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 were obtained from their parents. All children performed NC and skin prick tests. LCA was applied for identifying AR endotypes based on NC, using the R package poLCA. All the statistical analyses were performed using R 4.0.5 software. Statistical significance was set at p ≤ .05. RESULTS: LCA identified two classes: Class 1 (n = 126, 75%): higher frequency of children with moderate/large number of neutrophils (31.45%); almost all the children in this class had no mast cells (91.27%) and Class 2 (n = 42, 25%): higher frequency of children with moderate/large number of eosinophils (45.24%) and moderate/large number of mast cells (50%). CONCLUSIONS: The present study used a machine learning approach for endotyping childhood AR, which may contribute to improve the diagnostic accuracy and to deliver personalized health care in the context of precision medicine.

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 semiquantitative food frequency questionnaire. Elastic net logistic regression was used to investigate whether increasing DII was associated with worse asthma burden. RESULTS: Two LCs were identified. Children in Class 1, "high burden," had higher symptom burden and worse lung function. Children in Class 2, "low burden," had lower symptom burden and less impaired lung function but were more subject to indoor exposures. DII was the only risk factor significantly associated with Class 1 membership. As the DII increased (from -4.0 to +4.0), the probability of Class 1 membership increased from 32% to 65% when compared with control group, whereas it increased from 41% to 72% when compared with Class 2. CONCLUSIONS: We identified two phenotypes of persistent asthma associated with different disease burden linked to indoor exposures. An increasing DII was associated with high-burden asthma, providing further evidence about the role of a pro-inflammatory diet in asthma morbidity.

Approximate or accurate? Efficacy of daily use of weather and air quality mobile applications for pollen allergy sufferers?

Nowadays, technology permeates every aspect of human activity, from the professional to the recreational side, and the recent pandemic crisis has only amplified a clearly defined trend. Through portable devices, people play, work, and get information. The immediacy of information and of many aspects of our life is a condition that, once acquired, is difficult to give up. However, immediate information must also be correct, and not all issues can easily be simplified to the point of being understandable in the absence of basic theoretical notions to a large audience. This aspect is particularly relevant when dealing with issues related to human health and the communication problems encountered in recent months concerning the spread of SARS-CoV-2, and the vaccination campaign is there to prove it. With the intent of clarifying the advantages and disadvantages of fast and accessible information, in this article, some of the most widespread applications for mobile devices, dedicated to pollen allergens, air quality, parks, gardens, and green areas, were examined. A widespread lack of clarity on the sources of the data and on the criteria used to formulate synthetic judgments-that often confuse the final users-was noted.

Validity and repeatability of the Pediatric Allergy Questionnaire for Athletes (AQUAped) for the screening of atopy.

BACKGROUND: High atopy prevalence has been reported in athletes. Having an age-specific questionnaire for predicting atopy is important for an optimal management of young athletes. The study objectives were as follows: (i) developing a scoring system for the Pediatric Allergy Questionnaire for Athletes (AQUAped); (ii) identifying the optimal age target within the range 7-14 years; (iii) assessing AQUAped validity and repeatability in the identified target population. METHODS: A total of 133 young athletes (age 7-14 years) were recruited. Following a screening visit, the participants filled AQUAped at baseline (T0) and after 7 days (T1), concomitantly undergoing skin prick testing. Using atopy as the gold standard (positivity to ≥1 aeroallergen), the 12 core items were scored based on their likelihood ratios, and a total score was calculated. The optimal cut-off was identified based on the Youden's criterion. The repeatability of AQUAped was assessed through the intra-cluster correlation coefficient (ICC). The optimal age target was identified as the largest age range associated with an acceptable cross-validated area under the receiver operating characteristic curve (AUC ≥ 0.70) and an excellent ICC (≥0.75). RESULTS: Forty (30%) children were atopic; the optimal age target was 10-14 years (cross-validated AUC = 0.70, ICC = 0.81). AQUAped total score ranged from -26 to 75, and only 5% of non-atopic children had AQUAped ≥ 24. AQUAped ≥ 2 had 82% specificity, 60% sensitivity, and 74% overall accuracy. CONCLUSION: Developing and testing a scoring system for AQUAped showed that it is a valid and reliable tool for the screening of atopy in young athletes aged 10-14 years.

