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Research Priorities in Pathophysiology for Sleep-Disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. An AMERICAN THORACIC SOCIETY DOCUMENTS Research Priorities in Pathophysiology for Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease An Official American Thoracic Society Research Statement Atul Malhotra, Alan R. Schwartz, Hartmut Schneider, Robert L. Owens, Pamela DeYoung, MeiLan K. Han, Jadwiga A. Wedzicha, Nadia N. Hansel, Michelle R. Zeidler, Kevin C. Wilson, and M. Safwan Badr; on behalf of the ATS Assembly on Sleep and Respiratory Neurobiology THIS OFFICIAL RESEARCH STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS APPROVED DECEMBER 2017 Background: Obstructive sleep apnea (OSA) and chronic was not a formal systematic review. Evidence was considered and obstructive pulmonary disease (COPD) are common conditions; supplemented with the panelists’ nonsystematic clinical the co-occurrence of these diseases, called the overlap syndrome observations. Important knowledge gaps were identified. (OVS), has been associated with poor health outcomes. Results: Recommendations for research to fill existing knowledge Purpose: The purpose of this Official American Thoracic Society gaps were made. The recommendations were formulated by Research Statement is to describe pathophysiology, epidemiology, discussion and consensus. outcomes, diagnostic metrics, and treatment of OVS, as well as to identify important gaps in knowledge and make recommendations Conclusions: Many important questions about OVS exist. This for future research. American Thoracic Society Research Statement highlights the types of research that leading clinicians and researchers believe will Methods: Clinicians and researchers with expertise in sleep have the greatest impact on better understanding the spectrum of medicine, pulmonary medicine, or both were invited to participate. disease, improving diagnosis, and optimizing therapy. Topics were divided among the participants according to their interest and expertise. A literature search was conducted; the search Keywords: lung; sleep; COPD; hypoxia; apnea Contents Is the AHI Useful in Patients with Should Supplemental Overview COPD? Oxygen Be Withdrawn Key Conclusions Is “Sleep Apnea” the for Overnight Recommendations Appropriate Term in Patients Polysomnography in Introduction with COPD? Patients with Suspected Methods Is REM-related Oxygen OVS? Significance of SDB in COPD Desaturation Predictive of Poor Revisiting the Sleep Study Pathophysiology Outcomes in Patients with Polysomnographic Features of Diagnosis COPD? SDB in COPD Epidemiology Is Capnometry Valuable in SDB in COPD Outcomes Sleep Studies of Patients with Sample Cases Appraisal of Existing Metrics COPD? Conclusions Correspondence and requests for reprints should be addressed to Atul Malhotra, M.D., University of California San Diego, Pulmonary, Critical Care, and Sleep Medicine, 9300 Campus Point Drive, #7381, La Jolla, CA 92037. E-mail: [email protected]. This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org. Am J Respir Crit Care Med Vol 197, Iss 3, pp 289–299, Feb 1, 2018 Copyright © 2018 by the American Thoracic Society DOI: 10.1164/rccm.201712-2510ST Internet address: www.atsjournals.org American Thoracic Society Documents 289 AMERICAN THORACIC SOCIETY DOCUMENTS Overview of hypoxemia, nadir of hypoxemia, increasing in epidemic proportions because and area under the oxygen desaturation of the aging population, indoor and The overlap syndrome (OVS) is the curve) as predictors of clinical outcomes outdoor air pollution, historical smoking co-occurrence of chronic obstructive in patients with COPD. trends, and other factors (1). Efforts to pulmonary disease (COPD) and obstructive d We recommend that future research slow the progression of COPD have failed sleep apnea (OSA). This statement evaluate sleep-disordered breathing in the majority of patients, and research summarizes the existing literature, identifies (i.e., central sleep apnea, OSA, increased seeks to identify new therapeutic knowledge gaps, and provides guidance upper airway resistance, hypoventilation, approaches to improve COPD-related regarding future priorities in research for sleep fragmentation, etc.), rather than outcomes. Like COPD, obstructive sleep sleep-disordered breathing (SDB) in OSA specifically, in patients with COPD. apnea (OSA) has a high prevalence patients with COPD and other lung diseases. d We recommend studies that seek to and is associated with adverse health determine the pathophysiology of consequences (2–4). Patients with both oxygen desaturation during REM OSA and COPD are considered to have Key Conclusions sleep in patients with COPD. the overlap syndrome (OVS), which is d OVS is common because COPD and d fi We recommend trials that compare associated