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Obstructive Sleep Apnea
Established and Emerging Treatment Options
Dragos Manta, MD
Assistant Professor of Medicine
Division of Pulmonary, Critical Care and Sleep Medicine
Objectives
• Review patho-physiologic mechanisms of obstructive
sleep apnea (OSA)
• Review the established positive airway pressure, oral
appliance and surgical therapy options
• Review emerging therapy options
Why OSA?
• OSA is the second most common sleep-related
breathing disorder after primary snoring.
• Prevalence in general populations
– up to 9% in women
– up to 24% in men
• Prevalence of symptomatic OSA
– 1-5% in women
– 3-8% in men
International Classification of Sleep
Disorders – 3rd Edition (ICSD-3)
• OSA is characterized by repetitive episodes of
complete (apnea) or partial (hypopnea) upper airway
obstruction occurring during sleep.
• Sleep testing is required for diagnosis
– 15 or more predominantly obstructive events per
hour of sleep in a asymptomatic patient
– 5 or more predominantly obstructive events per
hour of sleep in a patient with sleep symptoms or
co-morbidities
Risk Factors
• Obesity
• Upper Airway Size
• Sedentary Behavior
Obesity
• The single most
important risk factor in
OSA in middle-age
adults
• 70% of OSA patients are
obese
• In a large cohort of
adults undergoing
bariatric surgery, 80%
had OSA (Khan A et al. JCSM.
2013;9(1):21-29)
OSA
Obesity
Obesity
• The relationship between obesity and OSA is
bi-directional.
• In a longitudinal cohort of Wisconsin residents
(Peppard PE et al. Jama. 2000;284(23):3015-3021)
– 10% weight gain predicted a 32% increase in the
AHI
– 10% weight loss predicted a 26% decrease in the
AHI
Obesity
• Mediators
– Increased neck circumference
• Men>17 inches
• Women >16 inches
– Fat deposition in the tongue
– Decreased “tracheal tug” due to decreased
functional residual capacity (FRC) (Gifford AH et al. CHEST
2010; 138( 3 ): 704 – 715)
Upper Airway (UAW) Size
• The upper airway size of OSA patient is smaller,
particularly lateral dimensions
–
–
–
–
Heritable factors
Developmental
Inflammatory
Obesity
Modified Mallampati Score (MMS)
• MMS is determined by
asking the patient to
open mouth widely
with tongue left in place
Other Signs of a Small UAW
•
•
•
•
Tongue volume is higher (lateral dental imprints)
High arched palate
Tonsillar/adenoid hypertrophy
Small retrognathic mandible
Upper Airway Abnormalities
• Craniofacial syndromes (like Pierre Robin Syndrome)
• Soft tissue abnormalities
– Increased tongue size ( Down syndrome)
– Upper airway tumors
Neural Component
• Reflex mechanisms
– Nasal flow receptors
– Laryngeal pressure
receptors
– Stretch receptors
activated by increasing
lung volumes
• Upper airway dilator
muscles are activated just
before and during
inspiration
– Tongue muscle
(genioglossus)
– Soft palate muscles
(tensor veli palatini)
Pcrit= Critical UAW Pressure
• Concept encompasses both passive and active
characteristics of the upper airway
• Intra-luminal upper airway pressure is subatmospheric during each inspiratory effort
• Pcrit= transmural pressure at which the airway
collapses
Pcrit
Normal
• -16 to -8 cm H2O
Snorer
• -12 to -2 cm H2O
Hypopnea
• -4 to +1 cm H2O
Apnea
• -1 to + 5 cm H2O
Adapted from Schwartz AR,
Smith PL, Kashima HK, et al.
Respiratory function of the
upper airways. In: Murray JF,
Nadel JA, eds. Textbook of
respiratory medicine. 2nd ed.
Philadelphia: WB Saunders,
1994; 1451-70).
