INTRODUCTION:Subcutaneous aeroallergen immunotherapy (SCIT) and venom immunotherapy (VIT) are established disease-modifying treatments, but treatment-related adverse reactions remain an important safety concern. Direct real-world comparisons of these modalities, particularly using injection-level analyses that account for repeated injections within patients, remain limited. This study aimed to compare adverse reactions and documented treatment discontinuation between SCIT and VIT at both the patient and injection levels. METHODS:This retrospective single-center study included 172 adults receiving SCIT (n = 144) or VIT (n = 28) between January 2023 and December 2025. Adverse reactions were evaluated at the patient level and across 2,251 administered injections. Injection-level local and systemic reactions were compared using generalized estimating equation models accounting for repeated injections within patients. RESULTS:At the patient level, local reactions (28.6% vs. 10.4%; p = 0.016) and systemic reactions (21.4% vs. 2.1%; p < 0.001) were more frequent with VIT than with SCIT. Four of the six VIT patients who experienced systemic reactions had a maximum severity grade of 3-4. At the injection level, local reaction frequencies were 95 versus 15 per 1,000 VIT and SCIT injections, respectively (odds ratio (OR) 4.33, 95% CI 1.36-13.76; p = 0.013), while systemic reaction frequencies were 95 versus 3 per 1,000 injections (OR 31.47, 95% CI 7.00-141.50; p < 0.001). Documented treatment discontinuation was numerically less frequent with VIT than with SCIT (3.6% vs. 13.9%), although the difference was not statistically significant (p = 0.205). Sensitization pattern was not associated with adverse reactions, and no exploratory biomarker association remained statistically significant after correction for multiple comparisons. CONCLUSION:VIT was associated with more frequent local and systemic reactions than SCIT, and higher-grade systemic reactions were observed among VIT recipients. Treatment persistence was numerically higher with VIT, although documented discontinuation did not differ significantly between modalities. Injection-level analyses complemented patient-level reporting by capturing repeated reaction episodes relative to treatment exposure.
BACKGROUND:Penicillin allergy labels are common and frequently inaccurate, leading to suboptimal antibiotic use. The PENFAST clinical decision rule has been validated to identify patients at low risk of true penicillin allergy; however, its performance may be limited in allergist-led settings, where specific low-risk clinical phenotypes are prevalent. OBJECTIVE:To develop and evaluate PENFAST-A, a modified version of the PENFAST score incorporating common allergy phenotypes observed in specialist practice, and to assess its diagnostic performance in a real-world cohort. METHODS:We conducted a retrospective study in a tertiary Allergy Unit including patients with a reported β-lactam allergy who underwent a standardized diagnostic workup. PENFAST and PENFAST-A scores were calculated retrospectively. Diagnostic performance metrics, including sensitivity, specificity, and predictive values, were compared between the two models. RESULTS:In our cohort, PENFAST-A demonstrated higher sensitivity than the original PENFAST score (94.9% vs 81.8%), with a corresponding increase in negative predictive value (97.4% vs 93.5%). PENFAST-A reclassified a larger proportion of patients into higher-risk categories, resulting in lower specificity (44.2%). Importantly, no patients with a PENFAST-A score <2 had a confirmed β-lactam allergy, supporting its safety for identifying low-risk patients suitable for delabeling without further testing. CONCLUSIONS:PENFAST-A improves the identification of low-risk patients with reported β-lactam allergy in allergist-led settings by incorporating clinically relevant phenotypes. This modified score may serve as a practical screening tool to guide safe delabeling and direct oral challenge in specialized clinical practice.
