Serum cytokines in pediatric neuropsychiatric syndromes: focus on Attention Deficit Hyperactivity Disorder.

BACKGROUND: Inflammation may represent a common underlying mechanism in a wide range of diseases, including neuropsychiatric disorders. Cytokine involvement has been investigated in some studies on patients with childhood neuropsychiatric diseases. The aim of this study was to determine whether cytokines are involved in ADHD to provide a rationale for immune-based therapeutic strategies in this disorder. METHODS: Sixty children were studied: 34 consecutive drug-naïve children with ADHD (30 males and 4 females; mean age of 10.10 years, SD=2.43 age) and 26 healthy control children (22 males and 4 females; mean age of 10.70 years, SD=1.81). All cytokines but IL-2 (IL4-IL6-IL10- IL17-TNFA and IFNG) were studied by ELISAs; IL-2 was instead studied by means of paired anti-cytokine Abs and cytokine standards obtained from PharMingen. RESULTS: Data reveal higher IL-6 and IL-10 levels in ADHD patients than in the control group (P=0.03). No differences emerged between the two groups for the other cytokines. CONCLUSIONS: Our study showed an imbalance between pro- and anti-inflammatory cytokines that may play a pivotal role in the pathogenesis of ADHD.

Salivary biomarkers of obstructive sleep apnea syndrome in children.

OBJECTIVES: The present pilot study was performed to evaluate the HPA axis and ANS activity by measuring salivary cortisol and α-amylase diurnal trajectory and production, respectively, in mild or moderate-to-severe (MS) OSA-affected, but otherwise healthy, children. Moreover, a correlative analysis was performed between the salivary biomarker concentrations and the PSG variables characterizing the OSA severity. METHODS: We studied 27 consecutive OSA patients (13 mild OSA; 14 MS OSA) and seven healthy children who were enrolled as controls by collecting salivary samples and measuring cortisol and α-amylase levels using enzyme-linked bioassays. RESULTS: Compared with controls, both mild and MS OSA children showed: (1) increased salivary cortisol diurnal production, (2) maintenance of the physiological circadian activity of the HPA axis, and (3) no changes in α-amylase diurnal trajectory and production. In addition, morning salivary cortisol concentrations was negatively associated with the disease severity in the MS OSA group. CONCLUSIONS: OSA is associated with dysregulation of the HPA axis activity in children, the latter potentially underlying some of the adverse consequences of the disease.

Relationship between atopic asthma and the population prevalence rates for asthma or atopy in children: atopic and nonatopic asthma in epidemiology.

Innumerable articles have tried to solve the "continuing enigma of atopic and nonatopic asthma" but notwithstanding the strenuous efforts to substantiate the few well-known clinico-epidemiologic differences between these two forms of asthma most studies have hitherto generated inconclusive statements. In a recent study based on the review of epidemiologic studies conducted worldwide in unselected populations of children, we documented that the prevalence of atopic asthma (AA) was high in the populations with a high prevalence of atopy. We systematically reviewed 36 articles that studied 48 populations of unselected children and reported prevalence rates for asthma and atopy in the total sample and in the subpopulations. No significant difference was found in the prevalence of asthma cases in the quartiles of childhood populations subdivided for the prevalence of atopy. In addition, atopy did not increase significantly in the subgroups of populations subdivided by asthma quartiles. In both subgroups, however, AA increased with increasing atopy or with increasing asthma (p < 0.001). Using a positive skin-prick test reaction to define cases of asthma as cases of AA is misleading because the prevalence of subjects so defined is heavily influenced by the environmentally generated changes in the prevalence of atopy or asthma. Asthma in a child should be labeled as a case of AA only if skin-prick tests yield a positive reaction and the clinical history documents asthma symptoms triggered by allergen exposure.

Pulse transit time for scoring subcortical arousal in infants with obstructive sleep apnea.

