Identification of a novel RPGR mutation associated with retinitis pigmentosa and primary ciliary dyskinesia in a Slovak family: a case report.

Background: The mutations in the RPGR (retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype. Methods: Two young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing. Results: We identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients. Conclusion: The identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype-phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.

Polysomnographic profile in children diagnosed with celiac disease before starting on a gluten free diet.

STUDY AIMS: The study assessed the presence of sleep abnormalities in children who had recently been diagnosed with celiac disease (CD) and not started a gluten free diet (GFD). The children's polysomnographic profiles were also characterized and further compared with healthy children of the same age. METHODS: This prospective cross-sectional study involved 46 pediatric subjects (aged 1-19 years) who had recently been diagnosed with CD and not started a GFD. The control group consisted of 32 healthy children (aged 2-17 years). All children underwent anthropometric measurement, laboratory testing and standard overnight observation with in-laboratory video-PSG. The study and control group were divided into subgroups according to the subjects' median ages (8.1 years): celiac children aged less than 8.1 years (n = 23) and more than 8.1 years (n = 23), healthy children less aged than 8.1 years (n = 16) and more than 8.1 years (n = 16). RESULTS: No significant differences in the basic demographic and anthropometric parameters between the celiac and control group were observed. Significantly prolonged sleep latency (SOL) was evident in the celiac subjects (21.89 ± 20.77 min. vs. 10.99 ± 7.94 min, p = 0.02), with a probability of prolonged SOL of 4.23-fold greater (OR = 4.23; 95 % CI 1.1-16.22) than the healthy controls, especially in the subgroup of older celiac patients. No significant differences in the sleep period time (SPT), total sleep time (TST), wake during sleep (WASO), sleep efficiency (SE) and sleep stage distribution and cyclization were found. The respiratory rates during sleep indicated a significantly greater incidence of the central apnea-hypopnea index (CAHI) (0.54 ± 0.78 vs. 0.18 ± 0.24, p = 0.03) with a 3.16-fold greater probability of pathological CAHI (OR = 3.16; 95 % CI 1.02-9.77) than the control group. An increased incidence of CSA in the subgroup of younger celiac patients compared to younger healthy controls was especially evident. CONCLUSIONS: The findings of our study suggest a difference in sleep architecture and an increased incidence of CSA in children with untreated CD, but additional research is required to verify the results.

Dysfunctional mucociliary clearance in asthma and airway remodeling - New insights into an old topic.

Bronchial asthma is a heterogeneous respiratory condition characterized by chronic airway inflammation, airway hyperresponsiveness and airway structural changes (known as remodeling). The clinical symptoms can be evoked by (non)specific triggers, and their intensity varies over time. In the past, treatment was mainly focusing on symptoms' alleviation; in contrast modern treatment strategies target the underlying inflammation, even during asymptomatic periods. Components of airway remodeling include epithelial cell shedding and dysfunction, goblet cell hyperplasia, subepithelial matrix protein deposition, fibrosis, neoangiogenesis, airway smooth muscle cell hypertrophy and hyperplasia. Among the other important, and frequently forgotten aspects of airway remodeling, also loss of epithelial barrier integrity, immune defects in anti-infectious defence and mucociliary clearance (MCC) dysfunction should be pointed out. Mucociliary clearance represents one of the most important defence airway mechanisms. Several studies in asthmatics demonstrated various dysfunctions in MCC - e.g., ciliated cells displaying intracellular disorientation, abnormal cilia and cytoplasmic blebs. Moreover, excessive mucus production and persistent cough are one of the well-recognized features of severe asthma and are also associated with defects in MCC. Damaged airway epithelium and impaired function of the ciliary cells leads to MCC dysfunction resulting in higher susceptibility to infection and inflammation. Therefore, new strategies aimed on restoring the remodeling changes and MCC dysfunction could present a new therapeutic approach for the management of asthma and other chronic respiratory diseases.

Cryotherapy in the paediatric airway: Indications, success and safety.

