Early initiation of the respiratory syncytial virus season in 2021-2022, Greece.

Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease in the pediatric population. An unexpected sudden upsurge of RSV infections among children was observed in September 2021 in Greece. Forty-one rhinopharyngeal samples from children under the age of 2 years with confirmed RSV bronchiolitis were tested to identify the genotype(s) of the RSV strain(s). The children were hospitalized during September-November 2021 in three tertiary hospitals in northern Greece. A one-step RT-PCR which amplifies a fragment of the second hypervariable region of the G protein gene was applied. PCR products were sequenced, and phylogenetic analysis was performed. Most (80.5%) RSV cases were typed as RSV-A, with RSV-B accounting for 19.5% of cases. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. As the same genotypes were detected in cases observed during 2016-2018 in northern Greece, it was suggested that the early upsurge of infections was not related to the emergence of novel strain(s), but it was the result of the absence of immunity among children and their mothers due to the restriction measures taken during the COVID-19 pandemic in the previous RSV season. Awareness is needed to diagnose even the out-of-season RSV infections, while molecular epidemiology plays a key role in monitoring the efficacy of currently available therapeutics and for those under development.

Novel Mutations Involved in Charcot-Marie-Tooth 4C and Intrafamilial Variability: Let's Not Miss the Forest for the Trees.

Charcot-Marie-Tooth 4C is characterized by early-onset, rapid progression, and mainly associated with SH3TC2 gene mutations. We reported a male patient carrying a novel heterozygous nonsense mutation in SH3TC2 gene along with a heterozygous known pathogenic mutation. Symptoms began at 15 months and by 14 years, he presented significant motor impairment. Both parents exhibited one of the mutations in the heterozygous state, while his 8-year-old brother carried the same compound heterozygosity, showing only a mild phenotype. In our case, we discussed the contribution of compound heterozygosity to intrafamilial variability in Charcot-Marie-Tooth and the role of modifying genes.

Therapies that are available and under development for Duchenne muscular dystrophy: What about lung function?

BACKGROUND: Respiratory failure is the principal source of morbidity and mortality among patients with Duchenne muscular dystrophy exerting a negative influence on their total quality of life. The aim of this review is to provide systematically current literature evidence about the effects of different treatment options (available or under development) for Duchenne muscular dystrophy on the pulmonary function of these patients. METHODS: A comprehensive search was undertaken using multiple health-related databases, while two independent reviewers assessed the eligibility of studies. A third person addressed any disagreements between reviewers. The quality of the methodology of the included studies was also assessed. RESULTS: A total of 19 original research papers (nine evaluating the role of steroids, six idebenone, three eteplirsen, one stem-cell therapy, and one ataluren) were found to fulfill our selection criteria with the majority of them (14 of 19) being prospective studies, not always including a control group. Endpoints mainly used in these studies were values of pulmonary function tests. Current and under development treatments proved to be safe and no significant adverse events were reported. A beneficial impact on pulmonary function was described by authors in the majority of these studies. The principal effect was slowing of lung disease progress, as expressed by spirometric values. However, the risk of bias was introduced in many of the above studies, while high heterogeneity in terms of treatment protocols and outcome measures limits the comparability of the results. CONCLUSION: Glucocorticoids remain the best-studied pharmacologic therapy for Duchenne muscular dystrophy and very likely delay the expected decline in lung function. With regard to new therapeutic agents, initial study results are encouraging. However, larger clinical trials are needed that minimize the risk of study bias, optimize the comparability of treatment groups, examine clinically meaningful pulmonary outcome measures, and include long-term follow up.

Sleep and prematurity: sleep outcomes in preterm children and influencing factors.

