International Archives of Allergy and Immunology最新文献

{"title":"Age-Related Differences in Asthma Recognition, Follow-Up and Home-Based Exacerbation Management among Children Hospitalized for Acute Asthma Exacerbations.","authors":"Seyma Butun Turk, Alp Kazancioglu, Ipek Turktas","doi":"10.1159/iaa/adfag018","DOIUrl":"10.1159/iaa/adfag018","url":null,"abstract":"<p><strong>Introduction: </strong>The objectives of the study were to evaluate age-related differences in asthma diagnosis and management among children hospitalized for moderate-to-severe asthma exacerbations and to examine the relationship of regular follow-up and home-based exacerbation management with clinical outcomes.</p><p><strong>Methods: </strong>This retrospective observational study included children aged 25 months to <18 years who were hospitalized for moderate-to-severe asthma exacerbations. Patients were categorized as preschool-aged (25-60 months) or school-aged (61 months to <18 years). Asthma diagnosis before hospitalization, regular follow-up, controller therapy use, caregiver education, initiation of home-based treatment, exacerbation history, and healthcare utilization were compared.</p><p><strong>Results: </strong>A total of 104 children were included. Preschool children were less likely than school-aged children to have received an asthma diagnosis before hospitalization (56.5% vs. 83.3%, p = 0.008) and were more frequently managed with diagnoses such as bronchiolitis or bronchitis. Antibiotic use before asthma diagnosis was reported in 87.5% of the cohort. Patients attending regular follow-up had higher rates of controller therapy use, home-based exacerbation management education, and initiation of treatment at home (all p < 0.001). They also had fewer moderate-to-severe exacerbations (p < 0.001) and fewer emergency department visits (p = 0.036). Although children initiating home treatment had a greater previous exacerbation burden, they had fewer moderate-to-severe exacerbations during the preceding year than those who did not initiate treatment at home (p = 0.004). In multivariable analysis, regular follow-up remained independently associated with lower odds of recurrent moderate-to-severe exacerbations (aOR 0.03, 95% CI: 0.004-0.20; p < 0.001).</p><p><strong>Conclusion: </strong>Asthma was less often recognized before hospitalization in preschool children, and antibiotic use before diagnosis was common. Children attending regular follow-up more often received controller therapy and home-management education and had fewer moderate-to-severe exacerbations and emergency department visits. These findings highlight the importance of timely asthma recognition, regular follow-up, and practical caregiver education in children with recurrent wheezing or asthma, while the observational design precludes causal inference.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of a Calcitonin Gene-related Peptide-Neutralizing Antibody in theTreatment of Allergic Rhinitis in a Murine Model.","authors":"Yongling Sun, Yiyun Zeng, Ying Guo, Yubiao Liu, Fu Li, Yue Zhang, Jun Ye, Guangyao Mao, Xuhui Kong","doi":"10.1159/iaa/adfag012","DOIUrl":"https://doi.org/10.1159/iaa/adfag012","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to characterize the expression of calcitonin gene-related peptide (CGRP) in patients with allergic rhinitis (AR) and to investigate the effects of CGRP intervention on AR symptoms, nasal mucosal inflammation, and the number of group 2 innate lymphoid cells (ILC2s) in a murine model.</p><p><strong>Methods: </strong>Peripheral blood and inferior turbinate mucosal samples were collected from 20 patients with AR and 20 control subjects. CGRP levels in serum and nasal mucosa were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Thirty-two C57BL/6J mice were randomly assigned to four groups: Control, AR, AR + isotype IgG, and AR + anti-CGRP. Mice in the AR group were sensitized and intranasally challenged with ovalbumin (OVA). During the challenge phase, mice in the AR + isotype IgG group and the AR + anti-CGRP group received isotype IgG and AR + anti-CGRP treatment, respectively, whereas mice in the Control group received phosphate-buffered saline (PBS) only. AR-related nasal symptoms were evaluated based on the frequency of nose rubbing and sneezing, as well as the severity of rhinorrhea. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were used to assess histopathological changes in the nasal mucosa and the increased number of goblet cells. IHC was used to detect the expression levels of IL-1β, IL-6, TNF-α, and CGRP. Double immunofluorescence staining was performed to quantify ILC2s in the nasal mucosa. Western blotting (WB) was used to determine the phosphorylation levels of the key proteins in the MAPK pathway, including JNK, ERK1/2, and p38.</p><p><strong>Results: </strong>CGRP expression levels in the nasal mucosa and serum of patients with AR were significantly higher than those in the control group. Serum CGRP levels were positively correlated with visual analog scale (VAS) scores, and nasal mucosal CGRP expression was positively correlated with the number of inflammatory cells. Compared with the AR group and the AR + isotype IgG group, mice in the Anti-CGRP group showed significantly alleviated nasal symptoms and markedly reduced inflammatory cell infiltration in the nasal mucosa. In addition, the expression levels of IL-1β, IL-6, TNF-α, and CGRP in the nasal mucosa were decreased, the number of ILC2s was reduced, and the phosphorylation levels of p-JNK, p-ERK1/2, and p-p38 were significantly lowered.</p><p><strong>Conclusion: </strong>CGRP may serve as a potential therapeutic target for AR. CGRP-neutralizing antibody can alleviate AR symptoms, suppress inflammatory responses, and regulate the number of ILC2s.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Algorithm and Real-Life Data in Pediatric Patients Suspected of NSAID Hypersensitivity.","authors":"Melis Ozturk Aykac, Eren Sari, Ozlem Yilmaz","doi":"10.1159/iaa/adfag034","DOIUrl":"https://doi.org/10.1159/iaa/adfag034","url":null,"abstract":"<p><p>Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in children, but NSAID hypersensitivity (NSAID-H) presents a heterogeneous clinical profile. Pediatric diagnostic approaches and real-life data after drug challenges (DCs) remain limited. Objective We aimed to evaluate the diagnostic algorithm for suspected pediatric NSAID-H and examine real-life drug use. Methods Children (1-18 years) evaluated for NSAID-H using WAO guidelines at a tertiary pediatric allergy center (Jan 2022-Nov 2025) were included. Clinical histories, co-morbidities, and DC outcomes were recorded. Patients were classified as having single- or multiple-NSAID induced hypersensitivity. Positive patients underwent DCs for safe alternatives, and real-life tolerance was assessed. Results Of 62 included children, five had suspected immediate paracetamol reactions (one confirmed). Fifty-seven reported reactions to ≥2 unrelated NSAIDs; six were diagnosed via history alone. Of 51 children challenged with ASA/ibuprofen, 14 (27.5%) were positive. Angioedema was the most frequent reaction; one experienced anaphylaxis following ibuprofen provocation. Single- and multiple-NSAID hypersensitivity rates were 20% (1/5) and 35.1% (20/57), respectively. Five patients already used paracetamol safely. For the remaining 14, safe alternatives identified were nimesulide (n=6) and meloxicam (n=4). One reacted to both, but tolerated codeine. Among 41 patients with excluded NSAID-H, 37 were contacted; 36 (97.3%) safely reused the culprit drug in real-life (one avoided due to maternal fear). Of 14 confirmed NSAID-H patients, 11 were contacted, all reporting safe alternative use without reactions. Conclusion Structured diagnostic algorithms and drug challenges ensure accurate diagnosis, reducing unnecessary NSAID restrictions and enabling safe real-life drug use in children. Key Words Acetyl salicylic acid, Children, Cyclooxygenase, Diagnosis, Drug allergy, Drug challenge, NSAID Hypersensitivity, Safe alternative, Real life.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Compartment Proteomic analysis reveals inflammatory signatures of sleep disturbance in allergic rhinitis.","authors":"Yilin Hou, Weiqiang Yang, Xiaochan Lu, Yaqi Zhou, Wei-Ping Wen, Mengqi Su, Hongyi Hu","doi":"10.1159/iaa/adfag031","DOIUrl":"https://doi.org/10.1159/iaa/adfag031","url":null,"abstract":"<p><p>Introduction Allergic rhinitis (AR) is often accompanied by sleep disturbance, while the molecular mechanisms underlying sleep-related exacerbation of nasal symptoms remain poorly understood. This study aimed to investigate the inflammatory protein signatures associated with poor sleep in AR using a dual-compartment proteomic approach. Methods We first analyzed 3,731 adult participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) cycle to validate the association between sleep duration and AR. We then enrolled 40 AR patients (20 poor sleepers, Pittsburgh Sleep Quality Index [PSQI] > 5; 20 normal sleepers, PSQI ≤ 5) and performed Olink proteomic profiling in paired serum and nasal secretion (NS) samples. Differential expression analysis, functional enrichment, cross-compartment correlation, Least Absolute Shrinkage and Selection Operator (LASSO) regression, receiver operating characteristic (ROC) analysis, and sequential multivariable linear regression were conducted. Results In NHANES, short sleep duration (<6 h) was significantly associated with increased odds ratio (OR) of AR (OR = 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.013) and elevated serum total immunoglobulin E (IgE). In the clinical cohort, poor sleepers had higher Total Nasal Symptom Score (TNSS) (P < 0.001), Multidimensional Fatigue Inventory (MFI) (P < 0.001), and blood eosinophil counts (P = 0.011). Proteomics identified 27 serum and 20 NS differentially expressed proteins (DEPs), with 9 overlapping DEPs enriched in interleukin-17 (IL-17), tumor necrosis factor (TNF), and chemokine signaling pathways. A four-marker panel (serum beta-nerve growth factor [β-NGF], serum transforming growth factor-beta 1 [TGF-β1], NS interleukin-8 [IL-8], NS matrix metalloproteinase-1 [MMP-1]) achieved an area under the curve (AUC) of 0.88 (95% CI 0.76-0.97, P < 0.001) for distinguishing poor from normal sleepers. Cross-compartment correlation analysis revealed significant serum-NS protein concordance, consistent with systemic-local inflammatory crosstalk. Sequential multivariable regression showed that serum β-NGF independently predicted TNSS severity even after PSQI adjustment (β = 2.22, P = 0.044), whereas nasal IL-8 was fully attenuated (β = 0.58, P = 0.391). Conclusion Poor sleep is associated with exacerbated AR through coordinated systemic and local inflammatory responses. Serum β-NGF is independently associated with nasal symptoms, whereas the association of NS IL-8 with symptoms appears to be explained by sleep disturbance. Integrating markers from both compartments enhances the identification of AR patients with poor sleep.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Immunological Determinants of Time to Open Oral Food Challenge-Confirmed Tolerance in Children With IgE-Mediated Food Allergy: A Retrospective Cohort Study.","authors":"Ozge Kangalli Boyacioglu, Özgen Soyöz, Semiha Erdem Bahçeci","doi":"10.1159/iaa/adfag028","DOIUrl":"https://doi.org/10.1159/iaa/adfag028","url":null,"abstract":"<p><strong>Background: </strong>The timing of tolerance acquisition in childhood IgE-mediated food allergy is clinically important but has been less well studied than persistence as a binary outcome. We examined clinical and immunological determinants of time to open oral food challenge (OFC)-confirmed tolerance.</p><p><strong>Methods: </strong>This retrospective cohort study included 157 children with physician-established IgE-mediated food allergy evaluated at a tertiary pediatric allergy clinic between January 2023 and July 2026. Time zero was defined as elimination-diet initiation; tolerance was defined exclusively by a successful supervised open OFC. One mutually exclusive index allergen was assigned to each child and used consistently to define the time-to-tolerance outcome. Kaplan-Meier analysis and parametric accelerated failure time models were used. The log-logistic model, adjusted for index allergen and the prespecified clinical and immunological covariates, was selected for multivariable analysis and internally validated using 1,000 bootstrap resamples.</p><p><strong>Results: </strong>Of 157 children, 120 achieved OFC-confirmed tolerance and 37 were right-censored. The mutually exclusive index-allergen distribution was hen's egg (n=103), cow's milk (n=35), tree nut (n=16), other food (n=2), and fish (n=1). In the index-allergen-adjusted log-logistic AFT model, food-induced anaphylaxis (adjusted TR 2.13, 95% CI 1.34-3.36; P=0.001), allergic rhinitis (adjusted TR 1.80, 95% CI 1.26-2.55; P=0.001), and each 10-fold increase in total IgE (adjusted TR 1.54, 95% CI 1.20-1.98; P<0.001) were associated with a longer time to tolerance. Tree-nut index allergy was also associated with longer time to tolerance than hen's egg (adjusted TR 2.74, 95% CI 1.19-6.29; P=0.018), although this estimate was based on few tolerance events.