Sleep Strategies

 

The definition of mild obstructive sleep apnea (OSA) has varied over the years depending upon several factors, but based upon all definitions, it is highly prevalent. Depending upon presence of symptoms and gender, the prevalence may be as high 28% in men and 26% in women. (Young et al. N Engl J Med. 1993;328:1230).

Typically, a combination of symptoms and frequency of respiratory events is required to make the diagnosis. Based upon the International Classification of Sleep Disorders-3rd edition (ICSD-3), the threshold apnea hypopnea index (AHI) for diagnosis depends upon the presence or absence of symptoms. If an individual has no symptoms, an AHI of 15 events per hour or more is required to make a diagnosis of OSA. However, there are several concerns about whether or not an individual may be “symptomatic.” This is most relevant when driving privileges may be at risk, such as with a commercial drivers’ licensing.

If a person knows that their response to a list of questions could lead to further testing, additional costs, and/or treatment, then symptoms could be unreported or underestimated. Notwithstanding, specific symptoms that are typically noted include some sign of sleepiness or non-restorative sleep and apneic episodes. The presence of snoring, gasping, choking, or breathing interruptions, either witnessed or noted by the individuals themselves, are included in the criteria. The Epworth Sleepiness Scale is the most common measure of sleepiness, which includes the likelihood of falling asleep in eight different scenarios. However, there is only a weak correlation between the scale and severity of OSA with sensitivity as low as 0.36 reported in some studies, especially if only mild OSA is present.

The presence of other comorbid disease can be used as criteria, including hypertension, mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, and type 2 diabetes mellitus. If no signs, symptoms, or comorbid diseases are present, then an AHI greater than 15 events per hour or more is required to make the diagnosis of OSA (Chowdrui et al. Am J Respir Crit Care Med. 2016;193:e37).

There is still debate regarding the association of mild OSA and cardiovascular disease and whether treatment may prevent or reduce cardiovascular outcomes. The four main clinical outcomes typically reported are hypertension, cardiovascular events, cardiovascular and all-cause mortality, and arrhythmias.

Regarding mild OSA and hypertension, 5 prospective and 18 cross-sectional studies have been reported with the two main studies being the Wisconsin Sleep Cohort study and the Sleep Heart Health Study. The Wisconsin Sleep Cohort study found mild OSA was associated with an increased risk of hypertension (Peppard et al. N Engl J Med. 2000;342:1378). However, the Sleep Heart Health study followed individuals without hypertension, including 629 with mild OSA, for 5.2 years and assessed risk of incident hypertension. Stratified analyses found no evidence for an elevated risk of hypertension in subgroups defined by age, sex, BMI, or degree of sleepiness (O’Connor et al. Am J Respir Crit Care Med. 2009;179:1159). Therefore, it appears current data are contradictory when it comes to mild OSA and subsequent risk of hypertension when stratified by age, sex, and BMI. Only retrospective analyses have been used to assess the risk of cardiovascular events.

A large clinical cohort of patients referred for sleep studies showed no association of mild OSA with different composite outcomes. Kendzerska and colleagues evaluated a composite outcome (myocardial infarction, stroke, CHF, revascularization procedures, or death from any cause) during a median follow-up of 68 months. No association of mild OSA with the composite cardiovascular endpoint was identified compared with those without OSA (Kendzerska et al. PLoS Med. 2014;11[2]:e1001599). Only one population-based study (MrOS Sleep Study) looked at the association between mild OSA and nocturnal arrhythmias in elderly men. The study did not find an increased risk for atrial fibrillation or complex ventricular ectopy in patients with mild OSA vs no OSA (Mehra et al. Arch Intern Med. 2009; 169:1147).

Several cohort studies have reported mild OSA is not associated with increased cardiovascular mortality. In the 18-year follow-up of the Wisconsin Cohort Study, it was found that mild OSA was not associated with cardiovascular mortality (HR, 1.8; 95% CI, 0.7–4.9). All-cause mortality was also not significantly increased in the mild OSA group compared with the no-OSA group in the Wisconsin cohort after 8 years of follow-up (adjusted HR, 1.6; 95% CI, 0.8–2.8). In summary, compared with subjects without OSA, available evidence from population-based longitudinal studies indicates that mild OSA is not associated with increased cardiovascular or all-cause mortality.

Does treatment of mild OSA vs no treatment change cardiovascular or mortality outcomes? This is still debated with no definitive answer. There have been several studies that have examined different therapies for OSA to reduce cardiovascular events. Typical events include coronary artery disease, hypertension, heart failure, stroke, arrhythmias, and cardiovascular disease-related mortality. However, most studies have examined cohorts with moderate to severe OSA with limited evaluation in the mild OSA category.

The effect of treatment of mild OSA on hypertension has been evaluated. A single clinical trial randomized patients with mild OSA to either a very low calorie diet with supervised lifestyle modifications vs control arm and followed patients for 1 year (Tuomilehto et al. Am J Respir Crit Care Med. 2009;179:320). Participants in the intervention arm lost more weight than the control group. Hypertension was a secondary outcome measured from the study. There was no significant change in systolic and diastolic blood pressure after successful weight loss with diet and lifestyle modifications. Follow-up at 2 and 5 years did not show significant changes in systolic and diastolic blood pressure. Patients in the treatment group lost more weight than the control group (10.7kg vs 2.4kg, respectively) and had greater resolution of sleep apnea (63% vs 35%, respectively).

