1. Understanding and Recognizing Obstructive Sleep Apnea Barbara Phillips, MD, MSPH, FCCP August 9, 2008

2. Disclosures Consulting, speaking –Boehringer Ingelheim –Department of Transportation, FMCSA –GSK –Jefferson County Metro Government –TempurPedic –Ventus Leadership position –American College of Chest Physicians –National Sleep Foundation

3. Pre-Test Questions

5. Walter is a 42 year old male complaining of daytime fatigue and depression. What additional risk factors should you consider for a diagnosis of sleep apnea? 1. BMI only 2. Large neck circumference only 3. BMI and allergies 4. BMI and respiratory disease 5. BMI, Respiratory disease and large neck circumference

6. Fred, a 56 year old Asian man, has been diagnosed with diabetes and obstructive sleep apnea. All of the following co-morbidities are likely affected by Fred’s sleep apnea EXCEPT: 1. Hypertension 2. Asthma 3. Erectile Dysfunction 4. Insulin resistance 5. Heart Failure

7. Jesse is a 52 year old executive who presents with fatigue. His wife has been complaining of his snoring over the past two years. He has been a two-pack a day smoker for 28 years. He weighs 260# and is sedentary. What symptoms would you ask Jesse about to make an initial diagnosis of obstructive sleep apnea? 1.Mild cough and frequent headaches 2.Restlessness and depression 3.Sore throat and difficulty swallowing 4.Dry eyes and shortness of breath

8. You confirm that Jesse has met the conditions for a diagnosis of OSA. What test would most likely confirm this diagnosis? 1.The Epworth Sleepiness Scale (ESS) 2.Polysomnography 3.Nighttime Oximetry 4.None of the above

9. Jesse’s test confirms OSA. He says he is motivated to lose weight. What other treatment regimens do you prescribe? 1.A beer or other alcoholic beverage at bed time 2.CPAP 3.Prescription sleeping aids and CPAP 4.Smoking cessation and CPAP

10. Meet Mr S Nora A 55 year old man complains that his wife will no longer sleep with him because he is too noisy and it is disrupting her sleep. This has been going on for several years, but has worsened in the past 18 months as he has gained weight. Last year, he ran off the road while driving back from a sales meeting in the evening.

11. Mr S Nora Past Medical History –Hypertension –Glucose intolerance Medications –Metoprolol –HCTZ Examination: bp 146/94, BMI 33 Kg/m 2 Neck circumference=18.5 inches

13. The Epworth Sleepiness Scale How likely are you to doze off or fall asleep in the following situations, in contrast to just feeling tired? This refers to your usual way of life in recent times. Even if you have not done some of these things recently, try to work out how they would have affected you. Use the following scale to chose the most appropriate number for each situation: 0=would never doze 1=slight chance of dozing 2= moderate chance of dozing 3=high chance of dozing SituationChance of Dozing Sitting and reading_____ Watching TV_____ Sitting, inactive, in a public place_____ As a passenger in a car for an hour_____ Lying down in the afternoon_____ Sitting and talking to someone_____ Sitting quietly after a lunch without alcohol_____ In a car, while stopped for a few minutes in traffic_____

15. ?

16. Mr S Nora: What Do You Do Next? 1.Counsel him on weight reduction 2.Add an antihypertensive 3.Recommend separate bedrooms and earplugs 4.Order polysomnography (PSG)

17. Risk Factors for Obstructive Sleep Apnea Obesity (Kripke DF 1997; Tsai WH 2003) Male Gender (until about age 50) Postmenopausal state (Young T, 2003) Upper airway anatomic obstruction African-American, Asian, or Hispanic ethnicity (Kripke DF 1997; Young T 2003; Stepanski E 1999; Li KK 1999) Being a football player (George CF 2003) or truck driver (Howard, 2005)

