Feasibility of shotgun urinary proteomics for investigating prematurely born preschoolers (PBP)

Background: Preterms and twins are at higher risk of respiratory morbidity later in life. Advances in proteomic approaches may allow the characterization of biomarkers involved in respiratory diseases (Mauri et al. Imm. Lett. 2014;162:2-10). Gel-free approach quantitatively identify differentially expressed proteins in relation to physiopathological conditions (Mauri&Dehò, Meth Enzymology 2008;447:99-117). This can improve the clinical reliability of the next generation of biomarkers to discriminate multiple phenotypes of childhood respiratory diseases. Aim: To assess the ability of gel-free proteomics for identifying specific protein profiles related to PBP. Methods: Urine samples were…

Activation-Induced Rigidity in Neurologically and Cognitively Healthy Individuals Aged 18-90 Years: A Cross-Sectional Study.

Background: Rigidity is a key clinical feature of Parkinson’s disease (PD), but in a very early phase of the disease it may be absent and can be enhanced through active movements of the arm contralateral to the one being tested. Objective: To evaluate in a large cohort of neurologically and cognitively healthy (NCH) subjects aged 18–90 years if activation-induced rigidity (AR) is present in all age classes, and if there are biological differences between subjects showing AR (AR+) and not showing AR (AR-). Methods: 2,228 NCH subjects categorized as young adult (18–44 years), adult (45–64 years), elderly (65–74 years), and old/oldest-old (75–90 years) were included in the analysis, and underw…

Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial

<b><i>Background:</i></b> Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. <b><i>Methods:</i></b> In this 21-day,<b> </b>open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS…

Nociceptive Primitive Reflexes in Neurologically and Cognitively Healthy Aging Subjects

ABSTRACT:Background:To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects.Objective:To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy.Methods:A total of 1246 NCH subjects aged 45–91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visu…

Additional file 1 of Identification of bronchiolitis profiles in Italian children through the application of latent class analysis

Additional file 1: Figure S1. Response probabilities among the three latent classes excluding children aged ≥12 months.

A Critical Review of Statistical Methods for Twin Studies Relating Exposure to Early Life Health Conditions

International audience; When investigating disease etiology, twin data provide a unique opportunity to control for confounding and disentangling the role of the human genome and exposome. However, using appropriate statistical methods is fundamental for exploiting such potential. We aimed to critically review the statistical approaches used in twin studies relating exposure to early life health conditions. We searched PubMed, Scopus, Web of Science, and Embase (2011–2021). We identified 32 studies and nine classes of methods. Five were conditional approaches (within-pair analyses): additive-common-erratic (ACE) models (11 studies), generalized linear mixed models (GLMMs, five studies), gene…

Machine learning: A modern approach to pediatric asthma

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.

Pharmacogenomics: A Step forward Precision Medicine in Childhood Asthma.

Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, …

Association between Asthma Control and Exposure to Greenness and Other Outdoor and Indoor Environmental Factors: A Longitudinal Study on a Cohort of Asthmatic Children

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…

Additional file 1: of Associations of greenness, greyness and air pollution exposure with childrenâ s health: a cross-sectional study in Southern Italy

Table S1. Risk factors for self-reported ocular, nasal, pulmonary and general symptoms from children questionnaires: estimated odds ratios (OR) and 95% confidence intervals (95% CI) from univariable logistic regression models. Table S2. Risk factors for self-reported ocular, nasal, pulmonary and general symptoms from children questionnaires: estimated odds ratios (OR) and 95% confidence intervals (95% CI) from multivariable logistic ridge regression models using the full quartile for NDVI and NO2. Table S3 Multivariable Poisson ridge regression models, using the full quartile for NDVI and NO2, for symptoms score: estimated rate ratios (RR) and 95% confidence intervals (95% CI). (DOCX 25 kb)

