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Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. This study investigates the cellular mechanisms of fish oil in an in vitro model of lung inflammation using lipopolysaccharide (LPS) on a healthy human bronchial epithelium cell line. LPS exposure for 24 h reduced cell viability, elevated reactive oxygen species (ROS), depleted glutathione (GSH), and induced mitochondrial depolarization, indicating oxidative stress and inflammation. Fish oil administration significantly mitigated ROS production, prevented GSH depletion, and reduced mitochondrial depolarization. This was associated with the upregulation of the endogenous antioxidant system, evidenced by restored GSH levels and the increased gene expression of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). Fish oil also suppressed IL-6 and IL-1β expression and increased anti-inflammatory cytokine IL-10 expression. Furthermore, fish oil upregulated the expression of pro-resolving mediator receptors, suggesting a role in inflammation resolution. These findings highlight the potential of fish oil supplementation as a preventive measure against pulmonary diseases characterized by unresolved inflammation such as lung inflammation.

We prove the existence of a solution to a quasilinear system of degenerate equations, when the datum is in a Marcinkiewicz space. The main assumption asks the off-diagonal coefficients to have support in the union of a geometric progression of squares.

Respiratory viruses represent the most frequent cause of mortality, morbidity and high healthcare costs for emergency visits and hospitalization in the pediatric age. Respiratory viruses can circulate simultaneously and can potentially infect the same host, determining different types of interactions, the so-called viral interference. The role of viral interference has assumed great importance since December 2019, when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) came on the scene. The aim of this narrative review is to present our perspective regarding research in respiratory virus interference and discuss recent advances on the topic because, following SARS-CoV-2 restrictions mitigation, we are experimenting the co-circulation of respiratory viruses along with SARS-CoV-2. This scenario is raising many concerns about possible virus-virus interactions, both positive and negative, and the clinical, diagnostic and therapeutic management of these coinfections. Moreover, we cannot rule out that also climatic conditions and social behaviours are involved. Thus, this situation can lead to different population epidemic dynamics, including changes in the age of the targeted population, disease course and severity, highlighting the need for prospective epidemiologic studies and mathematical modelling able to predict the timing and magnitude of epidemics caused by SARS-CoV-2/seasonal respiratory virus interactions in order to adjust better public health interventions.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years. Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled. Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52. Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Abstract Nutrition has a central role in child growth with long-term effects, and nutrition management in gastrointestinal disorders has great importance for child health and disease outcomes. Breast milk is the first choice for infant nutrition. When it is not available, special milk formulas are adopted in specific conditions, as a medical treatment. Moving from the strong guidelines, recommendations and the new possibilities of special diet treatment, this review will analyse the current diet treatment in different gastrointestinal disorders, including food allergy, cystic fibrosis, inflammatory bowel diseases, short-bowel syndrome, gastroesophageal reflux, and eosinophilic esophagitis. The review also aimed at understanding the role of diet and its effects on these diseases. The growth monitoring can prevent malnutrition and improve disease outcomes, particularly in children, and an appropriate dietary management targeted to specific disorders is the best therapeutic choice alone or in combination with pharmacological therapy.

Vernal keratoconjunctivitis (VKC) is a severe ocular allergic disease characterized by chronic inflammation of the cornea and conjunctiva that may lead to loss of visual acuity and blindness. The disease occurs primarily in children and is more common in geographical regions characterized by warm temperatures and high humidity. The clinical manifestations of VKC, when inadequately treated, may lead to severe complications and corneal damage. The prevalence of allergen sensitization, specific serum immunoglobulin E (IgE), and specific tear IgE was reported in approximately 55%–60% of patients with VKC, confirming the involvement of IgE-mediated and non−IgE-mediated mechanisms in the pathophysiology of the condition. This article explores current knowledge on the immunological pathways of VKC and the role of the monoclonal anti-IgE antibody, omalizumab, in its management. The review evaluated the effects of omalizumab beyond the direct IgE-mediated reactions and discusses its potential as a therapeutic target for VKC. Multiple retrospective analyses, case series, and case reports have reported the effectiveness of omalizumab in the management of VKC. A summary of the clinical data from these studies revealed that in children with VKC omalizumab treatment was well tolerated with improvement or resolution of ocular symptoms, reduction in steroid use, and enhancement of quality of life. Omalizumab may serve as a promising treatment option for VKC due to its ability to target both IgE-mediated and non−IgE-mediated pathophysiological pathways. Larger, controlled clinical trials are needed to support these findings.

