Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measure... more Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measurements, has recently gained substantial attention from its application as a continuous monitoring tool for large and small airways. However, low frequency (< 8 Hz) continuous oscillometry faces high breathing noise, and hence requires high oscillation amplitudes to maintain an acceptable signal-to-noise ratio. Therefore, PAP machines that utilize low frequency oscillometry do so intermittently to distinguish airway patency several seconds after a breathing pause has occurred. We hypothesized that high frequency and low amplitude (HFLA) oscillometry may be as sensitive and applicable for monitoring upper airway patency to distinguish between central and obstructive apnea and hypopnea events, and for monitoring respiratory impedance. An inline oscillometry prototype device was developed and connected to commercial PAP machines to test whether oscillometry at 17, 43, and 79 Hz are as sensitive to airway patency as oscillometry at 4 Hz. Analysis of 11 patients with 171 apneas and hypopneas showed that all frequency oscillometry inputs were equally sensitive in distinguishing between central and obstructive apneas, while 17 Hz and 43 Hz oscillometry were most sensitive in distinguishing between central and obstructive hypopneas. Observations during normal breathing also showed the same periodicity and cross-correlation between impedance measurements from HFLA oscillometry compared to 4 Hz. Our findings provide an unobtrusive means of distinguishing airway patency during sleep and a means of continuous monitoring of respiratory function, with the potential for detection and prediction of developing respiratory diseases and significantly richer context for data analytics.
Patients with severe complaints of insomnia are sometimes investigated in a sleep laboratory in o... more Patients with severe complaints of insomnia are sometimes investigated in a sleep laboratory in order to test for other causes of their complaints such as sleep disordered breathing or other sleep disorders. We investigated 64 patients with primary insomnia with cardiorespiratory polysomnography. Sleep stages, arousal and respiratory events were scored according to AASM criteria. ECG was analyzed by a special software (Hypnocore) which can provide a sleep evaluation and a respiratory event score by a new automated analysis. All patients were analyzed in two steps. The second analysis was performed on 54 patients after removing those with bad signal quality, arrhythmias and a total sleep time below 3 hours. The analysis of respiratory events based on ECG in the group of 64 subjects resulted in 52 subjects (48 true negative, 4 false negative) with an RDI0 5/h. Agreement was 0.91. For the second analysis agreement remained the same. Sleep stages in the second analysis were scored surpr...
Drug Discovery and Evaluation: Methods in Clinical Pharmacology, 2018
Sleep disorders are frequently reported complaints. Insomnia and hypersomnolence are symptoms oft... more Sleep disorders are frequently reported complaints. Insomnia and hypersomnolence are symptoms often reported by patients and study participants. Sleep disorders with clinical consequences are not as common as complaints and symptoms might suggest. Sleep medicine is a new discipline which has developed its own curricula and physician specialization. Sleep medicine has developed a classification of sleep disorders with a manual with definitions and severity criteria. This classification will become part of the ICD-11 currently developed. The classification defines insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, sleep-related movement disorders, and other sleep disorders. Diagnostic procedures include validated questionnaires; daytime testing of alertness and sleepiness; home recording of sleep-wake behavior, activity, and physiological signals; and finally a sleep laboratory investigation, cardiorespiratory polysomnography, with all signals recorded which change during normal and pathological sleep. Quantitative assessment of sleep, sleep stages, arousals from sleep, and vegetative functions during sleep is T. Penzel (*) · I. Fietze Interdisciplinary Sleep Medicine Center, Charitécentrum für HerzKresilaufund Gefäßmedizin CCM11, Charité – Universitätsmedizin Berlin, Berlin, Germany e-mail: thomas.penzel@charite.de; ingo.fietze@charite.de # Springer International Publishing AG 2018 F. J. Hock, M. R. Gralinski (eds.), Drug Discovery and Evaluation: Methods in Clinical Pharmacology, https://doi.org/10.1007/978-3-319-56637-5_41-1 1 well-established, and normative values including age as modifier are well described. Sleep disorders are recognized as risk factors for many other medical and mental disorders. Sleep disorders impair performance and may be perceived as early aging. Untreated sleep disorders cause costs at all levels of health care and need to be recognized and treated as appropriate. Sleep disorders are a target to clinical pharmacology by being recognized and potentially excluded in any pharmacological trial. And sleep disorders are subject to drug discovery and development. Purpose and Rationale Sleep disorders have a high prevalence in the population. Prevalence is reported to be between 10% and 30% in the general population (Ohayon 2011). According to a health survey by the Robert-Koch Institute in 