterial blood pressure, cardiovascular disease, metabolic morbidity, growth failure, attention deficit/hyperactivity (ADHD), poor learning, and nocturnal enuresis. More importantly, these morbid complications will follow with longlasting consequences without timely diagnosis and intervention, which can cause marked increases in healthcare-related costs. Pathophysiology The definite pathophysiologic mechanism of pediatric OSA is still not well understood. Obstructive cycling, increased respiratory effort, flow limitation, tachypnea, and/or gas exchange abnormalities resulting variable abnormal respiratory effort and disturbance of sleep homeostasis. Imbalance neuromuscular activation, ventilatory control, and arousal threshold 99 cause the instability of the upper airway. Hypertrophy of the tonsils and adenoid are frequently encountered in childhood OSA, and adenotonsillectomy reduces adverse respiratory events defined by PSG and decrease risks of related morbidities.5 However, residual morbidity after adenotonsillectomy indicates that there were other factors need to be implicated for OSA to develop. For example, obesity increases airflow resistance and pharyngeal collapsibility, particularly in obesed children.6 Craniofacial deformities increase upper airway resistance which may be decreased by craniofacial reconstruction..2-4 Accordingly, OSA is the consequence of one or more disorders with comorbid diseases that mandate further evaluation and management. Diagnosis Coexisting medical disorders are frequently present in children with OSA.2-4 Accordingly, information such as clinical indicators of childhood OSA, such as symptoms, signs, anatomical and physiologic characteristics, and family history (Table 1), and underlying diseases and morbidities (Table 2) should be obtained. The most commonly applied tool to quantify the symptoms and quality of life in childhood OSA is the OSA-18 questionnaire.7 For the children with OSA, this structured questionnaire, scored by parents or caregivers, is valid, reliable, and easy-to-administer for the evaluation of child’s quality of life at baseline and after treatment.8 The items cover sleep disturbance, physical suffering, emotional distress, daytime problems, caregiver concerns and total quality of life (Table 3). Each symptom frequency is rated from ‘none’’ to ‘‘all of the time’’ by a 7-point ordinal scale and thereby, the OSA-18 survey score is between 18 and 126. The total scores less than 60 have been suggested to be a small impact on OSA child’s quality of life, scores between 60 and 80 suggest a moderate impact, and scores above 80 suggest a large impact.7 Although OSA-18 questionnaire has been originally designed for measuring the quality of life, the “sleep disturbance” subscale including loud snoring, witnessed apnea, labored breathing, and restless sleep are important clinical indictors for childhood OSA.8 For example, Current treatment for childhood OSA Table 1. Clinical indicators of childhood obstructive sleep apnea Symptoms and signs Anatomical and physiological characters Snoring Underweight or overweight Witnessed apnea Tonsillar hypertrophy Labored breathing Adenoidal hypertrophy Restless sleep Allergic rhinitis Mouth breathing Micrognathia/retrognathia Impaired behavior High-arched palate Nasal blockage Laryngomalacia Sweating during sleep Neuromuscular disorder, Cyanosis Prematurity Daytime sleepiness Failure to thrive Family history Hypertension Obstructive sleep apnea Table 2. Medical conditions associated with childhood obstructive sleep apnea Underlying disease Morbidities Obesity Cardiovascular disorder Allergic rhinitis or asthma Elevated systolic and diastolic blood pressure (> 95%), pulmonary hypertension, cor pulmonale Craniofacial problem Growth problem Mild abnormal structures Inadequate somatic growth, failure to thrive Neurocognitive problem Small mandible ± mandibular malpositioning Narrow nasomaxillary complex ± high and narrow Attention deficit hyperactivity disorder, poor learning hard palate (decreasing cognitive and academic functions), mental retardation Urinary dysfunction Marked midface (nasomaxillary) deficiency Apert syndrome, Crouzon syndrome, Pfeiffer Nocturnal enuresis syndrome, repaired cleft palate Metabolic syndrome Marked mandibular hypoplasia Pierre Robin sequence, severe juvenile rheumatoid Insulin resistance, dyslipidemia arthritis, Treacher Collins syndrome, Nager syndrome, Stickler syndrome Neuromuscular disorder Ear problems Cerebral palsy, Duchenne muscular dystrophy Recurrent otitis media Complex disease Oral-motor dysfunction Down syndrome, achondroplasia, Prader-Willi Phonological impairment syndrome, Mucopolysaccharidoses 100 Lee LA, et al. Table 3. Quality of life survey questionnaire for children with obstructive sleep apnea (OSA-18)7 hardly a good none of a little of some of most of any of bit of the the time the time the time the time the time time Sleep Disturbance During the past 4 weeks, how often has your child had… …loud snoring? 