Sleep Medicine

Clinicians are well aware of the acute effects of hypoxemia when encountered in conditions such as pulmonary embolism, pulmonary edema, COPD exacerbation, and others, whereas effects of chronic hypoxemia, such as pulmonary hypertension and polycythemia, are more difficult to recognize. Chronic hypoxemia is frequent in chronic lung diseases, such as COPD, but how it leads to increased mortality in severe COPD is unknown (NHLBI Working Group for LTOT in COPD. Am J Respir Crit Care Med. 2006;174:373). Chronic hypoxemia following high altitude exposure tends to have more unpredictable effects. Chronic hypoxemia, greater than that expected for the altitude of residence, is encountered frequently in high altitude dwellers. Here it has been implicated in the pathophysiology of chronic mountain sickness (Villafeurte and Corante. High Alt Med Biol. 2016;17[2]:61) and low birth weights (Maatta J, et al. Sci Rep. 2018;8[1]:13583), even though high altitude residence has been linked to better cardiovascular outcomes and reduced cancer-related deaths (Burstcher M. Aging Dis. 2013;5[4]:274). Chronic hypoxia effects at high altitude may, therefore, be variegated depending on a number of factors that include organ-system-specific effects, severity of chronic hypoxia, and a propensity to disease determined by genetic background and generations of residence.

Such diverse effects of chronic sleep-related hypoxemia are also being reported with obstructive sleep apnea (OSA). While sleep can result in sustained drops in ventilation and consequent hypoxemia similar to what is seen in COPD, OSA is typified by a form of sleep-related hypoxemia in a pattern termed as chronic intermittent hypoxia (CIH). CIH is characterized by rapid fluctuations in oxygen saturations (Figure 1) that is virtually pathognomonic of sleep apnea either from recurrent upper airway obstructions (as in OSA) or pauses in respiratory generator firing (as in central sleep apnea). OSA-driven CIH has received most attention, given its purported role in in the causation of the wide range of pathologic conditions associated with OSA. Outcomes from cross-sectional and longitudinal studies have correlated time spent below 90% or recurrent oxygen desaturations to a number of OSA-related outcomes such as cardiovascular disease, diabetes, and cognitive dysfunction (Dewan et al. Chest. 2015;147[1]:266). While these effects of OSA-related intermittent hypoxemia occur over long periods of time, as with other forms of chronic hypoxia, some effects, such as hypertension, are demonstrable in animal models after much shorter durations of sleep-related intermittent hypoxia exposure. As seen with other forms of chronic hypoxemia, an opposing beneficial effect has also been demonstrated on the size of myocardial infarct during acute coronary events and from mild OSA-related mortality in elderly subjects (Javaheri et al. J Am Coll Cardiol. 2017;69[7]:841).

Given how common sleep-related hypoxemia and OSA are, it is important to understand the implications of different patterns of sleep-related hypoxemia that a vast segment of the population experiences on a nightly basis. A number of factors may determine chronic outcomes with sleep-related hypoxemia that include the pattern of sleep-related hypoxemia (chronic sustained hypoxemia associated with sleep-related hypoventilation vs chronic intermittent hypoxemia of OSA), degree of hypoxemia, presence of underlying disease, and hitherto undescribed individual factors. While a correlation between hypoxemic burden secondary to sleep-disordered breathing and cardiovascular outcomes has been shown (Azabarzin A, et al. Eur Heart J. 2018 Oct 30), CPAP interventional studies that address OSA-related CIH have shown mixed results for prevention of cardiovascular disease (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919). It has also been difficult to draw upon results of oxygen supplementation in other forms of hypoxemia, such as COPD, when specifically targeted to addressing the hypoxemia seen only at night or with exercise (LOTT Research Group. N Engl J Med. 2016;375:1617 ). To complicate this further, high altitude residence (that may result in similar levels of sleep-related hypoxemia) is not associated with any differences in life-expectancy but may provide a reduction in cardiovascular outcomes (Ezzati, et al. J Epidemiol Community Health. 2012;66[7]:e17).

How do we reconcile such disparate effects of chronic hypoxemia? Part of difference may be in the pattern of chronic intermittent hypoxemia noted with OSA characterized not only by rapid drops in oxygen but also rapid reoxygenation events secondary to arousals terminating an apnea – these reoxygenation events have been attributed to the increased oxidant stress demonstrable in multiple tissues. While chronic hypoxia itself may cause increased oxidant stress, such effects seen with sustained forms of hypoxia, such as sleep-related hypoventilation or high altitude residence, may be more gradual resulting in lesser degrees of tissue effects and regulation of antioxidant defenses with sustained exposure. Herein lies the importance of understanding physiologic and biological effects stemming from chronic hypoxia to explain its variegated effects on different organ systems. In this regard, the role of carotid body, a structure with unique vascular supply and with the ability to respond to minor changes in oxygen saturation as is seen in patients with OSA is key to the causation of hypertension associated with OSA (Shell et al. Curr Hyperten Rep. 2016;18[3]:19). Carotid body activation by intermittent hypoxia and long-term sensory facilitation drives the elevated sympathetic activity and consequent increases in blood pressure that can be improved by supplemental oxygen (Turnbull CD, et al. Am J Respir Crit Care Med. 2019;199[2]:211).

