Pediatric Allergy and Immunology最新文献

Respiratory infections are a leading cause of morbidity and mortality during the early life period, and experiencing recurrent infections may increase the risk of developing chronic respiratory diseases, such as asthma. Over the last several decades, metabolomics methods have been applied to inform upon the underlying biochemistry of pediatric respiratory infection response, to discriminate between respiratory infection types, and to identify biomarkers of severity and susceptibility. While these studies have demonstrated the power of applying metabolomics to the study of pediatric respiratory infection and contributed to an understanding of respiratory infections during the unique period of immune development, key differences in study design, infection type(s) of interest, biosamples, metabolomics measurement methods, and lack of external validation have limited the translation of these findings into the clinic. The purpose of this review is to summarize overlaps across existing studies of commonly reported metabolomics findings and emphasize areas of opportunity for future study. We highlight several metabolomics pathways-such as the citric acid cycle and sphingolipid metabolism-that have been reported consistently in respiratory infection response. We then discuss putatively identified metabolomic markers to discriminate between respiratory infection types and possible markers of infection severity and proneness. Finally, we close with a summary and perspective of future directions of the field.

Background: Invasive fungal disease (IFD) is a common complication observed in inborn errors of immunodeficiency (IEI) patients, and little is known about the overall prevalence of IFD in IEI patients. We aimed to summarize the fungal spectrum and outcomes of IFDs in a Chinese cohort of hospitalized patients with IEI.

Methods: In this retrospective study, 607 IEI patients hospitalized from January 2018 to June 2022 were included. Demographic, clinical, and fungal infection data and IEI patient characteristics were collected and analyzed according to the IEI classification.

Results: One hundred and two IEI patients were diagnosed with proven or probable IFD. The overall prevalence of IFD was 17% (102/607). There were 29 different genotypes, among which CYBB (25%), CD40LG (9%), and RAG1 (7%) mutations were the most common. Most IFD infections (87/102) were caused by one fungus. Invasive Aspergillus, Pneumocystis jirovecii pneumonia, and Penicillium infections were more commonly observed in patients with congenital defects in phagocytes, immunodeficiencies affecting cellular and humoral immunity, and defects in innate immunity, respectively. Most IFDs observed in IEI patients were single-site infections, most of which were lung infections (74%). Seventeen patients were diagnosed with disseminated IFDs, nine of which were caused by Penicillium. All patients received antifungal treatments. Eight patients (8%) died within 3 months of IFD diagnosis.

Conclusions: IFD occurrence suggests the presence of immunity impairment. The IFD fungal profile may indicate different types of IEI. Early recognition of immunodeficiency and optimal timing of antifungal therapy can reduce fatality in IEI patients.

Epcutaneous immunotherapy (EPIT) is a novel, non-oral route of allergen immunotherapy, utilizing the skin and its robust density of epidermal Langerhans cells (LC) for antigen presentation. This space is non-vascularized and impermeable, which limits allergen exposure into the bloodstream but preserves antigen presentation to regional lymph nodes to generate gut-homing regulatory T cells. The EPIT patch utilizes natural water loss from the skin to absorb electrosprayed allergen through condensation. EPIT represents an alternative, non-oral route of immunotherapy for food allergy, with good efficacy and strong safety profiles across multiple phase 2 and 3 studies for milk and peanut. Efficacy appears the best in very young children (1-3 years old), which has been shown to continue to enhance with extended treatment duration up to 36 months. Efficacy in slightly older children ages 4-11 years of age is less clear, but appears to be better in children ages 4-7 years of age. In clinical trials of milk and peanut EPIT, most subjects experienced adverse effects, mainly mild-to-moderate skin reactions localized around the patch placement site, which improve with continued duration of wear. Rates of treatment-related anaphylaxis have been very low across all studies and ages, ranging from 1.6% to 4%, and were lowest in the infant and toddler population. While further studies of safety (1- to 3-year-olds) and efficacy (4- to 7-year-olds) are ongoing, EPIT is a potentially valuable addition to the current landscape of food allergy therapies, in particular for infants and toddlers where families may be seeking a non-oral route of treatment.

Background: Symptoms of hereditary angioedema (HAE) typically first present during childhood, but the frequency/severity of attacks often increases at puberty. Real-world data on long-term HAE prophylaxis in adolescents are limited. We report pooled data from adolescent patients enrolled in two Phase 4 studies (EMPOWER, ENABLE) evaluating the effectiveness/safety of lanadelumab (monoclonal antibody directed against plasma kallikrein) for the prevention of HAE attacks.

