Sleep Medicine

Children with Down syndrome often have sleep‐disordered breathing (SDB), and a new study suggests that long-term monitoring via sleep studies is warranted because the condition frequently persists and recurs.

©DenKuvaiev/Thinkstock

“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”

The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.

According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).

“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.

Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.

The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”

The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).

Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.

Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.

Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).

As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”

In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”

No study funding was reported. The study authors reported no disclosures.

SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.

Children with Down syndrome often have sleep‐disordered breathing (SDB), and a new study suggests that long-term monitoring via sleep studies is warranted because the condition frequently persists and recurs.

©DenKuvaiev/Thinkstock

“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”

The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.

According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).

“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.

Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.

The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”

The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).

Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.

Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.

Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).

As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”

In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”

No study funding was reported. The study authors reported no disclosures.

SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.

Children with Down syndrome often have sleep‐disordered breathing (SDB), and a new study suggests that long-term monitoring via sleep studies is warranted because the condition frequently persists and recurs.

©DenKuvaiev/Thinkstock

“Current screening recommendations to assess for SDB at a particular age may not be adequate in this population,” the authors of the study stated, adding that “persistence/recurrence of SDB is not easily predicted.”

The study, led by Joy Nehme, BSc, of Children’s Hospital of Eastern Ontario and the University of Ottawa, was published in Pediatric Pulmonology.

According to the study, research suggests that 43%-66% of children with Down syndrome have SDB, a category that encompasses sleep apnea (both obstructive and central) and hypoventilation. Those numbers are several times higher than the prevalence of SDB in children in the general population (1%-5%).

“Because SDB is associated with cardiometabolic and neurocognitive morbidity, its prompt and accurate diagnosis is important,” the researchers wrote. However, diagnosis requires a sleep study, which is not always performed although the American Academy of Pediatrics recommends children with Down syndrome undergo one by age 4.

Treatments include adenotonsillectomy (considered first-line), positive airway pressure, and lingual tonsillectomy.

The study aims to fill in gaps in knowledge about the condition over the long term since “there is little available literature on the trajectory of SDB in children and youth with Down syndrome over time.”

The researchers launched a retrospective study of 560 children with Down syndrome who were treated from 2004 to 2015 at Children’s Hospital of Eastern Ontario. Of those, 120 showed signs of SDB and underwent sleep studies (48% male, median age 6.6 years [range 4.5-10.5], median total apnea‐hypopnea index events per hour = 3.4 [1.6-10.8]).

Of the 120 children, 67 (56%) had obstructive-mixed SDB, 9 (8%) had central sleep apnea, and 5 (4%) had hypoventilation. The others (39, 32%) had no SDB.

Fifty-four children underwent at least two sleep studies during the period of the study, with at least one undergoing seven.

Researchers found weak, nonsignificant evidence that SDB persistence/occurrence varied by age (odds ratio per year = 1.15; 95% confidence interval, 0.96-1.41; P = .13).

As for treatment, adenotonsillectomy was most common, although “previous studies have ... shown that moderate to severe OSA in children with Down syndrome is likely to persist after a tonsillectomy.”

In regard to obstructive sleep apnea (OSA) specifically, the authors wrote, “our study ... showed that OSA‐SDB persisted or recurred in the vast majority of children. Further, persistence/recurrence could not be predicted by clinical features or SDB severity in our study. This, therefore, highlights the need for serial longitudinal screening for SDB in this population and for follow‐up PSG to ensure the success of treatment interventions.”

No study funding was reported. The study authors reported no disclosures.

SOURCE: Nehme J et al. Pediatr Pulmonol. 2019 Jun 6. doi: 10.1002/ppul.24380.

CRYSTAL CITY, VA. – Insomnia is a neuropsychiatric disorder of hyperarousal that should be evaluated as a disorder and treated with any associated comorbid conditions, Karl Doghramji, MD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Karen Winton/iStockphoto

“When I was a resident, I used to say insomnia is never a disorder. It’s always a symptom; you’ve got to find the primary disorder to know what the insomnia is caused by,” said Dr. Doghramji, medical director of the Jefferson Sleep Disorders Center at Jefferson Medical College, Philadelphia. “We no longer believe that. Throw that out the window.”

According to the new definition under the DSM-5, insomnia is characterized by dissatisfaction with sleep quality or quantity in the presence of adequate opportunity for sleep that causes significant distress or impairment for more than 3 nights per week over a period of 3 months. A survey of almost 7,500 U.S. health plan subscribers conducted a few years ago found that the prevalence of insomnia was estimated at 23.2% (Sleep. 2011 Sep 1;34[9]:1161-71).

Insomnia is also not well identified in clinical practice: In results published from his own group, Dr. Doghramji and colleagues evaluated 97 patients who were administered the Insomnia Severity Index; of those patients, 79.4% met the criteria for insomnia, but there was no mention of insomnia in the discharge notes for those patients (J Nerv Ment Dis. 2018 Oct;206[10]:765-9).

Many cognitive impairments can occur as a result of insomnia, which affects performance at work; decreases enjoyment of social activities; can lead to motor vehicle accidents or falls; and can affect health in the form of diabetes, hypertension, and increased mortality. Insomnia also can predict the risk of future depression and is a risk factor for suicide, Dr. Doghramji said at the meeting presented by Global Academy for Medical Education.

Adults can have insomnia for many reasons, including genetics, stress, negative conditioning, intrapsychic conflict, and bad habits, as well as medical and psychiatric conditions. While knowledge surrounding insomnia has advanced under a hyperarousal model, “It is really a hyperarousal disturbance which defies psychological understanding,” said Dr. Doghramji, who is also professor of psychiatry, neurology, and medicine at the university.

Evaluating the type of insomnia a patient is experiencing should be the first step in managing the disorder, followed by determining whether the insomnia is contributing to daytime impairment or decreased quality of life for the patient. From there, the insomnia can be treated with behavioral or pharmacotherapy. However, if insomnia is associated with another comorbid condition, the condition should be treated alongside the insomnia.

Sleep is highly comorbid with psychiatric and medical conditions (Sleep Med Clin. 2019 Jun;14[2]:167-75). Initial insomnia is more likely to be associated with delayed sleep phase disorder and restless legs syndrome, while middle insomnia is associated with sleep apnea and depression. Patients who wake early and are unable to go back to sleep (terminal insomnia) are likely to have depression, shift work disorder, or advanced sleep phase disorder.

“Once you identify [insomnia], there are all sorts of wonderful ways to manage it, including behavioral and pharmacological therapy,” said Dr. Doghramji. The comorbid condition also should be considered when deciding how to treat insomnia. For example, a patient with gastroesophageal reflux disease and insomnia would be more suited to cognitive-behavioral therapy than pharmacologic agents to help with sleep, because being able to wake up during the night from acid building in the esophagus is the body’s defense mechanism for the disease, Dr. Doghramji said.

Dr. Doghramji reported serving as a consultant for Eisai, Merck, and Pfizer. He also receives research funding from and owns stock in Merck.

Global Academy for Medical Education, Current Psychiatry, and this news organization are owned by the same company.

CRYSTAL CITY, VA. – Insomnia is a neuropsychiatric disorder of hyperarousal that should be evaluated as a disorder and treated with any associated comorbid conditions, Karl Doghramji, MD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Karen Winton/iStockphoto

“When I was a resident, I used to say insomnia is never a disorder. It’s always a symptom; you’ve got to find the primary disorder to know what the insomnia is caused by,” said Dr. Doghramji, medical director of the Jefferson Sleep Disorders Center at Jefferson Medical College, Philadelphia. “We no longer believe that. Throw that out the window.”

According to the new definition under the DSM-5, insomnia is characterized by dissatisfaction with sleep quality or quantity in the presence of adequate opportunity for sleep that causes significant distress or impairment for more than 3 nights per week over a period of 3 months. A survey of almost 7,500 U.S. health plan subscribers conducted a few years ago found that the prevalence of insomnia was estimated at 23.2% (Sleep. 2011 Sep 1;34[9]:1161-71).

Insomnia is also not well identified in clinical practice: In results published from his own group, Dr. Doghramji and colleagues evaluated 97 patients who were administered the Insomnia Severity Index; of those patients, 79.4% met the criteria for insomnia, but there was no mention of insomnia in the discharge notes for those patients (J Nerv Ment Dis. 2018 Oct;206[10]:765-9).

Many cognitive impairments can occur as a result of insomnia, which affects performance at work; decreases enjoyment of social activities; can lead to motor vehicle accidents or falls; and can affect health in the form of diabetes, hypertension, and increased mortality. Insomnia also can predict the risk of future depression and is a risk factor for suicide, Dr. Doghramji said at the meeting presented by Global Academy for Medical Education.

Adults can have insomnia for many reasons, including genetics, stress, negative conditioning, intrapsychic conflict, and bad habits, as well as medical and psychiatric conditions. While knowledge surrounding insomnia has advanced under a hyperarousal model, “It is really a hyperarousal disturbance which defies psychological understanding,” said Dr. Doghramji, who is also professor of psychiatry, neurology, and medicine at the university.

Evaluating the type of insomnia a patient is experiencing should be the first step in managing the disorder, followed by determining whether the insomnia is contributing to daytime impairment or decreased quality of life for the patient. From there, the insomnia can be treated with behavioral or pharmacotherapy. However, if insomnia is associated with another comorbid condition, the condition should be treated alongside the insomnia.

Sleep is highly comorbid with psychiatric and medical conditions (Sleep Med Clin. 2019 Jun;14[2]:167-75). Initial insomnia is more likely to be associated with delayed sleep phase disorder and restless legs syndrome, while middle insomnia is associated with sleep apnea and depression. Patients who wake early and are unable to go back to sleep (terminal insomnia) are likely to have depression, shift work disorder, or advanced sleep phase disorder.

