1. Anuj Chandra MD, D-ABSM Medical Director- Advanced Center for Sleep Disorders Adjunct Assistant Professor- University of Tennessee College of Medicine Chattanooga, TN

2. Disclosures I have no financial relationships with commercial entities

3. When is snoring concerning ? Habitual snoring: > 3 times/week without OSA “Benign”  poor concentration, school performances History alone cannot differentiate habitual snoring from OSA When to treat snoring ?

4. Obstructive Sleep Apnea (OSA) (American Thoracic Society) Disorder of breathing during sleep characterized by prolonged partial upper airway (Uaw) obstruction and/or intermittent complete obstruction (obstructive apneas) that disrupts normal ventilation during sleep and normal sleep patterns Sleep fragmentation Intermittent hypoxemia Intermittent hypercarbia

5. OSA: Epidemiology Prevalence of snoring: 7-12% Prevalence of OSA Infants: 1 - 2% Children: 2 - 4% Adults: Women 2 - 4% Men 3 - 7% Lean Obese Snoring 8 – 10%50% OSA2 – 3%36% OSA 60% (metabolic syndrome) Gender Prepubertal: M=F Post pubertal: M>F Peak incidence - 1.5 – 5 years (coincides with ATH) - Adolescence

6. Risk factors for OSA Obesity Male African-American Prematurity Cigarette smoke exposure Adenotonsillar hypertrophy Sickle cell disease Down syndrome Prader Willi syndrome Cranio-facial disorders Neuromuscular disorders Cerebral palsy Asthma Allergic rhinitis

7. Pediatric OSA: Overview Anatomy Craniofacial size Soft tissues Fat distribution Ethnicity Neuromuscular Airway collapsibility Arousal threshold Ventilatory control Fluid shift Lung Volume Sleep Thoracic pressure changes Sleep Fragmentation Hypercarbia Intermittent Hypoxia Consequences Metabolic Cardiovascular Neurocognitive Autonomic Gene trait, susceptibility Environment, diet, exercise OSA Pathophysiology

8. Anatomical factors

9. Treacher Collins Hemi-hypoplasia Crouzon Apert Craniofacial Factors/Syndromes Ziteli and Davis. Atlas of Pediatric Physical Diagnosis. 1997

10. Abnormal Dental Alignment

11. Obesity & OSA: Partners in Crime ! Fatty infiltrates of UAw Decrease lung compliance Increased resistive load Affect upper airway patency Risk of OSA in obese: Odds ratio of 4.5 ~ 36% - 55% have OSA Post-T&A ~ 2/3 rd have residual OSA

12. OSA: Adverse Sequelae Intermittent Hypoxemia Hypercarbia Sleep fragmentation  Respiratory Effort Cardiovascular BP dysregulation Endothelial Dysfunction Metabolic Dyslipidemia Endocrine Insulin resistance Neuro-cognitive EDS, ADD, poor memory Poor concentration Nocturnal Enuresis OSA Individual genetic and environmental susceptible factors influences the ultimate expression of OSA sequelae….

13. OSA:Neuro-behavioral consequences Hyperactivity/Inattentive Chervin et al, 2002; 109:449- Poor school performance Gozal et al, Pediatrics 1998: 102: 616- Aggressive behavior Gottlieb et al, Pediatrics 2003; 112:870- Excessive daytime sleepiness uncommon with AHI <20/hr Gozal et al, Pediatrics 2001; 108: 693-  Cognitive deficits co-vary with endothelial dysfunction Gozal et al, Pediatrics 2010; 126; e1161-

14. Diagnosis of OSA Evaluate symptoms and morbidity History, questionnaires Assessment for severity of obstruction Polysomnogram (Sleep Study) Assessment for site of obstruction: Clinical examination Radiological evaluation UA endoscopy

15. Clinical features of OSAS Night time symptoms Daytime symptoms Snoring Apneas Mouth breathing Choking or snorting arousals Paradoxical breathing Restless sleep Hyper-extended neck Frequent awakening Recent onset parasomnias Excessive daytime sleepiness Morning headaches Mid-afternoon dip Hyperactivity Attention deficits Poor school performance Aggressive behaviors Chronic cough

16. Physical Examination Weight BMI Neck circumference Mouth Bite Tonsils Malampatti/Friedman Airway crowding Macroglossia Nose: Deviated septum Turbinates Polyp Adenoids Face Mid-face hypoplasia Retro/micrognathia Allergic shiners Respiratory Cardiac: S2 and murmur r

17. Staging of airways Friedman Classification Tonsils size

18. Polysomnography (Sleep Study) EEG - For sleep stages EMG – for chin tone and leg movements EOG – eye movements Nasal pressure Oro-nasal thermister Chest and abdominal belts/summary – respiratory effort Oximetry with waveform ETCO2 with waveform Snoring microphone EKG - heart rate and rhythm Body position Video Grigg-Damberger et al, JCSM 2007: 3: 201 Airflow Gas exchange

19. Indications for Sleep Studies IndicationsNot indicated Respiratory Sleep related breathing disorders OSA Central sleep apnea Sleep Hypoventilation Periodic breathing Sleep hypoxemia Non-Respiratory Periodic limb movement of sleep (PLMS) Narcolepsy Nocturnal events seizures vs. parasomnia REM behavior disorders Typical Parasomnias Insomnia Circadian rhythm sleep disorders Restless legs syndrome

21. Obstructive apnea

22. Severity of OSA Children Adults Mild OSA AHI 1 – 5/hour Moderate OSA 5-10/hour Severe OSA > 10/hour AHI > 5/hour with Symptoms AHI > 15/hour (without Sx) Mild: 5-15/hour Moderate: 15-30/hour Severe: > 30/hour

23. Classification of OSA severity on PSG Principles and Practice of Pediatric Sleep Medicine 2 nd Edn. 2014

24. Biomarkers of Pediatric OS A Helps with screening (urine, saliva, blood, exhaled breath) Early detection, cheap Bedside and can be done in clinic Follow up of response to medical or surgical intervention Potential biomarkers: Pediatrics: Combination of kallikrein-1, uromodulin, urocortin-3 and orosomucoid-1 appears to provide sufficient accuracy to be considered a potential OSA diagnostic test in children. Adults: IL- 6 and IL-10 appear to exhibit a favorable profile as biomarkers aiming to discriminate patients with and without OSA.

25. Treatment of OSA in children Life style changes Weight loss: Diet, exercise Positional Alcohol avoidance Pharmacological treatment Inhaled steroids Leukotriene antagonist High flow nasal cannula Oxygen Surgical treatment Adenoidectomy Tonsillectomy Supraglottoplasty Positive airway pressure therapy CPAP Bi-PAP

26. Pharmacological Treatment

27. Effect of Intranasal Budesonide on OSA Randomized double blind placebo controlled trial with the cross over design on children with mild OSA Kheirandish-Gozal et al, Pediatrics 2008 62 recruited, 48 completed Budesonide or Placebo 6 weeks on treatment 2 week washout 6 weeks other treatment

28. Anti-inflammatory therapy outcomes for mild OSA Retrospective analysis 2-14 years old 2007 – 2012 Mild OSA Combination ICS and oral montelukast x 12 weeks N = 3027, 836 fulfilled criteria, 752 received Rx Overall beneficial effect > 80% Normalization of PSG 62% (17% no change) Non responders: age > 7 years and obesity Kheirandish-Gozal Chest 2014

29. Adeno-tonsillectomy First line of therapy Recent data: 25-60% have residual OSA Discrepancy between tonsillar size & OSA severity No consensus AHI cut-off to perform T&A Adenoidectomy alone: 30% likely for 2 nd surgery within 3 yr 2 Complications: pain, bleeding and death 1. Guilleminault et al. J Pedriatr 1989 2. Brietzke, Katz and Roberson et al: Int J Ped Otorhinol 2006

