Allergy, Asthma & Immunology Research最新文献

Purpose: The sino-nasal outcome test (SNOT-22) is a patient-reported outcome measure for chronic rhinosinusitis (CRS), assessing treatment response after 6 months of biologic uses in patients with severe CRS. We investigated score changes in each domain of SNOT-22 with biologics in patients with severe asthma.

Methods: A total of 229 patients with severe asthma and nasal symptoms were enrolled from a prospective, observational, multicenter cohort study. After 6 months of treatment with biologics or conventional GINA Step 4-5 management, SNOT-22 changes were evaluated by analyzing total and rhinological, extranasal rhinological, ear/facial, psychological, and sleep domain scores.

Results: The adjusted odds ratio (OR) of being a responder was significantly higher for dupilumab in the total (OR, 2.29; 95% confidence interval [CI], 1.08-4.87), extranasal rhinological (OR, 2.80; 95% CI, 1.20-6.56), physiologic (OR, 2.23; 95% CI, 1.03-4.83), and sleep dysfunction (OR, 2.50; 95% CI, 1.14-5.47) domain scores of SNOT-22 than those for conventional or anti- interleukin (IL)-5 antibody treatment. After adjusting for the history of CRS diagnosis, dupilumab users had higher ORs for total SNOT-22 (OR, 2.20; 95% CI, 1.02-4.77) and extranasal rhinological (OR, 2.77; 95% CI, 1.16-6.60) scores. When SNOT-22 was plotted by the type of treatment at 0, 1, and 6 months, an overall trend of decreased total/domain scores of SNOT-22 was observed in the biologic-treated group compared to the conventional group, with the most pronounced decrease in dupilumab-treated group.

Conclusions: Dupilumab demonstrates a significant improvement not only in total SNOT-22 scores but also in the extranasal rhinological, physiologic, and sleep dysfunction domain scores compared to conventional or anti-IL-5 treatment in patients with severe asthma and nasal symptoms.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a multifactorial pathophysiology. Although AD has been characterized by a T helper type 2 cell response, the role of the myeloid populations in the pathogenesis of AD remains unclear.

Methods: Peripheral blood mononuclear cells from 48 AD patients and 48 healthy controls were profiled using mass cytometry, primarily focusing on dendritic cells (DCs) and monocytes. Further analysis of a public single-cell RNA sequencing (scRNA-seq) dataset and immunofluorescence staining of lesional skin in AD were conducted for further validation.

Results: The frequency of circulating cDC1 was significantly decreased in AD compared with healthy controls. The frequency of cDC1 was negatively correlated with disease severity scores and serum immunoglobulin E levels. The expression of FcεRIa was significantly increased in the DC populations, including cDC1, cDC2, plasmacytoid DC, and Axl+ DC. CD163, a marker of the inflammatory DC subset DC3, was increased in AD patients, suggesting an increased DC3 signature in AD patients. Analysis of a public scRNA-seq dataset further corroborated the decreased frequency of cDC1. The expression of cutaneous lymphocyte antigen was increased in cDC1 of AD compared with HC, suggesting increased migration of cDC1 to the skin. Aligned with this hypothesis, the frequency of cDC1 was shown to be increased in AD lesional skin using immunofluorescence staining.

Conclusions: These results provide insight into the potential role of DC and monocyte populations in AD. We report decreased circulating cDC1 frequency and increased DC3 signature. The corresponding increased frequency of cDC1 in AD lesional skin implies their role in modulating AD pathophysiology.

Cold urticaria (ColdU) is characterized by wheals, angioedema, or both, which are triggered by exposure to cold. A subset of patients experiences cold-induced anaphylaxis (ColdA), a potentially life-threatening systemic reaction. The pathogenesis of ColdU remains incompletely understood, but mast cell activation plays a central role. Most hypotheses are decades old and require further investigations. ColdU and ColdA are clinically diagnosed and typically supported by cold stimulation testing (CST). However, standard CST methods may yield negative results despite a clear clinical history. ColdU is classified into typical and atypical forms based on CST responses. ColdA occurs more frequently in patients with mucosal angioedema involving the oropharynx. It is most commonly triggered by full-body cold exposure, such as swimming. Diagnostic workup should include a detailed history, CST, and evaluation for underlying conditions, particularly in patients with clinical signs and symptoms extending beyond the skin. First-line treatment involves second-generation H₁-antihistamines, often needed at increased doses for disease control. Omalizumab has shown efficacy in clinical trials and case reports for refractory cases. Adrenaline is the first-line therapy for ColdA; high-risk patients should be prescribed autoinjectors and receive proper training in their use. This review provides an overview of the pathophysiology, classification, diagnostic procedures, and management of ColdU and ColdA, emphasizing clinical variability and unmet research needs.

