Genetic and Epigenetic Factors in Risk and Susceptibility for Childhood Asthma

Asthma is a common respiratory disease that affects people of all ages, characterized by considerable heterogeneity in age, clinical presentation, genetics, epigenetics, environmental factors, treatment response, and prognostic outcomes. Asthma affects more than 330 million people worldwide, of which 33% are children under 14 years, and 27% are adults whose first symptoms occurred in childhood. However, the genetic and epigenetic mechanisms of childhood allergic diseases and asthma are still not fully understood. Here, we conducted a biomedical narrative review of genes associated with the risk, severity, and susceptibility of childhood asthma since it differs from asthma in adults regarding their pathophysiology, development, and outcomes. We also systematized the available information on epigenetic changes associated with childhood asthma

Food Sensitization Impact on Asthma Attacks in Children According to Age Group

Introduction: The progression of allergy disorders is termed “atopic march.” Having one allergic disorder increases the likelihood of acquiring others. Asthma and food allergies often coexist. There are no thresholds for specific IgE (sIgE) associated with the presence of clinical symptoms. Each allergen shows a particular trend with age. Objective: Our study and analysis aim to identify food sensitization in children with asthma and evaluate its impact on asthma attacks and clinical control. Material and methods: As a part of a bigger study, 56 children (mean age 11.07 years (5.3–17.5), 38 boys, and 18 girls) with bronchial asthma were tested for total IgE and sIgE against food and inhalator allergens. All children performed baseline and post-BD spirometry and were assessed for asthma control. Results: In the studied population of children, sIgE against several food allergens was positive in the same patient. A significant correlation was found between the positive sIgE for milk and soy (p p = 0.01), compared to milk and peanuts (p = 0.004), compared to egg yolk and fish (p p p p < 0.05). In the studied population, sensitization to food allergens among asthmatics does not contribute to the number of asthma attacks. Conclusions: Food sensitivity is associated with eczema, while mite sensitization is strongly associated with rhinitis and asthma. Food sensitization is not a risk factor for asthma exacerbation in children older than five years old

Immunomodulators Containing Epicor, Colostrum, Vitamin D, Zinc, <i>Lactobacilli</i> and <i>Bifidobacterium</i> Reduce Respiratory Exacerbations in Children and Adults with Chronic Pulmonary Diseases

(1) Background: A number of studies have demonstrated the connection between developing or exacerbating chronic respiratory diseases in adults and children. However, still, few studies focus on reducing exacerbations via immunomodulation. (2) Methods: In this pilot study, a total of 25 pediatric and adult patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD)/persistent bacterial bronchitis (PBB) were included, administered over-the-counter (OTC) immunomodulators and followed up for 6 or 12 months. (3) Results: We observed a decrease in the frequency of exacerbations with slight improvements in functional respiratory indicators in adults on their second and third visits and a reduced number of exacerbations and improved spirometry indices in children with BA, although exacerbations requiring hospital admission remained at a similar rate. (4) Conclusions: We confirmed that the number of exacerbations of underlying chronic respiratory disease in adults and children could be reduced after the administration of OTC immunomodulators, probably by optimizing the immune resistance to common viral infections

Immunomodulators Containing Epicor, Colostrum, Vitamin D, Zinc, Lactobacilli and Bifidobacterium Reduce Respiratory Exacerbations in Children and Adults with Chronic Pulmonary Diseases

(1) Background: A number of studies have demonstrated the connection between developing or exacerbating chronic respiratory diseases in adults and children. However, still, few studies focus on reducing exacerbations via immunomodulation. (2) Methods: In this pilot study, a total of 25 pediatric and adult patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD)/persistent bacterial bronchitis (PBB) were included, administered over-the-counter (OTC) immunomodulators and followed up for 6 or 12 months. (3) Results: We observed a decrease in the frequency of exacerbations with slight improvements in functional respiratory indicators in adults on their second and third visits and a reduced number of exacerbations and improved spirometry indices in children with BA, although exacerbations requiring hospital admission remained at a similar rate. (4) Conclusions: We confirmed that the number of exacerbations of underlying chronic respiratory disease in adults and children could be reduced after the administration of OTC immunomodulators, probably by optimizing the immune resistance to common viral infections

Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C&mdash;Can We Match the Puzzle?