“Once you identify [insomnia], there are all sorts of wonderful ways to manage it, including behavioral and pharmacological therapy,” said Dr. Doghramji. The comorbid condition also should be considered when deciding how to treat insomnia. For example, a patient with gastroesophageal reflux disease and insomnia would be more suited to cognitive-behavioral therapy than pharmacologic agents to help with sleep, because being able to wake up during the night from acid building in the esophagus is the body’s defense mechanism for the disease, Dr. Doghramji said.

Dr. Doghramji reported serving as a consultant for Eisai, Merck, and Pfizer. He also receives research funding from and owns stock in Merck.

Global Academy for Medical Education, Current Psychiatry, and this news organization are owned by the same company.

CRYSTAL CITY, VA. – Insomnia is a neuropsychiatric disorder of hyperarousal that should be evaluated as a disorder and treated with any associated comorbid conditions, Karl Doghramji, MD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Karen Winton/iStockphoto

“When I was a resident, I used to say insomnia is never a disorder. It’s always a symptom; you’ve got to find the primary disorder to know what the insomnia is caused by,” said Dr. Doghramji, medical director of the Jefferson Sleep Disorders Center at Jefferson Medical College, Philadelphia. “We no longer believe that. Throw that out the window.”

According to the new definition under the DSM-5, insomnia is characterized by dissatisfaction with sleep quality or quantity in the presence of adequate opportunity for sleep that causes significant distress or impairment for more than 3 nights per week over a period of 3 months. A survey of almost 7,500 U.S. health plan subscribers conducted a few years ago found that the prevalence of insomnia was estimated at 23.2% (Sleep. 2011 Sep 1;34[9]:1161-71).

Insomnia is also not well identified in clinical practice: In results published from his own group, Dr. Doghramji and colleagues evaluated 97 patients who were administered the Insomnia Severity Index; of those patients, 79.4% met the criteria for insomnia, but there was no mention of insomnia in the discharge notes for those patients (J Nerv Ment Dis. 2018 Oct;206[10]:765-9).

Many cognitive impairments can occur as a result of insomnia, which affects performance at work; decreases enjoyment of social activities; can lead to motor vehicle accidents or falls; and can affect health in the form of diabetes, hypertension, and increased mortality. Insomnia also can predict the risk of future depression and is a risk factor for suicide, Dr. Doghramji said at the meeting presented by Global Academy for Medical Education.

Adults can have insomnia for many reasons, including genetics, stress, negative conditioning, intrapsychic conflict, and bad habits, as well as medical and psychiatric conditions. While knowledge surrounding insomnia has advanced under a hyperarousal model, “It is really a hyperarousal disturbance which defies psychological understanding,” said Dr. Doghramji, who is also professor of psychiatry, neurology, and medicine at the university.

Evaluating the type of insomnia a patient is experiencing should be the first step in managing the disorder, followed by determining whether the insomnia is contributing to daytime impairment or decreased quality of life for the patient. From there, the insomnia can be treated with behavioral or pharmacotherapy. However, if insomnia is associated with another comorbid condition, the condition should be treated alongside the insomnia.

Sleep is highly comorbid with psychiatric and medical conditions (Sleep Med Clin. 2019 Jun;14[2]:167-75). Initial insomnia is more likely to be associated with delayed sleep phase disorder and restless legs syndrome, while middle insomnia is associated with sleep apnea and depression. Patients who wake early and are unable to go back to sleep (terminal insomnia) are likely to have depression, shift work disorder, or advanced sleep phase disorder.

“Once you identify [insomnia], there are all sorts of wonderful ways to manage it, including behavioral and pharmacological therapy,” said Dr. Doghramji. The comorbid condition also should be considered when deciding how to treat insomnia. For example, a patient with gastroesophageal reflux disease and insomnia would be more suited to cognitive-behavioral therapy than pharmacologic agents to help with sleep, because being able to wake up during the night from acid building in the esophagus is the body’s defense mechanism for the disease, Dr. Doghramji said.

Dr. Doghramji reported serving as a consultant for Eisai, Merck, and Pfizer. He also receives research funding from and owns stock in Merck.

Global Academy for Medical Education, Current Psychiatry, and this news organization are owned by the same company.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

[email protected]

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

[email protected]

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

[email protected]

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.

SAN ANTONIO – Key determinants of no-show rates to a sleep clinic include being a new patient and lacking health insurance coverage, results from a single-center study showed.

Doug Brunk/MDedge News

“There are lots of people with sleep problems,” one of the study’s authors, Alvan Nzewuihe, MD, said in an interview at the annual meeting of the Associated Professional Sleep Societies. “However, we have to identify these patients to be able to help them. If they don’t come to the sleep clinic [for assessment], we are going nowhere.”

In an effort to better understand determinants of no-show rates among sleep clinics, Dr. Nzewuihe and colleagues performed a 10-month, retrospective chart review of 2,532 patients scheduled at Saint Louis University’s SLUCare Sleep Disorders Center during the months of July and October 2017 and April 2018. A no-show was determined if the patient failed to show up at their scheduled appointment on time or if they canceled their appointment. The researchers used multivariable logistic regression to determine which factors were independently associated with no-show rates.

Dr. Nzewuihe, a sleep medicine physician at the university, reported that the overall no-show rate during the study period was 21.2% and did not change with age, sex, or appointment factors such as time of day, day of week, or season of the year. Significant determinants of no-show rates included being a new patient (39.1% vs. 28.8% among established patients; P less than .0001) and having no health insurance (47.5% vs. public 28.3% vs private 24.2%; P less than .0001). Multivariate logistic regression confirmed the associations. New patients were 1.96 times more likely to not show up to the sleep clinic, compared with established patients, while patients with no health insurance coverage were 1.55 times more likely to not show up, compared with those with public health insurance.

The researchers wrote in their poster abstract, “Patients who are new to the clinic or have no insurance coverage have a higher odds of not showing up to their appointment and delaying their care. Efforts to prioritize high-risk patients of nonadherence will help contribute to better care and outcomes. Further studies are needed to develop methods to decrease no-show rates once high-risk appointments have been identified.”

Dr. Nzewuihe acknowledged certain limitations of the study, including its retrospective design and the fact that other possible contributing factors were not evaluated such as literacy level, employment status, and length of time between appointment booking and appointment date. The study’s first author was Julie Sahrmann, DO. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Sahrmann J et al. Sleep 2019, Abstract 0965.

SAN ANTONIO – Key determinants of no-show rates to a sleep clinic include being a new patient and lacking health insurance coverage, results from a single-center study showed.

Doug Brunk/MDedge News

“There are lots of people with sleep problems,” one of the study’s authors, Alvan Nzewuihe, MD, said in an interview at the annual meeting of the Associated Professional Sleep Societies. “However, we have to identify these patients to be able to help them. If they don’t come to the sleep clinic [for assessment], we are going nowhere.”

In an effort to better understand determinants of no-show rates among sleep clinics, Dr. Nzewuihe and colleagues performed a 10-month, retrospective chart review of 2,532 patients scheduled at Saint Louis University’s SLUCare Sleep Disorders Center during the months of July and October 2017 and April 2018. A no-show was determined if the patient failed to show up at their scheduled appointment on time or if they canceled their appointment. The researchers used multivariable logistic regression to determine which factors were independently associated with no-show rates.

Dr. Nzewuihe, a sleep medicine physician at the university, reported that the overall no-show rate during the study period was 21.2% and did not change with age, sex, or appointment factors such as time of day, day of week, or season of the year. Significant determinants of no-show rates included being a new patient (39.1% vs. 28.8% among established patients; P less than .0001) and having no health insurance (47.5% vs. public 28.3% vs private 24.2%; P less than .0001). Multivariate logistic regression confirmed the associations. New patients were 1.96 times more likely to not show up to the sleep clinic, compared with established patients, while patients with no health insurance coverage were 1.55 times more likely to not show up, compared with those with public health insurance.

The researchers wrote in their poster abstract, “Patients who are new to the clinic or have no insurance coverage have a higher odds of not showing up to their appointment and delaying their care. Efforts to prioritize high-risk patients of nonadherence will help contribute to better care and outcomes. Further studies are needed to develop methods to decrease no-show rates once high-risk appointments have been identified.”

Dr. Nzewuihe acknowledged certain limitations of the study, including its retrospective design and the fact that other possible contributing factors were not evaluated such as literacy level, employment status, and length of time between appointment booking and appointment date. The study’s first author was Julie Sahrmann, DO. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Sahrmann J et al. Sleep 2019, Abstract 0965.

SAN ANTONIO – Key determinants of no-show rates to a sleep clinic include being a new patient and lacking health insurance coverage, results from a single-center study showed.

Doug Brunk/MDedge News

“There are lots of people with sleep problems,” one of the study’s authors, Alvan Nzewuihe, MD, said in an interview at the annual meeting of the Associated Professional Sleep Societies. “However, we have to identify these patients to be able to help them. If they don’t come to the sleep clinic [for assessment], we are going nowhere.”

In an effort to better understand determinants of no-show rates among sleep clinics, Dr. Nzewuihe and colleagues performed a 10-month, retrospective chart review of 2,532 patients scheduled at Saint Louis University’s SLUCare Sleep Disorders Center during the months of July and October 2017 and April 2018. A no-show was determined if the patient failed to show up at their scheduled appointment on time or if they canceled their appointment. The researchers used multivariable logistic regression to determine which factors were independently associated with no-show rates.

