Pediatric Allergic Diseases Research Articles

New opportunities with biologic treatments in pediatric allergic and respiratory diseases.

In the last 20 years, the introduction of monoclonal antibodies has dramatically changed allergic diseases. At present, several monoclonal antibodies are approved for treating asthma, atopic dermatitis, chronic spontaneous urticaria, and chronic sinusitis with nasal polyps in children.Biologics have also changed the management of these diseases in the pediatric population, tending toward personalized medicine based on the type‐2 inflammatory pattern.

Expression and clinical significance of IL-33 and its receptor ST2 in children with obstructive sleep apnea syndrome.

BackgroundObstructive sleep apnea syndrome (OSAS) is characterized by a majority population of respiratory sleep disorders, which consists of simple snoring as well as increased upper airway resistance syndrome. Adenoid hypertrophy has been suggested as the main cause of OSAS in children. The role of interleukin-33 (IL-33) and its receptor suppressor of tumorigenicity 2 (ST2) in a variety of pediatric allergic diseases has been confirmed. We hypothesized that IL-33/ST2 path way might play a pivotal role in the pathogenesis of adenoid hypertrophy-associated OSAS in children.MethodsA total of 40 children undergoing adenoidectomy due to OSAS in the Otolaryngology of Tianjin Children’s Hospital were selected as the study participants. The quantity of IL-33 and ST2 positive cells in adenoids was detected by immunohistochemical (IHC) streptavidin-peroxidase conjugate (SP) method.ResultsThe IL-33 positive cells were mainly distributed in the submucosa epithelium and vascular endothelium, and expressed in the nucleus and cytoplasm. Meanwhile, ST2 positive cells were primarily observed in the mucosa and expressed in the nucleus and cytoplasm, with a little expression of intercellular substance. There was a positive correlation between the proportion of adenoids in the posterior nostril diameter and the number of IL-33 positive cells. The expression of IL-33 in adenoids was positively correlated with the level of ST2 (r=0.809, P=0.000). The expression of IL-33 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.859, P=0.000). Moreover, the expression of ST2 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.814, P=0.000). The number of IL-33 positive cells was significantly higher in the moderate hypoxemia group than that in the mild hypoxemia group (P<0.05). There was no significant difference in the number of ST2 positive cells between the moderate hypoxemia group and mild hypoxemia group (P>0.05).ConclusionsBoth IL-33 and its receptor ST2 were expressed in adenoids of OSAS children. The severity of airway obstruction caused by adenoid hypertrophy was positively correlated with the expression of IL-33.

Gender disparities in the pediatric allergy-related guidelines in Japan.

Inclusion of female authors has been noted as potentially beneficial in the development of medical guidelines. Japanese professional committees representing allergic subspecialties develop practical guidelines with recommendations to caregivers, but these committees may be influenced by their gender composition. The objective of our study was to examine the influence of gender in developing pediatric allergic disease guidelines in Japan from 1999 to 2020. We examined the gender parities among the guideline committee members in allergic rhinitis, atopic dermatitis, bronchial asthma, and food allergy guidelines in Japan. We examined the gender composition of the committees, annual trends, and differences in guideline content. The median proportion of women members among the 22 guidelines committees was 6.6% (range: 0%-27.3%). The analysis of the quadrant period did not show a significant increase in the proportion of female members. The food allergy group had a significantly higher proportion of female members than other guidelines (P < 0.01), but the proportion decreased from 25% to 14.3% during the observation period. For the pediatric asthma guidelines, the proportion of female committee members decreased from 5.3% in the 2000 version to 0% in the most recent revision in 2017. The proportion of women on the committees that develop pediatric guidelines continues to be low and has not improved over the past 20 years.

Examining the role of pre-pregnancy weight and gestational weight gain in allergic disease development among offspring: A population-based cohort study in Ontario, Canada.

