Sleep Disordered Breathing


 

A Comparison of Different Success Definitions in Non-Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea Using Cardiopulmonary Coupling

Authors:
Woo Hyun Lee, Seung-No Hong, Hong Joong Kim, Chae-Seo Rhee, Chul Hee Lee, In-Young Yoon, Jeong-Whun Kim

Reference:
Journal of Clinical Sleep Medicine 2016;12(1):35–41.

Objectives:
The definition and the criteria for the successful treatment of obstructive sleep apnea vary, depending on the study. This study aimed to compare different success criteria of non-continuous positive airway pressure (non-CPAP) treatment for obstructive sleep apnea in terms of sleep quality by using cardiopulmonary coupling.


 

Conclusions:
Cardiopulmonary coupling analysis showed that a reduction in the apnea-hypopnea index of more than 50% might be the optimal criterion to determine the success or failure of non-CPAP treatment in terms of sleep quality.

Practical Significance:
The parameters of cardiopulmonary coupling indicated that sleep quality improved with non-CPAP treatment: low-frequency coupling decreased from 57.4% ± 17.7% to 46.9% ± 16.5%, whereas high-frequency coupling increased from 30.2% ± 17.1% to 37.4% ± 16.7%. In multiple regression analysis, only the criterion of a reduction in the apnea-hypopnea index greater than 50% was significantly associated with sleep quality improvement (p = 0.016; 95% confidence interval, 1.008–1.076 in the high-frequency coupling increment; p = 0.001; 95% confidence interval, 1.025–1.099 in the low-frequency coupling decrement).

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Ambulatory screening tool for sleep apnea: analyzing a single-lead electrocardiogram signal (ECG)

Authors:
S Magnusdottir, H Hilmisson

Reference:
Sleep Breath 2017; 22(2): 421-429. DOI: 10.1007/s11325-017/-1566-6

Objectives:
The goal was to determine the utility and accuracy of automated analysis of single-lead electrocardiogram (ECG) data using two algorithms, cardiopulmonary coupling (CPC), and cyclic variation of heart rate (CVHR) to identify sleep apnea (SA).

Conclusions:
The CPC+CVHR technology performed as accurately as the automated scoring software to identify patients with moderate to severe SA, demonstrating a clinically powerful tool that can be implemented in various clinical settings to identify patients at risk for SA.

Practical Significance:
A high degree of agreement was noted between the CPC-CVHR against both the manually rescored AHI and the computerized scored AHI to identify patients with moderate and severe sleep apnea (AHI > 15). The combined CPC+CVHR algorithms, when compared to the manually scored PSG output presents sensitivity 89%, specificity 79%, agreement 85%, PPV (positive predictive value) 0.86 and NPV (negative predictive value) 0.83, and substantial Kappa 0.70. Comparing the output of the automated scoring software to the manual scoring demonstrated sensitivity 93%, specificity 79%, agreement 87%, PPV 0.87, NPV 0.88, and substantial Kappa 0.74.

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An Early Indicator of Complex Sleep Apnea

Authors:
Schramm PJ.

Reference:
Advance for Respiratory Care and Sleep Medicine June 21, 2010

Objectives:
Demonstration of the impact on a Complex Sleep Apnea patient’s sleep quality with CPAP versus ASV using CPC to detect stable and unstable sleep.

Conclusions:
CPC variables indicated that the patient’s sleep quality had improved objectively. Subjectively, the patient reported his sleep more restful when using the combination of ASV at 9cm H2O and added dead space compared to CPAP.

Practical Significance:
This study highlights that the presence of e-LFCNB can help identify complex sleep apnea both before and after initiation of PAP therapy. A second CPC study following the application of ASV with dead space showed improved quality of sleep in the form of increased HFC, which corresponded well with the patients subjective findings.

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An electrocardiogram-based analysis evaluating sleep quality in patients with obstructive sleep apnea.

Authors:
Harrington J, Schramm PJ, Davies CR, Lee-Chiong TL Jr.

