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(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

Wheezing is a common condition in childhood, and its prevalence has increased in the last decade. Up to one-third of preschoolers develop recurrent wheezing, significantly impacting their quality of life and healthcare resources. Artificial Intelligence (AI) technologies have recently been applied in paediatric allergology and pulmonology, contributing to disease recognition, risk stratification, and decision support. Additionally, the COVID-19 pandemic has shaped healthcare systems, resulting in an increased workload and the necessity to reduce access to hospital facilities. In this view, AI and Machine Learning (ML) approaches can help address current issues in managing preschool wheezing, from its recognition with AI-augmented stethoscopes and monitoring with smartphone applications, aiming to improve parent-led/self-management and reducing economic and social costs. Moreover, in the last decade, ML algorithms have been applied in wheezing phenotyping, also contributing to identifying specific genes, and have been proven to even predict asthma in preschoolers. This minireview aims to update our knowledge on recent advancements of AI applications in childhood wheezing, summarizing and discussing the current evidence in recognition, diagnosis, phenotyping, and asthma prediction, with an overview of home monitoring and tele-management.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm and is still associated with increased mortality and morbidity. The great interest lies in identifying early biomarkers that can predict the development of BPD. This pilot study explores the potential of e-nose for the early identification of BPD risk in premature infants by analyzing volatile organic compounds (VOCs) in the exhaled breath condensate (EBC). Fourteen mechanically ventilated very preterm infants were included in this study. The clinical parameters and EBC were collected within the first 24 h of life. The discriminative ability of breath prints between preterms who did and did not develop BPD was investigated using pattern recognition, a machine learning algorithm, and standard statistical methods. We found that e-nose probes can significantly predict the outcome of “no-BPD” vs. “BPD”. Specifically, a subset of probes (S18, S24, S14, and S6) were found to be significantly predictive, with an AUC of 0.87, 0.89, 0.82, 0.8, and p = 0.019, 0.009, 0.043, 0.047, respectively. The e-nose is an easy-to-use, handheld, non-invasive electronic device that quickly samples breath. Our preliminary study has shown that it has the potential for early prediction of BPD in preterms.

Abstract Background Fusobacterium necrophorum is an anaerobic, gram-negative, non-motile, filamentous, non-spore forming bacillus found in the oral cavity, gastrointestinal tract, and female genital tract, responsible of a rare disease named Lemierre Syndrome, characterized by septic thrombophlebitis of the internal jugular vein, which mainly affects previously healthy adolescents and young adults; some risk factors are reported, as smoking or primary viral or bacterial infection leading to the disruption of mucosa. The syndrome originates commonly from an upper respiratory infection such as pharyngotonsillitis, acute otitis media, cervical lymphadenitis, sinusitis, or odontogenic abscess, and may result in multiorgan metastasis, more frequently leading to pulmonary complications, especially lung abscesses. Case presentation We describe two cases of adolescents with atypical Lemierre Syndrome evaluated in a tertiary care center, one with a confirmed infection by Fusobacterium necrophorum and one with a presumptive diagnosis based on clinical features, who developed lung abscesses needing a prolonged antibiotic course and hospitalization. Of interest, both were user of electronic cigarette, configuring a possible new risk factor. The proper diagnosis of Lemierre Syndrome is often difficult to establish, so a high degree of suspicion is needed, especially in the case of lung abscesses in otherwise healthy adolescents. Conclusion The current study will contribute to providing insight into Lemierre Syndrome clinical presentation and management in adolescents, promoting awareness for a rare but potentially fatal disease. Moreover, it suggests a possible relationship between Lemierre syndrome and the use of electronic cigarette, that should be investigated by future studies.

Asthma is a disease that has been described since the times of Hammurabi. However, it is only since the 1960s that effective therapeutic strategies have been available. Pathogenic mechanisms underlying the disease have been deeply studied, contributing to creating a “patient-specific asthma” definition. Biological drugs have been approved over the last twenty years, improving disease management in patients with severe asthma via a “precision medicine-driven approach”. This article aims to describe the evolution of scientific knowledge in childhood asthma, focusing on the most recent biological therapies and their indications for patients with severe asthma.

