Obstructive Sleep Apnea in Children

Number: 0752

Policy

  1. Diagnosis

    1. Aetna considers nocturnal polysomnography (NPSG) for children and adolescents younger than 18 years of agemedically necessary when performed in a healthcare facility for any of the following indications:

      1. To diagnose obstructive sleep apnea syndrome (OSAS) and differentiate it from snoring
      2. To evaluate hypersomnia
      3. Suspected narcolepsy (with MSLT)
      4. Suspected parasomnia
      5. Suspected restless leg syndrome
      6. Suspected periodic limb movement disoder
      7. Suspected congenital central alveolar hypoventilation syndrome
      8. Suspected sleep related hypoventilation due to neuromuscular disorders or chest wall deformities.
    2. Aetna considers NPSG for children medically necessary when performed in a healthcare facility after an adenotonsillectomy or other pharyngeal surgery for OSAS when any of the following is met (study should be delayed 6 to 8 weeks post-operatively):

      1. Age younger than 3 years; or
      2. Cardiac complications of OSAS (e.g., right ventricular hypertrophy); or
      3. Craniofacial anomalies that obstruct the upper airway; or
      4. Failure to thrive; or
      5. Neuromuscular disorders (e.g., Down syndrome, Prader-Willi syndrome and myelomeningocele); or
      6. Obesity; or
      7. Prematurity; or
      8. Recent respiratory infection; or
      9. Severe OSAS was present on pre-operative PSG (a respiratory disturbance index of 19 or greater); or
      10. Symptoms of OSAS persist after treatment.
    3. Aetna considers the use of abbreviated or screening techniques, such as videotaping, nocturnal pulse oximetry, unattended home PSG, or facility based, daytime, abbreviated cardiorespiratory sleep studies (daytime nap PSG, Pap Nap testing) experimental and investigational for diagnosis of OSAS in children because their effectiveness for this indication has not been established.
    4. Aetna considers measurements of circulating adropin concentrations, plasma pentraxin-3 or TREM-1 levels experimental and investigational for obstructive sleep apnea in children.
    5. Aetna considers measurement of DNA methylation levels experimental and investigational for the diagnosis and prognosis of OSA because the effectiveness of this approach has not been established.
    6. Aetna considers the use of surface electromyography (EMG) for the evaluation of OSA experimental and investigational because the effectiveness of this approach has not been established.
  2. Treatment

    Aetna considers the following treatments for OSAS in children with habitual snoring medically necessary when the apnea index is greater than 1 on a NPSG.

    1. Aetna considers adenoidectomy and/or tonsillectomy medically necessary for treatment of OSAS in children.  Childhood OSAS is usually associated with adenotonsillar hypertrophy, and the available medical literature suggests that the majority of cases will benefit from adenotonsillectomy.
    2. Aetna considers continuous positive airway pressure (CPAP) medically necessary for treatment of OSAS in children when any of the following is met:

      1. Adenoidectomy or tonsillectomy is contraindicated; or
      2. Adenoidectomy or tonsillectomy is delayed; or
      3. Adenoidectomy or tonsillectomy is unsuccessful in relieving symptoms of OSAS.

      Aetna considers CPAP medically necessary for treatment of tracheomalacia.

    3. Aetna considers oral appliances or functional orthopedic appliances medically necessary in the treatment of children with craniofacial anomalies with signs and symptoms of OSAS. 
    4. Aetna considers oral appliances or functional orthopedic appliances experimental and investigational for treatment of OSAS in otherwise healthy children.  There is insufficient evidence that oral appliances or functional orthopedic appliances are effective in the treatment of OSAS in healthy children.
    5. Aetna considers palatopharyngoplasty (uvulopalatopharyngoplasty (UPPP), uvulopharyngoplasty, uvulopalatal flap, expansion sphincter pharyngoplasty, lateral pharyngoplasty, transpalatal advancement pharyngoplasty, relocation pharyngoplasty) medically necessary for the treatment of OSAS in children with neuromuscular disorders who are deemed to be at high risk for persistent upper airway obstruction after adenotonsillectomy alone. Aetna considers palatopharyngoplasty experimental and investigational for the treatment of OSAS in otherwise healthy children. 
    6. Aetna considers supraglottoplasty medically necessary for laryngomalacia if the member is 2 years of age or younger, and there is documented hypoxia, hypercapnia, failure to thrive, infantile sleep apnea, cor pulmonale or pulmonary hypertension unresolved with conservative management.
    7. Lingual tonsillectomy (e.g., endoscopic-assisted coblation lingual tonsillectomy) and/or tongue base reduction to treat tongue base collapse in children with persistent OSA after adenotonsillectomy (e.g., in children with obesity, Down syndrome, and craniofacial or neuromuscular disorders) 
    8. Note on orthodontic treatment: Expenses associated with orthodontic treatments (such as rapid maxiallary expansion) are considered dental in nature and are not covered under Aetna's medical plans. Please check benefit plan descriptions. See CPB 0082 - Dental Services and Oral and Maxillofacial Surgery: Coverage Under Medical Plans.
    9. Aetna considers the following interventions experimental and investigational for obstructive sleep apnea in children because their effectiveness for this indication has not been established (not an all-inclusive list):

      1. Cautery-assisted palatal stiffening procedure (CAPSO);
      2. Chiropractic/osteopathic manipulation;
      3. Flexible positive airway pressure;
      4. Hypoglossal nerve stimulation;
      5. Injection snoreplasty;
      6. Laser-assisted uvuloplasty (LAUP);
      7. Mandibular distraction osteogenesis;
      8. Maxillary expander;
      9. Maxillary protraction;
      10. Midline/partial glossectomy;
      11. Montelukast;
      12. Nasal surgery;
      13. Pillar palatal implant system;
      14. Pre-fabricated myofunctional appliances (e.g., Myobrace/MyOSA);
      15. Repose system;
      16. Respiratory muscle therapy (i.e., breathing exercises, oropharyngeal exercises, and wind musical instruments);
      17. Somnoplasty;
      18. Uvulectomy.

Background

Obstructive sleep apnea syndrome (OSAS) is a disorder of breathing in which prolonged partial upper airway obstruction and/or intermittent complete obstruction occurs during sleep disrupting normal ventilation and normal sleep patterns.  The signs and symptoms of OSAS in children include habitual snoring (often with intermittent pauses, snorts, or gasps) with labored breathing, observed apneas, restless sleep, and daytime neurobehavioral problems.  Nocturnal enuresis, diaphoresis, cyanosis, mouth breathing, nasal obstruction during wakefulness, adenoidal facies, and hyponasal speech may also be present.  Daytime sleepiness is sometimes reported but hyperactivity can frequently occur.  Case studies report that OSAS in children can lead to behaviors easily mistaken for attention-deficit/hyperactivity disorder as well as behavioral problems and poor learning; however, most case studies have relied on histories obtained from parents of snoring children without objective measurements, control groups, or sleep studies.  Severe complications of untreated OSAS in children include systemic hypertension, pulmonary hypertension, failure to thrive, cor pulmonale, and heart failure. 

History and physical examination have been shown to be sensitive but not specific for diagnosing OSAS in children.  Primary snoring is often the presenting symptom reported by parents, and should warrant careful screening for OSAS.  Primary snoring is defined as snoring without obstructive apnea, frequent arousals from sleep or abnormalities in gaseous exchange.  It is estimated that 3 % to 12 % of children are habitual snorers but only 2 % will be diagnosed with OSAS.  Although surgical treatment has been shown to improve quality of life, it is not without risks (e.g., bleeding, velopharyngeal insufficiency, post-obstructive pulmonary edema).  Thus, clinicians must be able to distinguish between primary snoring and OSAS.  Primary snoring among children without obstructive sleep apnea is usually considered a benign condition although this has not been well evaluated.

Nocturnal polysomnography (NPSG) remains the gold standard diagnostic test to differentiate primary snoring from OSAS in children.  It is the only diagnostic technique that is able to quantitate the ventilatory and sleep abnormalities associated with sleep-disordered breathing and can be performed in children of any age. A polysomnogram (PSG) is a sleep study that is performed in a facility/laboratory setting and requires an overnight stay. PSG is designed to capture multiple sensory channels including blood pressure, brain waves, breathing patterns and heartbeat as an individual sleeps. It can also record eye and leg movements and muscle tension which can be useful in diagnosing parasomnias. A PSG performed at a facility will record a minimum of 12 channels which involves at least 22 wire attachments to the individual. Sensors that send electrical signals to a computer are placed on the head, face, chest and legs. This test is attended by a technologist and the results are evaluated by a qualified physician. A PSG may be performed in conjunction with a positive airway pressure (PAP) machine to determine the titration of oxygen flow. 

Positive airway pressure (PAP) titration study is used to set the right level of PAP which can be administered as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) once individual tolerance and optimal levels are determined by a sleep technologist. PAP titration may be performed in conjunction with a PSG as part of a split night study if the diagnosis of moderate or severe OSA can be made within the first two hours of recorded sleep and at least three hours of PAP titration, including the ability of PAP to eliminate respiratory events during both rapid eye movement (REM) sleep and non-REM sleep, is demonstrated. If this is not possible, a second night in the sleep center may be necessary for the CPAP titration study.

It should be noted that interpretation of NPSG values in children with OSAS is not unanimously agreed upon in the literature (Sargi and Younis, 2007) and only a limited number of studies designed to establish normal values for sleep-related respiratory variables in children have been reported.  However, based on normative data, an obstructive apnea index of 1 is frequently chosen as the threshold of normality.  Other normative values reported in the literature for children aged 1 to 15 years include: central apnea index 0.9; oxygen desaturation, 89 %; baseline saturation, 92 %; and PETCO2 (end-tidal carbon dioxide pressure) greater than 45 mm Hg for less than 10 % of total sleep time (Verhulst, 2007; Uliel, 2004; Schechter, 2002).

Studies have shown that abbreviated or screening techniques, such as videotaping, nocturnal pulse oximetry, and daytime nap PSG tend to be helpful if results are positive but have a poor predictive value if the results are negative. Facility based, daytime, abbreviated, cardiorespiratory sleep studies (PAP NAP testing) uses a therapeutic framework that includes mask and pressure desensitization, emotion focused therapy to overcome aversive emotional reactions, mental imagery to divert the individual’s attention from mask or pressure sensations and physiological exposure to PAP therapy during a 100 minute nap period which is purported to enhance PAP therapy adherence.  

Home/portable monitoring sleep testing is a sleep study performed in the home utilizing portable monitoring (PM) devices that are designed to be used by an individual without supervision of a sleep technologist. PM devices measure fewer parameters than a laboratory based sleep study and are therefore not recommended for assessment of sleep disorder in the pediatric population. Unattended home PSG in children was evaluated by 1 center (Jacob, 1995) and produced similar results to laboratory studies; however, the equipment was relatively sophisticated and included respiratory inductive plethysmography, oximeter pulse wave form and videotaping.  Unattended home studies in children using commercially available 4-  to  6-channel recording equipment has not been studied.  Portable monitoring based only on oximetry is inadequate for identifying OSAS in otherwise healthy children (Kirk, 2003).

Actigraphy is a technique for monitoring body movement during sleep to detect sleep disorders by using a portable device known as an actigraph, which is worn on the individual’s wrist or ankle. An example of an actigraph device is the Actiwatch.

Prescreening devices or procedures purportedly predict pretest probability of obstructive sleep apnea (OSA) prior to performing a sleep study. Examples of prescreening techniques include, but may not be limited to, acoustic pharyngometry and SleepStrip.

According to the American Academy of Pediatrics guideline on the diagnosis and management of childhood OSAS (2002), complex high-risk patients should be referred to a specialist with expertise in sleep disorders.  These patients include infants and children with any of the following: craniofacial disorders, Down syndrome, cerebral palsy, neuromuscular disorder, chronic lung disease, sickle cell disease, central hypoventilation syndrome, and genetic/metabolic/storage diseases. 