Dr. Nzewuihe, a sleep medicine physician at the university, reported that the overall no-show rate during the study period was 21.2% and did not change with age, sex, or appointment factors such as time of day, day of week, or season of the year. Significant determinants of no-show rates included being a new patient (39.1% vs. 28.8% among established patients; P less than .0001) and having no health insurance (47.5% vs. public 28.3% vs private 24.2%; P less than .0001). Multivariate logistic regression confirmed the associations. New patients were 1.96 times more likely to not show up to the sleep clinic, compared with established patients, while patients with no health insurance coverage were 1.55 times more likely to not show up, compared with those with public health insurance.

The researchers wrote in their poster abstract, “Patients who are new to the clinic or have no insurance coverage have a higher odds of not showing up to their appointment and delaying their care. Efforts to prioritize high-risk patients of nonadherence will help contribute to better care and outcomes. Further studies are needed to develop methods to decrease no-show rates once high-risk appointments have been identified.”

Dr. Nzewuihe acknowledged certain limitations of the study, including its retrospective design and the fact that other possible contributing factors were not evaluated such as literacy level, employment status, and length of time between appointment booking and appointment date. The study’s first author was Julie Sahrmann, DO. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Sahrmann J et al. Sleep 2019, Abstract 0965.

SAN ANTONIO – Compared with their cisgender counterparts, transgender college students are nearly three times more likely to be diagnosed with and treated for insomnia symptoms, results from a large national population-based survey showed.

Doug Brunk/MDedge News

“That was a stronger association than we expected,” one of the study’s researchers, Lisa B. Matlen, MD, said during an interview at the annual meeting of the Associated Professional Sleep Societies.

According to Dr. Matlen, a fellow in the division of sleep medicine at the University of Michigan, Ann Arbor, the transgender population is “extremely understudied” when it comes to research on sleep disturbances. In an effort to examine the prevalence of sleep disturbances and the association between transgender identity and sleep disturbances among transgender college students in the United States, she and her colleagues drew from the 2016 and 2017 American College Health Association National College Health Assessment II, a confidential, voluntary, electronically administered survey of college and university students. In all, 224,233 students were polled, and the researchers analyzed their responses to questions about gender identity, sleep symptoms, and diagnoses.

The mean age of the respondents was 23 years, and most (82%) were undergraduate students. Of the 224,233 students, 3,471 (1.6%) self-identified as transgender. More than half of the transgender population (61.9%) was white, 10.6% were Hispanic/Latino, 10.5% were Asian or Pacific Islander, 6.3% were biracial or multiracial, 4.6% were black, and the rest were from other ethnicities. Compared with cisgender students, transgender students had increased odds of sleep disturbances (odds ratio, 1.6), not feeling well rested on 4 or more days per week (OR, 1.8), going to bed early on 3 or more days per week due to sleepiness (OR, 1.3), and having insomnia 3 or more days per week (OR, 1.7). In addition, transgender students were nearly three times more likely to have an insomnia diagnosis and treatment, compared with their cisgender counterparts (OR, 2.9).

Dr. Matlen acknowledged certain limitations of the study, including the fact that it drew from a population-based sample and that the survey was based on self-reported information. The study’s first author was Ronald R. Gavidia Romero, MD. The researchers reported having no financial disclosures.

[email protected]

SAN ANTONIO – Compared with their cisgender counterparts, transgender college students are nearly three times more likely to be diagnosed with and treated for insomnia symptoms, results from a large national population-based survey showed.

Doug Brunk/MDedge News

“That was a stronger association than we expected,” one of the study’s researchers, Lisa B. Matlen, MD, said during an interview at the annual meeting of the Associated Professional Sleep Societies.

According to Dr. Matlen, a fellow in the division of sleep medicine at the University of Michigan, Ann Arbor, the transgender population is “extremely understudied” when it comes to research on sleep disturbances. In an effort to examine the prevalence of sleep disturbances and the association between transgender identity and sleep disturbances among transgender college students in the United States, she and her colleagues drew from the 2016 and 2017 American College Health Association National College Health Assessment II, a confidential, voluntary, electronically administered survey of college and university students. In all, 224,233 students were polled, and the researchers analyzed their responses to questions about gender identity, sleep symptoms, and diagnoses.

The mean age of the respondents was 23 years, and most (82%) were undergraduate students. Of the 224,233 students, 3,471 (1.6%) self-identified as transgender. More than half of the transgender population (61.9%) was white, 10.6% were Hispanic/Latino, 10.5% were Asian or Pacific Islander, 6.3% were biracial or multiracial, 4.6% were black, and the rest were from other ethnicities. Compared with cisgender students, transgender students had increased odds of sleep disturbances (odds ratio, 1.6), not feeling well rested on 4 or more days per week (OR, 1.8), going to bed early on 3 or more days per week due to sleepiness (OR, 1.3), and having insomnia 3 or more days per week (OR, 1.7). In addition, transgender students were nearly three times more likely to have an insomnia diagnosis and treatment, compared with their cisgender counterparts (OR, 2.9).

Dr. Matlen acknowledged certain limitations of the study, including the fact that it drew from a population-based sample and that the survey was based on self-reported information. The study’s first author was Ronald R. Gavidia Romero, MD. The researchers reported having no financial disclosures.

[email protected]

SAN ANTONIO – Compared with their cisgender counterparts, transgender college students are nearly three times more likely to be diagnosed with and treated for insomnia symptoms, results from a large national population-based survey showed.

Doug Brunk/MDedge News

“That was a stronger association than we expected,” one of the study’s researchers, Lisa B. Matlen, MD, said during an interview at the annual meeting of the Associated Professional Sleep Societies.

According to Dr. Matlen, a fellow in the division of sleep medicine at the University of Michigan, Ann Arbor, the transgender population is “extremely understudied” when it comes to research on sleep disturbances. In an effort to examine the prevalence of sleep disturbances and the association between transgender identity and sleep disturbances among transgender college students in the United States, she and her colleagues drew from the 2016 and 2017 American College Health Association National College Health Assessment II, a confidential, voluntary, electronically administered survey of college and university students. In all, 224,233 students were polled, and the researchers analyzed their responses to questions about gender identity, sleep symptoms, and diagnoses.

The mean age of the respondents was 23 years, and most (82%) were undergraduate students. Of the 224,233 students, 3,471 (1.6%) self-identified as transgender. More than half of the transgender population (61.9%) was white, 10.6% were Hispanic/Latino, 10.5% were Asian or Pacific Islander, 6.3% were biracial or multiracial, 4.6% were black, and the rest were from other ethnicities. Compared with cisgender students, transgender students had increased odds of sleep disturbances (odds ratio, 1.6), not feeling well rested on 4 or more days per week (OR, 1.8), going to bed early on 3 or more days per week due to sleepiness (OR, 1.3), and having insomnia 3 or more days per week (OR, 1.7). In addition, transgender students were nearly three times more likely to have an insomnia diagnosis and treatment, compared with their cisgender counterparts (OR, 2.9).

Dr. Matlen acknowledged certain limitations of the study, including the fact that it drew from a population-based sample and that the survey was based on self-reported information. The study’s first author was Ronald R. Gavidia Romero, MD. The researchers reported having no financial disclosures.

[email protected]

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

[email protected]

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

[email protected]

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

[email protected]

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke and may also, infrequently, be a consequence of stroke. It is significantly underdiagnosed in the general population and is highly prevalent in patients who have had a stroke. Many patients likely had their stroke because of this chronic untreated condition.

This review focuses on OSA and its prevalence, consequences, and treatment in patients after a stroke.

DEFINING AND QUANTIFYING OSA

OSA is the most common type of sleep-disordered breathing.^1,2 It involves repeated narrowing or complete collapse of the upper airway despite ongoing respiratory effort.^3,4 Apneic episodes are terminated by arousals from hypoxemia or efforts to breathe.⁵ In contrast, central sleep apnea is characterized by a patent airway but lack of airflow due to absent respiratory effort.⁵

In OSA, the number of episodes of apnea (absent airflow) and hypopnea (reduced airflow) are added together and divided by hours of sleep to calculate the apnea-hypopnea index (AHI). OSA is diagnosed by either of the following^3,4:

• AHI of 5 or higher, with clinical symptoms related to OSA (described below)
• AHI of 15 or higher, regardless of symptoms.

The AHI also defines OSA severity, as follows³:

• Mild: AHI 5 to 15
• Moderate: AHI 15 to 30
• Severe: AHI greater than 30.

Diagnostic criteria (eg, definition of hypopnea, testing methods, and AHI thresholds) have varied over time, an important consideration when reviewing the literature.

OSA IS MORE COMMON THAN EXPECTED AFTER STROKE

In the most methodologically sound and generalizable study of this topic to date, the Wisconsin Sleep Cohort Study⁶ reported in 2013 that about 14% of men and 5% of women ages 30 to 70 have an AHI greater than 5 (using 4% desaturation to score hypopneic episodes) with daytime sleepiness. Other studies suggest that 80% to 90% of people with OSA are undiagnosed and untreated.^1,7

The prevalence of OSA in patients who have had a stroke is much higher, ranging from 30% to 96% depending on the study methods and population.^1,8–12 A 2010 meta-analysis¹¹ of 29 studies reported that 72% of patients who had a stroke had an AHI greater than 5, and 29% had severe OSA. In this analysis, 7% of those with sleep-disordered breathing had central sleep apnea; still, these data indicate that the prevalence of OSA in these patients is about 5 times higher than in the general population.

RISK FACTORS MAY DIFFER IN STROKE POPULATION

Several risk factors for OSA have been identified.

Obesity is one of the strongest risk factors, with increasing body mass index (BMI) associated with increased OSA prevalence.^4,6,13 However, obesity appears to be a less significant risk factor in patients who have had a stroke than in the general population. In the 2010 meta-analysis¹¹ of OSA after stroke, the average BMI was only 26.4 kg/m² (with obesity defined as a BMI > 30.0 kg/m²), and increasing BMI was not associated with increasing AHI.

Male sex and advanced age are also OSA risk factors.^4,5 They remain significant in patients after a stroke; about 65% of poststroke patients who have OSA are men, and the older the patient, the more likely the AHI is greater than 10.¹¹

Ethnicity and genetics may also play important roles in OSA risk, with roughly 25% of OSA prevalence estimated to have a genetic basis.^14,15 Some risk factors for OSA such as craniofacial shape, upper airway anatomy, upper airway muscle dysfunction, increased respiratory chemosensitivity, and poor arousal threshold during sleep are likely determined by genetics and ethnicity.^14,15 Compared with people of European origin, Asians have a similar prevalence of OSA, but at a much lower average BMI, suggesting that other factors are significant.¹⁴ Possible genetically determined anatomic risk factors have not been specifically studied in the poststroke population, but it can be assumed they remain relevant.

Several studies have tried to find an association between OSA and type, location, etiology, or pattern of stroke.^{10,11,16–19} Although some suggest links between cardioembolic stroke and OSA,^16,20 or thrombolysis and OSA,¹⁰ most have found no association between OSA and stroke features.^11,12,21,22

HOW DOES OSA INCREASE STROKE RISK?

Untreated severe OSA is associated with increased cardiovascular mortality,^21,22 and OSA is an independent risk factor for incident stroke.²³ A number of mechanisms may explain these relationships.

Intermittent hypoxemia and recurrent sympathetic arousals resulting from OSA are thought to lead to many of the comorbid conditions with which it is associated: hypertension, coronary artery disease, heart failure, arrhythmias, pulmonary hypertension, and stroke. Repetitive decreases in ventilation lead to oxygen desaturations that result in cycles of increased sympathetic outflow and eventual sustained nocturnal hypertension and daytime chronic hypertension.^1,5,9,13 Also implicated are various changes in vasodilator and vasoconstrictor substances due to endothelial dysfunction and inflammation, which are thought to play a role in the atherogenic and prothrombotic states induced by OSA.^1,5,13

Cerebral circulation is altered primarily by the changes in partial pressure of carbon dioxide (Pco₂). During apnea, the Pco₂ rises, causing vasodilation and increased blood flow. After the apnea resolves, there is hyperpnea with resultant decreased Pco₂, and vasoconstriction. In a patient who already has vascular disease, the enhanced vasoconstriction could lead to ischemia.^1,5

Changes in intrathoracic pressure result in distortion of cardiac architecture. When the patient tries to breathe against an occluded airway, the intrathoracic pressure becomes more and more negative, increasing preload and afterload. When this happens repeatedly every night for years, it leads to remodeling of the heart such as left and right ventricular hypertrophy, with reduced stroke volume, myocardial ischemia, and increased risk of arrhythmia.^1,5,13

Untreated OSA is believed to predispose patients to develop atrial fibrillation through sympathetic overactivity, vascular inflammation, heart rate variability, and cardiac remodeling.²⁴ As atrial fibrillation is a major risk factor for stroke, particularly cardioembolic stroke, it may be another pathway of increased stroke risk in OSA.^16,20,25

OSA typically causes both daytime symptoms (excessive sleepiness, poor concentration, morning headache, depressive symptoms) and nighttime signs and symptoms (snoring, choking, gasping, night sweats, insomnia, nocturia, witnessed episodes of apnea).^3,4,26 Unfortunately, because these are nonspecific, OSA is often underdiagnosed.^4,26

Identifying OSA after a stroke may be a particular challenge, as patients often do not report classic symptoms, and the typical picture of OSA may have less predictive validity in these patients.^1,27,28 Within the first 24 hours after a stroke, hypersomnia, snoring history, and age are not predictive of OSA.¹ Patients found to have OSA after a stroke frequently do not have the traditional symptoms (sleepiness, snoring) seen in usual OSA patients. And they have higher rates of OSA at a younger age than the usual OSA patients, so age is not a predictive risk factor. In addition, daytime sleepiness and obesity are often absent or less prominent.^1,9,27,28  Finally, typical OSA signs and symptoms may be attributed to the stroke itself or to comorbidities affecting the patient, lowering suspicion for OSA.

OSA MAY HINDER STROKE RECOVERY, WORSEN OUTCOMES

OSA, particularly when moderate to severe, is linked to pathophysiologic changes that can hinder recovery from a stroke.

Intermittent hypoxemia during sleep can worsen vascular damage of at-risk tissue: nocturnal hypoxemia correlates with white matter hyperintensities on magnetic resonance imaging, a marker of ischemic demyelination.²⁹ Oxidative stress and release of inflammatory mediators associated with intermittent hypoxemia may impair vascular blood flow to brain tissue attempting to repair itself.³⁰ In addition, sympathetic overactivity and Pco₂ fluctuations associated with OSA may impede cerebral circulation.

Taken together, such ongoing nocturnal insults can lead to clinical consequences during this vulnerable period.

A 1996 study³¹ of patients recovering from a stroke found that an oxygen desaturation index (number of times that the blood oxygen level drops below a certain threshold, as measured by overnight oximetry) of more than 10 per hour was associated with worse functional recovery at discharge and at 3 and 12 months after discharge. This study also noted an association between time spent with oxygen saturations below 90% and the rate of death at 1 year.

A 2003 study³² reported that patients with an AHI greater than 10 by polysomnography spent an average of 13 days longer on the rehabilitation service and had worse functional and cognitive status on discharge, even after controlling for multiple confounders. Several subsequent studies have confirmed these and similar findings.^8,33,34

OSA has also been linked to depression,³⁵ which is common after stroke and may worsen outcomes.³⁶ The interaction between OSA, depression, and poststroke outcomes warrants further study.

In the general population, OSA has been independently associated with increased risk of stroke or death from any cause.^21,22,37 These associations have also been reported in the poststroke population: a 2014 meta-analysis found that OSA increased the risk of a repeat stroke (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2–2.6) and all-cause mortality (RR 1.69, 95% CI 1.4–2.1).³⁸

TESTING FOR OSA AFTER STROKE

Because of the high prevalence of OSA in patients who have had a stroke and the potential for worse outcomes associated with untreated OSA, there should be a low threshold for evaluating for OSA soon after stroke. Objective testing is required to qualify for therapy,  and the gold standard for diagnosis of OSA is formal polysomnography conducted in a sleep laboratory.^2–4 Unfortunately, polysomnography may be unacceptable to some patients, is costly, and is resource-intensive, particularly in an inpatient or rehabilitation setting.²⁸ Ideally, to optimize testing efficiency, patients should be screened for the likelihood of OSA before polysomnography is ordered.

Questionnaires can help determine the need for further testing

Questionnaires developed to assess OSA risk³⁹ include the following:

The Berlin questionnaire, developed in 1999, has 10 questions assessing daytime and nighttime signs and symptoms and presence of hypertension.

The STOP questionnaire, developed in 2008, assesses snoring, tiredness, observed apneic episodes, and elevated blood pressure.

The STOP-BANG questionnaire, published in 2010, includes the STOP questions plus BMI over 35 kg/m², age over 50, neck circumference over 41 cm, and male gender.

A 2017 meta-analysis³⁹ of 108 studies with nearly 50,000 people found that the STOP-BANG questionnaire performed best with regard to sensitivity and diagnostic odds ratio, but with poor specificity.

These screening tools and modified versions of them have also been evaluated in patients who have had a stroke.

In 2015, Boulos et al²⁸ found that the STOP-BAG (a version of STOP-BANG that excludes neck circumference) and the 4-variable (4V) questionnaire (sex, BMI, blood pressure, snoring) had moderate predictive value for OSA within 6 months after sroke.

In 2016, Katzan et al⁴⁰ found that the STOP-BAG2 (STOP-BAG criteria plus continuous variables for BMI and age) had a high sensitivity for polysomnographically diagnosed OSA within the first year after a stroke. The specificity was significantly better than the STOP-BANG or the STOP-BAG questionnaire, although it remained suboptimal at 60.5%.

In 2017, Sico et al⁴¹ developed and assessed the SLEEP Inventory (sex, left heart failure, Epworth Sleepiness Scale, enlarged neck, weight in pounds, insulin resistance or diabetes, and National Institutes of Health Stroke Scale) and found that it outperformed the Berlin and STOP-BANG questionnaires in the poststroke setting. The SLEEP Inventory had the best specificity and negative predictive value, and a slightly better ability to correctly classify patients as having OSA or not, classifying 80% of patients correctly.

These newer screening tools (eg, STOP-BAG, STOP-BAG2, SLEEP) can be used to identify with reasonable accuracy which patients need definitive testing after stroke.

Pulse oximetry is another possible screening tool          

Overnight pulse oximetry may also help screen for sleep apnea and stratify risk after a stroke. A 2012 study⁴² of overnight oximetry to screen patients before surgery found that the oxygen desaturation index was significantly associated with the AHI measured by polysomnography. However, oximetry testing cannot distinguish between OSA and central sleep apnea, so it is insufficient to diagnose OSA or qualify patients for therapy. Further study is needed to examine the ability of overnight pulse oximetry to screen or to stratify risk for OSA after stroke.

Polysomnography vs home testing

Polysomnography is the gold standard for diagnosing OSA. Benefits include technical support and trouble-shooting, determining relationships between OSA, body position, and sleep stage, and the ability to intervene with treatment.² However, polysomnography can be cumbersome, costly, and resource-intensive.

A home sleep apnea test, ie, an unattended, limited-channel sleep study, may be an acceptable alternative.^2–4,43,44 Home testing does not require a sleep technologist to be present during testing, uses fewer sensors, and is less expensive than overnight polysomnography, but its utility can be limited: it fails to accurately discriminate between episodes of OSA and central sleep apnea, there is potential for false-negative results, and it can underestimate sleep apnea burden because it does not measure sleep.²

Institutional resources and logistics may influence the choice of diagnostic modality. No data exist on outcomes from different diagnostic testing methods in poststroke patients. Further research is needed.

