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Lung function is a central issue in diagnosis and determination of asthma severity and asthma control has been previously reported to improve after a stay in mountain environment for at least 2 weeks. No data are available for shorter periods of stay, in particular for small airways during a stay at altitude. The aim of this study is to focus on changes in respiratory function, regarding both the central airways and the peripheral airways in the first 2 weeks of stay in a mountain environment in asthmatic children. In this study, 66 asthmatic children (age: 14 ± 2.8 years) were evaluated through spirometric and oscillometric tests at the time of arrival at the Istituto Pio XII, Misurina (BL), Italy, 1756 m above sea level (T0), after 24 h (T1), and 168 h (T2) of stay. FEV1%, FEF25%-75%, and FEV1/FVC increased significantly from T0 value both at T1 and T2 (respectively, p = 0.0002, p 0.0001, p = 0.0002). Oscillometry showed a significant improvement in R5, R20, and R5-20 at both T1 and T2 as compared to T0 (respectively, p = 0.0001, p = 0.0002, and p = 0.049). Reactance at 5 Hz (X5) improved significantly at T2 versus T0, p = 0.0022. The area under reactance curve between Fres and 5 Hz (AX) was significantly reduced (p = 0.0001) both at T1 and T2 as compared to T0. This study shows an improvement in respiratory indices as soon as after 24 h of stay at altitude, persisting in the following week.

Italy was the first European country to fight the Covid-19 outbreak. To limit the transmission of the virus, the Italian Government imposed strict domestic quarantine policies and temporary closure of non-essential businesses and schools from March 10th,2020. Although more and more literature is exploring the impact of the pandemic on non-referred children and families, only a few studies are focused on the psychosocial impact of Covid-19 in chronically ill children and their caregivers. The present study investigates asthma control and children and mothers’ psychological functioning (i.e.: psychological well-being, fear of contagion, and mothers’ Covid-19 related fears) in 45 asthmatic children aged 7-to-14, compared to a control sample. The subjects were administered an online survey after the lockdown (from 28th May to 23rd August 2020). The analysis shows that asthmatic children presented higher concern in relation to contagion, however, no difference in psychological functioning was displayed between the two cohorts. Mothers reported more Covid-19 related fears, and greater worries according to the resumption of their children’s activities. Moreover, they indicated a global worsening of their psychological well-being during the lockdown. Furthermore, regarding the clinical sample, the multivariate regression model showed that a worsening of mothers' psychological and children’s physical well-being was associated with a worsening of children’s psychological well-being during the lockdown. The results of this study indicate that mothers of asthmatic children can be more prone to experience psychological fatigue in a pandemic scenario. Special programs should be developed to support caregivers of chronically ill children.

Fin dal 1880, anno di apertura del San Giacomo di Tomba di Verona, furono costantemente ricoverati nel manicomio veronese bambini e bambine dai quattro ai tredici anni. Attraverso l’analisi delle loro cartelle cliniche, il presente saggio esamina le dinamiche di ricovero e dimissione di questi fanciulli intrecciandole alle trasformazioni (e alla nascita) degli istituti preposti alla loro cura e assistenza e all’attenzione degli psichiatri verso l’infanzia, sino alle soglie del primo conflitto mondiale. Sono inoltre studiate le relazioni economiche e sociali sorte tra famiglie, istituti ospedalieri e istituzioni municipali veronesi.

Questa raccolta di saggi si propone di indagare sul lungo periodo, dalla fine del Settecento agli anni Quaranta del secolo scorso, e in vari contesti geografici un tema alquanto trascurato dalla storiografia: si tratta dei bambini ‘diversi’ con particolare attenzione a quelli qualificati ‘discoli’ e folli. L’obiettivo è di delinearne meglio il profilo, senza però volerli ingabbiare in rigide definizioni; di avere maggiore contezza dei luoghi preposti al ricovero e/o alla reclusione di questi minori, delle loro finalità e modalità organizzative; e del rapporto, spesso collaborativo, ma talvolta conflittuale, tra genitori e autorità di governo per gestire i figli difficili. This collection of essays aims to focus on a topic – 'different' children with particular attention to those qualified as naughty and fool children - almost neglected by historiography, considering it in a long-term, from the end of XVIII century to the forties of XXth century, and in the various geographical milieu. The objectives are to delineate their identities, avoiding fixed and rigid definitions, and to improve the knowledge of the places where minors were hospitalized and/or cloistered, including their aims and organizational methods. Furthermore, the dossier examines the relation, mostly collaborative, but sometimes conflicting, between parents and public authorities related to the management of the ‘different’ children.

