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![Page 1: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/1.jpg)
How can Obstructive Sleep Apnea be Evaluated Beyond
Anatomy?
David P. White, MD
Professor of Medicine
Harvard Medical School
Chief Medical Officer:
Philips Respironics
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Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop Gain/Control of breathing.
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Hyoid Bone
Mandible
Maxilla
Nasal Passage
Trachea
Epiglottis
Tongue(Genioglossus)
Soft Palate
Choanae
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Richard SchwabClinics in Chest Medicine, 1998
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Pcrit measurement
60s
10
2
Pmask
+0.5
-0.5
Flow
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Pcrit measurement
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 1 2 3 4 5 6 7 8
Mask pressure (cm H2O)
Flo
w
Pcrit
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Sforza and KreigerAm J Respir Crit Care Med, 1999
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Pharyngeal Anatomy in Obstructive Sleep Apnea
Anatomy alone, at least as measured by Pcrit, explains little of the variability
in apnea severity (as measured by RDI).
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Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop gain/ control of breathing.
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Arousal andObstructive 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.
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Berry et al – AJRCCM, 1997
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Gleeson et al – 1990Am Rev Respir Dis
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Guilleminault et al – Chest, 1993
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Arousal andObstructive 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.
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Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal threshold.• Loop gain/ Control of breathing.
![Page 18: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/18.jpg)
Ventilatory Instability
and
Upper Airway Obstruction
RUA
Ventilatory Motor Output
Nadir of motor output
Obstruction
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Baseline
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Chemical Feedback Loop
PCO2 Circulatory Delay
VE (R)
PCO2
PC02
Ve
Ventilatory disturbance
VE (D)
Plant
Controller
Ve
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Loop Gain
• A measure of the susceptibility to periodic breathing.
Ventilatory Response
Ventilatory DisturbanceLoop Gain =
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Loop Gain = 0.5
Disturbance Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
LG = 0.5
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Loop Gain = 0.5
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
LG = 0.5
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Loop Gain = 0.5
Disturbance
Response
Ventilatory Response
Ventilatory DisturbanceLoop Gain =
LG = 0.5
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Loop Gain 1
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
Disturbance
Response
LG = 0.5
LG = 1
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Loop Gain 1
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
Disturbance
Response
LG = 0.5
LG = 1
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• 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 DisturbanceLoop Gain =
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Proportional Assist Ventilation
PAV amplifies the underlying loop gain and can induce periodic breathing.
LG = 0.5
LG = 0.2
PAV amplification
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0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
0 50 100 150 200 250 300 350 400 450 500s
50% assist
VTAF 1.65
VTAFs
60% assist
VTAF 2.08
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1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
900 950 1000 1050 1100 1150 1200 1250 1300 1350s
75% assist
VTAF 2.44
80%
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1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800s
80%75%
VTAF 2.44
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1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
1800 1825 1850 1875 1900 1925 1950 1975 2000 2025 2050 2075 2100 2125 2150 2175 2200 2225 2250s
80%85%
60%
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Loop gain vs. AHI
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur) r = 0.36
p = 0.076
![Page 34: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/34.jpg)
Pcrit measurement
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 1 2 3 4 5 6 7 8
Mask pressure (cm H2O)
Flo
w
Pcrit
![Page 35: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/35.jpg)
Baseline info
N Age BMI
Low risk
(Pcrit < -1) 7 47.4 2.7 34.3 3.2
Borderline risk
(Pcrit -1 to +1) 9 44.9 3.2 31.9 2.5
High risk
(Pcrit > +1) 7 42.7 3.8 34.2 4.0
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Negative Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur)
r = -0.31p = 0.45
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Atmospheric Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur)
r = 0.88p = 0.0016
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Positive Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur) r = 0.19
p = 0.66
![Page 39: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/39.jpg)
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.
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Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop Gain/Control of breathing.
![Page 41: How can Obstructive Sleep Apnea be Evaluated Beyond Anatomy? David P. White, MD Professor of Medicine Harvard Medical School Chief Medical Officer: Philips.](https://reader036.fdocuments.us/reader036/viewer/2022062423/56649ec65503460f94bd18a2/html5/thumbnails/41.jpg)