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 reducing the risk of underestimating the diagnosis of AR. Diagnostic tests with a high level of accuracy are able to provide immediate results, which can sustain the doctor in diagnostic-therapeutic framework. The development of Point of Care Tests (POCTs) could be a useful tool. Considering that nasal obstruction is the most common symptom in patients with AR, the rhinomanometry (RM) test is the most indicated objective evaluation for nasal obstruction. Several studies have also shown the practicability of such diagnostic techniques applied in children. So far, no study has evaluated whether all the applicable requirements are fulfilled by RM in order to be considered as a POCT. The purpose of this perspective was to assess whether all the POCT requirements are fulfilled by RM by conducting a narrative review of the existing literature in which RM has been used in the diagnosis and management of AR in children. A few but encouraging results of studies on children supported the potential use of RM in the area of POCT. However, costs of instruments and the training of personnel involved remain to be explored. The studies support the potential use of RM in POCTs.

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 differences between LP and T were found. Unbiased clustering, based on proteomic signatures, stratified three groups of children (A, B, C) with significantly different patterns of respiratory impedance, which was slightly worse in group A than in groups B and C. Six proteins (Tripeptidyl peptidase I (TPP1), Cubilin (CUBN), SerpinA4, SerpinF1, Thy-1 membrane glycoprotein (THY1) and Angiopoietin-related protein 2 (ANGPTL2)) were identified in order to type the membership of subjects to the three groups. The differential levels of the six proteins in groups A, B and C suggest that proteomic-based profiles of urinary fractionated exosomes could represent a link between respiratory impedance and underlying biological profiles in healthy preschool children.

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 (PAQLQ, age >6 years), Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Childhood Asthma Control Test (CACT), KiddyKindl® (age 6 years) or KidKindl® (age >6 years), and a Visual Analogue Scale for nasal symptoms (VAS). At the final visit, a Global Rating of Change (GRC) scale was administered. The approved study was registered on the central registration system ClinicalTrials.gov (ID: NCT03276416). RESULTS: RAPP-children fairly reproduced RhinAsthma-children scores (concordance correlation coefficients between 0.91 and 0.95). RAPP-children showed adequate convergent validity (absolute Spearman's rho larger than 0.5 with PAQLQ, PRQLQ, CACT, KiddyKindl/KidKindl, and VAS), internal consistency (Cronbach's alpha > 0.70), repeatability (intra-cluster correlation coefficient between 0.61 and 0.8) in the presence of clinical stability (GRC = 0), discriminant validity (sensitivity to asthma control status and rhinitis severity), and sensitivity to symptom improvements (GRC > 1). The minimal important difference (MID) was -20. Floor and ceiling effects were minimal. RAPP-children showed fair usability also in younger children (6-8 years). CONCLUSION & CLINICAL RELEVANCE: RAPP-children is a valid, five-item questionnaire for assessing HRQoL in children aged 6 to 11 years with concomitant asthma and rhinitis. Although further investigation is required in moderate and severe asthmatics, this tool can be useful in clinical trials and in routine medical practice for improving the management of respiratory allergy in children.

Telemedicine for allergic patients during COVID-19.

In the last few years, we have witnessed an important development in the medical field of both Mobile Health, such as the use of mobile communication devices, and other telemedicine tools in general, in order to support the surveillance of diseases from the moment of the first diagnosis to the therapeutic follow-up. Long before COVID-19, some authors had analyzed various possible evidence-based scenarios and had indicated how the use of telemedicine could prove to be extremely useful in epidemic situations, especially for the management of chronic patients, such as immune-allergic ones, who are notoriously in greater need of regular follow-up; however, as expected, the advent of the COVID-19 pandemic has amplified the differences between various countries, from the point of view of the propensity to use technological solutions in the health sector. The hope is that one positive outcome of the ongoing pandemic is that it will lead to an acceleration, by all the stakeholders involved, of the process of modernization of health care.

Assessing repeatability and reproducibility of Anterior Active Rhinomanometry (AAR) in children.