Fluid Shifts at Night
• Observational study of 23
non-obese male subjects
referred for evaluation for
sleep apnea
• Decrease in leg fluid
volume at night correlates
positively
– neck circumference
– AHI
– a sedentary behavior
during the day
Major Pathophysiologic Mechanisms
of OSA
• Sleep fragmentation causes lighter sleep
• Excessive daytime sleepiness
• When associated with inability to wake up
• Increased risk of postoperative complications
• Repetitive arousals/ epinephrine bursts/ cyclical
deoxygenation/ reoxygenation (repetitive
ischemia/reperfusion)
•
•
•
•
Hypertension
Cardio- and cerebro-vascular disease
Insulin resistance and diabetes
Increase mortality
Mortality
• Untreated OSA is associated with increased mortality
– Largely in patients with severe OSA
– Independent of sleepiness in patients with severe OSA
• Driven mostly by increased mortality in those
younger than 65
Diagnosis
• Subjective clinical
impression that OSA is
likely present has a
sensitivity of 60% and
specificity 63%. (Hoffstein V,
et al. Sleep. 1993;16(2):118-122)
• Nocturnal pulse
oximetry lacks sufficient
sensitivity and
specificity for diagnosis
(Gyulay S et al. The Am rev of res dis.
1993;147(1):50-53)
• Attended
Polysomnogram
• Ambulatory testing or
un-attended portable
monitors
Treatment of OSA
•
•
•
•
•
PAP (positive airway pressure)
Oral Appliances
Surgery
Adjunctive therapies
Emerging therapies
PAP
• Most efficacious option
• Continuous PAP (or
CPAP) is most
commonly prescribed
• Acts as a “pneumatic
splint” splinting the
upper airway and
preventing airway
collapse during sleep.
• Improves PSG (AHI, etc.)
• Improves quality of life ,
daytime sleepiness
• Improves hypertension
control
• Improves glycemic
control in patients with
diabetes
PAP Prescription
• Titration during monitored overnight PSG
• Auto-CPAP trial
CPAP pressure
•
•
•
•
Severity of OSA
Body position
Weight
Sleep stage ( N2 and REM sleep require
highest pressures)
Auto-CPAP or APAP
• Respond to variation in flow limitation, airflow
magnitude, airway impedance and snoring
Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway
pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep
2004;27:249-253
Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway
pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep
2004;27:249-253
Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway
pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep
2004;27:249-253
Auto-CPAP for Failed Fixed CPAP
• For high pressure intolerance
• For OSA concentrated by
– sleep stage (N2, REM)
– position (supine)
Morgenthaler TI et al. Practice parameters for the use of autotitrating continuous positive airway
pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea
syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep.
2008;31(1):141-147.
• Certain APAP devices may be initiated and
used in the self-adjusting mode for unattended
treatment of patients with moderate to severe
OSA without significant comorbidities (Option)
Patients Not Candidates for Auto-CPAP
•
•
•
•
CHF
Patients with central sleep apnea syndrome
Significant lung disease such as COPD
Patients expected to have nocturnal arterial
oxyhemoglobin desaturation due to conditions
other than OSA (e.g., obesity hypoventilation
syndrome)
• Patients who do not snore (either naturally or as
a result of palate surgery)
Morgenthaler TI et al. Practice parameters for the use of autotitrating continuous positive
airway pressure devices for titrating pressures and treating adult patients with obstructive sleep
apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep.
2008;31(1):141-147.
More Recent Meta-Analysis
• APAP compared with fixed CPAP
• improved compliance by 11 minutes per night
• reduced ESS by 0.5 points
• Fixed CPAP improved minimum oxygen
saturation by 1.3% more than APAP
• Clinical difference is unclear
Auto-titrating versus fixed continuous positive airway pressure for the treatment of
obstructive sleep apnea: a systematic review with meta-analyses. Systems Review. 1:20,
2012
Empiric Auto-Titrating CPAP in Patients
with Suspected OSA
1020 Patients Referred for PSG
• Prior diagnosis of OSA
• Comorbidities
109 Patients with
positive Berlin
questionnaire ,
baseline ESS +FOSQ
Auto-CPAP 5-20 cm
H20 (N=54)
Usual Care ( waiting
for sleep study) (
n=55)
ESS and FOSQ at 1 mo
ESS and FOSQ at 1 mo
NPSG +Titration
NPSG+Titration
1mo ESS + FOSQ
(n=42)
Exclusion Criteria
1 mo ESS +FOSQ(
n=44)
– Age greater than 80 years
– History of congestive heart
failure
– Myocardial infarction in the
prior 6 months
– Chronic obstructive pulmonary
disease with a forced
expiratory volume in 1 second
of less than 60% predicted
– Stroke
– Alternate sleep diagnosis
• Refused
Drummond F et Al. J Clin Sleep Med. 6(2):140-5, 2010 Apr 15
Drummond F et Al. J Clin Sleep Med. 6(2):140-5,
2010 Apr 15
Drummond F et Al. J Clin Sleep Med.