Indications for a repeat NPSG after an adenotonsillectomy or other pharyngeal surgery for OSAS include
  1. high-risk children, or
  2. if symptoms of OSAS persist after treatment. 
High-risk children include those of age younger than 3 years, severe OSAS was present on pre-operative PSG (a respiratory disturbance index of 19 or greater), cardiac complications of OSAS (e.g., right ventricular hypertrophy), failure to thrive, obesity, prematurity, recent respiratory infection, craniofacial anomalies, and neuromuscular disorders.  Patients with mild to moderate OSAS who have complete resolution of signs and symptoms do not require repeat NPSG (AAP, 2002).
The American Academy of Pediatrics’ practice guideline on “Diagnosis and management of childhood obstructive sleep apnea syndrome” (Marcus et al, 2012) focused 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.  Of 3,166 articles from 1999 to 2010, 350 provided relevant data.  Most articles were level II to IV.  The resulting evidence report was used to formulate recommendations.  The following recommendations were 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,
  3. Adenotonsillectomy is recommended as the first-line treatment of patients with adenotonsillar hypertrophy,
  4. High-risk patients should be monitored as inpatients post-operatively,
  5. Patients should be re-evaluated post-operatively to determine whether further treatment is required.  Objective testing should be performed in patients who are high-risk or have persistent symptoms/signs of OSAS after therapy,
  6. CPAP is recommended as treatment if adenotonsillectomy is not performed or if OSAS persists post-operatively,
  7. Weight loss is recommended in addition to other therapy in patients who are over-weight or obese, and
  8. Intra-nasal corticosteroids are an option for children with mild OSAS in whom adenotonsillectomy is contraindicated or for mild post-operative OSAS. 
The updated guideline did not mention the use of lingual tonsillectomy as a management tool for OSA in children and adolescents.

Treatment of OSAS in children depends on the severity of symptoms and the underlying anatomic and physiologic abnormalities.  Childhood OSAS is usually associated with adenotonsillar hypertrophy, and the available medical literature suggests that the majority of cases (75 % to 100 %) will benefit from adenotonsillectomy (the role of adenoidectomy alone is unclear). Tonsillectomy and/or adenoidectomy are procedures that are performed for airway obstruction, especially in children. Tonsillectomy is the surgical removal of the tonsils, which are a collection of lymphoid tissue covered by mucous membranes located on either side of the throat. An adenoidectomy is the surgical removal of the adenoid glands. The adenoids are masses of lymphoid tissue located at the back of the nose in the upper part of the throat.

Other causes of pediatric OSAS include obesity, craniofacial anomalies, and neuromuscular disorders.  Obese children may have less satisfactory results with adenotonsillectomy, but it is generally considered the first-line therapy for these patients as well.  If the patient is not a candidate for adenotonsillectomy, other treatment options include weight loss (if patient is obese) and continuous positive airway pressure (CPAP).  Nocturnal masks for CPAP or procedures for mask respiration are effective in children, but are only used in exceptional cases, such as when adenotonsillectomy is delayed, contraindicated, or when symptoms of OSAS remain after surgery. 

Severely affected children may require uvulopalatopharyngoplasty (UPPP) or tracheostomy to relieve their obstruction; however, neither have been well studied in children and is rarely indicated.  Tracheostomy is a surgical procedure in which an opening is created through the neck into the windpipe (trachea) and a tube placed through this opening to provide an airway. Uvulopalatopharyngoplasty (UPPP) is the surgical revision of the posterior soft palate and adjacent tissue to relieve partial obstruction of the nasopharyngeal airway that causes OSA.

The success of pharmacological treatment of OSAS in children has not been evaluated in controlled clinical trials (Erler and Paditz, 2004).

A Cochrane review (2007) on oral appliances and functional orthopedic appliances for OSA in children 15 years old or younger reported that there is insufficient evidence to state that oral appliances or functional orthopedic appliances are effective in the treatment of OSAS in children.  Oral appliances or functional orthopedic appliances may be helpful in the treatment of children with craniofacial anomalies that are risk factors of apnea.

In a meta-analysis of mandibular distraction osteogenesis, Ow and Cheung (2008) concluded that mandibular distraction osteogenesis is effective in treating craniofacial deformities, but further clinical trials are needed to evaluate the long-term stability and to compare the treatment with conventional treatment methods, especially in cases of OSA or class II mandibular hypoplasia.

Pang and Woodson (2007) evaluated the effectiveness of a new method (expansion sphincter pharyngoplasty [ESP]) to treat OSA.  A total of 45 adults with small tonsils, body mass index (BMI) less than 30 kg/m2, of Friedman stage II or III, of type I Fujita, and with lateral pharyngeal wall collapse were selected for the study.  The mean BMI was 28.7 kg/m2.  The apnea-hypopnea index (AHI) improved from 44.2 +/- 10.2 to 12.0 +/- 6.6 (p < 0.005) following ESP and from 38.1 +/- 6.46 to 19.6 +/- 7.9 in the uvulopalato-pharyngoplasty group (p < 0.005).  Lowest oxygen saturation improved from 78.4 +/- 8.52 % to 85.2 +/- 5.1 % in the ESP group (p = 0.003) and from 75.1 +/- 5.9 % to 86.6 +/- 2.2 % in the uvulopalato-pharyngoplasty group (p < 0.005).  Selecting a threshold of a 50 % reduction in AHI and AHI less than 20, success was 82.6 % in ESP compared with 68.1 % in uvulopalato-pharyngoplasty (p < 0.05).  The authors concluded that ESP may offer benefits in a selected group of OSA patients.  These findings need to be validated by studies with larger sample sizes and long-term follow-up.

In a retrospective institutional review board-approved analysis, Wootten and Schott (2010) described their experience of treating retroglossal and base-of-tongue collapse in children and young adults with OSA using combined genioglossus advancement (Repose THS; MedtronicENT, Jacksonville, FL) and radiofrequency ablation of the tongue base.  A total of 31 patients with a mean age of 11.5 years (range of 3.1 to 23.0) were included in this analysis.  Pre-operative and post-operative polysomnographic data were evaluated for each patient.  Success of surgery was determined using the criteria of a post-operative AHI of 5 or fewer events per hour, without evidence of hypoxemia (oxygen saturation as measured by pulse oximetry), and without prolonged hypercarbia (end-tidal carbon dioxide).  Nineteen (61 %) of the 31 subjects had Down syndrome.  The overall success rate was 61 % (19 of 31) (58 % [12 of 19] success among patients with Down syndrome and 66 % [7 of 12] success among patients without Down syndrome).  Overall, the mean AHI improved from 14.1 to 6.4 events per hour (p < 0.001); the mean nadir oxygen saturation as measured by pulse oximetry during apnea improved from 87.4 % to 90.9 % (p = 0.07).  The authors concluded that pediatric OSA refractory to adenotonsillectomy that is due to retroglossal and base-of-tongue collapse remains difficult to treat.  However, most patients in this analysis benefited from combined genioglossus advancement and radiofrequency ablation.  The findings of this small, retrospective study need to be validated by well-designed studies.  furthermore, these finding are confounded by the combinational use of the Repose system and radiofrequency ablation of the tongue base.  It should be noted that the European Respiratory Society's task force on non-CPAP therapies in sleep apneas (Randerath et al, 2011) stated that nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement can not be recommended as single interventions".

Tracheomalacia is a disorder of the large airways where the trachea is deformed or malformed during respiration.  It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnea to common respiratory symptoms such as chronic cough and wheeze.  Current practice following diagnosis of tracheomalacia include medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of CPAP and bilevel positive airway pressure (BiPAP) as well as surgical interventions aimed at improving the caliber of the airway.

In a prospective, randomized, controlled study, Essouri et al (2005) evaluated the efficacy of CPAP ventilation in infants with severe upper airway obstruction and compared CPAP to BiPAP ventilation.  A total of 10 infants (median age of 9.5 months, range of 3 to 18) with laryngomalacia (n = 5), tracheomalacia (n = 3), tracheal hypoplasia (n = 1), and Pierre Robin syndrome (n = 1) were included in this analysis.  Breathing pattern and respiratory effort were measured by esophageal and trans-diaphragmatic pressure monitoring during spontaneous breathing, with or without CPAP and BiPAP ventilation.  Median respiratory rate decreased from 45 breaths/min (range of 24 to 84) during spontaneous breathing to 29 (range of 18 to 60) during CPAP ventilation.  All indices of respiratory effort decreased significantly during CPAP ventilation compared to un-assisted spontaneous breathing (median, range): esophageal pressure swing from 28 to 10 cm H(2)O (13 to 76 to 7 to 28), esophageal pressure time product from 695 to 143 cm H(2)O/s per minute (264 to 1,417 to 98 to 469), diaphragmatic pressure time product from 845 to 195 cm H(2)O/s per minute (264 to 1,417 to 159 to 1,183).  During BiPAP ventilation a similar decrease in respiratory effort was observed but with patient-ventilator asynchrony in all patients.  The authors concluded that this short-term study showed that non-invasive CPAP and BiPAP ventilation are associated with a significant and comparable decrease in respiratory effort in infants with upper airway obstruction.  However, BiPAP ventilation was associated with patient-ventilator asynchrony.

An UpToDate review on "Tracheomalacia and tracheobronchomalacia in adults" (Ernst et al, 2012) states that "[c]ontinuous positive airway pressure (CPAP) can maintain an open airway and facilitate secretion drainage.  This is often initiated in the hospital during an acute illness.  The patient initially receives continuous CPAP and is gradually transitioned to intermittent CPAP as tolerated.  Patients may use intermittent CPAP as long-term therapy.  However, CPAP does not appear to have a long-term impact on dyspnea or cough.  Positive airway pressure other than CPAP (e.g., bilevel positive airway pressure) may be used instead if hypercapnic respiratory failure exists".

An eMedicine article on "Tracheomalacia Treatment & Management" (Schwartz) stated that "[s]upportive therapy is provided to most infants.  Most respond to conservative management, consisting of humidified air, chest physical therapy, slow and careful feedings, and control of infection and secretions with antibiotics.  The use of continuous positive airway pressure (CPAP) has been recommended in patients having respiratory distress and may be successful in patients requiring a short-term intervention as the disorder spontaneously resolves".  

The American Academy of Pediatrics’ practice guideline on “Diagnosis and management of childhood obstructive sleep apnea syndrome” (Marcus et al, 2012) focused 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.  The updated guideline did not mention the use of lingual tonsillectomy as a management tool for OSA in children and adolescents.

Kim and colleagues (2013) noted that OSA is a common health problem in children and increases the risk of cardiovascular disease (CVD).  Triggering receptor expressed on myeloid cells-1 (TREM-1) plays an important role in innate immunity and amplifies inflammatory responses.  Pentraxin-3 is predominantly released from macrophages and vascular endothelial cells, plays an important role in atherogenesis, and has emerged as a biomarker of CVD risk.  Thus, these researchers hypothesized that plasma TREM-1 and pentraxin-3 levels would be elevated in children with OSA.  A total of 106 children (mean age of: 8.3 ± 1.6 yrs) were included after they underwent over-night polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study.  Endothelial function was assessed with a modified hyperemic test after cuff-induced occlusion of the brachial artery.  Plasma TREM-1 and pentraxin-3 levels were assayed using commercial enzyme-linked immunosorbent assay kits.  Circulating microparticles (MPs) were assessed using flow cytometry after staining with cell-specific antibodies.  Children with OSA had significantly higher TREM-1 and pentraxin-3 levels (versus controls: p < 0.01, p < 0.05, respectively).  Plasma TREM-1 was significantly correlated with both BMI-z score and the obstructive AHI in uni-variate models.  Pentraxin-3 levels were inversely correlated with BMI-z score (r = -0.245, p < 0.01), and positively associated with endothelial MPs and platelet MPs (r = 0.230, p < 0.01 and r = 0.302, p < 0.01).  Both plasma TREM-1 and pentraxin-3 levels were independently associated with AHI in multi-variate models after controlling for age, sex, race, and BMI-z score (p < 0.001 for TREM-1 and p < 0.001 for pentraxin-3).  However, no significant associations emerged between TREM-1, pentraxin-3, and endothelial function.  The authors concluded that plasma TREM-1 and pentraxin-3 levels were elevated in pediatric OSA, and may play a role in modulating the degree of systemic inflammation.  Moreover, they stated that the short-term and long-term significance of elevated TREM-1 and pentraxin-3 in OSA-induced end-organ morbidity remains to be defined.

