Coexisting type2 inflammatory diseases such as allergic rhinitis (AR), atopic dermatitis (AD), chronic rhinosinusitis (CRS) and/or nasal polyposis (NP), eosinophilic esophagitis (EoE), and urticaria are common in asthma. RAPID (NCT04287621), a global prospective registry, aimed to characterize patients with asthma initiating dupilumab in a real-world clinical setting. This analysis investigated the prevalence of coexisting type2 inflammatory diseases in these patients. Patients aged ≥ 12years initiating dupilumab for asthma (primary indication) according to country-specific prescribing information were enrolled in RAPID. Patients had regular assessments at 1month and thereafter every 3months for up to 3years, per standard of care across study sites. At the time of analysis, 205 patients were enrolled. Mean age of patients (stratified by type2 coexisting disease) ranged from 42.3 to 57.3years and mean body mass index from 29.9 to 31.8kg/m2. Most patients were female (67.3% to 77.4%), and mean time since asthma diagnosis was 17.3 to 24.0years, with mean duration of coexisting diseases ranging from 9.8 to 17.0years. A total of 189 (92%) patients had ≥ 1 ongoing type2 coexisting disease (AR, 80%; CRS and/or NP, 45% [CRS with NP, 47%; CRS without NP, 41%; NP, 12%]; AD, 27%; urticaria, 15%; and EoE, 3%). This analysis from the RAPID registry shows that type2 coexisting diseases are highly prevalent in patients with asthma initiating dupilumab in a clinical practice setting and highlights the importance of properly assessing patients to improve patient care. ClinicalTrials.gov: NCT04287621.

Background and ObjectivesTo investigate the impact of pathogenic bacterial distribution in the nasal cavity on postoperative nasal function recovery in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), and to analyze the risk factors for postoperative recurrence.MethodsA total of 178 CRSwNP patients who underwent ESS in our hospital from May 2021 to May 2023 were selected. Based on preoperative nasal secretion pathogen culture results, patients were categorized into the pathogen-negative group (42 cases), bacterial-positive group (90 cases), and fungal-positive group (46 cases). The nasal symptom visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and Lund-Mackay computed tomography (CT) score were assessed preoperatively and at 12 weeks postoperatively. Patients were followed up for 24 months and categorized into the recurrence group (36 cases) and the recurrence-free group (142 cases) based on postoperative recurrence. Relevant risk factors for recurrence were analyzed.ResultsAmong the 178 patients, the bacterial positivity rate was 50.56% (mainly Corynebacterium, Staphylococcus, and Haemophilus influenzae), while the fungal positivity rate was 25.84% (mainly Candida albicans and Aspergillus). Postoperatively, the nasal symptom VAS scores for individual items, Lund-Kennedy endoscopic scores, and Lund-Mackay CT scores showed significant improvement compared to preoperative values (P < 0.05). Comparisons among the 3 groups revealed a trend of pathogen-negative group < bacterial-positive group < fungal-positive group in nasal symptom VAS scores, Lund-Kennedy endoscopic scores, and Lund-Mackay CT scores, with significant differences observed between each pair of groups (P < 0.05). Univariate analysis showed that the proportions of asthma, history of revision surgery, eosinophilic (EOS)-type nasal polyps, and preoperative Lund-Mackay CT scores were all higher in the recurrence group than in the recurrence-free group (P < 0.05). Multivariate analysis identified history of revision surgery (OR = 6.963, 95% CI: 2.275-21.313), EOS-type nasal polyps (OR = 4.566, 95% CI: 1.449-14.392), and high preoperative Lund-Mackay CT scores (OR = 1.928, 95% CI: 1.475-2.522) as independent risk factors for postoperative recurrence (P < 0.05). Corynebacterium infection might reduce the risk of recurrence (P = 0.065).ConclusionNasal bacterial and fungal colonization in patients with CRSwNP are associated with poor postoperative nasal function recovery, with fungal colonization leading to the worst prognosis. Postoperative recurrence is closely related to EOS-type nasal polyps, a history of previous surgery, and a high preoperative Lund-Mackay CT score. Corynebacterium may serve as a protective microbial population.

