Sleep Medicine

To the Editor: The review by May et al¹ of 3 neglected numbers in the complete blood cell count (CBC) was a good reminder to look more closely at the results of the CBCs we often order in primary care. I was surprised to see no mention of the red cell distribution width in relation to another cardiovascular disorder—obstructive sleep apnea.^2,3 I wonder if the authors would comment on this association?

To the Editor: The review by May et al¹ of 3 neglected numbers in the complete blood cell count (CBC) was a good reminder to look more closely at the results of the CBCs we often order in primary care. I was surprised to see no mention of the red cell distribution width in relation to another cardiovascular disorder—obstructive sleep apnea.^2,3 I wonder if the authors would comment on this association?

To the Editor: The review by May et al¹ of 3 neglected numbers in the complete blood cell count (CBC) was a good reminder to look more closely at the results of the CBCs we often order in primary care. I was surprised to see no mention of the red cell distribution width in relation to another cardiovascular disorder—obstructive sleep apnea.^2,3 I wonder if the authors would comment on this association?

In Reply: We thank Dr. Homler for his question and for highlighting another important disease state, obstructive sleep apnea, in which a high red cell distribution width (RDW) has correlated with disease severity.^1,2 The 2 retrospective studies he mentioned indicated that RDW is negatively correlated with metrics such as oxygen saturation, sleep time, and sleep quality. Interestingly, another retrospective study showed that RDW was significantly higher in patients with concurrent obstructive sleep apnea and cardiovascular disease than in patients with obstructive sleep apnea alone, suggesting that the presence of anisocytosis in obstructive sleep apnea may be due to its link to cardiovascular disease.³

Although we focused on cardiovascular disease in our review, RDW has also shown prognostic significance in many other disorders including ischemic stroke,⁴ pneumonia,^5,6 chronic kidney disease,⁷ and gastrointestinal disorders.⁸ Collectively, these studies indicate that RDW may serve as a red flag for clinicians, raising concern for increased disease severity and potential adverse outcomes. However, further research is needed to determine if and how RDW monitoring should be used to prompt interventions to improve patient outcomes.

In Reply: We thank Dr. Homler for his question and for highlighting another important disease state, obstructive sleep apnea, in which a high red cell distribution width (RDW) has correlated with disease severity.^1,2 The 2 retrospective studies he mentioned indicated that RDW is negatively correlated with metrics such as oxygen saturation, sleep time, and sleep quality. Interestingly, another retrospective study showed that RDW was significantly higher in patients with concurrent obstructive sleep apnea and cardiovascular disease than in patients with obstructive sleep apnea alone, suggesting that the presence of anisocytosis in obstructive sleep apnea may be due to its link to cardiovascular disease.³

Although we focused on cardiovascular disease in our review, RDW has also shown prognostic significance in many other disorders including ischemic stroke,⁴ pneumonia,^5,6 chronic kidney disease,⁷ and gastrointestinal disorders.⁸ Collectively, these studies indicate that RDW may serve as a red flag for clinicians, raising concern for increased disease severity and potential adverse outcomes. However, further research is needed to determine if and how RDW monitoring should be used to prompt interventions to improve patient outcomes.

In Reply: We thank Dr. Homler for his question and for highlighting another important disease state, obstructive sleep apnea, in which a high red cell distribution width (RDW) has correlated with disease severity.^1,2 The 2 retrospective studies he mentioned indicated that RDW is negatively correlated with metrics such as oxygen saturation, sleep time, and sleep quality. Interestingly, another retrospective study showed that RDW was significantly higher in patients with concurrent obstructive sleep apnea and cardiovascular disease than in patients with obstructive sleep apnea alone, suggesting that the presence of anisocytosis in obstructive sleep apnea may be due to its link to cardiovascular disease.³

Although we focused on cardiovascular disease in our review, RDW has also shown prognostic significance in many other disorders including ischemic stroke,⁴ pneumonia,^5,6 chronic kidney disease,⁷ and gastrointestinal disorders.⁸ Collectively, these studies indicate that RDW may serve as a red flag for clinicians, raising concern for increased disease severity and potential adverse outcomes. However, further research is needed to determine if and how RDW monitoring should be used to prompt interventions to improve patient outcomes.