Gozal and associates (2013) tested the hypothesis that concentrations of adropin, a recently discovered peptide that displays important metabolic and cardiovascular functions, are lower in OSA, especially when associated with endothelial dysfunction.  Age-, sex-, and ethnicity-matched children (mean age of 7.2 ± 1.4 years) were included into 1 of 3 groups based on the presence of OSA in an over-night sleep study, and on the time to post-occlusive maximal re-perfusion (Tmax greater than 45 seconds) with a modified hyperemic test.  Plasma adropin concentrations were assayed using a commercial enzyme-linked immunosorbent assay kit.  Among controls, the mean morning adropin concentration was 7.4 ng/ml (95 % confidence interval [CI]: 5.2 to 16.3 ng/ml).  Children with OSA and abnormal endothelial function (EF) (OSA+/EF+ group) had significantly lower adropin concentrations (2.7 ± 1.1 ng/ml; n = 35) compared with matched controls (7.6 ± 1.4 ng/ml; n = 35; p < 0.001) and children with OSA and normal EF (OSA+/EF- group; 5.8 ± 1.5 ng/ml; n = 47; p < 0.001).  A plasma adropin concentration less than 4.2 ng/ml reliably predicted EF status, but individual adropin concentrations were not significantly correlated with age, BMI z-score, obstructive AHI, or nadir oxygen saturation.  Mean adropin concentration measured after adenotonsillectomy in a subset of children with OSA (n = 22) showed an increase in the OSA+/EF+ group (from 2.5 ± 1.4 to 6.4 ± 1.9 ng/ml; n = 14; p < 0.01), but essentially no change in the OSA+EF- group (from 5.7 ± 1.3 to 6.4 ± 1.1 ng/ml; n = 8; p > 0.05).  The authors concluded that plasma adropin concentrations were reduced in pediatric OSA when endothelial dysfunction is present, and returned to within normal values after adenotonsillectomy.  They stated that assessment of circulating adropin concentrations may provide a reliable indicator of vascular injury in the context of OSA in children.  These preliminary findings need to be validated by well-designed studies.

Posadzki and colleagues (2013) critically evaluated the effectiveness of osteopathic manipulative treatment (OMT) as a treatment of pediatric conditions.  A total of 11 databases were searched from their respective inceptions to November 2012.  Only randomized clinical trials (RCTs) were included, if they tested OMT against any type of control in pediatric patients.  Study quality was critically appraised by using the Cochrane criteria.  A total of 17 trials met the inclusion criteria; 5 RCTs were of high methodological quality.  Of those, 1 favored OMT, whereas 4 revealed no effect compared with various control interventions.  Replications by independent researchers were available for 2 conditions only, and both failed to confirm the findings of the previous studies.  Seven RCTs suggested that OMT leads to a significantly greater reduction in the symptoms of asthma, congenital nasolacrimal duct obstruction (post-treatment), daily weight gain and length of hospital stay, dysfunctional voiding, infantile colic, otitis media, or postural asymmetry compared with various control interventions.  Seven RCTs indicated that OMT had no effect on the symptoms of asthma, cerebral palsy, idiopathic scoliosis, obstructive apnea, otitis media, or temporo-mandibular disorders compared with various control interventions.  Three RCTs did not perform between-group comparisons.  The majority of the included RCTs did not report the incidence rates of adverse effects.  The authors concluded that the evidence of the effectiveness of OMT for pediatric conditions remains unproven due to the paucity and low methodological quality of the primary studies.

There is also a lack of evidence regarding the clinical effectiveness of chiropractic manipulation for the treatment of sleep apnea.

The evidence on the use of midline/partial glossectomy for the treatment of OSA is not RCT-based; the data are mostly from case-series studies.

The Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine's clinical guideline on "The evaluation, management and long-term care of obstructive sleep apnea in adults" (Epstein et al, 2009) stated that " Tracheostomy can eliminate OSA but does not appropriately treat central hypoventilation syndromes (Consensus).  Maxillary and mandibular advancement can improve PSG parameters comparable to CPAP in the majority of patients (Consensus).  Most other sleep apnea surgeries are rarely curative for OSA but may improve clinical outcomes (e.g., mortality, cardiovascular risk, motor vehicle accidents, function, quality of life, and symptoms) (Consensus).  Laser-assisted uvulopalatoplasty is not recommended for the treatment of obstructive sleep apnea (Guideline)".  This guideline does not mention the use of midline glossectomy.

The American Sleep Disorders Association's practice parameters on "The surgical modifications of the upper airway for obstructive sleep apnea in adults" (Aurora et al, 2010) did not mention midline/partial glossectomy as a therapeutic option.

The European Respiratory Society task force on non-CPAP therapies in sleep apnea (Randerath et al, 2011) noted that "Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement cannot be recommended as single interventions".

Furthermore, an UpToDate review on “Management of obstructive sleep apnea in children” (Paruthi, 2014) states that “Tongue reduction surgery has been proposed for the management of OSA related to macroglossia (e.g., Beckwith-Wiedemann syndrome, Down syndrome).  Additional studies are needed to determine the efficacy of this procedure in such patients, especially since a case series of 13 patients with Beckwith-Wiedemann syndrome found that adenotonsillectomy was more effective than tongue reduction in relieving upper airway obstruction”.

Kerschner et al (2002) noted that children with neurologic impairment often present with airway obstruction that may require intervention.  No single method of airway intervention is universally appropriate and effective in this patient population.  These researchers examined the effectiveness of using adenotonsillectomy and UPPP in resolving obstructive apnea (OA) in patients with neurologic impairment.  These investigators performed a retrospective chart review of 15 patients with neurologic impairment and OA treated with adenotonsillectomy and UPPP between 1986 and 1998 at Children's Hospital of Wisconsin (CHW).  All patients in the series had their primary area of obstruction in the posterior oropharynx involving the soft palate, pharyngeal walls and base of tongue.  Post-operative improvement following adenotonsillectomy and UPPP was examined.  Measures of improvement were based primarily on recorded lowest oxygen saturations, but clinical parameters, flexible upper airway endoscopy and PSG were used as well.  Patient improvement was documented in 87 % of patients treated with this modality.  For the group, the mean lowest recorded oxygen saturation demonstrated a statistically significant improvement from 65 % pre-operatively to 85 % post-operatively (p = 0.005).  In long-term follow-up of these patients, 77 % (10 of 13) of those showing initial improvement have done well and have required no further airway intervention.  However, 23 % of these patients demonstrated the need for further airway intervention during follow-up.  The authors concluded that adenotonsillectomy with UPPP is worthy of consideration in certain neurologically impaired patients with moderate-to-severe OA, limited primarily to the posterior pharyngeal area.  Moreover, they stated that initial improvement may not be permanent and close long-term follow-up of patients is imperative.

Randerath and colleagues (2011) stated that in view of the high prevalence and the relevant impairment of patients with OSAS, lots of methods are offered that promise definitive cures for or relevant improvement of OSAS.  These investigators summarized the effectiveness of alternative treatment options in OSAS.  An inter-disciplinary European Respiratory Society task force evaluated the scientific literature according to the standards of evidence-based medicine.  Evidence supports the use of mandibular advancement devices in mild-to-moderate OSAS.  Maxillo-mandibular osteotomy seems to be as efficient as CPAP in patients who refuse conservative treatment.  Distraction osteogenesis is usefully applied in congenital micrognathia or mid-face hypoplasia.  There is a trend towards improvement after weight reduction.  Positional therapy is clearly inferior to CPAP and long-term compliance is poor.  Drugs, nasal dilators and apnea-triggered muscle stimulation cannot be recommended as effective treatments of OSAS at the moment.  Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser mid-line glossectomy, tongue suspension and genioglossus advancement cannot be recommended as single interventions.  Uvulopalatopharyngoplasty, pillar implants and hyoid suspension should only be considered in selected patients and potential benefits should be weighed against the risk of long-term side-effects.  Multi-level surgery is only a salvage procedure for OSA patients.

The American Academy of Pediatrics’ clinical practice guideline on “Diagnosis and management of childhood obstructive sleep apnea syndrome” (Marcus et al, 2012) did not mention UPPP as a management tool.

Furthermore, an UpToDate review on “Management of obstructive sleep apnea in children” (Paruthi, 2015) states that “Uvulopalatopharyngoplasty (UPPP) is not widely used for the management of OSA in children because it is associated with significant complications, such as nasopharyngeal stenosis, palatal incompetence, and speech difficulties.  It has been successfully combined with adenotonsillectomy in children with neuromuscular disorders who are deemed to be at high risk for persistent upper airway obstruction after adenotonsillectomy alone”.

Hypoglossal Nerve Stimulation

Hypoglossal nerve stimulation technology (eg, Inspire UAS system) utilizes an implantable, programmable device that electrically stimulates the hypoglossal nerve which leads to the contraction of the genioglossus muscle. This purportedly prevents airway collapse and the development of upper airway obstruction during sleep.

Certal et al (2015) systematically reviewed the evidence regarding the safety and effectiveness of hypoglossal nerve stimulation (HNS) as an alternative therapy in the treatment of OSA. Scopus, PubMed, and Cochrane Library databases were searched (updated through September 5, 2014).  Studies were included that evaluated the effectiveness of HNS to treat OSA in adults with outcomes for AHI, oxygen desaturation index (ODI), and effect on daytime sleepiness (Epworth Sleepiness Scale [ESS]).  Tests for heterogeneity and subgroup analysis were performed.  A total of 6 prospective studies with 200 patients were included in this review.  At 12 months, the pooled fixed effects analysis demonstrated statistically significant reductions in AHI, ODI, and ESS mean difference of -17.51 (95 % CI: -20.69 to -14.34); -13.73 (95 % CI: -16.87 to -10.58), and -4.42 (95 % CI: -5.39 to -3.44), respectively.  Similar significant reductions were observed at 3 and 6 months.  Overall, the AHI was reduced between 50 % and 57 %, and the ODI was reduced between 48 % and 52 %.  Despite using different hypoglossal nerve stimulators in each subgroup analysis, no significant heterogeneity was found in any of the comparisons, suggesting equivalent effectiveness regardless of the system in use.  The authors concluded that the findings of this review showed that HNS therapy may be considered in selected patients with OSA who fail medical treatment.  They stated that further studies comparing HNS with conventional therapies are needed to definitively evaluate outcomes.

Diercks et al (2016) noted that OSA is more common in children with Down syndrome, affecting up to 60 % of patients, and may persist in up to 50 % of patients after adenotonsillectomy. These children with persistent moderate to severe OSA require CPAP, which is often poorly tolerated, or even tracheotomy for severe cases.  Hypoglossal nerve stimulation produces an electrical impulse to the anterior branches of the hypoglossal nerve, resulting in tongue protrusion in response to respiratory variation.  It supposedly allows for alleviation of tongue base collapse and improving airway obstruction.  These researchers described the first pediatric HNS; it was performed in an adolescent with Down syndrome and refractory severe OSA (AHI: 48.5 events/hour).  The patient would not tolerate CPAP and required a long-standing tracheotomy.  Hypoglossal nerve stimulation was well-tolerated and effective, resulting in significant improvement in the patient's OSA (overall AHI: 3.4 events/hour; AHI: 2.5 to 9.7 events/hour at optimal voltage settings depending on sleep stage and body position).  Five months after implantation, the patient's tracheotomy was successfully removed and he continues to do well with nightly therapy.  This was a single-case study; its findings need to be validated in well-designed studies.

Uvulopharyngopalatoplasty

An UpToDate review on “Adenotonsillectomy for obstructive sleep apnea in children” (Garetz, 2016) states that “Uvulopalatopharyngoplasty (UPPP) is not widely used for the management of OSA in children, but has been successfully combined with adenotonsillectomy in small studies of children with neuromuscular disorders who are thought to be at high risk for persistent upper airway obstruction after adenotonsillectomy alone, including children with Down syndrome or other developmental delays. Only one of these studies employed objective evaluation of improvement in OSA.  In this study, 15 children with neurologic impairments and OSA were treated with UPPP in conjunction with adenotonsillectomy.  There was a statistically significant improvement in mean oxygen saturation nadir from 65 to 85 % (p = 0.005).  In long-term follow-up, 77 % (10 of 13) of the patients did not require additional airway intervention.  Small sample size, absence of control groups, and paucity of validated outcome measures preclude analysis of the utility of this procedure in the broader pediatric population.  Potential complications include nasopharyngeal stenosis, palatal incompetence, and speech difficulties”.

