Search Results (635)

Interleukin-5 (IL-5) has long been positioned as a lineage-restricted cytokine primarily responsible for eosinophil differentiation and survival. However, emerging mechanistic and clinical evidence supports a broader conceptual shift: IL-5 should no longer be viewed solely as an eosinophil growth factor, but as a context-dependent regulator embedded within dynamic airway immune networks. Drawing on advances in eosinophil subset biology, receptor signaling, and tissue-level immune crosstalk, this review reframes IL-5 biology through the lens of systems-level inflammatory regulation across airway and systemic eosinophilic diseases. Recent data reveal functional heterogeneity between resident and inflammatory eosinophil subsets, challenging the assumption that blood eosinophilia uniformly reflects pathogenic activity. In parallel, functional IL-5 receptor expression has been identified on multiple structural and immune cell populations—including epithelial cells, mast cells, plasma cells, basophils, neutrophils, and fibroblasts—supporting a broader tissue-signaling paradigm. Experimental and translational studies further link IL-5 to epithelial integrity, airway remodeling, and mucus pathology, suggesting structural and network-level effects beyond simple eosinophil depletion. Comparative analyses across asthma, chronic rhinosinusitis with nasal polyps, and COPD demonstrate that eosinophilic inflammation is biologically heterogeneous and context-dependent. While IL-5-targeted therapies yield consistent benefit in severe asthma, therapeutic responses in other airway diseases appear to be shaped by local tissue architecture and mixed inflammatory programs. Together, these observations illustrate a paradigm shift from pathway-specific inhibition toward network-informed disease control and highlight key areas for future mechanistic investigation. Full article

Eosinophils are multifunctional granulocytes that reside constitutively within mucosal tissues, where they engage in bidirectional communication with the epithelial cells lining the respiratory and gastrointestinal (GI) tracts. Once regarded solely as terminal effectors of the type 2 immunity, eosinophils are now recognized as key regulators of epithelial homeostasis and barrier integrity. Epithelial cells initiate crosstalk by releasing the alarm cytokines such as interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25, which drive eosinophil recruitment, activation, and tissue retention. Conversely, eosinophils modulate epithelial function through the release of granule proteins, cytokines, and growth factors with both damaging and reparative consequences. In the airway, this crosstalk underpins the pathogenesis of eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), in part via eosinophil-derived mediators that disrupt tight junction integrity and fuel remodeling. In the GI tract, homeostatic eosinophils support villous architecture, epithelial turnover, and goblet cell differentiation through microbiota-driven IL-33 signals and neuropeptide-mediated neuroimmune pathways, whereas dysregulated crosstalk promotes eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). This review synthesizes recent research to delineate the molecular mechanisms of eosinophil–epithelial crosstalk across mucosal compartments, highlight tissue-specific differences and shared mechanistic themes, and discuss the implications of these findings for targeted therapy. Full article

Inflammation at the superior airway level has multiple manifestations, and allergic rhinitis and chronic rhinosinusitis with or without polyps are two of the most frequent and troublesome of them, with innate and adaptive immunity being implicated. Dendritic cells, epithelial cells, neutrophils, macrophages, mucosal mast cells, eosinophils, basophils, innate lymphoid cells (ILCs), and NK cells are the players in innate immunity, while regulatory T (Treg), TH1, TH2, TH17, T follicular helper, and B cells are components of the adaptative immune system. Th9 cells, a subset of T helper cells discovered in 2008 that produce interleukin-9 (IL-9), play a vital role in the adaptive immune response and have advantageous and harmful effects in different diseases due to the induction pattern. We queried international databases for current, up-to-date information regarding the interplay between interleukin 9 (IL-9) and helper T cells (especially Th9 cells), and by other immune cells. Interleukin-9 has multiple immunological functions, acting on various target cells through its specific receptor (IL-9R), such as the following: the regulation of allergic (Th2-type) immune responses; effects on epithelial and mucosal cells, mast cells, and eosinophils; chronic inflammation; and autoimmunity. Thus, there is a further need to translate laboratory findings into clinical practice regarding IL-9. Full article

