Search Results (697)

Tuft cells are a rare type of epithelial cell that are essential to regulate innate and adaptive immune responses. Mucosal immunity is also composed primarily of IgA produced by B cells that is secreted onto mucosal surfaces as secretory IgA via the polymeric immunoglobulin receptor (pIgR). The homing of B cells in lymphoid organs is mediated by certain adhesion receptors, such as α4β7 and chemokine receptor 9 (CCR9), that bind to the specific vascular ligands, mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) and chemokine ligand 25 (CCL25), respectively. It is unclear whether tuft cells, MAdCAM-1, CCL25, and pIgR are present or expressed in the nasal cavities of pigs. Our study aimed to develop immunohistochemistry (IHC) or immunofluorescence (IF) staining for the detection of tuft cells, MAdCAM-1, CCL25, pIgR, and IgA- or IgG-positive cells in porcine nasal turbinates. The tissues were acquired from the piglets of two different treatment groups in our previous studies that investigated the impact of oral vitamin A supplementation (VA) on the maternal immunity of vitamin A-deficient (VAD) sows and the passive protection of their piglets against rotavirus A (RVA): (1) VAD + VA + RVA and (2) VAD + RVA piglets. Our IHC staining revealed that low numbers of advillin-positive, bottle-shaped cells that morphologically resemble tuft cells were present in the mucosal epithelium and the mucous duct or glands. There were also moderate to large amounts of MAdCAM-1 and CCL25 in the endothelial cells lining the vascular structures present in the lamina propria of nasal turbinates and moderate to large amounts of pIgR in the turbinate mucosal epithelium. Moderate to high numbers of IgA- or IgG-positive cells were present in the lamina propria. There were no differences in IF- or IHC-positive scores or the positive cell numbers of all parameters tested between VAD + VA + RVA and VAD + RVA piglets, suggesting little or no effect of VA on the parameters tested. Our study demonstrated the use of IHC/IF staining methods for the detection of tuft cells, MAdCAM-1, CCL25, pIgR, and IgA- or IgG-positive cells in porcine nasal turbinates, expanding our understanding of the in situ distribution and comparison in the nasal cavity of pigs born to the sows fed vitamin A-deficient diets with or without vitamin A supplementation. Full article

Background: Telemedicine may improve access to care and streamline patient pathways, but real-world uptake in otorhinolaryngology remains uncertain. This single-center study evaluated an online appointment module with an option for video consultation at ENT University Hospital Freiburg and compared real-world utilization with patients’ hypothetical willingness to use telemedicine. Materials and Methods: The online module was implemented from March to June 2021. We recorded symptom category, age, gender, distance to the clinic, insurance status, type of consultation requested, and preference for video versus face-to-face consultation. Video consultations were evaluated separately in March and April. In addition, an independent survey was conducted in February 2021 among patients presenting with otological symptoms to assess hypothetical willingness to substitute an equivalent telemedical consultation for an in-person visit. Results: Of 7435 outpatient contacts, 507 (6.8%) used the online appointment module. Among these, 35 (6.9%) requested a video consultation and 472 (93.1%) requested a face-to-face appointment; video requests therefore represented 0.47% of all outpatient contacts. By contrast, 35 of 55 survey respondents (63.6%) stated that they would forgo an in-person visit if equivalent telemedical care were available. In March and April, 29 video consultations were scheduled or requested after telephone counseling, of which 11 were completed. Nine of the 11 completed video consultations (81.8%) did not require a subsequent in-person visit, whereas two (18.2%) required additional audiometry or nasal endoscopy. Because only 11 video consultations were completed, these findings are descriptive and exploratory. Conclusions: Hypothetical willingness to use telemedicine was substantially higher than real-world video consultation utilization. This gap indicates that stated acceptance does not necessarily translate into actual use and may reflect clinical suitability, awareness, organizational or technical barriers, or patient preference. ENT departments considering telemedicine should therefore use targeted patient selection and pre-consultation triage, particularly for follow-up visits, counseling, and second opinions that do not require immediate examination or diagnostic testing. Generalizability is limited by the single-center design, the short observation period, the small number of completed video consultations, and the COVID-19 pandemic context. Full article

