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Arterial stiffness has been associated with cardiovascular events and correlated with cardiovascular risk factors. In the new guidelines of the European Society of Hypertension, the evaluation of arterial stiffness, and specifically carotid-femoral pulse wave velocity (c-f PWV), was taken into account for the detailed screening of the hypertensive population. Despite the importance of arterial stiffness as a target organ damage, the measurement is time-consuming, not practical, needs expensive equipment and experienced staff. For all these reasons, c-f PWV is not recommended for the everyday clinical practice and its current use is restricted for research purposes. The importance of arterial properties in clinical practice and cardiovascular prevention is well known. Hence, the estimation of arterial stiffness and vascular health based on parameters that affect arterial stiffness, but without the use of a machine, is a new promising field. Furthermore, the relationship between age-related MRI abnormalities as well as ultrafast ultrasound with vascular effect gives a new promise for future vascular aging assessment.

Observational studies show that serum uric acid levels associate with cardiometabolic risk factors and subclinical target organ damage. The aim of the present study is to investigate the association of traditional cardiometabolic risk factors and uric acid with the executive performance in children and adolescents. Ninety-nine children and adolescents aged 5 to 18 years referred for assessment of primary hypertension were included. Traditional cardiometabolic risk factors, uric acid, and ambulatory blood pressure parameters were assessed. Executive performance was assessed by the validated Behavior Rating Inventory of Executive Function parent questionnaire. Serum uric acid correlated with cardiometabolic parameters, daytime and nighttime systolic blood pressure. High uric acid levels and ambulatory hypertension were associated with behavior regulation independently of other cardiometabolic risk factors or presence of metabolic syndrome. Participants with combined hypertension and high uric acid levels presented the lowest behavior regulation performance. Children with high uric acid had worse behavior regulation indices T scores with estimated marginal means 56.47 (95% CI, 51.68–61.27) compared with 49.22 (95% CI, 45.91–52.53) in those with low uric acid levels ( P =0.023, adjusted for age, sex, nighttime systolic blood pressure, daytime and nighttime heart rate). Mediation analysis showed that part of the effect of high uric acid levels on behavior regulation was mediated by nighttime systolic blood pressure. In conclusion, we found a positive association of serum uric acid with worse executive performance in children at risk for primary hypertension. Extending these cross-sectional findings with longitudinal studies may determine whether high uric acid levels increases the risk of cognitive decline in youth.

ObjectiveThe impact on executive function performance of sleep-related disorders in asthmatic children has been scarcely studied in community settings. The aims of the present study were to assess the prevalence of sleep-related breathing disorders (SRBD) in children with intermittent or mild persistent asthma in primary care settings, and to examine the possible correlations with measures of executive function.MethodsWe performed a case–control study including 76 children with asthma (intermittent or mild persistent) and 85 healthy controls. The parents of both patients and controls completed the Paediatric Seep Questionnaire (PSQ) and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire.ResultsWe did not find any statistically significant differences regarding the scales of PSQ. Additionally, there were no statistical differences between asthmatic children and controls regarding the scales of the BRIEF questionnaire. In both asthmatic children and controls the score of the scale of obstructive sleep-related breathing disorder was significantly correlated with the T scores of the two composite scales (BRI and MI) and the Global Executive Composite.ConclusionIn children with intermittent or mild persistent asthma under the care of private general paediatricians there were no statistically significant differences regarding subjective SBD compared to the healthy controls. Also there were no statistical differences between asthmatic children and controls regarding behavioural correlates of executive function during everyday life.

Objectives The aims of the study were to assess executive function performance in children and adolescents with primary and secondary hypertension, and to investigate for associations with central SBP and ambulatory blood pressure. Methods Forty-six pediatric patients with secondary hypertension because of kidney diseases and 46 patients with primary hypertension underwent ambulatory blood pressure monitoring, pulse wave analysis, and assessment of executive function using Behavior Rating Inventory of Executive Function. Results for comparisons are presented as mean (SD). Analysis of covariance was performed to examine the effect of blood pressure parameters and hypertension cause. Results Patients with secondary hypertension had higher T scores in parent and self-reported Metacognition Indices compared with those with primary hypertension (51.2 ± 8.9 vs. 47.6 ± 7.5, P = 0.05 and 49.6 ± 9.1 vs. 42.1 ± 7.9, P = 0.001, respectively), but did not differ in Behavior Regulation Index T scores, as well as in mean arterial pressure z-score. Patients with secondary hypertension had higher central SBP z-scores (P = 0.05). Adjustment for central SBP attenuated differences in parent Metacognition Index between groups. Central SBP z-score associated with parent Metacognition (B = 0.95, 95% CI 0.02-1.87), Behavior Regulation (B = 1.14, 95% CI 0.07-2.21), and self-reported Metacognition Indices T scores (B = 1.48, 95% CI 0.39-2.56), independent of mean arterial pressure z-score, age, sex, socioeconomic status, hypertension cause, and antihypertensive treatment. Conclusion Central SBP associates with executive function performance in youth with hypertension and could have complementary role to ambulatory blood pressure for identifying children at risk for adverse cognitive outcomes.