It is commonly acknowledged that the human factor and the interaction between the human factor and the road environment are among the most common causes of road accidents. Physiological signals can provide a real-time assessment of the driver's state because they can be collected continuously without interfering with the driver's task performance or the drivers' perception of the road. This study presents a method for measuring and quantifying drivers' physiological responses when approaching T-junctions and roundabouts using electrodermal activity and speed variations. Speed and electrodermal activity were collected continuously during a driving study which took place on a test environment based at Cranfield University and surrounding roads. Twenty participants were involved in the study. The analysis focused on four crossing manoeuvres on two T-junctions and a roundabout. The association Rule with the Apriori algorithm was used in order to evaluate associations between the variables related to electrodermal activity, i.e. the number and amplitude of the SCR peaks (assessed by the Electrodermal Impact Index in aggregate form), and the variables related to speed, i.e. the speed variation and its sign (positive or negative), for each type of intersection. The main results of this study can be summarized as follows: 1) the rules obtained for the manoeuvres on the T-Junctions show that the T-junctions induce low variations in the electrodermal activity and are often associated with a significant speed increase (between 20% and 30%); 2) the rules obtained for the manoeuvres on the roundabout highlights that the roundabout induces high variations in the electrodermal activity and is associated with a significant speed reduction (between 20% and 40%).

Abstract Background The cystic fibrosis transmembrane conductance regulator (CFTR) gene has been traditionally linked to cystic fibrosis (CF) inheritance in an autosomal recessive manner. Advances in molecular biology and genetics have expanded our understanding of the CFTR gene and its encoding products expressed in different tissues. Aim The study’s aim consists of reviewing the different pathological CF phenotypes using the existing literature. We know that alterations of the CFTR protein’s structure may result in different pathological phenotypes. Methods Open sources such as PubMed and Science Direct databases have been used for this review. We focused our selection on articles published within the last 15 years. Critical terms related to the CFTR protein have been used: “CFTR AND cancer,” “CFTR AND celiac disease,” “CFTR AND pancreatitis,” “children,” “adults,” “genotype,” “phenotype,” “correlation,” “mutation,” “CFTR,” “diseases,” “disorders,” and “no cystic fibrosis.” Results We analyzed 1,115 abstracts in total. Moreover, only 189 were suitable for the topic. We focused on the role of CFTR in cancer, gastrointestinal disorders, respiratory diseases, reproductive system, and systemic hypertension. Conclusions Mutations in CFTR gene are often associated with CF. In this review, we highlighted the broad spectrum of alterations reported for this gene, which may be involved in the pathogenesis of other diseases. The importance of these new insights in the role of CFTR relies on the possibility of considering this protein/gene as a novel therapeutic target for CF- and CFTR-related diseases.

Abstract Background Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children’s normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.

Background: The COVID-19 pandemic has had a significant impact on the epidemiology of respiratory viruses. Non-pharmaceutical interventions (NPIs) led to a dramatic reduction in respiratory infections. However, the long-term effects on respiratory virus epidemiology remain unclear. Materials and Methods: We conducted a comparative study on hospitalized pediatric patients with respiratory illness during two seasons: 1 October 2021 to 15 March 2022 and 1 October 2022 to 15 March 2023. We compared the type of virus, mean duration of hospitalization, and disease severity. Results: In the first season, 47.1% of patients (65/138) tested positive for at least one respiratory virus, with respiratory syncytial virus (RSV) being the most frequent (23.2%). In the second season, 82.9% of patients (102/123) tested positive, with RSV and Rhinovirus being the most prevalent (28.38% and 27.03%, respectively). Other viruses, such as Influenza A/B, Metapneumovirus, and Adenovirus, also showed increased prevalence. Disease severity and mean duration of hospitalization were similar between the two seasons. Conclusions: Our study highlights increased prevalence in respiratory viruses, including RSV and Rhinovirus, following the easing of NPIs. The prevalence in respiratory viruses, including RSV and Rhinovirus, increased in the second season compared to the first one. Interestingly, RSV’s peak incidence shifted from February to November. The emergence of rhinovirus as the most prevalent respiratory virus during certain months suggests viral competition and dynamic changes in viral circulation. The overall severity of respiratory infections remained relatively stable between the seasons.