1 2 3 4 5 6 …breath holding spells or pauses 1 2 3 4 5 6 in breathing at night? …choking or gasping sounds while 1 2 3 4 5 6 asleep …restless sleep or frequent 1 2 3 4 5 6 awakenings from sleep? Physical symptoms During the past 4 weeks, how often has your child had… …mouth breathing because of 1 2 3 4 5 6 nasal obstruction? …frequent colds or upper 1 2 3 4 5 6 respiratory infections? …nasal discharge or runny nose? 1 2 3 4 5 6 …difficulty swallowing foods? 1 2 3 4 5 6 Emotional distress During the past 4 weeks, how often has your child had… …mood swings or temper 1 2 3 4 5 6 tantrums? …aggressive or hyperactive 1 2 3 4 5 6 behavior? …discipline problems? 1 2 3 4 5 6 Daytime function During the past 4 weeks, how often has your child had… …excessive daytime drowsiness or 1 2 3 4 5 6 sleepiness? …poor attention span or 1 2 3 4 5 6 concentration? …difficulty getting out of bed in 1 2 3 4 5 6 the morning? Caregiver concerns During the past 4 weeks, how often have the problems described above… …caused you to worrying about 1 2 3 4 5 6 child’s general health? …caused concern that your child is 1 2 3 4 5 6 not getting enough air? …interfered with your ability to 1 2 3 4 5 6 perform daily activities? …made you frustrated? 1 2 3 4 5 6 all of the time 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 For each question above, parents or caregivers rated symptom frequency during the previous 4 weeks using a 7-point ordinal scale. 101 Current treatment for childhood OSA habitual-snoring-group (scales 6-7) is associated with 3.5 times higher risk for AHI >1 episode/h comparing to never-snoring-group (scale 0).8 However, the OSA18 questionnaire does not accurately detect OSA, and all children with snoring and symptoms/signs of OSA should undergo PSG studies.2 Mouth breathing, night enuresis, sleeping in a seated position or with the neck hyperextended, cold sweating, cyanosis, headaches on awakening, daytime sleepiness, ADHD, and learning problems are other important clinical indictors of OSA.2-4 Family history of OSA is also a clue to indicate OSA. At first clinic visit, anatomical abnormalities of the upper airway and predisposing factors of OSA should be carefully identified. Recommended items of physical examination include underweight/overweight, tonsillar hypertrophy, adenoid facies, allergic shiners, micrognathia/retrognathia, high-arched palate, and stridor should be identified.2-4 Direct inspection of the mid-face, nose, tonsil, teeth, mandible, maxilla can be easily performed. Tests for allergic rhinitis and asthma, x-ray examinations of the head, and neck, and flexible fibro-optic endoscopy of the upper airway should be considered individually. Neuromuscular disorder (e.g., cerebral palsy, and Duchenne muscular dystrophy), prematurity, failure to thrive, and hypertension should be evaluated by physical examination. Moreover, history of OSA-related medical conditions should be taken. Should a pediatric patient with habitual snoring has any clinical indicator of OSA (Table 1), pediatricians should obtain a PSG study or refer the patient to a sleep specialist or otolaryngologist for a more extensive evaluation..2 However, extremely long waiting periods of PSG studies frequently stop clinicians and parents to undergo this examination. Therefore, a quick PSG arrangement may be made for (1) a child snores habitually and has any of the OSA-associated medical condition (Table 2), and (2) a snoring child has some clinical indicators that suggest a high index of suspicion for moderate-severe OSA. A regular arrangement may be suitable for snoring children having equivocal history and physical examinations. Overnight in-laboratory PSG studies assess respiratory and sleep distrubances objectively and quantitatively.. However, the criteria of interpretation for PSG have varied over time. The most recent diagnosis criteria and equipment requirements for PSG have been summarized in the American Academy of Sleep Medicine (AASM) Manual in 2007.9 Apnea is a pause in breathing lasting at least two respiratory cycles with no airflow detected. An obstructive apnea exhibits