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Sleep Medicine 12 (2011) 483–488
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Sleep Medicine
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Original Article
Increased sympathetic activity in children with obstructive sleep apnea:Cardiovascular implications
Denise M. O’Driscoll a,⇑, Rosemary S.C. Horne a, Margot J. Davey b, Sarah A. Hope c, Vicki Anderson d,e,John Trinder e, Adrian M. Walker a, Gillian M. Nixon a,b
a The Ritchie Centre, Monash Institute of Medical Research, Monash University, Victoria, Australiab Melbourne Children’s Sleep Unit, Department of Sleep and Respiratory Medicine, Monash Medical Centre, Victoria, Australiac Monash Cardiovascular Research Centre, Monash Heart Southern Health and Department of Medicine, Southern Clinical School, Monash University, Victoria, Australiad Critical Care and Neurosciences, Murdoch Children’s Research Institute, Victoria, Australiae Psychological Sciences, University of Melbourne, Victoria, Australia
a r t i c l e i n f o
Article history:Received 12 July 2010Received in revised form 6 September 2010Accepted 13 September 2010
Keywords:Urinary catecholaminesObstructive sleep apneaSympatheticPediatricPolysomnographyBlood pressure
1389-9457/$ - see front matter � 2011 Elsevier B.V. Adoi:10.1016/j.sleep.2010.09.015
⇑ Corresponding author. Address: The Ritchie CentCentre, 246 Clayton Rd., Clayton Victoria 3168, Austrafax: +61 (0)3 9594 6811.
E-mail addresses: [email protected],sh.edu.au (D.M. O’Driscoll).
a b s t r a c t
Background: Obstructive sleep apnea (OSA) is associated with increased sympathetic activity and hyper-tension in adults. We tested the hypothesis that children with OSA also have increased sympathetic activ-ity as measured by overnight urinary catecholamines, and that this increase is related to the severity ofOSA and to blood pressure (BP).Methods: Seventy snoring children referred for assessment of sleep disordered breathing and 26 healthynon-snoring control children (age range: 3–12 years, 59M/37F) were studied. Overnight polysomnogra-phy was performed coincident with a 12 h overnight urine collection. Urinary catecholamine levels weredetermined using high performance liquid chromatography (noradrenaline, adrenaline and dopamine,with levels adjusted for creatinine excretion). Simple linear and stepwise multiple linear regressionswere used to determine the independent associations between catecholamine levels and age, gender,BMI z-score, systolic BP z-score, diastolic BP z-score, and apnea hypopnea index (AHI).Results: Simple linear regressions revealed significant associations between noradrenaline and AHI(r = 0.32) and age (r = �0.20, p < 0.05 for both). Significant associations were also found between adren-aline and AHI (r = 0.27) and age (r = �0.25, p < 0.05 for both). Systolic BP z-score and diastolic z-scorewere both significantly associated with adrenaline (r = 0.22 and r = 0.20 respectively, p < 0.05 for both).Multivariate analysis revealed that only AHI was a significant independent predictor of noradrenaline(model R2 = 0.10, p = 0.001). Similarly, only AHI and age were significant independent predictors of adren-aline (model R2 = 0.12, p < 0.05).Conclusions: This study demonstrates that levels of overnight urinary noradrenaline and adrenaline arerelated to the severity of OSA in children. These data indicate that children with OSA have increased sym-pathetic tone that may contribute to the cardiovascular consequences of the condition.
� 2011 Elsevier B.V. All rights reserved.
1. Introduction
Obstructive sleep apnea (OSA) in adults is associated with in-creased sympathetic activity and cardiovascular morbidities suchas hypertension, ischemic heart disease and stroke [1]. The mech-anisms responsible for these cardiovascular complications in OSAinclude frequent arousal from sleep and intermittent hypoxiaand hypercapnia, which can each elicit sustained activation of
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the sympathetic nervous system [2,3]. There are now increasing re-ports that pediatric OSA is also associated with cardiovascularchanges that could lead to cardiovascular disease over time,including acute increases in heart rate (HR) and blood pressure(BP) during sleep [4,5], as well as increased diurnal and nocturnalBP [6–9]. Furthermore, there are reports of left ventricular hyper-trophy [10] and decreased diastolic [11] and systolic function[12] associated with pediatric OSA.