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.

ObjectiveWe aim to predict eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) employing preoperative clinical parameters and machine learning algorithms, evaluating, and selecting the optimal model.MethodsRetrospective collection of preoperative clinical parameters from 331 individuals suffering from chronic rhinosinusitis with nasal polyps. Independent predictors for ECRSwNP were determined through the application of the least absolute shrinkage and selection operator in conjunction with multivariate logistic regression. Four ML models for classification were constructed and cross-validated through the training set (223 patients), with predictive performance further evaluated on the testing set (98 patients). Shapley additive explanations (SHAP) technology provides importance rankings for predictive variables and explains personalized predictions from optimal models. Net reclassification improvement and integrated discrimination improvement values assessed the improvement in predictive performance. The prognostic value of the model further validated through Kaplan-Meier analysis.ResultsPeripheral eosinophil percentage, visual analog scale, ethmoid/maxillary sinuses ratio, and nasal polyps score were identified as key variables for model construction. Extreme gradient boosting (XGBoost) proved to be the superior prediction model, attaining an area under the receiver operating characteristic curve of 0.981 in the training cohort and 0.928 in the testing cohort. The model demonstrated optimal net benefit across various risk thresholds and effectively predicted postoperative recurrence in patients with ECRSwNP.ConclusionWe constructed an XGBoost predictive model and visualized its interpretation using the SHAP method, providing a reference for preoperative noninvasive assessment of ECRSwNP patients and guiding individualized treatment.

This study aimed to elucidate the therapeutic effects of boric acid (BA) in human nasal polyp cultures, specifically investigating its ability to modulate oxidative stress, inflammation, and remodeling, and to assess its potential as an adjuvant to triamcinolone acetonide (TA). Nasal polyp tissues from 30 patients with CRSwNP, obtained prior to functional endoscopic sinus surgery, were cultured ex vivo for 72 h. Within-patient randomized groups were: control, BA 2.5 mM, TA 10 µM, BA 2.5 mM + TA 10 µM, and BA 2.5 mM + TA 5 µM. At the endpoint, cytokines (IL-2, IL-4, IL-5, IL-13, TNF-α) and MMP-9/TIMP-1 (ELISA/RT-qPCR), oxidative–antioxidant markers (MDA, GSH, CAT, TAS, TOS; spectrophotometry/ELISA), apoptosis and cell cycle (flow cytometry), and histopathology (H&E) were assessed. Relative to the control samples, both BA and TA significantly suppressed type-2 cytokines and TNF-α at protein and mRNA levels (all p < 0.01). Antioxidant responses increased with reductions in MDA and TOS and elevations in TAS and CAT (p < 0.01). MMP-9 decreased while TIMP-1 increased (p < 0.001), indicating improved ECM balance. At the cellular level, early apoptosis increased and G0/G1 accumulation suggested an antiproliferative effect. Histology showed a reduced inflammatory burden and oedema. In human nasal polyp tissue, we observed that BA attenuated inflammation and oxidative stress while supporting tissue homeostasis, demonstrating a multimodal therapeutic signal. Its combined effect profile with corticosteroids supports clinical evaluation of BA as an innovative adjuvant and a potential component of steroid-sparing strategies in CRSwNP management.