Inhaled corticosteroids (ICSs) are the foundation of asthma management, yet a subset of patients exhibits poor clinical response despite adequate treatment. Understanding the cellular and molecular mechanisms underlying this heterogeneity is essential for developing targeted therapies. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from 6 healthy controls, 6 ICS responders, and 4 ICS poor responders with asthma. We analyzed transcriptional profiles of immune cell subsets, focusing on CD14+ monocytes, and assessed signaling pathways using differential gene expression and receptor-ligand interaction analysis. ICS poor responders exhibited a reduced frequency of circulating CD14+ monocytes and upregulation of chemotaxis-related genes, including CCR1, CCL2, CCL7, and CXCL2. ANXA1 and its receptor FPR2, key regulators of anti-inflammatory responses, were downregulated in poor responders, while MIF and its receptors were upregulated. Receptor-ligand analysis identified T cells as a potential paracrine source of MIF signaling. Our findings highlight MIF-ANXA1 dysregulation in CD14+ monocytes as a key immune signature associated with poor ICS response in asthma.

Purpose: Peanut anaphylaxis is a widespread challenge, particularly in children. We aimed to confirm the therapeutic effects of transdermal immunotherapy (TDIT) in a murine model of peanut anaphylaxis.

Methods: We developed a biodegradable microneedle array patch (MAP) by incorporating peanut extract (PE) with hyaluronic acid. The allergenicity of the PE in MAP was assayed by enzyme-linked immunosorbent assay inhibition. The peanut anaphylaxis model was made with BALB/c or C3H/Hej mouse strains. We measured anaphylaxis clinical scores, as well as the levels of mouse mast cell protease-1 (MCPT-1), PE-specific immunoglobulin E (sIgE), specific immunoglobulin G (sIgG)1, and sIgG2a in serum. T cell populations in the spleen and jejunum were examined using immunohistochemical stains with confocal microscopy. Histological analysis of the jejunum was performed. The production of T helper cell type 2 (Th2) and regulatory T cell (Treg) cytokines by stimulated splenocytes were also measured.

Results: The inhibitory capacity of the PE in MAP for PE sIgE was comparable to that of native PE. TDIT with 10 μg of PE-MAP recovered anaphylaxis score, sIgE, and the MCPT-1 levels, and enhanced sIgG1 and sIgG4 in serum. TDIT also reduced the recruitment of Th2 cells while increasing Treg and Th1 cells in both the spleen and jejunum. However, the efficacy of applying 10 μg of PE-MAP TDIT twice a week was more pronounced than applying once a week. Additionally, TDIT led to reduced production of Th2 cytokines (interleukin [IL]-4, IL-5, IL-13) and increased production of transforming growth factor-β by stimulated splenocytes. TDIT attenuated inflammation, mast cell infiltration, and villous damage in the jejunum.

Conclusions: PE-MAP TDIT demonstrated therapeutic effects in peanut anaphylaxis, suggesting its potential for developing a novel TDIT for patients with peanut anaphylaxis.

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is highly complex and heterogeneous. Many patients still respond poorly to current medications that combine with surgical treatment strategies, resulting in uncontrolled outcomes. However, identifying uncontrolled CRSwNP remains challenging. We aimed to develop an effective predictive procedure to assess uncontrolled CRSwNP based on clinical features.

Methods: The clinical features of 952 adult CRSwNP patients were subjected to a decision tree analysis, with the uncontrolled outcome at follow-up considered the positive predictive event.

Results: A predictive procedure was developed to categorized CRSwNP patients into 6 clusters with different uncontrolled rates. classification indicators were determined as the total computed tomography (CT) scores and age, as well as tissue and blood eosinophil counts . The uncontrolled rates in Clusters 1-6 were 2.75%, 12.31%, 21.28%, 33.16%, 13.54%, and 38.27%, respectively. Additionally, Cluster 1 patients had the lowest tissue and blood eosinophil count and ratio, and the lowest total CT score. Cluster 3 patients had the highest tissue eosinophil count and ratio. Cluster 5 patients >2-fold tissue eosinophil count and ratio than Cluster 2 patients. Cluster 6 patients had the highest value for blood eosinophil count and ratio, total CT score, and endoscopic score. After surgery, the primary disturbing symptoms were nasal congestion (11.01% in Cluster 1 patients and 22.31% in Cluster 2 patients), rhinorrhea/postnasal drip (27.66% in Cluster 3 patients), and olfactory dysfunction (43.68%, 26.56%, and 50.62% in Clusters 4-6 patients, respectively).

Conclusions: The decision tree constructed from the total CT scores, tissue and blood eosinophil counts, and age can generate an effective predictive procedure to guide the identification of uncontrolled CRSwNP.

Purpose: Subcutaneous immunotherapy (SCIT) can trigger systemic reactions (SRs) that pose potential life-threatening risks. To date, no cluster analysis has been conducted to delineate sub-phenotypes of SRs. This study aims to identify and characterize diverse SR phenotypes during SCIT for house dust mite (HDM) allergies in China.

