Outcome Measures in OSA Defining Our Treatment Goal

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1 Outcome Measures in OSA Defining Our Treatment Goal Andrew N. Goldberg, MD, MSCE Professor Department of Otolaryngology-Head and Neck Surgery University of California-San Francisco

2 Overview What are the effects of SDB? What changes do our treatments make? What metrics are available? What metrics should we follow? Conclusions

3 Effects of Sleep Disordered Breathing (SDB) Physiologic Increased incidence of MI, CVA, H/T Behavioral / Cognitive Daytime sleepiness, increased MVA incidence up to 7x MVA risk in men evident w/ snoring alone w/o OSA Young 1997 Social Snoring, disruption of marital harmony

4 What metrics are available? Cardiovascular morbidity Cognitive function / motor vehicle accidents Other physiologic / metabolic parameters Snoring (after all, that s what brings them in, and that s what patients judge treatment by) PSG

5 Cardiovascular Disease (SHHS) Heart failure, stroke Shahar 2001 Ischemic changes in the brain Ding 2004 Arousals, not AHI Association with Hypertension Redline 2005 Could not correlate a specific parameter of PSG Right Heart Function Dursunoglu

6 Cardiovascular disease (SHHS) cont. Carotid plaques No association with RDI (AHI) Also looked at degree of hypoxemia and freq of arousals All differences explained by confounding factors (for CVD) Is there NO association of carotid plaques with OSA, or just not with these parameters? Wattanakit 2007

7 Neurophysiologic Effects - testing Attention is impaired PVT (reliable, no learning, sensitive) Balkin 2004 Vigilance and cognitive functioning impaired Intellectual and verbal functioning relatively spared These improve with treatment (CPAP) Beebe 2003 Cognitive function testing does not correlate w/ AHI Boland 2002 (SHHS)

8 Cognitive Function - patient report measures Epworth Sleepiness Scale Johns scale for chance of dozing Average if 7 for medical students, 14 for OSA patient Functional Outcomes of Sleep Questionnaire (FOSQ) Weaver 1997 Measures impact of sleepiness on functioning Calgary Sleep Apnea Quality of Life Index Flemons 1997 Captures QOL, performance, mood Stanford Sleepiness Scale Hoddes 1973 Measure of sleepiness on a 1-7 scale meant to be used at different times during the day for comparison

9 Metabolic measures? Inflammatory Elevated IL-6, TNF-alpha, CRP O2 radicals Schultz 2000 Teramoto 2003 Hormonal changes ft4, testosterone, LH, SHBG Meston 2003 Diabetes, ILGF-1, sympathetic tone Ischemic changes in the brainstem related to arousals, but not apnea or hypopnea Ding 2004 Will these measures ultimately be what we follow to determine treatment effectiveness? For diagnosis? HbA1c for OSA?

10 Snoring Subjective spouse measures Surrogate measure with VAS, bother scale, etc Objective sound measurements difficult, but possible, to quantify SNAP frequency analysis analyzes snoring frequency and amplitude algorithm proprietary Liesching 2004

11 Polysomnography Measures Multiple measures possible, a few are popular Apnea Hypopnea Index (AHI) Respiratory Disturbance Index (RDI) Minimum O2 Saturation Arousals Time in REM sleep Total apnea time Total sleep time below 90% saturation Does a polysomnogram alone define this disease?

12 Definitions of Disease Sleep Disordered Breathing - Recurrent episodes of cessation of respiration (apnea) or decrements in air flow (hypopnea) which may disrupt sleep

13 Definition of Apneic Events on PSG Apnea- Cessation of breathing during sleep for >10 sec Hypopnea - Decrease in air flow of >50% associated with a fall in SaO2 >4% +/- EEG arousal Apnea Hypopnea Index (AHI) - The number of apneas + hypopneas per hour of sleep; add RERAs/hour to get the Respiratory Distrbance Index (RDI)

14 Definitions of Disease by PSG Obstructive Sleep Apnea (25% males, 9% females, Young 1993) AHI >5 events/hour Obstructive Sleep Apnea Syndrome (4% m, 2% f, Young 1993) AHI >5 events/hour with symptoms (eg. daytime sleepiness) Upper Airway Resistance Syndrome Repeated arousals 2 0 to upper airway resistance or snoring