Reference:
Sleep Breath. 2013 Sep;17(3):1071-8.

Objectives:
The study compares polysomnography (PSG) and cardiopulmonary coupling (CPC) sleep quality variables in patients with (1) obstructive sleep apnea (OSA) and (2) successful and unsuccessful continuous positive airway pressure (CPAP) response.

Conclusions:
Tests differentiated no and moderate to severe OSA groups by REM %, HFC, VLFC, and LFC/HFC ratio variables. The successful CPAP therapy group had more HFC, less LFC, and e-LFCBB compared to the unsuccessful CPAP therapy group. HFC ≥ 50 % showed high sensitivity (77.8 %) and specificity (88.9 %) in identifying successful CPAP therapy.

Practical Significance:
The results support the use of the SleepImage system to investigate and objectively measure sleep quality in patients complaining of a sleep disorder.

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Analysis of cardiopulmonary coupling to assess adaptive servo-ventilation success in complex sleep apnea management.

Authors:
Ramar K, Desrues B, Ramar P, Morgenthaler TI.

Reference:
Sleep Breath. 2013 May;17(2):861-6.

Objectives:
ASV success would correlate with elevated proportions of periodic breathing as marked by elevated narrow band low-frequency cardiopulmonary coupling (eNB-LFC) on cardiopulmonary coupling (CPC) analysis.

Conclusions:
ASV brought AHI to 11.0 ± 13.0, with success in 81.1 % of patients, as defined by an AHI of <10/h. NB-LFC was elevated (>0) in 45.3 %; however, the percentage of eNB-LFC did not correlate with ASV treatment success (p = 0.518). No clinical factors were found to be associated with ASV success.

Practical Significance:
ASV was successful in 81 % of patients with CompSAS. However, eNB-LFC calculated from CPC, a marker for periodic breathing, did not correlate with ASV success and therefore may not be a useful tool to predict ASV success.

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Assessment of therapeutic options for mild obstructive sleep apnea using cardiopulmonary coupling measures.

Authors:
Schramm PJ, Thomas RJ

Reference:
J Clin Sleep Med. 2012 Jun 15;8(3):315-20.

Objectives:
To examine the efficacy of various therapeutic modalities for mild obstructive sleep apnea using cardiopulmonary coupling variables of sleep quality.

Conclusions:
Baseline sleep quality estimated using the ratio of high-frequency and low-frequency coupling (1.03) was below the expected normal adult values ranging from 1.67-4.0. The sleep quality ratio was significantly higher (2.08) using the MAA alone compared to baseline, sleep position restriction (1.61), oxygen therapy (0.81), and the combination of MAA with oxygen (1.66).

Practical Significance:
Sleep quality measured objectively using cardiopulmonary coupling variables differentiated the efficacy of therapeutic options for mild obstructive sleep apnea.

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Cardiopulmonary coupling analysis: changes before and after treatment with a mandibular advancement device.

Authors:
Lee WH, Ahn JC, We J, Rhee CS, Lee CH, Yun PY, Yoon IY, Kim JW.

Reference:
Sleep Breath. 2014 Apr 4.

Objectives:
To evaluate the changes of sleep quality in patients using a mandibular advancement device (MAD) for obstructive sleep apnea (OSA) based upon cardiopulmonary coupling (CPC).

Conclusions:
The CPC parameters showed a significant improvement with the use of MAD.

Practical Significance:
CPC parameters of sleep quality was improved by MAD therapy and could be used as a measure of treatment efficacy.

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Differentiating Obstructive from Central & Complex Sleep Apnea Using an Automated Electrocardiogram-based Method

Authors:
Thomas RJ, Mietus JE, Peng CK, Gilmartin G, Daly RW, Goldberger AL, Gottlie DJ.

Reference:
Sleep. 2007 Dec;30(12):1756-69.

