UGent
Obstructive Sleep Apnea
(adult)
International Sleep Medicine Course
Cardiff June 7th, 2016
Dirk Pevernagie, MD, PhD
Sleep Medicine Centre Kempenhaeghe, Heeze, The Netherlands
Dpt. Internal Medicine, Faculty of Medicine and Health Sciences, Ghent
University, Belgium
Outline
• Pathophysiology of OSA: (1) recurrent
obstruction of the upper airway (UA)
• Pathophysiology of OSA: (2) causes of
UA obstruction: anatomic and nonanatomic factors
• Systemic effects of OSA
• Severity and operational definition
• Summary
OSA: recurrent obstruction of the UA
Concept of OSA
• Functional disturbance caused by passive
narrowing of the pharynx (UA) during sleep
• Cyclic breathing pattern with alternating
reductions in ventilation (sleep) and
restoration of breathing (arousal);
• Duration of events > 10 sec;
• Complete collapse = apnoea
Partial obstruction = hypopnoea
• Apnoea-Hypopnoea-Index (AHI) =
#apnoeas+hypopnoeas/hour of sleep
OSA: obstruction of the UA
The OSA cycle: overview
Sleep fragmentation
Increasing effort
Hypoxia
Strollo PJ et al. NEJM 1996; 334:99-104
The OSA cycle: recurrence of events
Causes of UA obstruction:
anatomic and nonanatomic factors
Pathophysiology of OSA: constricting
and dilating forces
Several anatomic factors may facilitate UA collapse
Anatomic factor #1: tonsillar hypertrophy
Anatomic factor #2: macroglossia
Mallampati score
I
II
III
IV
Anatomic factor #3: obesity
Anatomic factor #4: retrognathia
Measuring the ‘anatomic factor’:
Critical closing pressure (Pcrit)
<-2
-2 <–> +2
>+2
UA CSA (cm²)
4
3 Pcrit
2
1
0
Normal
OSA pt
-5
0
5
10
15
20
AIRWAY PRESSURE (cm H2O)
Isono S et al. JAP 1997; 82:1319-26
ODI <20/h
ODI >=20/h
Pathophysiology of OSA: Pcrit
and nonanatomic factors
• Pcrit is a measure of the anatomic factor of the UA
• Important nonanatomic factors are also involved in the
pathogenesis of obstructive respiratory events
– Arousal threshold
– Loop gain (sensitivity of respiratory control system)
– Genioglossus Muscle responsiveness
• These four parameters (‘PALM score’) define the
phenotypical characteristics of OSA. The PALM profile
may be important for the choice of therapy
Eckert D et al. AJRCCM 2013, 188, 996-1004
‘PALM score’ and choice of therapy
PALM # Pcrit
% Pts Features
Treatment targets
1
>+2
23% Highly collapsible UA
severe OSA
‘Anatomic’ intervention
(CPAP)
2a
-2 to +2
‘Anatomic’ intervention
(CPAP, MRA, ...)
2b
-2 to +2
21% Moderately collapsible UA
mainly anatomically driven
overall severe OSA
(wide range)
37% Moderately collapsible UA
one or more nonanatomic
factors are important
overall severe OSA
(wide range)
3
<-2 hPa
19% Slightly collapsible UA
all have one or more nonanatomic factors
mild to moderate OSA
(wide range)
Combination of targeted
therapies based on
‘nonanatomic’ interventions
Eckert D et al. AJRCCM 2013, 188, 996-1004
‘Anatomic’ + ‘nonanatomic’
interventions (e.g. oxygen
supplement, sedatives,
acetazolamide, HGNS)
Systemic effects of OSA
Cardiac rhythm disorders
Recurrent surges of blood pressure
Pre-arousal
Shepard JW, Med Clin North Am 1985; 69:1243-63
Arousal
Chronic Intermittent Hypoxia
oxidative stress
Lavie L – Sleep Medicine Reviews 2015; 20:27-45
Morbid conditions related to the
systemic effects of chronic untreated OSA
•
•
•
•
•
•
•
•
•
Arterial hypertension
Cardiac arrhythmias
Heart failure
Atheromatosis
Stroke, myocardial infarction
Systemic inflammation
Dyslipidaemia
Insulin resistance
…
Severity of OSA and operational definition
Severity of OSA
• Defined by AHI:
–
–
–
–
Normal :
Mild :
Moderate:
Severe:
• However:
0-5/h
6-15/h
16-30/h
>30/h
– These are arbitrary cut-offs
– Different scoring rules for AHI have been applied
– AASM 2012: high sensitivity for hypopnea scoring
AHIAASM’12 = AHIAASM’07 x 3
– Yet cut-offs have not been adapted
• AHI is poor predictor of symptoms,
comorbidities and outcomes of OSA
ODI (4%) has better predictive power
Ruehland WR et al. Sleep 2009; 32(2):150-7
Operational definition: AASM ICSD-3
OSA = AHI > 5 + clinical phenomena
OSA = AHI > 15
Disorders that may explain symptoms must NOT be excluded
Clinical phenomena (any of these items):
Daytime symptoms
•
excessive daytime sleepiness
•
cognitive dysfunction (memory, concentration)
•
fatigue
•
nonrestorative sleep
Nighttime symptoms
•
insomnia
•
awakening with breath holding, gasping, or choking
•
observed snoring, breathing interruptions, or both
Complications
•
hypertension
•
coronary artery disease
•
stroke
•
congestive heart failure
•
atrial fibrillation
•
type 2 diabetes mellitus
•
mood disorders
Pitfalls in the diagnosis of OSA “syndrome”
• High prevalence of OSA in general population
– AHIAASM’12 > 15 in 49·7% men and 23·4% women
(middle aged/older)
– AHIAASM’12 > 15 + EDS in ±6% men and ±3% women
(thus >85% not sleepy)
• Therefore association between increased AHI and
symptoms may be due to coincidence
• Often, complex sleep disorders are present
(e.g. OSA + insomnia)
• OSA “syndrome” implies response to therapy
Heinzer R et al., « HypnoLaus study » Lancet Respir Med 2015, 3: 310–18
Diagnostic treatment of OSA “Syndrome”
• To control OSA = to reduce
AHI < 5/hour
• Achievable with CPAP
• If symptoms abate, there is
proof of principle for
OSA syndrome
OSA: summary
• OSA: recurrent episodes of sleepdisordered breathing due to partial/
complete obstruction of the UA
• Both anatomic and nonanatomic
factors are important in the pathogenesis
of OSA
• Systemic effects of OSA include cardiac
arrhythmias, hypertension, cardiovascular disease, oxidative stress and
inflammation
• Severity of OSA comprises three
arbitrarity defined classes, based on AHI
scores. The operational definition of
OSA in ICSD-3 is problematic.
• Diagnostic treatment is an important
concept in the OSA ‘syndrome’
Thank you for your attention…
…Sleep Medicine Centre Kempenhaeghe