persistent respiratory effort present on the chest or abdominal belt sensor. A central apnea exhibits no effort present on the chest or abdominal sensor, whereas a mixed apnea shows a combination of the two. For clinical research, the AASM currently defines a hypopnea as a respiratory event lasting at least two respiratory cycles with either a 50% reduction in the airflow amplitude compared to baseline, and accompanied by desaturation ≥3%, an awakening, or an arousal. The AASM hypopnea rules for adults include a respiratory event lasting at least 10 seconds with (rule A) ≥4% desaturation or (rule B) ≥3% desaturation or arousal. Use of adult rule A results in fewer children fulfilling the criteria for OSA, whereas both pediatric or adult criteria rule B can be used in adolescents without significant change diagnostic category between these two criteria.10 Finally, AHI is defined as the mean number of apneas and hypopneas per hour of total sleep time. If PSG data are available, diagnosis and severity of childhood OSA can be confirmed and other SDB disorders can be managed immediately. Moreover, priority for treatment and step-wised therapy should be decided according to the severity of PSG findings and OSA-associated morbidities. Recently, the American Academy of Otolaryngology-Head and Neck Surgery Foundation issued a clinical practice guideline to arrange a PSG for SDB prior to tonsillectomy in children.11 These recommendations include: (1) Before determining the need for tonsillectomy, the clinician should refer children with SDB for PSG if they exhibit certain complex medical conditions. (2) Clinicians should advocate for PSG prior to tonsillectomy for SDB in children without any of the comorbidities for whom the need for surgery is uncertain or when there is discordance between tonsil size and the severity of SDB. (3) Clinicians should communicate PSG results to the anesthesiologist prior to the induction of anesthesia before operation. (4) Clinicians should admit children with OSA documented on PSG for inpatient, overnight monitoring after tonsillectomy if they are younger 102 Lee LA, et al. than age 3 or have severe OSA (AHI ≥10 episodes/h, oxygen saturation nadir <80%, or both). (5) In children for whom PSG is indicated to assess SDB prior to tonsillectomy, clinicians should obtain laboratorybased PSG, when available. Treatment Adenotonsillectomy is recommended as the firstline treatment of OSA patients with adenotonsillar hypertrophy. Although snoring and obstructed episodes are greatly reduced by adenotonsillectomy, residual morbidity is common. Meanwhile, nasal continuous positive airway pressure (CPAP) is currently recommended as the first-line treatment for OSA children with additional co-morbidity or complex disease.2-4 Weight control, antiinflammatory therapy, CPAP, oral appliance, rapid maxillary expansion, supraglottoplasty, craniofacial reconstruction, and tracheostomy are adjuvant therapies to adenotonsillectomy in varying conditions. For providing a brief scheme for the management of childhood OSA, we categorize these treatments into (A) first-line treatment (adenotonsillectomy, nasal CPAP) and (B) second-line treatment (weight control, anti-inflammatory therapy, oral appliance, rapid maxillary expansion, supraglottoplasty, craniofacial reconstruction, and tracheostomy). Moreover, the studies of “treatment benefits” and “treatment harms” are categorized in levels of evidence according to the “The Oxford 2011 Levels of Evidence”.12 A systematic review of randomized trials or n-of-1 trials (level 1) is generally better than an individual randomized trial or observational study with dramatic effect (level 2). Non-randomized controlled cohort/follow-up studies provide level 3 evidences. Case-series, case-control studies, or historically controlled studies are graded as “level 4”. Mechanismbased reasoning is graded as “level 5”. Figure 1. Scheme for adenoidectomy, tonsillectomy, and adjunctive surgical procedures in childhood obstructive sleep apnea 103 Current treatment for childhood OSA (A)First-line treatment Adenotonsillectomy Adenotonsillectomy continues to be the firstline and principle treatment at our sleep center because the most common cause of childhood OSA is adenotonsillar hypertrophy. Adenotonsillectomy is simple and efficient and has low morbidity for the therapy of OSA. Adenotonsillectomy is associated with a low complication rate (5% to 10%) in general population, but its complication rate is significantly higher in patients with OSA (18% to 34%; level 3).2 