18. Clinical Practice Recommendation Practice Recommendation: The risk for obstructive sleep apnea correlates on a continuum with obesity, large neck circumference, and hypertension. Combinations of these factors increase the risk for OSAHS in a non-linear manner. Evidence-Based Source: Institute for Clinical Systems Improvement Web Site of Supporting Evidence: http://www.icsi.org/sleep_apnea/sleep_apnea__diagnosis_and_treatment_o f_obstructive_.html Strength of Evidence: Class A: Randomized, controlled trial; Class B: Cohort study; Class C: Non- randomized trial with concurrent or historical controls, Case-control study, Study of sensitivity and specificity of a diagnostic test, Population-based descriptive study; Class D: Cross-sectional study, Case series, Case report; Class R: Consensus statement, Consensus report, Narrative review

19. Clinical Practice Recommendation Practice Recommendation: Polysomnography is the accepted standard test for the diagnosis of obstructive sleep apnea syndrome. The benefit of using attended polysomnography for diagnosis is the ability to establish a diagnosis and ascertain an effective CPAP treatment pressure. Evidence-Based Source: Institute for Clinical Systems Improvement Web Site of Supporting Evidence: http://www.icsi.org/sleep_apnea/sleep_apnea__diagnosis_and_treatment_of_obs tructive_.html Strength of Evidence: Class C: Non-randomized trial with concurrent or historical controls, Case-control study, Study of sensitivity and specificity of a diagnostic test, Population-based descriptive study; Class D: Cross-sectional study, Case series, Case report; Class M: Meta-analysis, Systematic review, Decision analysis, Cost-effectiveness analysis; Class R: Consensus statement, Consensus report, Narrative review

20. Weight Loss for OSA Modest (10%) weight loss results in significant improvement in AHI (Yee BJ, Int J Obes 2006) Bariatric Surgery results in 75-88% cure rate at 1 year, independent of approach. (Guardiano SA Chest 2003, Crooks, PF, Annu Rev Med 2006)

21. Change in Weight and BMI over 4 Yrs (Peppard PE, JAMA 2000, WSCS, n=690) -20% to < -10% (n = 22) -10% to < - 5% (n = 39) - 5% to < + 5% (n = 371) + 5% to < + 10% (n = 179) + 10% to + 20% (n = 79) Mean Change in AHI, Events/h Change in Body Weight

22. From JNC7…

24. Refractory HTN in OSA (Logan J Hypertension 2001) N = 41 BP > 140/90 on  3 antiHTN meds Excluded causes of secondary HTN, poor compliance Prevalence of 95% in men and 65% of women

25. Effect of CPAP on Blood Pressure in Hypertensive Patients (Becker HF, Circ, 2003)

26. Polysomnography Results AHI 42 events/hour Sa02 lowest 76%; 26 minutes with Sa02 below 85% Sleep Efficiency 64%, TST 4.8 hours No Stage 3 sleep, 5% REM sleep

27. CMS’s Definition of Obstructive Sleep Apnea (OSA) CPAP will be covered for adults with sleep- disordered breathing if: –AHI or RDI > 15 OR –AHI or RDI > 5 with (“mild, symptomatic”) Hypertension Stroke Sleepiness Ischemic heart disease Insomnia Mood disorders

28. Apnea + Hypopnea Index (AHI), AKA Respiratory Disturbance Index (RDI) And Oxygen Desaturation Index (ODI) AHI = Apneas + Hypopneas Total Sleep Time, in Hours RDI = AHI, more or less (may include RERA’s) ODI = Number of 4% desats/hr SDB = Sleep-Disordered Breathing (What you say when you are not sure what you are including. May include snoring, RERA’s, oxygen desaturation)

29. Sleep Heart Health Study: Apneas and Hypopneas  Decrease in airflow or chest wall movement to an amplitude smaller than approximately 25% ( apnea ) or 70% ( hypopnea ) of baseline  At least 10 seconds  Associated with oxyhemoglobin desaturation of 4% or greater as compared with baseline