6(2):140-5, 2010 Apr15
• Safety And Complications of Auto-CPAP Trial
• No adverse events were observed.
• No subject deaths or cerebrovascular accidents
• No motor vehicle crashes or other catastrophic
adverse events
• Five patients (12%) in the auto-CPAP group and 4
(9%) in the usual-care group were admitted to the
hospital for chest pain.
BIPAP S
• Offers no significant advantage over CPAP for
OSA patients (Gay PC et al. Sleep. 2003;26(7):864-869)
• For patients that require high pressures of
CPAP > 15 cm H2O
• For patients intolerant to CPAP due to
perceived difficulties with exhalation
• For patients with OSA and OHS or COPD
• Back-up rate usually not required ( no BIPAP
S/T )
Masks Interfaces
• Nasal masks are the standard of care
• Nasal inserts (“pillows”) are popular
• Nasal-oral ( full face) masks
Randomized Nasal vs Oronasal Mask
Equivalence of Nasal and Oronasal Masks during Initial CPAP Titration for Obstructive
Sleep Apnea Syndrome. Sleep. 34(7):951-5, 2011 Jul.
Patient Selected Nasal vs Oronasal
Mask
Oronasal masks require higher levels of positive airway pressure than nasal masks to treat
obstructive sleep apnea.Sleep Breath. 18(4):845-9, 2014 Dec.
Follow Up after Initiation of PAP
• Office visit
• Data Download
– Compliance
– Residual AHI
– Mask Leaks
Oral Appliance (OA) Therapy
• Mandibular Advancement
Devices (MADs)
• Others like Tongue retaining
devices
Effectiveness of MADs
• No significant difference
between OAs and CPAP in
the percentage of mild OSA
patients achieving their
target AHI/RDI.
• For moderate to severe
OSA, however, the odds of
achieving the target AHI
were significantly greater
with CPAP than with OAs.
Oral Appliance Therapy
OAs
• No factors consistently predicted treatment
success
• Sleep studies with oral appliance in place are
essential as some patients do not respond
• Despite reduction of OSA indeces, sleep
efficiency and architecture are not improved
• Result in an improvement in ESS and quality of
life.
Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, Chervin RD. Clinical practice
guideline forthe treatment of obstructive sleep apnea and snoring with oral appliance therapy: an
update for 2015. J Clin Sleep Med2015;11(7):773–827.
Summary of Recommendations
• OAs are recommended for
– primary snoring after OSA is ruled out by sleep
physician
– Patients with OSA who are intolerant of CPAP therapy
or prefer alternate therapy
• Qualified dentist use a custom, titratable
appliance over non-custom oral devices
– Custom/titratable >> custom/non-titratable > noncustom
• Sleep physicians and qualified dentists provide
follow up
Summary of Recommendations
• Sleep physicians conduct follow-up sleep
testing
– To document or improve treatment efficacy
– If patients develop recurrent symptoms
– If substantial weight gain
– With diagnoses of comorbidities relevant to OSA
• Impact of OAs on resistant HTN not well
studied
Contraindications of MADs
• Poor dentition
• Temporo-mandibular joint (TMJ) disorders
Surgical Treatment
• Apart from tracheostomy, surgery is less
predictable and effective
• Counseling about alternative therapies, success
rates and complications
• Can be considered for selected patients that
failed or not willing to consider PAP and OA
therapy
• Further research is needed to clarify patient
selection, safety and efficacy of surgical
approaches for OSA
Surgical Treatment
• Not generally effective and
not recommended
– Uvulo-palatopaharyngoplasty (UPPP)
– Laser-assisted uvulopalatoplasty (LAUP)
• Can be considered
– Radio-frequency ablation
(RFA) for mild-moderate OSA
– Palatal implants for mild OSA
• Relief of nasal obstruction in
order to increase CPAP
tolerance is helpful in
selected cases
• Maxillo-mandibular
advancement (MMA)
– Has been performed as phase
2 or phase 1
– Is effective in patients with
severe OSA
– Invasive (entails maxillary and
mandibular osteotomies)
Adjunctive Therapies
• Weight loss should be advised for all obese
patients with OSA
– Caveat: the magnitude of correlation of OSA
severity and weight is greater with weight gain
