Long-term changes in blood pressure control in elementary school-aged children with sleep-disordered breathing

ObjectiveIn adults sleep-disordered breathing (SDB) has been associated with impaired baroreflex control of blood pressure (BP), which has been linked to increased cardiovascular morbidity. In children, the long-term effects of SDB on baroreflex sensitivity (BRS) and BP variability (BPV) are unknown.MethodsChildren previously diagnosed with SDB (n = 40) and 20 nonsnoring controls aged 11–16 y underwent overnight polysomnography with continuous BP measurement, four years after the original diagnosis. At follow-up, SDB was categorized as resolved (absence of snoring and obstructive apnea hypopnea index (OAHI) ⩽ 1) or unresolved (continued to snore or had an OAHI > 1). BRS and BPV were calculated using cross-spectral analysis and power spectral analysis, respectively.ResultsOnly children with resolved obstructive sleep apnea (OSA) at follow-up demonstrated an increase in BRS from 9.7 ± 3 (ms mmHg⁻¹) at baseline to 11.8 ± 4 (ms mmHg⁻¹) at follow-up (P = .03). However, children with all severities of both resolved and unresolved SDB showed a significant decrease in BPV from baseline to follow-up (a decrease in total power BPV (P < .05) and a shift in BPV spectra away from respiratory-related frequencies (increased low-frequency/high-frequency [LF/HF] ratio, P < .01). The change in OAHI was the sole determinant of change in BRS, HF power, and LF/HF ratio.ConclusionsImprovement in SDB was associated with improved BP control, regardless if SDB was treated or spontaneously resolved four years after initial diagnosis. Our findings highlight the importance of monitoring children to ensure improvement of SDB and reduce the risk for cardiovascular morbidity in the future.     

Characterization of the acute pulse transit time response to obstructive apneas and hypopneas in preschool children with sleep-disordered breathing

Background

Surges in heart rate (HR) and blood pressure (BP) at apnea termination contribute to the hypertension seen in obstructive sleep apnea (OSA). Because childhood OSA prevalence peaks in the preschool years, we aimed to characterize the cardiovascular response to obstructive events in preschool-aged children.

Methods

Clinically referred children aged 3–5 years were grouped by obstructive apnea–hypopnea index (OAHI) into the following: primary snoring (PS) (OAHI ? 1 event/h [n = 21]), mild OSA (OAHI > 1– ? 5 [n = 32]), and moderate to severe (MS) OSA (OAHI > 5 [n = 28]). Beat-to-beat pulse transit time (PTT), an inverse continuous indicator of BP changes, and HR were averaged during the two halves (early and late) and during the peak after (post) each obstructive event and were expressed as percentage change from late- to post-event.

Results

We analyzed 422 events consisting of 55 apneas and 367 hypopneas. A significant post-event increase in HR and fall in PTT occurred in all severity groups (P < .05 for all). A greater response was associated with OSA, nonrapid eye movement sleep (NREM), cortical arousal, hypopneas, and oxygen desaturation (P < .05 for all).

Conclusions

Obstructive events elicit acute cardiovascular changes in preschool children. Such circulatory perturbations have been implicated in the development of hypertension, and our findings complement previous studies to suggest a cumulative impact of snoring on the cardiovascular system from childhood into adulthood.     

Alteration of esophageal pressure in sleep-disordered breathing

Abstract We investigated the alteration of esophageal pressure (Pes) in 10 patients with upper-airway sleep-disordered breathing (UASDB) and the relationship among Pes, breathing patterns and EEG arousals. Increased negative Pes without apnea or hypopnea, appeared not only in upper airway resistance syndrome but also in obstructive sleep apnea syndrome. This phenomenon produced frequent EEG microarousals leading to sleep fragmentation and daytime sleepiness. Moreover, increased negative Pes occasionally continued for more than 20 min without an EEG arousal, which might be considered to be one of the factors to cause complications of UASDB.     

Oximetry in obese children with sleep-disordered breathing

BackgroundObesity is an important risk factor for obstructive sleep apnea syndrome (OSAS), and obese children with OSAS have frequently shown oxygen desaturations when compared with normal-weight children. The aim of our study was to investigate the oximetry characteristics in children with obesity and sleep-disordered breathing (SDB).MethodsChildren referred for suspected OSAS were enrolled in the study. All children underwent sleep clinical record (SCR), pulse oximetry, and polysomnography (PSG).ResultsA total of 248 children with SDB were recruited (128 obese and 120 normal-weight children). Obese children showed higher oxygen desaturation index (ODI) and lower nadir oxygen saturation (nadir SaO₂) compared to non-obese children (p < 0.05). ODI and nadir SaO₂ correlated with obesity (p < 0.05). The SCR evaluation showed that deep bite and overjet were more common among obese children (p < 0.05), whereas habitual nasal obstruction and arched palate were more common among non-obese children (p < 0.05). Furthermore, skeletal malocclusion and tonsillar hypertrophy were significant risk factors in obese children associated with severe desaturation (p < 0.05).ConclusionObese children with SDB have a more significant oxygen desaturation; adeno-tonsillar hypertrophy is not the only important risk factor for its development but also the presence of malocclusions.     

Nocturnal autonomic function in preschool children with sleep-disordered breathing

BackgroundObstructive sleep apnea (OSA) is associated with autonomic dysfunction in adults and school-aged children; however, this association has not been investigated in preschool children. We aimed to analyze heart rate variability (HRV) and catecholamine levels in preschool children with OSA.MethodsOne hundred and forty-two snoring children aged 3–5 years and 38 nonsnoring control group children underwent overnight polysomnography (PSG). Nocturnal urinary catecholamines were measured in 120 children. Children were grouped according to their obstructive apnea–hypopnea index (OAHI) (control [no snoring], OAHI ⩽ 1 event/h; primary snoring, OAHI ⩽ 1 event/h; mild OSA OAHI > 1 ⩽ 5 events/h; moderate to severe [MS] OSA, OAHI > 5 events/h). The HRV parameters for each child were averaged during rapid eye movement (REM) and non-REM (NREM) sleep.ResultsDuring stable sleep, low-frequency (LF) HRV was similar between groups. High-frequency (HF) HRV was higher in the MS OSA group compared with the control group during all sleep stages (NREM sleep stages 1 and 2 [NREM1/2], 4234 ± 523 ms² vs 2604 ± 457 ms²; NREM sleep stages 3 and 4 [NREM3/4], 4152 ± 741 ms² vs 3035 ± 647 ms²; REM, 1836 ± 255 ms² vs 1456 ± 292 ms²; P < .01 for all). The LF/HF ratio was lower in the MS OSA group compared with the control group (NREM1/2, 0.4 ± 0.06 vs 0.7 ± 0.05; NREM3/4, 0.3 ± 0.06 vs 0.4 ± 0.05; REM, 0.8 ± 0.1 vs 1.3 ± 0.1; P < .01 for all). Catecholamine levels were not different between groups.ConclusionsIn preschool children, OSA is associated with altered HRV, largely due to the HF fluctuations in heart rate (HR) which occur during respiratory events and are still evident during stable sleep. The preschool age may represent a window of opportunity for treatment of OSA before the onset of the severe autonomic dysfunction associated with OSA in adults and older children.     

The effect of seasonality on sleep-disordered breathing severity in children

Objective

Sleep-disordered breathing (SDB) is a common disorder associated with substantial morbidity that occurs in otherwise healthy children. Atopy, asthma, and viral upper respiratory tract infections are known risk factors for pediatric SDB that exhibit seasonal variability. The aim of our study was to investigate the effect of seasonality on SDB severity in children and adolescents referred for polysomnographic evaluation for suspected SDB and to examine the effect of atopy/asthma on this variability.

Methods

The medical records of all children and adolescents referred for a polysomnography (PSG) for suspected SDB between 2008 and 2010 were retrospectively assessed for seasonal patterns. The effect of atopy/asthma, age, and obesity on seasonal variability was investigated.

Results

A total of 2178 children and adolescents (65% boys) were included. The mean age of the cohort was 4.9 ± 3.5 years (range, 3 months–18 years). Eighteen percent of patients had a history of asthma/atopy. The mean obstructive apnea–hypopnea index (OAHI) in the winter was significantly higher compared to the summer (9.1 ± 9.6 vs 7.5 ± 7.0; P = .01; Cohen d = 0.19), particularly in children younger than the age of 5 years (10.2 ± 10.5 vs 7.9 ± 7.3; P = .008; Cohen d = 0.25). Asthma/atopy had no significant effect on seasonal variability.

Conclusions

SDB severity alters in a season-dependent manner in children and adolescents referred for polysomnographic evaluation for suspected SDB. These alterations are more prominent in children younger than the age of 5 years. The presence of asthma/atopy does not contribute to this seasonal variability. These findings suggest that viral respiratory infections are most likely the major contributor for the seasonal variability observed in pediatric SDB; additionally, the time of the year when a child is evaluated for suspected SDB may affect the clinical management and outcome in borderline cases.     

Esophageal pressure and apnea hypopnea index in sleep-disordered breathing

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in six cases of upper airway resistance syndrome (UARS) and 11 cases of obstructive sleep apnea syndrome (OSAS). The severity of negative Pes was represented by the highest peak (Pes Max) and the number of increased episodes (more than 13.5 cmH2O) per h (NPesI13.5). There was no significant correlation between Pes indices and AHI. Pes Max and NPesI13.5 were not different among severe OSAS (AHI > 30), mild OSAS (AHI < 30) and UARS. Apnea hypopnea index failed to represent the severity of negative Pes, which is an important aspect of the pathophysiology of sleep-disordered breathing.     

Two cases of sleep-disordered breathing in climacteric

Abstract Two cases of sleep disordered-breathing in climacteric were reported. Polysomnography including esophageal pressure (Pes) measurement was performed. Case 1 was diagnosed as upper airway resistance syndrome. Case 2 was diagnosed as obstructive sleep apnea syndrome, while many episodes of upper airway resistance also existed. Hormone replacement therapy improved clinical symptoms, and in case 1, Pes nadir was improved but incidence of arousals which was induced by breathing disturbances was not significantly changed. Sleep disordered-breathing should be suspected as a cause of sleep disorder even in females, especially in climacteric age. Pes measurement and evaluation of arousals is required. Hormone replacement therapy may release the upper airway resistance.     

Variants in C-reactive protein and IL-6 genes and susceptibility to obstructive sleep apnea in children: a candidate-gene association study in European American and Southeast European populations

BackgroundPreliminary evidence indicates that variants of the C-reactive protein (CRP) and IL-6 genes might be associated with the presence of obstructive sleep apnea (OSA) in childhood. Thus a candidate-gene association study was conducted to investigate the association of four variants of the CRP gene (1444C/T, −717T/C, 1861C/T, and 1919A/T) and two variants of the IL-6 gene (−174G/C and 597G/A) with OSA in a cohort of European American and Greek children.MethodsThe genetic risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR_G), which is a model-free approach. The mode of inheritance was assessed using the degree of dominance index. The impact of haplotypes was also examined.ResultsIn the American population, the allele contrast and the model-free approach produced significant ORs for the CRP 1444C/T variant (OR, 3.82 [95% confidence interval {CI}, 1.91–7.63] and OR_G, 4.37 [95% CI, 1.96–9.76]), respectively, and the mode of inheritance was recessiveness of allele T. Significance was also shown for the CRP 1919A/T variant (OR, 2.45 [95% CI, 1.23–4.85] and OR_G, 2.76 [95% CI, 1.26–6.03]) with the mode of inheritance being nondominance of allele T. For the IL-6-174G/C variant, there was an indication of recessiveness of allele C. Finally, the IL-6-174C/IL-6 597A haplotype was associated with OSA. In the Greek population, no association was detected for any variant or haplotype.ConclusionsGenetic variation in the IL-6/CRP pathway was associated with increased risk for OSA in European American children and may account for the higher CRP levels in the context of pediatric OSA compared to Greek children.     