BackgroundStudies suggest maternal weight and weight gain during pregnancy may influence foetal immunological development. However, their role in the aetiology of allergic disease is unclear.ObjectivesWe sought to examine the impact of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain (GWG) on the incidence of four common paediatric allergic diseases.MethodsWe conducted a retrospective, population‐based cohort study of all singleton live births in Ontario, Canada between 2012 and 2014, using maternal‐newborn records from the provincial birth registry linked with health administrative databases. Neonates were followed up to 7 years for anaphylaxis, asthma, dermatitis and rhinitis, identified through validated algorithms based on healthcare encounters. We multiply imputed missing data and employed Cox proportional‐hazards models to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). To test the robustness of our findings, we also conducted several sensitivity analyses, including probabilistic bias analyses for exposure and outcome misclassification. All methods were prespecified in a published protocol.ResultsOf the 248,017 infants followed, 52% were born to mothers with a pre‐pregnancy BMI in the normal range and only 19% were born to mothers with adequate weight gain during pregnancy. Incidence rates (per 100,000 person‐days) for anaphylaxis, asthma, dermatitis and rhinitis were 0.22, 6.80, 12.41 and 1.54, respectively. Compared with normal BMI, maternal obesity was associated with increased hazards of asthma in offspring (aHR 1.08, 95% CI 1.05, 1.11), but decreased hazards of anaphylaxis (aHR 0.83, 95% CI 0.69, 0.99) and dermatitis (aHR 0.97, 95% CI 0.94, 0.99). In contrast, maternal underweight was associated with increased hazards of dermatitis (aHR 1.06, 95% CI 1.02, 1.10). We found no associations between pre‐pregnancy BMI and rhinitis or GWG and any allergic outcome, and no evidence of effect measures modification by infant sex.ConclusionsThese findings provide support for the involvement of maternal pre‐pregnancy BMI in paediatric allergic disease development.

Effect of Carbon Black Nanoparticle on Neonatal Lymphoid Tissues Depending on the Gestational Period of Exposure in Mice.

Introduction: Particulate air pollution, containing nanoparticles, enhances the risk of pediatric allergic diseases that is potentially associated with disruption of neonatal immune system. Previous studies have revealed that maternal exposure to carbon black nanoparticles (CB-NP) disturbs the development of the lymphoid tissues in newborns. Interestingly, the CB-NP-induced immune profiles were observed to be different depending on the gestational period of exposure. It is important to identify the critical exposure period to prevent toxic effects of nanoparticles on the development of the immune system. Therefore, the present study was aimed to investigate the effect of CB-NP on the development of neonatal lymphoid tissues in mice, depending on the gestational period of exposure. Methods: Pregnant ICR mice were treated with a suspension of CB-NP (95 μg/kg body weight) by intranasal instillation; the suspension was administered twice during each gestational period as follows: the pre-implantation period (gestational days 4 and 5), organogenesis period (gestational days 8 and 9), and fetal developmental period (gestational days 15 and 16). The spleen and thymus were collected from offspring mice at 1, 3, and 5-days post-partum. Splenocyte and thymocyte phenotypes were examined by flow cytometry. Gene expression in the spleen was examined by quantitative reverse transcription-polymerase chain reaction. Results: The numbers of total splenocytes and splenic CD3−B220− phenotype (non-T/non-B lymphocytes) in offspring on postnatal day 5 were significantly increased after exposure to CB-NP during the organogenesis period compared with other gestational periods of exposure and control (no exposure). In contrast, expression levels of mRNA associated with chemotaxis and differentiation of immune cells in the spleen were not affected by CB-NP exposure during any gestational period. Conclusion: The organogenesis period was the most susceptible period to CB-NP exposure with respect to lymphoid tissue development. Moreover, the findings of the present and previous studies suggested that long-term exposure to CB-NP across multiple gestational periods including the organogenesis period, rather than acute exposure only organogenesis period, may more severely affect the development of the immune system.

Current status and treatments to pediatric allergic diseases in upper airway from the otorhinolaryngologist’s point of view

Current status and treatments to pediatric allergic diseases in upper airway from the otorhinolaryngologist’s point of view

Artificial intelligence in the diagnosis of pediatric allergic diseases.

Artificial intelligence (AI) is a field of data science pertaining to advanced computing machines capable of learning from data and interacting with the human world. Early diagnosis and diagnostics, self-care, prevention and wellness, clinical decision support, care delivery, and chronic care management have been identified within the healthcare areas that could benefit from introducing AI. In pediatric allergy research, the recent developments in AI approach provided new perspectives for characterizing the heterogeneity of allergic diseases among patients. Moreover, the increasing use of electronic health records and personal healthcare records highlighted the relevance of AI in improving data quality and processing and setting-up advanced algorithms to interpret the data. This review aimed to summarize current knowledge about AI and discuss its impact on the diagnostic framework of pediatric allergic diseases such as eczema, food allergy, and respiratory allergy, along with the future opportunities that AI research can offer in this medical area.