Despite advances in research, the pathophysiology of food allergy has not yet been fully elucidated. IL-10 has both a pro- and anti-inflammatory effect on the development of food allergy and in order to understand its different immune-modulatory effects the factors that influence the inflammatory microenvironment need to be taken into account. Specific single nucleotide polymorphisms of the IL-10 gene seem to confer an increased risk of developing food allergy, but to date there is a substantial lack of genome- wide association studies regarding the genetic and epigenetic underpinnings of the disease. Special interest has been drawn to the development of allergen-specific regulatory CD4+CD25+ T-cells secreting IL-10 in the immunotherapy of allergic diseases. In addition, a distinct population of human tolerogenic dendritic cells (DC), DC-10 seems to hold great potential and could potentially serve as a therapeutic tool to improve the management of food allergy.

AIMS OF THE STUDY: It is well known that parenting stress is an important but often underestimated psychosocial variable. Data regarding the impact of the corona virus disease 2019 (COVID-19) outbreak on parental psychology are currently lacking. The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. METHODS: An Internet e-survey was conducted adhering to CHERRIES guidelines of the EQUATOR network and released from 16 March to 22 March 2020, using the Perceived Stress Scale (PSS) and Revised Impact of Event Scale (IES-R). A convenience sample of 1105 Greek parents of children with or without chronic or severe underlying disorders was enrolled, identified by a network of collaborating paediatricians across the country, and invited via personal emails. RESULTS: The participation rate was 91.6% and the completion rate was 100%. A total of 178 (16.1%) of the participants had children with underlying disorders (198 affected children in total). Parents of children with underlying disorders had significantly higher stress levels than those of healthy children (PSS 21.22 ± 5.06 vs 19.02 ± 6.85, p

The impact of sleep-related disorders in children and adolescents with chronic kidney disease on executive function performance has been scarcely studied. The aims of the present study were to assess the prevalence of sleep-related disorders in chronic kidney disease pediatric patients, and to examine possible correlations with measures of executive function.We performed a case-control study including 51 children with chronic kidney disease stages 2-5, aged 5-18 years, and 51 healthy controls. The parents of both patients and controls completed the Pediatric Seep Questionnaire (PSQ), and the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire.Children with chronic kidney disease presented lower executive performance with higher scores in scales of executive function, and an increased risk of presenting a sleep-related disorder (odds ratio (OR) = 7.58, 95% confidence interval (CI) 2.36-24.31, p 0.005) compared to controls. In the patient group, age of chronic kidney disease onset correlated with Behavior Regulation Index T-score (r = 0.32, p 0.05). In multivariate analysis, differences between patients and controls for Metacognition Index T-scores did not persist after adjustment for sleep-related breathing disorder and insomnia scores, while differences in Behavior Regulation Index T-scores remained significant (54.15 vs 49.14, p 0.02). Moreover, mediational analyses showed that sleep-related disorders mediated the effect of chronic kidney disease on metacognition, but not on behavioral regulation.Sleep-related disorders may in part explain the lower executive function performance during everyday life in chronic kidney disease pediatric patients. However, additional disease-related factors may influence executive function, especially in the domains of behavior regulation.

BACKGROUND Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. AIM To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. METHODS The single nucleotide polymorphisms (SNPs) at -1082A > G (rs1800896), -819 T > C (rs1800871), and -592A > C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. RESULTS Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. CONCLUSION Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.

Background: Correlated long-range fluctuations of lung function have been demonstrated in asthmatic adults. Objective: To determine the pattern of FEV1 fluctuation and its potential age dependence in healthy children and adolescents. Methods: The study of lung function variability in children and adolescents (NCT04163146) includes subjects aged 6-18 years who perform spirometry twice daily for 3 months (180 trials) using a portable device (Spirobank Smart). Here, we applied detrended fluctuation and sample entropy (SampEn) analysis to FEV1 data of healthy participants (no asthma, normal baseline spirometry). We evaluated the scaling exponent α (long-range correlations) and SampEn (regularity of data series) of consecutive FEV1 recordings in relation to age. Results: Our preliminary results (N=11; target >75) indicate the presence of correlated long-range (over weeks/months) fluctuations of FEV1. The scaling exponent α decreases with increasing age (r –0.738; P=0.0095) while SampEn increases (r 0.694; P=0.0178) (Figure). Conclusions: Healthy children and adolescents present correlated long-range fluctuations of FEV1, the pattern of which changes with age. Our findings suggest that developmental aspects may influence the complex temporal interaction between environmental stimuli and airway tone, hypothetically affecting the stability and adaptability of the respiratory system.