Abstract Background Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of “indirect” and “direct” cardiac and pulmonary lung ultrasound signs. Methods LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged > 65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns—each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5. Conclusions Lung ultrasound (LU), as a tool within the anesthesiologist’s armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.

Background Aspergillus fumigatus is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF. Objective To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF. Methods A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932). Results A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA. Conclusion Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged

High-flow nasal cannula (HFNC) oxygen therapy has rapidly become a popular modality of respiratory support in pediatric care. This is undoubtedly due to its ease of use and safety, which allows it to be used in a wide variety of settings, ranging from pediatric intensive care to patients' homes. HFNC devices make it possible to regulate gas flow and temperature, as well as allowing some nebulized drugs to be administered, features very useful in children, in which the balance between therapeutic effectiveness and adherence to treatment is pivotal. Although the physiological effects of HFNC are still under investigation, their mechanisms of action include delivery of fixed concentration of oxygen, generation of positive end-expiratory pressure, reduction of the work of breathing and clearance of the nasopharyngeal dead space, while providing optimal gas conditioning. Nevertheless, current evidence supports the use of HFNC mainly in moderate-to-severe bronchiolitis, whereas for asthma exacerbations and breath sleeping disorders there is a lack of randomized controlled trials comparing HFNC to continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV), which are essentials for the identification of response and non-response predictors. In this regard, the development of clinical guidelines for HFNC, including flow settings, indications, and contraindications is urgently needed.

Introduction: Pedestrians aged over 65 are known to be a critical group in terms of road safety because they represent the age group with the highest number of fatalities or injured people in road accidents. With a current ageing population throughout much of the developed world, there is an imminent need to understand the current transportation requirements of older adults, and to ensure sustained safe mobility and healthy. Objectives: The aim of this study is to capture and analyze the key components that influence the identification of design solutions and strategies aimed at improving the safety of pedestrian paths for elderly. Method: A survey was conducted in 5 different locations in Catania, Italy. The locations were specifically chosen near to attraction poles for elderly pedestrians (e.g. centers for the elderly, squares, churches). Participants were recruited in person, so as to select exclusively people over 70. The sample comprised 322 participants. Both Hierarchical and K-Means clustering were used in order to explore which solutions elderly pedestrian propose for improving the safety of pedestrian path. Results: The results show that the judgment expressed by the elderly on the solutions for improving pedestrian safety is linked to the gender, to the experience as road users, and to mobility and vision problems. All solutions proposed regard road infrastructure (improvement of pedestrian crossings and of sidewalks, implementation of traffic calming measures, improvement of lighting), except for police supervision. Conclusion: This study has identified the factors that influence the identification of the best solutions to increase the safety level of pedestrian paths for elderly people. The aspects related to human factors considered were the gender, the factors associated with the experience as road users and the factors related to age related problems (mobility, vision and hearing problems). The results of this research could support traffic engineers, planners, and decision-makers to consider the contributing factors in engineering measures to improve the safety of vulnerable users such as elderly pedestrians.

Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure in utero is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.

Abstract Background Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. Methods 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5–1 mg on need, based on parents/caregivers’ decision (group A) or betamethasone 0.5-1 mg on need, based on parents/caregivers’ decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment. Results Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of pharyngitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups. Conclusions We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.

Abstract Background Recurrent respiratory infections (RRIs) are defined by the presence of at least one of the following criteria: (i) > 6 annual respiratory infections (RIs); (ii) > 1 monthly RIs involving the upper airways from September to April; (iii) > 3 annual RIs involving the lower airways represent a very common health problem in the first years of life. We conducted a multi-centre, prospective, single-open study to assess the efficacy and the safety of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a in the prevention of upper respiratory tract infections (URTIs) in children. Methods Ninety-one children (M:F = 47:44, mean age 7.4 ± 2.3 years) with RRIs were enrolled in the study between September and November 2018. At baseline, children received Streptococcus salivarius 24SMBc and Streptococcus oralis 89a as 2 puffs for nostril twice/day for 7 days/months. The treatment lasted for 3 consecutive months. Efficacy was expressed in terms of absence or presence of fever, cough, bronchospasm, rhinorrhea and otalgia, at 1 month (T1), and 3 (T3) months. Safety and tolerability of the probiotic were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment. Results Children treated with Streptococcus salivarius 24SMBc and Streptococcus oralis 89a showed a significant decrease of symptoms including episodes of fever, cough, bronchospasm, rhinorrhea, and otalgia (p 0.05). Conducting a subgroup analysis according to the age, it has been reported that children aged 1–3 years old showed an improvement in all symptoms, however, they become statistically significant only at the end of the 3 months of treatment (p

Abstract Cetirizine is a second-generation antihistamine, derived from the metabolism of hydroxyzine, highly specific for the H1 receptors, and with marked antiallergic properties. Although its history began more than 30 years ago, it remains one of the most used drugs in children with a leading role in the medical care of children with allergic diseases. Cetirizine use is licensed for paediatric patients for the treatment of allergic rhinitis, and chronic spontaneous urticaria, in Europe in children older than 2 years old and in the USA in children older than 6 months old. This review provides a practical update on the use of cetirizine in children and adolescents.

Abstract Antihistamines are currently one of the most commonly administered categories of drugs. They are used to treat symptoms that are secondary to histamine release, which is typical of certain allergic conditions, including rhinitis, conjunctivitis, asthma, urticaria, and anaphylaxis. Cetirizine belongs to the second-generation family, so, it is very selective for peripheral H1 receptors, is potent and quickly relieves symptoms, exerts additional anti-allergic/anti-inflammatory effects, and is usually well-tolerated. It has been marketed 30 years ago. In these years, a remarkable body of evidence has been built. The current review provides a practical update on the use of cetirizine in clinical practice.

Background: Children’s interstitial lung disease (chILD) is a rare group of pediatric lung diseases affecting the lung interstitium diffusely. In this work, we focused our attention on a specific infant group of chILD, also known as “specific conditions of undefined aetiology”, including pulmonary interstitial glycogenosis (PIG) and neuroendocrine cell hyperplasia of infancy (NEHI). Methods: PubMed was searched to conduct this narrative review. We searched for articles in English using the following keywords: (1) neuroendocrine cell hyperplasia of infancy; (2) NEHI; (3) pulmonary interstitial glycogenosis; (4) PIG; (5) chILD. Results: An increasing interest and insight into these two conditions have been reported. The updated literature suggests that it is possible to look at these disorders as a continuum of diseases, rather than two different entities, since they share a pulmonary dysmaturity. Conclusions: NEHI and PIG are featured by dysmaturity of airway development and consequent respiratory distress. Understanding the underlying pathogenic mechanisms would lead to identifying new targeted therapies to ameliorate the mortality and morbidity of these rare conditions.

Background: The COVID-19 pandemic has dramatically affected the global epidemiology of other infectious respiratory diseases, leading to a significant decrease in their incidence. Hence, we aimed to characterize the epidemiology of RSV-bronchiolitis in children. Methods: children aged ≤2 years diagnosed with RSV-mediated bronchiolitis admitted to our Unit from October 2018 to December 2021, were retrospectively enrolled. Results: We included 95 patients (M/F = 46/49; mean age 7.56 ± 6.6 months). Specifically, 17 infants in 2018, 34 in 2019, 0 during 2020 lockdown, 1 during 2020 post-lockdown, and 43 in 2021. Incidence was significantly lower in 2020 compared with 2018, 2019 and 2021 (p < 0.05). No differences were found concerning need for respiratory support. Discussion: Several factors related to SARS-CoV-2 pandemic, especially restrictive measures, may have contributed to a significant reduction in hospitalizations due to RSV. The new outbreak in RSV infection-related hospitalizations reported between October and December 2021 has been suggested it may be due to an increased number of susceptible individuals to RSV infection. Conclusion: The experience of the SARS-CoV-2 outbreak has led to a marked decrease in other viral respiratory infections, such as RSV. This may pave the way for new approaches in preventing respiratory infections, highlighting the role of preventive measures.

Background: Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy. Methods: This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3–6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy. Results: DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0). Conclusions: This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.

Background Asthma exacerbations in children is one of the most common medical conditions requiring urgent visits to primary healthcare providers or emergency departments, and even hospitalisations. Currently, there is significant variation in the management of asthma exacerbations expressed in guideline recommendations versus clinical practice. This disconnect affects diagnostic and treatment decisions for the clinician and patient. Objective We systematically reviewed the available guidelines providing recommendations for diagnostic and therapeutic management of asthma exacerbations in the paediatric population. Methods A systematic review of the literature for guidelines published between January 2009 and October 2019 was conducted, using a protocol registered with the international prospective register of systematic reviews (PROSPERO CRD42020221562). Results 16 asthma exacerbation clinical practice guidelines for children were included. Despite general agreement between guidelines on the definition of asthma exacerbation, there was great variability in the definition of disease severity and assessment of asthma control. This systematic review also highlighted a paucity of recommendations for criteria for hospitalisation and discharge. Many guidelines scored poorly when measured for stakeholder involvement and editorial independence. Conclusion Comprehensive and updated guidelines compliant with international standards for clinical guidelines may significantly improve clinical practice quality, promote evidence-based recommendations and provide uniformity of treatment between countries.

