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Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non–IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a therapeutic challenge because of the high recurrence rate. Surgical intervention should be considered in patients who fail to improve after medical treatment. We monitored recurrence and revision surgery over 12 years after endoscopic sinus surgery in CRSwNP patients. Methods In this prospective cohort study, 47 patients with CRSwNP, who underwent primary or revision extended endoscopic sinus surgery, were followed. Clinical symptoms and total nasal endoscopic polyp score were evaluated before, 6 years and 12 years after surgery. Results Twelve years after surgery, 38 out of 47 patients (80.9%) were available for examination. There still was a significantly better symptom score and total nasal endoscopic polyp score compared to before surgery (P < 0.001). Within the 12-year follow-up period, 30 out of 38 patients developed recurrent nasal polyps, of which 14 patients underwent additional revision surgery. Comorbid allergic sensitization and tissue IL-5 levels were found to be significant predictors for the need of revision surgery. Conclusions This long-term cohort study, investigating the outcome after surgery in CRSwNP, showed that, despite the low number of patients, 78.9% of patients with CRSwNP were subject to recurrence of the disease and 36.8% to revision surgery over a 12-year period.

Chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms are frequently driven by type 2 inflammation. Depemokimab is the first ultra-long-acting biological drug engineered with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice per year dosing and sustained type 2 inflammation inhibition. The ANCHOR-1 and ANCHOR-2 trials investigated the efficacy and safety of depemokimab in people with CRSwNP. ANCHOR-1 and ANCHOR-2 were randomised, double-blind, placebo-controlled, parallel-group, replicate phase 3 trials conducted concurrently at 190 centres (hospitals, specialised clinics, and clinical trial sites) in 16 countries (Argentina, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Romania, Spain, Sweden, Türkiye, the UK, and the USA). Individuals aged 18 years or older at the time of consent, with inadequately controlled CRSwNP, an endoscopic bilateral nasal polyps score of 5 or more, previous surgery for CRSwNP or previous treatment with or intolerance to systemic corticosteroids, and severe symptoms were stratified by previous CRSwNP surgery and randomly assigned 1:1 to receive either depemokimab (100 mg subcutaneously) or placebo every 26 weeks (with standard of care). Allocation was computer generated. The trial sponsor, site staff, and participants were masked. The coprimary endpoints were change from baseline in total endoscopic nasal polyps score (0–8) at week 52 and mean nasal obstruction score (verbal response scale [0–3]) over weeks 49–52, assessed in the full analysis set. Integrated analyses were conducted. Adverse events on treatment and after treatment were monitored. The trials are complete and are registered with ClinicalTrials.gov (NCT05274750 and NCT05281523). Between April 18, 2022, and Aug 7, 2023, 540 individuals were randomly assigned across ANCHOR-1 and ANCHOR-2; 528 participants comprised the full analysis set (depemokimab, n=272; placebo, n=256). Depemokimab had statistically significant improvements from baseline versus placebo in the coprimary endpoints of total nasal polyps score (treatment difference: ANCHOR-1, –0·7, 95% CI –1·1 to –0·3; p<0·001; ANCHOR-2, –0·6, –1·0 to –0·2; p=0·004; integrated, –0·7, –0·9 to –0·4) and mean nasal obstruction verbal response scale score (ANCHOR-1, –0·23, –0·46 to 0·00; p=0·047; ANCHOR-2, –0·25, –0·46 to –0·03; p=0·025; integrated, –0·24, –0·39 to –0·08). Adverse events were similar between depemokimab and placebo in ANCHOR-1 (74% [n=106] vs 79% [n=101]) and ANCHOR-2 (76% [n=98] vs 80% [n=102]). Depemokimab significantly improved clinically relevant coprimary endpoints versus placebo and was well tolerated, supporting its use as a twice per year treatment option, with the potential to reduce treatment burden for people with CRSwNP. GSK.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.

In chronic rhinosinusitis (CRS) different phenotypes have been reported based on cytokine profile and inflammatory cell patterns. The aim of this study was to characterize the intracytoplasmatic cytokines of T cells infiltrating the inflamed sinonasal mucosa. Infiltrated T cells and tissue homogenates from sinonasal mucosal samples of 7 healthy subjects, 9 patients with CRS without nasal polyp (CRSsNP), 15 with CRS with nasal polyps (CRSwNP) and 5 cystic fibrosis patients (CF-NP) were analyzed for cytokine expression using flow cytometry and multiplex analysis respectively. Intracytoplasmic cytokinesin T cells were analyzed after stimulation of nasal polyps with Staphylococcus aureus enterotoxin B for 24 hours. The number of T cells per total living cells was significantly higher in patients with CRSwNP vs. CRSsNP and controls. 85% of the CD4(+) T cells showed to be memory T cells. The effector T cells present in all tissues have a predominant Th1 phenotype. Only in CRSwNP, a significant fraction of T cells produced the Th2 cytokines IL-4 and IL-5, while nasal polyps from CF patients were characterized by a higher CD4/CD8 T cell ratio and an increased number of Th17 cells. 24 h stimulation with SEB resulted in a significant induction of CD4(+) T cells producing IL-10 (Tr1 cells). T cell cytokine patterns in healthy and inflamed sinonasal mucosa revealed that Th2 cells (IL-4 and IL-5 producing cells) are significantly increased in CRSwNP mucosal inflammation. Exposure to SEB stimulates Tr1 cells that may contribute to the Th2 bias in CRSwNP.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that—potentially severe—side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.