DALLAS – Continuous positive airway pressure (CPAP) is an effective, feasible treatment for infants with obstructive sleep apnea (OSA), according to a study.

“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.

The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.

Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).

None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.

In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).

Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.

Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).

Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.

In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.

The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.

SOURCE: Cielo CM et al. ATS 2019. Abstract A2786.

DALLAS – Continuous positive airway pressure (CPAP) is an effective, feasible treatment for infants with obstructive sleep apnea (OSA), according to a study.

“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.

The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.

Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).

None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.

In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).

Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.

Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).

Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.

In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.

The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.

SOURCE: Cielo CM et al. ATS 2019. Abstract A2786.

DALLAS – Continuous positive airway pressure (CPAP) is an effective, feasible treatment for infants with obstructive sleep apnea (OSA), according to a study.

“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.

The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.

Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).

None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.

In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).

Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.

Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).

Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.

In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.

The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.

SOURCE: Cielo CM et al. ATS 2019. Abstract A2786.

DALLAS – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, but nighttime use of technology may contribute more to sleep problems, according to a new study.

“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.

Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.

Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.

Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.

The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.

Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.

The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.

The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.

SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.

DALLAS – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, but nighttime use of technology may contribute more to sleep problems, according to a new study.

“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.

Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.

Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.

Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.

The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.

Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.

The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.

The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.

SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.

DALLAS – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, but nighttime use of technology may contribute more to sleep problems, according to a new study.

“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.

Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.

Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.

Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.

The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.

Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.

The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.

The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.

SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

Unrecognized severe obstructive sleep apnea is a risk factor for cardiovascular complications after major noncardiac surgery, according to a study published in JAMA.

The researchers state that perioperative mismanagement of obstructive sleep apnea can lead to serious medical consequences. “General anesthetics, sedatives, and postoperative analgesics are potent respiratory depressants that relax the upper airway dilator muscles and impair ventilatory response to hypoxemia and hypercapnia. Each of these events exacerbates [obstructive sleep apnea] and may predispose patients to postoperative cardiovascular complications,” said researchers who conducted the The Postoperative vascular complications in unrecognised Obstructive Sleep apnoea (POSA) study (NCT01494181).

They undertook a prospective observational cohort study involving 1,218 patients undergoing major noncardiac surgery, who were already considered at high risk of postoperative cardiovascular events – having, for example, a history of coronary artery disease, stroke, diabetes, or renal impairment. However, none had a prior diagnosis of obstructive sleep apnea.

Preoperative sleep monitoring revealed that two-thirds of the cohort had unrecognized and untreated obstructive sleep apnea, including 11.2% with severe obstructive sleep apnea.

At 30 days after surgery, patients with obstructive sleep apnea had a 49% higher risk of the primary outcome of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, or stroke, compared with those without obstructive sleep apnea.

However, this association was largely due to a significant 2.23-fold higher risk among patients with severe obstructive sleep apnea, while those with only moderate or mild sleep apnea did not show a significant increased risk of cardiovascular complications.

Patients in this study with severe obstructive sleep apnea had a 13-fold higher risk of cardiac death, 80% higher risk of myocardial injury, more than sixfold higher risk of heart failure, and nearly fourfold higher risk of atrial fibrillation.

Researchers also saw an association between obstructive sleep apnea and increased risk of infective outcomes, unplanned tracheal intubation, postoperative lung ventilation, and readmission to the ICU.

The majority of patients received nocturnal oximetry monitoring during their first 3 nights after surgery. This revealed that patients without obstructive sleep apnea had significant increases in oxygen desaturation index during their first night after surgery, while those with sleep apnea did not return to their baseline oxygen desaturation index until the third night after surgery.

“Despite a substantial decrease in ODI [oxygen desaturation index] with oxygen therapy in patients with OSA during the first 3 postoperative nights, supplemental oxygen did not modify the association between OSA and postoperative cardiovascular event,” wrote Matthew T.V. Chan, MD, of Chinese University of Hong Kong, Prince of Wales Hospital, and coauthors.

Given that the events were associated with longer durations of severe oxyhemoglobin desaturation, more aggressive interventions such as positive airway pressure or oral appliances may be required, they noted.