While carotid body responses are key to the pathophysiology of OSA, every organ in the body (in fact, every cell within the body) has the ability to sense and respond to hypoxia. This ability to sense oxygen tensions is ingrained in every cell by virtue of oxygen’s critical role in the genesis of life and evolution. These cellular responses to hypoxia are mediated by hypoxia-inducible factors (HIFs), isoforms of which include the more ubiquitous HIF-1 found in all parenchymal cells and HIF-2 found in specialized erythropoietin-producing cells of the kidney and the pulmonary circulation (the polycythemia and pulmonary vasoconstrictive responses from hypoxia are mediated through HIF-2 ). HIFs mediate the transcription of hundreds of genes, and they have been implicated in the pathobiology of a wide range of phenomena, from cancer to atherosclerotic vascular disease, metabolic syndrome, neurodegenerative disorders, pulmonary hypertension, and nonalcoholic fatty liver disease (Prabhakar and Semenza. Physiol Rev. 2012;92[3]:967). While HIF activation is an attractive target for examining the effects of chronic hypoxia of high altitude and sleep-disordered breathing, HIF activation varies from tissue to tissue and interacts with a number of other cellular systems in leading to differential effects. The short half-life of HIF proteins make them difficult to detect in tissues, so a number of secondary HIF-effects has been measured with mixed results depending on animal model utilized, pattern and degree of hypoxia studied, and the target effect measured. Comparative effects of intermittent vs sustained hypoxemia need to be systematically studied in different organ systems in different species, given the differing oxygen thresholds of individual cells due to unique blood flows and variations in the system of co-factors and prolyl hydroxylases that regulate the activation of HIFs. While the thrust of the work has been centered on HIF-related effects and the role of NF-kB-driven inflammation seen in OSA, there is substantial evidence to the role of oxidant stress that may be directly related to reoxygenation events occurring with CIH (Lavie L. Sleep Med Rev. 2015;20:27).

For life that has been intricately involved with oxygen from its genesis, it is not unreasonable to expect adaptations of cells, organs, and the whole individual to a wide range of oxygen tensions. Attempts to understand the import of sleep-disordered breathing has led to a need to unravel the implications of OSA-related chronic intermittent hypoxia and sleep-hypoventilation. This has led to a resurgence of interest in hypoxia-related research. Whether such chronic sleep-related sustained and intermittent hypoxemia is a harbinger of chronic disease is still not fully clear. A number of challenges exist with the understanding of these chronic hypoxia effects that include the long time needed for disease occurrence, its differential effects on organ systems, the role of hypoxia vs reoxygenation injury, importance of local blood flow, etc. Understanding these pathways will be crucial in prognosticating the role of sleep-related hypoxemia, the recognition of which has become part and parcel of routine management in sleep medicine.

Dr. Sundar is Medical Director, Sleep-Wake Center, Clinical Professor, Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah.

Clinicians are well aware of the acute effects of hypoxemia when encountered in conditions such as pulmonary embolism, pulmonary edema, COPD exacerbation, and others, whereas effects of chronic hypoxemia, such as pulmonary hypertension and polycythemia, are more difficult to recognize. Chronic hypoxemia is frequent in chronic lung diseases, such as COPD, but how it leads to increased mortality in severe COPD is unknown (NHLBI Working Group for LTOT in COPD. Am J Respir Crit Care Med. 2006;174:373). Chronic hypoxemia following high altitude exposure tends to have more unpredictable effects. Chronic hypoxemia, greater than that expected for the altitude of residence, is encountered frequently in high altitude dwellers. Here it has been implicated in the pathophysiology of chronic mountain sickness (Villafeurte and Corante. High Alt Med Biol. 2016;17[2]:61) and low birth weights (Maatta J, et al. Sci Rep. 2018;8[1]:13583), even though high altitude residence has been linked to better cardiovascular outcomes and reduced cancer-related deaths (Burstcher M. Aging Dis. 2013;5[4]:274). Chronic hypoxia effects at high altitude may, therefore, be variegated depending on a number of factors that include organ-system-specific effects, severity of chronic hypoxia, and a propensity to disease determined by genetic background and generations of residence.

Such diverse effects of chronic sleep-related hypoxemia are also being reported with obstructive sleep apnea (OSA). While sleep can result in sustained drops in ventilation and consequent hypoxemia similar to what is seen in COPD, OSA is typified by a form of sleep-related hypoxemia in a pattern termed as chronic intermittent hypoxia (CIH). CIH is characterized by rapid fluctuations in oxygen saturations (Figure 1) that is virtually pathognomonic of sleep apnea either from recurrent upper airway obstructions (as in OSA) or pauses in respiratory generator firing (as in central sleep apnea). OSA-driven CIH has received most attention, given its purported role in in the causation of the wide range of pathologic conditions associated with OSA. Outcomes from cross-sectional and longitudinal studies have correlated time spent below 90% or recurrent oxygen desaturations to a number of OSA-related outcomes such as cardiovascular disease, diabetes, and cognitive dysfunction (Dewan et al. Chest. 2015;147[1]:266). While these effects of OSA-related intermittent hypoxemia occur over long periods of time, as with other forms of chronic hypoxia, some effects, such as hypertension, are demonstrable in animal models after much shorter durations of sleep-related intermittent hypoxia exposure. As seen with other forms of chronic hypoxemia, an opposing beneficial effect has also been demonstrated on the size of myocardial infarct during acute coronary events and from mild OSA-related mortality in elderly subjects (Javaheri et al. J Am Coll Cardiol. 2017;69[7]:841).

Given how common sleep-related hypoxemia and OSA are, it is important to understand the implications of different patterns of sleep-related hypoxemia that a vast segment of the population experiences on a nightly basis. A number of factors may determine chronic outcomes with sleep-related hypoxemia that include the pattern of sleep-related hypoxemia (chronic sustained hypoxemia associated with sleep-related hypoventilation vs chronic intermittent hypoxemia of OSA), degree of hypoxemia, presence of underlying disease, and hitherto undescribed individual factors. While a correlation between hypoxemic burden secondary to sleep-disordered breathing and cardiovascular outcomes has been shown (Azabarzin A, et al. Eur Heart J. 2018 Oct 30), CPAP interventional studies that address OSA-related CIH have shown mixed results for prevention of cardiovascular disease (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919). It has also been difficult to draw upon results of oxygen supplementation in other forms of hypoxemia, such as COPD, when specifically targeted to addressing the hypoxemia seen only at night or with exercise (LOTT Research Group. N Engl J Med. 2016;375:1617 ). To complicate this further, high altitude residence (that may result in similar levels of sleep-related hypoxemia) is not associated with any differences in life-expectancy but may provide a reduction in cardiovascular outcomes (Ezzati, et al. J Epidemiol Community Health. 2012;66[7]:e17).

