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.

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.

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.

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.

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.

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.