Abstract Background Lertal®, an oral nutraceutical, contains extract of Perilla, quercetin, and Vitamin D3. The current polycentric, randomized, parallel-group, controlled study aimed in the Phase II to evaluate the efficacy and safety of Lertal® in preventing allergic rhinitis (AR) exacerbations in children after the end of the pharmacological treatment phase. Materials and methods One hundred twenty-eight children completed Phase II. Sixty-four children continued Lertal® treatment (Lertal® Group: LG) and 64 ones did not assume any medication (Observation Group: OG) for 4–12 weeks. The study endpoints were the number, intensity, and duration of AR exacerbations, and the length of symptom-free time. Results Children of LG halved the risk (HR = 0.54) of having AR exacerbation. Children of LG had significantly (p = 0.039) less AR exacerbations than OG children. In children with AR exacerbations, the total number of days in which each patient took at least one rescue medication was significantly (p = 0.018) lesser in LG children than OG ones. In the global population, the cumulative days treated with rescue medication was significantly (p

The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.

There is substantial evidence in the literature that patients with cystic fibrosis (CF) have higher oxidative stress than patients with other diseases or healthy subjects. This results in an increase in reactive oxygen species (ROS) and in a deficit of antioxidant molecules and plays a fundamental role in the progression of chronic lung damage. Although it is known that recurrent infection–inflammation cycles in CF patients generate a highly oxidative environment, numerous clinical and preclinical studies suggest that the airways of a patient with CF present an inherently abnormal proinflammatory milieu due to elevated oxidative stress and abnormal lipid metabolism even before they become infected. This could be directly related to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency, which appears to produce a redox imbalance in epithelial cells and extracellular fluids. This review aims to summarize the main mechanism by which CFTR deficiency is intrinsically responsible for the proinflammatory environment that characterizes the lung of a patient with CF.

The aim of this paper is to identify the roundabout geometric characteristics affecting the safety perception while the typical maneuvers (entry, circulation, exit) are being carried out. The tool used was an on-line questionnaire, filled out by about 1.650 respondents. Four different dimensionality reduction methods (Cluster Analysis, Correspondence Analysis, Exploratory Factor Analysis and Confirmatory Factor Analysis) were used to analyze the data collected from the survey, in order to examine the key factors affecting the safety perception during the typical roundabout maneuvers. The considerations arising from the final model are the following: 1) the respondents' opinions regarding the safety perception of maneuvers are not preconceived ideas, but they originate from specific safety perceptions due to roundabout geometric configurations; 2) the users prefer definitely single lane roundabouts; this is an important confirmation of most results in the literature; 3) it was quantified the extent of the relationship between the safety perception of the typical roundabout maneuvers and the following aspects: a) maneuver type, b) geometric characteristics of the roundabouts design elements. This is the innovative aspect of the present research whose results have implications regarding theory, infrastructure and the application of new safety technologies. Keywords: Road safety, Statistical analysis, Dimensionality reduction methods, Roundabout design, Driving behavior

COVID-19 is less serious in children than in adults. However, respiratory management dominates the clinical picture of hospitalized COVID-19 even in children. In some case series, deterioration of the clinical picture wherein dyspnea, cyanosis, and the onset of acute respiratory distress syndrome (ARDS) emerged ~8–10 days after the onset of SARS-CoV-2 infection, which could rapidly progress to multiple organ failure and death. This review aimed to evaluate the characteristics of COVID-19 pneumonia in pediatric populations, beginning from its etiology and pathological mechanisms and closing with its clinical management.