How do we reconcile such disparate effects of chronic hypoxemia? Part of difference may be in the pattern of chronic intermittent hypoxemia noted with OSA characterized not only by rapid drops in oxygen but also rapid reoxygenation events secondary to arousals terminating an apnea – these reoxygenation events have been attributed to the increased oxidant stress demonstrable in multiple tissues. While chronic hypoxia itself may cause increased oxidant stress, such effects seen with sustained forms of hypoxia, such as sleep-related hypoventilation or high altitude residence, may be more gradual resulting in lesser degrees of tissue effects and regulation of antioxidant defenses with sustained exposure. Herein lies the importance of understanding physiologic and biological effects stemming from chronic hypoxia to explain its variegated effects on different organ systems. In this regard, the role of carotid body, a structure with unique vascular supply and with the ability to respond to minor changes in oxygen saturation as is seen in patients with OSA is key to the causation of hypertension associated with OSA (Shell et al. Curr Hyperten Rep. 2016;18[3]:19). Carotid body activation by intermittent hypoxia and long-term sensory facilitation drives the elevated sympathetic activity and consequent increases in blood pressure that can be improved by supplemental oxygen (Turnbull CD, et al. Am J Respir Crit Care Med. 2019;199[2]:211).

While carotid body responses are key to the pathophysiology of OSA, every organ in the body (in fact, every cell within the body) has the ability to sense and respond to hypoxia. This ability to sense oxygen tensions is ingrained in every cell by virtue of oxygen’s critical role in the genesis of life and evolution. These cellular responses to hypoxia are mediated by hypoxia-inducible factors (HIFs), isoforms of which include the more ubiquitous HIF-1 found in all parenchymal cells and HIF-2 found in specialized erythropoietin-producing cells of the kidney and the pulmonary circulation (the polycythemia and pulmonary vasoconstrictive responses from hypoxia are mediated through HIF-2 ). HIFs mediate the transcription of hundreds of genes, and they have been implicated in the pathobiology of a wide range of phenomena, from cancer to atherosclerotic vascular disease, metabolic syndrome, neurodegenerative disorders, pulmonary hypertension, and nonalcoholic fatty liver disease (Prabhakar and Semenza. Physiol Rev. 2012;92[3]:967). While HIF activation is an attractive target for examining the effects of chronic hypoxia of high altitude and sleep-disordered breathing, HIF activation varies from tissue to tissue and interacts with a number of other cellular systems in leading to differential effects. The short half-life of HIF proteins make them difficult to detect in tissues, so a number of secondary HIF-effects has been measured with mixed results depending on animal model utilized, pattern and degree of hypoxia studied, and the target effect measured. Comparative effects of intermittent vs sustained hypoxemia need to be systematically studied in different organ systems in different species, given the differing oxygen thresholds of individual cells due to unique blood flows and variations in the system of co-factors and prolyl hydroxylases that regulate the activation of HIFs. While the thrust of the work has been centered on HIF-related effects and the role of NF-kB-driven inflammation seen in OSA, there is substantial evidence to the role of oxidant stress that may be directly related to reoxygenation events occurring with CIH (Lavie L. Sleep Med Rev. 2015;20:27).

For life that has been intricately involved with oxygen from its genesis, it is not unreasonable to expect adaptations of cells, organs, and the whole individual to a wide range of oxygen tensions. Attempts to understand the import of sleep-disordered breathing has led to a need to unravel the implications of OSA-related chronic intermittent hypoxia and sleep-hypoventilation. This has led to a resurgence of interest in hypoxia-related research. Whether such chronic sleep-related sustained and intermittent hypoxemia is a harbinger of chronic disease is still not fully clear. A number of challenges exist with the understanding of these chronic hypoxia effects that include the long time needed for disease occurrence, its differential effects on organ systems, the role of hypoxia vs reoxygenation injury, importance of local blood flow, etc. Understanding these pathways will be crucial in prognosticating the role of sleep-related hypoxemia, the recognition of which has become part and parcel of routine management in sleep medicine.

Dr. Sundar is Medical Director, Sleep-Wake Center, Clinical Professor, Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah.

Clinicians are well aware of the acute effects of hypoxemia when encountered in conditions such as pulmonary embolism, pulmonary edema, COPD exacerbation, and others, whereas effects of chronic hypoxemia, such as pulmonary hypertension and polycythemia, are more difficult to recognize. Chronic hypoxemia is frequent in chronic lung diseases, such as COPD, but how it leads to increased mortality in severe COPD is unknown (NHLBI Working Group for LTOT in COPD. Am J Respir Crit Care Med. 2006;174:373). Chronic hypoxemia following high altitude exposure tends to have more unpredictable effects. Chronic hypoxemia, greater than that expected for the altitude of residence, is encountered frequently in high altitude dwellers. Here it has been implicated in the pathophysiology of chronic mountain sickness (Villafeurte and Corante. High Alt Med Biol. 2016;17[2]:61) and low birth weights (Maatta J, et al. Sci Rep. 2018;8[1]:13583), even though high altitude residence has been linked to better cardiovascular outcomes and reduced cancer-related deaths (Burstcher M. Aging Dis. 2013;5[4]:274). Chronic hypoxia effects at high altitude may, therefore, be variegated depending on a number of factors that include organ-system-specific effects, severity of chronic hypoxia, and a propensity to disease determined by genetic background and generations of residence.

Such diverse effects of chronic sleep-related hypoxemia are also being reported with obstructive sleep apnea (OSA). While sleep can result in sustained drops in ventilation and consequent hypoxemia similar to what is seen in COPD, OSA is typified by a form of sleep-related hypoxemia in a pattern termed as chronic intermittent hypoxia (CIH). CIH is characterized by rapid fluctuations in oxygen saturations (Figure 1) that is virtually pathognomonic of sleep apnea either from recurrent upper airway obstructions (as in OSA) or pauses in respiratory generator firing (as in central sleep apnea). OSA-driven CIH has received most attention, given its purported role in in the causation of the wide range of pathologic conditions associated with OSA. Outcomes from cross-sectional and longitudinal studies have correlated time spent below 90% or recurrent oxygen desaturations to a number of OSA-related outcomes such as cardiovascular disease, diabetes, and cognitive dysfunction (Dewan et al. Chest. 2015;147[1]:266). While these effects of OSA-related intermittent hypoxemia occur over long periods of time, as with other forms of chronic hypoxia, some effects, such as hypertension, are demonstrable in animal models after much shorter durations of sleep-related intermittent hypoxia exposure. As seen with other forms of chronic hypoxemia, an opposing beneficial effect has also been demonstrated on the size of myocardial infarct during acute coronary events and from mild OSA-related mortality in elderly subjects (Javaheri et al. J Am Coll Cardiol. 2017;69[7]:841).