Studies of allergic rhinitis (AR) have increasingly recognized that reactive oxygen species (ROS) are not simply byproducts of oxidative metabolism but function as modulators of the type 2 inflammatory network during the pathogenesis of this disease. This narrative review summarizes the role of ROS in the pathophysiology of AR by analyzing studies that examined markers of systemic oxidative stress, dysfunction of the epithelial barrier, ROS derived from immune cells, mitochondrial redox signaling, and inflammasome-related pathways. Our structured search of the literature reviewed five major databases (PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar) and identified 17 eligible studies published between 2000 and 2026. Clinical studies suggest that patients with AR exhibit altered systemic redox homeostasis, including thiol–disulfide imbalance and increased lipid peroxidation. However, these findings are primarily from measurements of markers in peripheral blood, not nasal mucosa. Experimental studies consistently demonstrated that allergen exposure increased the levels of ROS in nasal epithelial and immune cells, disrupted the epithelial barrier, downregulated tight junction proteins, and activated inflammatory signaling pathways. Although direct nasal tissue data remain limited, evidence extrapolated from peripheral blood and bronchial challenge models suggests that eosinophils and neutrophils contribute to the generation of ROS during the late phase of the allergic response, thereby potentially amplifying and sustaining airway inflammation. There is also evidence that mitochondrial ROS and DUOX-dependent signaling contribute to epithelial dysfunction, including the release of damage-associated molecular patterns and activation of inflammasome pathways. In parallel, antioxidant defense mechanisms, such as the KEAP1/NRF2 axis and mitophagy-related pathways, appear to modulate disease severity by maintaining redox homeostasis. Experimental strategies such as ROS scavengers and oxidative stress-responsive drug delivery systems have shown early proof-of-concept potential in preclinical and pilot studies, but rigorous and large-scale clinical support is strictly required before any clinical application can be considered. Overall, current evidence indicates that ROS function in AR as context-dependent redox mediators rather than as primary causes. The biological effects of ROS appear to depend on site of synthesis, subcellular localization, and the balance between oxidant generation and antioxidant defenses. Further studies that directly assess the dynamics of nasal mucosal ROS and well-designed clinical trials are needed to clarify the translational relevance of these studies and the therapeutic potential of different treatments for AR. Full article

Acute lung injury (ALI) is characterized by alveolar-capillary barrier disruption, increased pulmonary permeability, impaired gas exchange, and inflammation. Lipopolysaccharide (LPS), a potent microbial trigger of inflammation, is widely used to model ALI. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1), also known as BPIFA1, is an abundant surfactant-like protein secreted by the airway epithelium with antimicrobial and immunomodulatory functions. However, its role in endotoxin-induced lung injury remains incompletely understood. We compared pulmonary responses to LPS in wild-type and SPLUNC1/BPIFA1-knockout mice. Mice received intranasal PBS or 5 μg LPS were evaluated 24 h later by bronchoalveolar lavage, histology, cytospin, flow cytometry, qPCR, ELISA, and whole-lung RNA sequencing. Compared with WT mice, LPS-challenged KO mice exhibited greater inflammatory-cell accumulation, enhanced neutrophil recruitment, increased cytokine and chemokine expression, and greater histologic lung injury. Transcriptomic analyses showed preferential activation of TNFα/NF-κB, IL-6-JAK-STAT3, complement, cytokine/chemokine, myeloid/neutrophil, and stress-response in KO lungs. These findings identify SPLUNC1/BPIFA1 as an epithelial-derived regulator that restrains endotoxin-induced inflammatory signaling, neutrophil recruitment, and tissue injury. Collectively, these results support a protective role for SPLUNC1/BPIFA1 in acute pulmonary inflammation and provide a rationale for investigating SPLUNC1/BPIFA1 augmentation to mitigate ALI. Further studies evaluating SPLUNC1-based interventions in preclinical models are warranted. Full article

Asthma and sinonasal diseases, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), frequently coexist as part of the United Airway Disease (UAD), reflecting shared inflammatory pathways and physiopathologic mechanisms. They both significantly contribute as additional comorbidities to patient burden of symptoms and disease severity, and may guide the treatment approach, particularly when presenting together. The aim of this review was to explore the clinical interplay between asthma and sinonasal diseases, emphasizing epidemiologic links, shared immunologic pathways, and emerging management strategies, namely biologic therapies targeting type 2 (T2) inflammation. This approach enables integrated diagnostic and therapeutic approaches by targeting specific inflammatory mediators in a precision-medicine perspective. This may lead to a higher chance of achieving better outcomes in both upper and lower airways. Future studies should refine the treatment selection and evaluate long-term effects of biologic therapy across the upper and lower airways. Full article

Objective: This systematic review evaluated the clinical application of autologous tissue grafts for chin augmentation performed with or without genioplasty. The primary outcomes included clinical and aesthetic improvement, graft stability and integration, resorption, complications, patient satisfaction, and the need for secondary procedures. Methods: The review was prospectively registered in OSF and conducted in accordance with the PRISMA 2020 statement. PubMed, Scopus, Embase, Web of Science, and WorldCat were searched using terms related to genioplasty, chin advancement, and autologous grafting materials, including bone, adipose tissue, cartilage, dermal tissue, and tooth-derived grafts. Eligible studies included original clinical publications involving human patients and reporting outcomes following chin augmentation with an autologous tissue graft, with or without genioplasty. Study selection and data extraction were conducted independently according to predefined eligibility criteria. Methodological quality was assessed using the appropriate Joanna Briggs Institute critical appraisal tools. Because of substantial clinical and methodological heterogeneity across the included studies, no meta-analysis was performed, and the findings were instead synthesized qualitatively. Results: Seventeen publications were included, comprising predominantly retrospective studies, case series, case reports, and technique-oriented clinical reports, with only one prospective randomized comparative trial; the overall level of evidence was therefore low, and comparative data across graft types remained limited. The evaluated materials comprised autologous adipose tissue, dermal grafts, iliac crest bone, costal cartilage and costochondral grafts, coronoid process bone, external oblique line corticocancellous bone, mandibular bone harvested during orthognathic surgery, a third-molar tooth graft, and an osteocartilaginous nasal hump graft. Most studies reported improvements in chin projection, facial profile, symmetry, or lower facial proportions. The available evidence suggests that autologous bone and cartilage grafts may provide integration and structural support, with limited clinically evident resorption reported; however, these observations derive from limited and heterogeneous evidence. Soft-tissue grafts improved chin contour but showed less predictable volume maintenance. Dermal graft resorption reached approximately 35% after 12 months, while fat grafting was associated with soft-tissue relapse and occasional secondary lipofilling. Serious graft-related complications were not frequently reported; however, adverse-event reporting was inconsistent, preventing reliable estimation of their incidence. Reported events included infections, temporary sensory disturbances, contour irregularities, and isolated graft removals. The certainty of the findings was limited by heterogeneous study designs, predominantly small or uncontrolled samples, variable outcome measures, and inconsistent follow-up. Conclusions: Autologous tissue grafts represent potentially effective options for chin augmentation when the graft source and surgical technique are selected according to the type and extent of the deformity. The available evidence suggests that bone and cartilage grafts may provide structural support, whereas adipose and dermal tissues may be considered for moderate soft-tissue augmentation; however, these conclusions are based on limited and heterogeneous evidence. However, the available evidence does not establish the superiority of autologous grafts over sliding genioplasty or alloplastic implants. Registration: Open Science Framework. Full article

Atopic dermatitis is a chronic inflammatory skin disease increasingly recognized as part of a broader atopic and type 2 inflammatory spectrum rather than a condition confined to the skin alone. Although its dermatologic burden is well established, its relevance to otorhinolaryngology remains relatively underrecognized. This narrative review examines atopic dermatitis from an otorhinolaryngology-centered perspective, focusing on ear, nose and throat (ENT) associations, clinical overlaps, shared inflammatory pathways, and practical implications for clinical care. Particular emphasis is placed on allergic rhinitis, chronic rhinosinusitis, ear-related eczematous manifestations, and the head and neck phenotype of atopic dermatitis. Shared pathophysiologic mechanisms, including epithelial barrier dysfunction, allergen sensitization, immune dysregulation, type 2 inflammation, microbiome alterations, and allergic multimorbidity, provide a framework for understanding these overlaps. Upper airway and ear-related conditions should not be interpreted as direct manifestations of atopic dermatitis in all patients, but as disorders that may coexist within a shared atopic or type 2 inflammatory background. The review further considers the implications of this perspective for targeted history-taking, differential diagnosis, referral decisions, therapeutic awareness, and multidisciplinary care. Overall, atopic dermatitis may serve as a clinically useful marker of broader allergic and inflammatory multimorbidity, with relevant implications for selected patients encountered in otorhinolaryngology practice. Full article