Background: Allergic rhinitis (AR) is the most common allergic disorder and its prevalence has significantly increased worldwide, nowadays affecting up to 40% of the population in young adults. The objective of the present survey was to evaluate the prevalence of allergic sensitization and the prevalence of clinically diagnosed AR in a sample of the Belgian population, and to estimate the effect of age and gender. Methods: We performed a cross-sectional population-based study at an annual public fair in Ghent. Participants underwent a skin prick test (SPT) to 3 aeroallergens: a mix of trees (hazel, alder, and birch), grass pollen, and house dust mite (HDM). The clinical relevance of sensitization was assessed by relating relevant symptoms of AR to the corresponding SPT. Results: A total of 2,320 participants (1,475 females, median age 44.7 years, range 3–86) were included in this study. The standardized prevalence rates of sensitization were 13.2% for tree mix, 25.9% for grass pollen, and 25.9% for HDM. Sensitization to at least one of the allergens was present in 40.3% of the subjects. Symptomatic sensitization related to trees was reported in 9.7% of cases, grass-related AR was 17.6%, and HDM-related AR was 17.1%. The overall prevalence of AR was 30.9%. Conclusion: In this study we demonstrated a 40.3% prevalence of a positive SPT to one or more common aeroallergens. A clinical diagnosis of AR was present in 30.9% of cases, peaking in the third and fourth decades of life. It is to be expected that in the next decades, when this generation grows older, the general AR prevalence will further increase.

Allergic rhinitis (AR) and asthma caused by cat dander have a highly variable prevalence across countries, which can reach 30% of the population in some regions. Cat allergens are widely distributed in the environment, making exposure nearly unavoidable, even in non‐cat‐owning households. Eight cat allergens have been identified, with Fel d 1 and Fel d 4 being particularly associated with the development and severity of asthma. Symptoms can range from mild nasal and eye symptoms to severe asthma exacerbations, with many patients experiencing polysensitization to other allergens. Management usually begins with allergen avoidance and pharmacotherapy, but these approaches are often insufficient. Allergen immunotherapy (AIT), both sublingual (SLIT) and subcutaneous (SCIT), offers a disease‐modifying strategy, though allergen potency, composition, standardization issues, and low prescription rates limit its use. AIT formulations that include allergens beyond Fel d 1, such as Fel d 4, show promise in improving cat‐induced asthma and rhinitis outcomes. Additionally, novel approaches for antigen presentation or combination therapies with monoclonal antibodies may enhance the effectiveness and safety of AIT. To increase treatment success, personalized care using component‐resolved diagnostics to identify sensitization profiles and better education for both physicians and patients are essential in the broader adoption of cat AIT.

Objectives To evaluate within‐patient symptom improvement in the dupilumab SINUS‐24/‐52 studies in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT02912468/NCT02898454). Methods Patients received dupilumab 300 mg or placebo every 2 weeks for 24 (SINUS‐24) or 52 weeks (SINUS‐52) on background intranasal corticosteroids. Patients daily reported symptoms of nasal congestion (NC), loss of smell (LoS) and rhinorrhoea on a scale of 0–3 (0 – no symptoms, 1 – mild, 2 – moderate, 3 – severe symptoms). The proportions of patients with moderate‐to‐severe symptoms (score ≥ 2) at baseline who improved to no‐to‐mild symptoms (score ≤ 1) were determined at Weeks 2, 24 (pooled studies) and 52 (SINUS‐52). Subgroups with prior sinonasal surgery and coexisting asthma were analysed. Results At baseline in the pooled intention‐to‐treat population (n = 724), the proportions of patients with scores ≥ 2 for NC, LoS and rhinorrhoea were 87, 94 and 64%, respectively. Significantly, more patients achieved scores ≤ 1 (no/mild symptoms) with dupilumab vs placebo for each symptom at each time point Week 2 NC 12% vs 2% [odds ratio 8.9 (95% CI 3.0–26.3)], LoS 5% vs 1% [4.6 (1.3–16.8)], rhinorrhoea 9% vs 2% [4.8 (1.5–15.4)], all P < 0.05; Week 24 NC 54% vs 14% [8.7 (5.6–13.5)], LoS 43% vs 6% [14.4 (7.9–26.0)], rhinorrhoea 53% vs 16% [6.6 (4.1–10.9)], all P < 0.0001. Results were similar in subgroups with prior surgery and coexisting asthma. Conclusion Significantly, more patients achieved improvement from moderate‐to‐severe symptoms to no‐to‐mild symptoms with dupilumab than placebo, regardless of prior surgery or coexisting asthma. Improvement was observed as early as Week 2 and continued through to Week 52. In this post hoc analysis of patients with chronic rhinosinusitis with nasal polyps from the SINUS‐24 and SINUS‐52 studies, with moderate‑to‑severe symptoms for nasal congestion, loss of smell, and rhinorrhoea at baseline, significantly more patients achieved improvement to no‐to‐mild symptoms with dupilumab than placebo. Improvement was observed as early as Week 2 and continued through to Week 52. Improvements were consistent regardless of whether patients had prior nasal polyp surgery or coexisting asthma.

Background Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy‐to‐use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. Methods To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow‐up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N‐PASS) tool. Results The N‐PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N‐PASS was revised to be used as an easy‐to‐use guidance tool that captures patient‐reported and physician‐assessed components for comprehensively assessing disease status and response to treatment. Conclusion The N‐PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Level of evidence Oxford Level 3. Nasal Polyp Patient Assessment Scoring Sheet (N‐PASS) was developed as an integrated tool for assessing chronic rhinosinusitis (CRS) severity and treatment response. Refined through expert validation, N‐PASS serves as a user‐friendly guide, capturing both patient‐reported and physician‐assessed components for comprehensive CRS diagnosis and management.