Kansas Association of Sleep
Professionals, 2014
Excessive Daytime Sleepiness:
Understanding the Most Important
Symptom in our Field
Charles Atwood, MD, FCCP, FAASM
University of Pittsburgh
VA Pittsburgh Healthcare System
Conflicts of Interest
• Consultant: Philips, Carecore National,
Vapotherm
• Grants: Philips, Forest Research,
Medimmune
• ABIM Pulmonary Board test writing cmte
• NAMDRC Sec-Treasurer
• BRPT BOD
My Background
• Pulmonary medicine, sleep medicine
practitioner
• VA Pittsburgh Healthcare System sleep
disorders program – 20 years as director
• UPMC Sleep Medicine Fellowship director
• Academic interests – sleep apnea
management, new diagnostic tests, costeffectiveness
Roadmap
• OSA background
• Epidemiology of OSA
• Impact of persistent sleepiness
– On patients
– On providers and the field of sleep med
• What we don’t know about sleepiness in
OSA (but wish we did)
Pathogenesis of OSA
Obesity
influence
Genetic factors
Small pharyngeal airway
Ventilatory
control
factors
Sleep effect
Airway Closure
Balance of Pressures in Upper
Airway Physiology
Small airway size
 Upper airway resistance
 Neg inspiratory pressure
 Extra lumenal tissue pressure
 Greater collapsibility
 Smaller mandible
Favors collapse
Pharyngeal dilator muscles
 Larger airway size
 Larger mandible
 Less collapsibility
 Higher lung volume
Favors patency
Sleep apnea is very common
SLEEP STUDY
Men 25%
Women 9%
SLEEP STUDY+SXs
Men
4%
Women 2%
• Study population is Wisconsin state employees
age 35-60 randomly selected
• N = ~1200
• from Young et al, NEJM, 1993
• confirmed by Bixler et al, AJRCCM, 1997
• Basically same values seen now in all community
populations studied on 5 continents
Affects all age groups…
Sleep disorders clinic criteria:
 AHI >10
 Hypersomnolence, or Htn, or other
CV disease
Racially homogenous
Bixler et al, AJRCCM, 1998
What Has Epidemiology Taught Us
About Clinical Presentation?
 Large difference betweenOSAand OSA Syndrome
 Men: 25% vs. 4%
 Women: 9% vs. 2%
 Implications/Questions:
 Large number of people without symptoms vs. subclinical
disease- may develop symptoms later?
 Are we asking the right questions about clinical
presentation?
 Relationship between clinical presentation and
objective testing?
Has a wide range of symptom - severity
relationships…
n = 4653
30
Epworth Sleepiness Scale
Sleepy Sleep Apnea
25
20
15
10
5
Non-Sleepy Sleep Apnea
0
0
10
20
30
40
50
60
Apnea – Hypopnea Index
70
80
90
100
Has serious health consequences…
Months
Cumulative Incidence of Non-fatal CV Events
Cumulative Incidence of Fatal CV Events
AIM: Observational study to compare incidence of fatal and non-fatal cardiovascular
events in simple snorers, patients with untreated OSA,patients treated with CPAP,
and healthy men recruited from the general population.
Design: Prospective observational cohort. 264 healthy men, 377 simple snorers, 403
with untreated mild-moderate OSA (AHI 5-30), 235 with untreated severe OSA (AHI > 30),
and 372 with OSA and treated with CPAP
Conclusion: In men, severe OSA significantly increases the risk of fatal and non-fatal
cardiovascular events. CPAP treatment reduces this risk.
.
Months
Lancet 2005
365: 1046–53
Is associated with stroke, death,
etc….
Yaggi et al, NEJM, 2005
But treatment improves outcomes…
Haentjens, et al, Arch Int Med, 2007
OSA is Easy to Diagnose
Hierarchy of OSA Diagnosis
SPECIALIST
PSG
Home OSA
Test
Questionnaires
PRIMARY
CARE
Clinical suspicion
DTC, PCP,
Specialist
OSA is Challenging to Treat
Easy to Initiate Therapy…
 80% acceptance
 better machines
Better masks
But difficult to sustain use…
Prospective cohort study of 1211
Scottish CPAP users
Mcardle et al, AJRCCM, 2001
Sleepiness and Sleep Apnea
• Measurement
• What it means
• Implications
– Car Crashes
– Associations with other conditions
– EDS and medication adherence
The Epworth Sleepiness Scale
How likely are you to doze off or fall asleep
in the following situations, in contrast to
feeling just tired?