This Month in Pediatric Urology

You have accessJournal of UrologyThis Month in Pediatric Urology1 Dec 2020This Month in Pediatric Urology Stacy T. Tanaka Stacy T. TanakaStacy T. Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001267AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Three articles in this issue of The Journal focus on common pediatric urological diagnoses: bladder-bowel dysfunction (BBD), febrile urinary tract infection (fUTI) in infants and distal hypospadias. These authors paused while seeing these everyday cases to ask how we can improve care for patients with these routine diagnoses. Development and Validation of Symptom Score for Total Bladder-Bowel Dysfunction: Subscales for Overactive Bladder and Dysfunctional Voiding Because bladder-bowel dysfunction encompasses such a wide range of symptoms, including infrequent voiding, genital pain and urinary frequency, many clinicians take an “I know it when I see it” approach to clinical assessment. BBD negatively affects outcomes in children with vesicoureteral reflux and recurrent urinary tract infections. However, research studies on these topics are limited unless we have a standardized assessment method. Sillén et al (1333) from Sweden present a validated BBD symptom score for children 3 to 16 years old.1 Children with monosymptomatic enuresis, which is not included in the definition of BBD, were excluded. This instrument improves on existing pediatric questionnaires. It is able to distinguish between storage and emptying dysfunction, and it can assess treatment response. Currently the questionnaire has only been validated in Swedish. Use of a standardized BBD questionnaire across research studies should be a common goal of the pediatric urology community. Impact of Long-Term Low Dose Antibiotic Prophylaxis on Gut Microbiota in Children Following febrile urinary tract infection antibiotic prophylaxis is routinely started in infants with vesicoureteral reflux. There has been concern that altering the microbiome can increase the risk of obesity and pediatric allergic diseases. Akagawa et al (1320) from Japan performed 16S ribosomal gene sequencing on stool samples of infants treated for fUTI before, during and 5 to 6 months after antibiotic treatment.2 Continuous antibiotic prophylaxis with trimethoprim-sulfamethoxazole was started in those infants diagnosed with vesicoureteral reflux, while those without reflux served as controls. Although gut microbiota diversity initially decreased after treatment of fUTI, diversity recovered 1 to 2 months after treatment and was maintained in both groups. Antibiotic resistance could not be measured by this methodology. The results from this small study are reassuring and offer novel insights regarding the many infants who are started on antibiotic prophylaxis. Competency in Tubularized Incised Plate Repair for Distal Hypospadias: Cumulative Sum Learning Curve Analysis of a Single Surgeon Experience Distal hypospadias repair is a common pediatric urological procedure. Zu’bi et al (1326) from Canada and Madison, Wisconsin asked the question “How long does it take after establishing independent practice for a single surgeon to become competent and proficient?”3 They found that the complication rate and operative time started to decrease after the 234th case. The study has limitations because complications can continue to arise long after the initial procedure. Although the results are not surprising, the study prompts frank discussion of the importance of tracking our own complication rates, whether just starting or in practice for many years, and the technical modifications we can make to lower them.

Anti-IL-5 in pediatric allergic diseases.

Interleukin (IL)-5 is a potent mediator of the inflammatory cascade in the allergic response. Its predominant role in atopic reactions makes this cytokine an ideal target for blocking the eosinophilic inflammatory hyper-responsiveness to allergens. The management of allergic diseases in childhood-such as severe asthma, atopic dermatitis, and eosinophilic esophagitis-is a challenge. In particular, there are concerns regarding the use of high-dose corticosteroids. Over the last few years, biologics targeting IL-5 or IL-5 receptor-that are mepolizumab, reslizumab, and benralizumab-represent a new, promising, and more personalized therapeutic option.

What impact of air pollution in pediatric respiratory allergic diseases.

Respiratory allergies are known to affect people all over the world. Environmental factors related to pollution play a significant etiopathogenic role in this regard. Polluting sources are industrial activities and urban traffic, capable of generating various types of pollutants that trigger inflammatory, direct, and indirect damage to tissues, promoting allergic symptoms, even serious ones, and interfering with the pharmacologic response. They are also able to modify pollen, promoting allergic sensitization. Pollution could have played a significant predisposing role in the ongoing morbidity and mortality of SARS-CoV-2.

Diagnosis and Management of Allergic Rhinitis in Children

Allergic rhinitis which is the most common pediatric allergic disease has a significant negative impact on quality of life in affected children. Further, overall poor control can lead to ‘allergic march’ and later development of bronchial asthma. The main symptoms of allergic rhinitis include nasal discharge, blockage and itchiness of nose, and sneezing. Clinical history focused on identification of nature and severity of symptoms, trigger factors and clinical features of non-allergic rhinitis is crucial for early and accurate diagnosis.The mainstay of non-pharmacological management of allergic rhinitis is allergen avoidance.Second-line antihistamines used either locally or orally are first-line treatment of mild to moderate allergic rhinitis whereas topical nasal corticosteroids are the first line treatment for moderate to severe disease, in whom the control of symptoms is not achieved with antihistamine and those with severe nasal obstruction.Combination therapy with antihistamines and intranasal steroids is more effective than either alone and is second line treatment for children who have poorly controlled rhinitis while on monotherapy. Oral steroids may be indicated in children with significant nasal obstruction and routine use of oral steroids should be avoided.Referral to specialist allergy clinic should be considered for those who are symptomatic despite optimal local and oral therapy. Consideration should be given for specialist otorhinolaryngologist evaluation of children who have features of non-allergic rhinitis and pharmacotherapy resistant nasal obstruction.International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Page: 159-162

An update on biological therapies for pediatric allergic diseases.

Allergic diseases represent a global health burden. Patients with allergic diseases may experience disability, reduced quality of life and productivity, emotional distress, and social restrictions, especially in the most severe cases. Current advances in unveiling the pathogenesis of allergic disorders have paved the way for the development of novel therapeutic strategies. Biological drugs have been widely studied in pediatric allergic asthma, with strong evidence of efficacy and safety. Moreover, promising results derive from studies on other conditions such as atopic dermatitis, chronic spontaneous urticaria, and food allergy. This review analyzes recent evidence on the role of biologic therapies for allergic diseases, focusing on the pediatric age.

Pediatric Allergic Diseases, Food Allergy, and Oral Tolerance.

Pediatric allergic disease is a significant health concern worldwide, and the prevalence of childhood eczema, asthma, allergic rhinitis, and food allergy continues to increase. Evidence to support specific interventions for the prevention of eczema, asthma, and allergic rhinitis is limited, and no consensus on prevention strategies has been reached. Randomized controlled trials investigating the prevention of food allergy via oral tolerance induction and the early introduction of allergenic foods have been successful in reducing peanut and egg allergy prevalence. Infant weaning guidelines in the United Sates were recently amended to actively encourage the introduction of peanut for prevention of peanut allergy.

Pediatric allergic diseases in the Indian subcontinent-Epidemiology, risk factors and current challenges.

India is low-middle-income country (LMIC) with a population of 1.3bn, comprising about 20% of the global population. While the high-income Western countries faced an "allergy epidemic" during the last three decades, there has been a gradual rise in prevalence of allergic diseases in India. Narrative review. Allergic diseases occur as a consequence of a complex interplay between genetic and environmental factors. There are multiple contrasting determinants that are important to consider in India including high levels of air pollution, in particular PM2.5 due to burning of fossil fuels and biomass fuels, diverse aero-biology, tropical climate, cultural and social diversity, religious beliefs/myths, linguistic diversity, literacy level, breastfeeding and weaning, diet (large proportion vegetarian), and high incidence rates of TB, HIV, malaria, filariasis, parasitic infestations, and others, that not only shape the immune system early in life, but also impact on biomarkers relevant to allergic diseases. India has a relatively weak and heterogeneous healthcare framework, and allergology has not yet been recognized as an independent specialty. There are very few post-graduate training programs, and allergic diseases are managed by primary care physicians, organ-based specialists, and general pediatricians. Adrenaline auto-injectors are not available, there is patient unaffordability for inhalers, nasal sprays, and biologics, and this is compounded by poor compliance leading to 40%-50% of asthmatic children having uncontrolled disease and high rates of oral corticosteroid use. Standardized allergen extracts are not available for skin tests and desensitization. This article provides a critical analysis of pediatric allergic diseases in India.

Pediatric allergic diseases and molecular targeting drugs

Pediatric allergic diseases and molecular targeting drugs

Human microbiome and its role in paediatric allergic disease

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

Early Life Risk Factors in Pediatric EoE: Could We Prevent This Modern Disease?

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated inflammatory disease that affects the esophagus. In the last 20 years, a large number of epidemiological studies showed a significant increase in the incidence and prevalence of EoE, especially in developed countries. This phenomenon might correlate to the overall increase in pediatric allergic diseases or might be a result of improved medical awareness and knowledge through modern diagnostic instruments. Since 1993, when EoE was first recognized as a distinct clinical entity, several signs of progress in the pathophysiology of EoE were achieved. However, a few studies reported data on early risk factors for pediatric EoE and how these factors may interfere with genes. Currently, the most defined risk factors for EoE are male sex, Caucasian race, and atopic comorbidities. Other putative risk factors may include alterations in epithelial barrier function and fibrous remodeling, esophageal dysbiosis, variation in the nature and timing of oral antigen exposure, and early prescription of proton pump inhibitors and antibiotics. Notably, the timing and nature of food antigen exposure may be fundamental in inducing or reversing immune tolerance, but no studies are reported. This review summarized the current evidence on the risk factors that might contribute to the increasing development of EoE, focusing on the possible preventive role of early interventions.

Transitional medicine for pediatric allergic diseases -Comments from internal medicine-

Transitional medicine for pediatric allergic diseases -Comments from internal medicine-

Cognitive and Quality of Life-Related Burdens of Illness in Pediatric Allergic Airway Disease.

To analyze the prevalence of pediatric allergic airway disease (PAA) and recognize its impact on cognitive function, childhood activities, use of early intervention, and missed school days. Cross-sectional analysis of National Health Interview Survey (NHIS), 2014 to 2017. US households. An NHIS survey of US children and responding caregivers was analyzed to determine the prevalence of PAA, including allergic rhinitis and allergic asthma. Associations were determined between the presence of PAA and activities limited by difficulty remembering, limitation in the amount of childhood play, use of special education/early intervention, and number of missed school days in the past 12 months. Multivariate analysis was used to adjust for age, sex, race, ethnicity, and income level. An estimated 11.1 million (10.6-11.6 million, 95% confidence interval) children (mean age, 9.9 years; 56.9% male) reported a diagnosis of PAA (15.1% [14.6-15.6%]). Children with PAA missed 4.0 (3.7-4.4) school days per year vs 2.2 (2.1-2.4) days for those without PAA (P < .001, adjusted). PAA was associated with limited daily activities due to difficulty with memory (odds ratio, 1.8 [1.2-2.9]), limitations in childhood play (3.2 [2.2-4.7]), and need for special education/early intervention services (1.6 [1.4-1.8]) after adjusting for age, sex, race, ethnicity, and income level. PAA is a common condition and is associated with declines in cognitive function and school attendance as well as increased use of special education/early intervention. Given the significant prevalence and burden of illness of PAA, further attention is needed to ensure timely diagnosis and treatment.

Association between exposure to traffic-related air pollution and pediatric allergic diseases based on modeled air pollution concentrations and traffic measures in Seoul, Korea: a comparative analysis

BackgroundPediatric allergic diseases are a major public health concern, and previous studies have suggested that exposure to traffic-related air pollution (TRAP) exposure is a risk factor. These studies have typically assessed TRAP exposure using traffic measures, such as distance to major roads, or by modeling air pollutant concentrations; however inconsistent associations with pediatric allergic diseases have often been found. Using road proximity and density, we previously found an association between TRAP and atopic eczema among approximately 15,000 children living in Seoul, Korea, heavily populated and highly polluted city in which traffic is a major emission source. We aimed to conduct a parallel analysis using modeled air pollution concentrations and thus examine the consistency of the association. Specifically, we examined the associations of individual-level annual-average concentrations of NO2, PM10, and PM2.5 with symptoms and diagnoses of three pediatric allergic diseases including asthma, allergic rhinitis, and atopic eczema.MethodsThe study population included 14,614 children from the Seoul Atopy Friendly School Project Survey in Seoul, Korea, in 2010. To assess individual exposures to TRAP among these children, we predicted annual-average concentrations of NO2, PM10, and PM2.5 at the children’s home addresses in 2010 using universal kriging and land use regression models along with regulatory air quality monitoring data and geographic characteristics. Then, we estimated odds ratios (ORs) of the three allergic diseases for interquartile increases in air pollution concentrations after adjusting for individual risk factors in mixed effects logistic regression.ResultsSymptoms and diagnoses of atopic eczema symptoms showed an association with NO2 (OR = 1.07, 95% confidence interval = 1.02–1.13; 1.08, 1.03–1.14) and PM10 (1.06, 1.01–1.12; 1.07, 1.01–1.13). ORs of PM2.5 were positive but not statistically significant (1.01, 0.95–1.07; 1.04, 0.98–1.10). No association was found between asthma and allergic rhinitis, although PM2.5 showed a marginal association with allergic rhinitis.ConclusionsOur consistent findings regarding the association between TRAP and the prevalence of atopic eczema using traffic measures and surrogate air pollutants suggested the effect of TRAP on children’s health. Follow-up studies should elucidate the causal link, to support subsequent policy considerations and minimize adverse health effects in children.