Given how common sleep-related hypoxemia and OSA are, it is important to understand the implications of different patterns of sleep-related hypoxemia that a vast segment of the population experiences on a nightly basis. A number of factors may determine chronic outcomes with sleep-related hypoxemia that include the pattern of sleep-related hypoxemia (chronic sustained hypoxemia associated with sleep-related hypoventilation vs chronic intermittent hypoxemia of OSA), degree of hypoxemia, presence of underlying disease, and hitherto undescribed individual factors. While a correlation between hypoxemic burden secondary to sleep-disordered breathing and cardiovascular outcomes has been shown (Azabarzin A, et al. Eur Heart J. 2018 Oct 30), CPAP interventional studies that address OSA-related CIH have shown mixed results for prevention of cardiovascular disease (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919). It has also been difficult to draw upon results of oxygen supplementation in other forms of hypoxemia, such as COPD, when specifically targeted to addressing the hypoxemia seen only at night or with exercise (LOTT Research Group. N Engl J Med. 2016;375:1617 ). To complicate this further, high altitude residence (that may result in similar levels of sleep-related hypoxemia) is not associated with any differences in life-expectancy but may provide a reduction in cardiovascular outcomes (Ezzati, et al. J Epidemiol Community Health. 2012;66[7]:e17).

How do we reconcile such disparate effects of chronic hypoxemia? Part of difference may be in the pattern of chronic intermittent hypoxemia noted with OSA characterized not only by rapid drops in oxygen but also rapid reoxygenation events secondary to arousals terminating an apnea – these reoxygenation events have been attributed to the increased oxidant stress demonstrable in multiple tissues. While chronic hypoxia itself may cause increased oxidant stress, such effects seen with sustained forms of hypoxia, such as sleep-related hypoventilation or high altitude residence, may be more gradual resulting in lesser degrees of tissue effects and regulation of antioxidant defenses with sustained exposure. Herein lies the importance of understanding physiologic and biological effects stemming from chronic hypoxia to explain its variegated effects on different organ systems. In this regard, the role of carotid body, a structure with unique vascular supply and with the ability to respond to minor changes in oxygen saturation as is seen in patients with OSA is key to the causation of hypertension associated with OSA (Shell et al. Curr Hyperten Rep. 2016;18[3]:19). Carotid body activation by intermittent hypoxia and long-term sensory facilitation drives the elevated sympathetic activity and consequent increases in blood pressure that can be improved by supplemental oxygen (Turnbull CD, et al. Am J Respir Crit Care Med. 2019;199[2]:211).

While carotid body responses are key to the pathophysiology of OSA, every organ in the body (in fact, every cell within the body) has the ability to sense and respond to hypoxia. This ability to sense oxygen tensions is ingrained in every cell by virtue of oxygen’s critical role in the genesis of life and evolution. These cellular responses to hypoxia are mediated by hypoxia-inducible factors (HIFs), isoforms of which include the more ubiquitous HIF-1 found in all parenchymal cells and HIF-2 found in specialized erythropoietin-producing cells of the kidney and the pulmonary circulation (the polycythemia and pulmonary vasoconstrictive responses from hypoxia are mediated through HIF-2 ). HIFs mediate the transcription of hundreds of genes, and they have been implicated in the pathobiology of a wide range of phenomena, from cancer to atherosclerotic vascular disease, metabolic syndrome, neurodegenerative disorders, pulmonary hypertension, and nonalcoholic fatty liver disease (Prabhakar and Semenza. Physiol Rev. 2012;92[3]:967). While HIF activation is an attractive target for examining the effects of chronic hypoxia of high altitude and sleep-disordered breathing, HIF activation varies from tissue to tissue and interacts with a number of other cellular systems in leading to differential effects. The short half-life of HIF proteins make them difficult to detect in tissues, so a number of secondary HIF-effects has been measured with mixed results depending on animal model utilized, pattern and degree of hypoxia studied, and the target effect measured. Comparative effects of intermittent vs sustained hypoxemia need to be systematically studied in different organ systems in different species, given the differing oxygen thresholds of individual cells due to unique blood flows and variations in the system of co-factors and prolyl hydroxylases that regulate the activation of HIFs. While the thrust of the work has been centered on HIF-related effects and the role of NF-kB-driven inflammation seen in OSA, there is substantial evidence to the role of oxidant stress that may be directly related to reoxygenation events occurring with CIH (Lavie L. Sleep Med Rev. 2015;20:27).

For life that has been intricately involved with oxygen from its genesis, it is not unreasonable to expect adaptations of cells, organs, and the whole individual to a wide range of oxygen tensions. Attempts to understand the import of sleep-disordered breathing has led to a need to unravel the implications of OSA-related chronic intermittent hypoxia and sleep-hypoventilation. This has led to a resurgence of interest in hypoxia-related research. Whether such chronic sleep-related sustained and intermittent hypoxemia is a harbinger of chronic disease is still not fully clear. A number of challenges exist with the understanding of these chronic hypoxia effects that include the long time needed for disease occurrence, its differential effects on organ systems, the role of hypoxia vs reoxygenation injury, importance of local blood flow, etc. Understanding these pathways will be crucial in prognosticating the role of sleep-related hypoxemia, the recognition of which has become part and parcel of routine management in sleep medicine.

Dr. Sundar is Medical Director, Sleep-Wake Center, Clinical Professor, Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah.

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

The Food and Drug Administration will now require that certain medications prescribed for insomnia carry a boxed warning because of associated complex sleep behaviors.

cpalmer@mdedge.com

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

koakes@mdedge.com

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

koakes@mdedge.com

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

koakes@mdedge.com

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

The prescription of positive airway pressure is associated with reduced all-cause mortality, according to the results of a cohort study published in JAMA Otolaryngology–Head & Neck Surgery.