The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first

Atopic Status in Children with Asthma and Respiratory Allergies&mdash;Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods&mdash;Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens&mdash;cats, mites, tree mix and food allergens&mdash;soy, wheat (&#1088; = 0.006), rice, &#1088; = 0.090), apple &#1088; = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer &gt; 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20&ndash;363.95) vs. 316.68, IQR 261.00 (109.20&ndash;552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the &ldquo;gold standard&rdquo; ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children

Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the Puzzle?

The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first

COVID-19 Vaccines for Adults and Children with Autoimmune Gut or Liver Disease

The SARS-CoV-2 pandemic raised many challenges for all patients with chronic conditions and those with autoimmune diseases, both adults and children. Special attention is paid to their immunological status, concomitant diseases, and the need for immunosuppressive therapy. All of these factors may impact their COVID-19 course and outcome. COVID-19 vaccination is accepted as one of the most successful strategies for pandemic control. However, individuals with immune-mediated chronic diseases, including autoimmune liver and gut diseases, have been excluded from the vaccine clinical trials. Therefore, we rely on real-world data from vaccination after vaccine approval for these patients to fill the evidence gap for the long-term safety and efficacy of COVID-19 vaccines in patients with autoimmune gut and liver diseases. Current recommendations from inflammatory bowel disease (IBD) societies suggest COVID-19 vaccination in children older than 5 years old, adults and even pregnant females with IBD. The same recommendations are applied to patients with autoimmune liver diseases. Nevertheless, autoimmune disease patients still experience high levels of COVID-19 vaccine hesitancy, and more studies have to be conducted to clarify this issue

Clinical and Laboratory Manifestation of Gastrointestinal Involvement in MIS-C: A Single-Center Observational Study

Background: Digestive symptoms and gastrointestinal issues in children with coronavirus 2019 disease (COVID-19) and Multisystem Inflammatory Syndrome in Children (MIS-C) are commonly reported in pediatric studies from different countries. Our retrospective observational study aimed to summarize the main digestive symptoms and objective data on gastrointestinal involvement in children with MIS-C. Methods: We present the clinical, laboratory, and imaging data of 51 children with MIS-C hospitalized in a single center from 25 November 2020 to 24 April 2021, focusing on gastrointestinal involvement. Results: A total of 46/51 children (90.2%) reported at least one abdominal symptom (abdominal pain (86%, N = 44), vomiting, nausea, diarrhea), predominantly at presentation. Most children were older than 5 years (N = 40, 78%), predominated by the male sex (N = 37, 72.5%), and with a mean age of 8.82 ± 4.16 years. We found a tendency for lymphopenia, neutrophilia, and higher levels of CRP, d-dimer, and ferritin in MIS-C patients with abdominal pain (R-squared 0.188, F-statistic vs. constant model: 11.9, p-value = 0.00122, 20% explanation of variation with p = 0.001). We found a statistically significant linear relationship (regression) between neutrophile percentage (NEU%) and hospital stay and a tendency for elevated transaminases to be more frequent in older children (27.3% under 5 years and 65% over 5 years; p = 0.0583). We found no significant associations between digestive symptoms and age or the predominant SARS-CoV-2 variant. Conclusions: Most of our MIS-C patients presented with abdominal pain, usually along with other GI symptoms, which could be applied in clinical practice to MIS-C in children visiting the emergency room with abdominal pain and evidence of recent COVID-19 contact or infection. Further information from larger cohorts of MIS-C patients is needed to better understand the epidemiology of gastrointestinal involvement in these patients