BackgroundOlfactory dysfunction (OD) is a significant symptom in non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), but its non-type 2 inflammation-driven mechanisms remain unclear.ObjectiveTo investigate the roles of local nasal non-type 2 inflammatory cytokines and systemic immune indicators in neCRSwNP-associated OD.MethodsSeventy-nine neCRSwNP patients were enrolled and divided into neCRSwNP with OD (neCRSwNP-wOD, n = 49) and neCRSwNP without OD (neCRSwNP-woOD, n = 30) groups. Olfactory function was assessed using the T&T Olfactometer. Nasal mucus cytokines (IFN-γ, TNF-α, IL-1β, IL-17) were measured by ELISA. Peripheral blood inflammatory indicators including absolute neutrophil count (Neut), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), were analyzed. Statistical methods included the Mann-Whitney U test, Spearman correlation analysis, multivariate logistic regression, and ROC curve analysis.ResultsNasal IFN-γ and IL-17 levels were significantly elevated in the OD group (both P < 0.05), while TNF-α and IL-1β showed no difference. Patients with OD also exhibited higher Neut, NLR, and SII (all P < 0.05). Olfactory scores strongly correlated with Neut (r = 0.639, P < 0.01) and moderately with IFN-γ (r = 0.533, P < 0.01). Multivariate regression identified IFN-γ, IL-17, and Neut as independent risk factors for OD. ROC analysis indicated that Neut had the highest predictive accuracy (AUC = 0.839), and a combined model of three indicators (Lund-Kennedy score, IL-17 and Neut) achieved excellent diagnostic performance (AUC = 0.964).ConclusionOlfactory dysfunction in neCRSwNP is associated with the combined involvement of local Th1/Th17 pathway activation (IFN-γ/IL-17) and neutrophil-mediated systemic inflammation. IFN-γ, IL-17, and peripheral blood neutrophils may be involved in the development of olfactory dysfunction in neCRSwNP.

This study investigates the impact of functional endoscopic sinus surgery (FESS) on happiness levels in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and examines the factors influencing postoperative happiness. This study included 55 patients (34 males, 21 females; mean age, 41.2 ± 14.7 years) who underwent FESS for CRSwNP. Preoperative and postoperative evaluations included the Sinonasal Outcome Test-22 (SNOT-22), Oxford Happiness Scale (OHS), Visual Analog Scale (VAS) for olfactory function, and saccharin clearance test for mucociliary clearance. Radiological and endoscopic disease severity was assessed preoperatively using the Lund-Mackay (LM) and Mackay-Lund Endoscopic Polyp Scores (MLEPS). A linear regression model was used to identify predictors of postoperative happiness. Postoperatively, SNOT-22 scores significantly decreased (p = 0.005), while OHS and olfactory VAS scores significantly increased (p < 0.001). Mucociliary clearance times were significantly shorter after surgery (p = 0.025). Regression analysis revealed that both the improvement in olfactory VAS scores (p = 0.006) and lower preoperative MLEPS values (p = 0.01) were independent predictors of increased OHS scores. FESS not only alleviates symptoms and enhances QoL in CRSwNP patients but also is associated with increased happiness at 1 month postoperatively. Improvement in olfactory function emerged as the strongest determinant of postoperative happiness, while patients with less extensive polyp disease experienced more favorable emotional recovery. Therefore, efforts aimed at optimizing olfactory outcomes, preserving existing olfactory function, and performing surgical intervention before widespread polyp formation may contribute to more favorable psychological outcomes after FESS.

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition affecting the sinuses, resulting in the appearance of nasal polyps and is often associated with comorbidities. Many cases do not respond to corticosteroid treatment or surgery.ObjectiveThis study aimed to explore the role of tezepelumab in the treatment of CRSwNP.MethodsPubmed, Embase, Scopus, Web of Science, and Cochrane Library were searched. Three randomized controlled trials (RCTs) comparing tezepelumab and placebo in 655 patients with CRSwNP were included. The main outcomes were nasal polyp size (nasal polyp score, NPS), nasal congestion or obstruction (nasal congestion score, NCS), and quality of life using the sino-nasal outcome test (SNOT-22).ResultsThree RCTS were included, in which tezepelumab was used to treat CRSwNP. The mean age was 50.9 years, with 56.9% male patients and 75.6% of patients with coexisting asthma. The mean difference (MD) for NPS ranged from -0.9 to -2.0 compared to placebo. Consistent benefits were observed for NCS with MD between -0.8 and -1.0 compared to placebo and SNOT-22 with MD ranging from -10 to -28 points compared to placebo.ConclusionIn conclusion, evidence suggests that tezepelumab may improve NPS and NCS, SNOT-22, loss of sense of smell, and clinically relevant endpoints (reduced need for surgery and corticosteroid use), as demonstrated in all included trials. However, the certainty and clinical applicability remain limited due to small trial size, industry sponsorship, and the lack of direct comparison with standard management and endoscopic sinus surgery. Large-scale, independent clinical trials are needed to confirm the position of tezepelumab in clinical practice for patients with moderate to severe CRSwNP.

