reduced exercise capacity in greek children with mild to moderate obstructive sleep apnea syndrome

Pediatric Pulmonology 48:1237–1245 (2013)

Reduced Exercise Capacity in Greek Children With Mildto Moderate Obstructive Sleep Apnea Syndrome

Labrini Damianidou,1* Maria Eboriadou, MD,2 Andreas Giannopoulos, MD,1

Katerina Haidopoulou, MD,2 Konstantinos Markou, MD,3 Irini Tzimou,1 Fotis Kirvasilis, MD,4

Kalliopi Kontouli,4 Ioannis Tsanakas, MD,4 and Fani Athanassiadou, MD1

Summary. Introduction: Obstructive sleep apnea syndrome (OSAS) is a common disease that

is increasingly recognized among pediatric population. The exercise capacity of adults with

OSAS has been demonstrated to be impaired, but there are no data about pediatric exercise

response. Aim: The aim of this study was to evaluate cardiopulmonary response to exercise

in children with OSAS and to correlate exercise capacity and severity of OSAS. Methods:

Twenty-seven children with habitual snoring (Group A) (mean age 10.5 � 1.8 years) referred

for overnight polysomnography and 13 apparently healthy controls (mean age 11 � 1.5 years)

were recruited. According to the apnea hypopnea index (AHI) group A consisted of 15 (55.6%)

children with mild OSAS and 12 (44.4%) with moderate–severe OSAS. All children completed

a maximal ramping cardiopulmonary exercise test (CPET) on cycle ergometer. Results: Accord-

ing to CPET children with OSAS had significantly lower VO2max (40.3 � 8.4 ml/kg/min vs.

47.6 � 7.9 ml/kg/min, P ¼ 0.013) significantly lower VO2max (%) (77.7 � 15 vs. 92.9 � 10.5,

P ¼ 0.002), lower maximum heart-rate at peak exercise (86.6 � 8.8 beat/min vs. 90.6 �7.2 beat/min) and higher systolic blood pressure level at peak exercise (145 � 27.4 mmHg vs.

143.92 � 20 mmHg) compared to control group. Conclusion: The present study demonstrates

that young patients with OSAS, even with mild OSAS, had reduced exercise capacity as com-

pared to control group. Pediatr Pulmonol. 2013; 48:1237–1245. � 2012 Wiley Periodicals, Inc.

Key words: aerobic capacity; exercise; children; maximal oxygen consumption; snoring.

Funding source: none reported.

INTRODUCTION

Obstructive sleep apnea syndrome (OSAS) is a con-dition that is increasingly recognized and the prevalenceamong pediatric population has been reported to be1–4%.1–3 This condition is characterized by repeatedepisodes of upper airway occlusion during sleep,despite increased respiratory effort.4,5 Episodes of upperairway obstruction often are associated with arousals,sleep fragmentation, intermittent hypoxia, and hyper-capnia. Therefore, OSAS can have serious neurobeha-vioral and cardiorespiratory consequences, includingexcessive daytime sleepiness, fatigue, school failure,behavioral problems, cor pulmonale, or even death.6,7

Daytime sleepiness and fatigue are the hallmarks ofadults’ OSAS, however in children are less frequentdue to different pathophysiology. The extent and severi-ty of these symptoms are many times underestimated inchildren, due to either inability to clearly express theirsymptoms on their own or due to their parent’s subjec-tivity when they describe the extend of the symptoms.8–11

Similar to adult OSAS, pediatric OSAS has beennow associated with a higher risk for cardiovascular

12nd Pediatric Department, School of Medicine, Aristotle University of

Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.

24th Pediatric Department, School of Medicine, Aristotle University of

Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece.

31st Department of Otorhinolaryngology Head and Neck Surgery, School

of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, The-

ssaloniki, Greece.

43rd Pediatric Department, School of Medicine, Aristotle University of

Thessaloniki, Ippokratio Hospital, Thessaloniki, Greece.

Conflict of interest: None.

*Correspondence to: Labrini Damianidou, 2nd Pediatric Department,

School of Medicine, Aristotle University, 27 Karditsis Street, Oraiokastro,

57013 Thessaloniki, Greece. E-mail: [email protected]

Received 16 May 2012; Accepted 26 July 2012.

DOI 10.1002/ppul.22730

Published online 28 November 2012 in Wiley Online Library

(wileyonlinelibrary.com).

� 2012 Wiley Periodicals, Inc.

morbidities, albeit with reduced severity of these mani-festations, most likely the corollary of the increasedcompensatory vascular capacitance in children. For ex-ample, increased prevalence of altered blood pressureregulation,12 systemic hypertension,13–15 and changesin left ventricular geometry16,17 have all now beenreported in children with OSAS, and appear to be dose-dependent.18 The mechanisms mediating cardiac andblood pressure changes are most likely associated withthe increases in sympathetic activity and reactivity thatprogressively develop in the context of OSAS19,20 andpersist during wakefulness.21,22 Chronic sympathetichyperactivity increases myocardial workload and pre-disposes individuals to increased cardiac ventricularseptal thickness, impaired left ventricular diastolic func-tion, endothelial dysfunction, and cardiac arryth-mias.17,16 Furthermore, the intermittent hypoxia duringsleep that occurs in children with OSAS may induceelevations of pulmonary artery pressures, at least duringsleep, and such events may lead to some degree of rightventricular dysfunction. However, the prevalence ofpulmonary hypertension in pediatric OSAS has notbeen systematically examined23,24 and such as, we stillhave not defined the main sleep-related determinants ofsuch potential occurrence.

Normally, cardiac output increases with exerciseto support the increasing metabolic demands of thetissues. In healthy subjects, it is a linear function ofoxygen uptake (VO2) and does not vary as a function ofeither sex or state of fitness. The increase in cardiacoutput is largely driven by vagal withdrawal and byincreases in either circulating or neurally produced cat-echolamine that elicits a greater ventricular contractileresponse and increments in venous return. Some authorshave suggested that REM sleep in OSAS can producecardiac stress as great as that produced by exercise.There is little information about the cardiovascularperformance during exercise, in adults OSAS patients,without other risk factors and there is a lack in litera-ture for pediatric OSAS patients.25 Interest in cardio-vascular responses in OSAS is both clinically relevantto discerning prediction of the morbidity from cardio-vascular disease and physiologically relevant to under-standing the adaptive changes that occur in response tohypoxia-reoxygenation episodes during sleep. There-fore, the main hypothesis of the current investigationwas that children with OSAS have decreased exercisecapacity associated with the severity of the disorder,

compared with normal counterparts of similar age,BMI, habitual physical activity patterns.

METHODS

Subjects

Thirty children (20 male, 7 female) with habitualsnoring (snoring for at least over four nights per week)or symptoms of sleep-disordered breathing (SDB) for atleast 6 months, who were referred to the sleep-disorderslaboratory of 2nd pediatric department of AHEPA uni-versity hospital in Thessaloniki between February 2009and September 2011, were eligible for participation.Children with SDB were referred to sleep-disorderslaboratory by the pediatric pulmonology outpatientdepartment of AHEPA university hospital, by theotorhinolaryngology—head and neck surgery depart-ment of AHEPA university hospital and by other com-munity hospitals. Additional, private pediatricians andear, nose, and throat surgeons also refer patients to thesame sleep-disorders laboratory, which is the only cen-ter in north Greece for pediatric sleep studies. Referralfor a sleep study was based solely on the presence ofhabitual snoring and on severity of SDB symptoms.Thirteen healthy children (10 males, three females)without snoring were also recruited as controls. Exclu-sion criteria were: (i) history of cardiovascular, renal,chronic pulmonary, neuromuscular, or genetic disordersand craniofacial anomalies, (ii) recent respiratoryinfection (�4 weeks), (iii) use of bronchodilators or an-tihypertensive medications, (iv) orthopedic or muscolos-keletal limitations, (v) history of regular participation(�3 days per week) in moderately vigorous physicalactivity. Each subject and their parents completed aSDB questionnaire assessing presence of nighttime anddaytime symptoms consistent with SDB and past medi-cal history. The study protocol was approved by theInstitutional Ethics Committee. Informed consent wasobtained from parents of participants.