The first-line treatment for OSA is positive airway pressure (PAP).³ For most patients, this is continuous PAP (CPAP) or autoadjusting PAP (APAP). In some instances, particularly for those who cannot tolerate CPAP or who have comorbid hypoventilation, bilevel PAP (BPAP) may be indicated. More advanced PAP therapies are unlikely to be used after stroke.

PAP therapy is associated with reduced daytime sleepiness, improved mood, normalization of sleep architecture, improved systemic and pulmonary artery blood pressure, reduced rates of atrial fibrillation after ablation, and improved insulin sensitivity.^45–49 Whether it reduces the risk of cardiovascular events, including stroke, remains controversial; most data suggest that it does not.^50,51 However, when adherence to PAP therapy is considered rather than intention to treat, treatment has been found to lead to improved cardiovascular outcomes.⁵²

Mixed evidence of benefits after stroke

Observational studies provide evidence that CPAP may help patients with OSA after stroke, although results are mixed.^53–58 The studies ranged in size from 14 to 105 patients, enrolled patients with mostly moderate to severe OSA, and followed patients from 10 days to 7 years. Adherence to therapy was generally good in the short term (50%–70%), but only  15% to 30% of patients remained adherent at 5 to 7 years. Variable outcomes were reported, with some studies finding improved symptoms in the near term and mixed evidence of cardiovascular benefit in the longer ones. However, as these studies lacked randomization, drawing definitive conclusions on CPAP efficacy is difficult.

Patients were enrolled in the index admission or when starting a rehabilitation service—generally 2 to 3 weeks after their stroke. No clear association was found between the timing of initiating PAP therapy and outcomes. All patients had ischemic strokes, but few details were provided regarding stroke location, size, and severity. Exclusion criteria included severe underlying cardiopulmonary disease, confusion, severe stroke with marked impairment, and inability to cooperate. Almost all patients had moderate to severe OSA, and patients with central sleep apnea were excluded.

The major outcomes examined were drop-out rates, PAP adherence, and neurologic improvement based on neurologic functional scales (National Institutes of Health Stroke Scale and Canadian Neurologic Scale). As expected, dropout rates were higher in patients randomized to CPAP (OR 1.83, 95% CI 1.05–3.21, P = .03), although overall adherence was better than anticipated, with mean CPAP use across trials of 4.5 hours per night (95% CI 3.97–5.08) and with about 50% to 60% of patients adhering to therapy for at least 4 hours nightly.

Improvement in neurologic outcomes favored CPAP (standard mean difference 0.54, 95% CI 0.026–1.05), although considerable heterogeneity was seen. Improved sleepiness outcomes were inconsistent. Major cardiovascular outcomes were reported in only 2 studies (using the same data set) and showed delayed time to the next cardiovascular event for those treated with CPAP but no difference in cardiovascular event-free survival.

PAP poses more challenges after stroke

The primary limitation to PAP therapy is poor acceptance and adherence to therapy.⁵⁹ High rates of refusal of therapy and difficulty complying with treatment have been noted in the poststroke population, although recent studies have reported better adherence rates. How rates of adherence play out in real-world settings, outside of the controlled environment of a research study, has yet to be determined.

In general, CPAP adherence is affected by claustrophobia, difficulty tolerating a mask, problems with pressure intolerance, irritating air leaks, nasal congestion, and naso-oral dryness. Many such barriers can be overcome with use of a properly fitted mask, an appropriate pressure setting, heated humidification, nasal sprays (eg, saline, inhaled steroids), and education, encouragement, and reassurance.

After a stroke, additional obstacles may impede the ability to use PAP therapy.⁶⁸ Facial paresis (hemi- or bifacial) may make fitting of the mask problematic. Paralysis or weakness of the extremities may limit the ability to adjust or remove a mask. Aphasia can impair communication and understanding of the need to use PAP therapy, and upper-airway problems related to stroke, including dysphagia, may lead to pressure intolerance or risk of aspiration. Finally, a lack of perceived benefit, particularly if the patient does not have daytime sleepiness, may limit motivation.

Consider alternatives

For patients unlikely to succeed with PAP therapy, there are alternatives. Surgery and oral appliances are not usually realistic options in the setting of recent stroke, but positional therapy, including the use of body positioners to prevent supine sleep, as well as elevating the head of the bed, may be of some benefit.^69,70 A nasopharyngeal airway stenting device (nasal trumpet) may also be tolerated by some patients.

A proposed algorithm for screening, diagnosing, and treating OSA in patients after stroke is presented in Figure 1.

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke and may also, infrequently, be a consequence of stroke. It is significantly underdiagnosed in the general population and is highly prevalent in patients who have had a stroke. Many patients likely had their stroke because of this chronic untreated condition.

This review focuses on OSA and its prevalence, consequences, and treatment in patients after a stroke.

DEFINING AND QUANTIFYING OSA

OSA is the most common type of sleep-disordered breathing.^1,2 It involves repeated narrowing or complete collapse of the upper airway despite ongoing respiratory effort.^3,4 Apneic episodes are terminated by arousals from hypoxemia or efforts to breathe.⁵ In contrast, central sleep apnea is characterized by a patent airway but lack of airflow due to absent respiratory effort.⁵

In OSA, the number of episodes of apnea (absent airflow) and hypopnea (reduced airflow) are added together and divided by hours of sleep to calculate the apnea-hypopnea index (AHI). OSA is diagnosed by either of the following^3,4:

• AHI of 5 or higher, with clinical symptoms related to OSA (described below)
• AHI of 15 or higher, regardless of symptoms.

The AHI also defines OSA severity, as follows³:

• Mild: AHI 5 to 15
• Moderate: AHI 15 to 30
• Severe: AHI greater than 30.

Diagnostic criteria (eg, definition of hypopnea, testing methods, and AHI thresholds) have varied over time, an important consideration when reviewing the literature.

OSA IS MORE COMMON THAN EXPECTED AFTER STROKE

In the most methodologically sound and generalizable study of this topic to date, the Wisconsin Sleep Cohort Study⁶ reported in 2013 that about 14% of men and 5% of women ages 30 to 70 have an AHI greater than 5 (using 4% desaturation to score hypopneic episodes) with daytime sleepiness. Other studies suggest that 80% to 90% of people with OSA are undiagnosed and untreated.^1,7

The prevalence of OSA in patients who have had a stroke is much higher, ranging from 30% to 96% depending on the study methods and population.^1,8–12 A 2010 meta-analysis¹¹ of 29 studies reported that 72% of patients who had a stroke had an AHI greater than 5, and 29% had severe OSA. In this analysis, 7% of those with sleep-disordered breathing had central sleep apnea; still, these data indicate that the prevalence of OSA in these patients is about 5 times higher than in the general population.

RISK FACTORS MAY DIFFER IN STROKE POPULATION

Several risk factors for OSA have been identified.

Obesity is one of the strongest risk factors, with increasing body mass index (BMI) associated with increased OSA prevalence.^4,6,13 However, obesity appears to be a less significant risk factor in patients who have had a stroke than in the general population. In the 2010 meta-analysis¹¹ of OSA after stroke, the average BMI was only 26.4 kg/m² (with obesity defined as a BMI > 30.0 kg/m²), and increasing BMI was not associated with increasing AHI.

Male sex and advanced age are also OSA risk factors.^4,5 They remain significant in patients after a stroke; about 65% of poststroke patients who have OSA are men, and the older the patient, the more likely the AHI is greater than 10.¹¹

Ethnicity and genetics may also play important roles in OSA risk, with roughly 25% of OSA prevalence estimated to have a genetic basis.^14,15 Some risk factors for OSA such as craniofacial shape, upper airway anatomy, upper airway muscle dysfunction, increased respiratory chemosensitivity, and poor arousal threshold during sleep are likely determined by genetics and ethnicity.^14,15 Compared with people of European origin, Asians have a similar prevalence of OSA, but at a much lower average BMI, suggesting that other factors are significant.¹⁴ Possible genetically determined anatomic risk factors have not been specifically studied in the poststroke population, but it can be assumed they remain relevant.

Several studies have tried to find an association between OSA and type, location, etiology, or pattern of stroke.^{10,11,16–19} Although some suggest links between cardioembolic stroke and OSA,^16,20 or thrombolysis and OSA,¹⁰ most have found no association between OSA and stroke features.^11,12,21,22

HOW DOES OSA INCREASE STROKE RISK?

Untreated severe OSA is associated with increased cardiovascular mortality,^21,22 and OSA is an independent risk factor for incident stroke.²³ A number of mechanisms may explain these relationships.