Latent class identification in wheezing preschool children

Background and aim Since the forced oscillation technique (FOT) has not been used in previous studies on wheezing phenotyping in preschool children, we applied FOT in a large series of outpatients visited at IBIM. Methods We analyzed 256 consecutively enrolled ≤5 years children with doctor diagnosis of wheezing. Latent Class Analysis (LCA) was performed considering the following personal characteristics: type, cause, recurrence in last 12 months, respiratory resistance (Avr_R(8)), atopy, history of eczema, rhinitis and upper airways infections. High resistance is defined as positive residual of regression on sex, age, height and weight. Risk factors were considered meaningful when they yiel…

Asthma-Related Knowledge and Practices among Mothers of Asthmatic Children: A Latent Class Analysis

Mothers’ knowledge about childhood asthma influences management practices and disease control, but validating knowledge/practice questionnaires is difficult due to the lack of a gold standard. We hypothesized that Latent Class Analysis (LCA) could help identify underlying mother profiles with similar knowledge/practices. A total of 438 mothers of asthmatic children answered a knowledge/practice questionnaire. Using answers to the knowledge/practice questionnaire as manifest variables, LCA identified two classes: Class 1, “poor knowledge” (33%); Class 2, “good knowledge” (67%). Classification accuracy was 0.96. Mothers in Class 2 were more likely to be aware of …

Machine Learning: An Overview and Applications in Pharmacogenetics.

This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant, anti-cancer and warfarin drugs) over the past 10 years. ML deals with the study, the design and the development of algorithms that give computers capability to learn without being explicitly programmed. ML is a sub-field of artificial intelligence, and to date, it has demonstrated satisfactory performance on a wide range of tasks in biomedicine. According to the final goal, ML can be defined as Supervised (SML) or as Unsupervised (UML). SML techniques are applied when prediction is the focus of the research. On the other hand, UML…

Associations of greenness, greyness and air pollution exposure with children's health: a cross-sectional study in Southern Italy

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 (C…

The Dietary Inflammatory Index and asthma burden in children: A latent class analysis

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 5–14 years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquant…

New insights in respiratory impedance in young children after repair of congenital diaphragmatic hernia: a cross-sectional study

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 usi…

Rhinomanometry: point of care test (POCT) for allergic rhinitis in children?

Allergic rhinitis (AR) is a global health problem: its prevalence is 23% in Europe, although it is underestimated because as many as 45% of the cases remain undiagnosed. Globally, almost 500 million people suffer from AR, which shows its increasing incidences. The diagnostic course of AR is based on clinical history, supported by anterior rhinoscopy. This inspects the anterior part of the nasal cavity accompanied by allergic sensitivity tests (cutaneous allergic skin tests or specific immunoglobulin E levels). The availability of standardised diagnostic proceduresis able to provide objective evaluations of inflammatory situation, and the degree of nasal obstruction may give an advantage in …

Beclomethasone dipropionate hydrofluoroalkane for the treatment of allergic rhinitis

Allergic rhinitis (AR) is a common respiratory disease, and its prevalence is increasing all over the world, both in adults and in children. Patients experience symptoms that may negatively impact on physical, social and psychological well-being. Hence, if left untreated, allergic rhinitis may significantly affect quality of life. Under current guidelines, intranasal corticosteroids are considered the most effective drugs and they are recommended as first-line therapy. Among the several corticosteroid intranasal sprays available, beclomethasone dipropionate is one of the most prescribed. Recently, new intranasal hydrofluoroalkane-propelled formulations with little or no impact on the ozone …

Apoe genotypes and brain imaging classes in normal cognition, mild cognitive impairment, and alzheimer’s disease: A longitudinal study

Objective: To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V−/A−, V−/A+, V+/A−, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes. Methods: Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyp…

Shotgun Proteomics of Isolated Urinary Extracellular Vesicles for Investigating Respiratory Impedance in Healthy Preschoolers

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 differen…

Surgical treatment of primary gastrointestinal stromal tumors (GISTs): Management and prognostic role of R1 resections

Abstract Background Surgery represents the best treatment for primary gastrointestinal stromal tumors (GISTs). The aim of this study is to analyse outcomes of surgical management in order to evaluate the influence of microscopically R1 margins on survival and recurrence in patients affected by GISTs. Methods The study reviewed retrospective data from 74 patients surgically treated for primary GISTs without metastasis at diagnosis. Clinical and pathological findings, surgical procedures, information about follow up and outcomes were analyzed. Results Recurrence rate was low and no patients died in the R1 group during the follow up period. The difference in recurrence free survival for patien…

Isolated, Subtle Neurological Abnormalities in Mild Cognitive Impairment Types.