Rapid Maxillary Expansion

Rapid maxillary expansion (RME) is an orthodontic treatment has been used to treat obstructive sleep apnea syndrome among children (Machado-Junior, et al., 2016). However only limited studies have evaluated this treatment for its efficacy in ameliorating obstructive sleep apnea syndrome symptoms. Therefore , there is no consensus about the benefits of using RME to treat obstrucive sleep apnea syndrome (OSAS) 

Marino and co-workers (2012) evaluated the effects of RME in a group of OSAS pre-school children.  Lateral cephalograms of 15 OSAS children (8 boys and 7 girls, age [mean (M) ± standard deviation (SD]): 5.94 ± 1.64 years) were analyzed at the start of treatment with RME (T0).  All subjects were re-evaluated after a mean period of 1.57 ± 0.58 years (T1).  At this time the sample was divided into 2 groups according to the change in the respiratory disturbance index (RDI)
  1. an improved group (I: 8 subjects) and
  2. a stationary/worsened group (SW: 7 subjects).  Differences between I and SW children with respect to values of cephalometric variables at T0 and to variations between T0 and T1 were evaluated using Mann-Whitney U test.  
  3. Differences between T0 and T1 values in the overall group of children and separately in I and SW groups were assessed using Wilcoxon test. 
At the start of treatment, the I group was characterized by more retrognathic jaws with lower values of SNA (maxillary prognatism; p = 0.055) and SNB (mandibular prognathism; p = 0.020) and higher age values (p = 0.093) when compared to SW group.  After treatment, the I group showed an increase in SNA and SNB angle significantly higher than SW group (p = 0.004 and p = 0.003, respectively).  On the contrary, I and SW groups did not differ as for variation in the skeletal divergency and in the total facial height.  The authors concluded that OSAS pre-school children with retrognathic jaws could benefit from RME treatment.  Moreover, they stated that further research may be needed to confirm the findings of the present study because of the small sample size (n = 15).

Ashok and  associates (2014) stated that RME is an orthopedic procedure routinely used to treat constricted maxillary arches and is also a potential  treatment in children presenting with sleep-disordered breathing (SDB).  These researchers evaluated the effects of RME on sleep characteristics in children.  Polysomnography was carried out in 15 children (9 boys and 6 girls) aged 8 to 13 years before expansion (T0), after expansion (T1) and after a period of 3 months after retention (T2).  Bonded rapid maxillary expander was cemented in all children.  Inter-molar distance was also measured at T0 and T2.  Non-parametric Friedman test was used for comparing the averages of sleep parameters at different time period (T0, T1, T2).  Wilcoxon signed ranks test was used for comparing the averages of inter-molar width (T0-T2); p < 0.05 were considered as significant.  All children showed an improvement in sleep parameters with an increase in sleep efficiency, decreased in arousal and desaturation index after expansion.  Total sleep time showed a statistically significant increase after expansion.  A statistically significant increase in inter-molar distance was obtained after expansion.  The authors concluded that RME is a potential additional treatment in children presenting with SDB; OSA may evolve during childhood before becoming clinically evident later in life.  The importance of these observations lies not only in the potential to treat the underlying craniofacial abnormalities, but more importantly raises the possibility that early detection and treatment of children at high risk of developing OSA may prevent the disorder.  Since maxillary constriction is a feature of chronic naso-respiratory obstruction, RME has the potential to play an important role in such a preventative strategy.  The quality of sleep of these children improved after RME, regardless of the severity of their respiratory obstruction.  The early detection and treatment of children at risk of developing OSA may prevent the sequelae of the disease.  These investigators stated that this study had several drawbacks, and thus it would be premature to make definitive conclusions about the benefit of RME on sleep characteristics in normal children, even though all patients showed an improvement in sleep parameters.  Moreover, all patients included in this sample had normal AHI.  Thus, decrease or increase in this AHI value could not be taken into consideration.  However, other than small sample size (n = 15), another drawback was the lack of the control group due to ethical reasons.

Camacho and colleagues (2017) performed a systematic review with meta-analysis for sleep study outcomes in children who have undergone RME as treatment for OSA; 3 authors reviewed the international literature through February 21, 2016.  A total of 17 studies reported outcomes for 314 children (7.6 ± 2.0 years old) with high-arched and/or narrow hard palates (transverse maxillary deficiency) and OSA.  Data were analyzed based on follow-up duration: less than or equal to 3 years (314 patients) and greater than 3 years (52 patients).  For less than or equal to 3-year follow-up, the pre- and post-RME AHI decreased from a mean ± standard deviation (M ± SD) of 8.9 ± 7.0/hr to 2.7 ± 3.3/hr (70 % reduction).  The cure rate (AHI less than 1/hr) for 90 patients for whom it could be calculated was 25.6 %.  Random effects modeling for AHI standardized mean difference (SMD) was -1.54 (large effect).  Lowest oxygen saturation (LSAT) improved from 87.0 ± 9.1 % to 96.0 ± 2.7 %.  Random effects modeling for LSAT SMD was 1.74 (large effect); AHI improved more in children with previous adenotonsillectomy or small tonsils (73 to 95 % reduction) than in children with large tonsils (61 % reduction).  For greater than 3-year follow-up (range of 6.5 to 12 years), the AHI was reduced from an M ± SD of 7.1 ± 5.7/hr to 1.5 ± 1.8/hr (79 % reduction).  The authors concluded that improvement in AHI and lowest oxygen saturation has consistently been observed in children undergoing RME, especially in the short term (less than 3-year follow-up).  Moreover, they stated that randomized trials and more studies reporting long-term data (greater than or equal to 3-year follow-up) would help determine the effect of growth and spontaneous resolution of OSA.

The American Academy of Pediatric Dentistry (AAPD) policy on “Obstructive sleep apnea” (AAPD, 2016) stated that “Although some studies have advocated the use of non-surgical interventions such as rapid maxillary/palatal expansion (RPE) or a modified monobloc appliance, these studies had small sample sizes”. Guidelines on pediatric obstructive sleep apnea from the American Academy of Pediatrics (Marcus, et al., 2012) state that rapid maxillary expansion may be effective in specially selected patients.

Furthermore, an UpToDate review on “Management of obstructive sleep apnea in children” (Paruthi, 2017) states that “Selected children with OSA may derive benefit from adjunctive therapies.  As examples, obese children with OSA may benefit from weight loss, and children with maxillary contraction may benefit from rapid maxillary expansion”. Garetz (2017) stated that RME can be used for children with OSA and narrow palate (crossbite) who have little adenotonsillar tissue, or for those with residual OSA after adenotonsillectomy.

In a review on “Oral interventions for obstructive sleep apnea”. Koretsi and colleagues (2018) stated that there is no evidence from high-quality research to support treatment with maxillary expansion (conventional or surgically assisted) in patients with OSA.

Glossectomy / Partial Glossectomy 

In a systematic review and meta-analysis, Murphy and colleagues (2015) examined the effect of glossectomy as part of multi-level sleep surgery on sleep-related outcomes in patients with OSA.  Two independent researchers conducted the review using PubMed-NCBI and Scopus literature databases.  Studies on glossectomy for OSA that reported pre- and post-operative AHI score with 10 or more patients were included.  A total of 18 articles with 522 patients treated with 3 glossectomy techniques (midline glossectomy, lingualplasty, and submucosal minimally invasive lingual excision) met inclusion criteria.  Pooled analyses (baseline versus post-surgery) showed a significant improvement in AHI (48.1 ± 22.01 to 19.05 ± 15.46, p < 0.0001), ESS (11.41 ± 4.38 to 5.66 ± 3.29, p < 0.0001), snoring visual analog scale (VAS; 9.08 ± 1.21 to 3.14 ± 2.41, p < 0.0001), and lowest O2 saturation (76.67 ± 10.58 to 84.09 ± 7.90, p < 0.0001).  Surgical success rate was 59.6 % (95 % CI: 53.0 % to 65.9 %) and surgical cure was achieved in 22.5 % (95 % CI: 11.26 % to 36.26 %) of cases.  Acute complications occurred in 16.4 % (79/481) of reported patients.  Glossectomy was used as a standalone therapy in 24 patients.  In this limited cohort, significant reductions in AHI (41.84 ± 32.05 to 25.02 ± 20.43, p = 0.0354) and ESS (12.35 ± 5.05 to 6.99 ± 3.84, p < 0.0001) were likewise observed.  The authors concluded that glossectomy significantly improved sleep outcomes as part of multi-level surgery in adult patients with OSA.  Moreover, they stated that there is currently insufficient evidence to analyze the role of glossectomy as a stand-alone procedure for the treatment of OSA, although the evidence suggested positive outcomes in select patients.

The authors stated that this study had some several drawbacks.  There is a lack of quality research involving glossectomy with the majority of available published data drawn from small case series without control arms.  This has made it difficult to determine the true effectiveness of glossectomy.  Similar procedures vary in surgical approach, the inclusion criteria for patient selection, and types of additional procedures, and definitions of and the amount of attention paid to complications in each series, while similar, were not standardized across studies.  Additionally, many of the isolated glossectomy patients analyzed received previous palate surgery.  This made it extremely difficult to truly compare treatments and complications.  It should also be noted that AHI, while the most popular and universally reported outcome metric used for sleep medicine, has its limitations.  Moreover, they stated that future directions for research include further evaluation of isolated glossectomy and direct comparisons of glossectomy to other tongue base surgeries in multi-level surgery.

Miller and associates (2017) examined the effect of TORS base of tongue (BOT) reduction on sleep-related outcomes in patients with OSA.  Data sources included PubMed, Scopus, Embase, CINAHL, Cochrane, and Ovid.  Literature search by 2 independent authors was conducted using the afore-mentioned databases.  Studies on TORS BOT reduction as part of OSA treatment in adult patients with pre- and post-operative AHI scores were included.  Studies on TORS as treatment for diseases other than OSA were excluded.  A total of 6 articles with 353 patients treated with TORS BOT reduction met inclusion criteria.  Pooled analyses (baseline versus post-surgery) showed significant improvement in the following: AHI (44.3 ± 22.4 to 17.8 ± 16.5, p < 0.01), ESS (12.9 ± 5.4 to 5.8 ± 3.7, p < 0.01), lowest oxygen saturation (79.0 ± 9.5 to 84.1 ± 6.5, p < 0.01), and snoring VAS (9.3 ± 0.8 to 2.4 ± 2.43, p < 0.01).  Surgical success rate, defined as a greater than 50 % reduction of AHI with a post-operative AHI less than 20, was 68.4 % (95 % CI: 63.0 % to 73.5 %).  Cure rate (post-operative AHI less than 5) was 23.8 % (95 % CI: 19.1 % to 29.2 %).  The authors concluded that TORS BOT reduction decreased AHI and symptoms of sleepiness in adult patients with OSA.  It is considered successful in a majority of cases; however, these researchers stated that further studies must be performed to optimize patient selection criteria to achieve higher rates of success.  The keywords of this study included trans-oral robotic surgery, base of tongue, glossectomy, lingual tonsillectomy, obstructive sleep apnea, and sleep surgery.

Cammaroto and co-workers (2017) noted that Coblation tongue surgery and TORS proved to be the most published therapeutic options for the treatment of patients affected by OSA.  These researchers carried out a systematic review of the literature and an analysis of the data.  The mean rates of failure were 34.4 % and 38.5 %, respectively in TORS and Coblation groups.  Complications occurred in 21.3 % of the patients treated with TORS and in 8.4 % of the patients treated with Coblation surgery.  The authors concluded that TORS appeared to give slightly better results, allowing a wider surgical view and a measurable, more consistent removal of lingual tissue.  However, the higher rate of minor complication and the significant costs of TORS must also be considered. 

Montevecchi and colleagues (2017) stated that pediatric OSAS is primarily caused by adeno-tonsillar hypertrophy.  However, tongue base hypertrophy is increasingly being recognized as a cause, even after adeno-tonsillectomy.  These investigators reported 3 cases of pediatric OSAS successfully treated by TORS BOT.  In all children, these investigators were able to achieve improved retro-lingual patency while avoiding significant procedure-related morbidity.  The authors concluded that tongue base reduction by TORS appeared to be a feasible solution for the base of tongue obstruction due to lingual tonsil hypertrophy in pediatric patients.

Vicini and associates (2017) reviewed TORS for the treatment of OSAHS.  The review presented the experience of the robotic center that developed the technique with regards to patient selection, surgical method, and post-operative care.  In addition, the review provided results of a systematic review and meta-analysis of the complications and clinical outcomes of TORS when applied in the management of OSAHS.  The rate of success, defined as 50 % reduction of pre-operative AHI and an overall AHI less than 20 events/hour, was achieved in up to 76.6 % of patients with a range between 53.8 % and 83.3 %.  The safety of this approach was reasonable as the main complication (bleeding) affected 4.2 % of patients (range of 4.2 % to 5.3 %).  However, transient dysphagia (7.2 %; range of 5 % to 14 %) did compromise the quality of life (QOL) and must be discussed with patients pre-operatively.  The authors concluded that TORS for the treatment of OSAHS appeared to be a promising and safe procedure for patients seeking an alternative to traditional therapy.  They stated that appropriate patient selection remains an important consideration for successful implementation of this novel surgical approach requiring further research.  The keywords of this study included midline glossectomy, obstructive sleep apnea, partial glossectomy, posterior glossectomy, sleep surgery, TORS, and transoral robotic surgery.