15 What should the definition of hypopnea be? Should it be based on what correlates with cardiovascular disease? Punjabi 2008 Hypopneas comprise a majority of SDB events Controversy exists with regard to definition In sample of 6,106 patients, hypopneas with a desaturation of at least 4% are associated with CVD There was NO correlation with milder desaturations or arousals

16 What level of disease on PSG justifies treatment? Is there an AHI cut off? Elevated AHI with no sleepiness, hypertension or co-morbidity? Tiredness with a normal AHI? Desaturation only? How about length of apneas and hypopneas? Other parameters? REM, delta sleep, >90% sat

17 Polysomnography measures How well do PSG measures correlate with other measures? Weaver 2005 Analyze PSG/non-PSG measures in mild-moderate OSAS FOSQ, SNORE, SF-36, ESS, PVT No significant association between AHI and any baseline or outcomes non-psg measure Conclusion: PSG measures do not capture all elements of OSAS and should not be used exclusively to evaluate treatment response

18 PSG and Tiredness from Sleep Heart Health Study Analysis of 1115 patients in the SHHS Kapur 2005 AHI > 15 AHI > % of patients with were sleepy 51.4% of patients with were sleepy AHI did correlate with sleepiness (p<.01) sleepy patients non-sleepy patients AHI Statistically significant, but clinically significant? Not very discriminating for the clinician

19 Is Tiredness Important?? Does self reported sleepiness by ESS modify the association between sleep apnea and hypertension? Yes! Odds ratio for H/T if sleepy 2.83 Odds ratio for H/T if NOT sleepy 1.22 Kapur 2008 Where is sleepiness in the definition of SDB???

20 Treatment Effectiveness Haraldsson tested patients with SDB and normals on a driving simulator (at the Saab factory) Performed UP3 on patients with SDB Found that patients w/ SDB uniformly improved after UP3 REGARDLESS OF CHANGES IN AHI Did these patients with improved alertness and no change in AHI FAIL treatment? Haraldsson 1995

21 Treatment Guidelines (cont) What metric describes the PHYSIOLOGY of the disease? PSG? Cardiovascular effects (H/T, MI, CAD) Sleepiness testing (MSLT, MWT, PVT) Endocrine/metabolic effects (CRP, sympathetic tone, IL-6) Are the physiologic changes that cause cardiovascular effects the same as the physiologic changes that cause sleepiness or metabolic effects?

22 Is there one metric for everyone? One physiologic measurement may not be sufficient - like measuring blood lipids (Total Chol, HDL, LDL) There is undoubtedly differential susceptibility in their physiologic measures, just as there are for patients with sleep deprivation and many other diseases

23 Treatment Guidelines In the majority of patients without coexisting conditions the primary reason to test for and treat sleep apnea is the potential to improve the quality of life Flemons NEJM 2002

24 Treatment Guidelines (cont) Clinicians do not make decisions about treatment on the basis of AHI alone because it correlates poorly with QOL and the severity of symptoms and does not help to determine the risk of MVA. Flemons NEJM 2002

25 Consensus Statement on Treatment Criteria in OSA Daniel I. Loube, MD, FCCP; Kingman P. Strohl, MD, FCCP David P. White, MD, FCCP Peter C. Gay, MD, FCCP Allan I. Pack, MD, PhD Nancy A. Collop, MD, FCCP CHEST 1999; 115: CPAP treatment All patients with an RDI>30, regardless of symptoms For patients with an RDI of 5 to 30 w/ symptoms or co-morbidities excessive daytime sleepiness, impaired cognition, mood disorders, insomnia, or documented cardiovascular diseases to include hypertension, ischemic heart disease, or stroke

26 Clinical Guideline for the Evaluation, Management and Long-term Care of OSA in Adults Lawrence J. Epstein, M.D. David Kristo, M.D. Patrick J. Strollo, Jr., M.D. Norman Friedman, M.D. Atul Malhotra, M.D. Susheel P. Patil, M.D., Ph.D. Kannan Ramar, M.D. Robert Rogers, D.M.D. Richard J. Schwab, M.D. Michael D. Weinstein, M.D. Edward M. Weaver, M.D., M.P.H. J Clin Sleep Med. 2009; 5(3): Diagnosis of OSA is confirmed if the number of obstructive events (apneas, hypopneas + RERA) > 15 events/hr or > 5/hour in a patient with symptoms PAP is the treatment of choice for mild, moderate, and severe OSA and should be offered as an option to all patients Alternative therapies may be offered depending on the severity of the OSA

