Konstantinos Chaidas

Urine levels of catecholamines in Greek children with obstructive sleep-disordered breathing†

Adults with obstructive sleep apnea have increased sympathetic activity. It was hypothesized that in children with symptoms of obstructive sleep‐disordered breathing (SDB), morning urine levels of catecholamines correlate with severity of nocturnal hypoxemia.

Absence of blood pressure, metabolic, and inflammatory marker changes after adenotonsillectomy for sleep apnea in Greek children.

Pediatric studies revealed associations of obstructive sleep‐disordered breathing (SDB) with inflammation, metabolic dysfunction, and elevated blood pressure. Evidence about effects of adenotonsillectomy on these abnormalities is scarce. Aim of this investigation was to assess changes in C‐reactive protein (CRP), circulating intercellular adhesion molecule‐1 (cICAM‐1), insulin and blood pressure levels after adenotonsillectomy for SDB in Greek children.

Urine Concentrations of Cysteinyl Leukotrienes in Children With Obstructive Sleep-Disordered Breathing

BACKGROUND Adenotonsillar tissue of children with obstructive sleep-disordered breathing (SDB) has increased content of cysteinyl leukotrienes (CysLTs) and expression of CysLTs receptors. Furthermore, CysLTs concentrations in the nasal exhaled breath condensate of children with sleep apnea are elevated. OBJECTIVE To investigate the relationship between urine levels of CysLTs and severity of SDB in children. METHODS Morning urine concentrations of CysLTs were measured in children with symptoms of SDB and in control subjects with recurrent tonsillitis and without snoring who underwent polysomnography and were expressed in pg/mL per mg/dL of urine creatinine. RESULTS Nineteen children with moderate-to-severe SDB (mean [+/- SD] age, 5.4 +/- 1.6 years; obstructive apnea-hypopnea index [OAHI]: 14.4 +/- 9.6 episodes/h), 29 subjects with mild SDB (5.1 +/- 1.5 years; OAHI: 2.9 +/- 0.8 episodes/h), 26 children with primary snoring (PS) [7 +/- 2.6 years; OAHI: 1.1 +/- 0.3 episodes/h], and 18 control subjects (6.4 +/- 2.5 years; OAHI: 0.7 +/- 0.3 episodes/h) were studied. Children with moderate-to severe SDB had higher log-transformed urine CysLTs levels than those with mild SDB, PS, or control subjects (2.39 +/- 0.51 vs 2.06 +/- 0.26 vs 2.11 +/- 0.25 vs 1.86 +/- 0.28; p < 0.05). Log-transformed CysLTs concentration, tonsillar size, and body mass index z score were significant predictors of log-transformed OAHI (p < 0.01). CONCLUSIONS Urine excretion of CysLTs is related to SDB severity in children. This finding indicates that 5-lipoxygenase pathway products participate in the pathogenesis of obstructive sleep apnea in childhood or alternatively that SDB promotes CysLTs biosynthesis.

Cysteinyl Leukotriene Receptors Are Expressed by Tonsillar T Cells of Children With Obstructive Sleep Apnea

BACKGROUND Increased expression of cysteinyl leukotriene receptors (cysteinyl leukotriene receptor-1 [LT1-R]; cysteinyl leukotriene receptor-2 [LT2-R]) has been detected in adenotonsillar tissue from children with sleep-disordered breathing (SDB) compared to control subjects. LT1-R has been localized in myeloperoxidase-positive cells. This phenomenon possibly contributes to lymphoid tissue enlargement and may be related to systemic inflammation. OBJECTIVE To characterize cells expressing LT1-R and LT2-R in tonsillar tissue and assess serum C-reactive protein (CRP) levels in children with and without SDB. METHODS Immunohistochemistry with LT1-R and LT2-R antibodies was used to examine tonsils from children who had tonsillectomy (with or without adenoidectomy) for SDB and from control subjects operated for recurrent tonsillitis/otitis. All participants underwent preoperative polysomnography and measurement of morning serum CRP. RESULTS Fifteen children with SDB (mean age +/- SD, 6.4 +/- 2.1 years; apnea-hypopnea index, 9.6 +/- 5.6 episodes per hour) and 11 control subjects (age, 7.5 +/- 2.8 years; apnea-hypopnea index, 7 +/- 0.3/h) were examined. Immunoreactivity for LT1-R and LT2-R was detected in tonsillar extrafollicular areas of all subjects with SDB but not of control subjects. Cells expressing leukotriene receptors were CD3+ lymphocytes. Children with SDB and control subjects were similar regarding CRP levels: 0.11 +/- 0.15 mg/dL vs 0.09 +/- 0.15 mg/dL, respectively (p > 0.05). CONCLUSIONS Tonsils of children with SDB but not of control subjects have enhanced expression of cysteinyl leukotriene receptors in T lymphocytes without an associated increase in serum CRP concentration. Up-regulation of LT1-R and LT2-R could potentially promote tonsillar enlargement in children with obstructive sleep apnea.