The aim of this study is to investigate the clinical application value of exhaled nasal nitric oxide (nNO) in the pathological diagnosis and classification of epithelial remodeling in nasal polyps (NP). The differences between the nNO levels in patients with NP exhibiting different types of epithelial remodeling and the correlations between nNO and clinical data were retrospectively analyzed. The diagnostic value of nNO in NP was evaluated using receiver operating characteristic curves. The levels of nNO in the control group were found to be significantly higher than those in the epithelial hyperplasia, goblet cell hyperplasia, and squamous metaplasia groups (p=0.001, p=0.001, p=0.02). Furthermore, the levels were found to be significantly higher in the squamous metaplasia group than those in the epithelial hyperplasia and goblet cell hyperplasia groups (p=0.025, p=0.018). The percentage and count of eosinophils in peripheral blood in the goblet cell hyperplasia group were significantly higher than in the control group (p=0.001). nNO levels were negatively correlated with the ethmoid-to-maxillary computed tomography score ratio (E/M ratio) and Lund-Mackay score (L-M score) in the epithelial hyperplasia group and the goblet cell hyperplasia group (r=-0.518, p<0.05; r=-0.640, p<0.01; r=-0.421, p<0.01; r=-0.599, p<0.001, respectively). Similarly, a negative correlation was identified between nNO levels and the L-M score in the squamous metaplasia group (r=-0.612, p<0.01). nNO levels exhibited moderate diagnostic value in differentiating non-chronic sinusitis patients from epithelial hyperplasia, goblet cell hyperplasia, and squamous metaplasia [area under the curve (AUC) =0.898, p<0.001; AUC=0.882, p<0.001; AUC=0.720, p=0.025, respectively]. nNO has been shown to have significant clinical value in the preliminary pathological diagnosis and prediction of NP lesions with nasal epithelial hyperplasia, goblet cell hyperplasia, and squamous metaplasia.

Background. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disorder that has been increasingly recognized over recent decades. It is characterized by a type 2 inflammatory response, shared with other type 2 inflammatory conditions such as allergic rhinitis (AR), food allergy (FA), atopic dermatitis (AD), bronchial asthma (BA), and chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. A total of 295 patients with EoE, followed at seven Italian allergy centers with expertise in managing EoE, were included. We analyzed annual EoE diagnoses, diagnostic delay, and the presence of type 2 comorbidities - including AR, FA, BA, AD and CRSwNP - assessed via allergological evaluations at the participating centers. Statistical analyses included non-parametric trend tests, linear and logistic regressions, chi-square tests, and descriptive analyses. Results. Annual EoE diagnoses showed a significant upward trend from 2014 to 2024 (p = 0.002). However, the diagnostic delay remained consistently high, showing no corresponding reduction despite the rise in diagnoses. The burden of type 2 comorbidities was substantial, with 83.4% of patients presenting at least one comorbidity, and most patients exhibited multiple comorbidities. Conclusions. Our findings are consistent with previously reported increases in EoE diagnoses in Italy, alongside persistent diagnostic delays, and highlight the substantial burden of type 2 comorbidities in these patients, emphasizing the importance of systematic allergological evaluation and multidisciplinary managementin patients with EoE.

To describe and assess the feasibility of a simple, low-cost retrograde transillumination technique for identifying and confirming the frontal sinus opening during endoscopic frontal sinus surgery in a small series of patients. This single-center descriptive surgical series, conducted between November 2024 and January 2025, included five patients who underwent endoscopic frontal sinus surgery. The technique's five steps were standardized: angled endoscopic view (45°) of the frontal recess, probing the probable opening with angled instruments, darkening the room, placing the light source of the endoscope superomedial to the eyebrow, and observing a retrograde endonasal glow at the true ostium. In all cases, localization of the frontal opening was achieved by retrograde transillumination and independently verified with neuronavigation. Representative scenarios included nasal polyposis, pansinusitis, revision surgery (Draf III), and a pediatric patient with complicated sinusitis with epidural abscess. Retrograde transillumination enabled identification of the frontal sinus opening in all five cases and guided the extent of surgery (Draf IIa-b/III as indicated). It proved especially helpful when landmarks were distorted or when frontal recess cell variants obscured the pathway. In this limited series, retrograde transillumination appeared to be a pragmatic, cost-effective adjunct that complemented anatomical expertise, surgical experience, and neuronavigation for intraoperative localization of the frontal sinus opening. Larger comparative studies are needed to further evaluate its accuracy and generalizability.

Background The Mid-term efficacy of endoscopic posterior nasal nerve neurectomy (PNN) combined with functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is a question. Aims/Objectives To evaluate the Mid-term efficacy and safety of PNN + FESS. Material and Methods This was a multicenter, randomized, controlled, assessor-blinded trial. 60 patients were randomly assigned to PNN + FESS group (n = 30) or the FESS group (n = 30). The primary outcome measures were the VAS, Total Nasal Symptom Score (TNSS), and SNOT-22 scores assessed at baseline and at 3, 6, and 12 months postoperatively. Secondary outcomes included changes in serum levels of IL-4 and IL-5. Results At 12 months, symptom scores in both groups showed significant improvement from baseline (p < 0.001). Intergroup comparisons revealed that the experimental group demonstrated significantly greater TNSS improvement at all time points (p < 0.05). The improvement in SNOT-22 score in the experimental group was also significantly greater at 12 months (p < 0.05). Both groups exhibited a decrease in serum IL-4 and IL-5 levels. Conclusions and Significance Combined PNN and FESS provides sustained medium-term improvements in nasal symptoms and quality of life for patients with CRSwNP, showing superior efficacy compared to FESS alone.

This study aimed to examine whether chronic obstructive pulmonary disease (COPD) is associated with the subsequentdevelopment of chronic rhinosinusitis (CRS) among Korean adults. Using the 2002-2019 Korean National Health Insurance database, we conducted a retrospective cohort study. Individuals with COPD, definted by relevant ICD-10 codes recorded on at least two occasions together with at least two prescriptions for COPD-related medicines (n=615,706), were matched with control participants (n=2,184,000) by age, sex, income, and region of residence. The incidence of CRS with and without nasal polyps was evaluated in both COPD and control groups. Hazard ratios (HRs) were estimated using stratified Cox proportional hazards models, and prespecified subgroup analyses were conducted. The incidence rate of CRS was higher in patients with COPD than in control participants. After adjustment, the HR for CRS was significantly higher in the COPD group compared with the control group. Likewise, the HRs for CRS with nasal polyps and CRS without nasal polyps were also significantly higher in the COPD group than in the control group. Statistical significance was observed in all subgroups according to age, sex, income, and region of residence. Kaplan-Meier analyses showed a higher cumulative incidence in participants with COPD. In this nationwide Korean cohort, COPD was associated with a higher incidence of CRS, both with and without nasal polyps.