Background/Objectives: The therapeutic effectiveness of chronic rhinosinusitis with nasal polyposis (CRSwNP) depends on an accurate diagnosis that identifies disease characteristics, evaluates sinus patency, and detects paranasal sinus obliteration. This study aims to assess a novel artificial intelligence (AI) system integrated with radiomic analysis for the radiological evaluation of CRSwNP, developing a reliable and predictive clinical-radiological scoring system. Methods: This study retrospectively evaluates CT scans of patients with CRSwNP. Image analysis was performed using Radiomica LifeX (Local Image Features Extraction) version 7.5. The extracted densitometric volumes were compared to the Lund-Mackay Score (LMS) to develop a novel scoring system (P-ABCD score) and assess its radiomic predictive capability. Results: Twenty patients with CRSwNP undergoing Dupilumab therapy participated in this study. The P-ABCD score, derived from sinus CT imaging data, served as a valuable objective measure of clinical improvement following CRSwNP treatment. Conclusions: Advanced radiomic imaging techniques of the sinus cavity provide precise volumetric data combined with texture analysis. These techniques offer high sensitivity by accurately quantifying the true extent of inflammatory involvement in the paranasal sinuses, enabling effective disease stratification. Full article

Nasal hyperreactivity (NHR) is a core symptom of allergic rhinitis (AR) and chronic rhinosinusitis (CRS), frequently induced by cold stimuli. Accumulating evidence indicates that NHR is largely mediated by neuroimmune mechanisms rather than classical allergen-driven inflammation alone. Among the molecular sensors involved, the cold-sensitive transient receptor potential channels transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential melastatin 8 (TRPM8) have emerged as key regulators linking environmental cold exposure to sensory nerve activation, neuropeptide release, and immune modulation. This review systematically summarizes the expression, functions, and neuroimmune mechanisms mediated by TRPA1 and TRPM8 in AR and CRS, with a particular focus on their roles in NHR. Furthermore, it discusses the therapeutic potential of targeting these channels to alleviate neurogenic inflammation and refractory nasal symptoms, aiming to provide new perspectives for understanding disease mechanisms and developing precise treatments. Full article

Background: Upper respiratory tract infections (URTIs), allergic rhinitis (AR), and chronic rhinosinusitis (CRS) are prevalent and burdensome inflammatory disorders. Probiotics may modulate immune responses via gut–respiratory axis signaling, but their clinical efficacy across these conditions remains uncertain and highly heterogeneous. Methods: We conducted a PRISMA-guided systematic review and random-effects meta-analysis of randomized controlled trials (RCTs) evaluating oral or topical probiotics for URTIs, AR, or CRS (MEDLINE, EMBASE, CENTRAL, and Web of Science; inception to July 2025). Disease severity category (acute, subacute, chronic), episode incidence, and duration of illness were extracted alongside symptom scores. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was graded using the GRADE framework. Results: Thirty-two RCTs were included. In URTIs, certain strains [e.g., Lactiplantibacillus plantarum DR7, Lactobacillus rhamnosus GG] reduced symptom duration and antibiotic use; however, the pooled incidence reduction was non-significant (RD = −0.07; 95% CI: −0.23 to 0.09; p = 0.38), with very high heterogeneity (I² = 93.12%), limiting interpretability. In AR, probiotics reduced TNSS and improved quality of life (SMDs −0.72 to −2.30) in individual trials supported by immune marker changes [e.g., increased IL-10, decreased IgE]. In CRS, only two small trials—differing in delivery route (topical vs. oral), CRS phenotype, and publication era (2009 and 2017)—with conflicting effect directions were identified; formal meta-analysis was not performed given insufficient and methodologically heterogeneous data, and CRS findings are reported descriptively only. GRADE certainty ranged from very low (URTI incidence) to low (AR symptoms, URTI illness burden). Conclusions: Probiotic effects appear strain- and condition-specific. URTI pooled incidence data are unreliable due to extreme heterogeneity; individual strains show consistent benefits on illness burden and AR symptoms/quality of life. Evidence for CRS is insufficient for meta-analytic conclusions; findings are reported descriptively pending adequately powered dedicated trials. Strain-targeted RCTs with standardized outcomes, formal GRADE appraisal, and adequate power are needed before clinical recommendations can be made. Full article