BACKGROUND:Drug provocation testing (DPT) is the gold standard for diagnosing drug hypersensitivity, but its implementation remains limited by heterogeneous protocols and concerns regarding safety. The clinical performance of simplified DPT protocols across the recently proposed EAACI/ENDA 2024 risk categories is unknown. OBJECTIVE:To evaluate the clinical performance of a standardized placebo-free two-step equal-dose DPT protocol after retrospective application of the EAACI/ENDA 2024 risk stratification in a historical real-world cohort. METHODS:We conducted a retrospective descriptive study including consecutive patients with suspected hypersensitivity to antibiotics or selective NSAIDs (nonsteroidal anti-inflammatory drugs) who underwent culprit-drug DPT between January 2017 and November 2023 at a tertiary allergy center. All patients had originally been managed using the same placebo-free two-step equal-dose DPT protocol before publication of the EAACI/ENDA 2024 recommendations. After data collection, index reactions were retrospectively classified according to the EAACI/ENDA 2024 framework. The primary outcome was DPT positivity overall and according to retrospectively assigned risk categories. RESULTS:A total of 161 patients were included. Overall, 17 DPTs were positive (10.6%; 95% CI, 6.7-16.3%). Positivity differed significantly across retrospectively assigned risk categories (p < 0.0001): 5.4% in the low-risk group, 9.1% in the low-to-intermediate-risk group, 6.0% in the intermediate-risk group, and 61.5% in the high-risk group. Among patients reclassified as high risk because of isolated early urticaria and/or angioedema, 7 of 8 (87.5%) had a positive DPT. Two patients (1.2%) developed anaphylaxis, both after the first dose; one had been retrospectively classified as high risk and the other as intermediate risk. CONCLUSIONS:In this historical cohort, retrospective application of the EAACI/ENDA 2024 framework identified marked differences in DPT positivity despite all patients undergoing the same standardized placebo-free two-step equal-dose protocol. These findings support the feasibility of this protocol in routine clinical practice while highlighting the clinical relevance of early urticaria and/or angioedema within the current EAACI/ENDA risk stratification and the need for prospective validation.
BACKGROUND:Oral food challenge test (OFC) is essential for the diagnosis and management of wheat allergy. In individuals considered to be at low risk, OFCs may be performed even in general clinical settings. Although ω-5 gliadin-specific IgE (sIgE) is associated with immediate allergic reactions to wheat, the safety of OFCs in cases with low ω-5 gliadin-sIgE levels has not been well investigated. We evaluated the safety of wheat OFCs in cases with ω-5 gliadin-sIgE levels < 3.5 kU/L. METHODS:We retrospectively analyzed wheat OFCs performed at two hospitals between 2017 and 2021. 337 cases with ω-5 gliadin-sIgE levels < 3.5 kU/L were included. These cases were further classified according to Wheat-sIgE levels: Wheat-sIgE < 3.5 kU/L (Low Wheat-sIgE [LW-sIgE] group; 115 cases) vs ≥ 3.5 kU/L (High Wheat-sIgE [HW-sIgE] group; 222 cases). The OFC-positive rate and its association with the challenge dose were evaluated. RESULTS:A total of 337 cases with ω-5 gliadin-sIgE levels (< 3.5 kU/L) were included. The OFC-positive rate was comparable between the LW-sIgE group (22.6%) and the HW-sIgE group (23.0%). Anaphylaxis occurred in six cases (1.8%); however, none required intramuscular adrenaline administration. In low-dose OFC (≤ 2 g of udon; ≤ 52 mg of wheat protein), more than 90% of cases in both groups were negative. Cases with positive low-dose OFC results had higher ω-5 gliadin-sIgE levels and a higher rate of complete wheat elimination. CONCLUSION:Wheat OFCs can be performed relatively safely in cases with low ω-5 gliadin-sIgE levels. Initiating OFCs at a low dose may improve their safety.
INTRODUCTION:Mycoplasma pneumoniae pneumonia (MPP) represents the most common cause of community-acquired pneumonia in Chinese children, where delayed pathogen detection and inadequate severity assessment frequently result in delayed intervention. Given that lncRNA ACTA2-AS1 is markedly downregulated in MP-infected epithelial cells and bioinformatics predicted to sponge miR-2278, this study investigated the molecular mechanism by which lncRNA ACTA2-AS1 regulates inflammatory response and epithelial barrier function via miR-2278, aiming to identify novel targets for precise MPP treatment. METHODS:ACTA2-AS1 and miR-2278 expression was quantified in serum and bronchoalveolar lavage fluid (BALF) from 152 MPP children and 106 healthy controls. The clinical utility of ACTA2-AS1 for diagnosing pediatric MPP and predicting severe disease was assessed. BEAS-2B and THP-1 cells were stimulated with lipid-associated membrane protein (LAMP) to establish MPP cell model. The targeting relationship and regulatory effects between ACTA2-AS1 and miR-2278 were validated by co-transfection and dual-luciferase reporter assays. RESULTS:ACTA2-AS1 was significantly lower in serum and BALF from MPP children, whereas miR-2278 was markedly higher, and the two were negatively correlated. ACTA2-AS1 demonstrated strong diagnostic performance for MPP. Low serum ACTA2-AS1 was associated with abnormal clinical indicators and independently predicted severe MPP. ACTA2-AS1 was confirmed to directly target miR-2278. In vitro, ACTA2-AS1 overexpression enhanced epithelial barrier repair and attenuated inflammation in BEAS-2B and THP-1 cells, while miR-2278 overexpression reversed these protective effects. CONCLUSION:ACTA2-AS1 represents a potential biomarker for diagnosing and stratifying MPP children. By sponging miR-2278, it preserves epithelial barrier integrity and modulates immune-inflammatory homeostasis, thereby attenuating MPP progression.
