children Article
Sleep Apnea and Hypoventilation in Patients with Down Syndrome: Analysis of 144 Polysomnogram Studies Zheng Fan 1, *, Mihye Ahn 2 , Heidi L. Roth 1 , Leping Li 3 and Bradley V. Vaughn 1 1 2 3
*
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] (H.L.R.); [email protected] (B.V.V.) Department of Mathematics and Statistics, University of Nevada, Reno, NV 89503, USA; [email protected] Biostatistics and Computational Biology, National Institute of Environmental Sciences, Research Triangle Park, NC 27709, USA; [email protected] Correspondence: [email protected]
Academic Editor: Sari A. Acra Received: 16 May 2017; Accepted: 27 June 2017; Published: 30 June 2017
Abstract: Patients with Down syndrome (DS) are at risk for both obstructive sleep apnea (OSA) and central sleep apnea (CSA); however, it is unclear how these components evolve as patients age and whether patients are also at risk for hypoventilation. A retrospective review of 144 diagnostic polysomnograms (PSG) in a tertiary care facility over 10 years was conducted. Descriptive data and exploratory correlation analyses were performed. Sleep disordered breathing was common (seen in 78% of patients) with an average apnea-hypopnea index (AHI) = 10. The relative amount of obstructive apnea was positively correlated with age and body mass index (BMI). The relative amount of central sleep apnea was associated with younger age in the very youngest group (0–3 years). Hypoventilation was common occurring in more than 22% of patients and there was a positive correlation between the maximum CO2 and BMI. Sleep disordered breathing, including hypoventilation, was common in patients with DS. The obstructive component increased significantly with age and BMI, while the central component occurred most in the very young age group. Due to the high risk of hypoventilation, which has not been previously highlighted, it may be helpful to consider therapies to target both apnea and hypoventilation in this population. Keywords: Down syndrome; hypoventilation; sleep apnea and sleep disordered breathing
1. Introduction Down syndrome (DS) is the most common genetic disorder [1] in humans and sleep disordered breathing is common among this population. A prior study estimated the obstructive sleep apnea (OSA) prevalence in this population to be 66% [2–5]. Patients with DS have multiple clinical characteristics that predispose them to OSA including midface hypoplasia, narrow nasopharynx, small pharynx, relative macroglossia and retroglossia, and increased body mass [6,7]. They also have features that can predispose them to central sleep apnea including hypotonia, central nervous system (CNS) impairment, and acid reflux. Additionally, these patients are at risk for hypoventilation, a risk which can be promoted by clinical features of DS including congenital heart disease, smaller lung volumes, hypotonia, and changes in respiratory control in the setting of elevated body mass index (BMI) [6,7]. Little is known about how sleep disordered breathing changes in DS as patients grow older and how changes in clinical features of the DS phenotype might impact sleep disordered breathing over time. Parameters that change as patients grow (e.g., maturity of the CNS, airway structure, weight,
Children 2017, 4, 55; doi:10.3390/children4070055
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Children 2017, 4, 55
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and muscle tone) and how they might result in changes in risk of sleep disordered breathing over time [8]. The risk for hypoventilation in DS and any changes in hypoventilation over time have also not previously been well characterized in this population and could have some important implications for treatment choices. We aimed to investigate how both obstructive apnea and central apnea change over time in patients with DS as well as to evaluate the risk for hypoventilation in these patients. We hypothesized that the risk for obstructive apnea would increase with age due to relative increase in BMI, but the risk for central apnea would decrease due to improved maturity of the respiratory control systems. We also hypothesized that patients would be at increased risk for hypoventilation at all ages due to cardiopulmonary conditions, residual inefficiency of respiratory control systems in the setting of elevated BMI, and hypotonia. Finally, we planned to explore correlations between sleep apnea, hypoventilation, and other indices from the polysomnograms (PSG) data to investigate how sleep related parameters might be different for patients with differing clinical characteristics and respiratory findings. 2. Results 2.1. Demographics and Descriptive Data A total of 168 diagnostic studies were identified that were performed in patients with DS over a 10-year span. Among these, 164 were diagnostic PSGs and 4 were split-night studies from which the diagnostic portion of the study was included. Twenty-four studies were excluded for the following reasons: a total sleep time less than 240 min or a technically inadequate study (e.g., lack of reliable breathing sensors). Demographics and basic polysomnographic characteristics of the 144 PSGs are summarized in Table 1. Among these 144 studies, 14 studies were done in DS patients of more than 18 years (20–45 years) of age. These older patients with DS had severe sleep disordered breathing with an average apnea-hypopnea index (AHI) of 46. Table 1. Demographics data and basic polysomnographic characteristics (n = 144).