1998, about 14% of the German male population and 27% of the German female population complain about frequent or moderate insomnia (suffering from not sleeping) (Penzel et al. 2005). The survey did not check for sleep disorders according to medical definitions nor did the survey use validated and approved. Only three questions could be related to sleep disorders. These were “complaints about insomnia,” “need too much sleep,” and “being tired.” Questions were rather unspecific. This had been recognized by many sleep researchers, and they initiated their own large sample surveys on sleep disorders (Ohayon and Zulley 2001). Assessment was performed on sleep dissatisfaction and sleep duration and more specific complaints on sleep problems. These extensive computer-driven interviews had a mean duration of 48 min per person. Definitely this is unpractical for general health surveys. A follow-up health survey by the Robert-Koch Institute between 2008 and 2011 contained much more specific questions compared to the first one in 1998 (Schlack et al. 2013). Some new questions were derived from the Pittsburgh Sleep Quality Index (Buysse et al. 1989), a well-validated questionnaire used in sleep medicine. The survey assessed the same complaints as previously and in addition more specific questions on sleep duration, problems in initiating and maintaining sleep, frequency of these complaints, perceived quality of sleep, and use of sleeping medication, all during the past 4 weeks. Based on the answers, the authors were able to estimate a prevalence of 5.7% for insomnia in Germany. This survey yielded the most recent and reliable prevalence data for Germany. However in the German health insurance system, sleep disorders play a very small role. Whereas depression, the third most common diagnosis, is responsible for 5.6% of all days on sickness leave, sleep disorders are only listed for 0.26% of days for sickness leave (DAK report 2017). Still days for sickness leave doubled over the last decade. This reflects very well an important fact. Sleep disorders remain not to be a reason for consulting a physician in the first line. Sleep disorders remain not to be a reason for requesting for sick leave. Many patients do not report sleep complaints in the first line but often as a secondary symptom. Still sleep complaints, being difficulties in initiating and maintaining sleep or in suffering from non-refreshing sleep, are very common. Therefore it is important to investigate sleep complains and sleep problems in detail. The first assessment…
SummaryRecent evidence supports the use of pulse wave analysis during sleep for assessing functio... more SummaryRecent evidence supports the use of pulse wave analysis during sleep for assessing functional aspects of the cardiovascular system. The current study compared the influence of pulse wave and sleep study‐derived parameters on cardiovascular risk assessment. In a multi‐centric study design, 358 sleep apnea patients (age 55 ± 13 years, 64% male, body mass index 30 ± 6 kg m−2, apnea–hypopnea index 13 [5–26] events per hr) underwent a standard overnight sleep recording. A novel cardiac risk index was computed based on pulse wave signals derived from pulse oximetry, reflecting vascular stiffness, cardiac variability, vascular autonomic tone and nocturnal hypoxia. Cardiovascular risk was determined using the ESC/ESH cardiovascular risk matrix, and categorized to high/low added cardiovascular risk. Comparisons between cardiac risk index and sleep parameters were performed for cardiovascular risk prediction. Apnea–hypopnea index, oxygen desaturation index and cardiac risk index were a...
BACKGROUND We developed objective definitions of extreme phenotypes of obstructive sleep apnea (O... more BACKGROUND We developed objective definitions of extreme phenotypes of obstructive sleep apnea (OSA) using a multivariate approach, and demonstrate their utility for identifying characteristics that confer predisposition towards or protection against OSA in a new prospective sample. METHODS In a large international sample, we calculated race-specific liability scores from a weighted logistic regression including age, gender and body mass index (BMI). Extreme Cases were defined as individuals with an apnea-hypopnea index (AHI) ≥30 events/hour, but low likelihood of OSA based on age, gender and BMI (liability scores >90th percentile). Similarly, Extreme Controls were individuals with AHI<5, but high likelihood of OSA (liability scores <10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) and differences in photography-based craniofacial and intraoral phenotypes evaluated. RESULTS Retrospective data included 81,338 individuals. We identified 4,168 Extreme Cases and 1,432 Extreme Controls using liability scores. Extreme Cases were younger (43.1±14.7 years), overweight (28.6±6.8 kg/m2), and predominantly female (71.1%). Extreme Controls were older (53.8±14.1 years), obese (34.0±8.1 kg/m2), and predominantly male (65.8%). These objective definitions identified 29 Extreme Cases and 87 Extreme Controls among 1,424 SAGIC participants with photography-based phenotyping; comparisons suggest greater cervicomental angle increases risk for OSA in the absence of clinical risk factors and smaller facial widths are protective in the presence of clinical risk factors. CONCLUSIONS This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic and physiological pathways to OSA.