An observational study evaluated the effects of CPAP specifically in patients with mild OSA. There was no significant difference in the risk of developing hypertension among those patients ineligible for CPAP therapy, active on therapy, or those who declined therapy (Marin et al. JAMA. 2012; 307:2169). In contrast, a retrospective longitudinal cohort with normal blood pressure at baseline (mild OSA without preexisting cardiovascular disease, diabetes, or hyperlipidemia) did show decrease in mean arterial blood pressure of 2 mm Hg in the treatment group (Jaimchariyatam et al. Sleep Med. 2010;11:837). The MOSAIC trial was a multicenter randomized trial that evaluated the effects of CPAP on cardiac function in minimally symptomatic patients with OSA. The use of CPAP reduced the oxygen desaturation index (ODI) and Epworth Sleepiness Scale values. However, 6 months of therapy did not change functional or structural parameters measured by echocardiogram or cardiac magnetic resonance scanning in patients with mild to moderate OSA (Craig et al. J Clin Sleep Med. 2015;11[9]:967). A single retrospective study reported the effects of CPAP in patients with mild OSA and all-cause mortality. The study compared treatment with patients using CPAP more than 4 hours vs a combined group of nonadherent and those who refused therapy (Hudgel et al. J Clin Sleep Med. 2012;8:9). There was no significant difference in all-cause mortality in the two groups. However, this study did not analyze the impact of therapy on cardiovascular-specific mortality.

To date, there have been no studies that have evaluated the impact of treatment of mild OSA on cardiovascular events, arrhythmias, or stroke. In addition, there have been no randomized studies assessing treatment of mild OSA on fatal and nonfatal cardiovascular events. There is inadequate evidence regarding the effect of mild OSA on elevated blood pressure, neurologic cognition, quality of life, and cardiovascular consequences. Future research is needed to investigate the impact of mild OSA on these outcomes.

In summary, mild OSA is a very prevalent disease but the association with hypertension remains unclear and the literature to date suggests no association with other cardiovascular outcomes. In addition, no clear prevention of cardiovascular outcomes with treatment has been proven in the setting of mild OSA.

Dr. Duthuluru is Assistant Professor, Dr. Nazir is Assistant Professor, and Dr. Stevens is Associate Professor at the University of Kansas Medical Center.

 

The definition of mild obstructive sleep apnea (OSA) has varied over the years depending upon several factors, but based upon all definitions, it is highly prevalent. Depending upon presence of symptoms and gender, the prevalence may be as high 28% in men and 26% in women. (Young et al. N Engl J Med. 1993;328:1230).

Typically, a combination of symptoms and frequency of respiratory events is required to make the diagnosis. Based upon the International Classification of Sleep Disorders-3rd edition (ICSD-3), the threshold apnea hypopnea index (AHI) for diagnosis depends upon the presence or absence of symptoms. If an individual has no symptoms, an AHI of 15 events per hour or more is required to make a diagnosis of OSA. However, there are several concerns about whether or not an individual may be “symptomatic.” This is most relevant when driving privileges may be at risk, such as with a commercial drivers’ licensing.

If a person knows that their response to a list of questions could lead to further testing, additional costs, and/or treatment, then symptoms could be unreported or underestimated. Notwithstanding, specific symptoms that are typically noted include some sign of sleepiness or non-restorative sleep and apneic episodes. The presence of snoring, gasping, choking, or breathing interruptions, either witnessed or noted by the individuals themselves, are included in the criteria. The Epworth Sleepiness Scale is the most common measure of sleepiness, which includes the likelihood of falling asleep in eight different scenarios. However, there is only a weak correlation between the scale and severity of OSA with sensitivity as low as 0.36 reported in some studies, especially if only mild OSA is present.

The presence of other comorbid disease can be used as criteria, including hypertension, mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, and type 2 diabetes mellitus. If no signs, symptoms, or comorbid diseases are present, then an AHI greater than 15 events per hour or more is required to make the diagnosis of OSA (Chowdrui et al. Am J Respir Crit Care Med. 2016;193:e37).

There is still debate regarding the association of mild OSA and cardiovascular disease and whether treatment may prevent or reduce cardiovascular outcomes. The four main clinical outcomes typically reported are hypertension, cardiovascular events, cardiovascular and all-cause mortality, and arrhythmias.

Regarding mild OSA and hypertension, 5 prospective and 18 cross-sectional studies have been reported with the two main studies being the Wisconsin Sleep Cohort study and the Sleep Heart Health Study. The Wisconsin Sleep Cohort study found mild OSA was associated with an increased risk of hypertension (Peppard et al. N Engl J Med. 2000;342:1378). However, the Sleep Heart Health study followed individuals without hypertension, including 629 with mild OSA, for 5.2 years and assessed risk of incident hypertension. Stratified analyses found no evidence for an elevated risk of hypertension in subgroups defined by age, sex, BMI, or degree of sleepiness (O’Connor et al. Am J Respir Crit Care Med. 2009;179:1159). Therefore, it appears current data are contradictory when it comes to mild OSA and subsequent risk of hypertension when stratified by age, sex, and BMI. Only retrospective analyses have been used to assess the risk of cardiovascular events.

A large clinical cohort of patients referred for sleep studies showed no association of mild OSA with different composite outcomes. Kendzerska and colleagues evaluated a composite outcome (myocardial infarction, stroke, CHF, revascularization procedures, or death from any cause) during a median follow-up of 68 months. No association of mild OSA with the composite cardiovascular endpoint was identified compared with those without OSA (Kendzerska et al. PLoS Med. 2014;11[2]:e1001599). Only one population-based study (MrOS Sleep Study) looked at the association between mild OSA and nocturnal arrhythmias in elderly men. The study did not find an increased risk for atrial fibrillation or complex ventricular ectopy in patients with mild OSA vs no OSA (Mehra et al. Arch Intern Med. 2009; 169:1147).

Several cohort studies have reported mild OSA is not associated with increased cardiovascular mortality. In the 18-year follow-up of the Wisconsin Cohort Study, it was found that mild OSA was not associated with cardiovascular mortality (HR, 1.8; 95% CI, 0.7–4.9). All-cause mortality was also not significantly increased in the mild OSA group compared with the no-OSA group in the Wisconsin cohort after 8 years of follow-up (adjusted HR, 1.6; 95% CI, 0.8–2.8). In summary, compared with subjects without OSA, available evidence from population-based longitudinal studies indicates that mild OSA is not associated with increased cardiovascular or all-cause mortality.