BACKGROUND AND OBJECTIVE: Cryotherapy in interventional bronchoscopy is a new treatment modality, which has recently been made available for the paediatric airway. Lack of experience and safety concerns have led to hesitant adaptation. The aim of this study was to assess indications, success rates and complications of airway cryotherapy in children. METHODS: Bronchoscopists from medical centre performing cryotherapy in patients between 0 and 18 years were invited to participate in a prospective study based on an online questionnaire. Patient and participant data were collected between June 2020 and June 2021. RESULTS: A total of 69 cryotherapy procedures were performed in 57 patients a for three main indications: Biopsy (30), restoration of airway patency (23) and foreign body aspiration (16). The overall success rate was 93%, the remaining 7% were performed for foreign body removal and required a switch of technique. Restoration of airway patency was successfully applied in various pathologies, including mucus plugs, bronchial casts and post traumatic stenosis. The diagnostic yield of transbronchial biopsies was 96%. No severe complications were encountered; one pneumothorax following a cryobiopsy required a chest drain for 48 h. No child was admitted to intensive care or died from a procedural complication. CONCLUSION: In this largest paediatric case collection to date, cryotherapy was safe and carried a high success rate. Cryobiopsy compares favourably to the widely used forceps biopsy and could replace it in the future. Paediatric bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions.

Changes in Cough Reflex Sensitivity in Children After Removal of Hypertrophied Adenoid Tissue.

Purpose: The co-occurrence of adenoids and chronic cough is common in children. The goal of this research was to specify changes in cough reflex sensitivity as a result of adenoid tissue removal. Patients and Methods: The sample group consisted of 17 children (six boys and 11 girls, aged 4-12 years, mean age 6.24 years), all of them possessing symptoms of chronic cough and adenoids, confirmed by nasal fiberoptic endoscopy. This sample group underwent cough reflex sensitivity assessment, which took place both prior to and after endoscopic adenoidectomy. The definition of the cough reflex sensitivity is the lowest capsaicin concentration that caused two (C2) or five (C5) coughs. Capsaicin aerosol in ascending concentrations (from 0.61 to 1250 µmol/L) was inhaled by a single-breath method (KoKo DigiDoser), with the addition of an inspiratory flow regulator valve (RIFR). Results: Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Cough sensitivity (geometric mean with 95% CI) for C2 was 31.86 (12.98-78.18) µmol/L preoperatively and 11.97 (6.16-23.26) µmol/L postoperatively (P=0.064). Cough sensitivity for C5 was 234.91 (97.19-567.77) µmol/L preoperatively and 69.13 (29.08-164.35) µmol/L postoperatively (P=0.022). The children's pulmonary function was within the normal range. Conclusion: In our study, adenoidectomy significantly increased cough reflex sensitivity in non-atopic children suffering from chronic cough.

Psychotic Episode and Schizophrenia in Slovakian Narcolepsy Database.

Narcolepsy type 1 (NT1), a central disorder of hypersomnolence, is associated with mood, anxiety or hyperactivity mental disorders. Association with psychotic episode or schizophrenia is rare and could be the source of diagnostic and therapeutic difficulties. Their frequency in the national narcolepsy database has not been systematically studied. The aim of the presented study was to calculate the frequency of NT1 patients diagnosed with psychosis and/or schizophrenia, to identify clinical characteristics of these cases, and to look for narcoleptic and psychotic symptoms during re-evaluation years later. We identified three (4%) cases diagnosed with a psychotic episode in the course of NT1. They were diagnosed with NT1 by age ≤18 years. In the re-evaluation (mean follow-up 9.8 years), we identified one case with a dual diagnosis of NT1 and schizophrenia; two cases were diagnosed with a solitary psychotic episode in the course of NT1. NT1 patients diagnosed in the age ≤18 years are at higher risk of psychotic episode, and this may be related to higher vulnerability during the ongoing neurodevelopmental period. Comorbid schizophrenia with NT1 in the Slovakian Narcolepsy Database was within the prevalence expected in the general population. The solitary psychotic episode in the course of NT1 did not reduce the possibility of subsequent symptomatic treatment afterwards.

Reference Values for Cardiopulmonary Exercise Testing in Young Male Slovak Athletes.