In a retrospective study, Folk and D'Agostino (2017) compared sleep-related outcomes in OSAHS patients following BOT resection via robotic surgery and endoscopic midline glossectomy.  A total of 114 robotic and 37 endoscopic midline glossectomy surgeries were performed between July 2010 and April 2015 as part of single or multi-level surgery.  Patients were excluded for indications other than sleep apnea or if complete sleep studies were not obtained.  Thus, 45 robotic and 16 endoscopic surgeries were included in the analysis.  In the robotic surgery group there were statistically significant improvements in AHI [(44.4 ± 22.6) events/hour - (14.0 ± 3.0) events/hour, p < 0.001], ESS (12.3 ± 4.6 to 4.5 ± 2.9, p < 0.001), and O2 nadir (82.0 % ± 6.1 % to 85.0 % ± 5.4 %, p < 0.001).  In the endoscopic group there were also improvements in AHI (48.7 ± 30.2 to 27.4 ± 31.9, p = 0.06), ESS (12.6 ± 5.5 to 8.3 ± 4.5, p = 0.08), and O2 nadir (80.2 % ± 8.6 % to 82.7 % ± 6.5 %, p = 0.4).  Surgical success rate was 75.6 % and 56.3 % in the robotic and endoscopic groups, respectively.  Greater volume of tissue removed was predictive of surgical success in the robotic cases (10.3 versus 8.6 ml, p = 0.02).  The authors concluded that both robotic surgery and endoscopic techniques for tongue base reduction improved objective measures of sleep apnea; greater success rates may be achieved with robotic surgery compared to traditional methods.  Moreover, they stated that these findings were limited by the retrospective nature of this study, and further clinical studies are needed despite these encouraging results.

In a retrospective study, Toh and colleagues (2014) examined the effectiveness of combined palatal surgery and transoral robotic surgical (TORS) tongue base reduction with partial epiglottidectomy in the treatment of OSA in an Asian context.  To the authors’ knowledge, this was the 1st report on TORS for OSA in Asian patients in the literature.  These investigators reported their preliminary experience with combined TORS tongue base reduction and partial epiglottidectomy with palatal surgery as a multi-level surgical treatment strategy for moderate-to-severe OSA in Asian patients for whom CPAP treatment had failed.  This was a study of prospectively collected data on 40 Asian patients who underwent primary TORS tongue base reduction with partial epiglottidectomy and palatal surgery for treatment of moderate-to-severe OSA at an academic tertiary surgical center.  A total of 20 patients with complete pre-operative and post-operative over-night PSG were evaluated for surgical success and cure, according to traditional surgical criteria, and for subjective outcome measures (snoring and satisfaction on VAS and ESS) as well as complications.  Traditional cure (AHI of less than 5/hour) was achieved in 7 of 20 patients (35 %), traditional success (AHI of less than 20 [greater than 50 % reduction in AHI]) was achieved in another 11 patients (55 %), and failure was observed in 2 patients (10 %).  Subjective improvement in snoring, satisfaction, and ESS score was observed.  Improvement in mean (SD) ESS score and snoring loudness on VAS were statistically significant, from 12.4 (2.87) to 6.4 (1.43) and 8.7 (0.8) to 3.5 (1.7), respectively (p < 0.001 for both).  None of the patients needed post-operative tracheostomy.  Recorded complications included tonsillar fossa bleeding, pain, temporary dysgeusia, numbness of the tongue, and temporary dysphagia.  The authors concluded that transoral robotic surgery for tongue base reduction and partial epiglottidectomy for moderate-to-severe OSA in Asian patients for whom positive airway pressure treatment had failed was associated with good efficacy and low complication rates.  This was a small study (n = 40) that examined combined palatal surgery and trans-oral robotic surgical tongue base reduction with partial epiglottidectomy.  These preliminary findings need to be validated by well-designed studies.

The authors stated that this study had several drawbacks.  These findings were limited to Asian patients and could not be extrapolated to other patient populations.  Because previously published data were on white patients, these researchers believed that it was important to publish their results.  They did not attempt to analyze predictive factor for success and cure because these researchers thought that they did not have enough subjects yet to make such analysis meaningful.  Because there was no statistical difference in the BMI of the patients before and after the surgery, these results were independent of weight loss frequently encountered after upper airway surgery in patients with OSA.  In patients with significant weight loss, this may confound results.

In a prospective, single-arm, observational cohort study, Turhan and Bostanci (2019) examined the feasibility, morbidity, and efficacy of TORS tongue-base resection (TBR) combined with tongue-base suspension (TBS) for OSA with tongue-base collapse.  The secondary objective included evaluation of factors influencing treatment success.  Patients were eligible if they had moderate-to-severe OSA (AHI of greater than 15) or positional OSA, had a tongue-base collapse and glossoptosis identified by drug-induced sleep endoscopy (DISE), and failed CPAP.  All patients underwent TORS-TBR combined with TBS.  Additionally, concomitant epiglottoplasty, uvulopalatopharyngoplasty, or expansion pharyngoplasty were performed based on DISE findings.  A total of 64 patients were enrolled in the trial.  The mean age was 45.9 years, BMI was 30.5 kg/m2 , and mean AHI was 41.7 events/hour.  The mean robotic surgical time, total volume of tongue-base tissue removed, and the length of hospital stay (LOS) were 21.4 mins, 15.16 ml, and 6.5 days, respectively.  Post-operatively, almost all PSG metrics improved significantly (AHI = 41.72 versus 18.82 events/hour, lowest oxygen saturation = 80.43 % versus 85.14 %, ESS = 10.49 versus 4.09).  The procedure provided an overall success rate of 75 %, with minor morbidity.  All patients experienced varying degrees of temporary lingual edema post-operatively; tracheotomy was not required for any patient.  Although no independent predictor of treatment success was determined, patients with more severe disease tended to exhibit lower response to the treatment.  The authors concluded that TORS-TBR combined with TBS was a feasible, safe, and efficient procedure for OSA with tongue-base collapse.  These findings were confounded by the combined use of TBR and TBS as well as the concomitant epiglottoplasty, uvulopalatopharyngoplasty, or expansion pharyngoplasty (based on DISE findings).  Level of evidence = IV. 

Measurement of DNA Methylation Levels for the Diagnosis and Prognosis of Obstructive Sleep Apnea

Chen and co-workers (2016) hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with OSA.  Illumina's (San Diego, CA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML).  DNA methylation levels were validated by pyro-sequencing.  A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with SDB.  Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension.  In the validation cohort, no significant difference in DNA methylation levels of 6 selected genes was found between the primary snoring subjects and OSA patients (primary outcome).  However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an ODI of greater than 30.  Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an ODI of greater than 30.  Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C-type natriuretic peptide protein were increased in the SDB patients with EDS.  Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS.  The authors concluded that IL1R2 hypo-methylation and AR hyper-methylation may constitute an important determinant of disease severity, whereas NPR2 hypo-methylation and SP140 hyper-methylation may provide a biomarker for vulnerability to EDS in OSA.

The authors stated that this study had several drawbacks.  First, the cause-and-effect relationship could not be determined in this cross-sectional clinical study design, because inherited DNA methylation patterns (epigenotype) may affect the development of disease, and environmental stimuli may cause disease progression through DNA methylation changes.  These preliminary in-vitro experiment with peripheral blood mononuclear cell samples from 6 healthy subjects showed that gene expression and DNA methylation levels of the 4 selected genes were not altered with 4 d of IHR treatment (7 h of alternative 0 % and 21 % O2 each day) compared to normoxic conditions, indicating that these CpG sites may be the initiators of different phenotypes in OSA but not responders to IHR.  However, the authors acknowledged that they could not exclude a role for IHR for 2 reasons: (a) the treatment period was very short (4 days) compared to months/years in patients with OSA; and (b) the paradigm for IHR did not mimic exactly cyclical intermittent hypoxia as occurred in humans.  Second, DNA methylation and protein expression changes were demonstrated independently in the patients with SDB with different phenotypes (secondary outcome), but not between patients with OSA and PS (primary outcome).  Further studies with sufficiently large sample sizes are needed for the internal and external validity and the reliability of the results.  However, % time of less than 90 % SaO2 has been demonstrated to be the strongest predictor of high-sensitivity C-reactive protein variability in patients with OSA, indicating that the AHI may not reflect the true characteristic of chronic intermittent hypoxia and inflammation.  Third, gene expression levels of the selected genes were not examined in the peripheral blood mononuclear cell samples of the discovery or validation cohorts because of inadequate RNA samples.  However, their protein expressions showed corresponding changes, indicating a potential functional role of these DML in regulating gene expressions.  Fourth, hypertension-related DMLs in the discovery cohort, such as IL1R2 and SP140, were shown to be associated with the ODI and EDS, respectively, in the validation cohort.  However, these results were not unexpected, because EDS in patients with OSA is a special phenotype, characterized by younger age, higher blood pressure, and more severe hypoxic load.  These researchers also acknowledged that the study design did not allow an understanding of whether these findings were unique to these outcomes solely in the setting of OSA or whether they represented general differences in those disease states.  Fifth, the identified changes in the peripheral blood mononuclear cells may be only partly responsible for the pathogenesis of OSA, and partly mirrored differences in other relevant tissues.  These investigators stated that further investigation is needed to clarify whether these changes could be translated to neurons, endothelium, or other end-organ tissues.  Finally, verification and validation of many enriched pathways identified in the discovery phase are ongoing.  Among them, the cyclic adenosine monophosphate (cAMP)-protein kinase A signaling-cAMP response element binding protein (CREB) pathway has been reported to play an important role in sleep-wake control, hippocampal neuronal plasticity, and memory processes.

Perikleous and colleagues (2018) noted that OSA is characterized by phenotypic variations, which can be partly attributed to specific gene polymorphisms.  Recent studies have focused on the role of epigenetic mechanisms in order to permit a more precise perception about clinical phenotyping and targeted therapies.  These researchers synthesized available evidence on the relation between DNA methylation patterns and the development of pediatric OSA, in light of the apparent limited literature in the field.  They performed an electronic search in PubMed, Embase, and Google Scholar databases, including all types of articles written in English until January 2017.  Literature was apparently scarce; only 2 studies on pediatric populations and 3 animal studies were identified  Forkhead Box P3 (FOXP3) DNA methylation levels were associated with inflammatory biomarkers and serum lipids.  Hyper-methylation of the core promoter region of endothelial nitric oxide synthase (eNOS) gene in OSA children were related with decreased eNOS expression.  Furthermore, increased expression of genes encoding pro-oxidant enzymes and decreased expression of genes encoding anti-oxidant enzymes suggested that disturbances in oxygen homeostasis throughout neonatal period pre-determined increased hypoxic sensing in adulthood.  The authors concluded that epigenetic modifications may be crucial in pediatric sleep disorders to enable in-depth understanding of genotype-phenotype interactions and lead to risk assessment.  They stated that epigenome-wide association studies are needed to validate certain epigenetic alterations as reliable, novel biomarkers for the molecular prognosis and diagnosis of OSA patients with high risk of end-organ morbidity.

Maxillary Protraction Appliances

In a systematic review and meta-analysis, Ming and colleagues (2018) examined the efficacy of maxillary protraction appliances (MPAs) on improving pharyngeal airway dimensions in growing class III patients with maxillary retrognathism.  These researchers carried out an electronic search in PubMed, Cochrane Library, Web of Science, and Embase until September 2, 2017.  The assessments of methodological quality of the selected articles were performed using the Newcastle-Ottawa Scale.  Review Manager 5.3 (provided by the Cochrane Collaboration) was used to synthesize the effects of MPAs on pharyngeal airway dimensions.  Following full-text articles evaluation for eligibility, a total of 6 studies (168 treated subjects and 140 untreated controls) were included in final quantitative synthesis and they were all high-quality.  Compared to untreated control groups, the treatment groups had increased significantly nasopharyngeal airway dimensions with the following measurements: PNS-AD1 (fixed: mean difference, 1.33 mm, 95 % CI: 0.48 mm to 2.19 mm, p = 0.002), PNS-AD2 (random: mean difference, 1.91 mm, 95 % CI: 0.02 mm to 3.81 mm, p = 0.05), aerial nasopharyngeal area (fixed: mean difference, 121.91 mm2, 95 % CI: 88.70 mm2 to 155.11 mm2, p < 0.00001) and total nasopharyngeal area (fixed: mean difference, 142.73 mm2, 95 % CI: 107.90 mm2 to 177.56 mm2, p < 0.00001).  Meanwhile, McNamara's upper pharynx dimension (fixed: mean difference, 0.96 mm, 95 % CI: 0.29 mm to 1.63 mm, p = 0.005), which was highly related to post-palatal airway dimension, was also improved significantly.  However, no statistically significant differences in adenoidal nasopharyngeal area (p > 0.05) and McNamara's lower pharynx dimension (p > 0.05) existed.  The authors concluded that MPAs could increase post-palatal and nasopharyngeal airway dimensions in growing skeletal class III subjects with maxillary retrusion.  Moreover ,they stated that it may be suggested that MPAs have the potential to reduce the risk of OSAS in children with maxillary retrusion by enlarging airway space.