Does treatment of mild OSA vs no treatment change cardiovascular or mortality outcomes? This is still debated with no definitive answer. There have been several studies that have examined different therapies for OSA to reduce cardiovascular events. Typical events include coronary artery disease, hypertension, heart failure, stroke, arrhythmias, and cardiovascular disease-related mortality. However, most studies have examined cohorts with moderate to severe OSA with limited evaluation in the mild OSA category.

The effect of treatment of mild OSA on hypertension has been evaluated. A single clinical trial randomized patients with mild OSA to either a very low calorie diet with supervised lifestyle modifications vs control arm and followed patients for 1 year (Tuomilehto et al. Am J Respir Crit Care Med. 2009;179:320). Participants in the intervention arm lost more weight than the control group. Hypertension was a secondary outcome measured from the study. There was no significant change in systolic and diastolic blood pressure after successful weight loss with diet and lifestyle modifications. Follow-up at 2 and 5 years did not show significant changes in systolic and diastolic blood pressure. Patients in the treatment group lost more weight than the control group (10.7kg vs 2.4kg, respectively) and had greater resolution of sleep apnea (63% vs 35%, respectively).

An observational study evaluated the effects of CPAP specifically in patients with mild OSA. There was no significant difference in the risk of developing hypertension among those patients ineligible for CPAP therapy, active on therapy, or those who declined therapy (Marin et al. JAMA. 2012; 307:2169). In contrast, a retrospective longitudinal cohort with normal blood pressure at baseline (mild OSA without preexisting cardiovascular disease, diabetes, or hyperlipidemia) did show decrease in mean arterial blood pressure of 2 mm Hg in the treatment group (Jaimchariyatam et al. Sleep Med. 2010;11:837). The MOSAIC trial was a multicenter randomized trial that evaluated the effects of CPAP on cardiac function in minimally symptomatic patients with OSA. The use of CPAP reduced the oxygen desaturation index (ODI) and Epworth Sleepiness Scale values. However, 6 months of therapy did not change functional or structural parameters measured by echocardiogram or cardiac magnetic resonance scanning in patients with mild to moderate OSA (Craig et al. J Clin Sleep Med. 2015;11[9]:967). A single retrospective study reported the effects of CPAP in patients with mild OSA and all-cause mortality. The study compared treatment with patients using CPAP more than 4 hours vs a combined group of nonadherent and those who refused therapy (Hudgel et al. J Clin Sleep Med. 2012;8:9). There was no significant difference in all-cause mortality in the two groups. However, this study did not analyze the impact of therapy on cardiovascular-specific mortality.

To date, there have been no studies that have evaluated the impact of treatment of mild OSA on cardiovascular events, arrhythmias, or stroke. In addition, there have been no randomized studies assessing treatment of mild OSA on fatal and nonfatal cardiovascular events. There is inadequate evidence regarding the effect of mild OSA on elevated blood pressure, neurologic cognition, quality of life, and cardiovascular consequences. Future research is needed to investigate the impact of mild OSA on these outcomes.

In summary, mild OSA is a very prevalent disease but the association with hypertension remains unclear and the literature to date suggests no association with other cardiovascular outcomes. In addition, no clear prevention of cardiovascular outcomes with treatment has been proven in the setting of mild OSA.

Dr. Duthuluru is Assistant Professor, Dr. Nazir is Assistant Professor, and Dr. Stevens is Associate Professor at the University of Kansas Medical Center.

 

The definition of mild obstructive sleep apnea (OSA) has varied over the years depending upon several factors, but based upon all definitions, it is highly prevalent. Depending upon presence of symptoms and gender, the prevalence may be as high 28% in men and 26% in women. (Young et al. N Engl J Med. 1993;328:1230).

Typically, a combination of symptoms and frequency of respiratory events is required to make the diagnosis. Based upon the International Classification of Sleep Disorders-3rd edition (ICSD-3), the threshold apnea hypopnea index (AHI) for diagnosis depends upon the presence or absence of symptoms. If an individual has no symptoms, an AHI of 15 events per hour or more is required to make a diagnosis of OSA. However, there are several concerns about whether or not an individual may be “symptomatic.” This is most relevant when driving privileges may be at risk, such as with a commercial drivers’ licensing.

If a person knows that their response to a list of questions could lead to further testing, additional costs, and/or treatment, then symptoms could be unreported or underestimated. Notwithstanding, specific symptoms that are typically noted include some sign of sleepiness or non-restorative sleep and apneic episodes. The presence of snoring, gasping, choking, or breathing interruptions, either witnessed or noted by the individuals themselves, are included in the criteria. The Epworth Sleepiness Scale is the most common measure of sleepiness, which includes the likelihood of falling asleep in eight different scenarios. However, there is only a weak correlation between the scale and severity of OSA with sensitivity as low as 0.36 reported in some studies, especially if only mild OSA is present.

The presence of other comorbid disease can be used as criteria, including hypertension, mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, and type 2 diabetes mellitus. If no signs, symptoms, or comorbid diseases are present, then an AHI greater than 15 events per hour or more is required to make the diagnosis of OSA (Chowdrui et al. Am J Respir Crit Care Med. 2016;193:e37).

There is still debate regarding the association of mild OSA and cardiovascular disease and whether treatment may prevent or reduce cardiovascular outcomes. The four main clinical outcomes typically reported are hypertension, cardiovascular events, cardiovascular and all-cause mortality, and arrhythmias.

Regarding mild OSA and hypertension, 5 prospective and 18 cross-sectional studies have been reported with the two main studies being the Wisconsin Sleep Cohort study and the Sleep Heart Health Study. The Wisconsin Sleep Cohort study found mild OSA was associated with an increased risk of hypertension (Peppard et al. N Engl J Med. 2000;342:1378). However, the Sleep Heart Health study followed individuals without hypertension, including 629 with mild OSA, for 5.2 years and assessed risk of incident hypertension. Stratified analyses found no evidence for an elevated risk of hypertension in subgroups defined by age, sex, BMI, or degree of sleepiness (O’Connor et al. Am J Respir Crit Care Med. 2009;179:1159). Therefore, it appears current data are contradictory when it comes to mild OSA and subsequent risk of hypertension when stratified by age, sex, and BMI. Only retrospective analyses have been used to assess the risk of cardiovascular events.

A large clinical cohort of patients referred for sleep studies showed no association of mild OSA with different composite outcomes. Kendzerska and colleagues evaluated a composite outcome (myocardial infarction, stroke, CHF, revascularization procedures, or death from any cause) during a median follow-up of 68 months. No association of mild OSA with the composite cardiovascular endpoint was identified compared with those without OSA (Kendzerska et al. PLoS Med. 2014;11[2]:e1001599). Only one population-based study (MrOS Sleep Study) looked at the association between mild OSA and nocturnal arrhythmias in elderly men. The study did not find an increased risk for atrial fibrillation or complex ventricular ectopy in patients with mild OSA vs no OSA (Mehra et al. Arch Intern Med. 2009; 169:1147).

Several cohort studies have reported mild OSA is not associated with increased cardiovascular mortality. In the 18-year follow-up of the Wisconsin Cohort Study, it was found that mild OSA was not associated with cardiovascular mortality (HR, 1.8; 95% CI, 0.7–4.9). All-cause mortality was also not significantly increased in the mild OSA group compared with the no-OSA group in the Wisconsin cohort after 8 years of follow-up (adjusted HR, 1.6; 95% CI, 0.8–2.8). In summary, compared with subjects without OSA, available evidence from population-based longitudinal studies indicates that mild OSA is not associated with increased cardiovascular or all-cause mortality.

Does treatment of mild OSA vs no treatment change cardiovascular or mortality outcomes? This is still debated with no definitive answer. There have been several studies that have examined different therapies for OSA to reduce cardiovascular events. Typical events include coronary artery disease, hypertension, heart failure, stroke, arrhythmias, and cardiovascular disease-related mortality. However, most studies have examined cohorts with moderate to severe OSA with limited evaluation in the mild OSA category.

The effect of treatment of mild OSA on hypertension has been evaluated. A single clinical trial randomized patients with mild OSA to either a very low calorie diet with supervised lifestyle modifications vs control arm and followed patients for 1 year (Tuomilehto et al. Am J Respir Crit Care Med. 2009;179:320). Participants in the intervention arm lost more weight than the control group. Hypertension was a secondary outcome measured from the study. There was no significant change in systolic and diastolic blood pressure after successful weight loss with diet and lifestyle modifications. Follow-up at 2 and 5 years did not show significant changes in systolic and diastolic blood pressure. Patients in the treatment group lost more weight than the control group (10.7kg vs 2.4kg, respectively) and had greater resolution of sleep apnea (63% vs 35%, respectively).

An observational study evaluated the effects of CPAP specifically in patients with mild OSA. There was no significant difference in the risk of developing hypertension among those patients ineligible for CPAP therapy, active on therapy, or those who declined therapy (Marin et al. JAMA. 2012; 307:2169). In contrast, a retrospective longitudinal cohort with normal blood pressure at baseline (mild OSA without preexisting cardiovascular disease, diabetes, or hyperlipidemia) did show decrease in mean arterial blood pressure of 2 mm Hg in the treatment group (Jaimchariyatam et al. Sleep Med. 2010;11:837). The MOSAIC trial was a multicenter randomized trial that evaluated the effects of CPAP on cardiac function in minimally symptomatic patients with OSA. The use of CPAP reduced the oxygen desaturation index (ODI) and Epworth Sleepiness Scale values. However, 6 months of therapy did not change functional or structural parameters measured by echocardiogram or cardiac magnetic resonance scanning in patients with mild to moderate OSA (Craig et al. J Clin Sleep Med. 2015;11[9]:967). A single retrospective study reported the effects of CPAP in patients with mild OSA and all-cause mortality. The study compared treatment with patients using CPAP more than 4 hours vs a combined group of nonadherent and those who refused therapy (Hudgel et al. J Clin Sleep Med. 2012;8:9). There was no significant difference in all-cause mortality in the two groups. However, this study did not analyze the impact of therapy on cardiovascular-specific mortality.

To date, there have been no studies that have evaluated the impact of treatment of mild OSA on cardiovascular events, arrhythmias, or stroke. In addition, there have been no randomized studies assessing treatment of mild OSA on fatal and nonfatal cardiovascular events. There is inadequate evidence regarding the effect of mild OSA on elevated blood pressure, neurologic cognition, quality of life, and cardiovascular consequences. Future research is needed to investigate the impact of mild OSA on these outcomes.

In summary, mild OSA is a very prevalent disease but the association with hypertension remains unclear and the literature to date suggests no association with other cardiovascular outcomes. In addition, no clear prevention of cardiovascular outcomes with treatment has been proven in the setting of mild OSA.

Dr. Duthuluru is Assistant Professor, Dr. Nazir is Assistant Professor, and Dr. Stevens is Associate Professor at the University of Kansas Medical Center.