The association becomes evident several years after positive airway pressure (PAP) initiation, according to the researchers. Obstructive sleep apnea (OSA) is among the top 10 modifiable cardiovascular risk factors, and is associated with increased risks of coronary artery disease, stroke, and death. PAP is the most effective treatment for OSA, but this treatment’s effect on all-cause and cardiovascular mortality is uncertain. Randomized trials have yielded inconclusive answers to this question, and evidence from observational studies has been weak.

To investigate the association between PAP prescription and mortality in patients with obesity and severe OSA, Quentin Lisan, MD, of the Paris Cardiovascular Research Center and his colleagues conducted a multicenter, population-based cohort study. The researchers examined data for 392 participants in the Sleep Heart Health Study, in which adult men and women age 40 years or older were recruited from nine population-based studies between 1995 and 1998 and followed for a mean of 11.1 years. With each participant who had been prescribed PAP, the investigators matched as many as four participants who had not been prescribed PAP, on the basis of age, sex, and apnea-hypopnea index. Of this sample, 81 patients were prescribed PAP, and 311 were not.

All participants had a clinic visit and underwent overnight polysomnography at baseline. At 2-3 years, participants had a follow-up visit or phone call, during which they were asked whether their physicians had prescribed PAP. Participants were monitored for cardiovascular and all-cause mortality.

In all, 319 of the 392 participants were men; the population’s mean age was 63 years. Patients who had received a PAP prescription had a higher body mass index and more education, compared with patients who had not received a prescription. Mean follow-up duration was 11.6 years in the PAP-prescribed group and 10.9 years in the nonprescribed group.

A total of 96 deaths occurred during follow-up: 12 in the PAP-prescribed group and 84 in the nonprescribed PAP group. The crude incidence rate of mortality was 24.7 deaths per 1,000 person-years in the nonprescribed group and 12.8 deaths per 1,000 person-years in the PAP-prescribed group. The difference in survival between the prescribed and nonprescribed groups was evident in survival curves after 6-7 years of follow-up. After adjustments for prevalent cardiovascular disease, hypertension, diabetes, body mass index, education level, smoking status, and alcohol consumption, the hazard ratio of all-cause mortality for the prescribed group was 0.38, compared with the nonprescribed group.

Dr. Lisan and his colleagues identified 27 deaths of cardiovascular origin, one of which occurred in the prescribed group. After adjusting for prevalent cardiovascular disease, the hazard ratio of cardiovascular mortality for the prescribed group was 0.06, compared with the nonprescribed group.

One reason that the reduction in mortality associated with PAP was not found in previous randomized, controlled trials could be that their mean length of follow-up was not long enough, the researchers wrote. For example, the mean length of follow-up in the SAVE trial was 3.7 years, but the survival benefit was not apparent in the present analysis until 6-7 years after treatment initiation.

These results are exploratory and require confirmation in future research, Dr. Lisan and his colleagues wrote. No information on adherence to PAP was available, and the researchers could not account for initiation and interruption of PAP therapy. Nevertheless, “prescribing PAP in patients with OSA should be pursued and encouraged, given its potential major public health implication,” they concluded.

The Sleep Heart Health Study was supported by grants from the National Institutes of Health.

egreb@mdedge.com

SOURCE: Lisan Q et al. JAMA Otolaryngol Head Neck Surg. 2019 Apr 11. doi: 10.1001/jamaoto.2019.0281.

The prescription of positive airway pressure is associated with reduced all-cause mortality, according to the results of a cohort study published in JAMA Otolaryngology–Head & Neck Surgery.

The association becomes evident several years after positive airway pressure (PAP) initiation, according to the researchers. Obstructive sleep apnea (OSA) is among the top 10 modifiable cardiovascular risk factors, and is associated with increased risks of coronary artery disease, stroke, and death. PAP is the most effective treatment for OSA, but this treatment’s effect on all-cause and cardiovascular mortality is uncertain. Randomized trials have yielded inconclusive answers to this question, and evidence from observational studies has been weak.

To investigate the association between PAP prescription and mortality in patients with obesity and severe OSA, Quentin Lisan, MD, of the Paris Cardiovascular Research Center and his colleagues conducted a multicenter, population-based cohort study. The researchers examined data for 392 participants in the Sleep Heart Health Study, in which adult men and women age 40 years or older were recruited from nine population-based studies between 1995 and 1998 and followed for a mean of 11.1 years. With each participant who had been prescribed PAP, the investigators matched as many as four participants who had not been prescribed PAP, on the basis of age, sex, and apnea-hypopnea index. Of this sample, 81 patients were prescribed PAP, and 311 were not.

All participants had a clinic visit and underwent overnight polysomnography at baseline. At 2-3 years, participants had a follow-up visit or phone call, during which they were asked whether their physicians had prescribed PAP. Participants were monitored for cardiovascular and all-cause mortality.

In all, 319 of the 392 participants were men; the population’s mean age was 63 years. Patients who had received a PAP prescription had a higher body mass index and more education, compared with patients who had not received a prescription. Mean follow-up duration was 11.6 years in the PAP-prescribed group and 10.9 years in the nonprescribed group.

A total of 96 deaths occurred during follow-up: 12 in the PAP-prescribed group and 84 in the nonprescribed PAP group. The crude incidence rate of mortality was 24.7 deaths per 1,000 person-years in the nonprescribed group and 12.8 deaths per 1,000 person-years in the PAP-prescribed group. The difference in survival between the prescribed and nonprescribed groups was evident in survival curves after 6-7 years of follow-up. After adjustments for prevalent cardiovascular disease, hypertension, diabetes, body mass index, education level, smoking status, and alcohol consumption, the hazard ratio of all-cause mortality for the prescribed group was 0.38, compared with the nonprescribed group.

Dr. Lisan and his colleagues identified 27 deaths of cardiovascular origin, one of which occurred in the prescribed group. After adjusting for prevalent cardiovascular disease, the hazard ratio of cardiovascular mortality for the prescribed group was 0.06, compared with the nonprescribed group.