Isolated, subtle neurological abnormalities (ISNA) are commonly seen in aging and have been related to cerebral small vessel disease (SVD) and subcortical atrophy in neurologically and cognitively healthy aging subjects.To investigate the frequency of ISNA in different mild cognitive impairment (MCI) types and to evaluate for each MCI type, the cross-sectional relation between ISNA and white matter hyperintensities (WMH), lacunes, caudate atrophy, and ventricular enlargement.One thousand two hundred fifty subjects with different MCI types were included in the analysis and underwent brain magnetic resonance imaging. WMHs were assessed through two visual rating scales. Lacunes were also rated…

Overrating Classifier Performance in ROC Analysis in the Absence of a Test Set: Evidence from Simulation and Italian CARATkids Validation

Background The use of receiver operating characteristic curves, or “ROC analysis,” has become quite common in biomedical research to support decisions. However, sensitivity, specificity, and misclassification rates are still often estimated using the training sample, overlooking the risk of overrating the test performance. Methods A simulation study was performed to highlight the inferential implications of splitting (or not) the dataset into training and test set. The normality assumption was made for the classifier given the disease status, and the Youden's criterion considered for the detection of the optimal cutoff. Then, an ROC analysis with sample split was applied to assess the disc…

Salt intake and asthma in children and adolescents

Comparative Effect of Beclomethasone Dipropionate and Cetirizine on Acoustic Rhinometry Parameters in Children With Perennial Allergic Rhinitis: A Randomized Controlled Trial.

Background and objectives The effect of intranasal corticosteroids and oral antihistamines on acoustic rhinometry parameters has not been directly compared. The primary objective was to compare the effect of a 21-day course of treatment with nasal beclomethasone dipropionate (nBDP) with that of cetirizine (CTZ) on nasal patency measured using acoustic rhinometry in children with perennial allergic rhinitis (PAR). The secondary objective was to compare the effect of both drugs on nasal cytology, symptom severity, sleep quality, and quality of life. Methods In this 21-day, open-label, randomized controlled study, 34 children with PAR (age 6-14 years) with a Total 5-Symptom Score (T5SS) ≥5 rec…

Assessing Repeatability and Reproducibility of Anterior Active Rhinomanometry (AAR) in Children

AbstractBackgroundRepeatability 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.MethodsA simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and …

From research question to dissemination: how to design, analyse and present study results

Today, the term “study” is very frequently used in quite a broad sense: survey, clinical trial, analysis, research and other terms with deeply different meanings are often generally indicated as “studies”. A “study” can be generally defined as a process composed of several actions aimed to verify one or more hypotheses (objectives), with the ultimate goal of sharing the answers (results) with a target audience, in the form of a scientific paper, presentation or poster.

New technologies for promoting physical activity in healthy children and in children with chronic respiratory diseases: A narrative review

Physical activity (PA) is proven to benefit children and adolescents in several ways. New technologies may provide children with stimulating modalities for organizing their leisure time, accessing fitness programs, and obtaining daily goal reminders and peer support. Due to the current COVID-19 pandemic, following WHO recommendations for PA is difficult for many children, especially for those living in urban areas. Therefore, the use of digital tools to support and maintain PA could be useful in healthy children, as well as in those with chronic respiratory diseases (CRDs). This narrative review aims to summarize the most recent evidence about the role of new technologies in promoting PA in…

VAS and PAQLQ association with level of asthma control by using C-ACT

Background: PAQLQ and C-ACT are standardized tool for assessment quality of life and asthma control in children.VAS (Visual Analogic Scale) is a scale for evaluation of the general wellness at the time of visit. Aim: To assess the relationships between VAS, PAQLQ and CACT in order to discriminate Controlled by Uncontrolled ones. Method: Cross-sectional study on 169 asthmatic children aged 5-11 yrs consecutively enrolled from Sept 2011 to Dec 2014 were studied. The Italian version of C-ACT and PAQLQ questionnaire were administered at baseline. Well controlled (WC) asthma and Uncontrolled/Partially controlled (UPC) resulted from C-ACT score >19 and ≤19, respectively. Total score of PAQLQ r…