Accordingly, pre-surgical PSG has been suggested to be necessary in guiding the intraoperative and postoperative management in children undergoing adenotonsillectomy. Patients with younger age (<2 years), AHI >24 episodes/h, intra-operative laryngospasm requiring treatment, oxygen saturations <90% on room air in PACU, PACU stay >100 min, or OSA-associated morbidities are at risk for postoperative complications (level 4).13 Common post-adenotonsillectomy complications include wound pain, poor oral intake, bleeding, infection, anesthetic complications, respiratory decompensation, velopharyngeal incompetence, and death; perioperative complications should be prevented and managed carefully. Of note, a significant proportion of patients are left with persistent OSA after adenotonsillectomy despite improvement of polysomnographic parameters; that is, the majority of moderate-severe OSA children become mild OSA following adenotonsillectomy.5 Two meta-analyses (level 1) suggest that the postoperative AHI <5 episodes/h are frequently observed (range, 66.2%-82.9%).14,15 Friedman et al. demonstrated that the pooled cure rate (i.e. postoperative AHI <1 episode/h) of adenotonsillectomy was 59.8%.15 However, Bhattacharjee et al. found that the cure rate was 27.2% in a larger multicenter retrospective study (level 3).5 Marked differences in cure rates among these outcome studies may be resulted from the usage of published hypopnea definitions differently.. Moreover, approximate 13% of subjects who had been successfully treated with adenotonsillectomy may have recurrence of OSA at adolescence (level 3).16 Therefore, a combination of adenoidectomy, tonsillectomy, and/or adjunctive surgical procedures should be considered according to patient’s age, obstructive sites, and OSA severity at our sleep center (Fig. 1). Adenoidectomy is unlikely to be the sole treatment of childhood OSA because it does not change oropharyngeal obstruction that may be related to the tonsils, and we recommend adenoidectomy as the initial treatment for an infant (<1 year) with OSA and its associated conditions since nasal breathing is obligatory or at least strongly preferential in infants. Even relatively small tonsils may rotate medially and superiorly to obstruct the retropalatal airspace and narrow upper airway (level 4).17 Moreover, childhood tonsillectomy is related to neither the increasing frequency nor the prolonged duration of upper respiratory tract infection comparing with age-matched controls (level 3).18 Accordingly, simultaneous tonsillectomy and adenoidectomy in cases of documented OSA seems to be more rationale comparing to single adenoidectomy in OSA patients older than 1 year. Partial tonsillectomy has been more favoring than before because of its relative low morbidity comparing to traditional tonsillectomy.2 Microdebrider intracapsular adenotonsillectomy, using a 10otonsillar blade (Medtronic ENT, FL, USA), spares a portion of tonsil to cover the musculature of the tonsillar fossa and decreases the morbidity associated with traditional tonsillectomy, seems to be as effective as total tonsillectomy in treatment of childhood OSA as validated by PSG (level 4).19 There exists a risk of tonsillar regrowth and the patients with residual or relapsing OSA may need a revised total tonsillectomy. Accordingly, we recommend younger children (<5 years) with mild-moderate OSA to undergo adenoidectomy and partial tonsillectomy. Several new techniques for alleviating the morbidity associated with total tonsillectomy have gained increasing use in recent years. Bipolar radiofrequency dissection tonsillectomy a radiofrequency bipolar forceps (El lman International, New York, USA) seems to be associated with shorter operating time and minimal intra-operative blood loss when compared to the conventional cold dissection tonsillectomy in a level 2 study.20 A different bipolar radiofrequency-based plasma device (Coblation®, ArthroCare Corp, CA, USA) also proves its advantages (less intraoperative bleeding and pain, similar minimal postoperative bleeding) over cold dissection with sutures for the treatment of 104 Lee LA, et al. children with OSA (level 2).21 In addition, coblation total tonsillectomy in children is further confirmed to be a reliable and safe procedure with a relatively low incidence of intraoperative and postoperative bleeding (level 3).22 In our institute, we recommend children (≥5 years) with high grade tonsillar hypertrophy and mildmoderate OSA to undergo complete adenotonsillectomy with electrocautery or coblation. Residual OSA is