Obstructive Sleep Apnea:

Transcription

1 Obstructive Sleep Apnea: A Physiological Approach Robert L. Owens, MD February 2018 Outline Cause(s) of OSA Can we measure the causes in an individual? Is that useful? 1

2 Thoracic pressure swings ( LV a erload) What happens when you fall asleep: normal Ventilatory Demand Wake Sleep Time 2

3 What happens when you fall asleep: normal or OSA Wake Sleep Ventilatory Demand Demand Because of poor anatomy Time What happens when you fall asleep: normal or OSA Ventilatory Demand Wake Sleep Hypoventilation leads to increased ventilatory demand, which will activate upper airway muscles to improve ventilation. But, muscle recruitment and improvement in ventilation is variable. Good muscle response achieves acceptable ventilation Time 3

4 What happens when you fall asleep: OSA Ventilatory Demand Wake Sleep Hypoventilation leads to increased ventilatory demand, which will activate upper airway muscles to improve ventilation. But, muscle recruitment and improvement in ventilation is variable. Poor muscle response does not achieve acceptable ventilation Time What happens when you fall asleep: OSA Wake Sleep Arousal Arousal Threshold Ventilatory Demand Poor muscle response does not achieve acceptable ventilation and the respiratory arousal threshold is crossed Time 4

5 What happens when you fall asleep: OSA Ventilatory Demand Wake Sleep Arousal Loop gain Arousal Threshold How quickly the ventilatory demand increases for a change in ventilation is the loop gain of the system Time What happens when you fall asleep: OSA Wake Sleep Arousal Arousal Threshold Ventilatory Demand This patient has OSA when they go to sleep they hypoventilate, and wake themselves up due to: Anatomy, upper airway muscles, arousal threshold, and loop gain Time 5

6 Better muscles can prevent OSA Wake Sleep Arousal Threshold Ventilatory Demand For same anatomy, better muscles can lead to stable flow limited breathing, no arousal Time arousal threshold may prevent OSA Wake Sleep Arousal Threshold Ventilatory Demand Similarly, with same anatomy and muscle response, a higher arousal threshold may allow respiratory drive to increase enough to recruit muscles sufficiently to sustain ventilation. Time 6

7 Decreased loop gain can help, too Wake Sleep Arousal Threshold Ventilatory Demand Similarly, a lower loop gain may prevent ventilatory demand from rising above the arousal threshold. Time Pathogenesis of sleep apnea High loop gain Poor upper airway muscle response Small, collapsible upper airway Low arousal threshold Obstructive Sleep Apnea 7

8 Outline Cause(s) of OSA It might be more than just a fat neck Can we measure the causes in an individual? Is that useful? Can we measure the response to hypoventilation during sleep? Ventilatory Demand Wake Sleep Time 8

9 Yes, by letting the airway collapse CPAP level (cmh 2 O) Therapeutic pressure CPAP level (cmh 2 O) Measuring anatomy CPAP level (cmh 2 O) Therapeutic pressure 8 (L/min) 6 Eupnea 4 2 Anatomy Time (seconds) With repeated drops, we can measure how much the upper airway is open at different pressures, or at atmospheric pressure (0cmH 2 O) 9

10 Measuring muscle response CPAP level (cmh 2 O) Therapeutic pressure (L/min) 8 6 Eupnea 4 2 Passive UA? UA muscle response Time (seconds) With hypoventilation, ventilatory demand will increase an unknown amount, and some muscle recruitment will occur Measuring loop gain CPAP level (cmh 2 O) (L/min) Eupnea 4 2 Passive UA UA muscle response Therapeutic pressure Obstruction removed, ventilation again matches ventilatory drive Time (seconds) Return to holding pressure opens upper airway and reveals ventilatory demand 10

11 Measuring loop gain CPAP level (cmh 2 O) Therapeutic pressure 8 Ventilatory Drive (L/min) 6 Eupnea 4 2 Passive UA UA gain = muscle response/ventilation deficit Time (seconds) With knowledge of the ventilatory drive, can calculate loop gain of the system, and upper airway gain Measuring loop gain CPAP level (cmh 2 O) Therapeutic pressure 8 Ventilatory Drive (L/min) 6 Eupnea 4 Loop gain = overshoot ventilation ventilation deficit 2 Passive UA UA gain = muscle response/ventilation deficit Time (seconds) With knowledge of the ventilatory drive, can calculate loop gain of the system, and upper airway gain 11