Background: since December 2019, the world has become victim of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The aim of our narrative review is to analyze the impact of COVID-19 in children suffering from chronic lung disease (CLD). Methods: we searched the MEDLINE/Pubmed database using the terms “SARS-CoV-2” or “COVID-19” or “Coronavirus Diseases 2019”; AND “chronic lung diseases” or “chronic respiratory diseases” or “asthma” or “cystic fibrosis” or “primary ciliary dyskinesia” or “bronchopulmonary dysplasia”; and limiting the search to the age range 0–18 years. Results and Conclusions: although COVID-19 rarely presents with a severe course in children, CLD may represent a risk factor; especially when already severe or poorly controlled before SARS-CoV-2 infection. On the other hand, typical features of children with CLD (e.g., the accurate adoption of prevention measures, and, in asthmatic patients, the regular use of inhaled corticosteroids and T2 inflammation) might have a role in preventing SARS-CoV-2 infection. Moreover, from a psychological standpoint, the restrictions associated with the pandemic had a profound impact on children and adolescents with CLD.

A growing number of scientific papers focus on the description and quantification of the detrimental effects of pollution exposure on human health. The respiratory system is one of the main targets of these effects and children are potentially a vulnerable population. Many studies analyzed the effects of short- and long-term exposure to air pollutants on children’s respiratory function. Aim of the present narrative review is to summarize the results of the available cohort studies which investigated how lung function of children and adolescents is affected by exposure to air pollution. In addition, an overview is provided on the association, in children, between pollution exposure and exhaled breath biomarkers, as possible indicators of the pathogenetic mechanisms involved in pollution-related lung damages. The identified cohort studies suggest that, beside the possible impact of recent exposure, early and lifetime exposure are the variables most consistently associated with a reduction in lung function parameters in both children and adolescents. As for the effect of air pollution exposure on exhaled breath biomarkers, the available studies show an association with increased exhaled nitric oxide, with increased concentrations of malondialdehyde and 8-isoprostane in exhaled breath condensate (EBC), and with EBC acidification. These studies, therefore, suggest lung inflammation and oxidative stress as possible pathogenetic mechanisms involved in pollution related lung damages. Taken together, the available data underscore the importance of the development and application of policies aimed at reducing air pollutant concentration, since the protection of children’s lung function can have a beneficial impact on adults’ respiratory health in the future.

Due to the COVID-19 pandemic, many families had to manage new difficulties, especially those of chronically ill children. More and more research has focused on the negative effects of the pandemic on psychological wellbeing, while less is known about the resources. The present study aimed to explore the role of time spent with mothers in chronically ill children’s populations during the COVID-19 pandemic. Moreover, it explored the differences in mothers’ and children’s psychosocial functioning in three clinical populations. Four groups were recruited and compared: 7–15 year old children with asthma (45), type 1 diabetes (52), and cancer (33), as well as their healthy counterparts (41), and their respective mothers. They were administered standardized questionnaires and ad hoc surveys assessing psychological wellbeing and worries. Children of the four groups scored significantly differently with respect to the concerns for contagion, internalizing symptoms, and prosocial behaviors; mothers had worries about the consequences of their children’s contagion related to the chronic illness, as well as time with the child. The multiple linear regression model showed an association of being affected by cancer, suffering from type 1 diabetes, and spending less time with the child with an increase in children’s internalizing problems. Time with mothers seemed to be a resource for psychological wellbeing during the pandemic. Clinical implications are discussed.