Methods: Adolescent patients (aged 12 to <18 years) with HAE-C1INH enrolled in EMPOWER and ENABLE received open-label lanadelumab 300 mg once every 2 weeks. Effectiveness outcomes were based on patient-reported assessments of on-treatment HAE attacks. Safety was assessed through the recording of treatment-emergent adverse events (TEAEs) and serious adverse events. This analysis categorized patients as "new" or "established" lanadelumab patients.

Results: Thirteen new and seven established patients on lanadelumab were included. The observed monthly attack rate in new patients fell from 3.8 (mean) and 2.8 (median) during the pre-enrollment period to 0.65 (mean) and 0.21 (median) during the cumulative study period after lanadelumab initiation (84.2% and 92.9% reductions, respectively). In established patients, mean (SD) HAE attack rate (as treated) during the overall study period was 0.04 (0.03) attacks/month. Most HAE attacks were of mild/moderate severity. Nine new patients reported 42 TEAEs, mostly mild/moderate in severity, with 3 TEAEs reported as serious. Seven established patients reported 12 TEAEs (all mild/moderate and non-serious). No TEAEs were related to lanadelumab.

Conclusion: These data support lanadelumab's effectiveness/safety in adolescents with HAE, consistent with results from Phase 3 lanadelumab studies in mixed adult/adolescent populations.

Clinical trial identifiers: NCT03845400 (EMPOWER) and NCT04130191 (ENABLE).

Component-resolved diagnostics (CRD) have revolutionized allergy diagnosis, offering enhanced accuracy and insights into allergen sensitization patterns. This review explores geographical variances in CRD for food and aeroallergens across the Asia-Pacific region. We examine the varying prevalence of allergic diseases and the utility of CRD in diagnosing common food allergies, including peanut, shellfish, fish, wheat, and fruits. Notable differences in serum-specific (sp)IgE sensitization patterns and the clinical relevance of particular allergen components are observed between populations in Asian countries and those in Europe and the United States. For food allergies, the literature reports significant differences in allergen components and their diagnostic utility across various countries. Peanut allergy diagnostics, particularly Ara h 2 spIgE, show varying sensitivity and specificity between Asian and Western populations. In shellfish allergy, emerging allergens beyond tropomyosin are gaining importance in the Asia-Pacific region. Fish and wheat allergies also demonstrate unique sensitization patterns, emphasizing the need for region-specific diagnostic approaches. Regarding aeroallergens, pollen sensitization profiles vary widely across the region, influenced by local flora and climate, to influence symptoms of pollen food allergy syndrome. House dust mite allergens remain a significant concern, with high sensitization rates to major components like Der p 1, Der p 2, and the emerging Der p 23. The cross-reactivity between house dust mite and shellfish allergens is particularly relevant in this region. These findings emphasize the need for region-specific CRD approaches, considering local allergen profiles and sensitization patterns. As the prevalence of allergic diseases continues to rise in the Asia-Pacific, further research into locally relevant allergens and their components is crucial for improving diagnosis, patient management, and targeted immunotherapy strategies in this diverse region.

Background: Since the early introduction of peanut to prevent IgE-mediated peanut allergy, other case series have suggested an increased incidence of peanut-triggered Food Protein Induced Enterocolitis Syndrome (FPIES). Data on the prevalence of peanut-induced FPIES in prospective cohorts are lacking.

Methods: The PeanutNL cohort is a prospective cohort that included infants at risk of peanut allergy (n = 706) as well as infants with reactions to peanut at home after early introduction (n = 186). They all introduced peanut before the age of 12 months. Oral food challenges were performed to introduce peanut or to evaluate reactions to peanut at home.

Results: Of the 706 infants that were included for first introduction of peanut, 2 had reactions with a phenotype compatible with FPIES (0.3%). Of the 186 infants with reactions to peanut at home, 6 were diagnosed with FPIES (3.2%). Seven out of 8 cases had ingestions of peanut without reactions at home or during clinical introduction before FPIES became apparent. During a 3-year follow-up, six infants (75%) were shown to be tolerant to peanut before the age of 3 years.

Conclusion: The prevalence of challenge-proven peanut-induced FPIES in a Dutch cohort of atopic infants that introduced peanut between the ages of 4 and 11 months is 0.3%. The majority of cases were tolerant to peanut before the age of 3 years. When introducing peanut in the first year of life, physicians should be aware of FPIES reactions, but it should not be a reason to avoid early introduction of peanut.