Isolated reports on children with OSA have indicated abnormalautonomic control in this group. Children with OSA have beenshown to have increased HR variability during sleep [13,14], whichreduces after treatment with adenotonsillectomy [15]. Further-more, sympathetic vascular reactivity, measured using pulse arterialtonometry, has been shown to be increased during wakefulness in
484 D.M. O’Driscoll et al. / Sleep Medicine 12 (2011) 483–488
children with OSA [16]. These modifications in autonomic functionmay alter BP via persistent increases in systemic vascular resistance.
Recently there have also been reports of increased morning uri-nary [17,18] and serum [19] catecholamines in children with OSA.However, these reports have not included a healthy non-snoringcontrol group confirmed by polysomnography (PSG). In this studywe hypothesized that, similar to adults, children with OSA have in-creased sympathetic activity as measured by overnight urinary cat-echolamines, and that this increase is related to the severity of OSAand elevated BP.
2. Methods
The Monash University and Southern Health Human ResearchEthics Committees granted ethical approval for this project. Writ-ten informed consent was obtained from parents and verbal assentfrom the children prior to commencement of the study.
2.1. Subjects
Seventy children (45M/25F) referred for investigation of sleepdisordered breathing (SDB) and 26 (14M/12F) healthy non-snoringcontrols took part in this study. Control children were recruitedfrom the general population as part of a larger study and had nohistory of SDB as determined by parental questionnaire and med-ical history, and this was confirmed on PSG. All children were agedbetween 3 and 12 years. No child had been born prematurely(<37 weeks gestation). All children were otherwise healthy andnone were taking medication.
2.2. Protocol
All children had office BP measured with a sphygmomanometeron the upper arm using standard techniques [20]. To account forthe effects of age, gender and height, systolic and diastolic mea-surements were converted to a z-score according to published cri-teria [20]. Height and weight were recorded, and body mass index(BMI) calculated. As with BP, BMI was converted to a z-scoreaccording to published criteria [21].
2.2.1. PolysomnographyAll children underwent routine overnight PSG using a commer-
cially available PSG system (E Series Sleep System, Compumedics,Melbourne, Australia). Electroencephalograms (EEG: C4/A1, O2/A1), electrooculograms (EOG: left and right outer canthus), an elec-tromyogram (EMG: submentalis muscle), electrocardiogram (ECG),left and right leg EMG and body position were recorded. Oxygensaturation (SaO2) was measured by pulse oximetry (Biox 3700e,Ohmeda, Boulder, CO, USA) and thoracic and abdominal breathingmovements recorded via uncalibrated respiratory inductanceplethysmography (z-RIP belts, Pro-Tech Services Inc., Mukilteo,WA, USA). Both end tidal and transcutaneous carbon dioxide (Pet-CO2: Capnocheck Plus, BCI Inc., Waukesha, WI, USA; TCO2: TCM3,Radiometer, Copenhagen, Denmark) were recorded, and airflowwas measured via nasal pressure and oronasal thermistor (Compu-medics, Melbourne, Australia).
2.2.2. Polysomnographic analysisSleep was scored in 30 s epochs according to standard criteria
[22]. Arousals were scored as either subcortical activations (see be-low) or as defined by ASDA criteria [23]. Subcortical activationswere scored when P2 of the following events occurred and metcriteria described by Mograss et al. [24]: an increase in EMG, an in-crease in HR or a body movement (i.e., autonomic arousals notmeeting ASDA criteria). Respiratory events were scored when P2
respiratory cycles in duration [25]. Obstructive apneas, mixedapneas and hypopneas were defined according to standard criteria:obstructive apnea was defined as the cessation of air flow in thepresence of respiratory effort; hypopnea was defined as a P50%decrease in the amplitude of the airflow signal with paradoxicalchest and abdominal movements and an associated arousal and/or fall of P3% in oxygen saturation [26]. Central apnea was definedas the cessation of air flow in the absence of respiratory effort,associated with an arousal and/or fall of P3% in oxygen saturation.
An obstructive apnea hypopnea index (OAHI) was calculated,defined as the total number of obstructive apneas, mixed apneas,and hypopneas per hour of total sleep time. Diagnostic criteriafor the classification of OSA severity followed current clinical prac-tice: children were categorized as having primary snoring (PS, OA-HI 6 1 event/h); mild OSA (OAHI between >1 and 5 events/h); ormoderate/severe OSA (OAHI > 5 events/h). Control children allhad an OAHI < 1 event/h and no snoring was reported. The total ap-nea hypopnea index (AHI) was calculated, defined as the totalnumber of all apneas (obstructive, mixed and central) and hypop-neas per hour of sleep.