Objectives:
Complex sleep apnea is defined as sleep disordered breathing secondary to simultaneous upper airway obstruction and respiratory control dysfunction. The objective of this study was to assess the utility of an electrocardiogram (ECG) based CPC technique to distinguish obstructive from central or complex sleep apnea

Conclusions:
ECG based spectral analysis allows automated, operator-independent characterization of probable interactions between impaired respiration and upper airway anatomical obstruction. The clinical utility of spectrographic classification, especially in predicting failure of positive airway pressure therapy, remains to be more thoroughly tested

Practical Significance:
Using the Heart Health Study population of 3989 subjects, this study shows that CPC not only differentiated obstructive vs. central vs. complex sleep apnea, but it positively correlated with periodic breathing episodes in PSG and was the strongest predictor of success or failure with PAP titration.

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Distinct polysomnographic and ECG-spectrographic phenotypes embedded within obstructive sleep apnea

Authors:
Robert Joseph Thomas, Chol Shin, Matt Travis Bianchi, Clete Kushida and Chang-Ho Yun

Reference:
Sleep Science and Practice 20171:11, 10.1186/s41606-017-0012-9

Objectives:
The primary metric extracted from the polysomnogram in patients with sleep apnea is the apnea-hypopnea
index (or respiratory disturbance index) and its derivatives. Other phenomena of possible importance such as periods of stable breathing, features suggestive of high respiratory control loop gain, and sleep fragmentation phenotypes are not commonly generated in clinical practice or research. A broader phenotype designation can provide insights into biological processes, and possibly clinical therapy outcome effects.
 

Conclusions:
Distinct phenotypes are readily seen at all severities of sleep apnea, and can be identified from conventional polysomnography. The ECG-spectrogram analysis provides further phenotypic differentiation.

Practical Significance:
The dataset used for this study was the archived baseline diagnostic polysomnograms from the Apnea Positive Pressure Long-term Efficacy Study (APPLES). The electrocardiogram (ECG)-derived cardiopulmonary coupling sleep spectrogram was computed from the polysomnogram. Sleep fragmentation phenotypes used thresholds of sleep efficiency (SE) ≤ 70%, non-rapid eye movement (NREM) sleep N1 ≥ 30%, wake after sleep onset (WASO) ≥ 60 min, and high frequency coupling (HFC) on the ECG-spectrogram ≤ 30%. Sleep consolidation phenotypes used thresholds of SE ≥ 90%, WASO ≤ 30 min, HFC ≥ 50% and N1 ≤ 10%. Multiple and logistic regression analysis explored cross-sectional associations with covariates and across phenotype categories. NREM vs. REM dominant apnea categories were identified when the NREM divided by REM respiratory disturbance index (RDI) was > 1.

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Electrocardiogram-Based Sleep Spectrogram Measures of Sleep Stability and Glucose Disposal in Sleep Disordered Breathing

Authors:
Pogach, MD; Naresh M. Punjabi, MD, PhD; Neil Thomas; Robert J. Thomas, MD

Reference:
SLEEP 201235(1):139-148

Objectives:
This analysis explored associations between glucose metabolism and an EEG-independent measure of sleep quality, the sleep spectrogram, which maps coupled oscillations of heart-rate variability and electrocardiogram (ECG)-derived respiration.

Conclusions:
The ECG-spectrogram analysis of sleep quality may provide information beyond that obtained by conventional polysomnography (PSG) in relationship to glucose metabolism

Practical Significance:
Experimental sleep fragmentation can impair insulin sensitivity. ECG-derived sleep-spectrogram measures of sleep quality are associated with alterations in glucose-insulin homeostasis. This could improve our understanding of sleep and sleep-breathing effects on glucose metabolism.

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Electrophysiological Difference in Obstructive Sleep Apnea with and without REM sleep Behavior Disorder: Cardiopulmonary Coupling Analysis

Authors:
Yun Kyung Park, Su Jung Choi and Eun Yeon Joo

Reference:
None cited.