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

Background: Central compartment atopic disease (CCAD) is a recently developed terminology used to describe a specific phenotype of chronic rhinosinusitis (CRS). The aim of this study is to provide a thorough analysis of the clinical and radiological characteristics by assessing the prevalence of symptoms, asthma, allergy, aeroallergen sensitization and radiological sinus involvement. Methods: The authors searched for articles on PubMed, Cochrane, and Embase databases. A review of the articles was carried out following PRISMA guidelines; all articles were assessed for quality according to NICE criteria. Afterwards, the meta-analysis was performed with STATA 18SE software. Studies were also assessed for heterogeneity and risk of publication bias. Mean Lund-Mackay (LMK) score of patients with and without CCAD was compared. Results: A total of 16 studies were included, including 1254 patients with CRS; 537 of these were diagnosed with CCAD. The most prevalent symptoms were obstruction at 78% and congestion at 70%, followed by rhinorrhea at 66%, hyposmia at 54%, and facial pain at 24%. Dust mite at 71% was the most prevalent sensitization. Overall, the prevalence of asthma in patients with CCAD was 26%, prevalence of allergy was 67%. The mean difference in LMK scores was −3.38 in CCAD. Conclusions: Patients frequently present with nasal obstruction and congestion; the most common allergen sensitization is to dust mites. Findings on allergy and asthma prevalence support the “Unified Airway Disease” concept and emphasize the importance of a multidisciplinary approach to managing this phenotype. CCAD patients usually do not develop very high LMK scores; high scores may rule out this diagnosis. PROSPERO registration number: CRD420261361696. Full article

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. Full article

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory syndrome of the sinonasal mucosa that is imperfectly captured by phenotypes with or without nasal polyps. Since allergic rhinitis (AR) and atopy often occur alongside CRS, the term “allergic CRS” is commonly used. However, it is uncertain whether this term indicates a specific allergen-related, IgE-mediated endotype or merely represents a clinical overlap. We synthesize epidemiologic data, mucosal immunobiology, epithelial barrier dysfunction, and host–microbe interactions that can generate IgE-rich type 2 inflammation in CRS. We propose an operational entity test (objective CRS; clinically relevant allergy; evidence of IgE relevance in target tissue; exposure–response patterns; and differential response to allergy-directed interventions) to guide hypothesis testing rather than diagnosis. Using this framework, allergic fungal rhinosinusitis and central compartment atopic disease emerge as the clearest clinical prototypes where allergen contact patterns and IgE relevance plausibly contribute to disease expression. In contrast, microbial superantigens and other non-allergen stimuli can drive local IgE amplification, limiting the specificity of systemic sensitization as a causal marker. We discuss therapeutic implications, including biologics targeting type 2 pathways and epithelial alarmin blockade, and outline research priorities for endotype-resolved cohorts and mechanism-informed trials to test whether allergic CRS should evolve from a heuristic descriptor into a validated endotype. Full article

