Georgia Malakasioti

Interactions of obstructive sleep-disordered breathing with recurrent wheezing or asthma and their effects on sleep quality

Snoring is the most characteristic symptom of obstructive sleep‐disordered breathing (SDB) and recurrent wheezing is the most common clinical manifestation of asthma. The purpose of the present review is to outline the impact of SDB and recurrent wheezing/asthma on sleep quality and to summarize the epidemiologic and pathophysiologic evidence supporting an association between the two disorders. Enlarged tonsils and adenoid or obesity predispose to obstructive sleep apneas and hypopneas which are accompanied by arousals, restless sleep, and frequently daytime sleepiness, inattention, hyperactivity, and academic difficulties. Subjects with history of wheezing are also at risk for sleep disturbance and daytime cognitive dysfunction.

Effects of adenotonsillectomy on R-R interval and brain natriuretic peptide levels in children with sleep apnea: A preliminary report

OBJECTIVES Obstructive sleep apnea is associated with decreased R-R interval length and overall R-R interval variability in the electrocardiogram along with increased morning brain natriuretic peptide (BNP) blood levels. These findings indicate enhanced sympathetic tone and cardiac strain. In this study, it was hypothesized that adenotonsillectomy (AT) in children with sleep apnea is accompanied by improvement in polysomnography indices, increase in length and variability of R-R interval, and reduction in BNP levels. METHODS Polysomnography and measurements of morning BNP levels were performed before and 4-6months after AT. Mean and standard deviation of R-R interval were calculated from polysomnography electrocardiogram recordings. RESULTS Twenty-one children were studied. Apnea-hypopnea index and log-transformed BNP levels decreased postoperatively from 8.4±7.6 episodes/h and 2.2±0.7, to 1.8±1.4 episodes/h and 1.9±0.3, respectively (p<0.05). Mean R-R interval increased from 703.2±137.4ms (Stage 2), 699.3±135.8ms (Stage 3), 707.4±128.9ms (Stage 4) and 660.5±140.1ms (Stage REM), to 773.5±122.7ms (Stage 2), 765.7±73.7ms (Stage 3), 771.2±71.6ms (Stage 4), and 738.6±81.7ms (Stage REM), respectively (p<0.05 for comparisons pre- vs. post-operatively). Standard deviation of R-R in Stage 2 increased from 88.5±29.6 to 122.7±67ms (p=0.045). CONCLUSIONS Increase in nocturnal length of R-R interval and decrease in BNP levels after AT for sleep apnea may reflect postoperative reduction in sympathetic tone and cardiac strain.

Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring

Background:Conflicting data suggest that prevalence of monosymptomatic primary nocturnal enuresis (NE) increases with increasing severity of obstructive sleep apnea (OSA) in childhood and especially in girls. We hypothesized that NE is associated with increased risk of moderate-to-severe OSA (obstructive apnea-hypopnea index (AHI) >5 episodes/hour) among children with snoring.Methods:Data of children (≥5 y old) with snoring who were referred for polysomnography over 12 y were reviewed.Results:Data of 525 children with mean age (±SD) 7.5 (± 2.2) y and median obstructive AHI (10th-90th percentiles) 1.9 (0.4–7.3) episodes/hour were analyzed. Three hundred and fifty-five children (67.6%) had NE and 87 (16.6%) had moderate-to-severe OSA. There was no interaction between NE and gender regarding the association with moderate-to-severe OSA (P > 0.05). NE was associated significantly with presence of moderate-to-severe OSA after adjustment for tonsillar hypertrophy, obesity, gender, and age (adjusted odds ratio = 1.92 (1.08–3.43); P = 0.03). Presence of NE had high sensitivity (78.2%) and low positive predictive value (19.2%) for detecting moderate-to-severe OSA and low specificity (34.5%) and high negative predictive value (88.8%) for ruling it out.Conclusion:Children with snoring and without NE referred for polysomnography are less likely to have moderate-to-severe OSA compared to those with NE.

Viral croup: Diagnosis and a treatment algorithm

Viral croup is a frequent disease in early childhood. Although it is usually self‐limited, it may occasionally become life‐threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate‐to‐severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15–0.6 mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate‐to‐severe croup. Nebulized budesonide (2 mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department. Pediatr Pulmonol. 2014; 49:421–429.

Family history of adenotonsillectomy as a risk factor for tonsillar hypertrophy and snoring in childhood.

Accumulating evidence supports a role for familial predisposition in the pathogenesis of OSA. In this study, it was hypothesized that parental history of adenoidectomy and/or tonsillectomy (AT), which is the standard treatment for pediatric OSA is a risk factor for tonsillar hypertrophy and habitual snoring (>3 nights/week) in the offspring.

Infants with viral bronchiolitis demonstrate two distinct patterns of nocturnal oxyhaemoglobin desaturation.

This study aimed to demonstrate that viral bronchiolitis is associated with intermittent oxygen saturation of haemoglobin (SpO2) drops (≥3%) and low basal SpO2 between episodes of haemoglobin desaturation.

Low morning serum cortisol levels in children with tonsillar hypertrophy and moderate-to-severe OSA.

BACKGROUND Hypertrophic tonsillar tissue in children with obstructive sleep apnea (OSA) has enhanced expression of glucocorticoid receptors, which may reflect low endogenous cortisol levels. We have evaluated the effect of the interaction between tonsillar hypertrophy and OSA severity on morning serum cortisol levels. METHODS Children with and without snoring underwent polysomnography, tonsillar size grading, and measurement of morning serum cortisol. RESULTS Seventy children (2-13 years old) were recruited: 30 with moderate-to-severe OSA (apnea-hypopnea index [AHI] > 5 episodes/h), 26 with mild OSA (AHI > 1 and ≤ 5), and 14 controls (no snoring; AHI ≤ 1). Tonsillar hypertrophy was present in 56.7%, 53.8%, and 42.9% of participants in each group, respectively. Application of a general linear model demonstrated a significant effect of the interaction between severity of OSA and tonsillar hypertrophy on cortisol levels (P = 0.04), after adjustment for obesity, gender, and age. Among children with tonsillar hypertrophy, subjects with moderate-to-severe OSA (n = 17; AHI 14.7 ± 10.6), mild OSA (n = 14; AHI 2.3 ± 1.2), and control participants (n = 6; AHI 0.7 ± 0.2) were significantly different regarding cortisol levels (P = 0.02). Subjects with moderate-to-severe OSA had lower cortisol (16.9 ± 8.7 mcg/dL) than those with mild OSA (23.3 ± 4.2; P = 0.01) and those without OSA (controls) (23.6 ± 5.3 mcg/dL; P = 0.04). In contrast, children with normal-size tonsils and moderate-to-severe OSA, mild OSA, and controls did not differ in cortisol levels. CONCLUSIONS Children with moderate-to-severe obstructive sleep apnea and the phenotype of hypertrophic tonsils have reduced morning serum cortisol levels and potentially decreased glucocorticoid inhibitory effects on tonsillar growth.

Obstructive sleep apnea, excessive daytime sleepiness, and morning plasma TNF-α levels in Greek children.

BACKGROUND Obstructive sleep apnea (OSA) has been associated with increased frequency of excessive daytime sleepiness (EDS). Increased plasma TNF-α levels may mediate this association in adults, but conflicting results have been reported in children. We hypothesized that: (i) the higher the OSA severity in childhood, the higher the frequency of EDS and morning plasma TNF-α levels; and (ii) high TNF-α levels predict presence of EDS. METHODS Children without and with snoring underwent polysomnography. EDS was determined by parental response to specific questions, and plasma TNF-α levels were measured. RESULTS Children with moderate-to-severe OSA (n = 24; 5.7 ± 2 years; apnea-hypopnea index [AHI] 11.5 ± 5.1/h), but not participants with mild OSA (n = 22; 6 ± 2.5 years; AHI 2.1 ± 1/h) were at significantly higher risk for EDS than controls (n = 22; 6.8 ± 2.1 years; AHI 0.5 ± 0.3/h) (OR [95% CI] adjusted for age, gender, and obesity: 9.2 [1.7-50.2] and 3.8 [0.7-21.8], respectively). The 3 groups did not differ regarding TNF-α concentration (0.63 ± 0.2 vs 0.65 ± 0.18 vs 0.63 ± 0.17 pg/mL; P > 0.05). TNF-α levels were associated significantly with body mass index z-score (P < 0.05) and not with polysomnography indices (P > 0.05). Subjects with high TNF-α levels (> 0.57 pg/mL) were not at higher risk for EDS than participants with low levels (OR [95% CI] adjusted for age, gender, and obesity: 1.7 [0.5-5.7]). CONCLUSIONS Increasing severity of OSA is associated with increasing frequency of EDS, but not with elevated plasma TNF-α concentration. High TNF-α levels cannot be used as predictor for the presence of EDS in children with sleep apnea.

Low-grade albuminuria in children with obstructive sleep apnea

Small urinary protein loss (low‐grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep‐disordered breathing. Albumin‐to‐creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea–hypopnea index < 1 episode h−1; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea–hypopnea index = 1–5 episodes h−1; n = 71); and (iii) moderate‐to‐severe obstructive sleep apnea (snoring, apnea–hypopnea index > 5 episodes∙h−1; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin‐to‐creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate‐to‐severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin‐to‐creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1–12.6); P = 0.04 and 1.5 (0.6–3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin‐to‐creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate‐to‐severe obstructive sleep apnea are at significantly higher risk of increased low‐grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea.

Serum leukotriene B4 levels, tonsillar hypertrophy and sleep-disordered breathing in childhood

OBJECTIVES In children with snoring, increased production of leukotriene B4 (LTB4) may promote tonsillar hypertrophy and sleep-disordered breathing (SDB) or conversely SDB may enhance LTB4 synthesis. We explored whether: i) high LTB4 serum levels predict tonsillar hypertrophy; and ii) SDB severity correlates with LTB4 serum concentration. METHODS Normal-weight children with SDB or controls underwent polysomnography and measurement of LTB4 serum concentration. Tonsillar hypertrophy was the main outcome measure and high LTB4 serum level (>75 t h percentile value in controls) was the primary explanatory variable. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) for tonsillar hypertrophy in children with versus without high LTB4 level were calculated. The control subgroup and subgroups of subjects with increasing SDB severity were compared regarding LTB4 concentration by Kruskal-Wallis test. Spearmans correlation co-efficient was applied to assess the association of LTB4 concentration with SDB severity. RESULTS A total of 104 children with SDB and mean obstructive apnea-hypopnea index-AHI of 4.8 ± 5.3 episodes/h (primary snoring: n = 19; mild SDB: n = 49; moderate/severe SDB: n = 36) and 13 controls (no snoring; AHI: 0.4 ± 0.2 episodes/h) were recruited. The four study subgroups were similar regarding LTB4 serum concentration (P = 0.64). High LTB4 (>170.3 pg/mL) was a significant predictor of tonsillar hypertrophy after adjustment for age and gender (OR 3.0 [1.2-7.2]; P = 0.01). There was no association between AHI or desaturation index and LTB4 serum concentration (r = -0.08; P = 0.37 and r = -0.1; P = 0.30, respectively). CONCLUSION No association was identified between SDB severity and LTB4 levels, but high LTB4 concentration predicted tonsillar hypertrophy.