30. Adenotonsillectomy Outcomes in Treatment of OSA in Children: A Multi-center Retrospective Study Rakesh Bhattacharjee, Leila Kheirandish-Gozal, Karen Spruyt, Ron B. Mitchell, Jungrak Promchiarak, Narong Simakajornboon, Athanasios G. Kaditis, Deborah Splaingard, Mark Splaingard, Lee J Brooks, Carole L Marcus, Sanghun Sin, Raanan Arens, Stijn L. Verhulst and David Gozal AJRCCM 2010 1< AHI < 5 (51%)  578 patents, 50% were obese  Mean age: 6.9 yrs  Risk of residual OSA Age (> 7 years) and high BMI

31. Washtenaw County Adenotonsillectomy Cohort Follow-up at 1 year: Sleep Variables Apnea Index Subjective Sleepiness MSLT OSA (n=40) 5.6 0.149% rare15.6 17.5 Snoring (n=38) 0.2 0.127% rare15.9 17.3 Surgical Controls (n=27) 0.1Rare17.4 17.3 Improvement over time. No Differences at Follow-up vs. Controls Giordani et al, J Int Neuropsych Soc 2012; 18: 212-

32. High Risk Groups for Residual OSA after T&A Older children: > 7 years Obese children Severe baseline OSA Syndromic patients: Down syndrome, Prader Willi, Craniofacial syndromes (Treacher Collins, Pierre Robin) Neuromuscular disorders: hypotonia, cerebral palsy Significant Allergies and Asthma Orthodontic disorders

33. 12 obese children BMI ~ 35 Age: 10 years Range of AHI: 2-36/hour High flow nasal cannula (20 L/min) room air 2 PSGs: on and off Nasal cannula High flow NC group: AHI reduction: 11+3 to 5+2 per hour) P<0.001 EEG arousal, RR, desaturation were also noted Pediatrics 2009

35. Positive airway pressure therapy First described use in OSA in 1981 Considered the "gold standard" of therapy Treatment, not cure Stents UAw open, preventing dynamic collapse Increases FRC, pulmonary reserve Indications Residual OSA Surgery contraindicated Hypoventilation

36. Pediatric CPAP mask Resmed Infant Bubble Mask Pixie nasal mask Mini Me 2 Respironics Petit Gel Full Face Mas k

37. Other upper airway surgeres NASAL CAVITY Septoplasty, Turbinate reduction NASOPHARYNX Revision adenoidectomy PALATE and OROPHARYNX Uvulopalatopharyngoplasty (UPPP)/ Expansion pharyngoplasty ORAL CAVITY Tongue reduction HYPOPHARYNX Lingual tonsillectomy, Tongue base reduction / Glossoptosis procedures LARYNX Supraglottoplasty, dilatation of subglottic stenosis

38. Rapid maxillary expanders: Increase in the width of the palate, nasal cavity, corrects deviated septum Age 5-13 years Mandibular repositioning devices

39. Role of Bariatric Surgery in Adolescence Failed clinical treatment with multidisciplinary and adequate therapy Body Mass Index: BMI > 40 kg/m 2 with comorbidities (DM2, HTN, dyslipidemia) BMI > 50 kg/m 2 without comorbidities Good comprehension and cognition to follow all necessary procedures before and after surgery Not pregnant in year before surgery Good family support.

40. Bariatric surgery Most centers: Age >16 years Roux-en-Y gastric bypass & adjustable gastric ban Sleeve gastrostomy Kalra et al 2005 34 obese adolescents 19 patients had AHI > 5/hour 10 had repeat sleep study After significant weight loss (mean, 58 kg), OSA severity markedly decreased in all patients Baseline median AHI vs. after weight loss = 9.1 vs. 0.65 per hr

41. 41 OSA is very common in children, but under recognized & under treated Carries many short & long term health risks, some of which are unique to children and may be irreversible Consider medical management for mild OSA Although A&T is effective, recent data shows increasing number of children with residual OSA despite surgery Consider referral to pediatric sleep specialist when indicated Take home messages

42. American Academy of Pediatrics: Guidelines for Pediatric OSA Screening of all children for snoring Specialty referral of complex high-risk patients Urgent evaluation of cardio-respiratory failure PSG as gold standard for diagnosis Adenotonsillectomy as first-line treatment Inpatient monitoring of high-risk patients Post-operative reevaluation to determine if additional treatment is required Pediatrics 2002;109:704