The increase in sleep medicine services has paralleled the increased in nocturnal ventilation the... more The increase in sleep medicine services has paralleled the increased in nocturnal ventilation therapy in patients with sleep apnea. Even if the sleep medicine expertise did increase in the past, this is not sufficient to cover the increasing demand for sleep medicine services. To serve patients with nonrestorative sleep, a clinical algorithm showing the pathway from the clinical interview to sleep laboratory investigations is available. However, there is a gap in the services offered by family physicians, other medical specialists, and sleep medicine practitioners. For sleep apnea, the diagnostic process and therapy are established; however, for other sleep disorders such as insomnia, parasomnia, movement disorders, hypersomnia, and circadian rhythm disorders, this is not the case. A basic investigation for sleep disorders is attended cardiorespiratory polysomnography, which is not always essential. There is a network of qualified sleep centers for stationary and ambulatory care, bu...
In the general population there is a high prevalence of sleep-related disorders of breathing (sle... more In the general population there is a high prevalence of sleep-related disorders of breathing (sleep apnea). In addition to being leading symptom of excessive day-time sleepiness they are also important predictors are cardiovascular disease such as arterial hypertension, heart failure, cardiac arrhythmias and stroke. Are the cardiologists the specialists who recognize such patients and refer them to diagnostic procedures and treatment? We sent out a questionnaires to cardiologists in private practice, to hospitals with cardiology departments and to cardiology rehabilitation units in Germany in order to assess the knowledge about sleep apnea and of the current diagnostic and therapeutic procedures in patients with suspected sleep apnea. All cardiology rehabilitation units and every other practice and cardiology department listed in the reference book 'Medführer' were approached. 98% of 388 cardiologists with private practice were found to know about the disorder sleep apnea. 9...
Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measure... more Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measurements, has recently gained substantial attention from its application as a continuous monitoring tool for large and small airways. However, low frequency (< 8 Hz) continuous oscillometry faces high breathing noise, and hence requires high oscillation amplitudes to maintain an acceptable signal-to-noise ratio. Therefore, PAP machines that utilize low frequency oscillometry do so intermittently to distinguish airway patency several seconds after a breathing pause has occurred. We hypothesized that high frequency and low amplitude (HFLA) oscillometry may be as sensitive and applicable for monitoring upper airway patency to distinguish between central and obstructive apnea and hypopnea events, and for monitoring respiratory impedance. An inline oscillometry prototype device was developed and connected to commercial PAP machines to test whether oscillometry at 17, 43, and 79 Hz are as sensitive to airway patency as oscillometry at 4 Hz. Analysis of 11 patients with 171 apneas and hypopneas showed that all frequency oscillometry inputs were equally sensitive in distinguishing between central and obstructive apneas, while 17 Hz and 43 Hz oscillometry were most sensitive in distinguishing between central and obstructive hypopneas. Observations during normal breathing also showed the same periodicity and cross-correlation between impedance measurements from HFLA oscillometry compared to 4 Hz. Our findings provide an unobtrusive means of distinguishing airway patency during sleep and a means of continuous monitoring of respiratory function, with the potential for detection and prediction of developing respiratory diseases and significantly richer context for data analytics.
Patients with severe complaints of insomnia are sometimes investigated in a sleep laboratory in o... more Patients with severe complaints of insomnia are sometimes investigated in a sleep laboratory in order to test for other causes of their complaints such as sleep disordered breathing or other sleep disorders. We investigated 64 patients with primary insomnia with cardiorespiratory polysomnography. Sleep stages, arousal and respiratory events were scored according to AASM criteria. ECG was analyzed by a special software (Hypnocore) which can provide a sleep evaluation and a respiratory event score by a new automated analysis. All patients were analyzed in two steps. The second analysis was performed on 54 patients after removing those with bad signal quality, arrhythmias and a total sleep time below 3 hours. The analysis of respiratory events based on ECG in the group of 64 subjects resulted in 52 subjects (48 true negative, 4 false negative) with an RDI0 5/h. Agreement was 0.91. For the second analysis agreement remained the same. Sleep stages in the second analysis were scored surpr...