BACKGROUND: Sleep undergoes changes from birth to adulthood, while sleep disorders are associated with various cognitive deficiencies in childhood. In parallel, prematurity is known to predispose to poor neurodevelopmental outcomes. Our aim is to provide literature data about factors influencing sleep in the premature infants and sleep outcomes in this population. METHODS: A systematic review was conducted using a variety of health-related databases. Original research papers were considered and no year-of-publication restriction was placed. RESULTS: In total, 22 articles fulfilled our selection criteria. Available studies present remarkable heterogeneity in terms of methodological design. Compared to full term, premature infants exhibit significant differences in sleep structure, which mainly include differences in electroencephalographic spectral values, in total sleep time and in arousal threshold. Furthermore, prematurity seems to be a risk factor of sleep breathing disorders in childhood and adolescence. Data about the effect of methylxanthines and the environment of neonatal intensive care unit is controversial. With regard to the impact of prematurity-related sleep disorders on future neurodevelopment, available research papers are generally few. CONCLUSIONS: The alterations in sleep patterns are an outcome of prematurity (immaturity of nervous system) as well as of postnatal factors and comorbidities. Sleep problems in this population of infants seems to be a missing piece of the puzzle of impaired neurodevelopment. Future studies should focus on interventions to improve sleep hygiene and limit neurodevelopmental problems.

Description of an ELANE Mutation in a Girl with Severe Congenital Neutropenia: A Paradigm of Targeted Genetic Screening Based on Clinical Findings.

We describe the case of a 5-year-old girl with severe congenital neutropenia presenting with recurrent skin and respiratory infections. Sequence analysis of ELANE and HAX1 genes identified a mutation in heterozygous state in exon 2 of the ELANE gene: c.157C > G (p.His53Asp), not previously described in the literature at the exon coding level. Given the autosomal dominant inheritance and the location of the mutation within a "hotspot," this mutation was considered as clinically relevant. ELANE should be screened in patients with congenital neutropenia of no obvious etiology. A detailed medical history and clinical evaluation can prevent unnecessary investigations allowing for a targeted diagnostic strategy.

Respiratory Syncytial Virus in Greece, 2016-2018.

Human respiratory syncytial virus (RSV) is the leading cause of acute bronchiolitis in infants and young children. Children under the age of 2 years, hospitalized for bronchiolitis in the pediatric clinic of a tertiary hospital in northern Greece, were tested for RSV infection during two RSV seasons (2016-2017 and 2017-2018). RSV was detected in 37 of 71 (52.1%) patients, most of them younger than 6 months. Both RSV subtypes were detected - RSV-A (54.1%) and RSV-B (45.9%) - with predominance of RSV-A during the 2016-2017 and RSV-B during the 2017-2018 season. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. Compared to the prototype strains, several amino acid substitutions were observed in the duplication region of the G gene. The study provides a first insight into the molecular epidemiology of RSV in Greece.

Dysphagia diagnosis with questionnaire, tongue strength measurement, and FEES in patients with childhood-onset muscular dystrophy.

INTRODUCTION: Dysphagia in progressive muscle diseases is primarily due to muscle weakness. Objective of our study is to investigate the prevalence and phenotypes of dysphagia in patients with childhood onset muscular dystrophy (MD) with the use of a validated questionnaire, the measurement of tongue strength and Flexible Endoscopic Evaluation of Swallowing (FEES). METHODS: Prospective observational longitudinal study of dysphagia in a cohort of 58 patients attending the Pediatric Department Center for Neuromuscular Diseases. Control participants were 56 age and sex matched healthy volunteers. Dysphagia was evaluated with the Eating Assessment Tool-10 (EAT-10), and the measurement of Maximal Isometric Tongue Pressure (MITP) and tongue endurance (Iowa Oral Performance Instrument-IOPI). Dysphagic patients were submitted to FEES. Recorded data included demographic and anthropometric characteristics, type of MD, feeding status, and spirometry. RESULTS: Our patients' cohort consisted of 41 children, 11 adolescents, and 6 adults. Based on EAT-10, 20.7% of the patients were dysphagic: 14.63% of children, 27.3% of adolescents and 50% of adults. The main complain was solid food dysphagia. Spirometry parameters mean values for children and adolescent patients corresponded to lower than the fifth percentile. Means of FVC and FEV1 expressed as % predicted for adult patients were 27.8 (SD:25.05) and 28.8 (SD:28.44) respectively. Reduced tongue strength was measured to children aged 9-10, adolescent and adult MD patients. The main FEES findings were pharyngeal residue, spillage of food before the swallow, and supraglottal penetration. DISCUSSION: This is the first study to use a validated questionnaire to evaluate dysphagia in childhood onset MD and report dyphagia prevalence at different patients' age. This is the first study reporting MITP in children and adults with generalised MD. Tongue pressures are reduced well before clinical signs of dysphagia are present. CONCLUSION: Screening of potentially dysphagic MD patients can be based on a validated questionnaire. Patients with an EAT-10 score suggestive of dysphagia at regular follow-up can have the MITP measured and in the case of reduced values a thorough dysphagia evaluation with FEES is indicated.