Methods: This large retrospective real-world study enrolled patients diagnosed with HDM-sensitized allergic rhinitis (AR) and/or asthma who underwent SCIT (Alutard SQ; ALK) between February 2013 and July 2024 at five allergy centers in China. Data on demographic profiles and SRs were collected, followed by a cluster analysis among SR patients.

Results: A total of 3,126 patients received 107,588 injections, with SRs observed in 354 patients (11.32%) and 1,056 injections (0.98%). A higher incidence of SRs was noted in younger patients (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.92; P < 0.001), those with asthma (OR, 2.12; 95% CI, 1.69-2.66; P < 0.001), those with longer disease duration (OR, 1.08; 95% CI, 1.04-1.12; P < 0.001), those with high sensitization (OR, 3.84; 95% CI, 1.66-8.88; P = 0.002), and those with polysensitization (OR, 1.69; 95% CI, 1.30-2.20; P < 0.001). Four distinct clusters of SRs were identified: Cluster 1 (16.5%) primarily comprised relatively older females with lower specific immunoglobulin E (sIgE) levels, predominantly cutaneous involvement, fewer SRs overall but with grade 4 SR; Cluster 2 (29.9%) mainly included AR patients without asthma, mostly exhibiting grade 1 SR; Cluster 3 (34.0%) predominantly consisted of asthma patients with monosensitization, higher injection doses, and mostly grade 2 SR; Cluster 4 (19.6%) mainly featured younger males with higher sIgE levels, polysensitization, lower injection doses, the highest number of SRs, and more grade 3 SR.

Conclusions: Asthma, disease duration, high sensitization, and polysensitization emerge as independent risk factors for SRs. Our cluster analysis delineates distinct clinical phenotypes of SRs, offering tailored interventions for the personalized management of patients experiencing SRs.

Chronic spontaneous urticaria (CSU) is a complex mast cell-driven disorder characterized by recurrent pruritic wheals and/or angioedema lasting over 6 weeks. This condition affects women more frequently than men, particularly between the ages of 20 and 40, and imposes considerable physical, psychological, and economic burdens, with annual healthcare costs in the U.S exceeding $200 million. Current management strategies emphasize a stepwise approach, initiating with the escalating doses of second-generation antihistamines, followed by biologics such as omalizumab or now dupilumab, and prescribing cyclosporine to refractory cases. Emerging therapies targeting specific endotypes of CSU, including Bruton's tyrosine kinase inhibitors and mast cell depleting agents, present new avenues for personalized treatment. Furthermore, validated patient-reported outcome measures and digital tools like the CRUSE application enhance symptom tracking and facilitate patient-physician communication. As the therapeutic landscape for CSU evolves, a focus on individualized, evidence-based care approaches is critical to optimizing patient outcomes. Future research priorities include identifying biomarkers predictive of treatment response, conducting long-term outcome studies, and evaluating treatment tapering strategies to achieve sustained remission. Addressing cost-effectiveness and accessibility of new therapies will be pivotal in ensuring equitable management of CSU across diverse populations. Ultimately, it is the goal that a comprehensive understanding of CSU's heterogeneity, with tailored therapeutic strategies, will significantly improve patient quality of life and outcomes.

Purpose: Although atopic dermatitis (AD) in adults has been prevalent, there has been a paucity of previous studies on the metabolic markers linked to its development. We investigated whether plasma metabolomic biomarkers are associated with incident middle-adulthood to late-adulthood AD and identified its predictors.

Methods: This study utilized data collected from the UK Biobank between 2006 and 2010. We prospectively analyzed metabolites in 79,414 participants aged 40 to 69 years, predominantly of European ancestry and free of AD, to assess the incidence of AD, which were collected using the International Classification of Diseases from hospital inpatient admission records from the baseline through 2022. The relationship between these metabolites and the incidence of AD was estimated using Cox proportional hazard models, and the predictive value of the metabolites for the incidence of middle-adulthood to late-adulthood AD was assessed.

Results: The incidence rate of middle-adulthood to late-adulthood AD was 7.81 per 10,000 person-years, and the median follow-up was 161 months. A total of 35 plasma metabolites included in lipoprotein lipids, fatty acids, amino acids, and biomarkers related to fluid balance were significantly linked to the risk of middle-adulthood to late-adulthood AD incidence. Significant non-linear associations of middle-adulthood to late-adulthood AD incidence were observed with triglycerides in medium very-low density lipoprotein, leucine, and the total concentration of branched-chain amino acids. The incorporation of the identified 35 metabolites with the covariates for middle-adulthood to late-adulthood AD risk prediction achieved an area under the curve of 0.71 (95% confidence interval, 0.67-0.75) and reclassification ability (net reclassification improvement = 21.4%, P < 0.001).

Conclusions: Findings from this prospective study suggest that the identified plasma metabolites could better clarify the underlying metabolic vulnerabilities and improve risk prediction associated with the development of middle-adulthood to late-adulthood AD.