Introduction Pediatric flexible laryngotracheal bronchoscopy (FB) is an integral part of diagnostics and treatment at tertiary pediatric respiratory centers. Aim FBs performed between 2013 and 2018 at our Pediatric Allergy and Respiratory Medicine Unit of the Department of Women's and Children's Health at Padua University were examined in terms of the indications, findings and adverse events. Materials and methods The electronic medical records of pediatric patients who underwent FB at least once between 1 January 2013 and 31 December 2018 were considered. Patients' clinical data, indications for FB, anatomical findings, information deriving from bronchoalveolar lavage (BAL) and bronchial brushing, and possible adverse events were analyzed. Results There were 447 pediatric FBs performed in 428 patients (aged from 1 month to 18 years) for diagnostic purposes (92.4%), to clear secretions (3.6%) or to monitor a known condition (4.0%). The main indications were recurrent lower respiratory tract infections (LRTI, 32.2%) and chronic wet cough (9.4%). Lower airway malacia was the most common abnormal finding in these two groups (36.1% and 28.6%, respectively). BAL bacterial culture was positive in 55 children (39.6%) with recurrent LRTI and in 25 (59.5%) with chronic wet cough, being Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis the microorganisms most commonly isolated. FB proved a safe procedure and was well tolerated. Conclusions Pediatric FB is an essential tool at our tertiary pediatric respiratory center. It helps establish the anatomical conditions underlying several chronic respiratory conditions and any correlated microbiological findings, with a significant impact on further patient management. This article is protected by copyright. All rights reserved.

Italy has been the first country outside Asia to struggle with the COVID-19 outbreak. To contain the transmission of the virus, by March 10th, 2020, the Italian Government imposed strict domestic quarantine policies and temporary closure of non-essential businesses and schools. Although growing literature explored the impact of the pandemic on non-referred children and families, few studies focused on the psychosocial impact of Covid-19 in chronically ill children and their caregivers. Methods. The present study investigated asthma control and children and mothers’ psychological functioning (i.e.: psychological well-being, fear of contagion, and mothers’ Covid-19 related fears) in 45 asthmatic children aged 7-to-14, compared to a control sample. They were administered an online survey after the lockdown (from the 28th May to 23rd August 2020). Results. Results showed higher levels of concern for contagion for asthmatic children, but no difference in psychosocial functioning. Mothers reported more Covid-19 related fears, and greater worries according to the resumption of their children’s activities. Moreover, they indicated a global worsening in their psychological well-being during the lockdown. Furthermore, as to the clinical sample, the multivariate regression model showed that a worsening of mothers' psychological and children’s physical well-being was associated with a worsening of children’s psychological well-being during the lockdown. Conclusions. The results of this study indicate that mothers of asthmatic children can be more prone to experience psychological fatigue in a pandemic scenario. Special programs should be scheduled to sustain caregivers of chronically ill children.

Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) have their roots in the womb. Together with a genetic predisposition, prenatal and early-life factors, including maternal smoking, prematurity, and bronchopulmonary dysplasia (BPD), have a pivotal role in later respiratory health. Then, inappropriate responses to respiratory viruses (especially respiratory syncytial virus and rhinovirus) and early allergic sensitization are the strongest contributors to the inception of wheezing and early-onset asthma. There is an urgent need for early disease biomarkers to identify profiles at higher risk of chronic respiratory conditions. Applying the "-omic" technologies to urine, blood and breath condensate, and non-invasive inflammometry seem promising in this regard. The description of specific risk profiles may be the key to the use of targeted personalized therapies.

The term children interstitial lung diseases (chILD) refers to a heterogeneous group of rare diseases that diffusely affect the lung. ChILD specific to children younger than 2 years of age include diffuse developmental disorders, growth abnormalities, specific conditions of undefined etiology (neuroendocrine cell hyperplasia of infancy and pulmonary interstitial glycogenosis) and surfactant protein disorders. Clinical manifestations are highly variable, ranging from the absence of relevant symptoms to a severe onset. Most commonly, chILD presents with nonspecific respiratory signs and symptoms, such as dyspnea, polypnea, dry cough, wheezing, recurrent respiratory infections and exercise intolerance. In the diagnostic approach to a child with suspected ILD, chest high resolution computed tomography and genetic tests play a central role. Then, if the diagnosis remains uncertain, laryngotracheal-bronchoscopy and lung biopsy are needed. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs including corticosteroids, hydroxychloroquine and azithromycin. Despite chILD overall rarity, pediatric pulmonologists must be familiar with these diseases in order to carry out a timely diagnosis and patient treatment.

Background Many children of preschool age present with recurrent wheezing. Most of them outgrow their symptoms, while some have early-onset asthma. Aim of this prospective preliminary study was to apply a metabolomic approach to see whether biochemical-metabolic urinary profiles can have a role in the early identification of the children with asthma. Methods Preschool children with recurrent wheezing were recruited and followed up for 3 years, after which they were classified as cases of transient wheezing or early-onset asthma. A urine sample was collected at recruitment and analyzed using a metabolomic approach based on UPLC mass spectrometry. Results Among 34 children aged 4.0 ± 1.1 years recruited, at the end of the 3-year follow-up, 16 were classified as having transient wheezing and 16 as cases of early-onset asthma. Through a joint multivariate and univariate statistical analyses, we identified a subset of metabolomic variables that enabled the 2 groups to be clearly distinguished. The model built using the identified variables showed an AUC = 0.99 and an AUC = 0.88 on sevenfold full cross-validation (P = .002). Conclusions Metabolomic urinary profile can discriminate preschoolers with recurrent wheezing who will outgrow their symptoms from those who have early-onset asthma. These results may pave the way to the characterization of early non-invasive biomarkers capable of predicting asthma development.

There is growing interest for studying how early-life influences the development of respiratory diseases. Our aim was to apply metabolomic analysis to urine collected at birth, to evaluate whether there is any early metabolic signatures capable to distinguish children who will develop acute bronchiolitis and/or recurrent wheezing. Urine was collected at birth in healthy term newborns. Children were followed up to the age of 3 years and evaluated for the development of acute bronchiolitis and recurrent wheezing (≥3 episodes). Urine were analyzed through a liquid-chromatography mass-spectrometry based untargeted approach. Metabolomic data were investigated applying univariate and multivariate techniques. 205 children were included: 35 had bronchiolitis, 11 of whom had recurrent wheezing. Moreover, 13 children had recurrent wheezing not preceded by bronchiolitis. Multivariate data analysis didn’t lead to reliable classification models capable to distinguish children with and without bronchiolitis or with recurrent wheezing preceded by bronchiolitis neither by PLS for classification (PLS2C) nor by Random Forest (RF). However, a reliable signature was discovered to distinguish children who later develop recurrent wheezing not preceded by bronchiolitis, from those who do not (MCCoob = 0.45 for PLS2C and MCCoob = 0.48 for RF). In this unselected birth cohort, a well-established untargeted metabolomic approach found no biochemical-metabolic dysregulation at birth associated with the subsequent development of acute bronchiolitis or recurrent wheezing post-bronchiolitis, not supporting the hypothesis of an underlying predisposing background. On the other hand, a metabolic signature was discovered that characterizes children who develop wheezing not preceded by bronchiolitis.

s Background Available diagnostics often fail to distinguish viral from bacterial causes of pediatric community‐acquired pneumonia (pCAP). Metabolomics, which aims at characterizing diseases based on their metabolic signatures, has been applied to expand pathophysiological understanding of many diseases. In this exploratory study, we used the untargeted metabolomic analysis to shed new light on the etiology of pCAP. Methods Liquid chromatography coupled with mass spectrometry was used to quantify the metabolite content of urine samples collected from children hospitalized for CAP of pneumococcal or viral etiology, ascertained using a conservative algorithm combining microbiological and biochemical data. Results Fifty‐nine children with CAP were enrolled over 16 months. Pneumococcal and viral cases were distinguished by means of a multivariate model based on 93 metabolites, 20 of which were identified and considered as putative biomarkers. Among these, six metabolites belonged to the adrenal steroid synthesis and degradation pathway. Conclusions This preliminary study suggests that viral and pneumococcal pneumonia differently affect the systemic metabolome, with a stronger disruption of the adrenal steroid pathway in pneumococcal pneumonia. This finding may lead to the discovery of novel diagnostic biomarkers and bring us closer to personalized therapy for pCAP.

Background and objective Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy in the developed countries. Outcomes for BPD patients have traditionally been assessed using physiological parameters such as lung function, and no data are available on the health-related quality of life (HRQOL) for adolescents with BPD. The aim of this study was to assess HRQOL in adolescents with BPD, in comparison with age-matched and sex-matched control groups of healthy volunteers and asthmatic subjects. Methods We enrolled 27 BPD patients (age range 11–19 years), 27 asthmatic patients and 27 healthy controls. HRQOL was assessed by the Short Form 36 (SF-36) questionnaire. Lung function was assessed by spirometry. Results The BPD group did not differ significantly from the healthy controls in any scale or dimension of the SF-36 (the BPD group's summary scores were as follows: physical component summary mean 55.6 + 4.98 and mental component summary 51.8 + 7.75 vs 55.8 + 6.25 and 49.2 + 9.45 for the healthy control group, P > 0.5 and P = 0.26, respectively). Asthmatic adolescents scored lower than those of both healthy controls and patients with BPD in several SF-36 dimensions despite adolescents with BPD having lower lung function. No correlation emerged between lung function and HRQOL in BPD subjects. Conclusion Despite their impaired lung function, BPD patients have an HRQOL comparable with healthy peers and better than asthmatic patients. We did not find any association between HRQOL and lung function parameters.

