Intranasal inflammatory polyps are commonly reported in cats but are rarely described in dogs. A pug dog was presented with chronic upper airway obstruction consistent with brachycephalic obstructive airway syndrome (BOAS). Computed tomographic examination of the skull revealed intranasal soft-tissue masses causing marked airflow obstruction. Surgical correction of BOAS was completed, including removal of the intranasal obstructive tissue. Histopathologic examination confirmed inflammatory polyps. Clinical signs improved markedly following surgery. This case highlights intranasal inflammatory polyps as an uncommon and potentially underrecognized comorbidity in dogs with BOAS and emphasizes the importance of considering this diagnosis in brachycephalic dogs with persistent or atypical respiratory signs. Key clinical message: Intranasal inflammatory polyps may represent an uncommon and underrecognized comorbidity in dogs with BOAS. Recognition of concurrent intranasal pathology is important, as surgical management may result in significant clinical improvement.

Chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits pronounced endotypic heterogeneity, with macrophages serving as key drivers of sustained mucosal inflammation. In this study, we identify S100A9 as a macrophage-derived alarmin that is markedly elevated in CRSwNP tissues. Integrative analyses of public bulk transcriptomic datasets and single-cell RNA-sequencing atlases demonstrated that S100A9 expression was predominantly enriched in macrophage clusters, where it showed strong co-expression with canonical M1-associated markers, while exhibiting limited expression in epithelial cell subsets. Spatial and correlation analyses further supported a close association between S100A9[+] macrophages and epithelial barrier-related gene signatures. Functionally, shRNA-mediated silencing of S100A9 attenuated M1-like macrophage polarization, as evidenced by reduced expression of pro-inflammatory mediators and polarization markers, accompanied by a shift toward a less inflammatory macrophage phenotype. Conditioned media derived from S100A9-deficient macrophages significantly mitigated epithelial injury, leading to restoration of epithelial barrier integrity, as indicated by enhanced expression of tight junction proteins, including occludin and claudins. Importantly, S100A9 knockdown disrupted the pathogenic macrophage-epithelial inflammatory feedback loop, thereby dampening sustained inflammatory signaling and limiting epithelial barrier breakdown that perpetuates tissue damage in CRSwNP. Clinically, elevated S100A9 levels correlated with disease severity indices and effectively distinguished a macrophage-enriched inflammatory endotype of CRSwNP, highlighting S100A9 as both a mechanistic driver and a potential biomarker for disease stratification. Collectively, these findings position S100A9 as a mechanistic mediator and a promising therapeutic target for CRSwNP.

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease frequently associated with recurrence after endoscopic sinus surgery (ESS). Although biologic therapies such as dupilumab have demonstrated efficacy in severe CRSwNP, the optimal timing of treatment initiation in relation to surgery remains unclear. This study aimed to evaluate the clinical outcomes of early postoperative initiation of dupilumab after revision ESS using a multidimensional assessment of disease control. Methods: This retrospective observational study included adult patients with severe CRSwNP treated with dupilumab at a tertiary referral centre. All patients had undergone at least two previous ESS procedures and initiated dupilumab within 30 days following revision surgery. Clinical outcomes were assessed at baseline and after 12 months, including Nasal Polyp Score (NPS), Sinonasal Outcome Test-22 (SNOT-22), nasal congestion and olfactory visual analogue scale (VAS) scores, and asthma control in patients with comorbid asthma. Treatment response was evaluated using a multidomain assessment. Results: Ten patients were included. After 12 months, significant improvements were observed in NPS (from 4.7 ± 2.3 to 0.4 ± 1.0; p = 0.0019) and SNOT-22 (from 61.9 ± 17.3 to 26.5 ± 14.7; p = 0.0019). Nasal congestion and olfactory VAS scores also improved significantly. Most patients (70%) achieved an excellent multidimensional response, while 30% showed a moderate response. No patients required systemic corticosteroids or revision surgery during follow-up. Conclusions: Early postoperative initiation of dupilumab after revision ESS was associated with improvements in endoscopic findings, symptom severity, and quality of life. These findings suggest that the early postoperative period may represent a therapeutic window in selected patients with severe recurrent CRSwNP. However, results should be interpreted with caution and considered hypothesis-generating.

Chronic rhinosinusitis (CRS) is a heterogeneous and often debilitating disease characterized by persistent sinonasal symptoms and inflammation and is phenotypically classified as CRS with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP). Although CRSsNP is the more prevalent phenotype (approximately 80%), it remains disproportionately understudied, leading to critical gaps in understanding and management. This systematic literature review synthesized current global evidence on the epidemiological, clinical, humanistic, and economic burden of CRSsNP, highlighting areas of unmet need and raising awareness of the impact of this disease. PRISMA-compliant searches were conducted for CRSsNP records published 2004-2024 (epidemiological studies 2014-2024) across six electronic databases. Targeted hand searches were performed for abstracts (2022-2024), health technology assessments, guidelines, and clinical trial registries. Of 2215 records identified, 157 met inclusion criteria. CRSsNP prevalence was 4.3-10.4% in the USA, South Korea, and Spain. Patients experienced a range of symptoms including nasal/sinus (obstruction, discharge, crusting), pain, sensory (anosmia, cacosmia), respiratory (cough, asthma), oral (dry throat, halitosis), and sleep impairment. There was considerable variability in the availability and use of tools to assess severity; this impeded cross-study comparisons, consistent disease staging, and treatment escalation criteria. Associated comorbidities included asthma, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and primary antibody deficiencies. Humanistic burden was assessed using a variety of outcome measures and was higher for patients with CRSsNP than for controls. Limited data were available on economic burden. Currently available therapies were associated with high rates of treatment failure, inadequately controlled symptoms, and the need for multiple lines of therapy. CRSsNP is associated with considerable burden across clinical, humanistic, and economic domains, exacerbated by diagnostic variability, treatment limitations, and a lack of standardized research methodologies. This highlights the need for coordinated efforts among stakeholders to better address this chronic condition and support future improvements in patient outcomes.

Interleukin-5 (IL-5) is central to eosinophil differentiation, survival, and activation. Subsequent studies confirmed IL-5 receptor expression and mapped downstream signaling, showing that IL-5 promotes not only survival but also trafficking and effector functions, including adhesion, degranulation, reactive oxygen species generation, mediator release (cytokines and cysteinyl leukotrienes), and extracellular trap formation. However, the roles of eosinophils vary across diseases and tissue compartments. Multi-omics analyses of blood and tissue eosinophils across transcriptomic, proteomic, and lipid-metabolic layers reveal disease- and site-specific molecular states. These data support two opposing classes of modulators that shape IL-5-driven programs: pro-inflammatory signals (IL-4/IL-13, IL-33, NOD2-mediated innate signaling, and IFN-γ) that drive inflammatory eosinophil changes and can cooperate in some settings, and counter-regulatory signals (IFN-α and all-trans retinoic acid [ATRA]) that restrain these changes. Such modulation may influence tissue retention, effector functions, and broader eosinophil activities, including antiviral and homeostatic roles. Clinical studies of anti-IL-5 and/or anti-IL-5Rα biologics in severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndromes, and other eosinophilic diseases have improved outcomes, underscoring that disease activity often depends on IL-5-driven eosinophil activation despite disease-specific IL-5-independent signals. In this review, we summarize IL-5 biology from mechanisms to therapy and discuss how integrated multi-omics signatures and clinical biomarkers may guide patient stratification, therapy selection, and treatment sequencing toward precision medicine for eosinophilic respiratory and systemic diseases. .

Recent advances in biological therapies, small molecules and allergen-specific immunotherapy are reshaping the management of immunoallergic diseases, progressively shifting therapeutic goals from short-term disease control toward the possibility of achieving sustained clinical remission. Despite increasing evidence across multiple conditions, a universally accepted and disease-transversal definition of clinical remission (CR) remains lacking. In this review we propose a comprehensive framework for defining clinical remission across a broad spectrum of immune-mediated diseases traditionally managed in Allergy and Clinical Immunology practice, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, atopic dermatitis, mastocytosis, food allergy, and eosinophilic esophagitis. Clinical remission is defined as a sustained state of absence of clinically relevant disease manifestations, independently of underlying biological activity; suppression of inflammatory pathways and normalization of biomarkers define biological remission, which may coexist with, but is not required for, clinical remission. We introduce the 3D-CR model, a pragmatic, disease-adaptable framework integrating 3 complementary domains - clinical, biological, and functional - to characterize remission states as complete, partial, or absent. Building on this model, we propose the Allergic Disease Remission Score (ADReS) as a modular tool designed to support standardized assessment, longitudinal follow-up, and cross-disease comparison in clinical trials and real-world settings. These tools are intended as conceptual and research instruments rather than prescriptive algorithms for individual therapeutic decision-making. Finally, we outline a World Allergy Organization call to action advocating for a harmonized global approach to defining, measuring, and implementing clinical remission as a meaningful treatment target. Establishing standardized remission endpoints has the potential to improve patient outcomes, facilitate precision medicine strategies, enhance comparability across studies, and reduce heterogeneity in clinical research and practice worldwide.