Herpeticum-like rash in a child with atopic dermatitis: early clinical suspicion is valuable.

Dermatological conditions may be associated with serious underlying medical conditions which require urgent treatment. We describe the case of a 6-year-old boy with erythematous vesicles with erosion and crusting on face, cheeks, and forehead. Due to the medical history of atopic dermatitis, eczema herpeticum was suspected and appropriate treatment was immediately initiated. This resulted in significant improvement of skin lesions.

A rare radiological finding in an infant with respiratory distress.

We report the case of an infant who presented with respiratory distress at the Emergency Department. A chest radiograph showed interposition of colon loops between the right hemidiaphragm and liver, while abdominal and thoracic ultrasound examinations were normal. The aforementioned radiological finding was considered to be Chilaiditi's sign. This sign usually presents as an incidental radiological finding and may be mistaken for a pneumoperitoneum or a diaphragmatic hernia. Clinicians' familiarity with rare radiological signs is necessary.

Impaired glucose metabolism and bronchial hyperresponsiveness in obese prepubertal asthmatic children.

INTRODUCTION: The prevalence of asthma and obesity has risen in parallel over the last decades, but the exact mechanisms linking these two diseases still remain unclear. The aim of the present study was to investigate the associations between bronchial hyperresponsiveness (BHR), impaired glucose metabolism, obesity, and asthma in prepubertal children. METHODS: A total of 71 prepubertal children were included in the study and divided in four groups according to the presence of asthma and their Body Mass Index (BMI): Group 1-Healthy Controls (HC), Group 2-Non Obese Asthmatics (NOA), Group 3-Obese Non Asthmatics (ONA), Group 4-Obese Asthmatics (OA) Αll children underwent spirometry and bronchial hyperresponsiveness testing by using the cumulative Provoking Dose of mannitol (PD15, primary study variable); homeostasis model assessment-estimated insulin resistance (HOMA-IR) index was calculated in order to evaluate insulin resistance. Obese children also underwent an oral glucose tolerance testing (OGTT). RESULTS: A statistically significant difference in bronchial hyperreactivity (mean ± SD) was detected in the group of obese asthmatic children who had lower values ​​of PD15 , (174.16 ± 126.42) as compared to normal weight asthmatic children (453.93 ± 110.27), (P < 0.001). Moreover, obese asthmatic children with confirmed insulin resistance (HOMA-IR ≥2.5), had significantly lower PD15 values (89.05 ± 42.75) as ​​compared to those with HOMA-IR <2.5 (259.27 ± 125.75), (P = 0.006). Finally, obese asthmatic children with impaired OGTT had likewise significantly lower PD15 (81.02 ± 42.16) measurements as compared to children with normal OGTT (267.3 ± 112.62), (P = 0.001). CONCLUSION: Our findings suggest that obesity per se does not correlate to airway hyperreactivity unless it is accompanied by glucose intolerance and insulin resistance. Pediatr Pulmonol. 2017;52:160-166. © 2016 Wiley Periodicals, Inc.

Sleep Disturbances in Children with Rolandic Epilepsy.

Background The aim of this study is to investigate through polysomnography sleep quality in children with rolandic epilepsy and compare sleep variables between these children and healthy controls. Methods Our study population included 15 children with rolandic epilepsy and 27 healthy children who underwent overnight polysomnography. Parameters about sleep architecture and sleep respiratory events were recorded and analyzed. The level of statistical significance was set at 0.05. Results Patients and controls did not differ in basic epidemiological traits. The percentage of sleep stage rapid eye movement was significantly lower in the epilepsy group. Moreover, the mean value of the obstructive apnea index and the obstructive apnea-hypopnea index was significantly higher in children with rolandic epilepsy compared with healthy children. Longest apnea duration and basal Spo 2 during sleep had also the trend to be higher and lower, respectively, in children with epilepsy. Conclusions Children with rolandic epilepsy exhibit alterations in sleep architecture, as well as in sleep respiratory patterns. Therefore, sleep quality should be routinely considered in the long-term follow-up of these children.