Intermittent hypoxemia and recurrent sympathetic arousals resulting from OSA are thought to lead to many of the comorbid conditions with which it is associated: hypertension, coronary artery disease, heart failure, arrhythmias, pulmonary hypertension, and stroke. Repetitive decreases in ventilation lead to oxygen desaturations that result in cycles of increased sympathetic outflow and eventual sustained nocturnal hypertension and daytime chronic hypertension.^1,5,9,13 Also implicated are various changes in vasodilator and vasoconstrictor substances due to endothelial dysfunction and inflammation, which are thought to play a role in the atherogenic and prothrombotic states induced by OSA.^1,5,13

Cerebral circulation is altered primarily by the changes in partial pressure of carbon dioxide (Pco₂). During apnea, the Pco₂ rises, causing vasodilation and increased blood flow. After the apnea resolves, there is hyperpnea with resultant decreased Pco₂, and vasoconstriction. In a patient who already has vascular disease, the enhanced vasoconstriction could lead to ischemia.^1,5

Changes in intrathoracic pressure result in distortion of cardiac architecture. When the patient tries to breathe against an occluded airway, the intrathoracic pressure becomes more and more negative, increasing preload and afterload. When this happens repeatedly every night for years, it leads to remodeling of the heart such as left and right ventricular hypertrophy, with reduced stroke volume, myocardial ischemia, and increased risk of arrhythmia.^1,5,13

Untreated OSA is believed to predispose patients to develop atrial fibrillation through sympathetic overactivity, vascular inflammation, heart rate variability, and cardiac remodeling.²⁴ As atrial fibrillation is a major risk factor for stroke, particularly cardioembolic stroke, it may be another pathway of increased stroke risk in OSA.^16,20,25

OSA typically causes both daytime symptoms (excessive sleepiness, poor concentration, morning headache, depressive symptoms) and nighttime signs and symptoms (snoring, choking, gasping, night sweats, insomnia, nocturia, witnessed episodes of apnea).^3,4,26 Unfortunately, because these are nonspecific, OSA is often underdiagnosed.^4,26

Identifying OSA after a stroke may be a particular challenge, as patients often do not report classic symptoms, and the typical picture of OSA may have less predictive validity in these patients.^1,27,28 Within the first 24 hours after a stroke, hypersomnia, snoring history, and age are not predictive of OSA.¹ Patients found to have OSA after a stroke frequently do not have the traditional symptoms (sleepiness, snoring) seen in usual OSA patients. And they have higher rates of OSA at a younger age than the usual OSA patients, so age is not a predictive risk factor. In addition, daytime sleepiness and obesity are often absent or less prominent.^1,9,27,28  Finally, typical OSA signs and symptoms may be attributed to the stroke itself or to comorbidities affecting the patient, lowering suspicion for OSA.

OSA MAY HINDER STROKE RECOVERY, WORSEN OUTCOMES

OSA, particularly when moderate to severe, is linked to pathophysiologic changes that can hinder recovery from a stroke.

Intermittent hypoxemia during sleep can worsen vascular damage of at-risk tissue: nocturnal hypoxemia correlates with white matter hyperintensities on magnetic resonance imaging, a marker of ischemic demyelination.²⁹ Oxidative stress and release of inflammatory mediators associated with intermittent hypoxemia may impair vascular blood flow to brain tissue attempting to repair itself.³⁰ In addition, sympathetic overactivity and Pco₂ fluctuations associated with OSA may impede cerebral circulation.

Taken together, such ongoing nocturnal insults can lead to clinical consequences during this vulnerable period.

A 1996 study³¹ of patients recovering from a stroke found that an oxygen desaturation index (number of times that the blood oxygen level drops below a certain threshold, as measured by overnight oximetry) of more than 10 per hour was associated with worse functional recovery at discharge and at 3 and 12 months after discharge. This study also noted an association between time spent with oxygen saturations below 90% and the rate of death at 1 year.

A 2003 study³² reported that patients with an AHI greater than 10 by polysomnography spent an average of 13 days longer on the rehabilitation service and had worse functional and cognitive status on discharge, even after controlling for multiple confounders. Several subsequent studies have confirmed these and similar findings.^8,33,34

OSA has also been linked to depression,³⁵ which is common after stroke and may worsen outcomes.³⁶ The interaction between OSA, depression, and poststroke outcomes warrants further study.

In the general population, OSA has been independently associated with increased risk of stroke or death from any cause.^21,22,37 These associations have also been reported in the poststroke population: a 2014 meta-analysis found that OSA increased the risk of a repeat stroke (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2–2.6) and all-cause mortality (RR 1.69, 95% CI 1.4–2.1).³⁸

TESTING FOR OSA AFTER STROKE

Because of the high prevalence of OSA in patients who have had a stroke and the potential for worse outcomes associated with untreated OSA, there should be a low threshold for evaluating for OSA soon after stroke. Objective testing is required to qualify for therapy,  and the gold standard for diagnosis of OSA is formal polysomnography conducted in a sleep laboratory.^2–4 Unfortunately, polysomnography may be unacceptable to some patients, is costly, and is resource-intensive, particularly in an inpatient or rehabilitation setting.²⁸ Ideally, to optimize testing efficiency, patients should be screened for the likelihood of OSA before polysomnography is ordered.

Questionnaires can help determine the need for further testing

Questionnaires developed to assess OSA risk³⁹ include the following:

The Berlin questionnaire, developed in 1999, has 10 questions assessing daytime and nighttime signs and symptoms and presence of hypertension.

The STOP questionnaire, developed in 2008, assesses snoring, tiredness, observed apneic episodes, and elevated blood pressure.

The STOP-BANG questionnaire, published in 2010, includes the STOP questions plus BMI over 35 kg/m², age over 50, neck circumference over 41 cm, and male gender.

A 2017 meta-analysis³⁹ of 108 studies with nearly 50,000 people found that the STOP-BANG questionnaire performed best with regard to sensitivity and diagnostic odds ratio, but with poor specificity.

These screening tools and modified versions of them have also been evaluated in patients who have had a stroke.

In 2015, Boulos et al²⁸ found that the STOP-BAG (a version of STOP-BANG that excludes neck circumference) and the 4-variable (4V) questionnaire (sex, BMI, blood pressure, snoring) had moderate predictive value for OSA within 6 months after sroke.

In 2016, Katzan et al⁴⁰ found that the STOP-BAG2 (STOP-BAG criteria plus continuous variables for BMI and age) had a high sensitivity for polysomnographically diagnosed OSA within the first year after a stroke. The specificity was significantly better than the STOP-BANG or the STOP-BAG questionnaire, although it remained suboptimal at 60.5%.

In 2017, Sico et al⁴¹ developed and assessed the SLEEP Inventory (sex, left heart failure, Epworth Sleepiness Scale, enlarged neck, weight in pounds, insulin resistance or diabetes, and National Institutes of Health Stroke Scale) and found that it outperformed the Berlin and STOP-BANG questionnaires in the poststroke setting. The SLEEP Inventory had the best specificity and negative predictive value, and a slightly better ability to correctly classify patients as having OSA or not, classifying 80% of patients correctly.

These newer screening tools (eg, STOP-BAG, STOP-BAG2, SLEEP) can be used to identify with reasonable accuracy which patients need definitive testing after stroke.

Pulse oximetry is another possible screening tool          

Overnight pulse oximetry may also help screen for sleep apnea and stratify risk after a stroke. A 2012 study⁴² of overnight oximetry to screen patients before surgery found that the oxygen desaturation index was significantly associated with the AHI measured by polysomnography. However, oximetry testing cannot distinguish between OSA and central sleep apnea, so it is insufficient to diagnose OSA or qualify patients for therapy. Further study is needed to examine the ability of overnight pulse oximetry to screen or to stratify risk for OSA after stroke.

Polysomnography vs home testing

Polysomnography is the gold standard for diagnosing OSA. Benefits include technical support and trouble-shooting, determining relationships between OSA, body position, and sleep stage, and the ability to intervene with treatment.² However, polysomnography can be cumbersome, costly, and resource-intensive.

A home sleep apnea test, ie, an unattended, limited-channel sleep study, may be an acceptable alternative.^2–4,43,44 Home testing does not require a sleep technologist to be present during testing, uses fewer sensors, and is less expensive than overnight polysomnography, but its utility can be limited: it fails to accurately discriminate between episodes of OSA and central sleep apnea, there is potential for false-negative results, and it can underestimate sleep apnea burden because it does not measure sleep.²

Institutional resources and logistics may influence the choice of diagnostic modality. No data exist on outcomes from different diagnostic testing methods in poststroke patients. Further research is needed.

The first-line treatment for OSA is positive airway pressure (PAP).³ For most patients, this is continuous PAP (CPAP) or autoadjusting PAP (APAP). In some instances, particularly for those who cannot tolerate CPAP or who have comorbid hypoventilation, bilevel PAP (BPAP) may be indicated. More advanced PAP therapies are unlikely to be used after stroke.

PAP therapy is associated with reduced daytime sleepiness, improved mood, normalization of sleep architecture, improved systemic and pulmonary artery blood pressure, reduced rates of atrial fibrillation after ablation, and improved insulin sensitivity.^45–49 Whether it reduces the risk of cardiovascular events, including stroke, remains controversial; most data suggest that it does not.^50,51 However, when adherence to PAP therapy is considered rather than intention to treat, treatment has been found to lead to improved cardiovascular outcomes.⁵²

Mixed evidence of benefits after stroke

Observational studies provide evidence that CPAP may help patients with OSA after stroke, although results are mixed.^53–58 The studies ranged in size from 14 to 105 patients, enrolled patients with mostly moderate to severe OSA, and followed patients from 10 days to 7 years. Adherence to therapy was generally good in the short term (50%–70%), but only  15% to 30% of patients remained adherent at 5 to 7 years. Variable outcomes were reported, with some studies finding improved symptoms in the near term and mixed evidence of cardiovascular benefit in the longer ones. However, as these studies lacked randomization, drawing definitive conclusions on CPAP efficacy is difficult.

Patients were enrolled in the index admission or when starting a rehabilitation service—generally 2 to 3 weeks after their stroke. No clear association was found between the timing of initiating PAP therapy and outcomes. All patients had ischemic strokes, but few details were provided regarding stroke location, size, and severity. Exclusion criteria included severe underlying cardiopulmonary disease, confusion, severe stroke with marked impairment, and inability to cooperate. Almost all patients had moderate to severe OSA, and patients with central sleep apnea were excluded.