 

Pulmonary hypertension (PH) is a progressive disease characterized by an increase in pulmonary arterial pressure and pulmonary vascular resistance (PVR) leading to right ventricular failure. Although substantial progress has been achieved in the treatment of PH, mostly due to improved pharmacotherapy, it remains a life-threatening disease with a poor prognosis. Increased pulmonary arterial pressure is a common feature of many chronic lung diseases, and chronic lung disease is the second most common cause of pulmonary hypertension. PH caused by chronic lung disease, including PH due to sleep-disordered breathing (SDB), is referred to as group 3 PH in the classification of pulmonary hypertension (Simonneau et al. J Am Coll Cardiol. 2013;62:D34 e41). Many reports since have linked pulmonary arterial hypertension to obstructive sleep apnea (OSA). These were validated in animal trials, when rodents were exposed to intermittent hypoxia for several hours over a few weeks, similar to what is seen in patients with OSA; this resulted in pulmonary vascular remodeling, sustained PH, and right ventricular hypertrophy. As with other chronic lung disease, prevalence rates of PH in SDB vary greatly, with some studies suggesting prevalence of pulmonary hypertension in OSA to be as high as 40%, although a lack of large-scale studies with clearly defined patient populations makes it difficult to determine the true prevalence rate. Most studies suggest that about 20% to 30% of patients with OSA have some degree of PH. OSA has been shown to be an independent causal factor for the development of PH (Hurdman et al. Eur Respir J. 2012; 39, 945–955). PH associated with OSA appears to be mild and may be due to a combination of precapillary and postcapillary factors, including pulmonary arteriolar remodeling, hyperreactivity to hypoxia, and left ventricular diastolic dysfunction resulting in left atrial enlargement. Despite differences in reported prevalence rates, most studies consistently reported mild increases in pulmonary arterial pressure with mPAP averaging less than 30 mm Hg. In one of the largest studies to date, the prevalence rate of PH in 220 patients with SDB was 17%, and the mPAP was 26 +/- 6 mm Hg (Chaouat et al. Chest. 1996;109[2]:380).

The other consistent finding in most studies was that PH correlated with the severity of obesity, daytime hypoxia and hypercapnia, obstructive airways disease, and nocturnal oxygen desaturation. PH seems to be more common and more severe in obesity hypoventilation syndrome (OHS) than in “pure” OSA patients (58% vs 9%) (Kessler et al. Chest. 2001;120[2]:369).

The incidence of OSA is rising in parallel with the rising global incide

nce of extreme obesity, and it is increasingly becoming a rapidly growing health problem in the United States and worldwide. It remains largely undiagnosed and has been linked to an increased incidence of stroke, heart failure, myocardial infarction, and arrhythmia. OSA is characterized by repetitive nocturnal arterial oxygen desaturations and hypercapnia, large intrathoracic pressure swings, and acute increases in pulmonary arterial pressure. PH in patients with OSA is thought to be due to hypoxia-related vasoconstriction that occurs during these apneic periods and can lead to progressive vascular damage resulting in accelerated inflammation and sympathetic activity; this eventually leads to subclinical myocardial injury and the potential development of biventricular systolic and diastolic dysfunction and resultant elevated cardiac biomarkers (Adegunsoye et al. Pulm Med. Published online 2012 Jul 11. doi: 10.1155/2012/273591). It is still unclear whether PH associated with chronic lung disease (CLD) and SDB is a direct consequence of hypoxemia (as seen in CLD and SDB) or whether this is due to a cascade of events that leads to pulmonary vascular disease that is separate from or out of proportion to the underlying lung injury from existing pulmonary processes.

Patients with OSA who have PH are more likely to be obese, have decreased respiratory function (FEV₁, vital capacity, and FEV₁/VC ratio), and lower oxygen saturation/higher carbon dioxide content in blood (Chaouat et al. Chest. 1996;109[2]:380). These patients frequently present with shortness of breath and dyspnea on exertion. Echocardiogram remains the main screening tool for evaluation of PH. With that said, right-sided heart catheterization remains the gold standard for the diagnosis of all classes of PH; however, use of right-sided heart catheterization in group 3 pulmonary hypertension is reserved for select patients. This is likely because PH in patients with OSA is accepted as a more benign prognostic marker compared with other group 3 forms. Furthermore, patients with OHS are more prone to developing PH and cor pulmonale compared with patients with isolated OSA. OSA with PH has lower survival rates than OSA without PH. Studies showed that patients with OHS tend to do worse than patients with OSA alone (Aljohara et al. J Thorac Dis. 2017;9[3]:779).

 

AHI and PH

Various studies have looked at different polysomnographic variables to understand the relationship between PH and OSA. Initial studies showed that the apnea hypopnea index (AHI) does not predict development of PH among patients with OSA. Decrements in nocturnal oxygen saturation, however, is predictive of the development of PH; the only predictor of developing PH among patients with OSA in one study was time spent with oxygen saturation below 70% during sleep (Wong et al. Eur Arch Otorhinolaryngol. 2017;74:2601). In addition, recent data suggest there is no statistically significant association between age, gender, body mass index, or AHI and chance for development of PH (Wong et al. 2017). It was found that the percentage of time during sleep with oxygen saturation below 90% was significant and independently associated with higher PAP. Furthermore, a recent study demonstrated that patients with moderate to severe OSA (AHI over 15/h) who develop PH tend to have worse hemodynamics (higher PVR and mPAP) and subclinical myocardial damage (evaluated by troponin T), as well as increased ventricular wall stress (assessed by proBNP) when compared with patients with mild OSA (AHI less than 15/h).