Background: &ldquo, breathomics&rdquo, enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography&ndash, mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical&ndash, metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p &lt, 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: &ldquo, can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP&mdash, in spite of a significant clinical improvement&mdash, was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

Objectives: To apply metabolomic analysis of amniotic fluid in a discovery cohort to see whether a specific biochemical-metabolic profile at birth is associated with the subsequent onset of wheezing over the first year of life. Study design: This prospective exploratory study was conducted in a healthy term-born Dutch cohort recruited at 2 hospitals in Utrecht (UMCU, Utrecht, and Diakonessenhuis, Utrecht), The Netherlands. A metabolomic approach based on mass spectrometry was applied to analyze 142 amniotic fluid samples collected at birth. The infants were followed up during their first year of life with recording any respiratory symptoms daily, and they were classified according to the onset of wheezing. Results: Orthogonally constrained projection to latent structures discriminant analysis was used to investigate differences in the metabolic profiles of the infants with (n = 86) and without (n = 56) wheezing. A search of the available databases for amniotic fluid metabolites identified by stability selection, combined with pathway analysis, highlighted the possible metabolic perturbations involved in this condition. The model built using 16 relevant variables with plausible biological significance, showed an area under the curve of 0.82 (P

Background Asthma is a chronic condition usually characterized by underlying inflammation. The study of asthmatic inflammation is of the utmost importance for both diagnostic and monitoring purposes. The gold standard for investigating airway inflammation is bronchoscopy, with bronchoalveolar lavage and bronchial biopsy, but the invasiveness of such procedures limits their use in children. For this reason, in the last decades there has been a growing interest for the development of noninvasive methods. Main body In the present review, we describe the most important non-invasive methods for the study of airway inflammation in children, focusing on the measure of the fractional exhaled nitric oxide (feNO), on the measure of the exhaled breath temperature (EBT) and on the analysis of both exhaled breath condensate (EBC) and exhaled air (Volatile Organic Compounds, VOCs), using targeted and untargeted approaches. We summarize what is currently known on the topic of exhaled biomarkers in childhood asthma, with a special emphasis on emerging approaches, underlining the role of exhaled biomarkers in the diagnosis, management and treatment of asthma, and their potential for the development of personalized treatments. Conclusion Among non-invasive methods to study asthma, exhaled breath analysis remains one of the most interesting approaches, feNO and “-omic” sciences seem promising for the purpose of characterizing biomarkers of this disease.

Summary Asthma represents the most common chronic respiratory disease of childhood. Its current standard diagnosis relies on patient history of symptoms and confirmed expiratory airflow limitation. Nevertheless, the spectrum of asthma in clinical presentation is broad, and both symptoms and lung function may not always reflect the underlying airway inflammation, which can be determined by different pathogenetic mechanisms. For these reasons, the identification of objective biomarkers of asthma, which may guide diagnosis, phenotyping, management and treatment is of great clinical utility and might have a role in the development of personalized therapy. The availability of non-invasive methods to study and monitor disease inflammation is of relevance especially in childhood asthma. In this sense, a promising role might be played by the measurement of exhaled biomarkers, such as exhaled nitric oxide (FE NO ) and molecules in exhaled breath condensate (EBC). Furthermore, recent studies have shown encouraging results with the application of the novel metabolomic approach to the study of exhaled biomarkers. In this paper the existing knowledge in the field of asthma biomarkers, with a special focus on exhaled biomarkers, will be highlighted.