Severe asthma is a rare disease affecting

Background: Obstructive sleep apnea can have a negative impact on children’s and adolescents’ neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored. Methods: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject’s parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings. Results: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up. Conclusions: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status.

Developmental age is particularly vulnerable to impacts of environmental exposures. Until recent years, the field of environment and child health has predominantly relied on the study of single exposure–health effect relationships. The exposome is an emerging concept in epidemiology, encompassing the totality of the exposures experienced by an individual throughout life and their changes over time. This innovative approach provides a risk profile instead of individual predictors. Exposome research may contribute to better understand the complex relationships between environmental exposures and childhood respiratory health, in order to implement prevention strategies and mitigate adverse health outcomes across the life span. Indeed, an accurate assessment of the exposome needs several measurements as well as different technologies. High-throughput “omics” technologies may be promising tools to integrate a wide range of exposures. However, analyzing large and complex datasets requires the development of advanced statistical tools. This narrative review summarizes the current knowledge on exposome-based approaches in pediatric respiratory health. Further, it explores practical implementation, associated evidence gaps, research limitations and future research perspectives.

Abstract Background Bronchiolitis is the primary infection of the lower respiratory tract in children under 2 years of age. Although it is generally considered a single nosological entity, recent studies suggested remarkable clinical heterogeneity. To date, no studies have identified classes of children with bronchiolitis within the Italian population. This study aimed to identify discrete profiles of Italian children hospitalized with bronchiolitis using a clustering approach and to compare findings with those obtained in international cohorts. Methods This was a retrospective single-centre study conducted on children aged ≤2 years hospitalised with bronchiolitis (n = 401) at the Department of Infectious Diseases and the University Department of General Pediatrics in “Giovanni Di Cristina” Pediatric Hospital of Palermo, Italy, between November 2012 and May 2019. Bronchiolitis profiles were determined by latent class analysis, classifying children based on clinical characteristics at admission and viral aetiology. Results Three profiles were identified. Class 1 (49%) was composed of 45% male children; all children were aged ≤6 months at hospitalization; 77% were infected with RSV; 100% had respiratory distress, 11% had apnea and none had cough. Class 2 (77%) was mainly composed of male subjects (51%); 19% were aged > 6 months at admission; 37% were infected with RSV; 12% had respiratory distress, 5% had apnea and 90% had cough. Class 3 (19%) included the largest proportion of male subjects (94%) and was mostly composed of children aged > 6 months at the time of admission (68%); 70% had cough, 12% showed respiratory distress and none presented with apnoea. Children in Class 1 were more frequently born near the epidemic season (p = 0.028); breastfeeding duration was significantly longer for children in Class 3 (p = 0.004). Conclusions The study identified distinct clinical profiles of bronchiolitis by a clustering approach in a single-centre study of children hospitalised for bronchiolitis in Italy. The three bronchiolitis profiles share some similarities with those identified in international studies using the same statistical approach. These findings may help to increase the understanding of the phenotypic variability that typically characterizes bronchiolitis, with relevant implications for future research.

Abstract Background Repeatability and reproducibility are essential for clinicians for several purposes. Although discouraged, use of the Coefficient of Variation (CV) for assessing repeatability and reproducibility, rather than the Intraclass Correlation Coefficient (ICC), is still widespread. The aim of the present study was to highlight how using inappropriate indices may lead to misleading results, and this is done by simulation study and using real data on Anterior Active Rhinomanometry (AAR) in both healthy children and ones with rhinitis. Methods A simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and ICC to assess repeatability and reproducibility of AAR, for which previous studies have given underestimated results. AAR is recommended as the gold standard tool for measuring nasal resistance in clinical practice. Results A simulation study showed that the ICCs estimated from data generated assuming a true CV yielded results in agreement with estimated CVs; by contrast, if data were generated assuming a true ICC, CVs yielded conflicting results. For AAR, ICCs showed good repeatability, whereas CVs showed unacceptable repeatability. AUC and 95% CI for AAR showed good performance in predicting current symptoms of rhinitis in the overall study population. Conclusions The present study focused on the importance of the choice of appropriate indices of repeatability and reproducibility, demonstrating the repeatability of AAR in both healthy children and ones with rhinitis. Trial registration ClinicalTrials.gov (ID: NCT03286049 ; Registration Date: September 15, 2017; Actual Study Start Date: January 10, 2018).

BackgroundSeasonal Allergic Rhinitis (SAR) is a heterogeneous inflammatory disease. We hypothesized that a cluster analysis based on the evaluation of cytokines in nasal lavage (NL) could characterize distinctive SAR endotypes in children.MethodsThis cross-sectional study enrolled 88 children with SAR. Detailed medical history was obtained by well-trained physicians. Quality of life and sleep quality were assessed through standardized questionnaires [Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Pittsburgh Sleep Quality Index (PSQI) respectively]. Children were grouped through K-means clustering using Interleukin (IL)-5, IL-17, IL-23, and Interferon (INF)-γ in NL.ResultsOut of the 88 patients enrolled, 80 were included in the cluster analysis, which revealed three SAR endotypes. Cluster 1 showed lower levels of IL-5 and IL-17 and intermediate levels of IL-23 and IFN-γ; Cluster 2 had higher levels of IL-5 and intermediate levels of IL-17, IL-23, and IFN-γ; Cluster 3 showed higher levels of IL-17, IL-23, and IFN-γ and intermediate levels of IL-5. Cluster 1 showed intermediate values of nasal pH and nasal nitric oxide (nNO), and a lower percentage of neutrophils at nasal cytology than Clusters 2 and 3. Cluster 2 had a lower level of nasal pH, a higher nNO, higher scores in the ocular domain of PRQLQ, and worse sleep quality than Clusters 1 and 3. Cluster 3 showed a higher percentage of neutrophils at nasal cytology than Clusters 1 and 2.ConclusionsOur study identified three endotypes based on the evaluation of cytokines in NL, highlighting that childhood SAR is characterized by heterogeneous inflammatory cytokines.

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

Exposure to cigarette smoke, allergens, viruses, and other environmental contaminants, as well as a detrimental lifestyle, are the main factors supporting elevated levels of airway oxidative stress. Elevated oxidative stress results from an imbalance in reactive oxygen species (ROS) production and efficiency in antioxidant defense systems. Uncontrolled increased oxidative stress amplifies inflammatory processes and tissue damage and alters innate and adaptive immunity, thus compromising airway homeostasis. Oxidative stress events reduce responsiveness to corticosteroids. These events can increase risk of asthma into adolescence and prompt evolution of asthma toward its most severe forms. Development of new therapies aimed to restore oxidant/antioxidant balance and active interventions aimed to improve physical activity and quality/quantity of food are all necessary strategies to prevent asthma onset and avoid in asthmatics evolution toward severe forms of the disease.

Physical activity (PA) has been seen to improve asthma symptoms, lung function, and quality of life, as well as to reduce airway inflammation and bronchial responsiveness. As a consequence of the COVID-19 pandemic, the minimal amount of PA recommended by the World Health Organization—i.e., about 60 min/day of moderate-to-high intensity—is difficult to achieve for many children, particularly those living in urban areas. Short-term changes in PA because of the COVID-19 pandemic may become habitual, increasing the risk of adverse asthma outcomes in children. Indeed, prolonged home confinement during the COVID-19 pandemic reduces PA levels and increases sedentary behaviors, possibly impairing immune system function and increasing susceptibility to inflammatory diseases. However, there is limited evidence regarding the effects of lockdown due to COVID-19 on PA and sedentary behaviors in asthmatic children. Given that children stay longer indoors, indoor air pollution represents a major issue to consider during home confinement. This narrative review aims to summarize the available evidence about the impact of decreased PA and increased sedentary behaviors on children with asthma during the COVID-19 pandemic. In addition, strategies for supporting PA in children with asthma during the COVID-19 pandemic are suggested, also looking at the issue of indoor air quality.

Abstract Background Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection. Main text The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic. Conclusion Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.

