Frontiers in allergy最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition often associated with type 2 inflammation. While biologics are a promising treatment for patients with uncontrolled CRSwNP, real-world evidence is needed to optimize their use. The InternatioNal seVerE CRSwNP (INVENT) registry aims to consolidate data on biologic use in CRSwNP from local and national registries. This study describes the identification of mandatory and optional variables for inclusion in the INVENT registry using a modified Delphi process.

Methods: A narrative literature review was performed to identify variables reported in real-world studies of biologic treatment for CRSwNP. A modified Delphi study was conducted between December 2024 and March 2025 involving 23 experts from Europe and Australia. Experts rated the clinical relevance of candidate variables in two online survey rounds using 9-point Likert scales. A positive response was defined as ≥70% of respondents rating a variable 7-9 and ≤15% rating it 1-3. Final agreement on mandatory and optional variables was reached through panel discussion. A validation survey was then conducted across registry centers to assess the feasibility of collecting the selected variables.

Results: The Delphi process resulted in consensus on a core set of mandatory and optional variables across nine domains: demographics, medical history, previous and current biologic therapy, biomarkers, comorbidities, asthma, CRSwNP-specific outcomes, and follow-up variables. The validation survey confirmed that most mandatory variables were available or obtainable across participating centers, supporting the feasibility of data collection.

Conclusions: This international Delphi study identified a consensus-based set of clinically-relevant and feasible variables for inclusion in the INVENT registry. The selected variables reflect current best practices in the management of CRSwNP and will enable robust comparisons of biologic effectiveness in real-world settings. The INVENT registry is well-positioned to inform treatment decisions, optimize use of biologics, and support a personalized approach to CRSwNP care.

Introduction: Asthma is often treated with oral corticosteroids (OCS), despite their association with significant adverse effects. While guidelines recommend minimizing OCS use through alternative therapies and patient-centered approaches, discrepancies between recommendations and real-world practices persist. This study evaluates OCS usage patterns and barriers to adherence to asthma treatment guidelines in Italy, using surveys conducted with healthcare professionals (HCPs) and patients.

Methods: Two cross-sectional surveys were administered between January and March 2024 to HCPs and asthma patients. The surveys assessed OCS prescription practices, treatment adherence, patient involvement, adverse event management, and perceptions of OCS use. Descriptive analysis was performed to identify patterns and highlight gaps in current practices.

Results: The surveys revealed considerable variability in OCS prescribing practices, treatment duration and daily dosages. Over 80% of patients reported using OCS and 18% of HCPs believed that the maximum daily doses of OCS are higher than the guideline-recommended doses. Patients did not feel fully involved in treatment decisions, with over 40% of patients reporting unsatisfactory communication about treatment alternatives or adverse effects. Barriers to optimal care included inadequate access to specialists, inconsistent monitoring protocols, and a lack of multidisciplinary approaches. Both HCPs and patients highlighted the need for clearer definitions of OCS dependency and enhanced tools for tracking treatment adherence.

Discussion: The findings underscore the urgent need for systemic reforms to align clinical practice with guidelines. These include establishing pragmatic definitions for OCS dependency, promoting multidisciplinary care, and leveraging technology for monitoring. Addressing psychosocial factors and empowering patients through education and shared decision-making are also critical.

Objectives: To conduct a systematic review and meta-analysis to identify Th1-, Th2, and Th17 related serum biomarkers that reflect disease activity in chronic urticaria (CU), thereby enhancing the assessment of disease activity in both trials and clinical practice.

Methods: Systematic searches of PubMed, EMBASE, and Web of Science were conducted through November 2024 to identify articles reporting the associations between CU and serum biomarkers. Serum Th1, Th2, and Th17 related biomarkers were identified in CU patients and correlated with disease severity and patient characteristics (ex. Age, sex, and comorbidities). The study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for case-control studies. Meta-analysis was performed using the random-effects model with Hedges' g to pool standardized mean differences (SMDs). For meta-analysis, data were included for biomarkers reported in at least four studies with available means and standard deviations (SDs). Data reported as medians with ranges or interquartile ranges (IQRs) were evaluated for skewness. If the data were found to be significantly skewed, the means and SDs were not calculated. Conversely, if the data were not skewed, the means and SDs were estimated using validated methods.

Results: A total of 6,013 studies were screened, of which 50 were included, reporting 22 serum Th1, Th2, and Th17 related cytokines. Meta-analyses revealed significant pooled standardized mean differences (SMDs) for serum TNF-α and IL-17.

Conclusions: Serum TNF-α and IL-17 levels are significantly increased in patients with CU compared to healthy age- and sex-matched controls. These findings have the potential to influence clinical guidelines for the diagnostic workup of CU to include testing the serum levels of TNF-α and IL-17.