30. L EOG R EOG O1 A2 C3 A2 Chin EMG ECG Leg EMG NC AF Th AF Chest Abd SaO 2 Apnea Arousal from sleep

31. L EOG R EOG O1 A2 C3 A2 Chin EMG ECG Leg EMG NC AF Th AF Chest Abd SaO 2

32. Severity Criteria Based on PSG From the American Academy of Sleep Medicine (Sleep, 1999) “Mild” sleep apnea is 5-15 events/hr “Moderate” sleep apnea is 15-30 events/hr “Severe” sleep apnea is over 30 events/hr (“Events” includes apneas, hypopneas, and RERA’s)

33. Which Patient Has “Mild” OSA? Patient 1Patient 2 AHI (events/hr)4010 Apnea duration (secs)10-2210-90 Lowest Sa02 (%)9071 % REM on study180 Arousals/hr 880 Cardiac arrhythmiasnonev tach

34. ?

35. Which of the Following is the Best Proven Risk of this Patient’s Apnea? 1.Car crash 2.Atrial fibrillation 3.Stroke 4.Death

37. Increased Risk of Crash with OSA (FMCSA, 2007)

38. Howard ME, AJRCCM 2004 N=3268

39. George, C F P Thorax 2001;56:508-512 Crashes and CPAP (n=210, with OSA, 210 controls)

40. BMI and OSA Predict Atrial Fibrillation (Gami AS, JACC 2007)

41. Association of nocturnal arrhythmias with sleep- disordered breathing. The Sleep Heart Health Study (Mehra et al, AJRCCM 2006) ( N= 228 with RDI > 30 c/w n=338 with RDI < 5) OR Adjusted for Age, Sex, BMI, CHD NSVT3.4 (1.03-11.2) CVE1.74 (1.11-2.74) Atrial Fibrillation4.02 (1.03-15.74)

42. Recurrence of Atrial Fibrillation Following Cardioversion Is Higher in Patients with Untreated Obstructive Sleep Apnea (Kanagala et al, Circ, 2003) *p<0.009 compared to controls **p<0.013 compared to treated OSA *,**

43. Stroke or Death (Yaggi HK NEJM 2005)

44. Hazard Ratios for Death by RDI Adjusted for BMI (Lavie P, Eur Respir J 2005)

45. Relative Mortality RDI > 50/hr (Lavie Eur Respir J 2005)

46. CPAP, OSA, and Death (Doherty LS, Chest 2005)

47. ?

48. Treating Mr S Nora Which of the following is the most effective treatment for Mr Nora’s condition? 1.Continuous Positive Airway Pressure (CPAP) 2.Uvulopalatopharyngoplasty 3.Use of an oral appliance 4.Behavioral change, including weight loss and reduced alcohol consumption

49. Clinical Practice Recommendation Practice Recommendation: Lifestyle modifications, particularly weight loss and reduced alcohol consumption can play a significant role in the reduction of severity of sleep apnea Evidence-Based Source: Institute for Clinical Systems Improvement Web Site of Supporting Evidence: http://www.icsi.org/sleep_apnea/sleep_apnea__diagnosis_and_treatment_ of_obstructive_.html Strength of Evidence: Class A: Randomized, controlled trial; Class B: Cohort study; Class C: Non-randomized trial with concurrent or historical controls, Case-control study, Study of sensitivity and specificity of a diagnostic test, Population- based descriptive study; Class D: Cross-sectional study, Case series, Case report; Class R: Consensus statement, Consensus report, Narrative review

50. Alcohol and OSA “Most but not all studies … have demonstrated harmful effects on nocturnal respiration, including increased number and duration of hypopnea and apnea events.” (Young T, AJRCCM 2002) Alcohol may not change CPAP pressure needed (Wessendorf TW, Sleep Med Rev 2002)