Roundabouts have become a common type of intersection design in many countries. The area of the center island can be used to install a photovoltaic system to power local loads such as lighting systems. The objective of this study is to evaluate the degree of self-sufficiency that a roundabout can achieve depending on the availability of the area for the installation of a photovoltaic system and the energy demand for lighting. The methodology is divided into five steps aimed at calculating the parameters required to characterize the roundabouts from the point of view of the electricity that can be generated by the photovoltaic systems installed, and then to evaluate the energy consumption required to operate the different system solutions for lighting. The mini roundabouts are not considered as a location for the photovoltaic system; in fact, the minimum diameter must be between 29 and 34 m. Considering the available irradiance in Italy, systems with monocrystalline silicon modules are sufficient to ensure energy self-sufficiency at diameters of 24 m or more. Systems with polycrystalline silicon modules are suitable to ensure energy self-sufficiency at diameters of 25/26 m or more. Photovoltaic (PV) technology continues to make progress in increasing efficiency, such as bifacial PV modules. This means that even smaller roundabouts could be eligible for a PV system sized to meet local electricity needs.

Severe asthma in children is a highly heterogeneous disorder, encompassing different clinical characteristics (phenotypes) and immunopathological pathways (endotypes). Research is focusing on the identification of noninvasive biomarkers able to predict treatment response and assist in designing personalised therapies for severe asthma. Blood and sputum eosinophils, serum IgE and exhaled nitric oxide fraction mostly reflect type 2 airway inflammation in children. However, in the absence of available point-of-care biomarkers, the diagnosis of non-type 2 asthma is still reached by exclusion. In this review, we present the most recent evidence on biomarkers for severe asthma and discuss their implementation in clinical practice. We address the methods for guiding treatment decisions and patient identification, focusing on the paediatric age group. Key points Severe asthma in children is a highly heterogeneous disorder, encompassing different clinical characteristics (phenotypes) and immunopathological pathways (endotypes). Research is focusing on the identification of noninvasive biomarkers able to predict treatment response and assist in designing personalised therapies for severe asthma. Blood and sputum eosinophils, serum IgE and exhaled nitric oxide fraction mostly reflect type 2 airway inflammation in children. However, knowledge regarding non-type 2 inflammation and related biomarkers is still lacking. Educational aims To summarise the most recent evidence on biomarkers for severe asthma in children. To discuss their implementation in clinical practice through guiding patient identification and treatment decisions.

The term ‘scenario’ is used in the safety field to designate a prototype or a model of an accident process characterised by chains of facts, actions, causal relations and consequences in terms of damage to people and property. The prototypical scenarios, properly realized, provide a basis on which to consider the action to be taken, but also a concrete backup for accident information for use in information campaigns or training. The objective of this study is to define the prototypical accident scenarios for a particular configuration of road intersection: the skewed intersection. Limited sight distance at skewed intersections leads to safety issues. A non-skewed intersection provides the best operating conditions as drivers can easily sense the direction in which they are travelling, estimate the speeds of the opposing traffic and smoothly complete a maneuver in shorter time. In skewed intersections, instead, the ability of drivers to recognize any conflicting vehicles diminishes in comparison to right-angle intersections. The logical-deductive approach used in this paper for the determination of accident scenarios is based on an analysis of a large database of incidents, which occurred on several roads in eastern Sicily on 35 skewed intersections at three-legs. The skew angle of the minor leg of all the intersections studied is between 15° and 20°. This research allowed to develop accident scenarios related to particular configurations of intersections, compatible with the Italian rules. Prototypical scenarios are constructed using samples of accidents occurring on a particular type of study area, especially when they are based on files from in-depth investigations. The method used is an inductive approach, based on an examination of each case, grouping together similar cases and building a prototypical scenario using this case grouping. From the in-depth analysis of database accidents 9 prototypical accident scenarios have been identified for the skewed intersections. Keywords: Road safety, Accident scenarios, In-depth analysis, Skewed intersections, Maneuvers accident

During the last several years, the interest in the role of microbiota in human health has grown significantly. For many years, the lung was considered a sterile environment, and only recently, with the use of more sophisticated techniques, has it been demonstrated that colonization by a complex population of microorganisms in lower airways also occurs in healthy subjects; a predominance of some species of Proteobacteria, Firmicutes, and Bacteroidetes phyla and with a peculiar composition in some disease conditions, such as asthma, have been noted. Lung microbiota derives mainly from the higher airways microbiota. Although we have some information about the role of gut microbiota in modulation of immune system, less it is known about the connection between lung microbiota and local and systemic immunity. There is a correlation between altered microbiota composition and some diseases or chronic states; however, despite this correlation, it has not been clearly demonstrated whether the lung microbiota dysbiosis could be a consequence or a cause of these diseases. We are far from a scientific approach to the therapeutic use of probiotics in airway diseases, but we are only at the starting point of a knowledge process in this fascinating field that could reveal important surprises, and randomized prospective studies in future could reveal more about the clinical possibilities for controlling lung microbiota. This review was aimed at updating the current knowledge in the field of airway microbiota.