</p><p><strong>Conclusions: </strong>Previous food-induced anaphylaxis, allergic rhinitis, higher total IgE, and index food type were associated with the timing of open OFC-confirmed tolerance in children with IgE-mediated food allergy. Routine quantitative IgG, IgA, and IgM measures were not independently associated with tolerance timing.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of molecular sensitization patterns identified by latent class analysis with clinical phenotypes in patients with allergic rhinitis with and without asthma.","authors":"Julijana Asllani, Edina Zhabjaku, Eris Mesonjesi, Mehmet Hoxha, Etleva Qirko","doi":"10.1159/iaa/adfag032","DOIUrl":"https://doi.org/10.1159/iaa/adfag032","url":null,"abstract":"<p><strong>Introduction: </strong>Sensitization to different allergen components is associated with distinct clinical characteristics including disease phenotypes and severity. A better understanding of the individual patterns of sensitization is important for the diagnosis and personalized management of the allergic patient. This is one of the first comprehensive studies of the molecular sensitization patterns investigating both indoor and outdoor allergens in Albanian patients.</p><p><strong>Methods: </strong>A cross-sectional study among patients with allergic rhinitis (AR) with and without asthma was conducted in Tirana. Patients underwent a detailed interview on clinical allergy history, skin prick testing and the Allergy Explorer Test 2 (ALEX 2) multiplex array. Latent class analysis was carried out to identify distinct sensitization profiles.</p><p><strong>Results: </strong>Data from 140 cases were analyzed. Four distinct sensitization classes were derived in our study population: Class 1, predominant sensitization to grass pollen molecular allergens (n=56,40%); Class 2, predominant sensitization to house dust mites (HDM) molecular allergens (n=38, 27.1%); Class 3, predominant sensitization to pathogenesis-related class 10 (PR-10) molecular allergens (n=25,17.9%) and Class 4, broad sensitization to multiple inhalant and food components (n=21, 15%). Patients in CL2 had higher odds of having AR with asthma compared to AR only (OR= 2.430, 95% CI [1.016-5.811], p=0.046), whereas patients in CL3 (OR=10.286, 95% CI [3.334-31.731], p<0.001) were associated with higher odds of Pollen-food allergy syndrome.</p><p><strong>Conclusion: </strong>Sensitization patterns are heterogeneous within a country-level cohort of patients and are associated with distinct clinical phenotypes. In the overall study population, sensitization to HDM and persistent, severe AR were associated with AR with concomitant asthma.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma miR-1 is downregulated in allergic rhinitis and alleviates IL-13-induced nasal epithelial inflammation via targeting BDNF.","authors":"Jinyan Wang, Yang Wang","doi":"10.1159/iaa/adfag030","DOIUrl":"https://doi.org/10.1159/iaa/adfag030","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR), a common chronic inflammatory disorder of the upper airway, currently lacks reliable non-invasive molecular biomarkers for dynamic disease monitoring and therapeutic guidance. This study aimed to evaluate the diagnostic value of plasma miR 1 in AR and to investigate its role in nasal epithelial inflammation and oxidative stress, along with the underlying molecular mechanism.</p><p><strong>Methods: </strong>Plasma miR 1 was quantified by RT qPCR in 118 AR patients and 100 healthy controls, followed by correlation analysis with disease severity indices. An IL 13-stimulated human nasal epithelial cell (HNEpC) model was employed to examine viability, apoptosis, pro-inflammatory cytokines (IL 6, IL 8), and oxidative stress markers (MDA, GSH) following miR 1 overexpression or knockdown. Bioinformatic screening and dual-luciferase reporter assays were utilized to identify and validate BDNF as a direct miR 1 target. Rescue experiments were performed through co-transfection of miR 1 mimic with BDNF overexpression vector.</p><p><strong>Results: </strong>Plasma miR 1 was significantly lower in AR patients and negatively correlated with TNSS and RQLQ scores, yielding an AUC of 0.864 for discriminating AR from controls. In IL 13 treated HNEpC, miR 1 overexpression enhanced cell viability, reduced apoptosis, decreased IL 6 and IL 8 secretion, and ameliorated oxidative stress (lowered MDA, elevated GSH). BDNF was confirmed as a direct target of miR 1. BDNF overexpression partially reversed the protective effects of miR 1 upregulation.</p><p><strong>Conclusions: </strong>Plasma miR 1 is downregulated in AR and correlates with disease severity, suggesting its potential as a non invasive diagnostic biomarker. Experimental evidence indicates that miR 1 may alleviate IL 13 induced inflammation and oxidative stress in HNEpC through direct targeting of BDNF.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Biologics for Patients with Severe Eosinophilic Asthma: A Network Meta-analysis.","authors":"Xubin Ren, Zhi Wen, Fei Long, Nie Xu","doi":"10.1159/iaa/adfag009","DOIUrl":"https://doi.org/10.1159/iaa/adfag009","url":null,"abstract":"<p><strong>Background: </strong>Severe eosinophilic asthma (SEA) remains morbid despite standard care. Lacking head-to-head trials, the comparative efficacy of biologics (mepolizumab, benralizumab, dupilumab, tezepelumab) is unclear. This network meta-analysis quantifies their relative efficacy and safety in SEA.</p><p><strong>Method: </strong>Following PRISMA-NMA, we searched databases (inception to July 23, 2025) for RCTs of adolescents/adults with SEA comparing these biologics against placebo or each other. Primary outcomes were annualized asthma exacerbation rate (AAER) and change in pre-bronchodilator FEV₁; secondary outcomes included change in post-bronchodilator FEV₁, ACQ/AQLQ scores, and safety. Bayesian random-effects network meta-analysis was performed, and treatment rankings were summarized using SUCRA. Certainty of evidence was assessed using GRADE.</p><p><strong>Results: </strong>Seventeen RCTs involving 7,173 participants were included. For AAER, tezepelumab ranked highest (SUCRA: 73.35%), followed by mepolizumab (72.65%), benralizumab (56.23%), and dupilumab (36.20%); the corresponding network estimates versus placebo were MD -1.23 (95% CrI: -2.99 to 0.58), -1.16 (95% CrI: -2.76 to 0.49), -0.75 (95% CrI: -1.54 to -0.17), and -0.37 (95% CrI: -2.13 to 1.42), respectively. For ΔPre-BD FEV₁, tezepelumab ranked highest (SUCRA: 79.64%), followed by dupilumab (54.42%), benralizumab (52.19%), and mepolizumab (45.71%). Benralizumab ranked highest for ΔPost-BD FEV₁ and ΔACQ-5, tezepelumab for ΔACQ-6, dupilumab for ΔAQLQ, and mepolizumab for lower SAE risk. For SAEs, network estimates versus placebo were OR 0.45 for mepolizumab (95% CrI: 0.23 to 0.72) and OR 0.58 for benralizumab (95% CrI: 0.35 to 0.84). Leave-one-out analyses showed stable rankings after exclusion of non-tezepelumab studies, whereas exclusion of Wechsler ME 2022 removed the tezepelumab node. GRADE certainty ranged from very low to high, and potential publication bias was detected for SAEs.</p><p><strong>Conclusion: </strong>This NMA suggests that biologics provide clinically relevant benefits for SEA, particularly in reducing exacerbations. Tezepelumab and mepolizumab had the highest ranking probabilities for AAER. Mepolizumab and benralizumab ranked favorably for lower SAE risk, but these safety estimates should be interpreted cautiously because of potential publication bias. Treatment rankings remain limited by low or very low certainty for many indirect active-treatment comparisons, underscoring the need for head-to-head trials.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Comorbidity of Upper and Lower Airways: Epidemiology, Mechanism, and Therapeutic Advances of Rhinitis Combined with Asthma.","authors":"Kang Wang, Yan Qin, Jun Liu","doi":"10.1159/iaa/adfag019","DOIUrl":"10.1159/iaa/adfag019","url":null,"abstract":"<p><strong>Background: </strong>Asthma and rhinitis are the most common chronic inflammatory diseases of the lower and upper airways, respectively, and frequently coexist as inflammatory disorders of the same respiratory tract. However, the relationship between these two conditions is not simply unidirectional, and the underlying mechanisms remain incompletely understood.