The latest medical research on Pediatric Allergy & Immunology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about pediatric allergy & immunology gathered by our medical AI research bot.

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Inhibitory Effect of Apolipoprotein A-I on Eosinophils in Allergic Rhinitis in vitro and in vivo.

Journal of Asthma and Allergy

Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain.

Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils.

Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines.

Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies.

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

Journal of Asthma and Allergy

Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.

This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV1 to Week 12.

At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%.

Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12.

NCT02948959.

Activation of Notch1-GATA3 pathway in asthma bronchial epithelial cells induced by acute PM2.5 exposure and the potential protective role of microRNA-139-5p.

J Asthma

PM2.5 is closed linked to asthma exacerbation. The Notch1 pathway acts as an important pathway, ultimately inducing T-helper cells that express GATA3 and its corresponding Th2 cytokines. The regulatory effects of miR-139-5p on the Notch1 pathway have been indicated in cancer. However, studies on miR-139-5p have not applied asthma related models. The role of miR-139-5p and its regulatory effects on the Notch1-GATA3 pathway in asthma exacerbation induced by acute PM2.5 exposure has not been elucidated. We hypothesize that acute PM2.5 exposure induces asthma exacerbation by regulating the expression of miR-139-5p and activating the Notch1-GATA3 pathway.

We first employed Diseased Human Bronchial Epithelial Cells-Asthma cells to establish an in vitro model of acute exposure to PM2.5, and explored the relationship between the different concentrations and durations of acute PM2.5 exposure and the activation of Notch1-GATA3 pathway. We investigated the protein and mRNA expression changes of Notch1, upstream Jagged1, downstream GATA3, as well as the regulatory effect of miR-139-5p involved in it.

The miR-139-5p expression increased within 24 hours of PM2.5 exposure. However, if PM2.5 exposure was sustained, miR-139-5p expression turned to decrease, accompanied by upregulations of the mRNA and protein expression of Notch1-GATA3 pathway. Overexpression of miR-139-5p blocked Notch1-GATA3 pathway activation induced by acute PM2.5 exposure.

Acute PM2.5 exposure can activate Notch1-GATA3 pathway in asthma bronchial epithelial cells model, which might be involved in PM2.5-induced asthma exacerbation. miR-139-5p has a potential protective role of inhibiting PM2.5-induced asthma airway inflammation by targeting Notch1.

Emergency Management and Asthma Risk in Young Medicaid-Enrolled Children with Recurrent Wheeze.

J Asthma

To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma.

Retrospective cohort study of Medicaid-enrolled children 0-3 years old with an index ED visit for wheeze (e.g., bronchiolitis, reactive airway disease) from 2009-13, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4-6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze.

During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4-6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze.

Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies.

Digitally monitored inhaled therapy: A 'Smart' way to manage severe asthma?

J Asthma

One of the fundamental challenges of managing patients with severe asthma is treatment adherence, particularly with inhaled corticosteroids. Adhere...

Smoking, Urban Housing and Work-Aggravated Asthma are Associated with Asthma Severity in a Cross-Sectional Observational Study.

Journal of Asthma and Allergy

Severe asthma affects 5 to 10% of asthmatics and accounts for a large part of asthma-related morbidity and costs. The determinants of asthma severity are poorly understood. We tested the hypothesis that asthma severity was associated with 1) atopy and allergy and 2) markers associated with environmental exposure.

Data from the FASE-CPHG study, a cross-sectional, observational, multicenter investigation, were analyzed to identify markers associated with asthma severity. Asthma severity was gauged using the ASSESS score, encompassing symptom control, exacerbations, FEV1 and therapeutic load. Bivariate and multivariate analyses were used to identify patient characteristics associated with the ASSESS score.

The analysis involved 948 patients, with 592 women, of which 447 patients (47%) had severe asthma. Among these, 491 patients (52%) had at least one positive aeroallergen skin prick test and 525 (55%) had at least one allergic disease among atopic dermatitis, chronic rhinitis and food allergy. The mean±SD ASSESS score was 11.2±3.4. Characteristics associated with a higher ASSESS score were female sex, secondary or lower education, unemployed occupational status, smoking, work-aggravated asthma and urban housing. There was no association between the ASSESS score and allergic diseases, aeroallergen-specific skin prick tests and IgEs, or blood eosinophil counts.

