Hereditary angioedema (HAE) is a rare, autosomal dominant, life-threatening disease characterized by recurrent attacks of swelling of the face, upper airway, gastrointestinal tract, limbs, and/or genitalia. Genetic mutations of the SERPING1 gene encoding the C1-inhibitor (C1-INH) plasma protein are associated with HAE-C1INH. HAE is also observed in patients with normal C1-INH (HAE-nC1INH). Icatibant is a selective bradykinin B2 receptor antagonist for treatment of acute attacks of HAE. Here we report safety and effectiveness data from a post-marketing, open-label, multicenter observational study of icatibant conducted in Japan (ClinicalTrials.gov ID: NCT04057131). Patients with HAE in Japan who initiated icatibant between November 2018 and June 2020 were enrolled; surveillance was completed in April 2023. In the Safety Analysis Set (n = 155), most patients were women (n = 116, 74.84%) and HAE types included HAE-C1INH-Type 1 (n = 83, 53.55%), HAE-C1INH-Type 2 (n = 9, 5.81%), unclassified HAE-C1INH (n = 16, 10.32%), and HAE-nC1INH (n = 22, 14.19%). Overall, 19 patients (12.26%) experienced adverse drug reactions (ADRs), most of which were mild in severity (n = 18, 11.61%). The most common ADRs were general disorders and administration site conditions (n = 18, 11.61%). No serious ADRs or ADRs of special interest other than hypersensitivity and injection site reaction were reported. In the Effectiveness Analysis Set (n = 100), 97 patients (97.00%) received 30 mg of icatibant. Among 417 HAE attacks, 234 were treated with icatibant alone and 48 with icatibant plus other. Among attacks treated with icatibant alone, median (interquartile range) time to first symptom relief was 60.0 (30.0-270.0) min, and median time to complete resolution of symptoms was 710.0 (148.5-1440.0) min. In conclusion, in this study of the real-world use of icatibant, no new safety concerns were reported. Icatibant was effective in providing early symptom relief for HAE attacks across a broad spectrum of patients, including patients with HAE-nC1INH, who were not included in previous clinical trials.

Prior evidence suggests that ion channel dysfunction plays a significant role in the pathogenesis of asthma, which provides a theoretical basis for the potential link between chloride homeostasis and asthma. However, epidemiological evidence regarding the association between circulating chloride levels and asthma risk remains limited. To our knowledge, no large-scale cross-sectional study has yet explored this relationship. This study aims to investigate the association between chloride levels and asthma, thereby providing new insights into the pathogenesis of asthma. We analyzed data from the National Health and Nutrition Examination Survey 2007 to 2012, including 8241 participants (1165 asthma cases). Seven machine learning algorithms (eXtreme Gradient Boosting, Random Forest, Light Gradient Boosting Machine, Categorical Boosting, Adaptive Boosting, Gradient Boosting, and logistic regression) were employed to rank feature importance using SHapley Additive exPlanations values, supplemented by least absolute shrinkage and selection operator regression for feature selection. Model performance was evaluated via receiver operating characteristic curves. Key variables were further examined using subgroup analyses and restricted cubic spline regression to assess linear and nonlinear associations while adjusting for confounders (age, sex, body mass index, smoking, socioeconomic status, and occupational exposures). Of the biochemical indicators analyzed, chloride was a stronger predictor of asthma than other conventional biomarkers in both least absolute shrinkage and selection operator and SHapley Additive exPlanations-based logistic regression analyses. Serum chloride was inversely associated with asthma prevalence (adjusted odds ratios = 0.96 per mmol/L, 95% confidence intervals: 0.94-0.98, P < .001). While this relationship was consistent across models, the overall predictive performance was moderate (area under the curve approximately 0.65). These findings suggest a potential statistical association between systemic chloride levels and asthma, though causality cannot be inferred from this cross-sectional design. Among numerous conventional biochemical indicators, serum chloride levels show the most consistent negative correlation with asthma prevalence. However, the effect size is small, the discriminative performance of models incorporating this marker is modest, and the observed association may be confounded by unmeasured factors including dietary patterns, comorbidities, and medication use. The clinical utility and biological mechanism of this association require further research incorporating detailed asthma phenotyping and longitudinal follow-up.

