Kansas Association of Sleep Professionals 2014 Excessive Daytime

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? n Large difference between. OSAand OSA Syndrome n Men: 25% vs. 4% n Women: 9% vs. 2% n Implications/Questions: n Large number of people without symptoms vs. subclinical disease- may develop symptoms later? n Are we asking the right questions about clinical presentation? n Relationship between clinical presentation and objective testing?

Has a wide range of symptom - severity relationships… n = 4653 Epworth Sleepiness Scale Sleepy Sleep Apnea Non-Sleepy Sleep Apnea – Hypopnea Index

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… Ø 80% acceptance Ø better machines ØBetter 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 Epworth Sleepiness Scale Sleepy Sleep Apnea Non-Sleepy Sleep Apnea – Hypopnea Index

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 T 2 DM 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 T 2 DM 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 Cytokines Oxidative stress Adipokines Other mediators 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