BACKGROUND:House dust mites (HDM) are the most prevalent indoor allergens and a major contributor to allergic diseases worldwide. Effective monitoring of HDM allergen exposure is critical for clinical management and environmental control, yet the current gold-standard ELISA method is costly, complex, and unsuitable for self-testing. OBJECTIVE:To develop and validate a rapid, semi-quantitative test kit for dust mite allergens that enables patient self-assessment and localized evaluation of environmental control measures. METHODS:A total of 80 dust samples were collected from 59 homes of HDM-allergic patients in Guangzhou, China. Samples were analyzed using both ELISA and a novel colorimetric guanine-based rapid test. Allergen concentrations of Der 1 were quantified, and correlation, consistency, sensitivity, and specificity of the rapid test were assessed against ELISA results. Patients and researchers independently performed and interpreted the test to assess inter-rater reliability. RESULTS:The rapid test strongly correlated with ELISA for total group I allergen concentrations (r = 0.83, P < 0.0001). All samples exceeding 10 μg/g were accurately identified (sensitivity = 100%, specificity = 79.1%). Classification agreement with ELISA was moderate (weighted κ = 0.557), and inter-rater agreement between patients and researchers was strong (weighted κ = 0.878). The test required only 20 mg of dust and delivered results within 5 minutes. CONCLUSION:The rapid test kit demonstrated high accuracy and reliability in identifying moderate- and high-level HDM allergen exposure. Its low cost, ease of use, and strong agreement with ELISA supports its utility in routine self-monitoring and localized environmental assessments, bridging a critical gap between clinical recommendations and real-world implementation.
OBJECTIVES:To estimate the pooled prevalence of objective eustachian tube dysfunction (ETD) or middle-ear dysfunction in allergic rhinitis (AR), to explore how this prevalence varies by operational definition and sample size, and to identify the main clinically relevant limitations that affect interpretation of the available evidence. METHODS:We searched PubMed, Embase, Scopus, Web of Science, Google Scholar, publisher platforms, and reference lists to March 2026 for original studies reporting objective ETD, abnormal tympanometry, middle-ear dysfunction, or otitis media with effusion (OME)-compatible dysfunction in AR. Manual reference tracing, duplicate removal, and independent screening by two reviewers were performed. Six studies with extractable numerator-and-denominator data were synthesized using a random-effects meta-analysis of proportions. RESULTS:The six studies included 923 AR participants. Prevalence estimates ranged from 18.0% to 49.2%. The pooled prevalence was 0.36 (95% confidence interval [CI], 0.25-0.49), with substantial heterogeneity (I² = 81.8%). Outcome-definition subgrouping indicated that estimates differed according to whether dysfunction was assessed by ETD-specific tests, tympanometric OME criteria, abnormal tympanograms, or broader middle-ear disease definitions. Sensitivity analysis did not identify a single influential study. CONCLUSION:Preliminary evidence suggests that objective ETD or middle-ear dysfunction is frequently reported in AR and may affect a clinically meaningful subset of assessed patients. However, the evidence base is small, geographically limited, and methodologically heterogeneous; therefore, the pooled estimate should be interpreted cautiously and confirmed by larger multicenter studies using standardized diagnostic criteria. Selective otologic and tympanometric assessment remains justified in AR patients with persistent nasal obstruction, severe symptoms, hearing complaints, or recurrent OME-like episodes.
INTRODUCTION:Chronic spontaneous urticaria (CSU) can be particularly burdensome for older adults. Real-world evidence regarding the use of omalizumab in this growing demographic remains limited. This study evaluated the effectiveness and safety of domestic Omalizumab for Injection (Enyitan®) in elderly patients with CSU under real-world conditions. METHODS:In this retrospective, single-center, observational cohort study, 71 CSU patients aged ≥65 years with moderate-to-severe disease activity were treated with omalizumab (Enyitan®, 300 mg every 4 weeks) between January and February 2025. Primary outcome was the proportion of patients achieving well-controlled disease (UAS7 ≤ 6) at Week 24. Secondary outcomes included changes in UAS7, Itch Severity Score (ISS), Wheal Score (WS), Urticaria Control Test (UCT), and Dermatology Life Quality Index (DLQI). Safety was assessed via adverse events (AEs) and laboratory parameters. RESULTS:Of 62 patients completing the 24-week study, 88.7% achieved a UAS7 ≤ 6. ISS and WS scores similarly improved (p<0.001). UCT scores increased from 5.2±2.1 to 14.8±3.2, and DLQI scores decreased from 15.6±4.3 to 3.1±2.8 (both p<0.001). Treatment was well-tolerated; only mild, transient AEs were reported, predominantly injection-site reactions (9.7%) and headache (3.2%). CONCLUSION:Domestic omalizumab (Enyitan®) demonstrated rapid, sustained effectiveness and a favorable safety profile in elderly patients with H1-antihistamine-resistant CSU, supporting its use as a first-line biologic therapy in this vulnerable population.