BACKGROUND: The reference values of young athletes for cardiopulmonary exercise testing are lacking. Expert opinions encourage production of local values specific for certain population. PATIENTS AND METHODS: The study population consisted of 136 healthy male caucasian athletic children and adolescents coming from one specific football school in northern Slovakia. Exercise testing with continuous electrocardiography was performed, and ventilatory parameters, oxygen uptake (VO2), and carbon dioxide (CO2) production were measured continuously with a respiratory gas analysis system. RESULTS: Peak VO2max/kg was changing very little across the childhood, whereas the peak work rate, heart rate and O2Pulse were. Linear regression analysis showed a significant effect of age on VE/VCO2. CONCLUSION: This work provides a reference values for the most important cardiopulmonary variables that can be obtained during cardiopulmonary exercise testing in athletic children.

Young and exhausted.

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a complicated disease characterized by extreme fatigue of at least six months duration. It is necessary to rule out the organic cause of CFS in the pediatric patient in order not to overlook the preventable or the treatable condition. In our case report we present a case of a patient with a surprising origin OF CFS/ME diagnosed by cardiopulmonary exercise testing.

Negative impact of anesthesia with midazolam, sufentanil, and propofol used in pediatric flexible bronchoscopy on the tracheal ciliary beat frequency in guinea pigs.

There is no direct evidence for the exact cilia-inhibitory effects of opioids, which are generally used to achieve general anesthesia in combination with other anesthetic drugs. These are the reasons, why we analysed direct concentration-dependent or systemic effects of anesthetics (propofol, sufentanil, and midazolam) at a recommended doses administered individually or simultaneously on the tracheal ciliary beat frequency (CBF) in in vitro experimental conditions. Brush biopsy technique was used to remove the tracheal epithelia of guinea pigs for microscopy evaluation of ciliary beating monitored by high-speed video camera and analysed by Ciliary Analysis software. The tracheal CBF was significantly lower in the presence of sufentanil (10-8 mol/L) than in the control group; similarly for midazolam-sufentanil (10-8 - 10-5 mol/L), as well as for midazolam-propofol (10-5 and 10-3 mol/L) combinations. The fact that concurrent administration of benzodiazepine significantly increased the risk of sufentanil-induced cilia-inhibition was pharmacologically confirmed using GABAA receptor antagonist, bicuculline methiodide. The benefit of propofol on the potent cilia-inhibitory effect achieved by benzodiazepine-opioid combination was non-significant. We highlight the pharmacodynamics interaction between anesthetic drugs mediated via GABAA receptor with negative impact on the CBF in a respiratory epithelium under experimental condition rather than the effect of individual anesthetic.

Ciliary beat frequency in children with adenoid hypertrophy.

BACKGROUND: Children with adenoid hypertrophy (AH) have impaired respiratory system defense mechanisms, such as mucociliary clearance. We hypothesized that AH negatively affects one of the most important aspects of mucociliary clearance-ciliary beat frequency (CBF) and that adenoidectomy could potentially restore this essential defence mechanism of the airways. This study evaluated the influence of AH and endoscopic adenoidectomy on the CBF of the nasal respiratory epithelium in children. METHODS: This prospective study included 64 children with confirmed AH aged 3 to 18 years and 43 age- and sex-matched healthy controls. Nasal CBF was analyzed using a digital high-speed video microscope and the software application Ciliary Analysis (NI LabVIEW). The preoperative adenoid size was assessed according to Cassano. Clinical symptoms of chronic rhinosinusitis were evaluated using the SNOT-20 questionnaire. RESULTS: Children with AH had a median CBF of 5.35 ± 1.06 Hz. Six months after surgery, the median CBF was significantly higher (6.48 ± 0.88 Hz; P < .001) and reached the values of healthy children (6.37 ± 0.71 Hz; P = .512). The size of the adenoid tissue did not correlate with the CBF. No influence of age or gender on the CBF was found. After adenoidectomy, a significant reduction of the mean total SNOT-20 score was recorded (P < .01). CONCLUSION: Children with clinically symptomatic AH have impaired mucociliary clearance due to decreased nasal CBF. Removal of hypertrophic adenoid tissue normalizes the CBF and reduces the presence of clinical symptoms of rhinosinusitis.