Abstract Lung function impairment is common in Congenital Diaphragmatic Hernia (CDH) survivors. The aim of this study was to evaluate, in children who underwent CDH surgical repair, mid and long-term consequences on respiratory impedance, investigating the impact of CDH on both resistance and reactance parameters, as well as bronchodilator response. Forced Oscillation Technique (FOT) parameters were collected from 12 patients (2–11 years). Resistance and reactance values at 8 Hz (Rrs8, Xrs8) and the area under the reactance curve (AX) were measured pre and post-salbutamol. Quantitative variables were compared using Mann-Whitney U test. Differences of categorical variables were evaluated using Fisher exact test. Statistically significant differences between measured and predicted values for Rrs8 (p = 0.04), Xrs8 (p = 0.02) and AX (p = 0.01) were found. When stratifying for age, significant difference between measured and predicted values was observed only in children

In the last decade, widespread use of E-cigarettes (EC) has occurred all over the world. Whereas, a large amount of evidence on harm to children from conventional cigarette exposure is available, data on health effects in this population throughout different vulnerability windows are still a matter of concern. Exposure to EC during pregnancy may compromise placental function, resulting in fetal structural abnormalities. Specifically, this may cause physio-pathologic changes in the developing lung, which in turn may impair respiratory health later in life. Furthermore, there is evidence that using EC can cause both short- and long-term respiratory problems in the pediatric population and there is great concern for future young people with nicotine addiction. The low parental perception of the risks connected to EC exposure for children increases their susceptibility to harmful effects from passive vaping. This minireview aims to summarize the current evidence focusing on: (i) prenatal effects of EC passive exposure; (ii) post-natal respiratory effects of EC exposure in youth; (iii) parental attitudes toward EC use and perception of children's health risks connected to EC exposure; and (iv) addressing gaps in our current evidence.

Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by severe acute respiratory syndrome coronavirus SARS-COV-2. Aberrant innate immunity response and cytokine storm are responsible for the syndrome. Apparently, in asthmatic patients, the inadequate antiviral immune response and the tendency for asthma exacerbation evoked by common respiratory viruses could explain increased susceptibility to SARS-COV-2 infection. However, asthma has not been suggested to be a risk factor in COVID-19 patients. Therefore, in asthmatic patients some potential protective mechanisms against SARS-COV-2 have been hypothesized, like type 2 immune response, number of eosinophils, overproduction of mucus, and asthma treatment, along with behavioral factors not strictly related to asthma, such as social distancing, hygiene measures and wearing facemasks, that contribute to reduce the individual susceptibility to SARS-COV-2 infection. In this mini-review, we will describe the current literature regarding potential protective factors against COVID-19 in children with asthma based on the evidence available so far.

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease.Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020.Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5–9 years and lymphopenia were statistically related to ICU admission (p < 0.05).Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

Respiratory tract infections (RTIs) are very common in children, especially in the first five years of life, and several viruses, such as the influenza virus, Respiratory Syncytial Virus, and Rhinovirus, are triggers for symptoms that usually affect the upper airways. It has been known that during respiratory viral infections, a condition of oxidative stress (OS) occurs, and many studies have suggested the potential use of antioxidants as complementary components in prophylaxis and/or therapy of respiratory viral infections. Preliminary data have demonstrated that antioxidants may also interfere with the new coronavirus 2’s entry and replication in human cells, and that they have a role in the downregulation of several pathogenetic mechanisms involved in disease severity. Starting from preclinical data, the aim of this narrative review is to evaluate the current evidence about the main antioxidants that are potentially useful for preventing and treating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in adults and to speculate on their possible use in children by exploring the most relevant issues affecting their use in clinical practice, as well as the associated evidence gaps and research limitations.

