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Objective: to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects. Results: The recent literature indicates that there is strong evidence for causal relationships between PM2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52.300 for PM2.5, 10.400 for NO2 and 3.000 for O3 in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas. Conclusions: adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients' associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.

Background: Asthma patterns are not well established in epidemiological studies. Aim: To assess asthma patterns and risk factors in an adult general population sample. Methods: In total, 452 individuals reporting asthma symptoms/diagnosis in previous surveys participated in the AGAVE survey (2011–2014). Latent transition analysis (LTA) was performed to detect baseline and 12-month follow-up asthma phenotypes and longitudinal patterns. Risk factors associated with longitudinal patterns were assessed through multinomial logistic regression. Results: LTA detected four longitudinal patterns: persistent asthma diagnosis with symptoms, 27.2%, persistent asthma diagnosis without symptoms, 4.6%, persistent asthma symptoms without diagnosis, 44.0%, and ex -asthma, 24.1%. The longitudinal patterns were differently associated with asthma comorbidities. Persistent asthma diagnosis with symptoms showed associations with passive smoke (OR 2.64, 95% CI 1.10–6.33) and traffic exposure (OR 1.86, 95% CI 1.02–3.38), while persistent asthma symptoms (without diagnosis) with passive smoke (OR 3.28, 95% CI 1.41–7.66) and active smoke (OR 6.24, 95% CI 2.68–14.51). Conclusions: LTA identified three cross-sectional phenotypes and their four longitudinal patterns in a real-life setting. The results highlight the necessity of a careful monitoring of exposure to active/passive smoke and vehicular traffic, possible determinants of occurrence of asthma symptoms (with or without diagnosis). Such information could help affected patients and physicians in prevention and management strategies.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome. PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

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Is it necessary - and possible - to discuss death with a child in palliative phase? How should one approach the subject? A recent Swedish study demonstrated the benefits for parents who discussed with their child his or her imminent death, and raised the question of the role nursing can play to help parents. The mother of one child treated in our unit recently wrote a story 48 hours before the child's death. The story served to broach a number of recurrent questions often raised by dying children and their families: fear of the unknown, of being replaced, the inevitability of death, grief, and fear of being forgotten... The story was given to 13 families with dying children. In order to evaluate the story's impact on families and to determine whether a document which stimulates dialogue should continue to be given to parents, we asked that they fill out a questionnaire. Fifty-five percent of parents answered, and confirmed that the story was experienced as a positive thing and helped parents to talk with their children. This study raises many questions and should be part of a global accompaniment strategy. A review of medical, general and children's literature, as well the results of our study, lead us to conclude that the medical body should lend its full support to families who wish to engage in this dialogue with their children.

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.

To date, a large number of mediators and biomarkers have been detected in childhood asthma, with a potential role in monitoring the disease course. Lung function evaluation through spirometry, forced oscillation technique and multiple breath washout proved its role in asthma monitoring, especially for investigating small airway impairment in children with more severe symptoms. Recently, novel specialized pro-resolving mediators, such as resolvins and lipoxins, have been recognized as crucial in promoting the resolution of lung inflammation. Increasing evidence suggests that miRNAs are crucially entailed in asthma. Partial least squares discriminant analysis (plsDA) is a modern technique for multiparametric analysis. The purpose of this study was to establish through plsDA the implications of resolvin D1 and miR-146a, along with prophlogistic and lung function parameters, for characterizing children with moderate and severe asthma.

Few data are currently available on the effects of aeroallergens in triggering respiratory symptoms in children. To evaluate the potential effects of daily outdoor aeroallergens loads on childhood admissions, in this case-crossover study, we analyzed data from 85 children hospitalized at the University Hospital of Pisa, Italy, for asthma or asthma-like symptoms without respiratory infection, between 2010 and 2019. Data were linked to outdoor allergens, temperature, nitrogen dioxide, and relative humidity observed during the same period. A 10-grains/m3 increase in the total aeroallergen concentration was associated with an increased risk of admission at lag 0 (OR = 1.054, 95% CI: 1.011–1.098), with a smaller effect at lag 1 (OR = 1.037, 95% CI: 1.008–1.067) and lag 2 (OR = 1.021, 95% CI: 1.003–1.039). Trends to larger effects were observed in children with sensitization to one or more aeroallergens (OR = 1.085, 95% CI: 1.004–1.173 at lag 0), in males (OR = 1.069, 95% CI: 1.009–1.132 at lag 0) and in older children (OR = 1.065, 95% CI: 1.007–1.127 at lag 0). Our study shows an association between increased outdoor allergens loads and asthma or asthma-like symptoms in children up to at least two days prior to hospitalization, suggesting that tracking aeroallergen counts may be useful to improve the management of respiratory allergic diseases.