One reason that the reduction in mortality associated with PAP was not found in previous randomized, controlled trials could be that their mean length of follow-up was not long enough, the researchers wrote. For example, the mean length of follow-up in the SAVE trial was 3.7 years, but the survival benefit was not apparent in the present analysis until 6-7 years after treatment initiation.

These results are exploratory and require confirmation in future research, Dr. Lisan and his colleagues wrote. No information on adherence to PAP was available, and the researchers could not account for initiation and interruption of PAP therapy. Nevertheless, “prescribing PAP in patients with OSA should be pursued and encouraged, given its potential major public health implication,” they concluded.

The Sleep Heart Health Study was supported by grants from the National Institutes of Health.

egreb@mdedge.com

SOURCE: Lisan Q et al. JAMA Otolaryngol Head Neck Surg. 2019 Apr 11. doi: 10.1001/jamaoto.2019.0281.

The prescription of positive airway pressure is associated with reduced all-cause mortality, according to the results of a cohort study published in JAMA Otolaryngology–Head & Neck Surgery.

The association becomes evident several years after positive airway pressure (PAP) initiation, according to the researchers. Obstructive sleep apnea (OSA) is among the top 10 modifiable cardiovascular risk factors, and is associated with increased risks of coronary artery disease, stroke, and death. PAP is the most effective treatment for OSA, but this treatment’s effect on all-cause and cardiovascular mortality is uncertain. Randomized trials have yielded inconclusive answers to this question, and evidence from observational studies has been weak.

To investigate the association between PAP prescription and mortality in patients with obesity and severe OSA, Quentin Lisan, MD, of the Paris Cardiovascular Research Center and his colleagues conducted a multicenter, population-based cohort study. The researchers examined data for 392 participants in the Sleep Heart Health Study, in which adult men and women age 40 years or older were recruited from nine population-based studies between 1995 and 1998 and followed for a mean of 11.1 years. With each participant who had been prescribed PAP, the investigators matched as many as four participants who had not been prescribed PAP, on the basis of age, sex, and apnea-hypopnea index. Of this sample, 81 patients were prescribed PAP, and 311 were not.

All participants had a clinic visit and underwent overnight polysomnography at baseline. At 2-3 years, participants had a follow-up visit or phone call, during which they were asked whether their physicians had prescribed PAP. Participants were monitored for cardiovascular and all-cause mortality.

In all, 319 of the 392 participants were men; the population’s mean age was 63 years. Patients who had received a PAP prescription had a higher body mass index and more education, compared with patients who had not received a prescription. Mean follow-up duration was 11.6 years in the PAP-prescribed group and 10.9 years in the nonprescribed group.

A total of 96 deaths occurred during follow-up: 12 in the PAP-prescribed group and 84 in the nonprescribed PAP group. The crude incidence rate of mortality was 24.7 deaths per 1,000 person-years in the nonprescribed group and 12.8 deaths per 1,000 person-years in the PAP-prescribed group. The difference in survival between the prescribed and nonprescribed groups was evident in survival curves after 6-7 years of follow-up. After adjustments for prevalent cardiovascular disease, hypertension, diabetes, body mass index, education level, smoking status, and alcohol consumption, the hazard ratio of all-cause mortality for the prescribed group was 0.38, compared with the nonprescribed group.

Dr. Lisan and his colleagues identified 27 deaths of cardiovascular origin, one of which occurred in the prescribed group. After adjusting for prevalent cardiovascular disease, the hazard ratio of cardiovascular mortality for the prescribed group was 0.06, compared with the nonprescribed group.

One reason that the reduction in mortality associated with PAP was not found in previous randomized, controlled trials could be that their mean length of follow-up was not long enough, the researchers wrote. For example, the mean length of follow-up in the SAVE trial was 3.7 years, but the survival benefit was not apparent in the present analysis until 6-7 years after treatment initiation.

These results are exploratory and require confirmation in future research, Dr. Lisan and his colleagues wrote. No information on adherence to PAP was available, and the researchers could not account for initiation and interruption of PAP therapy. Nevertheless, “prescribing PAP in patients with OSA should be pursued and encouraged, given its potential major public health implication,” they concluded.

The Sleep Heart Health Study was supported by grants from the National Institutes of Health.

egreb@mdedge.com

SOURCE: Lisan Q et al. JAMA Otolaryngol Head Neck Surg. 2019 Apr 11. doi: 10.1001/jamaoto.2019.0281.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

About a quarter of patients with obstructive sleep apnea also had clinical depression and used antidepressants, recent research has shown.

Although patients in the study associated their sleep disorder with poorer quality of life as well as symptoms of anxiety and depression, it is unclear whether treating their obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) would alleviate these symptoms, said Melinda L. Jackson, PhD, from Monash University in Clayton, Victoria, Australia, and her colleagues.

“OSA is a modifiable factor that, if treated, may reduce the economic, health care, and personal burden of depression,” Dr. Jackson and her colleagues wrote in their study, recently published in the journal Sleep Medicine. “Findings from the treatment phase of this study will help us determine whether clinical depression is alleviated with CPAP use, taking into account antidepressant use; whether there are subgroups of patients who respond better to treatment; and what are the characteristics of patients who respond compared to those who remain depressed.”

The researchers used baseline data from 109 patients in the CPAP for OSA and Depression trial who were diagnosed with OSA. Participants (mean age, 52.6 years; 43.1% female) consecutively presented to a sleep laboratory where they answered interview questions to assess clinical depression and sleep habits. Data were collected using the structured clinical interview for depression (SCID-IV), Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), Epworth Sleepiness Scale, and Assessment of Quality of Life questionnaire. In addition, the researchers performed a meta-analysis of seven studies, including the current study, to determine the prevalence of clinical depression among patients with untreated OSA.

Overall, SCID-IV scores identified clinical depression in 25 participants (22.7%), and these participants said they had greater sleep disturbance and reported higher depressive, anxiety and stress as well as lower quality of life as a result of their clinical depression. Researchers found these participants also had significantly worse quality of sleep (P less than .05) and daytime dysfunction (P less than .05) as identified by PSQI scores, while FOSQ results showed participants with clinical depression had significantly lower activity levels, social outcomes, and general productivity, compared with patients without clinical depression (P less than .05). In a meta-analysis, Dr. Jackson and her colleagues found a pooled prevalence of 23% for clinical depression among participants with OSA.

