Research Priorities in Pathophysiology for Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Research Statement

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Abstract

Background: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common conditions; the co-occurrence of these diseases, called the overlap syndrome (OVS), has been associated with poor health outcomes. Purpose: The purpose of this Official American Thoracic Society Research Statement is to describe pathophysiology, epidemiology, outcomes, diagnostic metrics, and treatment of OVS, as well as to identify important gaps in knowledge and make recommendations for future research. Methods: Clinicians and researchers with expertise in sleep medicine, pulmonary medicine, or both were invited to participate. Topics were divided among the participants according to their interest and expertise. A literature search was conducted; the search was not a formal systematic review. Evidence was considered and supplemented with the panelists’ nonsystematic clinical observations. Important knowledge gaps were identified. Results: Recommendations for research to fill existing knowledge gaps were made. The recommendations were formulated by discussion and consensus. Conclusions: Many important questions about OVS exist. This American Thoracic Society Research Statement highlights the types of research that leading clinicians and researchers believe will have the greatest impact on better understanding the spectrum of disease, improving diagnosis, and optimizing therapy.

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A putative flip-flop switch for control of REM sleep.

Jun Lu, David Sherman, Marshall Devor … (2006)

Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip-flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip-flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions-for example, in narcolepsy.

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Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome.

Santiago Carrizo, Ray M. Marín, Bartolome R Celli … (2010)

Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) (overlap syndrome) are more likely to develop pulmonary hypertension than patients with either condition alone. To assess the relation of overlap syndrome to mortality and first-time hospitalization because of COPD exacerbation and the effect of continuous positive airway pressure (CPAP) on these major outcomes. We included 228 patients with overlap syndrome treated with CPAP, 213 patients with overlap syndrome not treated with CPAP, and 210 patients with COPD without OSA. All were free of heart failure, myocardial infarction, or stroke. Median follow-up was 9.4 years (range, 3.3-12.7). End points were all-cause mortality and first-time COPD exacerbation leading to hospitalization. After adjustment for age, sex, body mass index, smoking status, alcohol consumption, comorbidities, severity of COPD, apnea-hypopnea index, and daytime sleepiness, patients with overlap syndrome not treated with CPAP had a higher mortality (relative risk, 1.79; 95% confidence interval, 1.16-2.77) and were more likely to suffer a severe COPD exacerbation leading to hospitalization (relative risk, 1.70; 95% confidence interval, 1.21-2.38) versus the COPD-only group. Patients with overlap syndrome treated with CPAP had no increased risk for either outcome compared with patients with COPD-only. The overlap syndrome is associated with an increased risk of death and hospitalization because of COPD exacerbation. CPAP treatment was associated with improved survival and decreased hospitalizations in patients with overlap syndrome.

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The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index.

Megan Thornton, R. Pierce, Warren R Ruehland … (2009)

To compare apnea-hypopnea indices (AHIs) derived using 3 standard hypopnea definitions published by the American Academy of Sleep Medicine (AASM); and to examine the impact of hypopnea definition differences on the measured prevalence of obstructive sleep apnea (OSA). Retrospective review of previously scored in-laboratory polysomnography (PSG). Two tertiary-hospital clinical sleep laboratories. 328 consecutive patients investigated for OSA during a 3-month period. N/A. AHIs were originally calculated using previous AASM hypopnea scoring criteria (AHI(Chicago)), requiring either >50% airflow reduction or a lesser airflow reduction with associated >3% oxygen desaturation or arousal. AHIs using the "recommended" (AHI(Rec)) and the "alternative" (AHI(Alt)) hypopnea definitions of the AASM Manual for Scoring of Sleep and Associated Events were then derived in separate passes of the previously scored data. In this process, hypopneas that did not satisfy the stricter hypopnea definition criteria were removed. For AHI(Rec), hypopneas were required to have > or =30% airflow reduction and > or =4% desaturation; and for AHI(Alt), hypopneas were required to have > or =50% airflow reduction and > or =3% desaturation or arousal. The median AHI(Rec) was approximately 30% of the median AHI(Chicago), whereas the median AHI(Alt), was approximately 60% of the AHI(Chicago), with large, AHI-dependent, patient-specific differences observed. Equivalent cut-points for AHI(Rec) and AHI(Alt), compared to AHI(Chicago) cut-points of 5, 15, and 30/h were established with receiver operator curves (ROC). These cut-points were also approximately 30% of AHI(Chicago) using AHI(Rec) and 60% of AHI(Chicago) using AHI(Alt). Failure to adjust cut-points for the new criteria would result in approximately 40% of patients previously classifled as positive for OSA using AHI(Chicago) being negative using AHI(Rec) and 25% being negative using AHI(Alt). This study demonstrates that using different published standard hypopnea definitions leads to marked differences in AHI. These results provide insight to clinicians and researchers in interpreting results obtained using different published standard hypopnea definitions, and they suggest that consideration should be given to revising the current scoring recommendations to include a single standardized hypopnea definition.