Achieving and maintaining asthma control (AC) is the main goal of asthma management. Indoor and outdoor environmental factors may play an important role on AC. The aim of this longitudinal study was to evaluate the association between AC and exposure to greenness and other outdoor or indoor environmental factors in a cohort of asthmatic children. This study involved 179 asthmatic children (5–16 years). Parents were interviewed through a modified version of the SIDRIA questionnaire. AC was assessed at each visit. Exposure to greenness was measured using the normalized difference vegetation index (NDVI). A logistic regression model was applied for assessing risk factors for uncontrolled asthma (UA). Low NDVI exposure was a risk factor for UA (OR: 2.662, 95% CI (1.043–6.799)); children exposed to passive smoke during pregnancy had a higher risk of UA than those non-exposed to passive smoke during pregnancy (OR: 3.816, 95% CI (1.114–13.064)); and a unit increase in the crowding index was associated with an increased risk of UA (OR: 3.376, 95% CI (1.294–8.808)). In conclusion, the current study provided a comprehensive assessment of urban-related environmental exposures on asthma control in children, using multiple indicators of greenness and other outdoor or indoor environmental factors.

Objective: to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects. Results: The recent literature indicates that there is strong evidence for causal relationships between PM2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52.300 for PM2.5, 10.400 for NO2 and 3.000 for O3 in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas. Conclusions: adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients’ associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.

Primary eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of emerging inflammatory diseases, which may involve any part of the gastrointestinal (GI) tract and lead to a pathological eosinophilic mucosal infiltration.1,2 Based on the anatomical site of the eosinophil inflammation, EGIDs are classified into eosinophilic esophagitis (EoE) and nonesophageal EGIDs.This study aimed to characterize EGIDs heterogeneity by performing cluster analysis on a cohort of children and adolescents followed at the Pediatric Center for Eosinophilic Gastrointestinal Disorders (CPED) in Pavia, Italy, using an extensive pediatric primary care database from our University Hospital

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Among modern methods of statistical and computational analysis, the application of machine learning (ML) to healthcare data has been gaining recognition in helping us understand the heterogeneity of asthma and predicting its progression. In pediatric research, ML approaches may provide rapid advances in uncovering asthma phenotypes with potential translational impact in clinical practice. Also, several accurate models to predict asthma and its progression have been developed using ML. Here, we provide a brief overview of ML approaches recently proposed to characterize pediatric asthma.

The current Covid-19 pandemic poses an unprecedented global challenge in the field of education and training. As we have seen, the lack of proper information about the virus and its transmission has forced the general population and healthcare workers to rapidly acquire knowledge and learn new practices. Clearly, a well-informed population is more likely to adopt the correct precautionary measures, thus reducing the transmission of the infection; likewise, properly educated healthcare workers are better equipped to manage the emergency. However, the need to maintain physical distancing has made it impossible to provide in-presence information and training. In this regard, new technologies have proved to be an invaluable resource by facilitating distance learning. Indeed, e-learning offers significant advantages because it does not require the physical presence of learners and teachers. This innovative method applied to serious games has been considered potentially effective in enabling rapid and large-scale dissemination of information and learning through content interactivity. We will review studies that have observed the development and use of serious games to foster information and practices about Covid-19 aimed at promoting behavioral changes in the population and the healthcare personnel involved on the front line.

Introduction: Unbalanced dietary intake has been increasingly recognized as an important modifiable risk factor for asthma. In this study, we assessed whether a pro-inflammatory diet is associated with higher asthma burden in three steps: (1) identification of asthma latent classes (LC) based on symptoms, indoor exposures, and pulmonary function; (2) identification of risk factors associated with LC membership; and (3) estimation of the probabilities of LC membership with variation in DII. Methods: A cross-sectional study on 415 children aged 5–14years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquantitative food frequency questionnaire. Elastic net logistic regression was used to investigate whether increasing DII was associated with worse asthma burden. Results: Two LCs were identified. Children in Class 1, “high burden,” had higher symptom burden and worse lung function. Children in Class 2, “low burden,” had lower symptom burden and less impaired lung function but were more subject to indoor exposures. DII was the only risk factor significantly associated with Class 1membership. As the DII increased (from −4.0 to +4.0), the probability of Class 1membership increased from 32% to 65% when compared with control group, whereas it increased from 41% to 72% when compared with Class 2. Conclusions: We identified two phenotypes of persistent asthma associated with different disease burden linked to indoor exposures. An increasing DII was associated with high-burden asthma, providing further evidence about the role of a pro-inflammatory diet in asthma morbidity.

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children with asthma. This single-center prospective study was conducted in Palermo, Italy, between March and July 2017 and involved 50 children with persistent mild-moderate asthma, aged 6–11 years. At each time visit (day 0, 30, 60, and 90), physical examination, spirometry, and urine collection for detection of urinary cotinine and PAHs were performed. A symptom score was computed. The sum of individually calculated molar mass of nine PAH metabolites (ΣPAH), naphthalene metabolites (ΣPAHn) and phenanthrene metabolites (ΣPAHp) were calculated. Three children withdrew from the study due to technical problems (n = 1) and adverse events (n = 2). PAHs indirect effects on FEV1 (ΣPAH: −0.011, p = 0.04; ΣPAHn: −0.011, p = 0.04; ΣPAHp: −0.012, p < 0.001) and FVC (ΣPAH: −0.012, p = 0.02; ΣPAHn: −0.0126, p = 0.02; ΣPAHp: −0.013, p < 0.001) were statistically significant. In conclusion, PAHs exposures have significant indirect (symptom-mediated) effects on lung function, emphasizing the role of PAHs-induced respiratory morbidity in decreasing lung function in children with asthma.

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.