The major outcomes examined were drop-out rates, PAP adherence, and neurologic improvement based on neurologic functional scales (National Institutes of Health Stroke Scale and Canadian Neurologic Scale). As expected, dropout rates were higher in patients randomized to CPAP (OR 1.83, 95% CI 1.05–3.21, P = .03), although overall adherence was better than anticipated, with mean CPAP use across trials of 4.5 hours per night (95% CI 3.97–5.08) and with about 50% to 60% of patients adhering to therapy for at least 4 hours nightly.

Improvement in neurologic outcomes favored CPAP (standard mean difference 0.54, 95% CI 0.026–1.05), although considerable heterogeneity was seen. Improved sleepiness outcomes were inconsistent. Major cardiovascular outcomes were reported in only 2 studies (using the same data set) and showed delayed time to the next cardiovascular event for those treated with CPAP but no difference in cardiovascular event-free survival.

PAP poses more challenges after stroke

The primary limitation to PAP therapy is poor acceptance and adherence to therapy.⁵⁹ High rates of refusal of therapy and difficulty complying with treatment have been noted in the poststroke population, although recent studies have reported better adherence rates. How rates of adherence play out in real-world settings, outside of the controlled environment of a research study, has yet to be determined.

In general, CPAP adherence is affected by claustrophobia, difficulty tolerating a mask, problems with pressure intolerance, irritating air leaks, nasal congestion, and naso-oral dryness. Many such barriers can be overcome with use of a properly fitted mask, an appropriate pressure setting, heated humidification, nasal sprays (eg, saline, inhaled steroids), and education, encouragement, and reassurance.

After a stroke, additional obstacles may impede the ability to use PAP therapy.⁶⁸ Facial paresis (hemi- or bifacial) may make fitting of the mask problematic. Paralysis or weakness of the extremities may limit the ability to adjust or remove a mask. Aphasia can impair communication and understanding of the need to use PAP therapy, and upper-airway problems related to stroke, including dysphagia, may lead to pressure intolerance or risk of aspiration. Finally, a lack of perceived benefit, particularly if the patient does not have daytime sleepiness, may limit motivation.

Consider alternatives

For patients unlikely to succeed with PAP therapy, there are alternatives. Surgery and oral appliances are not usually realistic options in the setting of recent stroke, but positional therapy, including the use of body positioners to prevent supine sleep, as well as elevating the head of the bed, may be of some benefit.^69,70 A nasopharyngeal airway stenting device (nasal trumpet) may also be tolerated by some patients.

A proposed algorithm for screening, diagnosing, and treating OSA in patients after stroke is presented in Figure 1.

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke and may also, infrequently, be a consequence of stroke. It is significantly underdiagnosed in the general population and is highly prevalent in patients who have had a stroke. Many patients likely had their stroke because of this chronic untreated condition.

This review focuses on OSA and its prevalence, consequences, and treatment in patients after a stroke.

DEFINING AND QUANTIFYING OSA

OSA is the most common type of sleep-disordered breathing.^1,2 It involves repeated narrowing or complete collapse of the upper airway despite ongoing respiratory effort.^3,4 Apneic episodes are terminated by arousals from hypoxemia or efforts to breathe.⁵ In contrast, central sleep apnea is characterized by a patent airway but lack of airflow due to absent respiratory effort.⁵

In OSA, the number of episodes of apnea (absent airflow) and hypopnea (reduced airflow) are added together and divided by hours of sleep to calculate the apnea-hypopnea index (AHI). OSA is diagnosed by either of the following^3,4:

• AHI of 5 or higher, with clinical symptoms related to OSA (described below)
• AHI of 15 or higher, regardless of symptoms.

The AHI also defines OSA severity, as follows³:

• Mild: AHI 5 to 15
• Moderate: AHI 15 to 30
• Severe: AHI greater than 30.

Diagnostic criteria (eg, definition of hypopnea, testing methods, and AHI thresholds) have varied over time, an important consideration when reviewing the literature.

OSA IS MORE COMMON THAN EXPECTED AFTER STROKE

In the most methodologically sound and generalizable study of this topic to date, the Wisconsin Sleep Cohort Study⁶ reported in 2013 that about 14% of men and 5% of women ages 30 to 70 have an AHI greater than 5 (using 4% desaturation to score hypopneic episodes) with daytime sleepiness. Other studies suggest that 80% to 90% of people with OSA are undiagnosed and untreated.^1,7

The prevalence of OSA in patients who have had a stroke is much higher, ranging from 30% to 96% depending on the study methods and population.^1,8–12 A 2010 meta-analysis¹¹ of 29 studies reported that 72% of patients who had a stroke had an AHI greater than 5, and 29% had severe OSA. In this analysis, 7% of those with sleep-disordered breathing had central sleep apnea; still, these data indicate that the prevalence of OSA in these patients is about 5 times higher than in the general population.

RISK FACTORS MAY DIFFER IN STROKE POPULATION

Several risk factors for OSA have been identified.

Obesity is one of the strongest risk factors, with increasing body mass index (BMI) associated with increased OSA prevalence.^4,6,13 However, obesity appears to be a less significant risk factor in patients who have had a stroke than in the general population. In the 2010 meta-analysis¹¹ of OSA after stroke, the average BMI was only 26.4 kg/m² (with obesity defined as a BMI > 30.0 kg/m²), and increasing BMI was not associated with increasing AHI.

Male sex and advanced age are also OSA risk factors.^4,5 They remain significant in patients after a stroke; about 65% of poststroke patients who have OSA are men, and the older the patient, the more likely the AHI is greater than 10.¹¹

Ethnicity and genetics may also play important roles in OSA risk, with roughly 25% of OSA prevalence estimated to have a genetic basis.^14,15 Some risk factors for OSA such as craniofacial shape, upper airway anatomy, upper airway muscle dysfunction, increased respiratory chemosensitivity, and poor arousal threshold during sleep are likely determined by genetics and ethnicity.^14,15 Compared with people of European origin, Asians have a similar prevalence of OSA, but at a much lower average BMI, suggesting that other factors are significant.¹⁴ Possible genetically determined anatomic risk factors have not been specifically studied in the poststroke population, but it can be assumed they remain relevant.

Several studies have tried to find an association between OSA and type, location, etiology, or pattern of stroke.^{10,11,16–19} Although some suggest links between cardioembolic stroke and OSA,^16,20 or thrombolysis and OSA,¹⁰ most have found no association between OSA and stroke features.^11,12,21,22

HOW DOES OSA INCREASE STROKE RISK?

Untreated severe OSA is associated with increased cardiovascular mortality,^21,22 and OSA is an independent risk factor for incident stroke.²³ A number of mechanisms may explain these relationships.

Intermittent hypoxemia and recurrent sympathetic arousals resulting from OSA are thought to lead to many of the comorbid conditions with which it is associated: hypertension, coronary artery disease, heart failure, arrhythmias, pulmonary hypertension, and stroke. Repetitive decreases in ventilation lead to oxygen desaturations that result in cycles of increased sympathetic outflow and eventual sustained nocturnal hypertension and daytime chronic hypertension.^1,5,9,13 Also implicated are various changes in vasodilator and vasoconstrictor substances due to endothelial dysfunction and inflammation, which are thought to play a role in the atherogenic and prothrombotic states induced by OSA.^1,5,13

Cerebral circulation is altered primarily by the changes in partial pressure of carbon dioxide (Pco₂). During apnea, the Pco₂ rises, causing vasodilation and increased blood flow. After the apnea resolves, there is hyperpnea with resultant decreased Pco₂, and vasoconstriction. In a patient who already has vascular disease, the enhanced vasoconstriction could lead to ischemia.^1,5

Changes in intrathoracic pressure result in distortion of cardiac architecture. When the patient tries to breathe against an occluded airway, the intrathoracic pressure becomes more and more negative, increasing preload and afterload. When this happens repeatedly every night for years, it leads to remodeling of the heart such as left and right ventricular hypertrophy, with reduced stroke volume, myocardial ischemia, and increased risk of arrhythmia.^1,5,13

Untreated OSA is believed to predispose patients to develop atrial fibrillation through sympathetic overactivity, vascular inflammation, heart rate variability, and cardiac remodeling.²⁴ As atrial fibrillation is a major risk factor for stroke, particularly cardioembolic stroke, it may be another pathway of increased stroke risk in OSA.^16,20,25

OSA typically causes both daytime symptoms (excessive sleepiness, poor concentration, morning headache, depressive symptoms) and nighttime signs and symptoms (snoring, choking, gasping, night sweats, insomnia, nocturia, witnessed episodes of apnea).^3,4,26 Unfortunately, because these are nonspecific, OSA is often underdiagnosed.^4,26

Identifying OSA after a stroke may be a particular challenge, as patients often do not report classic symptoms, and the typical picture of OSA may have less predictive validity in these patients.^1,27,28 Within the first 24 hours after a stroke, hypersomnia, snoring history, and age are not predictive of OSA.¹ Patients found to have OSA after a stroke frequently do not have the traditional symptoms (sleepiness, snoring) seen in usual OSA patients. And they have higher rates of OSA at a younger age than the usual OSA patients, so age is not a predictive risk factor. In addition, daytime sleepiness and obesity are often absent or less prominent.^1,9,27,28  Finally, typical OSA signs and symptoms may be attributed to the stroke itself or to comorbidities affecting the patient, lowering suspicion for OSA.

OSA MAY HINDER STROKE RECOVERY, WORSEN OUTCOMES

OSA, particularly when moderate to severe, is linked to pathophysiologic changes that can hinder recovery from a stroke.

Intermittent hypoxemia during sleep can worsen vascular damage of at-risk tissue: nocturnal hypoxemia correlates with white matter hyperintensities on magnetic resonance imaging, a marker of ischemic demyelination.²⁹ Oxidative stress and release of inflammatory mediators associated with intermittent hypoxemia may impair vascular blood flow to brain tissue attempting to repair itself.³⁰ In addition, sympathetic overactivity and Pco₂ fluctuations associated with OSA may impede cerebral circulation.