Histamine is a central mediator in immunoglobulin E (IgE)-mediated allergic responses, and diamine oxidase (DAO) contributes to extracellular histamine degradation. Altered histamine metabolism has been proposed as a potential modifier of symptom burden in atopic conditions. However, whether circulating DAO protein concentrations differ in patients with allergic asthma and/or allergic rhinitis remains unclear. This study aimed to compare serum DAO concentrations between patients with allergic asthma and/or allergic rhinitis and healthy controls and to examine their associations with immunological and respiratory parameters. In this cross-sectional study, 141 patients with allergic asthma and/or allergic rhinitis and 78 healthy controls were enrolled between January 1, 2025, and March 1, 2025. Serum DAO protein concentrations were measured using enzyme-linked immunosorbent assay. Additional assessments included total IgE, eosinophil count, eosinophil cationic protein, and spirometric parameters. Statistical analyses comprised group comparisons, Spearman's correlation analysis, and receiver operating characteristic curve analysis. Median serum DAO concentrations were significantly lower in patients with allergic asthma and/or allergic rhinitis than in healthy controls (13.8 U/mL vs 28.2 U/mL; P < .001). DAO levels were not significantly correlated with age, sex, total IgE, eosinophil indices, eosinophil cationic protein, or pulmonary function parameters. Receiver operating characteristic analysis demonstrated good discriminatory performance (area under the curve = 0.84, 95% confidence interval = 0.79-0.89; P < .001). The optimal cut-off value of 22.2 U/mL yielded 80% sensitivity and 87% specificity, although this threshold requires external validation. Circulating DAO protein concentrations were reduced in patients with allergic asthma and/or allergic rhinitis compared with healthy individuals. Given the cross-sectional design and the lack of direct enzymatic activity assessment, the results should be interpreted as hypothesis-generating. Prospective studies are warranted to clarify the clinical relevance of DAO measurement in allergic diseases.

Increasing evidence suggests that oxidative stress plays a key role in the pathogenesis of asthma; however, research on the association of the comprehensive dietary antioxidant index (CDAI) with asthma remains limited. Therefore, this study aims to explore the association between CDAI and asthma. Data from the National Health and Nutrition Examination Survey (NHANES) (2003-2018) were analyzed to examine the association between CDAI, derived from two 24-hour dietary recalls, and asthma, defined by self-reported physician diagnosis. Logistic regression was used to examine the overall association, while restricted cubic spline models were applied to explore potential nonlinear relationships. A total of 35,945 adult participants were included, with 14.2% diagnosed with asthma. In the unadjusted model, higher CDAI levels, particularly within a moderate range, were generally associated with a lower risk of asthma. After adjustment for potential confounders, the highest CDAI quartile showed lower odds of asthma than the lowest quartile; however, this comparison did not reach statistical significance (odds ratio = 0.88, 95% confidence interval: 0.76-1.02; P = .078). Importantly, restricted cubic spline analysis demonstrated a significant nonlinear association between CDAI and asthma (P for nonlinearity <.05), with asthma risk declining at moderate CDAI levels and rising at very high levels. Subgroup analyses showed stronger protective effects among adults aged 40 to 60 years, females, non-Hispanic Blacks, other Hispanic populations, former smokers, and individuals with obesity. Sensitivity analyses indicated that most individual dietary antioxidants exhibited nonlinear associations with asthma, except for vitamin A. CDAI is nonlinearly associated with asthma risk, with moderate levels generally reducing risk, while very high intake may diminish this benefit, highlighting the role of antioxidant-rich diets in asthma prevention. Future prospective cohort studies and mechanistic investigations are warranted to clarify causal relationships and to determine optimal dietary antioxidant intake ranges for asthma prevention.