Association between greenspace and lung function in Italian children-adolescents

Background: Few studies have examined the impact of urban greenspace exposure on lung function in children-adolescents, and the available evidence is still inconsistent. The aim of the current study was to verify the hypothesis that the effects of greenspace exposure vary with differing levels of lung function of children-adolescents. Methods: Between November 2005 and May 2006, 2150 children-adolescents (age-range: 10-15 years) living in the city of Palermo were enrolled in a cross-sectional survey. Parents were interviewed through a modified version of the Italian Studies on Respiratory Disorders in Children and the Environment (SIDRIA) questionnaire. All children-adolescents performed sp…

Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

Background: miRNAs are master regulators of signaling pathways critically involved in asthma and are transferred between cells in extracellular vesicles (EV). We aimed to investigate whether the miRNA content of EV secreted by primary normal human bronchial epithelial cells (NHBE) is altered upon asthma development. Methods: NHBE cells were cultured at air-liquid interface and treated with interleukin (IL)-13 to induce an asthma-like phenotype. EV isolations by precipitation from basal culture medium or apical surface wash were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blot, and EV-associated miRNAs were identified by a RT-qPCR-based prof…

Identification of bronchiolitis profiles in Italian children through the application of latent class analysis

AbstractBackgroundBronchiolitis 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.MethodsThis was a retrospective single-centre study conducted on children aged ≤2 years hospitalised with bronchiolitis (n = 401) at the Department of…

Global Lung Function Initiative 2012 reference values for spirometry in South Italian children

Rationale Despite the widespread use of the Global Lung Function Initiative (GLI) 2012 reference values, there is still the need of testing their applicability in local areas. Objectives The aims of this study are to evaluate applicability of GLI reference equations in a large population-based sample of normal schoolchildren from Sicily, and to compare GLI and previous prediction equations in terms of spirometry test interpretation. Methods GLI equations were evaluated in 1243 normal schoolchildren, 49% males, aged 7–16 years, height 116–187 cm. Normality assumptions for the GLI z-scores (FEV1, FVC, FEV1/FVC) were tested, and bootstrap confidence intervals for the mean (0 expected) and …

Lower probability of FEV1 improvement in asthmatic children exposed to passive smoke

Background: Guidelines advocate the use of spirometry to assess lung function in asthmatic. Inhaled corticosteroid(ICS) therapy is a mainstay of treatment for asthma, but the clinical response is variable. Aim: To assess the time variation of FEV1% in treated children with Persistent Asthma (PA). Methods: 110 children with PA, with two visits between September 2011 and December 2014 at the IBIM pediatric clinic were studied. Spirometry was performed using Pony FX, Cosmed, Italy; values were expressed as %pred using GLI-2012equation. The time trend of FEV1% for each subject was estimated through separate regressions. A linear regression model for the individual slopes (FEV1% average month va…

A model-based approach for assessing bronchodilator responsiveness in children: The conventional cutoff revisited

An increase in FEV1 >=12% has been proposed in international guidelines as a clue to airway reversibility for diagnosing asthma in both adults and children. However, the validity of this cut-off has been questioned in the pediatric population. The aim of this study was to provide evidence that different cut-off values in BDR may be associated with better performance in discriminating among outpatient children with naïve asthma (A) and without asthma (NA). We compared three approaches: i) the conventional cutoff (12%); ii) the cut-off estimated by Youden's criteria; and iii) the cut-off based on a model-driven approach. we found that the conventional cut-off of 12% showed poor sensitivity in…

Endotyping allergic rhinitis in children: A machine learning approach.