Anthropometry and Physical Assessment

The weight and standing height of the subjects weremeasured with a calibrated scale and stadiometerby standard anthropometric methods26 and body massindex (BMI) was calculated as weight/height2 (kg/m2).Normal BMI was defined below 85th percentile,overweight 85th � BMI < 95th percentile and obeseBMI � 95th percentile). All children underwent a phys-ical examination and the sizes of the tonsils were grad-ed according to a standardized scale from 0 (absent) to4 (kissing tonsils) (Brodsky Scale). A tonsillar size of2þ or greater was defined as tonsillar hypertrophy.27

For evaluation of the presence of hypertrophy adenoids

ABBREVIATIONS:

AHI Apnea hypopnea index

CPET Cardiopulmonary exercise test

OSAS Obstructive sleep apnea syndrome

SDB Sleep-disordered breathing

1238 Damianidou et al.

Pediatric Pulmonology

and rhinal disorders subjects referred to Otorhinolaryn-gology department of AHEPA university hospital.Morning blood pressure (BP) was measured three times(DinamapPro 100, Critikon, Tampa, FL) using the rightarm. Prior to the measurement, the child was sittingquietly for 5 min, with her back supported and theright cubital fossa at the level of the heart.28 NormalBP was defined as systolic and diastolic blood pressuresthat were <90th percentile for age, height, sex, pro-hypertension as systolic and diastolic blood pressures�90th percentile kai < 95th percentile and hyperten-sion as systolic and diastolic blood pressures �95thpercentile.29

Sleep Study

An overnight polysomnography (PSG) was per-formed on each subject with habitual snoring or withsymptoms indicating SDB using PSG monitor (SmithsMedical Systems, Germany) to record the followingparameters: electroencephalogram from six leads (C3/A2, C4/A1, O1/A2, and O2/A1), bilateral electrooculo-gram, electromyogram of mentalis activity and anteriortibialis. Thoracic and abdominal wall motions wererecorded via belts (piezoelectric transducers). Electro-cardiogram and heart rate were continuously recordedfrom two anterior chest leads. Arterial oxyhemoglobinsaturation (SaO2) was monitoring by oximeter. Respira-tory airflow was detected by a nasal pressure transducerfor identification of hypopnea and an oronasal thermalsensor for identification of apnea. Snoring was assessedby a snoring microphone and placed near the throat andbody position was recorded by a body position sensor.30

Bedtime was determined by each child’s routine andpolysomnography was terminated upon final awaken-ing. Arousals and sleep stages were assessed using stan-dard criteria.31,32 Obstructive apnea was defined as thepresence of chest/abdominal wall motion in the absenceof airflow for at least two breaths in duration 38 ob-structive hypopnea was: (i) a reduction in the airflowsignal amplitude of at least 50% compared to baselineand (ii) associated with oxygen desaturation of hemo-globin equal to or greater than 3% or with an arousal.30

Apnea hypopnea index (AHI) was defined as the totalnumber of obstructive apneic and hypopneic episodesper hour of sleep. Oxygen saturation nadir and the per-centage of total sleep time where oxygen saturationwas below 90% were noted. Arousal was defined bystandard criteria.32 We defined OSA as AHI > 1.0 epi-sode per hour of sleep, mild OSAS as 1 � AHI �5,as moderate OSAS 5 < AHI � 10 and severe OSASAHI > 10.33 Subjects who had an AHI value <1 epi-sode per hour of sleep were grouped as primary snorers(PS).

Cardiopulmonary Exercise Testing

All subjects completed cycle ergometer test at thepediatric pulmonology laboratory of Ippokratio univer-sity hospital, in the morning hours. Spirometry wasperformed via pneumotachograph prior to exercise test,according to the guidelines of American Heart Associa-tion.34 Exercise tests were performed on an electroni-cally braked cycle ergometer with gas exchange andventilatory variables being analysed breath-by-breathusing a calibrated computer based exercise system(Ergoline 200P MH BD, Germany).34 Periodically,the overall output data system was validated againsta respiratory gas exchange simulator which allows arange of metabolic rates to be established between0.2 � 5.0 L/min, with a resulting accuracy of 2%.35

During cardiopulmonary exercise test (CPET) standard-ized protocol was used. This continuous graded proto-col uses stages at which the speed and grade areprogressively increased at 3 min intervals. Respiratorygas exchange measurements, including ventilation (VE),oxygen consumption (VO2) and carbon dioxide output(VCO2) were obtained during exercise using a computercontrolled breath-by-breath gas exchange system.The ventilatory threshold (VT) was determined by theV-slope method.36,37 Age and gender specific maximalpredicted values of remaining exercise parameters werecalculated according to American Thoracic Society.37

Electrocardiogram and heart-rate were monitored on astandard 12-lead tracing and SaO2 was monitored con-tinuously with a pulse oximeter. Blood pressure wasmeasured using standard cuff manometry at rest, everyminute during the exercise and throughout 8 min of re-covery. Prior to exercise the subjects were acclimatedto the cycle ergometer with a 2 min warm up period.Each test was terminated by subjects fatigue or maxi-mal exercise level. It was consider maximal if the sub-ject achieved two or three of the following test criteria:(1) heart rate reaching 80% of age predicted maximalheart rate, (2) respiratory exchange ratio (RER) >1.1,3. Plateau of oxygen consumption with increasingwork-load. Subjects fasted before exercise and abstain-ed from strenuous exercise for a week prior to exercise.All tests were performed in an air-conditioned laborato-ry room at 20–228C and 40% relative humidity airto minimize thermal stress. Exercise was monitoredby trained technicians and supervised by a licensedphysician.

Data Analysis

The subjects were divided originally into two groups.Group A consisted of children with OSAS (AHI � 1),Group C was the control group. According to AHI thegroup A was divided into mild OSAS (AHI ¼ 1–5) and

Reduced Exercise Intolerence in Children With Obstructive Sleep Apnea Syndrome 1239


moderate to severe OSAS (AHI > 5). Data analyseswere performed using the Statistical Package for theSocial Sciences, version 14.0 (SPSS Statistical Soft-ware, Chicago, IL). The demographic data and labora-tory results were expressed as median with interquartileranges (IQR).

Values of polysomnography indices were applied totest for normality. Chi-squared test was applied forcomparisons regarding categorical characteristics. Wil-coxon test was used when data distribution was not nor-mal. Independent t-tests were used to evaluate baselinedescriptive differences between groups. Mann–Whitneytest was used to evaluate qualitative variables amongthe groups. Relationships between variables weredetermined by Pearson’s correlation analysis. AP-value < 0.05 was used throughout to determine dif-ferences that were statistically significant.

RESULTS

Subjects Characteristics

A total of 30 children with habitual snoring or symp-toms indicating SDB were considered for participationin the study. Two subjects were excluded: the first hada history of cardiovascular disease and the secondhad severe sickle cell disease. Finally, 27 participants(20 boys, 7 girls) were recruited. In, addition, 13 chil-dren (10 boys, 3 girls) without any symptoms of SDBwere included in the study as control group. Group A(OSAS group) consisted of 27 children with AHI � 1and mean age 10.5 � 1.8 years. Group C included 13children with mean age 11 � 1.5 years. There were nostatistical differences regarding age, male to femaleratio, BMI, BMI z-score between the study groups(Group A and C) (Table 1). In Group A there were 14(51.9%) with normal BMI, 4 (14.8%) overweight and 9

(33.3%) obese children and in Group C 9 (69.2%) withnormal BMI, 1 (7.7%) overweight and 3 (23.1%) obese,respectively. Even when subjects were divided in twogroups according to BMI: normal BMI 14 (51.9%) andoverweight-obese 13 (48,1%) children in Group Aand normal BMI 9 (69.2%) and overweight-obese 4(30,8%) children in Group C, there were no statisticaldifferences. Subjects with OSAS (Group A) had signi-ficantly more often adenoids (85.1% vs. 15.4%,P ¼ 0.000) and hypertrophy of tonsils (85.1% vs.53.9%, P ¼ 0.09) compared with Group C children.According to Brodsky Scale, in Group A 10 (37%) hadmild, 11 (40.7%) had moderate and 2 (7,4%) childrenhad severe hypertrophy of tonsils. Systolic blood pres-sure (SBP) at rest was not statistically different betweenthe two groups but DBP at rest was significantly higherin OSAS group (P ¼ 0.02) (Table 1).

Sleep Study

Subjects’ polysomnography results according to sleepstudy are summarized in Table 2. All children hadpathological sleep study according to AHI, 15 (55.6%)children had mild OSAS, 11 (40.7%) moderate and 1(3.7%) severe OSAS. There were no statistical differen-ces in the characteristics of sleep between children withmild and moderate-to-severe OSAS (Table 2).

Pulmonary Function

All subjects from both groups had normal pulmonaryfunction as compared to the percentage of predictedvalues. In OSAS group (Group A) FVC was 93 �15.3%, FEV1 89.7 � 13.8%, and FEV1/VC 97 � 7.7%and in control group (Group C) 99.6 � 7.7%, 98.3 �8.5%, and 100 � 7.5%, respectively. OSAS childrenshowed significantly decreased FEV1 (P ¼ 0.045) com-pared to control group (Fig. 1). Children with mild

TABLE 1— Subjects’ Characteristics of Both Groups

Group A C P

Age (years) 10.5 � 1.8 11 � 1.5 0.382

Weight (kg) 46.28 � 10.5 41.69 � 12.9 0.239

Height (cm) 146.81 � 10.8 144.38 � 11.2 0.515

M/F 2.35 3.33 0.85

BMI 21.27 � 3.2 19.67 � 3.9 0.181

BMI z-score 1.08 � 0.57 0.68 � 1.03 0.07

SBP at rest (mmHg) 109.7 � 11.7 109.4 � 5.8 0.927

DBP at rest (mmHg) 63.74 � 7.5 56.38 � 3 0.02

Hypertrophy of

tonsils (�þ2)a1.7 � 1.2 0.69 � 0.75 0.09

Adenoids (%) 81.5 15.4 0.000

M, male; F; female; BMI; body mass index; SBP; systolic blood

pressure; DBP, diastolic blood pressure.aAccording to Brodsky Scale.

TABLE 2— Characteristics of Sleep in OSAS group(Group A)

Sleep Group A

TST (h) 7.53 � 1

Sleep latency (min) 18.6 � 8.7

REM latency (min) 89.5 � 18.9

Mean SaO2 (%) 93 � 16.7

SaO2 nadir (%) 85.4 � 7.7

(%) TST SaO2 <90% (min) 0.7 � 0.21

ETCO2 (mmHg) 38.8 � 4.1

AHI 4.97 � 2.1

Heart-rate (beat/min) 72 � 12.3

Arousal index 4.4 � 2.7

TST, total sleep time; SaO2, oxygen saturation; ETCO2, end tidal

carbon dioxide; AHI, apnea hypopnea index.



OSAS compared to moderate–severe OSAS had FVC94.33 � 16.8% vs. 91.5 � 13.7%, FEV1 92.67 �16.1% vs. 85.9 � 9.5%, and FEV1/VC 97.9 � 8.2%vs. 95.8 � 7.1%, but not statistically significant(Fig. 1).

Cardiopulmonary Exercise Testing

All subjects completed the exercise test without com-plications, when children could no longer maintain the

desired pedal rate. Maximal exercise test endpointswere confirmed in both groups, as verified by achieve-ment of heart rate reaching 80% of age predicted maxi-mal heart-rate (OSAS group 86.6 � 8.8% vs. controlgroup 90.6 � 7.2%). The mean SaO2 in OSAS group atrest was 97.3 � 1.2 and at peak exercise 97.2 � 0.7(P ¼ 0.751) and in control group was 98.1 � 0.8 andat peak exercise 97.7 � 0.9 (P ¼ 0.542). Results ofCPET are presenting in Table 3. Work-rate was signifi-cantly higher in OSAS group compared to control

Fig. 1. Boxlots of 1.FVC in (i) OSAS Group (A) and (ii) control Group (C), 2.FEV1 in (i) OSAS

Group (A) and (ii) control Group (C), and 3. FEV1/VC in (i) OSAS group (Group A) and

(ii) control group (Group C).

TABLE 3— Comparisons of Cardiopulmonary Exercise Test Results Between (i) OSAS (Group A) and Control (Group C)and (ii) Mild OSAS and Moderate–Severe OSAS

Group A Group C P Mild OSAS Moderate–severe OSAS P

SBP at peak exercise (mmHg) 145 � 27.4 143.92 � 20 0.904 148.1 � 22.8 141 � 33 0.513

DBP at peak exercise (mmHg) 69 � 12.9 74.08 � 12.1 0.893 70 � 11.9 67.8 � 14.6 0.684

Work-rate (Watt) 101.5 � 30 78.6 � 18.5 0.015 106 � 31.6 95.8 � 27.6 0.385

VO2max (ml/kg/min) 40.3 � 8.4 47.6 � 7.9 0.013 39.3 � 5.2 40.5 � 3.7 0.421

VO2/WR 13.2 � 2.5 14.7 � 4.3 0.17 12.5 � 1.7 14 � 3 0.105

VO2max (%) 77.7 � 15 92.9 � 10.5 0.002 80.8 � 9.3 73.8 � 19.7 0.231

VO2AT (%) 48.2 � 14.7 43.7 � 19.8 0.425 50.3 � 14.3 45.6 � 15.4 0.422

VE (%) 61 � 9.6 59 � 9.9 0.529 59.9 � 9.5 62.6 � 9.9 0.474

VO2/HR (%) 114.59 � 23.1 115.46 � 22 0.911 116 � 24.7 112.8 � 21.8 0.719

BR (%) 33.78 � 11.3 37.08 � 11.3 0.392 36.4 � 11 30.5 � 11.2 0.182

PETO2 (mmHg) 108.9 � 5.1 108.2 � 6.9 0.706 109 � 4.6 108.8 � 5.7 0.907

PETCO2 (mmHg) 44.8 � 4.3 43.6 � 5.1 0.455 45.6 � 3.8 43.7 � 4.7 0.242

VE/VO2 27.5 � 4.3 27.6 � 4.2 0.926 26.8 � 4 28.3 � 4.7 0.367

VE/VCO2 30.3 � 3.1 30.2 � 3.2 0.924 29.8 � 2.7 31 � 3.6 0.333

VD/VT 0.09 � 0.02 0.11 � 0.04 0.039 0.08 � 0.23 0.09 � 0.01 0.247

HRmax (%) 86.6 � 8.8 90.6 � 7.2 0.163 86 � 7.9 84.8 � 9.8 0.351

Duration of test (min) 12.4 � 2.6 13.3 � 2 0.755 12.2 � 1.8 12 � 2 0.345

SBP, systolic blood pressure; DBP, diastolic blood pressure; VO2max, oxygen consumption; WR, work-rate; VO2AT, anaerobic threshold;

VO2/HR, oxygen pulse; VE, minute ventilation; BR, breathing reserve; PETO2, end-tidal oxygen tension; PETCO2, end-tidal carbon dioxide

tension; VT, tidal volume; VE/VO2, ventilatory equivalent for oxygen; VE/VCO2, ventilatory equivalent for carbon dioxide; VD/VT, ratio of

physiologic dead space to tidal volume; HRmax, maximal heart-rate.



group (101.5 � 30 W vs. 78.6 � 18.5 W, P ¼ 0.015).Oxygen consumption—VO2max (ml/kg/min) and VO2max

(%) were significantly lower in OSAS group (40.3 �8.4 ml/kg/min and 77.7 � 15% vs. 47.6 � 7.9 ml/kg/min and 92.9 � 10.5%, P ¼ 0.013 and P ¼ 0.002)(Fig. 2). VO2max is an objective index of exercisecapacity and cardiopulmonary function, so lowerVO2max levels in the OSAS group confirmed thereduced exercise capacity as compared to the controlgroup. Children with OSAS had SBP level at peak exer-cise 145 � 27.4 mmHg and maximum heart rate atpeak exercise 86.6 � 8.8% compared to control group143.92 � 20 mmHg and 90.6 � 7.2% respectively. Inaddition, VE (%) at peak exercise level in OSAS groupwas 61 � 9.6% compared to control group 59 � 9.9%,but it was not significantly different (Table 3).

Comparing mild OSAS to moderate–severe OSASthe levels of VO2max (%) were 80.8 � 9.3% versus73.8 � 19.7%, not statistically significant different(Fig. 3). Furthermore, maximum heart rate at peakexercise and VE in children with mild OSAS was86 � 7.9% and 59.9 � 9.5 L/min, respectively com-pared to 84.8 � 9.8% and 62.6 � 9.9 L/min in childrenwith moderate–severe OSAS. Comparisons betweenmild and moderate–severe OSAS were shown inTable 3.

DISCUSSION

In the present study we evaluate cardiopulmonaryresponse to exercise in recently diagnosed OSAS chil-dren, without any risk factor and therapeutic inter-vention, and assess exercise capacity and severity ofOSAS. We compared their exercise responses with

control subjects of similar age, BMI, habitual physicalactivity patterns. Our findings provide evidence suggest-ing that pediatric OSAS, in agreement with findings inadults, results in decreased exercise capacity. Researchdata on the CPET response characteristics in adultsOSAS are limited and there are no published data inthe literature about cardiopulmonary exercise responsein pediatric OSAS and thus results are referred toadults’ OSAS and exercise response.

One of the main results of our study was that OSASgroup had statistically significant lower VO2max andVO2max (%) than control group, thus pediatric OSAShad an impaired exercise response similar to adults’OSAS. Additional, when moderate–severe OSAS wascompared with mild OSAS, lower levels of VO2max (%)were demonstrated, but with no significant difference.Oxygen consumption (VO2) is an objective index of ex-ercise capacity and cardiopulmonary function. It is re-lated to workload and it is linearly related to energyexpenditure. As the exercise intensity increases, VO2

increases proportionally. However, there comes a pointat which the VO2 ceases to rise even though the exer-cise intensity continues to rise. This point is referred toas the maximal oxygen uptake (VO2max) and it is con-sidered to be the benchmark of maximal aerobic power.

A number of studies in adults revealed that OSASpatients have, as shown by lower relative peak oxygenconsumption (VO2pk) or lean body mass VO2pk, areduced exercise capacity.38–41 Lin et al.38 found thatVO2pk and work peak were reduced in 20 OSASpatients by 27% and 22% respectively, as compared to20 control subjects, mainly due to cardiac impairmentand poor sleep efficiency and architecture. Similarresults were found by Vanuxem et al.40 who suggested

Fig. 2. Boxplots of VO2max in: (i) OSAS group (A) and (ii) con-

trol group (C).Fig. 3. Boxplots of VO2max (%) in: (i) mild OSAS group (A) and

(ii) moderate to severe group (C).



that in OSAS patients, exercise limitations in theirstudy were due to muscle metabolic factors, low levelof blood lactate at maximal exercise (4.9 mmol/L vs.7.9 mmol/L, Pb0.005) and slow lactate removal rateduring recovery (0.13 mmol/L/min vs. 0.18 mmol/L/min, Pb0.025). A recent study lends credence to theview that OSAS severity is inversely related to aerobicfitness.41

On the other hand, there are studies that do not sup-port the idea of decreased exercise capacity in OSASpatients.22,25,42 Fernandez et al.25 reported no differen-ces in peak exercise capacity between 31 patients withmoderate–severe OSAHS and 15 matched controls(25.0 ml/kg/min vs. 25.3 ml/kg/min, respectively).Although OSAS subjects showed the same VO2pk ascontrols, the use of age- and gender-specific formulasrevealed that their exercise capacity was lower.42

A mechanism responsible for possible reduced aero-bic capacity in OSAS may be a function of its basicpathology. During exercise, VO2 is higher in responseto the increase in metabolic demand of active muscle.The cardiovascular system is responsible for increasingthe delivery of blood and oxygen to both the workingskeletal muscle and the pulmonary vascular beds. Exer-cise capacity is largely explained by the extent to whichcardiac output increases. Therefore, attenuation in anyfactor that defines the upper limit of cardiac output (fill-ing pressure, ventricular compliance, contractility, after-load, or ultimately stroke volume) would limit aerobicexercise capacity. OSAS has a detrimental effect on leftventricular systolic function.43 During an obstructiveevent, occlusion of the upper airway creates large nega-tive intrathoracic pressures, leading to an increasedventricular afterload. As a result, transient changes instroke volume and heart-rate, lead to temporary fluctua-tions in cardiac output. Impaired vagal activity, in-creased platelet aggregation and insulin resistance mayalso be responsible for the left ventricular impairmentin OSAS.44 Recurrent hypoxemia may be responsiblefor impaired release and/or bioavailability of endotheli-al nitric oxide (NO), may disturb the hyperemicresponse to exercise, resulting in diminished exercisecapacity.45

The reduced exercise capacity in OSAS group(Group A) is due to cardiovascular parameters and notto ventilatory limitations. This result comes from thepattern of CPET. There were significant decreasedvalues of VO2max and VO2max (%) in OSAS group withnormal breathing reserve (BR), minute ventilation (VE)(%) and VE/VCO2. Also, there were no differences inSaO2 between rest to peak exercise and the main causeof CPET termination was muscular fatigue, whichmade them unable to maintain the desired pedal rate.All these parameters are, mainly, differentiated bycardiovascular causes.46,47

Increased prevalence of altered blood pressureregulation12 and systemic hypertension13–15 have beenreported in children with OSA, and appear to be dosedependent.18 The mechanisms mediating cardiac andblood pressure changes are most likely associated withthe increases in sympathetic activity and reactivity thatprogressively develop in the context of OSAS.19,20

