Adiposity and low-grade systemic inflammation modulate matrix metalloproteinase-9 levels in Greek children with sleep apnea.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C-reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children. METHODS: Consecutive children with snoring who underwent polysomnography and were found to have OSA (obstructive apnea-hypopnea index-OAHI > or = 1 episode/hr) were recruited. Subjects without OSA (OAHI < 1 episode/hr) were included for comparison. Morning plasma MMP-9 and CRP were measured. RESULTS: Twenty-nine children with moderate-to-severe OSA (age 5.4 +/- 1.5 years; OAHI 13.9 +/- 13.0 episodes/hr), 55 participants with mild OSA (6.4 +/- 2.6 years; OAHI 2.4 +/- 1.1 episodes/hr) and 22 subjects without OSA (6.8 +/- 2.6 years; OAHI 0.6 +/- 0.2 episodes/hr) were studied. Children with moderate-to-severe OSA were similar to those with mild OSA or without OSA regarding ln-transformed MMP-9 values (5.87 +/- 0.60 vs. 5.84 +/- 0.55 vs. 5.80 +/- 0.46; P > 0.05) and CRP concentrations (0.22 +/- 0.29 mg/dl vs. 0.21 +/- 0.36 vs. 0.13 +/- 0.16 mg/dl; P > 0.05). In multiple linear regression, body mass index (P = 0.027) and CRP levels (P = 0.008), but not OAHI or SpO(2) nadir (P > 0.05), were significantly related to MMP-9 values. CONCLUSIONS: Adiposity and systemic inflammation unrelated to OSA severity, modulate MMP-9 levels in Greek children.

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.

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.

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.