“However, high-level evidence demonstrating the effect of these measures on perioperative outcomes is lacking [and] further clinical trials are now required to test if additional monitoring or alternative interventions would reduce the risk,” they wrote.

The study was supported by the Health and Medical Research Fund (Hong Kong), National Healthcare Group–Khoo Teck Puat Hospital, University Health Network Foundation, University of Malaya, Malaysian Society of Anaesthesiologists, Auckland Medical Research Foundation, and ResMed. One author declared grants from private industry and a patent pending on an obstructive sleep apnea risk questionnaire used in the study.

SOURCE: Chan M et al. JAMA 2019;321[18]:1788-98. doi: 10.1001/jama.2019.4783.

Unrecognized severe obstructive sleep apnea is a risk factor for cardiovascular complications after major noncardiac surgery, according to a study published in JAMA.

The researchers state that perioperative mismanagement of obstructive sleep apnea can lead to serious medical consequences. “General anesthetics, sedatives, and postoperative analgesics are potent respiratory depressants that relax the upper airway dilator muscles and impair ventilatory response to hypoxemia and hypercapnia. Each of these events exacerbates [obstructive sleep apnea] and may predispose patients to postoperative cardiovascular complications,” said researchers who conducted the The Postoperative vascular complications in unrecognised Obstructive Sleep apnoea (POSA) study (NCT01494181).

They undertook a prospective observational cohort study involving 1,218 patients undergoing major noncardiac surgery, who were already considered at high risk of postoperative cardiovascular events – having, for example, a history of coronary artery disease, stroke, diabetes, or renal impairment. However, none had a prior diagnosis of obstructive sleep apnea.

Preoperative sleep monitoring revealed that two-thirds of the cohort had unrecognized and untreated obstructive sleep apnea, including 11.2% with severe obstructive sleep apnea.

At 30 days after surgery, patients with obstructive sleep apnea had a 49% higher risk of the primary outcome of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, or stroke, compared with those without obstructive sleep apnea.

However, this association was largely due to a significant 2.23-fold higher risk among patients with severe obstructive sleep apnea, while those with only moderate or mild sleep apnea did not show a significant increased risk of cardiovascular complications.

Patients in this study with severe obstructive sleep apnea had a 13-fold higher risk of cardiac death, 80% higher risk of myocardial injury, more than sixfold higher risk of heart failure, and nearly fourfold higher risk of atrial fibrillation.

Researchers also saw an association between obstructive sleep apnea and increased risk of infective outcomes, unplanned tracheal intubation, postoperative lung ventilation, and readmission to the ICU.

The majority of patients received nocturnal oximetry monitoring during their first 3 nights after surgery. This revealed that patients without obstructive sleep apnea had significant increases in oxygen desaturation index during their first night after surgery, while those with sleep apnea did not return to their baseline oxygen desaturation index until the third night after surgery.

“Despite a substantial decrease in ODI [oxygen desaturation index] with oxygen therapy in patients with OSA during the first 3 postoperative nights, supplemental oxygen did not modify the association between OSA and postoperative cardiovascular event,” wrote Matthew T.V. Chan, MD, of Chinese University of Hong Kong, Prince of Wales Hospital, and coauthors.

Given that the events were associated with longer durations of severe oxyhemoglobin desaturation, more aggressive interventions such as positive airway pressure or oral appliances may be required, they noted.

“However, high-level evidence demonstrating the effect of these measures on perioperative outcomes is lacking [and] further clinical trials are now required to test if additional monitoring or alternative interventions would reduce the risk,” they wrote.

The study was supported by the Health and Medical Research Fund (Hong Kong), National Healthcare Group–Khoo Teck Puat Hospital, University Health Network Foundation, University of Malaya, Malaysian Society of Anaesthesiologists, Auckland Medical Research Foundation, and ResMed. One author declared grants from private industry and a patent pending on an obstructive sleep apnea risk questionnaire used in the study.

SOURCE: Chan M et al. JAMA 2019;321[18]:1788-98. doi: 10.1001/jama.2019.4783.

Unrecognized severe obstructive sleep apnea is a risk factor for cardiovascular complications after major noncardiac surgery, according to a study published in JAMA.