Quo and colleagues (2019) stated that mid-face retrusion creates a size deficiency problem in the upper airway that has been improved in children using surgical mid-face advancement and orthopedic protraction of the maxilla.  The results of these treatments have been mostly promising at enlarging the pharyngeal airway.  Recently introduced bone-anchored maxillary protraction (BAMP) uses implant inserted devices in the jaws to pull the maxilla forward against a backward pressure to the lower jaw.  In a pilot study, these researchers examined the use of BAMP as a strategy to treat maxillary retrusion, malocclusion and children with OSA.  A total of 15 children, aged 9 to 16 years with maxillary retrusion creating a skeletal malocclusion were treated with BAMP and the results were compared against an untreated control group; 8 children in the treatment group also had sleep disordered breathing/OSA.  All subjects had lateral cephalograms before and after BAMP therapy.  The OSA cohort completed the pediatric sleep questionnaire (PSQ) and PSG prior to and at the end of BAMP.  The majority of the OSA children (n = 5) showed improvement in their AHI and OSA symptoms following BAMP.  Preliminary results of BAMP therapy showed improvement in respiratory and airway parameters in OSA children with a highly significant change in the forward position of the upper jaw and enlargement in the nasopharyngeal to oropharyngeal junction as compared to an age- and sex-matched untreated control group.  The outcomes were dependent on the age of treatment initiation and patient compliance.  The authors concluded that this preliminary work suggested that BAMP may be considered as an adjunctive therapeutic option in adolescents for improving mid-face retrusion and OSA, but more research is needed to examine this therapy.

In a systematic review and meta-analysis, Yanyan and colleagues (2019) examined the effect of mandibular advancement appliances (MAAs) for OSA in children.  To this end, several electronic databases (PubMed, Embase, Cochrane Library) were systematically searched until June 18, 2018.  Randomized and non-randomized clinical trials were included.  Articles of high-quality were included for the meta-analysis.  Data extraction and quality assessment were conducted by 2 independent reviewers.  A total of 4 RCTs and 3 non-RCTs were finally included in the review; of these, 2 RCTs of high-quality were included in the meta-analysis.  The MD in AHI change for mandibular advancement group compared with control group was -1.75 events/h (95 % CI: -2.07 to -1.44; p < 0.00001).  Sensitivity analysis including the quasi-randomized RCT and non-RCTs showed stable favorable results for MAAs.  The authors concluded that this meta-analysis showed supportive evidence for MAA treatment in pediatric OSA patients.  Subgroup analysis suggested that MAA can be effective for mild-to-severe patients before the end of the pubertal peak.  Long-term treatment (at least 6 months) may be more effective than short-term treatment.

Pre-Fabricated Myofunctional Appliances (e.g., Myobrace/MyOSA)

Levrini and colleagues (2018) examined the efficacy of the Myobrace/MyOSA myofunctional appliance for the treatment of mild-to-moderate OSA in children, by means of the AHI.  A total of 9 children with a diagnosis of mild-to-moderate OSA were included in the study.  Participants wore the Myobrace/MyOSA myofunctional appliance for a period of 90 days.  The initial AHI, determined by means of a sleep test, was used as baseline (To), and a second AHI, computed at the end of the experimental period, was used as final data (T1).  The differences between the AHIs at To and T1 were calculated (diff AHI) and used for statistical purposes.  The level of oxygen saturation (SaO2) was also recorded before and after treatment, and their differences calculated as diff SaO2.  Statistical analysis was performed with a paired t-test and statistical significance was established at 95 % level of confidence.  A statistical significant reduction in the AHI of the studied subjects was computed at the end of the experimental period (p = 0.0425).  Although there was an improvement in the SaO2, it did not reach a statistically significant difference.  The authors concluded that the findings of this study suggested that the Myobrace/MyOSA myofunctional appliance can be an alternative to treat mild-to-moderate OSA in children.  Moreover, they stated that further studies are needed to determine the stability of the results after treatment.

Surface Electromyography (EMG) for the Evaluation of Pediatric Obstructive Sleep Apnea (OSA)

Chuang and colleagues (2019) stated that recent studies have suggested potential utility of non-normalized respiratory muscle electromyography (EMG) as an index of neural respiratory drive (NRD).  Whether NRD measured using non-normalized surface EMG of the lateral chest wall overlying the diaphragm (sEMGcw) recorded during nocturnal clinical PSG can differentiate children with and without OSA is unknown.  These investigators examined if NRD measured by non-normalized sEMGcw could differentiates children with and without OSA.  Polysomnography data of children aged 0 to 18 years were divided into the 3 groups: primary snorers (PS); snoring children without OSA but with increased work of breathing (incWOB; subjective physician report of increased respiratory effort during sleep); and children with OSA [obstructive apnea-hypopnea index (OAHI) greater than 1/hour].  Excerpts of sEMGcw obtained during tidal unobstructed breathing from light, deep and REM sleep were exported for quantitative analysis.  Overnight PSG data from 45 PS [median age of 4.4 years (interquartile range [IQR] 3.0 to 7.7 years), OAHI 0/hour (0.0 to 0.2/hour )], 19 children with incWOB [aged 2.8 years (2.4 to 5.7 years), OAHI 0.1/hour (0.0 to 0.4/hour)] and 27 children with OSA [aged 3.6 years (2.6 to 6.2 years), OAHI 3.7/hour (2.3 to 6.9/hour)] were analyzed.  The sEMGcw was higher in those with OSA [8.47 μV (5.98 to 13.07 μV); p < 0.0001] and incWOB [8.97 μV (5.94 to 13.43 μV); p < 0.001] compared with PS [4.633 μV (2.98 to 6.76 μV)].  There was no significant difference in the sEMGcw between children with incWOB and OSA (p = 0.78).  Log sEMGcw remained greater in children with OSA and incWOB compared with PS after age, BMI centiles, sleep stages and sleep positions were included in the mixed linear models (p < 0.0001).  The correlation between sEMGcw and OAHI in children without OSA was small (rs  = 0.254, p = 0.04).  The sEMGcw was increased in children with OSA and incWOB compared with PS.  The authors concluded that non-normalized sEMGcw was increased in children with OSA and an additional group of snoring children without OSA but subjectively increased respiratory effort compared with primary snorers.  They stated that sEMGcw has potential clinical utility in evaluation of children with sleep-disordered breathing as an objective, non-invasive, non-volitional marker of NRD.  These preliminary findings need to be validated by well-designed studies.

Montelukast for the Treatment of Pediatric OSA

In a systematic review and meta-analysis, Liming and colleagues (2019) evaluated the literature on anti-inflammatory medications for treating pediatric OSA.  Data sources included PubMed/Medline and 4 additional databases.  Three authors independently and systematically searched through June 28, 2018, for studies that assessed anti-inflammatory therapy for treatment of pediatric OSA.  Data were compiled and analyzed using Review Manager 5.3 (Nordic Cochrane Centre).  After screening 135 studies, a total of 32 were selected for review with 6 meeting inclusion criteria.  A total of 668 patients aged 2 to 5 years met inclusion criteria for meta-analysis.  Of these, 5 studies (166 children) that evaluated montelukast alone as treatment for pediatric OSA found a 55 % improvement in the AHI (mean [SD] 6.2 [3.1] events/hour pre-treatment and 2.8 [2.7] events/hour post-treatment; MD of -2.7 events/hour; 95 % CI: -5.6 to 0.3) with improvement in LSAT from 89.5 (6.9) to 92.1 (3.6) (MD, 2.2; 95 % CI: 0.5 to 4.0).  Two studies (502 children) observing the effects of montelukast with intra-nasal corticosteroids on pediatric OSA found a 70 % improvement in AHI (4.7 [2.1] events/hour pre-treatment and 1.4 [1.0] events/hour post-treatment; MD of -4.2 events/hour; 95 % CI: -6.3 to -2.0), with an improvement in LSAT from 87.8 (3.1) to 92.6 (2.2) (MD, 4.8; 95 % CI: 4.5 to 5.1).  The authors concluded that treatment with montelukast and intra-nasal steroids or montelukast alone was potentially beneficial for short-term management of mild pediatric OSA.

Bluher and associates (2019) noted that research has shown improvement in AHI in children with mild OSA treated with anti-inflammatory medications.  Data on QOL outcomes in children receiving these medications is lacking.  These researchers evaluated QOL in children with mild OSA treated with montelukast and fluticasone.  Children aged 3 to 16 years with mild sleep apnea (AHI greater than 1 and less than or equal to 5) presenting to a pediatric otolaryngology clinic were recruited prospectively and treated with 4 months of montelukast and fluticasone.  Participants' caregivers completed the OSA-18, a validated QOL survey, at baseline and 4 months.  Children with ongoing obstruction at follow-up underwent adenotonsillectomy.  A total of 31 patients were included.  Mean (SD) age was 6.8 (3.9) years.  Most subjects (54.8 %) were black and 48 % were obese.  Mean (SD) AHI of the subjects was 2.8 (1.0).  The mean (SD) baseline OSA-18 score was 60.2 (18.5), indicating a moderate impact of sleep disturbance on QOL.  Following treatment, there was significant improvement (p < 0.005) in mean OSA-18 score; 4 children discontinued montelukast due to behavioral side effects; 7 children (22 %) underwent adenotonsillectomy after failing medical therapy.  Demographic factors such as obesity (odds ratio [OR] 0.63 (0.11, 3.49)) and AHI (OR 1.38 (0.59, 3.66)) failed to predict who would respond to anti-inflammatory medications.  The authors concluded that children with mild OSA treated with montelukast and fluticasone experienced significant improvements in QOL.  Moreover, these researchers stated that further research is needed to determine optimal duration of therapy.

An UpToDate review on “Management of obstructive sleep apnea in children” (Paruthi, 2019) states that “Leukotriene modifier therapy -- Montelukast (Singulair) appears to modestly reduce AHI and adenotonsillar size”.  However, montelukast is not mentioned in the “Summary and Recommendations” section of this review.  Furthermore, OSA is not a FDA-approved indication of montelukast.

Supraglottoplasty for Laryngomalacia

In a systematic review and meta-analysis, Camacho and colleagues (2016) examined if AHI and lowest oxygen saturation (LSAT) improve following isolated supraglottoplasty for laryngomalacia with OSA in children.  A total of 9 databases, including PubMed/Medline, were searched through September 30, 2015; 517 studies were screened; 57 were reviewed; and 13 met criteria.  A total of 138 patients were included (age range of 1 month to 12.6 years); 64 patients had sleep exclusive laryngomalacia, and in these patients: AHI decreased from a M ± SD of 14.0 ± 16.5 (95 % CI: 10.0 to 18.0) to 3.3 ± 4.0 (95 % CI: 2.4 to 4.4) events/hour (relative reduction: 76.4 % [95 % CI: 53.6 to 106.4]); LSAT improved from a M ± SD of 84.8 ± 8.4 % (95 % CI: 82.8 to 86.8) to 87.6 ± 4.4 % (95 % CI: 86.6 to 88.8); SMD demonstrated a small effect for LSAT and a large effect for AHI; and cure (AHI of less than 1 event/hour) was 10.5 % (19 patients with individual data); 74 patients had congenital laryngomalacia, and in these patients: AHI decreased from a M ± SD of 20.4 ± 23.9 (95 % CI: 12.8 to 28.0) to 4.0 ± 4.5 (95 % CI: 2.6 to 5.4) events/hour (relative reduction: 80.4 % [95 % CI: 46.6 to 107.4]); LSAT improved from a M ± SD of 74.5 ± 11.9 % (95 % CI: 70.9 to 78.1) to 88.4 ± 6.6 % (95 % CI: 86.4 to 90.4); SMD demonstrated a large effect for both AHI and LSAT; and cure was 26.5 % (38 patients with individual data).  The authors concluded that supraglottoplasty improved AHI and LSAT in children with OSA and either sleep exclusive laryngomalacia or congenital laryngomalacia; however, the majority of them were not cured.