Narcolepsy in Slovakia - Epidemiology, clinical and polysomnographic features, comorbid diagnoses: a case-control study.

OBJECTIVE: An increase in the incidence of narcolepsy after the pandemic influenza with the H1N1 vaccination in 2009 resulted in an interest in narcolepsy epidemiology. The aim of the study was to examine the incidence and prevalence rates of narcolepsy and to describe the associated characteristics in Slovakia. METHODS: Epidemiology data were calculated for each year from 2000 to 2017 based on records found in specialized centres. In sum, 61 narcoleptic patients were diagnosed, of which 51 (84%) had narcolepsy type 1 (NT1). Clinical data and results of polysomnography (PSG), Human Leukocyte Antigen (HLA)-typing, hypocretin (HCRT)-1 levels and body mass index (BMI) were summarised and evaluated for NT1 and narcolepsy type2 (NT2). Later, 244 sex and age matched controls were chosen to evaluate the comorbid diagnoses. RESULTS: The prevalence of narcolepsy in 2017 in Slovakia was 10.47 (CI 95% 8.26-14) cases/million inhabitants, and the mean incidence rate (2000-2017) was 0.57 (CI 95% 0.4-0.74) cases/million inhabitants. Narcoleptic patients were comorbid with arterial hypertension (17%), ischemic heart disease (8%), dyslipidaemia (18%), diabetes mellitus type 2 (10%), cardiac arrhythmia/atrial fibrillation (5%), autoimmune disorders (20%), allergy (11%), malignancy (3%), headache (15%) and mental disorders (20%). Patients with narcolepsy showed double the excess prevalence in mental disorders (OR 2.15, p < 0.05), and dyslipidaemia (OR 2.22, p < 0.05). The presence of autoimmune disorders and allergy showed a mild increase in the narcolepsy group (OR 1.46, resp. 1.63). Hashimoto thyroiditis (HT) was the most frequent autoimmune disorder. CONCLUSIONS: Narcolepsy is a rare disorder in Slovakia. From the phenotype, genetic characteristics and comorbidities the disorder does not vary from other European countries.

Endothelial Dysfunction in Children with Juvenile Psoriatic Arthritis.

BACKGROUND: To evaluate the presence of endothelial dysfunction in Slovak children with juvenile psoriatic arthritis in the absence of classic cardiovascular risk factors in order to assess its relationship to the disease activity and disability. METHODS: 25 juvenile psoriatic arthritis patients (JPSA) and 25 healthy controls aged 6-19 years were enrolled into this study. In all subjects vascular measurements over a period of three years (January 2013 - January 2016) were performed, in accordance with the guidelines for ultrasonographic evaluation of FMD% (flow-mediated endothelial dependent vasodilatation) of the brachial artery. The measured items were compared to the variables reflecting the disease activity and disability. RESULTS: Significantly lower FMD% values in patients with JPSA when compared to healthy controls {mean(SD), median, range: 5.49% (3.77), 3.55, 0.3-13.0 vs. 9.28% (1.72), 9.3, 6.4-13.1} (p < 0.001) have been documented. Strong correlations between FMD% values and disease duration (p < 0.01), non-specific inflammatory markers levels (p < 0.001) or functional disability (p < 0.01) have been observed. Significantly lower FMD% values in patients with an early disease onset (JPSA onset < 5 years of age) when compared to the rest of JPSA group {mean (SD), median, range: 4.39% (2.47), 4.45, 0.9-13.2 vs. 6.38% (1.42), 6.3, 3.2-12.1} (p < 0.01) have also been detected. CONCLUSION: Study is the only one addressing endothelial dysfunction development in Slovak children with psoriatic arthritides. We state that endothelial dysfunction is present in these patients even during childhood and in the absence of classic cardiovascular risk factors. Its development seems to be related to an early disease onset as well as to the increased disease activity and disability. Potential genetic predictors have also been identified.

Association of Polymorphisms in CYBA, SOD1, and CAT Genes with Type 1 Diabetes and Diabetic Peripheral Neuropathy in Children and Adolescents.

AIMS: The aim of our study was to investigate possible associations between three SNPs: rs4673 in the CYBA gene; rs1041740 in the SOD1 gene; and rs1001179 in the CAT gene, and type 1 diabetes (T1D) or diabetic peripheral neuropathy (DPN) in T1D patients. MATERIALS AND METHODS: Allelic variants of the selected SNPs were determined by allelic discrimination assays in 114 T1D patients enrolled in the study group and in 90 healthy individuals from a control group. Associations between each of the three SNPs were tested in subgroups of T1D patients divided according to the presence of DPN. RESULTS: The TT genotype of rs4673 in the CYBA gene was associated with DPN in T1D patients (OR 4.997, 95% CI 1.403-19.083, p = 0.016). Weak significance was observed for a protective effect of the TT genotype of rs1041740 in the SOD1 gene relative to T1D development (OR 0.318, 95% CI 0.092-0.959, p = 0.056). There was no significant association between the CAT gene SNP rs1001179 and T1D or DPN. CONCLUSION: We showed a strong association of the CYBA polymorphism rs4673 with DPN in Slovak children and adolescents with T1D. Further studies are necessary to assess the relationship between rs1041740 and T1D or DPN.

Short-term metabolic control and sleep in children and adolescents with type 1 diabetes mellitus.

AIMS: The aim of this study was to examine sleep in T1D children and in healthy controls by polysomnographic (PSG) examination and to determine the influence of short-term metabolic compensation on sleep quality and sleep disordered breathing (SDB). METHODS: The prospective cross-sectional study included 44 T1D subjects and 60 healthy controls, aged 10-19 years. Subjects underwent anthropometric measurements, laboratory testing and standard overnight in-laboratory video polysomnography with continuous glucose monitoring (CGM). RESULTS: No significant differences were found in total sleep time, sleep efficiency, percentage of sleep stages and respiratory parameters between T1D and healthy group. T1D children with more optimal short-term metabolic control (AvgSG < 10 mmol/l, n = 18) had a significantly lower apnea-hypopnea index (AHI) (0.3(0-0.5) vs. 0.6 (0.2-0.9) events/h, p < 0.05)and respiratory arousal index (0(0-0,1) vs. 0.2(0-0.3)), p < 0.01) compared to children with suboptimal short-term control(n = 26), no significant differences were found in parameters of sleep architecture. Obstructive sleep apnea (OSA) was diagnosed in only one T1D patient, nine T1D children had mild central apnea. CONCLUSIONS: There may be an association between short-term metabolic compensation and SDB in T1D children without chronic complications, obesity or overweight and hypoglycemia. Further research is needed to confirm this result.

The effect of adenoidectomy on transnasal airflow in children with hypertrophy of adenoid tissue.

BACKGROUND: The aim of this study was to clarify changes of transnasal airflow resulting from adenoidectomy and to assess the effect of surgery depending on adenoid hypertrophy (AH) obstruction grade. MATERIALS AND METHODS: Altogether fifty children having symptoms of nasal obstruction and adenoids were submitted to a rhinomanometric assessment before and after adenoidectomy. At the same time, using the nasal fiberoptic endoscopy, the grade of AH obstruction was determined, according to which the children were divided into four classes. We assessed the change of total transnasal inspiratory airflow and total nasal resistance due to adenoidectomy. RESULTS: Values of transnasal airflow and nasal resistance measured in the study group of fifty children were preoperatively 262 mL/s and 0.565 kPa/L/s; postoperatively 288 mL/s and 0.52 kPa/L/s. We have noticed statistically significant increase of the airflow (P = 0.015); however, decrease of the resistance (P = 0.054) was not significant. In the group of children suffering from the 1st to 2nd grade (29 children) preoperatively measured values presented 280 mL/s and 0.52 kPa/L/s; postoperatively, 276 mL/s and 0.54 kPa/L/s; change of the airflow (P = 0.634) and resistance (P = 0.829) was not significant. In the study group having the 3rd and 4th grade (21 children), the values indicated preoperatively 240 mL/s and 0.62 kPa/L/s; postoperatively, 340 mL/s and 0.44 kPa/L/s; there were significant airflow increase (P = 0.012) and resistance decrease (P = 0.033). CONCLUSIONS: Adenoidectomy significantly increased the airflow; however, we observed the different effect in the group of children with the 1st and 2nd grade compared to the group with the 3rd and 4th grade. A significant increase of the airflow and decrease of the resistance were present only in the group with the 3rd and 4th grade; therefore, the significant reduction of nasal obstruction symptoms might be expected only in this group of patients.