Prevalence of residual excessive sleepiness during effective oral appliance therapy for sleep-disordered breathing

BackgroundOral appliance therapy with a mandibular advancement device (OA_m) can yield to complete therapeutic response (apnea–hypopnea index [AHI] < 5 events/h), though some patients show little or no improvement in daytime sleepiness. The prevalence of residual excessive sleepiness (RES) despite effective treatment with OA_m therapy is unknown. We aimed to determine the prevalence of RES in patients treated with a titratable custom-made duobloc OA_m.MethodsA prevalence study was performed, collecting data from 185 patients with an established diagnosis of sleep-disordered breathing (SDB) under OA_m therapy with a titratable custom-made duobloc device (baseline data were male:female ratio, 129:56; age, 48 ± 9 years; body mass index [BMI], 27 ± 4 kg/m²; Epworth Sleepiness Scale [ESS] score, 10 ± 5; and AHI, 19 ± 12 events/h). A full-night polysomnography was performed at baseline and after 3 months of OA_m therapy. Daytime sleepiness was assessed using the ESS with RES defined as an ESS score of 11 or higher out of 24, despite complete therapeutic response.ResultsOut of 185 patients, 84 patients (45%) showed a complete therapeutic response with an AHI of <5 events per hour after 3 months of OA_m therapy. Despite this normalization of AHI, 27 out of these 84 patients (32%) showed RES and had a significantly higher baseline ESS (15 ± 4 vs 9 ± 4; P < .001) and were younger (43 ± 9 vs 47 ± 9; P = .028) compared to patients without RES.ConclusionRES under OA_m therapy showed a prevalence of up to 32% in SDB patients effectively treated with respect to AHI. Patients with RES were younger and had higher baseline daytime sleepiness.     

Airflow limitations in pregnant women suspected of sleep-disordered breathing

Background and aimPregnancy physiology may predispose women to the development of airflow limitations during sleep. The goal of this study was to evaluate whether pregnant women suspected of sleep-disordered breathing (SDB) are more likely to have airflow limitations compared to non-pregnant controls.MethodsWe recruited pregnant women referred for polysomnography for a diagnosis of SDB. Non-pregnant female controls matched for age, body mass index (BMI), and apnoea–hypopnoea index (AHI) were identified from a database. We examined airflow tracings for changes in amplitude and shape. We classified airflow limitation by (a) amplitude criteria defined as decreased airflow of ⩾10 s without desaturation or arousal (FL 10), or decreased airflow of any duration combined with either 1–2% desaturation or arousal, (FL 1–2%); and (b) shape criteria defined as the presence of flattening or oscillations of the inspiratory flow curve.ResultsWe identified 25 case-control pairs. Mean BMI was 44.0 ± 6.9 in cases and 44.1 ± 7.3 in controls. Using shape criteria, pregnant women had significantly more flow-limited breaths throughout total sleep time (32.4 ± 35.8 vs. 9.4 ± 17.9, p < 0.0001) and in each stage of sleep (p < 0.0001) than non-pregnant controls. In a subgroup analysis, pregnant women without a diagnosis of obstructive sleep apnoea (OSA) who had an AHI <5 had similar findings (p < 0.0001). There was no difference in airflow limitation by amplitude criteria between pregnant women and controls (p = 0.22).ConclusionsPregnant women suspected of OSA have more frequent shape-defined airflow limitations than non-pregnant controls, even when they do not meet polysomnographic OSA criteria.     

Obstructive sleep apnea is associated with cancer mortality in younger patients

ObjectiveThe association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion.MethodsThis was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea–hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat₉₀). The association between OSA severity and cancer mortality was assessed using Cox’s proportional regression analyses after adjusting for relevant confounders.ResultsIn all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat₉₀ was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02–1.41). The closest association was shown in patients <65 years in both the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1–3.2; upper vs lower AHI tertile: HR, 3.98; 95% CI, 1.14–3.64) and the TSat₉₀ (continuous log-transformed TSat₉₀: HR, 1.73; 95% CI, 1.23–2.4; upper vs lower TSat₉₀ tertile: HR, 14.4; 95% CI, 1.85–111.6).ConclusionsOSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.     

Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing

BackgroundThe co-existence of obstructive and central sleep apnea/hypopnea syndrome (OSAS) and periodic breathing is common in patients with and without underlying heart diseases. While automatic continuous positive airway pressure (APAP) has proven to effectively treat OSAS, the adaptive servo-ventilation (ASV) sufficiently improves periodic breathing. This is the first trial on a device which combines both treatment modes.MethodsPilot study on a two-week treatment in patients with co-existing obstructive and central and periodic breathing disturbances during sleep. Twelve consecutive patients (9 male, 3 female, age 56.9 ± 10.6 years, BMI 32.4 ± 5.5 kg/m²) were treated with a new algorithm which combines APAP and ASV (also called anticyclic modulated ventilation (ACMV), SOMNOventCR^®, Weinmann, Hamburg, Germany). Seven suffered from arterial hypertension, coronary heart disease and mitral regurgitation, none from congestive heart failure.ResultsThe total apnea–hypopnea index (AHI) improved from 43.8 ± 24.0/h to 2.1 ± 2.4 (p < 0.01), the obstructive AHI from 12.8 ± 14.3/h to 0.3 ± 0.6/h (p < 0.01) and the central AHI from 31.0 ± 17.5/h to 1.7 ± 2.0/h (p < 0.01). Moreover, there was a significant improvement in the total number of arousals, respiratory induced arousals, oxygen saturation and sleep profile.ConclusionThe algorithm combining automatic continuous positive airway pressure (CPAP) and ASV normalizes all types of co-existing obstructive and central apnea/hypopnea and periodic breathing.     

Impact of sleep-disordered breathing treatment on upper airway anatomy and physiology

Sleep-disordered breathing (SDB) is a major public health problem. Various anatomic, pathophysiologic, and environmental changes contribute to SDB. The successful treatment of SDB reverses many of these abnormal processes. The present article discusses the current clinical evidence that supports the reversibility and its potential application in the management of SDB. Continuous positive airway pressure reduces angiogenesis and inflammatory edema, increases pharyngeal size, and improves surrogate markers of vascular inflammation and tongue muscle fiber types. Mandibular advancement devices lead to favorable maxillary and mandibular changes, increase pharyngeal area, and improve hypertension. Uvulopalatopharyngoplasty increases posterior airway space and pharyngeal volume, reduces nasal and oral resistance, and lowers response to high CO₂. Weight loss reduces nasopharyngeal collapsibility, critical closing pressure of the airway, apnea–hypopnea index, and improves oxygen saturations. Potential clinical benefits of these changes in the management of SDB and patient compliance with treatment are discussed.     

Sleep-disordered breathing and pulmonary function in obese children and adolescents

ObjectiveObese children have an increased risk of developing obstructive sleep apnea syndrome (OSAS) compared to normal-weight children. In obese children, OSAS is more frequently associated with oxygen desaturations, which might be caused by pulmonary function abnormalities. Our goal was to investigate the association between OSAS and pulmonary function in obese children and adolescents.MethodsThere were 185 children included and distributed in groups based on their obstructive apnea–hypopnea index (151 controls, 20 mild OSAS, and 14 moderate-to-severe OSAS). All subjects underwent polysomnography and pulmonary function testing.ResultsSeveral differences in pulmonary function were observed between groups. Vital capacity (VC) and forced expired volume in 1 s (FEV₁) were significantly decreased in patients with moderate-to-severe OSAS, as were expiratory reserve volume (ERV), total lung capacity, and functional residual capacity (FRC). Correlations between FEV₁, FRC, and ERV with OSAS severity remained significant independent of the degree of adiposity. Correlations between FEV₁/VC and sleep-related respiratory parameters did not persist after correction for adiposity.ConclusionAn association between awake pulmonary function and sleep-related respiratory parameters could be observed in our population of obese children. These results suggest that OSAS severity is correlated with a diminished lung function. However, the level of obesity remains an important confounding factor in both OSAS severity and pulmonary function.     