52. Cigarette Smoking and OSA Most data indicates relationship –OR 2.05 (Khoo SM, Respir Med 2004, n=2298) –OR 2.5 (Kashyap R, Sleep Breath 2001, n=108) –OR 4.4 (Wetter D, Arch Intern Med 1994, n=811) Some does not –No diff (Casasola, Sleep Breath 2002, n=38) Ex-smokers do NOT appear to have increased risk of OSA Parental smoking appears to be a risk for SDB in children (Kadatis AG, Pediatr Pulmonol 2004, n=3680)

53. Cigarette Smoking and Other Problems Reduced CPAP compliance (Russo-Magno P, J Am Geriatr Soc 2001, n=33) Greater oxygen desaturation (Casasola, Sleep Breath 2002, n=38)

54. Exercise for OSA? (Quan SF, Sleep Breath 2007) 4275 SHHS participants Logistic regression analysis > 3 hrs/week of self-reported vigorous exercise reduced risk of AHI > 15 (Adjusted OR, 0.68; 95%CI, 0.51-0.91 ) Similar but weaker associations for less vigorous exercise or different definitions of OSA

55. Oral Appliance Reviews Cochrane Database Review (Lim, 2004) –OA improved sleepiness and SDB compared to controls, but CPAP is the more effective of the two treatment modalities Ferguson KA, Sleep 2006 –52% chance of control of sleep apnea with OA –Successful treatment more likely in mild-to-moderate sleep apnea –Greater degrees of mandibular protrusion more successful. – High BMI predicts failure Hoekema, Crit Rev Oral Biol Med, 2004 –OA are more effective than controls for treating OSA, and possibly more effective than UPPP –OA are less effective than CPAP, but patients generally preferred OA therapy to CPAP –OA are a viable treatment for mild-moderate OSA

56. Do Oral Appliances Work? (Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001106) “CPAP is effective in reducing symptoms of sleepiness and improving quality of life measures in people with moderate and severe obstructive sleep apnea (OSA). It is more effective than oral appliances in reducing respiratory disturbances in these people but subjective outcomes are more equivocal. Certain people tend to prefer oral appliances to CPAP where both are effective. This could be because they offer a more convenient way of controlling OSA.”

57. Indications for Oral Appliances (Kushida C, Sleep 2006) –Primary snoring –Mild to moderate OSA patients who: Prefer OAs to CPAP Do not respond to CPAP Are not appropriate candidates for CPAP Fail treatment attempts with CPAP or behavioral changes –Patients with severe OSA should have an initial trial of nasal CPAP [before considering OAs] –Upper airway surgery may also supersede use of OAs in patients for whom these operations are predicted to be highly effective in treating sleep apnea

58. Types of Oral Appliances (OA) There > 50 different OAs commercially available; only about 30 have been approved by the FDA for OSA Two basic types: –Mandibular repositioners (MRD); reposition and maintain the mandible and tongue in a forward position –Tongue retainers (TRD); engage and hold only the tongue in a forward position without affecting the mandible or teeth (not FDA approved for OSA)

59. Consequences of Sleep Apnea Sleepiness Impaired quality of life Decreased cognitive function Increased hospitalizations and health care costs Increased car accidents Impaired glucose control Hypertension Increased cardiac risk Increased mortality rate Impotence

60. Effectiveness of Nasal CPAP Decreases sleepiness Improves quality of life Improves cognitive function Decreases hospitalizations and health care costs Decreases car accidents Improves glucose control Lowers blood pressure Reduces cardiac risk Reduces mortality rate Reverses impotence

61. Meet Ms S Nora Mr Nora’s 52 year-old wife presents with a complaint of sleep onset insomnia. This started at about the time of menopause, but has gotten worse; she blames her husband’s snoring She notes that she has gained weight recently, and wonders if her poor sleep is related

62. Ms S Nora Past Medical History –Hypothyroidism –Depression Medications –Thyroxin –Buproprion Examination: bp 128/74, BMI 28 Kg/m 2

63. ?