INTRODUCTION: An altered autonomic control and response to respiratory events during sleep have been reported in infants with obstructive sleep apnea but appropriate methods are not established. We assessed the feasibility of pulse transit time (PTT) in detecting subcortical arousals in eight infants (median age 7 days) suffering from the Pierre Robin sequence and obstructive sleep apnea. METHODS: Sleep studies including recordings of PTT performed before and after successful orthodontic treatment for their OSA were analyzed. PTT arousals (i.e., fall in PTT by > or =15 ms lasting for > or =3 s) were visually scored using specific analysis software. Apnea-related PTT arousals and spontaneous PTT arousals were distinguished and predicting factors for the occurrence of uninterpretable PTT signal and PTT arousals were analyzed. RESULTS: Six-hundred and seven apneas were analyzed. Uninterpretable PTT signal appeared in 394 (65%) apneas and were due to a disturbed pulse waveform in 63%. Predictors for the occurrence of uninterpretable PTT signal were type of apnea (odds ratio, 95% confidence interval for obstructive apnea = 0.5, 0.4-0.9) and duration of apnea (odds ratio, 95% confidence interval per second duration = 1.4, 1.3-1.5). Of 213 apneas with interpretable PTT signal, 43 (7% of all apneas) were followed by a PTT arousal. Predictor for their occurrence was treatment status (odds ratio, 95% confidence interval for pre-treatment status = 3.4, 1.3-8.8). Spontaneous PTT arousals during control periods appeared more frequently pre-treatment compared to post-treatment (41% vs. 16%; p-value = 0.001). There were only weak correlations between changes in PTT, heart rate, and arterial oxygen saturation (correlation coefficient <0.3). CONCLUSION: The feasibility of PTT in scoring apnea-related subcortical arousals in infants may be questionable. However, scoring spontaneous PTT arousals may be an approach for assessing sleep disruption in infants with obstructive sleep apnea.

Reduced exhaled nitric oxide in children after testing of maximal expiratory pressures.

Spirometry in adult subjects can induce a fall in concentration of exhaled nitric oxide (FE(NO)). Scarce information is available on the FE(NO) decrease after spirometry or after other forced lung-function maneuvers in children. We compared changes in FE(NO) induced by repeated spirometry and testing of maximal expiratory pressures (P(Emax)). Twenty-four sex- and age-matched children aged 9-18 years (mean age +/- SD, 13.3 +/- 2.8 years; 12 healthy, 12 asthmatic) were allocated to 1-week-apart sessions of repeated maneuvers of either forced vital capacity (FVC) or P(Emax). Baseline FE(NO) measurements were followed by FVC or P(Emax) maneuvers every 15 min for 45 min, whereas FE(NO) was measured at each step for 60 min. After repeated P(Emax) but not after FVC maneuvers, FE(NO) values decreased significantly from baseline in both groups. In healthy children, geometric mean FE(NO) (95% confidence intervals) decreased from 9.1 (7.0-11.8) ppb at baseline to 8.2 (6.3-10.6) ppb at 15 min and 7.7 (5.6-10.6) ppb at 30 min (P < 0.05 and P < 0.01, respectively), and remained unchanged at 45 and 60 min. In asthmatic children, FE(NO) levels fell from 21.6 (13.3-34.9) ppb at baseline to 15.1 (9.1-25.1) ppb at 15 min and remained low at 30, 45, and 60 min: 17.8 (10.7-29.5) ppb, 17.5 (10.2-30.1) ppb, and 17.6 (10.6-29.2) ppb, P < 0.01, for all differences from baseline. Repeated P(Emax) and FVC maneuvers increased FE(NO) variability, as compared with repeated FE(NO) measurements alone. Previous forced lung-function maneuvers may affect FE(NO) measurements in children. Although P(Emax) testing has a greater influence than spirometry on FE(NO) levels in children, both procedures should be avoided before measuring FE(NO).

Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms.

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.

Randomized controlled study of an oral jaw-positioning appliance for the treatment of obstructive sleep apnea in children with malocclusion.

To evaluate the clinical usefulness and tolerability of an oral jaw-positioning appliance in the treatment of obstructive sleep apnea syndrome in children, we studied 32 patients (mean age, 7.1 +/- 2.6 yr; 20 males) with symptoms of obstructive sleep apnea, malocclusion, and a baseline apnea index > 1 event/h. A group of 19 subjects was randomly assigned to a 6-mo trial of an oral appliance; the remainder acted as control subjects. At baseline and after the trial all patients underwent physical examination, a standard polysomnography, and orthodontic assessment. A modified version of the Brouillette questionnaire related to obstructive sleep apnea symptoms was administered to parents before and after the trial and a clinical score was calculated. Of the 32 subjects enrolled, 4 treated subjects and 5 control subjects were lost to follow-up. Polysomnography after the trial showed that treated subjects all had significantly lower apnea index (p < 0.001) and hypopnea index values (p < 0.001) than before the trial, whereas in untreated control subjects these values remained almost unchanged. Clinical assessment before and after treatment showed that in 7 of the 14 subjects (50%) the oral appliance had reduced (a fall of at least 2 points in the respiratory score) and in 7 had resolved the main respiratory symptoms, whereas untreated patients continued to have symptoms. In conclusion, treatment of obstructive sleep apnea syndrome with an oral appliance in children with malocclusion is effective and well tolerated.