The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial

BackgroundObstructive sleep apnea (OSA) is a chronic progressive disease, and it is well-documented that severe OSA is associated with an increased cardiovascular morbidity and mortality. Weight reduction has been shown to improve OSA; however, we need further evidence to determine if it may prevent the progression of OSA in the long term. The aim of our study was to assess the impact of weight change during a 5-year observational follow-up of an original 1-year randomized controlled trial.MethodsThe participants were divided into the two groups according to the weight change at 5-year follow-up using the 5% weight loss as a cutoff point, which was later referred to as the successful (n = 20) or unsuccessful groups (n = 27). The change in apnea–hypopnea index (AHI) was the main objective outcome variable.ResultsFifty-seven patients participated in the 5-year follow-up. At 5 years from the baseline, the change in AHI between the groups was significant in the successful group (−3.5 [95% confidence interval {CI}, −6.1 to −0.9]) compared with the unsuccessful group (5.0 [95% CI, 2.0–8.5]) (P = .002). Successful weight reduction achieved an 80% reduction in the incidence of progression of OSA compared to the unsuccessful group (log-rank test, P = .016).ConclusionsA moderate but sustained weight reduction can prevent the progression of the disease or even cure mild OSA in obese patients.     

Idiopathic edema is associated with obstructive sleep apnea in women

BACKGROUND AND PURPOSE: This study was undertaken to clarify whether idiopathic edema is a marker for obstructive sleep apnea (OSA), independent of level of obesity, in patients with normal left ventricular function. PATIENTS AND METHODS: Seventy-eight ambulatory, obese, adults, 44 with bilateral, pitting pre-tibial edema, and 34 without edema, from an inner city family practice and a suburban family practice enrolled from July 1995 until March 2003. Edematous subjects, but not non-edematous subjects, underwent echocardiography, urinalysis, and blood test evaluations to ensure that cardiac, renal, hepatic, and thyroid functions were normal. All subjects underwent spirometry, pulse oximetry on room air, and polysomnography evaluations. RESULTS: Compared to the non-edematous subjects, the edematous subjects were more obese (body mass index=47.0+/-9.3 versus 36.5+/-4.6 kg/m2, P=0.002), had more severe OSA (apnea-hypopnea index (AHI)=34.1+/-27.7 versus 17.0+/-19.4, P=0.002), and had lower oxygen saturations (96.2+/-2.0 versus 97.1+/-1.5%, P=0.05). Using an AHI > or = 15 as the criteria for diagnosing OSA, there was an association between edema and OSA in women (P=0.02) but not men. CONCLUSIONS: In subjects with normal left ventricular function, idiopathic edema is associated with OSA in women.     

Amyotrophic lateral sclerosis associated with insomnia and the aggravation of sleep-disordered breathing.

A case of amyotrophic lateral sclerosis (ALS) diagnosed by sleep-disordered breathing is described. The patient's chief complaints were insomnia and nocturnal dyspnea after taking a hypnotic drug. On examination, he showed restrictive ventilatory impairment, alveolar hypoventilation and hypoxia. Polysomnographic examination revealed marked hypoxia during REM sleep periods, decreased duration of REM sleep periods, and increased sleep disruption. Amyotrophic lateral sclerosis was diagnosed by the neurological finding of paraspinal muscle weakness and neurogenic changes revealed by needle electromyography and muscle biopsy. The daytime and nocturnal respiratory insufficiency improved after nasal bilevel positive airway pressure therapy. Amyotrophic lateral sclerosis should be suspected as a cause of insomnia and nocturnal dyspnea.