Introduction and Clinical Significance: Skeletal dysplasias comprise a genetically heterogeneous group of disorders with substantial phenotypic overlap, often complicating diagnosis. Clinical exome sequencing (CES) can facilitate molecular diagnosis in children with unexplained disproportionate short stature. Case Presentation: An 8-year-old boy presented with severe short stature (−3.24 SDS), brachydactyly, relative macrocephaly, broad nasal bridge, and mild calf hypertrophy. Endocrine evaluation confirmed growth hormone deficiency (GHD). Following negative SHOX testing, CES identified a heterozygous likely pathogenic IHH variant (c.446G>A; p.Arg149His), establishing the diagnosis of brachydactyly type A1 (BDA1). Recombinant human growth hormone (rhGH), initiated for GHD, resulted in improved growth velocity and height SDS. Transient unilateral prepubertal gynecomastia developed during treatment and resolved after temporary rhGH withdrawal, with no recurrence following reinitiation. Conclusions: This case highlights the diagnostic value of CES in children with disproportionate short stature after unrevealing targeted testing and illustrates that GHD may coexist with IHH-related skeletal dysplasia. An integrated genetic and endocrine evaluation can refine diagnosis, identify coexisting treatable endocrine disorders, and guide individualized management. Full article

Background: Bacillus anthracis spores pose a major biosecurity threat, in light of their use in several documented bioterror attacks and the fact that it was weaponized. The absence of specific and accurate treatment instructions in the 2001 anthrax letter attacks and the poor prognosis of patients receiving ineffective treatment emphasized the need for reliable guidelines for treating exposed (prophylaxis) or symptomatic populations. The recent 2023 CDC guidelines for treating systemic anthrax recommend a combined treatment of a tetracycline (minocycline or doxycycline) with meropenem or a fluoroquinolone. These recommendations differ from the 2001 and 2015 updates, and in the absence of significant clinical data, rely on animal studies. Previously, we demonstrated, based on a rabbit model, that these recommendations are effective in treating various stages of anthrax, ranging from post-exposure prophylaxis to systemic involvement and involvement of the CNS. Methods: We used a trigger-to-treat type of experiment using non-human primates (NHP) infected by nasal spray of a lethal dose of B. anthracis spores. Results: We confirmed our rabbit results by demonstrating the efficacy of doxycycline as a monotherapy or in combination with levofloxacin in treating late-stage systemic anthrax in non-human primates (NHP), in a trigger-to-treat type of experiment. Our experiments show high efficacy of the mono or combined therapy. Conclusions: Our results support the CDC guidelines placing doxycycline as first-choice therapeutics by demonstrating the efficacy of using it as a monotherapy or in combination with levofloxacin, in a second highly relevant NHP model. Full article

Background/Objectives: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired ciliary function, leading to chronic airway disease. Loss-of-function mutations in ODAD3 (CCDC151) represent an established cause in patients, and Odad3-deficient mice recapitulate key disease traits. However, the impact of Odad3 ablation on upper airway development and function remains unexplored. This study investigated the consequences of Odad3 disruption on upper airway structures during development and in adult animals. Methods: Constitutive (Odad3^−/−) and inducible conditional (Odad3^icKO) mouse models were analyzed alongside heterozygous and wild-type littermates during embryonic, postnatal, and adult stages. Optimized high-resolution 3D micro-computed tomography (micro-CT or µCT) combined with histology was utilized to conduct systematic genotype-phenotype evaluations, map upper airway anatomical architecture, and assess PCD disease onset. Results: Genetic dissection revealed a marked dependence of the phenotype on whether Odad3 loss occurred during development or in adulthood. Constitutive Odad3 deletion resulted in pervasive craniofacial remodeling and turbinate hypoplasia during embryonic stages and early postnatal development. Conversely, adult-induced conditional ablation produced localized caudal atrophy of the nasal turbinates accompanied by massive mucus accumulation, consistent with impaired mucociliary clearance and providing a 3D structural and morphological characterization of chronic rhinosinusitis-like pathology in PCD mouse models. Heterozygous Odad3^icKO/+ and Odad3^+/− mice were phenotypically indistinguishable from wild-type controls, indicating that single-allele loss does not disrupt upper airway morphology. Conclusions: This study characterizes the structural timeline of upper airway pathology in PCD and validates the Odad3^icKO model as a robust 3D structural phenotyping platform for investigating airway disease in ciliopathies. Combining targeted genetic disruption with 3D µCT virtual histology offers a powerful framework for comprehensive studies of human genetic variants and gene knockouts in mouse models of PCD. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which type 2 inflammation predominates in most patients in Western populations. Galectin-10 (Gal-10) and Charcot-Leyden crystals (CLCs), linked to eosinophil activation, cytolysis and eosinophil extracellular trap cell death (EETosis), have emerged as potential biomarkers and mediators of eosinophilic inflammation. This narrative review summarises current evidence on their biological role and clinical relevance in CRSwNP. The literature was identified through searches of PubMed/MEDLINE, Web of Science and Google Scholar, with emphasis on mechanistic studies, clinical investigations and recent evidence concerning type 2 inflammatory airway diseases. Available evidence suggests that Gal-10 and CLCs are associated with eosinophil activation and may contribute to persistent type 2 inflammation through epithelial injury, increased mucus viscosity, impaired mucociliary clearance, tissue remodelling and inflammatory amplification. Gal-10/CLCs may have value as investigational biomarkers of disease activity, postoperative recurrence and response to biologic therapy. Current biologics may indirectly modulate the Gal-10/CLC pathway by reducing eosinophil survival, recruitment or activation, although direct evidence remains limited. Gal-10 and CLCs are promising investigational biomarkers and mechanistically plausible therapeutic targets in CRSwNP. However, clinical application is limited by the lack of standardised analytical methods, validated cut-off values and prospective studies demonstrating incremental value beyond established biomarkers. Further research is required to clarify their role in stratification, prognosis and monitoring of biologic therapy. Full article