Participants using antidepressants were examined separately from participants who had clinical depression. The researchers found 27 participants (24.8%) using antidepressants who also had reported higher symptoms of anxiety, depression and stress, lower quality of life, and poorer sleep outcomes. Participants using antidepressants also were more likely to have bipolar disorder or a condition such as hypertension, chronic obstructive pulmonary disease, high cholesterol, or type 2 diabetes, and 75% of these participants reported having some type of comorbid condition.

Dr. Jackson and her colleagues noted they were uncertain whether depression or OSA occurred first, or whether depression exacerbated symptoms of OSA through other factors such as weight gain, sleep disruption, inactivity, or alcohol use. Depression and OSA may also present independently of one another, they added.

“Development of scales to better capture information about when symptoms commenced and the length of time an individual has experienced OSA will provide a clearer understanding of the consequences of OSA on psychological and medical conditions,” the researchers said.

This study was funded by the Austin Medical Research Fund, and one authors reported support from an National Health and Medical Research Council Early Career Fellowship. The authors report no relevant conflicts of interest.

SOURCE: Jackson ML et al. Sleep Med. 2019 Mar 27. doi: 10.1016/j.sleep.2019.03.011.

About a quarter of patients with obstructive sleep apnea also had clinical depression and used antidepressants, recent research has shown.

Although patients in the study associated their sleep disorder with poorer quality of life as well as symptoms of anxiety and depression, it is unclear whether treating their obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) would alleviate these symptoms, said Melinda L. Jackson, PhD, from Monash University in Clayton, Victoria, Australia, and her colleagues.

“OSA is a modifiable factor that, if treated, may reduce the economic, health care, and personal burden of depression,” Dr. Jackson and her colleagues wrote in their study, recently published in the journal Sleep Medicine. “Findings from the treatment phase of this study will help us determine whether clinical depression is alleviated with CPAP use, taking into account antidepressant use; whether there are subgroups of patients who respond better to treatment; and what are the characteristics of patients who respond compared to those who remain depressed.”

The researchers used baseline data from 109 patients in the CPAP for OSA and Depression trial who were diagnosed with OSA. Participants (mean age, 52.6 years; 43.1% female) consecutively presented to a sleep laboratory where they answered interview questions to assess clinical depression and sleep habits. Data were collected using the structured clinical interview for depression (SCID-IV), Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), Epworth Sleepiness Scale, and Assessment of Quality of Life questionnaire. In addition, the researchers performed a meta-analysis of seven studies, including the current study, to determine the prevalence of clinical depression among patients with untreated OSA.

Overall, SCID-IV scores identified clinical depression in 25 participants (22.7%), and these participants said they had greater sleep disturbance and reported higher depressive, anxiety and stress as well as lower quality of life as a result of their clinical depression. Researchers found these participants also had significantly worse quality of sleep (P less than .05) and daytime dysfunction (P less than .05) as identified by PSQI scores, while FOSQ results showed participants with clinical depression had significantly lower activity levels, social outcomes, and general productivity, compared with patients without clinical depression (P less than .05). In a meta-analysis, Dr. Jackson and her colleagues found a pooled prevalence of 23% for clinical depression among participants with OSA.

Participants using antidepressants were examined separately from participants who had clinical depression. The researchers found 27 participants (24.8%) using antidepressants who also had reported higher symptoms of anxiety, depression and stress, lower quality of life, and poorer sleep outcomes. Participants using antidepressants also were more likely to have bipolar disorder or a condition such as hypertension, chronic obstructive pulmonary disease, high cholesterol, or type 2 diabetes, and 75% of these participants reported having some type of comorbid condition.

Dr. Jackson and her colleagues noted they were uncertain whether depression or OSA occurred first, or whether depression exacerbated symptoms of OSA through other factors such as weight gain, sleep disruption, inactivity, or alcohol use. Depression and OSA may also present independently of one another, they added.

“Development of scales to better capture information about when symptoms commenced and the length of time an individual has experienced OSA will provide a clearer understanding of the consequences of OSA on psychological and medical conditions,” the researchers said.

This study was funded by the Austin Medical Research Fund, and one authors reported support from an National Health and Medical Research Council Early Career Fellowship. The authors report no relevant conflicts of interest.

SOURCE: Jackson ML et al. Sleep Med. 2019 Mar 27. doi: 10.1016/j.sleep.2019.03.011.

About a quarter of patients with obstructive sleep apnea also had clinical depression and used antidepressants, recent research has shown.

Although patients in the study associated their sleep disorder with poorer quality of life as well as symptoms of anxiety and depression, it is unclear whether treating their obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) would alleviate these symptoms, said Melinda L. Jackson, PhD, from Monash University in Clayton, Victoria, Australia, and her colleagues.

“OSA is a modifiable factor that, if treated, may reduce the economic, health care, and personal burden of depression,” Dr. Jackson and her colleagues wrote in their study, recently published in the journal Sleep Medicine. “Findings from the treatment phase of this study will help us determine whether clinical depression is alleviated with CPAP use, taking into account antidepressant use; whether there are subgroups of patients who respond better to treatment; and what are the characteristics of patients who respond compared to those who remain depressed.”

The researchers used baseline data from 109 patients in the CPAP for OSA and Depression trial who were diagnosed with OSA. Participants (mean age, 52.6 years; 43.1% female) consecutively presented to a sleep laboratory where they answered interview questions to assess clinical depression and sleep habits. Data were collected using the structured clinical interview for depression (SCID-IV), Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), Epworth Sleepiness Scale, and Assessment of Quality of Life questionnaire. In addition, the researchers performed a meta-analysis of seven studies, including the current study, to determine the prevalence of clinical depression among patients with untreated OSA.

Overall, SCID-IV scores identified clinical depression in 25 participants (22.7%), and these participants said they had greater sleep disturbance and reported higher depressive, anxiety and stress as well as lower quality of life as a result of their clinical depression. Researchers found these participants also had significantly worse quality of sleep (P less than .05) and daytime dysfunction (P less than .05) as identified by PSQI scores, while FOSQ results showed participants with clinical depression had significantly lower activity levels, social outcomes, and general productivity, compared with patients without clinical depression (P less than .05). In a meta-analysis, Dr. Jackson and her colleagues found a pooled prevalence of 23% for clinical depression among participants with OSA.