Taken together, such ongoing nocturnal insults can lead to clinical consequences during this vulnerable period.

A 1996 study³¹ of patients recovering from a stroke found that an oxygen desaturation index (number of times that the blood oxygen level drops below a certain threshold, as measured by overnight oximetry) of more than 10 per hour was associated with worse functional recovery at discharge and at 3 and 12 months after discharge. This study also noted an association between time spent with oxygen saturations below 90% and the rate of death at 1 year.

A 2003 study³² reported that patients with an AHI greater than 10 by polysomnography spent an average of 13 days longer on the rehabilitation service and had worse functional and cognitive status on discharge, even after controlling for multiple confounders. Several subsequent studies have confirmed these and similar findings.^8,33,34

OSA has also been linked to depression,³⁵ which is common after stroke and may worsen outcomes.³⁶ The interaction between OSA, depression, and poststroke outcomes warrants further study.

In the general population, OSA has been independently associated with increased risk of stroke or death from any cause.^21,22,37 These associations have also been reported in the poststroke population: a 2014 meta-analysis found that OSA increased the risk of a repeat stroke (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2–2.6) and all-cause mortality (RR 1.69, 95% CI 1.4–2.1).³⁸

TESTING FOR OSA AFTER STROKE

Because of the high prevalence of OSA in patients who have had a stroke and the potential for worse outcomes associated with untreated OSA, there should be a low threshold for evaluating for OSA soon after stroke. Objective testing is required to qualify for therapy,  and the gold standard for diagnosis of OSA is formal polysomnography conducted in a sleep laboratory.^2–4 Unfortunately, polysomnography may be unacceptable to some patients, is costly, and is resource-intensive, particularly in an inpatient or rehabilitation setting.²⁸ Ideally, to optimize testing efficiency, patients should be screened for the likelihood of OSA before polysomnography is ordered.

Questionnaires can help determine the need for further testing

Questionnaires developed to assess OSA risk³⁹ include the following:

The Berlin questionnaire, developed in 1999, has 10 questions assessing daytime and nighttime signs and symptoms and presence of hypertension.

The STOP questionnaire, developed in 2008, assesses snoring, tiredness, observed apneic episodes, and elevated blood pressure.

The STOP-BANG questionnaire, published in 2010, includes the STOP questions plus BMI over 35 kg/m², age over 50, neck circumference over 41 cm, and male gender.

A 2017 meta-analysis³⁹ of 108 studies with nearly 50,000 people found that the STOP-BANG questionnaire performed best with regard to sensitivity and diagnostic odds ratio, but with poor specificity.

These screening tools and modified versions of them have also been evaluated in patients who have had a stroke.

In 2015, Boulos et al²⁸ found that the STOP-BAG (a version of STOP-BANG that excludes neck circumference) and the 4-variable (4V) questionnaire (sex, BMI, blood pressure, snoring) had moderate predictive value for OSA within 6 months after sroke.

In 2016, Katzan et al⁴⁰ found that the STOP-BAG2 (STOP-BAG criteria plus continuous variables for BMI and age) had a high sensitivity for polysomnographically diagnosed OSA within the first year after a stroke. The specificity was significantly better than the STOP-BANG or the STOP-BAG questionnaire, although it remained suboptimal at 60.5%.

In 2017, Sico et al⁴¹ developed and assessed the SLEEP Inventory (sex, left heart failure, Epworth Sleepiness Scale, enlarged neck, weight in pounds, insulin resistance or diabetes, and National Institutes of Health Stroke Scale) and found that it outperformed the Berlin and STOP-BANG questionnaires in the poststroke setting. The SLEEP Inventory had the best specificity and negative predictive value, and a slightly better ability to correctly classify patients as having OSA or not, classifying 80% of patients correctly.

These newer screening tools (eg, STOP-BAG, STOP-BAG2, SLEEP) can be used to identify with reasonable accuracy which patients need definitive testing after stroke.

Pulse oximetry is another possible screening tool          

Overnight pulse oximetry may also help screen for sleep apnea and stratify risk after a stroke. A 2012 study⁴² of overnight oximetry to screen patients before surgery found that the oxygen desaturation index was significantly associated with the AHI measured by polysomnography. However, oximetry testing cannot distinguish between OSA and central sleep apnea, so it is insufficient to diagnose OSA or qualify patients for therapy. Further study is needed to examine the ability of overnight pulse oximetry to screen or to stratify risk for OSA after stroke.

Polysomnography vs home testing

Polysomnography is the gold standard for diagnosing OSA. Benefits include technical support and trouble-shooting, determining relationships between OSA, body position, and sleep stage, and the ability to intervene with treatment.² However, polysomnography can be cumbersome, costly, and resource-intensive.

A home sleep apnea test, ie, an unattended, limited-channel sleep study, may be an acceptable alternative.^2–4,43,44 Home testing does not require a sleep technologist to be present during testing, uses fewer sensors, and is less expensive than overnight polysomnography, but its utility can be limited: it fails to accurately discriminate between episodes of OSA and central sleep apnea, there is potential for false-negative results, and it can underestimate sleep apnea burden because it does not measure sleep.²

Institutional resources and logistics may influence the choice of diagnostic modality. No data exist on outcomes from different diagnostic testing methods in poststroke patients. Further research is needed.

The first-line treatment for OSA is positive airway pressure (PAP).³ For most patients, this is continuous PAP (CPAP) or autoadjusting PAP (APAP). In some instances, particularly for those who cannot tolerate CPAP or who have comorbid hypoventilation, bilevel PAP (BPAP) may be indicated. More advanced PAP therapies are unlikely to be used after stroke.

PAP therapy is associated with reduced daytime sleepiness, improved mood, normalization of sleep architecture, improved systemic and pulmonary artery blood pressure, reduced rates of atrial fibrillation after ablation, and improved insulin sensitivity.^45–49 Whether it reduces the risk of cardiovascular events, including stroke, remains controversial; most data suggest that it does not.^50,51 However, when adherence to PAP therapy is considered rather than intention to treat, treatment has been found to lead to improved cardiovascular outcomes.⁵²

Mixed evidence of benefits after stroke

Observational studies provide evidence that CPAP may help patients with OSA after stroke, although results are mixed.^53–58 The studies ranged in size from 14 to 105 patients, enrolled patients with mostly moderate to severe OSA, and followed patients from 10 days to 7 years. Adherence to therapy was generally good in the short term (50%–70%), but only  15% to 30% of patients remained adherent at 5 to 7 years. Variable outcomes were reported, with some studies finding improved symptoms in the near term and mixed evidence of cardiovascular benefit in the longer ones. However, as these studies lacked randomization, drawing definitive conclusions on CPAP efficacy is difficult.

Patients were enrolled in the index admission or when starting a rehabilitation service—generally 2 to 3 weeks after their stroke. No clear association was found between the timing of initiating PAP therapy and outcomes. All patients had ischemic strokes, but few details were provided regarding stroke location, size, and severity. Exclusion criteria included severe underlying cardiopulmonary disease, confusion, severe stroke with marked impairment, and inability to cooperate. Almost all patients had moderate to severe OSA, and patients with central sleep apnea were excluded.

The major outcomes examined were drop-out rates, PAP adherence, and neurologic improvement based on neurologic functional scales (National Institutes of Health Stroke Scale and Canadian Neurologic Scale). As expected, dropout rates were higher in patients randomized to CPAP (OR 1.83, 95% CI 1.05–3.21, P = .03), although overall adherence was better than anticipated, with mean CPAP use across trials of 4.5 hours per night (95% CI 3.97–5.08) and with about 50% to 60% of patients adhering to therapy for at least 4 hours nightly.

Improvement in neurologic outcomes favored CPAP (standard mean difference 0.54, 95% CI 0.026–1.05), although considerable heterogeneity was seen. Improved sleepiness outcomes were inconsistent. Major cardiovascular outcomes were reported in only 2 studies (using the same data set) and showed delayed time to the next cardiovascular event for those treated with CPAP but no difference in cardiovascular event-free survival.

PAP poses more challenges after stroke

The primary limitation to PAP therapy is poor acceptance and adherence to therapy.⁵⁹ High rates of refusal of therapy and difficulty complying with treatment have been noted in the poststroke population, although recent studies have reported better adherence rates. How rates of adherence play out in real-world settings, outside of the controlled environment of a research study, has yet to be determined.

In general, CPAP adherence is affected by claustrophobia, difficulty tolerating a mask, problems with pressure intolerance, irritating air leaks, nasal congestion, and naso-oral dryness. Many such barriers can be overcome with use of a properly fitted mask, an appropriate pressure setting, heated humidification, nasal sprays (eg, saline, inhaled steroids), and education, encouragement, and reassurance.

After a stroke, additional obstacles may impede the ability to use PAP therapy.⁶⁸ Facial paresis (hemi- or bifacial) may make fitting of the mask problematic. Paralysis or weakness of the extremities may limit the ability to adjust or remove a mask. Aphasia can impair communication and understanding of the need to use PAP therapy, and upper-airway problems related to stroke, including dysphagia, may lead to pressure intolerance or risk of aspiration. Finally, a lack of perceived benefit, particularly if the patient does not have daytime sleepiness, may limit motivation.

Consider alternatives

For patients unlikely to succeed with PAP therapy, there are alternatives. Surgery and oral appliances are not usually realistic options in the setting of recent stroke, but positional therapy, including the use of body positioners to prevent supine sleep, as well as elevating the head of the bed, may be of some benefit.^69,70 A nasopharyngeal airway stenting device (nasal trumpet) may also be tolerated by some patients.

A proposed algorithm for screening, diagnosing, and treating OSA in patients after stroke is presented in Figure 1.

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.