Drug Discovery and Evaluation: Methods in Clinical Pharmacology, 2018
Sleep disorders are frequently reported complaints. Insomnia and hypersomnolence are symptoms oft... more Sleep disorders are frequently reported complaints. Insomnia and hypersomnolence are symptoms often reported by patients and study participants. Sleep disorders with clinical consequences are not as common as complaints and symptoms might suggest. Sleep medicine is a new discipline which has developed its own curricula and physician specialization. Sleep medicine has developed a classification of sleep disorders with a manual with definitions and severity criteria. This classification will become part of the ICD-11 currently developed. The classification defines insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, sleep-related movement disorders, and other sleep disorders. Diagnostic procedures include validated questionnaires; daytime testing of alertness and sleepiness; home recording of sleep-wake behavior, activity, and physiological signals; and finally a sleep laboratory investigation, cardiorespiratory polysomnography, with all signals recorded which change during normal and pathological sleep. Quantitative assessment of sleep, sleep stages, arousals from sleep, and vegetative functions during sleep is T. Penzel (*) · I. Fietze Interdisciplinary Sleep Medicine Center, Charitécentrum für HerzKresilaufund Gefäßmedizin CCM11, Charité – Universitätsmedizin Berlin, Berlin, Germany e-mail: thomas.penzel@charite.de; ingo.fietze@charite.de # Springer International Publishing AG 2018 F. J. Hock, M. R. Gralinski (eds.), Drug Discovery and Evaluation: Methods in Clinical Pharmacology, https://doi.org/10.1007/978-3-319-56637-5_41-1 1 well-established, and normative values including age as modifier are well described. Sleep disorders are recognized as risk factors for many other medical and mental disorders. Sleep disorders impair performance and may be perceived as early aging. Untreated sleep disorders cause costs at all levels of health care and need to be recognized and treated as appropriate. Sleep disorders are a target to clinical pharmacology by being recognized and potentially excluded in any pharmacological trial. And sleep disorders are subject to drug discovery and development. Purpose and Rationale Sleep disorders have a high prevalence in the population. Prevalence is reported to be between 10% and 30% in the general population (Ohayon 2011). According to a health survey by the Robert-Koch Institute in 1998, about 14% of the German male population and 27% of the German female population complain about frequent or moderate insomnia (suffering from not sleeping) (Penzel et al. 2005). The survey did not check for sleep disorders according to medical definitions nor did the survey use validated and approved. Only three questions could be related to sleep disorders. These were “complaints about insomnia,” “need too much sleep,” and “being tired.” Questions were rather unspecific. This had been recognized by many sleep researchers, and they initiated their own large sample surveys on sleep disorders (Ohayon and Zulley 2001). Assessment was performed on sleep dissatisfaction and sleep duration and more specific complaints on sleep problems. These extensive computer-driven interviews had a mean duration of 48 min per person. Definitely this is unpractical for general health surveys. A follow-up health survey by the Robert-Koch Institute between 2008 and 2011 contained much more specific questions compared to the first one in 1998 (Schlack et al. 2013). Some new questions were derived from the Pittsburgh Sleep Quality Index (Buysse et al. 1989), a well-validated questionnaire used in sleep medicine. The survey assessed the same complaints as previously and in addition more specific questions on sleep duration, problems in initiating and maintaining sleep, frequency of these complaints, perceived quality of sleep, and use of sleeping medication, all during the past 4 weeks. Based on the answers, the authors were able to estimate a prevalence of 5.7% for insomnia in Germany. This survey yielded the most recent and reliable prevalence data for Germany. However in the German health insurance system, sleep disorders play a very small role. Whereas depression, the third most common diagnosis, is responsible for 5.6% of all days on sickness leave, sleep disorders are only listed for 0.26% of days for sickness leave (DAK report 2017). Still days for sickness leave doubled over the last decade. This reflects very well an important fact. Sleep disorders remain not to be a reason for consulting a physician in the first line. Sleep disorders remain not to be a reason for requesting for sick leave. Many patients do not report sleep complaints in the first line but often as a secondary symptom. Still sleep complaints, being difficulties in initiating and maintaining sleep or in suffering from non-refreshing sleep, are very common. Therefore it is important to investigate sleep complains and sleep problems in detail. The first assessment…
SummaryRecent evidence supports the use of pulse wave analysis during sleep for assessing functio... more SummaryRecent evidence supports the use of pulse wave analysis during sleep for assessing functional aspects of the cardiovascular system. The current study compared the influence of pulse wave and sleep study‐derived parameters on cardiovascular risk assessment. In a multi‐centric study design, 358 sleep apnea patients (age 55 ± 13 years, 64% male, body mass index 30 ± 6 kg m−2, apnea–hypopnea index 13 [5–26] events per hr) underwent a standard overnight sleep recording. A novel cardiac risk index was computed based on pulse wave signals derived from pulse oximetry, reflecting vascular stiffness, cardiac variability, vascular autonomic tone and nocturnal hypoxia. Cardiovascular risk was determined using the ESC/ESH cardiovascular risk matrix, and categorized to high/low added cardiovascular risk. Comparisons between cardiac risk index and sleep parameters were performed for cardiovascular risk prediction. Apnea–hypopnea index, oxygen desaturation index and cardiac risk index were a...