rather than weight loss
• Bariatric surgery related weight loss provides
either resolution of OSA (around 40%) or
major improvements of AHI, sleep
architecture, CPAP requirements and daytime
sleepiness
Adjunctive Therapies
• Exercise
• Avoidance of alcohol or sedatives before
bedtime
Positional Therapy
• For purely positional (supine) apnea
• Tennis ball sawn in a back pajama pocket
• Commercially available devices that prevents
rolling to supine position
• Objectively document effectiveness with
position monitor
Central Nervous System Stimulants
• Persistent symptoms of daytime sleepiness
• After objectively documented compliance
with CPAP
• Modafinil or the longer acting analogue
armodafinil
Emerging Therapies
• Nasal expiratory PAP devices (Nasal EPAP)
• Oral pressure therapy (OPT)
• Electrical Stimulation (ES)
Nasal Expiratory PAP Devices
• Unidirectional flow
resistance valves
• Expiratory flow
resistance without any
inspiratory resistance
• Pilot study with 24
subjects AHI 2414
– Mild OSA: AHI 104
– Mod OSA : AHI 198
– Severe OSA: AHI 5940
Nasal Expiratory PAP Devices
Auto-PEEP
Lung hyperinflation
Tracheal traction
Decreases UAW collapsibility
Nasal Expiratory PAP Devices
• 3 center study
• 34 subjects
• AHI 24+/-23 13+/-18
(p<0.01)
• After 30 days AHI 13+/19
• 94% subjective
adherence
•
•
•
•
•
19 center study in US
144 subjects
Baseline AHI 13.8
AHI 52% reduction
Severe OSA 39%
reduction
• ESS 9.97.2
Nasal Expiratory PAP Devices
• Excluded patients
– Nasal blockage
– Nasal allergies/sinusitis
– Severe nocturnal
desaturations
– Use of sedating
medications
• Testing is required to
document effectiveness
– Special nasal pressure
transducer
• Valves are single use
night
Oral Pressure Therapy (OPT)
• Gentle oral suction
sufficient to displace
the soft palate and the
tongue anterior and
superior
• AHI 3119
• 25/60 responders ( 50%
decrease in AHI to <20)
Oral Pressure Therapy (OPT)
• MRI imaging revel 75%
increase in retro-palatal
airway space
• FDA approved
Electrical Stimulation (ES)
•
•
•
•
Percutaneous genioglossus muscle stimulation
Trigger: decrease in tracheal breath sounds
Six subjects
AHI 3911.7
Electrical Stimulation (ES)
• Hypoglossal nerve
stimulator
• 8 subjects
• NREM AHI 5222
• REM AHI 4816
• Tolerance at 3-6 month
Electrical Stimulation
• Multicenter trial
• 21 patients
• Respiratory sensing uses thoracic bioimpedance
• AHI 4319
• MIF 215 509 mL/s
• Pain/numbness at insertion site
Choosing the Right Candidates
• Prospective validation of positive predictors
factors
– BMI<32
– AHI<50
– Lack of concentric palatal collapse during druginduced sleep endoscopy
• 7/8 patients had a 50% decrease of AHI to <20
The STAR Trial
Upper-Airway Stimulation for Obstructive Sleep Apnea.
New England Journal of Medicine. 370(2):139-149, January 9, 2014
The STAR Trial Exclusion Criteria
• BMI over 32
• AHI less than 20 or more than 50 events per hour
• central or mixed sleep-disordered breathing events
more than 25% of all episodes
• AHI score while the person was not in a supine position
was less than 10 events per hour
• pronounced anatomical abnormalities (e.g., tonsil size
of 3 or 4)
• if complete concentric collapse at the retro-palatal
airway was observed on endoscopy performed during
drug-induced sleep
Upper-Airway Stimulation for Obstructive Sleep Apnea.
New England Journal of Medicine. 370(2):139-149, January 9, 2014
The STAR Trial
Upper-Airway Stimulation for Obstructive Sleep Apnea.
New England Journal of Medicine. 370(2):139-149, January 9, 2014
The STAR Trial
Upper-Airway Stimulation for Obstructive Sleep Apnea.
New England Journal of Medicine. 370(2):139-149, January 9, 2014
Electrical Stimulation (ES)
• Promising for moderate and severe OSA in
non-obese patients
• Adherence was improved
• For selected patients
• ?Long term efficacy and side effects
Thank You!
• Review patho-physiologic mechanisms of
obstructive sleep apnea (OSA)
• Review the established positive airway
pressure, oral appliance and surgical therapy
options
• Review emerging therapy options