Recent studies confirm that OSAS in children is an in-dependent risk factor for nocturnal hypertension as wellas daytime elevated diastolic blood pressure. In ourstudy, SBP at rest was not statistically different betweenthe two groups but DBP at rest was significantly higherin OSAS group (P ¼ 0.02).48,49

As a consequence of increased blood flow velocitythrough arterial vessels, endothelium releases NO,50

which serves to counteract neural vasoconstrictor toneand to regulate blood flow and pressure.51 Consideringthe acute increase of blood flow into the skeletal muscleduring exercise, a vasodilatory defect due to failure ofNO release might be an important pathophysiologicmechanism of elevated exercise blood pressure. Duringexercise tests, DBP may not increase or may often de-crease, but SBP should increase at a steady rate as afunction of rising oxygen demand and enhanced cardiacoutput, in relation to changes in peripheral vascular re-sistance that assure perfusion pressure needed in variousactive and inactive tissue beds.52 Tryfon et al.53 indicat-ed that even in the absence of daytime hypertension,normotensive OSAS patients demonstrate an elevationof BP during peak exercise.53 In the present study therewere higher SBP levels at peak exercise in OSASgroup, although there were higher DBP levels at rest.

In patients with OSAS, some investigators havereported finding the heart rate (HR) response to duringexercise as being lower than for healthy peers,39,42 sug-gesting chronotropic incompetence. Kaleth et al.42

reported that OSAS subjects exhibited mean peak exer-cise HR that were 86.5% of age adjusted predictedmaximal HR compared to 93.5% for controls. That HRresponse was initially suggested by Aguillard et al.54 in1998. They concluded, from a correlation analysis of32 OSAS patients, that 66% of subjects felt at least10 bt/min below their predicted maximal HR, while50% of patients were 20 bt/min under their predictedvalues. The authors caution that apnea severity did notaccount for the inappropriate HR response and the lattermay be more a function of REM sleep percentage. Ourresults are in agreement with adults findings. There wasa lower maximum heart rate at peak exercise in OSASgroup; however heart rate response in moderate–severeOSAS was lower than mild OSAS.

In the present study, higher VE (%) was detected inOSAS group at peak exercise level, suggesting relativehyperpnea. Higher ventilation in exercise response hasbeen, also, found in adults’ patients with OSAS.22



Furthermore, shorter duration of exercise (12.4 � 2.6 minvs. 13.3 � 2 min), lower breathe reserve (BR) (%),higher VO2AT (%) (48.2 � 14.7 vs. 43.7 � 19.8) andsignificantly higher work-rate, were recorded in ourstudy.

Finally, all children with habitual snoring (Group A)had an AHI � 1 and so they were diagnosed as havingOSAS. This finding probably reflects the strict criteriawe used for the participants, since only children withhabitual snoring (�4 nights per week) for at least6 months were eligible for participation. Also, all chil-dren referred to sleep-disorders laboratory by assentfrom experts in Pediatric Pulmonology and Otorhinolar-yngology—Head and Neck Surgery. Thus, experiencedexperts to sleep apnea examined all children and chosethe most serious cases.

The major limitation of the present study was thatthe number of children observed was relative small andonly one child had severe OSAS. These results do notallow any further conclusions or recommendation and.made it difficult to acknowledge a dose dependenteffect. Furthermore, the control group subjects did notundergo polysomnography sleep study, in order todetect latent form of OSAS. Therefore, there may beundiagnosed OSAS in the control group.

In conclusion, our results suggest that children withOSAS demonstrate impaired exercise capacity. InOSAS group we detected significant lower VO2max thancontrol group, the objective index of exercise/aerobiccapacity and cardiopulmonary function. Furthermore,our findings confirm that there is an early unfavorableeffect in cardiovascular system in children with OSAS,as showed by CPET results. This effect was observed incases with mild and moderate OSAS; only one childhad severe form. We believe that the results of ourstudy are significant and might ultimately find usein clinical practice. However, the number of childrenobserved is relative small to allow any further conclu-sions. As such, we are anxious to see other studies beenmade on the subject, to possibly confirm our results andextend the data on OSAS. Therefore, we anticipatefuture studies that could possibly confirm our resultsand extent the data on OSAS.

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reduced exercise capacity in greek children with mild to moderate obstructive sleep apnea syndrome

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