BACKGROUND We developed objective definitions of extreme phenotypes of obstructive sleep apnea (O... more BACKGROUND We developed objective definitions of extreme phenotypes of obstructive sleep apnea (OSA) using a multivariate approach, and demonstrate their utility for identifying characteristics that confer predisposition towards or protection against OSA in a new prospective sample. METHODS In a large international sample, we calculated race-specific liability scores from a weighted logistic regression including age, gender and body mass index (BMI). Extreme Cases were defined as individuals with an apnea-hypopnea index (AHI) ≥30 events/hour, but low likelihood of OSA based on age, gender and BMI (liability scores >90th percentile). Similarly, Extreme Controls were individuals with AHI<5, but high likelihood of OSA (liability scores <10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) and differences in photography-based craniofacial and intraoral phenotypes evaluated. RESULTS Retrospective data included 81,338 individuals. We identified 4,168 Extreme Cases and 1,432 Extreme Controls using liability scores. Extreme Cases were younger (43.1±14.7 years), overweight (28.6±6.8 kg/m2), and predominantly female (71.1%). Extreme Controls were older (53.8±14.1 years), obese (34.0±8.1 kg/m2), and predominantly male (65.8%). These objective definitions identified 29 Extreme Cases and 87 Extreme Controls among 1,424 SAGIC participants with photography-based phenotyping; comparisons suggest greater cervicomental angle increases risk for OSA in the absence of clinical risk factors and smaller facial widths are protective in the presence of clinical risk factors. CONCLUSIONS This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic and physiological pathways to OSA.
The increase in sleep medicine services has paralleled the increased in nocturnal ventilation the... more The increase in sleep medicine services has paralleled the increased in nocturnal ventilation therapy in patients with sleep apnea. Even if the sleep medicine expertise did increase in the past, this is not sufficient to cover the increasing demand for sleep medicine services. To serve patients with nonrestorative sleep, a clinical algorithm showing the pathway from the clinical interview to sleep laboratory investigations is available. However, there is a gap in the services offered by family physicians, other medical specialists, and sleep medicine practitioners. For sleep apnea, the diagnostic process and therapy are established; however, for other sleep disorders such as insomnia, parasomnia, movement disorders, hypersomnia, and circadian rhythm disorders, this is not the case. A basic investigation for sleep disorders is attended cardiorespiratory polysomnography, which is not always essential. There is a network of qualified sleep centers for stationary and ambulatory care, bu...
In the general population there is a high prevalence of sleep-related disorders of breathing (sle... more In the general population there is a high prevalence of sleep-related disorders of breathing (sleep apnea). In addition to being leading symptom of excessive day-time sleepiness they are also important predictors are cardiovascular disease such as arterial hypertension, heart failure, cardiac arrhythmias and stroke. Are the cardiologists the specialists who recognize such patients and refer them to diagnostic procedures and treatment? We sent out a questionnaires to cardiologists in private practice, to hospitals with cardiology departments and to cardiology rehabilitation units in Germany in order to assess the knowledge about sleep apnea and of the current diagnostic and therapeutic procedures in patients with suspected sleep apnea. All cardiology rehabilitation units and every other practice and cardiology department listed in the reference book 'Medführer' were approached. 98% of 388 cardiologists with private practice were found to know about the disorder sleep apnea. 9...
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