BACKGROUND/OBJECTIVES:The ongoing Ukrainian conflict constitutes a grave humanitarian emergency, with refugees facing significant language and cultural barriers hindering access to health care. The UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) initiative was launched to support Ukrainian refugees through the MASK-air® and CRUSE® apps. The UCRAID@Apulia study aimed to assess the feasibility of UCRAID via a joint medical and socio-linguistic approach. METHODS:A multidisciplinary, cross-sectional study was conducted from July 2023 to June 2024 involving adult Ukrainian refugees with asthma, allergic rhinitis, atopic dermatitis or chronic urticaria recruited via a network of Ukrainian associations and institutional partners. Participants were introduced to MASK-air® and CRUSE® and administered a 20-item questionnaire assessing sociocultural and healthcare needs, linguistic barriers, comorbidities (Charlson Comorbidity Index) and health-related quality of life (EQ-5D-5L). RESULTS:Among the 381 eligible patients being offered participation, 53 (13.91%) accepted enrolment. While literacy and occupation levels were high, issues with accommodation and bureaucracy were often cited. Mistrust and fear of reprisals emerged as key deterrents to participation. Chronic urticaria and atopic dermatitis were the prevalent allergic conditions. EQ-5D-5L showed good overall health but was characterized by anxiety/depression (32.1%) and pain (17%). Despite significant language barriers in both Italian and English, all participants successfully used both applications. At a 30-day follow-up, 71% reported at least 5 days of consecutive usage with high satisfaction. CONCLUSIONS:Despite low enrolment driven by fear and distrust, mHealth tools like MASK-air® and CRUSE® proved feasible and well-received, with trust building and long-term support being key elements for wider future adoption.
INTRODUCTION:Fruit and vegetable allergies in childhood present with heterogeneous clinical features and are often influenced by cross-reactivity with aeroallergens. Despite their growing clinical importance, data on diagnostic accuracy and clinical phenotypes remain limited, particularly in regions where component-resolved diagnostic tests are not available. METHODS:This five-year retrospective cohort study evaluated children aged 0-18 years who presented to a tertiary pediatric allergy clinic between 2020 and 2025 with suspected fruit or vegetable allergy. Clinical history, skin prick test (SPT), specific IgE (sIgE), prick-by-prick test results, aeroallergen sensitization profiles, laboratory parameters, and oral food challenge (OFC) outcomes were reviewed. Only patients whose diagnoses were confirmed by OFC were included in the study. RESULTS:A total of 19 OFC-confirmed cases were included. The median age at symptom onset was 41.5 months. Based on the total number of triggering foods (n = 23), the most common allergens were kiwi (17.4%) and strawberry (17.4%), while urticaria was the most frequent clinical manifestation at initial presentation (52.2%). Reaction types did not significantly differ across different allergen subgroups; however, patients with oral allergy syndrome had a significantly higher age of symptom onset (p=0.002). Sensitization tests demonstrated limited diagnostic performance for predicting OFC-confirmed fruit and vegetable allergy, with a sensitivity of 47.4%, specificity of 80.0%, positive predictive value of 52.9%, negative predictive value of 76.2%, and an overall diagnostic accuracy of 69.5%. CONCLUSIONS:Fruit and vegetable allergies in childhood are generally mild but may exhibit considerable clinical variability. Skin prick test and serum specific IgE tests alone are insufficient for diagnosis, and OFC remains the gold standard for diagnostic confirmation. Larger, multi-center studies are needed to better characterize sensitization patterns and to establish reliable diagnostic cut-off values.