This study aimed to identify novel biomarkers of atopic dermatitis (AD) and investigate their pathogenic mechanisms. We analyzed 7 AD-related datasets from the gene expression omnibus database and identified overlapping differentially expressed genes through integrated analysis of differential expression and weighted gene co-expression networks. Functional enrichment analysis revealed that these genes were primarily associated with skin development and keratinization. Using the least absolute shrinkage and selection operator and support vector machine recursive feature elimination, we further refined the candidate biomarkers to 6 key genes (betacellulin, C1orf68, cytochrome p450 family 2 subfamily J member 2, family with sequence similarity 234 member B, insulin-like growth factor like family member 2, and whey acidic protein 4-disulfide core domain 12). Immune infiltration analysis using CIBERSORT revealed significant correlations between these hub genes and specific immune cells. Single-cell RNA sequencing analysis revealed that these genes were predominantly expressed in endothelial cells and keratinocytes. Subsequent validation using an independent cohort confirmed distinct expression dysregulation: 5 genes (betacellulin, C1orf68, cytochrome p450 family 2 subfamily J member 2, family with sequence similarity 234 member B, and insulin-like growth factor like family member 2) were downregulated, whereas whey acidic protein 4-disulfide core domain 12 was significantly upregulated in AD samples. These findings not only provide novel mechanistic insights into AD pathogenesis but also identify promising therapeutic targets for future research.

Rosacea and atopic dermatitis (AD) are 2 chronic inflammatory skin diseases. Studies have revealed that patients with rosacea and AD exhibit elevated risks of cardiovascular disease. However, the impact of these conditions on the ventricular structure and function remains to be elucidated. This study employed a two-sample Mendelian randomization (MR) approach, utilizing genetic variants as instrumental variables, to explore the genetic associations between rosacea and AD with alterations in ventricular function (including stroke volume and ejection fraction) and structural ventricular variations (including end-diastolic volume and end-systolic volume). The research design adhered to 3 core assumptions. Primary analyses were performed using the inverse-variance weighted method, complemented by 4 additional MR models and sensitivity analyses to ensure robustness. Additionally, multivariate MR was further integrated to adjust for potential confounders, such as systolic blood pressure and diastolic blood pressure. Genetically predicted AD exhibited a positive association with right ventricular end-systolic volume (odds ratio = 1.3640, 95% confidence interval = 1.0002-1.8601, P = .0498). However, this association was no longer statistically significant after adjusting for systolic blood pressure and diastolic blood pressure. Furthermore, no causal association was observed between rosacea and ventricular parameters (P > .05). Multiple sensitivity analyses confirmed the stability of the findings, with no evidence of horizontal pleiotropy (P > .05). Genetic prediction suggested a potential link between AD and impaired right ventricular function. However, no significant causal associations were identified between rosacea and ventricular structural or functional parameters.

Some authors suggest a link between gut microbiota and allergic diseases; however, the genetically predicted relationship and the role of inflammatory proteins as mediators are still uncertain. Gut microbiota, inflammatory proteins, and 5 types of allergic diseases, namely allergic rhinitis (AR), atopic dermatitis, allergic conjunctivitis, food allergy, and asthma, were identified from large-scale genome-wide association studies summary data. In a 2-sample, bidirectional Mendelian randomization (MR) study, we systematically conducted 2980 primary tests (298 exposures tested bidirectionally against 5 allergic diseases). We used the inverse-variance weighted method as our primary estimator, with a prespecified false discovery rate threshold of q < 0.1 to identify robust associations. We further employed a 2-step MR and multivariable MR approach to test for potential mediation by inflammatory proteins. This study provides evidence of potential genetically predicted associations between specific gut microbiota, inflammatory proteins, and allergic diseases, along with exploratory mechanistic observations regarding mediation. These findings support that host-gut microbiota interactions may play a role in allergic disease susceptibility, although further validation using colocalization and cis-protein Quantitative Trait Locus analyses is required to establish clinical relevance. We identified numerous potential genetically predicted associations between the gut microbiota, inflammatory proteins, and the 5 allergic diseases. Notably, 2 of these associations remained robust after stringent false discovery rate correction and were identified as robust MR-supported associations. Specifically, a 1 standard deviation increase in genetically predicted relative abundance log-ratio of the species Collinsella aerofaciens was associated with a 23.5% higher risk of AR (odds ratio = 1.235, 95% confidence interval = 1.097-1.391, P = 4.83 × 10-4, adjustP = .098). Furthermore, genetically predicted higher levels of the CD40L receptor (CD40) were associated with a reduced risk of asthma (odds ratio = 0.939, 95% confidence interval = 0.906-0.974, P = 7.52 × 10-4, adjustP = .068). In exploratory mediation analyses, Fractalkine (CX3CL1) was found to potentially mediate the genetically predicted association between the genus Flavonifractor and AR (mediated proportion 18.5%; P = .024), and CD40 potentially mediated the genetically predicted association between the species Ruminococcus obeum and asthma (mediated proportion 11.02%; P = .046).

To determine the proportion of children labelled as allergic to amoxicillin who are truly allergic and to assess whether a direct oral amoxicillin challenge, without prior skin testing, is a safe and effective way to remove incorrect allergy labels in low-risk pediatric patients in Northwestern Ontario. We conducted a retrospective review of pediatric patients (6 months-15 years) referred for suspected amoxicillin allergy at two Northwestern Ontario hospitals between 2015 and 2025. Eligible patients underwent oral amoxicillin challenge. Clinical data were summarized descriptively. Of 96 patients, 93 (96.9%) tolerated the oral amoxicillin challenge, while 3 (3.1%) developed mild, delayed rashes. All three had previously reported delayed reactions (5-10 days) after their initial amoxicillin exposure. Two patients developed delayed rashes that were consistent with their previously documented maculopapular reactions, based on EMR documentation and caregiver-reported descriptions.Conclusion: The prevalence of true amoxicillin allergy among low-risk pediatric patients carrying a reported "penicillin allergy" label in our cohort of 96 patients evaluated at our pediatric allergy clinics in Northwestern Ontario was 3.1%. Oral amoxicillin challenge without prior skin testing proved to be a safe and effective approach for delabelling low-risk children. Broader implementation of this strategy could enhance antibiotic stewardship, reduce healthcare-related costs, and improve patient care.

A man in his 20s with a background of severe atopic eczema presented with a 24-hour history of intense pain, redness and blurred vision in his left eye. The day before symptom onset, the patient recalls applying Epimax to above the left eyelid. Examination of the left eye revealed findings consistent with a presentation suggestive of chemical injury, demonstrating a total corneal epithelial defect with associated stromal haze. The patient initially declined topical corticosteroid therapy due to prior complications with steroid-induced dermatitis that had necessitated prolonged hospitalisation. After treatment with intensive lubricant, antibiotic and dexamethasone drops, the patient made a good clinical recovery over 1 week. A modified, time-limited course of steroid drops was prescribed and the patient experienced no recurrence of steroid dermatitis. Healthcare professionals should counsel patients on the risks of periocular application of Epimax and maintain awareness of its potential to cause ocular surface toxicity.

