Obstructive Sleep Apnea and COPD overlap syndrome Chitra Lal, MD, FCCP, FAASM Associate Professor of Medicine, Pulmonary, Critical Care, and Sleep, Medical University of South Carolina Financial Disclosures Grant support from Invado Pharmaceuticals, Jazz Pharmaceuticals and SCOR at MUSC Consultant for Ikaria Pharmaceuticals Outline Overview of Sleep Apnea Shared Symptoms of COPD and OSA Epidemiologic Data on COPD-OSA overlap Why OSA diagnosis matters in COPD Special Considerations for OSA treatment in COPD 1
Epidemiology of Obstructive Sleep Apnea Prevalence of moderate to severe Obstructive Sleep Apnea (OSA) is high and increases with age (1): - 10% in men and 3% in women between 30-49 years of age - 17% in men and 9% in women between 50-70 years of age OSA is seen in a large proportion of patients who have hypertension, coronary artery disease, neurocognitive deficits, stroke and atrial fibrillation (2) (1) Peppard PE et al, Am J Epidemiol 2013; May 1;177(9):1006-14 (2) Lattimore JD et al, J Am Coll Cardiol 2003;41:1429-1437 Apnea: 90% in airflow for > 10 seconds Hypopnea (AASM definition): in airflow by 30% for 10 seconds with 3% desaturation or arousal RERA: in airflow with an arousal which does not met the definition of apnea/hypopnea Definitions Medicare definition of hypopnea: in airflow by 30% for 10 seconds with 4% desaturation AHI: apnea-hypopnea index (apneas + hypopneas/hour of sleep) RDI: respiratory disturbance index (apneas + hypopneas + RERA s/hour of sleep) Obstructive Apnea on Polysomnography Image courtesy emedecine.medscape.com 2
OSA in Adults Mild OSA: AHI/RDI 5 and <15/hour Moderate OSA: AHI/RDI 15 to 30/hour Severe OSA: AHI/RDI >30/hour Treatment for mild OSA with symptoms or moderate OSA with/without symptoms Patients at high risk for OSA (1): - Obesity (BMI > 35) - Congestive Heart Failure - Atrial Fibrillation - Refractory hypertension - Type 2 Diabetes - Nocturnal Dysrhythmias - Stroke - Pulmonary Hypertension - High-risk driving populations - Preoperative for bariatric surgery Physical exam findings consistent with OSA: - Mallampati score 3 or 4 - Macroglossia - BMI 30 - Tonsillar hypertrophy - Elongated uvula - High arched palate - Large neck circumference Screen for OSA Clinical features of OSA: - Daytime Sleepiness - Non-restorative sleep - Witnessed apneas - Snoring - Insomnia - Memory loss - Lack of concentration - Mood changes - Morning headaches - Polycythemia - Hypercapnia - Nocturia - Irritability - Decreased libido Sleep Study (1) LJ Epstein et al, JCSM, 2009 Cardinal symptoms of COPD and OSA Mieczkowski B et al, Int J Chron Obstruct Pulmon Dis 2014 3
STOP-BANG questionnaire Snoring Tiredness Observed you stop breathing Blood Pressure BMI > 35 Age > 50 Neck Circumference > 40 cm Gender Male High Risk : Yes to 3 items Refer for sleep testing Chung F. et al, Anesthesiology, May 2008 Johns MW, Sleep 1991 Sleep Apnea Clinical Score Components: Neck Circumference, hypertension, habitual snoring and partner reports of nocturnal choking/gasping Sleep Apnea Clinical Score (SACS) of < 5 had a likelihood ratio of 0.25 ( 95% CI 0.15-0.42) and a post-test probability of 17% for having OSA SACS of > 15 had a likelihood ratio of 5.17 (95% CI 2.54-10.51) and a posttest probability of 81% for having OSA Flemons WW et al, AJRCCM 1994 4
Sleep Apnea Clinical Score Flemons WW et al, AJRCCM 1994 Predictor of OSA in patients with COPD SACS outperformed Berlin Questionnaire and Epworth Sleepiness Score in predicting OSA in COPD patients in one study, with area under the curve 0.82, 95% CI 0.606-0.943, p = 0.02 Faria AC et al, Int J Gen Med 2015 Authors Chaouat 265 Resta 213 De Miguel 193 Number of patients Sanders 1132 Zamarrón 300 Bednarek 676 O Brien 120 Sample Group Prevalence Sleep Laboratory Sleep Laboratory Sleep Laboratory General population Sleep Laboratory General population Sleep Laboratory OSAS 11% OSAS 13.6% OSAS 28.5% COPD 14% OSAS 15.4% OSAS 9.2% OSAS 11.9% Prevalence of OSA-COPD Overlap Syndrome 5
McNicholas, WT, Impact of Sleep on Respiration, Chest 2000 A) Forces affecting thoracic function and FRC in supine sleep B) Limitation of diaphragm excursion with hyperinflation Mieczkowski B et al, Int J Chron Obstruct Pulmon Dis 2014 COPD McSharry DG et al, Sleep Quality in COPD, Respirology, July 2012 Daytime Hypoxemia REM sleep 6
Factors in COPD that influence OSA risk Promoting factors for OSA Oxygen desaturation Protective factors against OSA Low BMI Rostral fluid shift when supine Cigarette smoking Decreased REM sleep Medications such as theophylline Steroids Pathogenesis of COPD-OSA Overlap Syndrome Owens RL et al, Respir Care, 10/2010 Prognosis of COPD-OSA Overlap Syndrome Owens RL et al, Respir Care, 10/2010 7