Background Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma. Objective The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation. Methods The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months. Results The study is funded by the “C. Caratheodory” Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020. Conclusions Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations. Trial Registration ClinicalTrials.gov NCT04163146; https://clinicaltrials.gov/ct2/show/NCT04163146 International Registered Report Identifier (IRRID) DERR1-10.2196/20350

BACKGROUND Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma. OBJECTIVE The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation. METHODS The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months. RESULTS The study is funded by the “C. Caratheodory” Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020. CONCLUSIONS Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations. CLINICALTRIAL ClinicalTrials.gov NCT04163146; https://clinicaltrials.gov/ct2/show/NCT04163146 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/20350

BACKGROUND AND AIM Neurocognitive impairment has recently emerged as a hypertensive target organ damage in children and adolescents. In the present study, we aimed to examine the effect of hypertension and overweight on executive function performance in youth. METHODS The study population included 116 consecutive children and adolescents referred to our outpatient hypertension clinic who underwent ambulatory blood pressure monitoring (ABPM) and assessment of executive function by Behavior Rating Inventory of Executive Function (BRIEF). RESULTS Children and adolescents with hypertension presented higher T scores in shift sub-scale of Behavior Regulation Index (BRI) compared with normotensives. Participants with hypertension in the ABPM also presented higher T scores in subscales of metacognition (metacognition index). Night-time SBP correlated with BRI (r = 0.21, P

Background Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 s (FEV1) has been used in research to predict exacerbations in adult individuals with asthma. However, there is a paucity of data regarding PEF and FEV 1 variability in healthy or asthmatic children and adolescents. The objective of the present study is the assessment of PEF and FEV 1 variability in: a) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV 1 and the parameters that may influence it, and b) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation.Methods The study will include 100 healthy children and adolescents aged 6 to 18 years (assessment of normal PEF and FEV 1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV 1 variability in asthmatics). PEF and FEV1 measurements will be performed using an ultra-portable spirometer (MIR Spirobank Smart) capable to smartphone connection. Measurements will be performed twice a day between 07:00-09:00 and 19:00-21:00 hours and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations (asthmatics). The anticipated duration of the study is 24 months.Discussion Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations.Trial registration ClinicalTrials.gov, NCT04163146. Registered on 14 November 2019

Every medical treatment—pharmacologic or not—carries an inherent risk of complications. Adverse pulmonary effects have been reported as a result of medications (drug-induced respiratory diseases, DIRD) (Foucher et al., The Euro Respir J 10:265–279, 1997), radiation, oxygen administration, and surgical procedures. More than 600 drugs have been reported to cause pulmonary toxicity. There is no accurate estimate of the incidence of these complications, since they are vastly underreported. The diagnosis of a pulmonary complication of a drug is a challenge, and it usually comes as a diagnosis of exclusion (Steinfeld and Schidlow, Pediatric respiratory medicine, Mosby Elsevier, Philadelphia, 2008; Henry and Noah, Kendig & Chernick’s disorders of the respiratory tract in children, W.B. Saunders, Philadelphia, 2012; Camus et al. Respiration 71:301–326, 2004). The challenge is the result of (a) the absence of a specific and sensitive test (Lindell and Hartman, Clin Chest Med 25:15–24, 2004; Rossi et al., Radiographics 20:1245–1259, 2000) that could conclusively provide the diagnosis, (b) the complexity of the interactions between multiple drugs, (c) the clinical resemblence of the pulmonary complication to the disease undertreatment (this is particularly common in the case of rheumatologic disorders (Kremer et al., Arthritis Rheum 40:1829–1837, 1997) and inflammatory bowel diseases (Mansi et al., Am J Respir Crit Care Med 161:1051–1054, 2000; Valletta et al., BMC Gastroenterology 1:13, 2001), (d) the variety of clinical patterns of lung toxicity that can arise even from a single drug, (e) the fact that lung biopsies are not commonly performed in pediatric patients and even when pathology is available it may not be pathognomonic (Flieder and Travis, Clin Chest Med 25:37–45, 2004), (f) the time course between exposure and onset of DIRD that can vary tremendously (Tashiro et al., Tohoku J Exp Med 216:77–80, 2008; Kubo et al., Respir Investig 51:260–277, 2013), and response to drug withdrawal that is not always predictable (Kubo et al., Respir Investig 51:260–277, 2013). Therefore, the pediatrician should always have a high index of suspicion (Liles et al., Cleveland Clin J Med 75:531–539, 2008) and obtain a thorough history, including usage of alternative medicines, supplements, and herbs; illicit drug abuse is also important. Since this field is constantly enriched with new knowledge, it is essential for the busy clinician to check for updates and resources in highly sophisticated relevant websites (http://www.pneumotox.com/).