BACKGROUND AND OBJECTIVE:Epithelial barrier dysfunction is an early feature of pediatric rhinitis, but the upstream epithelial events that initiate this process remain incompletely defined. Because lipid remodeling and epithelial-derived alarmins may interact during type 2 inflammation, this study examined whether acid sphingomyelinase (ASM)-ceramide signaling is associated with thymic stromal lymphopoietin (TSLP) release and barrier impairment in a pediatric rhinitis-related nasal epithelial model. METHODS:Primary human nasal epithelial cells were stimulated with interleukin-4 (IL-4)/interleukin-13 (IL-13) (10 ng/mL each, 24 h) to model a type 2 inflammatory epithelial milieu. ARC39 was used to inhibit ASM, and siRNA was used to knock down TSLP. TSLP was quantified by enzyme-linked immunosorbent assay (ELISA); barrier function was assessed by FITC-dextran permeability and ZO-1 immunofluorescence; ceramide levels were measured using a commercial kit; and sphingomyelin phosphodiesterase 1 (SMPD1) expression was evaluated by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS:IL-4/IL-13 stimulation increased TSLP release and impaired epithelial barrier integrity (P < 0.001). ARC39 reduced ceramide levels and decreased TSLP output (P < 0.001) in a concentration-dependent manner, with an evident effect at approximately 5 µM, whereas SMPD1 expression remained largely unchanged. TSLP knockdown improved barrier function indicators (P < 0.05), and combined ARC39 treatment did not produce an additional effect beyond TSLP knockdown. CONCLUSION:ASM-ceramide axis modulation was associated with TSLP release and epithelial barrier dysfunction in this in vitro model. These findings suggest a possible link among sphingolipid remodeling, epithelial alarmin responses, and barrier injury, but further mechanistic and clinical validation is needed.
Introduction: Allergic rhinitis (AR) represents a prevalent chronic inflammatory disease affecting the nasal mucosa, yet effective diagnostic biomarkers and therapeutic targets remain elusive. This investigation sought to examine plasma miR-337-5p expression and its diagnostic utility in AR patients, additionally dissecting its role and molecular mechanism during IL-13-induced nasal epithelial inflammatory injury. Methods: RT-qPCR quantified plasma miR-337-5p in 100 AR patients versus 100 controls, with ROC curve analysis establishing diagnostic value. For in vitro experiments, IL-13 exposure generated a Th2-type inflammation model in HNEpC cells. Post-transfection with miR-337-5p mimic or inhibitor, assessments encompassed cell viability, apoptosis, inflammatory cytokines (IL-6, IL-8), plus oxidative stress markers (SOD, MDA). Bioinformatics predicted target genes, subsequently validated through dual-luciferase reporter assay. Rescue experiments further clarified WNK1 involvement. Results: AR patients exhibited significantly higher plasma miR-337-5p concentrations, which correlated positively with TNSS scores and eosinophil counts. The resulting ROC curve demonstrated an AUC of 0.840, reflecting good diagnostic value. Within IL-13-stimulated HNEpC cells, miR-337-5p overexpression worsened cell injury, apoptosis, inflammatory cytokine release, and oxidative stress, while miR-337-5p inhibition conferred protection. Bioinformatics, coupled with dual-luciferase reporter assay, identified WNK1 as a direct miR-337-5p target. WNK1 expression was reduced in AR patients and showed a negative correlation with miR-337-5p levels. WNK1 knockdown partially abrogated the protective impact of miR-337-5p inhibition. Conclusions: Increased plasma miR-337-5p holds potential as a diagnostic biomarker for AR. Through WNK1 targeting, miR-337-5p aggravates IL-13-induced nasal epithelial inflammatory injury, implicating its contribution to AR pathogenesis.
INTRODUCTION:Severe pneumonia in children is a critical cause of childhood mortality. miR-766-3p is a known anti-inflammatory factor. The aim of our study is to investigate the clinical value of miR-766-3p and the molecular mechanisms by which miR-766-3p regulates severe pneumonia. METHODS:The relative levels of miR-766-3p in participants' plasma were detected by quantitative real-time PCR (RT-qPCR). The diagnostic performance and prognostic value of miR-766-3p were assessed using receiver operating characteristic (ROC) curves, Kaplan-Meier curves, and Cox regression models. In vitro, lipopolysaccharide (LPS) was employed to mimic the pneumonia environment. Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. The levels of inflammatory factor were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA). RESULTS:The levels of miR-766-3p were decreased by 0.36-fold in children with severe pneumonia, and it effectively distinguished between children with severe pneumonia and healthy children. In pediatric patients, the accumulative survival rate was lower in low miR-766-3p expression group (average miR-766-3p level ≤ 0.65) compared to high expression group (average miR-766-3p level > 0.65). Multivariable Cox proportional-hazards regression model analysis indicated that miR-766-3p was an independent risk factor for poor patient outcomes. Moreover, miR-766-3p mimic attenuated the inhibition of cell viability and interleukin-10 (IL-10) levels as well as the promotion of levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) caused by LPS. These effects were further abolished by Mucin 19 (MUC19) upregulation. CONCLUSION:miR-766-3p has potential as a diagnostic and prognostic biomarker. Mechanistically, miR-766-3p alleviates LPS-induced inflammation in MRC-5 cells by modulating MUC19.
INTRODUCTION:Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus driven by type-2 inflammation. Dupilumab, a monoclonal antibody targeting the IL-4Ra subunit shared by the IL-4 and IL-13 receptor complexes, has recently emerged as a targeted biologic therapy for EoE. This systematic review evaluates the evidence for dupilumab in EoE across pediatric and adult populations, focusing on efficacy, safety, and symptom improvement. METHODS:MEDLINE and Embase were searched from inception to June 30, 2025. Eligible studies included randomized controlled trials (RCTs), cohort studies, case-control studies, and case reports reporting dupilumab use in confirmed EoE. Study screening and quality assessment were performed in duplicate. Data on demographics, atopic comorbidities, dosing regimens, histologic outcomes, symptom improvement, and adverse events were extracted and summarized descriptively. RESULTS:Nineteen studies (three randomized trials, nine cohorts, seven case reports) comprising 760 patients were included. Dupilumab was most commonly initiated following inadequate response or intolerance to proton pump inhibitors, swallowed corticosteroids, or dietary therapy. Across RCTs, histologic remission (≤15 eos/hpf) occurred in 60%-84% of dupilumab-treated patients versus <10% of placebo-treated patients. Cohort studies demonstrated comparable rates (68%-93%), with pediatric cohorts showing particularly robust responses (up to 90% remission). Meta-analysis using a random-effects logit model demonstrated a pooled histologic remission rate of 75.5% (95% CI: 67.4-82.1%) and a symptom improvement rate of 84.1% (95% CI: 77.8-88.9%). CONCLUSIONS:Dupilumab represents a promising therapeutic option, particularly for patients with inadequate response to proton pump inhibitor therapy, including those unable to maintain dietary restrictions. Future research should focus on predictors of response, durability of remission beyond 1 year, and comparative effectiveness relative to other therapies.
BACKGROUND:Some food and pollen allergic reactions, including anaphylaxis disproportionate to IgE titres, are not fully explained by IgE-mediated mechanisms. MRGPRX2, a polyspecific sensor of cationic ligands, mediates IgE-independent mast-cell degranulation and requires a salt bridge to aspartate D184. Whether protein allergens can adopt D184-engaging poses is unknown. METHODS:Eleven peach, cedar pollen, peanut, birch and yam allergens were docked against the experimental MRGPRX2 cryo-EM structure (PDB 7VV6) with HADDOCK3 under three protocols. Three agonists calibrated a D184 salt-bridge consistency threshold, four size-matched non-allergen proteins probed the determinants of engagement, and in silico mutagenesis tested D184 dependence. RESULTS:Five allergens met a HIGH-consistency threshold (≥2/3): Pru p 7, Cry j 7, Cry j 1, Pru p 3 and Ara h 6; Ara h 2 was MODERATE, and mature-chain Cry j 2 did not engage D184. Engagement was charge-driven yet determined by a single accessible residue rather than net charge: HADDOCK score tracked the electrostatic term (ρ = 0.84) but not molecular weight (ρ = 0.36), the net-acidic Ara h 6 engaged through ARG4 while the net-neutral ubiquitin did not, and D184A abolished the salt bridge. Accordingly, size-matched non-allergen proteins presenting a surface lysine/arginine (ribonuclease A, carbonic anhydrase II) also formed genuine D184 salt bridges, whereas the acidic maltose-binding protein did not. CONCLUSIONS:Allergens presenting an accessible surface lysine or arginine can form the MRGPRX2 D184 salt bridge in agonist-like geometry, but engagement is governed by local cationic-residue accessibility rather than net charge or allergen identity - non-allergen proteins engage equally - so docking alone establishes neither specificity nor binding affinity, receptor activation or clinical relevance. We propose a charge-based, exposure-gated hypothesis for experimental and clinical validation.
INTRODUCTION:This study aimed to investigate the association between serum LGALS3BP levels and acute exacerbations, airway inflammation, lung function, and airway remodeling in children with asthma. METHODS:A total of 93 children with asthma (57 with stable condition and 36 with acute exacerbation) and 100 healthy controls were enrolled. Pulmonary function tests, markers of allergic and airway inflammation, pro-inflammatory cytokines, and airway remodeling-related biomarkers were also assessed. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the independent factors associated with and the diagnostic performance for acute exacerbations. RESULTS:Serum LGALS3BP levels were significantly higher in children with asthma than in healthy controls and were further elevated during acute exacerbations (all p < 0.001). Increased LGALS3BP levels were independently associated with a higher risk of acute exacerbations (odds ratio = 1.073, 95% confidence interval: 1.003-1.147; p = 0.040). ROC analysis demonstrated strong discriminatory performance for identifying exacerbations (AUC = 0.910), with 76.3% sensitivity and 91.0% specificity. Serum LGALS3BP levels showed significant moderate negative correlations with lung function parameters and positive correlations with eosinophil counts, total immunoglobulin E, fractional exhaled nitric oxide, pro-inflammatory cytokines, and airway remodeling markers, including transforming growth factor-β1, matrix metalloproteinases-2, matrix metalloproteinases-9, and stromal cell-derived factor-1α (all p < 0.05). CONCLUSION:Elevated serum LGALS3BP levels are closely associated with acute exacerbations, airway inflammation, impaired lung function, and airway remodeling in pediatric asthma. These findings suggest that LGALS3BP may serve as a promising noninvasive biomarker for disease activity and exacerbation risk.
INTRODUCTION:Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of drug hypersensitivity reactions, yet comparative real-world data on drug-specific anaphylaxis reporting remain limited. This study aimed to evaluate reporting patterns and disproportionality signals of NSAID-associated anaphylaxis in the FDA Adverse Event Reporting System (FAERS), compare severe outcomes across individual NSAIDs, and describe the indication context of these reports. METHODS:In this cross-sectional pharmacovigilance study, FAERS reports from 2015Q1 to 2025Q2 were analyzed. Five NSAIDs were included: ibuprofen, diclofenac, naproxen, celecoxib, and meloxicam. Anaphylaxis was defined by 4 MedDRA preferred terms and restricted to reports listing the target NSAID as the primary suspect drug. Disproportionality was assessed using reporting odds ratio, proportional reporting ratio, empirical Bayes geometric mean, and information component. RESULTS:Total adverse event reports were 51,837 for ibuprofen, 43,979 for diclofenac, 27,043 for naproxen, 13,085 for celecoxib, and 2,591 for meloxicam. Corresponding anaphylaxis reports were 938 (1.81%), 919 (2.09%), 320 (1.18%), 178 (1.36%), and 38 (1.47%). All 5 NSAIDs showed disproportionality signals versus all other drugs. Female predominance was observed across agents. Most reports involved adults aged 18-64 years, except meloxicam, which was concentrated in those aged 65-85 years. Diclofenac reports mainly originated outside the USA, whereas naproxen had the highest proportion of US reports. Among submitted FAERS reports of NSAID-associated anaphylaxis, the reported proportion of DE/LT outcomes varied across the 5 NSAIDs. Pain and back pain were common indications, but the broader indication patterns showed drug-specific features. CONCLUSION:NSAIDs showed consistent disproportionality signals for anaphylaxis in FAERS, with observable heterogeneity in reporting patterns across individual agents.
Introduction: Sjogren’s syndrome (SS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and a T1/T3-skewed inflammation. Chronic rhinosinusitis (CRS) is more prevalent in SS, most likely due to the specific cytokine milieu, and the loss of secretory glands and secretion associated antimicrobials. However, the impact of SS on CRS immunopathology and symptomatology is unclear. This study evaluated whether CRS in SS patients exhibits a distinct clinical profile compared to CRS alone. Methods: In this retrospective study, 14 patients with co-morbid SS and CRS were compared to 90 CRS patients without rheumatologic or other comorbid systemic disease. CRS severity was assessed using the Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay Score (LMS), Lund-Kennedy Score (LKS), and T2 inflammatory markers (IgE, absolute eosinophil count, and nasal polyp presence). Results: Demographics were similar between groups. Objective disease burden was greatest in CRS with nasal polyps, with higher LMS (p < 0.001) and LKS (p < 0.001) than the other groups. Despite this, SS patients reported the highest SNOT-22 total scores (p = 0.027). SS showed significantly higher scores in several domains, including nasal obstruction (p < 0.001), ear fullness (p < 0.001), reduced concentration (p < 0.001), frustration or irritability (p = 0.022), and fatigue (p = 0.044), with trends for need to blow the nose (p = 0.051), thick nasal discharge (p = 0.073), facial pain or pressure (p = 0.063), waking up tired (p = 0.096), and reduced productivity (p = 0.052). Conclusions: SS appears to confer a distinct CRS phenotype marked by heightened symptom burden not reflected by conventional disease metrics. This discrepancy may reflect neuroinflammatory amplification driven by SS’s T1/T3 cytokine profile. These findings highlight the need for symptom-focused, multidisciplinary care in this population.