Treatment

The mainstay treatment for OSA and OHS is positive airway pressure (PAP). This therapy has been shown to improve sleep and respiratory parameters, including sleep quality, overall quality of life, as well as promote reduction in mean pulmonary arterial pressure. The regular use of noninvasive positive-pressure ventilation has also been shown to reverse daytime hypoxia and hypercapnia, as well as influence inflammatory markers: decrease circulating levels of endothelin-1, interleukin-6, and C-reactive protein, thereby improving vascular endothelial function and reducing platelet activation and aggregation (Yokoe et al. Circulation. 2003;107[8]:1129). Indeed, there is a decrease in mean pulmonary arterial pressure in some patients with long-term daily use of PAP, but, in some patients, both pulmonary and right ventricular dysfunction persists, suggesting vascular remodeling and/or endothelial dysfunction. These findings indicate the need for early recognition of OSA and early treatment for patients, thus preventing remodeling and further development of PH and right ventricular dysfunction. Adequate control of OSA/OHS has important long-term effects on overall health, because it significantly reduces the risk of systemic hypertension, congestive heart failure, arrhythmias, and stroke. It is imperative to control underlying SDB before considering PAH-specific medications to treat PH associated with OSA or OHS unless the patient is demonstrating signs of right-sided heart failure; in such cases, concomitant therapy may be considered upfront. It is recommended that

patients with SDB should have an assessment for PH before starting therapy for their SDB and then again after 3 to 4 months of effective PAP confirmed by device data monitoring. For patients who have persistent PH despite achieving adequate control of their SDB, pulmonary vasodilator therapy may be indicated following standard treatment guidelines for WHO group 1 PAH (Galie et al. J Am Coll Cardiol. 2013;62[suppl 25]:D60–72). Medications that are currently approved for the treatment of PAH have not been well studied in PH associated with SDB and, at present time, the available data do not demonstrate sustained benefit.

Dr. Singhal is a second-year fellow in Pulmonary/Critical Care and Dr. Minkin is Director, Pulmonary Hypertension Program, New York Presbyterian-Brooklyn Methodist Hospital. Dr. Minkin is also Assistant Professor of Clinical Medicine, Weill Cornell Medical College, New York.

 

Pulmonary hypertension (PH) is a progressive disease characterized by an increase in pulmonary arterial pressure and pulmonary vascular resistance (PVR) leading to right ventricular failure. Although substantial progress has been achieved in the treatment of PH, mostly due to improved pharmacotherapy, it remains a life-threatening disease with a poor prognosis. Increased pulmonary arterial pressure is a common feature of many chronic lung diseases, and chronic lung disease is the second most common cause of pulmonary hypertension. PH caused by chronic lung disease, including PH due to sleep-disordered breathing (SDB), is referred to as group 3 PH in the classification of pulmonary hypertension (Simonneau et al. J Am Coll Cardiol. 2013;62:D34 e41). Many reports since have linked pulmonary arterial hypertension to obstructive sleep apnea (OSA). These were validated in animal trials, when rodents were exposed to intermittent hypoxia for several hours over a few weeks, similar to what is seen in patients with OSA; this resulted in pulmonary vascular remodeling, sustained PH, and right ventricular hypertrophy. As with other chronic lung disease, prevalence rates of PH in SDB vary greatly, with some studies suggesting prevalence of pulmonary hypertension in OSA to be as high as 40%, although a lack of large-scale studies with clearly defined patient populations makes it difficult to determine the true prevalence rate. Most studies suggest that about 20% to 30% of patients with OSA have some degree of PH. OSA has been shown to be an independent causal factor for the development of PH (Hurdman et al. Eur Respir J. 2012; 39, 945–955). PH associated with OSA appears to be mild and may be due to a combination of precapillary and postcapillary factors, including pulmonary arteriolar remodeling, hyperreactivity to hypoxia, and left ventricular diastolic dysfunction resulting in left atrial enlargement. Despite differences in reported prevalence rates, most studies consistently reported mild increases in pulmonary arterial pressure with mPAP averaging less than 30 mm Hg. In one of the largest studies to date, the prevalence rate of PH in 220 patients with SDB was 17%, and the mPAP was 26 +/- 6 mm Hg (Chaouat et al. Chest. 1996;109[2]:380).

The other consistent finding in most studies was that PH correlated with the severity of obesity, daytime hypoxia and hypercapnia, obstructive airways disease, and nocturnal oxygen desaturation. PH seems to be more common and more severe in obesity hypoventilation syndrome (OHS) than in “pure” OSA patients (58% vs 9%) (Kessler et al. Chest. 2001;120[2]:369).

The incidence of OSA is rising in parallel with the rising global incide

nce of extreme obesity, and it is increasingly becoming a rapidly growing health problem in the United States and worldwide. It remains largely undiagnosed and has been linked to an increased incidence of stroke, heart failure, myocardial infarction, and arrhythmia. OSA is characterized by repetitive nocturnal arterial oxygen desaturations and hypercapnia, large intrathoracic pressure swings, and acute increases in pulmonary arterial pressure. PH in patients with OSA is thought to be due to hypoxia-related vasoconstriction that occurs during these apneic periods and can lead to progressive vascular damage resulting in accelerated inflammation and sympathetic activity; this eventually leads to subclinical myocardial injury and the potential development of biventricular systolic and diastolic dysfunction and resultant elevated cardiac biomarkers (Adegunsoye et al. Pulm Med. Published online 2012 Jul 11. doi: 10.1155/2012/273591). It is still unclear whether PH associated with chronic lung disease (CLD) and SDB is a direct consequence of hypoxemia (as seen in CLD and SDB) or whether this is due to a cascade of events that leads to pulmonary vascular disease that is separate from or out of proportion to the underlying lung injury from existing pulmonary processes.

Patients with OSA who have PH are more likely to be obese, have decreased respiratory function (FEV₁, vital capacity, and FEV₁/VC ratio), and lower oxygen saturation/higher carbon dioxide content in blood (Chaouat et al. Chest. 1996;109[2]:380). These patients frequently present with shortness of breath and dyspnea on exertion. Echocardiogram remains the main screening tool for evaluation of PH. With that said, right-sided heart catheterization remains the gold standard for the diagnosis of all classes of PH; however, use of right-sided heart catheterization in group 3 pulmonary hypertension is reserved for select patients. This is likely because PH in patients with OSA is accepted as a more benign prognostic marker compared with other group 3 forms. Furthermore, patients with OHS are more prone to developing PH and cor pulmonale compared with patients with isolated OSA. OSA with PH has lower survival rates than OSA without PH. Studies showed that patients with OHS tend to do worse than patients with OSA alone (Aljohara et al. J Thorac Dis. 2017;9[3]:779).