Objectives:
Although rapid eye movement behavior disorder (RBD) and obstructive sleep apnea syndrome (OSA) have different pathophysiology, RBD patients with OSA appeared to have more stable sleep compared to patients with OSA and to verify it by cardiopulmonary coupling (CPC) method.

Conclusions:
In terms of autonomic-respiratory interaction, RBD with OSA showed similar CPC profile (higher LFC and lower HFC than normal) to OSA group but less severe than pure OSA group. It suggests that RBD may have a protective effect on OSA.

Practical Significance:
The polysomnography (PSG) data of 138 subjects with OSA (AHI ≥ 15), RBD with OSA (AHI ≥ 15), RBD, normal control (N=32, 26, 29, 51, respectively) were collected. For conducting case control study between RBD with OSA and patients with OSA only, a total of 32 OSA controls, matched for age, AHI and BMI were recruited. CPC parameters were obtained using CPC analyzer in Rem Logic. Sleep spectrogram by CPC analyses revealed the percentage of stable tidal volume [high-frequency coupling (HFC), 0.1–0.4 Hz] and fluctuation tidal volume [lowfrequency coupling (LFC), 0.01 Hz to 0.1 Hz)] during sleep.

Although there was no significant Apnea-Hypopnea index (AHI) difference between RBD with OSA and OSA group (AHI 29.1 ± 15.6/hr vs. 34.1 ± 18.9, p=0.332), there was significant difference in CPC measurements. In RBD-OSA group showed lower LFC (35.9 ± 16.8 vs. 49.7 ± 21.3, p=0.010) than OSA group. Unlike higher AHI in RBD with OSA than RBD group (29.1 ± 15.6/hr vs. 3.2 ± 1.6, p<0.001), there was no significant difference in CPC study. Both OSA group and RBD with OSA group showed higher LFC (OSA vs. normal: 49.7 ± 21.3 vs. 28.4 ± 13.3, p<0.001, RBD with OSA vs. normal: 35.9 ± 16.8 vs. 28.4 ± 13.2 p=0.035) and lower HFC (OSA vs. normal: 37.5 ± 20.0 vs. 56.2 ± 16.2, p<0.001, RBD with OSA vs. normal: 46.8 ± 20.8 vs. 56.2 ± 16.2, p=0.031) when compared with normal control group, respectively.

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Heritability of Abnormalities in in Sleep Apnea: Use of an Electrocardiogram-based Technique

Authors:
Ibrahim LH, Jacono FJ, Patel SR, Thomas RJ, Larkin EK, Mietus JE, Peng CK, Goldberger AL, Redline S

Reference:
SLEEP 2010;33(5):643-646

Objectives:
To evaluate the familial aggregation of distinctive spectrographic biomarkers of unstable sleep, related to elevated-low frequency (e-LFC), and to assess their utility in genetic studies.

Conclusions:
Approximately 30% of the variability of e-LFC, measured from a continuous ECG during sleep is explained by familial factors other than BMI. ECG-based spectrographic measures of heart rate variability & breathing rate may provide novel markers for characterizing subgroups of individuals with different propensities and genetic etiologies for sleep apnea or for other conditions associated with sleep fragmentation.

Practical Significance:
This study suggests that CPC provides an objective measure aimed to enhance our understanding of the genetics of OSA by identifying intermediate traits with high heritability.

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Obstructive Sleep Apnea and Chronic Pulmonary Diseases

Authors:
Magnusdottir S.

Reference:
Magnusdottir, J Respir Med 2017, 1:1

Objectives:
Sleep is associated with adaptive changes of the airways and the lungs. In patients with chronic pulmonary diseases such physiologic changes and the pathophysiologic changes induced by obstructive sleep apnea (OSA) may result in worsening of the pulmonary disease and can contribute to worsened outcomes. Pulmonologists need to be aware of the importance of screening patients with chronic pulmonary disease for OSA, as patients suffering from both chronic pulmonary disease and OSA, termed “overlap syndrome”, have increased morbidity and mortality. It is equally important to initiate appropriate treatment as CPAP treatment will improve quality of life, and prevent long-term respiratory and cardiovascular complications, with improved survival rates and decreased hospitalizations. The purpose of this review is to increase awareness of this association and provide pulmonologist with knowledge of how recent advances in sensor technology and computing now offer simple and cost-effective ambulatory methods to accurately screen for sleep disorders. This review should encourage more attention to symptoms of sleep apnea in patients with chronic pulmonary diseases. 