Acute bronchiolitis is a common paediatric disease of infancy. Its association with subsequent asthma development has puzzled clinicians and epidemiologists for decades. This article reviews the current state of knowledge regarding the role of acute bronchiolitis in the inception of asthma. There is little doubt that acute bronchiolitis is associated with an increased risk of recurrent wheezing throughout the primary school years although the direction of causality—i.e. whether bronchiolitis in infancy leads to asthma or it merely represents the first clinical presentation of predisposition to asthma—is uncertain. Existing evidence suggests that both host factors (e.g. prematurity, atopic predisposition) and acute viral infection characteristics (e.g. type of virus, severity) are operating in this relationship, perhaps with variable involvement in different individuals. Further clarification of these issues will help paediatricians provide evidence-based information regarding the long-term prognosis of this common disease to the families, and at the same time, it will facilitate prophylactic approaches and therapeutic strategies.

Wheeze is both a symptom to parents (reported as noisy breathing) and a sign to clinical staff - with very differing perspectives between parents and clinicians on what constitutes "wheeze". The purpose of this article is to consider these differences of understanding from the perspective of different stakeholders so that nobody is "lost in translation". Misunderstandings may lead to epidemiologic and treatment faults. Every effort should be made to educate parents and improve their communications with clinicians.

Neonatal urinary ascites is a rare entity, usually associated with a spontaneous rupture of the bladder with an underlying pathology such as high pressure or wall disruption. Its presentation involves abdominal distension, metabolic derangement and respiratory compromise. We report the case of a male neonate with solitary functioning kidney presented with life-threatening persistent hyponatremia and acute renal failure due to iatrogenic bladder rupture after catheterization. The aim of our report is to raise awareness on the possibility of bladder perforation in neonates even in the absence of technical faults. We discuss the uncommon presentation of our case and highlight the need for early recognition and management of urinary ascites, addressing all subspecialties involved in diagnostic or therapeutic procedures of neonates with urinary abnormalities.

Extended-spectrum beta-lactamase (ESBL)-producing pathogens are emerging as a cause of urinary tract infections (UTI) worldwide. In this matched-case control study, clinical characteristics and associated risk factors for ESBL UTI were evaluated. In a total of 463 positive urine cultures, 48 (10.4%) (from 39 patients, 23 boys) were phenotypically ESBL-producing bacteria. The most frequently isolated microorganism was , followed by Klebsiella spp. and Enterobacter cloacae. Children with ESBL UTI (n=39) were on prophylaxis more (21% vs. 6%, p=0.01), had higher rates of urinary tract anomalies (36% vs. 10%, p=0.0007), presented abnormal 99m Tcdimercaptosuccinic acid (DMSA) findings (i.e. scars) (23% vs. 4%, p=0.001), and had longer hospitalization (9.8 vs. 7.4 days, p=0.004) compared to those with non-ESBL UTI (n=117). The recognition of risk factors for UTI caused by ESBL bacteria in children may aid in the identification of high-risk cases and may enable proper management of these patients.

Acute bronchiolitis is a common paediatric disease of infancy. Its association with subsequent asthma development has puzzled clinicians and epidemiologists for decades. This article reviews the current state of knowledge regarding the role of acute bronchiolitis in the inception of asthma. There is little doubt that acute bronchiolitis is associated with an increased risk of recurrent wheezing throughout the primary school years although the direction of causality--i.e. whether bronchiolitis in infancy leads to asthma or it merely represents the first clinical presentation of predisposition to asthma--is uncertain. Existing evidence suggests that both host factors (e.g. prematurity, atopic predisposition) and acute viral infection characteristics (e.g. type of virus, severity) are operating in this relationship, perhaps with variable involvement in different individuals. Further clarification of these issues will help paediatricians provide evidence-based information regarding the long-term prognosis of this common disease to the families, and at the same time, it will facilitate prophylactic approaches and therapeutic strategies.