Identifying asthma comorbidities in children is fundamental for improving disease management. We aimed to investigate the frequency of allergy-related comorbidities in children and adolescents with asthma, and to identify associated risk factors and disease burden. Between September 2015 and December 2018, 508 asthmatic patients (5–17 years) were consecutively enrolled. Parents answered a standardized questionnaire on the history of disease and risk factors. Comorbidities were classified based on the involvement of respiratory and/or extra-respiratory districts: asthma only (A, 13%), asthma with respiratory comorbidities (AR, 37%), asthma with extra-respiratory comorbidities (AER, 10%), and asthma with both respiratory and extra-respiratory comorbidities (ARER, 40%). Multinomial logistic regression showed that membership in the AR group was significantly associated with a maternal history of asthma (OR = 3.08, 95% CI: 1.23–7.72), breastfeeding ≥ three months (OR = 1.92, 1.06–3.46), early mold exposure (OR = 2.39, 1.12–5.11), and current environmental tobacco smoke exposure (OR = 2.06, 1.11–3.83). Membership in the AER group was significantly associated with the female gender (OR = 3.43, 1.54–7.68), breastfeeding ≥ three months (OR = 2.77, 1.23–6.22). ARER was significantly associated with all the aforementioned exposures. Patients with AR reported exacerbations in the last 12 months more frequently (p = 0.009). Several personal and environmental risk factors are associated with comorbidities in asthmatic children and adolescents, possibly worsening the disease burden.

The transition from prenatal to postnatal life causes a significant increase in arterial oxygen tension and the activation of metabolic pathways enabling the newborn's adaptation to the extra-uterine environment. The balance between pro-oxidant and anti-oxidant systems is critical to preserve cellular functions. Indeed, oxidative stress (OS) occurs when the production of free radicals is not balanced by the activity of intracellular antioxidant systems, contributing to cellular and tissue damage. Perinatal OS may have serious health consequences during the postnatal period and later in life. Namely, OS has been recognized as the major cause of lung injury in newborns, especially those preterm born, due to their immature lung and antioxidant systems. The development of OS biomarkers has gained increasing research interest since they may provide useful insights about pathophysiological pathways underlying OS-mediated pulmonary diseases in newborns. Moreover, their implementation in clinical settings may help to early identify high risk-newborns and to provide targeted treatment. Ideally, a biomarker should demonstrate ease of use, biological validity and reproducibility, high sensitivity and specificity. However, none of the clinically validated biomarkers so far have been qualified for neonatal lung disease. Additionally, the complex technical procedures and the high cost of such determinations have hampered the use of OS biomarkers in clinical practice. This review aims to evaluate the current evidence on the application of biomarkers of oxidative stress for neonatal lung disease and exploring the most relevant issues affecting their implementation in practice, as well as the associated evidence gaps and research limitations.

The incidence of allergic diseases in childhood appears to have significantly increased over the last decades. Since environmental factors, including diet, have been thought to play a significant role in the development of these diseases, there is great interest in identifying prevention strategies related to early nutritional interventions. Breastfeeding is critical for the immune development of newborns and infants through immune-modulating properties and it impacts the establishment of a healthy gut microbiota. However, the evidence for a protective role of breastfeeding against the development of food allergy in childhood is controversial, and there is little evidence to support the benefits of an antigen avoidance diet during lactation. Although it is not possible to draw a definitive conclusion about the protective role of breast milk against allergic diseases, exclusive breastfeeding is still recommended throughout the first 6 months of life due to associated health benefits. Furthermore, recommendations regarding complementary feeding in infancy have been significantly modified over the last few decades. Several studies have shown that delayed exposure to allergenic foods does not have a role in allergy prevention and recent guidelines recommend against delaying the introduction of complementary foods after 6 months of age, both in high- and low-risk infants. However, trials investigating this dietary approach have reported equivocal results so far. This review summarizes the available high-quality evidence regarding the efficacy of the principal dietary interventions proposed in early life to prevent allergic diseases in children.

Asthma is one of the most widespread chronic respiratory conditions. This disease primarily develops in childhood and is influenced by different factors, mainly genetics and environmental factors. DNA methylation is an epigenetic mechanism which may represent a bridge between these two factors, providing a tool to comprehend the interaction between genetics and environment. Most epidemiological studies in this field have been conducted using blood samples, although DNA methylation marks in blood may not be reliable for drawing exhaustive conclusions about DNA methylation in the airways. Because of the role of nasal epithelium in asthma and the tissue specificity of DNA methylation, studying the relationship between DNA methylation and childhood asthma might reveal crucial information about this widespread respiratory disease. The purpose of this review is to describe current findings in this field of research. We will present a viewpoint of selected studies, consider strengths and limitations, and propose future research in this area.