</p><p><strong>Summary: </strong>Approximately 80% of asthma patients have comorbid rhinitis, whereas 30-40% of rhinitis patients develop asthma, with comorbidities associated with greater symptom burden, reduced quality of life, and higher healthcare costs. The underlying mechanisms involve shared type 2 inflammation, neural reflexes, and systemic inflammatory spread. However, emerging evidence reveals significant clinical and therapeutic discordance between the upper and lower airways: biologics targeting the same type 2 pathway show differential efficacy, and only a subset of rhinitis patients progress to asthma. These findings challenge the one airway, one disease model and support conceptualizing the relationship as an overlap syndrome with both shared and distinct components. Current management has evolved toward an integrated strategy, with combined nasal and inhaled glucocorticoids as the cornerstone, leukotriene receptor antagonists offering additional benefits, and biologic agents (anti-IgE, anti-IL-4Rα) together with allergen immunotherapy providing targeted or etiological options.</p><p><strong>Key messages: </strong>The rhinitis-asthma comorbidity involves shared type 2 inflammation but also exhibits compartment-specific molecular and therapeutic differences. Biologic agents show discordant efficacy between upper and lower airways, underscoring the need for phenotype-driven endotyping rather than a one-size-fits-all approach. Future research should focus on compartment-specific biomarkers and precision management strategies to optimize outcomes for patients with airway comorbidities.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Heterogeneity Links Inflammatory Microenvironments to Tissue Remodeling in Chronic Rhinosinusitis.","authors":"Jiayu Cao, Zeli Feng, Chengshuo Wang, Mu Xian, Mi Lu, Yuzhoujia Deng, Liying Zheng, Bing Yan, Luo Zhang","doi":"10.1159/iaa/adfag025","DOIUrl":"10.1159/iaa/adfag025","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disorder with distinct endotypes and tissue remodeling. Fibroblasts contribute to extracellular matrix remodeling and immune regulation, but their heterogeneity in CRS remains unclear.</p><p><strong>Methods: </strong>Public single-cell transcriptomic data from 21 CRS and healthy control samples were integrated with bulk RNA-sequencing data from primary fibroblasts derived from nasal polyps stimulated with phosphate-buffered saline, interferon (IFN)-γ, interleukin (IL)-4, or IL-17A. Fibroblast subsets, pseudotime trajectories, and inferred communication between fibroblasts and immune cells were analyzed. Cytokine-induced signatures were projected onto the fibroblast atlas. A subset of longitudinal RNA-seq data from the COMPASS cohort (NCT05598424) was used to validate predefined candidate marker genes, including IL-4-associated markers of the C8 subset and IL-17A-associated markers of the C5/C10 subsets, during glucocorticoid treatment across V1 (baseline), V2 (after 4 weeks of intranasal corticosteroid treatment), and V3 (after subsequent systemic glucocorticoid therapy). Temporal expression changes were assessed using linear mixed-effects models with V1-V2 and V2-V3 comparisons.</p><p><strong>Results: </strong>Twelve transcriptionally distinct fibroblast subsets (C0-C11) were identified across CRS subtypes. C8 fibroblasts were enriched in eosinophilic CRSwNP and associated with type 2 inflammation-related genes, including CCL26 and POSTN, whereas C5 and C10 were associated with non-eosinophilic CRSwNP- and IL-17A-related inflammatory features. Pseudotime analysis suggested two trajectories from C4 toward C8 and C10, respectively. CellChat revealed bidirectional communication between fibroblasts and immune cell subsets. Cytokine stimulation induced distinct transcriptional responses: IFN-γ mainly induced antigen presentation and interferon response; IL-4 induced contraction- and cytoskeleton-related features; and IL-17A activated IL-17, nuclear factor κB, and tumor necrosis factor signaling pathways. Signature projection linked IL-4-related features mainly to C8 fibroblasts and IL-17A-related features mainly to C5 and C10 fibroblasts. Longitudinal analysis of glucocorticoid-treated patients identified a stable C8-associated transcriptional signature characterized by sustained downregulation of CCL26, POSTN, CISH, and CCL13 across V1-V3 time points.</p><p><strong>Conclusions: </strong>Fibroblasts in CRS exhibit marked heterogeneity and may contribute to tissue remodeling and immune regulation in response to distinct inflammatory stimuli. The IL-4-associated C8 state and IL-17A-associated C5/C10 states may represent distinct fibroblast states associated with different CRS inflammatory microenvironments. The C8-associated transcriptional module shows stable and sustained suppression under glucocorticoid treatment.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}