Bifidobacteria are known for their health-promoting effects, particularly in the context of gut microbiota modulation and immune system support. Bifidobacterium animalis subsp. lactis BLa80 is a novel probiotic strain isolated from human breast milk. This article evaluates the immunomodulatory effects of BLa80 on healthy mice through indicators such as cellular immunity, humoral immunity, monocyte-macrophage phagocytic function, natural killer cell activity, and immunoglobulins in serum. Concurrently, animal pathogenicity tests were conducted to complement earlier safety studies of BLa80. The mice were treated with low, middle and high doses (12.5, 25, 75 mg/kg BW; 0.25 × 106, 0.5 × 106, 1.5 × 106 cfu/d) of BLa80 solution for 30 days. Body weight, organ-to-body weight ratio, cellular immune function (delayed-type hypersensitivity and lymphocyte transformation), humoral immune function (antibody-forming cell and serum haemolysin), monocyte-macrophage phagocytic function (monocyte-macrophage carbon clearance, Peritoneal macrophage phagocytosis of chicken red blood cells) and natural killer cell activity were observed and recorded. Additionally, the contents of IgG, IgM and IgA in serum of mice, as well as the concentrations of cAMP and cGMP in the spleen and serum, were detected. Healthy mice were administered a certain dose of BLa80 solution through both intraperitoneal injection (BLa80 Group: 1 × 107 cfu/d) and oral gavage (BLa80 Group: 1 × 108 cfu/d, 5 × Concentrated BLa80: 5 × 108 cfu/d). After the mice consumed the BLa80 solution, their general health condition, body weight, and mortality were observed and recorded daily. Compared with the blank control group, the haemolysis values of the middle and high dose groups were significantly different ( P < 0.05), and the monocyte-macrophage carbon clearance values of each dose group were significantly different ( P < 0.05). The carbon clearance phagocytic index in all three dosage groups was better than that in the blank control group. Additionally, the IgM levels in all three dosage groups were higher than those in the blank control group, with the high-dose group showing a significant difference compared to the blank control group ( P < 0.05). During the 21-day observation period, the test substance had no adverse effects on the general health of the mice, and there was no statistically significant difference in weight and other indicators compared to the control group ( P < 0.05), with no deaths observed among the mice. Based on the 'Testing and Evaluation Methods for Health Food Functions (2023 Version)', it is determined that Bifidobacterium animalis subsp. lactis BLa80 can enhance the immune function of healthy mice. Concurrently, according to the 'Guidelines on Safety Assessment and Evaluation of Microbial Strains Used as Health Food Raw Materials (2020 Edition, Appendix A)', BLa80 is determined to be non-pathogenic to animals.

Neuropathic pain is a disorder that represents a significant clinical challenge, while is refractory to therapeutic interventions. Given that the histamine H3 receptor (H3R) is a promising target for new analgesics, we aimed to determine the effects of a novel H3R antagonist (pKi=8.2), LINS01022 (1-(2,3-dihydrobenzofuran-2-yl)methylpiperazine), in neuropathic pain model (chronic constriction injury). Recognizing the significant impact of sex on chronic pain, all experiments were conducted in male and female mice. We investigated the effects of a single intraperitoneal (i.p.) LINS01022 injections (10, 20, 30 mg/kg) on mechanical (von Frey) and thermal (cold plate, tail flick) stimuli to determine dose-, time-, and sex-dependent analgesic profile. To characterize LINS01022 (20 mg/kg) influence on the metabolism parameters, we conducted behavioral profiling studies using an innovative, high-resolution Promethion Metabolic Cages system. Mechanical and thermal thresholds were also assessed after repeated LINS01022 (20 mg/kg/day) treatment, and the possible participation of spinal glutamine, glutamate and γ-aminobutyric acetic acid, and supraspinal glia activation was determined. Additionally, we investigated the LINS01022 influence on locomotor activity (open-field). LINS01022 reduced hypersensitivity in a dose- and time-dependent manner, with greater efficacy in males, and this analgesic effect was not corelated with changes in neurotransmitters level or glia activation. Importantly, the H3R antagonist did not impair locomotor activity and metabolic parameters. This research provides the first evaluation of LINS01022's analgesic efficacy and its favourable safety profile in neuropathic pain. These results suggest that a novel H3R antagonist is a promising drug candidate and a valuable pharmacological tool for further investigation.