64. Ms S Nora: What Do You Do Next? 1.Change her antidepressant medication 2.Obtain more history 3.Treat her with a benzodiazepine 4.Reassure

65. The effects of gender and BMI change with aging AFTER THE AGE OF 50, GENDER BECOMES AN UNIMPORTANT VARIABLE AFTER THE AGE OF 60, BMI BECOMES AN UNIMPORTANT VARIABLE Tischler PV. JAMA. 2003

66. Menopause and Sleep Apnea (Young T, AJRRC, 2003, n=589)

67. Changes in Airway Age - MRI findings Soft palate gets longer Pharyngeal fat pads increase in size Shape of bony structures around pharyngeal airway change Response of genioglossus muscle to negative pressure stimulation diminishes Malhotra et al. Am J. Med, 2006. 119:72.e9-e14 Midsagittal magnetic resonance image illustrating anatomic structures of interest

69. Women with Sleep Apnea Are Different from Men Women with OSA are more likely to –present with insomnia –be depressed –have thyroid disease –report nightmares, palpitation, and hallucinations –have comorbid Restless Legs Syndrome They are less likely to have snoring and witnessed apneas Valipour A. Sleep 2007 Shepertycky and Kryger, Sleep 2005

70. Women Are Under-diagnosed Symptoms of insomnia, chronic fatigue or depression may not be recognized as attributable to OSA –delay in diagnosis and treatment Severe cases of OSA are more likely to be referred; UARS may not be diagnosed or treated Women are less likely to be accompanied to clinic by a bed partner, whose complementary sleep history is often important in identifying sleep symptoms

71. The Stereotype….

72. The Reality.

73. Ms S Nora: Polysomnography Results AHI 18 events/hour Sa02 lowest 86% Sleep Efficiency 54%, TST 4.1 hours No Stage 3 sleep, 15% REM sleep

74. Treatment of Sleep Apnea Behavioral Therapy –Avoid alcohol, nicotine and sleep medications –Lose weight if overweight Physical or Mechanical Treatment –CPAP (Continuous Positive Airway Pressure) –Oral appliance Surgery in very rare cases

77. Understanding and Recognizing Obstructive Sleep Apnea Sleep apnea is common, treatable, and associated with morbidity and mortality. The best-proven consequences of sleep apnea are hypertension and car crashes. Which kill. History and physical findings differ between men and women; PSG is the definitive test. CPAP treatment is safe, effective and inexpensive. Lifestyle changes can help. Oral appliances are safe, somewhat effective, and inexpensive.

78. Post-Test Questions

79. ?

80. Walter is a 42 year old male complaining of daytime fatigue and depression. What additional risk factors should you consider for a diagnosis of sleep apnea? 1. BMI only 2. Large neck circumference only 3. BMI and allergies 4. BMI and respiratory disease 5. BMI, Respiratory disease and large neck circumference

81. Fred, a 56 year old Asian man, has been diagnosed with diabetes and obstructive sleep apnea. All of the following co-morbidities are likely affected by Fred’s sleep apnea EXCEPT: 1. Hypertension 2. Asthma 3. Erectile Dysfunction 4. Insulin resistance 5. Heart Failure

82. Jesse is a 52 year old executive who presents with fatigue. His wife has been complaining of his snoring over the past two years. He has been a two-pack a day smoker for 28 years. He weighs 260# and is sedentary. What symptoms would you ask Jesse about to make an initial diagnosis of obstructive sleep apnea? 1.Mild cough and frequent headaches 2.Restlessness and depression 3.Sore throat and difficulty swallowing 4.Dry eyes and shortness of breath

83. You confirm that Jesse has met the conditions for a diagnosis of OSA. What test would most likely confirm this diagnosis? 1.The Epworth Sleepiness Scale (ESS) 2.Polysomnography 3.Nighttime Oximetry 4.None of the above

84. Jesse’s test confirms OSA. He says he is motivated to lose weight. What other treatment regimens do you prescribe? 1.A beer or other alcoholic beverage at bed time 2.CPAP 3.Prescription sleeping aids and CPAP 4.Smoking cessation and CPAP