2.2.3. Urine collection and analysisTwelve hour overnight urine collection was performed in all
children (approximately 7 pm–7am). Children were asked to voidupon arrival to the sleep laboratory and all urine passed thereafterwas collected until morning, including the first morning void. Ur-ine was acidified with sulfamic acid to a pH between 2 and 3,and stored at 4 �C until analysis. Urinary catecholamine levels weredetermined using high performance liquid chromatography (HPLC)with electrochemical detection [27]. Noradrenaline, adrenaline anddopamine levels were measured, and divided by the urine concen-tration of creatinine.
In a subset of children who wore nappies (n = 8), a representa-tive overnight spot sample of urine was collected by extracting ur-ine from a cotton pad insert placed within the nappy. Total urinaryoutput over 12 h was calculated by subtracting the final weight ofthe used nappy and insert from the weight before the study. In themorning, urine was squeezed from the cotton pad insert using ahydraulic press applying a maximum pressure of 4 tonnes. If thechild passed urine in the nappy and a bottle, the spot sample sentfor analysis was comprised of equal proportions of the output fromboth. This method of collecting urine from nappies has previouslybeen used to perform a wide range of biochemistry tests in urinefrom children [28–31].
2.3. Statistical analysis
Statistical analysis was performed using Sigma Plot, Version 11(Systat Software Inc). Demographics, PSG variables and catechola-mines were compared between groups using one way ANOVA orone way ANOVA on ranks with Dunn’s posthoc testing where datafailed normality testing. Simple linear regressions were performedbetween each catecholamine (corrected for creatinine excretion)and age, gender, BMI z-score, OAHI, AHI, oxygen saturation nadir,4% oxygen desaturation index (ODI), total arousal index and respi-ratory arousal index. Simple linear regressions were also per-formed between systolic and diastolic blood pressure z-scoresand each catecholamine. Forward stepwise multiple linear regres-sions were used to assess the associations between each catechol-amine (corrected for creatinine excretion) and age, gender, BMIz-score, AHI, and oxygen saturation nadir. The total AHI was usedas both obstructive and central apneas are associated with hemo-dynamic changes that may impact levels of sympathetic activity[4,5]. Oxygen desaturation index and arousal indices were not in-cluded due to high collinearity with AHI. Data are presented asmean ± SEM with statistical significance taken at the p < 0.05 level.
D.M. O’Driscoll et al. / Sleep Medicine 12 (2011) 483–488 485
3. Results
Demographic and polysomnographic data of the 96 childrenstudied are presented according to severity of SDB in Table 1. Ofthe 70 children referred for investigation of SDB, 33 were diag-nosed with primary snoring, 20 with mild OSA and 17 with mod-erate/severe OSA. There were no significant differences betweengroups for age, BMI or office BP. As expected, subjects with OSAhad a significantly increased OAHI compared to controls and sub-jects with PS (p < 0.001). Furthermore, the OSA groups (both mildand mod/sev OSA) had significantly increased central apnea indices(CAIs) compared to controls and subjects with PS. Subjects withmoderate/severe OSA also had significantly increased rates of 4%oxygen desaturations/h and arousals/h (p < 0.001 for both).
3.0.1. Urinary catecholamines
The mean overnight urine output was 237 ± 13 ml. Althoughthere were trends for urinary catecholamines to increase with de-gree of SDB, these did not reach statistical significance (Fig. 1, Nor-adrenaline ANOVA p = 0.15, Adrenaline ANOVA p = 0.14, DopamineANOVA p = 0.07). However, all catecholamines were significantlyincreased in the OSA group (mild and mod/sev OSA combined)compared with the non-snoring controls.
Results of simple linear regressions are presented in Table 2.Simple linear regressions revealed significant associations betweennoradrenaline and AHI (Fig. 2A), OAHI, age, 4% ODI and respiratoryarousal index. Significant associations were also found betweenadrenaline and AHI (Fig. 2B), OAHI, age, 4% ODI, total arousal indexand respiratory arousal index. Furthermore, systolic BP z-score anddiastolic z-score were both significantly associated with adrenalinelevels (Systolic: r = 0.22, p = 0.029, Fig. 2C. Diastolic: r = 0.20,p = 0.046, Fig. 2D). Dopamine was only significantly associatedwith age. No catecholamine was associated with oxygen saturationnadir, BMI z-score or gender. To avoid the effect of multiple sub-jects having an OAHI of 0, we also performed the regression anal-yses only on children with OSA (i.e., mild and moderate/severe OSAgroups) and similar results were obtained (Noradrenaline: OAHIr = 0.36, age r = �0.21; Adrenaline: OAHI r = 0.31, age r = �0.11,
Table 1Subject demographics and polysomnographic characteristics.
Controls PS
n (males) 26 (14) 33 (20)Age (years) 6.9 ± 0.5 5.2 ± 0.4BMI (kg/m2) 17.4 ± 0.5 17.4 ± 0.5BMI z-score 0.5 ± 0.2 0.8 ± 0.2
Office BPSystolic (mmHg) 98 ± 2 97 ± 1z-score 0.0 ± 0.2 0.1 ± 0.1Diastolic (mmHg) 56 ± 1 55 ± 1z-score �0.1 ± 0.1 0.1 ± 0.1OAHI (events/h) 0.1 ± 0.0a,b 0.3 ± 0.1a,b
CAI (events/h) 0.9 ± 0.1a 1.2 ± 0.2a
AHI (events/h) 1.0 ± 0.1a,b 1.5 ± 0.2a,b
4% ODI (events/h) 0.3 ± 0.1a 0.4 ± 0.1a
Arousal index (events/h) 13.7 ± 0.7a 10.9 ± 0.5a
Noradrenaline (umol/molCR) 24.7 ± 1.3 25.3 ± 2.024.7 ± 1.3
Adrenaline (umol/molCR) 2.2 ± 0.3 3.5 ± 0.62.2 ± 0.3
Dopamine (umol/molCR) 293.3 ± 26.3 335.1 ± 22.9293.3 ± 26.3
PS: primary snorers, OSA: obstructive sleep apnea, BMI: body mass index, BP: blood presapnea hypopnea index, ODI: oxygen desaturation index.
a Compared with Mod/Sev OSA.b Compared with Mild OSA.
systolic BP z-score r = 0.23, diastolic BP z-score r = 0.05; Dopamine:age r = �0.42).
Results from the forward stepwise multiple linear regressionsare presented in Table 3. Multivariate analysis revealed that onlyAHI (p = 0.001) was a significant independent predictor of nor-adrenaline. Similarly, only AHI (p = 0.021) and age (p = 0.028) weresignificant independent predictors of adrenaline, and only age(p < 0.001) significantly predicted dopamine.
4. Discussion
This study has demonstrated that levels of overnight urinarynoradrenaline and adrenaline are independently related to theAHI in children. Furthermore, overnight urinary adrenaline is re-lated to both systolic and diastolic BP z-scores in children.
As urine collection in our study was performed on one night,our data indicate that the catecholamine levels are related to AHImeasured on the study night. In an assessment of night-to-nightvariability of PSG measures in children, Katz et al. [32] showed thatthe clinical diagnosis of OSA or primary snoring remained the samein all children undergoing two PSG studies, supporting the viewthat a single PSG is sufficient for the diagnosis of OSA. Therefore,from our data, we can infer that children with OSA will be exposedto nightly elevations in catecholamines, suggesting a relationshipbetween OSA and elevated catecholamines. Overall our findingsindicate that pediatric OSA is associated with increased sympa-thetic nervous activity that may contribute to the cardiovascularconsequences of the condition, namely hypertension.
Several studies have reported that urinary catecholamines areincreased in adults with OSA [33–35], and these elevations areindependent of obesity [36]. Some [33,35] but not all [34] of thesestudies have also shown that catecholamine levels significantly re-duce with the abolition of OSA with continuous positive airwaypressure (CPAP) treatment. Importantly, this reduced sympatheticactivity with treatment of OSA has been shown to mirror a reduc-tion in BP and arterial stiffness [33]. Circulating catecholamines arederived from the sympathetic nerves and adrenal medullae and aretherefore an indirect measure of sympathetic activity. Whilst uri-nary catecholamines as a measure of whole body sympathetic
Mild OSA Mod/Sev OSA ANOVA P
20 (15) 17 (10) n.s.5.4 ± 0.3 5.2 ± 0.6 n.s.
17.6 ± 0.7 18.0 ± 0.8 n.s.0.6 ± 0.5 0.9 ± 0.3 n.s.