Abstract Asthma and rhino-conjunctivitis are common chronic diseases in childhood. In this cross-sectional study, we performed a gene association analysis with current asthma and rhino-conjunctivitis in a cohort of Sicilian children aged 10–15 years. Overall, our findings reveal the importance of different genetic variants at 4p14, 16p12.1, 17q12, 6p12.2 and 17q21.1, identifying possible candidate genes responsible for susceptibility to asthma and rhino-conjunctivitis.

Abstract Background Due to the complex interplay among different urban-related exposures, a comprehensive approach is advisable to estimate the health effects. We simultaneously assessed the effect of “green”, “grey” and air pollution exposure on respiratory/allergic conditions and general symptoms in schoolchildren. Methods This study involved 219 schoolchildren (8–10 years) of the Municipality of Palermo, Italy. Data were collected through questionnaires self-administered by parents and children. Exposures to greenness and greyness at the home addresses were measured using the normalized difference vegetation index (NDVI), residential surrounding greyness (RSG) and the CORINE land-cover classes (CLC). RSG was defined as the percentage of buffer covered by either industrial, commercial and transport units, or dump and construction sites, or urban fabric related features. Two specific categories of CLC, namely “discontinuous urban fabric - DUF” - and “continuous urban fabric - CUF” - areas were found. Exposure to traffic-related nitrogen dioxide (NO2) was assessed using a Land-Use Regression model. A symptom score ranging from 0 to 22 was built by summing affirmative answers to twenty-two questions on symptoms. To avoid multicollinearity, multiple Logistic and Poisson ridge regression models were applied to assess the relationships between environmental factors and self-reported symptoms. Results A very low exposure to NDVI ≤0.15 (1st quartile) had a higher odds of nasal symptoms (OR = 1.47, 95% CI [1.07–2.03]). Children living in CUF areas had higher odds of ocular symptoms (OR = 1.49, 95% CI [1.10–2.03]) and general symptoms (OR = 1.18, 95% CI [1.00–1.48]) than children living in DUF areas. Children living in proximity (≤200 m) to High Traffic Roads (HTRs) had increased odds of ocular (OR = 1.68, 95% CI [1.31–2.17]) and nasal symptoms (OR = 1.49, 95% CI [1.12–1.98]). A very high exposure to NO2 ≥ 60 μg/m3 (4th quartile) was associated with a higher odds of general symptoms (OR = 1.28, 95% CI [1.10–1.48]). No associations were found with RGS. A Poisson ridge regression model on the symptom score showed that children living in proximity to HTRs (≤200 m) had a higher symptoms score (RR = 1.09, 95% CI [1.02–1.17]) than children living > 200 m from HTRs. Children living in CUF areas had a higher symptoms score (RR = 1.11, 95% CI [1.03–1.19]) than children living in DUF areas. Conclusions Multiple exposures related to greenness, greyness (measured by CORINE) and air pollution within the urban environment are associated with respiratory/allergic and general symptoms in schoolchildren. No associations were found when considering the individual exposure to greyness measured using the RSG indicator.

AIM:To identify subgroups regarding paediatricians' awareness, attitude, practice and satisfaction about management of Sleep-Disordered Breathing (SDB) in Italy using Latent Class Analysis (LCA). METHODS:A cross-sectional study was conducted on a large sample of Italian paediatricians. Using a self-administered questionnaire, the study collected information on 420 Paediatric Hospital Paediatricians (PHPs) and 594 Family Care Paediatricians (FCPs). LCA was used to discover underlying response patterns, thus allowing identification of respondent groups with similar awareness, attitude, practice and satisfaction. A logistic regression model was used to investigate which independent variables influenced latent class membership. Analyses were performed using R 3.5.2 software. A p-value