Gender Age in years (median) BMI BMI z score Heart rate Respiratory rate CO2 (torr) O2 % TST (min) S Efficiency (%) SOL REM latency (min) N3 (%) REM (%) AHI Obstructive index Obstructive ratio Central Index Central apnea ratio RDI Average O2 Sat (%) Lowest Desats (%) Time < 88% (min) Mean CO2 Max CO2 PLMI Arousal index
Mean
SD
n*
Min
Max
0.6 7.6 (4.7) 21.3 1.7 99.6 24.7 42.2 96.0 425.5 84.6 20.0 159.0 29.6 15.0 9.8 8.6 0.7 0.7 0.1 9.7 95.2 82.7 14.3 43.6 49.8 2.3 8.7
n/a 8.5 8.1 2.1 19.4 10.8 6.5 2.8 71.9 9.8 25.0 94.6 12.3 9.1 16.0 15.5 0.3 1.6 0.2 17.5 2.2 9.2 28.5 9.0 5.5 6.7 5.6
144 144 144 104 124 137 105 122 144 144 144 117 144 144 144 144 144 139 138 39 143 138 142 20 96 144 137
n/a 0.1 11.3 −1.2 56.0 12.0 24.0 77.0 242.0 50.1 0.0 7.5 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 82.9 51.0 0.0 34.0 36.0 0.0 0.0
n/a 45.4 56.4 9.4 140.0 87.0 63.0 99.0 643.5 99.0 144.0 449.0 68.4 50.3 103.4 103.4 1.0 9.8 1.0 103.5 99.0 96.0 192.9 75.5 60.0 58.0 38.6
AHI: apnea/hypopnea index; BMI: body mass index; PLMI: periodic limb movement index; RDI: respiratory disturbance index; REM: rapid eye movement; REMOL: rapid eye movement sleep onset latency; SD: standard deviation; SOL: sleep onset latency; TST: total sleep time. * Total sample size was 144 and those fewer than 144 were resulted from missing data for the specific parameters.
Obstructive ratio 0.7 0.3 144 0.0 1.0 Central Index 0.7 1.6 139 0.0 9.8 Central apnea ratio 0.1 0.2 138 0.0 1.0 RDI 9.7 17.5 39 0.0 103.5 95.2 2.2 143 82.9 99.0 Average O2 Sat (%) Children 2017, 4, 55 3 of 8 Lowest Desats (%) 82.7 9.2 138 51.0 96.0 Time
Sleep Apnea and Hypoventilation in Patients with Down Syndrome: Analysis of 144 Polysomnogram Studies Zheng Fan 1, *, Mihye Ahn 2 , Heidi L. Roth 1 , Leping Li 3 and Bradley V. Vaughn 1 1 2 3
*
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] (H.L.R.); [email protected] (B.V.V.) Department of Mathematics and Statistics, University of Nevada, Reno, NV 89503, USA; [email protected] Biostatistics and Computational Biology, National Institute of Environmental Sciences, Research Triangle Park, NC 27709, USA; [email protected] Correspondence: [email protected]
Academic Editor: Sari A. Acra Received: 16 May 2017; Accepted: 27 June 2017; Published: 30 June 2017
Abstract: Patients with Down syndrome (DS) are at risk for both obstructive sleep apnea (OSA) and central sleep apnea (CSA); however, it is unclear how these components evolve as patients age and whether patients are also at risk for hypoventilation. A retrospective review of 144 diagnostic polysomnograms (PSG) in a tertiary care facility over 10 years was conducted. Descriptive data and exploratory correlation analyses were performed. Sleep disordered breathing was common (seen in 78% of patients) with an average apnea-hypopnea index (AHI) = 10. The relative amount of obstructive apnea was positively correlated with age and body mass index (BMI). The relative amount of central sleep apnea was associated with younger age in the very youngest group (0–3 years). Hypoventilation was common occurring in more than 22% of patients and there was a positive correlation between the maximum CO2 and BMI. Sleep disordered breathing, including hypoventilation, was common in patients with DS. The obstructive component increased significantly with age and BMI, while the central component occurred most in the very young age group. Due to the high risk of hypoventilation, which has not been previously highlighted, it may be helpful to consider therapies to target both apnea and hypoventilation in this population. Keywords: Down syndrome; hypoventilation; sleep apnea and sleep disordered breathing
1. Introduction Down syndrome (DS) is the most common genetic disorder [1] in humans and sleep disordered breathing is common among this population. A prior study estimated the obstructive sleep apnea (OSA) prevalence in this population to be 66% [2–5]. Patients with DS have multiple clinical characteristics that predispose them to OSA including midface hypoplasia, narrow nasopharynx, small pharynx, relative macroglossia and retroglossia, and increased body mass [6,7]. They also have features that can predispose them to central sleep apnea including hypotonia, central nervous system (CNS) impairment, and acid reflux. Additionally, these patients are at risk for hypoventilation, a risk which can be promoted by clinical features of DS including congenital heart disease, smaller lung volumes, hypotonia, and changes in respiratory control in the setting of elevated body mass index (BMI) [6,7]. Little is known about how sleep disordered breathing changes in DS as patients grow older and how changes in clinical features of the DS phenotype might impact sleep disordered breathing over time. Parameters that change as patients grow (e.g., maturity of the CNS, airway structure, weight,