44. Childhood Parasomnias Undesirable events or experiences occurring: At entry into sleep Within sleep During arousal from sleep

45. Disorders of Arousal (from NREM sleep) Parasomnias Associated with REM Sleep Other Parasomnias Parasomnia Classification

46. Sleep Terrors Peak age: 5-7 years Prevalence rate of 2.0 - 6.5% Most will later sleepwalk Usual duration in children:- 4 years –50% end by age 8 –36% continue into adolescence

47. Sleep Terrors Begin abruptly from NREM sleep Episodes of agitation and apparent terror Heralded by a blood-curdling scream or cry Followed by confusion, agitation and autonomic disturbances Patient difficult to arouse If patient can be awakened, may describe: –Vague sense of terror –Isolated or fragmented dream imagery

48. Parasomnias Associated with REM Sleep Nightmares Sleep paralysis REM Sleep Behavior Disorder

49. Nightmares 75% of children experience nightmares 10 - 50% of children have nightmares severe enough to disturb their parents Proportion of children reporting nightmares reaches a peak around ages 6-10 years and decreases thereafter

50. Nightmares: Clinical Characteristics Usually during last half of night Complex dream mentation: - “Good dream gone bad” Emotional reaction more significant than autonomic response Fully alert upon awakening Responsive to comforting

51. Nightmares: Precipitating Factors Anxiety / Stress Personality – association with creativity Post-traumatic stress disorder

52. Nightmares: Treatment Explanation and reassurance Sleep hygiene Behavioral therapies

53. Nightmares vs Sleep Terrors REM sleep Most common parasomnia Second half of night Delayed return to sleep Easily comforted Detailed narrative description of episode Mild autonomic activity Alert upon awakening NREM sleep 2.0 - 6.5% prevalence First half of night Rapid return to sleep Resists comforting Fragmented recall / amnesia Intense autonomic activity Confusion on waking NightmaresSleep Terrors

54. Enuresis: Definition Persistent bedwetting more than twice a month past the age of five years Primary enuresis: Patient has never been dry on a regular basis Secondary enuresis: Patient becomes enuretic after being dry for at least six months

55. Enuresis: Declines with Age

56. Plasma Vasopressin (pg/ml) Enuresis: Theories

57. Enuresis: Other Theories Functionally small bladder capacity Dysfunctional detrusor activity Higher arousal threshold

58. Enuresis and Pediatric OSA Obstructive sleep apnea should be considered in the differential diagnosis of enuresis in children Frequent enuresis is more common in children with a higher apnea hypopnea index (AHI)

59. Enuresis: Evaluation History Developmental milestones Family history Physical / neurological exam Urinalysis Evaluation of urinary stream and bladder capacity

60. Enuresis: Behavioral Treatment Limit fluids / caffeine near bedtime Positive reinforcement Hypnosis and imagery Bladder stretching Sphincter training Scheduled wakings Urine alarms

61. Enuresis: Pharmacologic Rx DDAVP (Desmopressin) Effective in most patients Tablets and nasal spray Low frequency of side effects:- Concern for diabetes insipidus Hyponatremia Imipramine ECG abnormalities Possible behavior problems

63. Disorders of Arousal Arousals from NREM sleep First half of night, typically short duration Prolonged or multiple episodes may occur Confusion / automatic behavior Difficult to awaken during event Fragmented imagery Rapid return to sleep after event Amnesia of events

64. Disorders of Arousal Partial or complete arousal from sleep Abrupt Arousal

65. Confusional Arousals: Clinical Characteristics Occur on arousal from NREM sleep May not recognize parents May cry, yell, or moan Speech often unintelligible, sounds like words Most common words: “No, No!”