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by type 2 inflammation, including M2 macrophage infiltration. Baicalein is a flavonoid with anti-inflammatory properties. This study aimed to investigate the therapeutic effect of baicalein in a papain-induced eosinophilic rhinosinusitis model and to determine whether it acts through arachidonate 15-lipoxygenase (ALOX15)-dependent M2 macrophage function. Clinical nasal samples from controls, non-eosinophilic CRSwNP (neCRSwNP), and eCRSwNP were analyzed for ALOX15 expression and localization. THP-1 cells were differentiated and polarized toward M2 macrophages, and the effects of baicalein on ALOX15 expression, lipid peroxidation, cytokine secretion, and transcriptomic profile were examined. The ALOX15 inhibitor PD146176 was used for target validation. A murine eosinophilic rhinosinusitis model was established by intranasal papain instillation, followed by baicalein treatment. Mucosal inflammation, IgE levels, proteoglycan 2 (PRG2)/ALOX15 expression, and immune cell infiltration were evaluated. ALOX15 was upregulated in eCRSwNP tissues and localized to CD68⁺CD206⁺ M2 macrophages. In vitro, M2 polarization increased ALOX15 expression and lipid peroxidation. Baicalein suppressed ALOX15 expression, lipid peroxidation, and the secretion of CCL22, CCL2, CXCL12, FGF-2, and IL-15. PD146176 produced similar effects, and baicalein showed no additional effect after ALOX15 blockade. RNA sequencing revealed transcriptional remodeling in M2 macrophages after baicalein treatment. In vivo, papain increased ethmoid sinus mucosal thickening, serum IgE, PRG2/ALOX15 positive cells, and infiltration of CD45⁺ immune cells, CD170⁺ eosinophils, F4/80⁺ macrophages, and B220⁺ B cells. Baicalein significantly alleviated all these pathological changes. In conclusion, baicalein attenuates papain-induced eCRSwNP-like inflammation by inhibiting lipid peroxidation and ALOX15-associated M2 macrophage secretory function. The ALOX15/M2 macrophage axis may represent a potential therapeutic target for eCRSwNP. Full article

Raccoon dog and fox amdoparvovirus (RFAV) has been reported in raccoon dogs and foxes, but natural infection in domestic dogs has not previously been documented. During March–April 2026, samples from four affected Dobermann dogs from a kennel near Novi Sad, Serbia, were submitted for laboratory investigation. After negative testing for canine adenovirus, canine coronavirus, herpesvirus, parvovirus, distemper virus, influenza A virus, and leptospirosis, metagenomic sequencing was performed on selected tissues, followed by bioinformatic analysis and targeted RFAV PCR screening of additional outbreak-associated samples. Affected dogs had prolonged illness characterized by conjunctivitis with ocular and nasal discharge, occasional blue eye appearance, progressive weight loss, poor coat quality, jaundice and biochemical evidence of hepatic injury, and neurologic signs including paraplegia in advanced cases. Sequencing generated 434,220 reads and identified multiple RFAV hits; pooled assembly produced a 4799 bp consensus genome with approximately 97% similarity to known RFAV strains and genome organization consistent with the genus Amdoparvovirus. RFAV DNA was subsequently detected by virus-specific PCR in an epidemiologically linked dog and across diverse specimen types including blood, urine, kidney, spleen, brain, lung, testicle, ileocecal lymph node, and throat swabs, whereas clinically healthy unrelated dogs were PCR-negative. Full article