Background: Environmental exposures across the life course may be a contributor to the increased worldwide prevalence of respiratory and allergic diseases occurring in the last decades. Asthma and rhinoconjunctivitis especially contribute to the global burden of disease. Greenness has been suggested to have beneficial effects in terms of reduction of occurrence of allergic respiratory diseases. However, the available evidence of a relationship between urban greenness and childhood health outcomes is not yet conclusive. The current review aimed at investigating the current state of evidence, exploring the relationship between children's exposure to residential urban greenness and development of allergic respiratory diseases, jointly considering health outcomes and study design. Methods: The search strategy was designed to identify studies linking urban greenness exposure to asthma, rhinoconjunctivitis, and lung function in children and adolescents. This was a narrative review of literature following PRISMA guidelines performed using electronic search in databases of PubMed and Embase (Ovid) from the date of inception to December 2018. Results: Our search strategy identified 2315 articles; after exclusion of duplicates (n = 701), 1614 articles were screened. Following review of titles and abstracts, 162 articles were identified as potentially eligible. Of these, 148 were excluded following full-text evaluation, and 14 were included in this review. Different methods for assessing greenness exposure were found; the most used was Normalized Difference Vegetation Index. Asthma, wheezing, bronchitis, rhinoconjunctivitis, allergic symptoms, lung function, and allergic sensitization were the outcomes assessed in the identified studies; among them, asthma was the one most frequently investigated. Conclusions: The present review showed inconsistencies in the results mainly due to differences in study design, population, exposure assessment, geographic region, and ascertainment of outcome. Overall, there is a suggestion of an association between urban greenness in early life and the occurrence of allergic respiratory diseases during childhood, although the evidence is still inconsistent. It is therefore hard to draw a conclusive interpretation, so that the understanding of the impact of greenness on allergic respiratory diseases in children and adolescents remains difficult.

Urine proteomic applications in children suggested their potential in discriminating between healthy subjects from those with respiratory diseases. The aim of the current study was to combine protein fractionation, by urinary extracellular vesicle isolation, and proteomics analysis in order to establish whether different patterns of respiratory impedance in healthy preschoolers can be characterized from a protein fingerprint. Twenty-one 3–5-yr-old healthy children, representative of 66 recruited subjects, were selected: 12 late preterm (LP) and 9 full-term (T) born. Children underwent measurement of respiratory impedance through Forced Oscillation Technique (FOT) and no significant differences between LP and T were found. Unbiased clustering, based on proteomic signatures, stratified three groups of children (A, B, C) with significantly different patterns of respiratory impedance, which was slightly worse in group A than in groups B and C. Six proteins (Tripeptidyl peptidase I (TPP1), Cubilin (CUBN), SerpinA4, SerpinF1, Thy-1 membrane glycoprotein (THY1) and Angiopoietin-related protein 2 (ANGPTL2)) were identified in order to type the membership of subjects to the three groups. The differential levels of the six proteins in groups A, B and C suggest that proteomic-based profiles of urinary fractionated exosomes could represent a link between respiratory impedance and underlying biological profiles in healthy preschool children.

Asthma is the most common chronic disease in children, imposing a consistent burden on health system. In recent years, prevalence of asthma symptoms became globally increased in children and adolescents, particularly in Low-Middle Income Countries (LMICs). Host (genetics, atopy) and environmental factors (microbial exposure, exposure to passive smoking and air pollution), seemed to contribute to this trend. The increased prevalence observed in metropolitan areas with respect to rural ones and, overall, in industrialized countries, highlighted the role of air pollution in asthma inception. Asthma accounts for 1.1% of the overall global estimate of “Disability-adjusted life years” (DALYs)/100,000 for all causes. Mortality in children is low and it decreased across Europe over recent years. Children from LMICs particularly suffer a disproportionately higher burden in terms of morbidity and mortality. Global asthma-related costs are high and are usually are classified into direct, indirect and intangible costs. Direct costs account for 50–80% of the total costs. Asthma is one of the main causes of hospitalization which are particularly common in children aged < 5 years with a prevalence that has been increased during the last two decades, mostly in LMICs. Indirect costs are usually higher than in older patients, including both school and work-related losses. Intangible costs are unquantifiable, since they are related to impairment of quality of life, limitation of physical activities and study performance. The implementation of strategies aimed at early detect asthma thus providing access to the proper treatment has been shown to effectively reduce the burden of the disease.