Characterization of Chronic Rhinosinusitis Patients Based on Markers of Type 2 Inflammation: Findings From the European CRS Outcome Registry (CHRINOSOR).

Background: Primary chronic rhinosinusitis (CRS) can be classified based on the sinuses involved and the dominant endotype of the mucosal inflammation. Since the introduction of type 2 targeted biologics as treatment option for CRS, assessment of the inflammatory status has gained importance in CRS patients. We here aimed to characterize CRS patients with and without elevated markers of type 2 inflammation.

The Development and Validation of the Smell-Qx Questionnaire, Based on a Systematic Review of the Literature and the COMET Initiative on the Development of Core Outcome Sets for Clinical Trials in Olfactory Disorders.

Background: Olfactory dysfunction affects up to 22% of the population. Accurate assessment is vital for diagnosis and tracking outcomes, often using patient-reported outcome measures (PROMs).

Aims: We aimed to develop and validate a novel questionnaire for assessing olfactory and gustatory dysfunction.

Benralizumab and the integrated management of co-morbid severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps.

Background: Type 2 (T2) inflammation, characterized by blood and airway eosinophilia, underlies severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). In line with the Global Airways theory, SEA and CRSwNP frequently co-occur, creating a multimorbid phenotype. Separately, SEA and CRSwNP are burdensome: when concomitant, they compound each other, creating a more difficult-to-treat disease with increased complications.

Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps.

Background: Treatment with tezepelumab has been effective for sinonasal symptoms in patients with severe, uncontrolled asthma and a history of chronic rhinosinusitis with nasal polyps, but its efficacy and safety in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps is unknown.

Methods: We randomly assigned adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps to receive standard care and either tezepelumab (at a dose of 210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The coprimary end points were the changes from baseline in the total nasal-polyp score (range, 0 to 4 [for each nostril]; higher scores indicate greater severity) and the mean nasal-congestion score (range, 0 to 3; higher scores indicate greater severity) at week 52.

Efficacy and safety of twice per year depemokimab in chronic rhinosinusitis with nasal polyps (ANCHOR-1 and ANCHOR-2): phase 3, randomised, double-blind, parallel trials.

Background: 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.

Thymic Stromal Lymphopoietin (TSLP): Evidence in Respiratory Epithelial-driven Diseases Including Chronic Rhinosinusitis with Nasal Polyps.

Purpose Of The Review: Thymic stromal lymphopoietin (TSLP) is increasingly recognized for its pivotal role in the pathogenesis of various epithelial-driven chronic inflammatory diseases. This review navigates the existing evidence on TSLP, with a particular focus on asthma, before delving into the current understanding of its role in chronic rhinosinusitis with nasal polyps (CRSwNP). We explore the role of TSLP in the pathogenesis of asthma and CRSwNP, two conditions often interconnected and collectively referred to as"Global Airway Disease".

Dupilumab improves sense of smell and clinical outcomes in patients with severe chronic rhinosinusitis with nasal polyps with anosmia.

Objective: Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP.

Current Goals of NSAID-ERD Management: Patient-Centered Approaches Involving NSAID Desensitization With and Without Biologics.

The classic approach of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of cyclooxygenase 1-inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions.

Association Between Smell Loss, Disease Burden, and Dupilumab Efficacy in Chronic Rhinosinusitis with Nasal Polyps.

Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.

Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.

Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%).

Systematic Review of Long Term Sinonasal Outcomes in CRSwNP after Endoscopic Sinus Surgery: A call for Unified and Standardized Criteria and Terms.

Purpose Of Review: To present current evidence in long-term (> 5 years) results after endoscopic sinus surgery (ESS) focusing on Patients Reported Outcome Measures (PROMs) and other sinonasal outcomes while assessing the role of ESS in the treatment of CRSwNP, and identifying outcomes which affect the results of ESS and defining recommendations for future studies.

Recent Findings: Long-term results of ESS in CRSwNP can be branched in PROMs and other objective measurements. Despite the heterogeneity of reported outcomes make it difficult to perform comparisons and meta-analysis, ESS improves PROMs, including symptoms, QOL and olfaction.

Prevalence and coexistence of type 2 inflammatory diseases.

Background: Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps, and asthma (CRSwNP).

Objective: The present study used population-based prevalence in Catalonia to analyse the coexistence of type 2 inflammatory diseases in patients primarily diagnosed with the above mentioned conditions.

Results: We found a high degree of coexistence of type 2 inflammatory diseases among these patients, with the prevalence being higher in the severe forms, except for AD.

Current Management of Allergic Rhinitis.

Allergic rhinitis (AR) is the most common allergic disease worldwide and one of the most common chronic diseases in general. Allergic rhinitis is caused by inhalant allergens from outdoor and indoor environments with varying significance of different allergens in global regions. We provide options for the current management for AR including pharmacological treatments and nonpharmacological options and allergen immunotherapy (AIT).

Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations.

Purpose Of Review: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases.

Recent Findings: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons.

Impact of Dupilumab on Sinonasal Symptoms and Outcomes in Severe Chronic Rhinosinusitis With Nasal Polyps.

Objectives: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures.

Study Design: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials.

Setting: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies.