Utilisation of machine learning to predict surgical candidates for the treatment of childhood upper airway obstruction.

OBJECTIVE: To investigate the effect of adenotonsillectomy on OSAS symptoms based on a data-driven approach and thereby identify criteria that may help avoid unnecessary surgery in children with OSAS. METHODS: In 323 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (eAT; N = 165) or a strategy of watchful waiting with supportive care (WWSC; N = 158), the apnea-hypopnea index, heart period pattern dynamics, and thoraco-abdominal asynchrony measurements from overnight polysomnography (PSG) were measured. Using machine learning, all children were classified into one of two different clusters based on those features. The cluster transitions between follow-up and baseline PSG were investigated for each to predict those children who recovered spontaneously, following surgery and those who did not benefit from surgery. RESULTS: The two clusters showed significant differences in OSAS symptoms, where children assigned in cluster A had fewer physiological and neurophysiological symptoms than cluster B. Whilst the majority of children were assigned to cluster A, those children who underwent surgery were more likely to stay in cluster A after seven months. Those children who were in cluster B at baseline PSG were more likely to have their symptoms reversed via surgery. Children who were assigned to cluster B at both baseline and 7 months after surgery had significantly higher end-tidal carbon dioxide at baseline. Children who spontaneously changed from cluster B to A presented highly problematic ratings in behaviour and emotional regulation at baseline. CONCLUSIONS: Data-driven analysis demonstrated that AT helps to reverse and to prevent the worsening of the pathophysiological symptoms in children with OSAS. Multiple pathophysiological markers used with machine learning can capture more comprehensive information on childhood OSAS. Children with mild physiological and neurophysiological symptoms could avoid AT, and children who have UAO symptoms post AT may have sleep-related hypoventilation disease which requires further investigation. Furthermore, the findings may help surgeons more accurately predict children on whom they should perform AT.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 + T cells expressing TNFα and IFNγ.

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

Adenotonsillectomy for childhood obstructive sleep apnoea reduces thoraco-abdominal asynchrony but spontaneous apnoea-hypopnoea index normalisation does not.

The efficacy of adenotonsillectomy for treating obstructive sleep apnoea syndrome (OSAS) in children has been established, but its precise effects on inspiratory effort are not well documented.In 353 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (n=182) or a strategy of watchful waiting with supportive care (WWSC) (n=171), thoraco-abdominal asynchrony (TAA) was analysed during quiet, non-apnoeic and non-hypopnoeic breathing during sleep at baseline and at 7 months using overnight polysomnography.Children who underwent early adenotonsillectomy demonstrated a reduction in TAA post-surgery while the WWSC arm showed no change. On assessing TAA with regard to normalisation of clinical polysomnography findings at follow-up, TAA was reduced in children who had surgical resolution of OSAS (based on apnoea-hypopnoea index), but not in children who displayed spontaneous normalisation of apnoea-hypopnoea index. In the latter group, TAA was inversely correlated with quality of life.We conclude that adenotonsillectomy reduces TAA during quiet sleep. Monitoring of instantaneous TAA may yield additional insight in the dynamic changes of inspiratory effort. In combination with traditional indices of obstruction, TAA may more accurately characterise the degree of sleep-disordered breathing in children.

Flow-mediated dilatation, using time course data, shows maturation of the brachial artery from young children to mid-adolescents.

Flow-mediated dilatation (FMD) is a tool widely used to measure arterial responsiveness to sheer stress. However, there is scant literature to show how the peripheral arterial response changes as the vascular system matures. One reason for this is that the feasibility of measuring FMD in younger children has not been established. The aim of the present study was to assess brachial artery function at rest and during the FMD response after 4 min ischaemia of the forearm in children aged 6-15 years. Time to reach maximum FMD (FMDmax ) was found to be correlated with age (r = 0.4, P < 0.05), resting brachial artery diameter (r = 0.4, P < 0.05), height (r = 0.4, P < 0.05), body mass index (BMI; r = 0.45, P < 0.05), body surface area (r = 0.44, P < 0.05) and resting blood flow (r = 0.37, P < 0.05). However, there was no correlation between the traditional FMD response at 60 s or FMD maximal dilation and age, resting brachial artery diameter, height, weight, BMI, body surface area and resting blood flow. In conclusion, the time taken to reach the maximal dilation response is related to age, brachial artery luminal diameter and body habitus, but not the traditional measure of FMD response at 60 s or the maximal dilatation percentage.

Heartbeat evoked potentials during sleep and daytime behavior in children with sleep-disordered breathing.

RATIONALE: Event-related brain potentials allow probing of cortical information processing, but when evoked with externally induced stimuli may disrupt sleep homeostasis and do not provide insight into intrinsic cortical information processing. To investigate if cortical processing of intrinsic information in children with sleep-disordered breathing (SDB) is different from healthy children and, if so, whether it resolves with treatment, we used heartbeat as a source of interoceptive event-related brain potentials. OBJECTIVES: To investigate heartbeat evoked potentials (HEP) during sleep in healthy children and in children with SDB before and after treatment and to explore if there are any associations between HEP and daytime behavioral deficits in children with SDB. METHODS: Heartbeat-aligned EEG was assessed for presence of HEP within stage 2, slow-wave sleep, and REM sleep in 40 children with primarily mild to moderate SDB before and after adenotonsillectomy and in 40 matched control subjects at similar time points. MEASUREMENTS AND MAIN RESULTS: In both groups, nonrandom HEP were present in all sleep stages analyzed; however, amplitude of HEP were significantly lower in children with SDB during non-REM sleep (stage 2: P = 0.03; slow-wave sleep: P = 0.001). This between-group difference was not significant post adenotonsillectomy. Significant negative associations between HEP and daytime behavioral scores were observed at baseline. CONCLUSIONS: Children with SDB displayed reduced HEP amplitude during sleep, which might be indicative of changes in afferent sensory inputs to the brain and/or signify differences in sensory gating of cardiac-related information in the insular cortex. Adenotonsillectomy appears to reverse this effect.

Increased thoracoabdominal asynchrony during breathing periods free of discretely scored obstructive events in children with upper airway obstruction.

OBJECTIVE: This study aims to investigate the impact of upper airway obstruction (UAO) in children by measuring thoracoabdominal asynchrony (TAA) during periods of sleep apnea/hypopnea and during scored-event-free (SEF) breathing periods. METHODS: Respiratory inductive plethysmographic signals were extracted from polysomnographic data, recorded before and after adenotonsillectomy in 40 children with UAO and 40 healthy, matched children at equivalent time points. Thoracoabdominal asynchrony was computed using a Hilbert transform-based phase difference estimation method in SEF periods during stage 2, stage 4 non-rapid eye movement (NREM), and rapid eye movement (REM) sleep and compared between the groups. RESULTS: At baseline, in the UAO group, TAA during obstructions were significantly higher than TAA during SEF periods in both stage 2 and REM sleep. Compared to controls, children with UAO had a significantly higher TAA during SEF periods in stage 2, stage 4 sleep, and REM sleep. This between-group difference was not significant post adenotonsillectomy. UAO group showed a significant decrease in TAA compared to their baseline during SEF stage 2 and 4 NREM, but not in REM. CONCLUSION: Upper airway obstruction in children is associated with increased TAA during SEF periods, indicative of continuous partial obstruction of the upper airway. Adenotonsillectomy decreased this effect significantly in non-REM sleep as evidenced by reduced asynchrony levels post-surgery. TAA assessment during sleep may therefore provide additional diagnostic information.

Respiratory sinus arrhythmia during sleep in children with upper airway obstruction.

Upper airway obstruction during adulthood is associated with cardiovascular morbidity; cardiovascular consequences of childhood upper airway obstruction are less well established. This study aimed at investigating the effect of childhood upper airway obstruction on respiratory sinus arrhythmia as a measure of cardiac vagal modulation during night-time sleep. Overnight polysomnography was conducted in 40 healthy children (20 M; age: 7.5 ± 2.6 years; body mass index percentile: 60.7 ± 26.4%) and 40 children with upper airway obstruction (24 M; age: 7.5 ± 2.7 years; body mass index percentile: 65.8 ± 31.9%). We used the phase-averaging technique to compute respiratory sinus arrhythmia amplitude and phase delay. To study sleep stage effects and the effect of upper airway obstruction, respiratory sinus arrhythmia was measured during all artefact-free sleep episodes, and after exclusion of respiratory events. A significant increase in respiratory sinus arrhythmia amplitude and phase delay was observed during stage 4 sleep as compared with rapid eye movement sleep in both groups (amplitude: controls = 0.10 ± 0.03 versus 0.07 ± 0.02 s, P < 0.01, respectively, and upper airway obstruction = 0.07 ± 0.03 versus 0.05 ± 0.03 s, P < 0.05, respectively; phase delay: controls = 3.1 ± 0.1 versus 3.0 ± 0.1 rad, P < 0.05, respectively, and upper airway obstruction = 3.13 ± 0.04 versus 3.04 ± 0.08 rad, P < 0.01, respectively). A significant association between respiratory sinus arrhythmia and apnea/hypopnea index was observed during stage 2 sleep in children with upper airway obstruction. Compared with healthy controls, a significant decrease in respiratory sinus arrhythmia amplitude during stage 2 sleep was observed in children with upper airway obstruction (0.09 ± 0.03 versus 0.06 ± 0.03 s, P < 0.05). However, this difference was not apparent when respiratory events were excluded from analysis. Importantly, respiratory sinus arrhythmia showed a strong negative correlation with body mass index. In conclusion, night-time respiratory sinus arrhythmia in children is sleep stage dependent and normal during quiet sleep in children with relatively mild upper airway obstruction.

Craniofacial and upper airway morphology in pediatric sleep-disordered breathing: Systematic review and meta-analysis.

INTRODUCTION: Pediatric sleep-disordered breathing is a continuum, with primary snoring at one end, and complete upper airway obstruction, hypoxemia, and obstructive hypoventilation at the other. The latter gives rise to obstructive sleep apnea. An important predisposing factor in the development and progression of pediatric sleep-disordered breathing might be craniofacial disharmony. The purpose of this systematic review and meta-analysis was to elucidate the association between craniofacial disharmony and pediatric sleep-disordered breathing. METHODS: Citations to potentially relevant published trials were located by searching PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. The MetaRegister of controlled trials database was also searched to identify potentially relevant unpublished trials. Additionally, hand-searching, Google Scholar searches, and contact with experts in the area were undertaken to identify potentially relevant published and unpublished studies. Inclusion criteria were (1) randomized controlled trials, case-control trials, or cohort studies with controls; (2) studies in nonsyndromic children 0 to 18 years of age with a diagnosis of sleep-disordered breathing or obstructive sleep apnea by either a sleep disorders unit, screening questionnaire, or polysomnography; and (3) principal outcome measures of craniofacial or upper airway dimensions or proportions with various modalities of imaging for the craniofacial and neck regions. The quality of the studies selected was evaluated by assessing their methodologies. Treatment effects were combined by meta-analysis with the random-effects method. RESULTS: Children with obstructive sleep apnea and primary snoring show increased weighted mean differences in the ANB angle of 1.64° (P <0.0001) and 1.54° (P <0.00001), respectively, compared with the controls. An increased ANB angle was primarily due to a decreased SNB angle in children with primary snoring by 1.4° (P = 0.02). Children with obstructive sleep apnea had a distance from the posterior nasal spine to the nearest adenoid tissue measured along the PNS-basion line reduced by 4.17 mm (weighted mean difference) (P <0.00001) and a distance from the posterior nasal spine to the nearest adenoid tissue measured along the line perpendicular to the sella-basion line reduced by 3.12 mm (weighted mean difference) (P <0.0001) compared with the controls. CONCLUSIONS: There is statistical support for an association between craniofacial disharmony and pediatric sleep-disordered breathing. However, an increased ANB angle of less than 2° in children with obstructive sleep apnea and primary snoring, compared with the controls, could be regarded as having marginal clinical significance. Therefore, evidence for a direct causal relationship between craniofacial structure and pediatric sleep-disordered breathing is unsupported by this meta-analysis. There is strong support for reduced upper airway width in children with obstructive sleep apnea. Larger well-controlled trials are required to address the relationship of craniofacial and upper airway morphology to pediatric sleep-disordered breathing in all 3 dimensions.

Craniofacial and upper airway morphology in pediatric sleep-disordered breathing and changes in quality of life with rapid maxillary expansion.