Introduction: The diversity of allergic rhinitis (AR) phenotypes is particularly evident in childhood, suggesting the need to analyze and identify new approaches to capture such clinical heterogeneity. Nasal cytology (NC) is a very useful diagnostic tool for identifying and quantifying nasal inflammation. Data-driven approaches such as latent class analysis (LCA) assign subjects to classes based on their characteristics. We hypothesized that LCA based on NC, including the assessment of neutrophils, eosinophils, and mast cells, may be helpful for identifying AR endotypes in children. Methods: A total of 168 children were enrolled. Sociodemographic characteristics and detailed medical history…

Barriers and incentives for Italian paediatricians to become smoking cessation promoters: a GARD-Italy Demonstration Project

Background: Paediatricians rarely devote any time to screening and treatment for parental tobacco use. The present project is part of a Global Alliance against Chronic Respiratory Diseases (GARD)-Italy Demonstration Project, aimed to increase the skills of primary care physicians and paediatricians as "promoter of smoking cessation". The aims of this study were: (I) to identify latent classes of barriers and incentives for smoking cessation counseling among paediatricians using latent class analysis (LCA); (II) to investigate risk factors for inclusion into the identified classes. Methods: In 2018, 1,500 Italian paediatricians were invited to complete an online survey on passive smoke expos…

Nasal budesonide efficacy for nasal nitric oxide and nasal obstruction in rhinitis

Nasal nitric oxide (nNO) is a noninvasive tool that may be helpful in evaluating the inflammatory status in the upper airways [1]. Previous studies report that nNO is elevated in children with Allergic Rhinitis (AR) [2], especially in perennial sensitized subjects [3], and that it may be affected by topical administration of intranasal steroids (INSs) [4]. This article is protected by copyright. All rights reserved.

Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral Small Vessel Disease and Mild Parkinsonian Signs in Neurologically and Cognitively Healthy Subjects Aged 45-84 Years: A Crosssectional Study

Background: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral Small Vessel Diseases (SVD) with no univocal results. Objective: The aim of this study was to investigate the cross-sectional relation between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of Neurologically and Cognitively Healthy (NCH) aging individuals. Method: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI. The items of the motor section of the Unified Parkinson’s Disease Rating Scale were used to evaluate tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction. Cau…

Traffic proximity and lung function. A case-control study in asthmatic children

Introduction: Respiratory conditions are strongly dependent on air pollution. Urban areas are typically characterized by risky environmental conditions. Objectives: To analyze the effect of traffic proximity on asthma and to explore the relationship between level of traffic proximity and lung function in asthmatic and non- asthmatic children. Methods: A case-control study on children visited for suspected respiratory diseases at IBIM from 2011 to 2014 was performed. All the children have been geocoded according to their residence address. Exposure to traffic air pollution was assessed through determination of number and types of streets in proximity of the place of residence. The relationsh…

Inquinamento ambientale, fumo e asma grave

The health burden of air pollution on the world’s children is immense. Environmental factors are responsible for an estimated 26% of all children’s death worldwide. A large body of research exists on the effects of air pollution on children’s health, including effects on fetal growth, birth outcomes, lung development and function, asthma, respiratory infection and otitis media. It is also clearly linked to a higher risk of developing asthma, a major cause of morbidity in children. Indoor environments contribute significantly to total human exposure to air pollutants. Overall, people spend most time indoors. Pollutants remain in the air longer inside than outside. Some pollutants may be two …

Rhinomanometry: point of care test (POCT) for allergic rhinitis in children?

Allergic rhinitis (AR) is a global health problem: its prevalence is 23% in Europe, although it is underestimated because as many as 45% of the cases remain undiagnosed. Globally, almost 500 million people suffer from AR, which shows its increasing incidences. The diagnostic course of AR is based on clinical history, supported by anterior rhinoscopy. This inspects the anterior part of the nasal cavity accompanied by allergic sensitivity tests (cutaneous allergic skin tests or specific immunoglobulin E levels). The availability of standardised diagnostic procedures is able to provide objective evaluations of inflammatory situation, and the degree of nasal obstruction may give an advantage in…

3D-Reconstruction of a Giant Posidonia oceanica Beach Wrack (Banquette): Sizing Biomass, Carbon and Nutrient Stocks by Combining Field Data With High-Resolution UAV Photogrammetry

