Complex pathways leading to future paediatric asthma exacerbations.

Childhood asthma studies to identify additional risk factors, triggers and biomarkers may reveal novel pathways leading to exacerbation https://bit.ly/3BOhSWy.

Pediatric Vaccine Hesitancy and the Utilization of Antibody Measurements: A Novel Strategy with Implications for COVID 19.

Vaccine hesitancy is a well researched area with implications for both public health and the health of children and their families The factors leading to vaccine hesitancy are often complex and involve fear of the healthcare system and the process of vaccine development, cultural viewpoints and experiences. Pediatric patients often rely on parental guidance and decision making, and this may result in a lack of immunization for some children. The availability of the COVID 19 vaccine has been widely anticipated, yet not all individuals will seek the vaccine. Once vaccines are available for children under the age of 16 years, this long-standing pediatric management issue may again emerge and impact public health. The clinical trial efficacy and safety data for children and adolescents less than 16 years of age are not yet available. A traditional approach is to discuss the concerns of the parent in relationship to presentation and review of American Association of Pediatrics (AAP) and CDC guidelines in the framework of medical and scientific explanations. This includes the presentation of efficacy and safety data. Therefore, the use of lab-based antibody testing adds scientific evidence and emphasizes the need for vaccination against SARS CoV-2 and other pathogens. The purpose of this commentary is to propose lab-based testing as a potential adjunctive strategy in addressing this public health concern. Further study of a pediatric population is required to assess the impact of the selective use of lab-based testing in improving vaccination rates among a pediatric population.

Pulmonary Nontuberculous Mycobacterial Infection in Infants: A Systematic Review.

Limited information and literature exist examining pulmonary infections caused by nontuberculous mycobacterial specifically in an infant population. The objective of our study was to summarize clinical characteristics and outcomes of infant patients with nontuberculous mycobacterial pulmonary infection via systematic literature review to identify common diagnostic and treatment regimens for this infection in infants. A search of MEDLINE and PubMed databases in October 2019 using MeSH search terms "infant," "NTM," "pulmonary," and "Mycobacterium abscessus" yielded 139 articles. Inclusion criteria were i) English-language studies including cases and case series with ii) established nontuberculous mycobacterial pulmonary infection in iii) a patient population of infants no older than 24 months. Patients with cystic fibrosis and any study which did not contain relevant information such as infection and age were excluded. This yielded data on 37 patients extracted from 28 studies analyzed. The most common strain was Mycobacterium avium complex, isolated in 56.8% of patient diagnoses. Bronchoscopy/thoracoscopy with a subsequent culture were the most common diagnostic techniques, utilized in 64.9% of cases. Drug therapeutic treatment was utilized in 86% of cases, with a median of three drugs administered. Notable limitations of this study are the small sample size and its retrospective nature, which relies on information reported in previous case studies. Although there is limited formal clinician consensus on the treatment of NTM pulmonary infection and how it may differ in an infant population, our findings indicate an informal consensus typically involving diagnostic lung specimen culture and antibiotic therapy.

Neurobiological evidence of longer-term physical activity interventions on mental health outcomes and cognition in young people: A systematic review of randomised controlled trials.

OBJECTIVE: To investigate putative neurobiological mechanisms that link longer-term physical activity interventions to mental health and cognitive outcomes using randomised controlled trials in children, adolescents and young adults. DATA SOURCES: A range of medical and psychological science electronic databases were searched (MEDLINE, EMBASE, Scopus, Web of Science, PsychINFO). REVIEW METHODS: Original research studies were selected, data were extracted and quality was appraised. RESULTS: Sixteen primary papers were included, ranging from healthy and community samples to subclinical and clinical populations across a variety of age ranges and using different neurobiological measures (e.g. magnetic resonance imaging, electroencephalography, cortisol, brain-derived neurotropic factor). DISCUSSION: The majority of studies report improvement in mental health and cognition outcomes following longer-term physical activity interventions which coincide with neurobiological alterations, especially neuroimaging alterations in activation and electrophysiological parameters in frontal areas. Future research should include measures of pre-existing fitness and target those who would benefit the most from this type of intervention (e.g. those with a lower level of fitness and at risk for or with mental health problems).

Amlexanox: A Novel Therapeutic for Atopic, Metabolic, and Inflammatory Disease.

Amlexanox, a small molecule targeted therapy which has been used in the treatment of atopic conditions was previously but is not currently available in the United States. Amlexanox has also been legally utilized and administered in Japan as a treatment for asthma, a chronic pulmonary disease characterized by inflammation of the lower respiratory tract. Amlexanox's immune modulatory effects have been the subject of studies which have repurposed the drug for potential therapeutic applications in metabolic and inflammatory disease. Because amlexanox inhibits TANK-binding kinase1 (TBK1) and nuclear factor kB kinase epsilon (IKKε), several studies have demonstrated its usefulness through its evidence downregulation of the immune system and attenuation of downstream TBK1 signaling. Novel therapies, such as amlexanox, for inflammatory conditions such as asthma will continue to be of value in clinical management. This report summarizes key applications of the drug based on animal and human studies and explores its potential in treatment of metabolic and inflammatory diseases.