Obesity and Persisting Sleep Apnea After Adenotonsillectomy in Greek Children

BACKGROUND The relative importance of obesity and adenotonsillar hypertrophy in the pathogenesis of obstructive sleep-disordered breathing (SDB) in childhood is unclear. Adenotonsillectomy (AT) for SDB is not always curative, and obese children are at increased risk for residual disease postoperatively. OBJECTIVE The aim of this investigation was to assess the efficacy of AT as treatment for SDB in obese and nonobese children. METHODS Children with adenoidal and/or tonsillar hypertrophy who underwent AT for the treatment of SDB underwent polysomnography preoperatively and postoperatively. A body mass index (BMI) z score of > 1.645 was used to define obesity. The achievement of a postoperative obstructive apnea-hypopnea index (OAHI) of less than one episode per hour (ie, the cure of SDB) was the primary outcome measure. RESULTS Twenty-two obese children (mean [+/- SD] age, 5.8 +/- 1.8 years; mean BMI z score, 2.6 +/- 0.8; mean OAHI, 9.5 +/- 9.7 episodes per hour) and 48 nonobese children (mean age, 6.9 +/- 2.6 years; mean BMI z score, 0.09 +/- 1.1; OAHI, 6 +/- 5.4 episodes per hour) were recruited. After surgery, obese and nonobese subjects did not differ in the efficacy of AT (postoperative OAHI of less than one episode per hour, 22.7% vs 25% of subjects, respectively; p > 0.05). The presence of obesity, adenoidal or tonsillar hypertrophy, gender, and postoperative BMI change were not significant predictors of SDB cure. CONCLUSIONS Obesity does not necessarily predict an unfavorable outcome of AT as treatment for SDB.

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.

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.

BACKGROUND Preliminary 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. METHODS The genetic risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (ORG), 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. RESULTS In 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 ORG, 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 ORG, 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. CONCLUSIONS Genetic 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.

Tonsilloplasty versus tonsillectomy in children with sleep-disordered breathing: Short- and long-term outcomes

Adenoidectomy and tonsillectomy (TE) is the standard treatment for obstructive sleep‐disordered breathing (SDB) in children with adenotonsillar hypertrophy. Tonsilloplasty (TP) is a new surgical technique that includes partial TE. The purpose of this study was to assess the short‐ and long‐term outcomes of TP compared to TE.

Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing.

BACKGROUND Diminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB). OBJECTIVES To assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure. METHODS Morning nitrite, the sum of nitrite and nitrate (NO(x)), and the average of evening and morning blood pressure were assessed in children with SDB referred for polysomnography and in controls without SDB. RESULTS Forty-three children with SDB (age: 5.8+/-2.1 years) had moderate-to-severe nocturnal hypoxemia (SpO(2) nadir: 85.6+/-4%), 54 subjects (6.6+/-2.7 years) had mild hypoxemia (SpO(2) nadir: 91.4+/-1.3%) and 20 subjects were controls free of SDB (6.7+/-3.7 years). Subjects with moderate-to-severe hypoxemia had significantly lower ln-transformed NO metabolites (1.4+/-0.7, nitrites; 2.6+/-0.5, NO(x)) compared to those with mild hypoxemia (1.9+/-0.8, nitrites; 3+/-0.6, NO(x)) and controls (2.2+/-0.7, nitrite; 3+/-0.6, NO(x); p<0.05). The effects of NO metabolites and SDB or their interaction on blood pressure were not significant (p>0.05). CONCLUSIONS Moderate-to-severe hypoxemia accompanying SDB is associated with reduced concentrations of morning serum NO metabolites, but NO levels do not seem to affect blood pressure.

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.