12 Measuring arousal threshold CPAP level (cmh 2 O) Therapeutic pressure 0 Ventilatory Drive? 8? (L/min) 6 Eupnea 4 X 2 Passive UA Time (seconds) Some CPAP drops, the ventilation will be so low, that the ventilatory drive gets so high that you have an arousal. Measuring arousal threshold CPAP level (cmh 2 O) Therapeutic pressure 0 Ventilatory Drive at arousal 8 (L/min) 6 Eupnea 4 X Loop gain = ventilatory drive ventilation deficit = arousal threshold 2 Passive UA Time (seconds) Use loop gain to predict ventilatory drive at this point = AT 12

13 Measuring the traits CPAP level (cmh 2 O) Therapeutic pressure 8 Ventilatory Drive (L/min) 6 Eupnea 4 Loop gain = overshoot ventilation ventilation deficit 2 Passive UA UA muscle response Time (seconds) Wellman JAP 2011 Automated methods to measure the traits! 13

14 Outline Cause(s) of OSA It might be more than just a fat neck Can we measure the causes in an individual? Yes Is that useful? N = 75 subjects

15 As expected, anatomy worse in those with OSA Worse Anatomy Better Anatomy AHI (OSA Severity) But no difference in muscle responsiveness Controls OSA 15

16 Or Loop Gain between controls and those with OSA And Arousal Threshold goes the wrong way?! Harder to wake up (Protective??) Controls OSA 16

17 Pathogenesis of sleep apnea High loop gain Poor pharyngeal muscle response Small, collapsible upper airway Low arousal threshold So is this true? Is it just having a fat neck? Obstructive Sleep Apnea A new model that includes Effect Modification Upper airway passive anatomy Exposure Open Closed Effect modifiers No OSA (High LG CSA?) (Low AT insomnia?) OSA Outcome 17

18 Non anatomical traits are important in some people Upper airway passive anatomy Exposure Open Vulnerable Anatomy Closed Loop gain Arousal threshold Upper airway gain Effect modifiers No OSA OSA Outcome Anatomy is important in everyone Worse Anatomy Always have OSA Vulnerable anatomy could go either way Better Anatomy Never have OSA AHI (Apnea Severity) 18

19 Loop gain is important if you have vulnerable anatomy LOW LG HIGH LG In this anatomically vulnerable group of patients, whether you have OSA is dependent on LG Muscle responsiveness is important if you have vulnerable anatomy Good muscles (no sleep apnea) Bad muscles (OSA) No difference in slope, until you get to vulnerable anatomy 19

20 Non anatomical traits are important in some people Upper airway passive anatomy Exposure Open Vulnerable Anatomy Closed Loop gain Arousal threshold Upper airway gain Effect modifiers No OSA OSA Outcome Will always have OSA Probably should have OSA, but many could be treated without CPAP? Probably should not have OSA 20

21 Outline Cause(s) of OSA It might be more than just a fat neck Can we measure the causes in an individual? Yes Is that useful? Potentially Physiology may help: Understand the cause of OSA in an individual (or group of people) Predict the improvement with non PAP anatomical therapy (e.g. surgery, oral appliance) Choose a primary treatment for OSA? Predict adherence to therapy? Predict symptoms related to OSA? 21

22 Why do different people have OSA? Why do different groups of people have OSA? 22

23 Can physiology predict those who respond to oral appliances and surgery? Can physiology predict those who respond to oral appliances and surgery? 23

24 Can physiology predict those who respond to oral appliances and surgery? Treatments to improve the non anatomical traits Arousal Threshold Sedative hypnotics (eszopiclone, trazodone)?behavioral therapy Loop Gain Oxygen Acetazolamide + non CPAP Anatomy Improvements Position Therapy Oral Appliance Upper airway muscles HGNS Drugs? 24

25 Targeting the problem Eckert Clin Sci 2011 Does low ArTH predict adherence? 25

26 Does low ArTH predict adherence? Ye ERJ

27 Endotype a subtype of a condition that has a distinct functional or pathobiological mechanism Phenotype observable consequences of a disease Genotype Endotype Phenotype Treatment Two copies of Delta 508 mutation CFTR dysfunction Cystic Fibrosis Many other mutations Supportive + Ivacaftor Supportive Associated with certain HLA Decreased insulin production genotypes Diabetes Mellitus Exogenous insulin Various genes implicated Insulin resistance Insulin-sensitizing drugs CPAP, but sedativehypnotics Low arousal threshold OSA disturbed sleep might be alternative? (unknown, area of active investigation) High Loop Gain OSA with cardiovascular disease CPAP, but Oxygen, acetazolamide might be alternatives Moderate AT, moderate LG OSA minimally symptomatic None needed Questions? rowens@ucsd.edu 27