Children 2017, 4, 55; doi:10.3390/children4070055
www.mdpi.com/journal/children
Children 2017, 4, 55
2 of 8
and muscle tone) and how they might result in changes in risk of sleep disordered breathing over time [8]. The risk for hypoventilation in DS and any changes in hypoventilation over time have also not previously been well characterized in this population and could have some important implications for treatment choices. We aimed to investigate how both obstructive apnea and central apnea change over time in patients with DS as well as to evaluate the risk for hypoventilation in these patients. We hypothesized that the risk for obstructive apnea would increase with age due to relative increase in BMI, but the risk for central apnea would decrease due to improved maturity of the respiratory control systems. We also hypothesized that patients would be at increased risk for hypoventilation at all ages due to cardiopulmonary conditions, residual inefficiency of respiratory control systems in the setting of elevated BMI, and hypotonia. Finally, we planned to explore correlations between sleep apnea, hypoventilation, and other indices from the polysomnograms (PSG) data to investigate how sleep related parameters might be different for patients with differing clinical characteristics and respiratory findings. 2. Results 2.1. Demographics and Descriptive Data A total of 168 diagnostic studies were identified that were performed in patients with DS over a 10-year span. Among these, 164 were diagnostic PSGs and 4 were split-night studies from which the diagnostic portion of the study was included. Twenty-four studies were excluded for the following reasons: a total sleep time less than 240 min or a technically inadequate study (e.g., lack of reliable breathing sensors). Demographics and basic polysomnographic characteristics of the 144 PSGs are summarized in Table 1. Among these 144 studies, 14 studies were done in DS patients of more than 18 years (20–45 years) of age. These older patients with DS had severe sleep disordered breathing with an average apnea-hypopnea index (AHI) of 46. Table 1. Demographics data and basic polysomnographic characteristics (n = 144).
Gender Age in years (median) BMI BMI z score Heart rate Respiratory rate CO2 (torr) O2 % TST (min) S Efficiency (%) SOL REM latency (min) N3 (%) REM (%) AHI Obstructive index Obstructive ratio Central Index Central apnea ratio RDI Average O2 Sat (%) Lowest Desats (%) Time < 88% (min) Mean CO2 Max CO2 PLMI Arousal index
Mean
SD
n*
Min
Max
0.6 7.6 (4.7) 21.3 1.7 99.6 24.7 42.2 96.0 425.5 84.6 20.0 159.0 29.6 15.0 9.8 8.6 0.7 0.7 0.1 9.7 95.2 82.7 14.3 43.6 49.8 2.3 8.7
n/a 8.5 8.1 2.1 19.4 10.8 6.5 2.8 71.9 9.8 25.0 94.6 12.3 9.1 16.0 15.5 0.3 1.6 0.2 17.5 2.2 9.2 28.5 9.0 5.5 6.7 5.6
144 144 144 104 124 137 105 122 144 144 144 117 144 144 144 144 144 139 138 39 143 138 142 20 96 144 137
n/a 0.1 11.3 −1.2 56.0 12.0 24.0 77.0 242.0 50.1 0.0 7.5 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 82.9 51.0 0.0 34.0 36.0 0.0 0.0
n/a 45.4 56.4 9.4 140.0 87.0 63.0 99.0 643.5 99.0 144.0 449.0 68.4 50.3 103.4 103.4 1.0 9.8 1.0 103.5 99.0 96.0 192.9 75.5 60.0 58.0 38.6
AHI: apnea/hypopnea index; BMI: body mass index; PLMI: periodic limb movement index; RDI: respiratory disturbance index; REM: rapid eye movement; REMOL: rapid eye movement sleep onset latency; SD: standard deviation; SOL: sleep onset latency; TST: total sleep time. * Total sample size was 144 and those fewer than 144 were resulted from missing data for the specific parameters.
Obstructive ratio 0.7 0.3 144 0.0 1.0 Central Index 0.7 1.6 139 0.0 9.8 Central apnea ratio 0.1 0.2 138 0.0 1.0 RDI 9.7 17.5 39 0.0 103.5 95.2 2.2 143 82.9 99.0 Average O2 Sat (%) Children 2017, 4, 55 3 of 8 Lowest Desats (%) 82.7 9.2 138 51.0 96.0 Time