66. Sleepwalking: Clinical Characteristics Quiet wandering (injury unlikely) Agitated wandering (injury more likely) Behaviors of variable complexity Inappropriate behaviors Most sleepwalkers have few daytime effects

67. –60% of children have positive family history –10-fold increased prevalence in first-degree relatives of an affected individual Disorders of Arousal: Familial Basis

68. Disorders of Arousal: Evaluation Video-PSG needed if: –Spells have atypical features –Spells are stereotyped –Patients describe potentially injurious behavior or have injured themselves or others PSG needed if OSA is suspected

69. Disorders of Arousal: Treatment Allow episodes to run their course: Interfere only to prevent injury May try to lead the patient calmly to bed Emphasize sleep hygiene Secure the bedroom to prevent injury: Consider ground floor bedrooms Window and door locks, pad bedrails Remove sharp objects or toys on bedroom floor Alarms or barriers at door/stairs Medications may be necessary in severe cases

70. Pediatric RLS An urge to move legs, caused by discomfort as described in child’s own words Begins or worsens during periods of inactivity Partially or totally relieved by movement Worse in the evening or night Biological parent / sibling with definite RLS Periodic limb movements of five or more per hour of sleep on PSG

71. Pediatric RLS: Clinical Features Attention sought for “growing pains” These present as: Sleep onset problems Sleep maintenance problems Daytime irritability and attention problems may occur, likely due to sleep deprivation Family history is positive for RLS Iron deficiency may play a role as in adults

72. Pediatric RLS: Prevalence “Night-Walkers” Survey 138 adults with RLS (mean age 60 years) 18% reported symptoms began before age 10 years 25% reported symptoms began before age 20 years Childhood RLS case reports Walters AS. Neurology 1996;46:92

73. Pediatric RLS: Treatment Strict sleep hygiene is necessary to avoid sleep deprivation Limiting setting often required (day and at bedtime) Treatment of iron deficiency Medications: Clonazepam 0.25 to 1.0 mg qHS

75. Insomnia Complaint of: Difficulty initiating sleep (bedtime resistance) Maintaining sleep (inability to sleep independently) Daytime impairment: Inattention, mood disturbance Problems with memory and concentration Impaired performance (at school in children)

76. Behavioral Insomnia of Childhood Symptoms meet criteria of insomnia Pattern consistent with either: Sleep-onset association type Limit-setting type

77. Behavioral Insomnia of Childhood Evaluation History Precise description of the problem Parent response and interaction with child Typical night, not extremes Careful description of bedtime routines, including naps Evaluate the 24-hour schedule (weekday, weekend, vacation)

78. Behavioral Insomnia of Childhood: Sleep-onset Association Type Child begins to associate sleep onset with circumstances that are problematic and demanding of the caregiver. Child is unable to fall asleep without these associations either at initial sleep onset or during nocturnal awakenings.

79. Treatments for Sleep-onset Association Type Education Awakenings during the night are normal Sleep onset associations are learned Sleep onset associations are present at all ages New sleep onset associations can be taught Behavioral treatment Place child in crib/bed awake and leave room If child is upset, return to comfort Do not pick up the child; comfort verbally Stay in room briefly, leave before child sleeps Increase time between responses Same routine for awakenings and naps

80. Treatments for Sleep-onset Association Type Usual response between three to five nights If symptoms persist, consider: –Instructions not followed –Co-existing problems –Error in diagnosis –More time needed –Modifying the technique Modified techniques: –Eliminate associations in stages –Parents present longer –Limit physical contact –Gradually withdraw

81. Behavioral Insomnia of Childhood: Limit-setting Type Refusal to go to bed at an appropriate time or following a nighttime awakening Insufficient or inappropriate limit setting demonstrated by the caregiver

82. “Mommy …” I’m hot. I’m cold. I’m scared. I’m not sleepy. I’m thirsty. My tummy hurts. I hear something. I have to go to the bathroom. Fix my blanket. I need to be tucked in again. “Daddy, I need…” A drink. One more kiss. One more hug. The light on. The light off. To tell you something A band-aid. My mommy. You to cover me up. You to rub my back. A tissue. Some medicine Behavioral Insomnia of Childhood Limit-setting Type: Favorite Delay Tactics

83. Bedtime refusals, stalling and repeated demands May also occur at naptime and nighttime awakenings May be straightforward or complex Behavioral Insomnia of Childhood: Limit-setting Type

84. Emphasize the importance of limit-setting Teach general limit-setting guidelines (day as well as night) Specific and individualized techniques (gate, progressive door closure) Positive reinforcement (star chart) Treatment of Limit-setting Type

85. 85 Thank you