98 ± 2 100 ± 2 n.s.0.2 ± 0.1 0.4 ± 0.1 n.s.58 ± 2 57 ± 3 n.s.0.3 ± 0.2 0.3 ± 0.2 n.s.2.8 ± 0.2 16.9 ± 3.1 <0.0011.9 ± 0.4 3.3 ± 0.6 <0.054.2 ± 0.3 20.2 ± 3.3 <0.0011.0 ± 0.2 5.8 ± 2.2 <0.001
13.7 ± 0.8a 28.9 ± 2.5 <0.00128.3 ± 2.3 30.2 ± 2.6 n.s.
29.2 ± 1.7 <0.054.1 ± 0.8 3.9 ± 0.8 n.s.
4.0 ± 0.6 <0.05345.7 ± 19.6 403.1 ± 46.2 n.s.
372.1 ± 23.8 <0.05
sure, OAHI: obstructive apnea hypopnea index, CAI: central apnea index, AHI: total
Nor
adre
nalin
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20
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02468
10121416
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Controls
A
B
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Mod/Sev OSA Mild OSAPS
Controls Mod/Sev OSA Mild OSAPS
Controls Mod/Sev OSA Mild OSAPS
Fig. 1. Boxplots of (A) urinary noradrenaline (corrected for creatinine), (B) urinaryadrenaline and (C) urinary dopamine in controls, primary snorers (PS), childrenwith mild OSA and children with moderate/severe OSA. The boundary of the boxclosest to zero indicates the 25th percentile, the line within the box marks themedian, and the boundary of the box farthest from zero indicates the 75thpercentile. Whiskers above and below the box indicate the 90th and 10thpercentiles.
Table 2Univariate linear regression results for urinary catecholamines corrected for creat-inine excretion (n = 96).
Noradrenaline Adrenaline Dopamine
b p b p b p
Age (years) �0.20 0.048 �0.25 0.012 �0.49 <0.001Gender 0.18 n.s. 0.04 n.s. 0.04 n.s.BMI z-score 0.05 n.s. �0.02 n.s. 0.02 n.s.SpO2 nadir (%) �0.09 n.s. �0.10 n.s. �0.14 n.s.OAHI (events/h) 0.31 0.002 0.27 0.008 0.16 n.s.AHI (events/h) 0.32 0.001 0.27 0.009 0.18 n.s.4% ODI (events/h) 0.24 0.018 0.26 0.010 0.02 n.s.Total arousal index
(events/h)0.20 n.s. 0.22 0.032 0.20 n.s.
Respiratory arousalindex (events/h)
0.31 0.002 0.28 0.006 0.19 n.s.
BMI: body mass index, OAHI: obstructive apnea hypopnea index, AHI: total apneahypopnea index, ODI: oxygen desaturation index, n.s.: not significant.
486 D.M. O’Driscoll et al. / Sleep Medicine 12 (2011) 483–488
activity have limitations to the extent that they also reflect cate-cholamine reuptake and renal clearance [37], they remain an effec-tive means of non-invasively comparing sympathetic activitybetween groups.
The pathophysiological mechanisms by which catecholaminesare elevated in OSA are most likely multiple. Obstructive apneacauses intermittent hypercapnia and hypoxia stimulating both thecentral and peripheral chemoreceptors, increasing sympathetic out-flow [3]. In addition, termination of apnea is coincident with arousalfrom sleep, which in itself is known to elicit sympathetic activationwith acute increases in both BP and HR [38]. Whilst any or all ofthese could contribute to increased sympathetic activity associatedwith OSA, a key mechanism is intermittent hypoxia which has beenshown to independently increase sympathetic activity, which thenremains elevated after the stimulus has been removed [39]. As theincrease in sympathetic activity associated with intermittenthypoxia is long-lasting, this may explain the elevated levels of day-time sympathetic activity in adults with OSA [2]. It is this increase insympathetic activity that has been postulated as a mechanism forsystemic hypertension in this group by peripheral vascular remod-
elling and increased vascular tone, as evidenced by impaired endo-thelium-dependent peripheral vasodilation [40]. As the measure ofintermittent hypoxia (i.e., ODI) is highly collinear with AHI, in thepresent study only AHI is represented in our multivariate regressionmodel. However, in our univariate analysis, 4% ODI was significantlyassociated with both noradrenaline and adrenaline levels.
When patient data from our study were categorized accordingto severity of disease, there was a trend for catecholamines to in-crease from non-snoring controls through primary snorers and pa-tients with mild and moderate/severe OSA, though these datafailed to reach significance. The relationship between OSA and cat-echolamines is better represented in our regression analyses wherewe have shown that, when age is controlled for, both noradrena-line and adrenaline levels are independently influenced by AHI.