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

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 (CLC). RSG was defined as the percentage of buffer covered by either industrial, commercial and transport units, or dump and construction sites, or urban fabric related features. Two specific categories of CLC, namely "discontinuous urban fabric - DUF" - and "continuous urban fabric - CUF" - areas were found. Exposure to traffic-related nitrogen dioxide (NO2) was assessed using a Land-Use Regression model. A symptom score ranging from 0 to 22 was built by summing affirmative answers to twenty-two questions on symptoms. To avoid multicollinearity, multiple Logistic and Poisson ridge regression models were applied to assess the relationships between environmental factors and self-reported symptoms. RESULTS: A very low exposure to NDVI ≤0.15 (1st quartile) had a higher odds of nasal symptoms (OR = 1.47, 95% CI [1.07-2.03]). Children living in CUF areas had higher odds of ocular symptoms (OR = 1.49, 95% CI [1.10-2.03]) and general symptoms (OR = 1.18, 95% CI [1.00-1.48]) than children living in DUF areas. Children living in proximity (≤200 m) to High Traffic Roads (HTRs) had increased odds of ocular (OR = 1.68, 95% CI [1.31-2.17]) and nasal symptoms (OR = 1.49, 95% CI [1.12-1.98]). A very high exposure to NO2 ≥ 60 µg/m3 (4th quartile) was associated with a higher odds of general symptoms (OR = 1.28, 95% CI [1.10-1.48]). No associations were found with RGS. A Poisson ridge regression model on the symptom score showed that children living in proximity to HTRs (≤200 m) had a higher symptoms score (RR = 1.09, 95% CI [1.02-1.17]) than children living > 200 m from HTRs. Children living in CUF areas had a higher symptoms score (RR = 1.11, 95% CI [1.03-1.19]) than children living in DUF areas. CONCLUSIONS: Multiple exposures related to greenness, greyness (measured by CORINE) and air pollution within the urban environment are associated with respiratory/allergic and general symptoms in schoolchildren. No associations were found when considering the individual exposure to greyness measured using the RSG indicator.

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

BACKGROUND: 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. METHODS: In this 21-day, 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 delivered through a nasal douche. Efficacy measures were least square mean changes (LSmc) in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: BHS improved the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p < 0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not. Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc -0.57, p = 0.009), whereas the improvement in PSQI score was comparable between the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall, BHS was well tolerated. CONCLUSIONS: In children with SAR, BHS is effective in improving nasal symptoms and NCC, with an associated beneficial effect on quality of life.

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 through a stepwise procedure starting from a full model with all C-ACT items, and predictive nomograms were created. RESULTS: Fifty-five (38%) well-controlled (WC) asthma, 37 (26%) partially controlled (PC) asthma, and 52 (36%) uncontrolled asthma (UA) patients were enrolled. Persistent asthmatics (PA) were significantly more uncontrolled (p < 0.0001). A significant reduction in FEV1 , FEV1 /FVC, and FEF25-75 (p = 0.005, p < 0.0001, and p < 0.001, respectively) was found in WC vs. UA. Through a stepwise process, a reduced model showed a positive relationship between the PAQLQ and the four items of C-ACT. The regression equations for predicted PAQLQ were ln(PAQLQ) = 1.17 + 0.05*C-ACT2 + 0.03*C-ACT3 + 0.04*C-ACT6 + 0.03*C-ACT7. Thus, a nomogram was constructed. CONCLUSION: The designed nomogram provides a highly predictive assessment of QoL in individual patients, facilitating a more comprehensive assessment of asthmatic children in usual clinical care.

RHINASTHMA-Adolescents: 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 experienced and, for each selected item, its importance on a four-point scale (1 = not at all; 4 = very much). Twelve items were excluded from the list, because of low importance. In the validation phase, 102 patients (54 M; mean age 15.36 ± 1.12) completed the KINDL, a generic HRQoL tool, and the new questionnaire (RHINASTHMA-Adolescents). RESULTS: Factor analysis revealed a five-dimensional structure, which explained up to 71.23% of the total variance. Association between RHINASTHMA-Adolescents and KINDL scores was all in the expected direction. Internal consistency for the extracted factors was satisfactory: Upper Airways (0.81), Lower Airways (0.89), Emotions (0.85), Social Relationship (0.79), Daily life management (0.74). Reliability was good for all factors with a Pearson coefficient ranged from 0.91 to 0.99. CONCLUSIONS: RHINASTHMA-Adolescents is the first tool for evaluating HRQoL in patients with rhinitis and/or asthma. It provides a simple assessment and met the standards of validity, internal consistency, and reliability.

25-Hydroxyvitamin D, IL-31, and IL-33 in children with allergic disease of the airways.

Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR) patients, and 35 allergic asthma with rhinitis (AAR) patients. We found significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH) Vit D. In AAR 25(OH) Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH) Vit D in AR and AAR. In conclusion, low levels of 25(OH) Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

Smoke exposure as a risk factor for asthma in childhood: a review of current evidence.