Participants using antidepressants were examined separately from participants who had clinical depression. The researchers found 27 participants (24.8%) using antidepressants who also had reported higher symptoms of anxiety, depression and stress, lower quality of life, and poorer sleep outcomes. Participants using antidepressants also were more likely to have bipolar disorder or a condition such as hypertension, chronic obstructive pulmonary disease, high cholesterol, or type 2 diabetes, and 75% of these participants reported having some type of comorbid condition.

Dr. Jackson and her colleagues noted they were uncertain whether depression or OSA occurred first, or whether depression exacerbated symptoms of OSA through other factors such as weight gain, sleep disruption, inactivity, or alcohol use. Depression and OSA may also present independently of one another, they added.

“Development of scales to better capture information about when symptoms commenced and the length of time an individual has experienced OSA will provide a clearer understanding of the consequences of OSA on psychological and medical conditions,” the researchers said.

This study was funded by the Austin Medical Research Fund, and one authors reported support from an National Health and Medical Research Council Early Career Fellowship. The authors report no relevant conflicts of interest.

SOURCE: Jackson ML et al. Sleep Med. 2019 Mar 27. doi: 10.1016/j.sleep.2019.03.011.

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

chestphysiciannews@chestnet.org

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

chestphysiciannews@chestnet.org

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.

Courtesy ResMed

No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.

In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.

“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.

“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.

In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.

In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.

That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.

For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.

Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.

It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.

However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.

For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.

Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.

chestphysiciannews@chestnet.org

SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.

NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.

Ted Bosworth/MDedge News

“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.

Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.

In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.

“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.

“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.

Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.

According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.

“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.

“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.

“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”

SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.

NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.

Ted Bosworth/MDedge News

“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.

Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.

In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.

“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.

“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.

Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.

According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.

“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.

“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.

“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”

SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.

NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.

Ted Bosworth/MDedge News

“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.

Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.

In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.

“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.

“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.

Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.

According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.

“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.

“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.

“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”

SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.

The Food and Drug Administration has approved solriamfetol (Sunosi) for the treatment of excessive daytime sleepiness in patients with narcolepsy or obstructive sleep apnea. It is the first dopamine and norepinephrine reuptake inhibitor approved to treat those conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval was based on results from TONES (Treatment of Obstructive Sleep Apnea and Narcolepsy Excessive Sleepiness), a phase 3 study that combined four randomized, placebo-controlled trials assessing solriamfetol at various doses, compared with a placebo. After 12 weeks, 68%-74% of patients taking solriamfetol at 75 mg and 78%-90% of those taking solriamfetol at 150 mg reported improvement as assessed by the Patient Global Impression of Change scale.

Solriamfetol is approved at 75 mg and 150 mg for patients with narcolepsy and at 37.5 mg, 75 mg, and 150 mg for patients with obstructive sleep apnea. The most common adverse events associated with solriamfetol are headache, nausea, decreased appetite, and anxiety.

“Excessive daytime sleepiness can negatively impact the daily lives of people living with narcolepsy or obstructive sleep apnea at work, at home, or in daily activities. With this approval, a new, daytime medicine that can provide sustained wakefulness throughout the day will be available for patients,” Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals, said in the press release.

Find the full press release on the Jazz Pharmaceuticals website.

lfranki@mdedge.com

The Food and Drug Administration has approved solriamfetol (Sunosi) for the treatment of excessive daytime sleepiness in patients with narcolepsy or obstructive sleep apnea. It is the first dopamine and norepinephrine reuptake inhibitor approved to treat those conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval was based on results from TONES (Treatment of Obstructive Sleep Apnea and Narcolepsy Excessive Sleepiness), a phase 3 study that combined four randomized, placebo-controlled trials assessing solriamfetol at various doses, compared with a placebo. After 12 weeks, 68%-74% of patients taking solriamfetol at 75 mg and 78%-90% of those taking solriamfetol at 150 mg reported improvement as assessed by the Patient Global Impression of Change scale.

Solriamfetol is approved at 75 mg and 150 mg for patients with narcolepsy and at 37.5 mg, 75 mg, and 150 mg for patients with obstructive sleep apnea. The most common adverse events associated with solriamfetol are headache, nausea, decreased appetite, and anxiety.

“Excessive daytime sleepiness can negatively impact the daily lives of people living with narcolepsy or obstructive sleep apnea at work, at home, or in daily activities. With this approval, a new, daytime medicine that can provide sustained wakefulness throughout the day will be available for patients,” Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals, said in the press release.

Find the full press release on the Jazz Pharmaceuticals website.

lfranki@mdedge.com

The Food and Drug Administration has approved solriamfetol (Sunosi) for the treatment of excessive daytime sleepiness in patients with narcolepsy or obstructive sleep apnea. It is the first dopamine and norepinephrine reuptake inhibitor approved to treat those conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval was based on results from TONES (Treatment of Obstructive Sleep Apnea and Narcolepsy Excessive Sleepiness), a phase 3 study that combined four randomized, placebo-controlled trials assessing solriamfetol at various doses, compared with a placebo. After 12 weeks, 68%-74% of patients taking solriamfetol at 75 mg and 78%-90% of those taking solriamfetol at 150 mg reported improvement as assessed by the Patient Global Impression of Change scale.

Solriamfetol is approved at 75 mg and 150 mg for patients with narcolepsy and at 37.5 mg, 75 mg, and 150 mg for patients with obstructive sleep apnea. The most common adverse events associated with solriamfetol are headache, nausea, decreased appetite, and anxiety.

“Excessive daytime sleepiness can negatively impact the daily lives of people living with narcolepsy or obstructive sleep apnea at work, at home, or in daily activities. With this approval, a new, daytime medicine that can provide sustained wakefulness throughout the day will be available for patients,” Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals, said in the press release.

Find the full press release on the Jazz Pharmaceuticals website.

lfranki@mdedge.com