INTRODUCTION: The association between pediatric sleep-disordered breathing caused by upper airway obstruction and craniofacial morphology is poorly understood and contradictory. The aims of this study were to evaluate the prevalence of children at risk for sleep-disordered breathing, as identified in an orthodontic setting by validated screening questionnaires, and to examine associations with their craniofacial and upper airway morphologies. A further aim was to assess the change in quality of life related to sleep-disordered breathing for affected children undergoing rapid maxillary expansion to correct a palatal crossbite or widen a narrow maxilla. METHODS: A prospective case-control study with children between 8 and 17 years of age (n = 81) at an orthodontic clinic was undertaken. The subjects were grouped as high risk or low risk for sleep-disordered breathing based on the scores from a validated 22-item Pediatric Sleep Questionnaire and the Obstructive Sleep Apnea-18 Quality of Life Questionnaire. Variables pertaining to a screening clinical examination, cephalometric assessment, and dental cast analysis were tested for differences between the 2 groups at baseline. Ten children who underwent rapid maxillary expansion were followed longitudinally until removal of the appliance approximately 9 months later with a repeated Obstructive Sleep Apnea-18 Quality of Life Questionnaire. All data were collected blinded to the questionnaire results. RESULTS: The frequency of palatal crossbite involving at least 3 teeth was significantly higher in the high-risk group at 68.2%, compared with the low-risk group at 23.2% (P <0.0001). Average quality of life scores in the high-risk group indicated reduced quality of life related to sleep-disordered breathing by 16% compared with children in the low-risk group at baseline (P <0.0001). Cephalometrically, mean inferior airway space, posterior nasal spine to adenoidal mass distance, and adenoidal mass to soft palate distance were reduced in the high-risk group compared with the low-risk group by 1.87 mm (P <0.03), 2.82 mm (P <0.04), and 2.13 mm (P <0.03), respectively. The mean maxillary intercanine, maxillary interfirst premolar, maxillary interfirst molar, mandibular intercanine, and mandibular interfirst premolar widths were reduced in the high-risk group compared with the low-risk group by 4.22 mm (P <0.0001), 3.92 mm (P <0.0001), 4.24 mm (P <0.0001), 1.50 mm (P <0.01), and 1.84 mm (P <0.01), respectively. Children treated with rapid maxillary expansion showed an average improvement of 14% in quality of life scores in the high-risk group compared with the low-risk group, which showed a slight worsening in quality of life related to sleep-disordered breathing by an average of 1% (P <0.04), normalizing the quality of life scores in the high-risk children to the baseline scores compared with the low-risk group. CONCLUSIONS: Children at high risk for sleep-disordered breathing are characterized by reduced quality of life, reduced nasopharyngeal and oropharyngeal sagittal dimensions, palatal crossbite, and reduced dentoalveolar transverse widths in the maxillary and mandibular arches. No sagittal or vertical craniofacial skeletal cephalometric predictors were identified for children at high risk for sleep-disordered breathing. In the short term, rapid maxillary expansion might aid in improvement of the quality of life for children with a narrow maxilla in the milder end of the sleep-disordered breathing spectrum.

Cardiorespiratory response to spontaneous cortical arousals during stage 2 and rapid eye movement sleep in healthy children.

Arousal from sleep is associated with transient and abrupt cardiorespiratory changes, and elevated arousals associated with sleep disorders may trigger adverse cardiovascular sequela. In this paper, we provide the first data in children on cardiorespiratory responses to cortical arousal. Heart rate and ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep were investigated in 40 normal, healthy Caucasian children (age: 7.7 +/- 2.6 years; body mass index z-score: 0.30 +/- 0.8). All children underwent overnight polysomnography studies. Cortical arousals were scored according to standard criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to cortical arousal onset. Breathing rates were quantified three breaths before and after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R-R interval shortening of about 15%, independent of age and gender. The R-R interval shortening initiated at least 3 s before the cortical arousal onset. The breathing interval immediately after cortical arousal onset was significantly shortened (P < 0.001). In conclusion, cortical arousals in children are associated with an increase in breathing rate and significant heart rate accelerations, which typically precede the cortical arousal onset.

The Inconsistent Nature of Heart Rate Variability During Sleep in Normal Children and Adolescents.

Introduction: Cardiac function is modulated by multiple factors including exogenous (circadian rhythm) and endogenous (ultradian 90-110 min sleep cycle) factors. By evaluating heart rate variability (HRV) during sleep, we will better understand their influence on cardiac activity. The aim of this study was to evaluate HRV in the dark phase of the circadian rhythm during sleep in healthy children and adolescents. Methods: One 3 min segment of pre-sleep electrocardiography (EEG) and 3, 6 min segments of electrocardiography recorded during polysomnography from 75 healthy children and adolescents were sampled during progressive cycles of slow wave sleep (SWS1, SWS2, SWS3). Three, 3 min segments of rapid eye movement sleep (REM) were also assessed, with REM1 marked at the last REM period before awakening. Studies that recorded REM3 prior to SWS3 were used for assessment. HRV variables include the following time domain values: mean NN (average RR intervals over given time), SDNN (Standard Deviation of RR intervals), and RMSSD (root Mean Square of beat-to-beat Differences). Frequency domain values include: low frequency (LF), high frequency (HF), and LF:HF. Results: Mixed linear effects model analysis revealed a significant difference in time and frequency domain values between sleep cycles and stages. Mean NN was lowest (highest heart rate) during pre-sleep then significantly increased across SWS1-3. Mean NN in SWS1 was similar to all REM periods which was significantly lower than both SWS2 and SWS3. SDNN remained at pre-sleep levels until SWS3, and then significantly increased in REM1&2. There was a large drop in LF from pre-sleep to SWS1. As cycles progressed through the night, LF remains lower than awake but increases to awake like levels by REM2. RMSSD and HF were lowest in pre-sleep and increased significantly by SWS1 and remain high and stable across stages and cycles except during the REM3 period where RMSSD decreased. Conclusion: Our results demonstrate that there are considerable changes in the spectral analysis of cardiac function occurring during different sleep stages and between sleep cycles across the night. Hence, time of night and sleep stage need to be considered when reporting any HRV differences.

A Method for Estimating Pulse Wave Amplitude Variability in children with Sleep Disordered Breathing.

Sleep disordered breathing (SDB) is a common pediatric disorder, which results in increasing respiratory workload during sleep, restless night time sleep and excessive daytime sleepiness. It has significant negative effects on children with SDB on their physical growth and cognitive related developments. Chronic autonomic activation was suggested to be one of the possible key drivers causing cardiovascular structural changes in SDB children and increasing the risk of developing cardiovascular disease in their future. The aim of this study was to investigate the effect of SDB on autonomic activation changes in children, by analyzing the pulse wave amplitude (PWA) dynamics using a simple envelope estimation method extracting PWA from PPG signal.Children with SDB (n = 40) showed a significantly a wider dynamic distribution in PWA compare to matched controls (n = 40), which suggests a higher and stronger level of autonomic response in SDB children.In conclusion, the PWA dynamic is altered in children with SDB during sleep and indicate changes in autonomic activation.

Differences in dentofacial morphology in children with sleep disordered breathing are detected with routine orthodontic records.

BACKGROUND: Residual snoring in children with obstructive sleep disordered breathing (SDB) may continue post-adenotonsillectomy. This study aims to identify baseline dentofacial differences in children with SDB using routine orthodontic records that might aid effective early intervention for the upper airway to prevent continued obstruction. METHODS: Children (6-16 years) with clinically diagnosed SDB from a paediatric Otolaryngology Clinic who required adenotonsillectomy were participants (n = 10). The control group (n = 9) comprised healthy non-snoring children from the community. Baseline overnight polysomnography (PSG), standardised frontal and right profile photographs and alginate impressions were taken of all children. Facial width, length, depth, convexity and mandibular position were measured from the photographs. The occlusion, arch width, arch depth, maxillary arch form, palatal height and volume were recorded from digitised dental models. Inter-group differences were compared. RESULTS: SDB patients had a significantly increased lower face height, maxillo-mandibular angle (1.73°; 95% CI 0.45-3.0) and a narrower maxillary arch in the upper posterior region. There was a trend towards a decreased palatal volume, increased posterior crossbite and Class II molar relationship. CONCLUSION: Dentofacial phenotypic differences between children with SDB and controls can be detected using facial photographs and dental models. Increased awareness of these features may help to identify children who to continue to snore post adenotonsillectomy.

Effect of adenotonsillectomy for childhood obstructive sleep apnea on nocturnal heart rate patterns.

Study Objectives: To assess the effect of adenotonsillectomy for relieving obstructive sleep apnea syndrome (OSAS) symptoms in children on cardiac autonomic modulation. Methods: In 354 children enrolled in the Childhood Adenotonsillectomy Trial, randomized to undergo either early adenotonsillectomy (eAT; N = 181) or a strategy of watchful waiting with supportive care (WWSC; N = 173), nocturnal heart rate control was analyzed during quiet, event-free sleep at baseline and at 7 months using overnight polysomnography (PSG). The relative frequency of patterns indicating monotonous changes in heart rate was quantified. Results: Children who underwent eAT demonstrated a significantly greater reduction in heart rate patterns postsurgery than the WWSC group. On assessing those heart rate patterns regarding normalization of clinical PSG, heart patterns were reduced to a similar level in both groups. In children whose AHI normalized spontaneously, heart rate patterns were already significantly less frequent at baseline, suggesting that upper airway obstruction was milder in this group at the outset. Conclusions: Adenotonsillectomy reduces monotonous heart rate patterns throughout quiet event-free sleep, reflecting a reduction in cardiac autonomic modulation. Heart rate pattern analysis may help quantifying the effect of OSAS on autonomic nervous system activity in children. Clinical Trial Registration: The study was registered at Clinicaltrials.gov (#NCT00560859).

Altered Nocturnal Cardiovascular Control in Children With Sleep-Disordered Breathing.

Study objectives: To assess cardiovascular control during sleep in children with sleep-disordered breathing (SDB) and the effect of adenotonsillectomy in comparison to healthy nonsnoring children. Methods: Cardiorespiratory signals obtained from overnight polysomnographic recordings of 28 children with SDB and 34 healthy nonsnoring children were analyzed. We employed an autoregressive closed-loop model with heart period (RR) and pulse transit time (PTT) as outputs and respiration as an external input to obtain estimates of respiratory gain and baroreflex gain. Results: Mean and variability of PTT were increased in children with SDB across all stages of sleep. Low frequency power of RR and PTT were attenuated during non-rapid eye movement (REM) sleep. Baroreflex sensitivity was reduced in children with SDB in stage 2 sleep, while respiratory gain was increased in slow wave sleep. After adenotonsillectomy, these indices normalized in the SDB group attaining values comparable to those of healthy children. Conclusions: In children with mild-to-moderate SDB, vasomotor activity is increased and baroreflex sensitivity decreased during quiet, event-free non-REM sleep. Adenotonsillectomy appears to reverse this effect.

The effect of adenotonsillectomy for childhood sleep apnoea on cardiorespiratory control.

The efficacy of adenotonsillectomy for relieving obstructive sleep apnoea symptoms in children has been firmly established, but its precise effects on cardiorespiratory control are poorly understood. In 375 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either adenotonsillectomy (n=194) or a strategy of watching waiting (n=181), respiratory rate, respiratory sinus arrhythmia and heart rate were analysed during quiet, non-apnoeic and non-hypopnoeic breathing throughout sleep at baseline and at 7 months using overnight polysomnography. Children who underwent early adenotonsillectomy demonstrated an increase in respiratory rate post-surgery while the watchful waiting group showed no change. Heart rate and respiratory sinus arrhythmia were comparable between both arms. On assessing cardiorespiratory variables with regard to normalisation of clinical polysomnography findings during follow-up, heart rate was reduced in children who had resolution of obstructive sleep apnoea syndrome, while no differences in their respiratory rate or respiratory sinus arrhythmia were observed. Adenotonsillectomy for obstructive sleep apnoea increases baseline respiratory rate during sleep. Normalisation of apnoea-hypopnoea index, spontaneously or via surgery, lowers heart rate. Considering the small average effect size, the clinical significance is uncertain.

Symbolic dynamics of pulse transit time and heart period in children with upper airway obstruction.