0 = no chance of dozing
1 = slight chance of dozing
2 = moderate chance of
dozing
3 = high chance of dozing
SITUATION
CHANCE OF
DOZING
Sitting and reading
_______
Watching TV
________
Sitting inactive in a public place (e.g a theater or a meeting)
________
As a passenger in a car for an hour without a break
________
Lying down to rest in the afternoon when circumstances permit
________
Sitting and talking to someone
________
Sitting quietly after a lunch without alcohol
________
In a car, while stopped for a few minutes in traffic
________
The Relationship of Self Reported
Sleepiness to Sleep Apnea
n = 4653
30
Epworth Sleepiness Scale
Sleepy Sleep Apnea
25
20
15
10
5
Non-Sleepy Sleep Apnea
0
0
10
20
30
40
50
60
70
80
Apnea – Hypopnea Index
90
100
Sleep Deprivation is Pervasive in Society
*2000 Omnibus Sleep in America Poll-NSF
Sleepy While Driving
NSF’s 1999 “Sleep in America” Poll:
• 62% reported driving drowsy in past
year
• 27% actually dozed off at the wheel
• 23% knew someone who had a fallasleep crash sometime in their life
© National Sleep Foundation
Sleepy While Driving
• 56,000 MVCs (motor vehicle crashes) per
year have been attributed to sleepiness
– 40,000 non-fatal injuries
– 1,550 fatalities
NCSDR/NHTSA Expert panel on driver fatigue & sleepiness;
www.nhtsa.gov/people/perform/human/drowsy.html
Odds ratio for having a traffic accident, by
apnea + hypopnea index
Or’s adjusted for BMI, alcohol, work schedule, hours driven, medications, age
Cases = MVC+PSG; Ctrls, No MVC+PSG
Teran – Santos, et al, NEJM, 99
Accidents 1 year before and after
initiation of CPAP for OSA
n = 547
Krieger et al, Chest, 97
Persistent Sleepiness and
OSA Management
What Causes the Sleepiness of
Sleep Apnea?
• Mechanism?
– Sleep disruption?
– Cumulative effects of hypoxia on brain?
– Inflammatory mediators?
• Effects of treatment
– Reversible vs. Irreversible sleepiness
– Much of the sleepiness is reversible, but some
patients only partial improvement is seen
Subjective Sleepiness Correlates
with Severity of Sleep Apnea
Sleep Heart Health Study
1824 subjects
age: 65 ± 11
M:F = 49:51
Gottlieb et al, AJRCCM, 1999
Age specific prevalence of
sleepiness
Bixler et al, JCEM, 2005
Sleep Efficiency: Age and Gender
Bixler et al, JCEM, 2005
EDS in a Community Cohort by
T2DM Status
Bixler et al, JCEM, 2005
EDS = “high end” answer to EDS questions
1.Are you frequently sleepy but manage
anyway?
2.Do you have irresistible sleepiness attacks
during the day?
EDS in a Community Cohort by
T2DM Status
Bixler et al, JCEM, 2005
Effect of BMI on Sleepiness
EDS in a Community Cohort by
Depression Status
Bixler et al, JCEM, 2005
Predictors of EDS in OSA
Bixler et al, JCEM, 2005
Effect of Sleep Apnea Therapy on
Daytime Sleepiness
from Jenkinson et al, Lancet, 1999
Effect of sleep apnea on
performance, behavior and QOL
• Impaired performance of monotonous, prolonged
tasks
• Learning new skills, abstract thought and creativity
are impaired
• Immediate recall is impaired
• Impaired measures of mood
– ability to think and concentrate
– insomnia predicts later depression
• Impaired quality of life
– Documented in numerous intervention trials
Sleepiness and Quality of Life
• OSA is associated with poor QOL
• Sleepiness is not always “teased out” in
the overall OSA picture – most studies
suggest that sleepiness has multiple
causes even in OSA patients
• QOL improves as OSA is treated and
sleepiness improves – for most people but
not all
EDS and Medication
Adherence
• CAATCH study – “Counseling African
Americans to Control Hypertension”
• 1058 AA subjects in NYC
• Collected sociodemographics, medical,
EDS, and medication adherence
• 71% female, 51% smokers, 33% drinkers
• 27% pos on ESS for EDS
• 44% of EDS subj were adherent to meds
CAATCH Study
• Found that OR of 2.28 for the association
of sleepiness with NON-Adherence
• Age was also statistically significant
Williams et al, Pat Pref Adher, 2014
Somnogenic Gut Hormones
and Adipokines
Potential mechanisms linking
obesity and EDS
Management of EDS in OSA
“Sorting the Somnolent”
1. Lifestyle – how much sleep, sleep quality
2. OSA – need to determine effective
treatment, need to use therapy as much
as possible
Determinants of Sleepiness
Sleep effects
Illness effects
Psychological
effects
Determinants of Sleepiness
Sleep effects
Homeostatic sleep drive
Circadian factors
Sleep deprivation
Neurotransmitters
Illness effects
Psychological
effects
Determinants of Sleepiness
Sleep effects
Illness effects
Psychological
effects
Determinants of Sleepiness
Sleep effects
Depression, anxiety
“Sleep hygiene”
Other effects
Illness effects
Psychological
effects
Determinants of Sleepiness
Sleep effects
Illness effects
Psychological
effects
“Sorting the Somnolent”
The clinical approach
• Make sure you have the right disorder
• Make sure that all the sleep disorders are
accounted for – can be more than 1
disorder
• Medications and sleepiness – under
appreciated
Tolerability and Efficacy of Armodafinil in
3 Important Sleep Disorders
Schwartz et al, JCSM, 2010
Clinical Global Impression of
Improvement
Schwartz et al, JCSM, 2010
Change in Epworth Score
Schwartz et al, JCSM, 2010
What are the gaps in our
current knowledge?
What do we need to know in order
to move this field forward?
Gaps in Knowledge
• Basic mechanisms of sleepiness in
disease, including sleep apnea
• Recognition of persistent sleepiness in
OSA by primary care
• Increase comfort level for management of
basic sleep problems by primary care
physicians
Sleepiness in sleep apnea –
what does the future hold?
1. Greater awareness among patients
- Most comes from DTC adds
- A little from the medical community
2. New portable monitoring regs will have an
unintended benefit: more attention on
clinical outcomes
What does the future hold?
3. Better understanding of the biology of
sleepiness
4. New therapies?
Thank You for Your
Attention