Sleep respiratory parameters in children with idiopathic epilepsy: A cross-sectional study.

BACKGROUND: The aim of this study is to explore and compare through polysomnography respiratory sleep parameters between children with idiopathic epilepsy and healthy children. METHODS: Our cross-sectional study included 40 children with idiopathic epilepsy and 27 healthy children, who underwent overnight polysomnography. Data about sleep respiratory parameters were obtained and statistically analyzed. The level of statistical significance was set at 0.05. RESULTS: The prevalence of Obstructive Sleep Apnea Syndrome was significantly higher in the epilepsy group (35% vs 7.4%, p<0.01). Moreover, the odds ratio of an obstructive apnea index ≥1 in the epilepsy group was 10.6 (95% Confidence Intervals: 3.08-37.08) in comparison to the control group. The mean value of the obstructive apnea-hypopnea index was significantly higher in children with epilepsy compared to healthy children (2.46±1.22 vs 1.21±0.83, p=0.027). The mean values of central apnea index and desaturation index were comparable between these two groups. Longest apnea duration was significantly higher in the group of poor seizure control. All other sleep respiratory variables did not differ significantly between children with poor and good seizure control and between children with generalized and focal epilepsy. CONCLUSIONS: Children with epilepsy seem to present more prominent sleep breathing instability in comparison to healthy children, which mainly includes a predisposition to obstructive respiratory events. More studies are needed to investigate the relationship between sleep apneas and seizure control.

Sleep apneas and epilepsy comorbidity in childhood: a systematic review of the literature.

PURPOSE: Our aim is to review studies which assess the prevalence of sleep apneas in children with epilepsy and discuss possible mechanisms linking these two conditions, as well as the impact of sleep apneas on the prognosis of these children. METHODS: PubMed was used as the medical database source, and articles were selected and classified according to their originality, level of evidence, and relevance to the broad scope of the review. RESULTS: Children with epilepsy have a higher prevalence of sleep breathing disorders in comparison to healthy children, but this prevalence varies widely depending on the methodology of each study. Major risk factors for sleep apneas in childhood epilepsy include mainly poor seizure control and antiepileptic drug polytherapy. Indeed, epilepsy can trigger sleep apneas, as abnormal electrical discharge amplifies sleep-induced breathing instability, antiepileptic drugs disturb muscle tone, and vagus nerve stimulation modulates neurotransmission to airway muscles. On the other hand, sleep apneas enhance sleep fragmentation, thus reducing the threshold for the appearance of seizures. Moreover, they have a negative effect on the neurocognitive profile of these children, as they disturb neuroplasticity mechanisms and also have a probable association with sudden unexpected death in epilepsy. The surgical treatment of sleep apneas has been found to reduce seizure frequency, and this can offer new therapeutic choices. CONCLUSIONS: Between sleep apneas and childhood epilepsy, there is a complex relationship with reciprocal interactions. The presence of sleep apneas should be taken into account when designing the management of these children, as it creates therapeutic opportunities and limitations.

Reduced exercise capacity in Greek children with mild to moderate obstructive sleep apnea syndrome.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common disease that is increasingly recognized among pediatric population. The exercise capacity of adults with OSAS has been demonstrated to be impaired, but there are no data about pediatric exercise response. AIM: The aim of this study was to evaluate cardiopulmonary response to exercise in children with OSAS and to correlate exercise capacity and severity of OSAS. METHODS: Twenty-seven children with habitual snoring (Group A) (mean age 10.5 ± 1.8 years) referred for overnight polysomnography and 13 apparently healthy controls (mean age 11 ± 1.5 years) were recruited. According to the apnea hypopnea index (AHI) group A consisted of 15 (55.6%) children with mild OSAS and 12 (44.4%) with moderate-severe OSAS. All children completed a maximal ramping cardiopulmonary exercise test (CPET) on cycle ergometer. RESULTS: According to CPET children with OSAS had significantly lower VO2max (40.3 ± 8.4 ml/kg/min vs. 47.6 ± 7.9 ml/kg/min, P = 0.013) significantly lower VO2max (%) (77.7 ± 15 vs. 92.9 ± 10.5, P = 0.002), lower maximum heart-rate at peak exercise (86.6 ± 8.8 beat/min vs. 90.6 ± 7.2 beat/min) and higher systolic blood pressure level at peak exercise (145 ± 27.4 mmHg vs. 143.92 ± 20 mmHg) compared to control group. CONCLUSION: The present study demonstrates that young patients with OSAS, even with mild OSAS, had reduced exercise capacity as compared to control group.