Sleep Architecture in Children With Common Phenotype of Obstructive Sleep Apnea.

STUDY OBJECTIVES: In children, the effect of the common phenotype of obstructive sleep apnea (OSA) on sleep architecture is not adequately documented. The aim of this study was to evaluate sleep architecture in a pediatric population with the common phenotype of OSA. METHODS: The prospective cross-sectional study included 116 children in the age range of 3 to 8 years with suspected OSA and 51 healthy children. All children underwent standard overnight in-laboratory video polysomnography. Patients with obstructive apnea-hypopnea index ≥ 1, adenotonsillar hypertrophy, a long face, narrow palate or minor malocclusions, and no obesity were defined as a common phenotype. Polysomnographic parameters of sleep architecture and sleep clinical record were statistically analyzed according to OSA and its severity. RESULTS: In total, 94 pediatric patients (59.60% male) received the diagnosis of the common phenotype of OSA (mean age of 5.25 ± 1.39 years). A lower percentage of stage N3 sleep (27.70 ± 3.76% versus 31.02 ± 4.23%; P < .05), a greater percentage of stage N1 sleep (8.40 ± 3.98% versus 2.68 ± 3.02%, P < .01), reduced deep sleep efficiency (46.01 ± 4.98% versus 50.25 ± 3.72%; P < .05) and longer sleep latency (18.40 ± 8.48 minutes versus 9.90 ± 11.55 minutes, P < .01) were found in children with the common phenotype of OSA compared with healthy controls. No significant differences were found in total sleep time, sleep efficiency, and percentage of stage R sleep and stage N2 sleep between groups and in sleep stage distribution and cyclization. CONCLUSIONS: These findings suggest that the most common phenotype of pediatric OSA has a negative effect on the structure of sleep, but other clinical studies are needed to confirm this result.

Pulmonary function tests in type 1 diabetes adolescents with diabetic cardiovascular autonomic neuropathy.

Chronic diabetic complications may afflict all organ tissues including cardiovascular and respiratory system. The aim of the study was to establish if the presence of cardiovascular autonomic neuropathy (CAN) was associated with impaired pulmonary function tests in adolescents with type 1 diabetes (T1D). 46 adolescents with T1D and 25 healthy subjects at the age 15-19years were enrolled to the study. Basic anthropometric data, diabetes onset and duration, plasma glucose and A1c were established. Pulmonary function tests were measured by spirometry and the presence of CAN was examined by heart rate variability. Adolescents with T1D had significantly lower pulmonary function test parameters - FVC (p<0.01), FEV1 (p<0.01), MMEF (p<0.05) and PEFR (p<0.05) compared to the control subjects. In diabetic group, patients with CAN (CAN+, n=19) had significantly lower FVC (p<0.05), FEV1 (p<0.05) and PEFR (p<0.05) compared to patients without CAN (CAN-, n=27). All spirometric parameters were significantly lower in CAN+ subjects compared to healthy controls; however, no significant difference was found in these parameters between CAN- subjects and healthy controls. Spirometric parameters (FVC, FEV1) significantly positively correlated with diabetes onset and body mass index; and negatively correlated with diabetes duration and resting heart rate. Our results indicate that CAN may be associated with reduced pulmonary functions in adolescents with T1D.

Exhaled carbon monoxide in adolescents with diabetic cardiovascular autonomic neuropathy.

The aim of the study was to determine if cardiovascular autonomic neuropathy (CAN) is associated with changed concentration of exhaled carbon monoxide (eCO) in adolescents with type 1 diabetes (T1D). A total of 46 T1D patients and 25 healthy controls (15-19 years) were enrolled. The parameters eCO and carboxyhemoglobin (HbCO) were established using a MICRO-4 Smokerlyser. CAN was examined by standard cardiovascular tests. Adolescents with T1D did not significantly differ in eCO compared to healthy subjects. eCO and HbCO were significantly lower in CAN-positive subjects (n=19) (1.36 ± 1.65 ppm vs. 3.09 ± 2.31, p=0.01 and 0.58 ± 0.49% vs. 1.04 ± 0.44, p<0.01, respectively) compared to CAN-negative subjects (n=27), whereas no significant difference was found in other measured parameters. By multivariate logistic regression, eCO and HbCO were associated with higher risk of CAN (OR=1.824, p<0.05 and OR=10.989, p<0.01). Our results indicate that eCO is decreased in CAN-positive diabetic subjects. Further studies are necessary to investigate the possible role of eCO as a marker for CAN.

SURGICAL AND NON-SURGICAL THERAPY OF OBSTRUCTIVE SLEEP APNEA SYNDROME IN CHILDREN.

Interventions of paediatric obstructive sleep apnea syndrome are complex, varied and multidisciplinary. The goal of the treatment is to restore optimal breathing during the night and to relieve associated symptoms. Evidence suggests that the surgical intervention with removal of the tonsils and adenoids will lead to significant improvements in the most incomplicated cases, as recently reported from a meta-analysis. However, post-operative persistence of this syndrome in paediatric population is more frequent than expected, which supports the idea of the complexity of this syndrome. Adenotomy alone may not be sufficient in children with OSAS, because it does not address oropharyngeal obstruction secondary to tonsillar hyperplasia. Continuous positive airway pressure can effectively treat this syndrome in selected groups of children, improving both nocturnal and daytime symptoms, but poor adherence is a limiting factor. For this reason, CPAP is not recommended as first-line therapy for OSAS when adenotonsillectomy is an option. It is now being investigated the incorporation of nonsurgical approaches for milder forms and for residual OSAS after surgical intervention. Althought adeno-tonsillar hypertrophy is the most common for OSAS in children; obesity is emerging as an equally important etiological factor. Therefore an intensive weight reduction program and adequate sleep hygiene are also important lifestyle changes that may be very effective in mitigating the symptoms of this syndrome. Pharmacological therapy (leukotriene antagonists, topical nasal steroids) is usually use for mild forms of OSAS and in children with associated allergic diseases. Special orthodontic treatment and oropharyngeal exercises are a relatively new and promising alternative therapeutic modality used in selected groups of children with OSAS.

The association between gene polymorphisms of glutathione S-transferase T1/M1 and type 1 diabetes in Slovak children and adolescents.

BACKGROUND: Considering a dramatic increase in the incidence of type 1 diabetes (T1D) worldwide, current research focuses on complex etiology of T1D where immune system, environmental and genetic factors play a significant role. Glutathione S-transferase family of enzymes protects tissue from oxidative damage which is discussed in the context of T1D. The aim of the study was to investigate an association of glutathione S-transferase mu 1 (GST M1) and glutathione S-transferase theta 1 (GST T1) polymorphisms with type 1 diabetes. METHODS: 163 children, 116 with type 1 diabetes and 47 healthy controls, at the age 6-19 years were enrolled to the study. Basic anthropometric, biochemical parameters and GST T1 diabetes and M1 polymorphisms were established in each subject. RESULTS: Subjects with T1D had significantly lower concentration of uric acid compared to the healthy subjects (212.85 +/- 57.10 micromol/l vs. 269.57 +/- 72.53; p < 0.001). GST T1 null genotype was more frequent in patients with diabetes compared to the healthy controls (36.2% vs. 21.3%) and represented 2.1-fold increased risk of T1D of borderline statistical significance (OR = 2.1; 95% Cl = 0.949-4.648; p = 0.06). GST T1 null/M1 wild genotype combination was more frequent in patients with diabetes (25.9% vs. 10.6%) and represented 2.9-fold increased risk for T1D development (OR = 2.93; 95% CI = 1.061-8.095; p = 0.032). CONCLUSION: The study indicates that GST T1 null genotype and GST T1 null/M1 wild combination could be considered a risk factor for type 1 diabetes development in Slovak children and adolescents.