Eosinophil-Derived Neurotoxin and Respiratory Tract Infection and Inflammation: Implications for COVID-19 Management.

The current pandemic of COVID-19 and the identification of accessible biomarkers of disease progression is of clinical importance in the management of this novel and serious disease. This study was completed to provide information regarding 1 possible uniquely upregulated marker in this illness, eosinophil-derived neurotoxin (EDN-1). A literature search was undertaken to provide medical data regarding EDN-1 as a biomarker in the clinical setting. The literature identified was further analyzed to identify its use in the clinical setting of viral disease and asthma.

Pediatric Coronavirus Disease 2019 and Radiographic Screening: Identification of Patients at Risk.

As the coronavirus disease 2019 (COVID-19) pandemic continues globally, there are an increasing number of pediatric cases. Since the initial symptoms of COVID-19 may overlap and co-exist with other respiratory infections typically affecting children, this review examines the use of computed tomography as a diagnostic and management tool. Children with preexisting conditions may be particularly prone to a more severe course. This study reviews and analytically summarizes the findings typically associated with severe acute respiratory syndrome coronavirus 2 in contrast with other more usual lower respiratory tract infections.

Airway Malformations and Bronchiectasis: A Pediatric Study.

Congenital airway malformations are most often identified in early childhood. The development of bronchiectasis in association with malformations of the lower airway has been described, particularly among adult patients. The coexistence in a pediatric population of these conditions is not well described. This study was conducted to identify whether younger patients with airway malformations commonly develop bronchiectasis. International Classification of Diseases, Ninth revision (ICD-9 codes) were defined for airway anomalies and bronchiectasis. The electronic medical records system of a children's hospital was then searched for the number of patients with upper airway anomalies with or without bronchiectasis. The airway database was then cross referenced with the ICD codes for bronchiectasis to identify patients with both conditions. There were 844 patients with airway anomalies and 117 with bronchiectasis in the electronic system during the time period of August 1, 2009 to September 30, 2014. There was only 3 patients identified with both bronchiectasis and airway anomalies. The coexistence of bronchiectasis is low among the pediatric population with upper airway anomalies studied. This would suggest that the children with airway anomalies have been treated with strategies that are effective in the prevention of recurrent lower respiratory tract infection. Further study may be done to define the effectiveness of various strategies in preventing aspiration and lower respiratory tract infection. In addition, this methodologic technique utilizing database integrative platforms is useful in the identification of patients for further study and to identify the coexistence of pediatric conditions.

Blood eosinophils and IgE levels among umbilical cord transplantation recipients with food allergies.

The use of immunosuppressive treatments and their related gastrointestinal adverse effects have been implicated in the development of food allergic responses following transplantation. There is limited information on the pathogenesis of the food allergic immune response among umbilical cord transplantation recipients. This study was conducted to identify a cohort of food allergic umbilical cord recipients in the literature. The literature was searched to systematically identify this cohort. Criteria for inclusion included umbilical cord transplantation, food allergic response, and reported laboratory data. Analysis of the laboratory data using the Pearson method revealed that there was a moderate negative correlation with a coefficient of r=-0.7016 and r 2=-0.49 between peripheral eosinophilia and serum immunoglobulin E (IgE) levels. Future studies on a larger population are needed, but this study may help to elucidate possible cellular mechanisms involved in this response.

Egg introduction: differential allergic responses.

The use of egg protein preparations in clinical trials to reduce the incidence of egg allergy among infants includes a number of preparations of egg. These include whole egg, egg white protein, and egg yolk preparations. The study of the differential immune responses to these allergenic proteins in comparison is suggested as a future research area of investigation.

Pediatric anaphylaxis and hyper IgE syndrome.

Patients with autosomal-dominant (AD) hyper immunoglobulin E (IgE) syndrome (HIES) or Job syndrome develop frequent dermatologic and pulmonary infections. As patients have an extreme elevation of IgE levels, this database analysis study sought to study the association between AD HIES, Job syndrome, and anaphylaxis. HIES is a heterogeneous group of immune disorders characterized by extremely elevated levels of serum IgE. Although the molecular defects and clinical phenotypes found in association with Job syndrome are well characterized, the association with severe allergic reactions and anaphylaxis is a subject of ongoing investigation.

New data analysis in a population study raises the hypothesis that particle size contributes to the pro-asthmatic potential of small pet animal allergens.