While atopy and allergy were frequent among asthmatics, neither was associated with asthma severity. Modifiable environmental factors such as smoking, urban housing and work-aggravated asthma were independently associated with asthma severity.

Reversible Elevation of Tryptase Over the Individual's Baseline: Why is It the Best Biomarker for Severe Systemic Mast Cell Activation and MCAS?

Current Allergy and Asthma Reports

Mast cell (MC) activation syndromes (MCAS) are conditions defined by recurrent episodes of severe systemic anaphylaxis or similar systemic events triggered by MC-derived mediators that can be measured in biological fluids. Since some symptoms of MC activation may occur due to other, non-MC etiologies and lead to confusion over diagnosis, it is of crucial importance to document the involvement of MC and their products in the patients´ symptomatology.

The most specific and generally accepted marker of severe systemic MC activation is an event-related, transient increase in the serum tryptase level over the individual baseline of the affected individual. However, baseline concentrations of serum tryptase vary among donors, depending on the genetic background, age, kidney function, and underlying disease. As a result, it is of critical importance to provide a flexible equation that defines the diagnostic increase in tryptase qualifying as MCAS criterion in all patients, all situations, and all ranges of baseline serum tryptase. In 2012, the consensus group proposed the 120% + 2 ng/ml formula, which covers the great majority of groups, including cases with low, normal, or elevated basal serum tryptase level. This formula has been validated in subsequent studies and has proven to be a robust and consistent diagnostic criterion of MCAS. The present article is discussing the impact of this formula and possible limitations as well as alternative markers and mediators that may be indicative of MCAS.

There is no association between serum endotoxin levels and inflammation in asthma.

J Asthma

Endotoxin, in lipopolysaccharide structure (LPS), is the main component of the outer membrane of gram negative bacteria. LPS levels were associated with inflammatory disease. Asthma is a chronic inflammatory disease involving many different cell types and cellular elements. The association between LPS serum levels and the asthma is not well known. The aim of this study was to investigate the association between the LPS serum levels and the severity of asthma, demographic data and laboratory parameters.

The study included 67 patients aged >18 years with a diagnosis of asthma, and 15 healthy volunteers with no history of chronic disease as a control group. The Asthma Control Test (ACT), Respiratory Function Tests (RFTs), fractional exhaled nitric oxide (FeNO), and endotoxin levels were measured and compared between the groups. The endotoxin measurements were performed using the ELISA method.

The mild-moderate asthma group included 33 patients and the severe asthma group, 34 patients. The endotoxin level was measured as 17.78 (range 3.59 to 304.55) EU/ml in the patient group and 15 (range 4.01 to 74.06) EU/ml in the control group with no statistically significant difference determined between the groups. In the subgroups, the endotoxin level was measured as 15.21 (range 3.69 to 304.55) EU/ml in the mild-moderate group and 14.46 (range 3.59 to 278.86) EU/ml in the severe asthma group with no statistically significant difference determined between the groups.

The results of this study showed no relationship between serum endotoxin level and asthma or asthma severity.

Evaluating the implementation of a community health worker-delivered intervention integrating asthma care in West Philadelphia public schools.

J Asthma

Schools are an important setting because students spend much of their time in school and engage in physical activity during the school day that could exacerbate asthma symptoms. Our objective is to understand the barriers and facilitators to implementing an experimental community health worker-delivered care coordination program for students with asthma within the context of the West Philadelphia Controls Asthma study.

Surveys (n = 256) and semi-structured interviews (n = 41) were completed with principals, teachers, nurses, and community health workers from 21 public and charter schools in West Philadelphia between January 2019 and September 2021. Survey participants completed the Evidence Based Practice Attitudes Scale, the Implementation Leadership Scale, and Organizational Climate Index. Semi-structured qualitative interview guides were developed, informed by the Consolidated Framework for Implementation Research.