Biological therapy is a newer line of treatment that has been utilized in practice for patients with chronic rhinosinusitis with nasal polyps, showing excellent results. However, some patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) do not respond to this therapy. Hence, this study aims to evaluate the efficacy and safety of biological switching in these patients. Using the Web of Science, Cochrane, MEDLINE, and Embase databases, we analyzed studies involving biological switching in CRSwNP patients published up to June 2025. The studies were extracted, and data were pooled for meta-analysis. Of 3,367 studies identified, eight studies (involving 470 patients) were included in the systematic review, four of which were included in the meta-analysis. The results showed that the most common reason for switching was insufficient CRS symptom control (59.7%), followed by undesirable side effects (10.8%). The findings demonstrated dramatic effects of biological switching in terms of the SNOT-22 score, with a mean improvement of 71.4%. In addition, studies that switched patients to dupilumab showed significant improvement after switching in both SNOT-22 and nasal polyp scores. Overall, the success rate of biological switching ranged from 59.6% to 100%, with an average success rate of 79.2%. This review demonstrated the effect of biological switching as an option for patients with refractory CRSwNP or those experiencing biological side effects. These findings highlight a new therapeutic alternative that can serve as a fundamental choice when managing CRSwNP patients.

The purpose of this meta-analysis was to assess whether the outcomes of endoscopic sinus surgery in chronic rhinosinusitis with nasal polyps could be improved by adjunctive corticosteroid therapy. This meta-analysis was conducted in accordance with the PRISMA statement. We systematically searched PubMed, Web of Science, and CNKI for clinical studies comparing ESS combined with corticosteroid therapy and ESS alone in patients with CRSwNP. Eight clinical studies with an aggregate of 776 patients were included. Meta-analysis revealed: (1) A lower rate of polyp recurrence in the ESS plus corticosteroid therapy group (OR = 0.57, 95% CI: 0.33-0.97, P = 0.04); (2) Better sinonasal quality of life (SNOT-22: SMD = - 1.09, 95% CI: - 1.30 to - 0.89, P < 0.00001); (3) Decrease symptom score (VAS: MD = - 3.80, 95% CI: - 4.53 to - 3.07, P < 0.00001); (4) Better endoscopic outcome (Lund-Kennedy: SMD = - 2.05, 95% CI: - 2.27 to - 1.83, P < 0.00001). Heterogeneity was low (I² = 0%-4%), and funnel plots were generated exploratorily because of the limited number of studies. ESS combined with adjunctive corticosteroid therapy was associated with lower recurrence and improved postoperative SNOT-22, VAS, and Lund-Kennedy scores compared with surgery alone in patients with CRSwNP. However, these findings should be interpreted cautiously because endotype-specific effects, corticosteroid delivery methods, surgical extent, and long-term symptomatic recurrence were not consistently reported.

Dupilumab is a fully human IgG4 monoclonal antibody that targets the interleukin-4 receptor alpha subunit, thereby inhibiting interleukin-4 and interleukin-13 signalling, two central drivers of type-2 (T2) inflammation. It is currently approved by both the Food and Drug Administration and the European Medicines Agency for multiple indications, including moderate-to-severe atopic dermatitis (from 6 months of age), add-on maintenance therapy for moderate-to-severe asthma with T2 inflammation (≥ 6 years), eosinophilic esophagitis (≥ 1 year and ≥ 15 kg), chronic rhinosinusitis with nasal polyps (≥ 12 years in the United States and ≥ 18 years in Europe), and chronic spontaneous urticaria (≥ 12 years in the United States and ≥ 2 years in Europe) who remains symptomatic despite antihistamine therapy. Additional adult indications include prurigo nodularis, bullous pemphigoid, and chronic obstructive pulmonary disease with an eosinophilic phenotype. Beyond these established indications, increasing evidence suggests a broader therapeutic potential for dupilumab in paediatric diseases characterized by T2 immune dysregulation. This narrative review synthesizes the emerging literature on off-label and investigational paediatric uses of dupilumab, focusing on inflammatory skin diseases, inborn errors of immunity with severe atopic phenotypes, transplant-associated immune dysregulation, selected respiratory conditions and food allergy. Although current evidence largely derives from case reports, small case series, and observational studies, reported outcomes consistently indicate significant improvements in disease severity, and quality of life, with a favourable safety profile. These findings highlight the expanding role of IL-4/IL-13 blockade in paediatrics and underscore the need for prospective studies to better define efficacy, long-term safety, and optimal patient selection in emerging indications.