Human bocavirus infections in hospitalized Greek children.

INTRODUCTION: The epidemiology of human bocavirus (HBoV) infections has not been described in Greece, a south-eastern European country. To define the epidemiological profile and the clinical characteristics associated with HBoV infection in a population of children hospitalized with respiratory tract infection. MATERIAL AND METHODS: During a one-year period throat swab samples were collected from 370 previously healthy children, aged 14 days to 13 years, admitted to two different paediatric wards because of respiratory tract infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene. RESULTS: Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases were observed only during the cold months. The mean age of children was 1.8 years (range 2 months to 4 years). The most common symptoms were fever, cough and various degrees of respiratory distress. All children were clinically diagnosed as having lower respiratory tract infections, mainly pneumonia and acute laryngotracheobronchitis, and recovered uneventfully. CONCLUSIONS: HBoV infections occur in Greece mostly among very young children. They accounted for 3.2% of children hospitalized with acute respiratory disease. Cases were observed only in late autumn to early spring.

Bronchiectasis secondary to primary immunodeficiency in children: longitudinal changes in structure and function.

BACKGROUND: Primary immunodeficiency is a common cause of bronchiectasis in children. The term bronchiectasis suggests an irreversible process; however, disease progression following treatment is controversial. The aim of this study was to evaluate the progression of bronchiectasis in children with primary immunodeficiency after institution of treatment. METHODS: A retrospective review of case notes of children with primary immunodeficiency was undertaken to identify patients with confirmed bronchiectasis. Children who had two high-resolution computed tomography scans of the chest (HRCT chest) with an interval of at least 2 years were identified. The HRCT-chest scans at diagnosis and follow up were scored using a Bhalla score. Spirometry results (FEV1, FVC, and FEV1:FVC ratios) were related to HRCT-chest scores, where available. Statistical analysis was by Wilcoxon signed rank test and Spearman's rank order correlation. RESULTS: Eighteen subjects were studied. The diagnosis of primary immunodeficiency was established at median (range) age 3.4 (1-13) years, and bronchiectasis at 9.3 (3.1-13.8) years. There was no significant difference between baseline and follow-up median (range) HRCT-chest scores (6 [1-13] and 7.5 [0-15], P = 0.21) respectively. The follow-up FEV1 and FVC percent predicted median (range) were significantly higher than baseline (86% [49-124%] vs. 75% [36-93%], P < 0.005, and 86% [47-112%] vs. 78% [31-96%], P < 0.05), respectively; there was no significant difference between baseline and follow-up FEV(1):FVC ratios. There was no significant correlation between HRCT-chest score changes and FEV1 or FVC changes. CONCLUSIONS: Bronchiectasis secondary to primary immunodeficiency in childhood is not always a progressive condition, suggesting a potential to slow or prevent disease progression with appropriate treatment.

Acute laryngotracheobronchitis and associated transient hyperphosphatasemia: a new case of transient hyperphosphatasemia in early childhood.

We report the case of a 20-month old boy with markedly elevated serum alkaline phosphatase (ALP) levels, documented during an episode of acute laryngotracheobronchitis. Biochemical investigations and imaging studies revealed no evidence of bone or liver disease. Transient hyperphosphatasemia (TH) was confirmed when serum ALP levels normalized within 2 months. Several theories were suggested for TH pathophysiology, viral infections among them; the exact causes, however, remain unclear. It is important to recognize TH and avoid misdiagnosis and unnecessary investigations.