present in a large proportion of children after adenotonsillectomy, particularly among older (>7 years) or obese children (level 3).5 Friedman et al.23 found that traditional adenotonsillectomy plus pharyngoplasty with suturing the muscle layer of the tonsillar wound to reduce the collapsibility of the pharynx is associated with an insignificantly increasing cure rate comparing to traditional adenotonsillectomy in a randomized control trial with minor limitations (level 2). For these reasons, we recommend adenoidectomy and total tonsillectomy with pharyngoplasty for young OSA children. In some cases such as obese adolescents or children with complex disease, modified uvulopalatopharyngoplasty including removal of parts of supratonsillar mucosa and adipose tissue may be more suitable. Although the use of electrocautery is not associated with an increase incidence of wound dehiscence compared with cold dissection, we observed tonsillar pillar dehiscence rate is particularly high in coblation pharyngoplasty in pediatric subjects. Recently, a randomized control trial (level 2) compared the effectiveness of plasma knife, bipolar electrocautery, and cold dissection, and concluded that the use of plasma knife (PEAK PlasmaBlade™, Medtronic ENT, FL, USA) reduces intraoperative blood loss and provides a fast tonsillectomy with acceptable morbidity.24 The sharp cutting edge incised by plasma knife looks like that by cold knife, and allows surgeons to suture the tonsillar pillar easily and precisely, and may prevent from early wound dehiscence, pain, and bleeding. Currently, we prefer to undergo adenotonsillectomy plus pharyngoplasty or relocation pharyngoplasty (modified uvulopalatopharyngoplasty)25 using electrocautery or plasma knife for a child with OSA who has older age at operation (>7 years), severe severity, obesity, or OSAassociated (co-morbidities). Nasal CPAP Currently, nasal CPAP is recommended for OSA 105 children unable to undergo adenotonsillectomy or patients with residual OSA following other treatment modalities (Table 4). 2-4 Stenting the pharyngeal lumen by nasal CPAP in order to reduce the obstructive effects caused by increasing upper airway resistance, raised pharyngeal collapsibility, decreased pharyngeal dilator muscle tone, and more negative intraluminal pressure is indicated for all OSA patients. However, adherence to CPAP treatment in childhood OSA is very poor despite its high efficacy. Poor adherence to nasal CPAP is a leading cause of therapeutic failure. Accordingly, if adenotonsillectomy is an option to treat childhood OSA, nasal CPAP can be reserved as a second-line therapy. Two level 2 study (randomized trial with low power) assessed two different sleep respiratory therapies (CPAP vs. bilevel positive airway pressure26 or CPAP vs. bilevel positive airway pressure with pressure release technology27), and found both treatment modalities can improve the patients’ snoring, AHI, and arterial oxygen saturation. About 39%-80% of patients adhere to nasal CPAP therapy (levels 2-3).26-28 If the caregivers accept nasal CPAP as a major treatment, behavioral techniques may help to improve its adherence. The most frequently endorsed barriers to CPAP were similar for parents and their children: almost half of the families reported “not using CPAP when away from home” as a top barrier.28 Of note, CPAP pressures and fitness of mask should be periodically reassessed because various changes of growth and development in children. In our institute, a highly motivated team approach consisting of physicians, nurses, psychologists, and sleep technicians work jointly in corroboration is proposed to maintain a CPAP adherence to promote high success rate of management. (B)Second-line treatment Weight loss Childhood OSA seldom resolves spontaneously but may deteriorate gradually (level 4).29 The severity of airway inflammation and sleep associated gas exchange abnormalities increase with progressive obesity in older children with OSA (level 3).30 Accordingly, weight control should be stressed in the temporal management of childhood OSA, particularly in elder children. Anti-inflammatory treatment The prevalence of OSA increases markedly among Current treatment for childhood OSA Table 4. Modalities of possibly curative treatment of childhood OSA Levels of Indications evidence* Reduce upper airway narrowing and its resistance: Adenotonsillectomy 1-4 1. Adenotonsillar hypertrophy Modality Reduce upper airway resistance and its collapsibility: Nasal CPAP 2-4 1. OSA associated with severe complex (co-) morbidities 2. Residual OSA after adenotonsillectomy 3. OSA associated with (co-) morbidities that fail to response to other treatment modalities Supraglottoplasty 4 1. Laryngomalacia Suggestions 1. Perioperative complications should be prevented and managed carefully. 2. Residual disease is common. 3. Recurrent disease is not unusual. 1. Nasal CPAP should be prescribed as the first-line treatment for children with complex disease or as an adjuvant treatment following other treatment modalities. 2. Poor adherence of nasal CPAP is common and should be overcome by behavior modifications and team approach. 3. CPAP pressures and fitness of mask should be periodically reassessed. 1. Infant or young children with moderate laryngomacia may have OSA. 2. Supraglottoplasty for laryngomalacia may also improve co-existing OSA severity. Reduce upper airway resistance and improve efficacy of neuromotor function Oral appliance 2-4 1. Small mandible 1. Mandibular advancement devices and rapid 2. Retrognathesia maxillary expansion can help to change the narrowing upper airway and can be used to treat Rapid maxillary 2-4 1. High narrow mild-moderate OSA. expansion maxilla 2. Distraction osteogenesis is usefully applied in Distraction 4 1. Mandibular congenital micrognathia or midface hypoplasia. osteogenesis of hypoplasia 3. Consistent follow-up and management are the mandible and 2. Midface deficiency needed to increase clinical success rates in dental midface or craniofacial treatment of OSA. Bypass the upper airway obstruction Tracheostomy 4 1. Intractable OSA 1. Tracheostomy is the most effective treatment for 2. Maintaining airway severe and intractable OSA. patency before 2. This modality is also the last choice reported by surgery parents. OSA: obstructive sleep apnea. CPAP: continuous positive airway pressure. *The studies of “treatment benefits” are categorized in levels of evidence according to the “The Oxford 2011 Levels of Evidence”.60 106 Lee LA, et al. children with history of allergic rhinitis, wheezing, and poorly controlled asthma (level 3).31,32 Moreover, viral respiratory infections may induce inflammation and oxidative stress in the allergic airway enhancing leukotrienes within pharyngeal lymphoid tissues, which promote adenotonsillar enlargement and OSA.31 Appropriate treatment of allergic rhinitis regularly can prevent the occurrence of OSA and reduce the severity of existing OSA. Of note, intranasal steroids may ameliorate mild-moderate OSA and provide a short-term benefit effect (level 2) 33 but be not used as the primary treatment of moderate or severe OSA.2 Because the long-term effects of intranasal steroids are not known, it can use to be a short-term treatment of OSA and follow-up evaluation is needed to ensure that the OSA does not recur and to monitor for adverse effects (level 1).34 In the past, montelukast have been reported to induce significant reductions in adenoid size and respiratory-related sleep disturbances in a small level 3 study,35 but it has not been recommended to be a single treatment of OSA because of insufficient data.34 In the most recent randomized control trial, a 12-week treatment with montelukast effectively reduced the magnitude of the underlying adenoidal hypertrophy and the severity of OSA (obstructive apnea index decreased by >50% in 65.2% of treated children) comparing with placebo in children with mild-moderate OSA (level 2).36 Supraglottoplasty Most children with laryngomalacia have breathing disturbance in daytime, but some children may present normal breathing while awake but stridor and increased work of breathing during sleep. PSG should be considered in the initial evaluation of infants with moderate laryngomalacia to rule out OSA (level 4).37 Moreover, laryngomalacia may contribute significantly to OSA in children older than 12 months (level 4).38 Drug-induced sleep endoscopy under light sedation can help to diagnose state-dependent laryngomalacia. When children with laryngomalacia and OSA is diagnosed, a supraglottoplasty can be an effective procedure and may significantly improve symptoms of OSA in three level 4 studies.37-39 The primary complications after supraglottoplasty are dysphagia, postoperative coughing, and throat clearing, those are transient in most children (level 4).39 107 Oral appliance Children with malocclusion and OSA have a narrow upper airway at the level of the mandible, tongue, and soft palate. Using an oral jar-positioning appliance to reposition these structures resulted from the small mandible or retrognathesia can help to maintain