Beach wracks are temporary accumulations of vegetal detritus that can be found along coastlines all over the world. Although beach wracks are often perceived as a nuisance for beach users, they play a crucial ecological role in carbon and nutrient connectivity across ecosystem boundaries, especially when they reach a relevant size, as in the case of the wedge-shaped seagrass accumulations called banquette. In this study, three-dimensional mapping of a giant Posidonia oceanica banquette was carried out for the first time using high-resolution UAV photogrammetry combined with field sampling and compositional and chemical analysis. The combined approach allowed a reliable estimation of the amo…

An association analysis to identify genetic variants linked to asthma and rhinoconjunctivitis in a cohort of Sicilian children

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.

The Induced Smoothed lasso: A practical framework for hypothesis testing in high dimensional regression.

This paper focuses on hypothesis testing in lasso regression, when one is interested in judging statistical significance for the regression coefficients in the regression equation involving a lot of covariates. To get reliable p-values, we propose a new lasso-type estimator relying on the idea of induced smoothing which allows to obtain appropriate covariance matrix and Wald statistic relatively easily. Some simulation experiments reveal that our approach exhibits good performance when contrasted with the recent inferential tools in the lasso framework. Two real data analyses are presented to illustrate the proposed framework in practice.

The induced smoothed LASSO

We propose a new lasso-type estimator of regression coefficients for regression models. Our proposal relies on the recent idea of induced smoothing and leads to estimators with sampling distribution somewhat close to the Normal one, regardless of their true value, along with the corresponding reliable covariance matrix. As a consequence inference (e.g. p-values) may be carried out relatively easily. We present results from some simulation experiments.

Measuring lung function in asthmatic children: A spirometry and forced oscillation technique (FOT) comparison

Background: Spirometry is the most common pulmonary function test used in asthma diagnosing. However, it requires good patient co-operation. FOT has gained increasing attention for the measurement of pulmonary function in children because it is performed at steady state breathing. Aim: To compare spirometry and FOT in order to discriminate severity of asthma according to GINA. Methods: Spirometry and FOT were performed in 176 out-patient asthmatic children (5-16 year), 100 (57%) with naive Persistent Asthma (PA) and 76 (43%) with Intermittent Asthma (IA), consecutively enrolled at the IBIM pediatric clinic. Two principal component analyses (PCA) were performed, the first (PCA1) based on FEV…

Anti-muscarinic drugs as preventive treatment of exercise-induced bronchoconstriction (EIB) in children and adults.

Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger airway symptoms and bronchoconstriction. The transient airway narrowing occurring because of exercise is named exercise-induced bronchoconstriction (EIB). Despite management according to guidelines, a significant proportion of patients experiences uncontrolled EIB, which thus represents a relevant unmet medical need. In particular, although prevention and treatment of EIB are effectively based on the use of beta-2 bronchodilator drugs, high heterogeneity in individual responses has been reported. Furthermore, even though beta-…

Climate advocacy among Italian pediatric pulmonologists: A national survey on the effects of climate change on respiratory allergies.

Climate change (CC) is expected to negatively impact respiratory health due to air pollution and increased aeroallergen exposure. Children are among the most vulnerable populations due to high ventilation rates, small peripheral airways, and developing respiratory and immunological systems. To assess the current knowledge among Italian pediatric pulmonologists on the potential effects of CC on pediatric respiratory allergic diseases, a national survey was launched online from February 2020 to February 2021. The members of the Italian Pediatric Respiratory Society (SIMRI) were contacted by email and 117 questionnaires were returned (response rate 16.4%). 72.6% of respondents were females, 53…

The Effect of Outdoor Aeroallergens on Asthma Hospitalizations in Children in North-Western Tuscany, Italy.