The way a postgraduate medical training program is organized and the capacity of faculty members to function as tutors and to organize effective professional experiences are among the elements that affect the quality of training. An evaluation system designed to target these elements has been implemented within the framework of the Pediatric Residency Program of the University of Padua (Italy). The aim of this report is to describe some aspects of the experience gained in the first 3 years of implementation of the system (2013–2015). Data were collected using four validated questionnaires: the “Resident Assessment Questionnaire”, the “Tutor-Assessment Questionnaire”, the “Rotation-Assessment Questionnaire”, and the “Resident Affairs Committee-Assessment Questionnaire”. The response rate was 72% for the “Resident Assessment Questionnaires”; 78% for the “Tutor-/Rotation-Assessment Questionnaires” and 84% for the “Resident Affair Committee-Assessment Questionnaires”. The scores collected were validated by psychometric tests. Conclusion: The high rates of completed questionnaires returned and the psychometric validation of the results collected indicate that the evaluation system reported herein can be effectively implemented. Efforts should be made to refine this system and, more importantly, to document its impact in improving the Pediatric Residency Program. What is known: • The elements that influence the quality of postgraduate training programs and the knowledge, performance, and competences of residents must be regularly assessed. • Comprehensive evaluation systems for postgraduate residency programs are not universally implemented also because quite often common guidelines and rules, well-equipped infrastructures, and financial resources are missing. What is new: • We show the feasibility of implementing an evaluation system that targets some of the key elements of a postgraduate medical training program in Italy, a European country in which the regulations governing training programs and, notably, the evaluation of residents are still being developed.

Recurrent respiratory infections (RRI) represent a widespread condition which has a severe social and economic impact. Immunostimulants are used for their prevention. It is crucial to better characterize children with RRI to refine their diagnosis and identify effective personalized prevention strategies. Metabolomics is a high-dimensional biological method that can be used for hypothesis-free biomarker profiling, examining a large number of metabolites in a given sample using spectroscopic techniques. Multivariate statistical data analysis then enables us to infer which metabolic information is relevant to the biological characterization of a given physiological or pathological condition. This can lead to the emergence of new, sometimes unexpected metabolites, and hitherto unknown metabolic pathways, enabling the formulation of new pathogenetic hypotheses, and the identification of new therapeutic targets. The aim of our pilot study was to apply mass-spectrometry-based metabolomics to the analysis of urine samples from children with RRI, comparing these children's biochemical metabolic profiles with those of healthy peers. We also compared the RRI children's and healthy controls' metabolomic urinary profiles after the former had received pidotimod treatment for 3 months to see whether this immunostimulant was associated with biochemical changes in the RRI children's metabolic profile. 13 children (age range 3-6 yeas) with RRI and 15 matched per age healthy peers with no history of respiratory diseases or allergies were enrolled. Their metabolomic urine samples were compared before and after the RRI children had been treated with pidotimod for a period of 3 months. Metabolomic analyses on the urine samples were done using mass spectrometry combined with ultra-performance liquid chromatography (UPLC-MS). The resulting spectroscopic data then underwent multivariate statistical analysis and the most relevant variables characterizing the two groups were identified. Data modeling with post-transformation of PLS2-Discriminant Analysis (ptPLS2-DA) generated a robust model capable of discriminating the urine samples from children with RRI from those of healthy controls (R2=0.92,Q2CV7-fold=0.75, p-value

S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients.We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole.Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a “severe asthma” diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow.An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.

Food allergy is an increasingly prevalent problem all over the world and especially in westernized countries, and there is an unmet medical need for an effective form of therapy. During childhood natural tolerance development is frequent, but some children with cow#039;s milk or hen's egg allergy and the majority of children with peanut allergy will remain allergic until adulthood, limiting not only the diet of patients but also their quality of life. Within the last several years, the usefulness of immunotherapy for food allergies has been investigated in food allergic patients. Several food immunotherapies are being developed; these involve oral, sublingual, epicutaneous, or subcutaneous administration of small amounts of native or modified allergens to induce immune tolerance. The approach generally follows the same principles as immunotherapy of other allergic disorders and involves administering small increasing doses of food during an induction phase followed by a maintenance phase with regular intake of a maximum tolerated amount of food. Oral immunotherapy seems to be a promising approach for food allergic patients based on results from small uncontrolled and controlled studies. Diet containing heated milk and egg may represent an alternative approach to oral immunomodulation for cow's milk and egg allergic subjects. However, oral food immunotherapy remains an investigational treatment to be further studied before advancing into clinical practice. Additional bigger, multicentric and hopefully randomized-controlled studies must answer multiple questions including optimal dose, ideal duration of immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment.

