Pediatric Allergy and Immunology最新文献

The Asia Allergy Birth Cohort (A2BC) network consolidates data from multiple independently established birth cohorts across Asia to enhance research on host-environment interactions in allergic diseases. These cohorts, established at different times with various methodologies, are reliable data sources. Our aim is to introduce the content, variables, and outcomes of these cohorts while highlighting their differences, laying the groundwork for future collaborative research. The A2BC network includes 10 cohort studies on allergic diseases from six Asian countries. Enrollment criteria, study aims, and an initial inventory were discussed and confirmed through five business meetings. A common database was developed to assess the study characteristics of these observational cohorts on allergic diseases, though harmonization efforts are retrospective. Five studies collected data on specific immunoglobulin E responses to various inhalant and food allergens, while six cohorts conducted skin prick tests. Lung function measurements were included in some studies, but without standardized procedures across cohorts. Asthma and allergic rhinitis were primarily assessed using questionnaires or doctor diagnoses, while assessments of eczema and food allergies varied across studies. The A2BC network also examines early-life environmental factors such as delivery mode, antibiotic usage, diet, and air pollutants, although these exposures were measured differently across the cohorts. Despite differences in the origins, methods, and objectives of each cohort, pooling data and conducting joint analyses offer valuable insights into the relationship between environmental exposures and allergic disease outcomes in Asian children. This approach can serve as a foundation for future collaborative research.

Background: Current knowledge of the impact of socioeconomic factors on the risk of admission to the pediatric intensive care unit (PICU) for asthma is limited. Using composite measures of social vulnerability-Social Vulnerability Index (SVI) and Child Opportunity Index (COI) 2.0-we compared patients admitted for status asthmaticus to the PICU and pediatric ward at Children's Hospital Los Angeles (CHLA). We hypothesized patients with a high SVI and low COI are at higher risk for PICU admission.

Methods: Patients were identified using ICD-10 codes for asthma. Primary outcome was admission to PICU versus ward for status asthmaticus. Patient-registered residential street addresses were geocoded and spatially joined to SVI and COI 2.0 data at the census tract level. Univariate and regression analyses using the patient's SVI, COI 2.0, and admission location were conducted.

Results: From January 2017 to March 2022, there were 2458 admissions matched to addresses from 1983 distinct patients. The overall median SVI for all patients was 0.86 (IQR 0.6, 0.9). Overall median COI was 25.0 (IQR 10, 50). There was no difference in SVI or COI for admission to the PICU versus the ward. However, children requiring multiple hospital admissions for asthma were associated with higher SVI and lower COI.

Conclusions: Children admitted to CHLA for asthma had an elevated SVI and low COI. There was no difference between admission locations based on SVI or COI scores. This indicates we care for children at increased socioeconomic risk, but this did not increase PICU use for asthma.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.

Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.

Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.

Results: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10^-20) and linoleic acid derivatives (q = 3.8 × 10^-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10^-8), eicosanoids (q = 7.9 × 10^-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.

Conclusions: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.

Background: In this study, we aimed to report long-term follow-up of our pediatric and adult patients with DCLRE1C (DNA cross-link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID).

Methods: Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls.

Results: Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B- and T-cell lymphopenia at the first admission. Recent thymic emigrants (RTE), T_naive, B_naive, CD56^dimCD16⁺ cell ratios were significantly lower in the patients than in control; however, follicular helper T T_FH and Th1 [interferon gamma (IFN-γ)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow-up times of transplant patients was 56 (9-67) months.

Conclusion: Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1-dominant immune response before and after HSCT. Increased IFN-γ and T_FH cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long-term follow-up of these patients after HSCT will help to better understand the disease and its pathophysiology.

Background: Parvalbumin Gad c1 is a major cod allergen used as a follow-up marker of fish-allergic children. However, the diagnostic efficacy of recombinant Gad c 1 (rGad c 1) for fish allergy diagnosis remains controversial. This study aimed to evaluate the efficacy of rGad c1 for diagnosing cod and horse mackerel allergy.

Methods: This single-centered, retrospective study obtained oral food challenges (OFCs) information performed for cod and horse mackerel. Cod-, horse mackerel-, and rGad c1-specific immunoglobulins (sIgEs) were investigated. Diagnostic performances of these parameters were compared using areas under the curve (AUC).

Results: We enrolled 45 and 38 children with suspected cod and horse mackerel allergies, respectively. The median age (interquartile range) of children with suspected cod allergy was 5.7 (0.7-11.7) years and that of children with suspected horse mackerel allergy was 6.0 (1.0-12.3) years. Fourteen and 22 children reacted to OFCs with 25 (10-40) g of cooked pacific cod and 40 (10-40) g of cooked horse mackerel, respectively. The cod sIgE and rGad c 1 sIgE AUCs for cod allergy diagnosis were 0.85 and 0.90, respectively. For horse mackerel allergy diagnosis, AUCs of horse mackerel and rGad c 1 sIgE were 0.76 and 0.72, respectively. Both AUCs for cod and mackerel allergy were significantly different.

Conclusion: rGad c 1 sIgE is more effective than cod sIgE as a diagnostic marker of cod allergy, but less effective than horse mackerel sIgE as a diagnostic marker of horse mackerel allergy. Further studies are warranted to explore the potential applications of rGad c 1 sIgE in the diagnosis of various fish allergies.

Background: Trajectories of asthma and allergy in children are heterogeneous and commonly derived from parental report of disease or clinical records. This study combined parental-reported and register-based dispensed medication data to characterize childhood trajectories of co-existing asthma, allergic rhinitis, and eczema.

Methods: From a Swedish population-based birth cohort (N = 5654), survey responses collected at the age of 1, 4.5, 8, and 12 years were linked to dispensed medication register data for the period of 2-13 years. Trajectories were identified with latent class analysis. Statistical metrics and clinical interpretability guided the model selection.

Results: Nine distinct trajectories were identified: three asthma-dominated (early-onset remitting [n = 189, 3.3%], late-onset [n = 117, 2.1%], and persistent [n = 149, 2.6%]), two eczema-dominated (persistent [n = 190, 3.4%] and remitting [n = 432, 7.6%]), one allergic rhinitis-dominated (late-onset [n = 259, 4.6%]), two multimorbidity (mid-childhood asthma and late-onset allergic rhinitis [n = 144, 2.5%], and persistent eczema and late-onset allergic rhinitis [n = 90, 1.6%]), and one low-disease burden trajectory (n = 4084, 72.2%). Differences were seen across the trajectories in the proportion of parental report of disease and dispensed medication as well as by class and quantity of medication dispensed.

Conclusion: Combined parental-reported and dispensed medication data enriches characterization of longitudinal trajectories of asthma and allergy in children by merging subjective experience of disease with healthcare utilization. The identified trajectories were characterized by distinct disease development and prescription patterns suggesting clinically differential morbidity burden.