 

AHI and PH

Various studies have looked at different polysomnographic variables to understand the relationship between PH and OSA. Initial studies showed that the apnea hypopnea index (AHI) does not predict development of PH among patients with OSA. Decrements in nocturnal oxygen saturation, however, is predictive of the development of PH; the only predictor of developing PH among patients with OSA in one study was time spent with oxygen saturation below 70% during sleep (Wong et al. Eur Arch Otorhinolaryngol. 2017;74:2601). In addition, recent data suggest there is no statistically significant association between age, gender, body mass index, or AHI and chance for development of PH (Wong et al. 2017). It was found that the percentage of time during sleep with oxygen saturation below 90% was significant and independently associated with higher PAP. Furthermore, a recent study demonstrated that patients with moderate to severe OSA (AHI over 15/h) who develop PH tend to have worse hemodynamics (higher PVR and mPAP) and subclinical myocardial damage (evaluated by troponin T), as well as increased ventricular wall stress (assessed by proBNP) when compared with patients with mild OSA (AHI less than 15/h).

Treatment

The mainstay treatment for OSA and OHS is positive airway pressure (PAP). This therapy has been shown to improve sleep and respiratory parameters, including sleep quality, overall quality of life, as well as promote reduction in mean pulmonary arterial pressure. The regular use of noninvasive positive-pressure ventilation has also been shown to reverse daytime hypoxia and hypercapnia, as well as influence inflammatory markers: decrease circulating levels of endothelin-1, interleukin-6, and C-reactive protein, thereby improving vascular endothelial function and reducing platelet activation and aggregation (Yokoe et al. Circulation. 2003;107[8]:1129). Indeed, there is a decrease in mean pulmonary arterial pressure in some patients with long-term daily use of PAP, but, in some patients, both pulmonary and right ventricular dysfunction persists, suggesting vascular remodeling and/or endothelial dysfunction. These findings indicate the need for early recognition of OSA and early treatment for patients, thus preventing remodeling and further development of PH and right ventricular dysfunction. Adequate control of OSA/OHS has important long-term effects on overall health, because it significantly reduces the risk of systemic hypertension, congestive heart failure, arrhythmias, and stroke. It is imperative to control underlying SDB before considering PAH-specific medications to treat PH associated with OSA or OHS unless the patient is demonstrating signs of right-sided heart failure; in such cases, concomitant therapy may be considered upfront. It is recommended that

patients with SDB should have an assessment for PH before starting therapy for their SDB and then again after 3 to 4 months of effective PAP confirmed by device data monitoring. For patients who have persistent PH despite achieving adequate control of their SDB, pulmonary vasodilator therapy may be indicated following standard treatment guidelines for WHO group 1 PAH (Galie et al. J Am Coll Cardiol. 2013;62[suppl 25]:D60–72). Medications that are currently approved for the treatment of PAH have not been well studied in PH associated with SDB and, at present time, the available data do not demonstrate sustained benefit.

Dr. Singhal is a second-year fellow in Pulmonary/Critical Care and Dr. Minkin is Director, Pulmonary Hypertension Program, New York Presbyterian-Brooklyn Methodist Hospital. Dr. Minkin is also Assistant Professor of Clinical Medicine, Weill Cornell Medical College, New York.

 

Pulmonary hypertension (PH) is a progressive disease characterized by an increase in pulmonary arterial pressure and pulmonary vascular resistance (PVR) leading to right ventricular failure. Although substantial progress has been achieved in the treatment of PH, mostly due to improved pharmacotherapy, it remains a life-threatening disease with a poor prognosis. Increased pulmonary arterial pressure is a common feature of many chronic lung diseases, and chronic lung disease is the second most common cause of pulmonary hypertension. PH caused by chronic lung disease, including PH due to sleep-disordered breathing (SDB), is referred to as group 3 PH in the classification of pulmonary hypertension (Simonneau et al. J Am Coll Cardiol. 2013;62:D34 e41). Many reports since have linked pulmonary arterial hypertension to obstructive sleep apnea (OSA). These were validated in animal trials, when rodents were exposed to intermittent hypoxia for several hours over a few weeks, similar to what is seen in patients with OSA; this resulted in pulmonary vascular remodeling, sustained PH, and right ventricular hypertrophy. As with other chronic lung disease, prevalence rates of PH in SDB vary greatly, with some studies suggesting prevalence of pulmonary hypertension in OSA to be as high as 40%, although a lack of large-scale studies with clearly defined patient populations makes it difficult to determine the true prevalence rate. Most studies suggest that about 20% to 30% of patients with OSA have some degree of PH. OSA has been shown to be an independent causal factor for the development of PH (Hurdman et al. Eur Respir J. 2012; 39, 945–955). PH associated with OSA appears to be mild and may be due to a combination of precapillary and postcapillary factors, including pulmonary arteriolar remodeling, hyperreactivity to hypoxia, and left ventricular diastolic dysfunction resulting in left atrial enlargement. Despite differences in reported prevalence rates, most studies consistently reported mild increases in pulmonary arterial pressure with mPAP averaging less than 30 mm Hg. In one of the largest studies to date, the prevalence rate of PH in 220 patients with SDB was 17%, and the mPAP was 26 +/- 6 mm Hg (Chaouat et al. Chest. 1996;109[2]:380).

The other consistent finding in most studies was that PH correlated with the severity of obesity, daytime hypoxia and hypercapnia, obstructive airways disease, and nocturnal oxygen desaturation. PH seems to be more common and more severe in obesity hypoventilation syndrome (OHS) than in “pure” OSA patients (58% vs 9%) (Kessler et al. Chest. 2001;120[2]:369).