Farhood and co-workers (2016) noted that surgical intervention is the main treatment alternative for patients with severe laryngomalacia.  Supraglottoplasty offers effective treatment results not only for laryngomalacia but also for concurrent OSA.  These researchers quantified the objective outcomes of supraglottoplasty for laryngomalacia with OSA via PSG data in the pediatric population.  They carried out a comprehensive literature search of the PubMed database on May 20, 2015, using the search terms supraglottoplasty, epiglottoplasty, aryepiglottoplasty, laryngomalacia, obstructive sleep apnea, Apnea-Hypopnea Index (AHI), children, and polysomnography.  There were no date restrictions.  The literature search identified English-language studies that used PSG to evaluate patients with laryngomalacia and OSA after supraglottoplasty; 2 reviewers screened titles and abstracts of the studies.  The full texts of the studies were examined to evaluate their relevance to the meta-analysis.  Numerical PSG data were extracted and compared among studies where appropriate.  A fixed- or random-effects model was used, when appropriate, to analyze the data and calculate effect sizes.  A total of 4 studies were included in various subsets of the meta-analysis.  After supraglottoplasty, the AHI improved by a mean of 12.5 points in 4 studies (95 % CI: -21.14 to -3.78; p = 0.005), oxygen saturation as measured by pulse oximetry nadir by 9.49 in 4 studies (95 % CI: 4.87 to 14.12; p < 0.001), and obstructive AHI by 21 points in 2 studies (95 % CI: -50.3 to -8.29; p = 0.16); 29 of 33 children (88 %) had residual disease.  Patients 7 months and older had significant improvement in the AHI (p = 0.03).  The authors concluded that supraglottoplasty was an effective treatment modality for patients with laryngomalacia and OSA with objectively measurable benefits; however, patients will frequently have residual disease.; additional PSG following treatment is advised to ensure adequate resolution of the disorder.

In a meta-analysis, Lee and associates (2016) reviewed changes in sleep parameters and the success rate of supraglottoplasty for treating OSA in children.  In particular, these investigators evaluated treatment modalities and factors affecting treatment outcomes in children with both laryngomalacia and OSA.  Two authors independently searched databases including PubMed, Medline, Embase, and the Cochrane Review database.  The keywords were "supraglottoplasty", "laryngomalacia", "OSA", "polysomnography", "child" and "humans".  Supraglottoplasty served as the primary treatment for OSA or secondary treatment for persistent disease after previous surgeries.  Subgroup analyses were conducted for children receiving supraglottoplasty as the primary or secondary treatment for OSA, and for children with and without co-morbidities.  A total of 11 studies with 121 patients were analyzed (mean age of 3.7 years; 64 % boys; mean sample size: of 11 patients).  After surgery, the MD between the pre- and post-operative measurements were a significant reduction of 8.9 events/hour in the AHI and an increase of 3.7 % in minimum oxygen saturation (MinSaO2; p < 0.05).  The overall success rate was 28 % according to a post-operative AHI of less than 1 and 72 % according to an AHI of less than 5.  Children receiving supraglottoplasty as the primary treatment had significantly younger ages (0.6 versus 6.4 years; p < 0.001) than those receiving supraglottoplasty as the secondary treatment, but the outcomes were similar (33 % versus 19 % for a post-operative AHI of less than 1; p = 0.27; 77 % versus 61 % for a post-operative AHI of less than 5, p = 0.233).  Moreover, children with co-morbidities, compared with those without, had a similar success rate according to a post-operative AHI of less than 1 (25 % versus 21 %, p = 0.805) and post-operative AHI of less than 5 (62 % versus 84 %, p = 0.166).  The authors concluded that supraglottoplasty was an effective surgery for AHI reduction and MinSaO2 increase in children with OSA and laryngomalacia.  However, complete resolution of OSA was not achieved in most cases, and factors affecting treatment outcomes in these children required future studies.

In a retrospective study, Sedaghat and colleagues (2017) reviewed the clinical manifestations and outcomes of supraglottoplasty in patients with moderate-to-severe laryngomalacia at Guillermo Grant Benavente Hospital between January 2015 and January 2017.  Patients with laryngomalacia who underwent CO2 laser supraglottoplasty at a tertiary referral center were included in this analysis.  A review of medical records of these patients was performed.  Epidemiological data along with symptoms, co-morbidities, morphological type of laryngomalacia, synchronous airway lesions, surgery outcomes and satisfaction of parents after the procedure were recorded.  Surgical success was defined as the resolution of the criteria of severity of laryngomalacia.  A total of 24 patients were operated, 1 was excluded due to prior tracheostomy; 23 patients were included, the median age at the time of surgery was 5.5 months.  All the patients had stridor, 87 % presented feeding difficulties, 34.8 % had cyanosis, and 21.7 % had failure to thrive; 6 cases had congenital anomalies and 4 cases had non-genetic co-morbidities; 15 patients (65.2 %) had synchronous airway lesions. 17.4 % had type I laryngomalacia and 82.6 % were type 2.  The post-operative average hospital stay was 1.3 days.  The average follow-up was 14 months and no complications were reported.  The overall success rate of surgery was 95 %.  The authors concluded that patients with laryngomalacia and any symptom of severity should undergo a full airway evaluation, to rule out synchronous airway lesions, and supraglottoplasty if needed, as it has been shown to be a safe and effective technique for the management of these patients.

Pu and associates (2018) stated that supraglottoplasty is the mainstay of surgical treatment for laryngomalacia.  A novel supraglottoplasty surgical technique is needed to achieve better efficacy.  These researchers introduced modified microscopic radiofrequency ablation supraglottoplasty (MMRAS) for the treatment of congenital laryngomalacia and examined the outcome and effectiveness of this novel approach.  A total of 17 children with severe laryngomalacia who underwent MMRAS were studied retrospectively.  Supraglottoplasty of type III laryngomalacia was different from classical method.  All the patients were kept intubated for 5 days after surgery to achieve a better epiglottal position and to avoid re-conglutination of aryepiglottic folds.  The patients' demographic information, symptoms, co-morbidities, type of laryngomalacia, synchronous airway lesions and final outcomes were examined.  The median age at the time of surgery was 3.36 months (3 months 10 days).  Operative indications included feeding difficulties, noisy breathing or respiratory distress (or both), and sleep-related symptoms.  The MMRAS success rate was 82.4 %.  Most patients were extubated successfully on post-operative day 5.  The major post-operative complication was pulmonary infection that occurred in 3 cases (17.6 %) and required anti-infective therapy.  No peri-operative deaths and no long-term complications occurred.  Failures were observed in 3 (17.6 %) of 17 cases, 2 patients presented with a neurological disease and required tracheostomy, 1 patient relapsed because of post-operative adhesions and later underwent revision supraglottoplasty.  The authors concluded that MMRAS was a safe and effective treatment for symptomatic laryngomalacia and has the potential to provide better breathing, feeding, and sleeping outcomes in children with severe laryngomalacia.  Post-operative intubation for 5 days may result in better therapeutic outcomes.

In a retrospective study, Ribeiro and co-workers (2018) evaluated the parents' perspective concerning the children's clinical picture before and after supraglottoplasty for the treatment of laryngomalacia.  A total of 110 children diagnosed with LM followed at the Pediatric Otorhinolaryngology out-patient clinics of S. João Hospital Center, between 2008 and 2016 were included in this study.  Children who underwent supraglottoplasty were reviewed in terms of demographics, symptoms, co-morbidities, treatment and follow-up.  Parents were interviewed and filled out a structured questionnaire designed to evaluate their perception of the child's clinical picture and their degree of comfort before and after surgery.  A total of 31 children (28.2 %) underwent supraglottoplasty at a median age of 6 months; 12 patients had 1 or more medical co-morbidities.  Stridor was present in all children on the pre-operative period and resolved in 92.3 % of the cases after supraglottoplasty; shortness of breath persisted in 3.8 % in contrast to the previous 57.7 %; and feeding difficulties remained in 15.4 % children against the 65.4 % before the procedure.  Failure in thriving was also a pre-operative complaint, that recovered as reported by parents in all children after supraglottoplasty.  No surgical complications were reported, and the median hospital stay was 2 days.  In a 0 to 10 points scale, the median level of the parents' comfort with their child's clinical picture before supraglottoplasty was 1 point that was significantly worse than the mean level of 10 points after surgery (p < 0.001).  The authors concluded that in severe cases, laryngomalacia can have a strong negative impact on family dynamics and functioning.  In selected cases, supraglottoplasty could be a safe and effective therapeutic option that was associated with a high degree of parental satisfaction.

In a prospective, cohort study, Vandjelovic and associates (2018) examined the impact of supraglottoplasty on the QOL of caregivers and infants with severe laryngomalacia and moderate laryngomalacia with feeding difficulties.  A total of 39 infants who underwent supraglottoplasty were examined.  The primary caregiver answered the 47-item short form of the Infant and Toddler Quality of Life Questionnaire-47 pre- and post-operatively; the subsection scores were compared.  A 1-way analysis of variance was performed to analyze the effect of age and sex.  A comparison was made between this cohort and a general population of healthy children.  The average age at surgery was 4.0 months, and 53 % of the patients were male.  There was significant post-operative improvement in overall health, physical ability, growth and development, bodily pain, temperament, emotional impact on the caregiver, impact on caregiver's time, and family cohesion scores (p < 0.05).  The same subscale scores remained significantly improved post-operatively after age and sex were controlled.  Pre-operative QOL scores were significantly worse than those of the general population in nearly all categories.  Post-operative physical ability (p = 0.009) and temperament (p = 0.011) QOL scores were higher than the those of the general population.  Scores for growth and development (p = 0.132), bodily pain (p = 0.481), and family cohesion (p = 0.717) were equivalent to those of the general population.  The authors concluded that QOL was significantly improved after supraglottoplasty for infants with severe laryngomalacia and moderate laryngomalacia with feeding difficulties.  After supraglottoplasty, QOL was similar to that of the general infant population in most categories.

Cortes and colleagues (2019) stated that laryngomalacia is the most common congenital laryngeal anomaly.  Because of supraglottic prolapse, laryngomalacia may be associated with OSA and sleep disturbances.  The effects of OSA and sleep disorders in children include failure to thrive, cognitive and behavioral disturbances, cardiovascular compromise, and an association with sudden infant death syndrome (SIDS).  These researchers evaluated the presence of OSA and sleep disturbances in children with severe laryngomalacia through complete NPSG, as well as to establish the effects of supraglottoplasty in each of the PSG parameters.  A total of 9 infants with severe laryngomalacia were included, all with a complete PSG study before and after supraglottoplasty.  The average age was 5.5 months.  All patients presented an AHI within the range of severe OSA.  After supraglottoplasty, a significant reduction in AHI was found, from 34.87 ± 20.34 to 9.44 ± 5.28 after surgery (p: 0.022).  Additionally, sleep efficiency had a significant increase, from 21.4 % to 56.29 % of total sleep time (p: 0.0013).  All patients presented a significant decrease in obstructive apnea episodes (p < 0.0001), as well as in hypopnea episodes (p: 0.0154).  The mean and minimum peripheral oxygen saturation (SpO2) had a significant increase following supraglottoplasty from 88.2 % to 94.09 % (p: 0.0002), and from 81.01 % to 89.33 % (p < 0.0001), respectively.  The authors concluded that PSG may provide better surgical sustenance in infants with severe laryngomalacia and OSA, as well as, serving as a monitoring tool of success.  However, the surgical decision should not be reduced to PSG results, and a good history and examination remain as the fundamental criteria.

Combined Surgical and Orthodontic Treatments

Templier and colleagues (2020) examined the evidence on the effectiveness of adenotonsillectomy (AT) and orthodontic treatment (i.e., mandibular advancement (MA) and rapid maxillary expansion (RME)) in the treatment of pediatric OSA.  These researchers carried out a literature search in several data-bases, including PubMed, Embase, Medline, Cochrane and LILACS up to April 5, 2020.  The initial search yielded 509 articles, with 10 articles being identified as eligible after screening.  AT and orthodontic treatment were more effective together than separately to cure OSA in pediatric patients.  There was a greater decrease in AHI and RDI, and a major increase in the lowest oxygen saturation and the ODI after undergoing both treatments.  However, re-appearance of OSA could occur several years after reporting adequate treatment.  In order to avoid recurrence, myofunctional therapy (MT) could be recommended as a follow-up.  The authors concluded that further studies with good clinical evidence are needed to confirm these findings.