Biologicals have revolutionized care for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Currently, real-world efficacy (RWE) data of dupilumab in patients who switch to dupilumab after having no or minimal therapeutic response to either omalizumab or mepolizumab are lacking. No comparison has been performed between patients switching from omalizumab or mepolizumab to dupilumab and those receiving dupilumab as their first biological. 55 CRSwNP patients receiving dupilumab in the RELIBIO trial were divided into those who were biological naive (n = 30) and those who showed no to poor therapeutic response to 6 months therapy with either omalizumab or mepolizumab (n = 25), with evaluation of the following parameters at baseline and 6 months: SNOT-22 scores, nasal congestion scores (NCS), VAS scores for nasal obstruction, smell loss and postnasal drip, ACQ-5, AQLQ and total nasal polyp scores (TNPS). We determined disease control and therapeutic response evaluation (TRE) at 6 months for both groups using the EUFOREA/EPOS criteria. Dupilumab showed significant improvements on all patient-reported outcome measures (PROMs) and TNPS in both groups. When comparing the efficacy between switchers and naive patients, dupilumab showed equal efficacy in both groups on SNOT-22, TNPS, NCS, VAS scores for smell loss, nasal blockage and postnasal drip, ACQ-5 and AQLQ. A good to excellent therapeutic response at 6 months was observed in 67% of switchers compared to 97% of the biological naive patients. Regarding disease control at 6 months, we observed 44% being controlled in the switchers and 67% in the biological naive group, with smell loss being the main reason for not being controlled. This prospective RWE study shows that dupilumab significantly reduced symptom severity and nasal polyp scores in CRSwNP patients at 6 months of therapy, also in those showing a minimal therapeutic response to mepolizumab or omalizumab. Patients in the biologic naive group showed a higher likelihood of achieving disease control.

Innate immunity in allergic diseases: Novel concepts.

Distinct peripheral coagulation-fibrinolysis profiles in eosinophilic and non-eosinophilic chronic rhinosinusitis.

Real-world evidence on the effectiveness of mepolizumab at reducing healthcare resource utilization (HCRU) and clinical symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. This real-world study used linked electronic medical record and claims data from the OM1 Real-World Data Cloud of clinician networks in the US, including an ear, nose and throat physician registry. CRSwNP-related HCRU, procedures, concomitant medications, and sign and symptom outcomes were assessed in adult patients with CRSwNP who initiated mepolizumab on/after July 29, 2021 (index date), with ≥1 mepolizumab record, data available for ≥12 months pre- and ≥6 months post-index (follow-up/post-mepolizumab period). There was a significant difference in CRSwNP-related HCRU 6-months post- versus pre-mepolizumab initiation (N = 245), mean difference in outpatient visits (95% confidence interval): -0.82(-1.10, -0.53), p < 0.0001; otolaryngologist visits: -0.35(-0.54, -0.16), p = 0.0004; allergist visits: -0.28(-0.43, -0.14), p = 0.0001. Similar reductions were observed for all-cause HCRU. At 6-months post-mepolizumab, proportion of patients with oral corticosteroid and oral antibiotic prescriptions substantially reduced (36% pre- vs. 27% post-; and 38% pre- vs. 23% post-, respectively). There were clinically meaningful improvements in symptoms recorded 6-months post- versus pre-mepolizumab, with fewer patients experiencing anosmia (-53%), facial pain/pressure (-35%), nasal discharge (-32%) and nasal obstruction (-29%). In real-world practice, mepolizumab is associated with reduced HCRU and improved clinical symptoms, potentially alleviating medication burden in patients with CRSwNP. These results indicate, beyond improvements shown in randomized controlled trials, mepolizumab may reduce HCRU disease burden as early as 6-months post-initiation. This study offers real-world insight that may support clinical decision-making with mepolizumab.