High Prevalence of Obstructive Sleep Apnea in Patients with Moderate to Severe COPD

Rationale: Chronic obstructive pulmonary disease (COPD) is the most common form of lung disease, the third leading cause of death in developed countries and, therefore, a major burden in morbidity and health care costs. (1) The prevalence is estimated to be at least 10% in adults in the western world. (2, 3) Obstructive sleep apnea (OSA), a form of sleep disordered breathing (SDB), is present in approximately 6-13% in the general US population. (4, 5) When both OSA and COPD co-exist, so called ‘overlap’ syndrome, a high risk for mortality and morbidity has been reported. There is controversy about the prevalence of OSA in people affected with COPD. (6-8) Objectives: The purpose of this study was to investigate objective meaures of SDB in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA. Methods: Fifty-four patients (54% male) with moderate to severe COPD were enrolled prospectively (mean ± SD, FEV1 = 42.8 ± 19.8 %pred, and FEV1/FVC = 42.3 ± 13.1). Twenty five patients were on supplemental oxygen at baseline. Exercise tolerance, questionnaires related to symptoms, sleep, and quality of life, and home polysomnography were obtained. Measurements and Main Results: Forty-four patients had full polysomnography suitable for analysis. OSA (apnea hypopnea index AHI greater than 5/h) was present in 23 subjects (52 %). Sleep efficiency was poor in 45% of subjects. Conclusions: Obstructive sleep apnea is highly prevalent in moderate to severe COPD patients referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greater-than-expected SDB which could be an important contributory Page 2 of 30 ANNALSATS Articles in Press. Published on 14-April-2015 as 10.1513/AnnalsATS.201407-336OC Copyright © 2015 by the American Thoracic Society factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD. Abstract Word Count: 296 Page 3 of 30 ANNALSATS Articles in Press. Published on 14-April-2015 as 10.1513/AnnalsATS.201407-336OCWord Count: 296 Page 3 of 30 ANNALSATS Articles in Press. Published on 14-April-2015 as 10.1513/AnnalsATS.201407-336OC Copyright © 2015 by the American Thoracic Society Chronic obstructive pulmonary disease (COPD) is a mostly preventable disease characterized by airflow obstruction that is not fully reversible. (9) COPD is a major global epidemic that occurs in >10% of adults over 40 years of age. COPD accounts for >5% of physician office visits and 13% of all hospitalizations and has recently become the 3 rd leading cause of death in the U.S.(1-3, 10, 11) In a multicenter epidemiological study, COPD was found in 15.8% of men and 5.5% of women. (12) A recognized cause of death and co-morbidity in COPD subjects is the presence of cardiovascular events such as stroke, acute coronary syndrome, pulmonary embolism, or arrhythmias. Because of lack of awareness and somewhat vague symptoms, COPD is underappreciated and underdiagnosed. Obstructive sleep apnea (OSA) is a form of sleep disordered breathing (SDB) defined by total or partial intermittent collapse of the upper airway, resulting in nocturnal hypoxemia and arousals from sleep. (7, 13) Peppard and colleagues found that 6-13% of people had clinically important OSA, a rate which has increased substantially over the past few decades. (4, 5, 13, 14) Prevalence of OSA increases with age, similar to COPD. (15) Also, COPD as well as OSA symptoms appear slowly over time, and therefore can be easily overlooked. Furthermore, the detrimental cardiovascular effects of OSA are well recognized and can be present even in patients without daytime sleepiness. (16-18) The presence of both OSA and COPD was termed the “Overlap” Syndrome by Flenley. (6, 8, 19-21) The prevalence of OSA among COPD varies across different studies. (6) Some epidemiologic studies have reported OSA to be present in about 10-15% of patients with COPD, similar to the general population. (7, 8) Page 4 of 30 ANNALSATS Articles in Press. Published on 14-April-2015 as 10.1513/AnnalsATS.201407-336OC Copyright © 2015 by the American Thoracic Society Little is known about the pathophysiological and clinical consequences of having concomitant COPD and OSA. Recent studies have demonstrated that patients with COPD-OSA have a high risk of death as well as increased risk of exacerbations if OSA remains untreated. (8, 22, 23) Also, people with COPD-OSA have more profound hypoxemia (both day and night) compared with patients having either condition alone. (21) The more pronounced nocturnal oxygen desaturation seen in overlap patients may predispose to pulmonary hypertension. (21) In patients with OSA, the presence of COPD increases the risk of death 7-fold. (24) Therefore, evaluating the presence of OSA in patients with advanced COPD seems logical as concurrence of these diseases may potentially explain the high cardiovascular morbidity and mortality in these patients. Pulmonary Rehabilitation (PR), a well-established treatment for patients with chronic lung diseases, enhances standard therapy and helps to control and alleviate symptoms, optimize function, and reduce medical and economic burdens of disease. (25-33) Patients are typically referred to PR at advanced stages of the disease with associated co-morbid conditions. The prevalence of the overlap syndrome in this at risk population is unknown. To that end, we investigated sleep characteristics of patient's enrolling in a single site pulmonary rehabilitation program to determine the prevalence and nature of disordered sleep. Page 5 of 30 ANNALSATS Articles in Press. Published on 14-April-2015 as 10.1513/AnnalsATS.201407-336OC Copyright © 2015 by the American Thoracic Society