Frontiers in allergy最新文献

Introduction: Angiotensin converting enzyme inhibitors (ACEI) have proven mortality and morbidity benefit in hypertension, ischemic heart disease, heart failure, and renal disease and are among the most prescribed medications globally. ACEI angioedema (AE-ACEI) is a potentially life-threatening adverse drug reaction that is reported to occur more frequently in African American populations. However, the clinical profile of AE-ACEI is poorly characterized in diverse African populations.

Methods: A case-controlled cohort study with enrolment of AE-ACEI cases and drug-tolerant controls in Cape Town, South Africa. Univariable and multivariable analysis was performed. Controls were defined as patients tolerating ACEI for a minimum of two years. Cases were defined as patients who had angioedema while using an ACEI, patients with a history of angioedema while not on an ACEI were excluded. Cases and controls were recruited from the same demographic areas, including both hospitals and clinics. Information regarding demographics and clinical history was captured via both in person interviews and folder review.

Results: A total of 237 AE-ACEI cases, and 466 ACEI tolerant controls were enrolled from seven sites in Cape Town. Features of IgE-mediated immediate drug hypersensitivity were present in 24 cases, which excluded them from analysis. The median age was 58 years (IQR: 47; 67) and 57% were female. AE-ACEI cases more frequently had Black genetic ancestry compared to controls [53% (81/154), vs. 29% (146/407), p < 0.001]. AE-ACEI occurred within 30 days of initiating ACEI therapy in only 31.1% (70/225), with median treatment time to AE-ACEI of 6.9 years (IQR: 2.9; 13). The ACEI tolerant controls were using ACEI for median 9.5 years (IQR: 5; 15.5). All AE-ACEI cases developed swelling above the shoulders, involving the lips and tongue in 72% (165/213) and 50% (107/213) cases respectively. Hospitalisation for AE-ACEI was required in 82% (175/213), however only two patients were intubated, and there were no mortalities. In multivariable analysis traditional risk factors of age, gender, immunosuppression and atopy did not differ between cases and controls. Black genetic ancestry [aOR 15.4 (95% CI 2.94-283), p value = 0.01] and calcium channel blocker use [aOR 1.77 (95% CI 1.17-2.72), p value = 0.008] were significant risk factors for developing AE-ACEI. Cardiac failure, chronic kidney disease, and statin use reduced the risk of AE-ACEI in this model.

Conclusion: In this South African population, Black genetic ancestry and calcium channel blocker use were the major risk factors for AE-ACEI. The majority of AE-ACEI occurred after several years of treatment, with most cases involving the lip and/or tongue. Long-term follow-up, genetic, and further mechanistic studies are warranted in additional diverse African populations.

Background: Patients with mastocytosis have a higher risk of anaphylactic reactions. This study aims to assess the prevalence and risk factors of anaphylaxis among patients diagnosed with Systemic Mastocytosis (SM), including pre-diagnostic Systemic Mastocytosis (pre-SM), a subgroup of patients often overlooked in current classifications.

Methods: A retrospective monocentric study was conducted at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy. Patients aged ≥18 years diagnosed with SM or pre-SM between January 2009 and May 2025 were included. Demographic, clinical and laboratory data were analyzed using chi-squared test or Wilcoxon-Mann-Whitney and Kruskal-Wallis tests.

Results: At the time of diagnosis, out of 162 patients (53% women), 29 (18%) experienced at least one episode of anaphylaxis. Hymenoptera venom was the main trigger (51.7%), followed by drugs (27.6%) and idiopathic cases (20.7%). Patients with anaphylaxis had 7% pre-SM, 48% BMM, 28% ISM, 0% SSM, 7% ASM, 10% SM-AHN, (p < 0.001). The prevalence of anaphylaxis in each subtype was as follows: 2/12 (17%) in pre-SM, 14/31 (45%) in BMM, 8/97 (8%) in ISM, 0/5 in SSM, 2/4 (50%) in ASM and 3/13 (23%) in SM-AHN, (p < 0.001). Hymenoptera venom-induced anaphylaxis occurred exclusively in indolent forms (pre-SM, BMM, and ISM) while drug-induced anaphylaxis was observed in both ISM and advanced SM subtypes. Idiopathic anaphylaxis was more evenly distributed across all SM subtypes, (p < 0.001). The presence of cutaneous lesions was associated with a lower risk of anaphylaxis: 10/114 (8.8%) vs. 19/48 (39.6%) without skin involvement (p < 0.001), with a confirmed protective effect in both ISM and pre-SM. Male sex was identified as an additional risk factor, (p = 0.03). A history of Hymenoptera sting was associated with a higher risk of Hymenoptera venom anaphylaxis: 15/113 (13%) vs. no reactions to the first sting in 47 patients, (p = 0.011).