the patency of the upper airway during sleep. A randomized control trial (level 2) have shown that an oral appliance is more effective than observation only to treat OSA in children.40 The most frequent reasons why patients discontinued wear are uncomfortable, having little or no effect, or switching to nasal CPAP; side effects, such as dry mouth and tooth and/or temporomandibular joint discomfort are frequently reported (level 4).41 We recommend the oral appliance as a therapeutic alternative in children with mild to moderate OSA. Consistent follow-up and management are needed to increase clinical success rates in oral appliance therapy for OSA. Rapid maxillary expansion Rapid maxillary expansion to correct the narrowed maxilla and malocclusion has been used to treat childhood OSA for many years. AHI and arousal index can be reduced by rapid maxillary expansion significantly in the first year and may persist 24 months after the end of treatment (level 4).42 However, rapid maxillary expansion may fail as a mono-therapy for OSA in patients with both adenotonsillar hypertrophy and narrowed maxillary complex. The orthodontic goal for these patients should include strategies to improve the narrowing upper airway while still achieving a functional occlusion. Guilleminault and his coworkers have undergone a randomized control trial to compare the outcomes of adenotonsillectomy followed by rapid maxillary expansion and rapid maxillary expansion followed by adenotonsillectomy (level 2).43 They found the differences in outcomes between both groups were statistically insignificant and continued clinical symptoms and abnormal PSG results frequently persisted in overall patients. Accordingly, mandibular advancement devices are recommended to be used for mild to moderate OSA. Distraction osteogenesis of the mandible and midface A high degree of suspicion in the population craniofacial anomalies is necessary to rule out the Current treatment for childhood OSA existence of OSA in a given pediatric patient. Childhood OSA associated with craniofacial anomalies frequently is refractory to traditional treatment modalities. Severe mandibular hypoplasia and midface deficiency can cause extreme narrowing of the upper airway and may be managed by tracheostomy in the past. Distraction osteogenesis of the mandible and midface can enable mandibular and midfacial lengthening and relieve severe upper airway obstruction; these surgical approaches may lead to earlier decannulation and treat abnormal sleep breathing. When comparing newborns and early infant patients, treatment success rates and the occurrence of complications following distraction osteogenesis seems to be similar; however, older pediatric patients may have no treatment failures and tend to have fewer postoperative complications compared to younger patients (level 4).44 Successful mandibular advancement can increase mandibular volume by an average of 28% and increase upper airway volume with a mean of 72%, and also can improve apnea index and arterial oxygen saturations (level 4).45 Le Fort III osteotomy with midface distraction osteogenesis can significantly improve the upper airway space above the uvula level in the cases of syndromic craniosynostosis and may ameliorate the severity of childhood OSA (level 4).46 Despite midface advancement, long-term dependence on, or indication for, CPAP or tracheostomy may be maintained in near a half of this population.47 Tracheostomy Childhood OSA complicated by congenital craniofacial malformations is frequent rigorous, which in severe cases leads to tracheostomy dependence. A tracheotomy can bypass upper airway obstruction and is extremely effective at treating OSA. However, this surgical approach is associated with increased morbidity and is typically a last resort if CPAP and other treatments fail to improve for a child who has severe OSA.2-4 Even in OSA children with syndromic craniosynostosis, adenotonsillectomy can avoid of tracheostomy in three of five patients (level 4).48 Distraction osteogenesis may be a useful method to improve the airway, to avoid the tracheostomy, or to lead decannulation. However, decannulation rate of the permanent tracheostomy following mandibular distraction osteogenesis seems to be varied differently in tracheotomized patients with complex congenital syndromes (13%-100%).46,49 Follow-up There are many treatment modalities to date, but there is no “one-size-fits-all” approach due to the multifactorial nature of childhood OSA. Even though adenotonsillectomy is the first-line treatment, residual OSA (AHI ≥5 episodes/h) may have frequently existed in 8%-34% subjects in previous meta-analyses.14,15 The BMI gain soon after operation6 and may result in recurrence of OSA.16 Accordingly, we recommend a period of observation following adenotonsillectomy is imperative even for younger OSA children. Of note, an average prevalence of residual OSA has reported to be 73% in a large multi-centric retrospective study5 when using an postoperative AHI ≥1 episodes/h. To our knowledge, obstructive apneas are frequently reduced by adenotonsillectomy, whereas hypopneas often persist postoperatively and result in residual OSA.7 Despite different definitions of hypopnea and residual OSA, skeletal abnormalities such as craniofacial anomalies, minor stenosis, or neuromuscular disorders, obesity, a high preoperative AHI (≥20 episodes/h), as well as an old age at surgery (>7 years) are important risk factors of persistent OSA.5 It is important to realize that adenotonsillectomy often does not achieve desired results in childhood OSA. Therefore, a longitudinal follow-up of OSA children with the risk factors listed above is able to reveal residual of respiratory disturbance after adenotonsillectomy and to suggest reevaluation of OSA-associated (co-)morbidities. Amin et al. have performed serial PSGs, BMI, and blood pressure examinations after adenotonsillectomy during the first 1 year.16 They found that AHI reduced from 9.2±14 episodes/h at baseline to 1.4±2 episodes/h at 6 weeks after surgery and their AHI increased gradually overtime. At 1 year postoperatively, the recurrence of OSA (AHI ≥3 episodes/h) seems to be associated with an accelerated BMI gain, obesity, and African American. Moreover, allergic rhinitis, regrowth of adenoid, craniofacial anomaly with abnormal bite, and lingual tonsil hypertrophy are also related to persistent or recurrent OSA. Noticeably, complete resolution of OSA in patients with complex disease such as Prader-Willi syndrome is difficult to obtain with adenotonsillectomy alone.50 OSA patients identified with Prader-Willi syndrome should be referred for adenotonsillectomy and/or CPAP therapy, and then 108 Lee LA, et al. reassessed for residual airway obstruction and/or OSA prior to instituting growth hormone therapy. Absence of symptoms such as snoring postoperatively is reassuring but may not be 100% specific for complete resolution of OSA. By contrast, postoperative reports of snoring and witnessed apneas correlate well with persistence of OSA after adenotonsillectomy.51 It may therefore be advisable to obtain a postoperative PSG in (1) very high-risk children even in the absence of reported persistent snoring or (2) patients with persistent or recurrent symptoms and signs of OSA. Nevertheless, “surgical success” should be defined not only by PSG but also by resolution of clinically relevant outcomes, such as cardiovascular function, neurocognition, behavior, and quality of life.7,52 Therefore, establishment of standardized data collection procedures, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel are major elements in the design and implementation of a fine controlled trial for a widely used “standard practice” surgical intervention in a pediatric OSA population. CONCLUSION Childhood OSA is a prevalent disease in the world. Clinical indicators can help pediatricians to decide whether or not a child is at risk for childhood OSA. Early consultations for a pediatric dentist, craniofacial surgeon, neurologist, cardiologist, or psychiatrist are particular important for intensive management of OSA-associated underlying disease and morbidities. Timely diagnosis and treatment of orthodontic problem, craniofacial anomaly, neuromuscular disorder, cardiovascular disorder, or ADHD are imperative because these diseases may trigger the occurrence of OSA or also may be aggravated by OSA. The true mechanism of childhood OSA is probably multifactorial and differentiation of the primary and secondary aspects enables clinicians to pinpoint the essentials of childhood OSA. To date, standard PSG is the “golden standard” diagnostic method for pediatric SDB and adenotonsillectomy continues to be the best and most acceptable treatment for childhood OSA. Despite there are many other treatment modalities such as nCPAP, weight loss, anti-inflammatory treatment, 109 supraglottoplasty, oral appliance, rapid maxillary expansion, distraction osteogenesis, and tracheostomy for childhood OSA, residual disease is quite common after any mono-therapy. 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