This study investigated the nature and causes of unsafe driving behavior at roundabouts through an on-road study. Four urban double-lane roundabouts with different layouts were selected for an on-road study. Sixty-six drivers (41 males and 25 females) aged 18–65 years took part in the study. Unsafe behaviors observed during the in situ survey were divided into three different categories: entry unsafe behaviors, circulation unsafe behaviors, and exit unsafe behaviors. Three chi-square automatic interaction detection (CHAID) analyses were developed in order to analyze the influence of roundabout characteristics and maneuvers on unsafe behaviors at double-lane roundabouts. The results confirmed the awareness that double-lane roundabouts are unsafe and inadvisable. More than half of unsafe driving behaviors were found to be entry unsafe behaviors. Moreover, the entry radius was found to be the geometric variable most influencing unsafe driving behaviors.

More than one accident of three that involve pedestrians in urban area occurs at road intersections. The users’ inproper behaviour, the geometrical characteristics of the intersections, and the high speeds of vehicles are the main causes of pedestrian accidents. In this field, the procedures of road safety analysis (Road Safety Audit and Road Safety Review) play a fundamental role: they are the techniques of investigation aimed at identifying the safety issues and the possible improvements. Nowadays, however, the safety analysis does not allow a quantitative assessment of the level of safety regarding pedestrians. The objective of this work, is to propose a procedure for the quantitative risk analysis. The first phase of the study has been oriented to the definition of the virtual schemes associated with the possible configurations for unsignalized intersections in urban areas, predominantly characterized by local roads. The urban areas in which the residential function prevails, while it is poorly available in the circulation function, were considered then. The criteria, aimed at the characterization of the level of safety, offered to pedestrians by the real urban intersections, have been developed in the second phase. For this purpose, three categories of information have been useful: 1) the data describing the geometry characteristic of the intersection; 2) the geometric characteristic of road elements responsible of the functional pedestrian protection; 3) vehicular and pedestrian traffic data.

Today the knowledge of genotype-phenotype correlation in cystic fibrosis is enriched by the growing discoveries of new mutations of the CFTR gene. Although the combination of two severe mutations usually leads to the classic disease (pulmonary and pancreatic insufficiency, sterility, nasal polyposis), the presence of a complex genotype characterized by severe and milder mutations or polymorphism can cause a hidden disease, which is often asymptomatic at early ages. We report on a case of a 15 years old boy, in whom the only clinical signs of CF were chronic hypertransaminasemia and hyperbilirubinemia, and in whom it was demonstrated the presence of the mutations F508del associated with TG11-9T-470M in one allele and TG12-5T-470V in the other allele. Although a clear genotype-phenotype correlation for liver disease is still missing for CF patients, it is possible to state that this isolated clinical presentation could represent an unusual phenotype of CF, related to a complex genotype characterized by a severe mutation and one (or more) polymorphism.

Food allergies are an increasingly public health problem, affecting up to 10% of children and causing a significant burden on affected patients, resulting in dietary restrictions, fear of accidental ingestion and related risk of severe reactions, as well as a reduced quality of life. Currently, there is no specific cure for a food allergy, so the only available management is limited to strict dietary avoidance, education on prompt recognition of symptoms, and emergency treatment of adverse reactions. Several allergen specific- and nonspecific-therapies, aiming to acquire a persistent food tolerance, are under investigation as potential treatments; however, to date, only immunotherapy has been identified as the most promising therapeutic approach for food allergy treatment. The aim of this review is to provide an updated overview on changes in the treatment landscape for food allergies.

A GIS for pedestrian safety management The improvement of pedestrian safety can be pursued through an innovative management system that can drive them through the safest pedestrian footpaths. Thanks to the support of GIS, one can now project future scenarios where pedestrians are warned in real time about the network elements offering the best safety performance. In this paper the characteristics of a GIS created for the dynamic characterization of level of safety provided by walkways will be explained. All the elements of an urban road network have been linked with attributes used to define the level of safety. The query space allows to identify the safest pedestrian route between origin and destination choices. Selecting the best route, the GIS also impute any barriers in the network.

We prove a Lax-Milgram type theorem using the concept of nearness between operators.