Our data support and extend two previous studies investigatingurinary catecholamines in children with SDB. Kaditis et al. [17]showed in 54 children that both noradrenaline and adrenaline cor-related significantly with OAHI using regression analyses. Further-more, Snow et al. [18] showed that adrenaline and noradrenalinewere increased in children with OSA compared to those withoutOSA in a referred population, independently of obesity. SupportingSnow et al. [18], we did not find any association between catechol-amine levels and BMI z-score in our data. However, neither of theseprevious studies included a group of non-snoring control childrenwithout SDB as confirmed by polysomnography, nor did they ana-lyse overnight urinary excretion (rather examining only urine fromthe first morning void). Whilst Kaditis et al. [17] did collect urinefrom a control group, these subjects were not confirmed as con-trols by polysomnography and urine was collected in the homeenvironment. These subjects therefore endured markedly differentexperimental conditions to the referred SDB group to which theywere compared, who experienced overnight hospitalization, whichin itself increases stress [41] and is likely to impact on catechol-amine levels. Our study extends these reports and is the first tocompare polysomnographic with 12 h overnight urinary catechol-amine data from non-snoring controls, primary snorers and chil-dren with both mild and moderate/severe OSA. Indeed, theinclusion of data from healthy control subjects is an important as-pect of our study as this population is unreferred and representstypical overnight catecholamine levels in children who, like the re-ferred group, are in the unfamiliar environment of a hospital.
In our cohort of non-snoring controls and children referred forinvestigation of SDB, we have shown for the first time an associa-tion between adrenaline levels and BP. Recently, it has also beenshown that BP is correlated with urinary catecholamines in adultswith OSA [36]. Simple linear regressions in our study revealed sig-nificant associations between adrenaline levels and both systolic
A
B
C
D
Fig. 2. Scatterplots of (A) urinary noradrenaline (corrected for creatinine) versusapnea hypopnea index (AHI), (B) urinary adrenaline versus AHI, (C) systolic bloodpressure z-score versus urinary adrenaline and (D) diastolic blood pressure z-scoreversus urinary adrenaline. N = 96. All linear regression lines are significant(p < 0.05).
Table 3Forward stepwise multiple linear regression results for urinary catecholaminescorrected for creatinine excretion (n = 96).
Noradrenaline Adrenaline Dopamine
b p b p b p
AHI (events/h) 0.32 0.001 0.23 0.021 – –Age (years) – – �0.22 0.028 �0.49 <0.001Gender – – – – – –BMI z-score – – – – – –SpO2 nadir (%) – – – – – –
Model R2 0.10 0.001 0.12 0.003 0.24 <0.001
AHI: total apnea hypopnea index, BMI: body mass index.
D.M. O’Driscoll et al. / Sleep Medicine 12 (2011) 483–488 487
and diastolic BP z-scores. These findings support the notion that in-creased sympathetic activity may contribute to the pathogenesis ofsystemic hypertension and lead to cardiovascular morbidity in thisgroup. Indeed, recent large population based studies have shownthat BP is strongly related to OSA in childhood in a severity depen-
dent manner [8,9]. Importantly, this increase in BP has been shownto predict cardiac remodelling of the left ventricle [10]. Further-more, our group has recently demonstrated that children experi-ence acute changes in BP and HR that are large and similar inmagnitude to those seen in adults with OSA [4,5]. These repetitiveacute surges in cardiovascular activity may precipitate endothelialdysfunction and contribute to the development of hypertension.
In conclusion, this study demonstrates that OSA in children isassociated with sympathetic activation as reflected by increasedovernight urinary noradrenaline and adrenaline. Sympathoadrenalhyperactivity in children with OSA may reflect early autonomicchanges before overt cardiovascular disease, namely systemichypertension, and highlights the need for early identification andtreatment in this group.
Conflict of Interest
The ICMJE Uniform Disclosure Form for Potential Conflicts ofInterest associated with this article can be viewed by clicking onthe following link: doi:10.1016/j.sleep.2010.09.015.
Acknowledgments
The authors would like to thank all the children and their par-ents who participated in this study and all the staff of the Mel-bourne Children’s Sleep Unit for invaluable technical assistance.
Dr. O’Driscoll is the recipient of a Thoracic Society of Australiaand New Zealand/Allen and Hanburys Respiratory Research Fel-lowship. This project was supported by a Windermere FoundationSpecial Grant (SG130-08) and NHMRC Project Grants (384142 and491001).
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