SARS-CoV-2 infection in patients with cystic fibrosian overwiew

The novel coronavirus SARS-CoV-2 was first identified in China in December 2019 and has since spread worldwide. People with Cystic Fibrosis (CF) have reduced survival mainly because of respiratory failure due to chronic pulmonary infections. Therefore, CF patients should be considered to have an increased risk of developing severe manifestations in case of SARS-CoV-2 infection. Surprisingly, the results of recent studies concerning SARS-CoV-2 infection in patients with CF show that in these patients the infection rate was lower than that of the general population. Various factors have been considered to explain a possible protective effect of CF against SARS-CoV-2 infection

An Overview of the Obese-Asthma Phenotype in Children

Asthma is the most common chronic disease in childhood. Overweight and obesity are included among the comorbidities considered in patients with difficult-to-treat asthma, suggesting a specific phenotype of the disease. Therefore, the constant increase in obesity prevalence in children and adolescents raises concerns about the parallel increase of obesity-associated asthma. The possible correlation between obesity and asthma has been investigated over the last decade by different authors, who suggest a complex multifactorial relationship. Although the particular non-eosinophilic endotype of obesity-related asthma supports the concept that high body weight precedes asthma development, there is ongoing debate about the direct causality of these two entities. A number of mechanisms may be involved in asthma in combination with obesity disease in children, including reduced physical activity, abnormal ventilation, chronic systemic inflammation, hormonal influences, genetics and additional comorbidities, such as gastroesophageal reflux and dysfunctional breathing. The identification of the obesity-related asthma phenotype is crucial to initiate specific therapeutic management. Besides the cornerstones of asthma treatment, lifestyle should be optimized, with interventions aiming to promote physical exercise, healthy diet, and comorbidities. Future studies should clarify the exact association between asthma and obesity and the mechanisms underlying the pathogenesis of these two related conditions with the aim to define personalized therapeutic strategies for asthma management in this population

Role of respiratory syncytial virus in pediatric pneumonia

Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population

Allergic bronchopulmonary aspergillosis in children with cystic fibrosis: An update on the newest diagnostic tools and therapeutic approaches

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF

Coronavirus infections in children: From SARS and MERS to COVID-19, a narrative review of epidemiological and clinical features

Emerging and re-emerging viruses represent an important challenge for global public health. In the 1960s, coronaviruses (CoVs) were recognized as disease agents in humans. In only two decades, three strains of CoVs have crossed species barriers rapidly emerging as human pathogens resulting in life-threaten-ing disease with a pandemic potential: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012 and the recently emerged SARS-CoV-2. This narrative review aims to provide a comprehensive overview of epidemiological, pathogenic and clinical features, along with diagnosis and treatment, of the ongoing epidemic of new coronavirus disease 2019 (COVID-19) in the pediatric population in comparison to the first two previous deadly coronavirus outbreaks, SARS and MERS. Literature analysis showed that SARS-CoV, MERS-CoV and SARS-CoV-2 infections seem to affect children less commonly and less severely as compared with adults. Since children are usually asymptomatic, they are often not tested, leading to an underestimate of the true numbers infected. Most of the documented infections belong to family clusters, so the importance of children in transmitting the virus remains uncertain. Like in SARS and MERS infection, there is the possibility that children are not an important reservoir for novel CoVs and this may have important implications for school attendance. While waiting for an effective against SARS-CoV-2, further prevalence studies in paediatric age are needed, in order to clarify the role of children in different age groups in the spread of the infection. (www.actabiomedica.it)

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

Silence of the lambs: The immunological and molecular mechanisms of covid-19 in children in comparison with adults

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19

Congenital malformations potentially affecting respiratory function: Multidisciplinary approach and follow-up

Background and aim. Congenital malformations such as oesophageal atresia (OA) and tracheoe-sophageal fistula (TOF), congenital pulmonary airway malformations (CPAMs), congenital diaphragmatic hernia (CDH) and vascular rings (VRs) can affect lung development and respiratory function. This observa-tional study describes our multidisciplinary approach and respiratory follow-up of children with such congenital malformations. Methods. Clinical data of children followed at the Pediatric Respiratory Unit of Parma University Hospital (Italy) between January 2015 and January 2020 were collected. Results. Twenty-three patients with congenital malformation affecting lung development were identified. Almost half of our patients were diagnosed with fetal ultrasound. Children attended the clinic at a mean age of 3 (3.7) years and follow-up visits were scheduled every 6 months average. More than half of our patients were hospitalized for lower respiratory tract infections. Six out of 9 children able to perform spirometry showed anomalies in lung function. Chest physiotherapy was recommended especially in children with OA. Conclusions. Children with congenital malformations affecting lung development are at risk of short and long-term respiratory complications, especially in the first years of life. OA was the malformation more associated to respiratory problems. Multidisciplinary approach and appropriate personalized follow-up are recommended for the best management of these children. (www.actabiomedica.it)

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

Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-severe TBI

Background: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. Methods: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls. Results: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. Conclusions: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration