Severe bronchial hyperresponsiveness along with house dust mite allergy indicates persistence of asthma in young children.

BACKGROUND: Significant risk factors for persistence of asthma later in life are family history of allergies, early allergic sensitization and bronchial hyperresponsiveness (BHR). The evolution of BHR in young children without allergic sensitization and with house dust mite allergy (HDM) was investigated. METHODS: In this retrospective analysis, electronic charts of 4850 young children with asthma and wheezy bronchitis between 2005 and 2018 were reviewed in order to study all patients ≤6 years with BHR assessed by methacholine provocation tests (MCT) at least once (n = 1175). Patients with more than two follow-up measurements were divided in group 1 (no allergic sensitization; n = 110) and group 2 (HDM allergy; n = 88). Additionally, skin prick test, exhaled nitrite oxide (eNO), and asthma treatment were analyzed. RESULTS: Forty-seven patients of group 1 aged median 4.3 years and 48 patients of group 2 aged median 4.7 years showed initially severe BHR <0.1 mg. At follow-up, patients with HDM were more likely to show persistence of severe BHR than non-sensitized patients (severe BHR group 1: n = 5 (10.6%) vs. group 2: n = 21 (43.8%), p < .001). In addition, 89.4% of group 1 had mild to moderate or no BHR, compared to only 56.2% of group 2. There was a significant difference in eN0 (median group 1: 9 ppb vs. group 2: 26 ppb, p < .001), at last follow-up. Age, sex, and asthma therapy had no effect on BHR. CONCLUSION: In young children without sensitization BHR normalizes, whereas HDM allergy indicates a persistence of asthma beyond infancy.

Impact of CFTR Modulators on the Impaired Function of Phagocytes in Cystic Fibrosis Lung Disease.

Cystic fibrosis (CF), the most common genetically inherited disease in Caucasian populations, is a multi-systemic life-threatening autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In 2012, the arrival of CFTR modulators (potentiators, correctors, amplifiers, stabilizers, and read-through agents) revolutionized the therapeutic approach to CF. In this review, we examined the physiopathological mechanism of chronic dysregulated innate immune response in the lungs of CF patients with pulmonary involvement with particular reference to phagocytes, critically analyzing the role of CFTR modulators in influencing and eventually restoring their function. Our literature review highlighted that the role of CFTR in the lungs is crucial not only for the epithelial function but also for host defense, with particular reference to phagocytes. In macrophages and neutrophils, the CFTR dysfunction compromises both the intricate process of phagocytosis and the mechanisms of initiation and control of inflammation which then reverberates on the epithelial environment already burdened by the chronic colonization of pathogens leading to irreversible tissue damage. In this context, investigating the impact of CFTR modulators on phagocytic functions is therefore crucial not only for explaining the underlying mechanisms of pleiotropic effects of these molecules but also to better understand the physiopathological basis of this disease, still partly unexplored, and to develop new complementary or alternative therapeutic approaches.

Impulse oscillometry bronchodilator response in preschool children.

BACKGROUND: In preschoolers, performing an acceptable spirometry and measuring bronchodilator response (BDR) is challenging; in this context, impulse oscillometry (IOS) represents a valid alternative. However, more studies on the standardization of BDR for IOS in young children are required. OBJECTIVE: The objective of the study was to identify optimal thresholds to define a positive BDR test with IOS in preschoolers with suspected asthma. METHODS: Children aged 3-6 years with suspected asthma and their lung function investigated with both IOS and spirometry pre- and post-BDR were retrospectively analyzed. The spirometric BDR was defined as positive when the change of FEV1 was ≥12% or ≥200 mL. The oscillometric BDR was defined as positive in case of change of at least -40% in R5, +50% in X5, and -80% in AX. RESULTS: Among 72 patients, 36 (age 5.2 ± 1 years; 64% boys) were selected for the subsequent analysis according to ATS/ERS quality criteria of measurements; specifically, 19 patients did not meet IOS and 36 did not meet spirometry criteria. The spirometric BDR was found positive in seven subjects (19.4%); conversely, a positive oscillometric BDR was identified in four patients (11.1%). No patient presented a positive BDR response with both methods. In IOS, the mean decrease in R5 and AX was 19.9% ± 10% and 44% ± 22.1%, and the mean increase in X5 was 23.3% ± 17.8%, respectively. A decrease in R5 of 25.7% (AUC 0.77, p = .03) and an increase in X5 of 25.7% (AUC 0.75, p = .04) showed the best combination of sensitivity and specificity to detect an increase of FEV1 ≥ 12% and/or ≥200 mL. CONCLUSION: The IOS represents a valid alternative to spirometry to measure BDR in preschool children and should be the gold standard in this age group. We are considering a decrease of 26% in R5 and an increase of 26% in X5 as diagnostic threshold for BDR.

Long COVID in Children and Adolescents.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.

Prevention of Surgical Site Infections in Neonates and Children: Non-Pharmacological Measures of Prevention.

A surgical site infection (SSI) is an infection that occurs in the incision created by an invasive surgical procedure. Although most infections are treatable with antibiotics, SSIs remain a significant cause of morbidity and mortality after surgery and have a significant economic impact on health systems. Preventive measures are essential to decrease the incidence of SSIs and antibiotic abuse, but data in the literature regarding risk factors for SSIs in the pediatric age group are scarce, and current guidelines for the prevention of the risk of developing SSIs are mainly focused on the adult population. This document describes the current knowledge on risk factors for SSIs in neonates and children undergoing surgery and has the purpose of providing guidance to health care professionals for the prevention of SSIs in this population. Our aim is to consider the possible non-pharmacological measures that can be adopted to prevent SSIs. To our knowledge, this is the first study to provide recommendations based on a careful review of the available scientific evidence for the non-pharmacological prevention of SSIs in neonates and children. The specific scenarios developed are intended to guide the healthcare professional in practice to ensure standardized management of the neonatal and pediatric patients, decrease the incidence of SSIs and reduce antibiotic abuse.

Management of Preschool Wheezing: Guideline from the Emilia-Romagna Asthma (ERA) Study Group.

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment.

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group.

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health.

State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators and Triple-Combination Therapy.

Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.

Non-Tuberculous Mycobacterial Diseases in Children.

Non-tuberculous mycobacteria (NTMs) are ubiquitous and opportunistic emerging bacteria with the potential to colonize and eventually infect either immunocompromised or immunocompetent individuals. In the last three decades, the prevalence of disease caused by NTMs has increased in several countries. The increased prevalence of NTM infection can be explained by an ageing population with rising comorbidities, HIV infection, the common use of immunosuppressive drugs, and improved diagnostic methods. The aim of this review is to demonstrate the clinical relevance of NTMs in children, describing their features and manifestations, diagnostic tools, and therapeutic approaches. We collected data from the literature about NTM infections in young patients over the past five years (2014-2019) using the keywords "non-tuberculous", "mycobacteria", "paediatric", "NTM", "cystic fibrosis", and "children". Recent literature points out that NTMs are ubiquitous, with several species including both those that are pathogens for humans and those that are not. This means that, if a mycobacterium is isolated from a patient's specimen, we have to distinguish between a simple colonization and an NTM-related disease. The start of treatment depends on many factors that are necessary to consider, such as clinical and imaging features, patient comorbidity and immunocompetence, drug adverse effects, and compliance with a very long therapy that can last many months. Due to the increasing prevalence and clinical relevance of NTMs, guidelines for their optimal management, especially in the presence of chronic underlying disease, are urgently needed.

An Atypical Presentation of Primary Hyperparathyroidism in an Adolescent: A Case Report of Hypercalcaemia and Neuropsychiatric Symptoms Due to a Mediastinal Parathyroid Adenoma.

Psychiatric disorders are rare clinical manifestations of hypercalcaemia in the pediatric population, are relatively more frequent during adolescence and are often overlooked in cases of severe hypercalcaemia. We described the case of a 17-year-old girl affected by anorexia nervosa, depression and self-harm with incidental detection of moderate hypercalcaemia. Clinical, laboratory and instrumental tests demonstrated that hypercalcaemia was secondary to primary hyperparathyroidism (PHPT) due to a mediastinal parathyroid adenoma in the thymic parenchyma. After parathyroidectomy with robot-assisted surgery, we observed the restoration of calcium and PTH levels in addition to an improvement in psychiatric symptoms. This case demonstrates that serum calcium concentration should be evaluated in adolescents with neurobehavioural symptoms and in cases of hypercalcaemia PHPT should be excluded. Surgery represents the cornerstone of the management of PHPT and may contribute to improving quality of life and psychological function in these patients. However, the complexity of neurological involvement in cases of hypercalcaemia due to PHPT requires further investigations to establish the real impact of this condition on the neurocognitive sphere.

An Unusual Dysphagia for Solids in a 17-Year-Old Girl Due To a Lusoria Artery: A Case Report and Review of the Literature.

Background: Dysphagia is a condition that can have many underlying causes, often different between adults and children and its early diagnosis is crucial especially during childhood and adolescence, given the importance of proper nutritional intake to ensure adequate growth and development. Case report: We described the case of a 17-year-old girl reporting dysphagia for solids for approximately one month. No symptoms were previously referred. Oesophagogastroduodenoscopy was performed, detecting an image of ab extrinseco compression at the level of the mid-cervical oesophagus. An upper gastrointestinal tract radiography confirmed an oesophageal impression above the arch of the aorta suggestive of vascular abnormality. Computed tomography angiography and three-dimensional reconstruction techniques showed the presence of a lusoria artery that originated from the medial margin of the descending aorta and crossed the trachea and oesophagus posteriorly to the distal third. The lusoria artery was transected via a left thoracotomy and re-implanted into the right common carotid artery with complete symptom resolution. Conclusions: Dysphagia lusoria is an impairment of swallowing due to compression from an aberrant right subclavian artery. The diagnosis is always difficult, as the symptoms are often nonspecific. It is imperative to accurately identify and properly manage dysphagia in pediatric age and this is only possible with an anamnestic, clinical and instrumental process that takes into account an adequate differential diagnosis.