Introduction: Anaphylaxis is the most severe manifestation of systemic immediate hypersensitivity, yet the underlying trigger often remains elusive. When routine history and allergy testing fail to identify a cause, the condition is classified as idiopathic anaphylaxis. Food additives, although uncommon culprits, may be overlooked, particularly in atopic individuals.

Methods: We report a case of a 39-year-old woman with recurrent anaphylaxis initially diagnosed as idiopathic. Standard allergy testing, including extended skin prick and specific IgE panels, was negative. Due to a temporal association with restaurant-prepared food, an additive hypersensitivity was suspected. A detailed dietary history and targeted skin prick testing were employed using both commercial and in-house preparations of food colorants.

Results: SPT was positive for carmine-containing red food colorants, including a commercially available gel and a prepared cochineal extract. Control subjects tested negative. sIgE to carmine was equivocal. The patient was educated about allergen avoidance and has remained symptom-free following elimination of carmine from her diet, cosmetics, and medications.

Conclusion: This case underscores the importance of considering food additives, particularly carmine, in patients with unexplained anaphylaxis. Structured re-evaluation, patient-guided dietary review, and custom allergen testing may be essential in identifying hidden allergens. Clinicians should be vigilant about uncommon triggers when routine investigations fail to identify the cause.

Background: Mycoplasma pneumoniae-induced rash and mucositis (MIRM) is a unique entity distinct from both erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis. There are limited data on pediatric cases of MIRM in China.

Objective: To evaluate the clinical characteristics and recurrence frequency of pediatric cases of MIRM and to summarize the co-infections beyond M. pneumoniae infection.

Methods: This retrospective study was conducted through a chart review of patients with MIRM admitted to dermatology inpatient department from September 2017 to July 2021. Pediatric patients with MIRM 4 years to 12 years who met Canavan's criteria were included in the study.

Results: A total of 23 patients with MIRM aged 7.86 ± 2.92 years were included. Oral mucosa was the most common site of mucosal involvement. Average number of involved mucous membranes was 2.83 ± 0.89. Average length of hospital stay was 10.30 ± 3.34 days. Length of hospital stay in recurrent cases was shorter than isolated cases (6.3 days vs. 10.17 days). Recurrence was observed in 21.7% of patients. The number of mucosal membranes involved was more in the first episode of recurrent cases than isolated cases (3.2 vs. 2.72). Of all patients, 47.8% were co-infected with pathogens apart from M. pneumoniae. Recurrence rate of the co-infection group was 36.4%.

Conclusion: We report observations from the largest pediatric cohort with MIRM in China. Patients with younger age at onset had more severe skin and mucosal involvement, even similar to SJS/TEN. A higher recurrence rate and incidence of co-infections were observed in our cohort. The co-infection group had a higher recurrence rate, which further supports the concept of reactive infectious mucocutaneous eruption.

Rationale: Genetic risk scores (GRS) of Th1/2/17-related loci may be associated with response to biologics. We leveraged previously published machine learning-derived GRSs associated with plasma proteins from the INTERVAL/UK-Biobank study.

Methods: We assessed 42 Th1/2/17-related GRSs and SNPs for association with response (≥50% reduction in exacerbations) to biologics in 172 White patients with moderate-to-severe asthma in the Mass General Brigham Biobank (MGBB: 92 omalizumab, 38 mepolizumab, 42 dupilumab). Replication was sought in 243 individuals in the All of Us (AoU) cohort (111 omalizumab, 58 mepolizumab, 74 dupilumab). Models adjusted for age, sex, BMI, baseline exacerbations, and principal components 1-10. AUROC was used to evaluate top predictors; type I error was assessed using random GRS sets (target FDR ≤20%).

Results: Females comprised a large proportion; mean BMI was 28-35 kg/m². IL21 GRS was associated with omalizumab response in MGBB (OR: 1.7, 95% CI: 1.03-2.87) with similar direction in AoU (1.5, 0.91-2.45). IL21 also predicted dupilumab response in MGBB (2.4, 1.05-5.44) but in the opposite direction in AoU (0.57, 0.31-1.06). IL21 replicated as a predictor of omalizumab [AUROC, 95% CI: MGBB 0.62 (0.50-0.74), AoU: 0.71 (0.61-0.81)] and dupilumab [AUROC, 95% CI, MGBB 0.76 (0.58-0.95), AoU: 0.75 (0.64-0.86)]. Adding IL5RA (omalizumab) or CCL17 (dupilumab) modestly improved AUROC but not significantly. No GRS predicted mepolizumab response.

Conclusions: Using ML-based GRS applied to an independent cohort of asthma patients, we found that IL-21-related GRSs were predictors of response to omalizumab and dupilumab.