BACKGROUND: The size of inhaled particles influences where they deposit and theoretically should be important for the development of airway inflammation and responsiveness. Our aim was to assess if sensitization to smaller-sized aeroallergens relates to higher prevalence of treated asthma, increased airway responsiveness, and airway and systemic inflammation. METHODS: Molecular-based IgE antibody determination was done in 467 subjects. Sensitized subjects were grouped based on the particle size of the aeroallergen: (1) Large particles only (mainly pollen); (2) Medium-sized particles (sensitized to mainly mite and mold and possibly to large particles); and 3) Small particles (sensitized to pet allergens and possibly to medium- and/or large-sized particles). Airway responsiveness to methacholine, exhaled nitric oxide (FENO), and serum eosinophil cationic protein (S-ECP) were measured. Asthma and rhinitis were questionnaire-assessed. RESULTS: Subjects sensitized to small particles had higher prevalence of treated asthma (35% versus 10%, P < 0.001), higher FENO50 (32 versus 17 ppb, P < 0.001), higher S-ECP (10 versus 7.5 ng/mL, P = 0.04), and increased bronchial responsiveness (dose-response slope, 5.6 versus 7.5, P < 0.001) compared with non-atopics. This was consistent after adjusting for potential confounders. Sensitization to only large or to medium and possibly also large aeroallergen particles was not related to any of these outcomes after adjustments. CONCLUSIONS: Sensitization to smaller particles was associated with a higher prevalence of asthma under treatment, higher airway responsiveness, and airway and systemic inflammation. Mapping of IgE sensitization to small particles might help to detect subjects having increased airway and systemic inflammation and bronchial responsiveness, indicating increased risk of developing asthma.

Autoimmunity and Immunodeficiency.

The references provided include data from evidence A and B studies based on the relevant populations. Because many primary immunodeficiencies associated with autoimmune diseases are rare, illustrative cases (evidence D) also are referenced. On the basis of level A evidence, immunoglobulin A deficiency is the most common primary immunodeficiency and is associated with defective mucosal immunity and autoimmune disease. On the basis of strong evidence (level A), Wiskott Aldrich syndrome presents early in life and is associated with autoimmune arthritis and anemia. On the basis of strong evidence in the literature, a number of primary immunodeficiencies are associated with defects in T regulatory cell number and development, cytokine aberrancies, and, as a consequence, production of autoantibodies. On the basis of strong evidence (level A) and case reports (level D), complement deficiency can be associated with autoimmune disease, most notably systemic lupus erythematosus.

Respiratory metapneumoviral infection without co-infection in association with acute and chronic lung allograft dysfunction.

BACKGROUND: Metapneumoviral respiratory infection is a community-acquired respiratory viral (CARV) infection. Lung transplantation recipients exposed to CARV are at risk for development of allograft rejection. The cellular and molecular pathways initiated by viral infection leading to allograft dysfunction are not completely understood. The aim of this study was to identify human metapneumoviral (hMPV) cases in association with allograft rejection. METHODS: A literature search was conducted to identify cases of both hMPV and allograft rejection within 6 months of the initial infection. This resulted in 1,007 lung transplantation recipients, with a total of 2,883 samples identified. Of these, 57 demonstrated isolated hMPV without co-infection with other agents. RESULTS: The results of the study indicate that 35% of acute hMPV infections without co-infection, at the time of detection by molecular diagnostic platforms, were associated with acute cellular rejection within 3 months. There were 9.4% of the cases subsequently associated with chronic allograft dysfunction/bronchiolitis obliterans syndrome, which was collectively termed chronic rejection for purposes of analysis. In conclusion, the prompt identification of isolated hMPV from lung transplantation patients is an important treatable risk factor for subsequent allograft dysfunction. The cellular and molecular pathogenesis of viral-induced allograft rejection remains a topic of future study.

Activation of eosinophil CCR3 signaling and eotaxin using a bioinformatics analysis of a mouse model of obliterative airway disease.

The role of eosinophils in the development and progression of chronic allograft rejection is recognized in multiple organ transplantation settings. The CCR3 signaling pathway is one of the key regulatory pathways in eosinophil migration to the engrafted tissue. Eotaxin is a ligand for CCR3 and reflects eosinophilic inflammation, which can lead to fibrosis. We hypothesized that the CCR3 pathway would be upregulated in obliterative airway disease (OAD) in an established model of chronic airway allograft rejection. The mouse gene microarray data from a heterotopic mouse model of OAD in the NIH Gene Expression Omnibus (GEO) repository were analyzed for differentially expressed eosinophil pathways, using the Partek Suite and Ingenuity Pathway Analysis. A P value of <0.005 was defined as significant for differential expression, and P value of <0.05 for pathways. Day 25 allografts were defined as chronic allograft rejection and day 4 as acute allograft rejection. The isografts and allografts at day 25 showed significant upregulation of the eosinophil CCR3 pathway (P=0.04), based on the analysis of 1,299 uniquely expressed genes. The isografts at day 4 were compared with those at day 25 based on the identification of 1,859 unique genes, and there was a trend toward the CCR3 pathway upregulation over time (P=0.06). CCR3 pathways were not upregulated during the progression of alloimmune rejection in the allografts at day 4 versus day 25 in comparison, based on the analysis of 1,603 genes. Eotaxin was upregulated in chronic allograft rejection by 2.5-fold. The eosinophil signaling pathway CCR3 and eotaxin were significantly expressed in chronic allograft rejection and our results imply a role in controlling early alloimmune damage in controls.