Conclusions:
Sensor technologies now offer additional ambulatory methods to easily collect bio-signals like ECG, which provides opportunities and possibilities to collect objective data to analyze and improve clinical diagnosis and treatment decisions. While the relationship between chronic pulmonary diseases and untreated sleep disorders may not be the most immediate obvious observation, it should not be ignored or overlooked given the implications of how untreated sleep disorders can adversely affect progression of various chronic pulmonary diseases. Therefore identifying the coexistence and severity of OSA in patients with comorbid pulmonary conditions, the presence of “overlap syndrome”, is highly important as these patients have worse quality of life and prognosis. Therefore for quality patient care, implementing simple, efficient, and accurate objective methods to identify OSA in patients with “overlap syndrome” is highly important and to initiate treatment when appropriate, as sleep disorder breathing therapy prevents long-term respiratory and cardiovascular complications, decreases hospitalizations and improves survival rate quality of life in these patients.

Practical Significance:
This improved ambulatory method to screen for sleep apnea will help clinicians to improve diagnosis accuracy for sleep apnea in patients with chronic pulmonary diseases. It can also provide objective evidence and feedback for these patients to assist in improving therapy management for both sleep apnea and related chronic pulmonary diseases. A crucial part of the disease management is to educate the patient on the association between OSA and chronic pulmonary diseases for them to understand that the treatment of the OSA not only benefits to improve their sleep symptoms but also their pulmonary disease and overall health and wellbeing. Regular tracking of therapy efficacy and adherence to treatment should also help to maximize medical benefits. Management of OSA and its associated conditions should involve the primary care physician as well as the pulmonologist and other specialists. Using objective and medically accurate methods regularly to track physiology during sleep may be key to optimizing sleep health that can incentivize preventative wellness behavior and improve patient care with cost benefits to patients and payers. 

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Prevalent Hypertension and Stroke in the Sleep Heart Health Study: Association with an ECG-derived Spectrographic Marker of Cardiopulmonary Coupling

Authors:
Thomas RJ, Weiss MD, Mietus JE, Peng CK, Goldberger AL, Gottlieb DJ.

Reference:
SLEEP 2009;32(7):897-904

Objectives:
The ECG-based sleep spectrogram generates a map of CPC based on heart rate variability and respiration derived from QRS amplitude variations. A distinct spectrographic type, designated as elevated Low Frequency Coupling Narrow Band (e-LFCNB), has been associated with central apneas and periodic breathing and predicts failure of CPAP therapy. This study assesses, at a population level, the associations of this spectrographic biomarker with prevalent cardiovascular disease using the Sleep Heart Health Study (SHHS)-I dataset.

Conclusions:
An ECG derived spectrographic marker related to low frequency is associated with greater sleep apnea severity. Whether this biomarker is solely a sign of more severe disease or whether it reflects primary alterations in sleep apnea pathophysiology, which may either cause or result from sleep apnea, is unknown. This ECG-based spectral marker is associated with a higher prevalence of hypertension and stroke.

Practical Significance:
The presence of e-LFCNB represents for the first time a biomarker for sleep disordered breathing independent of age, sex and body mass has been described.

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Sleep quality change after upper airway surgery in obstructive sleep apnea: Electrocardiogram-based cardiopulmonary coupling analysis

Authors:
Choi JH1, Thomas RJ, Suh SY, Park IH, Kim TH, Lee SH, Lee HM, Yun CH, Lee SH.

Reference:
Laryngoscope. 2015 Feb 3. doi: 10.1002/lary.25101.