Computed tomography (CT) of the paranasal sinuses is essential in diagnosing odontogenic chronic rhinosinusitis. Treatment primarily targets the dental focus, with endoscopic sinus surgery (ESS) indicated when necessary. Assessing CT findings using the Lund–Mackay score (LMS) may guide therapeutic decisions. This study retrospectively compared LMS, dental pathology type, and reported symptoms with treatment choices in patients treated for odontogenic chronic rhinosinusitis between 2012 and 2022 at a tertiary otorhinolaryngology center. Of 2067 chronic rhinosinusitis patients, 61 had an odontogenic cause. LMS was determined in 57 patients and correlated with treatment strategy. Dental pathology subtypes and presenting symptoms were also analyzed. A control group of 25 patients with localized, non-odontogenic chronic rhinosinusitis was included. Fifteen patients not undergoing ESS had lower LMS values (median one), while 42 surgical patients had higher scores (median six). Periapical pathology (47.4%) and oroantral fistula (26.3%) were the most common causes. Nasal discharge and pain were the most frequent symptoms. Neither dental pathology type nor symptoms significantly influenced treatment decisions. The extent of CT-detected pathology, reflected by LMS, can serve as a key criterion in determining treatment for odontogenic chronic rhinosinusitis, independent of symptoms or specific dental pathology type. Full article

Background: “Remission” is a primary therapeutic goal in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), though definitions vary regarding olfactory function. We evaluated “Dual Remission” kinetics in patients treated with dupilumab over 24 months. Methods: This single-center retrospective study analyzed 28 patients with comorbid severe asthma and CRSwNP. Dual Remission was defined as simultaneous asthma remission (ACT ≥ 20, no exacerbations, no OCS and stable lung function) and CRSwNP remission (SNOT-22 < 40, NPS ≤ 1). We additionally analyzed “Complete Recovery” by applying a stricter composite definition requiring the restoration of normosmia (Sniffin’ Sticks score ≥ 12). Results: At baseline, patients exhibited uncontrolled disease (median ACT 19, NPS 6). Treatment led to rapid asthma remission (85.7% at 12 months, 100% at 24 months). CRSwNP remission was slower but progressive, rising from 57% at 12 months to 88% at 24 months, demonstrating a significant “catch-up” phenomenon. Consequently, Dual Remission rates increased from 54% to 88% by month 24. When applying the stricter “Complete Recovery” criteria requiring normosmia, only 32% met the goal. Conclusion: Dupilumab is highly effective, enabling 88% of patients to achieve Dual Remission after 24 months. However, full olfactory restitution is distinct from structural polyp regression and harder to achieve, likely due to persistent neuroepithelial damage. Full article

Background: CD8A-related CD8α deficiency (Immunodeficiency 116) is a rare autosomal recessive primary immunodeficiency disease characterized by absent CD8⁺ T cells and variable sinopulmonary disease. Case Presentation: A seven-year-old boy from a consanguineous family was referred for chronic wet cough and “uncontrolled asthma” despite being prescribed high-dose inhaled corticosteroids and montelukast. He was hospitalized seven times over a two-year period for presumed asthma exacerbations complicated by pneumonia. An examination revealed bilateral crackles without wheezing. Throat culture tested positive for Haemophilus influenzae. CT imaging showed signs of chronic rhinosinusitis (maxillary mucosal thickening) and chronic airway disease with bronchiectatic changes. The patient’s immunoglobulin levels were within normal ranges for his age group. Flow cytometry revealed profound CD8⁺ T-cell lymphopenia (CD8⁺ 0.21%; 11 cells/µL; near-absent after excluding dual-positive cells) with expansion of CD3⁺CD4⁻CD8⁻ T cells (29.5%). CD8A gene sequencing identified a novel homozygous nonsense variant NM_001768.7:c.319C>T (p.Arg107Ter; GRCh38: chr2:86790412G>A), consistent with loss of CD8α and secondary loss of CD8β surface expression. A literature review identified three previously reported symptomatic patients (and two asymptomatic sisters in the first family), all with recurrent respiratory infections and variable structural lung disease. Conclusions: This case highlights CD8A deficiency as a rare mimic of pediatric asthma and expands the genotype spectrum with a truncating CD8A variant. Early lymphocyte immunophenotyping in children with recurrent sinopulmonary infections may prevent delayed diagnosis and progressive airway damage. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article