How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips Respironics

Obstructive Sleep Apnea Phenotypic Traits Anatomy. Pharyngeal dilator muscle control asleep. Arousal Threshold. Loop Gain/Control of breathing.

Hyoid Bone Mandible Maxilla Nasal Passage Trachea Epiglottis Tongue (Genioglossus) Soft Palate Choanae

Richard Schwab Clinics in Chest Medicine, 1998

Pcrit measurement 60s 10 2 Pmask Flow

Pcrit measurement Mask pressure (cm H 2 O) Flow Pcrit

Sforza and Kreiger Am J Respir Crit Care Med, 1999

Pharyngeal Anatomy in Obstructive Sleep Apnea Anatomy alone, at least as measured by P crit, explains little of the variability in apnea severity (as measured by RDI).

Obstructive Sleep Apnea Phenotypic Traits Anatomy. Pharyngeal dilator muscle control asleep. Arousal Threshold. Loop gain/ control of breathing.

Arousal and Obstructive Sleep Apnea What is required for the pharyngeal dilator muscles to open the upper airway during sleep? The muscles must be recruitable and effective. The individual must stay asleep long enough for the muscles to be recruited.

Berry et al – AJRCCM, 1997

Gleeson et al – 1990 Am Rev Respir Dis

Guilleminault et al – Chest, 1993

Arousal and Obstructive Sleep Apnea Combined individual variability in: Respiratory arousal threshold. Upper airway muscle responsiveness and effectiveness. May explain much of the variability in the severity of obstructive sleep apnea.

Obstructive Sleep Apnea Phenotypic Traits Anatomy. Pharyngeal dilator muscle control asleep. Arousal threshold. Loop gain/ Control of breathing.

Ventilatory Instability and Upper Airway Obstruction R UA Ventilatory Motor Output Nadir of motor output Obstruction

Baseline

Chemical Feedback Loop PCO 2 Circulatory Delay  V E (R)  PCO 2 PC02 Ve Ventilatory disturbance  V E (D) Plant Controller Ve

Loop Gain A measure of the susceptibility to periodic breathing. Ventilatory Response Ventilatory Disturbance Loop Gain =

Loop Gain = 0.5 Disturbance Response Ventilatory Response Ventilatory Disturbance Loop Gain = LG = 0.5

Loop Gain = 0.5 Disturbance Response Ventilatory Response Ventilatory Disturbance Loop Gain = LG = 0.5

Loop Gain = 0.5 Disturbance Response Ventilatory Response Ventilatory Disturbance Loop Gain = LG = 0.5

Loop Gain  1 Disturbance Response Ventilatory Response Ventilatory Disturbance Loop Gain = Disturbance Response LG = 0.5 LG = 1

Loop Gain  1 Disturbance Response Ventilatory Response Ventilatory Disturbance Loop Gain = Disturbance Response LG = 0.5 LG = 1

Proportional Assist Ventilator (PAV) delivers pressure in proportion to the patients effort. Thus we can increase the Ventilation Response for a given Ventilatory Disturbance. Loop Gain Measurement Ventilatory Response Ventilatory Disturbance Loop Gain =

Proportional Assist Ventilation PAV amplifies the underlying loop gain and can induce periodic breathing. LG = 0.5 LG = 0.2 PAV amplification

50% assist VTAF 1.65 VTAFs 60% assist VTAF 2.08

75% assist VTAF %

75% VTAF 2.44

80% 85% 60%

r = 0.36 p = 0.076

P crit measurement Mask pressure (cm H 2 O) Flow P crit

Baseline info NAgeBMI Low risk (Pcrit < -1)   3.2 Borderline risk (Pcrit -1 to +1)   2.5 High risk (Pcrit > +1)   4.0

r = p = 0.45

r = 0.88 p =

r = 0.19 p = 0.66

Loop Gain Can probably be determined fairly easily during NREM sleep. Will likely turn out to be an important cause of OSA is a subset (20-25%) of patients. As loop gain can be manipulated with drugs, oxygen etc, novel therapies may emerge for these patients if they can be identified.

Obstructive Sleep Apnea Phenotypic Traits Anatomy. Pharyngeal dilator muscle control asleep. Arousal Threshold. Loop Gain/Control of breathing.