The authors stated that this study had several drawbacks.  At the study level, the most important drawback was that most of the articles retrieved displayed limited-to-poor clinical evidence and this was the reason why it was not possible to conduct a meta-analysis.  One notable weakness that impacted the methodological quality/risk of retrieved articles was that, in most of studies, the number of subjects undergoing surgical and orthodontic treatment was too low.  Another drawback was that, in most studies, treatments were only applied in young children.  Before undergoing treatment, only 2 case reports had patients older than 10 years and the oldest participant was 12-year old.  Another important drawback was that various studies did not report the BMI of their population.  However, OSA syndrome is considered as one of the adverse consequences of childhood obesity.

Respiratory Muscle Therapy

In a systematic review and meta-analysis, Hsu and colleagues (2020) examined the effects of respiratory muscle therapy (i.e., breathing exercises, oropharyngeal exercises, and wind musical instruments) compared with control therapy or no treatment in improving AHI( primary outcome), sleepiness, and other polysomnographic outcomes for patients diagnosed with OSA.  Only RCTs with a placebo therapy or no treatment searched using PubMed, Embase, Cochrane, and Web of Science up to November 2018 were included, and assessment of risk of bias was completed using the Cochrane Handbook.  A total of 9 studies with 394 adults and children diagnosed with mild-to-severe OSA were included, all assessed at high risk of bias; 8 of the 9 studies measured AHI and showed a weighted average overall AHI improvement of 39.5 % versus baselines after respiratory muscle therapy.  Based on the meta-analyses in adult studies, respiratory muscle therapy yielded an improvement in AHI of -7.6 events/hour (95 % CI: -11.7 to -3.5; p ≤ 0.001), apnea index of -4.2 events/hour (95 % CI: -7.7 to -0.8; p ≤ .016), ESS of -2.5 of 24 (95 % CI: -5.1 to -0.1; p ≤ .066), Pittsburgh Sleep Quality Index of -1.3 of 21 (95 % CI: -2.4 to -0.2; p ≤ 0.026), snoring frequency (p = 0.044) in intervention groups compared with controls.  The authors concluded that this systematic review highlighted respiratory muscle therapy as an adjunct management for OSA; however, further studies are needed due to limitations including the nature and small number of studies, heterogeneity of the interventions, and high risk of bias with low quality of evidence.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

Diagnosis:

CPT codes covered if selection criteria are met:

95808 Polysomnography; any age, sleep staging with 1-3 additional parameters of sleep, attended by a technologist
95810     age 6 years or older, sleep staging with 4 or more additional parameters of sleep, attended by a technologist [nocturnal]
95811     age 6 years or older, sleep staging with 4 or more additional parameters of sleep, with initiation of continuous positive airway pressure therapy or bilevel ventilation, attended by a     technologist [nocturnal]
95782     younger than 6 years, sleep staging with 4 or more additional parameters of sleep, attended by a technologist
95783     younger than 6 years, sleep staging with 4 or more additional parameters of sleep, with initiation of continuous positive airway pressure therapy or bi-level ventilation, attended by     a technologist

CPT codes not covered for indications listed in the CPB:

Hypoglossal nerve stimulation:

76120 - 76125 Cineradiography/videoradiography, except where specifically included
95800 Sleep study, unattended, simultaneous recording; heart rate, oxygen saturation, respiratory analysis (eg, by airflow or peripheral arterial tone) and sleep time
95801     minimum of heart rate, oxygen saturation, and respiratory analysis (eg, by airflow or peripheral arterial tone)
95806 Sleep study, simultaneous recording of ventilation, respiratory effort, ECG or heart rate, and oxygen saturation, unattended by a technologist
95807 Sleep study, simultaneous recording of ventilation, respiratory effort, ECG or heart rate, and oxygen saturation, attended by a technologist
96002 Dynamic surface electromyography, during walking or other functional activities, 1-12 muscles
96004 Review and interpretation by physician or other qualified health care professional of comprehensive computer-based motion analysis, dynamic plantar pressure measurements, dynamic surface electromyography during walking or other functional activities, and dynamic fine wire electromyography, with written report
94762 Noninvasive ear or pulse oximetry for oxygen saturation; by continuous overnight monitoring (separate procedure)

Other CPT codes related to the CPB:

42700 - 42999 Surgery of pharynx, adenoids, and tonsils

HCPCS codes not covered for indications listed in the CPB:

E0445 Oximeter device for measuring blood oxygen levels non-invasively [nocturnal]
G0398 Home sleep study test (HST) with type II portable monitor, unattended; minimum of 7 channels: EEG, EOG, EMG, ECG/heart rate, airflow, respiratory effort and oxygen saturation
G0399 Home sleep test (HST) with type III portable monitor, unattended; minimum of 4 channels: 2 respiratory movement/airflow, 1 ECG/heart rate and 1 oxygen saturation
G0400 Home sleep test (HST) with type IV portable monitor, unattended; minimum of 3 channels

ICD-10 codes covered if selection criteria are met:

E64.3 Sequelae of rickets [chest wall deformities]
F11.182, F11.282, F11.982, F13.182, F13.282, F13.982 Drug induced sleep disorders [hypersomnia]
F51.11 Primary hypersomnia [Hypersomnia associated with depression (major) (minor)]
F51.19 Other hypersomnia not due to a substance or known physiological condition [Hypersomnia associated with acute or intermittent emotional reactions or conflicts]
F51.8 Other sleep disorders not due to a substance or known physiological condition
G25.81 Restless legs syndrome
G47.10 - G47.19 Hypersomnia
G47.33 Obstructive sleep apnea (adult) (pediatric) [OSAS]
G47.35 Congenital central alveolar hypoventilation syndrome
G47.36 Sleep related hypoventilation in conditions classified elsewhere
G47.41 - G47.429 Cataplexy and narcoplexy
G47.50 - G47.59 Parasomnia
G47.61 Periodic limb movement disorder
G70.00 - G70.9 Myasthenia gravis and other myoneural disorders
G71.00 - G71.09 Muscular dystrophy
M26.00 - M26.09 Major anomalies of jaw size [Craniofacial anomalies that obstruct the upper airway]
M26.10 - M26.19 Anomalies of jaw-cranial base relationship [Craniofacial anomalies that obstruct the upper airway]
M95.4 Acquired deformity of chest and rib
Q05.0 - Q05.9 Spina bifida
Q67.8 Other congenital deformities of chest [wall]
Q87.1 Congenital malformation syndromes predominantly associated with short stature. [Prader-Willi syndrome]
Q90.0 - Q90.9 Down syndrome
R06.83 Snoring [habitual, during sleep]

Treatment: tonsils & adenoids:

CPT codes covered if selection criteria are met:

42820 - 42821 Tonsillectomy and adenoidectomy
42825 - 42826 Tonsillectomy, primary or secondary
42830 - 42831 Adenoidectomy, primary
42835 - 42836 Adenoidectomy, secondary

ICD-10 codes covered if selection criteria are met:

J35.03 Chronic tonsillitis and adenoiditis
J35.3 Hypertrophy of tonsils with hypertrophy of adenoids

Treatment: CPAP:

CPT codes covered if selection criteria are met:

94660 Continuous positive airway pressure ventilation (CPAP), initiation and management

HCPCS codes covered if selection criteria are met:

A7027 Combination oral/nasal mask, used with continuous positive airway pressure device, each
A7028 Oral cushion for combination oral/nasal mask, replacement only, each
A7029 Nasal pillows for combination oral/nasal mask, replacement only, pair
A7030 Full face mask used with positive airway pressure device, each
A7031 Face mask interface, replacement for full face mask, each
A7032 Cushion for use on nasal mask interface, replacement only, each
A7033 Pillow for use on nasal cannula type interface, replacement only, pair
A7034 Nasal interface (mask or cannula type) used with positive airway pressure device, with or without head strap
A7035 Headgear used with positive airway pressure device
A7036 Chinstrap used with positive airway pressure device
A7037 Tubing used with positive airway pressure device
A7038 Filter, disposable, used with positive airway pressure device
A7039 Filter, non-disposable, used with positive airway pressure device
A7044 Oral interface used with positive airway pressure device, each
A7045 Exhalation port with or without swivel used with accessories for positive airway devices, replacement only
A7046 Water chamber for humidifier, used with positive airway pressure device, replacement, each
E0470 Respiratory assist device, bi-level pressure capability, without back-up rate feature, used with noninvasive interface, e.g., nasal or facial mask (intermittent assist device with continuous positive airway pressure device)
E0472 Respiratory assist device, bi-level pressure capability, with back-up rate feature, used with invasive interface, e.g., tracheostomy tube (intermittent assist device with continuous positive airway pressure device)
E0485 Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, prefabricated, includes fitting and adjustment [covered for children with craniofacial anomalies only]
E0486 Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, custom fabricated, includes fitting and adjustment [covered for children with craniofacial anomalies only]
E0561 Humidifier, non-heated, used with positive airway pressure device
E0562 Humidifier, heated, used with positive airway pressure device
E0601 Continuous positive airway pressure (CPAP) device

ICD-10 codes covered if selection criteria are met:

G47.33 Obstructive sleep apnea (adult) (pediatric) [OSAS]
J39.8 Other specified disease of upper respiratory tract [tracheomalacia]
P28.3 Primary sleep apnea of newborn

Treatment: Lingual tonsillectomy and/or tongue base reduction:

CPT codes covered if selection criteria are met:

42870 Excision or destruction lingual tonsil, any method (separate procedure)
41530 Submucosal ablation of the tongue base, radiofrequency, 1 or more sites, per session [not covered for somnoplasty]

ICD-10 codes covered if selection criteria are met:

G47.33 Obstructive sleep apnea (adult) (pediatric)

Other Treatments:

CPT codes covered if selection criteria are met:

Supraglottoplasty – no specific code:

42145 Palatopharyngoplasty (e.g., uvulopalatopharyngoplasty, uvulopharyngoplasty) [for transpalatal advancement pharyngoplasty] [covered for obstructive sleep apnea syndrome in children with neuromuscular disorders who are deemed to be at high risk for persistent upper airway obstruction after adenotonsillectomy alone]

CPT codes not covered for indications listed in the CPB:

Maxillary protraction – no specific code:

20692 - 20697 Multiplane external fixation system [mandibular distraction osteogenesis]
30000 - 30999 Surgery/Respiratory System, nose/nasal
30801 Cautery and/or ablation, mucosa of inferior turbinates, unilateral or bilateral, any method; superficial [for somnoplasty or coblation]
30802     intramural [for somnoplasty or coblation]
41512 Tongue base suspension, permanent suture technique [Repose System]
42140 Uvulectomy, excision of uvula
42160 Destruction of lesion, palate or uvula (thermal, cryo or chemical) [for laser assisted uvuloplasty]
42890 Limited pharyngectomy
42950 Pharyngoplasty (plastic or reconstructive operation on pharynx) [for CAPSO] [expansion sphincter pharyngoplasty]

HCPCS codes covered if selection criteria are met:

E0485 Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, prefabricated, includes fitting and adjustment [covered for children with craniofacial anomalies only]
E0486 Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, custom fabricated, includes fitting and adjustment [covered for children with craniofacial anomalies only]

HCPCS codes not covered for indications listed in the CPB:

Montelukast – no specific code:

C9727 Insertion of implants into the soft palate; minimum of three implants
G0237 Therapeutic procedures to increase strength or endurance of respiratory muscles, face-to-face, one-on-one, each 15 minutes (includes monitoring)
G0238 Therapeutic procedures to improve respiratory function, other than described by G0237, one-on-one, face-to-face, per 15 minutes (includes monitoring)
G0239 Therapeutic procedures to improve respiratory function or increase strength or endurance of respiratory muscles, two or more individuals (includes monitoring)
S2080 Laser-assisted uvulopalatoplasty (LAUP)

ICD-10 codes covered if selection criteria are met:

G12.0 - G12.9 Spinal muscular atrophy and related syndromes
G47.33 Obstructive sleep apnea (adult) (pediatric) [OSAS]
G70.00 - G70.9 Myasthenia gravis and other myoneural disorders
G71.00 - G71.9 Primary disorders of muscles

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