Conclusion: Anaphylaxis is a relevant issue not only in acknowledged variants of SM, but also in pre-diagnostic forms. Idiopathic anaphylaxis may occur across different subtypes. Hymenoptera venom is the main trigger in indolent forms, whereas drug-induced reactions predominate in ISM and advanced SM, mainly through IgE-independent mechanisms. The risk of anaphylaxis is higher in pre-SM and ISM without cutaneous involvement, particularly in case of Hymenoptera venom sensitization. Our results highlight the need for allergological risk assessment and close monitoring especially in patients without skin lesions or with Hymenoptera venom sensitization.

Introduction: Airway epithelial cells function as the first physical barrier against pathogens and are key regulators of immune responses by producing a wide array of cytokines involved in both innate and adaptive immunity.

Methods: This review summarizes recent advances in our understanding of epithelial-derived cytokines in severe asthma (SA) pathogenesis and highlights promising therapeutic strategies.

Results: Epithelial-derived cytokines can be functionally classified into the following four main groups: alarmins [interleukin [IL]-25, IL-33, thymic stromal lymphopoietin [TSLP]], proinflammatory cytokines (IL-1, IL-6, tumor necrosis factor-α), chemokines (CCL2, CCL5), and antiviral cytokines [interferon (IFN)-α, IFN-β, IFN-λ]. Alarmins are rapidly released in response to epithelial injury and play a pivotal role in initiating immune responses by activating dendritic cells, type 2 innate lymphoid cells, and eosinophils. Proinflammatory cytokines intensify inflammation by promoting immune cell activation and cytokine cascades, while chemokines guide immune cells to sites of injury. Antiviral cytokines enhance epithelial defenses by inducing the expression of antiviral genes. In SA, epithelial-derived cytokines play a central role in initiating and sustaining type 2 (T2) inflammation by activating the IL-4, IL-5, and IL-13 axis, leading to increased eosinophils, elevated serum IgE, and heightened airway hyperresponsiveness. These cytokines are also implicated in non-T2 inflammation, particularly in refractory asthma phenotypes.

Discussion: Growing insights into epithelial cytokines and their complex signaling networks with the airway microenvironment have opened new avenues for developing targeted and personalized treatment in SA.

Background: Symptom control in patients with moderate-to-severe persistent allergic rhinitis (PAR) who remain inadequately controlled on intranasal corticosteroid monotherapy remains challenging, highlighting the urgent need for more effective treatments. This study aimed to determine whether the addition of nasal saline irrigation to a regimen of intranasal corticosteroids and antihistamines can further improve symptoms in patients with moderate-to-severe PAR.

Methods: A multicenter, randomized, open-label, controlled trial was conducted, enrolling 248 eligible patients aged 12 years and above from six clinical centers. They were randomized 1:1 into two groups. The experimental group received nasal saline irrigation combined with azelastine-fluticasone (Aze-Flu) nasal spray, and the control group was treated with azelastine nasal spray and fluticasone nasal spray. The primary outcome was the least-squares-mean (LSmean) change in total nasal symptom score (TNSS) from baseline to four weeks, with secondary outcomes including LSmean change in TNSS from baseline to two weeks, subscores, rhinoscopic scores, visual analogue scale (VAS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores.

Results: Both groups exhibited significant reductions in TNSSs from baseline (p < 0.001). In comparison to the control group, the experimental group exhibited greater LSmean changes in TNSS scores following either two or four weeks of treatment (p < 0.001 at both time points). The experimental group presented more favorable changes in rhinoscopy scores, VAS scores, and RQLQ scores. Both groups showed no substantial differences in adverse events, indicating a comparable safety profile.

Conclusion: Nasal saline irrigation combined with Aze-Flu nasal spray provides additional benefits in managing moderate-to-severe PAR, with good safety and tolerability. This combination therapy could be a valuable option in primary care settings.

Clinical trial registration: http://www.medicalresearch.org.cn, identifier (MR-32-23-044661).

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.