Major airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and chronic rhinosinusitis without nasal polyps (CRSsNP), frequently coexist and share inflammatory, epithelial and remodeling features. However, whether these clinically distinct airway disorders are driven by a unified genetic liability and how this shared liability maps to disease-relevant tissues, genes and immune-regulatory programs remain incompletely understood. We integrated GWAS summary statistics for COPD, asthma, bronchiectasis and CRSsNP using linkage disequilibrium score regression, local genetic correlation analysis and Genomic structural equation modeling. A latent shared airway disease factor, termed gAirwayDisease, was constructed to capture common genetic liability across the four conditions. We then applied an integrative functional genomics framework, including gsMap spatial enrichment, PoPS gene prioritization, MAGMA gene-set enrichment, GTEx v8 lung MTWAS, OneK1K and DICE immune-cell MTWAS, scMORE regulon analysis and phenome-wide Mendelian randomization. All six airway disease pairs showed positive genetic correlations, with estimates ranging from 0.508 to 0.685. Genomic SEM supported a single shared factor, with positive standardized loadings for COPD, asthma, bronchiectasis and CRSsNP and excellent model fit. Spatial mapping localized gAirwayDisease-associated signals to airway- and epithelial-associated anatomical domains. PoPS prioritized immune and airway-relevant genes, including SMAD3, GATA3, IL1R1, RUNX3 and STAT6, while MAGMA enrichment highlighted B-cell activation, T-cell activation and transcriptional regulatory pathways. Lung MTWAS identified SLC9A2 and ORMDL3 as top genetically regulated expression signals. OneK1K immune-cell MTWAS highlighted recurrent IL18R1 associations across CD4 and CD8 T-cell subsets. scMORE further identified 36 significant regulon–cell type pairs across dendritic cells, B cells, monocytes, T cells and NK cells, including BCL11A, TCF4, KLF4, RUNX1 and STAT4 regulons. MR-PheWAS linked genetically predicted gAirwayDisease to respiratory, allergic, lung function and immune-related traits. This study defines gAirwayDisease as a genetically informed latent factor capturing shared liability across major airway diseases. Integrated functional genomic analyses highlight airway epithelial and immune regulatory programs associated with shared disease susceptibility and prioritize candidate genes and regulons for future experimental validation. Full article

Background/Objectives: Real-world evidence on dupilumab-induced clinical remission on treatment and on the predictors of complete response in severe uncontrolled asthma (SUA) is still limited. Methods: We conducted a single-centre ambispective uncontrolled observational study including 152 adults with SUA who started dupilumab. Lung function, type-2 (T2) biomarkers, patient-reported outcomes, exacerbations, oral corticosteroid (OCS) use, emergency-department (ED) visits and hospitalisations were compared between baseline and last follow-up. Response was graded with FEOS and EXACTO. Independent predictors of complete response (EXACTO = 1) were explored by multivariable logistic regression. Results: Mean age was 50 ± 12 years, 67.1% were women, baseline FEV1 was 82 ± 22% predicted, blood eosinophils were 612 ± 577 cells/µL and FeNO was 55 ± 46 ppb. After 21 ± 8 months, ACT improved from 15.7 to 23.3, ACQ-5 from 4.0 to 0.35, mini-AQLQ from 2.18 to 4.53, SNOT-22 from 52 to 16, and FEV1 by 275 ± 180 mL (all p < 0.001). Annual exacerbations decreased from 7.9 to 0.7, ED visits from 3.17 to 0.28, hospitalisations from 0.71 to 0.08, and maintenance OCS use from 11.8% to 3.9%. According to EXACTO, 95 patients (62.5%) achieved complete response/super-response. Independent predictors were higher baseline FEV1, higher eosinophil count, allergic rhinitis, rhinosinusitis with nasal polyps and atopic dermatitis, whereas prior OCS bursts and higher FeNO were inversely associated. Model discrimination was adequate (AUC = 0.91). Conclusions: Dupilumab achieved clinical remission on treatment in almost two-thirds of patients with SUA and markedly reduced healthcare utilisation. A T2-comorbidity-rich profile identified patients with the highest probability of complete response. Full article