with particularly poor outcomes, OSA are common. There is no de nitive bilevel positive airway pressure to both including high mortality (5, 6). This evidence that patients with COPD are at continuous positive airway pressure and observation has led to an increased focus increased risk for developing OSA. no positive airway pressure therapy in on sleep as an important factor in the care d Mortality associated with OVS is higher patients with COPD who desaturate of the patient with COPD. than mortality associated with either during REM sleep. There exist many important questions COPD alone or OSA alone. Other d We recommend trials that compare about sleep-disordered breathing (SDB) in outcomes are likely worse too but have various methods of measuring gas COPD. Is the pathophysiology of SDB not been adequately measured. exchange in patients with OVS. As unique/special in COPD? How prevalent is d fi The optimal criteria for con rming examples, trials that compare pulse SDB in COPD? Does SDB affect clinical OSA in patients with COPD are unclear. oximetry plus transcutaneous CO2 outcomes in COPD? Should different The usual criteria for OSA rely on measurement to pulse oximetry alone, metrics be used to identify SDB in counting apneas and hypopneas, but the pulse oximetry plus transcutaneous CO2 COPD? Are there polysomnographic predictive values of these respiratory measurement to arterial blood gas characteristics of SDB that are unique in events are unclear in COPD and, measurement, and pulse oximetry plus COPD? How should positive airway therefore, might lead to missed transcutaneous CO2 measurement to pressure therapy be used to treat SDB in diagnoses. fl pulse oximetry plus end-tidal CO2 COPD, given the con icting evidence measurement. (7–10)? How should supplemental oxygen Recommendations d We recommend trials that compare be used in patients with SDB and COPD, d We recommend investigations that supplemental oxygen to both continuous given the uncertain benefits in patients seek to understand mechanisms positive airway pressure therapy and with COPD and either exertional or underlying impaired respiratory bilevel positive airway pressure in nocturnal hypoxemia (11)? mechanics during sleep and how this patients with COPD who exhibit The purpose of this American Thoracic understanding might guide therapy nocturnal oxygen desaturation. Society research statement is to summarize to prevent complications. d We recommend research to develop existing evidence, identify knowledge gaps, d We recommend studies that improve our devices that can identify and characterize and make specific recommendations that understanding of gas exchange sleep without EEG. The goal is to pertain to SDB in patients with COPD. impairment during sleep in COPD. improve the assessment of the severity of d We recommend studies that investigate sleep-disordered breathing in patients whether there is a direct correlation with disruptions in sleep architecture. Methods between the prevalence of OSA and d We recommend studies that compare the severity of COPD. various methods to assess and quantify This research statement was developed d We recommend observational studies ventilation, the severity of inspiratory according to the rules of the American that compare clinical outcomes among and expiratory flow limitation, and the Thoracic Society. Details are provided in the patients with OVS to clinical outcomes presence of hyperinflation during online supplement. among patients with OSA alone or sleep (e.g., pneumotachography, nasal COPD alone. pressure signaling, and flow sensors) in d We recommend randomized trials that patients with COPD. Significance of SDB in COPD compare clinical outcomes among patients with OVS whose OSA is treated Pathophysiology to clinical outcomes among patients Introduction COPD is associated with abnormalities in with OVS whose OSA is untreated. respiratory mechanics and gas exchange d We recommend studies that compare the Chronic obstructive pulmonary disease (12). As a result, sleep is not a period of rest apnea–hypopnea index with other (COPD) is a major source of morbidity, for the respiratory system, but rather a measures of OSA severity (e.g., duration mortality, and healthcare costs. It is physiological challenge for patients with 290 American Journal of Respiratory and Critical Care Medicine Volume 197 Number 3 | February 1 2018 AMERICAN THORACIC SOCIETY DOCUMENTS impaired pulmonary mechanics. During hyperinflation and increase the work of Patients with COPD may manifest sleep, the drive to breathe that is normally breathing. Patients with COPD have a subtle oscillations in ventilation, sleep provided by wakefulness is lost (Figure 1). physiological need to lengthen their architecture, and oxygenation that do not This change is associated
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