27 Conclusions The proper metric or groups of metrics to measure this disease and guide our treatment is unclear PSG alone does not appear to fully describe the disease It is likely that measures of physiology (tiredness, CV morbidities, serology) are what we should ultimately treat, not a number on the PSG Metrics should reflect what is important to the doctor (CV morbidity, MVA) AND the patient (how do I feel)? We should strive to define the physiology more completely and develop more robust metrics to define sleep disordered breathing

29 Outcomes Measures in Obstructive Sleep Apnea References 1. Balkin TJ, Bliese PD, Belenky G, Sing H, Thorne DR, Thomas M, Redmond DP, Russo M, Wesensten NJ. Comparative utility of instruments for monitoring sleepiness-related performance decrements in the operational environment. J Sleep Res Sep;13(3): Beebe DW, Groesz L, Wells C, Nichols A, McGee K. The neuropsychological effects of obstructive sleep apnea: a meta-analysis of norm-referenced and casecontrolled data. Sleep May 1;26(3): Boland LL, Shahar E, Iber C, Knopman DS, Kuo TF, Nieto FJ; Sleep Heart Health Study (SHHS) Investigators. Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study. J Sleep Res Sep;11(3): Ding J, Nieto FJ, Beauchamp NJ Jr, Harris TB, Robbins JA, Hetmanski JB, Fried LP, Redline S. Sleep-disordered breathing and white matter disease in the brainstem in older adults. Sleep May 1;27(3): Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med Jun 15;5(3): Flemons WW. Obstructive Sleep Apnea. NEJM, 347:77, , Flemons WW, Tsai W. Quality of life consequences of sleep-disordered breathing. J Allergy Clin Immunol Feb;99(2):S Haraldsson PO, Carenfelt C, Lysdahl M, Tornros J. Long-term effect of uvulopalatopharyngoplasty on driving performance. Arch Otolaryngol Head Neck Surg Jan;121(1): Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep Dec;14(6): Kapur VK, Resnick HE, Gottlieb DJ for the Sleep Heart Health Study Group. Sleep Disordered Breathing and Hypertension: Does Self-Reported Sleepiness Modify the Association? Sleep 2008; 31: Liesching TN, Carlisle C, Marte A, Bonitati A, Millman RP. Evaluation of the accuracy of SNAP technology sleep sonography in detecting obstructive sleep

30 apnea in adults compared to standard polysomnography. Chest Mar;125(3): Meston N, Davies RJ, Mullins R, Jenkinson C, Wass JA, Stradling JR. Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea. J Intern Med Nov;254(5): Punjabi NM, Newman AB, Young TB, Resnick HE, Sanders MH. Sleepdisordered Breathing and Cardiovascular Disease: An Outcome-based Definition of Hypopneas. Am J Respir Crit Care Med 2008; 177: Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med Aug;162(2 Pt 1): Teramoto S, Kume H, Matsuse T, Ishii T, Miyashita A, Akishita M, Toba K, Ouchi Y. Oxygen administration improves the serum level of nitric oxide metabolites in patients with obstructive sleep apnea syndrome. Sleep Med Sep;4(5): Wattanakit K, Boland L, Punjabi NM, Shahar E. Relation of sleep-disordered breathing to carotid plaque and intima-media thickness. Atherosclerosis Weaver TE, Laizner AM, Evans LK, Maislin G, Chugh DK, Lyon K, Smith PL, Schwartz AR, Redline S, Pack AI, Dinges DF. An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep Oct;20(10): Weaver EM, Woodson BT, Steward DL. Polysomnography indexes are discordant with quality of life, symptoms, and reaction times in sleep apnea patients. Otolaryngol Head Neck Surg Feb;132(2): Young T, Blustein J, Finn L, Palta M. Sleep-disordered breathing and motor vehicle accidents in a population-based sample of employed adults. Sleep Aug;20(8): Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep disordered breathing among middle-aged adults. N Engl J Med Apr 29;328(17):

Outcome Measures in OSA Defining Our Treatment Goal. Defining common outcome metrics in OSA Al-Shawwa Sleep Med Rev 2008

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