The incidence of OSA is rising in parallel with the rising global incide

nce of extreme obesity, and it is increasingly becoming a rapidly growing health problem in the United States and worldwide. It remains largely undiagnosed and has been linked to an increased incidence of stroke, heart failure, myocardial infarction, and arrhythmia. OSA is characterized by repetitive nocturnal arterial oxygen desaturations and hypercapnia, large intrathoracic pressure swings, and acute increases in pulmonary arterial pressure. PH in patients with OSA is thought to be due to hypoxia-related vasoconstriction that occurs during these apneic periods and can lead to progressive vascular damage resulting in accelerated inflammation and sympathetic activity; this eventually leads to subclinical myocardial injury and the potential development of biventricular systolic and diastolic dysfunction and resultant elevated cardiac biomarkers (Adegunsoye et al. Pulm Med. Published online 2012 Jul 11. doi: 10.1155/2012/273591). It is still unclear whether PH associated with chronic lung disease (CLD) and SDB is a direct consequence of hypoxemia (as seen in CLD and SDB) or whether this is due to a cascade of events that leads to pulmonary vascular disease that is separate from or out of proportion to the underlying lung injury from existing pulmonary processes.

Patients with OSA who have PH are more likely to be obese, have decreased respiratory function (FEV₁, vital capacity, and FEV₁/VC ratio), and lower oxygen saturation/higher carbon dioxide content in blood (Chaouat et al. Chest. 1996;109[2]:380). These patients frequently present with shortness of breath and dyspnea on exertion. Echocardiogram remains the main screening tool for evaluation of PH. With that said, right-sided heart catheterization remains the gold standard for the diagnosis of all classes of PH; however, use of right-sided heart catheterization in group 3 pulmonary hypertension is reserved for select patients. This is likely because PH in patients with OSA is accepted as a more benign prognostic marker compared with other group 3 forms. Furthermore, patients with OHS are more prone to developing PH and cor pulmonale compared with patients with isolated OSA. OSA with PH has lower survival rates than OSA without PH. Studies showed that patients with OHS tend to do worse than patients with OSA alone (Aljohara et al. J Thorac Dis. 2017;9[3]:779).

 

AHI and PH

Various studies have looked at different polysomnographic variables to understand the relationship between PH and OSA. Initial studies showed that the apnea hypopnea index (AHI) does not predict development of PH among patients with OSA. Decrements in nocturnal oxygen saturation, however, is predictive of the development of PH; the only predictor of developing PH among patients with OSA in one study was time spent with oxygen saturation below 70% during sleep (Wong et al. Eur Arch Otorhinolaryngol. 2017;74:2601). In addition, recent data suggest there is no statistically significant association between age, gender, body mass index, or AHI and chance for development of PH (Wong et al. 2017). It was found that the percentage of time during sleep with oxygen saturation below 90% was significant and independently associated with higher PAP. Furthermore, a recent study demonstrated that patients with moderate to severe OSA (AHI over 15/h) who develop PH tend to have worse hemodynamics (higher PVR and mPAP) and subclinical myocardial damage (evaluated by troponin T), as well as increased ventricular wall stress (assessed by proBNP) when compared with patients with mild OSA (AHI less than 15/h).

Treatment

The mainstay treatment for OSA and OHS is positive airway pressure (PAP). This therapy has been shown to improve sleep and respiratory parameters, including sleep quality, overall quality of life, as well as promote reduction in mean pulmonary arterial pressure. The regular use of noninvasive positive-pressure ventilation has also been shown to reverse daytime hypoxia and hypercapnia, as well as influence inflammatory markers: decrease circulating levels of endothelin-1, interleukin-6, and C-reactive protein, thereby improving vascular endothelial function and reducing platelet activation and aggregation (Yokoe et al. Circulation. 2003;107[8]:1129). Indeed, there is a decrease in mean pulmonary arterial pressure in some patients with long-term daily use of PAP, but, in some patients, both pulmonary and right ventricular dysfunction persists, suggesting vascular remodeling and/or endothelial dysfunction. These findings indicate the need for early recognition of OSA and early treatment for patients, thus preventing remodeling and further development of PH and right ventricular dysfunction. Adequate control of OSA/OHS has important long-term effects on overall health, because it significantly reduces the risk of systemic hypertension, congestive heart failure, arrhythmias, and stroke. It is imperative to control underlying SDB before considering PAH-specific medications to treat PH associated with OSA or OHS unless the patient is demonstrating signs of right-sided heart failure; in such cases, concomitant therapy may be considered upfront. It is recommended that

patients with SDB should have an assessment for PH before starting therapy for their SDB and then again after 3 to 4 months of effective PAP confirmed by device data monitoring. For patients who have persistent PH despite achieving adequate control of their SDB, pulmonary vasodilator therapy may be indicated following standard treatment guidelines for WHO group 1 PAH (Galie et al. J Am Coll Cardiol. 2013;62[suppl 25]:D60–72). Medications that are currently approved for the treatment of PAH have not been well studied in PH associated with SDB and, at present time, the available data do not demonstrate sustained benefit.

Dr. Singhal is a second-year fellow in Pulmonary/Critical Care and Dr. Minkin is Director, Pulmonary Hypertension Program, New York Presbyterian-Brooklyn Methodist Hospital. Dr. Minkin is also Assistant Professor of Clinical Medicine, Weill Cornell Medical College, New York.

 

Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).

Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.

OSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).

A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).

In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.

Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).

The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.

Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.

Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.

It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.

 

Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.

 

Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).

Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.

OSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).

A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).

In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.

Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).

The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.

Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.

Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.

It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.

 

Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.

 

Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).

Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.

OSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).

A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).

In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.

Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).

The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.

Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.

Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.

It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.

 

Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.