When should COPD patients be screened for OSA? Waking hypercapnia out of proportion to the severity of airflow obstruction Moderate to severe nocturnal desaturation Pulmonary and systemic hypertension Heart Failure Lower tidal volume and higher respiratory rate seen in overlap syndrome patients (1) (1) Radwan L et al, Eur Respir J April 1995 Diagnosis of OSA in COPD patients Overnight oximetry: Assessment of the desaturation index can help to screen patients with a high pre-test probability of OSA (1) Utility of oximetry as a screening tool for OSA declines in moderate to severe COPD (2) Nocturnal end tidal/transcutaneous CO2 In-laboratory polysomnography is the gold standard (1) Bogdan M et al, Maedica Sept 2013 (2) Scott AS et al, Can Respir J 2014 Characteristics of nocturnal oxygen desaturation In COPD patients Occurs mainly in REM sleep Night to night variability Awake SO2 does not predict nocturnal oxygen desaturation Statistically significant correlation between nocturnal desaturation and daytime hypoxemia and hypercarbia In OSA patients Episodic intermittent oxygen desaturation which recovers with end of the apneic event More pronounced in REM sleep Nocturnal variability related to %REM and %supine sleep 8
Intermittent Hypoxemia pattern in OSA Bogdan M et al, Maedica Sept 2013 Nocturnal Oximetry and heart rate in COPD Overnight hypnogram showing continued oxygen desaturation in REM sleep despite positive airway pressure titration in COPD-OSA overlap syndrome Mieczkowski B et al, Int J Chron Obstruct Pulmon Dis 2014 9
Types of Sleep Studies Type I: in-lab attended polysomnogram (gold standard, 7 channels) Type II: comprehensive portable unattended polysomnogram ( 7 channels) Type III: modified portable sleep apnea testing (cardiorespiratory sleep studies, 4-7 channels) Type IV: 1 or 2 channels, oximetry is 1 channel Practice parameters for the use of portable recording in the assessment of obstructive sleep apnea. Sleep 1994 Types of sleep studies Diagnostic PSG Split PSG Titration PSG AHI 40/hour or 20-40/hour with low SO2 Physician specified AHI Indications for Portable Monitoring PM is done only in conjunction with a comprehensive sleep evaluation PM is only indicated in patients with a high pretest probability of moderate to severe OSA No PM in patients with co-morbid conditions or other sleep disorders PM is NOT for screening asymptomatic individuals PM measures AHI/total recording time, so underestimates AHI Collop, N. et al, JCSM, October 2007 10
Treatment of OSA Positive Airway Pressure Oral appliances Upper airway surgery New treatments Adjunctive therapy -CPAP -BIPAP -BIPAP ST -APAP -Tongue retaining device - Mandibular repositioning device -UPPP -Adenotonsillectomy -Genioglossus advancement -Hyoid suspension -Mandibular advancement -Tongue reduction -Maxillomandibular advancement -Tracheostomy -Hypoglossal nerve stimulation -Provent -Bariatric surgery -Leukotriene inhibitors -Nasal steroids AASM guidelines on Positive Airway Pressure treatment CPAP is indicated for moderate to severe OSA and is optional for mild OSA BIPAP can be used where high pressure is needed with difficulty on exhalation and with coexisting central hypoventilation (1) Auto-titrating CPAP should not be used in patients with comorbidities such as COPD and congestive heart failure (2) (1) Kushida CA et al, Sleep 2006 (2) Morgenthaler TI et al, Sleep 2008 Nocturnal oxygen in Overlap Syndrome Oxygen (1): improves pulmonary hypertension Shortens sleep onset latency Increases REM and N3 sleep Decreases nocturnal arousals Careful titration of oxygen flow rate to avoid hypercapnia Recommended as adjunctive treatment to correct hypoxemia after optimal titration of positive airway pressure (1) C Zamarron et al, Int Journal of COPD, 2008 11
Other treatment considerations Bronchodilators: theophylline, ipratropium, tiotropium Avoid hypnotics and alcohol Protriptyline as a REM suppressant Lung volume reduction surgery (1): improved total sleep time, sleep efficiency, mean and lowest nocturnal SO2 in the National Emphysema Treatment Trial (1) Krachman SL et al, Chest 2005 BIPAP in COPD-OSA Overlap Syndrome No evidence of survival benefit in the overlap syndrome BIPAP may improve gas exchange, dyspnea, quality of life, and decrease hospitalizations in chronic stable, hypercapnic COPD (1) (1) Duiverman ML et al, Respir Care, 2011 Treatment options for COPD-OSA overlap syndrome Jen R et al, Can Respir J 2016 12
Conclusions Better epidemiologic studies are needed to determine the exact prevalence of COPD-OSA overlap syndrome COPD-OSA overlap syndrome is associated with significant adverse consequences and should be aggressively treated 13