The researchers state that perioperative mismanagement of obstructive sleep apnea can lead to serious medical consequences. “General anesthetics, sedatives, and postoperative analgesics are potent respiratory depressants that relax the upper airway dilator muscles and impair ventilatory response to hypoxemia and hypercapnia. Each of these events exacerbates [obstructive sleep apnea] and may predispose patients to postoperative cardiovascular complications,” said researchers who conducted the The Postoperative vascular complications in unrecognised Obstructive Sleep apnoea (POSA) study (NCT01494181).

They undertook a prospective observational cohort study involving 1,218 patients undergoing major noncardiac surgery, who were already considered at high risk of postoperative cardiovascular events – having, for example, a history of coronary artery disease, stroke, diabetes, or renal impairment. However, none had a prior diagnosis of obstructive sleep apnea.

Preoperative sleep monitoring revealed that two-thirds of the cohort had unrecognized and untreated obstructive sleep apnea, including 11.2% with severe obstructive sleep apnea.

At 30 days after surgery, patients with obstructive sleep apnea had a 49% higher risk of the primary outcome of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, or stroke, compared with those without obstructive sleep apnea.

However, this association was largely due to a significant 2.23-fold higher risk among patients with severe obstructive sleep apnea, while those with only moderate or mild sleep apnea did not show a significant increased risk of cardiovascular complications.

Patients in this study with severe obstructive sleep apnea had a 13-fold higher risk of cardiac death, 80% higher risk of myocardial injury, more than sixfold higher risk of heart failure, and nearly fourfold higher risk of atrial fibrillation.

Researchers also saw an association between obstructive sleep apnea and increased risk of infective outcomes, unplanned tracheal intubation, postoperative lung ventilation, and readmission to the ICU.

The majority of patients received nocturnal oximetry monitoring during their first 3 nights after surgery. This revealed that patients without obstructive sleep apnea had significant increases in oxygen desaturation index during their first night after surgery, while those with sleep apnea did not return to their baseline oxygen desaturation index until the third night after surgery.

“Despite a substantial decrease in ODI [oxygen desaturation index] with oxygen therapy in patients with OSA during the first 3 postoperative nights, supplemental oxygen did not modify the association between OSA and postoperative cardiovascular event,” wrote Matthew T.V. Chan, MD, of Chinese University of Hong Kong, Prince of Wales Hospital, and coauthors.

Given that the events were associated with longer durations of severe oxyhemoglobin desaturation, more aggressive interventions such as positive airway pressure or oral appliances may be required, they noted.

“However, high-level evidence demonstrating the effect of these measures on perioperative outcomes is lacking [and] further clinical trials are now required to test if additional monitoring or alternative interventions would reduce the risk,” they wrote.

The study was supported by the Health and Medical Research Fund (Hong Kong), National Healthcare Group–Khoo Teck Puat Hospital, University Health Network Foundation, University of Malaya, Malaysian Society of Anaesthesiologists, Auckland Medical Research Foundation, and ResMed. One author declared grants from private industry and a patent pending on an obstructive sleep apnea risk questionnaire used in the study.

SOURCE: Chan M et al. JAMA 2019;321[18]:1788-98. doi: 10.1001/jama.2019.4783.

PHILADELPHIA – Nearly a quarter of adults with epilepsy have moderate or severe insomnia, and insomnia symptoms are associated with depression, anxiety, worse seizure control, and poorer quality of life, according to a prospective analysis presented at the annual meeting of the American Academy of Neurology. Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.

“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.

Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.

To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.

The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).

Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.

“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.

Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.

[email protected]

SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.

PHILADELPHIA – Nearly a quarter of adults with epilepsy have moderate or severe insomnia, and insomnia symptoms are associated with depression, anxiety, worse seizure control, and poorer quality of life, according to a prospective analysis presented at the annual meeting of the American Academy of Neurology. Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.

“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.

Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.

To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.

The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).

Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.

“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.

Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.

[email protected]

SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.

PHILADELPHIA – Nearly a quarter of adults with epilepsy have moderate or severe insomnia, and insomnia symptoms are associated with depression, anxiety, worse seizure control, and poorer quality of life, according to a prospective analysis presented at the annual meeting of the American Academy of Neurology. Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.

“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.

Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.

To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.

The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).

Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.

“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.

Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.

[email protected]

SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.

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.

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

[email protected]

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

[email protected]