Participant responses indicate that they perceived benefits for schools and students related to the community health worker-based care coordination program. Several barriers and facilitators to implementing the program were noted, including challenges associated with incorporating the program into school nurse workflow, environmental triggers in the school environment, and challenges communicating with family members. An important facilitator that was identified was having supportive school administrators and staff who were engaged and saw the benefits of the program.

This work can inform implementation planning for other locales interested in implementing community-based pediatric asthma control programs delivered by community health workers in schools.

Cognitive Impairment and Depression in Mastocytosis: A Synthesis of the Literature.

Current Allergy and Asthma Reports

Symptoms of depression and cognitive dysfunction are commonly reported in mastocytosis. The aims of this review paper are to summarize the current literature on cognitive dysfunction and depressive symptoms, elucidate some of the mechanistic pathways underlying depressive symptoms in mastocytosis, identify gaps in the literature, and offer guidance for future research in this area.

The study of cognition and depression in mastocytosis is in its infancy and the methodological flaws of the current literature limit interpretability. There is preliminary evidence that some individuals with mastocytosis might experience mild deficits in memory. On average, depression symptom scores fell within the mild to moderate or sub-syndromal range. Regrettably, only one study utilized a standardized diagnostic instrument to assess major depressive disorder. The authors' tendency to inaccurately equate depressive symptoms with a diagnosis of major depressive disorder presents a notable issue. The prevalence of cognitive deficits and depression appears to be similar to other chronic illnesses. Future work needs to better characterize cognition and characterize "depression" in this population.

Near Fatal Asthma in a case of allergic bronchopulmonary Aspergillosis(ABPA) treated with ECMO.

J Asthma

Fatal asthma is a rapidly progressing and highly fatal form of asthma. Mechanical ventilation, although necessary for respiratory support, can exacerbate the condition and lead to ventilator-associated lung injury. ECMO therapy is crucial in allowing the lungs to rest and recover, as it provides extracorporeal membrane oxygenation.

A 40-year-old man presented with dyspnea following a mountain climb, which rapidly worsened, leading to respiratory failure and loss of consciousness. Despite drug therapy and mechanical ventilation, arterial blood gas analysis showed persistent hypercapnia. After 3 days of ECMO support, the patient was successfully extubated and underwent treatment for Aspergillus infection. Chest CT returned to normal after 3 months of anti-aspergillus therapy.

When drug therapy and mechanical ventilation fail to improve respiratory failure in fatal asthma, prompt initiation of ECMO support is essential to create opportunities for subsequent etiological treatment.

Efficacy of Bronchial Thermoplasty in a Patient Panel with Uncontrolled Severe Persistent Asthma.

J Asthma

Bronchial thermoplasty (BT) is an approved procedure to manage uncontrolled severe persistent asthma. Many insurance providers are reluctant to pay for BT without proven benefit among their specific patient panel.

Determine if BT is effective in a panel patient panel with uncontrolled severe persistent asthma.

This was an unblinded prospective study of adult subjects with uncontrolled severe persistent asthma who underwent BT. Outcomes were assessed at baseline and then 3-, 6-, 12-, 18- and 24-months post-BT. The primary metric was an improved Asthma Quality of Life Questionnaire (AQLQ) score. Other metrics included improved Asthma Control Test (ACT), peak expiratory flow rates (PEFR), spirometry, fractional excretion of nitric oxide (FeNO), number of unscheduled medical visits, and lost days of work/activity. Respiratory adverse events were assessed during the BT treatment period and at each post-BT visit.

Twenty-nine subjects completed the study; the median interquartile range (IQR) age was 47 (42-61), and the majority were female (69%), white (93%), and non-Hispanic (90%). After BT, mean (±std) AQLQ scores improved by 1.6(±1.1) at 3 months (p < 0.0001), 1.6(±1.2) at 6 months (p < 0.0001), 1.4(±1.0) at 12 months (p < 0.0001), 1.8(±1.1) at 18 months (p < 0.0001), and 1.6 (±1.5) at 24 months (p < 0.0001). There were significant improvements in ACT, PEFR, unscheduled medical visits and lost days of work and activity. Spirometry and FeNO metrics were unchanged. The average cost for subjects completing all 3 BT procedures was approximately $15,000.

BT is an effective adjunctive therapeutic modality in subjects with uncontrolled severe persistent asthma.