Asthma is a common chronic multifactorial disease that affects >300 million people worldwide. Outdoor and indoor pollution exposure has been associated with respiratory health effects in adults and children. Smoking still represents a huge public health problem and millions of children suffer the detrimental effects of passive smoke exposure. This study was designed to review the current evidences on exposure to passive smoke as a risk factor for asthma onset in childhood. A review of the most recent studies on this topic was undertaken to provide evidence about the magnitude of the effect of passive smoking on the risk of incidence of asthma in children. The effects of passive smoking are different depending on individual and environmental factors. Environmental tobacco smoke (ETS) is one of the most important indoor air pollutants and can interact with other air pollutants in eliciting respiratory outcomes during childhood. The increased risk of respiratory outcomes in children exposed to prenatal and early postnatal passive smoke might be caused by an adverse effect on both the immune system and the structural and functional development of the lung; this may explain the subsequent increased risk of incident asthma. The magnitude of the exposure is quite difficult to precisely quantify because it is significantly influenced by the child's daily activities. Because exposure to ETS is a likely cause for asthma onset in childhood, there is a strong need to prevent infants and children from breathing air contaminated with tobacco smoke.

Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections.

Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties. This study explores in vitro the effects of a TB blend on the immune activation of airway epithelium. 16HBE bronchial epithelial cells were exposed to different concentrations of TB. Cell viability, TB internalization, TLR2 expression, IL-6, IL-8 and TGF-ßl expression/release, E-cadherin expression and wound healing were assessed. We found that TB were tolerated, internalized, increased TLR2, E-cadherin expression, IL-6 release and wound healing but decreased both IL-8 and TGF-ßl release. In conclusion, TB activate TLR2 pathway without inducing a relevant pro-inflammatory response and improve barrier function, leading to the concept that TB preserve epithelial homeostasis and could be used as strategy to prevent and to manage respiratory infection, exacerbations included.

Oxidative Stress, Environmental Pollution, and Lifestyle as Determinants of Asthma in Children.

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

Tyndallized Bacteria Preferentially Induce Human Macrophage M1 Polarization: An Effect Useful to Balance Allergic Immune Responses and to Control Infections.

Macrophage polarization is a dynamic process through which macrophages acquire specific features whose extremes are represented by M1 and M2 polarization. Interleukin (IL)-6, IL-1ß, IL-12 and IL-8 belong to M1 macrophages while transforming growth factor-beta (TGF-ß belongs to M2 cytokines. M2 polarization prevalence is observed in allergic diseases. Tyndallization is a thermal process able to inactivate microorganisms and to allow their use for chronic respiratory disease treatment via immune response modulation. The present study explores the effects of a blend of tyndallized bacteria (TB) on macrophage polarization. THP-1-derived macrophages were exposed to different concentrations of TB (106, 5 × 106, 107, 5 × 107, 108 CFU/mL) and then cell viability and TB phagocytosis, and IL-8, IL-1ß, IL-6, IL-12 and TGF-ß1 gene expression and release were assessed. TB were tolerated, phagocyted and able to increase IL-8, IL-1ß and IL-6 gene expression and release IL-12 gene expression, as well as decrease TGF-ß1 gene expression and release. The effects on IL-8, IL-6 and TGF-ß1 release were confirmed in human monocyte-derived macrophages (hMDMs) exposed to TB. In conclusion, TB promote M1 polarization, and this mechanism might have valuable potential in controlling allergic diseases and infections, possibly preventing disease exacerbations.

Serious Games in the new era of digital-health interventions: A narrative review of their therapeutic applications to manage neurobehavior in neurodevelopmental disorders.

Children and adolescents with neurodevelopmental disorders generally show adaptive, cognitive and motor skills impairments associated with behavioral problems, i.e., alterations in attention, anxiety and stress regulation, emotional and social relationships, which strongly limit their quality of life. This narrative review aims at providing a critical overview of the current knowledge in the field of serious games (SGs), known as digital instructional interactive videogames, applied to neurodevelopmental disorders. Indeed, a growing number of studies is drawing attention to SGs as innovative and promising interventions in managing neurobehavioral and cognitive disturbs in children with neurodevelopmental disorders. Accordingly, we provide a literature overview of the current evidence regarding the actions and the effects of SGs. In addition, we describe neurobehavioral alterations occurring in some specific neurodevelopmental disorders for which a possible therapeutic use of SGs has been suggested. Finally, we discuss findings obtained in clinical trials using SGs as digital therapeutics in neurodevelopment disorders and suggest new directions and hypotheses for future studies to bridge the gaps between clinical research and clinical practice.