Mast cells play a critical role in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disease characterized by itch, eczema, and barrier dysfunction. These immune cells are abundant in the skin and are activated in response to allergens, irritants, and microbial products. Upon activation, mast cells release a variety of mediators, including histamine, proteases, cytokines, and chemokines, which contribute to the inflammation and pruritus observed in AD. Recent studies have highlighted the importance of mast cell-derived IL-4, IL-13, and IL-31 in promoting Th2-type immune responses and itch sensation. Moreover, interactions between mast cells and sensory neurons may further exacerbate neuroimmune inflammation. Mast cells also influence skin barrier integrity by modulating keratinocyte function and disrupting tight junctions. Their numbers and activation state are often elevated in AD lesions, correlating with disease severity. Targeting mast cell activation or blocking their mediators has shown promise in preclinical models, offering potential therapeutic strategies. Overall, mast cells are increasingly recognized as key contributors to the initiation and amplification of AD, making them an important focus for understanding disease mechanisms and developing new treatments.

On separate occasions nearly a decade apart, two large-scale accidental releases of industrial chemicals exposed substantial "bystander" (non-worker) populations to highly toxic air pollutants. The first of these events, occurring in Bhopal, India in 1984, generated worldwide attention and concern given its geographic scope and significant lethality. The second incident, occurring in Dunsmuir, CA in 1991 - while less publicized - yielded new insights into the pathogenesis of irritant-induced asthma. Linking these events is the fact that the toxicants involved - methyl isocyanate (MIC) in Bhopal and methyl isothiocyanate (MITC) in Dunsmuir - preferentially bind to the same TRPA1 nociceptive ion channel. This review examines each of these exposure events, including their mechanistic implications for anticipating (and potentially preventing) future long-term health effects from accidental chemical exposures.

Background: Respiratory viruses such as rhinovirus and respiratory syncytial virus (RSV) are common triggers of asthma exacerbations in children. The COVID-19 pandemic introduced non-pharmaceutical interventions (NPIs) that altered viral circulation; however, their long-term effects on pediatric asthma outcomes remain unclear.

Objective: To evaluate how the epidemiology and severity of respiratory viral infections in children with asthma changed before, during, and after COVID-19-related NPIs.

Methods: We conducted a cross-sectional analysis of pediatric asthma patients (ages 4-18) with laboratory-confirmed respiratory viral infections from 2018 to 2024 at Arkansas Children's (AC) and AC Northwest (ACNW). Viral detection was performed using the BioFire® Respiratory Panel. Clinical severity was evaluated using a modified World Health Organization Ordinal Scale for Clinical Improvement (mWHO OSI). Patients were categorized by period (pre-NPI, NPI, post-NPI), viral type, rurality, and Childhood Opportunity Index (COI).

Results: This study included 9,391 pediatric asthma patients with laboratory-confirmed viral infections. RV/EV was the most common virus during all periods. Viral incidence decreased during NPIs but rebounded post-NPI with unusual seasonality. mWHO OSI scores declined over time (pre-NPI: 2.98; NPI: 2.49; post-NPI: 2.28), with significant reductions in hospitalizations, PICU admissions, and oxygen use (p < 0.0001). Severe disease (mWHO OSI 6-8) was infrequent. Rural and low-COI patients exhibited higher severity, although disparities narrowed post-NPI.

Conclusions: NPIs were associated with sustained reductions in asthma-related illness severity, even with increased viral detection post-pandemic. These findings highlight the long-term impact of public health measures on pediatric asthma outcomes and emphasize the need for ongoing surveillance of respiratory viruses and health disparities.

Background: Birch pollen-food allergy syndrome is triggered by cross-reactive allergens in plant-based foods. Environmental factors such as nitrogen fertilization may influence food allergenicity, but this has not been studied before.

Methods: We compared and optimized protein extraction protocols for birch-homologue foods, including apple, carrot, and soybean. Various extraction buffers and mixing methods were tested for consistency and protein yield. We applied this to a pilot study assessing potential changes in the allergenic potential of plant-based foods due to altered nitrogen availability. A greenhouse experiment was conducted in which soybean plants were subjected to different nitrogen fertilization treatments. Allergenicity was evaluated using ex vivo basophil activation testing in five individuals with birch pollen-food allergy syndrome.

Results: No major differences were observed between the tested extraction protocols, and key allergens were detectable in all food sources. In the pilot experiment, fertilized soybeans showed visible changes in size, a smaller shape, a different protein profile, and lower basophil reactivity compared to unfertilized soybeans.

Conclusion: Our findings support the feasibility of standardized extraction methods. Varying nitrogen fertilization in soybeans resulted in altered physical, proteomic, and allergenic characteristics in this pilot study. Our results highlight the need for further research on environmental influences on food allergy.