INTRODUCTION:The 2020 Protection of Students with Life-Threatening Allergies Act, obligates schools across Alberta, Canada to hold a common use stock of at least one epinephrine autoinjector (EAI) and to maintain a protocol for the prevention and management of anaphylaxis. Herein, we assessed the effectiveness of this policy by comparing pre-hospital EAI use before and after implementation of the act. METHODS:The Cross-Canada Anaphylaxis Registry (C-CARE) enrolls patients presenting to a participating emergency department with anaphylaxis defined as the involvement of ≥2 systems and/or hypotension. Specific to this project, we extracted data on pediatric patients recruited from the Stollery Children's Hospital in Edmonton, Alberta from 2016 to 2024. Data were collected on demographics, comorbidities, symptomatology, pre- and intra-hospital management, and outcome of anaphylaxis by standardized chart review. Multivariable logistic regression was used to assess pre-hospital EAI use for cases occurring at school before versus after the enactment of the Act on January 1, 2020. Evaluating pre-hospital EAI use in Quebec and Ontario and antihistamine use pre versus post act in Alberta were used as negative controls. RESULT:Of the 59 cases of in-school anaphylaxis identified over the study period, 52.5% occurred post-act. The median age was 13.0 years (IQR = 9.5-15.8) and 40.7% were male. EAI use in schools was greater post-act versus pre-act (64.5% versus 35.7%, aOR = 3.82, 95% confidence interval [CI] = 1.24-11.7). There was no difference in pre-hospital EAI use pre versus post 2020 in Quebec and Ontario, that did not use the act (aOR = 0.72, 95% CI = 0.31-1.70). There was no difference in pre-hospital antihistamine use pre versus post act (aOR = 0.31, 95% CI = 0.07-1.41). CONCLUSION:Implementation of the provincial policy was associated with an increase in pre-hospital EAI use in cases of pediatric anaphylaxis occurring at school. These preliminary results support the effectiveness of policy interventions for anaphylaxis management.
INTRODUCTION:Hereditary angioedema (HAE) has a heterogeneous clinical presentation, and symptoms can vary in severity and frequency. The aim of this post hoc analysis was to describe the burden of disease in patients with HAE according to the impact of the disease and patient characteristics. METHODS:A cross-sectional, web-based survey in 13 countries was conducted to assess the burden of disease in patients aged ≥18 years with HAE. This post hoc analysis assessed disease control, HRQoL, anxiety, depression, and work productivity by subgroups defined by sex, perception of disease control and HRQoL impairment. Patient-reported outcomes included the Angioedema Quality of Life (AE-QoL), Angioedema Control Test (AECT), Hospital Anxiety and Depression Scale (HADS), and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaires. Descriptive statistics were used to describe the results by subgroups. RESULTS:Of 260 respondents (189 female; 71 male) who completed the survey, 195/260 (75.0%) perceived their HAE was poorly controlled (AECT score <10) and 137/260 (52.7%) had moderate-to-large HRQoL impairment (AE-QoL score ≥39). Relative to male respondents, females reported higher HRQoL impairment (AE-QoL total score mean ± SD 46.5 ± 23.3 vs. 33.3 ± 20.1), a perception of more poorly controlled disease (AECT score 7.1 ± 3.0 vs. 8.3 ± 3.0), and a higher proportion reported moderate or severe anxiety (33.9% vs. 7.0%) and depression (12.2% vs. 5.6%) according to the HADS. Respondents who perceived their HAE was poorly controlled had a higher number of HAE attacks in the last 6 months, reported greater HRQoL impairment, higher scores on HADS anxiety and depression subscales, and greater WPAI:GH work and activity impairment than those who perceived their HAE to be well controlled (AECT ≥10). Similarly, patients reporting moderate-to-large HRQoL impairment reported more HAE attacks in the last 6 months, higher scores on HADS anxiety and depression subscales, and greater WPAI:GH work and activity impairment than those with an AE-QoL score <39. CONCLUSION:In this post hoc analysis, the burden of HAE was consistently higher in females than males, in respondents who reported their disease to be poorly controlled versus well-controlled, and in those with moderate-to-large versus minimal HRQoL impairment. Findings support the use of patient-reported outcomes to assess burden of disease in routine clinical practice to understand the broader burden of disease beyond metrics such as attack rate and to consider individual circumstances and experiences.