Objectives:
Sleep quality change after upper airway surgery in obstructive sleep apnea: Electrocardiogram-based cardiopulmonary coupling analysis

Conclusions:
Successful upper airway surgery can improve objective sleep quality in adult patients with OSA. CPC metrics of sleep quality are potentially useful to monitor therapeutic responses during long-term postoperative follow-up, as the ECG-based analysis is available as a standalone option outside laboratory polysomnography.

Practical Significance:
Sleep quality measured by CPC analysis improved significantly (HFC, P = .001; LFC, P = .002; e-LFC, P = .003), along with parallel reduction in ESS, respiratory parameters (AHI, AI, minimum SaO2), and sleep fragmentation (ArI) in the group with surgical success after upper airway surgery.

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The association between leukocyte telomere lengths and sleep instability based on cardiopulmonary coupling analysis

Authors:
Kwon AM1, Baik I, Thomas RJ, Shin C.

Reference:
Sleep Breath. 2015 Jan 28.

Objectives:
The purpose of the study is to examine the objective association between sleep stability and leukocyte telomere lengths (LTL) using cardiopulmonary coupling (CPC) analysis, which is an electrocardiogram (ECG)-based technique to quantify physiologic sleep stability.

Conclusions:
The present study suggested that shorter LTL might contribute to reduced sleep stability by interacting with OSA severity due to the stress of chronic sleep fragmentation or invariant sympathetic activity by respiratory chemoreflex activation.

Practical Significance:
LTL showed a significant association with elevated narrow-band low frequency coupling (e-LFCNB, a CPC marker of periodic breathing or sleep fragmentation due to pathological respiratory chemoreflex activation) by interacting with obstructive sleep apnea (OSA) severity (p value of <0.0001). Especially, sleep stability significantly reduced with shortened LTL in OSA patients (Apnea-Hypopnea Index (AHI) ≥15) based on increased e-LFCNB which had a negative correlation with high-frequency coupling band (HFC), a marker of stable sleep.

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The effect of continuous positive airway pressure on cardiopulmonary coupling.

Authors:
Cho, J.H. & Kim, H.J.

Reference:
Sleep Breath. 2017 May;21(2):341-345. doi: 10.1007/s11325-016-1419-8. Epub 2016 Oct 8.

Objectives:
The aim of the study was to investigate cardiopulmonary coupling (CPC) as a tool for evaluating the efficacy of continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA).

Conclusions:
The apnea-hypopnea index, CPC variables, and sleep stage (%) during the first 2 h of the sleep study did not differ between the PSG-only and CPAP titration groups. A comparison of data collected over the first 2 h and that collected over the rest of the sleep study revealed that high-frequency coupling (HFC) increased, and low-frequency coupling (LFC) and elevated LFC (e-LFC) decreased only for the CPAP titration group, while they did not change for the PSG-only group. The proportions of N1 and N3 stages and arousal index decreased while the proportion of R stage increased for both groups. The proportion of N2 stage and mean O2saturation increased only for the CPAP titration group, while they did not change significantly for the PSG-only group. HFC increased while LFC and e-LFC decreased linearly as apnea-hypopnea index decreased for the CPAP titration group.

Practical Significance:
CPC effectively reflects the treatment effect of CPAP when compared with an electroencephalography-based sleep stage assessment.

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The Sleep Quality Recovery of a Snorer's Bed Partner

Authors:
Schramm PJ, Neville AN, Baker D

Reference:
Respiratory Therapy Vol. 5 No. 3 June-July 2010 pg. 39

Objectives:
To demonstrate, through the use of CPC technology, the negative impact of snoring and Obstructive Sleep Apnea (OSA) and the response to PAP initiation the bed partner’s sleep quality.

Conclusions:
Both the snorer and his bed partner’s sleep quality improved significantly with the application of PAP therapy.

Practical Significance:
Proof to a reticent CPAP user of the benefit of CPAP compliance to their bed partner as well as themselves

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