Background: In the context of the so-called unified airway theory, chronic rhinosinusitis (CRS) and asthma may coexist. The inflammation underlying these conditions can be studied through the aid of biomarkers. Main body: We described the main biological mediators that have been studied in pediatric CRS and asthma, and, according to the available literature, we reported their potential role in the diagnosis and management of these conditions. As for CRS, we discussed the studies that investigated nasal nitric oxide (nNO), pendrin, and periostin. As for asthma, we discussed the role of fractional exhaled nitric oxide (feNO), the role of periostin, and that of biological mediators measured in exhaled breath condensate (EBC) and exhaled air (volatile organic compounds, VOCs). Conclusion: Among non-invasive biomarkers, nNO seems the most informative in CRS and feNO in asthma. Other biological mediators seem promising, but further studies are needed before they can be applied in clinical practice.

Background. Few studies have prospectively followed respiratory function of bronchopulmonary dysplasia (BPD) survivors from infancy to adult age. Objectives. This study was conducted from March 1991 to March 2016 to longitudinally investigate the evolution of lung function in 17 survivors of BPD (birth weight Methods. Maximum flow at functional residual capacity(VmaxFRC ) at 2 years (yrs), and lung function(FEV 1, FVC and FEF 25-75 ) at ages 9, 15, 20 and 24 yrs were obtained for each subject. Repeated measures analysis of variance ANOVA, t test, and linear regression were used for data analysis. Results. Survivors of BPD showed a consistent lung function tracking from 2 years till 24 years of age. No significant change in mean z-score emerged between expiratory flow measures at ages 2 years(zVmaxFRC -1.48, SD 1.38), 9 yrs (zFEV 1 -1.74, SD 1.03), 15 yrs (zFEV 1 -1.71, SD 1.72), 20 yrs (zFEV 1 -1.73, SD 1.65) and 24 yrs(zFEV 1 -2.14, SD 1.74)(P=0.42). Mean z-scores for FVC and FEF 25-75 did not change significantly between different ages as well(P>0.5 and P=0.45 respectively). A significant correlation was found between the z-scores for VmaxFRC at 2 years and the z-scores for FEV 1 at ages 15 yrs(r=0.74, P=0.001), 20 yrs(r=0.75, P 1 ≥12%) was observed in 23.5% of subjects. Comment . Our findings show that BPD survivors present a tracking of lung function until adulthood, with flow limitation still persisting at 24 years of age. Reduced expiratory flow at 2 years identifies patients at greater risk of developing a COPD-like phenotype at adult age.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy in the developed countries. Outcomes for BPD patients have traditionally been assessed using physiological parameters such as lung function, and no data are available on the health-related quality of life (HRQOL) for adolescents with BPD. The aim of this study was to assess HRQOL in adolescents with BPD, in comparison with age-matched and sex-matched control groups of healthy volunteers and asthmatic subjects.We enrolled 27 BPD patients (age range 11-19 years), 27 asthmatic patients and 27 healthy controls. HRQOL was assessed by the Short Form 36 (SF-36) questionnaire. Lung function was assessed by spirometry.The BPD group did not differ significantly from the healthy controls in any scale or dimension of the SF-36 (the BPD group's summary scores were as follows: physical component summary mean 55.6 + 4.98 and mental component summary 51.8 + 7.75 vs 55.8 + 6.25 and 49.2 + 9.45 for the healthy control group, P 0.5 and P = 0.26, respectively). Asthmatic adolescents scored lower than those of both healthy controls and patients with BPD in several SF-36 dimensions despite adolescents with BPD having lower lung function. No correlation emerged between lung function and HRQOL in BPD subjects.Despite their impaired lung function, BPD patients have an HRQOL comparable with healthy peers and better than asthmatic patients. We did not find any association between HRQOL and lung function parameters.

IMPORTANCE Anakinra, an interleukin 1 beta recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. OBJECTIVE To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. DESIGN, SETTING, AND PARTICIPANTS The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with >= 3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. INTERVENTIONS Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. MAIN OUTCOMES AND MEASURES The primary outcomes were recurrent pericarditis and time to recurrence after randomization. RESULTS Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06% of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of -1.95%(95% CI, -3.3% to -0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P