Upper airway obstruction (UAO) is a relatively common condition during childhood that is characterized by periods of partial or complete upper airway closure, resulting in restless sleep. It has also been suggested that UAO triggers early cardiovascular changes that may predispose to an increased risk of developing cardiovascular diseases later in life. The aim of this study was to assess the temporal dynamics of heart period (HP) and pulse transit time (PTT) during quite, event-free periods of sleep in children with UAO (n = 40) and matched healthy controls. The dynamics of HP and PTT were symbolized based on the sextiles of their distribution and words of length three were formed and classified into four types based on their patterns. Joint symbolic dynamics represent the concomitant occurrence of words in HP and PTT. Children with UAO showed a significantly increased frequency in word types of monotonously increasing and decreasing HP and PTT as well as joint dynamics across all stages of sleep. The dynamics of HP showed a marked sleep stage dependence, while PTT dynamics appeared to be relatively unaffected. In conclusion, cardiovascular dynamics are altered in children with UAO during scored event-free sleep, indicative of frequent bursts in sympathetic nervous system activity, possibly reflecting subcortical arousal responses to brief and subtle increases in UAO.

Effect of respiration on heartbeat-evoked potentials during sleep in children with sleep-disordered breathing.

OBJECTIVE: Heartbeat-evoked potentials (HEPs) in electroencephalogram (EEG) provide a quantitative measure of cardiac interoception during sleep. We previously reported reduced HEPs in children with sleep-disordered breathing (SDB), indicative of attenuated cardiac information processing. The objective of this study was to investigate the link between HEP and respiration. PATIENTS/METHODS: From the overnight polysomnograms of 40 healthy children and 40 children with SDB, we measured HEPs during epochs of stage 2, slow-wave and rapid eye movement (REM) sleep free of abnormal respiratory events. HEPs were analysed with respect to respiratory phase. RESULTS: We observed a marked association between respiratory phase and HEP in children with SDB during REM sleep, but not in normal children. In children with SDB, HEP waveforms were attenuated during expiration compared to inspiration. Following adenotonsillectomy, expiratory HEP peak amplitude increased in the SDB children and was no longer different from those of normal children. CONCLUSIONS: The expiratory phase of respiration is primarily associated with attenuated cardiac information processing in children with SDB, establishing a pathophysiological link between breathing and HEP attenuation.

Delayed brachial artery dilation response and increased resting blood flow velocity in young children with mild sleep-disordered breathing.

AIM: This study aimed to evaluate whether the vascular dysfunction perceived in adults with sleep-disordered breathing (SDB) was also evident in children with snoring referred for evaluation of clinically suspected SDB. OBJECTIVES: This study compared flow-mediated dilatation (FMD), measured at the brachial artery, at rest and during hyperaemic stress between children who snore [n = 23; mean standard deviation (SD) age = 7.51 (1.3) years] and healthy, non-snoring children [n = 11; age = 8.0 (1.3) years]. METHODS: Children with suspected obstructive sleep apnoea (OSA) and healthy non-snoring controls underwent overnight polysomnography (PSG). Using standard techniques, non-invasive FMD and brachial arterial blood flow velocity during rest and hyperaemia were subsequently measured by ultrasound imaging MEASUREMENTS: Resting and hyperaemic velocity time integral (area under the curve of mean systolic velocity × ejection time), maximal dilation response (highest percentage difference from baseline diameter) and the time taken to reach maximal dilation were calculated. RESULTS: Children awaiting adenotonsillectomy compared to healthy non-snoring control children had higher velocity time integrals at rest (14 ± 3 m vs. 20 ± 8 m, p < 0.01) and during hyperaemic stress (56 ± 6m vs. 63 ± 13m, p < 0.01) despite having only mild SDB on polysomnographic assessment. Lower nadir oxygen saturation values during non-rapid eye movement sleep were negatively associated with higher resting (r = -0.58, p <0.001) and hyperaemic (r = -0.36, p < 0.05) velocity time integrals. Maximal FMD dilatation response was not significantly different between snoring and non-snoring groups, but the estimated time to reach maximal dilation was significantly delayed in children who snored (60.7 ± 28.4 vs. 39.2 ± 13.2 s, p < 0.05). CONCLUSIONS: Children with mild SDB showed increased blood flow velocity at rest and during hyperaemic stress suggesting altered cardiovascular and haemodynamic function. The delay in time to maximal vessel dilatation in children who snored also suggests possible reduced vascular compliance in response to hyperaemic sheer stress. Mild SDB appears to alter the peripheral vascular response in young children. The long-term vascular implications of these changes in the growing child are unknown and warrant further investigation.