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&ndash…

Development of a nomogram to estimate the quality of life in asthmatic children using the Childhood Asthma Control Test

Background: Pediatric Asthma Quality of Life Questionnaire (PAQLQ) provides detailed information on QoL in asthmatic children, whereas Childhood Asthma Control Test (C-ACT) Questionnaire is the most validated instrument for asthma control. No study assessed the relationship between C-ACT and QoL in children by means of those instruments. The aim of this study was to determine whether a QoL estimation is possible using the C-ACT questionnaire in asthmatic children. Methods: Medical history, spirometry, C-ACT, and PAQLQ were assessed in 144 (60% male) outpatient asthmatic children from September 2011 to November 2014. A generalized linear model (GLM) for the prediction of PAQLQ was obtained t…

A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction t…

RAPP-children: A new tool for assessing quality of life in patients with asthma and rhinitis

Background: RhinAsthma Patient Perspective (RAPP) is a short, validated questionnaire for assessing health-related quality of life (HRQoL) in adult patients with comorbid asthma and rhinitis, while a paediatric version is still not available. Objective: The current study aimed to develop and validate the RAPP-children questionnaire. Methods: RAPP-children was derived by combining RhinAsthma-children subscales into five unique items. At baseline (T0) and after 30 days (T1), 150 children (6-11 years) with comorbid asthma (predominantly intermittent or mild persistent) and rhinitis were given the following: RAPP-children, RhinAsthma-children, Paediatric Asthma Quality of Life Questionnaire (PA…

Targeting quality of life in asthmatic children: The MyTEP pilot randomized trial

Abstract Background Quality of life (QoL) is an important outcome in the management of children with asthma. Mobile Health (m-Health) and Therapeutic Education Programs (TEPs) are increasingly recognized as essential components of pediatric asthma management to improve disease outcomes. Objective To evaluate the effect of an education program (MyTherapeutic Education Program, MyTEP) that couples multidisciplinary TEP intervention with an m-Health Program (mHP) in improving QoL in asthmatic children. Methods This single-center study employed a nonblinded randomized clinical trial design. Italian-speaking children (6–11 years) with mild-moderate asthma were eligible for participation. Partici…

Co-existing with the alien: evidence for environmental control on trophic interactions between a native (Atherina boyeri) and a non-indigenous fish species (Gambusia holbrooki) in a Mediterranean coastal ecosystem

Biological invasions are a widespread problem worldwide, as invasive non-indigenous species (NIS) may affect native populations through direct (e. g., predation) or indirect (e.g., competition) trophic interactions, leading to changes in the food web structure. The trophic relationships of the invasive eastern mosquitofish Gambusia holbrooki and the native big-scale sand smelt Atherina boyeri coexisting in three Mediterranean coastal ponds characterized by different trophic statuses (from oligotrophic to hypereutrophic) were assessed in spring through isotopic niche analysis and Bayesian mixing models. The two fish relied on the distinctive trophic pathways in the different ponds, with the …

The effect of residential urban greenness on allergic respiratory diseases in youth: A narrative review

Abstract 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 dev…

Cluster analysis of clinical data reveals three pediatric eosinophilic gastrointestinal disorder phenotypes

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

Asthma control, severity and lung function impairment through network analysis in children

Background: Achieving and maintaining asthma control in children is the primary goal recommended by current guidelines. Aim: To identify risk factors associated with Asthma control and severity, as well as their relative weight. Methods: Within a consecutive series of outpatients visited in a three years period at the IBIM pediatric clinic, we selected 128 persistent asthmatics. A standardized medical interview was carried out to collect information on environmental risk factors, symptoms and comorbidities. Spirometry was performed using Pony FX, Cosmed, Italy; spirometric values were expressed as %pred using GLI-2012equation. Statistical analyses were performed by using R. Results: The ide…

Endotyping Seasonal Allergic Rhinitis in Children: A Cluster Analysis.

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.R…

Effects of Polycyclic Aromatic Hydrocarbons on Lung Function in Children with Asthma: A Mediation Analysis.

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…

Nonlinear parametric quantile models

Quantile regression is widely used to estimate conditional quantiles of an outcome variable of interest given covariates. This method can estimate one quantile at a time without imposing any constraints on the quantile process other than the linear combination of covariates and parameters specified by the regression model. While this is a flexible modeling tool, it generally yields erratic estimates of conditional quantiles and regression coefficients. Recently, parametric models for the regression coefficients have been proposed that can help balance bias and sampling variability. So far, however, only models that are linear in the parameters and covariates have been explored. This paper …

Investigating the Relationship between Parental Education, Asthma and Rhinitis in Children Using Path Analysis.

Parental socioeconomic position (SEP) is a known determinant of a child’s health. We aimed to investigate whether a low parental education, as proxy of SEP, has a direct effect on physician-diagnosed asthma, current asthma and current allergic rhinitis in children, or whether associations are mediated by exposure to other personal or environmental risk factors. This study was a secondary data analysis of two cross-sectional studies conducted in Italy in 2006. Data from 2687 adolescents (10–14 years) were analyzed by a path analysis model using generalized structural equation modelling. Significant direct effects were found between parental education and family characteristics (n…

Impact of a Supervised Training Course on Spirometry Competency for Primary Care Pediatricians

Objective: Spirometry is the most commonly performed lung function test, and performance, adherence to acceptability and repeatability criteria, and accurate interpretation of results help optimize the test's usefulness. This study aimed to measure the effects of spirometry training courses supported by the Italian Pediatric Respiratory Society (IPRS) on primary care pediatricians' (PCP) knowledge of spirometry test quality, ability to interpret results, and overall degree of satisfaction with the course.Methods: Of the six face-to-face courses, four lasted two days and two lasted one day: mean duration of theoretical lessons was five and four hours respectively; and practical sessions last…

Asthma Comorbidities: Frequency, Risk Factors, and Associated Burden in Children and Adolescents

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%…

Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis

Background: Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). Forboth aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. Methods: 47 pre-pubertal GHD children (aged 5–14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Contr…

Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study

Background:Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results.Objective:To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes.Methods:A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated…

RHINASTHMA-Children: A new quality of life tool for patients with respiratory allergy

Background Specific instruments for health-related quality of life (HRQoL) assessment in adolescents with rhinoconjunctivitis or asthma are available. None of them evaluates rhinitis and asthma together, although they often coexist. Our aim was to validate a HRQoL questionnaire for adolescents with rhinoconjunctivitis, asthma, or both. Methods A pool of 38 items covering the main symptoms and problems related to respiratory allergy was generated based on literature review, clinical experience, and unstructured interviews to 54 adolescents. The items were randomly listed and presented to 88 consecutive outpatients (44 M; mean age 15.2 ± 3.1). Patients had to indicate which item they had expe…

Twenty-year follow-up of children with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in children is associated with acute metabolic, cardiovascular, and neurocognitive abnormalities. The long-term outcomes of childhood OSA into adulthood have not been established. We performed a 20-year follow-up of patients with polysomnography-documented OSA in childhood compared to a healthy control group to evaluate the long-term anthropometric, sleep, cognitive, and cardiovascular outcomes. METHODS: Children diagnosed with severe OSA between ages 1 and 17 years (mean, 4.87 ± 2.77) were prospectively contacted by telephone as young adults after approximately 20 years. Data collected included reported anthropometric information, educational…

Cluster Analysis of Home Polygraphic Recordings in Symptomatic Habitually-Snoring Children: A Precision Medicine Perspective

(1) Background: Sleep-disordered breathing (SDB) is a frequent problem in children. Cluster analyses offer the possibility of identifying homogeneous groups within a large clinical database. The application of cluster analysis to anthropometric and polysomnographic measures in snoring children would enable the detection of distinctive clinically-relevant phenotypes; (2) Methods: We retrospectively collected the results of nocturnal home-based cardiorespiratory polygraphic recordings and anthropometric measurements in 326 habitually-snoring otherwise healthy children. K-medoids clustering was applied to standardized respiratory and anthropometric measures, followed by Silhouette-based statis…

sj-zip-1-smm-10.1177_0962280220941159 - Supplemental material for Nonlinear parametric quantile models

Supplemental material, sj-zip-1-smm-10.1177_0962280220941159 for Nonlinear parametric quantile models by Matteo Bottai and Giovanna Cilluffo in Statistical Methods in Medical Research