Francesca Occasi

Endothelial dysfunction and oxidative stress in children with sleep disordered breathing: Role of NADPH oxidase

OBJECTIVE Oxidative stress plays a crucial role in impairing endothelial function in sleep disordered breathing (SDB) but the underlying mechanism is still undefined. The objective of this study was to evaluate the interplay between oxidative stress, assessed by serum isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function, assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls (HC). METHODS One-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post adeno-tonsillectomy (AT). RESULTS Compared with HC, OSA and PS children had significantly higher sNOX2-dp and serum 8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p<0.001) and with serum 8-iso-PGF2α (p<0.001). In multiple linear regression analysis, sNOX2-dp (p<0.001) and serum 8-iso-PGF2α (p<0.001) were the only independent predictive variables associated with FMD. AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2±8.8 to 22.4±11.1 pg/ml, p<0.001, and from 281.4±69.7 to 226.0±66.4 pg/ml, p<0.001, respectively); conversely, FMD significantly increased after AT in OSA children (from 3.0±1.5 to 8.0±2.8%, p<0.001). CONCLUSION This study suggests that NOX2-derived oxidative stress is involved in artery dysfunction in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally with oxidative stress lowering. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.

High‐mobility group box‐1 (HMGB‐1) and serum soluble receptor for advanced glycation end products (sRAGE) in children affected by vernal keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) is a chronic disease affecting conjunctiva even though the immunopathogenetic mechanisms underlying this inflammation are unclear. The aim of our study is to investigate serum levels of HMGB1 and circulating sRAGE in children affected by VKC before and after treatment with cyclosporine A (CsA) eye drops and in a group of healthy children.

Local Allergic Rhinitis in Children: Novel Diagnostic Features and Potential Biomarkers

Background Local allergic rhinitis (LAR) is a phenotype of rhinitis that has been poorly studied in children. It is characterized by the same symptoms of allergic rhinitis but with the absence of markers of systemic atopy. Objective To identify children affected by LAR and to analyze the pathogenesis of this disease. We chose to focus our attention on interleukin (IL) and thymic stromal lymphopoietin (TSLP). Methods We enrolled 20 children affected by nonallergic rhinitis (negative skin-prick test results and serum specific immunoglobulin E [sIgE] values). Each patient underwent a nasal allergen provocation test (NAPT) with dust mite and grass pollen. Before and after NAPT, nasal lavage was performed to detect sIgE, IL-5, and TSLP; anterior active rhinomanometry was used to evaluate changes in nasal obstruction. Results Two patients were positive to a nonspecific NAPT and, thus, were excluded from the study. Of the remaining 18 children, 12 (66.7%) had positive results to at least one NAPT. Among these 12 patients, nasal sIgE levels for Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Lolium perenne increased significantly after NAPT (D. pteronyssinus, p < 0.005; D. farinae, p < 0.05; L. perenne, p < 0.05). Nasal IL-5 levels showed a significant increase after NAPT (p ≤ 0.006), and this increase was significantly higher in children who had positive NAPT results than in those patients with negative NAPT results (p ≤ 0.03). Among the 12 children who had a positive NAPT result, nasal TSLP was detected in 4 patients (33.3%) and its levels showed a relevant increase after NAPT, even though the difference did not reach statistical significance (p ≤ 0.061). Conclusion Observed results raise the importance of better refining the diagnostic protocol for LAR in children. Nasal TSLP and IL-5 levels offer new insights concerning localized allergic inflammation, although the role of nasal sIgE has still to be clarified.

Cephalometric pattern and nasal patency in children with primary snoring: The evidence of a direct correlation

Introduction Sleep disordered breathing (SDB) might affect craniofacial growth and children with obstructive sleep apnea syndrome present an increase in total and lower anterior heights of the face and a more anterior and inferior position of the hyoid bone when compared to nasal breathers. Objective To investigate the correlation between rhinomanometric and cephalometric parameters in children with primary snoring (PS), without apnea or gas exchange abnormalities. Materials and Methods Thirty children with habitual snoring (16 females and 14 males) aged 4–8 years (mean age 6.85±1.51 years) were selected by a SDB validate questionnaire. All subjects underwent lateral cephalometric, panoramic radiographies. Results In our sample 10 children (33%) had snoring 3 nights/week, 11 (37%) 4–6 nights/week and 9 (30%) every night/week. Overall 7 patients (23.3%) were affected by adenoid hypertrophy (AH), 4 (13.3%) by tonsillar hypertrophy (TH) and 13 (43.3%) by AH and TH. We found a more vertical position of the hyoid bone to the mandibular plane (H⊥VT) in patients with a higher frequency (7.3±2.7 vs 7.6±3.7 vs 10.9±2.5 in children snoring 3 nights/week, 4–6 nights/week and every night/week respectively; p = 0.032). Concerning nasal patency significant correlations were found with ANB (maxillary and jaw position with respect to the cranial base), NS∧Ar (growth predictor), sumangle, FMA (total divergence), SnaSnp∧GoMe (inferior divergence), BaN∧PtGn (facial growth pattern), Phw1_PsP (posterosuperior airway space), AHC3H (the horizontal distance between the most anterosuperior point of the hyoid bone and the third cervical vertebra). Conclusion The present study supports the relationship between nasal obstruction and specific craniofacial characteristics in children with primary snoring and lead us to hypothesize that nasal obstruction might explain the indirect link between snoring and cephalometric alterations.

Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

Introduction Studies on Mean Platelet Volume (MPV) in children with Sleep Disordered Breathing (SDB) report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS) since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP) levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS). Materials and Methods We enrolled 137 children: 70 healthy controls (HC), 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D. Results Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%). MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT) and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; p<0.001), vitamin D (r = -0.39; p<0.001) and CRP (r = 0.21; p<0.01). A multiple regression was run to predict MPV levels from vitamin D, CRP and PLT and these variables significantly predicted MPV (F = 17.42, p<0.0001; adjusted R2 = 0.37). Only platelet count and vitamin D added statistically significantly to the prediction (p<0.05). Conclusion The present study provides evidence of higher MPV and lower vitamin D levels in children with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this previously considered benign form of SDB.

Intranasal budesonide in children affected by persistent allergic rhinitis and its effect on nasal patency and Nasal Obstruction Symptom Evaluation (NOSE) score.

Abstract Background: Intranasal steroids are recognized as an effective treatment for allergic rhinitis (AR) although their effect on nasal patency has never been evaluated with an objective instrument such as anterior rhinomanometry in children. Moreover this effect has been widely assessed with total Nasal Symptom Scores (NSS) including all symptoms of allergic rhinitis and not with scores specifically focused on nasal obstruction such as the Nasal Obstruction Symptom Evaluation score (NOSE). Materials and methods: Sixty children (42 males and 18 female) aged 6–10 years, affected by persistent AR, were randomized and divided in two groups of 30 children to be included in an unblinded trial: one group treated with intranasal budesonide and isotonic nasal saline for 2 weeks and the other group treated only with isotonic nasal saline for 2 weeks. Each child underwent rhinomanometry and completed the NSS and the NOSE scores before and after treatment. Results: At the baseline nasal patency and NSS total score, NOSE total scores were correlated (r = −0.29, p < 0.001; r = −60, p < 0.001). After 2 weeks of treatment improvements in nasal patency, NSS and NOSE were seen (Δ NSS 4.13 ± 1.38 vs 1.33 ± 1.93, p < 0.001; Δ NOSE 34 ± 17.97 vs 9 ± 18.21, p < 0.001; Δ nasal patency −26.13 ± 25.25 vs −11.83 ± 11.31, p < 0.001). Correlations were found between rhinitis duration and Δ nasal patency and Δ NOSE (r = −0.84, p < 0.001; r = 0.43, p < 0.01). Conclusion: Intranasal budesonide is effective in increasing nasal patency in children. Moreover the NOSE score was strongly correlated with nasal flow and, hence, this score should be regarded as a valid and reliable instrument in children.

Primary school children often underestimate their nasal obstruction.

BACKGROUND No consensus has ever been reached about the correlation between nasal resistance and the subjective sensation of nasal patency. The aim of the present study was to better de ne whether primary school and secondary school aged children correctly estimate their nasal obstruction. MATERIALS AND METHODS Two hundred eighty four children (168 males and 116 female) aged between 6 and 14 years (9.5+2.9 years) affected by Pediatric Allergic Rhinitis underwent Rhinomanometry and they were considered as correctly estimating their nasal obstruction when the grade of nasal patency corresponded to the severity of the NOSE score, overestimating when the grade of nasal patency was <1 when compared to the severity of the score, underestimating when the grade of nasal patency was >1 when compared to the severity of the score. RESULTS Correlation between NOSE score and nasal patency was statistically significant (r -0.74; p<0.001). Children between 6 and 9 years of age underestimate (43.7%) and children >12 overestimate (34.7%) their symptoms more frequently than children among other age ranges (p<0.001). CONCLUSION Although NOSE score approximately allow to quantify nasal obstruction, in children, especially between 6 and 9 years of age, an objective measurement of nasal patency should be performed to better define the therapeutic approach.

Stroke and migraine is there a possible comorbidity

The association between migraine and stroke is still a dilemma for neurologists. Migraine is associated with an increased stroke risk and it is considered an independent risk factor for ischaemic stroke in a particular subgroup of patients. The pathogenesis is still unknown even if several studies report some common biochemical mechanisms between these two diseases. A classification of migraine-related stroke that encompasses the full spectrum of the possible relationship between migraine and stroke includes three main entities: coexisting stroke and migraine, stroke with clinical features of migraine, and migraine-induced stroke. The concept of migraine-induced stroke is well represented by migrainous infarction and it is described in the revised classification of the International Headache Society (IHS), representing the strongest demonstration of the relationship between ischaemic stroke and migraine. A very interesting common condition in stroke and migraine is patent foramen ovale (PFO) which could play a pathogenetic role in both disorders. The neuroradiological evidence of subclinical lesions most typical in the white matter and in the posterior artery territories in patients with migraine, opens a new field of research. In conclusion the association between migraine and stroke remains an open question. Solving the above mentioned issues is fundamental to understand the epidemiologic, pathogenetic and clinical aspects of migraine-related stroke.

Sublingual immunotherapy in children and its potential beneficial collateral effect on respiratory tract infections.

Abstract Although directed to the control of allergic symptoms, a possible effect of sublingual immunotherapy (SLIT) on susceptibility to infections has been hypothesized. Two hundred sixty-five children aged between 3 and 4 years of age affected by allergic rhinitis completed a 6 year prospective case–control study. One hundred forty-three children after 2 years of SLIT reported a lower prevalence of respiratory tract infections when compared to children not undergoing SLIT.

Serum resistin levels in children with primary snoring.

Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described as an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS.